Towards the conquest of vitamin A deficiency disorders

TOWARDS THE
CONQUEST OF VITAMIN A
DEFICIENCY DISORDERS
TOWARDS THE
CONQUEST OF VITAMIN A
DEFICIENCY DISORDERS
Donald S. McLaren
© Task Force SIGHT AND LIFE
PO Box 2116
4002 Basel
Switzerland
Phone +41 61 688 7494
Fax
+41 61 688 1910
E-mail: [email protected]
http://www.sightandlife.org
Layout and cover design: Martin Frigg
ISBN 3-906412-02-4
SIGHT AND LIFE
Foreword
We casually and habitually talk about “scientific
progress” or refer to the “current state of research” as if the advancement and growth of human knowledge were somehow inevitable. In
fact, though, this is not the case. Major breakthroughs invariably depend on individual people being in the right place at the right time and
doing the right thing.
The present book is a testimonial to the life’s
work of Professor Donald S. McLaren, who for
over half a century now has persistently been
doing the right things in the right places at just
the right moments. He made early and decisive
contributions to the general recognition of vitamin A deficiency as a public health problem and
to our current ability to combat this condition
effectively.
At first glance, this book appears to be an autobiography. But Donald McLaren’s “personal
odyssey” has always led him to areas directly or
indirectly involving vitamin A. And so the book
can also be read as a kind of history of vitamin
A, told from a medical point of view. The value
of such a publication lies in the way it reveal-
ingly draws the reader’s attention to the element
of time. Those prepared to take a cold hard look
at the aberrations and confusions of the past
run less of a risk of accepting today’s received
wisdom as definitive and absolute. The insight
that the current state of our knowledge is also
a measure of our current ignorance is a crucial impetus for the improvements and advances
of tomorrow.
There is no question that Donald McLaren is an
irredeemably inquisitive investigator and a man
who argues his views elegantly and incisively.
Over the years his contacts with the Task Force
SIGHT AND LIFE have been many and varied,
and this long-standing relationship was intensified further last year when the Task Force published the Manual on Vitamin A Deficiency Disorders.
SIGHT AND LIFE feels honoured to have been
entrusted by Donald McLaren with the publication of the present work. We are issuing this book,
which offers an articulate plea for dedication to
research, as a way of saying thank you to an exceptional scientific figure.
Dr Andres F. Leuenberger
Chairman, Task Force SIGHT AND LIFE
5
SIGHT AND LIFE
Contents
Foreword
Introduction
5
9
Chapter 1
An outline history
Vitamin A deficiency disorders (VADD)
Panel 1: Misunderstandings about night
blindness
Panel 2: The story of cod-liver oil
Panel 3: Vitamins and the arrow of time
Panel 4: The early neglect of xerophthalmia
Discovery of the vitamin
Panel 5: Abandoning of the anti-infective
vitamin
13
13
15
17
18
20
21
22
Chapter 3
Chapter 2
A personal odyssey
Growing up between two world
wars (1924–1949)
Panel 6: The Edinburgh Medical School
and Nutrition
Panel 7: Nutrition at the London School
Mission in India (1950–1954)
Panel 8: William Carey, the Baptist
Missionary Society and the
Kui people
Panel 9: Cicely Delphine Williams
(1893–1992)
Back in London (1954–1957)
Panel 10: The East African Institute for
Medical Research
Panel 11: The Princeton conference
in June 1958
Medical research in Tanganyika (1958–1962) 60
Panel 12: H. A. P. C. Oomen (1902–1986) 61
The Switzerland of the
Middle East (1962–1976)
77
Panel 13: The American University
of Beirut, Lebanon
78
Panel 14: The Xerophthalmia Club Bulletin 94
Panel 15: Xerophthalmia prevention
in Madurai, India
95
Panel 16: The International Vitamin A
Consultative Group
102
Return to Edinburgh (1976–1988)
106
Panel 17: Four uneasy bedfellows
107
Retirement in Worthing (1988)
113
25
26
34
38
40
43
47
48
56
58
Update and commentary
117
Chapter 4
Looking to the future
Introduction 121
Problems with xerophthalmia
No magic bullet for intervention
No gold standard for assessment
Unanswered questions
Unlearned lessons
Questionable concepts
Future for some “institutions”
121
Epilogue
References
Index
129
131
141
122
122
123
123
124
126
126
7
SIGHT AND LIFE
Introduction
This book has rather unusual origins. Dr Martin Frigg
of SIGHT AND LIFE and I entered into a collaboration in 1996–97 to produce the SIGHT AND LIFE
Manual of Vitamin A Deficiency Disorders (VADD)
(1) and the slide set on the same subject. These have
been made freely available by SIGHT AND LIFE,
and it is gratifying to think that they are making a
significant contribution towards the conquest of vitamin A deficiency disorders, which is also the title
of this present volume.
In the course of undertaking this task I reviewed a
great deal of material in the field, both ancient as
well as modern. With the help of diary entries and
old notes, I then began to write an account of what
amounted to “how I got into vitamin A”. Readers of
the Xerophthalmia Club Bulletin, which will feature
prominently later (Panel 14, page 94), may recall that
as its editor I ran a series there on that theme which
provided some fascinating accounts of the very diverse backgrounds of those of us working on this
problem. Martin read a rough draft of this account,
and I am happy to acknowledge that it is entirely due
to his encouragement and many helpful suggestions
that this work is coming to fruition here.
The original concept has been transformed and the
value of the final product has, I am sure, been greatly
enhanced. It consists of four chapters that are to a
considerable extent independent of each other. It will
probably be helpful to the reader for something to be
said in explanation about the topics covered in each
of the chapters.
Chapter 1, An outline history of vitamin A deficiency
disorders and of the discovery of the vitamin, gives
an account of the main events. No attempt is made
here to be exhaustive in the treatment of the subject.
There are already detailed accounts available elsewhere to which interested readers are referred.
In this chapter I have inserted several “panels”, which
present topics that seem to merit separate discussion.
This form of presentation, whilst giving some prominence to subjects that might interest the specialist
reader, permits the more general reader to pass these
panels over readily.
Chapter 2, A personal odyssey, forms the main part
of the book. It includes my own experiences when I
was living and working in many countries while on
the trail of VADD. It was a very exciting period to be
working on a problem that was gradually revealed to
be of enormous public health importance in many
parts of the world. I have tried to be as objective as
possible, and although I have made every effort to
avoid factual errors, I hope that the reader will forgive me if perhaps I have given way to excessive
enthusiasm at times.
Along with the story of my own experiences I have
again included at intervals a series of panels which
serve as vignettes of various people, places or institutions that are intertwined with my own story in
some way. At first I thought I could write a separate
chapter on the work of others in the VADD field at
that time. However, as things began to unfold I realised that it was not possible to separate those I needed
to mention in connection with my own work and others not so clearly associated. I am sure that for the
average reader this unified approach will be more
satisfactory. It is probably more important to understand how knowledge in a certain area unfolded over
a period of time, than to be told who did what and
when.
My account is based on the written evidence and the
memory I have of what others were contributing during the period of my own active participation. The
world of medical research was very different in those
days from what it is today. Research was usually car9
Introduction
ried on by individuals or very small groups, not like
the multidisciplinary forces of today. Projects were
on a smaIl scale and funding often both limited and
of uncertain duration. It should also be recognised
that those of us who were working on nutritional
diseases were for the most part living in isolated
parts of the world. We had few and uncertain means
of communication. Scientific meetings were held
much less frequently than today. We only rarely had
opportunities to meet face to face.
If some who read this feel that I have omitted or
diminished their own contribution or that of others
they know, then I truly regret this, for any such error was entirely unintentional.
Chapter 3 consists of an Update and commentary. It
may be said that a new era for VADD began when
it was demonstrated in the early 1980s in large-scale
field studies for the first time that vitamin A plays
an important role in the survival of young children.
I have found the unfolding of this major development especially fascinating to follow. Two decades
or so previously our group in Beirut had been carrying out clinical (page 82) and field (page 86) studies of a preliminary nature that were pointing in this
direction.
It so happens that it was about that time when I
ceased to make original contributions in the field.
However, my continuing participation in such
activities as teaching at the International Centre
for Eye Health (ICEH), attendance at meetings
of the International Vitamin A Consultative Group
(IVACG) (see Panel 16, page 102) and serving as
the editor of the Xerophthalmia Club Bulletin
since 1985 has meant that I have remained closely
in touch with subsequent developments. Achievements in the field over the past 20 years or so
have entered the body of scientific knowledge and
have been extensively documented, most notably in the book by Sommer and West (2). They
have also been recorded in a more general form
in the SIGHT AND LIFE manual (1) and elsewhere. This chapter provides the salient information for this period to help the reader to bridge
the gap in time between recent history and the
final chapter.
Chapter 4 is called Looking to the future. It seems
appropriate that in a book that looks towards the
conquest of a health problem, like VADD, there
should be a place for a final section that takes a
look into the future and tries to point out some lessons that need to be learned from past experience.
Here again the views expressed are bound to be very
personal and therefore open to challenge by others.
Any such controversy of a constructive nature
should be warmly welcomed. It could bring the day
of the conquest of VADD nearer than might otherwise be possible. That, indeed, is the primary purpose of this book.
Donald S. McLaren
Summer 1999
10
SIGHT AND LIFE
11
SIGHT AND LIFE
Chapter 1
An outline history
Vitamin A deficiency
disorders (VADD)
enon is clearly described and there are no difficulties over translation then one may be fairly satisfied
that VAD is being described. There are other causes
of night blindness but these are all quite rare.
This is intentionally a brief introduction to the subject. Wolf has recently written an excellent history
of vitamin A and retinoids (3). My main purpose here
is to set the scene for the next chapter of personal
experiences. I think it is important to view these in
perspective. At the time it rather seemed as though
very little was known about vitamin A deficiency
disorders (VADD). Although this was true the position was that this was because the disease had fallen
into a period of neglect. When one comes to review
the history it is quite remarkable what a lot of work
had gone on.
On the other hand, dryness or xerosis of the conjunctiva or cornea and keratomalacia require close
and expert examination of the eye for their identification. Not surprisingly therefore, it is not possible
to identify them precisely in ancient literature. Usually no clear distinction is made between various eye
diseases that lead to haziness of the cornea and/or
the lens.
There are several topics about which there is some
controversy or consideration of which may provide
a lesson for the present from the past. These would
seem to merit separate treatment, and this has been
set out within several panels.
Most historical accounts of vitamin A deficiency start
back in antiquity by reference to what are interpreted
as descriptions of the use of liver in various ways for
the treatment of night blindness. It is claimed that
several medical papyri from Egypt and accounts from
India and China convey this kind of information.
Recent research casts some new light on the subject
and Panel 1 discusses this topic.
A good deal of care must be exercised when one is
seeking information about the occurrence of VAD in
pre-scientific times. True night blindness is a very
distinctive symptom and providing that this phenom-
It is quite a surprise to realise that it was as late as
1913, the very year when “fat-soluble A” was discovered by McCollum, that the first connection was
made between night blindness, rhodopsin and
keratomalacia (4). Ishihara proposed that a fatty substance in the blood was needed for the synthesis of
visual purple in the retina and “keratohyalin” in the
surface layer of the cornea.
Celsus, the most famous Roman author on medicine,
sometimes called “the Latin Hippocrates”, is credited as the source of the first description of xerophthalmia (9). His account of the disease and recommended treatment goes as follows: “There is a kind
of dry inflammation of the eyes called by the Greeks
xerophthalmia. The eyes neither swell nor run, but
are nonetheless red and heavy and painful and at night
the lids get stuck together by very troublesome
rheum; the less violent the onset of this kind of trouble is, the less readily it is terminated. In this lesion
there is need for much walking, much exercise, frequent bathing, sitting in the bath and sweating, and
much rubbing. The food should not be too flesh13
History
making, neither is acid food suitable, but a mean
between the two. In the morning when it is plain that
all food has been digested, it is not inappropriate to
gargle with mustard, then next to rub the hands and
face for a considerable time.”
in the treatment of rickets and other bone disorders.
How cod-liver oil came to occupy an important role
in nutritional medicine in general and VAD in particular and its continuing popularity to the present
day is described in Panel 2.
I have given this quotation in full to make it clear
that Celsus made no mention at all of liver. This implies that no association was made between xerosis
of the eyes and night blindness at that time. Knowledge
of the efficacy of liver for the treatment of night blindness persisted through mediaeval times in Europe.
At about the same time the germ theory of disease
received a tremendous boost from the discoveries of
Pasteur, Koch and colleagues of bacteria as causative agents of major diseases. Also, accepted teaching about nutrition stated that carbohydrates, fats,
proteins and some other elements comprised all the
components of a complete diet. The scientific community was reluctant, however, to entertain the possibility of an essential role for health of small amounts
of organic compounds in the diet, later to be known
as vitamins. Possible reasons for this are pursued
further in Panel 3.
A book on diseases of the cornea published in 1729
first associated corneal blindness with measles (10),
but without any suggestion that a faulty diet was involved. A few years later it was proposed that night
blindness could result from either dietary deficiency
or excessive exposure to sunlight (11). We now know
that bleaching of visual purple (rhodopsin) in the
retina can exacerbate the condition.
Serendipity is well-known to play a part frequently
in medical discovery. An interesting example occurred in the early years of the 19th century when
the celebrated French physiologist Magendie was
examining food components as nutrients (12). He
noted in passing that dogs restricted to wheat gluten,
starch, sugar, or olive oil as their sole food developed ulcers of the cornea. This seems to have been
the first experimental production of a deficiency disease, i.e., keratomalacia.
This chance observation might not have received
much attention unless the medical missionary and
African explorer David Livingstone years later had
not described how the eyes of some of his native
carriers who had to subsist on sugarless coffee,
manioc, and meal “became affected as in the case
of animals fed on experiment on pure gluten or
starch” (13).
In the middle of the 19th century cod-liver oil was
recognised as curative in night blindness and xerosis
conjunctivae. This was many years after its first use
14
Throughout the earlier years of the 19th century
there were sporadic reports of keratomalacia in severely malnourished patients in Europe. The famous German ophthalmologist von Graefe reported seeing two or three cases a week in his clinic
(29). The first report from a tropical country,
Brasil, at about the same time (30) spoke of night
blindness among plantation workers and keratomalacia in their children. de Hubbenet (31), chief
medical officer of the small French force in the
Crimean War, gave the first description of conjunctival patches of xerosis and noted their association with night blindness and a poor diet. A few
years later Bitot noted the same phenomenon in
orphan children in Bordeaux, and his name became
associated with the dry spots (32).
The relationship of poor general health and infectious disease to xerophthalmia was noted in relation
to intestinal disease (33) and liver disease (34) at
about that time. Rather later, in 1897, Herbert appears to have been the first to note that other mucous
membranes besides the eye were affected (35). These
early observations pointed the way to recognition
much later on that VAD has important implications
beyond the eye for health.
Panel 1
Misunderstandings about night blindness
It is generally agreed that liver was recommended
for the treatment of an eye complaint that fits with
the description of night blindness from very early
times. There are reports from Egypt, India and China
of animal liver being roasted or fried and fed as a
cure. Many writers have seized upon the fact that
liver is a rich source of vitamin A and drawn the conclusion that as a consequence it would over the
years be found to be effective in night blindness.
Against this has to be set the evidence that liver
was also recommended for other eye conditions that
from their description had no relation to VAD, and
even for disease of other organs. More often than
not the descriptions of disease were so vague, in
our terms, that interpretation into our system is impossible. Moreover, in the magical systems of medicine prevailing in those times in some cultures, study
of the liver, hepatoscopy, played an important part.
According to an earlier paper by Wolf (5) the earliest sources of a treatment for night blindness in
Egypt proposed topical application of an extract from
the liver to the eye. He made the suggestion that
some of the extract containing vitamin A that was
applied to the surface of the eye would have passed
down the naso-lacrimal duct and been absorbed into
the blood stream. It is not unknown for xerophthalmia to be treated by local application of fish liver oil
in this way in some societies in present times. Two
sources for this proposed topical use were cited by
Wolf (5) – both are Egyptian papyri dating from many
centuries BC. Other, much later recommendations
in the Greek literature for topical application of liver
appear to derive from these Egyptian sources. The
less important is known as “The London Medical
Papyrus” and dates from about 1400 BC. Recipe
number 35 states, “Another recipe. Beef liver placed
on a fire of straw of emmer or barley and smoked in
their smoke; their (the liver’s) liquid squeezed
against the eyes.” The problem is that there is no
An attempt to visualise the problem of night blindness.
From the SIGHT AND LIFE poster.
specific use of a term that can be translated as night
blindness.
A similar problem arises with the even more important Papyrus Ebers, dating from about 1520 BC. This
is recognised to be the oldest book on medicine (6).
It has a large section on eye diseases. While the
prescriptions are carefully detailed, the diseases are
only mentioned by name. Frequently the latter cannot be positively identified in modern medical terms.
It is Ebers 351 that is of special concern to us here.
It refers to the treatment of “sharu-disease with
roasted ox liver, pressed, applied thereon, really
effective”. Sharu was first interpreted as night blindness by Ebbell in 1937 (7). This incorrect interpretation has been accepted by many. However, it is
15
now universally agreed by scholars of the subject
that Ebbell’s version is full of mistakes, even he
(Ebbell) admitted that “most of his attempts at identification were highly conjectural”.
In the Hippocratic collection the word nyktalops occurs five times. The word contains the root nyx, night,
and ops, the face – suggesting “somebody who only
sees at night”.
Nunn has recently published a very thorough study
of ancient Egyptian medicine (8). With regard to
Ebers 351 he points out that the word sharu or shau
denotes only an eye disease that cannot be specified now. The ideogram for “night” does not appear
in the word. Other recent authors cited by Nunn also
translate sharu only as “eye disease”. Wolf’s later
paper (3) accepts the interpretation by Nunn.
From the descriptions we have it would appear that
photophobia is being referred to. This might have
resulted from keratitis associated with prolonged
exposure to bright sunlight. However, Galen and his
successors used nyctalopia in the entirely contrary
sense of night blindness. Hirschberg cites many instances of this confusion through the ages. This is
how the word is usually used today.
There is another area of confusion that has persisted
for hundreds of years over the terminology of night
blindness. On the face of it, the symptom of night
blindness is clear-cut and can be explained in very
simple words. However, as Hirschberg (6) states,
the terminology that has been in use since the time
of Hippocrates means that “we face a controversy
which has continued into our days”. It is primarily
the meaning that has been given to the word nyctalopia, and to a lesser extent the use of the term hemeralopia, that have resulted in all the confusion.
Hirschberg’s classic (6) is the source for the comments that follow.
It is not clear when the term hemeralopia (hemera,
day) was introduced. When used, it is now usually
regarded as being synonymous with nyctalopia. This
practice persists today especially in the French use
of nyctalopie and hemeralopie.
In Britain in 1898 Stephenson (36), in what seems
to have been the first extensive field study of VAD,
examined more than 6000 children in orphanages
and schools and found 1.87% with “epithelial xerosis of the conjunctiva”. Night blindness was usually also present and occasionally contraction of
the visual fields was demonstrated.
years later it was suggested that night blindness might
be due to retarded regeneration of this visual pigment (38). An accurate description of the histological changes in the conjunctiva and cornea in VAD
was given at about the same time (39). These changes
could be cured by an adequate diet, using raw cow’s
milk (40).
A greater understanding of the nature of VAD began to develop towards the end of the 19th century. The visual pigment, known as visual purple
or rhodopsin, was identified in 1878 (37). Three
The first account of truly epidemic proportions was
that of the 1400 cases of conjunctival xerosis and
keratomalacia in children aged 2–5 years in Japan
reported by Mori in 1904 (41). He observed that the
16
In conclusion, Hirschberg’s advice to abandon the
Greek terms and use only the unequivocable English or German words available, appears eminently
sound. He concludes, “It is nonsensical to continue
using Greek words which were even to the Greeks
2000 years ago not quite clear”.
Panel 2
The story of cod-liver oil
This story is sufficiently important for a book entitled
“Cod: A biography of the fish that changed the world”
to have been written about it recently (14). Here we
are primarily concerned with that part of the story
that tells how this oil came to occupy its place as a
firm favourite among nutritional supplements in general and as a source of vitamin A in particular.
In a crude form, sometimes mixed with mutton tallow, fish oil had been used as a home remedy for as
long as can be remembered along the coasts of
Northern Europe. It seems to have been first used
medicinally in England in the 18th century for “rheumatism” (15). In this connection it is interesting to
note that a revival in the use of cod-liver oil in rheumatoid arthritis has been shown to have a scientific
basis. Some of the polyunsaturated fatty acids it contains decrease production of leukotrienes involved
in the inflammatory process.
Cod-liver oil seems to have been first recommended
for the treatment of rickets in 1824. The famous
French physician Armand Trousseau, who played an
important part in the discovery of vitamins
(see Panel 3), recommended the liver oils
of cod and other fish for the treatment of
rickets in the 1830s. This use of the oil
tended to overshadow an appreciation of
its efficacy in night blindness at about that
time. Later on cod-liver oil became standard treatment for all forms of VAD.
The first demonstration that cod-liver oil
contained vitamin A, or a “fat-soluble complex” as they called it, was made by
Osborne and Mendel (16). Zilva and
Drummond (17) showed it to be present,
sometimes in much higher concentrations,
in other fish livers.
Attention has been drawn to the frequent association of VAD with infections. The fascinating story of
the era when vitamin A was known as the “anti-infective” vitamin is told in Panel 5. Here it may be
noted that in almost all the trials carried out during
that time cod-liver oil was given as the source of
vitamin A. The pharmaceutical companies were
quick to promote the product as a routine preventive measure for young children. The disagreeable
taste was sometimes masked in treacle; at others
mothers would boast of their “good little boy taking
his cod-liver oil” – I remember being such a one!
Many years on, cod-liver oil has managed to retain
its place as a popular home remedy, but for very
different reasons. Now it is generally older people
who take it – very often the survivors from the earlier days! This time it is partly for rheumatism, as
has been mentioned. Some of the polyunsaturated
fatty acids also prevent the aggregation of platelets
and the tendency to coronary thrombosis. The oil is
also quite a good source of vitamin E, which may
also help to prevent heart attacks.
The rich decoration of this cod-liver oil bottle still reflects the value
its content once had.
17
Panel 3
Vitamins and the arrow of time
It is sometimes said that science gives history its
time arrow. By this is meant that science is cumulative, with a definite development and progression
with time. The arts show this to a much smaller extent and morality would seem to ignore the arrow
altogether! Mayer (18) described in a truly thoughtful article how the abandonment of the discovery of
the aetiology and treatment of rickets by the great
French physician, Armand Trousseau, is an astonishing example of the reversal of the arrow. His association of rickets with a defective diet and its cure
by cod-liver oil put forward in the first half of the
19th century were generally forgotten by 1900. It is
likely that Trousseau’s contributions, along with other
evidence for a defective diet in the aetiology of disease, were, as Mayer says, “swept away in the enthusiasm for Pasteur’s germ theory of disease”.
Follis, a nutritional pathologist (19), and Carter, a
philosopher (20), have provided convincing evidence for this concept.
In their review Ihde and Becker (21) point out that
all four of the following diseases – rickets, scurvy,
beriberi and pellagra – at about that time were seriously considered by some to be due to infectious
organisms.
A medical historian, Rosenberg (22), makes the additional point that although physicians of the time were
aware of a relation between diet and disease, they
found it difficult to believe that a disease might be
caused by the absence of a factor in minute amounts.
In 1929 F. G. Hopkins of Britain and C. Eijkman of
the Netherlands shared a Nobel Prize in physiology
and medicine for the discovery of vitamins. In recent
years there has been considerable historical research
into the lives and work of many scientists over a period of almost 100 years who made contributions in
this field. As so often happens when hindsight is
18
brought to bear on a matter like this, it is very doubtful if either deserved the special honour they received.
In the mid 19th century the ideas of the German
chemist, Justus von Liebig (1803–73) dominated
scientific and lay thinking alike on nutrition. He taught
that foodstuffs contained only “water, mineral matter,
proteins, carbohydrates and fats”. The body was like
an engine, protein from the diet built up the tissues,
carbohydrates and fats provided energy.
N. I. Lunin (1853–1937) was probably the first to provide evidence to challenge Liebig (23). He showed
that mice cannot survive on purified diets of fat, carbohydrate, protein and salts alone. They could when
milk was added. He concluded, “other substances
indispensable for nutrition must be present in milk
besides casein, fat, lactose and salts”. In Holland in
the early years of the 20th century C.A. Pekelharing
(24) demonstrated that mice were able to survive on
diets to which small amounts of milk were added. W.
Stepp (25) extracted the milk with alcohol ether, removing the lipids, and the mice did not live.
C. Eijkman was sent to the Dutch East Indies (Indonesia) in 1886 to try to discover the cause of beriberi
(vitamin B1 or thiamin deficiency). He returned to Holland convinced the disease was caused by a toxin. It
was his successor Grijns who showed it to be a nutritional deficiency; but no Nobel Prize for Grijns!
Hopkins, the joint Nobel Prize winner with Eijkman,
became a towering figure in the new discipline of biochemistry in the years just before and after World
War I. He coined the term “accessory food factors”,
which did not last. It is ironic that Casimir Funk’s term
“vitamine” did. Funk popularised the subject (26), but
made no fundamental contribution. Careful
reevaluation of the work of Hopkins on vitamins casts
doubt on its quality (27, 28).
SIGHT AND LIFE
associated diet was deficient in fat and there was a
good response to cod-liver oil. He noted that the
children of fishermen were protected. The disease
was so common at that time that the Chinese term
“hikan” was used to describe it. Wolf has recently
written an interesting overview of the work of
Mori (3).
During the early years of the 20th century evidence
grew that fat from certain dietary sources was essential. In a series of experiments Stepp (25) demonstrated that a small amount of lipid in the diet of mice
was essential if they were to survive normally. Falta
and Noeggerath (42) induced a more severe VAD in
rats that led to xerophthalmia. Some years later Holm
(43) studied the feeding habits of chickens exposed
to different intensities of light and was able to demonstrate the phenomenon of dark adaptation. Holm
(44) also showed that deficient animals have a subnormal rate of regeneration of visual purple.
The impression may have been given here that considerable attention was being paid to xerophthalmia
in the later part of the 19th and the early years of the
20th century. However, this was not in fact the case.
With certain notable exceptions VAD was almost always omitted from any discussion of vitamin deficiency diseases. The possible reasons for this are considered in Panel 4.
Just before World War I Osborne and Mendel of Yale
(48) and McCollum and associates of Wisconsin (49)
showed that certain animal fats like butterfat, egg
yolk or cod-liver oil contained a substance essential
for the growth of rats and which also cured eye disorders. McCollum termed this substance “fat-soluble A” as it was the first of what Hopkins earlier (50)
called “accessory food factors” to be identified.
McCollum had studied separately under Osborne and
also Mendel at Yale before he moved to Wisconsin.
It has been suggested (51) that he was rather lucky
to have been credited with the discovery of the first
vitamin. A paper by Osborne and Mendel (52) appeared in the same journal as McCollum’s paper and
was received for puplication only three weeks later.
It is also interesting that Osborne and Mendel paid
much more attention than did McCollum to the eye
lesions that afflicted their animals (53).
At about the same time the paediatrician Bloch (54)
in Denmark described 40 cases of xerophthalmia in
young children from poor households subsisting on
diets of bread, potatoes, and fat-free milk. He extended his work to a children’s home and showed
that a group that did not receive whole milk developed xerophthalmia while those who did were protected. Cod-liver oil caused the xerosis to disappear
within one week. Bloch thus confirmed for humans
the essential nature of dietary vitamin A.
Somewhat later Blegvad (55) reviewed over 600
cases of children suffering from xerosis conjunctivae and keratomalacia in Denmark between 1909
and 1920. The peak of the epidemic occurred from
1914 to 1918, the years of World War I, when Bloch
was carrying out his studies. During this period
butter, a major product of Denmark, attracted such
high prices abroad that it was unobtainable at home
except by the rich. The poor had to make do with
margarine, which was not fortified with vitamins
then.
Blegvad, for the first time, made a careful study of
the outcome of the disease. Of 438 treated cases there
was sufficient information available on 391. 93 died
despite the treatment. Of the remaining 298, 79 were
totally blind, 71 had greatly reduced vision in both
eyes, in 105 cases vision was greatly reduced in one
eye, and in only 43 both eyes recovered. These early
survival figures may be compared with those of later
studies (see pages 54, 82).
Shortly afterwards interest turned to the suggestion
that certain yellow pigments in plants had vitamin A
activity. A colleague of McCollum’s at Wisconsin,
Steenbock, showed that carotene, but not
xanthophylls, induced growth in deficient rats (56).
About ten years later Moore (57) demonstrated the
conversion of carotene to vitamin A in the body.
19
Panel 4
The early neglect of xerophthalmia
The present intention is to try to understand why, in
the previtamin era of the 19th and early 20th centuries, xerophthalmia was excluded from the group of
diseases considered to be due to dietary deficiency.
I call this early neglect because it was to be followed by further periods of neglect (see pages 52,
73, 106).
Attention has been drawn (page 14) to the occurrence of eye lesions, almost certainly due to
keratomalacia, in dogs fed deficient diets by
Magendie in 1816. This chance observation went
unnoticed until much later. As we have seen (page
14), sporadic cases were reported in Europe and
xerophthalmia was known to occur in the tropics.
Nevertheless, when nutritional deficiency diseases
began to be considered as a group xerophthalmia
was not among them.
The only exception of which I know is a series of
five articles on “Disorders resulting from defective
nutriment” published by a London physician George
Budd (1808–82) in 1842 (45). Budd drew on his experience as a physician to the Dreadnought Seaman’s Hospital Ship and visits to prisons and asylums. He grouped three diseases in this category;
scurvy, rickets, and “a peculiar ulceration of the cornea”. In recent times Hughes (46) drew attention to
this pioneering work, but he made no mention of
the fact that Budd was alone in including xerophthalmia in the group of disorders attributable to dietary deficiency.
Almost all those writing on the subject mentioned
scurvy and rickets and by the beginning of the 20th
century the group numbered four members – scurvy,
rickets, beriberi and pellagra. Funk (26) adhered to
this view and was frequently quoted as a result. As
we have seen (Panel 3), at one time or another each
of these diseases had been attributed to a causa-
20
tive pathogenic organism. Xerophthalmia is not mentioned in this connection, but it is interesting to observe that the eye signs of xerophthalmia in experimental animals were considered at one time to be
due primarily to infection (47).
It is particularly intriguing that of all the vitamins,
and indeed of all micronutrients, it was deficiency
of vitamin A that was subsequently shown to be
especially associated with infectious diseases. The
historical aspects of this subject form the topic of
Panel 5.
It has been mentioned (page 19) how the final demonstration of the existence of “fat-soluble A” was a
closely run thing between McCollum at Wisconsin
and his previous associates Osborne and Mendel
at Yale. Both groups used rats and while McCollum
and his associates relied on growth retardation as
evidence of deficiency, the Yale workers frequently
commented upon the occurrence of eye lesions
which they likened to those of xerophthalmia described in man. Even so, like Stephenson (47)
quoted above, they regarded the lesions as being
due to infection rather than nutritional deficiency.
At this distance in time it is difficult to try to unravel
the reasons behind this striking neglect of xerophthalmia. The eyes have always been regarded as
special and not to be tampered with by the uninitiated. Even general physicians are quick to refer any
eye disease to the specialist ophthalmologist. The
belief that the eye lesions in animals and man were
infectious in nature would have made it difficult to
include xerophthalmia as a nutritional disease.
Ihde and Becker (21) in their historical review make
an observation which appears to confirm what has
already been said. They say that “the nutritional
breakthrough came not from medical circles but from
agricultural circles”. They are referring to the contributions made in the United States to the discovery
of vitamins that came from Mendel, Osborne,
McCollum and others.
They later comment on vitamin A in particular – “It is
strange that the real breakthrough occurred in connection with vitamin A deficiency, since this deficiency had not been clearly identified with human
The final separation of vitamin A from vitamin D
was accomplished by McCollum and colleagues (58)
in 1922. At about that time there was intense interest
in the possibility that vitamin A might have curative
effects in a variety of infectious diseases. It became
known as the “anti-infective” vitamin (59). However,
despite considerable evidence for this, even in those
early years, interest was not sustained. The extent of
the interest at the time and the reasons for its disappearance are discussed in Panel 5.
Wolbach gave a classic account of the keratinising
metaplasia changes throughout the epithelial tissues
of the body from his pathological examinations in
Boston (60). The Carr Price colour reaction with
antimony trichloride (61) made it possible for vitamin A concentrations to be estimated in serum, body
tissues and in foodstuffs. From the 1930s George
Wald and his colleagues at Harvard studied the visual
pigments and elucidated the role of forms of vitamin
A in vision (62). In 1967 he was awarded a Nobel
Prize.
During the years before World War II reports from
India (63, 64) and China (65) provided evidence of
keratomalacia as a widespread problem among ricedependent populations. Unusual features of the accounts from China were the large numbers of adults
affected and the frequent presence of skin changes,
known as perifollicular hyperkeratosis, phrynoderma
or toad skin, that responded to cod-liver oil (66). In
or animal diseases”. In other words, despite all the
prominence given to scurvy, rickets, beriberi and
pellagra in this context, it was the factor responsible for maintenance of healthy eyes that was discovered first. There is perhaps a lesson to be learned
here. Researchers need to have open as well as
enquiring minds if they are to pick up clues from
Nature that often come from the least expected
sources.
the Dutch East Indies, now Indonesia, de Haas (67)
showed that the milk and blood of women with babies with keratomalacia were very deficient in retinol. Most cases of xerophthalmia were associated with
the feeding of sweetened condensed and skim milk.
A human vitamin A deprivation experiment in volunteers carried out by the Medical Research Council in
the UK (68) reproduced the earlier eye changes and
determined the approximate daily requirements of βcarotene or vitamin A to treat the deficiency or prevent it occurring.
Discovery of the vitamin
Once something termed fat-soluble A and found in
certain foods had been shown to have functions as a
nutrient, the chemists made rapid progress.
Paul Karrer, Professor of Chemistry in Zurich, elucidated the structure of β-carotene (71). This led him
to the general building principle of carotenoids and
their relationship with vitamin A. The elucidation of
the structure of vitamin A itself followed in 1931, and
some of its derivatives were then also synthesised. In
1937 Karrer and Walter Haworth received a Nobel
Prize. Haworth’s award was for the crystallisation of
vitamin C.
21
Panel 5
Abandoning of the anti-infective vitamin
Anti-xerophthalmia, fat-soluble vitamin A was the
first vitamin to be identified, in 1913. We have followed in the preceeding text and panels the chequered career of disease and vitamin to this point.
After only a few years, perhaps not surprisingly, this
vitamin was being dubbed “the anti-infective vitamin” and hailed as a cure for a variety of diseases.
By about two decades later, round about the outbreak of World War II, it sank into obscurity. Apart
from a few isolated instances, noted in Chapter 2,
what little attention there was was focussed on
xerophthalmia as a cause of blindness. Only in the
1980s (see Chapter 3) did the present-day intense
interest in vitamin A and infectious diseases commence. The title of an unsigned editorial for the
Lancet (69), which I wrote, “The fall and rise of the
anti-infective vitamin” summed up the mood of the
time.
The extent of the influence of the anti-infective vitamin concept, and the reasons for its sudden demise have only recently come to light. This is the
result of the painstaking work of Richard Semba, a
brilliant young immunologist-ophthalmologist at
Johns Hopkins University (70). His interest in the
history of VADD is complimentary to his numerous
original contributions to our understanding of the
disease itself (see Chapter 3).
22
Semba’s search of the literature for the years 1920
to 1940 reveals about 30 clinical trials of vitamin A
therapy, usually in the form of cod-liver oil, for a variety of infectious diseases. These include respiratory disease, measles, puerperal sepsis, and other
infections. Most of the studies were carried out in
the United States or in the UK. These early studies
lacked the strict conditions required now for such
trials. Some of the results seem to have been very
favourable. Those that do not might have suffered
from poor study design or inadequate dosing. In any
case the pharmaceutical industry waxed enthusiastic. The public became convinced of the value of
regular cod-liver oil for their children.
The mid 1930s saw the advent of the sulpha drugs,
the first really effective drugs against some common infections, such as puerperal fever and lobar
pneumonia. The anti-infective vitamin retreated into
the background; not to emerge until the 1980s (see
Chapter 3).
