research - edition 27 - research

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research - edition 27 - research
The Bayer Scientific Magazine
EDITION 27 | December 2014
Revolution in the plant kingdom
Innovative crop protection against global pests
Healthy
bees
Screening
in 3D
Special report:
The protein engineers
Safety in the hive
and the field
High-tech for new
cancer therapies
Life science research in medicine
and crop protection
EDITORIAL
Innovations for humans,
­animals and plants
Point of view
2
News
4
Masthead 
49
MEDICINE
Screening in 3D
Using high-tech to search for new
drugs
6
A matter of form
Active ingredients under the
light microscope
Sights set on the eye
Eye drops for a healthy retina Two-fold effect
New treatment for endometriosis
19
20
44
MATERIALS
Dr. Marijn Dekkers, Chairman of the Board of Management of Bayer AG
Dear reader,
Our success is based on change. One of the ways that we change is by strengthening our company with acquisitions and extending our worldwide collaboration
network. In early October, for example, we completed the acquisition of the
consumer care business of Merck & Co., Inc. for US$14.2 billion. And just a few
weeks ago, we announced one of the biggest ever changes in the evolution of
Bayer: in the future, we will concentrate entirely on our Life Science businesses.
This significant step will lead to the emergence of two global companies:
Bayer will become a pure life science company that is respected for its success in
science and innovation – something we can build on, while MaterialScience, as
an independent company with direct access to the capital market, will be able to
focus on the crucial factors for success in the global high-tech polymers market.
Bayer, as a global life science company, will continue to generate value through
its achievements in the research-intensive areas of medicine and state-of-the-art
agriculture. Our main focus is always on novel molecules that act on molecular
pathways. We conduct research in the fields of human, animal and plant health,
and combine all of these activities under one roof. We are committed to innovation,
and this ongoing commitment is reflected not only in our increased research
budget but also in our deliberate strengthening of interdisciplinary research – in
line with our mission “Bayer: Science For A Better Life.”
Best regards,
Magic materials
Sustainable textile coatings
28
AGRICULTURE
Cover story:
Revolution from the ground up
Integrated strategy for
nematode control
Profile
Coralie van Breukelen-Groeneveld
Protecting a precious resource
Water conservation in agriculture
10
37
48
DOSSIER
Healthy pollinators – high-quality
harvests
Help for bees
38
SPECIAL FEATURE
The protein engineers
Highly effective protein molecules
for medical and plant research
32
FOUNDATIONS
Bayer foundations promote science,
medicine and social innovation
24
CONTENTS
Cover story
Magic materials
28
Revolution from the ground up
Today’s textiles have to be robust, comfortable to
wear and above all produced sustainably. Bayer
researchers are helping to make this a reality with
the new INSQIN™ coating technology.
Sights set on the eye 20
Tiny pests: nematodes cause huge harvest losses worldwide. Bayer scientists have now developed an integrated crop protection strategy to combat the global pest. Jaap Smedema tests optimized formulations of new
nematicides in the laboratory (above). Dr. Heiko Rieck and Anja Niggemeier
(small photo, left to right) check the properties of these active substances
under a sprinkler system that simulates tropical rainfall.
10
Bayer Foundations
Bayer scientists are currently testing the active
ingredient regorafenib as a potential treatment
for wet age-related macular degeneration. As eye
drops, it could represent a new alternative to
­conventional treatments.
24
Photos: Ingo Rappers/WiWo (1), Peter Ginter/Bayer AG (3), Zhang Chi/Studio Stare/Bayer AG (1), Marcus Müller-Saran (1), Sabine Bungert/Bayer AG (1), Bayer AG (1)
Bee health dossier
38
The Bayer Science & Education Foundation supports
frontier research and talents in life sciences and
­medicine. The Bayer Cares Foundation invests in social
innovations like the healthcare app “Explain TB.”
Special feature
The protein engineers
In the search for new drug targets and diagnosis
options, Bayer scientists are collaborating
with crop protection experts and medical
specialists in an interdisciplinary project.
32
Bees help farmers all over the world produce food crops. But these busy workers need help themselves at the moment, for example in the battle against the
lethal Varroa mite. Bayer scientists are working to improve bee health, both in
the hive and in the field.
Bayer research 27 December 2014
1
PACKAGING ARTISTS
Drug products are sensitive. To ensure that they are fully effective, they need packaging that will provide optimum
protection right up until the time when they are used. That’s why Bayer scientists not only work intensively on new active
substances but also develop safe and innovative packaging technologies. After all, the pharmaceutical quality of a drug
product must be assured all the way through to the expiry date – provided that it is stored according to instructions.
Equally important is that the packaging is protected against external manipulation. Bayer employee Nancy Lück checks
a robot that packs a drug in tablet form into blister strips in a Bayer HealthCare facility in Berlin.
2
Bayer research 27 December 2014
Photo: Peter Ginter/Bayer AG (1)
POINT OF VIEW
Bayer research 27 December 2014
3
Corporate strategy
Concentration on Life Sciences
Bayer has decided to realign its business. The
company plans to focus in future entirely
on the Life Science businesses – HealthCare
and CropScience – and float Material­Science
on the stock market as a separate company. In this way Bayer is positioning itself
as a world-leading company in the field of
human, animal and plant health (see edi-
torial). “Our intention is to create two top
global corporations: Bayer as an innovation
company of world rank in the Life Science
businesses, and MaterialScience as a leading
player in polymers,” Bayer CEO Dr. Marijn
Dekkers announced. He said both companies
have excellent prospects for success in their
respective industries. In recent years, Bayer’s
Times of change: Bayer is strengthening its expertise in the Life Sciences and plans to carve
out MaterialScience as an independent world-ranking industrial company. The photo shows Bayer
HealthCare employee Julin Tong in the laboratory in Morristown, New Jersey, USA.
center of gravity has greatly shifted toward
its Life Science activities with the successful
launch of novel pharmaceutical products, the
acquisition of the over-the-counter products
business of Merck & Co., Inc., United States,
and the very successful development of the
CropScience business. About 70 percent of
­Bayer’s sales today are generated by the Life
Science businesses. The aim is to continue
the positive development of these activities
in the future through further investment in
growth. “Bayer will continue as an enterprise
with an attractive and balanced portfolio and
a primary focus on organic growth,” Dekkers
explained. To this end, the company intends
to raise its research and development spending, selectively strengthen early research at
the interface between HealthCare and CropScience, and continue driving the successful
commercialization of the recently launched
pharmaceutical products.
The aim is to float MaterialScience on
the stock market as a separate stock corporation by mid-2016 at the latest. “We firmly
believe that MaterialScience will use its
­separate status to deploy its existing strength
even more rapidly, effectively and flexibly
in the global competitive arena,” Dekkers
commented.
Paraguay
Soy is an essential crop for the global food supply. Bayer CropScience is
therefore strengthening its business with the high-protein beans and to
this end has acquired the seeds business of Granar S.A., headquartered
in Encarnacion, Paraguay. Granar – established in 2001 – specializes in
the breeding, production and marketing of improved seed, especially
soybean seed, that is adapted to the growing conditions in subtropical
regions. “Soybeans are a crop with great strategic importance for the
region and for Bayer CropScience. This acquisition gives us access to
quality germplasm for future variety and trait development,” said Eduardo Estrada, Head of Bayer CropScience Latin America. For Bayer CropScience, this acquisition represents one more step towards achieving
an international soybean seed platform. It also underscores the importance of the Latin American region for the soybean seed business. The
company has announced various acquisitions over the past three years,
primarily in Brazil.
4
Bayer research 27 December 2014
Bayer scientists like Bernard Pelissier are working on breeding improved
soybean seeds.
Photos: Peter Ginter/Bayer AG (2), Dirk Hansen/Bayer AG (1), Michael Rennertz/Bayer AG (1)
Developing soybean seeds
NEWS
Further development
Aspirin with enhanced action
Acute pain relief: Bayer Bitterfeld produces the
new, improved Aspirin™ tablet in a new production facility.
Doctors have been using Aspirin™ containing
the active ingredient acetylsalicylic acid for the
treatment of pain for 115 years, and now Bayer
HealthCare has launched a new, improved
tablet formulation of the product, with a new
micro-active technology that ensures that
the new presentation delivers meaningful
pain relief twice as fast as the previous formulation. The active ingredient particles are
smaller and dissolve particularly rapidly in the
body. In addition, a coating has been added
to the new Aspirin™ tablet to make it easier
to swallow. “We are extremely proud that we
have overcome this technological production
challenge so successfully,” said Dr. Christian
Schleicher, Managing Director of Bayer Bitterfeld GmbH, where the new generation of
Aspirin™ tablets is manufactured. The company
has manufactured Aspirin™ in various presentations for more than 50 countries around the
world since August 1995. The 100 billionth
tablet from the range of OTC drugs is scheduled to roll off the conveyor belt in Bitterfeld
in 2015.
Japan
Crop protection and Seeds
Bayer forms alliance with
Kyoto University
US$1 billion for the United States
Bayer HealthCare and Kyoto University have signed a two-year collaboration agreement aimed at identifying approaches for future alliances in
which the two organizations will conduct joint research into cancer and
heart disease, ophthalmology, gynecology and hematology. Bayer plans
to support these projects by contributing its global research and development expertise with the company’s recently established Open Innovation
Center Japan in Osaka. The University’s SACI (Society-Academia Collaboration for Innovation) is also playing a key role. “Our common mission is to
bridge the gap between fundamental research and new drug development,
and thus also strengthen university research,” said Kyoto University.
Bayer CropScience is expanding in the United States. The objective of
this major project: to grow faster than the U.S. market. Bayer CropScience sees positive long-term market developments in North America and is therefore committing significant resources to spur further
growth. The company plans to invest nearly US$1 billion in the United
States through 2016, primarily to expand its research and development
and the production of its principal crop protection brands. “There is
increasing and sustained demand from customers for improved seeds
and innovative crop protection products,” said Bayer CropScience CEO
Liam Condon at the official inauguration of the company’s new integrated R&D site in West Sacramento, California. The company is also
establishing new locations and expanding existing sites.
Ophthalmology
Sharp vision despite diabetes
The risk of eye diseases is particularly high for people with diabetes:
3 to 4 percent of diabetics are affected with visual impairment due to
so-called diabetic macular edema (DME), which can lead to blindness.
Bayer HealthCare has developed a promising therapy for the treatment
of DME in close collaboration with its partner Regeneron in the United
States: an injection of the active ingredient into the vitreous body of
the eye. DME is a common microvascular complication that occurs
when fluid leaks into the center of the macula, the part of the retina
responsible for sharp, direct vision. Fluid in the macula can cause severe
vision loss or blindness. The clinical Phase III study program has shown
that treatment with the Bayer drug is more effective for visual acuity
than conventional laser therapy. After approval of the drug in the USA
and Europe, Bayer has also recently been granted regulatory approval
for DME in Japan.
Clear vision: researchers at Bayer HealthCare are developing innovative
therapeutic options for eye diseases.
Bayer research 27 December 2014
5
Always on the lookout for nutrients: tumor cells (pink) grow between the pulmonary alveoli (turquoise).
6
Bayer research 27 December 2014
3D tumor screening MEDICINE
BAYER RESEARCHERS USE INNOVATIVE METHODS TO TRACK DOWN EFFECTIVE DRUGS FOR FIGHTING CANCER
Screening in 3D
The purpose of chemotherapy is to destroy all cancer cells in the body – and heal the patient. Using a process known
as 3D tumor screening, Bayer researchers are heading in a new direction in the hunt for active substances that may be
able to supplement conventional therapies and make them more effective.
Tumors are extremely voracious. To
grow – and for their cells to keep dividing – they need vital substances from
a patient’s blood. New blood vessels
therefore form and grow into the tumor
to supply the cancer cells with oxygen
and nutrients. Frequently, however, a
tumor grows so fast that the blood supply cannot keep up. In consequence, the
cells inside a tumor are undernourished.
They respond to this scarcity of supply
with a trick: they feign sleep, cease to
divide and wait for replenished supplies.
This mechanism is a cause for concern
among cancer researchers and physicians ­everywhere, because many cancer
drugs, known as cytostatics, mainly target the well-nourished cells multiplying
in the peripheral region of a tumor.
Photos: Corbis Creative (1), Matthias Lindner/Bayer AG (1), Bayer AG (2), Privat (1)
Dormant cancer cells can
wake up again at any time
They attack these sites directly, put a
stop to cell division and shrink the diseased tissue. Frequently, however, a tiny
core of the tumor remains behind after
chemotherapy: the dormant cells inside
the tumor. It is these cells that can reawaken all too quickly in some cases and
continue to grow when the supply of
nutrients from the blood resumes after
treatment has ended.
“This is one of the main reasons why
a cancer can reoccur even after apparently successful treatment,” explains
Dr. Patrick Steigemann, a biologist who
works in Lead Discovery at Bayer HealthCare. To prevent such an outcome, he
new cancer drug that joins forces with
standard cytostatics to attack these
sleeping cancer cells as well and thus
minimize the risk of recurrence. “There’s
still a gap here in cancer treatment,”
Steigemann says.
