here - The Triple Helix Cambridge
Transcription
here - The Triple Helix Cambridge
Volume 24 Lent 2015 University of Cambridge POLICY Evidence-based Policymaking GENETICS Epigenetics and Lamarckian Inheritance IMMUNOLOGY The Immune System: A cure for cancer? SYNTHETIC BIOLOGY The next revolution? the triple helix cambridge ASU · Berkeley · Brown · Cambridge · CMU · Cornell · Georgetown · George Washington · Georgia Tech camtriplehelix.com Harker · Harvard · JHU · NUS · OSU · Oxford · UC Davis · UCSD · UChicago · Melbourne · Yale Write for us! the triple helix A global forum for science in society THE INTERNATIONAL TEAM Chief Executive Officer Yucheng Pan Chief Operating Co-officers Melina Gyparaki Tahsin Rahman Leslie Sibener Co-editors-in-chief Sofia Hu Raagini Suresh Stephanie Vereb Helen Zhao Chief Social Media Officer Jai Thakor Chief Multimedia Officer Siddhartha Jena Chief Technology Officer Angela Bai Chief Marketing Officer Divya “Nikki” Raghani Marketing Officer Soyeun Yang The Triple Helix, Inc. is the world’s largest completely student-run organization dedicated to taking an interdisciplinary approach toward evaluating the true impact of historical and modern advances in science. Work with tomorrow’s leaders Our international operations unite talented undergraduates with a drive for excellence at over 25 top universities around the world. Imagine your readership Bring fresh perspectives and your own analysis to our academic journal, The Science in Society Review, which publishes International Features across all of our chapters. Reach our global audience The E-publishing division showcases the latest in scientific breakthroughs and policy developments through editorials and multimedia presentations. Catalyze change and shape the future Our new Science Policy Division will engage students, academic institutions, public leaders, and the community in discussion and debate about the most pressing and complex issues that face our world today. All of the students involved in The Triple Helix understand that the fast pace of scientific innovation only further underscores the importance of examining the ethical, economic, social, and legal implications of new ideas and technologies — only then can we completely understand how they will change our everyday lives, and perhaps even the norms of our society. Come join us! North America Arizona State University Brown University Carnegie Mellon University Cornell University Georgetown University Georgia Institute of Technology Harvard University Harker School Johns Hopkins University Massachusetts Institute of Technology Northwestern University Ohio State University University of California, Berkeley University of California, Davis University of California, San Diego University of Chicago Yale University Europe University of Cambridge University of Oxford Asia National University of Singapore Australia University of Melbourne TABLE OF CONTENTS 4 5 How should evidence affect policymaking? 8 Message from the President Cambridge features 5 Evidence-based Policymaking and its Importance Afham Raoof 8 Epigenetics and Lamarckian Inheritance Jane Phea Cover Article 13 Synthetic Biology The Next Revolution? Hugh Wilson 16 A potential cure for cancer? Wearn Xin Yee Understanding the Immune System Epigenetics saves Lamarck’s theory of inheritance INTERNATIONAL FEATURES 16 How the immune system may ‘cure’ cancer 23 The Great Pacific Garbage Patch Johns Hopkins 20 Implications of Synthetic Life Sohail Zahid Johns Hopkins 23 Why the World’s Largest Landfill is in the Ocean Stephen Jenkins Cornell 26 The New “Black Gold”: Biochar Jennifer Sun Cornell 28 Reading Reinvented How Computers and the Internet are Inf luencing our Society Latha Panchap 31Acknowledgements THE SCIENCE IN SOCIETY REVIEW ∙ LENT 2015 INSIDE TTH THE CAMBRIDGE TEAM President Justin Koh (Queens’) Editors-in-Chief Justin Koh (Queens’) Jessica Xie (Newnham) Managing Editor Digory Smith (Selwyn) Outreach DIrector Alice McGenity (Trinity Hall) Events DIrector Tengo Meskhi (Homerton) Skill Development Officer Tiffany Mak (Sidney Sussex) Production Manager Fred Zhu (Jesus) Assistant Production Manager Joanna Wolstenholme (Jesus) Sponsorship Director James Farr (Clare) Junior Treasurer Maria Tang (St John’s) SENIOR REVIEWERS Dr Gos Micklem A Message from the President Happy New Year, everyone! The Triple Helix is back for another term of scientific perspective! This time, we learn a little more about the most complex form of technology—Biology! Who says that space is the final frontier of human endeavor, when some of the greatest mysteries and potential lie are written in our genes? Speaking of genes, look out for a fresh perspective on why giraffes have long necks. (Hint: It’s not a tall story.) We also have an article on how our body may be greater than we could ever imagine, where scientists are trying to discover ways to exploit the immune system to treat cancer. That Zen quote about “change must come from within” may just hold true in this respect. And how are the higher-ups handling research? Are they making the right decisions? In a critical take on government policy with respect to research, we have reason to think that we could do better than we are faring now. And finally, a big shout-out to… everyone who is reading this! We are always looking for writers, so that we can continue writing good science and promoting a greater scientific literacy and encouraging public interest in science! We need your ideas, people. Do you think we should write about something in particular? Do you have suggestions on how we should improve our publication’s focus? Are we addressing your needs and wants? Or do you just want to cut to the chase and write something for us, no nonsense? Contact us. Dr Elizabeth Radford Dr Rahia Mashoodh Justin Koh Professor Anne Ferguson-Smith President The Triple Helix Cambridge Łukasz Magiera Dr Alex Morris Journal design by Fred Zhu. 4 REPRODUCED FROM [8] THE TRIPLE HELIX CAMBRIDGE CAMBRIDGE Afham Raoof Evidence-based Policymaking and its Importance Afham Raoof is a second year Natural Sciences student at Selwyn College. He enjoys reading, quizzes, badminton and spending an inordinate amount of time watching sports, especially American ones. He hopes to one day help make the world a better and more sensible place. E vidence. The principle upon which all scientific endeavour is founded. It has long been undisputed that the analysis of evidence is integral to improved understanding of the world, and, especially in the case of medicine, integral to the decision making process for issues that affect people’s lives. Yet the use of evidence is not given its requisite importance in the sphere where people are perhaps affected the most— that of government policymaking. For too long, governments have worked upon predetermined principles, dependent on their political ideologies. I am advocating a change in this approach, and an increased importance in the role of evidence in policymaking. 5 THE SCIENCE IN SOCIETY REVIEW ∙ LENT 2015 CAMBRIDGE what is evidence-based policy? An evidence-based approach to policymaking is one where governments attempt to gather data about the results of different courses of action, and thus determine which course will be most beneficial for their citizens. Governments often do not do this. Historically, they have come in promising a broad range of ideas that all can be defined under one political umbrella: “left”, “right”, “socialist”, “libertarian” or something similar. Political parties base their overall policy theme around what they believe to be the values and beliefs of the electorate (or what beliefs they think will best get them elected). However, representation is not the only important function of governments. Another is creating the set of policies that best helps all of their citizens. An evidence-based approach, when possible, is the only way to achieve this. It is extremely unlikely that the optimum set of policies will all come from one part of the political spectrum. Governments should seek out the best policies in a similar way to how scientists seek out the best theories—by gathering evidence on multiple possibilities, and coming to a reasoned and considered decision. There are of course some areas where such an approach is not feasible, and a moral or social judgement has to be made (the definition of marriage being an obvious example). But there