It is quite ironic to ponder that the second eclipse of
vitamin A, like the first, can also be attributed to attention becoming focussed on infections.
SIGHT AND LIFE
The synthesis of vitamin A, or retinol, was carried
out by two groups in 1936; Fuson and Christ (72)
and Kuhn and Morris (73). Kuhn was awarded a
Nobel Prize, but was not permitted to accept it by
Adolf Hitler. Retinol was isolated by Holmes and
Corbett in 1937 (74).
In 1945–46 a commercially feasible process for the
synthesis of vitamin A was developed by Otto Isler
and his team at Roche in Basel from β-ionone (75).
The official start of the production of vitamin A at
Roche began in 1948. Later on another excellent
commercial process was developed by Pommer (76).
At the present time in the synthesis of vitamin A very
simple compounds like acetone and formaldehyde
are used, making this vitamin available commercially
at very low cost. For example, a child’s requirement
for vitamin A for one year could be met now at the
cost of only 5 US cents.
Thus, by about the 1950s, when the author came on
the scene, vitamin A had been synthesised and was
available commercially. Its relationship to β-carotene
had been demonstrated, and the main clinical signs
of deficiency in the eye had been recognised. Little,
however, was known about the physiology of the vitamin, apart from its role in vision, and nothing about
its mode of action. The magnitude of VAD as a public health problem remained to be determined, the
underlying causes were not understood and there
were no measures for its control.
23
SIGHT AND LIFE
Chapter 2
A personal odyssey
“Ophthalmology is to medicine what physics is to astronomy – a model.”
A letter of von Helmholtz to his friend von Graefe
“It is an old saying, abundantly justified, that where sciences meet, their
growth occurs. It is true moreover to say that in scientific borderlands not
only are facts gathered that are often new in kind, but it is in these regions
that wholly new concepts arise.”
Sir F. Gowland Hopkins, Linacre Lecture, 1938
Fifty years ago, when my encounter with VADD began, almost nothing was known about the extent or
the underlying causes of this nutritional deficiency
disease. Over the intervening years, with the slow
but steady increase in scientific knowledge, has come
a rising tide of interest and concern. Now there is a
constant flow of publications on every aspect of the
subject. Scientific meetings addressing various aspects of the subject of VADD are regularly held and
are attended by large numbers of experts. Progress
in control of the disease has been considered by some
to be so promising in recent years that its “virtual
elimination” by the year 2000 (now less than one
year ahead as I write) has been widely accepted internationally as a part of the “Health for All by the
Year 2000” goal (77). However, I have had my reservations on this subject from the start (78). The most
appropriate place to discuss this issue is when the
way ahead is considered in Chapter 4.
I stumbled quite unexpectedly on the problem of
VADD in India, but in order to understand how this
came about I need to go back to much earlier times.
The author with his parents.
25
Growing up between two world wars (1924–1949)
The Prime Minister, David Lloyd George, a few
days after the end of World War I in November 1918,
boasted that Britain was “a fit country for heroes to
live in”. I was born a little later, on 4 February 1924,
in London, into an era very different from this; one
of depression, unemployment, begging on the streets
and civil unrest. I grew up as an only child, my parents having previously lost a baby boy shortly after
his birth. We lived in Upper Tooting in south west
London. I knew all my four grandparents. In the
1880s my father’s parents had come from different
parts of Scotland to “seek their fortune” as many
Wedding of the author’s parents in 1913.
26
young hopefuls did, attracted by the lights of London. My father’s father was a plumber and my mother’s a printer. The two families were brought together through these men being office bearers in
the very large Baptist church The Metropolitan Tabernacle, at Newington Butts in south east London.
It had been built in the middle of the 19th century
to house the thousands who were drawn to hear the
famous preacher Charles Haddon Spurgeon. More
than a century after his death, volumes of his sermons are still best sellers, especially in the United
States.
SIGHT AND LIFE
Christmas card with a nursery rhyme in pidgin English.
27
Growing up
Spurgeon played a large part in my early life. My
father was Secretary of the Tabernacle from 1929
to 1965, i.e., the senior unpaid official, largely responsible for the administration of the church. He
was also superintendent (1932–42) of the orphanage that Spurgeon founded and which in other forms
continues to work among needy children in Britain
and abroad. I joined the church in 1939 and was
made a deacon in 1955, but transferred my membership when we moved abroad.
As a child I attended the Sunday School of a small
church near our home, and when I was about six it
was visited by a Mr Owen Warren working with
the China Inland Mission (now the Overseas Missionary Fellowship). He asked us to collect farthings
for the work (farthings or “fourth things”, long obsolete, were tiny coins worth less than the one cent
US coins that they resembled). I did this, or rather
persuaded my mother to do so, with some enthusiasm and was commended some weeks later for having brought along the largest number. I thought that
was the end of the matter but, some time later, I
received a letter from Hankow in China. It was a
thank-you note from Mr Warren and there were two
paper bookmarks with scripture texts in Chinese and
English and sketches of the countryside. There was
also a Christmas card with a well-known nursery
rhyme in pidgin English.
I have treasured these gifts ever since because of
the influence this incident had on my life. From that
time onward I decided I wanted to go to China as a
missionary.
Scripture book mark from Hangkow.
28
Many years later, during World War II when I was
a medical student, I somehow learned that Owen
Warren was addressing a meeting in someone’s
house nearby. It must have surprised him when I
told him how that small act of kindness years before had borne fruit in this remarkable way. Long
before the term Public Relations (PR) was invented
for this sort of thing, Warren had recognised the
importance of the personal touch. It also seems to
me to be a good example of what the translators of
SIGHT AND LIFE
“Empire Day” at Fircroft Road Primary School in 1931. An early example of “reverse sex discrimination” – ! – all the girls in the class are in traditional English, Scots, Irish and Welsh dress but only the
two top boys were chosen. The author is with a rosette.
the King James’ version of the Bible called “Directions for charity” – Ecclesiastes ch 11 v 1, “Cast
thy bread upon the waters: for thou shalt find it after many days”.
When I was seven I suffered an attack of acute
rheumatic fever that kept me away from school
for about nine months. At that time the disease
was one of the commonest serious infections of
childhood among the working classes in Europe.
It does not seem to have set me back academically or in sports in the long term; even after a
three months’ relapse just as I was starting in
secondary school at age eleven. These brushes
with pain and disease may have made me interested in medicine, although no one else in our
family was in the medical profession or had been
to university.
29
Growing up
The facade of The Metropolitan Tabernacle, London, after the building was restored
in 1959 following destruction by fire bombs during the Battle of Britain in 1940.
On one summer holiday I remember coming across
in a second-hand bookshop a very old edition of
Price’s Textbook of Medicine, then the leading British textbook on the subject. I paid a shilling or two
for it and remember being especially interested in
the heart tracings in the cardiology section.
In 1932 we moved to Stockwell, a few miles nearer
the centre of London, when my father was appointed
superintendent of Spurgeon’s Orphan Homes for
more than 400 boys and girls. The outbreak of war
in 1939 necessitated the evacuation of the orphans
from London to what was considered to be a safer
place; in this case to Reigate, then a very pleasant
small county town about 20 miles south of London. It was not that safe, we had to sleep at the
orphanage and have our classes at Reigate Grammar School in underground shelters. During the
Battle of Britain in 1940 bombs demolished one
wing of our school, fortunately on a Sunday. It
meant that the summer holidays had to be extended
30
by three weeks – we boys considered it good coming out of evil!
On my entry into the sixth form I had to decide what
subjects I was to specialise in. I still wanted to be a
missionary and go to China. So I consulted the
Headmaster, Mr Clarke, a gruff yet kindly man who
served as a lay preacher in the Methodist church
and was nearing retirement.
He told me that he and his wife had had an only
son, also named Donald, who had been a medical
student at Guy’s Hospital in London. During a practical bacteriology class he had contracted septicaemia, which had proved fatal in those days before
antibiotics had been discovered. He said that I reminded him of his son and he advised me to take up
medicine. He lent me a copy of On the Edge of the
Primaeval Forest by Albert Schweitzer. This book
greatly influenced me, as it has many others (see
page 89). At that time Schweitzer was one of the
SIGHT AND LIFE
Balquihiddar, Perthsire, in the highlands of
Scotland – the ancestral home of the clan
MacLaren. The old churchyard shown here contains the graves of many clansmen.
Ceremony to mark the silver jubilee of the founding of the clan society. Dedication of a
cairn on Creag an tuirc (the Boar’s rock in Gaelic). It overlooks Balquihiddar and
Loch Voil (seen in the background). In the days of the clan system in Scotland this rock
was the rallying point for the clan in time of war.
31
Growing up
Reigate Grammar School.
Author as captain of 1st Eleven cricket team in 1942.
32
SIGHT AND LIFE
Headmaster, Mr A.Clarke, with school prefects in 1941–42. Author on headmaster’s left.
most charismatic figures in the world. He had given
up brilliant careers in both music and philosophy to
study medicine late in life and then to go and work
in a bush hospital at Lambarene in west Africa.
I applied to the medical school in Edinburgh and to
King’s College in London and was accepted by both.
I opted for Edinburgh because I wanted to get back
to my Scottish origins (Panel 6). A quite unforseen
bonus of this choice came about in the following way.
My father wrote to his friend, the minister of a large
Baptist church in Edinburgh, asking if he could help
with my accommodation. A widowed lady member
of his church responded positively to the request by
the minister. I arrived in Edinburgh off the Flying
Scotsman from King’s Cross railway station in London one cool, misty evening at the beginning of October in 1942. My future wife, Olga, opened the door
to me in her mother’s home!
At medical school in war time the men students were
obliged to join the Senior Training Corps. After about
a year a diastolic murmur was picked up at a medical examination. This was indicative of damage to
the aortic valve in the heart as a result of the earlier
rheumatic fever infection. It took me some time to
get over the unwelcome knowledge that I had a weak
heart. At first I kept on listening with my stethoscope
to the characteristic diastolic murmur in the left side
of my chest. Other students found it useful for increasing their knowledge!
I have been very fortunate in that I have never had
any trouble with my heart, especially having spent
many years abroad, often beyond the reach of proper
healthcare. The damaged aortic valve might become
infected at any time or it might even rupture suddenly.
33
Panel 6
The Edinburgh Medical School and nutrition
In the second half of the 18th century Edinburgh
became the centre of what has become known as
the Scottish Enlightenment. This remarkable movement brought about great advances in all aspects
of thought and learning and many famous names
are associated with it. The leading medical figure
of the time was William Cullen, who became pro-
fessor of medicine in 1766. Cullen’s special interests included dietetics, and his published lectures
on the subject were very popular. In addition, more
than 2000 of his letters about patients to their doctors have survived. Most of these contain advice
on diet that would even today be considered sound
(79).
Sir Stanley Davidson (centre, front row), Professor of Medicine in Edinburgh, while the author was a medical student
(third from right in the back row).
34
Towards the end of the 19th century Robert
Hutchison (later knighted) taught dietetics in Edinburgh before he moved to London, where his lectures on the subject, the most popular of that day,
were published in many editions (80).
In the latter half of the 20th century history has repeated itself in Edinburgh with the publication of nine
editions to date of the best-selling “Human Nutrition
and Dietetics” by Davidson and Passmore (81).
Stanley Davidson (1894–1981) was my professor
of medicine and Reg Passmore (1910–) was my
colleague in the Department of Physiology. Both also
became close friends when we had to settle back in
Edinburgh.
Davidson was a haematologist and his interest in
nutrition came through his early work on pernicious
anaemia in Edinburgh and on iron deficiency anaemia in young women when he moved to Aberdeen
as professor of medicine during the economic depression of the 1930s. He returned to Edinburgh in
1938 to occupy the chair of medicine, held all those
years previously by Cullen. There he was heavily
involved in development and expansion of the teaching hospitals and was a major adviser to the Labour
government on the introduction of the National
Health Service (NHS) in 1948.
Davidson’s medical textbook The Principles and
Practice of Medicine was first published in 1952 and
more copies of recent editions have been sold worldwide than of any other medical textbook. It is a sad
fact that the nutrition section of this book has not
been written from Edinburgh for many editions.
Reg Passmore is an Oxford graduate and distinguished physiologist. During World War II he was in
Dr Reg Passmore while Deputy Editor of the Proceedings of the Royal College of Physicians of Edinburgh (of which we are both fellows).
the Indian Medical Service and worked at the Nutrition Research Laboratories at Coonoor (now the National Institute of Nutrition in Hyderabad). After the
war Passmore came to Edinburgh and over many
years until his retirement in 1980 he made important contributions to our knowledge of human nutrition, especially on the energy requirements of man.
Although the Edinburgh Medical School has made
significant contributions to nutrition over many years
that are recognised worldwide, it is disappointing
that no lasting impact in that field has been made
on the school itself. One is reminded of the proverb
quoted by Jesus Christ “A prophet is not without
honour, save in his own country” (Matthew 13 v 57).
35
Growing up
Olga when I first met her.
In 1945 Olga and I became engaged and as I intended
to serve abroad as a missionary doctor she agreed to
enter nursing training. I qualified in 1947 with an
MB ChB degree and at about that time offered for
service in China to the Baptist Missionary Society
(BMS). Olga finished her nursing training the following year at the Deaconess Hospital run by the
Church of Scotland until it was incorporated into the
new National Health Service in 1948. This was just
before our marriage on 23 October 1948.
Still my eyes were on China and there was an opening at Cheeloo University; but the Communists were
taking over. Some years later I met a group of exChina missionaries who said that they had begun to
36
get things ready for our arrival just before they were
told to move out.
The BMS also had medical work in India and Congo.
My recollection is that after a visit to the hot and
humid equatorial plant house at Kew Gardens we
thought we might stand up to the climate better in
the Khond Hills, India, than in Congo! I also had the
totally unrealistic idea then that India would be nearer
to move on into China when the situation “improved”!
After medical and surgical house jobs in Edinburgh
and Hull, in February 1949 I enrolled for the 6-month
course for the Diploma in Tropical Medicine and Hy-
SIGHT AND LIFE
giene at the London School of
Hygiene and Tropical Medicine
(Panel 7). Almost everbody else
on the course was either from a
tropical country, mostly from India, or expatriate colonial administrators, tea planters, or missionaries. I had to work hard to keep
up with all the information that
was new to me. However, it
would stand me in good stead in
the isolated conditions to which I
was going.
Of special importance for the future was to be an encounter I had
in the field of nutritional deficiency diseases. Nutrition was
then, is now, and probably ever
will be, a much neglected subject
in medical schools (84). The only
professorial chair within a medical institution in the UK at that
time was that in Human Nutrition
at the London School, as it is
known. Benjamin Platt was the
first occupant and was also Director of the Human Nutrition Research Unit (HNRU) funded by
the Medical Research Council
(MRC). At that time he was also
trying to develop another MRC
unit in Gambia, west Africa. He
gave us a single lecture and then
We were married in Charlotte Chapel in Edinburgh.
left for Gambia. His assistant was
Dr Dean Smith, who was an extremely good lecturer. We learned
he had much to teach us from his
personal experiences, a few years previously, in a Japathat the most common nutritional deficiencies were
nese prisoner-of-war camp. In 1951 with M. F. A.
beriberi (thiamin or vitamin B1 deficiency) and defiWoodruff, who became an eminent surgeon in Edinciency of some other vitamins of the B complex. What
burgh, Dean Smith published an MRC report on the
is astonishing to me and has never been explained as
subject of nutritional deficiencies in prisoner-of-war
far as I am aware, is the fact that xerophthalmia was
camps (85). Diets in camps in the Far East were based
virtually never seen.
on rice, usually highly polished. It is not surprising
37
Panel 7
Nutrition at the London School
The London School of Hygiene and Tropical Medicine is celebrating its Centenary in 1999. It was
founded in 1899 by Sir Patrick Manson, the discoverer of the cause of malaria and often known as the
father of tropical medicine. The present building
dates back to 1929 and was a gift of the Rockefeller
Foundation. It is part of the University of London.
The department of nutrition was the first in any medical school in the United Kingdom and only second
in the world to that at Harvard in Boston. Its origins
can be traced back to Edward Mellanby, who made
important contributions after World War I in nutrition, including the role of vitamin A in infectious
diseases (59) (see page 21). While he was professor of pharmacology at the medical school in
Sheffield he greatly influenced a young doctor,
Benjamin Platt. Later Mellanby succeeded to the
most powerful position in Britain in medical research,
as Secretary of the Medical Research Council
(MRC). Platt went to the Lester Institute in Shanghai for five years, where he carried out research on
beriberi that was endemic there. Through the years
of World War II Platt was involved under Mellanby
on work concerning the British diet in wartime.
After the war Platt was appointed to the newly created chair and department in nutrition at the London School. He also obtained the directorship of the
newly created Human Nutrition Research Unit
(HNRU). In the 1950s and 60s many students, including the author, received their PhD degree under Platt for experimental research in animals that
related to malnutrition problems in developing
coutries. Mention has been made of the indebtedness of the author to Dean Smith and Cicely Williams
while they were in Platt’s department, and indeed
to the professor himself.
38
Benjamin Platt, the first Professor of Human Nutrition at the
London School.
John Waterlow succeeded Platt after he died.
Waterlow had for many years been director of the
MRC Tropical Metabolism Unit in Jamaica and was
a leading authority on PEM of the kwashiorkor variety. Other departments of nutrition were springing
up around the country and overseas interest was
shifting away from clinical and biochemical studies
of patients to field surveys and policy making.
In more recent years a major research interest in
VADD has been developed in the department of
population studies, especially by Dr David Ross and
Professor Betty Kirkwood. They have carried out
an extensive study of the effect of vitamin A supplementation on childhood morbidity and mortality in
an area in the north of Ghana (82). The author participated in one aspect of this research (83).
SIGHT AND LIFE
Rice is devoid of carotene and prisoners received almost no source of preformed vitamin A. I have heard
it said that the prison authorities received instructions
for the daily intake of energy, almost entirely from
rice, to be restricted to as little as 900 calories per day.
This had been carefully calculated to be just enough
to keep a person alive, but too weak to try to escape.
Dean Smith was to play a key role in the next phase of
my career.
50th anniversary reunion of the graduating class of 1947, taken in 1997. Strong evidence for an aging
population considering that about 150 graduated originally (the author is in the centre of third row).
39
Mission in India (1950–1954)
On 10 December 1949 we sailed from Liverpool to
Bombay. Olga was three months pregnant with our
son Gavin. We joined colleagues of the Baptist Missionary Society at the Moorshead Memorial Hospital, at Gumsur Udayagiri in the Khond Hills, Orissa
(Panel 8).
After several years of hospital practice I began to realise that the pattern of disease was sufficiently different in certain respects from that in the UK to warrant
it being written up for publication in some form. This
was especially so for those diseases that seemed to be
related in some way to diet and nutrition.
I turned to Dean Smith for help and his replies to my
letters were always helpful and inspiring. Without
his encouragement I doubt if I would have persisted
with this research. I have always tried to model my
own behaviour on this experience in more recent
years when people have frequently turned to me for
help in a similar way. The hospital was always extremely busy and sometimes for long periods there
would be only one doctor to do all the work. Even so
I set aside any spare time I had to collect all the information I could on the diseases of the area.
The most significant research I was able to do originated in the course of routine collection and observation of hospital data over the period of nearly five
years that I was working in Udayagiri.
I recall reviewing the case records of some of my
patients late one night in the little office of the hospital. The night was unbearably oppressive, just before the long-awaited monsoon rains in early June
were due to bring relief. The pressure lamp overhead was adding almost as much to the heat as it
provided light. I noticed something interesting as I
turned over the records of the group of pathetic cases
made up mostly of young children, who had been
40
brought to us with their sight almost always irrevocably destroyed by vitamin A deficiency. These were
advanced cases of corneal destruction termed
keratomalacia.
It occurred to me that almost without exception they
were of Oriya families from far away on the plains
of Orissa, and not from our own local Khond Hills
Kui tribes people. In the final account of the work
for publication there were 32 Oriyas and only 4 Kui.
The difference is all the more striking in view of the
fact that in general we saw 5 or 6 times more local
Kui children than Oriya.
As I have been looking over my notes while writing
this I have noticed that each of the 4 Kui cases had
some unusual feature. One child of 3 years was described as a “borderline case”, another aged 3 had
“leashes of corneal vessels”, suggestive of keratitis
due to an infection rather than to VAD. Another 3year old had milder changes of xerophthalmia in one
eye and keratomalacia in the other. The fourth case
was a 15-year-old male with accompanying skin
changes described as perifollicular hyperkeratosis.
This was one of only two cases in the whole series in
which the age was outside the range of 6 months to 6
years. The second case in an adult was a 26-year-old
Oriya woman who was brought to the hospital after
the period of one month following delivery during
which custom dictated that she could not leave the
house. By that time both corneae were undergoing liquefaction from severe VAD. There was no evidence
of infection. Unfortunately at that late stage even large
doses of vitamin A failed to prevent permanent blindness. Amazingly, the infant was healthy! How its eyes
had escaped destruction is a complete mystery, but
several similar cases have been reported (88).
What was it that made this devastating disease so
much more common among the relatively affluent
SIGHT AND LIFE
Oriyas? The staple food was rice, devoid of vitamin
A, for both groups. I carried out a dietary survey in
which the food consumption of fifty individuals was
observed for a week. In addition, more than 20 families were questioned about their diet. From these
admittedly imprecise observations it was likely that
“the diet was deficient in protein and fat, rather than
calories and also probably vitamin A and in members of the B group”. These conclusions appeared to
apply equally to Oriyas and Khonds, except that the
richer Oriyas had rather more food to eat.
I then examined the eyes of 100 children of each
group aged 6 months to 6 years in their villages.
Signs attributable to early VAD were present in both
groups at approximately similar levels. Something
must be happening to the young Oriya children to
make them frequently fall prey to the advanced
stages of the disease.
At that time my knowledge of both Oriya and Kui
languages was good and I began to make a detailed
investigation of the respective customs concerning
the upbringing of the young child.
The answer came quite unexpectedly one afternoon
when I was conducting the usual outpatients clinic.
An Oriya woman stood before me holding a young
child of about 18 months by the hand. Both eyes had
been destroyed by keratomalacia. As I talked to her
it was evident that she was pregnant again. On questioning she revealed that as soon as she had realised
that she was pregnant again she had weaned the first
child because “she knew that her milk would be
turned to pus and be bad for the child”. To discourage the child seeking the breasts she had smeared
them with the juice of raw peppers.
After this, enquiry of several other mothers in similar circumstances confirmed this practice to be general among the Oriyas. When I discussed this finding with my Kui colleagues it became clear that
among them it was regarded as a “very shameful
thing” if a mother of a young child became pregnant
The Moorshead Memorial Hospital and the mission compound in the 1950s.
41
Mission in India
Our family establishment in Udayagiri in 1954.
again soon. It was expected that the customary period of abstention from intercourse until the child
had begun to walk at the earliest would be observed.
Villagers would poke fun at a woman who had frequent pregnancies, the inference being that her husband was abnormal, having failed to observe social
custom.
I later discovered that this kind of inbuilt “child-spacing” custom was common among African tribal peoples, especially in polygamous communities (89).
There is a sura of the Koran that advises that a woman
should be left alone as far as intercourse is concerned
by her husband for about two years after a child has
been born, in order for it to be nourished properly.
As Islam permits polygamy this advice may be realistic and beneficial in practice. However, in my experience among impoverished Moslem communities
42
only the wealthy can afford that luxury. The Oriyas
had no such tabu and intercourse was resumed within
a month or two of delivery.
It occurred to me that this tragic situation paralleled
that described by Dr Cicely Williams, the first
woman medical officer in the British colonial medical service, in Gold Coast (now Ghana) (Panel 9).
She found that among the Ga people there was in
use the term “kwashiorkor” for a common disease
among young children that meant “the disease that
the first child gets when the second child is on the
way” (90). She attributed this to malnutrition, a consequence of the sudden weaning of the child onto
the family diet of maize, which had poor-quality
protein. This “deposed child” situation in each circumstance resulted in malnutrition in the young
child; the kind of deficiency disease depending on
Panel 8
William Carey, the Baptist Missionary Society
and the Kui people
The Khond Hills countryside.
William Carey (1761–1834), the founder of the modern Protestant missionary movement, was one of the
most remarkable men of his time. He received no
formal schooling and worked as a shoemaker. At night
he taught himself Latin, Greek, Hebrew and Theology. In 1792 the Baptist Missionary Society (BMS)
was founded – Carey was its first missionary. He
settled at Serampore, near Calcutta. He translated,
with Indian scholars, the complete Bible into five Indian languages and smaller portions into 35 other
languages and dialects. Other achievements included
the founding of the Botanic Gardens in Calcutta,
Serampore College (now part of Calcutta University),
and the first printing press in India.
The Baptist Missionary Society today works with
churches in many countries all over the world. Formal responsibility for mission work in Orissa and other
parts of India was handed over to the local church
Traditional dress of a young Kui girl.
43
many years ago. The church in the Khond Hills is
now part of the Church of North India. Membership
of local Kui churches has continued to grow, and in
1998 they were constituted a separate diocese.
The population of the province of Orissa is made
up of a larger proportion of aboriginal tribal peoples
than almost any other part of the subcontinent. They
are numbered in the tens of millions. Those that inhabit the hills of the Phulbani and Balliguda districts,
the Khond Hills (known to the people as the Kui
dina), are two groups, the Khonds and the Pans.
They are among the Dravidian peoples, the original
inhabitants of India, who in the distant past were
driven into the hills of central and southern India by
the Aryan invaders from the north.
In their hill fastnesses the Kui people were untouched by Hinduism in the early days and practiced
Animism, worshipping gods in hills, streams and
stones. Their mother tongue is Kui, which is a minor member of the Dravidian group of south Indian
languages of which Tamil is the major member.
Outside the home they speak Oriya, the provincial
language of the Oriyas. The Khonds have traditionally been the more powerful and conservative people and owners of most of the land. They were notorious in the history of British Rule in the 19th Century for the widespread practices of female infanticide and the meriah or human sacrifice. A young
boy was captured from the plains and after prolonged ceremonies he was led to a sacrificial site,
hacked to pieces, and the “living flesh” buried in ancestral fields. The purpose was to ensure the success of the rice harvest. This is described in detail
as an example of the theme of the “dying king” by
the early anthropologist James Frazer in his
multivolume work The Golden Bough (86). Several
punitive expeditions had to be mounted by the British authorities before these practices were put down
towards the end of the 19th century (87). Buffalo
sacrifice was substituted.
Missionary activity in that part of India, particularly
by the Baptist Missionary Society, began at about
that time and by the middle of the 20th century
scores of thriving village churches had been
founded. The Moorshead Memorial Hospital was
opened in January 1939. In the 1950s and 60s it
drew patients from all parts of the province, but later
the work declined, it became the subject of numerous law suits and was closed for many years.
The animistic “priest” of a Khond village. The stone just
to the right of the priest’s left arm is the “darni” of the
village, the residence of the local spirit which is in his
care. The post is for tying the “meriah” sacrifice.
44
The story of keratomalacia among the Oriyas has
been described in detail (see page 40). Other diseases of special interest included the frequent occurrence of severe duodenal peptic ulceration leading to pyloric stenosis. This was known to be common throughout the rice-dependent south of India,
but very rare in the wheat-eating north. The reason
for this difference is still not understood. As far as I
know the occurrence of
Helicobacter pylori infection,
now known to play an important part in the causation of
peptic ulcer, has not been investigated. Cirrhosis of the
liver was also very common;
almost always in men, and
especially in those with a frequent history of heavy indulgence in toddy from the sago
palm. Not infrequently imbibing occurred at the top of the
tree where the palm was cut
for the alcohol and serious
and often fatal injuries from
falls were common. In the
1950s patients bitten by
snakes, or mauled by bears
or tigers were often seen. Malaria was endemic and everyone lost many working days
from “fever”. The cerebral
form was highly fatal in young
children. Insecticide spraying
brought the disease under
control, but after resistance
developed malaria once
again became endemic, as it
has in many other parts of the
developing world.
A typical Kui village.
Nowadays even in remote villages there are television
sets, mobile phones, motorcycles and four-wheel drive
vehicles. It is probable that,
as reported from elsewhere
in rural India, with increasing
affluence and “westernisation” coronary heart disease
and other late-onset degenerative diseases are on the
increase here too.
The “meriah” sacrifice of the buffalo.
45
Mission in India
the particular inadequacy of the diet: protein in west
Africa, vitamin A in India.
From the present perspective many years later, I regard this piece of amateur research as of great significance. It launched me into this most profitable
field of research where in the course of more than
40 years I have been privileged to see a total transformation from neglect to concern. Recognition of
the significance of VAD for public health has increased enormously over the years and the problem is gradually being brought under control everywhere.
Later on this work was the subject of my first research publication, became a prize-winning essay,
formed a major part of a thesis for a higher degree
(page 49), and was awarded the status of a classic
(page 112). In the SIGHT AND LIFE manual (1) I
again compared this work with that of Cicely
Williams on the “deposed child” and pointed out
that in the intervening decades there has really been
no strictly comparable research. It is true to say that
in all areas of the world where VADD continue to
be a serious problem there is little detailed and intimate understanding of precisely why the problem
occurs.
We completed our almost five years’ tour in
Udayagiri in November 1954 and sailed home on
the Pacific & Orient ship “Canton”. I had become
fascinated with the opportunities in the Khond Hills
area for an innovative programme of primary
healthcare (a term coined much later) through the
extensive network of the village churches. My senior colleague, Stanley Thomas, was more interested
in making the hospital into a large centre of surgical excellence with patients travelling from all over
the province. He was not prepared to see me take
over some degree of responsibility. I had to make
46
Sailing for home on the P & O liner “Canton” after
five years in India.
the difficult choice between committing myself to
a lifetime of mission hospital work in India and
making a completely fresh start elsewhere. I decided that this was the parting of the ways. We left
India with much regret, leaving behind many Kui
people who had become our friends, knowing nothing of what the future might hold, and with two
small children.
Panel 9
Cicely Delphine Williams (1893–1992)
In his obituary notice for Cicely, David Morley wrote
that she would always be remembered as a mother
figure by those who have worked in tropical child
health. This was not only because she initiated the
subject, but because of her loving approach whenever she was with young children. Yet she never
married. She was born into an old Jamaican family
but was educated in England. She graduated BA at
Oxford in 1920 on the first day that women were
granted the degree. In 1923 she was a member of
the first group of women physicians to graduate from
Oxford. She was inspired by her great teacher, Sir
William Osler, then Professor of Medicine. She lived
by his famous dictum: service, training, and research; in that order.
Her name will always be linked with the Ga word
“kwashiorkor” (see page 42). In 1936 she moved to
Malaya and when Singapore was overrun by the
Japanese in 1942 she was interned in the notorious
Changi Prison and Sime Road Camp for more than
Cicely in retirement in Oxford.
three years. She proved to be a tower of strength in
many different ways to her fellow prisoners, despite
appalling mistreatment. On her final release she was
emaciated and had developed beriberi.
Williams was well aware of the problem of xerophthalmia and included it in her writings on child malnutrition (91). This was especially so during her
years in Malaysia and Singapore. Here she found it
associated with the substitution of sweetened condensed milk for breast feeding, particularly common
among the Chinese community.
Her later contributions were of a more conceptual
nature, but no less important. She was among the
first to challenge the international milk marketing
corporations over the harm they were causing by
selling breast milk substitutes to the third world’s
poor. Cicely pioneered the concept of primary
healthcare in child services, in which curative and
preventive care were not artificially partitioned, but
combined.
Cicely Williams and Henry Sebrell at an archaeological
site in Lebanon while she was Professor of Maternal and
Child Health at the American University of Beirut.
Her fascinating life story has been told a number
of times (92–95) and should continue to inspire
all those who read it, but especially those of us
who were so privileged to know her and work with
her.
47
Back in London (1954–1957)
For about one year I was committed to going round
the country telling the churches about the mission
work which the members were supporting. This
meant spending a lot of time away from the family,
who had to stay either with my parents in Morden,
south London, or with Olga’s mother in Edinburgh.
However, it also gave me a vital breathing space to
work on the material I had collected in India. The
natural place for me to turn to for help was the London School. There I met Cicely Williams, who was a
lecturer in Nutrition for a short period (see Panel 9).
She was interested in the keratomalacia story and I
had helpful discussions with her.
Later, in the early 1960s, we were colleagues at The
American University of Beirut in Lebanon. Later still,
Olga and I often visited her when we were in the UK
in London and then when she retired to Oxford.
Cicely was a most colourful character and enthusiast in the cause of child care in the tropics. She has a
prominent place in the ranks of pioneering medical
women of all time.
I also received very helpful advice on my MD thesis
from Dr Reg Passmore (see Panel 6) in Edinburgh.
Years later when we had to leave Beirut in the civil
war, he was to become my colleague in the Department of Physiology in Edinburgh (1976–80).
Through my visits to the London School I met Professor Platt and he told me that he was looking for a
suitable person to work with him for a PhD on the
effects of malnutrition in animals on vision. It seemed
as though the opportunity and myself had been singularly made for each other! Platt got me a Colonial
Research Studentship which amounted to about £600/
year. This would hardly have covered the fees and
provided for a wife and two young children.
48
I looked for a general practitioner who wanted help
with evening and weekend surgeries. I received a
small fee for this work and had to make a special
case with the University of London authorities so
that I could be considered a bona-fide full-time PhD
student. Most importantly, the arrangement provided
us with rent-free accommodation situated over the
spartan consulting room of the general practitioner,
Dr Oscar Stern, a Jewish refugee from Hitler’s Germany, in Tottenham High Road, north London.
Night calls to emergencies in the winter after a long
day in the laboratories were particularly trying. Once
the car had been got going in the cold, the engine
had to be cranked with a handle, I had to find my
way around a part of London completely strange to
me. Most vividly I remember three calls out one night
at the height of the last London “pea soup” smog
(sulphur dioxide and smoke from domestic coal fires)
when several thousand people died of respiratory illnesses. The last patient turned out to have had a heart
attack and as he lived in an area quite unknown to
me I called in the help of a policeman who guided
the car to the door by walking ahead with a torch.
Our flat was about six miles from the Human Nutrition Research Unit (HNRU) of the Medical Research
Council where I did my research. It was while the
HNRU was still at the Medical Research Council
Laboratories in Holly Hill, Hampstead, that I met
Dick Jelliffe for the first time.
In some ways Dick was to become the successor of
Cicely Williams. He was another paediatrician who
made great contributions to maternal and child health
in many developing countries. At that time he had
just founded what is still now, several years after his
sudden death in 1992, the foremost journal in the
field: the Journal of Tropical Pediatrics. I told him
SIGHT AND LIFE
My fellow research student Kalyan Bagchi with Gavin and Jill.
about my work on keratomalacia in India and he invited me to submit it to his journal. It became my
first research publication (96).
I was putting the finishing touches about this time to
the thesis I submitted to the University of Edinburgh
entitled rather ambitiously “Health and disease in the
Khond Hills, India: a contribution to global epidemiology”. The work on keratomalacia formed a major part of the thesis awarded the degree of MD (Doctor of Medicine) in 1955 (97). I also wrote up the
work at the same time for submission to the British
Medical Association and received the Oliver
Hawthorne prize. Thirty years later it was given classic status (see page 112).
I shared a laboratory with Dr Kalyan Bagchi, who
started his PhD at about the same time as I did. It
transpired that he had also been recruited by Platt to
work on the eye! It soon became clear that we could
both profit by collaborating. Kalyan concentrated on
the lens and I on the cornea. We were the only medically qualified students or staff in the Unit, apart from
the professor. Kalyan and I became great friends; I
had just spent five years in his country, he was Associate Professor at the All India Institute of Hygiene
and Public Health in Calcutta, and is a Bengali. He
had had to leave a wife and two little children behind in India, so he was often in our home and was
“uncle” to Gavin and Jill. Kalyan spent most of his
subsequent career with the World Health Organization (WHO), in Geneva, and later in Alexandria. We
keep in touch but I greatly regret that we have met so
infrequently over the subsequent years.
Antoinette “Tony” Pirie, head of the Nuffield Laboratory of Ophthalmology in Oxford, was appointed
Kalyan’s external examiner and we both went to see
her early on in our studies. She later became the first
editor of the Xerophthalmia Club Bulletin (Panel 14,
page 94) and we both attended early IVACG Meetings. She was a PhD and was the only other British
49
Back in London
worker at that time interested in xerophthalmia. Her
experience was in experimental animal work rather
than deficiency disease in humans. There were no
Americans yet on the scene, Oomen was nearing retirement in the Netherlands and some work was going on in India, but that was about all.