Searching for a completely
new active ingredient
3D tumor spheroids on the screen:
Dr. Steigemann and his colleagues have
essentially taught the computer how to
see. This technology is very useful in the
search for suitable candidates among
approximately 500,000 substances.
and his colleagues in oncology research
are studying how to also effectively
eliminate the dormant cells inside tumors in the course of chemotherapy.
Their long-term goal is to develop a
Searching for an active substance with
these characteristics is like searching for
the proverbial needle in the haystack.
“The known substances obviously don’t
help us at all; we need an entirely new
active substance,” Steigemann says. He
and his colleagues therefore started off
by consulting Bayer’s in-house substance
library encompassing some three-anda-half million compounds, and together
with the experts from Medicinal Chemistry initially selected 500,000 sub­stances
that were as diverse as possible. “An interesting trail could potentially lead to a
whole range of related substances that
500,000
substances screened
Steigemann and his team are screening
500,000 substances to find potential hits.
Source: Bayer
Bayer research 27 December 2014
7
Inside the tumor
For cancer treatment to be successful, every last tumor cell must be eliminated. If any remain, new tumors can quickly develop
again, leading to a recurrence of the disease. Bayer scientists are therefore looking for a substance that primarily targets the cells
inside the tumor and, combined with conventional cytostatics, has the potential to completely eradicate the cancer cells.
With conventional
chemotherapy, the risk
remains that dormant
cells are left intact.
Lung tumor
The outer cell layer of a lung tumor divides very quickly. The cells on the inside however are under­
supplied with nutrients. They therefore switch into energy-saving mode: they stop dividing, feign sleep
and wait for the supply to recommence.
This plate with 96 wells is filled with spheroids
treated with substance candidates. After 72
hours in the incubator, the results are visible: in
the middle of the second row from the top, one
tumor spheroid shows the desired outcome of
green on the inside (dead cells) and red on the
outside (living cells). In the center below is a
test substance that has destroyed all the cells,
appearing as a green patch. This active ingredi­
ent is useless. The columns on the left and right
contain reference substances such as respirato­
ry chain toxins and cytotoxic substances.
could include new drug candidates,”
­Steigemann explains.
“We can’t just test these compounds
on individual cancer cells in a Petri dish,
however,” says Steigemann. Since he
and his colleagues are searching for
substances that specifically attack dormant cells in cancerous tissue, they need
access to spatial cell structures that are
as similar as possible to real tumors in
patients, because cancer cells behave differently in the body than individual cells
8
Bayer research 27 December 2014
in a laboratory. “In a tumor, cancer cells
react to one another. And every single
cell reacts in turn with its extracellular
environment,” Steigemann says.
To recreate the situation inside the
human body as realistically as possible
in the laboratory and make possible sequential testing by means of automated
screening, he and his colleagues breed
micro-tumors – microscopically small
cancer structures that act like real tumors in the body. They first fill a nu-
trient liquid and individual cancer cells
into the wells of microtiter plates. Over
a period of four days, the cells inside the
wells in these plastic trays form small,
round cancer cell clusters, also referred
to as tumor spheroids. The researchers
then add a test substance to each well
and place them in incubators heated to
body temperature for three days to give
them enough time to exhibit their effects on the tumor spheroids. Some 320
substances per plate can be screened
3D tumor screening MEDICINE
Guido
­K römer
Bayer scientists use dyes to make the individual parts of the tumor spheroid appear in
different colors. The green elements in the image above are dead cells, the cell nuclei are
red and the cytoskeleton, which is important for mechanical stability, is blue.
“Cancer develops if
the immune system
fails”
research talked to Dr. Guido Krömer from the French
research institution INSERM and Paris Descartes
University in France about current and future developments in cancer research.
in this way using special automated
robot systems.
The subsequent analysis process has
also been automated by the researchers. An automated microscope camera
shoots two photos of the spheroids in
each well, marked beforehand with a
­fluorescent stain: living cells glow red,
dead cells green. The computer superimposes the two images to produce a
two-color photo, which clearly separates the living cells from the dead ones,
thereby showing if the substance has
had the hoped-for effect.
Understanding how cells behave
in their natural environment
“We’ve essentially taught the computer how to see,” Steigemann says.
“High-content analysis” is the term
that he and his colleagues use for this
method. A total of some 2,000 plates
are analyzed in each screening cycle.
Thanks to the new automation technology, the Bayer researchers needed only
three months to complete their analysis instead of several years like before.
“Testing the tumor spheroids helps us
to understand how cells behave in their
natural, three-dimensional environment,
and we can then use this knowledge
for our therapeutic approaches,” says
Steigemann. The images are evaluat-
ed to detect the precise phenotype, or
­visual result, that they are looking for:
a spheroid with as many green, dead
cells inside as possible and a red, living
outer cell layer. The researchers are not
overjoyed about every dead cell they
come across in their trials, however. As
Steigemann says, “Our approach aims to
specifically target only the undernourished, dormant cells inside the tumor.“
If an active substance simply kills off all
cells, without making a distinction, that
usually also includes the healthy cells
in an organism. “We need a therapeutic
window that makes healing possible,” the
scientist explains.
With their high-tech approach, the
active substance detectives at Bayer
have already found promising substance classes among the investigated
compounds. Their task now is to investigate how exactly the substances work
and whether the results in the lab can
be transferred to humans. Only after the
researchers have tested these aspects
sufficiently can they send their active
substances on the long road through
clinical development. It will take at
least ten years before these discoveries
in the laboratory can be turned into a
drug, but Steigemann is optimistic. “The
dream of every cancer researcher is for
his work to be able to help seriously
ill people.”
What has cancer research accomplished in the
last years?
Nowadays, it is possible to understand the particular molecular makeup of each tumor. However,
the most important thing was understanding that
cancer is not just the disease of cells that have adopted a selfish behavior. Rather, cancer is a systemic
disease that can only develop and spread if immunosurveillance – that is the immune system – fails.
What challenges does it meet today?
We have to understand the complexity of the tumor
– at the level of the cancer cells themselves. The
tumor is a system composed of different body cells.
We need to understand the relationships among
these cells because they ultimately drive or suppress
the development of cancer and tumor progression.
What are the most promising approaches?
We are all hoping that the improved understanding
of each tumor on the molecular level will ultimately
lead to a “personalized” therapy. I believe that there
will be spectacular advances in the field of immuno­
therapy. We have the opportunity to stimulate
anticancer immune responses by specific and hence
“personalized” interventions.
www.research.bayer.com/3d-tumorscreening
More information on this subject
Bayer research 27 December 2014
9
Hunting down the global pest: Bayer scientists Marc Rist and Dr. Heiko Rieck (left to right) scrutinize the roots of crop plants in
Monheim in preparation for nematode tests.
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Bayer research 27 December 2014
Cover story AGRICULTURE
SECURING WORLD FOOD SUPPLIES WITH INTEGRATED CROP PROTECTION
Photos: Peter Ginter/Bayer AG (8), Privat (2)
Revolution from the ground up
Enormous harvest losses all over the world are caused by tiny pests – nematodes that
often go unnoticed as they drain crop roots of essential nutrients and open the doors
to other pathogens that damage those roots. Bayer CropScience researchers are now
taking a two-fold approach to control these global pests, combining a completely
new chemical principle with a biological agent. This not only enables them to protect
­banana plantations in Costa Rica against these voracious nematodes, but also ensures
successful harvests for vegetable crops, corn and soybeans on a global scale.
Fresh from the trunk into the water bath: at the Finca Acorsa I near Matina in Costa Rica, Blanca Torres washes still unripe bananas and prepares them
for packaging. From here, they travel all over the world.
Costa Rica is a true Garden of Eden. This Latin American country
situated between the Caribbean and the Pacific Ocean provides
fertile ground for all kinds of important crops like sugar, cocoa,
cotton and different fruits and vegetables. Costa Rican pineapples and coffee are exported all over the world. But the real bestseller is a small and curved yellow fruit, the jewel in Costa Rica’s
crown – otherwise known as the banana. According to the UN
Food and Agriculture Organization (FAO), the country exported
more than two million metric tons of bananas in 2012, with the
majority of them ending up in European and American supermarkets and fruit bowls. But the banana isn’t just a globetrotting
fruit – it is also a healthy and extremely nutritious food, with a
high potassium and magnesium content that strengthens nerves
and muscles. Its combination of vitamins and easily digestible
carbohydrates also provides a quick energy boost after a jog or
as an office snack. “The banana has become a staple food that is
helping to feed the global population. According to the FAO, its
nutrients make it the fourth most important crop in developing
countries after rice, wheat and corn,” says Dr. Heiko Rieck, a project manager at Bayer CropScience in Monheim.
But the banana is at risk, posing a major issue for both Costa
Rica’s economy and the global food chain. The problem is that
the plant is also very popular with nematodes (eelworms). These
tiny pests that wriggle through the soil in search of food have a
preference for the roots of banana plants. They use their sharp
mouthparts to burrow deep into the finely branched structure
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Bayer research 27 December 2014
of the roots and suck out everything that the plant needs for
its survival – both nutrients and water. This method of attack
causes serious damage to the roots, which then begin to decay,
allowing fungi and bacteria to enter the plant and accelerate
the decomposition process. Rieck’s team of researchers at Bayer
CropScience knows all about the main culprit. Radopholus similis,
also known as the “burrowing nematode,” is what is making life
difficult for banana plants. “These eelworms are not even one
millimeter long, but they are one of the ten most destructive
nematodes for plants,” says Rieck.
Nematodes damage harvests in many countries
and crops
Radopholus similis originally comes from the American continent. However, as a result of the globalization of agriculture
and the vegetative propagation that occurs in the banana plant
when shoots or roots are separated from the tree, the parasite has already spread to many countries in Europe, Africa and
Asia, where it is causing huge harvest losses. The effects of other
nematode species on other plants tell a similar story. In fact,
almost every important crop is vulnerable to these subterranean
root vampires. “Soybean cyst nematodes, root knot nematodes
in vegetables, wheat cyst nematodes and both white and yellow
potato cyst nematodes are decimating global harvests of the
most important staple foodstuffs,” says Rieck.
Cover story AGRICULTURE
No chance for hungry root vampires: Bayer employee Jaap Smedema returns plants treated with fluopyram to the greenhouse chambers in Monheim.
Nematodes: a global pest
The threat they represent should not be underestimated. From tomatoes and potatoes to corn and grapes – nematodes cause
immense harvest losses of up to 50 percent in all of these crops worldwide.
Harvest losses
France
Midwest
20 to 30%
5 to 10%
California
up to 20%
China
10 to 30%,
in extreme cases up to 50%
New York
up to 50%
Mexico
up to 40%
South Africa
up to 15% up to 20%
Bayer research 27 December 2014
13
AGRICULTURE Cover story
Crop protection secures
food supplies
The agriculture sector is facing major challenges worldwide – rising
populations, higher demands for food and changing eating habits.
More than seven billion people around the globe now need feeding
every day, and each year the figure increases by another 82 million.
Some 8.8 million people die as a result of famine and its consequences
annually – more than the total for HIV/Aids, malaria and tuberculosis
put together. Every three seconds, someone somewhere in the world
dies of hunger, which is equivalent to the entire population of Berlin disappearing in just 140 days. Without modern crop protection
methods, securing global food supplies is virtually impossible. Wheat
yields for example have been increased by 50 percent since the 1960s.
However, even using pesticides cannot provide absolute crop protection. Currently, only around 60 percent of worldwide harvests can be
secured.
But back to Costa Rica. “Nematodes are one of the most significant threats in banana cultivation,” says Boris Coto Calvo, Head
of Development for Central America and the Caribbean at Bayer
CropScience in Costa Rica. “Up to 20,000 nematodes or even
more can live in 100 grams of banana roots. Once a banana plant
has been severely affected, it is difficult to treat. And without
the nutrients they need, banana trees grow slowly and are late
producing fruit, which furthermore often ends up being smaller
than usual,” says Coto Calvo. In the worst cases, the plants can
fall over and die completely. “Plants are particularly at risk when
they are in fruit,” adds Dr. Helmut Fürsch from Global Agronomic Development at Bayer CropScience. Strong winds frequently
sweep across the coastal plains of Costa Rica, and a fully laden
banana plant that is no longer able to keep a stable grip on the
ground through its roots will simply be knocked down and die.
“Up to 18 percent of all banana plants in Central and South
America that are affected by nematodes are ripped out of the
ground this way,” estimates Coto Calvo.
Harvest losses threaten the existence of both big
farms and small-holdings worldwide
This is a serious loss for farmers, as each banana trunk comes
into fruit only once per lifetime. This means that a whole year’s
work is wasted, which can be disastrous for big farms, but even
more so for small-scale farmers. Besides, banana plants can live
up to 40 years. Once a plant is infected, each new shoot is at risk,
so the farmer’s yield is threatened year after year. “The damage
caused by nematodes is responsible for global harvest losses
worth several hundred million euros,” says Fürsch. This total figure relates to many different countries and farmers of course,
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Bayer research 27 December 2014
Healthy and infected banana roots side by side for comparison:
the cross section of the rotting plant at the front shows clear
signs of pest damage.
but in a developing country, even losing just a few hundred euros can mean the loss of a small-holder’s entire livelihood. For
this reason, Bayer CropScience researchers have already spent
many years looking for an effective nematicide that will also
be safe for both plants and humans. Now the scientists have
found an approach that at first glance seems rather unusual.