are many where it is. Such an approach would also help mitigate the petty arguing that so pervades politics nowadays, as can be seen in the terrible behaviour by MPs at Prime Minister’s Questions. Evidence promotes the attitude of working together towards a problem, rather than merely trying to prove your party’s ideas are better than the other’s. where can it be helpful? The best example of where ideological policymaking has been harmful is probably the drug war. Drug policy lends itself to an evidence-based approach more than other areas of government policy (as will be discussed later). It is largely a medical issue that governments have insisted as treating as a criminal or ideological one. The harms of drug use to society are similar to the harms caused by illnesses—personal misery, healthcare costs, effects on families, etc. I will not get on my soapbox about drug decriminalisation here, but instead point out that governments are not considering the right variables. Fundamentally, as an issue of public health, a cost-benefit based approach should be used. Governments should consider whether the immense cost and effort spent on drug enforcement, combined with the loss or benefit to those who either enjoy taking drugs or are helped by them, is outweighed by the benefit to society caused by the reduction in harm due to reduced drug consumption. A similar approach is used by the National Institute of Clinical Excellence when deciding whether to fund a drug for the NHS. Instead the British 6 government punishes drug users to “send a message” that they are wrong, as David Cameron said in 2014. Making moral, ideological judgements on drug users is not conducive to an overall increase in social welfare. While I think it is obvious what the conclusion would be if this analysis was carried out, that is not the issue. The issue is that governments utterly refuse to consider the issue in these terms. The British government’s refusal to consider evidence in this sphere is seen by their sacking of Professor David Nutt as an advisor, after he attempted to suggest, evidentially, that the harms of drugs such as ecstasy were not commensurate with their penalties for consumption.1 Professor Nutt suggested that ecstasy was “no more dangerous than riding a horse”, making a mockery of the government’s harsh penalties for its possession. He was censured as a result. It is extremely unlikely that the optimum set of policies will all come from one part of the political spectrum alternate approaches It is true, however, that not all areas of government policy lend themselves to such an approach as well. Friedrich Hayek, the 1974 Nobel Laureate in Economics, mentioned in his Nobel speech the difficulty of applying scientific methods to social sciences, saying “…in the social sciences, often that is treated as important what is available for measurement.”2 As the quote says, it is true that in areas such as economics, obtaining reliable evidence for the effects of such policies is extremely difficult. A purely evidential approach is not possible in these cases. Indeed, a government that has an agenda which it is able to pretend is evidence-based can be extremely dangerous. A modification of the evidential method is needed. In this scenario, a Bayesian approach, where economic theories are modified depending on available evidence weighted with a prior probability of this evidence occurring, would be the most sensible. Immigration is another issue where while a purely evidential approach may not be possible, it is still necessary to gather evidence and consider the evidence available. Recent studies showing the benefits of legal immigration to Britain3 should be driving forces behind our policies, not anecdotes and preconceived notions of what Britain should be like. Equally, studies showing the negative effects of immi- REPRODUCED FROM [9] THE TRIPLE HELIX CAMBRIDGE gration, if they were to be published, should be considered. Countries such as Sweden, which have liberal immigration policies as a matter of principle,4 should reconsider such ideas if they are found to be having a negative impact on its citizens. The paramount principle is simple. Governments must do what is best for everyone. Evidence is the best way to achieve this. the current state of evidence-based policy It must be said that the use evidence-based policy is in a much better state than it was even 20 years ago. The government of Tony Blair explicitly set out the use of evidence as one of its main plans, with Blair saying in 1999 “We will ensure that all policies and programs are clearly specified and evaluated, and the lessons of success and failure are… acted upon”.5 Barack Obama has also stated that he is in favour of such an approach. However, it is extremely difficult to be confident in the ability of governments to deliver on such promises when people who show ignorance of the most basic science are given senior positions in government. In America, a recent storm has broken out due to Senator James Inhofe, a man who has previously said that global warming is “The greatest hoax ever perpetrated on the American people”, likely being appointed chair of the Environment and Public Works committee.6 Inhofe, by his statements, has clearly shown himself unable to sensibly analyse the vast corpus of evidence available in favour of anthropogenic climate change. The fact that the US Congress is willing to appoint such a man to a position that is largely scientific in nature clearly shows that the ability to consider evidence is not a valued attribute. In the UK, the fact that David Tredinnick MP, a supporter of astrology and homeopathy, is allowed to sit on the Commons Health Committee,7 gives a similar vibe. It is in this context that the work of MPs such as Cambridge’s Julian Huppert become even more important. As the only former research scientist in the Commons, Huppert is best acquainted with the scientific method— not only its benefits, but, crucially, its limitations. It is no surprise that Julian has been a key part of the Lib CAMBRIDGE Governments must do what is best for everyone. Evidence is the best way to achieve this Dems’ move towards an evidence-based drugs policy. The advocacy of Huppert and MPs of similar disposition is vital to ensure that the government can move towards the right balance. No-one is advocating technocracy. The situation is far better than it has been in the past. Yet, despite science’s increasingly high profile in the world, governments have yet to strike the right balance. They need to go further to give evidence its rightful place in policymaking. The sooner they do, the sooner they can be said to be truly serving their people. references 1. Tran, M. (2009). Government drug adviser David Nutt sacked. The Guardian. [online] Available at: http://www.theguardian.com/politics/2009/oct/30/drugs-adviser-david-nutt-sacked [Accessed 27 Dec. 2014]. 2. Hayek, F. (2014). Friedrich August von Hayek - Prize Lecture: The Pretence of Knowledge. [online] Nobelprize.org. Available at: http://www.nobelprize.org/ nobel_prizes/economic-sciences/laureates/1974/hayek-lecture.html [Accessed 27 Dec. 2014]. 3. Dustmann, C. and Frattini, T. (2014). The Fiscal Effects of Immigration to the UK. Econ J, 124(580), pp.F593-F643. 4. The Japan Times, (2014). Sweden can’t avoid debate on immigration, analysts say | The Japan Times. [online] Available at: http://www.japantimes.co.jp/ news/2014/12/28/world/social-issues-world/sweden-cant-avoid-debate-on-immigration-analysts-say/#.VKlUCSusWGo [Accessed 4 Jan. 2015]. 5. Australian Government Productivity Commission 2010, Strengthening Evidence Based Policy in the Australian Federation, Volume 2,Chapter 1, Roundtable Proceedings, Productivity Commission, Canberra. 6. Goldenberg, S. (2014). Climate change denier Jim Inhofe in line for Senate’s top environmental job. The Guardian. [online] Available at: http://www.theguardian. com/environment/2014/nov/06/climate-denier-jim-inhofe-in-line-for-senates-topenvironmental-job [Accessed 27 Dec. 2014]. 7. BBC News, (2014). Astrology can aid healthcare - MP. [online] Available at: http:// www.bbc.co.uk/news/uk-politics-28464009 [Accessed 27 Dec. 2014]. 8. http://commons.wikimedia.org/wiki/File:International_law_books_(8147928376). jpg 9. Photo by DAVID ILIFF. License: CC-BY-SA 3.0 7 THE SCIENCE IN SOCIETY REVIEW ∙ LENT 2015 CAMBRIDGE Jane P epigene lamarckian Jane is a first year studying Natural Sciences at Peterhouse. Often found in deep trance simulating intelligent activity or scouring the streets of Cambridge for things that catches her fancy. 