My adviser for my PhD thesis was Hugh Davson, an
eminent research worker supported by the Medical
Research Council at University College, London. He
made important contributions to our knowledge of
vision and wrote several treatises on the physiology
of the eye. When the time came for me to defend my
thesis Davson seemed to accept the results of my
experiments without much comment and spent more
time on its grammatical construction. I remember him
predicting that I would publish a lot of work and that
it was therefore important that I should get the English right!
The HNRU was very much a one-man show. Within
days of my being appointed in August 1955 Platt was
admitted as an emergency to University College Hospital with severe haematemesis (bleeding from a peptic ulcer). He was away for months and when he did
return he was not a fully healthy man. We last met in
1967 at a meeting on calorie deficiencies and protein deficiencies held at Sydney Sussex College,
Cambridge, and organised by Professor McCance.
Platt told me that he was finding the treatment he
was receiving for high blood pressure and kidney
complications was worse than the disease. He died
the following year.
Dr Hugh Davson, external examiner for my PhD in Nutrition from
London University.
needed to be done, but young PhD candidates straight
out of university were left floundering.
More than any other individual Platt had been responsible for giving me the opportunity to make a
career in nutrition research in general and in relation
to eye disease in particular. He was not an easy person to work for or to get to know. I came to realise,
probably too late on, that much of the problem was
due to the very poor health from which he suffered
for most of the time I knew him.
For nearly three years I carried out animal experiments, mostly on rats, but some on pigs, on the effects of various deficient diets on the eye. Vitamin A
deficiency was overshadowed by the overriding interest of the professor, and therefore the Unit as a
whole, in protein malnutrition, as it was called then.
By that time Platt had fallen out with the authorities
in Gambia and the MRC Unit there had to be handed
over for research to be done on malaria. Our work in
London was greatly hampered by our not having direct access to malnourished patients in developing
countries. In retrospect it is perhaps surprising that it
did not occur to any of us at HNRU that the general
medical and surgical wards of hospitals in the UK
were then, as indeed they still are to some extent,
full of patients suffering from malnutrition as a secondary effect of various serious illnesses.
Kalyan Bagchi and I were both in our early thirties,
with considerable experience and knew what work
In my research I was able to show that protein deficiency did not usually directly damage the eye. In
50
SIGHT AND LIFE
fact, if it accompanied vitamin A deficiency the development of xerophthalmia due to the latter was
delayed. The reason for this delay appears to be the
decreased requirements for vitamin A in the animal
failing to grow because of protein deficiency (98)
(see also page 80).
Just at about the time the Unit was due to move from
Hampstead to the National Institute for Medical Research at Mill Hill, north London, I was about half
way through my research and became very excited
with some results. These were written up fully in my
PhD thesis (99) and were summarised in my book
Malnutrition and the Eye (88).
Two types of lesions occurred in the cornea of a
number of the rats on deficient diets. The first was a
localised hyperplasia of the endothelium in a few rats
deficient in vitamin A. It was never seen again. The
second type of lesion was much more widespread,
affecting 28 out of 36 rats deficient in vitamin A.
There was a subepithelial infiltration of mononuclear
cells that took different forms when the cornea was
viewed under the slit lamp microscope. These I described as dendritic, punctate, or granular in appearance. Some of the animals were also restricted in
protein or in certain vitamins of the B complex. The
lesions remained stationary, appeared several weeks
before the usual xerosis changes of xerophthalmia,
and underwent no change in a group that was given
large doses of vitamin A. After the move to Mill Hill
attempts to repeat the changes were entirely unsuccessful. I thought at first I had discovered new, very
early changes in the cornea due to nutritional deficiency. I never did discover the cause, but later on I
realised that there must have been some environmen-
Kalyan Bagchi (back row 2nd from right) and the author (middle row extreme right) in the class on
medical statistics at The London School of Hygiene and Tropical Medicine. Prof. Austin Bradford Hill
(front row middle) and Dr Richard Doll (front row 3rd from left).
51
Back in London
tal factor responsible, probably a viral infection. I
was very near to making a premature announcement
in my enthusiasm which I would have regretted later.
I wonder how often the inability of research workers
to repeat earlier sensational claims may be due to
over-zealousness on the part of the former. When
unexpected experimental results occur it is rare for
those experiments to be repeated in the same laboratory, just to make sure.
Kalyan and I took a course in medical statistics at
the London School which stood us in good stead later.
We had the privilege of being taught by some of the
most famous medical statisticians and epidemiologists in the world.
I recall an amusing, but acutely embarrassing, experience I had earlier with a group of epidemiologists.
Shortly after my return from India I received an invitation to a cocktail party at the London School for
former students to meet teaching staff. As I planned
to visit the School regularly I thought I would attend. Not surprisingly I found I knew almost nobody.
I found myself with a group of strangers and asked
one of them what he did. This was met with cries of
derisory laughter! I later found out that I had spoken
to Dr (now Sir) Richard Doll, who had very recently
become famous for his work showing that cigarette
smoking causes lung cancer. This brought home to
me how out of touch I had become after five years in
India.
It soon became clear to me that very little attention
was being paid to xerophthalmia (the term generally
adopted later for all effects of vitamin A deficiency
on the eye). Only brief mention had been made of
xerophthalmia at several of the early Joint FAO/WHO
Expert Committees on Nutrition. Almost nothing was
known about its occurrence outside India and Indonesia.
While I was seeking support for my work I visited
The British Empire (later Commonwealth) Society
for the Blind (now Sight Savers International). It had
52
been founded by John (later Sir) Wilson in 1949.
Wilson had himself been blinded in an accident while
at school and had gone on to study law at Oxford. I
found that he appeared indifferent to what I had to
say about the severity and likely magnitude of the
xerophthalmia problem. I could not get him away
from the work the Society was then supporting on
“river blindness” – onchocerciasis – in west Africa.
Years later, not only in private, but also in public
meetings when we have met, Sir John has been very
generous in pointing out that he had been slow to
realise the importance of xerophthalmia when we had
first met, but he has worked hard to set the matter
right later on.
Sir John, now in his eighties, has turned his boundless enthusiasm to the prevention of disability in general in recent years. At a lecture he gave on this work
at the Royal Society of Medicine in London recently
I was pleased to be asked to give the vote of thanks.
During the summer of 1957, when I had completed
my experiments and was writing up my thesis, Platt
called me into his office on his return from WHO
headquarters in Geneva. He told me that there was
an opportunity for someone interested in going to
Indonesia for a month for them to report on a serious
xerophthalmia problem there. I leaped at the chance,
even though it meant postponing my thesis writing,
getting a paper ready to present at the 3rd International Congress of Nutrition in Paris ahead of time,
and going direct to Paris from Indonesia after my
consultancy. Platt’s last words to me were spur
enough to succeed – “If you fail, that’s the end of
you!”.
I had forgotten these remarks over the years, but another quote of his early on in my work I have often
repeated as I believe it to carry an important message for young researchers: “There are only two requirements for research – running water, and one
idea.” The implication is that there is no lack of “running water” – the hardware for research, but a real
dearth of original ideas.
SIGHT AND LIFE
These were days before the introduction of commercial jet aircraft. I flew to Geneva for my briefing on
the consultancy and then to Rome to catch a Super
Constellation to Jakarta, Indonesia, taking most of
three days in all. These planes flew at only a few
thousand feet and there was plenty to see out of the
cabin windows. In those days WHO flew its consultants first class and my travel was made very
comfortable.
On the way to a stopover in Damascus I caught my
first glimpse of Beirut. Little did I know that I was
to go to live there 15 years later. In the tiny, shedlike terminal building I also caught my first, and
much too intimate for my liking, view of something
else – Aleppo (in northern Syria) or Baghdad boil
(cutaneous leishmaniasis) on the faces of many pilgrims crowding onto an aircraft to go on the Hajj to
Mecca. Many lesions were very active and covered
with flies.
trition situation and I was to concentrate on xerophthalmia. All the negotiations with government officials were conducted by Bill Darby. He was an extremely experienced and diplomatic negotiator. Sitting in on these discussions was an invaluable learning experience for me for the future.
While our itinerary was being discussed with the
Ministry of Health officials in Jakarta we encountered resistance to any suggestion that we might visit
Bali. On several occasions officials pointed out that
this would not be advisable. Bill had not been there
and I had a special reason for wanting to go there. I
had made friends at the London School with Dr
Jelantic from Bali. He was the son of a chief and
The next day we flew low over Rangoon, the capital of Burma, and the captain said he was going to
circle the famous Buddhist pagoda, the Shwedagon,
for us all to get a good look at this enormously impressive building with its long tapering upper part
covered in gold leaf. I made a mental note to the
effect that one day I would try to return to see it
from the ground.
This happened in 1973 when I was able to obtain a
visa to give some lectures at the Medical Research
Institute and visit the central hospital, where I saw
many cases of xerophthalmia. This was quite valuable information about the occurrence of xerophthalmia, as Oomen had been unable to obtain entry
to Burma for his part of our global survey in 1963
(100) (see page 82).
In Indonesia I was to work with the man who was
probably then the leading international authority on
human nutrition problems – William J. Darby, Professor of Biochemistry and Nutrition at Vanderbilt
University School of Medicine in Nashville, Tennessee, USA. Bill was to report on the overall nu-
Bill Darby with the author in his historic home
outside Nashville, Tennessee, when we last met in
1994.
53
Back in London
At the Central Government General Hospital in Jakarta in 1957 these parents holding
their children had all been refused admission towards the end of the morning session
in the Paediatric Outpatient Department because both the eyes of these children had
already been destroyed by keratomalacia.
very influential. He had given me an open invitation
to visit.
Towards the end of our time in Indonesia we learned
the reason for our difficulties. A prominent American physician in the field of nutrition had paid an
official visit to Indonesia shortly before ours. After a
brief stay in Jakarta he had made straight for Bali
with his wife and later left the country without telling
anyone. Not surprisingly, this had gone down very
badly with the local officials. Bill Darby was too much
of a diplomat to press his point, even when he did not
know the underlying reason for the opposition.
We visited hospitals in several large cities of Java,
including Jakarta the capital, Semarang in the north,
Jogjakarta in the south, and Surabaya in the east.
Everywhere I saw large numbers of severely malnourished children in hospital wards and outpatient
clinics. The majority had evidence of xerophthalmia.
54
Many of those seen in paediatric or ophthalmology
outpatient departments had their eyes already destroyed by keratomalacia and these were usually
turned away.
The enormity of the problem was fully appreciated
in Java, but our visit for WHO helped to bring it to
the attention of the world. In Surabaya the Dutch nun
ophthalmologist Ann ten Doesschate was meticulously documenting hundreds of cases of xerophthalmia for a thesis. In this she showed the extent of the
mortality over several years after admission to hospital. Within that period about 40% had died (101).
This was a considerably higher rate than Blegvad
(see page 19) had reported from Denmark many years
before. The difference might have something to do
with the likelihood of better health and social welfare provision in Europe.
SIGHT AND LIFE
The most massive experience of corneal xerophthalmia ever recorded is that of the Yap Eye Hospital in
Jogjakarta that we visited. Oomen had recorded the
unique experience of more than 6300 cases of xerophthalmia treated there by Drs Yap senior and junior,
both ophthalmologists, over less than 20 years (102).
The young Dr Yap was a gentle, cultured man and it
was a real shock to learn that not long after our visit,
in a time of persecution of the Chinese population in
Indonesia, he had taken his life.
Xerophthalmia of some degree was present in about
75% of all malnourished children in hospital, which
confirmed the earlier experiences of the Dutch physicians de Haas (103) and Oomen (104). This is the
highest rate ever reported. As I recall, this was the
first time massive-dose vitamin A prophylaxis was
discussed as a possible emergency measure. It was
not tried until the early 1960s – in our WHO-supported study in Jordan (105) (see page 86) and by
workers in India (106), where in 1972 the first national vitamin A supplementation programme was
initiated (see page 87).
I had a memorable departure from the airport in Jakarta. Before we were called to our plane there was a
flurry of activity by security officials in the area of a
red carpet. The figure of President “Bung” Sokarno
with his dark glasses was recognisable. He appeared
to be seeing off a white middle-aged elegant couple
accompanied by teenage son and daughter. On the
plane I found myself the only other occupant of first
class besides this group. Once we were airborne the
youngsters went to sit in economy with people more
of their age. I noticed that the woman was very
plainly, but tastefully, dressed, with a simple bangle
for ornament. We exchanged a few pleasantries before we soon touched down at Singapore and were
all taken to lunch. I had hazarded a guess in Jakarta
that the mystery family might be that of the governor of Singapore, but then they would have left the
plane. Our passports were taken from us and after
lunch we had to wait while our names were called
out. Imagine my surprise when Mr and Mrs John D.
Rockefeller III and family were called! Then I remembered that I had read in a local paper that
Rockefeller had been on a goodwill mission for the
US government. They had no security personnel with
them and were most unaffected and self-effacing. It
is interesting how breeding shows.
The report I wrote with Bill Darby to WHO was rapidly produced and published in November 1957
(107). Nothing really new resulted, but there were
three important consequences in my view. WHO finally acknowledged the importance of xerophthalmia as a public health problem. This was the first
WHO publication on the subject. The consultancy
was considered a success and I was recognised as a
budding expert in the field. I got on very well with
Darby and through his influence my career greatly
benefited.
On my return Platt offered me a full-time research
position in his department, but I wanted to extend
my studies to humans. There were very few opportunities to do this, especially at that time, when Britain was in the process of dismantling its empire. I
turned down an offer to work on the eye lesions of
onchocerciasis in west Africa; I wanted to stay with
nutritional diseases. Eric Holmes, Director of the East
African Institute for Medical Research in Mwanza,
Tanganyika (now Tanzania), visited Mill Hill to recruit personnel. I explained my interests and he said
that although he knew nothing about eye disease he
was sure that if I looked sufficiently hard for it I would
find it there. When I discussed the appointment with
Platt I received a verbal commitment from him that
he would try to develop a close link between London and Mwanza. Unfortunately this never materialised.
Eric had studied medicine at Cambridge and while
doing biochemistry research under Sir Fredrick
Gowland Hopkins (see Panel 3) he married the
boss’s daughter Barbara, also a biochemist. Eric had
remarried by the time I knew him. He had been just
the “right” age to serve in both the World Wars, in
55
Panel 10
The East African Institute for Medical Research
After World War II the British colonial territories in
East Africa, Kenya, Uganda and Tanganyika (Tanzania), were administered in a federation by the East
Africa High Commission (later the Common Services
Organisation). Many public services were jointly
administered, and included under this umbrella were
numerous research institutes. These specialised in
subjects from agriculture, forestry and fisheries to
malaria, yellow fever and trypanosomiasis. The institute in Mwanza on the southern shore of Lake
Victoria had no clear remit. It was originally known
as the East African Survey and in the early years
carried out field studies which included nutrition.
Eric Holmes changed all this and attempted to turn
it into a reputable research institute with its main
emphasis on nutritional studies. The name was
View of the shores of Lake Victoria from the bungalows
of the staff of the East African Institute for Medical Research in Mwanza.
The semi-nomadic Gogo tribe of Central Province put on a traditional dance for
the Governor’s visit. Most of the research on nutritional eye disease was carried
out among these people.
56
The East African Institute for Medical Research in the 1950s.
changed and new staff, like myself, recruited. The
other main interest was schistosomiasis (bilharziasis), which was endemic in the area and caused a
great deal of illness. Holmes’ period as director
barely spanned the five years of my stay there
(1958–62). After his retirement, with funding from
the Rockefeller Foundation, the institute concentrated on schistosomiasis. I was fortunate to be leaving at that time for Beirut. In recent years the institute has been the base for research on a malaria
vaccine and research on sexually transmitted diseases, including HIV infection and AIDS.
The transition to independence in December 1961
took place peacefully. Julius Nyerere, leader of the
Sir Richard Turnbull, the last Governor of Tanganyika
visiting the Institute.
predominant political party TANU (Tanganyika African National Union), became president. He introduced throughout the country a Chinese-style commune system that proved to be unworkable and disruptive of the traditional rural way of life. Tanzania
is today one of the poorest nations on earth. Despite much activity in the field of prevention of VADD
the country is classified as having a serious public
health problem (113).
As described already most of the research undertaken on VADD took place in Central Province, far
from the institute, among the Wagogo people. The
terrain consists of cultivation steppe. Wide undulating plains are interspersed with low ridges, hill blocks
and ranges. The Gogo are one of 11 tribes of Bantu
origin, each with their own language but having
Swahili, the lingua franca of much of east and central Africa, in common. Forty years or so ago the
Gogo were under considerable Masai influence,
imitating them in dress and following a nomadic lifestyle to some extent. Sorghum was the principal
crop, growing best, as does maize, in heavy black
cotton soil. Cassava and millet predominated in the
more hilly, sandy areas. Unlike most other parts of
the country, Central Province had experienced numerous periods of food scarcity, sometimes amounting to famine, as in 1953–54. It was to be here then,
as the result of following up a chance observation
(see page 60) that Holmes’ prediction of “seek and
ye shall find” (see page 55) was vindicated, and
research funds from a surprising source (see page
63) were justified.
57
Panel 11
The Princeton conference in June 1958
The group outside the Nassau Tavern Hotel. The original historic building dated from 1756. The Yankee Doodle Tap
Room, with its famous Mural by Norman Rockwell, has been a favourite meeting place of the Princeton undergraduates for many years.
From left, front row: B. S. Platt; V. N. Patwardhan; C. G. Mackenzie; W. J. Darby; W. R. Aykroyd; R. H. Follis, Jr; T.
D. Kinney; R. C. Burgess; P. Handler; N. S. Scrimshaw. Middle row: projectionist; S. B. Andrus; D. S. McLaren; E.
M. Nadel; E. A. Uehlinger; J. B. Hazard; H. D. Moon; C. Tejada; H. A. P. C. Oomen; A. E. Schaefer; K. E. Mason.
Back row: projectionist; V. Ramalingaswami; P. J. Fitzgerald; F. J. Stare; E. Orent-Keiles; R. E. Olson; J. B. Stanbury;
J. Matovinovic; J. Higginson; J. M. Hundley.
58
Reference has been made to the author’s participation in this seminal conference. In retrospect it
is easy to see that this meeting was just one of
many examples of the way in which the United
States after World War II was establishing its influence in many fields over the nations of the developing world. They were then in the process of obtaining their independence from the European colonial powers who had been greatly weakened by
that war.
In the area of nutrition the US National Institutes
of Health funded and organised this meeting. Another branch of the government set up the ICNND
surveys (see page 65), which much later developed into the periodic nationwide health and nutrition assessments (NHANES) in the USA itself.
During this period Bill Darby at Vanderbilt, Henry
Sebrell at Columbia, Bob Olson at St Louis, Fred
Stare at Harvard, Nevin Scrimshaw at MIT, and
many others developed collaborative nutrition research and teaching programmes with centres in
the third world.
Of the 29 nutrition scientists in this 40-year-old photograph the fate to date of only about half is known
to me. The known survivors include Darby, Burgess (then head of the nutrition unit, WHO, Geneva), Scrimshaw, Stanbury, Olson, Stare, Ramalingaswami (one of India’s foremost medical scientists today).
Those of us who made formal presentations at the
conference in the section on hypovitaminosis A
were: Aykroyd (introduction), Patwardhan (epidemiology), Oomen (clinical), Mason (pathology),
Handler (biochemical), McLaren (pathogenesis).
Many others contributed during the extensive periods of discussion, all of which was scrupulously
recorded in the final proceedings.
As an interesting footnote attention might be drawn
to the only female participant. This was Dr E. OrentKeiles, who was with the NIH at the time, but previously had been a research collaborator of the
great E.V. McCollum (see Chapter 1).
Africa in World War II. He had been drawn back to
Africa after the war, partly because of his liking for
big-game hunting. He had become director in
Mwanza after a spell as Professor of Physiology at
Makerere College in Kampala, Uganda.
nent and pensionable” terms, which meant that
when Tanganyika gained its independence in 1962,
I received quite generous compensation
(“compers”) from “loss of career” and a small pension which continues to this day!
Holmes’ research interests were in the rather esoteric
area of body composition changes in African adults.
In a series of elegant metabolic studies, using radioactive isotopes for the first time in medical research
in Africa, his group showed that the values were very
different from those for well fed Europeans. However, these results did not lead to any practical recommendations about diet as far as I am aware.
We sailed for Dar es Salaam just before Christmas
1957. Only days before leaving, surrounded by
packing cases in my parents’ front room, I had typed
three papers from my thesis work and sent them
off to the editors (98, 108, 109). I spent much of
the time on the voyage writing another paper on the
“Involvement of the eye in protein malnutrition”.
This showed that in all reported instances deficiency
of vitamin A was almost certainly responsible for
the eye lesions, and not protein deficiency (110), as
was sometimes suggested (111, 112).
I joined Her Majesty’s Overseas Research Service
as Medical Research Officer. This was on “perma-
59
Medical research in Tanganyika (1958–1962)
Today Tanzania (Tanganyika until independence in
1961) is classified by WHO as being among a number
of African countries that have a serious VAD public
health problem (113). A nationwide control programme has been in place for a number of years.
Forty years ago when I went there it was a complete
toss-up as to whether I was wasting my time and others’ money. I was not aware of any reports from anywhere in Africa to suggest that VAD was a problem
of public health magnitude. A few isolated reports I
collected several years later for Malnutrition and the
Eye (88) confirmed this.
Mwanza was the capital of Lake Province, situated
in the north west of a large and varied country (Panel
10). I made some enquiries and clinical examinations
in the large government general hospital and on a
few field trips. I came to the conclusion that if I was
to find xerophthalmia I would have to start looking
in a more impoverished area. I recalled a conversation I had had on the boat coming out with a district
officer, which was to prove most helpful. He had
mentioned that some years previously, in 1954, in
Central Province there had been a severe famine as a
result of prolonged drought in which many of the
local semi-nomadic Gogo tribe had died.
Central Province appeared to be a good place to look
for VAD, but first I needed research funds for the
project. Application was made to the Tropical Medicine Research Board, our masters in London. The
reply came back that the leading authority on eye
disease in the UK, Sir Stewart Duke-Elder, Director
of the Institute of Ophthalmology in London, had
reviewed the request and turned it down. He was quite
sure that there was no xerophthalmia in Africa. That
appeared to be the end of that; stuck in the middle of
Africa on a three-year contract with no research
funds.
60
At about that time I received an invitation to present
a paper at the “Conference on Beriberi, Endemic
Goiter and Hypovitaminosis A”, to be held at
Princeton, New Jersey, 1–5 June 1958 (Panel 11). It
was organised by the Pathology Study Section,
Division of Research Grants, US Public Health
Service and supported by WHO, the Food and Agriculture Organization (FAO) and the Pan American
Sanitary Bureau (PASB). I suspected that Bill Darby
had put my name forward.
The meeting brought together top US scientists in
the field of nutritional deficiency disease and several of us with experience of the problems from
abroad. I got to know many famous scientists, who
hitherto had only been names to me, many of them
on the train from New York to Princeton as that was
the only way to get there then.
This was to be one of the most enjoyable meetings I
have ever attended. It was organised in a quite informal way, there were only 29 of us. It was held in the
intimate and relaxed atmosphere of the historic Nassau Tavern Hotel. I reproduced the group photograph
on the front of the July 1988 issue of the Xerophthalmia Club Bulletin to mark the thirtieth anniversary
of this, the first international scientific meeting on
VAD. The proceedings of the meeting were published
in September 1958 (114).
When the turn of hypovitaminosis A came on the third
day the proceedings were dominated by the presentation by H. A. P. C. Oomen (Panel 12). His pictures
of the destructive eye lesions and his impassioned
account of his clinical experiences made a powerful
impression, especially on the Americans. I had been
allotted the rather dry subject of pathogenesis, which
I defined as “methods by which lesions are produced
by etiological factors”.
Panel 12
H. A. P. C. Oomen (1902–1986)
In the era of which I am writing “Janus”, as he
was always known to his close friends, was the
father figure. After studying botany and zoology
at the University of Utrecht he received his medical degree in 1932 and went to work as a Catholic mission doctor to 300,000 patients in north
Celebes, now Sulawesi, in Indonesia. He and his
family survived internment in World War II. Later
he studied the problems of childhood malnutrition
on Java, where he was especially impressed by
the importance of xerophthalmia.
The government of Indonesia appointed him representative for WHO and he served that and other
UN organisations on many occasions in the field
of child nutrition. Oomen was head of tropical nutrition and director of The Tropical Medicine Institute in Amsterdam after he left Indonesia. He and
his wife had five sons – three of whom became
H. A. P. C. Oomen.
doctors, and to my knowledge at least two of these
saw mission service in Africa.
I frequently received greetings cards at Christmas from
Janus -nearly always they were scenes like this from his
beloved Sulawesi.
Oomen served as the first, and only, chairman of
the Xerophthalmia Club Bulletin when it was
formed at the Jerusalem Seminar on Prevention
of Blindness in 1971. At early IVACG Meetings
and the two WHO Expert Committees on xerophthalmia Oomen made especially important contributions with his detailed colour photographs of
the eye lesions of xerophthalmia and by giving
the strongest support to the concept of the importance of dark green leafy vegetables in prevention. One of his medical missionary colleagues,
Dr Ann ten Doesschate, wrote a very fitting obituary for Janus after he died at the age of 84 (Xerophthalmia Club Bulletin no. 33, July 1986).
61
None of us who were at the meeting in Princeton in
1958 (see page 58, Panel 11) will forget the impassioned conclusion to his presentation: “Xerophthalmia has been the most bitter pill for me to swallow
during 18 years of doctor’s work in Indonesia. The
over and over repeated experience of discovering
a child, recently blinded, in the arms of the mother;
having to tell her that I now could do nothing more
to save its eyesight; remembering that I could have
done so with a few spoonsful of cod-liver oil some
days ago; these things still enter my nightmares.
They belong to the most vivid examples of what
disprivileged people in underdeveloped regions
sometimes miss.
More printing space nowadays is devoted to a few
cases of hypervitaminosis A, induced by an irresponsible vitamin racket, than to the thousands of small
children who die or get blind every year due to the
lack of a handful of vitamin A units. What on earth is
nutritional science good for, if, even in the atom age,
it is not capable to counteract one of the foulest consequences of bad nutrition?”
Oomen contributed other key publications on VADD,
not already mentioned in the text (116, 117, 118).
Some of the members of the expert group that advised UNICEF on the fortification of skim milk with vitamin
A. From left to right, Bill Darby, “Jim” Burgess (WHO), Glen King (The Nutrition Foundation), and second
from right Paul Gyorgy, a prominent American professor of paediatrics.
62
SIGHT AND LIFE
Nevertheless, my talk must have made some impression because I was invited to breakfast the next day
by two staff members of the Pathology Study Section. It turned out to be the most profitable breakfast
I have ever had. They were very polite about my work
and went on to point out that it was not possible, of
course, for this kind of disease to be studied in the
United States. The National Institutes of Health (NIH)
were deeply interested in supporting such research
and they wondered if I would be so kind as to agree
to submit a grant proposal. Nowadays it is very difficult for scientists to get funding from the NIH even
for research on diseases that threaten the life and
damage the health of the American tax payer, who
ultimately puts up the money.
Within only a few months my proposal had been accepted in full; US$ 80,000 over three years. This was
an awful lot of money in those days, especially with
the very low costs of most things in Africa. From
this totally unexpected quarter my work had been
rescued. I was particularly fortunate in being so successful in view of the fact that at that point I did not
have firm evidence that there was really a VAD problem in Tanganyika upon which to work!
On this my first of many visits to the United States I
was also able to visit a number of leading institutions in New York, Washington D.C., Cincinatti and
Nashville. I was invited to the latter by Bill Darby to
address a group he had called together to a meeting
in his lovely home in the countryside. This was to
discuss the need to fortify skim milk going to developing countries with vitamins A and D. I put the case
for vitamin A fortification and Cal Woodruff, a young
paediatrician at Nashville, who was later to be my
colleague for several years in Beirut, spoke for vitamin D fortification.
After World War II there were moves in the United
States and Europe to gain influence with developing
countries by helping to tackle the problem of malnutrition in children which was then being shown to be
widespread. At that time childhood malnutrition was
(wrongly) considered mainly to take the form of pro-
tein malnutrition. It was pointed out that the dairy
industry usually had a large surplus of skim milk,
the most commercially desirable part of milk at that
time being the cream. Skim milk was rich in highquality protein, so it was proposed that it be shipped
to the third world.
This appeared to be a good idea as this aid should
create a good impression and might help to alleviate
the problem. Furthermore, it seemed to solve the
problem of what to do with the skim milk. I was told
privately by a scientist at the United States Department of Agriculture (USDA) in 1960 that before this
idea came along they had been about to make the
decision, reluctantly, that there was nothing for it but
to bury the stuff in enormous pits somewhere!
It was realised that skim milk was devoid of fat-soluble vitamins, and in order to counteract that deficiency cod-liver oil capsules were to be distributed
along with the milk. Unfortunately these often went
missing or were sold on the black market. Several
outbreaks of blindness from xerophthalmia associated with skim milk distribution programmes occurred.
The recommendations of the meeting in Nashville
were acted upon in due course by the US State Department and the United Nations Children’s Fund
(UNICEF). However, it was many years before
sources of skim milk from some other countries were
fortified. Even today, VAD may present a serious
health hazard in emergency feeding situations (115).
While in New York I stayed overnight at the home
of the eminent Professor of Chemistry at Columbia
University, Glen King. At the time Glen was President of the Nutrition Foundation, a body funded by
the powerful food industry; Darby was later to succeed him. Glen was noted for his contributions to
the discovery of the vitamin C properties of ascorbic acid. Many consider that he should at least have
had a share of the Nobel Prize awarded for this work.
King was later associated with W. Henry Sebrell Jr
at the Institute of Nutrition Sciences at Columbia
63
Tanganyika
The first pictures of keratomalacia from Africa which I took at the CMS Hospital in Mvumi in the late 1950s.
University, New York, with whom I was myself to
collaborate for many years when I moved to Beirut
in 1962.
into a mobile eye clinic and laboratory and we started
to carry out extensive eye surveys in Lake and Central Provinces.
Also in New York, at the Presbyterian Medical
Center, it was arranged for me to meet George
Smelser, an anatomist who was a world authority on
the structure of the cornea. I remember telling him
in his laboratory about the way in which thousands
of young children were losing their sight from corneal damage and dying as a result of the lack of a
few units of vitamin A in the diet. It was evident to
me that this news moved him greatly. He asked me
to let him know if ever I was to plan an extended
visit to the States and he would arrange for me to
visit a number of centres of eye research to tell them
of my work. Smelser proved to be as good as his
word in 1960 (see page 70).
The Church Missionary Society hospital at Mvumi,
in Central Province, south of the main town Dodoma,
became the base for our work there. A previous medical superintendent of this hospital was an Australian,
Paul White, who had written a series of books of stories for children based on his experiences as “The
Jungle Doctor” which were extremely popular in
missionary and church circles at the time.
Back in Mwanza, with the new funding from NIH I
was able to purchase a vehicle that was converted
64
At Mvumi and Dodoma I identified several children
in the hospitals with keratomalacia which was being
misdiagnosed (119). The doctors were attributing the
damage to “muti” or traditional medicine. Decoctions
of the bark of a tree known as “mowa” were applied,
or “lukaka” or aloe was put in the eye. Even powdered cowrie shell had been applied in one case. The
dramatic response when large doses of vitamin A
SIGHT AND LIFE
were given soon convinced the mission doctors of
the true cause. I have had similar experiences in several countries in Africa and in this way I was able to
provide evidence that xerophthalmia was indeed a
problem worthy of investigation.
However, it took a great deal more work over a
number of years to convince most ophthalmologists
practising in Africa that VAD, as well as measles,
played an important part in childhood blindness resulting from corneal damage. In addition, traditional
eye medicine and herpes simplex infection may also
be involved. It is of interest to note that much of this
story was pieced together at Mvumi, long after I had
left for Beirut, by Allen Foster (120). Allen is now a
colleague of mine at the International Centre for Eye
Health (ICEH) in London and a leading authority on
childhood blindness.
In Mwanza I interpreted my remit to carry out research on nutrition and the eye in the broadest sense
and published papers at this time on other eye problems, including refractive errors, onchocerciasis, leprosy, cataract, and trachoma. I also took the opportunity to study the growth of young children and the
composition of depot fat in different races (121–124).
Bill Darby and I with one of the Ethiopian army
jeeps on the ICNND Survey.
Not long after the NIH grant came through I received
an invitation from Bill Darby to join him in Ethiopia. After World War II the United States set up the
Interdepartmental Committee on Nutrition for National Defense (later Development) (ICNND). The
purpose of this organisation was to carry out nutrition surveys in developing countries friendly to the
United States. These surveys were confined to the
military at first, thus their scientific interest was limited. Bill Darby was early on associated with these
surveys. The first director of the ICNND surveys was
Harold Sandstead, a colleague of Bill’s. Sandstead
was on duty with the surveys when he was among
the occupants of a plane that was blown up over the
United States by a youth who had placed a bomb on
it with the intent of collecting the insurance he had
taken out on the life of his mother, also on the plane.
Harold Sandstead Jr in due course became an associate of Bill’s and is a distinguished worker in public
health nutrition.
Bill Darby was the director of the ICNND survey in
Ethiopia in 1958, in which for the first time the civilian population was studied; the army provided transport. Bill told me that the survey team had been finding many examples in school children of changes in
Typical bilateral non-responsive Bitot’s spots (X1B)
in an older Ethiopian school boy.
65
Tanganyika
the conjunctiva with the appearance of Bitot’s spots.
He wanted me to confirm the nature of these lesions
and to investigate whether they were caused by VAD.
I soon confirmed that they were indeed typical Bitot’s spots. They were occurring in about 4% of the
hundreds of school children being examined. At that
time their relationship to vitamin A deficiency was
usually considered not to be in doubt.
Examination of much younger children in hospitals
failed to find any cases of xerophthalmia or keratomalacia, suggesting that in the absence of blinding VAD
the Bitot’s spots might not be due to nutritional deficiency. Serum retinol estimated in blood samples
from these subjects showed values within the normal range. It was decided that the children with Bitot’s spots should be given vitamin A capsules at regular intervals for six months and blood would be examined again at the end of this period. It was arranged
for me to come back again in April 1959 and to repeat the clinical examinations.
This time I was joined by Dr David Paton, a recently
qualified ophthalmologist from the NIH in the United
States. He brought with him a radium plaque US
One of many schools in Ethiopia being used for the
ICNND Survey.
66
Navy portable dark adaptometer for measuring night
vision. I had brought my portable slit lamp microscope specially made in London for my field work
in Africa.
Blood retinol after dosing was again normal and no
abnormal night vision tests were found in over 200
students. In fact, they tended to see better than the
American children upon whom the instrument had
been tested by David!
The test, dark adaptometry, was carried out in complete darkness with the small dark adaptometer,
which was about the size of a portable typewriter.
When we set up our equipment in each school we
first had to choose a classroom with as few chinks in
the doors and windows as possible. We took along
great rolls of blackout material and filled every nook
and cranny with it. This was not easy, as can be
imagined, when it is realised that the schools were
made of mud brick walls and corrugated iron roofs.
Willing helpers would be seen clambering all over
the roof, filling gaps and nail holes on the shouted
directions from those incarcerated in the increasing
darkness within. When all was ready to start a timer
was set going to mark the passage of 30 minutes.
Bill Darby and Bill McGanity (later professor of obstetrics and gynecology at Galveston, Texas) examining subjects.
SIGHT AND LIFE
We found that the Bitot’s spots had remained completely unchanged after the vitamin A treatment.
Under the slit lamp Paton found that there was more
dryness of the conjunctiva than in children of similar age he had previously examined in Washington
D.C. The conclusion was that in this group the lesions were definitely not related to active vitamin A
deficiency.
They might have been residual changes from VAD
in the past. On the other hand they might have been
related to such local factors as excessive UV exposure at the high altitude of Addis Abeba, chronic conjunctivitis, which was common, or irritation from
smoke which filled the huts these children lived in.
This research resulted in two publications (125, 126)
in the American literature that attracted considerable attention. It is now generally recognised that
Bitot’s spots in children older than 6 years are unlikely to respond to vitamin A treatment. Under this
age a high proportion respond to vitamin A.
The author examining an eye of a patient with the
portable slit lamp microscope.
This was the time required to allow the rods of the
retina to become adapted as fully as possible to the
dark before the actual testing could begin.