The substance that the crop protection specialists are using to
control the greedy eelworms is in fact one that has been used by
fruit and vegetable farmers as a fungicide against harmful fungal
diseases since 2012 – fluopyram.
Discovery of the century: fluopyram is effective
against fungal diseases and nematodes
Rieck and his team received the crucial tip from colleagues in
Costa Rica involved in fungicide research. Initially, the product
had been sprayed as a foliar treatment in banana plants to treat
their leaves against Black Sigatoka. But after their colleagues’
tip the researchers tried out the product in the soil to see if they
could find an additional application method for the fungicide.
This demonstrated for the first time that the substance also benefits the roots and reduces nematode counts. And although only
a relatively low dosage was applied, it had a long-term effect.
“Our researcher Rodolfo Ceciliano and technical manager Omar
Arias, who first observed the nematicidal effect of fluopyram in
bananas, were immensely impressed by the effects observed in
the field trials,” says Dr. Robert Brinkmann from the Global Field
Trials Operations team at Bayer CropScience. He was there in
person for the first tests in Costa Rica in 2009. “I had never seen
anything like it in my twenty years of work – the roots looked
truly healthy,” says Brinkmann, who is still enthusiastic about it
even now. A closer examination under the microscope quickly
brought the team its confirmation – fungicidal treatment using fluopyram also provides protection against nematodes. “Our
objective was to investigate and look for other substances until
we found a new solution that would be both effective and safe
for farmers and consumers,” says Fürsch. Fluopyram met those
Confirmation from laboratory tests: Bayer employee Thekla Taufferner prepares a variety of root samples for high-throughput sensitivity
monitoring, which will show clearly whether the agent has been effective or not.
criteria perfectly. Soon after the first tests, Bayer scientists set
about studying the effects of fluopyram even further in fields
in Costa Rica, the United States, Italy and South Africa, and in
laboratories and greenhouses in Germany.
Marc Rist, a Monheim researcher who works in the Research
Pest Control department at Bayer CropScience, explains how the
substance works. “We ‘switch off’ the nematodes by interrupting their power supply.” This works because eelworms, like any
other living organism, need energy so that they can get into
the banana roots. This is why their cells produce adenosine triphosphate molecules – ATP for short. It is thanks to this cellular
energy source that living organisms can respire, digest food,
move and reproduce. “Fluopyram interferes with these processes by preventing the formation of ATP,” says Rist. The result is
that the nematodes become paralyzed – they remain immobile
and stretched out like needles in the soil until they finally die.
“The substance also affects the early stage of nematode development,” says Fürsch. “The eggs hatch later and the growth of
the next generation of nematodes is interrupted.”
But fluopyram, marketed under the brand names Velum™ and
Verango™, is only one part of the Bayer team’s successful battle
against the nematode problem. The researchers are using this
chemical crop protection product in combination with a natural
organism – the soil fungus Purpureocillium lilacinum strain 251,
“We need new strategies”
research talked to Miguel Quesada Badilla, former head
­nematologist at fruit and vegetable producer Del Monte, about
the global nematode problem.
Miguel
Quesada
How dangerous are nematodes to crops?
Root-knot and cyst nematodes are the two most widespread and
economically important plant-parasitic nematodes. They cause serious losses to all crops, including fruit trees, vegetables, cereals, oil
seeds, flowers, ornamental plants, turf grasses, etc.
Are nematodes a problem outside Costa Rica as well?
The problem has global dimensions. Nematodes are found in almost all habitats. Plant-parasitic nematodes have been described as
the “hidden enemy” due to their microscopic nature and the fact
that they live in the soil. National and international quarantine
measures are crucial to avoid infestation with this pest.
Can nematodes threaten the global food supply?
It is expected that over the next decades farmers will face deadly
crop pests that have never been seen before. Nematode management will then become a huge issue for our food supply. We need
new strategies – especially in developing countries.
Bayer research 27 December 2014
15
The earth from below: agricultural engineer Rodolfo Ceciliano Solis uses his penknife to check the roots of a banana plant,
measure its growth and search for signs of infestation.
16
Bayer research 27 December 2014
Cover story AGRICULTURE
“Without crop protection,
the food supply is at risk”
Experts say that yields would plummet worldwide without crop
protection. research talked to Professor Harald von Witzke, an
agricultural researcher at Humboldt-Universität in Berlin.
Harald
von Witzke
What role does crop protection play in helping to safeguard
­harvests?
How reliable are these figures?
We did a study to compare what happens when we use crop protection products with the outcome when we don’t use them. We
found that the added value generated by using crop protection is
of the order of EUR 4 billion annually in Germany alone. This means
that crop protection in Germany is safeguarding the food supply
for up to 200 million people.
Can you be more specific?
Wheat is a good example. On average, farmers in Germany who use
modern methods have yields that are over 120 percent higher than
those obtained on comparable organic farms. Our study showed
that the difference is less marked with canola, but here too, conventional farmers produce yields that are about 50 percent higher.
Why are there such enormous differences?
Because 40 percent of the world’s potential agricultural production
is still being lost to crop diseases and pests. We could reduce this
by half if farmers all over the world had adequate access to crop
protection.
a so-called biologic, marketed as BioAct™. This product colonizes
nematode eggs so that hatching of larvae is inhibited.
One single treatment per year in combination
with a biologic is sufficient
Consequently, if the fluopyram treatment has already been applied to remove adult nematodes from the soil, using the biologic prevents a new generation from growing and damaging the
plant at a later stage. “This combination of the complementary
technologies of biological agents and fluopyram provides the
best of both worlds,” says Rieck. “The chemical product efficiently
kills off the living nematodes, and the biological substance impairs their reproduction.” The tests so far have shown that this
integrated crop protection strategy is the way forward. Using
fluopyram on its own was already a breakthrough in these tests.
However, in combination with the biologic it is unique because
We only use validated, publicly accessible data. For example, we
use the results generated by farms in the test farm network organized by the Federal Ministry for Agriculture. Every year this
resource documents the differences in yields between conventional and organically operating farms. Never before have such
comprehensive sets of data on yield differences in agriculture
been analyzed.
What do these figures from Germany mean for the global food
supply?
The global demand for food products will more than double in
the first half of the 21st century. The only way for us to meet this
rapidly growing demand is to increase the area under crops or to
improve productivity. The options for increasing the area under
crops are very limited since the amount of land available worldwide for growing food is finite. Our main approach must therefore
be to boost productivity on the land that is already being used for
agriculture. And this is where crop protection plays a major role.
the Bayer substance isn’t just extremely effective – it also offers
farmers some very practical advantages. Just one single application of fluopyram per year along with a biological control
agent or a chemical nematicide that the grower might choose
is enough to protect plantations from nematodes. By contrast,
nematicides used in the past brought a number of disadvantages: “In the 1970s, there were certainly some very effective
nematicides on the market,” says Rieck. “But most of them had
highly toxic properties. Fluopyram as a substance is much less
toxic than the previous products.” For each hectare, farmers had
to treat their plants three to four times each year with several
kilograms of the nematicides, as they were only effective in high
doses. But thanks to the innovation of the Bayer researchers,
that is now history. “Even a dose of 500 grams of fluopyram per
hectare is enough not just to counter a nematode infestation
in the short term, but also to guarantee healthy roots months
after treating the crops,” says Fürsch. An increase in yield is not
Bayer research 27 December 2014
17
AGRICULTURE Cover story
Tests in Costa Rica: Bayer experts Boris Coto Calvo, Rodrigo Olivares and Rodolfo Ceciliano Solis (photo left, left to right) check whether their treatment
with fluopyram has been effective. In Monheim, Bayer employee Katja Twelker counts nematodes that have been paralyzed by fluopyram (photo, right).
the only advantage. Since the banana plants are systematically
strengthened by the fluopyram treatment, farmers who use the
Bayer product also have a reduced need for substances that protect the plants from other diseases. Given the current trend for
increasing health awareness, this is a significant point. “The rise
in consumer expectations regarding quality affects our partners
throughout the entire food chain, including wholesalers such
as Chiquita, Del Monte, Dole and Univeg,” says Heiko Rieck. For
many years now, these companies have been pressing for a sustainable way to keep supermarket shelves sufficiently stocked
with bananas.
75
percent
of potato harvests worldwide would fall
­victim to pests or disease if modern crop
protection was not used.
Source: European Crop Protection Association (ECPA)
Yet fluopyram is securing more than just the world’s supply of
bananas – this integrated strategy works on nearly all species
of nematode, offering improvements for both corn cultivation
and soybean crops. The product is especially effective on rootknot nematodes such as Meloidogyne incognita, which affect
many vegetable varieties and cause considerable quality and
yield losses. Carrots, for example, become deformed and develop characteristic swellings at the roots that are known as galls.
“Carrots with these substantial quality deficits are unfortunately
unmarketable,” says Rist. Affected vegetables can no longer be
18
Bayer research 27 December 2014
sold, with serious consequences for farmers. “For many crops,
this leads to massive yield losses,” estimates Rist, who is currently
further investigating the compound and its effect on tomatoes
and cucumbers.
Well received by farmers and wholesalers
in Costa Rica
All of this explains why fluopyram has caused such a sensation
among banana farmers in Costa Rica and other countries in Central America. “Its popularity with farmers and wholesalers has
been immense,” says Coto Calvo. They praise the product’s ease
of use, the reduced chemical exposure and the health and abundance of roots. The effectiveness of the nematicide is regularly
checked on test fields by researchers such as Fürsch, Brinkmann
and Coto Calvo, who examine the roots after treatment. Their
tests show that the banana plant roots are healthy. However, the
research does not end here. How much fluopyram is taken up by
the root systems of each type of plant? What is the influence of
the soil condition? And how long does fluopyram protect a plant
from infestations by nematodes? These are some of the questions
that researchers at Bayer are looking into in the field, greenhouse
and laboratory. But there is an even more fundamental one: how
can we make sure that farmers all over the world know about
these pests and the damage they can cause? “In many developing
countries, people are not even aware that nematodes can cause
crop failure. Many simply don’t understand why their harvests
are so poor,” Rist explains. “If we manage to raise awareness of
the risk that nematodes pose, we will be contributing to increasing yields – and we will help farmers protect their crops and
secure our global food supply.”
www.research.bayer.com/integrated-crop-protection
More information about this topic
Optimal drug form MEDICINE
USING LIGHT MICROSCOPE TO FIND STABLE CRYSTAL STRUCTURES
A matter of form
An active substance that forms fine needles or tiny cubes is an absolute highlight for researchers. To manufacture a
drug or plant protection agent, scientists need to know what its stable crystalline form looks like, as many substances
only display the desired properties in this state. Bayer researchers therefore structure promising active substances
into a suitable crystalline shape right at an early phase of development in order to obtain crystals with optimum properties, such as the best possible solubility.
Be it a pharmaceutical drug or plant protection ingredient, three factors always
count: the right time, the right place and
the right dose. “A substance must be released in a controlled manner and made
available to an organism at the required
concentration,” explains Dr. Britta Olenik,
a chemist in Global Chemical & Pharmaceutical Development at Bayer HealthCare.
For an active substance to reach its full
potential, it has to be accompanied by an
entire chemical package of additives.
“To be administered effectively, it is
very important for an active substance to
be available in a stable crystalline form,”
Olenik says. Take carbon atoms for instance. They can arrange themselves in
a graphite or diamond lattice, with each
structure leading to different properties.
“Similarly, active substances for drugs or
plant protection agents can crystallize
in different solid shapes,” the chemist
explains. This has an effect on the substance’s properties, for example its solubility or bioavailability.
Photos: Bayer AG (2)
Crystalline form influences the
quality and efficacy
Together with her team, Olenik therefore takes a very close look at the candidate molecules identified in research:
she examines the physical and chemical
properties of each substance and tests
the different salts to determine which
display, say, the best solubility. Then she
analyzes the crystals, for example under
the microscope. In a process known as
polymorphism screening, Olenik tries to
identify and characterize all crystalline
forms of candidate active substances.
“With the help of thermomicroscopy,
we observe how our substances melt on
exposure to polarized light to form new
and different crystals. We can actually see
how the bonds change and the molecules
re-organize to form new lattice structures,” Olenik explains. “Because the light
is refracted to different degrees by the
areas of a crystal, we often obtain very
colorful images – mosaic-like surfaces,
thin needles, or feathery structures in all
sorts of colors.”
Selectively changing active
ingredient properties
Polymorphism screening plays a critical
role in process engineering, chemical
development and production. “It can
be problematic if a compound in a formulation changes its crystal structure,”
the Bayer expert explains. Researchers
attempt to prevent such occurrences by
using a thermodynamically stable crystalline form that no longer will convert into
a different crystal.
In some cases, it is also necessary to
specifically alter other properties of an
active substance, such as its solubility.
Active substance molecules can only detach from their solid structure and reach
the target location if they are in the
right form.