8 THE TRIPLE HELIX CAMBRIDGE CAMBRIDGE Phea etics & inheritance an underlying paradox of the Darwinian theory of evolution is that while living organisms are constantly adapting to the environment, these adaptations are not passed on to the DNA in the reproductive cells and are consequently not inherited. Rather, random mutations seem to be fixed by natural selection (biased selection of mutations based on the benefits it confers to an organism in a particular environment) or by genetic drift (random fluctuations in frequencies of mutations that results in them being either fixed or diminished in a population). Lamarck’s “use and disuse” theory may be a solution to this paradox, but there remains parts of his theory that lack satisfactory explanation. 9 THE SCIENCE IN SOCIETY REVIEW ∙ LENT 2015 CAMBRIDGE In Lamarck’s theory, body parts that are in constant use will be strengthened, while those unused will be diminished. A classic example is that of a giraffe’s neck. It is postulated that the predecessor of the giraffe had somewhat short necks, and that the muscles in their necks were strengthened and lengthened by persistent stretching to reach leaves on high trees. This lengthening was subsequently inherited through the generations, each having slightly longer necks, gradually yielding the organism we now call a giraffe. It is unlikely that the strengthening of muscles (adaptation) will result in corresponding changes to the DNA (inheritance), and therefore this is a gap in his theory. Epigenetics appears to be the ‘missing link’ connecting adaptation and inheritance that bridges the gap in Lamarck’s theory, akin to the modern synthesis that unifies genotype (the sum total of genes present in an organism) and phenotype (observable traits of an organism). In this article, I shall attempt to address the plausibility of epigenetics as a mechanism of adaptation and the controversies surrounding it. ence in morphology between the queen bee and worker bee, dependent solely on whether a bee was fed royal jelly during its developmental phases. These differences arise despite the fact that both the worker bee and queen bee share identical DNA sequences2.3 Another example would be the divergence of mammalian cells from the initial zygote to form such hereditawry cell lineages as the nerve cells and muscle cells. After differentiating in the early stages of development, nerve cells will only give rise to nerve cells and muscle cells to muscle cells, and cells would not generally revert to other cell types.4 These phenotypic differences arise due to the modulation of gene expression patterns (the activation or repression of certain genes) by the epigenetic factors without changing the underlying DNA sequence. Such is epigenetics. The current interest lies in the mechanisms by which the environment may cause these changes, and subsequently, whether these changes may transcend both the organismal and cellular level and persist through several generations, the importance of which cannot be comprehended fully without a brief understanding of inheritance. Epigenetics appears to be the missing link… that bridges the gap in Lamarck’s theory epigenetics The definition of epigenetics that shall be adopted in this article is the study of modifications to the DNA that are heritable and does not change the underlying DNA sequence. These modifications consequently contribute to a perpetuation of altered states (phenotypes) in an organism.1 The types of modifications that constitute epigenetics are numerous, but the most closely studied ones are1 DNA methylation, which involves the addition of methyl groups to regions of DNA and2 modifications of histone proteins (proteins around which DNA is wrapped to facilitate the formation of a compact chromatin structure), which entails the addition of certain groups, e.g. methyl, phosphate and acetyl. As both these modifications involve DNA, it may be that changes in these modifications would subsequently be passed on to an organism’s offspring via the nucleus of reproductive cells, though this remains the subject of much controversy. There are some striking examples of phenotypic variability which are thought to be due to underlying epigenetic rather than genetic differences. One of the most powerful examples of epigenetics is that of the differ- 10 Jean Baptiste Lamarck lamarckian inheritance: a valid proposal? The generally accepted mode of inheritance is that akin to August Weismann’s proposal, which consists of a few main thrusts: 1. 2. 3. The soma (all cells in the body except the egg and sperm cells) and germ-plasm (egg and sperm cells) are disparate. Changes, if any, acquired through the lifetime of an individual due to such factors as stress or changes in the environment, accumulate in the soma, not in the germplasm. These changes are not passed on to the offspring. THE TRIPLE HELIX CAMBRIDGE CAMBRIDGE REPRODUCED FROM [11] Therefore, the Lamarckian idea of “use and disuse” is duly discredited, as (according to this theory) the environment has no means of inducing changes in the germ cells.5 Currently, developments in epigenetics has prompted a resurgence in interest in the inheritance of acquired characteristics as a valid mechanism for evolution, as epigenetics could be a means of mediating heritable changes induced by the environment. These changes must affect the germ-plasm, and subsequently be transferred along with the germ cell during fertilization in order to effect changes. experimental evidence for transgenerational inheritance A recent experiment published in Nature Neuroscience seems particularly promising.6 Male mice (F0) were conditioned to associate fear with the smell of acetophenone by being administered a mild foot shock when exposed to the smell. These conditioned mice were more prone to shuddering when exposed to loud sounds when compared to normal mice and this sensitivity was passed on to first (F1) and second generation (F2) offspring. Remarkably, F0, F1 and F2 mice have lower methylation levels in the gene (in the sperm) that codes for the acetophenone receptor, which translates to higher sensitivity to that particular odour. Lower methylation levels often correlate with increased gene expression. This experiment is noteworthy for the precautions taken to eliminate certain confounding factors.1 The mice were conditioned with two different odours (acetophenone and propanol), yielding near identical results.2 A maze test was carried out, and the offspring of conditioned mice responded as per normal mice, which rules out the possibility that they were simply more anxious in general.3 Some mice were conceived using IVF to prevent transmission of odor sensitivity due to interactions between the father and mother mice.4 Cross-fostering of mice (offspring of conditioned mothers were fostered by non-conditioned mothers and vice-versa) were carried out to eliminate maternal effects.5 Methylation levels were screened in two different genes, one coding for the acetophenone-detecting receptor and another that codes for a receptor detecting a separate odour, and it was found that only the former showed statistically significant differences in DNA methylation levels. In two separate stress-related experiments on mice, alterations in DNA methylation were found to correlate with1 stress levels experienced by the father and2 attention received from the mother.78 In the former experiment, offspring of stressed mice had a higher susceptibility to depression-like states while in the latter experiment, mice who received more attention from their mothers were shown to cope better under stress. Meanwhile, Agouti variable yellow female mice who had varying amounts of methyl supplements in their diets during gestation had offspring with differing colour coats and susceptibility to obesity, the effects of which is also attributed to DNA methylation. For all these experiments mentioned above, it is postulated that induced changes in the environment would result in changes in methylation patterns on DNA in mice, which are subsequently passed through the generations. This supports the notion that epigenetics may indeed facilitate the inheritance of acquired characteristics. But for complete acceptance of this theory, some hurdles remain to be overcome. 