The testing consisted of spinning on a number of
occasions a very faintly illuminated figure in the
shape of a cross and asking the subject to indicate
the direction in which the long part of the cross
pointed.
I leave it to the imagination of the reader to picture
what it was like to spend this apparent eternity in a
room packed full of highly spirited Ethiopian school
boys or girls (taken separately!), with no access to
light or air from the outside! However, everything
always passed off without undue incident.
There is one incident in relation to the work in
Ethiopia which I have often used as a salutory lesson in my teaching and writing. The full story is
told in the Report of the ICNND Nutrition Survey, Ethiopia, September 1959 (127, pp 67–70).
Just prior to the ICNND survey the FAO/WHO nutrition consultant Dr Postmus had examined over
7000 pre-school and school age children and found
Bitot’s spots (0.9% in girls and 2.2% in boys – a
similar ratio to that which we found in over 6000
school children, both studies showing the usual
male preponderance). He had recommended an
extended programme of supplementation in
schools with capsules containing vitamin A. This
was about to be implemented as the ICNND
survey started.
When our negative findings were reported to the government the expensive and difficult supplementation
programme was abandoned. The lesson to be learned
is that whilst we confirmed the UN expert’s findings
we did not agree with his interpretation that they
67
Tanganyika
indicated VAD. From our extensive and thorough
studies we were able to prove the point. Observations may concur, but interpretations may not.
I have kept a cutting from the Sunday Telegraph of
17 October 1965. It relates how a team from the Westminster Hospital in London under a renowned ophthalmic surgeon from there had flown to Addis Abeba
with deep-frozen corneas to carry out grafts on 30
children with blinding corneal opacities. The paper
stated, “The project was being so enthusiastically
received that the Emperor was meeting him [the surgeon] to convey his appreciation”. The surgeon said,
“Our technique of freezing eyes which can be kept
indefinitely could mean a breakthrough in the fight
against blindness caused by opaque corneas”.
This is an example of the popular misconception that
the surgeon in shining armour can slay the ugly
dragon of disease. More than 30 years later large
numbers of children continue to go blind with
keratomalacia and many die, in Ethiopia and in many
other countries. Corneal grafting under these circumstances remains a futile exercise, as it was well known
to us then, and would be considered only by someone seeking cheap publicity. Most of these young
children also have internal damage to the eye which
makes even successful corneal grafting ineffective
in restoring even a vestige of vision. The only ethical approach to the problem of the control of VADD
is through public health preventive measures that lack
any glamour and require patience and persistence.
There is no short cut.
In Tanganyika I had been making a study of damage caused to the eyes in leprosy, a subject little
investigated previously. I was allowed to borrow
the dark adaptometer and I decided to try to use it
to investigate whether the Bitot’s spots I had been
coming across might be related to VAD. Over the
course of several days I examined the eyes of all
the inmates, over 400, of the leprosarium at
Makutupora, run by the Church Missionary Society of Australia (128). Patients came from several
provinces of the country to be treated in this insti68
tution situated in remote bush country on the western slopes of the Great Rift Valley of East Africa. It
had an imposing view over the desolate Bahi
Swamp, with hardly a rondeval in sight.
In quite a number of patients I came across Bitot’s
spots. The blackout facilities were none too good;
but I chose a moonless and starless night. I shut myself in with a group of patients to wait for our eyes to
adapt. It was then that I learned the truth of the saying that you can diagnose leprosy by the characteristic smell! Dark adaptation was normal, as I expected.
A year or so later I was one of a team investigating
another tropical disease, widespread in parts of Africa – onchocerciasis. As it may be recalled (see page
52), this disease, also called river blindness, had preoccupied John Wilson of the British Empire Society
for the Blind several years previously when I had
sought his interest for xerophthalmia.
A group of scientists had been brought together by
Allan Woodruff, for many years Professor of Clinical Tropical Medicine at the London School. After
retirement he spent a number of years at the medical
school in Juba, helping the people of southern Sudan during their long-running war with the north. He
died there a few years ago.
The study was carried out among the Mukonjo tribe
in the Bugoye region of western Uganda, in the foothills of the Ruwenzori mountains, also called the
“mountains of the moon” for their spectacular landscape. My job was to examine the eyes, and as an
additional investigation I decided to measure dark
adaptation in some subjects.
One of the rooms in the dispensary where we had
our base was easily made lightproof and I sat down
with about a dozen of the rather ferocious-looking
tribesmen. They came from huts scattered up the
wooded slopes of the foothills.
Everything went according to plan for the first 20
minutes or so, but then some of my captive tribes-
SIGHT AND LIFE
men began to get restive. All of a sudden there was a
stampede for the door with wild shouts and, I presume, gesticulations. I am afraid I do not have the
words to describe what it was like to be with a group
of hysterical African tribesmen under such circumstances. Needless to say, you will not find in our paper (129) any account of dark adaptation in onchocerciasis.
Vitamin A levels in serum were measured in this study
and no association was found between these and the
presence of onchocerciasis lesions of either the anterior or posterior segment of the eye. This confirmed
the view that VAD does not play a part in the disease, as some had supposed.
It is evident in retrospect that many of the eye changes
we reported in our surveys in Tanganyika (119), such
as bulbar conjunctival wrinkling and pigmentation,
pinguecula and pterygium, which played a large part
in our thinking at the time, turned out later to be unrelated to nutritional status. It was to be the experience gained through the Global Survey (100, page
77) that prepared the way for the resolution of these
issues at the first WHO technical meeting on the subject (130, page 96).
I see now that it would have been very worthwhile if
I had extended the cultural studies I had started in
Udayagiri and if I had in a more thorough way tried
to get to understand precisely what were the factors
that precipitated xerophthalmia in a relatively small
group of any population.
The extensive field surveys in the Mwanza and
Mvumi areas showed that xerophthalmia was much
more common in the latter (119). However, Bitot’s
spots in school age children were found equally in
both places. This was consistent with the studies in
Ethiopia, suggesting again that these lesions are not
related to active VAD in this older age group.
With the NIH grant I was able to recruit an ophthalmologist, Bill Johnstone, from the United States to
assit me in the research. He was some years older
than I was and I do not know whether it was cultural
shock in the African bush, but he was the only individual whom I have employed with whom I have
had serious personal problems.
During the early days of my PhD work Ben Platt had
directed me to a paper from East London, South Africa, by C. J. Blumenthal, an ophthalmologist in private practice, entitled “Malnutritional Keratitis”
(131). Although many of the cases he described
seemed to be due to infection there was a small group
in which the cornea appeared to melt in one area with
a “silent” prolapse of the iris.
I saw several cases fitting this description during my
years in Mwanza. They were readily distinguishable
from keratomalacia. I gave the name Discrete Colliquative Keratopathy (DCK) to the condition and a
full acount was given in Malnutrition and the Eye
(88) and repeated in Nutritional Ophthalmology
(132), when no further accounts had appeared. At
the time I gave considerable importance to this condition and went specially to Entebbe to discuss the
matter with Blumenthal when he was flying between
the UK and South Africa.
An example of what the author termed Discrete Colliquative Keratopathy.
Over time it became evident that DCK, if a true entity, was very rare. In retrospect I suspect that some
kind of injury may have been responsible. Even
69
Tanganyika
They did some very convenient “baby-sitting” of
Gavin and Jill, aged 10 and 6 at the time. This enabled Olga to accompany me when I gave some of
the lectures at centres on the eastern seaboard and in
the midwest which George Smelser of the Presbyterian Medical Center, New York, had arranged.
Rolling Chair Parade on Atlantic City’s famous
Boardwalk which extends several miles south to
Ventnor where we stayed. The FASEB Annual Meetings were held in these and other nearby seaside hotels.
though this was always enquired about, its occurrence may have been concealed by the patient.
In mid 1960 I was due home leave of about six
months. For the first month, at the invitation of Nevin
Scrimshaw, Director of the Institute of Nutrition for
Central America and Panama (INCAP), I was in
Guatemala to assess the vitamin A situation there and
in El Salvador. Although there was biochemical evidence of deficiency in the former I saw no xerophthalmia. In El Salvador there were many cases. I met
the Professor of Ophthalmology and Minister of
Health at the time, Humberto Escapini, who was well
aware of the problem.
Due to some very good fortune as a family we were
able to spend much of our remaining leave in the
United States. My father knew Malcolm Bradbury,
the editor of The Watchman Examiner, a religious
newspaper in the United States. He arranged for us
to stay at no charge in the “Houses of Fellowship”, a
luxurious apartment building in Ventnor, just south
of Atlantic City, New Jersey. It provides accommodation for missionary families during furlough. They
were generous in their interpretation of eligibility in
our case. Olga’s mother and Olga’s sister, Hazel, it
so happened were just visiting relatives in Ohio then.
70
One of these lectures was at the Wilmer Institute at
Johns Hopkins University in Baltimore. David Paton
was on the staff there and made the arrangements.
These included Olga and I staying overnight in the
house of the widow of a famous former professor of
medicine at Hopkins. David drove out to the suburbs in the dark and I followed him in our car. Next
morning I had to find my own way back in the rush
hour. The most vivid memory of the whole visit is
going round a roundabout the wrong way in my confusion. All my previous driving experience had been
on the left! On the return journey a car on the road
ahead of us in the dark suddenly exploded into flames
and two youths leaped out!
David Paton went on to become head of the department of Ophthalmology at Baylor School of Medicine in Houston,Texas. His father, Townley Paton,
was an eminent eye surgeon in New York.
At that time I made one long trip on my own. The
end point was to give the guest lecture at the First
Congress of the Asia-Pacific Academy of Ophthalmology in Manila, on “Nutritional Blindness” (133).
On the way out I stopped in Los Angeles to lecture.
In 1960 at the University of California, Los Angeles, (UCLA) ophthalmology was part of the department of Surgery. Not long afterwards a wealthy
cataract patient donated money for what became the
famous Jules Stein Eye Institute. Two young eye
doctors, Christopherson and Stretsma, entertained
me and I was surprised that my lecture was to be to
the class of chiropractors to whom they taught
anatomy! Interestingly, I received my most generous fee of the whole trip – $300! Brad Stretsma has
become one of the leading ophthalmologists in the
United States and now edits the American Journal
of Ophthalmology.
SIGHT AND LIFE
I went on to Tokyo, where I stayed in the new 11storey Hotel Nippon run by Japan Air Lines, then
the tallest building in the city! The problem of making buildings safe from earthquakes in Japan had not
been fully overcome at that time.
I was entertained by several professors of ophthalmology. I learnt from them that at that time they had
hardly any contact with the outside world and were
very eager to meet any visitors. I raised with them
the description Mori had given of the epidemic of
xerophthalmia at the beginning of the century (see
Chapter 1, page 16). I learned from my hosts that
there were a few survivors of that epidemic still alive
in blind institutions. Otherwise xerophthalmia had
virtually been banished from their country in recent
years.
I wrote the following comments on the incident in
1965 – “Undoubtedly this transformation has resulted
from the phenomenal rise in the standard of living,
with the economic expansion and spread of education in the post-war period. Japan is the only nation
in Asia, or throughout the world for that matter, where
a serious xerophthalmia problem has been conquered.
This has been achieved ‘without a shot having been
fired’, as it were, in the form of specific measures
against the disease itself. The lesson to learn here is
that nutritional diseases are symptomatic of a sick
society, sick from ignorance and poverty. The problem is too fundamental and basic for superficial tampering measures, but requires a concerted effort such
as only the Japanese have in our time demonstrated
themselves to be capable of making; to universalise
education, control population growth, and promote
economic prosperity.” Thirty years later I see no reason to alter anything.
Illustrative to me of the remarkable spirit for selfimprovement that animated the Japanese at that time
was an incident on my second day in Tokyo. Shortly
after breakfast I was informed by the hotel receptionist that a Professor Irinoda wanted to see me. This
professor of ophthalmology at a small medical school
in the northern part of the main island had published
several papers on nutritional eye disease and we had
been in correspondence. I had told him I would be in
Tokyo. I learned that he had been travelling through-
Professor Irinoda is standing.
71
Tanganyika
In this group at a reception for the 1st Asia-Pacific Academy of Ophthalmology Meeting in
Manila in October 1960, besides the author are Dr Gordon Holmes, Secretary-General,
and Professor Barraquer of Barcelona, Spain.
out the night by train from his home and had brought
his assistant with him. Very soon in my hotel bedroom we had the projector he had brought along
rigged up and spent the rest of the morning exchanging ideas and comparing our experiences using our
slide illustrations. Irinoda described a disease affecting the skin and eyes in patients whose diet was based
on highly polished rice (72).
My final stop before Manila was Hong Kong and
here I had the British government ophthalmologist
Dr Dansey-Browning to brief me on the local situation. He was well aware of the problem of xerophthalmia and all children received cod-liver oil in his
clinics. Many cases occurred in the children of refugee families from mainland China. He had special
access to the old walled city of Kowloon and took me
round the opium dens where gambling went on con72
tinuously on the mah-jong games played at a furious
pace. I can still hear the hypnotic clatter of the tiles.
All this was swept away completely a few years ago.
I arrived in Manila in a typhoon, we were drenched
leaving the aircraft and on the following day I had to
roll my trousers above my knees and wade through
flood waters to enter the General Hospital where the
meeting was being held. Manila is not my favourite
city; on the next visit in 1968 as part of a family
travel to the East (see page 92) the four of us were
caught in an earthquake that shook Hotel Manila for
40 seconds in the early hours of the morning and
cracked some of the walls. Elsewhere in the city an
apartment block called “Ruby Towers” completely
collapsed, killing about 400 of its occupants, mostly
of the Chinese community. On my third visit to Manila, to attend the Third Asian Conference of Nutri-
SIGHT AND LIFE
tion in 1973, my hotel caught fire and I had to get
out in a hurry.
I was very well received by my hosts as guest lecturer coming out of Africa. After my lecture some of
the prominent ophthalmologists who were involved
in organising the meeting stated during the discussion that xerophthalmia was now no longer a problem in the Philippines. However, several younger eye
doctors, from the remote rural areas of this country
made up of an archipelago, came up to me afterwards
and explained that they were seeing many cases. They
were not surprised that their leaders did not see cases
now as their patients were exclusively private and
rich. Throughout these years I often faced similar
experiences when authorities in central offices and
hospitals denied the existence of xerophthalmia, even
though I was being shown cases in local hospitals
and clinics.
I learned from the many leading ophthalmologists
whom I met that most of them had seen one or two
cases of xerophthalmia in their own clinics in the
United States. Some of these had been children of
the poorer sections of the black population. Others
had arisen through the failure of the general physician to ensure additions of vitamin A to a non-milk
formula being fed to a baby who was considered to
be allergic to mother’s or cow’s milk. Several instances were reported in the medical literature (88).
On a lecture tour of some of the central states of the
US Olga and I stayed a few days with Bill and Elva
Darby in Nashville and he invited me to join his department. This was a very tempting offer, but I still
had both my aged parents in London, my mother
being especially unwell at that time, and I felt I still
had contributions to make towards resolving some
of the problems of malnutrition in young children in
developing countries. I declined with great regret.
At the invitation of the Secretary General of the Congress, Dr Gordon Holmes, I stayed over on my way
back to the United States at his beautiful mountain
home overlooking the city of Honolulu in Hawaii.
Also as a result of a contact at the meeting Dr Phillips
Thygeson of San Francisco had me stay with him
and lecture on xerophthalmia in his department. He
was a world authority on trachoma and in charge of
the programme to eradicate this disease among
American Indians.
Everywhere I lectured in the States I met appreciative
audiences who were amazed that so little was being
done to prevent this tragic disease. Someone got so
frustrated that he asked why we could not just spray
them with vitamin A from the air! Another common
reaction was, “Why can’t every child be injected with
vitamin A from birth?” I knew just how they felt.
At the 5th International Congress of Nutrition held
in Washington D.C. that summer there was not a
single paper devoted to vitamin A deficiency and
xerophthalmia, although one of the plenary sessions
purported to cover “Worldwide problems in human
nutrition”.
W. Henry Sebrell, Jr on receiving the Order of
the Cedars from the Lebanese Government.
73
Tanganyika
Bill Darby turned down the opportunity shortly afterwards to head up nutrition at WHO headquarters
in Geneva. Later he declined the invitation to be director of the institute at NIH responsible for nutrition. Overseas he built up a team of researchers at
the US Navy Medical Research Unit (NAMRU 3) in
Cairo where it was shown that severe zinc deficiency
in man could result in dwarfism and hypogonadism
(dysfunction of testes and ovaries).
On the same visit while in New York I met W. Henry
Sebrell Jr for the first time at the Institute of Nutrition Sciences which he was setting up in the Columbia-Presbyterian Medical Center at 163rd Street in
upper Manhattan. Henry had just retired after 30 years
of service with the US Public Health Service, rising
to be Director of the National Institutes of Health for
five years. In his view his major achievements then
had been to set up the famous Clinical Research
Center at NIH and to institute the external research
grants system which has been the life blood of innumerable medical researchers, all over the world, until the present. This meeting may have played a part
in my being invited a year or so later to head up the
Nutrition Research Program Henry was developing
at the American University of Beirut.
Our time in the United States drew to a close and we
made our way to New York and spent Thanksgiving
Day there seeing the sights. I was sleeping in the
residency of the Eye Hospital at the Presbyterian
Medical Center and the others were in a lodging
across the street. After a good night’s rest I turned up
to find that Olga had been up all night nursing the
elderly landlord who had collapsed on returning from
a friend’s. The New York police force likewise only
arrived when it was all over. We just had time to get
down to the docks where I saw the others off on the
“Queen Mary”.
I had to fly to Edinburgh to give a special lecture in
the Royal Infirmary arranged by the Royal Medical
Society, of which I had been a president when a student. My old Professor of Medicine, Sir Stanley
Davidson (Panel 6, page 34), was in the chair and
74
the familiar old lecture theatre was packed. The audience was very attentive, as was almost everywhere
the case, as I had again the privilege of telling the
tragic story of children blinded by xerophthalmia.
We returned to Africa as a family just after Christmas
1960 and arrived at Nairobi Embakasi airport just in
time to see the small DC3 aircraft taking off for
Mwanza with Sir Harold Himsworth aboard. As Secretary of the Medical Research Council in London he
was making a final tour of British research establishments in east Africa before the imminent programme
of independence for the three territories. The next plane
was not for another five days. We were put up by the
airline we came on, South African Airways, in the New
Stanley Hotel at their expense and had a wonderful
time over New Year – with the added bonus that I did
not get inspected by Himsworth in Mwanza! Instead
about a month later I had dinner with him at the Nairobi Club, where he was staying, and talked about my
work in that very relaxed atmosphere.
At just about the time I was leaving Platt in 1957 he
gave me my first opportunity to contribute a chapter
to a book (I have done this on more than 50 occasions
since). This was for World Review of Nutrition and
Dietetics and was to be on “The effects of malnutrition on the eye in experimental animals” (134).
This led me to think I might go on to write my first
book which would also include nutritional eye disease in man. Bill Darby proved very supportive and
was instrumental in having my manuscript accepted
by the Academic Press in New York. Bill wrote a Foreword. I was able to do the necessary extensive library
research on visits to the United States and the UK.
I was keen to have several pictures of the eye lesions
of xerophthalmia in colour, but in those days this was
very expensive. I mentioned the problem to Henry
Sebrell and he suggested I apply to the WilliamsWaterman Fund, of which he was president, for a grant.
I was successful in obtaining $ 500 and Academic Press
agreed for this amount to have the colour pictures included.
SIGHT AND LIFE
The Williams-Waterman Fund was set up by R. R.
Williams and his associate to assist research on nutritional diseases. Williams was a chemist working
for the Bureau of Science in Manila and while in the
Philippines he used his spare time to discover vitamin B1 or thiamin, the lack of which causes beriberi.
Williams took a unique approach to the financial aspects of his discovery. He took out a patent on the
vitamin and arranged for all the profits to be put into
this fund. Williams wrote an account of his work
which has the title Towards the conquest of beriberi
(135).
By the summer of 1961 things had become very difficult in Mwanza. Johnstone and I were hardly talking. My mother’s condition had worsened since our
return to Africa and I was wondering whether for
family reasons I should accept the offer Platt had
made once more for me to join him in London. Independence – uhuru – for the country was due in December 1961 and nobody knew what would happen
then.
In the midst of this turmoil I received a letter from
Henry Sebrell in New York inviting me to become
head of an NIH-supported Nutrition Research Program at the American University of Beirut (AUB) in
Lebanon, associated with his institute in New York
(Panel 13). The university arranged for me to visit
Lebanon for ten days in September. I had to catch a
connecting flight in Nairobi but none was flying in
from South Africa because of severe weather. A second attempt was successful some time later, but on
reaching Nairobi on the return trip I found out that
the dirt airstrip in Mwanza was flooded and only a
three-seater Piper aircraft was able to take off. Olga
came up for the ride and for much of the way we had
wonderful low-level views over the Serengeti Safari
Park. Tribes people and game animals alike had had
to congregate on what little high ground there was to
avoid the rising floods.
My appointment was confirmed with a starting date
of 1 May 1962. Just a few days before we left for the
UK in March I received two visits which gave me
considerable encouragement. The first was from a
friend and colleague over a number of years, Dr V.
N. Patwardhan of India, former Director of the Nutrition Research Laboratories in Hyderabad (now the
National Institute of Nutrition). He had recently taken
up the post as head of the Nutrition Section at WHO,
Geneva.
Patwardhan had obtained a three-year grant from the
NIH to work towards the solution of the problem of
xerophthalmia. “Pat” explained that the first year was
to be devoted to a world-wide survey of the extent of
the problem in countries where it was likely to occur, but from which information was at present lacking. He asked me to undertake travel in North Africa
and the Middle East. Oomen was to cover Asia, and
Escapini from El Salvador, Latin America. At last
WHO was interested in finding out whether xerophthalmia was really as serious a public health problem as some of us had been saying for years.
The second visit came about as the result of correspondence I had had with John Wilson of the Royal
Commonwealth Society for the Blind (RCSB). I was
informed that Dr Cobb, a young eye surgeon from St
Thomas’ Hospital in London, was being sent out to
investigate the cause of the high rate of blindness
among young children in the Luapula Valley area of
Northern Rhodesia (now Zambia).
By the time Cobb arrived he was lucky to find me
still in Mwanza. I met him at the airport in the morning and saw my family off to Dar es Salaam on the
train the same evening. I was finishing the packing
before leaving by air for Cairo en route to London
two days later. As a result of our discussions it was
soon clear to both of us that while measles was probably a serious disease among children there, and no
doubt some damage was done by indigenous medicines, the real problem was nutritional and the blindness was due to VAD.
Subsequently, in his report to the RCSB Cobb provided convincing evidence, both clinical and biochemical, that xerophthalmia is indeed the major
75
Tanganyika
cause of childhood blindness in this part of Africa
(136). I think this piece of evidence weighed the
scales very heavily in favour of xerophthalmia being made subsequently one of the major emphases
of the RCSB’s prevention of blindness efforts.
I left Tanganyika after nearly five years of full-time
research on nutritional eye problems. I felt very privileged to have had the opportunity to work in this
important and previously neglected area.
My surgical experience in India meant that I was allowed by the district hospital in Mwanza to carry
out cataract and other straight-forward eye operations
in the absence of an ophthalmic surgeon. This gave
me an entree to the hospital to carry out some research projects. Today the old hospital building,
erected during German colonial times, is no more.
Burgando Medical Centre is a tertiary referral hospital for an incredible population of eight million!
The last major operation I ever carried out, about 8
years after the previous one (!), was under very
strange circumstances. On one of my visits to
Mvumi hospital to carry out nutritional surveys the
hospital had been left in the sole charge of a young
female doctor only recently qualified in the UK.
One evening she sought me out and asked if I could
see a woman admitted with severe abdominal pain.
76
We agreed that something had ruptured internally
and that emergency surgery was needed. I agreed
to assist her, but once we were on either side of the
operating table she felt unable to carry on and asked
me to take over. There was serious bleeding and it
became evident that it was coming from a rupture
in the uterus, almost certainly due to a rare type of
cancer (choriocarcinoma). The entire mass had to
be removed as completely as possible. I tried to recall where the large blood vessels were for ligature, and the two ureters taking urine into the bladder – not to be cut at any cost. It was a relief to
learn two or three days later that the patient had
passed urine satisfactorily. On my next visit I
learned that she had gone home without any complications, but I knew that her ultimate prognosis
had to be guarded.
My book was finally ready just before we were due
to go to Beirut. I well recall the excitement of handing the manuscript in at the London headquarters of
Academic Press, at that time in Berkeley Square.
There certainly was a nightingale singing just then!
I looked forward keenly to the prospect of being on
the medical faculty of the finest university in the
Middle East situated at the crossroads of Europe, Asia
and Africa. There was the added stimulus of the ancient Arabic culture, new to me.
SIGHT AND LIFE
The Switzerland of the Middle East (1962–1976)
I realise now that the broadening of my research in
Africa to include eye problems other than those related to VAD and to take in more generalised effects
of malnutrition paved the way for my translation to
the stimulating setting of the School of Medicine at
the American University of Beirut (Panel 13).
In the early 1960s AUB, and particularly its medical
school, was still the academic leader and trend setter
in the Middle East. The MD degree was incorporated in the State of New York and most of its professors were Lebanese, former students who had done
their speciality training in the States. Throughout my
14 years there, expatriate physicians were in a very
small minority.
I was appointed as Research Professor of Nutrition,
supported by a large programme/project grant from
the NIH for “Nutrition Problems in the Middle East”.
The programme was linked with Henry Sebrell’s Institute of Nutrition Sciences at Columbia University,
New York. I was given several rooms in Van Dyck
Hall, the basic medical sciences building, and I set
about getting them equipped and hiring staff. Plans
were already underway for the building of a large
new teaching hospital. Nutrition was included in these
plans and in 1968 we moved into a total of 17 laboratories and offices. This later move from the basic
to the clinical departments gave us much more influence with the mainstream of clinical medicine.
As I was settling in, in the summer of 1962, I was
planning at the same time visits to countries in the
Middle East and north Africa as part of the global
survey of xerophthalmia coordinated by Patwardhan
at WHO headquarters. This gave me a very good opportunity to learn about these countries, which were
new to me, and also to build up associations with
personnel there. Altogether about 50 countries were
visited by Oomen, Escapini and myself, and our report appeared in 1964 (100).
We collected impressions rather than hard data and
did it on the basis of what has come to be known as a
preliminary assessment. In this interviews are held
with central and regional government health personnel, hospitals and clinics are visited and attention is
especially directed to child-feeding practices and eye
diseases. It is interesting to observe that the conclusions reached in our report have stood up very well
subsequently to the test of time. The main objective,
to determine whether xerophthalmia constituted a
public health problem beyond countries like India
and Indonesia, was achieved; it certainly did.
In the spring of 1963 my book Malnutrition and the
Eye was published. It is a 390-page monograph with
over 2000 references (88). It underwent a complete
revision and updating later and in 1980 appeared as
Nutritional Ophthalmology (132). This work remains
the standard reference on the subject. The largest
sections of the book cover all aspects of vitamin A in
relation to the eye, in both man and experimental
animals.
VADD in various ways have also had a place in other
books I have written (Nutrition and its Disorders, 4
editions; Colour Atlas of Nutritional Disorders, 2
editions) or edited (Nutrition in the Community, 2
editions; Textbook of Paediatric Nutrition, 3 editions).
It has been my hope that readers of these books will
have gained a true impression of the importance of
vitamin A in human health and disease.
I planned my travel for WHO in 1962–63 to coincide with the peak seasonal incidence of malnutrition in children – in the autumn and early winter.
This follows upon the stress of repeated diarrhoeal
disease in the hot summer months. Throughout the
countries of north Africa, the Near East, and as far
east as Iran the clinical pattern of predominantly the
marasmic form of protein-energy malnutrition (PEM)
was found, with about 5% on average of these cases
77
Panel 13
The American University of Beirut, Lebanon
Daniel Bliss, an American missionary to Syria, raised
the funds in the United States and the UK to open
what was then the Syrian Protestant College in 1866.
It was the first western-style, university-level institution in the Ottoman Empire. The school of medicine
was opened two years later. By 1920 the college had
grown into a true university, Lebanon had become
an independent state from Syria, and the institution
was secular and American. Thereafter it has been
known as the American University of Beirut (AUB).
Beirut in the 1960s. The AUB campus is the area close to
the aircraft beacon on the extreme left.
View from the balcony of our apartment over the port to Mt
Lebanon (c. 10,000 feet and snow-covered in the winter).
78
In 1966–67 AUB entered into a year of centennial
celebrations that were planned to contribute hugely
to the endowment fund and to culminate at the commencement exercises in early June at the end of the
academic year. Many high-ranking officials in nearly
all the countries of the region were alumni of AUB,
as were many prominent people in all walks of life in
the United States. As fate would have it these celebrations were never to take place. At the last minute
everything had to be cancelled with the rise in tension between Israel and Egypt and the outbreak of
war on 5 June. America and Britain were accused of
assisting Israel, and the university closed down and
evacuated all its expatriate personnel.
Throughout the subsequent years, until civil war broke
out in Lebanon in 1975, there was continual unrest
in the country, especially among the various groups
of students at AUB. Amazingly, the university continued to operate throughout the civil war, but since the
closure of the Nutrition Research Program in the
School of Medicine there has been no nutrition presence there. The Department of Food Technology and
Nutrition in the School of Agriculture has continued
throughout. Through Professor Nahla Baba, one of
my former students, that department is responsible
for training dietitians. On a return visit we paid in
March 1998 there were signs that the former link with
the institute in New York might be reforged.
The campus with Van Dyck Hall, the Basic Medical Sciences Building (home of the Nutrition Research Laboratories until 1968) on the right.
SIGHT AND LIFE
showing accompanying xerophthalmia. This was a
much lower incidence than was being reported from
south and east Asia, but would still constitute a major cause of blindness in young children.
There was probably less known about nutritional status in the region I covered than in those visited by
Oomen and Escapini. This provided an opportunity
and a challenge to gather new information there. It
also meant that it proved very difficult to convince
authorities of the importance of VAD in the causation of disease. Not infrequently officials were embarrassed to be confronted with reports of young
children going blind and dying in hospitals and for
there to be no preparations of vitamin A with which
to treat them.
The problem of ineffective treatment took a strange
form in Tunisia and Morocco. I was told there by
several French paediatricians that they were puzzled
by the cause of the destructive corneal lesions they
were seeing because there was no response to injections of vitamin A. I was able to point out that the
oily preparations they were using were quite unsuitable for emergency treatment. The oily solution
stayed in the muscle at the site of the injection from
where the vitamin was only very slowly released into
the circulation. These preparations were originally
manufactured for veterinary use, to prevent VAD in
cattle. Water-miscible vitamin A disperses readily,
but is not always available in hospitals. I was able to
advise them to break the ampoule of oily vitamin A
and give it by mouth as, even in a severely malnourished child, absorption is quite good. The issue of
the formulation of vitamin A for injection loomed
large on the agenda at early IVACG Meetings (see
page 100).
A few individual experiences have stayed with me
and they complement what can be gleaned from our
official report. In the children’s hospital in Alexandria, Egypt, under the care of Professor Hanafy I saw
a little girl aged 18 months. She was one of nine children born to a “felah”, a peasant farmer, who had
come into the city ten years previously from Upper
Egypt to try to raise the family as a casual labourer.
Of the previous eight children, all except one aged 4
years, had died before the age of 3. The patient
seemed to thrive until the age of 8 months while she
was being breast-fed. The mother then became ill
and upon her admission to a fever hospital the child
was weaned onto buffalo milk with starch water and
caraway extracts. Sickness of the mother all too frequently results in this way in sudden weaning of the
child and leads directly to malnutrition as in this case.
After the age of 1 year, bread and some vegetables
were introduced into the diet of this little girl. She
did not thrive well but things only went seriously
wrong when she caught measles two months before
I saw her. She had frequent attacks of diarrhoea, and
for the treatment of this at home the diet was limited
to drinks of caraway tea. Six weeks later it was noticed that she was unable to see, and only three days
after this was she brought to the hospital when the
sight had already been destroyed in both eyes.
In the General Hospital in Tripoli, Libya, I took the
picture of two extremely marasmic infants (see page
80). It was this that first set me wondering about the
reason why some severely malnourished children,
General state of the child in Alexandria described in
the text. The skin changes and oedema of kwashiorkor
are evident. There is also noma (cancrum oris) in
the cheek area.
79
Middle East
such as these, escaped xerophthalmia. Several experiments we carried out on young rats indicated that
the amount of vitamin A required by the body is
closely dependent upon the rate of growth (98). Later
we further investigated the matter in patients in Amman, Jordan, and it was clear that these “skin and
bone” babies use up practically no vitamin A while
they are suffering from severe growth failure. However, it was evident that once these children begin to
recover and put on weight there is a real danger that
xerophthalmia can actually be precipitated unless liberal amounts of vitamin A are included in the diet
(137). I encountered several instances of skim milk
used for recovery in PEM doing just this.
This picture of one eye of the patient in Alexandria
shows complete keratomalacia with sloughing of the
entire cornea. There is no sign of accompanying local infection. The other eye was similarly affected.
In both Morocco and Iraq I was taken around the
children’s wards of general hospitals by paediatricians who were obviously interested in the problems
of malnutrition as they pointed out cases of kwashiorkor and marasmus. Nevertheless, in each place as
I carefully examined the eyes of these children I discovered at least one child who had suffered damage
to the cornea. This had developed under the eyes and
without the knowledge of the doctors in charge.
In Baghdad I saw a gross instance of medical ignorance and neglect. In one of the government maternal and child health centres I saw a young child who
had recovered from an attack of measles. The faint
evidence of the skin rash could just be seen still.
During measles the boy had developed a mysterious
eye condition for which he was referred to the eye
specialist. He ordered drops to be put in the eyes daily,
but did not disclose what the condition was due to.
By the time I saw the patient both eyes had been irrevocably destroyed by keratomalacia.
I noted at the time that xerophthalmia is so often precipitated by measles in the malnourished child. It was
only a number of years later that this important relationship was properly investigated, especially in Africa (see page 118).
Severely marasmic infants in Tripoli, Libya, weighing 3.8 kg at 12 months and 2.25 kg at 4 months,
respectively.
80
Another instance of professional ignorance I came
across in Damascus, capital city of Syria. On the same
SIGHT AND LIFE
for eye cases. He produced statistics which showed
that xerophthalmia was the most important cause of
corneal disease in his practice. Nearly 100 cases of
xerophthalmia at all stages of the condition were seen
in the course of a single year.
In Lebanon we estimated serum retinol levels in more
than 100 severely malnourished infants. Only two
had xerophthalmia, but among the vast majority with
normal eyes more than 30% had very low retinol levels (<10 µg/dl). We also found breast milk of some
of the mothers to be low, compared with values for
the United States.
This child in Baghdad had marked photophobia; the
eyes were destroyed as described in the text.
day it was arranged for me to visit two ophthalmologists. The first took me round his wards and showed
me three young children all of whom were reputedly
recovering from injury to the cornea resulting from
the application of “kohl” to the eyelids. This consists of a black powder, usually made from antimony
and used throughout the Near East to “beautify the
eyes”. It has also the reputation of “strengthening
the eyes” in children with measles. Like eyeliner this
preparation is applied to the edges of the eyelids. I
have never heard it suggested elsewhere that “kohl”
could cause anything more serious than the rare instance of a sensitivity reaction to antimony.
Each of the three children I examined had scarring
of the cornea in a healing stage, but with considerable impairment of vision. The scars were in the position typical of those due to xerophthalmia, that is
to say in the infero-lateral part of the cornea. When I
suggested VAD as a possible cause it was emphatically denied.
In the afternoon I talked with the ophthalmologist of
the Nouasat Hospital of the University with 54 beds
In retrospect this seems to me to be important evidence for a serious problem of subclinical VAD in
some sections of the Lebanese population at that time.
However, I did not draw this conclusion then, nor
was the work considered to be worth publishing separately. This is a further example of how, at that time,
such attention as there was was focussed entirely on
the eye problem. I now regard it as another instance
of an opportunity I missed.
Bilateral healed scars in the typical position on the
cornea almost certainly resulting from previous
xerophthalmia (XS) but not so recognised. One of
three children in Damascus.