Colorful patterns under the microscope: the crystalline
structure of a crop protection agent changes as it warms up
and cools down, altering the light refraction and therefore
its color.
www.research.bayer.com/optimal-drug-form
More information on this subject
Bayer research 27 December 2014
19
FIGHTING WET AGE-RELATED MACULAR DEGENERATION WITH EYE DROPS
Sights set on the eye
The destruction of cells in the retina often results in severe visual impairment and a significant loss of quality of life.
Underlining Bayer’s presence in ophthalmology, researchers from Bayer HealthCare are now testing a new eye drop formulation which is under investigational use for the potential treatment of wet age-related macular degeneration.
Blood vessels play a vital role for our organs; not only do they supply each cell
with the nutrients and oxygen it needs,
but they also rid the body of the waste
products of metabolism. The responsibility
for maintaining these transport pathways
and growing new vessels lies mainly with
a protein molecule known as Vascular
Endothelial Growth Factor (VEGF). It is
transported in the blood and promotes
the formation of new blood vessels by
binding to what are termed VEGF receptors, which are located in the vessel walls.
“This is the signal for the cells there to
start growing,” explains Dr. Jürgen Klar, a
biologist in Bayer HealthCare’s Ophthalmology Research Department in Wuppertal, Germany. The resultant protrusion
of the vessel wall eventually leads to the
formation of a new blood vessel.
Advanced macular degenera­
tion makes reading impossible
In the context of wet age-related macular
degeneration (wet AMD for short), however, this mechanism can cause severe
visual impairment and serious damage to
the eye. The setting for this disease is a
yellow area in the middle of the retina,
known as the macula. Although only a
few millimeters in diameter, it has amazing capabilities: it has a particularly high
density of the light-sensing cells which
are responsible for high-resolution vision.
It also helps us to see detail and distinguish between thousands of different
shades of color. Wet AMD is characterized by abnormal blood vessel proliferation in the vicinity of the retina. Unfor-
20
Bayer research 27 December 2014
Focus on the retina: Dr. Jürgen Klar and
Dr. Michael Böttger (left to right) from
Bayer HealthCare in Wuppertal evaluate
images showing the condition of the blood
vessels at the back of the eye.
tunately, the walls of the new, abnormal
blood vessels are leaky, enabling blood to
enter the retina and causing edema, or
swelling. This causes the light-sensing
cells of the macula to gradually degenerate. Sufferers generally notice a loss
of vision within a short period of time,
and the visual impairment worsens as
the disease progresses. “Patients usually
end up losing the ability to read or drive,”
explains Dr. Brigitte Stemper, a physician
who works in Clinical Development at
Bayer HealthCare. Straight lines appear
wavy, road signs are blurry and colors
look faded. There is a rapid loss of visual acuity. By later stages, the central
field of vision may have deteriorated to
such an extent that it is just a gray patch.
“Although patients may be able to see a
clock, they are no longer able to make out
its hands. Or they can no longer recognize
the face of the person in front of them,”
says Stemper.
The condition mainly affects people
over 65 years of age. “The number of
patients with wet AMD is increasing as
life expectancy rises,” comments Dr. G
­ esa
Deeg, Global Program Head at Bayer
HealthCare. Left untreated, the condition
leads to blindness in most cases. But although wet AMD can still not be cured
today, current treatments involving an injection into the patient’s eye several times
a year are now able to delay or even stop
progression of the disease. The Bayer research team headed up by Deeg is now
looking for new approaches that could
open up additional therapeutic options
for wet AMD for doctors and patients, for
example in the form of eye drops containing the active ingredient regorafenib.
Active substance inhibits abnormal growth of blood vessels
Regorafenib is a multikinase inhibitor
which blocks the function of VEGF receptors that play a part in the formation of
new blood vessels by inhibiting specific
kinases (enzymes). The mechanism and
active ingredient are familiar from cancer medicine. For the treatment of eye
diseases like wet AMD, however, the oral
tablet formulation used to treat cancer
patients is not suitable. In eye indications,
regorafenib must only be effective in the
eye and must reach the retina in sufficient quantities. The researchers therefore
Photos: BSIP/Your Photo Today (1), Sabine Bungert/Bayer AG (1), Thorsten Futh/Bayer AG (1)
Regorafenib MEDICINE
Enhanced vision: a new eye drop formulation may help patients with wet age-related macular degeneration.
Bayer research 27 December 2014
21
Clarity for the retina
Patients suffering from wet age-related macular degeneration (AMD) face a rapid loss of visual acuity, affecting above all the central
­visual field. The active ingredient regorafenib – administered as eye drops – targets the cause of the disease: the uncontrolled growth of
new blood vessels.
Before
What is happening in the retina
What a wet AMD
patient sees
Uncontrolled growth of blood vessels leads to
leaks and the accumulation of fluid. These edemas
destroy the visual cells.
Therapy
Applied as eye drops, the active
ingredient regorafenib makes its way
into the retina. Here the substance
intervenes in signal transmission
and inhibits the uncontrolled growth
of new blood vessels.
After
What is happening in the retina
What a patient treated
with regorafenib sees
22
Bayer research 27 December 2014
The active ingredient regorafenib suppresses
the formation of new blood vessels, leading to
improved vision.
Regorafenib MEDICINE
When the retina drowns
The macula is a site of high metabolic activity. Any waste products which arise
are disposed of via a pigment layer under the retina. But as aging progresses, the
eye loses its natural ability to remove these substances. Instead, they accumulate in the area of the macula, disrupting the supply of oxygen and nutrients to
the retinal cells. This causes the cells to gradually die off, and the patient’s central visual acuity deteriorates. When the body now tries to compensate for the
damage to the retina by forming new blood vessels, the disease may progress in
a rather aggressive way. The new vessels are leaky and abnormal: blood and fluid
escape, causing edemas which destroy the light-sensing cells. Wet age-related
macular degeneration (AMD), as this condition is termed, affects approximately
10 to 15 percent of all patients. If left untreated it can lead to irreparable visual
damage within a few months.
had to enter completely new territory and
overcome numerous hurdles to develop
their own ophthalmological formulation
that would make the active ingredient
usable for the treatment of eye diseases.
“A brand new development was needed,”
explains Dr. Annett Richter, a pharmacist
in Formulation Development at Bayer
HealthCare. “Our objective was to develop a formulation of the active ingredient
which we could administer in the form
of eye drops.”
Eye drops deliver the active
ingredient to the retina
This is a major challenge, since the new
formulation needs to be not only effective, but also stable and well tolerated,
while at the same time capable of ensuring that the active ingredient will find its
way to the back of the eye. In the early
research phase, Richter worked closely
with her research colleagues, testing different types of formulation. An oily suspension formulation emerged as the most
suitable delivery form. The team then had
to develop a suitable manufacturing and
sterilization process. The eye drops have
since been tested successfully in animal
models and the data give the researchers
reason to hope that it will be possible to
improve the symptoms of wet AMD in
humans by treatment with regorafenib
eye drops. “And this despite the fact that
experts had previously been skeptical
about whether sufficient efficacy could
be achieved to treat a condition such
as wet AMD with eye drops,” explains
­Richter, not without pride. “There is good
evidence to show that the active ingredient is delivered from the cornea to its
site of action in the retina,” she says. Once
administered into the eye, regorafenib inhibits the function of the VEGF receptors,
thereby blocking transmission of the signal for new blood vessel formation in the
retina. “Although VEGF is still able to dock
onto the receptors in the vessel wall, the
cells are now deaf to the growth signal,”
explains Klar.
The risk of unwanted new vessel formation and edema may then be reduced.
“Interruption of the VEGF growth signal in
the eye may suppress the pathologic vessels and improve vision in AMD patients,”
adds the biologist. It took around five
years to get from the idea stage to initial
testing in humans, which began with a
Phase I trial in which healthy volunteers
were tested to determine how well tolerated the new eye drops are. And the trial
had a positive outcome. “Regorafenib is
well tolerated in this formulation,” states
Dr. Michael Böttger, the physician at
­Bayer HealthCare responsible for the early
clinical development of the project. “The
active ingredient was hardly detectable
in the systemic circulation, which is an
advantage of local administration in eye
disorders.” Moreover, when asked, the trial
participants indicated that they could well
Research for clear vision: Dr. Brigitte Stemper, Dr. Annett
Richter and Dr. Gesa Deeg, Bayer HealthCare Berlin (left to
right), have conducted ground-breaking work to find a suitable formulation for the active substance regorafenib.
envisage using the medication on a daily
basis over an extended time.
Research team is delighted
with the progress to date
“We’re pleased that the preclinical development and Phase I trials have gone
so well,” says Böttger. The researchers
entered Phase II of clinical development
in October 2014 with great optimism. As
Böttger explains, “In this study, we want
to test whether regorafenib eye drops
are effective in wet AMD patients.” If the
outcome is positive, investigations will
follow on directly as part of the same
study to determine the optimum dosage
and frequency of administration. “The
innovative two-phase study design and
close cooperation between Research and
Development could shorten the overall
development time,” adds Stemper. The oily
formulation is a new approach. “These
drops have the potential to become the
first non-invasive treatment option for
wet AMD,” explains Project Head Deeg.
“Patients can administer eye drops by
themselves.” This could potentially lead
to a completely new form of treatment
that differs from the currently available
products, which have to be injected into
the eye.
www.research.bayer.com/regorafenib
More information on this subject
Bayer research 27 December 2014
23
BAYER FOUNDATIONS Current highlights
AWARD-WINNING RESEARCHER: CHEMIST PROFESSOR ABIGAIL DOYLE
When molecules go new ways
Molecules containing fluorine are put to a wide range of uses but they are often difficult to produce. Now, new methods
developed by a working group led by Professor Abigail Doyle from Princeton University in New Jersey, USA, enable fast,
efficient synthesis with fluorine. In recognition of her research work, Professor Doyle received the Bayer Early Excellence
in Science Award in June 2014.
A passion for chemistry and
humanities
New approaches in chemistry: Professor Abigail Doyle has
tamed the element fluorine. The methods developed by her
team enable completely new chemical reactions.
As a core component of many active ingredients used in areas from crop protection to medicine, fluorine is highly prized
by chemists. “Molecules containing fluorine play an important role in almost all
areas of the chemical industry. The element is present in agrochemicals, anesthetics, pharmaceuticals and contrast media, but also in materials such as Teflon,”
says Professor Abigail Doyle. However,
24
Bayer research 27 December 2014
Her working group also studies catalysts materials that work alone or in combination with other substances to initiate difficult reactions more easily. For this, the
researchers used transition metals such
as cobalt and nickel. “They tame the stubborn fluorine and make it a more willing
reaction partner,” says Doyle. For example,
she and her colleagues have developed a
new method for producing contrast media using the radioactive fluorine isotope
18F, which are used in cancer diagnostics, among other things. “We changed
the reaction in such a way that it now
also works for the industrial production
of contrast media,” continues Doyle. This
method could also help to develop entirely new contrast media.
Chemistry that wasn’t always Doyle’s
first love. “At high school I was more interested in the humanities and music,”
she says. It was only during an introductory course in organic chemistry at
­Harvard University that she discovered
her passion for laboratory work. “I discovered that chemistry gave me the oppor-
tunity to combine my love of the logical
nature of science with the creativity you
find in the humanities and when playing
a musical instrument,” she explains.
Doyle’s success proves she made the
right choice. At 34, her CV covers s­ even
closely-typed pages and numerous
awards, such as the Thieme Chemistry
Journal Award. A very special honor was
added to this list in June 2014, when
Doyle received the Bayer Early Excellence
in Science Award for her work on chemical synthesis. “This award was exceptionally important to me. The Bayer award has
recognized my program early on, and that
has drawn international attention to the
research work done by my group,” says
Doyle. With the prize money, she is also
able to pursue new paths of research.
Catalyst combinations open up
new reactions
Her research group studies cross-coupling
reactions, a process used to combine two
different organic molecules. Working with
researchers led by her colleague David
MacMillan, her team recently managed to
combine two types of catalyst – a photoredox catalyst and a nickel catalyst. This
opens the door for reactions that were
virtually impossible previously. For example, carboxylic acids can now be combined
with complex cyclic molecules that serve
as the basis of new active pharmaceutical
ingredients.
Despite her heavy workload, Abigail
Doyle feels it is extremely important to
leave enough time for her family. When
she’s not in her lab coat, she spends most
of her time with her husband and son,
“preferably out enjoying nature, hiking or
diving.”
Photos: Bayer AG (2), Peter Allgaier/Bayer AG (2), Dirk Hansen/Bayer AG (1), Privat (1)
fluorine doesn’t bond easily, particularly
not with carbon. “Fluorine is the element
with the highest electronegativity. In other words, it resists sharing its electrons
within a compound,” she explains. She
and her colleagues are therefore working
on developing new strategies that will
make it easier to combine fluorine and
carbon – and it’s paying off. “We have
developed a new raw material for fluorination reactions which overcomes some
of the issues we experienced previously,”
explains Doyle.
BAYER FOUNDATIONS Current highlights
Open your mind and think bigger
The Bayer Foundation gives 20 young scientists the chance to attend the Lindau Nobel Laureate Meeting.