11 THE SCIENCE IN SOCIETY REVIEW ∙ LENT 2015 CAMBRIDGE REPRODUCED FROM [12] limitations and uncertainties 1. 2. 3. How exactly does the environment posit these changes? Do receptor molecules, in the case of the odour experiment, interact with and somehow activate proteins that methylate or de-methylate DNA? Given that the environment is able to induce changes in the methylation status of DNA, how are these modifications passed on to the offspring? During the process of gamete synthesis and post-fertilization, most DNA modifications are removed, resulting in a blank state of sorts. Changes can only be propagated if the modifications escape this process or if modifications were made directly to the reproductive cells. A limitation of the Nature Neuroscience study is that it was confined to the settings of an experimental laboratory. Thus, any changes in the epigenetic status of the DNA would have been artificially induced, and it is hard to argue that nature would disrupt DNA in a similar manner, or that “mutations” of this kind will have a discernible effect on inheritance. 4. Another question to note is whether these modifications persist long enough to be transmitted through the generations? Are the effects sufficient to posit long-term evolutionary change or do they simply act as short-term adaptations that are muffled and counterbalanced over the course of time? All in all, it may be surmised that epigenetics may be a plausible channel to propagate Lamarckian inheritance, and that there is a plethora of experimental evidence in plants and worms to support this school of thought, though similar evidence in mammals are fewer and far-between. A dose of skepticism is still warranted in the face of intricacies surrounding this new field, but “the inheritance of differential epigenetic information” that “could potentially contribute to altered traits or disease susceptibility in offspring and future descendants” “has a deliciously Lamarckian flavour… difficult to resist.”1,20 references 1. Bird, A. Perceptions of epigenetics Nature 2007;447 : 396-398 http://www.nature. com/nature/journal/v447/n7143/full/nature05913.html?message=remove&lang=en (Accessed 24 December 2014) 2. Kucharski R, Maleszka J, Foret S, Maleszka R. Nutritional Control of Reproductive Status in Honeybees via DNA Methylation. Science 2008; 319 (5871) : 1827-1830. http://www.sciencemag.org/content/319/5871/1827.full (Accessed 24 December 2014) 3. Herb BR, Wolschin F, Hansen KD, Aryee MJ, Langmead B, Irizarry R, Amdam GV, Feinberg AP. Reversible switching between epigenetic states in honeybee behavioral subcastes. Nature Neuroscience. 2012. 15: 1371–1373. http://www.nature.com/neuro/ journal/v15/n10/full/nn.3218.html (Accessed 24 December 2014) 4. Jablonka E, Transgenerational Epigenetic Inheritance: Prevalence, Mechanisms, and Implications for the Study of Heredity and Evolution. The Quarterly Review of Biology. 2009; 84(2) : 131-176. http://www.jstor.org/stable/10.1086/598822 (Accessed 24 December 2014) 5. Weismann A, The germ plasm : a theory of heredity. Trans Parker WN, Rönnfeldt H. New York: Charles Scribner’s Sons; 1893. p 463 6. Dias BG, Ressler KJ. Parental olfactory experience influences behavior and neural structure in subsequent generations. Nature Neuroscience. 2014;17 : 89-96 http://www.nature.com/neuro/journal/v17/n1/abs/nn.3594.html (Accessed 24 Dec 12 2014) 7. Dietz DM, LaPlant Q, Watts EL, Hodes GE, Russo SJ, Feng J, Oosting RS, Vialou V, Nestler EJ. Paternal Transmission of Stress-Induced Pathologies. Biol Psychiatry.2011; 70(5): 408–414. http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3217197/ (Accessed 24 December 2014) 8. Chen Z, Riggs AD. DNA Methylation and Demethylation in Mammals. J. Biol. Chem. 2011, 286:18347-18353 http://www.jbc.org/content/286/21/18347.long (Accessed 24 December 2014) 9. Schmitz RJ, The Secret Garden—Epigenetic Alleles Underlie Complex Traits. Science 2014;343 (6175):1082-1083. http://www.sciencemag.org/content/343/6175/1082.full (Accessed 24 December 2014) 10. University of Cambridge. Scientists discover how epigenetic information could be inherited. http://www.cam.ac.uk/research/news/scientists-discover-how-epigenetic-information-could-be-inherited (Accessed 24 December 2014) 11. ttp://cnx.org/contents/41c4c77e-a44c-431f-bbc032eb72726630@1/Basic_Principles_of_Genetics 12. http://commons.wikimedia.org/wiki/File:Lab_mouse_mg_3216.jpg THE TRIPLE HELIX CAMBRIDGE CAMBRIDGE Hugh Wilson is studying Part III Physics at Downing College. He is especially interested in Biophysics and Biotechnology. synthetic biology: the next revolution? hugh wilson 13 H CAMBRIDGE umans may not be the only tool users, but more than any other life we have augmented our powers beyond the base established by nature. Early efforts in any new technology rely on trial and error guided by intuition. As our understanding improves, the guiding principle changes from trial and error to predictive design. However, the technology does not truly affect people until we capture our ability to manipulate the world in predictable devices (think of electrical circuits as devices which manipulate electromagnetic fields). The importance of this step is that one set of engineers can make the devices, while another can ignore how the devices work, but combine them into systems which solve problems. The technological revolutions which have shaped human history rest on this principle of dividing work between specialised groups. In the 18th Century, there was a revolution in transforming energy: the Industrial Revolution. In the 20th Century, there was a revolution in information processing: the advent of widespread computing. In the 21st Century, Synthetic Biology is poised to revolutionise our ability to manipulate matter. The current bespoke efforts of biotechnology will be replaced by a paradigm in which predictable biological components are combined to create devices. The process will shadow the construction of electronic devices from electrical components and the power of biology will become accessible to all. At least, this is the view of proponents of the field. The truth is much less certain. After long theoretical discussion, Synthetic Biology came into existence as a practical discipline near the turn of the millennium when the first synthetic genetic devices were demonstrated in live cells. In a short time, the field has garnered a huge amount of interest. The media attention has been intense;1,2 DARPA has declared that rapid engineering of biological systems is one of the highest national priorities;3 and a presidential commission was formed to report on how America can reap “the benefits of this developing field of science while identifying appropriate ethical boundaries and minimising identified risks”.4 The reason for this attention is that Synthetic Biology makes big promises. We will harness microbes to produce biofuel;5 engineer more efficient photosynthetic plants to meet the global energy shortage;6 and perhaps even make ourselves immune to viruses.7 A more sober 14 THE SCIENCE IN SOCIETY REVIEW ∙ LENT 2015 inspection of the field reveals that many of these claims are hopes for the future. However, there has been real progress towards solving significant problems. A good example is the construction of a toggle switch in E. coli by Collins et al.8 The bacterium they produced could be switched from expressing one gene to another using chemical and thermal stimuli. A second example is the work of Jay Keasling.9 He and his team have genetically engineered yeast to artificially produce a potent anti-malarial, artemisinin. The new synthetic source is more stable and cheaper than existing sources, which means the work will significantly improve the lives of many people. Yet doubt still hangs over Synthetic Biology: to solve global problems we need a library of predictable and interchangeable components to rival that of electronics. This library would be a significant milestone in the development of Synthetic Biology, but progress towards it has been mixed. A large number of components have been generated, but many are poorly described and fail to work when removed from their original organism and system. Will we ever reach the goal? It is difficult to be certain; the success of Synthetic Biology will hinge on our progress against technical hurdles and on the attitude and