81
Middle East
While I was preparing Malnutrition and the Eye (88)
for publication I made the first attempt to estimate
the global prevalence of blindness due to xerophthalmia, and this appeared in the book (page 215) as
about 20,000 annually. On the basis of the notification figures from Jordan (105) (see page 86) I presented a paper at a meeting of the Nutrition Society
of the UK (138) which suggested that the previous
figure was a considerable underestimate and that it
might be nearer to about 100,000 per year. Alfred
Sommer (139) after the Indonesian national survey
was to propose a figure of about 500,000 annually
for corneal xerophthalmia throughout the world, not
all of which would cause total blindness.
A recent assessment from WHO (140) puts the
number of blind children worldwide at about 1.5
million, mainly from xeropthalmia. About 300,000
new cases of corneal xerophthalmia are occurring
each year, and about ten times this number (3 million) with non-blinding xerophthalmia – Bitot’s spots
and/or night blindness. A very high proportion of preschool age children in developing countries, nearly
250 million, are estimated to be subclinically vitamin A-deficient.
After the WHO global survey was completed in
1963 there were still two more years of the research
grant to run. The objective for these was to choose
a country in which there was a severe problem and
carry out detailed studies concerning aetiology and
work towards a solution. An ICNND survey in the
previous year and my own visits to Jordan had
shown that there was a serious problem among both
Palestinian refugee and non-refugee Jordanian
populations.
Patwardhan decided to concentrate the effort there
and he took charge of field studies which were located in the most densely populated areas around
Amman, the capital, and Jerusalem. Dr Wadie Kamel,
an Egyptian physician previously working with the
United Nations Relief and Works Agency (UNRWA),
providing services for Palestinian refugees in Arab
countries, was appointed to carry out the work.
82
I was given responsibility for biochemical and clinical studies which were located at the Sisters of Nazareth Children’s Hospital (later Luzmila Hospital) in
Amman. A ten-bed unit was set up for admission of
severely malnourished children with preference being given to those with xerophthalmia. This also gave
us the opportunity to study PEM, and some of our
most significant research on this subject came from
Amman, in addition to the work done in and around
Beirut.
After only two years or so in Beirut I was invited by
the editor of the American Journal of Clinical Nutrition to provide original papers from the Nutrition
Research Program for a complete issue of the journal. The issue for September 1965 consisted of 12
papers of more than 70 pages. Three related to vitamin A.
In the first paper we described the characteristics of
severe xerophthalmia (keratomalacia) in Jordan
(141). Most of the patients were aged less than 2
years; all also had severe PEM (either marasmus or
kwashiorkor). Despite intensive treatment, including
large doses of vitamin A, the mortality (64%) was
about four times higher than in other severely malnourished children without eye lesions (15%) (see
also pages 19, 54). Even this latter group was shown
to have low serum retinol levels and severely depleted
liver reserves of vitamin A. Serum vitamin E was
low in all groups, but lowest in those with very low
levels of serum retinol.
In a later study (142) in the same ten-bed unit there
was the suggestion that the chances of survival over
the short term in children with severe PEM was reduced in those with low serum retinol levels. This
was another piece in the vitamin A and survival jigsaw that has tended to be overlooked.
The second paper was on studies on experimental
rats whose dams had been made deficient before birth
of the offspring and presented early biochemical
changes (143). Once again it was shown that those
that had the most rapid growth developed xeroph-
SIGHT AND LIFE
firmation of the phenomenon came in 1972 (144),
but its possible significance seems not to be appreciated at the present time (Chapter 3, page 119).
The third paper described the effects of a very large
oral dose of water-miscible vitamin A (600,000 IU)
given by our group to 44 parturient women at the
time of delivery. Levels in breast milk remained significantly raised until the fourth week after delivery
(145). A smaller dose is now part of recommended
VAD prophylaxis.
An example of keratomalacia from the study in Jordan. Most of the cornea is opaque. There is no sign
of infection or inflammation.
Another case from the study in Jordan. The cornea
has perforated and the lens is about to be extruded
through the softened cornea.
thalmia first (see page 51). Coincident with the start
of a falling off in growth rate it was found that there
was a proportionate rise in haemoglobin and haematocrit, suggesting haemoconcentration. This effect
was reversed by treatment with vitamin A. Of considerable interest is the fact that in the human study
in paper 1 mentioned above, the group of patients
with xerophthalmia had significantly higher haemoglobin and haematocrit levels than those without eye
lesions. The opportunity to pursue these interesting
haematologic findings further was never taken. Con-
In my 1965 account of the work in Jordan I wrote,
“Anyone concerned about a disease that causes blindness in Jordan will very soon be directed to the St
John Ophthalmic Hospital situated on a hill overlooking the old part of Jerusalem”. This fine institution,
run by the Ancient Order of St John of Jerusalem,
was built in its present form as recently as 1960. A
previous large hospital served the needs of the people of Palestine for nearly 80 years. The first hospital of the Order goes back to Crusader times. The
Hospitaller of the Order at that time was the same
Sir Stewart Duke-Elder who had stated that there was
no xerophthalmia in Africa!
At my first visit to the hospital in 1962 I found little
interest in xerophthalmia on the part of the staff. The
in-patient record of one malnourished girl, with both
corneas affected, showed merely two “squiggles” to
represent the eyes and the word “ulcer” indicating
the situation of the softened areas of the cornea. There
was no more highly concentrated form of vitamin A
in the hospital for treatment than cod-liver oil. No
attempt in the hospital statistics was made to differentiate xerophthalmia cases from other causes of
corneal ulceration and scarring. However, I was
pleased to note later that my plea for greater attention to be given to xerophthalmia did not fall on deaf
ears and matters did improve.
David Paton, with whom I had worked on the ICNND
Survey in Ethiopia, had moved on to spend a year at
St John’s. He helped to set up there the first eye bank
in the Middle East. In an account of his time there
83
Middle East
(146) he wrote, “As in all countries of the East, corneal scarring is the major cause of blindness.
Keratomalacia is seen with regularity, especially in
the winter months. An old local custom of starving
children as part of the treatment of measles is undoubtedly a chief cause of nutritional deficiency of
the cornea and consequent secondary infections. Corneal ulcers or their scars are the medical hallmark of
the population.”
Dr Boase, the Warden of St John’s, told me that most
of their very young patients with xerophthalmia were
seriously ill from general malnutrition and infectious
diseases on arrival at the hospital.They had recently
made an arrangement with the American Colony
Hospital in the old part of the city to transfer such
cases there. The renowned founder of the American
Colony, Mrs Bertha Spafford Vester, who had spent
all her long life in Palestine, showed me round.
Among the 60 children admitted at the time of my
visit there were no less than four with keratomalacia. They were three boys aged 7 months, 1 year and
8 months, and 3 years; and a girl of 1 year. The 3year-old boy had been referred from St John’s three
weeks previously with a note from one of the British
ophthalmologists which I was shown. It was to the
effect “Would you kindly take over the care of this
child as the visual prognosis is hopeless”. Fortunately
for this little boy he was not given up as hopeless by
the Arab paediatricians. He was given large doses of
vitamin A on admission and when I saw him, although
the vision in one eye was destroyed by a total leucoma, in the other it was saved.
Subsequently I have often shown this picture to various medical audiences and drawn the lesson that even
training at the famous Moorfields Eye Hospital in
London, which has special links with St John’s in
The dense and healing leucoma on the left cornea and the clear cornea on
the right are evident. The child clutched at my fingers when asked to do so
(see text).
84
SIGHT AND LIFE
Jerusalem, may not be an adequate preparation for
eye work in developing countries.
Dr Dajani, the young Baghdad- and US-trained paediatrician, told me that the previous week he had
admitted three other children with keratomalacia, all
of whom had died. This gave me my first real insight
into how fatal severe VAD might be. We were able
to document this more fully in the WHO-supported
study in Amman over the following two years (141).
I used to fly from Beirut once a month on an UNRWA
plane which made the circuit of Amman and Jerusalem with supplies for Palestinian refugees. I collected
blood and other samples for analysis in our labs at
AUB and kept an eye on the research. I often stayed
overnight and got to know the director of the hospital, an Armenian AUB graduate, Emmanuael
Shirajian. He was a very cultured man, like many of
his countrymen, and played viola in a small chamber group in Amman.
About one sixth of the population of Lebanon was
Armenian, including many of my colleagues in the
medical school at AUB. Many were from families
who had managed to escape the genocide that had
been perpetrated by the Turks just before World War
I. The tragic story of some of them was described in
the book The Forty Days of Musa Dagh by the famous writer Franz Werfel, author also of The Song
of Bernadette. At the American University Hospital
(AUH) the Night Nursing Superintendent, a friend
of ours, was herself as a little girl the sole survivor in
her family. One of the community, a female assistant
professor in my department, was murdered under
very strange circumstances. The appearance in the
country of a former lover raised suspicions, but he
was never charged.
An integral part of the field research in Jordan was
to be the institution by The Ministry of Health of a
notification system for xerophthalmia over one year
throughout the country. In order to assist its implementation I addressed several meetings of physicians
in Amman and Jerusalem to familiarise them with
the disease. In particular, I discussed clinical pictures
with them to assist in the recognition of the eye manifestations.
The meetings were very well attended, by about half
of all the 300 or so physicians in the country of about
1.8 million population at that time. Around one third
were AUB graduates. In the subsequent weeks Wadie
Kamel toured the headquarters of all the nine districts of the country and repeated the lecture materials. Thus almost all the doctors were briefed.
It had been my experience over the years that undue
attention was drawn to trachoma as a major cause of
preventable blindness. In my surveys in Tanzania and
during visits to other countries I had repeatedly observed evidence in children of the spontaneous remission of trachoma without involvement of the cornea
and no impairment of vision. Bilateral scarring of the
cornea in young children was frequently wrongly attributed to trachoma, rather than to xerophthalmia.
A WHO survey in the border area with Israel had
reported trachoma to be the most important cause of
preventable blindness and a trachoma control programme had been set up. At one of the meetings Dr
Schaefel, the Austrian doctor in charge of the trachoma control programme in Hebron, asked to talk
with me when the meeting was over. He stated that I
had been able to provide the answer to a question
that had been troubling him for a long time. He had
started work on the assumption that most of the blindness was due to trachoma. However, a preliminary
survey he made showed that the great majority of
those who were blind had gone blind when very
young children. Trachoma would not have behaved
like this but would have led to serious visual impairment only in much later life. This served to illustrate
the point that Oomen and I had always insisted upon
and which should be quite elementary – noting that
the age of onset of blindness is crucial information
for determining the cause of corneal scarring.
The system of notification of xerophthalmia covered
12 months of 1963–64. This was the third year of
85
Middle East
drought in the country and this may have contributed to the high number of cases. 472 cases were
notified; 276 being in children under 6 years. Most
of the cases in older subjects were of night blindness. The notification rate in children under 6 years
of age was 7.2 per 10,000. This was a rate three times
greater than that for poliomyelitis or diphtheria at
the time, and slightly higher than that for pertussis
(whooping cough). The xerophthalmia rate was several times higher than the WHO criteria for the presence of a public health problem subsequently recommended (130, 147).
The field study, with which I was only indirectly associated, was never published definitively. It was
written up as a restricted document (105) and was
summarised at a symposium on VAD held at the
Massachusetts Institute of Technology (MIT) in the
USA (148).
In my view Kamel and Patwardhan made an important contribution to our understanding of xerophthalmia at that time. For example, they came across considerable evidence of community awareness of the
problem in the villages and among the nomads of
Jordan. Vernacular (Arabic) terms discovered to be
in common use for night blindness were: el hidbal
(stumbling), el asha (blindness after dusk), ama eljaj
(chicken blindness) and el wutwat (the bat). Bitot’s
spots were termed: kushour beid (egg shells), kushour
beida (white scales) or kushour samak (fish scales).
That night blindness results from dietary deficiency
was recognised by the practice of feeding various
fatty foods. Liver (el sawda or el zaida) is widely
used for night blindness. It is eaten almost raw; or it
is boiled, the vapour directed to the child’s eyes, and
then the child is fed with the boiled liver. For topical
application the juice is pressed from the liver or oil
is added; it is then ground well and the oily juice is
dropped into the eyes. This is all very reminiscent of
ancient practice in this region (Chapter 1).
The belief that the milk of the pregnant mother becomes harmful after the quickening of the fetus is
86
perceived, which we encountered among the Khonds
in India (see page 41), is also deep rooted in Jordan.
Such milk is called “assassinating milk” (halib al
gheil).
In the field study households with young children
were selected at random. There were 73 households
with at least one child with xerophthalmia (Control
Positive); 459 with no xerophthalmia (Control Negative); and 122 with xerophthalmia taken from the
notification system (Notified Positive). Questionnaires covering social, dietary, and health data were
applied to each. Selective biochemical and anthropometric tests were performed. In general, households in the Notified Positive group gave the poorest
results, as might be expected. Respiratory infections
and to a greater extent diarrhoeal episodes were
closely associated with xerophthalmia. This association was shown many years later in Indonesia (see
Chapter 3).
Of particular interest was that part of the work
which consisted of the first-ever vitamin A prophylactic intervention study. A placebo group had
90 children and the vitamin A group also 90, all of
them being 35 to 180 days old at the start. The
vitamin A group received a single oral dose of
100,000 µg (about 300,000 IU), quite a large dose
for such young infants. There was not a single case
of adverse reaction, although others have reported
that a small percentage of child recipients have
had adverse reactions such as vomiting, headache
or diarrhoea. Subsequent studies have shown that
the slight risk of temporary illness is outweighed
by the benefit of vitamin A supplementation where
appropriate (149).
In the study in Jordan vitamin A levels in blood and
growth were not significantly different in the two
groups. Infectious disease experience was also similar. There were 9 deaths recorded over a period of
more than a year, all from infections. Only 3 of these
were in the vitamin A group and 6 in the control
group. This difference was not commented upon at
the time.
SIGHT AND LIFE
If this work had been published at the time it is likely
that long-term large-dose vitamin A prophylaxis
would have been investigated in larger trials and
probably introduced earlier than it was. This occurred
in 1972 in India (106), and Kalyan Bagchi, in the
Ministry of Health of central government in New
Delhi by then, was responsible for the implementation of the nation-wide programme.
Even though the numbers of cases found in the field
study in Jordan were rather small, if the morbidity
and mortality data had been made widely known this
would probably have stimulated the funding of more
adequate studies in the mid or late 1960s. It was only
about 20 years later that Sommer and colleagues carried out the first of many definitive studies (see Chapter 3, page 118).
With the advantage of hindsight one may philosophise that in the midst of the hurly-burly of research
work it may sometimes be just as difficult to avoid
the mistake of erring on the side of remaining silent
as of rushing into print.
Finally, it is interesting to note an acknowledgement
at the end of the report. This was for “the assistance
of Messrs Hoffmann-La Roche of Basle, Switzerland. The firm not only made a gift of the vitamin A
and the placebo preparations used in the trial but also
made available the expert advice of Professor O.
Wiss, the Director of Biochemical Research.”
After termination of the WHO-supported work in
Jordan my association with Luzmila Hospital was
lessened. Both there and in Beirut my attention turned
more to PEM. There were several reasons for this.
Nowhere did xerophthalmia have a prevalence as
high as the various degrees and forms of PEM. The
severe degrees of xerophthalmia that we were dealing with then invariably occurred against a background of marasmus, kwashiorkor, or marasmickwashiorkor. The reasons for the occurrence of the
different forms of severe PEM were not understood
and the solution of this problem was considered to
be of great importance.
It became increasingly evident to me from our experience in Lebanon and Jordan that the marasmic end
of the spectrum of severe PEM was neglected (150)
and that the element of protein deficiency in PEM
was greatly overemphasised (151).
Our work hereafter relating to vitamin A was mostly
biochemical in our laboratories (152). We reported a
case of a refugee girl aged 9 years consuming a diet
lacking any animal source of preformed vitamin A
(153). The plasma had high levels of β-carotene and
non-provitamin A carotenoids, but hardly any retinol.
Large doses of β-carotene failed to raise serum retinol, but dosing with retinyl ester did and cured the
deficiency. This was clearly a rare case of absence of
the enzyme that converts β-carotene to retinol.
When I was writing my book Malnutrition and the
Eye (88) in 1960–62 I had not been to west Africa. I
copied what other nutrition texts said about the universal consumption of red palm oil (Elaeis
guineensis), a very rich source of β-carotene protecting the population of the tropical rain forest area from
xerophthalmia, despite the poor quality of their diet
in some nutrients.
The first inkling I received that matters might not be
quite so simple was a conversation I had with Dr
Hendrickse, who was then Professor of Paediatrics
at Ibadan, Nigeria, when we both attended a conference in Dar es Salaam in 1963. I had read reports
that measles was a serious disease in west Africa,
frequently precipitating malnutrition. From my experience in the Near East I knew that the eyes could
often be affected, leading to blindness. Although
measles itself sometimes causes a keratitis we knew
that the children were often severely malnourished.
Hendrickse confirmed that in his cases the eyes were
often seriously affected.
In 1964 I had a visit from a young black American
paediatrician, Jim Carter from Nashville, who had
spent a year in west Africa. He showed me his collection of slides, and among these were several of
serious eye lesions which I identified as xerophthal87
Middle East
mia. Carter observed that it would not be surprising
if severe VAD occurred among the infants of the
poorer section of the community as they did not receive the adult diet cooked in red palm oil until they
were well into the second year of life.
A few weeks later I had a phone call from Bill Darby.
He was on his way from Lagos to Cairo but due to a
sandstorm there the plane was diverted to Beirut. He
had been making preliminary arrangements for an
ICNND Nutrition Survey in Nigeria and asked me
to meet him for discussion of a mission he had for
me. Over lunch I learned that he too had heard of
what Carter had found and suggested that there were
two contrasting aspects of the vitamin A story that I
could investigate. In addition to the possibility of
xerophthalmia being missed in infants there was also
the possible harmful effects of too much carotene
(hypercarotenosis) in the adults habitually consuming diets rich in palm oil.
In early February 1965 I was in Rome at the FAO
headquarters assisting with the arrangements for an
FAO/WHO Expert Group meeting on vitamin requirements when I received the news, from Olga in
Beirut, that my mother had died suddenly in London. I quickly completed my part of these talks and
flew to London for the funeral. It snowed heavily
and our small family was represented by Gavin from
school at Eltham College, myself and my father. The
next day I flew to Lagos.
During two weeks in the country, mostly in Ibadan, I
examined a large number of children in outpatients
with severe PEM. One had classical keratomalacia.
The serum of several others proved to be very low in
vitamin A, as was the breast milk of some of the
mothers.
We were also able to show that much of the
carotenoids in serum from adults with hypercarotenosis was composed of non-provitamin
carotenoids, like lycopene or lutein (154). At that time
the possible beneficial antioxidant effects of
carotenoids were not known.
88
As I flew into Beirut after this stressful period I developed a severe pain in my chest. A heart attack
was suspected and I was rushed into our hospital. It
turned out that I had a lung infection that was probably due to a coxsackievirus. I was on oxygen for
eight days and had to have my chest drained of fluid
at one point. With my history of valvular disease of
the heart it was considered necessary for me to receive twice daily much larger doses of penicillin
intramuscularly than normal to try to prevent endocarditis. With devoted care from all I pulled through,
being hors de combat for nearly two months.
During that period of serious illness I received some
very sad news. Dick Jelliffe, whom I had met in London (see page 48), was Professor of Paediatrics at
Makerere medical school in Kampala, Uganda. He
had invited me to participate in a teaching seminar
in nutrition for doctors throughout that part of Africa. I had been looking forward to this, but had to
withdraw when I fell ill. Another participant was
someone I had come to admire on my visits to Addis
Abeba. Dr Edgar Mannheimer was a renowned paediatric cardiologist in Sweden. He had been involved
in the medical care of pioneering open-heart surgery
in young children. In the late 1950s he had decided
to give all this up and to set up the Swedish Nutrition Institute in Addis Abeba.
The news came that he had been killed in Uganda. A
group he was in had been on a field trip in a minibus
when it overturned as a result of reckless driving.
Mannheimer was thrown out and was killed instantly.
This was a terrible blow for the cause of child nutrition in the tropics. The Unit for International Child
Health in Uppsala continues as a memorial to this
great paediatrician.
When I was well enough to leave hospital my summer home leave was due. We caught a ferry to
Venice and viewed that lovely city in the best way
there is; sailing up the Grand Canal in the early
morning sunlight. We took the train to London and
my recuperation was completed through the summer months.
SIGHT AND LIFE
My father returned with us to Beirut and spent the
last few months of his life very happily with us. He
is buried in the Anglo-American cemetery in a part
of Beirut that became a constant battle ground during the civil war.
I broke my journey back to Beirut by attending the
FAO/WHO meeting in Rome. This dealt with requirements for vitamin A, and some of the water-soluble
vitamins of the B group (thiamin, riboflavin and niacin). The report of the meeting, published in 1967,
made several important new contributions in the vitamin A area (155).
These included the introduction of the concept of
Retinol Equivalents (RE), which enables the vitamin
A activity of a diet to be assessed by allowing for the
differences in activity of vitamin A from animal and
vegetable sources. In addition, the vitamin A activity of β-carotene was set at one sixth that of vitamin
A itself, and the activity of other provitamin A
carotenoids was set at one twelfth that of vitamin A.
The actual levels of requirements recommended in
terms of Retinol Equivalents remain much the same
today. However, the experimental evidence upon
which the conversion figures for carotenoids were
based was sparse. The bioavailability of provitamin
A carotenoids has become the subject of intense research in recent years and the recommended values
for the conversion figures are currently being actively
discussed (see Chapter 3, page 120).
Oomen was at the meeting in Rome and I recall that
one evening, as we were having a very pleasant
evening meal together alfresco, he told me that he
also had become a medical missionary through reading Schweitzer’s “On the edge of the primaeval forest”. He gave up his studies in botany, entered medical school in Holland and went to Celebes (now
Sulawesi), one of the islands of Indonesia. Xerophthalmia was common among his young patients there.
His botanical knowledge stood him in good stead
later when he became a strong advocate of dark green
leafy vegetables (DGLV) for the prevention of VADD
(see also Panel 12).
Over the years I have made many visits to the United
States, usually to present research papers at conferences at which VADD often figured prominently. I
was admitted to membership of the American Society for Clinical Nutrition and the American Institute
of Nutrition in 1965. I was paid the rare honour for a
non-American to be elected a Fellow in 1993 of what
is now the American Society of Nutritional Sciences.
While I was Director of the Nutrition Research Program at AUB I was an Adjunct Professor at the Institute of Nutrition Sciences at Columbia University,
New York, and lectured there annually. Henry Sebrell
and I consulted on the research supported by NIH
and I presented our research at the Federation Meetings held usually in Atlantic City at that time and at
other centres. Henry would visit AUB for a week or
so each year and discuss their research with the various investigators who were receiving grants through
the Nutrition Research Program. He would be involved in the decisions concerning the allocation of
grants for the forthcoming year. His experience was
of great value in our work and we became very good
friends.
Ali Ahmad on admission to our unit in Beirut: age
14 months, weight 6.15 kg. Severe kwashiorkor is
evident, the eyelids are swollen and both corneae
are destroyed.
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Middle East
One Saturday morning in September 1967 we were
holding our usual staff meeting and reviewing our
work in the department at AUB when word came
from the Outpatients’ Department that there was a
14-month-old boy who should interest us. I found
that Ali Ahmad Saloum had very severe kwashiorkor
and that both eyes were destroyed with keratomalacia. He was admitted straight away to our metabolic
unit. Although we were able to cure the kwashiorkor,
the eyes were too far gone despite large doses of vitamin A and Ali Ahmad became permanently blind.
This was a unique case in my 14 years in Lebanon.
All of the others of our several hundred malnourished child patients in our unit had marasmus and
none had xerophthalmia.
Ali Ahmad just before discharge home after about
three months’ treatment.
It so happened that at the time of Ali Ahmad’s admission we were carrying out metabolic studies of
PEM of the marasmic form using the stable isotope
N15, measured by mass spectrometry. Samples from
Ali Ahmad provided unique data representative of
kwashiorkor in contrast to those from our usual marasmic patients (156).
We delivered Ali Ahmad back to his parents in northern Lebanon.
In the mean time a baby sister had arrived.
90
SIGHT AND LIFE
On a visit several years later we gave him a letter for admission to a
school for the blind.
When Ali Ahmad had recovered we took him back
to his village, very near the northern border with
Syria. I would visit them once a year and in due
course his parents were persuaded to allow him to
enter a school for the blind in the hills above Beirut.
On a visit there just before the outbreak of the civil
war he appeared to be very happy and doing well.
Shortly after this, Lebanon was plunged into civil
war that lasted until 1991. I often wonder if Ali
Ahmad survived the war and what would be the fate
now of this man approaching 30. So many questions
about friends and colleagues will remain unanswered
because of the disruption of normal life that engulfed
us all.
Some time in the late 1960s I heard from Dr Teng
Khoen Hing, an ophthalmologist in Bandung, Indonesia, who had reported a number of cases of the
rarely described xerophthalmic fundus (157). Many
workers in the field of VADD, including myself, have
never seen an example of these lesions. Teng was
writing a thesis on the subject and he wondered if I
could send him films for his fundus camera to record
the changes. This I was able to do and in due course
The last time I saw Ali Ahmad was in about
1975. He was doing very well in the blind school.
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Middle East
In the village of Kirikuti, in the Khond Hills, where we met Pahano
Digal and his mother. I had amputated his leg to save his life from septicaemia. We have corresponded ever since. Now he is near to retirement as a teacher, has seven daughters and a son and the eldest has
become a penpal for our granddaughter Hannah.
he very kindly sent me a copy, suitably inscribed, of
this most interesting monograph (158). In all Teng
reported an astonishing 208 cases of xerophthalmic
fundus, in children 5–14 years of age. Most complained of night blindness; Bitot’s spots were frequently present. In a number of cases treated with
vitamin A and followed up for many weeks, the lesions “seemed to have become less”, but in no instance did the spots disappear.
In the summer of 1968 I was invited by WHO to be
a short-term consultant in nutrition in Singapore. This
afforded an opportunity for extended holiday travel
as a family through Asia. Gavin had just completed
his first year at university and Jill was 14. The opportunity was taken to visit colleagues in nutrition in
Tehran, Kabul, Delhi, Kathmandu, Bangkok,
Chiangmai, Hong Kong and Manila en route. Perhaps the highlights were days on a houseboat called
“Miss America” on Dal Lake in Kashmir, and our
92
return visit to Udayagiri, where we were overwhelmed by meeting so many old friends after 14
years. Our children saw the birth place they had been
too young to remember. Some of our former colleagues have been there recently, and they tell of the
transformation of this once remote tribal area to a
place with television, mobile phones and four-wheel
drive vehicles!
In 1968 Singapore was a rather strictly regimented
society with the strongest emphasis by the Ministry
of Health being given to hygiene and sanitation. There
was no childhood malnutrition and primary
healthcare delivery was exemplary. The Chinese
quarter still had real character and charm, but was
beginning to be pulled down to make way for yet
more tower blocks. After a few days Olga and Jill
decided they wanted to enjoy the rest of the summer
on the beaches at home in Beirut. Gavin stayed on to
act as my “secretary” and we moved to the Chinese
SIGHT AND LIFE
YMCA, where we enjoyed the culture and sport facilities.
An international symposium on the “Metabolic Function of Vitamin A” was held at MIT towards the end
of November 1968 (148). This is where Patwardhan
presented some of the results of the WHO epidemiologic study of VAD in Jordan (see page 82). I gave a
four-page discussion summary in the clinical aspects
of VAD section of the meeting.
This meeting adjourned on the eve of Thanksgiving
Day and a number of us had been invited to attend
another meeting in Washington D.C. organised by
the Pan American Health Organization (PAHO), the
section of WHO for the Americas. I recall leaving
the plane on arrival in the capital and several of us
making our way through enormous crowds to the
baggage hall. Many flights were arriving at about
the same time and just as one of our bags would be-
Family group on the balcony of our faculty apartment at AUB.
come visible on the rather limited type of carousel
used in those days it would be swamped by newly
arriving bags. We were put up in some kind of apartment and as it was the biggest holiday of the year
there was no service and it was very difficult to find
anywhere open for a meal.
We were members of the Caledonian Society of Lebanon.
On Thanksgiving Day morning itself about 20 of us
were in conference when a call came through from
Bill Darby in Nashville to say that his associate Bill
Pearson had been killed in a car accident in downtown Nashville that morning. Pearson was a very
good nutritional biochemist. I had met him first on
the ICNND survey in Ethiopia and frequently later.
At AUB we adopted his method using trifluoracetic
acid for the determination of vitamin A in micro-samples of serum (159).
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Panel 14
The Xerophthalmia Club Bulletin
The so-called Xerophthalmia Club was formed in
1971 in Jerusalem at the Conference on the Prevention of Blindness held there. Oomen was elected
president and Pirie became secretary. There has
never really been any more to the club idea than the
production of a bulletin. The first number appeared
in June 1972 with Tony Pirie as editor.
A foreword to the first issue was written by John
Wilson, who had found the money to get the project
off the ground. It goes, “After languishing for too many
years as a textbook curiosity and a specialist’s
specialism, xerophthalmia has now emerged as a
subject of intense international interest, demanding
vigorous action on a world scale. We have perhaps
reached that critical point in the development of a
world movement when scientific, economic, humanitarian and political considerations can fuse into a single coordinated effort which can cover continents and
affect multitudes of lives. May this bulletin, written
and read by people with varied disciplines in many
countries, play its part in generating the knowledge,
energy and resources which are now needed to convert world interest into world action.”
Pirie produced the first 31 issues and retired in 1984.
At the IVACG Meeting in Hyderabad that year I was
appointed to succeed her. In the subsequent years I
have edited a further 39 issues at regular intervals
three times a year until the latest number (no. 70 in
March 1999). Both Tony Pirie and I have been responsible single-handed for all the work involved and
on an honorary basis. The cost of producing and mailing about 3500 copies three times a year is borne
equally by Sight Savers and IVACG.
The Xero Bulletin, as it is often known, is quite unlike
most of the many newsletters that are distributed free
on health topics. The editors have been experts in
the field and therefore in a position to make comments that are likely to be well informed, as well as
94
critical. They have also been free to a large extent to
choose the contributions without any bias.
In recent years the eight pages of the bulletin have
followed a standard format. Certain features appear
in each issue: these include Notes and News, Literature Digest (abstracts and comments on recent
scientifc papers), Reviews (of books, reports, etc.)
and Correspondence. From time to time original articles appear, as do notices of meetings and review
articles on various topics. Among the latter in recent
years have been contributed articles on such subjects as micronutrient surveillance standards, demographic entrapment, the relative dose response
(RDR) test; the progress in the accumulation of evidence for the effect of vitamin A supplementation on
child health and survival, and an ongoing series pointing out the neglect VADD receive in standard textbooks, especially those written for and by the medical profession.
Perhaps the only regret of the present editor is that
the readership does not contribute more to the columns of the bulletin. Although knowledge and circumstances have changed enormously since Sir John
Wilson’s foreword to the first number quoted above,
the need for the bulletin remains as great as ever.
Panel 15
Xerophthalmia prevention in Madurai, India
The Nutrition Rehabilitation Centre (NRC) at the Government Erskine Hospital in Madurai, Tamil Nadu, in
south India, was opened in 1971. It was, and still is,
the only centre of its kind started specifically to help
children with xerophthalmia. It was the product of the
collaboration of G. Venkataswamy, Professor of Ophthalmology in Madurai, and Dr A. Pirie (see page 49).
Funding from the Royal Commonwealth Society for
the Blind made this possible.
Madurai is one of India’s oldest cities and is a major
Hindu pilgrimage site with important temples. The surrounding area is predominantly rural with rice-based
agriculture. Poverty is widespread.
In the foreword to a popular account of this work (160)
Sir John Wilson, founder and former director of Sight
Savers (see page 52), described how this idea grew
out of the prevailing concept of nutrition rehabilitation promoted at the time for the rehabilitation of children with severe PEM. The underlying concept was
for mothers to be admitted to the centre with their
malnourished children and for them to receive practical training in every aspect of child nutrition and care.
Detailed accounts of the work of the centre and the
results achieved have been published (161, 162).
The mothers and children stayed in the centre for at
least 15 days and often for as long as a month. Regular follow-up visits were paid to the homes, where
medical examination and advice were given. In due
course the work was extended to villages in three
blocks near Madurai. Over the period 1971–87 more
than 2500 children with all degrees of xerophthalmia
were admitted to the centre.
At about the same time one of the most ambitious
schemes in the entire history of ophthalmology was
hatching in the mind of that most remarkable man,
Venkataswamy. From 1976 there grew the concept
of the Aravind Eye Hospital under the inspiration of
Professor Venkataswamy of Madurai, the
founder and inspiration behind the
Aravind Eye Hospitals, including the
Xerophthalmia Rehabilitation Centre.
Sri Aurobindo (1872–1950), one of the foremost leaders in the early stages of India’s struggle for freedom. Satellite hospitals have been opened as has
an institute of community ophthalmology. The Aravind
Children’s Hospital in recent years cares for cases of
xerophthalmia. A recent report (163) suggests that
the number of cases with keratomalacia has diminished greatly in recent years. Young infants seem to
be more susceptible now, and this may be due to
poorer maternal nutrition and early cessation of
breast-feeding.
NRCs around the world have not withstood the test
of time. The reasons for their closure depend on different circumstances. In general they proved costly
in terms of human and financial investment. Some
were overwhelmed by international debt or by the
AIDS/HIV or other epidemics. Perhaps the spread of
the concept of primary healthcare for all was most
influential. Good nutrition as part of good health was
seen to be the concern of all, and not just of those
who had already encountered problems.
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Middle East
In August 1971 a Conference on the Prevention of
Blindness was held in Jerusalem. Although Beirut
was so close it was possible to visit Israel from the
Arab world only by transiting Cyprus. One could not
return if one’s passport had been stamped in Israel.
In any case, it was not considered diplomatic of expatriates like me to try to do so, as it might upset
Arab colleagues. Consequently I was not present
when at that meeting the Xerophthalmia Club was
formed (Panel 14). There is no “club” in reality, but
the very informal eight-page newsletter produced
three times a year has provided a means of keeping
people, especially those in remoter parts, in touch
with the latest developments over many years.
In 1972 I returned from leave to Beirut inspired by
what I had seen of the new nutritional support programmes in hospitals. An Intensive Care Unit had
recently been opened at AUH and with the support
of the surgeons total parenteral nutrition (TPN) was
introduced with considerable success. I have found
this to be one of the most effective ways of demonstrating to medical students and doctors the relevance
of nutrition in medical practice.
I have always believed that the way to increase the
knowledge of doctors about nutrition is to work on
the problem from within the medical school at the
undergraduate level. After my retirement I obtained
a research grant from The Wellcome Trust to research
the origins of the failure over the years of nutrition
to gain its rightful place in the medical school, and
this resulted in a paper that has contributed to the
progress that is being made in this area, especially in
the United States (84).
1973 saw the start of a unique approach to the problem of xerophthalmia (Panel 15). Once again John
Wilson of RCSB played a key role in this establishment in south India of a nutrition rehabilitation centre specially for xerophthalmia.
In November 1974 an expert group of WHO was convened in Jakarta, Indonesia, on “Vitamin A Deficiency and Xerophthalmia”. This was a milestone in
96
the field. In addition to bringing together all the available information on the nature and extent of the problem the experts agreed finally on a “Xerophthalmia
Classification” and also, of great practical importance, recommended “Criteria for Community Diagnosis of Xerophthalmia and Vitamin A Deficiency”.
Perhaps of most lasting importance was the resolution of a potential source of conflict. The members
of the group gathered to write the report were drawn
from just two areas of expertise at that early stage:
1) nutritional biochemistry and 2) ophthalmology.
The blinding effects of VAD dominated discussion
in those days. Biochemists, like Guillermo Arroyave
of INCAP in Guatemala and Barbara Underwood of
the US, repeatedly pointed out that subclinical deficiency was much more widespread than clinical.
However, at that time there was no proof that it was
significant for public health. Oomen and myself had
expertise to some extent in both fields and were able
to see both points of view. Debate was quite heated
at times, but both emphases were brought out in the
report, the first draft of which I wrote as rapporteur.
This consensus is appropriately reflected in its title –
“Vitamin A Deficiency and Xerophthalmia” (130).
My colour slides were used to illustrate the eye lesions in the report.