“Open your mind and think bigger.” That was the message that Liangliang Hao from Northwestern University in Illinois in the United
States took away from the 2014 Lindau Nobel Laureate Meeting. She
was one of the 20 Bayer Lindau Fellows, talented young scientists
from 18 countries, whose visit was sponsored by the Bayer Foundation. This year the conference, which has been bringing together Nobel Prize winners with young researchers over the course of a week
for 63 years now, was firmly focused on medicine. Other participants
were equally impressed by the inspirational atmosphere. “I met lots
of interesting people who were filled with the spirit of invention,”
says Dr. Christian Herzmann from Borstel Research Center, winner of
the 2014 Aspirin Social Award. Like Hao, he had been invited to the
event by the Bayer Foundation. Selected guests were also able to take
part in a special highlight – the Bayer Lindau Foundation Dialog, an
evening event devoted to scientific dialog. As part of this, they had
the opportunity to use posters to present their research work and
engage in discussions with Bayer scientists and Nobel Prize winners
such as Professor Harald zur Hausen (Medicine). Liangliang Hao was
awarded the prize for the best poster, winning a week at the Bayer
research centers in Berlin and Wuppertal.
Scientific dialog: biomedicine technician Cheryl H. Cui (left) from
Canada was one of 20 Bayer Lindau Fellows. She swapped notes with
Bayer’s Management Board member responsible for Innovation Kemal
Malik (right), the host of the Bayer Dialog evening.
School teams and Bayer experts
develop prototypes for multicopters
The winners of the schools technology competition developed crash protection for a remote-controlled aircraft.
Safety for miniature aircraft: the winners of the Bayer schools technology competition panel’s award Felix Wieland, Ben Preuss and Benedikt
Schmitz (left to right) proudly present their multicopter. They devised a
sophisticated system that protects the aircraft in the event of a crash.
Eleven school teams from all over Germany had the opportunity to
explore for themselves how ideas become prototypes. In June 2014,
the finalists in Bayer’s schools technology competition presented their
ideas to a panel of experts. The ideas included a rapid test for heart
attacks and a garbage can for biodegradable waste that can stand up
to winter weather. After that, the students had three months to put
their ideas into practice. Each group received support from a Bayer
expert. The engineers helped the students deal with tricky technical
problems. This year’s winners were three 9th graders from the August
Dicke High School in Solingen. Along with their teacher, they were
presented with the panel’s award and prize money of EUR 5,000 in the
BayArena soccer stadium in Leverkusen. The three students had developed crash protection for multicopters, i.e. remote-controlled aircraft.
The panel of judges said that the device could well be translated
into practical applications. A parachute and type of airbag ensure
that the aircraft can land undamaged in an emergency. “The students
impressed us with their quality, professionalism and problem-solving
abilities,” said Thimo V. Schmitt-Lord, Managing Director of the Bayer
Foundations, at the award ceremony.
Bayer research 27 December 2014
25
BAYER FOUNDATIONS Current highlights
New approaches in a global social mission
Employees from Bayer Business Consulting are working in social foundation projects in countries such as Kenya
and the Philippines.
Employee development paired with social work – that is the aim of the
“Bayer People Care for Society” program. In this new initiative launched
by Bayer Business Consulting and the Bayer Cares Foundation, consultants
lend their support to the Foundation’s international social and healthcare
projects. “In addition to the fact that we are actively supporting Bayer’s
social commitment, we also regard these activities as a new aspect of
employee development, as our consultants are deployed to social projects
that are far away from their usual office environments,” explains Alexander
Meyer auf der Heyde, Head of Business Consulting.
Yuchen Li, for example, is supporting a health education project run
by the Deutsche Stiftung Weltbevölkerung (DSW) in Kenya. She talked to
research about her experiences.
sexually transmitted diseases. I analyze the influence and effectiveness of this network and try to implement improvements. My
knowledge of project management, market research, data analysis
and marketing stands me in very good stead.
What appeals to you about a project in Kenya?
I’ve been volunteering in social projects for a long time now. Health
education in Kenya actually fits in very well with my professional
background. It’s a once-in-a-lifetime opportunity for me to make a
positive contribution to society and I can also develop my own professional skills so that I can become a more versatile manager.
How do you help on the ground?
The DSW supports 400 youth clubs in East Africa. They teach young
people about contraception, family planning and protection against
Yuchen Li, shown here at a youth club, works as a management consultant at Bayer Business Consulting in Morristown, the Bayer Group’s
global center of management consulting expertise.
Better patient care via smartphone
“Explain TB” – the name says it all. This smartphone app provides multilingual information about tuberculosis and is therefore
a valuable instrument in the treatment of TB patients who do not understand German. In 2014, the project took first place in
the Aspirin Social Award, which recognizes charitable projects in the healthcare sector. research spoke with the man behind
“Explain TB”: Dr. Christian Herzmann, a respiratory medicine specialist at Borstel Research Center.
How did you come up with the idea for “Explain TB”?
Because of my day-to-day work. It’s often difficult because many tuberculosis
(TB) patients don’t speak German. As a doctor, that makes it tricky to give them
information about the need to screen contact persons like relatives and friends
for TB.
How does the app work?
It contains information about all the key issues relating to tuberculosis in a
total of 37 languages. There is also information in audio format for illiterate users. For example, if a doctor has to explain that a patient needs to take an HIV
test, she can play the relevant audio section on the app.
How will the Aspirin Social Award help you?
First place: Bayer Management Board member Michael König
(right) congratulates Cordula Ehlers and Dr. Christian Herzmann
(left to right) on “Explain TB.” The app can be downloaded free
of charge.
26
Bayer research 27 December 2014
We’ll use the EUR 15,000 prize money to develop the app further. For instance,
we could develop tests that patients can carry out themselves to check the side
effects of certain drugs. The app could also automatically translate patient data
into a different language.
BAYER FOUNDATIONS Current highlights
World-class scientific network – promoting
excellence in tandem
The Alexander von Humboldt Foundation – one of the world’s largest and most outstanding associations dedicated to promoting scientific excellence – has been a cooperation partner of the Bayer Science & Education Foundation since 2013. Each
year, it finances ten scholarships for postdoctoral students in the fields of life sciences and medicine. In addition to the support
provided by the Humboldt Foundation, scholarship holders can also benefit from opportunities offered by Bayer.
Before now, Dr. Titiwat Sungkaworn was
not very interested in industrial research.
“My main focus was on fundamental research,” reports the scientist from Thailand.
As a postdoctoral researcher at the Institute
of Pharmacology and Toxicology at the University of Würzburg, he researches G-protein-coupled receptors in the cell membrane.
However, a visit to the research center of
Bayer HealthCare in Wuppertal changed his
perspective. “I learned a lot about industrial drug research and development,” he reports. Thanks to this experience, he can “well
imagine working with pharmacologists from
Bayer” once he returns to Thailand and establishes his own working group.
Sungkaworn is one of the first generation of Humboldt Bayer Fellows. The ten
scholarship holders each receive EUR 50,000
annually from the Bayer Science & Education Foundation for a period of up to two
years. Outstanding young scientists from
all over the world can apply for a Humboldt
scholarship, which funds a period of research in Germany. The Bayer scholarship is
designed specifically for postdocs from the
fields of life sciences and medicine. “It’s a
unique opportunity to gain an insight into
the world of applied research,” says Titiwat
Sungkaworn. Each of the ten scholarship
holders is paired with an experienced Bayer
scientist working in a similar research area.
Sungkaworn’s mentor, for example, is Dr.
Bernd Kalthof, Head of Screening Technologies at Bayer HealthCare in Wuppertal. The
two regularly engage in intensive dialog and
have already met on several occasions.
Insights, knowledge and
­experience for their careers
Bayer also invites the young researchers and
their mentors to attend events such as the
Bayer Science Dialog at the Nobel Laureate Meeting in Lindau on Lake Constance,
to awards ceremonies or the regular Bayer
­Science Days. “They were all very interesting
events and offered excellent opportunities
for networking,” says Sungkaworn.
Bayer has also opened up its internal
training and development program to the
Humboldt Bayer Fellows. Sungkaworn has
opted for a two-day course in project management. He is keen to learn how to orga-
Insights into applied pharmaceutical research:
Dr. Titiwat Sungkaworn from Thailand presented his
work at the 2014 Bayer Science Day.
nize his own research project, keep control
of finances and optimize the use of laboratory equipment. And the man from Thailand
is certain: “It was the right decision to join
the Humboldt Bayer Fellowship. I’ve gained
new insights, knowledge and experience
from a world-class pharmaceuticals company. That will give me a huge boost for my
further career.”
The Bayer foundations – committed to progress since 1897
Bayer foundations have been promoting education, science and social innovation all over the world since 1897. As part of the innovation company Bayer, the foundations see themselves above all as initiators, promoters and partners for progress at the interface
between industry, science and the social sector. Their programs are focused on pioneers – their commitment to public welfare, their
wealth of ideas in resolving social tasks, and their creativity in the fields of science and medicine. The Bayer Science & Education
Foundation, for example, grants scholarships and awards which encourage young talents and top researchers alike to deliver out­
standing achievements in their field. The Bayer foundations also
support efforts to resolve social issues. For example, the Bayer
Cares Foundation focuses on citizens’ projects and resolving issues
www.bayer-foundations.com
in the field of social medicine. The objective of the foundations is
Visit this site to apply or to obtain more information
(see back cover flap).
always to improve human life through innovation and initiatives.
Bayer research 27 December 2014
27
Durable artificial skin: Bayer employee Anson Xue in Shanghai tests a polyurethane layer fabricated with the sustainable INSQIN™ method.
28
Bayer research 27 December 2014
INSQIN MATERIALS
SUSTAINABLE POLYURETHANE FOAMS ARE REVOLUTIONIZING THE TEXTILE INDUSTRY
Magic materials
Photos: Zhang Chi/Studio Stare/Bayer AG (1), Jan Schumacher/Bayer AG (1), Dieter Klein/Bayer AG (1), Privat (1), FILK/Freiberg (1)
Whether in a handbag, jacket or shoes, today’s textiles must be both durable and comfortable. Such demands can only
be fulfilled with the help of innovative coatings. Specialists at Bayer MaterialScience have now developed a technology
for manufacturing water-based synthetic leather - a material that is significantly more sustainable than those manufactured by conventional processes.
Life in the big city is hard, most of all
for shoes: rough asphalt, sharp sidewalk
edges and stones scratch the soles and
wear away the material. Only durable
materials can withstand this abrasion and
make shoes last longer. But whether they
are sneakers or elegant high-heels, shoes
also face another challenge: they have
to be comfortable. The material from
which they are made must not only be
good-looking and soft, it must stay that
way for a long time.
To better reconcile these apparent
contradictions, material experts at Bayer
MaterialScience work continuously on
innovative materials for coating textiles. One important example is synthetic leather, a woven or nonwoven fabric
coated with a layer of polyurethane only
1 mm thick or less. “Compared to genuine
leather, the synthetic version is not only
cheaper and more durable, it can be also
be washed and dried without stiffening,”
explains Nicholas Smith, Global Head of
Textile Coatings at Bayer MaterialScience.
What’s more, the very complicated tanning process can be eliminated. But the
synthetic leather coating made of polyurethane (PU) can still be optimized – and
produced more efficiently and sustainably. Specialists at Bayer MaterialScience
have developed a new technology for
this very purpose: with INSQIN™, a polyurethane layer can be applied to textiles
without using any solvents at all.
“INSQIN enables the production of
PU-coated textiles that are absolutely on
a par with the conventionally fabricated
“We need 95 percent
less water and 50 percent less energy than in
the conventional process.”
Nicholas Smith,
Global Head of Textile Coatings
at Bayer MaterialScience
– solvent-based – fabrics in terms of performance, but also offer tremendous sustainability advantages,” explains Smith.
Water-based synthetic leather
coatings
The key to this achievement: “The new
coatings are supplied in water instead
of in organic solvents,” Smith says. The
starting substance for the synthetic
leather skin is a milky liquid with PU particles suspended in it. The advantage of
water-based polyurethane dispersions is
that they can be foamed. Billions of tiny
air bubbles fizz through the liquid, adding
volume to the final PU coating. To give
it lasting stability, the Bayer researchers
mix foam stabilizers into the formulation.
“In the final drying process, the stabilizers
begin to stiffen the foam, and keep it in
shape,” explains Thomas Michaelis, Head
of Textile Coatings EMEA/LA at Bayer
­MaterialScience. Together with additional
layers, this foam produces a lightweight,
fine-pored PU skin, which gives the coated lengths of fabric good haptic properties and volume.
Compared to the standard manufacturing process, the new method is much
more environmentally friendly. Manufacturers previously consumed large quantities of the solvent dimethylformamide
(DMF). This substance is required for
a key step called coagulation. “In this
phase, the polyurethane dissolved in the
DMF is spread on the textile fabric and
the material runs through a water bath
that precipitates the polyurethane,” explains Michaelis. After additional, intensive rinsing, the DMF is finally washed
out of the fabric. “Thanks to the new
Bayer research 27 December 2014
29
Unique effects: Bayer expert Nicholas Smith (photo right, left) shows photographer William So and model Nicky B (from right) the textile team’s latest
invention: synthetic leather that changes color. Bayer employee Bruno Stübben tests the viscosity and pore size of a polyurethane dispersion for producing synthetic leather (photo left).