policies we adopt as a society. Synthetic Biology is poised to revolutionise our ability to manipulate matter The technical problems can be broken into four main areas.10 Firstly, many of the components are not well characterised: for example, certain components code for the creation of coloured proteins, but it is unclear exactly how the absorption spectrum of the cell will be affected. This lack of information is a problem. We must know how a component behaves before we can include it in the design of a complex system. Secondly, even with well-characterised components, the behaviour of a system can differ from what we would predict. Thirdly, even when a component works exactly as expected it can have an adverse, even fatal, effect on the viability of the host. Finally, random fluctuations within the cell can mean the behaviour of a system is not consistent over time. These four technical problems lead to a question: is the apparent modularity of nature a genuine property or is it an artefact of how humans try to understand it? To answer this question scientists are attempting to build lifelike systems which are less extensively THE TRIPLE HELIX CAMBRIDGE interlinked and so more amenable to the goal of packaging biological function into devices. In 2005 Drew Endy altered the bacteriophage (virus) T7 by rewriting its genome to reduce the interaction between different genes.11 The altered bacteriophage maintained the key features of the original, but was easier to understand, model and manipulate. Now an international consortium is doing the same for the whole yeast genome12 and they have already published one chromosome.13 This field of research is often termed “synthetic genomics” and an important practical goal is to develop generic platforms for biotechnology. It is not only technical hurdles which face Synthetic Biology. People hold strong views about whether it is morally acceptable to manipulate life. Synthetic genomics is subject to claims that scientists are trying to play God.14 Additional concerns are centred around the problem of “dual-use”: Synthetic Biology lays the foundation for bioterrorism as well as for a host of beneficial applications. In 2002 Professor Eckard Wimmer was able to synthesise poliovirus from scratch from the publicly available viral sequence and mail-order pieces of DNA.15 As with any new technology the potential benefits of Synthetic Biology are accompanied by risks. However, safety controls, such as a switch to kill modified organisms, can be used to push the balance of opinion towards continued development. There is an additional problem of perception. GM technology is partly unpopular because it is seen as a mechanism by which control is transferred from individuals to unaccountable trans-national corporations. This sentiment is evident in the animosity directed at agribusiness companies such as Monsanto.16 The same fears should not be applied to Synthetic Biology, which is fundamentally a force for the democratisation of science and technology. An annual demonstration of this fact is present in the form of the iGEM (international Genetically Engineered Machine) competition, which invites school, undergraduate and postgraduate teams from around the world to develop new applications of CAMBRIDGE Synthetic Biology and share them openly at a global meeting.17 The further impact of society on Synthetic Biology comes in how we deal with the issues of ownership and intellectual property. The mixed parentage of the field manifests itself in the range of solutions offered to this problem. Ideas from engineering and software development have led to the BioBricks Foundation with the mission statement: “to ensure that the engineering of biology is conducted in an open and ethical manner to benefit all people and the planet”.18 On the other side, bio-tech organisations, such as the Venter Institute, believe that a proprietary climate is necessary. They argue patents are required to encourage investors to support vital foundational research. However, it is certainly possible for overly broad patents to stymie new technology. For example, zinc finger nucleases were a promising technology that allows segments of DNA to be inserted at a specific site in the genome. The Californian company Sangamo Biosciences holds a comprehensive patent for the technology and many believe progress with the tool has been slow as a result.19 It seems Synthetic Biology is a field which has promised much and not yet completely delivered. Whether it will ultimately be able to fulfil its promises depends equally on our progress against technical hurdles and on how as a society we choose to interact with the possibilities it presents. references 1. Michael Specter; “A life of its own: where will synthetic biology lead us?”; The New Yorker 2009; September 28 2. W. Wayt Gibbs; “Synthetic Life”; Scientific American; May 2004 3. DARPA (Defense Advanced Research Projects Agency) http://www.darpa.mil/ our_work/ 4. Presidential Commission for the Study of Bioethical Issues; “NEW DIRECTIONS: The Ethics of Synthetic Biology and Emerging Technologies”; December 2010; available from: http://bioethics.gov/sites/default/files/PCSBI-Synthetic-Biology-Report-12.16.10_0.pdf 5. Michael S Ferry, Jeff Hasty, Natalie A Cookson; “Synthetic biology approaches to biofuel production”; Biofuels (2012); 3(1), 9-12 6. Biotechnology and Biological Sciences Research Council; “Human-made photosynthesis to revolutionise food and energy production” February 17, 2012; available at: http://www.sciencedaily.com/releases/2012/02/120217145755.htm 7. George Church, Ed Regis; “Regenesis: How Synthetic Biology Will Reinvent Nature and Ourselves” ISBN-10: 0465021751; ISBN-13: 978-0465021758 8. Timothy S. Gardner, Charles R. Cantor, James J. Collins; “Construction of a genetic toggle switch in Escherichia coli”; Nature (2000); 403: 339-342 9. C. J. Paddon et al.; “High-level semi-synthetic production of the potent antimalarial artemisinin”; Nature (2013); 496; 528-532 10. Roberta Kwok; “Five Hard Truths For Synthetic Biology”; Nature (2010); 463: 288-290 11. Leon Y. Chan, Sriram Kosuri, Drew Endy; “Refactoring bacteriophage T7”; Mol Syst Biol (2005) 12. Synthetic Yeast 2.0: Building the world’s first synthetic eukaryotic genome together; http://syntheticyeast.org/ 13. Annaluru et al.; “Total Synthesis of a Functional Designer Eukaryotic Chromosome”; Science (2014); vol. 344; pp. 55-58; published online: http://www.sciencemag.org/ content/344/6179/55.abstract 14. Fiona Macrae; “Scientist accused of playing God after creating artificial life by making designer microbe from scratch – but could it wipe out humanity?”; Mail Online June 2010; available at: http://www.dailymail.co.uk/sciencetech/article-1279988/Artificial-life-created-Craig-Venter--wipe-humanity.html 15. Eckard Wimmer; “The test-tube synthesis of a chemical called poliovirus: The simple synthesis of a virus has far reaching societel implications”; EMBO Rep. (2006) 7: S3-S9 16. Lessley Anderson: “Why Does Everyone Hate Monsanto?”; http://modernfarmer. com/2014/03/monsantos-good-bad-pr-problem/ 17. The International Genetically Engineered Machine (iGEM) Foundation: Synthetic Biology based on standard parts; http://igem.org/About 18. BioBricks Foundation: Biotechnology in the public interest; http://biobricks.org/ 19. Thomas Scott; “The zinc finger nuclease monopoly”; Nature Biotechnology (2005); 23: 915-918 15 THE SCIENCE IN SOCIETY REVIEW ∙ LENT 2015 CAMBRIDGE Understanding the Immune System— A potential cure for cancer? Wearn Xin Yee Wearn Xin is currently a first year Natural Sciences (Biological) student at Trinity Hall who likes reading about pathogenic things and working in the lab. She decided to write on this topic when she discovered a side of the immune system she wasn’t aware of before. 