At this meeting Alfred Sommer, a young American
ophthalmologist-epidemiologist, entered upon the international scene and it was clear that he would take
a leading role in the future. With massive US governmental funding and based at The Johns Hopkins
University in Baltimore, he and his colleagues there
and in many developing countries, especially Indonesia and Nepal, have pioneered the role of vitamin
A in young child and latterly maternal mortality and
morbidity. In 1997 Al received a Lasker Medical
Award and has been honoured by Helen Keller International (HKI) and other bodies. Al has been Dean
of the Johns Hopkins School of Hygiene and Public
Health for a number of years. Over the many years
of our association our relationship has remained close
and one of mutual respect and admiration. In the field
SIGHT AND LIFE
might have played a part in the apparent reduction in
blinding cases. However, general social improvement
probably played a major part.
Years later (165) data were compiled that showed
steady improvement in vitamin A status in Indonesia.
As this book is written, it is tragic to see the unravelling of all these achievements with the descent of
Indonesia into social and economic chaos.
In the early 1970s I became aware of a study being
carried out in Bengal, India (166, 167). Dr Bang from
Johns Hopkins was principal investigator and
dropped by Beirut to discuss the work being carried
out in several villages. Dr Sinha moved to the area
with his family and made frequent and detailed observations. These documented the marked seasonality
of the eye signs of VAD and the lack of response of
many Bitot’s spots to treatment with vitamin A.
Alfred Sommer MD, MHS in the
1980s.
of VADD Al Sommer has demonstrated a unique
ability to unite science with public health action
(164).
I took with me to Jakarta in 1974 a vacuum flask
with dry ice and sample tubes for blood. I left this
with the paediatricians on the children’s ward of the
Central Hospital where, in 1957, I had seen so many
patients with xerophthalmia. I was hoping to be able
to take back to my laboratory in Beirut some samples for research. I returned to the hospital when the
meeting was over, only to learn that not a single case
of xerophthalmia had been admitted during that period of a week or so. Clearly things had improved
immensely in the intervening years.
In the 1960s red palm oil distribution had been proposed as a public health measure in Indonesia but
had not been well accepted. Vitamin A capsule distribution had been started a year or so earlier and
Of greatest interest was the finding that evidence of
VAD showed two peaks, in April–June and November–December. This presented a paradox, because
from July to September food became scarce, and in
November–December green leafy vegetables became
abundant. It was suggested that during the food shortage from July to September the poor would forage
locally available edible leaves, rich in carotene. During November–December rice is harvested and general food intake, but not that of vitamin A, would
increase. This might lead to a growth spurt, stores of
vitamin A would be depleted, and overt VAD might
be precipitated several months later in April–June.
Sinha was also monitoring the growth of the children and this showed an inverse relationship to the
signs of VAD. This is some of the strongest human
evidence for the concept (see also pages 51 and 80)
that growth rate has a strong influence on vitamin A
requirements.
In the mid 1970s I was approached by representatives of the International Agency for Research on
Cancer (IARC) in Lyons, France, about research they
were doing in north-east Iran on the aetiology of cancer of the oesophagus. The Turkoman of that area
97
Middle East
had one of the highest rates in the world. Nutritional
deficiency was suspected as a likely factor.
From Beirut and later from Edinburgh I made extended visits, conducting dietary and nutritional surveys. In March 1977 our daughter Jill had completed
her RGN (Registered General Nurse) training in
Brighton and was due to start her specialised children’s nurse training at Great Ormond Street in London in May. She came as my assistant, and with members of the team from the School of Public Health in
Tehran we spent three weeks under canvas outside
the village of Korand in the Turkoman Sahro; a basalt desert area within sight of the Soviet border.
Our previous surveys had shown low intake of most
nutrients but the only common clinical evidence we
had observed was suggestive of riboflavin deficiency
– angular stomatitis, cheilosis, and magenta tongue.
Overt xerophthalmia was not seen, but there was the
possibility of subclinical deficiency. For our study
in Korand school children were chosen. Riboflavin
deficiency signs were recorded, blood was taken and
high doses of riboflavin were given by mouth. The
signs cleared rapidly after the treatment. Blood sent
for analysis in the laboratories in Tehran showed low
levels of glutathione reductase in red blood cells (a
reliable test of riboflavin deficiency) before treatment. Levels returned to normal after dosing (168).
Jill giving the vitamin tablets to the school children in the study in Korand.
98
SIGHT AND LIFE
The author in a borrowed Turkoman leather coat and purchased Turkoman headgear,
with Jill and two of the local school masters.
While on a subsequent, and final, visit for survey
work to the Caspian Sea area in 1978 the news was
received of the uprising against the Shah in the capital and the work had to be terminated.
Several years later IARC shifted its research operations to Linxian in China, where a similar high prevalence of carcinoma of the oesophagus was found. At
one stage deficiencies of vitamin A and riboflavin
were suspected to be important, but supplementation
trials were ineffective.
In September 1998 I was very interested to meet Dr
Li Jun-Yao, the chief epidemiologist on the project,
at a meeting on Nutrition and Cancer in Pavia, Italy,
and to learn the latest ideas twenty years later (169).
Two very large field intervention trials have been
going on there for many years. β-carotene is among
many other micronutrients that are being given. Impact on other forms of cancer and on other condi-
tions such as hypertension, stroke and nuclear cataract is also being studied.
The First World Conference on Food was held in
Rome in November 1974. Henry Kissinger, US Secretary of State, gave the keynote address. He was
briefed by the Office of Nutrition at the State Department, the head of which at that time was Martin
Forman. Marty suggested that in addition to talking
about world famine and widespread childhood malnutrition, Kissinger should stress that there were two
specific deficiency diseases that might yield rather
readily to intervention. The first of these was VAD
and xerophthalmia, the most common cause of blindness in young children in the world and carrying a
very high mortality. The second disease was nutritional anaemias, most importantly deficiency of iron.
It was argued that both these diseases should respond
readily to interventions consisting of supplementation with the single micronutrient.
99
Middle East
This advice was followed and as a result in due course
two budgets of 10 million US dollars each were voted
by Congress to set up the International Vitamin A
Consultative Group (IVACG) and the International
Nutritional Anemias Consultative Group (INACG).
Both organisations continue to the present.
IVACG (Panel 16) was formally constituted in 1975
at a small meeting hosted by UNICEF in the United
Nations Building in New York and chaired by Les
Teply, head of nutrition at UNICEF. I was in New
York at the time to help prepare the final version of
the WHO report, which appeared the following year.
Marty Forman’s idea has certainly paid handsome
dividends as far as IVACG is concerned over the
years. Its meetings, 19 to date in 1999, and to a less
extent the monographs and statements it has produced, have provided a focal point for ever-increasing attention being paid to the need to eliminate VAD
– one of the goals of the UN “Health for All by the
Year 2000” campaign.
On looking back over the proceedings of the earlier
meetings I have been surprised to see how often recommendations were made concerning the perceived
need for water-miscible preparations of vitamin A
for intramuscular injection to be made available by
the pharmaceutical industry for the treatment of severe, clinical vitamin A deficiency. For example, the
first three recommendations from the second IVACG
Meeting in Geneva in May 1977 were on various
aspects of this subject. The background to this was
mentioned earlier. It became clear later that oily
preparations of vitamin A are well absorbed by
mouth, even in severely ill children, and that this
should be the route of treatment in most cases.
Hoffmann-La Roche was represented at IVACG
Meetings from the beginning and took a great deal
of interest in the problem. They made available water-miscible preparations on request through WHO.
Looking back, it is evident that this involvement led
eventually to the setting up by Roche of the Task
Force SIGHT AND LIFE in 1986. This resulted in a
100
significant increase in their involvement in the control of VADD.
Although this issue of parenteral administration of
vitamin A in the treatment of active xerophthalmia is
no longer discussed, I believe there may still be a
problem. We do not know whether oily preparations
are still being used intramuscularly in some hospitals. The latest recommendations from WHO (170)
have dropped any mention of this route for treatment.
I have twice become involved in criticism of studies
in the UK in which secondary VAD, due to impaired
absorption or utilisation, was treated with oily intramuscular preparations of vitamin A, without effect
(171, 172). There is still a tendency to assume that
because vitamin A is a fat-soluble vitamin it is bound
to be effective by any route, in an oily form.
It was mainly through attendance at IVACG Meetings, receipt of the early monographs written by experts for IVACG, and the news and views appearing
in the columns of the Xerophthalmia Club Bulletin
that one was able to keep up with the increasing
number of contributions from around the world. This
was long before the internet.
Key contributions came from a small, but growing,
group of truly international investigators. Guillermo
Arroyave at INCAP in Guatemala pioneered the fortification of sugar with vitamin A (173) and was at
the forefront of the use of biochemical methods for
the assessment of vitamin A status (174). Barbara
Underwood developed the relative dose response
(RDR) method for assessment of vitamin A status
(175) and became a leading figure in the area of prophylactic use of vitamin A, especially in pregnant
and lactating women (176). Throughout this period
the workers at the National Institute of Nutrition in
Hyderabad, India, have contributed many papers on
all aspects of VADD (137, 177, 178). In the Philippines Florentino Solon and his coworkers identified
the problem of VADD (179) and introduced the fortification of monosodium glutamate (MSG) and other
methods of control (180). Jim Olson, of the State
SIGHT AND LIFE
University of Iowa, combined an understanding of
the human problem gained by periods of living in
Thailand and Brasil, with his expertise in biochemistry (181, 182). A fellow countryman of mine, Nick
Cohen, spent many years in Asia on the control of
VADD and did notable field work with HKI in Bangladesh (183). I am surprised, but very pleased, to realise that all of these colleagues mentioned continue
to be active in various ways in the cause of the control of VADD.
I served as rapporteur for the first twelve IVACG
Meetings. I missed the next two meetings but attended the subsequent ones in Kathmandu, Nepal;
Chiang Rai, Thailand; Guatemala City, Guatemala;
and Cairo, Egypt (the XVIIIth in September 1997).
101
Panel 16
The International Vitamin A Consultative Group
The first scientific meeting of IVACG held in Port-au-Prince, Hotel Castelhaiti, Haiti, 22 to 26 March 1976. At the
table from left to right: D. S. McLaren, H. A. P. C. Oomen, D. Karyadi, E. M. DeMaeyer, W. Fougere (Bureau de
Nutrition, Haiti), G. Arroyave, B. A. Underwood.
Attendees: E. M. DeMaeyer (Chairman), WHO, Geneva, Switzerland; S. G. Kahn (Secretary), AID, USA; G.
Arroyave, INCAP, Guatemala; J. Bauernfeind, Hoffman-La Roche, USA; C. O. Chichester, Nutrition Foundation,
USA; J. H. Costello, International Eye Foundation, USA; W. J. Darby, Nutrition Foundation, USA; C. H. Daza,
PAHO/WHO, Washington, D.C.; M. J. Forman, AID, Washington, D.C., USA; W. Fougere, Bureau de Nutrition,
Haiti; W. W. Kamel, University of Illinois, Chicago, USA; D. Karyadi, Ministry of Health, Indonesia; C. Kupfer,
National Eye Institute, NIH, USA; M. A. Lemp, International Eye Foundation, USA; D. S. McLaren, American
University of Beirut, Lebanon; J. Olson, Iowa State University, USA; H. A. P. C. Oomen, Royal Tropical Institute
102
of Medicine, Amsterdam, The Netherlands; S. Pettiss, American Foundation for Overseas Blind, USA; A. Pirie,
Nuffield Laboratory of Ophthalmology, England; A. Sommer, Johns Hopkins University, USA; B. A. Underwood,
Pennsylvania State University, USA; G. Venkataswamy, Madurai Medical College, India.
Invitees from Haiti: D. Beaulieu, Public Health Minister; S. Behoteguy, USAID Mission; R. Berret, PRONUDERU;
H. Bordes, Div. d’Hygiène Familiale; C. Boulos; G. Deslouches, Public Health; J. C. Desmangles; S. D. Burak; E.
Franklin, HACHO; G. Frederique; R. Germain, Public Health; G. Hudicourt; Dr Jeannot Cadet, Hôpital de
l’Université d’Etat d’Haiti; Rev. Sister Joan Margaret, St. Vincent School for the Handicapped; M. Mesidor, Nutrition Bureau; A. Pellerin, WHO; V. Rathauser, WHO; S. Toureau, AFOB Vitamin A Program; Dr Charles Weldon,
USAID Mission.
Mention has been made of the way in
which the idea of IVACG was born and
how the organisation came into being
in 1975. The mission of IVACG is described as “to guide international activities aimed at reducing vitamin A deficiency in the world. The group offers
consultation and guidance to various
operating and donor agencies that are
seeking to reduce vitamin A deficiency
and its accompanying blindness.”
More than 20 monographs have been
published and these are distributed
free of charge in developing countries.
Guidelines and recommendations
have been prepared on a number of
topics.
The IVACG has a Secretariat staff of
six, with which Laurie Lindsay Aomari,
has been associated for a number of
years. The IVACG Chair has from the
beginning been from a UN agency.
Edouard DeMaeyer of WHO was succeeded by Lester (Les) J. Teply of
UNICEF and more recently the incumbent has been Abraham Horwitz,
emeritus Director of PAHO. IVACG has
a ten-member Steering Committee,
currently chaired by Alfred Sommer.
Front page of the Cairo meeting 1997 report
103
The IVACG group that met in our home in Edinburgh in May 1979 to write their monograph on clinical signs of
vitamin A deficiency. The final title was:“The Symptoms and Signs of Vitamin A Deficiency and their Relationship to Applied Nutrition”. From left to right: A. Sommer; E. M. DeMaeyer; J. ten Doesschate; E. J. Ballintine;
D. S. McLaren; O. McLaren; V. Beyda; J. McKigney; G. Venkataswamy; Mrs P. Hodges; R. Hodges; C. Chichester. Also member of the group but not on the picture was R. Pararajasegaram.
IVACG has no formal permanent membership as
such. As the need may arise, experts are co-opted
for certain tasks, such as preparation of monographs
or delivery of addresses at meetings. The most highprofile activity of IVACG has been the meetings
which it has held at approximately yearly intervals.
With the exception of two meetings held at WHO
headquarters in Geneva (and the inaugural meet-
104
ing at UNICEF, New York), these have all been held
in developing coutries where VADD have been identified to be a public health problem. This has undoubtedly served to give great encouragement to
the people of that particular country and those in
the region who have been working in this field. Local personnel have been able to attend in considerable numbers, especially on the first day, the pro-
ceedings of which in recent years have been devoted to reports from the host country.
The latest IVACG Meeting (no. XIX) was held in
March 1999 in Durban, Republic of South Africa.
From only 22 members at the first scientific meeting held in Port-au-Prince, Haiti, in March 1976 there
has been steady growth in the number of those attending to more than 500. This growth certainly reflects the enormous increase in the interest worldwide in the problem of VADD. This is especially gratifying to those of us who have been involved for many
years. However, it does necessarily bring with it the
challenge of trying to make successful the outcomes
of such large meetings. Presentations tend to be
too short and too formal, discussion time is often
curtailed, and resolutions and recommendations for
future action are difficult to achieve in a democratic
way.
IVACG will enter on its Silver Jubilee year with the
new millennium and many will be looking to it for
continuing leadership and guidance as they have
received from it in the past.
105
Return to Edinburgh (1976–1988)
The civil war in Lebanon is usually dated from Easter
1975 when a bus load of Palestinian militia was massacred by Maronite Christians in Ain-el-Romaneh, a
suburb of Beirut where I had our ten-bed Pediatric
Metabolic Research Unit at the Solarium du Liban.
However, ever since the 5-day-war between Egypt,
Jordan and Syria and Israel in May 1967 trouble had
been building up with the rise of Palestinian resistance, arming of refugee camps in Lebanon, and the
alliance of these with the Lebanese left. Olga and I
were on our own. Gavin had completed his Masters
degree in history and was in the UK. Jill was in the
middle of her nursing training in Brighton, UK.
My research was concentrating on field studies of
growth failure in children in different parts of Lebanon. All this became impossible to continue. After
over a year of living under siege, with sniping from
rooftops, shelling from the hills and what amounted
to the first occurrence of modern urban guerilla warfare, we came home for Christmas in 1975. Our party
was hijacked briefly by militia on the airport road.
Through my contact with Reg Passmore in Edinburgh
it was arranged for me to join him in the Department
of Physiology. In Beirut the seaport was destroyed
and the airport closed for long periods. Even so, Olga
managed to return there in March, as everything we
had was still there. Many of the AUB staff had fled
abroad. By a fortunate turn of circumstances I was
able to join Olga in April.
I paid a visit to the United States earlier in the year,
to write a monograph for IVACG in Washington D.C.
with Al Sommer and Jim Olson (184). Later in New
York I had been able to persuade the authorities in
the New York office of AUB that those of us who
were over the age of 55 and had considerable length
of service should be allowed to retire and receive
our pension fund proceeds.
106
As I got dressed in my New York hotel room one
morning I turned on the radio and heard the news
that two of my friends and colleagues at AUB, Bob
Najemi, the Dean of Students, and Ray Ghusan, the
Dean of Engineering, had been shot dead by an Arab
student on the campus.
Several years later during the hostage taking, a
number of our colleagues and friends were among
those kidnapped and Malcolm Kerr, the son of
Stanley Kerr, the professor of Biochemistry and my
neighbour at AUB, was gunned down on the campus
a few months after he had been appointed President
of the AUB.
I had been invited to attend a meeting from 29 March
to 1 April 1976 in Baghdad. The WHO Interregional
Meeting on the Prevention of Blindness was timed
to precede the World Health Day whose theme for
that year was “Foresight prevents blindness”. When
I saw the literature issued to mark this day I was astonished to find that there was not a single mention
of xerophthalmia. When I pointed this out to WHO I
was told that a professor of ophthalmology in Geneva was responsible for writing the piece. I remember being in Geneva and getting an appointment with
him. I explained what a missed opportunity this was.
He clearly did not see the importance of my criticism and just made the excuse of not being familiar
with the global situation.
The following year it so happened that the theme on
Child Malnutrition was similarly featured for World
Health Day, and again xerophthalmia hardly had a
look in.
We have noted previously the neglect suffered by
xerophthalmia (page 52). Xerophthalmia lies on the
indistinct borderland between nutrition and ophthalmology and is neglected from both sides. Once the
Panel 17
Four uneasy bedfellows:
A statement presented and circulated at the WHO Interregional Meeting on the
Prevention of Blindness in Baghdad, 29 March to 1 April 1976.
TRACHOMA
ONCHOCERCIASIS CATARACT
XEROPHTHALMIA
NATURE
Eye infection
Systemic
infestation
Metabolic
Vitamin
deficiency
PATHOGENS
Flies,
Hygiene
Fly
?
Diet
ROLE OF
THE EYE
Eye only
General:
eye most
important
Eye only
General:
eye most
important
AGE
Mainly
adult
Mainly
adult
Old age
Very
young
Foci in
Africa,
S. America
Worldwide
Asia, foci in
Africa, South
America
GLOBAL
Drier subOCCURRENCE and tropics
KEY
SPECIALIST
Public
Entomologist
Health
Ophthalmologist
Clinical
Paediatrician
Ophthalmologist
CONCLUSION: These diseases have little in common besides their target organ. There is no
more reason for linking them for action programmes than there is for linking such diseases as
bronchogenic carcinoma, pulmonary tuberculosis, emphysema, and pneumonia, just because
they all affect the lung.
Four uneasy bedfellows came to Baghdad
Xero, Oncho, Trachoma and Cataract
They proved incompatible – too bad
All they had in common was to blind
Good for jerking tears and raising money
For prevention planning, no way to find.
107
Return to Edinburgh
role of vitamin A in child survival came to prominence in the 1980s, matters in this regard tended to
improve. However, even now, especially among the
medical fraternity, there is an astonishing degree of
ignorance and indifference (Panel 14).
ing there were escorted to the airport by armed guard
as hijacking of goods as well as people was commonplace. Everything reached Edinburgh airport
safely a day after we did, except for a broken vase
and glass in a picture!
At the meeting in Baghdad (185) Sir John Wilson, as
President of the International Agency for the Prevention of Blindness, gave the introductory address.
In this he identified what he called the “four giants”
– blinding infection including trachoma, blinding
filaria (onchocerciasis), cataract, and blinding malnutrition (xerophthalmia). Three were preventable
and cataract could be cured by surgery. The term
“avoidable” encompassed them all.
The Edinburgh University accountant had never seen
such a large bill for the transfer of the effects of a
new member of staff, but once the circumstances had
been explained he did not demur.
This was the first meeting I had been to at which
blindness as an entity had been presented. [Years later
at a similar meeting (186) held at the Institute of Ophthalmology in London my feelings in Baghdad were
to be repeated]. As the meeting progressed I became
increasingly uneasy about the concept of making a
unified attack on the problem of blindness worldwide. By the last day I had crystallised my thoughts
and I prepared a statement under the heading “Four
Uneasy Bedfellows” which I had reproduced and
circulated to the delegates (Panel 17).
It proved very difficult for both of us to try to make
a new life in our mid fifties. Beirut in its good days
had seen the happiest period in our family life, as
well as provided for me a unique opportunity to carry
out research on childhood malnutrition problems.
Almost all expatriate staff of AUB and other organisations in Lebanon left the country about the time
when we did. Many Lebanese colleagues went abroad
too, to work elsewhere in the Middle East or in the
United States. My department depended largely on
research funding from abroad and this soon ceased.
Colleagues and friends with whom one had worked
for ten years or more left at just a day’s notice in the
prevailing danger and uncertainty.
The very poor standard of composition might be forgiven in the circumstances. The message, at least, is
quite clear. I think it came as too much of a shock for
most of the delegates.
The fighting in Lebanon was intense while the meeting was going on in Baghdad. I had my ear to the
radio for the latest news on the BBC World Service
even during the presentations! The day I was booked
to go to Beirut things quietened down and as we flew
over the city before landing, everywhere was deserted.
Within a few days Olga and I were able to settle our
affairs. I even managed to sell my car and not to have
it stolen from me on the road as was usual. The 53
packing cases with our belongings after 14 years liv108
Walter Read and his wife Marie Tchalian working
on the mass spectrometer in our labs in Beirut.
SIGHT AND LIFE
Walter Read, who had been my chief technician in
the laboratory and whom I had brought with me from
the institute in Mwanza, went home to England and
joined the MRC Clinical Research Centre in north
London. He had his name on more than 30 research
papers from our department over the years.
Zuheyr Audeh, who had been my first appointment
locally, had come from UNRWA. He did his Master
of Science with us and then went to the National Institute for Medical Research in London, where I had
been, for his PhD. Zuheyr is now an eminent immunologist with Harvard, and I have visited him several times.
Abdullah Kanawati, a medical graduate from Damascus, worked closely with me in the field studies, and
the last I heard of him is that he is with one of his
sons in Saudi Arabia. All of these, and many others,
made vital contributions to what I was able to achieve
in the field of VADD while in Beirut.
Zuheyr using the technique of isoelectric focussing,
which he developed in our labs.
In Edinburgh things did not work out well in Physiology and in 1980 I transferred to the Department of
Medicine in the Royal Infirmary (following in the
footsteps of Cullen and Davidson), where I remained
very happily until retirement in 1988. I had ample
opportunity for international work, was representative of the Scottish Office on the influential government Food Advisory Committee for many years, and
I published a number of papers and several books.
My big disappointment was that despite the influence in the past of Davidson and Passmore I was
never able to establish a programme of clinical nutrition as I had done in Beirut. My position was isolated and therefore lacked authority. However, I was
able to influence the course of medical education in
some ways because of my unique experience which
had been in developing and developed countries, in
the British and the American systems, and in both
preclinical and clinical departments (187).
Dr Kanawati with one of the recovering malnourished infants in our Unit at Christmas time.
By 1980 a number of surveys on the prevalence of
VAD had been carried out, following the guidelines
laid down in the WHO report of 1976 (130). This
had been widely circulated and its recommendations
were beginning to be implemented. Most importantly,
the first nationwide survey had been carried out in
Indonesia under Al Sommer’s direction (Chapter 3).
109
Return to Edinburgh
The participants of the WHO Task Force on the Programme of “Research on Control of Vitamin A Deficiency and Xerophthalmia”, Manila, 22–24 November 1979, (left to right ) D. S. McLaren, R. Florentino,
N. V. K. Nair, R. Pararajasegaram, A. Sommer, B. A. Underwood, G. Arroyave, E. M. DeMaeyer,
D. Karyadi, A. Pradilla.
WHO, UNICEF, HKI, and IVACG jointly sponsored
a second technical meeting in October 1980 (see page
111). Again it was in Jakarta, and again I was rapporteur. This meeting was followed by the Third
Asian Nutrition Congress which I also attended.
An intervening free weekend allowed me to pay a
long-delayed visit to Bali (see page 53). I stayed with
110
Gordon Sweatman, a former biologist colleague from
AUB, who was doing an assignment for FAO there.
There was no obvious evidence of a VAD problem
on the island. This was probably due to a relatively
low population density, highly structured society and
income from increasing tourism. I learned that
Jelantic had become chief, but unfortunately he was
out of the country at the time.
SIGHT AND LIFE
The Joint WHO/UNICEF/HKI/IVACG meeting on “Control of Vitamin A Deficiency and Xerophthalmia”
held in Jakarta, Indonesia, 13–17 October 1980.
The second WHO report (147) made relatively minor revisions to the classification and the criteria that
had been set in 1976. It was, however, able to provide much more evidence on the worldwide prevalence of VAD and the results of a number of intervention programmes.
My last involvement with the production of a report
for WHO was with the 1988 report on Vitamin A
supplements (188). A second edition was issued in
1997 (170).
Most academics manage to take at least one full sabbatical year during their careers. Over the years I
had enjoyed several periods of home leave from
abroad but have never taken the full year off. The
nearest I came to it was in early 1982 when I spent
about three months in California at The City of Hope
National Medical Center near Los Angeles. Michael
Meguid, a surgeon interested in nutritional support
of the hospitalised patient, invited me there with a
possible view to joining him on a long-term basis.
The clinical and research facilities were excellent,
but in the end I felt I was too old to make such a
radical move. I had the opportunity there to carry
out a piece of research in the vitamin A and carotenoid field (189).
At that time the interest in the possible antioxidant effect of carotenoids in cancer and other chronic diseases
was just beginning. We submitted a large grant proposal
in this area but were unsuccessful – all proposals submitted were turned down. My work would have concerned the activity of non-provitamin A carotenoids,
such as lycopene and lutein, not previously investigated.
Much research is now going on on this.
111
Return to Edinburgh
Dr Gopa Kothari on my first visit to Dharavi in
Mumbai.
Aerial view of part of Dharavi slum in Mumbai.
Michael shortly afterwards moved to the medical
centre at Syracuse in upstate New York. In addition
to his busy life in general surgery Michael founded
and is editor-in-chief of the journal Nutrition. I have
been editor of a classics section for some years, and
a number of these articles have been in the VAD field.
In 1986 my paper on keratomalacia in Orissa was
included as a classic, and I was asked to write an
overview (190).
ventive Medicine at one of the medical schools in
the city. She was carrying out a very effective programme with the support of Sight Savers to combat
VADD in Dharavi. This was known as “the largest
slum in Asia”, with over 700,000 people living in
about one square mile at that time. Over subsequent
years we have collaborated in several studies (191,
192), and Gopa has extended her primary healthcare
work to other slum areas. She has participated in the
teaching at ICEH for a number of years now.
In 1984 an academic link funded by the British Council was established with Dr Sumati Mudambi at SVT
College of Home Science in Mumbai (Bombay).
There was exchange of staff in both directions over
several years. In this way I got to know Dr Gopa
Kothari, who was then Professor of Social and Pre112
In 1987 I was invited by Professor Gordon Johnson,
head of the Department of Preventive Ophthalmology at the Institute of Ophthalmology in London, attached to Moorfields Eye Hospital, to lecture on nutritional blindness on the course there.
SIGHT AND LIFE
Retirement in Worthing (1988)
We moved to the seaside south of London in June.
From October 1988 I again took up the link with
ICEH. I worked two days each week at ICEH to develop the component of the programme on nutritional
blindness for several years. More recently my participation has been less, but I am still “Honorary
Head, Nutritional Blindness Prevention Programme”.
I still lecture to students, who are mostly ophthalmologists and ophthalmic nurses from developing
countries. I also tutor those who have their MSc thesis work in the area of VADD. Early on I helped to
obtain financial support for students from suitable
countries from SIGHT AND LIFE, and this has continued to the present.
My experience at ICEH exposed me to the dilemma
I had faced previously (see page 108) over the rationale underlying prevention of blindness pro-
grammes. A discussion paper I circulated there among
my colleagues was politely received, but I sensed
that as they were inevitably “part of the system” they
could hardly be expected to be enthusiastic.
In 1991 the British Medical Journal published an
editorial (193) on avoidable blindness from an ophthalmologist working in Africa. It went over the old
ground, urging the need for greater awareness and
increased resources and personnel to deal with the
growing problem of blindness. My response was
printed shortly afterwards (194). I suggested that a
change of concept was required. I criticised the lumping together for preventive purposes of widely disparate diseases. I pointed out that the misconception
was deeply entrenched in international, national,
WHO, and NGO (Non-Governmental Organisation)
programmes of prevention of blindness worldwide.
Two of the ICEH students from Viet Nam and Zambia in our home.
113
Retirement in Worthing
What they have to do if they are to achieve their objectives is to promote total primary healthcare and
stop dealing with the eyes in isolation – as Oomen
used to say, “as if the eyes were on a silver platter”.
In 1994 Karl Kupfer, Director of the National Eye
Institute at NIH, whom I knew well through our attendance at many IVACG Meetings, wrote an editorial (195). He strongly supported the traditional approach to blindness prevention. My response (196)
and his reply (197) appeared together in February
1995. I thus had opportunities to address those interested through journals on both sides of the Atlantic.
Gavin and family recently (in a friend’s garden).
114
Dr Kupfer agreed that most of the nonclinical community eye care could and should be integrated into
the primary healthcare system.
On the positive side I do value the support that this
concept has received from Gordon Johnson in contributions he has made to a book (198) and at a recent meeting (199). As I see it, most of the preventable blindness in the world could be prevented without an ophthalmologist or ophthalmic nurse within
sight! Improved personal hygiene will greatly reduce
trachoma (200), adequate diet will banish VADD,
onchocerciasis is controlled by a yearly ivermectin
SIGHT AND LIFE
Jill was working for Save the Children Fund in Malawi when we visited her in 1992. At
present she is working with Kosovar refugees in Macedonia.
tablet or getting rid of the Simulium fly. Cataract
cannot be prevented until we know the cause(s) –
much more research should be devoted to this number
one cause of blindness in every country.
In 1999 I remain in touch with the latest developments in the field of VADD, although not engaged
anymore in original research. Postgraduate teaching,
editing the Xerophthalmia Club Bulletin, attending
scientific meetings continue. The SIGHT AND LIFE
manual (2) and the Slide set on VADD are continuing to be distributed widely, without charge, and
should be helping to make a significant contribution
towards the control of the problem. These may both
be taken to a second edition soon.
I have written the section on VADD in The Wellcome
History of Tropical Diseases (201). The first book
on The Epidemiology of Eye Disease was published
early in 1998; it was edited by Gordon Johnson and
two colleagues. I contributed the chapter on VADD
(202).
We have as our immediate family our son Gavin, his
wife Hazel and their children Hannah, aged 12, and
Alistair, aged 9. This young man is the fifth generation of single male members of the clan to carry on
the family name! Our daughter Jill could write an
odyssey of her own. She has served as a primary
healthcare aid worker for the last twenty years with
many organisations, mostly in Africa and Asia.
115
Retirement in Worthing
As I have been writing this and looking back over a
career dominated by VADD I have been pondering on
the way in which diseases wax and wane in importance. In Chapter 1 it was pointed out how in the early
part of the vitamin era xerophthalmia was almost completely neglected (Panel 4). Scurvy, beriberi, pellagra
and rickets were repeatedly grouped together as the
then known dietary deficiency diseases.
I have tried to describe in these pages how xerophthalmia rose from obscurity and neglect to reach a
position of worldwide public health significance. At
the same time I think it is of considerable interest
and probably importance for the future, to note what
was happening to the “big four” nutritional deficiency
diseases of an earlier era.
In a word, none of these diseases has anywhere
reached public health significance in the sense that
is used concerning VADD during the years we have
116
been concerned with it. Beriberi epidemics, such as
those studied by Eijkman in Indonesia, have not recurred. Nor have those of pellagra, for example in
the southern United States in the inter-war years when
Henry Sebrell assisted Joseph Goldberger in his classic studies that finally proved the disease’s dietary
deficiency origin. Sporadic scurvy affects only a few
vulnerable infants or elderly, and primary rickets is
largely confined to members of some ethnic minorities or to those who from custom or location are rarely
exposed to sunlight.
My own long experience falls into just that pattern. I
have encountered only a handful of patients with
beriberi, secondary to alcoholism, only two with pellagra, three with scurvy and several with rickets.
However, who is to say that circumstances may not
change in the future such that any one or all of these
now largely forgotten diseases may once again pose
a serious threat to human health?
SIGHT AND LIFE
Chapter 3
Update and commentary
The purpose of this section is to bridge the gap between approximately 1980 and the present; a period
of almost two decades. Although I have been in touch
with the developments in the field during this time, I
have not been involved, except peripherally, in making original contributions.
It is not my intention here to try to include in detail
all of the significant contributions in the field that
have been made during this period. I hope I do not
make the mistake of omitting any major contribution, but for the definitive account I would draw attention again to Sommer and West (2). For a shorter
and simplified account the SIGHT AND LIFE
manual is available (1).
It so happens that around about 1980 there is a natural watershed in the field of VADD research. Several
factors coincided at that time in a way that seems to
me to be a good example of the well-known quotation from Shakespeare’s Julius Caesar: “There is a
tide in the affairs of men, which, taken at the flood,
leads on to fortune.”
First of all, medical epidemiology may be said to
have come of age at about that time, and as a result
well-controlled field studies date from about then.
Biostatistics was developing, and strict application
of statistical requirements meant that statistical analysis could be applied to the results. The pioneering
field studies in VAD in Indonesia of Sommer and his
colleagues (203) were probably also among the first
of their kind in community nutrition as a whole.
Massive funding began to be made available, almost
all of it government money in the United States. The
formation and funding of IVACG in the mid 1970s
played a key role in paving the way for this support.
Without it such large, expensive studies could not
have been carried out.
In the field of vitamin A deficiency and xerophthalmia Alfred Sommer had what at that time was a
unique combination of qualifications and training in
ophthalmology and epidemiology. He was thus fully
competent in what might be called the old approach,
but equally able to lead research into the new era.
As a result of the work in Indonesia and other field
studies the emphasis in VAD soon shifted away from
xerophthalmia and the eye and back to mortality and
morbidity. I say “back” because decades earlier the
association between VAD and infectious disease had
been very strong for a period (Chapter 1, Panel 5)
before blindness took centre stage. Our study of
xerophthalmia in Jordan (141) in the mid 1960s (see
page 82), in which we showed a fourfold increase in
mortality if children with severe PEM also had
xerophthalmia, and work of ten Doesschate (101) in
Surabaya, Indonesia, that showed a very high mortality up to one year after discharge (see page 54)
were isolated hospital studies. Neither the methodology nor the funding for massive field prevalence
surveys or intervention trials were available at that
time.
The nationwide study of Sommer and colleagues in
Indonesia (203) gave accurate prevalence figures for
the first time for an entire country. These were also
used to update the rough estimate of global prevalence of xerophthalmia (139). In addition, some outstanding questions were answered about the ocular
lesions, such as development of a simple tool for assessing night blindness (204); the complex nature of
Bitot’s spots (205); early corneal xerosis (206); and
xerophthalmic fundus changes (207).
117
Update and commentary
Perhaps of greatest significance for the first time at
the field level was that these studies showed the increase in mortality risk that accompanies night blindness and/or Bitot’s spots (208) and went on to report
increased rates of diarrhoeal disease (209) and respiratory infections (210) in these same subjects.
The next logical step was a vitamin A intervention,
the first of its kind also, and which demonstrated to
most people’s satisfaction a significant reduction of
mortality risk in the treated group, despite some shortcomings in the study design (211).
Over several years the group at Hopkins and others
carried out similar trials elsewhere in Asia and in
Africa. A meta-analysis of eight such studies showed
an overall reduction in mortality of 23%, although
those in Hyderabad, India, and in Sudan failed to
show a significant improvement (212).
The precise mechanisms of this dramatic effect have
not been fully elucidated. Cell-mediated immunity
appears to be impaired (213) but this seems to be far
from the whole story (214). Morbidity studies have
tended not to produce clear-cut results, unlike those
on mortality. In general diarrhoeal diseases respond
to vitamin A by a reduction in severity. Acute lower
respiratory tract infection (ALRI) tends not to respond to vitamin A (2).