Water-based synthetic leather
1
Fresh polyurethane foam
Foam stabilizers
Air bubbles
The INSQIN™ technology developed by Bayer MaterialScience
is based on water instead of solvents. The polyurethane dispersions are beaten like whipped cream. Stabilizers keep the
resulting foam in shape. The lightweight, fine-pore plastic
skin can then be used to coat textiles.
Polyurethane particles
Water
2
Diagram of synthetic leather
Drying process
Surface with
leather-like grain
Stabilizers keep the
foam in shape
Pore structure of
the polyurethane
foam
Textile substrate
Water evaporates
3
Finished coating
Foam pores
Polyurethane
pore layer
30
Bayer research 27 December 2014
Products with a synthetic leather coating
INSQIN MATERIALS
“Coatings have to be
functional”
research spoke with Professor Michael Stoll of the Research Institute
of Leather and Plastic Sheeting in Freiberg about the significance of
plastic coatings.
In which industries do plastic coatings play an important role
and why?
In addition to the fashion industry, they are being used increasingly
in many technical applications, from special packaging and protective clothing in the medical sector to the semiconductor industry,
which uses plastic-coated textiles as polishing cloths, for instance.
To fabricate coatings, the raw materials and auxiliaries can be selected individually, formulated for specific purposes and processed
by different methods, making the coatings suitable for use in a
wide variety of industries.
I­NSQIN technology, we can dispense
with this step entirely and save water at
the same time,” Michaelis continues. Furthermore, the important and costly drying step in the old process also becomes
superfluous.
Efficient technology: lower
water and energy consumption
“We need 95 percent less water and 50
percent less energy than in the conventional process,” explains Smith. In view of
the global PU synthetic leather demand,
that adds up to a tremendous amount,
because massive volumes of the textiles
we use every day are already manufactured on the basis of polyurethane technology: worldwide production of synthetic PU leather amounts to over four
billion square meters annually, enough
to cover over 560,000 soccer pitches.
This PU leather goes into the production of some seven billion pairs of shoes,
two billion handbags and one billion
articles of clothing made of PU-coated
materials.
Michael
Stoll
What do plastic coatings contribute to the shoe, textile and
­leather industries – now and in the future?
In the past, they often served as cheap substitutes for natural
products, but had to measure up to their natural counterparts.
That’s not enough today: apart from a convincing design, plastic
coatings must have various functionalities. In the future, textiles
and shoes will undoubtedly become information carriers, and
even generate electric power. In any case, the demand will rise
for ecological, intelligent, high-quality products that can be fully
recycled.
These improvements to sustainability
are in strong demand. Brand owners are
increasingly seeking more sustainable
materials, while customers are opting
for textiles that bear an environmental
quality seal, as shown in a study by the
auditing and advisory firm KPMG. Customers today want to know where their
clothing comes from, what kind of working conditions prevail in the producing
countries and how many chemicals are
used along the entire value chain. “At the
hubs of textile production, for example
in Asia, this could be an important step
towards greater sustainability and significantly improved working conditions,”
explains Smith.
In this sense, water-based PU dispersions offer critical advantages for both
synthetic leather producers and consumers. “If we can dispense with solvents in
the manufacturing process, then the final
product does not contain them either,”
points out Bayer expert Michaelis. In the
previous process, the residual DMF had
to be removed from the coated material
in an extremely water-intensive process.
And that could soon be of interest to
other industries as well. “The fashion and
sporting goods industries have taken the
first step, but the major auto manufac­
turers also prefer sustainable materials
for vehicle interiors,” Smith says.
Improving working conditions
in the textile industry
With solutions like INSQIN™, they would
be c­ apable of producing cushions and
door trim for vehicle interiors without
any ­solvents at all.
These coated materials are equipped
to meet the challenges of the big city,
and even fulfill another objective: greater sustainability. Bayer’s experts already
have their eyes on the next innovation:
products made from renewable raw
­materials.
www.research.bayer.com/insqin
More information on this subject
Bayer research 27 December 2014
31
32
Bayer research 27 December 2014
Photos: Peter Ginter/Bayer AG (4), Uwe Nölke/Bayer AG (1), Matthias Sandmann/Bayer AG (1)
SPECIAL FEATURE Life science research
INTERDISCIPLINARY BAYER TEAMS ACCELERATING LIFE SCIENCE RESEARCH
The protein engineers
Bayer scientists are working in interdisciplinary teams to search for new targets for active
substances or diagnostic options. Synergies in medical and crop protection research result in
completely new approaches, from the design of therapeutic antibodies to improved production of new crop protection products. One key to success is highly effective protein molecules,
­constructed in Bayer’s laboratories by protein engineers.
High-throughput high-tech: Dr. Wayne Coco uses fully automated robot systems as a tool in the development of therapeutic antibodies.
In this photo, autonomous robots operate incubators, pipetters and detection systems.
Bayer research 27 December 2014
33
The biological tools are small but indis­
pensable: enzymes are protein building
blocks that keep the respiratory, metabol­
ic and immune systems functioning, and
people, animals and plants alive. These
biocatalysts are like molecular workhorses
and they play a central role in every single
cell. They are the reason why special che­
mical reaction paths are taken: enzymes
are particularly effective at opening and
relinking only selected molecular bonds.
The number of naturally existing enzymes
is estimated at more than 10,000.
Improving the quality
of ­biotechnology research
“Out of this treasure trove of enzymes,
biotechnologists have long been discov­
ering numerous ‘chemistry talents’ that
they are now utilizing and optimizing as
miniature tools for specific purposes,”
says Dr. Wayne Coco, Head of Protein
Engineering at Bayer HealthCare in Co­
logne, Germany. The range of applications
of these versatile molecules is enormous:
the protein building blocks are not only
valuable helpers in the body but can also
be used as catalysts in large-scale chemi­
cal production.
“We can now
use the talents
of enzymes
throughout the
Bayer Group.”
Dr. Mark James Ford,
Process Research
Bayer CropScience
Bayer intends to expand its know-how
and technologies relating to these min­
iature biological tools and increase its
efficiency in this area. With this aim
specifically in sight, Bayer has initiated
two projects, “Biotransformations” and
34
Bayer research 27 December 2014
Research breakthroughs
are a matter of teamwork
Science thrives on the exchange of experiences – and there are
plenty of opportunities for this when it comes to the health of
people, animals and plants. The Bayer Group is now focusing more
closely on these interfaces, and initiated the Nimbus Initiative to
this end back in 2012 (see also research 26, Special Feature). The
company has provided EUR 30 million for new research projects
aimed at more closely interlinking the life sciences. The researchers
are working on issues such as epigenetics, high-throughput screening for drug discovery and biotransformations. Their objective: to
more intensively exchange acquired knowledge and further improve
the quality of research.
“Protein Engineering,” as part of the
Nimbus initiative, which aims to fos­
ter closer networking in life sciences
among the departments of the Bayer
subgroups, and promote the exchange
of information with the objective of le­
veraging synergies to find approaches
for new active ingredients and their
production.
The intensive dialog across geograph­
ic sites and specialist disciplines has not
just improved the quality of biotechnolo­
gy research. “The Nimbus initiative brings
together specialists from different disci­
plines to enable cross-subgroup research
projects,” reports Coco. As a molecular
biologist and head of the Protein Engi­
neering Nimbus project, he and his team
are focused above all on the design of
therapeutic antibodies – in other words,
special protein molecules that are used in
areas such as cancer therapy. “We engi­
neer these proteins to ensure their safety
and efficacy,” explains Coco. To do this,
­Bayer’s researchers intervene specifical­
ly in the blueprint of a protein that is
found in a specific gene sequence. They
produce thousands of variations of this
candidate and then test them in the lab­
oratory in a fully automated, robot-based
high-throughput screening procedure
“until we find a suitable protein among
the wide range of candidates,” the protein
engineer says.
The Cologne-based team’s know-how
with regard to how to design enhanced
antibodies can also be applied to a wide
variety of protein optimization goals
within the scope of Nimbus projects. For
Bayer CropScience, such technologies are
extremely interesting because they accel­
erate the search for new protein-based
plant traits and broaden the founda­
tion of this process. “Cooperation with
Bayer HealthCare’s researchers within
­
the N
­ imbus project gives us access to a
highly innovative technology platform, in­
cluding robot facilities for high-through­
put tests,” explains Dr. Marc Linka, who
is working on the development of novel
traits together with his colleagues at Bayer
CropScience.
Protein engineering enhances
crop traits
This teamwork has already borne fruit:
within the scope of the collaboration,
the Bayer researchers have constructed
several new proteins that are now being
integrated into crops and then studied in
greenhouses and field tests. “The entire
Nimbus team is of course looking forward
with great anticipation to see whether the
promising results from the laboratory are
confirmed in practice,” says Linka.
The protein engineering expertise
of Coco’s Cologne-based Bayer team is
Life science research SPECIAL FEATURE
Man and machine: Dr. Michael Strerath and Konrad Odendahl (photo above, left to right)
check the pipetting quality of a screening system while their colleagues Petra Helfrich
and Fabian Scholz (photo right, left to right) use the new proteins for initial biotrans­
formations in the Berlin fermentation laboratory.
a­ lso in demand in other areas – such as
designing proteins that can be used as
biocatalysts to create production routes
for new active substance candidates.
They are frequently also suited for estab­
lishing more cost-effective production
processes.
Interdisciplinary scientists work
to improve production processes
“The Nimbus project makes it possible for
us to systematically exchange biocatalysts
between crop protection and pharmaceu­
ticals research for the first time,” explains
Dr. Ingo Hartung, Head of BHC’s Biocata­
lysis group in Berlin. “And with the team
of colleagues headed by Wayne C
­ oco, we
also have the specialists we need to op­
timize them perfectly and give them the
requisite finishing touches.”
Yet how can enzymes worth optimizing be identified? The Biotransformations
Nimbus project was initiated to answer
this question and leverage the poten­
tial of the biocatalysts in all areas of
the Bayer Group – from their discovery
to their production. An interdisciplinary
team headed up by Dr. Mark James Ford
from Process Research at Bayer Crop­
Science has been working for nearly two
years to establish a Group-wide enzyme
collection. The team has undertaken to
realize technical biotransformations for
improved production processes, as well
as to explore the spectrum of further
application opportunities in research and
development. “The knowledge required to
systematically exploit biocatalysts already
existed to some extent prior to the launch
of the Nimbus project,” explains Ford. Yet
the transfer of knowledge and direct co­
operation between the individual experts
have improved substantially as a result of
the Group-wide initiative – and ultimately
enabled the realization of customized en­
zymes. “We had no idea just how much
we could achieve together: this is synergy
in the most positive sense of the word,”
says Ford.
Bayer research 27 December
27 Dezember 2014
35
SPECIAL FEATURE Life science research
this process ultimately results in a cus­
tomized biocatalyst that is suitable for
industrial use. But even during the often
time-consuming development cycles,
both smaller and larger breakthroughs
often occur.
New enzymes benefit modern
society
Library of biocatalysts in service: first hits are identified from the collection of
microorganisms in Berlin (photo above). Together with colleagues, Dr. André Pütz
from Bayer Technology Services (photo below) is constantly working on finding,
­isolating and characterizing new biocatalysts.
Within the Nimbus team, specialists from
Bayer Technology Services are working on
establishing an extensive enzyme collec­
tion. “Through academic interactions as
well as extensive literature and database
searches, we acquire enzymes of interest
which are subsequently prepared in the
lab ready for the problems HealthCare
and CropScience would like to address.
In this way we are continually expanding
the platform’s biocatalyst collection with
the aim of reducing the time required to
36
Bayer research 27 December 2014
find the necessary enzymatic activity,”
explains Dr. André Pütz, Biochemistry &
Biocatalysis at Bayer Technology Ser­
vices. Once the experts at Bayer Tech­
nology Services, Bayer HealthCare and
Bayer CropScience have found, isolated
and characterized suitable enzymes a­ fter
screening the new collection, Coco’s
team starts up the optimization machin­
ery to further perfect the biocatalysts’
properties. Coupled with a wealth of
know-how and innovative approaches,
“Thanks to the Nimbus platform, we were
not only able to substantially reduce
screening times. In addition, we have
frequently had quick wins. The knowledge compiled in the project to date
has already been put into practice in a
few cases. This is only possible because
we are now well networked internally
and nurture a lively scientific discourse,”
explains Ford. Bayer’s scientists gain ad­
ditional knowledge with every project
cycle, every enzyme and every custo­
mized biocatalyst. And ultimately, it is
doctors, patients, farmers and consumers who will benefit from this wealth
of knowledge.
www.research.bayer.com/nimbus
More information on this subject
Coralie van Breukelen-Groeneveld PORTRAIT
PROJECT MANAGER CORALIE VAN BREUKELEN-GROENEVELD
Keeping an eye on the
big picture
Teamwork is a priority for environmental specialist Coralie van Breukelen-Groeneveld. As a project manager at Bayer
­CropScience, she coordinates the development of new active substances and the associated products for crop protection. To
get all her co-workers on board for their common goal, she relies on both her organizational talents and communication skills.