16 THE TRIPLE HELIX CAMBRIDGE C ancer is one of the leading causes of death in industrialised nations and is caused by the progressive growth of the progeny of one transformed cell. One way in which the body protects itself is through the immune system. In a healthy human body, the immune system is able to recognise potentially cancerous cells and destroy them before they invade the tissues.1 CAMBRIDGE MHC class 1 molecules and can no longer be recognised by cytotoxic T cells, it might still be susceptible to NK cells.3 However, cancer cells are also able to evade the immune system. For one, tumours seem to be able to evade immune attack by creating a generally immunosuppressive environment. They may secrete immunosuppressive cytokines such as TGF-beta that suppresses inflammatory T-cell responses and cell-mediated immunity necessary for tumour cell control. Also, tumour cells can secrete molecules such as collagen and mucin to create a physical barrier to the immune system, thus preventing their detection and destruction,3,4 These mechanisms allow tumours to avoid immune recognition and continue to grow in the body. immune system and cancer immunotherapy—how the immune system may ‘cure’ cancer Tumour cells are usually recognised by cells of the adaptive immune system such as CD4 helper T cells, CD8 T cells, and natural killer (NK) cells. Upon recognition, CD8 and NK cells kill cells by releasing cytotoxic granules, whilst CD4 helper T cells activate other cells of the immune system to kill the target cells. IFN-gamma (secreted by NK and CD8 cells) and IFN-alpha are important in the elimination of tumour cells, either directly or indirectly through actions on other cells. Another important player in cancer is the Treg cells, which can hamper anti-tumour immune response and thus influence the body’s reaction to cancerous cells.2 One example of the immune system in action is that when cells mutate, these cellular transformations are frequently associated with the expression of MHC class 1b proteins (such as MIC-A and MIC-B) on the cell surface. NK cells recognize and kill the cells. The variety of ways that the immune system can kill cancerous cells means that there are several ‘safety nets’ in place: for example, even when a tumour loses expression of all As the search for a cure to cancer continues, some scientists are turning to modifying what the human body already has for a safe and efficient cure. Considering that a healthy immune system can recognise cancerous cells, one target for modification and exploitation is the immune system — indeed, immunotherapy research involves the exploitation of components of the immune system to attempt to cure cancer. One such ‘drug’ involving components in the immune system is IFN-alpha. Belonging to the interferon family, one of its roles is to activate NK cells to increase their cytotoxic activity.5 Currently, it is the only interferon approved by FDA to treat certain cancers such as kidney cancer, and melanoma; other IFNs are currently under research. As a form of therapy, it has been shown to slow the growth of cancer and blood vessels supporting tumour growth and to boost the ability of cytotoxic immune cells to attack cancer cells.6 However, IFN-alpha must be administered with caution as it demonstrates high levels of toxicity: during a trial, 67% of patients on Figure 1: Examples of immune responses against tumour cells (role of IFN alpha not shown). [A] 17 THE SCIENCE IN SOCIETY REVIEW ∙ LENT 2015 CAMBRIDGE Figure 2: An example of genetically modified T-cell research on ovarian cancer. [B] IFN-alpha2b adjuvant therapy presented Grade 3 toxicities.7 Another area that has shown success is in using monoclonal antibodies for treatment. This form of treatment involves using these antibodies to bind to proteins expressed by cancerous cells, thereby flagging them out for detection and destruction by components of the immune system. This field is certainly promising, as drugs such as Alemtuzumab (MabCampath) treating chronic lymphocytic leukaemia (CLL) are already in the market.8 Alemtuzumab binds to the CD52 protein, forming a complex that favours the deposition of activated complement molecules and facilitates the necessary contacts for cell mediated killing.9 The preferential targeting of CLL cells is hypothesised to be due to different membrane proteins associated with CD52 on CLL but not on T cells.10 However, major disadvantages to monoclonal antibodies are that their large size prevent easy penetration of tumours, and that it may be expensive to mass produce as the complexity of the active antibodies require sophisticated eukaryotic machinery to produce.11 Genetically modifying cells involved in the immune system is another approach scientists are trying; specifically, scientists have worked to engineer T cells to target cancerous cells. In one experiment targeting leukaemia, T cells from the peripheral blood were isolated and reprogrammed into induced pluripotent stem cells before being transfected with a gene coding for a receptor for antigen CD19 using disarmed retroviruses. Upon redifferentiation into T cells, they are injected back into the patient, whereby they can track down and kill cells presenting CD19 (i.e. both cancerous and normal B cells),12 and research is being done to improve specificity to cancerous B cells only13 Such a therapy shows promise as a study showed that the conditions of all 13 multiple myeloma patients treated with genetically engineered T cells that can recognise proteins found on tumour cells but not on healthy cells (such as NY-ESO-1) improved.14 18 Figure 3: Development of cancer vaccine [C] Unfortunately, there may be adverse effects in this approach due to on-target but off-tumour effects. These may be as serious as causing cardiac death, as was the case in a trial when mutations to the alpha chain of the T cell receptor aimed to enhance affinity to tumour cells recognised and targeted other peptides found in cardiomyocytes instead.15 ‘Vaccine’ for cancer? Indeed, researchers are aiming to do so using dendritic cell lines by firstly removing monocytes from the patient and differentiating in vitro into dendritic cells. Dendritic cells are then exposed to cancer cells or antigens to ‘prime’ them before they are proliferated. These dendritic cells are then injected back in to the body, where they in turn prime T cells to recognise the tumour-specific antigen, thus mounting an immune response to cancerous cells,16,17 However, its success is limited as some cancer cells no longer express cancer cell specific molecules, thus reduction in tumour load has not been frequently observed.18 Lastly, another promising approach to cancer therapy is the blocking of immune checkpoints. Immune Figure 4: Ipilimumab mechanism of action [D] THE TRIPLE HELIX CAMBRIDGE checkpoints control signals involved in self-tolerance and T-cell responses, and many tumours use this to be resistant to the immune system. To block these checkpoints, ligand-receptor interactions at these checkpoints are interfered such as by antibodies. Currently, there are three immune checkpoint inhibitors in the market, the earliest being ipilimumab, which had a large impact on metastatic malignant melanoma treatment,19,20 It works by blocking an important negative regulator of the antitumor T-cell response, eventually allows for increasing T-cell activation which can then seek out tumours.21 However, there are side effects too as by blocking immune checkpoint inhibitors, autoimmune side effects may occur, ranging from rash to endocrinopathies.22 Overall, there are several methods in immunotherapy, not limited to those discussed here, currently being developed. Many of these processes are complex, mainly because many mutations in the cancerous cell allow it to escape detection. Moreover, antigens presenting on tumour cells may be similar to proteins presenting on normal cells. Taken together, it becomes extremely difficult to find a single cure that cures all cancer effectively without any dangerous side effects. Yet, as research continues, current cancer treatments and survival rates may hopefully improve. CAMBRIDGE scientists are looking to combining different drugs and different therapies with immunotherapy for better treatment. The understanding of immunotherapy has even led some researchers to believe that successful chemotherapy and radiation treatment may be partly due to the release of antigens through these therapy that the immune system can respond to—a form of natural ‘immunotherapy’.23 Whilst much research still needs to be done before immunotherapy can be officially introduced as a form of cancer treatment, it is certainly an area of large potential. the future of immunotherapy Immunotherapy certain holds a bright future—in 2013, cancer immunotherapy was named the breakthrough of the year by the Science magazine. As immunotherapy offers a more targeted approach to cancer treatment, references 1. ‘Huge breakthrough’ in understanding how the immune system recognises cancer. (2014, November 21). Retrieved January 23, 2015, from http://www.cancerresearchuk. org/about-us/cancer-news/news-report/2014-11-21-huge-breakthrough-in-understanding-how-the-immune-system-recognises-cancer 2. Acton, Q. (2012) Cancer: New Insights for the Healthcare Professional: 2011 Edition. ScholarlyEditions 3. Murphy, K. (2012). Janeway’s immunobiology (8th ed.). New York: Garland Science. 