On the other hand, studies of very clearly defined
infectious diseases such as measles (215) and HIV
(216) provide clear evidence of improvement in various ways with vitamin A.
To me this is consistent with what one might instinctively expect. The groups of diarrhoeal and respiratory infections are much less well defined. Their
symptomatology does not constitute a clear-cut syndrome as do measles and HIV. They have a very
mixed aetiology and microbiological tests do not
form part of the field studies undertaken so far. Degree of infection and severity of disease probably
influence the outcome but are difficult to assess. A
recent review has called for such objections to be
118
taken account of in the design of studies in future
(217).
In 1987 WHO and UNICEF recommended that vitamin A be given to all children with measles in parts
of the world where VAD is a recognised problem
(218). There is evidence that corneal scarring associated with VAD and measles has been greatly reduced after successful immunisation against measles
in the WHO Extended Programme of Immunisation
(EPI) (219). Studies have demonstrated the advantage of combining vitamin A dosing with EPI, and
this has been recommended by WHO (220).
Although there is good evidence of benefit to vitamin A-deficient patients who are HIV positive, especially in the case of women to their offspring, no
UN recommendation has been issued on the subject
to date. Recent work suggests that there may be some
disparity over results reported (221).
Considerable advances have been made in the area
of methods of assessment of vitamin A status. Along
with the passing of the “xerophthalmia era”, in which
attention was focussed on the definition and use of
the eye signs in the assessment of clinical vitamin A
deficiency, there have subsequently been efforts to
develop indicators at the subclinical level (222). RDR
(175) and MRDR (223) are being used mainly in research studies and more recently isotope dilution
(224) has been introduced. However, because of the
dangers of transmission of hepatitis, HIV and other
infectious diseases by blood these are unlikely to be
used on a large scale. They also require sophisticated
technology.
Breast milk retinol has been introduced as an indicator of vitamin A status fairly recently (222). There
are still technologic difficulties to be overcome, but
the test is non-invasive and looks promising.
Conjunctival impression cytology received enthusiastic support when it was introduced for the detection of VAD at a preclinical stage (225). The early
promise has been sustained to a considerable extent
SIGHT AND LIFE
and various modifications have tended to produce
similar results (226). There are difficulties over reproducibility, especially in marginal cases, and eye
infections may interfere (227). The tissue may be
readily obtained by experienced workers and the technique is not invasive. The results have tended to correlate well with those of other types of test.
Other eye tests for use under field conditions are
being developed (e.g. the vision restoration test)
(228). In my view there must be some cause for doubt
as to whether there is now any need for further development of field tests. Although the signs of
xerophthalmia in pre-school age children exceed the
criteria for a public health problem in a relatively
small proportion of low socio-economic communities it is evident that subclinical deficiency is widespread. General evidence of community disadvantage is virtually a sine qua non for undernutrition, of
which subclinical VAD is an integral part. It is estimated that something like half of the pre-school age
children in developing countries are subclinically vitamin A-deficient (229). In terms of prophylactic intervention at the community level, all would seem to
need it.
It has been believed for many years that vitamin A
plays some part in haemopoiesis. Recently the subject has received renewed attention (2). The mechanism is still not understood. In communities where
subclinical deficiency of both vitamin A and iron are
common, and there are many of these, there is a good
case for intervention programmes to take account of
both nutrients. Added vitamin A or β-carotene may
enhance absorption of non-haem iron (230).
The effect of VAD on growth is another area that
lends support to the concept introduced in the SIGHT
AND LIFE manual (1) of the comprehensive term
“Vitamin A Deficiency Disorders (VADD)”. Many
factors, including a variety of nutrient deficiencies
and infections, can adversely affect growth. This
makes such a role for a single nutrient like vitamin A
very difficult to prove. A few studies, but not all,
suggest there is such an effect (2).
In recent years the phenomenon known as the acutephase response (APR) occurring in serious infections
and trauma has been investigated. As part of this response the concentration of some nutrients in the
plasma, including retinol, falls dramatically (231). It
is thought that this results from a combination of factors. These include transient reduction in production
in the liver, loss of holo-retinol-binding protein in
urine, movement into extra-cellular fluid, and increased uptake by certain tissues (232).
This clearly creates difficulty in the interpretation of
serum levels of retinol while APR is operating. Recently Rosales (233) has proposed the use of the
molar ratio of retinol-binding protein (RBP) to
transthyretin (TTR) to overcome this problem.
Alvarez and colleagues (234) have provided evidence
that during severe infections large amounts of vitamin A may be lost in the urine. This could be a significant cause of VAD under these circumstances that
has not been sufficiently considered previously. It
might also be at least partly responsible for the
marked fall in serum vitamin A noted in APR. Confirmatory evidence from elsewhere would be important.
Recently the effects of intervention with retinol/
β-carotene on the morbidity and mortality of women
in pregnancy have been studied in Nepal. Weekly
doses of 7000 µg RE during pregnancy showed significant reduction in mortality (235). This work opens
up the prospect of a whole new area of vitamin A/
β-carotene intervention in relation to maternal mortality from all causes and morbidity. Maternal mortality exceeds 500,000 deaths annually, almost all in
developing countries.
Experimental studies for a number of years have demonstrated an interrelationship between zinc and vitamin A (236). Deficiency of these two nutrients as
well as of others, including protein and energy
sources, are likely to occur together. A series of recent studies (237) suggests that effects similar to those
found with vitamin A may also occur in undernour119
Update and commentary
ished subjects with zinc supplementation. At the same
time it has been found that underweight in children,
presumed to result from deficiency in protein and
energy, is associated with increased risk of mortality. The majority of deaths attributable to underweight
are associated with milder degrees of underweight,
rather than with severe underweight (238). This is
because the milder forms are so much more common. The same is true of subclinical versus clinical
VAD. At present it is not at all clear what the relative
contributions of different nutrients in these circumstances may be.
In recent years WHO has taken over the task of documenting and updating the global prevalence of VAD
(113). Although there are gaps in the statistics and
also some defects this record is vital if the achievement of goals is to be monitored. There is no doubt
that the increasing appreciation of the widespread
occurrence of subclinical VAD and its importance in
child survival has led to surveys of vitamin A status
being carried out in many countries from which previously there were no data.
120
The bioavailability of β-carotene and other provitamin carotenoids has been the subject of intensive
research recently (239, 240). Many factors in food
and in the body influence the availability of these
carotenoids. The evidence at present suggests that
the factors traditionally used to obtain REs have overestimated, sometimes considerably, the potency of
carotenoids.
In the area of control of VAD the four traditional types
of intervention have been continued and extended.
Supplementation using periodic large doses of vitamin A has been in place, with usually diminishing
effect, in many countries over long periods. There
has sometimes been reluctance to replace it by longerterm measures, such as fortification or dietary modification. Vitamin A fortification of food is undergoing renewed interest, and combinations of nutrients
are being employed in some cases. It is being recognised that advice on dietary modification may need
to place some emphasis on the need for some animal
sources of vitamin A if provitamin bioavailability is
less than previously thought.
SIGHT AND LIFE
Chapter 4
Looking to the future
Introduction
I would like to make it plain at the outset that the
views expressed here are entirely personal. They are
based on my own experiences and my reading of
passed experience of others. It is a sad commentary
on human nature that “history teaches us that history
teaches us nothing”. We should be aware of this common failing and try to exercise the humility and insight that will help us to learn from the mistakes made
in the past.
I would suggest that we have no cause for complacency as we take both backward and forward glances
from our present position. In a few years’ time it may
be that we will be celebrating the centenary of the
discovery of vitamins in general and vitamin A in
particular (see Chapter 1). We may well ask the question as to why it is that, despite the fact that we have
had available the cure for VADD for all those years,
the disease continues to take a heavy toll of death,
blindness and ill health around the world. I suggest
that at least part of the answer may lie in our unwillingness to learn from the past.
In addition, I would suggest that the present time,
which happens to be at the close of the second millennium, is a time of peculiar uncertainty. A number
of things are conspiring to make it so. The present
total human population of about 6 billion is far larger
than has ever previously been seen. Although the rate
of population growth is beginning to slow down for
the first time in decades the total number will continue to grow until well into the next century.
are being used up at an increasingly greater rate. This
is only partly due to the greater number of humans
to feed, clothe and shelter. In addition, there is gross
overconsumption on the part of the well-off minority. A combination of these factors – in some communities in particularly acute form – is resulting in
what has been called demographic entrapment of
some communities (241).
All of this has been going on for quite some time and
institutions like the Worldwatch Institute in Washington D.C. have been calling attention to the threat
of dire effects for years. Of more recent occurrence,
dating rather precisely from July 1997 when the currency crisis hit Thailand, bush fires of financial disaster have spread around the world and no one appears to feel entirely safe.
When all of this bad news is put together it is difficult not to be pessimistic if one is also to be realistic.
I do not think it is right for those of us involved in
the control of VADD to turn our backs on these ethical issues and say that we should leave them to others as they are not our concern. In vitamin A supplementation we have one of the most cost-effective of
all health interventions (242). If fully implemented,
millions of lives each year would be saved (243). Is
it ethical to continue to implement vitamin A or even
multi-nutrient measures without taking into account
also the impact they are having on these other demographic considerations?
I would now like to turn from these rather general
remarks to make some observations about VADD in
particular.
This has to be set alongside the even more disturbing fact that the world’s natural resources of all kinds
121
Looking to the future
Problems with xerophthalmia
No magic bullet for intervention
Sommer and West (2) at the beginning of their chapter on xerophthalmia and keratomalacia point out four
ways in which concentration on xerophthalmia has
had a retarding effect on efforts to control the problem. Briefly stated these are: 1) Its relative infrequency in any population as a whole has been
wrongly interpreted as suggesting that VAD at a lesser
level does not constitute a significant health problem. 2) Frequent association of corneal xerophthalmia with severe general malnutrition (PEM) has
tended to mask the underlying effects of VAD on the
rest of the body. 3) High mortality in xerophthalmia
has in effect “removed” the problem from attention
because of the few survivors. And 4) the dramatic
eye lesions have drawn clinical and research attention away from the more prevalent, and less dramatic,
systemic consequences of VAD.
There are four main types of intervention for VADD
• Supplementation
• Fortification
• Diet modification
• Infection control
I fully agree with all of these points and would only
observe here that they are likely to continue to make
it more difficult to mobilise efforts to control VADD.
I would point out an additional factor that acts in a
rather similar way. Blindness has always had a greater
emotive influence over the public than other disabilities. Furthermore, the picture of a young child blinded
for life through lack of a few basic items of food is
among the most moving. The same can be said, in
reverse, for the prospect of saving a child’s eyesight
with a few US cents’ worth of vitamin A. I have argued (Chapter 2, page 108) that considering the problem as part of primary eye care is not defensible from
a conceptual point of view. Here I want to point out
that because this is so often the popular approach, it
has resulted in a great deal of well-motivated effort
that might not otherwise have occurred. VADD
looked at in the way Sommer and West are suggesting, and with which, as I said, I entirely agree conceptually, will not have the advantage of this emotive element.
122
We used to think that the vast majority of even the
poorest people in developing countries managed to
avoid VAD. They certainly avoid xerophthalmia, but
now we know that this is not the same as avoiding
VAD and, moreover, they only need to be subclinically deficient to have a significantly increased risk
of disease and death. This changes the whole picture, for it means that perhaps about half of the
young children in developing countries have that
degree of VAD and run that risk (113). There are
also other high-risk groups, such as pregnant and
lactating women and school age children. So the
task of ensuring an adequate vitamin A intake
throughout life becomes that much more difficult
to achieve in the future.
It is not necessary here to go over in detail why none of
the interventions is ideal. These matters have been fully
considered in Sommer and West (2) and in lesser detail
in the SIGHT AND LIFE manual (1) and elsewhere.
Suffice it to say…
• Supplementation is really an emergency
measure; it does nothing to eradicate the problem, and it has repeatedly proved to be incapable of maintenance at a high level of uptake in
routine practice.
• Fortification is difficult to initiate and implement and may be costly. Often the vehicle for
fortification is not a desirable food item in
itself, such as sugar or MSG. However, it does
not have to rely on the cooperation of the public
for its implementation. Once fortification is
established it can bring about a lasting improvement in vitamin A intake of all groups.
SIGHT AND LIFE
• Dietary modification requires full cooperation
from the public, may not be applicable to the
poorest and is difficult to sustain. Increased
consumption of dark green leaves and yellow
fruits is the usual modification recommended.
Serious doubts are now being raised about the
much lower bioavailability of carotenoids than
we used to think (page 120). On the positive
side, however, it brings with it benefits such as
income generation and increased intake of other
nutrients and fibre.
• Infection control. There is no doubt that the
synergistic effect of VAD and infections works
in both directions often. Ideally vitamin A
interventions and measures to control infectious disease, such as immunisation, should go
hand in hand. Even when this is not possible, a
really effective measure, such as measles
immunisation, has been shown to reduce
greatly the prevalence of corneal scarring in
children.
No gold standard for assessment
This statement is generally accepted to be true, and
it applies not only to vitamin A status but also to nutritional status in general. This is because existing
indices are surrogates for a more basic expression of
status. It is bound to be so because nutritional status
is a broad concept, incapable of precise definition.
In this respect nutritional deficiency is unlike infectious disease, in which not only will a typical clinical syndrome usually be present, but with suitable
laboratory facilities it will be possible to isolate, identify and quantitate the causative organism. Nothing
so precise is possible in nutrition.
Sommer and West (2) in their book have described
and discussed the problems associated with each
exisiting index of vitamin A status, a subject to which
they have made significant original contributions.
The group responsible for the WHO document Indicators for assessing vitamin A deficiency and their
application in monitoring and evaluating intervention programmes (222) produced a document which,
in my opinion, has a number of weaknesses. As it is
being put to the test of practical use in the field it
may not prove to be much of a step forward in this
difficult field.
This is not the place to do more than draw attention
to the existence of the problem and the need to continue active research to develop better indicators at
the subclinical level of deficiency and perhaps refine those available at present (244).
To end this comment on a more optimistic note, it
has to be acknowledged that more progress in assessment of nutritional status has been made in the
field of vitamin A than for any other nutrient.
Unanswered questions
• It has always puzzled me why, in the generally
malnourished child (with PEM), clinical
evidence of VAD is the most common associated deficiency. When extensive biochemical
tests have been carried out levels of almost all
nutrients have been found to be subnormal, but
apart from vitamin A these have not been
accompanied by clinical signs. Vitamin A after
all is one of the few nutrients of which the
body normally has considerable stores. We
know that liver levels of vitamin A are quite
low at birth in health and normally increase 60fold during the first 6 months of life. The stress
of growth and infectious disease tend to deplete these stores. Furthermore, milk, breast or
cow’s milk, normally contains no more vitamin
A than serum. We do not fully understand why
in a certain community only a few children
become clinically deficient. Of course it must
not be forgotten that even subclinical deficiency may have serious consequences.
123
Looking to the future
•
A related question is, “why does the age of
peak incidence vary between different places
so much?” I am referring to evidence of
xerophthalmia, non-corneal and corneal. In my
own experience this was particularly evident in
the 1960s between our work in Jordan and
reports from India. Most of our patients with
keratomalacia were infants, many only a few
months old. In India and in Indonesia the peak
age was more like 2–4 years. Our study from
Jordan was met with some surprise in this
regard. Many years later another hospital study
from Brasil (245) also had most patients young
infants.
•
Finally, I do not believe it has ever been
explained why in areas where severe PEM is
common, accompanying xerophthalmia might
be either virtually absent or vary in incidence
all the way up to 75% or so, as it was in Indonesia in the 1950s. I used to suspect that the
answer lay in the amount of carotene, small
though it might be, provided by the respective
diets. In particular I suspect that the carotene in
the staple food is all-important; rice-dependent
populations have always been especially
vulnerable.
•
Another question along the same lines: How is
it that in famine conditions, such as those all
too familiar to us in southern Sudan at the
present time, babies dying with extreme
wasting show no evidence of xerophthalmia?
Xerophthalmia has by no means been eliminated and
I think there is still a need for detailed hospital-based
studies in suitable areas to try to provide answers to
these and perhaps other outstanding questions of this
nature.
124
Unlearned lessons
More thought and more research will hopefully bring
progress in the areas I have outlined above, but how
can one deal with those who, for whatever reason,
fail to learn and profit from the lessons which have
resulted from such dedicated efforts in the past? I do
not know the answer – here are some examples which
I have found particularly exasperating.
•
The misuse of X1A, conjunctival xerosis.
The WHO Technical Reports of both 1976 and
1982 (130, 147) gave the reasons why it was
unanimously agreed that this sign could not be
used in field studies. In essence the changes are
highly subjective, cannot be quantified or
determined as “present” or “absent” with any
certainty in a study population. They are
subject to large inter- and intra-observer error.
Nevertheless, X1A is continually being reported, often in studies that state that they have
been carried out according to the WHO guidelines! Very often “conjunctival xerosis” is by
far the most reported sign of xerophthalmia
and makes up a high proportion of the total
signs. Consequently this “creates” a problem of
xerophthalmia where in fact none exists.
•
X1B, Bitot’s spots. Most workers probably
know that not all Bitot’s spots are indicators of
active VAD. It is perhaps less well appreciated
that those that can be related to active VAD are
usually confined to pre-school age children.
This is one reason why it is recommended that
field surveys for VAD in children are confined
to those aged 6 years and under. Frequently
older children are also included and X1B rates
in them are included in an analysis. Again this
tends to create a problem or inflate it. However, it should not be forgotten that active
Bitot’s spots may occur in older children when
they are, of course, an indication for supplementation. Unfortunately, the only practical
way to prove the point is by therapeutic test.
SIGHT AND LIFE
•
The acute-phase response (APR) and serum
retinol. During the 1960s I was fascinated by
several reports, one at least from the 1930s,
which showed that in acute infections vitamin
A seemed to “disappear” from the blood. We
also showed, as did Arroyave at about the
same time, that serum albumin did the same
sort of thing. The acute-phase response had
not been invented then, but it did seem clear
that this might cast some doubt on the validity
of the use of serum retinol, and perhaps other
nutrients in the circulation, as indices of
nutritional status in the presence of infections,
which most undernourished patients have.
When this possibility was raised at meetings
or in correspondence columns it met with
open opposition. As might be expected, this
came mainly from the proponents of these
tests as 100% reliable indicators of vitamin A
status! It is only in recent years when the
mechanism has been better understood and its
occurrence has been shown to be widespread
that views have begun to change.
•
Sample size. This is a very simple general
point. Besides meeting other statistical requirements a sample should be sufficiently large to
satisfy these requirements. Many surveys of
vitamin A status, including some of those
considered in the report on worldwide prevalence by WHO (113), are quite inadequate in
terms of numbers to be at all representative.
•
Absence of evidence is not evidence of
absence. When studies have failed to show a
significant effect of a vitamin A intervention it
has often been concluded that “vitamin A does
not improve growth, reduce morbidity etc.”.
All that has been shown is that in the particular
instance an absence of a difference between
experimental and control groups has been
shown. Other trials might just as readily show
a significant difference, in which case it would
be equally erroneous to say that these have
proved a particular effect to occur. Unfortunately, with such difficult and complex issues
the combined results of a number of large,
well-designed and well-executed trials are
usually required before a consensus can be
reached.
•
Effectiveness of interventions. A vitamin A
intervention, like any other public health
measure, occurs in a certain place at a certain
time, neither of which can be precisely duplicated elsewhere or at another time. Moreover,
in precise detail no two interventions will be
identical, however much effort is expended to
try to make them so. By their very nature
interventions of this kind often need to be
implemented, and certainly to be observed,
over long periods of time. All possible variables cannot be known at the start, nor can the
way in which they may change over the course
of the intervention be known either. Great
caution should be exercised in coming to
conclusions about cause and effect in these
circumstances. It is doubtful if any specific
public health measure can be as effective as
general economic and social development in
bringing about improvement in, for example,
nutritional status. It might also be added that
the reverse is probably equally true; economic
collapse or rapid cultural change may be
expected to bring about a rapid precipitation of
malnutrition. Unfortunately the truth of these
words will probably be tested in a number of
countries in the near future. On a more optimistic, but speculative, note it is understood
that genetic modification of rice is being
undertaken in order that it might become a rich
source of provitamin A carotenoids. If successful, this might make a major contribution to the
control of VADD in many countries.
125
Looking to the future
Questionable concepts
Four uneasy bedfellows
I described in some detail in Chapter 2 (see page 108)
how more than twenty years ago I was forced to the
conclusion that the prevailing concept, which regarded xerophthalmia merely as a blinding disease
and to be prevented by primary eye care, was fundamentally flawed and a major factor in hampering efforts to promote control measures.
This is a broader issue than just the nature of xerophthalmia. The concept applies equally to the other
“bedfellows” and there may be other instances of illconceived concepts in other areas of medicine.
At the present time blindness per se continues to be
the focus of efforts at local, national and international
level. Looking to the future there is little cause for
optimism that a more rational, and I believe effective, approach will prevail.
Micronutrient malnutrition
In the 1990s this has become a popular concept with
agencies and others concerned with nutrition interventions. It has usually been applied to vitamin A,
iron, and iodine deficiency, but recently there is a
tendency to include also deficiency of zinc and calcium and possibly other micronutrients.
This concept seems to have arisen to fill the gap in
nutrition policy left by the collapse of the “impending protein crisis” concept in the mid 1970s. For decades PEM had been acknowledged to be the most
widespread and serious nutritional deficiency problem. I have told the story (151) of how protein deficiency came to be mistakenly blamed for most of
the problem and how this led in the 1960s and 70s to
the protein-rich food mixture solution and other similar misconceived attempts that constituted the “great
protein fiasco”. Following upon this in the past two
decades nothing much has been heard about controlling PEM. However, recently Ramalingaswami,
Levinson, and Schuftan have expressed their con-
126
cern about the overemphasis on micronutrient malnutrition and the neglect of PEM (246). This trio is
greatly experienced in international child nutrition
problems and they provide more evidence for the
point I have been trying to make here.
The micronutrient malnutrition concept seems at a
superficial glance to have the attraction of requiring
relatively simple measures for the solution of the
problem. It is perhaps too early to say, but I have the
feeling that this concept has flaws in it not dissimilar
to those that are inherent in the “uneasy bedfellows”
misconception.
The three main micronutrient deficiencies, of vitamin A, iron, and iodine, do not share a common global distribution or vulnerable groups. There are efforts at present to fortify cereals with both iron and
vitamin A, which certainly makes sense in view of
the interrelationships between these nutrients. However, although fortification of foods has become common practice in industrialised countries, experience
to date in developing countries has not been equally
successful. Only time will tell whether or not the
present measures will prove to be sustainable.
Future for some “institutions”
From statements put out in recent years by the UN
and other agencies about the “virtual elimination of
vitamin A deficiency and all its consequences including blindness by the year 2000” (247) one might reasonably expect that bodies like IVACG, SIGHT AND
LIFE, the Xerophthalmia Club Bulletin that are exclusively devoted to the prevention of VADD might
not be in existence anymore after that crucial year,
i.e. next year!
It might also be argued whether giving so much attention to a single vitamin is justifiable. However,
my own view is that there will be the need for such
institutions to continue into the forseeable future,
although they probably will need to undergo considerable change and development in the process.
SIGHT AND LIFE
It has to be recognised that no one now takes the
goal of “Health for All by the Year 2000”, formulated by WHO in 1978 at Alma-Ata, seriously and
in a literal sense with the deadline almost here. Some
of us had our doubts at the beginning and said so
(69). Even those associated with WHO are now admitting this. Not so long ago all kinds of efforts
were being made for the goal’s achievement by the
stated deadline. However, we are now expected to
forget all that has ever happened. Our attention is
now being drawn to the recent publication of a document and a policy, endorsed by the World Health
Assembly, the governing body of WHO, in May
1998 entilted “Health for All in the 21st Century”.
That part of the “Global health targets to 2020” that
applies in the present context reads as follows,
“eradicate and eliminate certain diseases” of which
VAD is one. Here, in effect, we see a reiteration of
the same old goals, but with the “deadline” just
pushed back another 20 years to the year 2020! In
my view slogan fatigue and a weary sense of déjà
vu will rapidly take over.
With all this in mind it seems inevitable to me that
institutions like IVACG, SIGHT AND LIFE and the
Xerophthalmia Club Bulletin are going to be needed
even more in the forseeable future. If the deepening
economic crisis bites ever harder in years to come
these kinds of efforts are going to become even more
important.
It is equally clear, however, that circumstances will
change radically, and this may require serious restructuring in order to face up to the new challenges. At
present IVACG is not much more than a cosy chat
shop where ideas can be readily aired and exchanged.
It has failed so far to tackle really controversial key
issues and the recommendations which its meetings
pass without comment are not brought up later to see
whether they have been implemented. It needs to be
given teeth and this is unlikely to happen while its
meetings continue to get bigger and more bland.
Despite the representation of UN agencies in IVACG
from the beginning it has not led to a really effective
collaboration. This is in marked contrast to what has
happened in the area of the control of iodine deficiency disorders. In 1985 the International Council
for Control of Iodine Deficiency Disorders
(ICCIDD) was set up as a nongovernmental organisation to work closely with WHO and UNICEF. It is
recognised as the expert group by the United Nations system and reports annually to the Subcommittee on Nutrition.
The contribution of SIGHT AND LIFE has grown
steadily in recent years and in addition to its regular
newsletters there are few studies, meetings or publications in the field in which it does not have some
kind of input. In my view these and other novel contributions which it will no doubt continue to make
will be needed for years to come.
As editor since 1985 I can perhaps speak about the
Xerophthalmia Club Bulletin with some authority. I
certainly know its weaknesses only too well. In the
natural course of events it will need a new editor in
the not too distant future and that may be the time
for radical change. At present it goes free of charge
to about 3500 people all over the world three times a
year. Each issue is about 9000 words long. Far too
much of it, sometimes almost all, is written by me.
Although people usually write something fully acceptable when requested, in my view not nearly
enough people bother to write in about issues that
concern them. It is not for want of encouragement.
It might surprise some to know how much goes on
behind the scenes between issues. The internet and
e-mail facilites open up a reliable means of communication in the remotest parts of the earth where
ordinary postal services cannot be relied upon. Increasingly, we all have less and less excuse for not
being up-to-date and on-the-ball in our combat of
VADD.
127
SIGHT AND LIFE
Epilogue
I suppose for all intents and purposes this must be
somewhere towards the end of my contributions towards the conquest of VADD. I shall never cease to
be interested in and concerned about the problem,
but I have to admit that the golf course and my other
sporting activities as well as interests like tapestry
and the electronic organ and involvement with Christian ecology take up more and more of my time so
long as my health lasts.
When I started out nearly fifty years ago only the tip
of the problem was recognised and we really had no
idea how to prevent it. Relatively recently what is
probably the full extent of the problem was revealed
and we had come to be rather confident that we knew
how it could be controlled. At the time of writing
this it seems that the clock of progress may be being
turned backwards by economic forces that are beyond our control. In these circumstances those who
continue to “bear the heat and burden of the day”
will need a strong nerve, ingenuity, dedication, patience and perhaps above all insight as they face the
difficult times ahead.
129
SIGHT AND LIFE
References
1. McLaren DS, Frigg M (1997). SIGHT AND
LIFE Manual on Vitamin A Deficiency Disorders (VADD) 1st ed. Roche, Basel
2. Sommer A, West KP Jr (1996). Vitamin A
Deficiency: Health, Survival, and Vision.
Oxford University Press, New York
3. Wolf G (1996). A history of vitamin A and
retinoids. FASEB J 10:1102-7
4. Ishihara S (1913). Zur Aetiologie der
idiopathischen Hemeralopie bzw. Xerosis
conjunctivae. Klin Monatsbl Augenheilkd
15:596-603
5. Wolf G (1978). A historical note on the mode
of administration of vitamin A for the cure of
night blindness. Am J Clin Nutr 31:290-2
6. Hirschberg J (1982). The History of Ophthalmology vol 1 Antiquity. Translated by Fred C.
Blodi, Brown, New York
7. Ebbell B (1937). The Papyrus Ebers: the
Greatest Egyptian Medical Document.
Munksgaard and Oxford University Press,
Copenhagen
8. Nunn JF (1996). Ancient Egyptian Medicine.
British Museum, London
9. Celsus AC (c. 25 BC-AD 50). De Medicina II
Book VI.6.27-29
10. Duddell B (1729). Treatise of the Diseases of the
Horny-Coat of the Eye. John Clark, London
11. Bergen CA, Weise JC (1754). De nyctalopia
seu caecitate nocturna. A. von Haller, Lausanne
12. Magendie F (1816). Mémoire sur les propriétés
nutritives des substances qui ne contiennent
pas d’Azote. Paris, 7
13. Livingstone D (1905). Travels and Researches
in South Africa. London, p 470
14. Kurlansky M (1997). Cod: A Biography of the
Fish that Changed the World. Jonathan Cape,
London
15. Drummond JC, Wilbraham A (1939). The
Englishman’s Food: a History of Five Centuries of English Diet. Jonathan Cape, London
16. Osborne TB, Mendel LB (1914). The influence
of cod liver oil and some other fats on growth.
J Biol Chem 17:401-8
17. Zilva SS, Drummond JC (1921). Lancet ii:753
18. Mayer J (1957). Armand Trousseau and the
arrow of time. Nutr Rev 15:321-3
19. Follis RH Jr (1960). Cellular pathology and
the development of the deficiency disease
concept. Bull Hist Med 34:291-317
20. Carter KC (1977). The germ theory, beriberi,
and the deficiency theory of disease. Med Hist
21:119-136
21. Ihde AJ, Becker SL (1957). Conflict of concepts
in early vitamin studies. J Hist Biol 4:1-33
22. Rosenberg C (1964). On the study of American
biology and medicine: some justifications. Bull
Hist Med 38:364-376
23. Lunin NI (1881). Ueber die Bedeutung der
anorganischen Salze für die Ernährung des
Thieres. Z Physiol Chem 5:31-51
24. Pekelharing CA (1905). Ned Tijdschr Geneeskd
70:111
25. Stepp W (1909). Versuche über Fütterung mit
lipoidfreier Nahrung. Biochem Z 22:453-460
26. Funk C (1922). The Vitamines. Williams &
Wilkins, Baltimore
27. Petty C (1989). Primary research and public
health: the prioritization of nutrition research
in inter-war Britain. pp 83-108 in: Historical
Perspectives on the Role of the Medical Research Council, eds. Austoker J, Bryder L,
Oxford University Press, Oxford
28. Aronson N (1986). The discovery of resistance:
historical accounts and scientific careers. Isis
77:286-306
131
References
29. von Graefe A (1866). Hornhautverschwarung
bei infantiler Encephalitis. Albrecht v Graefes
Arch Ophthal 12:250-6
30. Gama Lobo (1866). Ophthalmia brasiliana.
Klin Monatsbl Augenheilkd 4:65
31. Hubbenet M (1860). Observations sur
l’hémeralopie. Ann Oculist (Paris) 44:293
32. Bitot C (1863). Sur une lésion conjonctivale
non encore décrite, coincidant avec
l’hémeralopie. Gaz Hebd Med Chir 10: 284-8
33. Teuscher R (1867). Jena Z Med Naturw 3:103
34. Baas KL (1894). Ueber eine Ophthalmia
hepatitica nebst Beiträgen zur Kenntnis der
Xerosis conjunctivae und zur Pathologie der
Augenmuskelerkrankungen. Albrecht von
Graefes Arch Ophthal 40:212-246
35. Herbert H (1897). Epithelial xerosis in natives
of India. Ind Med Gaz 32:130-4
36. Stephenson S (1898). On epithelial xerosis of the
conjunctiva. Trans Ophthal Soc UK. 18:55-102
37. Ewald A, Kuhne W (1877). Ueber künstliche
Bildung des Sehpurpurs. Centr Med Wissensch
15:753-4
38. Parinaud M (1881). Des modifications
pathologiques de la perception de la lumière,
des couleurs et des formes, et des différentes
espèces de sensibilité oculaire. Gaz Med Paris
3:411-3
39. Leber T (1883). Ueber die Xerosis der
Bindehaut und die infantile
Hornhautverschwärung; neben Bemerkungen
über die Entstehung des Xerophthalmus.
Albrecht von Graefes Arch Ophth 29:225-290
40. Jensen E (1903). Xerophthalmia in small
children. Hospitalstidende 11:749-758
41. Mori M (1904). Ueber den sogenanten Hikan
(Xerosis conjunctivae infantum eventuell
Keratomalacie). Jb Kinderheilkd 59:175-195
42. Falta W, Noeggerath CT (1905).
Fütterungsversuche mit künstlicher Nahrung.
Beitr Chem Physiol Path 7:313-322
43. Holm E (1925). Demonstration of hemeralopia
132
in rats nourished on food devoid of fat-soluble
A-vitamin. Am J Physiol 73:79-84
44. Fridericia LS, Holm E (1925). Experimental
contribution to the study of the relation
between night blindness and malnutrition. Am
J Physiol 73:63-78
45. Budd G (1842). Disorders resulting from
defective nutriment. Lon Med Gaz 2:632-749
46. Hughes RE (1973). George Budd (1808-1882)
and nutritional deficiency diseases. Med Hist
17:127-135
47. Stephenson M, Clark AB (1920). A contribution to the study of keratomalacia among rats.
Biochem J 14:502-521
48. Osborne TB, Mendel LB (1913). The relation
of growth to the chemical constituents of the
diet. J Biol Chem 15:311-326
49. McCollum EV, Davis M (1913). The necessity
of certain lipins in the diet during growth. J
Biol Chem 15:167-175
50. Hopkins FG (1912). Feeding experiments illustrating the importance of accessory factors in
normal dietaries. J Physiol (Lond) 49:425-460
51. Rosenfeld L (1997). Vitamine-vitamin. The early
years of discovery. Clin Chem 43:680-5
52. Osborne TB, Mendel LB (1921). Ophthalmia
and diet. J Am Med Assoc 76:905-8
53. McCollum EV (1957). A History of Nutrition.
Houghton Mifflin, Boston
54. Bloch CE (1921). Clinical investigation of
xerophthalmia and dystrophy in infants and
young children. J Hyg Camb 19: 283-304
55. Blegvad O (1924). Xerophthalmia, keratomalacia and xerosis conjunctivae. Am J Ophthal
7:89-117
56. Steenbock H (1919). White corn vs. yellow
corn and a probable relation between the fatsoluble vitamin and yellow plant pigments.
Science 50:352-3
57. Moore T (1930). Vitamin A and carotene.
Biochem J 24:692-702
SIGHT AND LIFE
58. McCollum EV, Simmonds N, Becker JE et al
(1922). An experimental demonstration of the
existence of a vitamin which promotes calcium
deposition. J Biol Chem 53:293-312
59. Green HN, Mellanby E (1928). Vitamin A as an
anti-infective agent. Brit Med J ii:691-6
60. Wolbach SB, Howe PR (1925). Tissue changes
following deprivation of fat-soluble A vitamin.
J Exp Med 42:753-778
61. Carr FH, Price EA (1926). Colour reactions
attributed to vitamin A. Biochem J 20:497-501
62. Wald G (1968). Molecular basis of visual
excitation. Science 162:230-9
63. Wright RE (1922). Keratomalacia in southern
India. Br J Ophthal 6:164-175
64. Aykroyd WR (1944). An early reference to
night-blindness in India, and its relation to diet
deficiency. Curr Sci 13:149
65. Pillat A (1929). Does keratomalacia exist in
adults? Arch Ophthal 2:256-287
66. Frazier CN, Hu CK (1936). Nature and distribution according to age of cutaneous manifestations of vitamin A deficiency. Arch Derm
Syph 33:825-852
67. de Haas JH, Meulemans P (1938). Vitamin A
and carotenoids in blood deficiencies in
children suffering from xerophthalmia. Lancet
i:1110-1
68. Hume EM, Krebs HA (1949). Vitamin A
requirements of human adults:an experimental
study of vitamin A deprivation in man. Spec
Rep Ser Med Res Coun no 264, HMSO, London
69. Anon (1986). The fall and rise of the
antiinfective vitamin. Lancet i:1191
70. Semba RD (1999). Vitamin A as “Anti-infective” therapy, 1920-1940. J Nutr 129:783-791
71. Karrer P, Jucker E (1950). Carotenoids.
Elsevier, Amsterdam
72. Fuson RE, Christ RE (1936). Science 84:294
73. Kuhn R, Morris CJOR (1937). Synthesis of
vitamin A. Chem Ber 70:853-8
74. Holmes HN, Corbett RE (1937). The isolation of
crystalline vitamin AJ Am Chem Soc 59:2042-7
75. Isler O (ed) (1971). Carotenoids. Birkhäuser
Verlag, Basel
76. Pommer cited in Mayer H, Isler O (1971).
Total synthesis. In: Carotenoids (ed Isler O).