What interests her most is the big picture. “I always like to see
how things are related and how they fit into an overall system,”
says van Breukelen. The 42-year-old from Holland – who spent
several years of her childhood in South Africa – recognized that
very early in life. This fundamental curiosity is also what motivated her to major in environmental science at Wageningen
University in the Netherlands, where her area of specialization
was biology and chemistry. She discovered that her main interest
lay in subjects like sustainability and environmental protection.
Human health was also one of her passions from the start, and
ultimately prompted her to finally choose toxicology. What effect
do substances have inside the body? How does the environment alter an active substance? Why and how does an active
substance change? “These are questions I’m still thinking about
today,” says van Breukelen.
Photos: Gaby Gerster/Bayer AG (1)
Developing new crop protection agents
takes patience
After earning her degree, she started her career at an institute
for food and nutrition research in Holland. “For research I was
simply too impatient, always trying to find the broader context as
quickly as possible,” she says today. So she initially worked in new
substance risk analysis for the Dutch authorities. She then joined
Bayer CropScience in early 2003, putting her analytical skills to
work representing the company’s innovative active substances
before the European Commission and the European Parliament.
“The first few weeks were really difficult,” van Breukelen recalls.
At the beginning of her job, she had to familiarize herself thoroughly with all legislation on crop protection. “It was a mountain
of dry, legal texts,” she relates. “And I now know that the development and registration of new crop protection agents requires
nearly as much patience as the research,” she says with a grin.
As project manager, she spends every day managing the tight
restrictions imposed on the development of new crop protection agents. Her responsibilities in Global Project Management
at Bayer CropScience start immediately after research ends. And
the path of a promising substance from discovery to application
Scientist with foresight: environmental protection and sustainability are
issues close to Coralie van Breukelen-Groeneveld’s heart.
in practice is long. After researchers have synthesized a new molecule and verified its efficacy, numerous additional steps then
follow. “We must prove that the substance is not harmful to
humans, has no unacceptable impacts on the environment and
is effective against the targeted pest. Only then can we satisfy
the requirements of the supervisory authorities,” van Breukelen
summarizes.
But that’s not all. “Even during development, we must consider how we can produce and market a new product as efficiently
and cost-effectively as possible – but also effectively and in sufficient quantities.” Her projects therefore range from a broad-spectrum herbicide for rice farmers in Asia (see research 26 “All-round
talent for rice fields”) to a universal fungicide with a new mode
of action. For her, this is the perfect assignment. “I’m right where
I always wanted to be!”
www.research.bayer.com/portrait-breukelen
More information on this subject
Bayer research 27 December 2014
37
DOSSIER Bees
BAYER EXPERTS ARE WORKING TO IMPROVE BEE HEALTH
Healthy pollinators for
high-quality harvests
Bees may be tiny, but their contribution is tremendous: together with
other animals like birds and bats, insects such as honey and wild bees,
flies, beetles and butterflies pollinate about one third of all crops
worldwide. These busy farm-hands
make sure that high-quality fruits
and vegtables grow in plantations
around the world. Apple trees, for
instance, produce significantly higher yields when their pollen is transported by insects and farmers do not
need to rely on the wind. “Without
the assistance of these animals, almond trees, pumpkin vines and melon plants would only produce very
few, low-quality fruits,” explains Dr.
Christian Maus, Global Pollinator
Safety Manager at the Bayer Bee
Care Center. Experts estimate that
the economic value of animal pollination worldwide amounts to more
than EUR 150 billion a year.
risk. Their greatest enemy is barely a
millimeter long, but it is annihilating
entire bee colonies around the world:
Varroa destructor is the name of the
mite that attaches to bees and feeds
on their hemolymph. The parasite
not only severely weakens bees, it
also frequently transmits deadly infectious diseases. “The Varroa mite
originated in Asia, where it is a natural parasite on the eastern honey bee
(Apis cerana). However, since it started infesting the western honey bee,
it has spread over almost the entire
globe,” explains Dr. Klemens Krieger
of Bayer HealthCare‘s Animal Health
Dr. Klemens Krieger knows all about life inside
Division, who is responsible for bee
the hive and also understands the bee’s greatest
health among other duties. “The only
enemy, the Varroa mite. He is also collaborating
significant place it hasn‘t spread to
with external partners to find effective ways of
yet is Australia.”
controlling this parasite.
Beekeepers have relatively few
means of controlling the parasite.
“Our arsenal includes organic acids,
essential oils and synthetic active
substances called acaricides. Used
The biggest enemy for bees is barely a ­millimeter properly, they kill the mites without affecting the bees or conlong: Varroa destructor
taminating the honey,” Krieger explains. Developing these highly
specific acaricides is a major challenge for research and develThe western honey bee (Apis mellifera) contributes a major share
opment (R&D) experts, however, which explains why only a few
of this service. In the United States, for instance, honey bees
active substances are currently approved for treating honey bees.
are used specifically to pollinate almond trees: some 1.7 million
“This is why we have to use them as efficiently and responsibly as
bee colonies with up to 50,000 insects per colony buzz through
possible. That means alternating between substances with differalmond plantations every year – over half of all the bee colonies
ent mechanisms of action,” K­ rieger says. This method is the only
in the entire country. “Honey bees have become important liveway to prevent the selection of mite strains that are resistant to
stock worldwide,” Maus points out. But these avid fliers are at
a specific active substance. “But many beekeepers underestimate
38
Bayer research 27 December 2014
Photos: Gaby Gerster/Bayer AG (1), Bayer AG (2), Alimdi.net (1), Colourbox (1), Privat (1)
Many of nature’s workers help farmers around the globe to provide an adequate supply of food to the growing
global population: honey bees and other pollinating insects are indispensable to agriculture, but they are impacted by a
­number of negative factors. Bayer experts are working to improve the health of these busy insects, both inside the beehives and out in the field.
Miniature farm-hands: honey bees are an important pollinator of numerous crops such as cherries, coffee and strawberries,
and therefore also an important production factor for agriculture.
Bayer research 27 December 2014
39
DOSSIER Bees
Mite migration
The Varroa mite originated in Asia, but has since spread towards the west and now threatens the western
honey bee almost all over the planet. Only Australia has managed to keep the parasite at bay to date.
1987 USA and Canada
1977 Germany
1959 China
2007 Hawaii
1961 India
1904 Indonesia
1972 Brazil
2000 New Zealand
No reports
No information
Spread of the Varroa mite over time in selected countries
2000s
1980s
1970s
1960s
1950s
the risk of resistance development,” Krieger says. Even if beekeepers treat their colonies against Varroa mites successfully, resistant
parasites may survive the treatment. If they are not eradicated by
a different active substance, they can multiply unchecked in the
hive and create a resistant population. What’s more, the bees constantly transport the pest into other hives, helping it to spread.
“Until we have bees that are resistant to mites, it is extremely
important for beekeepers to repeatedly check how severely a
hive has been infected with Varroa. It is the only way they can
effectively adjust their mite control activities and keep infestation
under the damage threshold,” says Krieger
2,000
Varroa mites
can kill a colony
of 30,000 honeybees.
Source: Dr. Stephen Martin, a University of Sheffield expert on the Varroa mite, 2010
40
Bayer research 27 December 2014
First detection
Source: After Webster TC, Delaplane KS 2001, Mites of the Honey Bee
Bayer experts are investigating mite DNA, looking for natural
mutations that make the parasites resistant to common acaricides. A minute change can alter the site of action enough
that an active substance no longer works and becomes entirely
ineffective at controlling mites. Krieger and his colleagues are
therefore collaborating closely with Rothamsted Research in the
United Kingdom. “We must first understand the mechanisms
underlying resistance, so that we can control the parasite in
the long term,” explains Martin Williamson, Senior Scientist at
­Rothamsted Research.
DNA testing: developing simple methods to
detect resistant mites
Williamson’s team has already identified how specific mites have
adapted to pyrethroids, one group of acaricidal active substances. On this basis, they then developed a molecular biological test
which shows if a mite is pyrethroid-resistant. Now they want to
team up with Bayer researchers and do the same for other acaricides. “Our goal is to develop fast, simple and cheap methods
for detecting all resistance types,” Krieger explains. Beekeepers
would then be able to determine if the mites in their hive are
resistant and if so to which agents, and could then select the
most effective treatment.
An initial and very practical test method has already been
developed by the Bayer bee experts in partnership with Dr.
Ralph Büchler, Head of the Kirchhain Bee Institute in Germany:
Focus on bees: the diligent work of beekeepers (photo, left) is not the only factor that has an impact on bee health. The weather also plays an important
role, and agricultural practices are also a relevant factor – crop protection products are frequently accused of causing harm to honey bees (photo, right).
Conscientious Bayer experts are therefore constantly working to make these products and the technology used to apply them even safer.
the Varroa Diagnosis Box. The beekeeper fills this hand-sized
box with about 500 live bees from the hive and then closes
the opening with a feed paste and gives them about six hours
to eat their way through the seal to freedom. During this time,
an acaricidal active substance kills any mites inside the box.
They can be seen afterwards, stuck to the bottom. From this
number, the beekeeper can then calculate the approximate
number of mites in the hive and determine the degree of risk
to his colonies. R&D experts are currently testing their innovation under different climatic and beekeeping conditions.
“We are considering using the box to diagnose resistances
as well, which could well be viable if we use different active
substances,” Krieger says. Beekeepers would then have a simple method on hand to test hives directly, determine if they
are infested with resistant mites, and combat the pests at the
same time.
However, the Varroa mite is not the only threat to the health
of honey bees: the weather as well as beekeeping and farming
practices also determine how honey bees and other pollinators
fare.
Brief history of
­neonicotinoids
Neonicotinoids came onto the market in the 1990s. For farmers
they were a welcome alternative to other compounds, against
which many pest insects had become resistant. But a damper
was put on this success in late 2013: the European Commission
imposed major restrictions on the use of some compounds in this
group, claiming that harmful effects of the active substances on
bees could not be ruled out. This issue is the subject of controversy around the world. However, numerous scientific studies have
come to the conclusion that no relationship exists between the
use of neonicotinoids and the decline of honey bees.
Controversy surrounding neonicotinoids in the
European Union
The use of crop protection products has frequently been a particularly controversial issue in the general debate surrounding this
topic. The focus in most cases is on a group of pesticides called
neonicotinoids, some of which are applied as a protective layer
on, for example, oilseed rape, corn and soybean seeds in a process experts call seed treatment. The systemic active ingredients
of these products protect seeds and young plants against voracious insects and take effect after germination, working from the
inside. “Seed treatment is essential for many crops,” explains Dr.
Reinhard Friessleben, Head of Application Technology at Bayer
CropScience. The chemicals protect oilseed rape, for instance,
against the ravenous cabbage flea beetle, and eliminate the wireworms that chew on the roots of corn. However, the product
needs to adhere well enough to the seeds. If the agent is partly
rubbed off the seeds during planting, it is difficult to totally avoid
emission of the resultant dust into the environment, as happened
during the 2008 corn-planting season in several regions of Germany. The dust settled on other flowering plants in the vicinity
of the fields. “That can be harmful to pollinating insects feeding
on these other plants,” explains Bayer researcher Friessleben.
High-quality seed treatment generates significantly less dust.
Many scientific studies, field observation data and risk assess-
Bayer research 27 December 2014
41
DOSSIER Bees
ments show that, under realistic conditions, neonicotinoids are
not harmful to bee colonies when used as directed and according
to best practice. The European Union nevertheless restricted the
use of some neonicotinoids, to the dismay of farmers (see box on
page 41), who lost a critical agent for protecting crops against
pests. And virtually no effective alternatives exist.
Bayer researchers are continuously looking for new ways to
make seed treatments even safer, and protect both beneficial insects and the environment. Experts from Bayer CropScience and
Bayer Technology Services are collaborating closely on a project
called ‘Zero’ Dust. Their goal is to further reduce dust generation and emissions when planting treated seed. The project name
­‘Zero’ Dust does not mean that there will be no dust emissions at
all, but rather refers to all measures that can help to minimize the
generation and emission of dust. The researchers and developers
are examining the entire process, from the makeup of the active
substances and additives in the treatment layer, to the planting
of the seeds on the field. In one sub-project, agricultural experts
The field vacuum cleaner
SweepAir helps to ensure that seed treatment agents do not escape into the atmosphere. The system separates the sowing
machinery’s exhaust air, blowing the air/dust mixture into a cyclone where centrifugal force causes the dust particles to strike the
inside wall of the cyclone container. From there they fall into a hopper and are then buried underground like the seeds.
Air from
sowing
machine
The SweepAir prototype has been
installed on conventional corn planting
machinery for field studies.
Air and dust
are separated
in cyclone
Abraded
dust
Airlock
Purified air
outlet
Dust is buried
42
Bayer research 27 December 2014
When seed grains rub against each
other, dust can be generated which
cannot be completely avoided.
“We need different modes
of action”
Martin Williamson is a molecular biologist and Senior Scientist in the
Biological Chemistry and Crop Protection Department of Rothamsted
Research in the United Kingdom. research spoke to him about the danger of resistance in parasites.
How does resistance evolve in parasites?
How can we tackle the resistance problem in the Varroa mite?