4. Kufe, D.W. (2010).Mucins in cancer: function, prognosis and therapy. Nature Reviews Cancer, 9(12), 874-885 5. Jewett, A. , & Bonavida, B. (1995). Interferon-alpha activates cytotoxic function but inhibits interleukin-2-mediated proliferation and tumour necrosis factor-alpha secretion by immature human natural killer cells. Journal Clinical Immunology, 15(1), 35-44. 6. Non-specific cancer immunotherapies and adjuvants. (n.d.). Retrieved December 27, 2014, from http://www.cancer.org/treatment/treatmentsandsideeffects/treatmenttypes/immunotherapy/cancer-immunotherapy-nonspecific-immunotherapies 7. Sabel, M. and Sondak, V. (2003) Pros and cons of adjuvant interferon in the treatment of melanoma. The Oncologist, 8(5), 451-458. 8. About monoclonal antibodies. (n.d.). Retrieved December 27, 2014, from http://www. cancerresearchuk.org/about-cancer/cancers-in-general/treatment/biological/types/ about-monoclonal-antibodies 9. Alinari, L., Lapalombella, R., Andritsos, L., Baiocchi, R.A., Lin, T.S. and Byrd, J.C. (2007). Alemtuzumab (Campath-1H) in the treatment of chronic lymphocytic leukaemia. Oncogene, 26, 3644-3653. 10. Mone, A.P., Cheney, C., Banks, A.L., Tridandapani, S., Mehter, N., Guster, S., Lin, T., Eisenbeis, C. F., Young, D.C. and Byrd, J.C. (2006) Alemtuzumab induces caspase-independent cell death in human chronic lymphocytic leukaemia cells through a lipid raft-dependent mechanism. Leukaemia, 20, 272-279. 11. Chames, P., Van Regenmortel, M., Weiss, E. and Baty, D. (2009) Therapeutic antibodies: successes, limitations and hopes for the future. British Journal of Pharmacology, 157(2), 220-233 12. Palmer, C. (2013, August 11). Tumour-Targeting T Cells Engineered. The Scientist. 13. Kershaw, M., Westwood, J., Slaney, C. and Darcy, P. (2014). Clinical application of genetically modified T cells in cancer therapy. Clinical and Translational Immunology, 3(16). 14. Coghlan, A. (2012, December 11). Souped-up immune cells force leukaemia into remission. New Scientist. 15. Heslop, H.E. (2013) Genetic engineering of T-cell receptors: TCR takes to titin. Blood, 122(6), 853-854. 16. Laborde, R.R., Lin, Yi., Gustafson, M.P., Bulur, P.A. and Dietz, A.B. (2014) Cancer vaccines in the world of immune suppressive monocytes (CD14+HLA-DR(lo/neg) cells): the gateway to improved responses. Frontiers in Immunology. doi: 10.3389/ fimmu.2014.00147 17. Dendritic Cell Therapy. (n.d.). Retrieved January 5, 2015, from http://cancer.stanford. edu/research/immunology/dendritic.html 18. Bodey, B., Bodey, B. Jr, Siegel, S and Kaiser, H. (2000) Failure of cancer vaccines: the significant limitations to this approach to immunotherapy. Anticancer Research, 20(4): 2665-2676. 19. Pardoll,D. (2012). The blockade of immune checkpoints in cancer immunotherapy. Nature Reviews Cancer, 12: 252-264 20. Webster, R. (2014). The immune checkpoint inhibitors: where are we now? Nature Reviews Drug Discovery, 13: 883-884 21. Tarhini, A., Lo, E. and Minor, D. (2010). Releasing the brake on the immune system: ipilimumab in melanoma and other tumours. Cancer Biotherapy and Radiopharmaceuticals, 25(6): 601-613 22. Corsello, S., Barnabei, A., Marchetti, P., De Vecchis, L., Salvatori, R. and Torino, F. (2013) Endocrine side effects induced by immune checkpoint inhibitors. Journal of Clinical Endocrinology Metabolism, 98(4): 1361-1375 23. Cancer Immunotherapy: The Next Decade? (n.d.). Retrieved December 27, 2014, from http://www.cancerresearch.org/news-publications/our-blog/january-2014/cancer-immunotherapy-the-next-decade Images [A] (Figure 1): Gilboa, E. (2004) The promise of cancer vaccines. Nature Reviews Cancer, 4, 401-411 [B] (Figure 2): Department of Obstetrics & Gynecology. (n.d.). Retrieved January 6, 2015, from http://www.uphs.upenn.edu/obgyn/research/ovarian_clinical.htm [C] {Figure 3}: Cancer Vaccines, CSA - Discovery Guides. (n.d.). Retrieved January 6, 2015, from http://www.csa.com/discoveryguides/cancer/review.php [D] (Figure 4): Weber, J. (n.d.). Anti-CTLA-4 Monoclonal Antibodies for the Treatment of Malignant Melanoma. Retrieved January 23, 2015, from http://www.medscape.org/ viewarticle/584180 19 JOHNS HOPKINS THE SCIENCE IN SOCIETY REVIEW ∙ LENT 2015 Implications of Synthetic Life Sohail Zahid in the past decade, scientists have made discoveries that challenge the foundation of commonly held beliefs. From the reclassification of Pluto to a dwarf planet in 20051 to the discovery that the moon contains significant reservoirs of water in 20092 and the assertion that gravity is simply a macroscopic phenomenon of entropic movement in 2010,3 the common perceptions of scientific truth become readjusted year after year. The notion of life itself became challenged when Craig Venter announced that researchers in his institution had successfully constructed the first instance of a replicating, synthetic organism. The research team of 46 scientists first built a comprehensive, synthetic genomic database of the bacterium, M. mycoides, which they assembled in yeast cells in DNA cassettes of approximately 1,000 base pairs each.4 Afterwards, the genome of M. capricolum was hallowed out and the synthetically created genome was transplanted from yeast to these target bacterium cells. The result, after 15 years and $40 million dollars in investment, was M. mycoides JCVI-syn1.0, an organism with synthetic origins from a computer. It is important to note that the Venter group did not write a new bacterium genome from scratch, but instead reengineered and modified a preexisting genome of M. myocoides. Hence, there is still controversy in the scientific community as to whether or not this achievement 20 Sohail Zahid studies Biomedical Engineering and Applied Math at Johns Hopkins University. constitutes synthetic life. Still, this feat in synthetic biological construction is unprecedented since a biological structure of this magnitude had never been created before;4 most chemical synthesis techniques stop working after the transcription of one thousand base pairs. To expand to the full genome of one million, the research team stitched together custom made DNA cassettes, specifically designed to bind to an adjacent genetic fragment. In a painstaking effort, scientists had to make sure each base pair in the multi-million sized genome was perfectly arranged since a single inaccuracy could have prevented the DNA cassettes from assembling or could have prevented the bacterium from self-replicating. However, with advanced DNA sequencing techniques, the research team was able to complete this daunting task with minimal error. Due to the sheer scale of this achievement, the upcoming consequences—which have been overlooked in the infant stages of synthetic biology—are just now entering the spotlight. Recently, Craig Venter opened up a company, Synthetic Genomics,5 to act as an innovator in the production of genomic-driven solutions to contemporary problems. THE TRIPLE HELIX CAMBRIDGE JOHNS HOPKINS “Designer viruses” or “Frankenstein bacteria” with significant resistive capabilities may pose a danger more serious than cancer or HIV today. This discovery, first and foremost, changes the landscape of basic biomolecular research. Synthetic biology, whether at the organismal level, chromosomal level, or even at the DNA level, can redefine the way gene pathways are regulated and how biochemical networks are assayed.6 Instead of working around possible roadblocks in biological networks or dealing with unwanted side effects from a required metabolite, researchers can conceivably custom design molecules to fit their own needs and specifications. This has unbounded long-term possibilities, as changes at the DNA sequence level can provide new research pathways that may someday produce vaccines and drugs for today’s more elusive diseases, including cancer, HIV, heart disease, and autism. Currently, synthetic biology techniques are being used in biotechnology companies such as Pfizer, Monsanto, and Merck to design specific medicinal drugs and agricultural products