Birkhäuser Verlag, Basel pp 325-575
77. WHO/UNICEF (1978). Primary Health Care.
Geneva, WHO
78. Anon (1983). How near is health for all?
Lancet ii:1179-1180
79. Passmore R (1993). William Cullen and dietetics. In: William Cullen and the Eighteenth
Century Medical World. (Doig A, Ferguson
JPS, Milne IA, Passmore R eds.) pp 167-185.
Edinburgh University Press, Edinburgh
80. Hutchison R (1900). Food and the Principles
of Dietetics. Arnold, London
81. Garrow JS, James WPT (eds) (1993). Human
Nutrition and Dietetics. 9th ed, ChurchillLivingstone, Edinburgh
82. Ross D (1991). Vitamin A Supplementation
Trials (VAST) in Ghana. Xero Club Bull, no 48
83. Ross DA, Arthur P, McLaren DS (1993). A
comparison of serum retinol levels and conjunctival impression cytology results in young
children in Ghana. XVI IVACG Meeting,
Arusha, Tanzania. Nutrition Foundation,
Washington DC
84. McLaren DS (1994). Nutrition in medical
schools: a case of mistaken identity. Am J Clin
Nutr 59:960-3
85. Smith DA, Woodruff MFA (1951). Deficiency
diseases in Japanese prison camps. Spec Rep
Ser Med Res Coun no 274, HMSO, London
86. Frazer JG (1993). The Golden Bough: a Study
in Magic and Religion. Wordsworth, London
87. Campbell J (1861). Narrative by Major-General
John Campbell on his Operations in the Hill
tracts of Orissa for the Suppression of Human
Sacrifices and Female Infanticide. Hurst and
Blackett, London
133
References
88. McLaren DS (1963). Malnutrition and the Eye.
Academic Press, New York
89. Krzywicki L (1934). Primitive Society and its
Vital Statistics. Macmillan, London
90. Williams CD (1933). A nutritional disease of
childhood associated with a maize diet. Arch
Dis Child 8:423-433
91. Baumslag N (ed) (1986). Primary Health Care
Pioneer: the selected works of Dr Cicely D.
Williams, Washington DC, World Federation of
Public Health Associations
92. Dally A (1968). Cicely: the Story of a Doctor.
London, Victor Gollancz
93. Craddock S (1983). Retired Except on
Demand. Green College, Oxford
94. Nutrition Reviews (1973). vol 31, no 11 a
special number marking the eightieth year of
Dr Cicely D. Williams
95. Williams CD, Jelliffe JB (1972). Mother and
Child Health: Delivery of the Services. Oxford
University Press, Oxford
96. McLaren DS (1956). A study of the factors
underlying the special incidence of keratomalacia in Oriya children in the Phulbani and
Ganjam districts of Orissa, India. J Trop
Pediatr 2:135-140
97. McLaren DS (1955). Health and Disease in
the Khond Hills, India: a contribution to
global epidemiology. MD Thesis, University
of Edinburgh
98. McLaren DS (1959). Influence of protein
deficiency and sex on the development of
ocular lesions and survival time of the vitamin
A-deficient rat. Br J Ophthalmol 43:234-241
99. McLaren DS (1957). Some Effects on the Eye
of Malnutrition, Especially of Deficiency of
Protein. Ph D Thesis in Nutrition, University of
London
100. Oomen HAPC, McLaren DS, Escapini H
(1964). Epidemiology and public health aspects of hypovitaminosis A. A global survey on
xerophthalmia. Trop Geogr Med 16:271-315
134
101. ten Doesschate J (1968). Causes of blindness
in and around Surabaja, East Java, Indonesia.
Thesis, University of Indonesia, Jakarta.
102. Oomen HAPC (1957). The incidence of
xerophthalmia in Java in relation to age and
sex. Doc Med Geogr Trop 7:1-9
103. de Haas JH, Posthuma JH, Meulemans O
(1940). Xerophthalmia among children in
Batavia. Geneeskd Tijdschr Ned-Indie
80:928-950
104. Oomen HAPC (1954). Xerophthalmia in the
presence of kwashiorkor. Brit J Nutr 8:307-318
105. Patwardhan VP, Kamel WW (1967). Studies
on vitamin A deficiency in infants and young
children in Jordan. Part I Epidemiology. WHO
Doc EMRO/NUTR/67.3
106.WHO (1972). Prevalence of xerophthalmia.
Hyderabad, India, WHO
107. Darby WJ, McLaren DS (1957). Nutrition in
Indonesia. SEA/Nutr.4 WHO
108. McLaren DS (1958). Growth and water
content of the eyeball of the albino rat in
protein deficiency. Brit J Nutr 12:254-9
109. McLaren DS (1959). The eye and related
glands of the rat and pig in protein deficiency.
Br J Ophthalmol 43:78-87
110. McLaren DS (1958). Involvement of the eye in
protein malnutrition. Bull World Health Organ
19:303-314
111. Yap Kie Tiong (1956). Protein deficiency in
keratomalacia. Br J Ophthalmol 40:502-3
112. Kuming BS, Politzer WM (136). Xerophthalmia and protein malnutrition in Bantu children.
Br J Ophthalmol 51:649-665
113. WHO (1995). Global prevalence of vitamin A
deficiency. WHO/NUT/95.3, Geneva, WHO
114. Kinney TD, Follis RH Jr (eds) (1958). Nutritional Disease. Proceedings of a Conference on
Beriberi, Endemic Goiter and Hypovitaminosis
A, Princeton, NJ, 1-5 June,1958, Suppl 2, Part
II, No 3, Vol 17
SIGHT AND LIFE
115. Nieburg P, Waldman RJ, Leavell R et al
(1988). Vitamin A supplementation for refugees
and famine victims. Bull World Health Organ
66:689-697
116. Oomen HAPC (1953). Infant malnutrition in
Indonesia. Bull World Health Organ 9:371-384
117. Oomen HAPC (1961). An outline of xerophthalmia. Int Rev Trop Med 1:131-213
118. Oomen HAPC, Grubber GJH (1977). Tropical
Leafy Vegetables in Human Nutrition. Amsterdam, Royal Tropical Institute
119. McLaren DS (1960). Nutrition and eye
disease in East Africa. J Trop Med Hyg
63:101-121
120. Foster A, Sommer A (1987). Corneal ulceration, measles, and childhood blindness in
Tanzania. Br J Ophthalmol 71:331-343
121. Johnstone WWJ, McLaren DS (1963). Refraction anomalies in Tanganyikan children.
Br J Ophthalmol 47:95-108
122. McLaren DS (1960). The pattern of early
growth in Sukumaland, Tanganyika. J Pediatr
56:803-813
123. McLaren DS, Read WWC (1962). Fatty acid
composition of adipose tissue: a study in three
races in East Africa. Clin Sci 23:247-250
124. McLaren DS (1960). Records of birth weight
and prematurity in the Wasukuma of Lake
Province, Tanganyika. Trans R Soc Trop Med
Hyg 53:173-8
125. Paton D, McLaren DS (1960). Bitot spots.
Am J Ophthalmol 50:568-574
126. Darby WJ, McGanity WJ, McLaren DS et al
(1960). Bitot’s spots and vitamin A deficiency.
Public Health Rep Wash 75:738-743
127. Interdepartmental Committee on Nutrition for
National Defense (ICNND) (1959). Nutrition
Survey: Ethiopia. ICNND, Washington DC
128. McLaren DS, Shaw MJ, Dalley KR (1961).
Eye disease in leprosy patients. A study in
central Tanganyika. Int J Lepr 29:20-8
129. Woodruff AW, Barnley GR, Holland JT et al
(1963). Onchocerciasis and the eye in western
Uganda. Trans R Soc Trop Med Hyg 57:50-63
130. World Health Organization (1976). Vitamin A
deficiency and xerophthalmia. Tech Rep Ser
World Health Organ no 590, WHO, Geneva
131. Blumenthal CJ (1950). Malnutritional keratoconjunctivitis disease of South African Bantu. S
Afr Med J 24:191-8
132. McLaren DS (1980). Nutritional Ophthalmology. Academic Press, London
133. McLaren DS (1961). Nutritional Blindness.
Guest lecture, Trans 1st Cong Asia-Pacific
Acad Ophthalmol, Manila pp 88-98
134. McLaren DS (1960). The effects of malnutrition on the eye: with special reference to work
with experimental animals. World Rev Nutr
Diet 2:25-51
135. Williams RR (1961). Towards the Conquest of
Beriberi. Harvard University Press, Cambridge,MA
136. Cobb B, Awdry PN (1968). Xerophthalmia.
Trans Ophthalmol Soc UK 88:579-585
137. Gopalan C, Venkatachalam PS, Bhavani B
(1960). Studies of vitamin A deficiency in
children. Am J Clin Nutr 8:833-840
138. McLaren DS, Read WWC, Tchalian M
(1966). Extent of human vitamin A deficiency.
Proc Nutr Soc 25:xxviii
139. Sommer A, Tarwotjo I, Hussaini G et al
(1981). Incidence, prevalence and scale of
blinding malnutrition. Lancet i:1407-8
140. WHO (1997). Global Initiative for the Elimination of Avoidable Blindness. WHO/PBL/
97.61,WHO, Geneva
141. McLaren DS, Shirajian E, Tchalian M et al
(1965). Xerophthalmia in Jordan. Am J Clin
Nutr 17:117-130
142. McLaren DS, Shirajian E, Loshkajian H et al
(1969). Short-term prognosis in protein-calorie
malnutrition. Am J Clin Nutr 22:863-870
135
References
143. McLaren DS, Tchalian M, Ajans ZA (1965).
Biochemical and hematologic changes in the
vitamin A-deficient rat. Am J Clin Nutr 17:131-8
144. Corey JE, Hayes KC (1972). Cerebrospinal
fluid pressure, growth, and hematology in
relation to retinol status of the rat in acute
vitamin A deficiency. J Nutr 102:1584-1594
145. Ajans AZ, Sarrif A, Husbands M (1965).
Influence of vitamin A on human colostrum
and early milk. Am J Clin Nutr 17:139-142
146. Paton D (1963). St Johns Ophthalmic
Hospital. Br Med J. June, 1st issue
147. WHO (1982) Control of vitamin A deficiency
and xerophthalmia. Tech Rep Ser no 672.
WHO, Geneva
148. Patwardhan VN (1969). Hypovitaminosis A
and epidemiology of xerophthalmia.
Am J Clin Nutr 22:1106-1118
149. Florentino RF, Tanchoco CC, Ramos AC et al
(1990). Tolerance of preschoolers to two
dosage strengths of vitamin A preparation.
Am J Clin Nutr 52:694-700
150. McLaren DS (1966). A fresh look at proteincalorie malnutrition. Lancet ii:485-8
151. McLaren DS (1974). The great protein fiasco.
Lancet ii:93-6
152. McLaren DS, Read WWC (1967).
Micromethods for the determination of vitamin
A and carotenoids in blood and other tissues.
In: Methods of Biochemical Analysis
(ed. D. Glick) 15:1-23, Wiley, New York
153. McLaren DS, Zekian B (1971). Failure of
enzymic cleavage of beta-carotene: the cause
of vitamin A deficiency in a child. Am J Dis
Child 121:278-280
154. ICNND (1967). Nutrition Survey: Nigeria,
ICNND, Washington, DC
155. FAO/WHO (1967). Requirements of Vitamin
A, Thiamine, Riboflavin and Niacin. WHO
Tech Rep Ser no 362, WHO, Geneva
156. McLaren DS, Read WWC, Tchalian M et al
(1969). Studies with 15N-labeled ammonia
136
and urea in the malnourished child. J Clin
Invest 48:1143-9
157. Teng Khoen Hing (1959). Fundus changes in
hypovitaminosis A. Ophthalmologica 137:81-5
158. Teng Khoen Hing (1964). Ocular fundus
changes in hypovitaminosis A. PhD Thesis,
University of Jakarta, Indonesia
159. Neeld JR, Pearson WN (1963). Macro and
micromethods for the determination of serum
vitamin A using trifluoracetic acid. J Nutr
97:454-462
160. Darnbrough A (1985). Under a drumstick
tree: a history of the nutritional rehabilitation
centre at Madurai. Royal Commonwealth
Society for the Blind, Haywards Heath
161. Venkataswamy G, Krishnamurthy KA,
Chandra P et al (1976). A nutrition rehabilitation centre for children with xerophthalmia.
Lancet i:1120-2
162. Venkataswamy G (1972). Xerophthalmia rehabilitation in S. India. Xero Club Bull no 39, 2-3
163. Anon (1998). Aravind Eye Hospital 1976-1996
164. Sommer A (1998). Moving from science to
public health programs: lessons from vitamin
A. Am J Clin Nutr 68 (Suppl 2) 513-6
165. Gillespie S, Mason J (1994). Controlling
Vitamin A Deficiency. ACC/SCN State-of-theArt Series Nutrition Policy Discussion Paper
no 14, United Nations
166. Sinha DP, Bang FB (1973). Seasonal variations in signs of vitamin A deficiency in rural
West Bengal children. Lancet ii:228-231
167. Sinha DP, Bang FB (1976). The effect of
massive doses of vitamin A on the signs of
vitamin A deficiency in preschool children.
Am J Clin Nutr 29:110-5
168. Kmet J, McLaren DS, Siassi F (1981). Epidemiology of esophageal cancer with special
reference to nutritional studies among the
Turkoman of Iran. In: Advances in Modern
Human Nutrition (Tobin RB, Mehlman MA eds.)
pp 343-365, Pathotox, New York
SIGHT AND LIFE
169. McLaren DS (1998). The role of nutrients in
dermatology, including cancer. In: Proceedings
of Pavia Meeting on Nutrition and Cancer,
16-19 September,1998
170. WHO (1997). Vitamin A Supplements:a guide
to their use in the treatment and prevention of
vitamin A deficiency and xerophthalmia. 2nd
ed, WHO, Geneva
171. McLaren DS (1969). Preparations of vitamin
A. Br Med J i:782
172. McLaren DS (1990). Reformulation of
injectable vitamin A. Br Med J 301:1277
173. Arroyave G (1986). Vitamin A deficiency
control in Central America. In: Vitamin A
Deficiency and its Control (ed Bauernfeind
JC), pp 405-424. Academic Press, Orlando
174. Arroyave G (1971). Standards for the diagnosis of vitamin deficiency in man. In: Metabolic
Adaptation and Nutrition. PAHO Sci Publ no
222, pp 88-100. Pan Am Health Organ,
Washington DC
175. Underwood BA (1990). Methods for
assessment of vitamin A status. J Nutr
120:1459-1463
176. Underwood BA (1986). The safe use of
vitamin A by women during the reproductive
years. IVACG, Washington DC
177. Reddy V, Sivakumar B (1972). Studies on
vitamin A absorption. Indian Pediatr
9:307-310
178. Reddy V, Srikantia SG (1966). Serum vitamin
A in kwashiorkor. Am J Clin Nutr 18:34-7
179. Solon FS, Popkin BM, Fernandez TL et al
(1978). Vitamin A deficiency in the Philippines:
a study of xerophthalmia in Cebu. Am J Clin
Nutr 31:360-8
180. Solon FS, Latham MC, Guirriec R et al
(1985). Fortification of MSG with vitamin A: the
Philippine experience. Food Tech 39:71-9
181. Olson JA (1991). Vitamin A. In: Handbook of
Vitamins, 2nd ed. (ed Machlin LJ) pp 1-57.
Marcel Dekker, New York
182. Olson JA (1996). Biochemistry of vitamin A
and carotenoids. In: Vitamin A Deficiency:
Health, Survival, and Vision (eds. Sommer A,
West KP Jr) pp 221-250. Oxford University
Press, New York
183. Cohen N, Rahman H, Mitra M et al (1987).
Impact of massive doses of vitamin A on
nutritional blindness in Bangladesh. Am J
Clin Nutr 45:970-6
184. Sommer A, McLaren DS, Olson JA (1976).
Guidelines for the evaluation of vitamin A
deficiency and xerophthalmia. IVACG,
Washington, DC
185. WHO (1976). The prevention of blindness.
WHO Chron 30:391-7
186. WHO (1992). Prevention of childhood blindness. WHO, Geneva
187. McLaren DS (1980). What to do about basic
medical science. Br Med J 281:171-2
188. WHO/UNICEF/IVACG Task Force (1988).
Vitamin A supplements. A guide to their use
in the treatment and prevention of vitamin A
deficiency and xerophthalmia. WHO, Geneva
189. Meguid MM, Landel AM, McLaren DS
(1988). Plasma carotenoid profiles in normals
and patients with cancer. J Par Ent Nutr
12:147-151
190. McLaren DS (1986). Nutrition/metabolism
classic: a study of factors underlying the
special incidence of keratomalacia in Oriya
children in the Phulbani & Ganjam districts of
Orissa, India. Nutr Intern 1:100-7
191. Kothari G, McLaren DS (1993). Keratinization in buccal mucosa – a practical index of
vitamin A nutriture. Bombay Hosp J 35:65-70
192. Kothari G, McLaren DS (1995). Assessment
of vitamin A nutriture in preschool children –
a multi approach. J Trop Pediatr 41:290-4
193. Potter AR (1991). Avoidable blindness.
Br Med J 302:922-3
194. McLaren DS (1991). Avoidable blindness.
Br Med J 302:1204
137
References
195. Kupfer C (1994). The International Agency
for the Prevention of Blindness. Am J
Ophthalmol 117:253
196. McLaren DS (1994). The International
Agency for the Prevention of Blindness.
Am J Ophthalmol 118:405-6
197. Kupfer C (1994). Reply. Am J Ophthalmol 118:407
198. Johnson GJ, Cartwright E (1996). Global
Perspectives on the Control of Blindness.
International Centre for Eye Health, London
199. Johnson GJ (1999). Prevention of visual
impairment. Submitted for publication
200. Dolin PJ, Faal H, Johnson GJ et al (1997).
Reduction of trachoma in a sub-Saharan
village in absence of a disease control programme. Lancet 349:1511-2
201. McLaren DS (1996). Xerophthalmia and
vitamin A. pp 378-385 In:Illustrated History
of Tropical Diseases (ed. Cox FEG),
Wellcome Trust, London
202. Arthur P (1998). Global situation of vitamin A
deficiency. Report of XVIII International
Vitamin A Consultative Group Meeting, 22-26
September 1997, Cairo, Egypt
203. Sommer A (1982). Nutritional Blindness:
Xerophthalmia and Keratomalacia. Oxford
University Press, New York
204. Sommer A, Hussaini G, Muhilal et al (1982).
History of night blindness:a simple tool for
xerophthalmia screening. Am J Clin Nutr
33:887-891
205. Sommer A, Emran N, Sugana T (1980).
Clinical characteristics of vitamin A responsive
and nonresponsive Bitot’s spots. Am J
Ophthalmol 90:160-171
206. Sommer A, Emran N, Tamba T(1979). Vitamin A-responsive punctate keratopathy in
xerophthalmia. Am J Ophthalmol 87:330-3
207. Sommer A, Tjakrasudjatma S, Djunaedi E et
al (1978). Vitamin A-responsive panocular
xerophthalmia in a healthy adult. Arch
Ophthalmol 96:1630-4
138
208. Sommer A, Tarwotjo I, Hussaini G (1983).
Increased mortality in children with mild
vitamin A deficiency. Lancet ii:585-8
209. Sommer A, Tarwotjo I, Katz J (1987).
Increased risk of xerophthalmia following
diarrhea and respiratory disease. Am J Clin
Nutr 45:977-980
210. Herrera MG, Fawzi WW, Nestel P (1996).
Effect of vitamin A supplementation on the
incidence of cough, diarrhea, and fever. XVII
IVACG Meeting Report, Guatemala City, p 95.
The Nutrition Foundation, Washington, DC
211. Sommer A, Tarwotjo I, Djunaedi E et al
(1986). Impact of vitamin A supplementation
on childhood mortality. A randomised controlled community trial. Lancet i:1169-1173
212. Beaton GH, Martorell R, Aronson KJ et al
(1993). Effectiveness of vitamin A supplementation in the control of young child morbidity and
mortality in developing countries. ACC/SCN
State-of-the-art Series, Nutrition Policy Discussion Paper no 13, United Nations, Geneva
213. Ross AC (1996). The relationship between
immunocompetence and vitamin A status.pp
251-273. In: Vitamin A Deficiency: Health,
Survival, and Vision. (eds. Sommer A, West KP
Jr), Oxford University Press, New York
214. Semba R (1998). The role of vitamin A and
related retinoids in immune function. Nutr Rev
56, no 1 (Part II) S38-48
215. Hussey GD, Klein M (1990). A randomized,
controlled trial of vitamin A in children with
severe measles. N Eng J Med 323:160-4
216. Coutsoudis A, Bobat R, Coovadia HM et al
(1994). Vitamin A prophylaxis reduced morbidity
in HIV-1 infected infants: a controlled trial. XVI
IVACG Meeting Report, Chiang Rai, Thailand.
The Nutrition Foundation, Washington DC
217. Wolf L, Keusch GT (1999). Nutrition and
infection. In: Modern Nutrition in Health and
Disease 9th ed (Shils ME, Olson JA, Shike
M, Ross AC eds.) pp 1569-1588, Baltimore,
Williams & Wilkins
SIGHT AND LIFE
218. WHO/UNICEF (1987). Joint statement on
vitamin A for measles. Wkly Epidemiol Rec
62:133-4
219. Yorston D, Foster A (1992). Corneal ulceration in Tanzanian children: relationship between malaria and herpes simplex keratitis.
Trans R Soc Trop Med Hyg 86:456-7
220. WHO/CND Immunisation-Linked Vitamin A
Supplementation Study Group (1998).
Randomized trial to assess benefits and safety
of vitamin A supplementation linked to immunisation in early infancy. Lancet 352:1257-1263
221. Maciaszek J, Talmage DA, Viglianti GA
(1994). Synergistic activation of simian immunodeficiency virus and human immunodeficiency virus type I transcription by retinoic acid
and phorbol ester through an NF-kappa Bindependent mechanism. J Virol 68:6598-6604
222. WHO (1996). Indicators for assessing vitamin
A deficiency and their application in monitoring and evaluating intervention programmes,
WHO, Geneva
223. Tanumihardjo SA, Koellner PG, Olson JA
(1990). The modified relative-dose response
assay as an indicator of vitamin A status in a
population of well-nourished American
children. Am J Clin Nutr 52:1064-7
224. Haskell MJ, Islam MA, Handelman GJ et al
(1998). Plasma kinetics of an oral dose of
[2H4] retinyl acetate in human subjects with
estimated low or high total body stores of
vitamin A. Am J Clin Nutr 68:90-5
225. Wittpenn JR, Tseng SCG, Sommer A (1986).
Detection of early xerophthalmia by impression
cytology. Arch Ophthalmol 104:237-9
226. Luzeau R, Carlier C, Ellrodt A et al (1988).
Impression cytology with transfer: an easy
method for detection of vitamin A deficiency.
Int J Vitamin Nutr Res 58:166-170
227. Lietman TM, Dhital SP, Dean D (1998).
Conjunctival impression cytology for vitamin A
deficiency in the presence of infectious trachoma. Br J Ophthalmol 82:1139-1142
228. Congdon N, Sommer A, Severns M et al
(1995). Pupillary and visual thresholds in
young children as an index of population
vitamin A status. Am J Clin Nutr 61:1076-1082
229. McLaren DS (1998). The epidemiology of
vitamin A deficiency disorders. In: The Epidemiology of Eye Disease (Johnson GJ,
Minassian DC, Weale R eds.) pp 209-225,
Chapman & Hall, London
230. Garcia-Casal MU, Layrisse M, Solano L et al
(1998). Vitamin A and β-carotene can improve
nonheme iron absorption from rice, wheat and
corn by humans. J Nutr 128:646-650
231. Blomhoff R, Green MH, Green JB et al
(1991). Vitamin A metabolism: new perspectives on absorption, transport, and storage.
Physiol Rev 75:951-1027
232. Christian P, Schulze K, Stoltzfus RJ et al
(1998). Hyporetinolemia, illness symptoms,
and acute phase protein response in pregnant
women with and without night blindness.
Am J Clin Nutr 67:1237-1243
233. Rosales FJ, Ross AC (1998). A low molar
ratio of retinol binding protein to transthyretin
indicates vitamin A deficiency during
inflammation:studies in rats and a posteriori
analysis of vitamin A-supplemented children
with measles. J Nutr 128:1681-7
234. Alvarez JO, Salazar-Lindo E, Kohatsu J et al
(1995). Urinary excretion of retinol in children
with acute diarrhea. Am J Clin Nutr 61:1273-6
235. West KP Jr, Katz J, Khatry SK et al (1999).
Double-blind, cluster randomised trial of lowdose supplementation with vitamin A or βcarotene on mortality related to pregnancy in
Nepal. Br Med J 318:570-5
236. Baly DL, Golub MS, Gershwin ME et al
(1984). Studies on marginal zinc deprivation in
rhesus monkeys. III. Effects on vitamin A
metabolism. Am J Clin Nutr 40:199-207
237. Shankar AH, Prasad AS (1998). Zinc and
immune function: the biological basis of altered
resistance to infection. 68 (Suppl 2), 447-463
139
References
238. Pelletier DL, Frongillo EA Jr, Schroeder DG
et al (1995). The effects of malnutrition on
child mortality in developing countries. Bull
World Health Organ 73:443-8
239. Bulux J, Quan de Serrano J, Guiliano A et al
(1994). Plasma response of children to shortterm chronic β-carotene supplementation. Am J
Clin Nutr 59:1369-1375
240. de Pee S, West CE, Muhilal et al (1995). Lack
of improvement in vitamin A status with increased consumption of dark-green leafy
vegetables. Lancet 346:75-81
241. King M (1990). Health is a sustainable state.
Lancet 336:664-7
242. World Bank (1993). World Development
Report: Investing in Health. World Bank,
Washington DC
140
243. Humphrey JH, West KP Jr, Sommer A
(1992). Vitamin A deficiency and attributable
mortality among under-5-year-olds. Bull
World Health Organ 70:225-232
244. Stoltzfus RJ (1998). Thoughts on micronutrient surveillance. Xero Club Bull
no 67: 1-3
245. Santos LMP, Dricot J, Asciutti LS (1983).
Xerophthalmia in the state of Paraiba,
Northeast Brazil: clinical findings. Am J
Clin Nutr 38:139-144
246. Schuftan C, Ramalingaswami V, Levinson
FJ (1998). Micronutrient deficiencies and
protein-energy malnutrition. Lancet
351:1812
247. United Nations (1990). World Summit for
Children, United Nations, New York
SIGHT AND LIFE
Index
A
acute phase response 119, 124
Ali Ahmad Saloum 89-91
American Society of Nutritional Sciences (ASNS)
89
American University of Beirut (AUB) 74-78, 85,
89, 96, 106
Aomari LL 103
Aravind Eye Hospitals 95
Arroyave G 96, 100, 110
Audeh Z 109
B
Baba N 78
Bagchi K 49-52, 87
Bang FB 97
Baptist Missionary Society 36, 40, 43-44
Bauernfeind JC 102
beriberi 18, 20-21, 37, 75, 116
Bitot’s spot (X1B) 14, 65-69, 82, 86, 92, 117-118,
124
Bliss D 78
British Empire (Commonwealth) Society for the
Blind (see Sight Savers)
Burma 53
C
cancer of the oesophagus 97, 99
Carey W 43
carotenoids 19, 21, 23, 87-89, 111, 120
cataract 65, 107-108, 115
Chichester CO 102, 104
China 28, 30, 36, 99
cod-liver oil 14, 17, 19-20, 22
Cohen N 101
Columbia University 89
conjunctival impression cytology 118
conjunctival xerosis (X1A) 16, 19, 124
corneal scar (XS) 81, 84
corneal xerosis (X2) 117
Cullen W 34
D
Darby WJ 53-54, 58, 59-60, 62-63, 65-66, 73-74,
88, 93
dark adaptation 19, 66, 68
dark green leafy vegetables (DGLV) 89
Davidson Sir LSP 34-35, 74
Davson H 50
DeMaeyer EM 102-104, 110
demographic entrapment 121
diarrhoeal disease 86
discrete colliquative keratopathy (DCK) 69
Doesschate, J ten 61, 104
Doll Sir R 51-52
Duke-Elder Sir S 60, 83
duodenal ulcer 44
E
East African Institute for Medical Research 55-57
Ebers papyrus 15
Edinburgh 33-34, 74, 106, 108-109
Escapini H 70, 75, 77, 79
Ethiopia 65
F
Florentino R 110
Food and Agriculture Organization
(FAO) 88-89
Forman M 99-100, 102
Foster A 65
Frazer Sir J 44
G
Ghana 38
Gogo 56-57, 60
141
Index
H
haemoconcentration 83
Helen Keller International (HKI) 110
hemeralopia 16
Hill Sir AB 51
Himsworth Sir H 74
HIV infection 118
Hodges R 104
Holmes E 55-57, 59
Hong Kong 72
Horwitz A 103
Human Nutrition Research Unit (HNRU) 48
Hutchison Sir R 35
I
India 36, 40, 46, 97
Indonesia 52-54, 61, 89, 96-97, 109, 117
Interdepartmental Committee on Nutrition for
National Defense (Development) (ICNND)
59, 65, 67, 82, 88, 93
International Agency for Research on Cancer
(IARC) 97, 99
International Centre for Eye Health (ICEH) 10, 113
International Nutritional Anemias Consultative
Group (INACG) 100
International Vitamin A Consultative Group
(IVACG) 10, 61, 79, 94, 100, 102-106, 110,
114, 117, 127
Iran 97
Irinoda K 71-72
iron 99
J
Jelliffe DB 48, 88
Johnson GJ 112, 114-115
Journal of Tropical Pediatrics 48
K
Kamel WW 82, 85-86, 102
Kanawati A 109
Karyadi D 102, 110
keratomalacia 13-14, 16, 19-21, 40-41, 44, 49, 54,
63, 65, 67, 80, 82-84, 88, 90, 95, 112
Khond Hills 36, 40, 43-44, 92
142
King G 62-63
Kirkwood B 38
Kissinger H 99
Kothari G 112
Kupfer C 102, 114
kwashiorkor 42, 47, 79, 90
L
Lebanon 77, 106, 108
leprosy 65, 68
Liebig J von 18
liver 13-15, 86
liver, cirrhosis of 45
Livingstone D 14
Lloyd George D 26
London 26, 30, 48
London School of Hygiene and Tropical Medicine
37-38, 48, 51-52
Luapula valley 75
M
Madurai 95
malaria 45
Manila 70, 72
Mannheimer E 88
Manson Sir P 38
McCance R 50
McKigney J 104
McLaren AS 115
McLaren GS 40, 49, 70, 88, 92, 106, 115
McLaren HJ 92, 115
McLaren JM 49, 70, 92, 98, 106, 115
McLaren OM 33, 36, 40, 70, 73-75, 88, 92, 104,
106, 108
measles 14, 22, 65, 80, 87, 118
Meguid MM 111
Mellanby Sir E 38
meriah 44
Metropolitan Tabernacle 26, 28, 30
Modified relative dose response 118
Morley D 47
Mudambi, S 112
Mvumi 64-65
Mwanza 60, 64-65, 74-76
SIGHT AND LIFE
N
Nair NVK 110
National Institute for Medical Research 51
National Institute of Nutrition, Hyderabad 100
National Institutes of Health (NIH) 59, 63-64, 74, 114
Nigeria 88
night blindness (XN) 13-16, 82, 86, 117-118
nutrition 34, 37-38, 77
nutrition rehabilitation centre 95
nyctalopia 16
O
Olson JA 100, 103, 106
onchocerciasis 52, 65, 68-69, 107-108, 114
Oomen HAPC 50, 55, 58-61, 75, 77, 79, 85, 89,
94, 96, 103, 114
Osler Sir W 47
Overseas Missionary Fellowship 28
P
Pan American Health Organization (PAHO) 93
Pararajasegaram R 104, 110
Passmore R 35, 48, 106
Paton D 66-67, 70, 83
Patwardhan VN 58-59, 75, 77, 82, 86, 93
Pearson WN 93
pellagra 18, 20-21, 116
perifollicular hyperkeratosis 21, 40
Pettiss S 103
Pirie A 49, 94-95, 103
Platt BS 37-38, 48, 50, 52, 55, 58, 74
Pradilla A 110
Princeton conference 58, 60
protein-energy malnutrition (PEM) 77, 80, 82,
87-88, 126
puerperal sepsis 22
R
Read WWC 108-109
red palm oil 87-88, 97
refractive errors 65
Reigate 30, 32
relative dose response (RDR) 118
respiratory disease 22, 118
retinol (see vitamin A )
retinol equivalent (RE) 89
rheumatic fever 29, 33
rheumatoid arthritis 17
rhodopsin 13, 19
riboflavin 98-99
rickets 14, 18, 20-21, 116
Ross D 38
S
schistosomiasis 57
Schweitzer A 30, 89
Scotland 31
Scrimshaw NS 58, 70
scurvy 18, 20-21, 116
Sebrell WH Jr 47, 59, 63, 73-75, 79
sharu 15-16
Shirajian E 85
SIGHT AND LIFE 9-10, 100, 113, 115,
117, 126
Sight Savers 52, 68, 75, 94-96, 112
Singapore 92
skim milk 63, 80
slit lamp microscope 67
Smelser G 64, 70
Smith D 37-40
Solon F 100
Sommer A 96-97, 103-104, 106,
109-110, 117
Spurgeon CH 26, 28
Spurgeon’s Orphan Homes 30
St John Ophthalmic Hospital 83
T
Tanganyika (Tanzania) 60
Teng Khoen Hing 91-92
Teply LJ 103
thiamin 75
Tokyo 71
trachoma 65, 85, 107-108, 114
Trousseau A 17-18
Turkoman 97
143
Index
U
Underwood B 96, 100, 103, 110
United Nations Children’s Fund (UNICEF) 63,
100, 104, 110, 118
United Nations Relief and Works Agency
(UNRWA) 85
V
Venkataswamy G 95, 103-104
Vester BS 84
vision restoration test 119
visual purple ( see rhodopsin)
vitamin A 13, 15, 17, 19, 20-21, 23, 40-41,
46, 62, 64, 77, 80, 83-84, 97, 99, 108
and growth 80, 119
and haemopoiesis 119
and zinc 119
anti-infective vitamin 17, 21-22
immunisation and 118
in breast milk 118
in serum 66, 69, 81-82, 86
interventions 118
intramuscular 100
loss in urine 119
meta-analysis 118
prophylaxis 86-87, 121-122
vitamin A deficiency (VAD) 13, 15, 17, 23,
40, 46, 51, 59-60, 63, 65-66, 69, 77,
79, 81, 83, 85-86, 88, 93, 96-97, 99,
111, 117-118, 120
vitamin A deficiency, control of 120
history of 115
mortality and 19, 54, 82, 86-87,
117-119
144
prevalence of 82, 109, 117, 120
Vitamin A Deficiency Disorders (VADD)
9-10,13, 25, 38, 46, 57, 67, 77, 89,
94, 105, 112-116, 121
neglect of 73
vitamin C 63
vitamin D 21, 63
vitamin E 17
W
Warren O 28
Waterlow JC 38
Williams CD 38, 42, 46-48
Williams RR 75
Wilson Sir J 52, 75, 94, 96, 108
Woodruff A 68
World Health Organization (WHO) 52-53,
55, 61, 69, 75, 77, 82, 85-87, 92-93,
96, 104, 106, 109-111, 118, 120
Worthing 113
X
xerophthalmia, 13, 15, 19-20, 22, 37, 40,
50-52, 54-55, 60-63, 65, 70-71,
73-76, 79-83, 87, 89, 95-97, 99,
107-108, 116-117
xerophthalmia, global survey of 69
neglect of 52, 106
notification of 85-86
problems with 122-126
Xerophthalmia Club Bulletin 9-10, 49, 60-61,
94, 96, 100, 115, 126
xerophthalmia rehabilitation centre 95
xerophthalmic fundus 91-92, 117