Resistance is usually caused by simple point mutations that occur
naturally in all organisms at extremely low frequencies; however,
when the mutation occurs in the target receptor for a pesticide,
for example, then that individual may be more likely to survive
subsequent treatments. The genetic changes are passed from one
generation to the next and further selection with the pesticide can
quickly result in a fully resistant population.
What are the challenges in detecting the underlying mechanisms?
Resistance is normally caused by two different types of mechanism. We have a good knowledge of both types from work that has
been done on a range of insect and mite pests. The main challenge
in Varroa mites is to obtain a range of samples with well-characterized resistance on which we can identify the mechanisms
involved.
and engineers are developing a kind of vacuum cleaner for corn
planting. “When handling and planting treated seed, dust can
be abraded. This dust is extracted from the air, transported to
the ground and buried there,” explains Dr. Lubos Vrbka of Environmental Modelling at Bayer CropScience. The heart of the
technology is a unit known as a cyclone separator: it sucks the
exhaust air pertinent to the pneumatic working principle from the
sowing machine, and with it the dust from the potentially abraded seed treatment agent and any dirt kicked up in the sowing
process. This air/particle mixture is blown into the cyclone, where
centrifugal force causes the dust particles to strike the inside
wall of the cyclone container. From there they fall into a hopper
and are buried underground. The clean air is released close to
the ground.
Positive reception from farmers and equipment
manufacturers
SweepAir is the name given by the Bayer experts to their field
vacuum cleaner, which farmers in Italy and Germany have already
tested successfully in field trials. The researchers did encounter
difficulties, however: for example, the fine, electrically charged
dust adhered to the inside wall of the cyclone. But engineers from
Bayer Technology Services found a solution. “We installed a shaker
that vibrates the container automatically every few seconds. This
Martin
­W illiamson
The key to effective resistance management is to have compounds
with different modes of action. They can be rotated regularly to
prevent resistance to any particular compound. Of course, this
is not always so simple. For Varroa mite control there are only a
few active compounds, and resistance is already known for each
of these. We need to manage the resistance more effectively by
understanding the underlying mechanisms and then by developing
rapid assays. In this way, it should be possible to predict which type
of resistance is present and to make informed recommendations
as to the most effective treatment in a particular group of hives or
region.
loosens the dust so that it drops downwards,” explains Dr. Volker
Michele, a fluid dynamics expert at Bayer Technology Services.
The SweepAir system has also passed a test at the distinguished
Julius Kühn Institute, where experts compare seed-sowing machine systems with a reference machine that blows air and dust
upwards. Compared to such reference machines, SweepAir releases 99 percent less dust into the atmosphere. European farmers have high hopes for the new technology. “They have been
waiting for a solution that enables an optimized risk management for seed treatment products, which is expected to positively
influence the perspectives for using neonicotinoids again,” Vrbka
says. The Bayer specialists have already received positive feedback from farmers and equipment manufacturers. Their next task
is to transfer the technology to machine manufacturers, who
could then produce and market the corresponding equipment.
“An important next step will now be to attain the endorsement
of government authorities for the use of these devices, and their
support for the new technologies as an optimized tool that assures the safe use of neonicotinoid seed treatment,” Friessleben
explains.
www.research.bayer.com/bees
Further information on this topic
Bayer research 27 December 2014
43
Peripheral nerve endings: messenger substances released in endometrial tissue can cause a direct sensation of pain.
44
Bayer research 27 December 2014
Endometriosis MEDICINE
NEW TREATMENT FOR ENDOMETRIOSIS
Two-fold effect
Photos: Photo Quest Ltd./Science Photo Library/Corbis (1), Thorsten Futh/Bayer AG (1) , Privat (1), Oredia/Your Photo Today (1)
For many women, endometriosis means severe abdominal pain, and not only during menstruation. Researchers at Bayer
HealthCare are now investigating new active substances for treatments that are aiming for a two-fold effect: rapidly
easing the pain and simultaneously treating the original abdominal inflammation that causes it, all without intervening in the female hormone balance.
Sometimes there is a state of emergency
inside the female body: once a month –
or in some cases even more frequently
– many women are plagued by extreme
abdominal pain. Their daily life is hugely
restricted by persistent menstrual bleeding, not to mention nausea and fainting.
The cause is endometriosis, a hormonal
and inflammatory disease in which menstrual blood and small bits of tissue shed
from the endometrium flow backwards
via the fallopian tubes into the abdominal cavity and begin growing there. The
abdominal pain is often chronic and leads
to problems during sexual intercourse,
Investigating endometriosis together: physicians Dr. Matthias Schäfers (right) and
urination and defecation. Endometriosis
Dr. Thomas Zollner (left) discuss new therapies with medicinal chemist and alliance manalso frequently turns out to be the cause
ager Dr. Christoph Huwe (center) at Bayer HealthCare in Berlin using a model of a uterus
of unwanted infertility.
for reference.
Although 10 percent of all women of
child-bearing age suffer from endometriosis, the disease is only identified after a
number of years in many patients: up to
ten years can pass between the onset of discomfort and diagder, intestines or pelvic wall, the characteristic pain can be
nosis. “Unlike comparable diseases in which pain is likewise the
very complex,” says PD Dr. Sylvia Mechsner from the Departprimary symptom, endometriosis is still frequently not recognized
ment of Gynecology at Charité University Hospital in Berlin.
in our society today, which can lead to a delay in reaching a diThe existing treatments are based on hormonal drugs that
agnosis and therefore lengthens the suffering experienced by the
suppress ovulation and keep estrogen at a low level. Howpatients,” says Dr. Thomas M. Zollner, Head of the Gynecological
ever, as many women are affected by the side effects of these
Therapies Research Department at Bayer HealthCare. “A lot of
drugs, they generally do not represent a long-term solution.
times, the symptoms are not taken seriously and palmed off as
‘completely normal’ menstrual pain, and that causes additional
Sensitive nerve fibers and neuropeptides
emotional stress for these women.” But the disease has other
lead to pain
implications as well: on account of their limited ability to work,
many women with endometriosis have to frequently call in sick,
In recent years, physicians have made significant discoveries
which leads to considerable financial losses every year. “The ecothat explain why endometriosis is so painful. The lesions in the
nomic cost of endometriosis is substantial as well,” says Zollner.
abdominal cavity are innervated by small nerve fibers which genThe significant pain associated with endometriosis is
erally grow along with the vessels supplying blood. Mechsner and
caused partly by inflamed tissue. “Because endometriosis can
her working group found that the sensitive nerve fibers that are
be located in many different places, for instance in the bladresponsible for pain perception are particularly common here.
Bayer research 27 December 2014
45
“We need new forms
of treatment”
research spoke with PD Dr. med. Sylvia Mechsner from the Department of Gynecology at Charité University Hospital in Berlin.
Sylvia
Mechsner
What treatment options are currently available for endometriosis?
The first step is to surgically remove the endometriosis lesions, while
at the same time sparing the organs involved as far as possible. Then
supportive hormone therapy should be initiated. Patients planning
to have children should also take advantage of the possibilities offered by reproductive medicine.
also support long-term therapy. However, these drugs frequently
have side effects that restrict a woman‘s quality of life. All round,
the situation is very unsatisfactory …
Where do you see a need for research?
What are the drawback to this treatment?
Most patients suffering extreme pain accept the need for surgery.
What is a problem however is when surgical removal does not have
the desired outcome, the pain remains unchanged or improves only
for a short time. In this case, more surgery must be given very critical consideration. The second pillar of treatment is hormones, which
The corresponding nerve cells also produce neuropeptides that
are released into the lesions and increase the symptoms of inflammation there. At the same time, the number of sympathetic
nerve fibers that regulate pain in the abdominal cavity is reduced.
Zollner and his colleagues in research at Bayer HealthCare therefore chose an entirely new approach to treatment, because they
discovered that a process known as retrograde menstruation,
which is under discussion as a main trigger of the disease, has
a direct influence on the peripheral nervous system. “The cells
in the endometrium contain a vast number of messenger substances which, when released, promptly lead to inflammation,”
Up to
6
million women
in Germany suffer from
­endometriosis.
Source: Endometriosevereinigung Deutschland
46
Bayer research 27 December 2014
For me as a clinical researcher who has patients suffering from
endometriosis, the most urgent goal is to find new, innovative
approaches to therapy. In addition to hormonal and surgical treatment, we also need therapies that target the inflammatory component of the disease, in other words counteract inflammation. We
urgently need new, non-hormonal forms of treatment that eliminate the underlying cause of the disease.
Zollner explains. What‘s more, these messenger substances can
activate structures known as peripheral nerve endings, which
cause a direct sensation of pain in the female body.
Collaborating with partners to develop new
active ingredients
In view of these findings, the Bayer researchers are working on
active substances that intervene simultaneously in both processes. “In our approach, we want to treat the site of inflammation
directly and at an early stage, but also minimize the resulting
pain perception,” Zollner explains. To drive research in the field
of endometriosis forward in this direction, the gynecology specialists at Bayer HealthCare are steadily expanding their international research network. Bayer has been collaborating with
Evotec AG in this area since October 2012. The objective of the
five-year research partnership is to develop three innovative
substances that support alternative forms of treatment in the
field of endometriosis and have both an anti-inflammatory and
pain-relieving effect. Roughly half of Bayer‘s endometriosis
product portfolio is currently being worked on in collaboration
with Evotec. In all activities, the two companies work together
closely. “Our research cooperation is a real partnership. We work
on every one of our projects in joint teams; both partners have a
significant share in their success,” comments Dr. Christoph Huwe, a medicinal chemist and the alliance manager for External
Endometriosis MEDICINE
Relieving pain
Endometrial tissues can migrate to various organs in the abdominal cavity and cause
inflammation there. Women who are affected by this condition generally suffer extreme
pain. Bayer scientists are now taking a two-fold approach to the disease: they are developing active substances that both inhibit inflammation and influence the onset of pain
signals in the endometrial lesions and the peripheral nervous system.
Inflammation signal
transmitted from
organs via the spinal
cord to the pain center
in the brain.
A crisis in the abdomen: endometriosis
causes extreme pain that can seriously
restrict the ­sufferer’s daily life.
Sites of action of new active substances:
Organs with
endometrial tissue
Innovation Therapeutics at Bayer HealthCare responsible for the
collaboration with Evotec.
The first active ingredient candidate is already in
preclinical development
The partners have made major progress over the last two years
in developing innovative active substances to treat the disease.
“This year already, our first candidate went into preclinical development,” Huwe adds. The active substances, however, must
have as little influence as possible on the hormone balance –
and thus on the female menstrual cycle and fertility. “We hope
that these newly discovered drugs will work faster than previous, hormone-based endometriosis medications. We expect
a significant reduction in pain just one month ­after a patient
takes the first tablet,” says Dr. Matthias Schäfers, Clinical Head
of Gynecological Therapies at Bayer HealthCare. “What‘s more,
Pain stimulus is suppressed
Inflammation is prevented
from spreading
thanks to their targeted effect, the new products could potentially be better tolerated than the conventional pain medications.” In addition to the partnership with Evotec, ­Bayer also
launched a joint venture with the University of Oxford, U.K., an
academic leader in the field of endometriosis and pain therapy, in July 2014. As all these activities show, Bayer HealthCare has set a course for long-term and successful treatment
of endometriosis.
www.research.bayer.com/endometriosis
More information on this subject
Bayer research 27 December 2014
47
AGRICULTURE Phytobac
WATER CONSERVATION IN AGRICULTURE
Protecting a precious resource
Water is the most vital resource for life, and water conservation is therefore an essential element of sustainable agriculture.
Experts at Bayer CropScience have developed an innovative system for farmers that is designed to prevent contamination of
surface waters by, for example, crop protection agents. Any pesticides in the rinse water that is left over after cleaning the
farmyard are broken down in exactly the same way as they would be naturally – only more efficiently.
3 %
of the world‘s water
­resources is fresh water.
It is used as follows:
Air flow
69% in agriculture
6
Water evaporates
23% in industry and
8% for private households
4
1
Farm soil (70%) with straw chaff (30%)
Impermeable container
Dirty water
Microbiological degradation
5
3
Mud tank
Water tank
2
Biological agricultural cleaning system
The Phytobac™ system developed by Bayer experts ensures that contaminants cannot get into sewage systems or nearby bodies
of water when spraying equipment is filled or cleaned on the farm 1 . The dirty water first flows into a mud tank 2 , where the
rough dirt settles as sediment. The clear residual liquid is stored in the second tank 3 and fed in doses into the substrate con­
tainer filled with farm soil and straw 4 . The straw serves as an additional source of carbon which promotes microbial degra­
dation. Measurement and control elements regulate the soil moisture levels, creating ideal living conditions for microorganisms 5 such as bacteria and fungi. The enzymes in these tiny helpers break down residues of fungicides, herbicides and insecticides
while the water evaporates 6 .
48
Bayer research 27 December 2014
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Responsible for the contents: Dr. Herbert Heitmann
Head of publications: Franz Rempe
Editorial team:
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transquer GmbH - wissen + konzepte, Munich
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More than 50 infographics can be downloaded at www.research.bayer.
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Published in December 2014
E 2910247633
ISSN 0179-86188
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