by manipulating the protein landscape surrounding cells.7 While this discovery opens up new implications in improving healthcare and improving agricultural production, it also opens up the reality of utilizing synthetic techniques to explore other commercial avenues such as energy. Synthetic biology solutions can optimize the conversion of fossil fuels such as coal and oil to energy with specific, synthetically manufactured biochemical.8 When fossil fuels become completely depleted, this technology may provide a new, more robust source of biofuel. For example, lignocellulosic biomass is an abundant and renewable plant that could become a low cost, accessible resource for energy production if this plant were to be manufactured synthetically.9 Some algal products have also been observed to degrade petroleum products.10 Using genetic engineering, society can not only create an efficient, self-sustaining biologically-derived fuel source, but also decrease the carbon footprint that centuries of fossil fuel use has caused. One way this is being accomplished is through analyzing the underlying gene regulation.6 By identifying key hubs in the genetic network and regulation with a genetic circuit controls system, specific proteins can be expressed, suppressed, or selectively promoted to improve function of the organism. Since synthetic biology has mostly dealt with smallscale solutions, the large-scale nature of this discovery opens up some serious legal implications. While Craig Venter’s scientific achievement is certainly commendable, his overwhelming influence in the field is also a cause for concern. Venter has already applied for patents on more than 300 artificially constructed genes.11 This raises grave concerns in the future as individuals begin to lay claim to the basic building blocks of life, which may be problematic if individuals need syntheti- 21 JOHNS HOPKINS cally derived solutions to combat disease, and companies are unable to help because of exclusive patent claims to a single amino acid.12 Similarly, since Venter may be the only individual with both the financial resources and the research team to derive these DNA-driven solutions, his company, Synthetic Genomics, may become a monopoly in the field. The barrier of entry into this specific synthetic biology market is significantly high as it encompasses both financial and academic concerns, so new competitors might be discouraged to enter despite the potential.13 Because this company will be difficult to break up since it resides with a sole individual, Craig Venter, at the helm, a scenario may result in which Synthetic Genomics can issue these necessary, life-saving solutions at ridiculous prices with no one, including the government, having the ability to do anything about it. One of the most serious consequences for this type of discovery is its role in possible bioterrorism activities, which can arise if resources and techniques fall into the wrong hands. While certain known diseases such as Variola, Smallpox, and the 1918 influenza virus are in locked laboratories, synthetic viruses unleashing these diseases may become a serious war tool in the future.14 If this technology were to become publically accessible rather than the property of Synthetic Genomics, the implications are vast and potentially troublesome. Although it is difficult to manufacture a biologically potent disease now, it may become considerably easier in the next decade or so as biochemistry research and development improves. Just as colonists spread blankets with smallpox to eradicate Native Americans, countries may send pandemic-inducing diseases through planes or mail to wipe out entire populations.15 “Designer viruses” or “Frankenstein bacteria” with significant resistive capabilities may pose a danger more serious than cancer or HIV today. Venter’s discovery is now the bioethical “Pandora’s box” of our age. It is difficult to ascertain all the outcomes, but it is also important to realize that both positive and negative scenarios will result. Society already THE SCIENCE IN SOCIETY REVIEW ∙ LENT 2015 has engaged in much debate about the ethical considerations in cloning and embryonic stem cell research. Synthetic biology will certainly join that forum of discussion as scientists become more successful in creating artificial life and unleash both positive and negative possibilities. What is important now is for public policy to keep up with the fast rate of scientific discovery. Education about the risks and benefits will become crucial in galvanizing this technology to create a better future. Venter’s discovery is now the bioethical “Pandora’s box” of our age. REPRODUCED FROM [16] references 1. NASA. Pluto: Overview [internet]. 2012 [cited 2012 Feb 19]. Available from: http:// solarsystem.nasa.gov/planets/profile.cfm?Object=Pluto 2. NASA. Lunar Impact Uncovered More Than Just Moon Water [internet]. 2012 [cited 2012 Feb 19]. Available from: http://science.nasa.gov/science-news/science-at-nasa/2010/21oct_lcross2/. 3. Verlinde, EP. “On the Origin of Gravity and the Laws of Newton”. JHEP. 2011 Apr; (4) 29: 1-26. 4. Gibson DG et al. “Creation of a Bacterial Cell Controlled by a Chemically Synthesized Genome.” Science. 2010: 52-56. 5. Synthetic Genomics. The Global Challenge: Sustainably meeting the increasing demand for critical sources [internet]. 2012 [cited 2012 Feb 19]. Available from: http:// www.syntheticgenomics.com/. 6. Alon, Uri. “An Introduction to Systems Biology. Design Principles of Biological Circuits”. Boca Raton: Taylor & Francis Group, LLC, 2007. 7. Smalley, Eric. “Synthetic Biology Gets Down to Business.” Nature Blogs. 2007 March. 8. Schmidt, CW. “Synthetic Biology: Environmental Health Implications of a New Field”. Environmental Health Perspectives. 2010 March; (118):a118-a123. 9. Kumar P et al. “Methods for Pretreatment of Lignocellulosic Biomass for Efficient 22 Hydrolysis and Biofuel Production”. Journal of American Chemical Society. 2009; (48) 8: 3713-3729. 10. Thomson, EA. Scientists Study Makeup of Oil-Eating Bacteria [internet]. 1992 [cited 2012 Feb 19]. Available from: http://web.mit.edu/newsoffice/1992/bacteria-0401.html. 11. Sample, Ian. Craig Venter creates synthetic life form [internet]. 2010 [cited 2012 Feb 19]. Available from: http://www.guardian.co.uk/science/2010/may/20/craig-ventersynthetic-life-form. 12. Guttman, Amy. New Directions: The Ethics of Synthetic Biology. Washington D.C. Presidential Commission for the Study of Bioethical Issues; 2010. 13. Geneva. Risk Governance of Synthetic Biology. International Risk Governance Council; 2009. 14. RA, Tucker and Zilinskas JB. “The Promise and Perils of Synthetic Biology.” The New Atlantis. 2006: 25-45. 15. Douglas T and Savulescu J. “Synthetic Biology and the ethics of knowledge”. Journal of Medical Ethics. 2010 Oct. (36) 10: 687-693. 16. http://commons.wikimedia.org/wiki/File:Physcomitrella_growing_on_agar_plates.jpg THE TRIPLE HELIX CAMBRIDGE JOHNS HOPKINS Why the World’s Largest Landfill is in the Ocean Stephen Jenkins humans have been using plastic in its modern form as an all-purpose tool since its invention in 1907. It can be found in all walks of life, but recent research has revealed potentially negative consequences on marine ecosystems from the ubiquitous use of the material. For instance, a study published in September, 2011 in Environmental Science and Technology discovered that “a single garment can release 1900 fibers per wash. The researchers theorized that a large amount of [the] mi- a striking example of how the actions of man can harm the environment. The Great Pacific Garbage Patch first gained attention in 1997. It has been difficult to determine the Garbage Patch’s exact size. With the information that is available though, researchers consider the “combined areas croplastic debris found in marine environments comes directly from washing clothes.”1 It is amazing that such a universal activity can potentially be so destructive to the environment. Unfortunately, this is the reality of the Great Pacific Garbage Patch. The Garbage Patch is characterized by a high concentration of plastic debris that has been trapped due to the currents of the North Pacific Gyre. The problems posed by the Great Pacific Garbage Patch are numerous, but, more often than not, they remain unknown to the general population. To further explain, it is important to clarify what exactly the Great Pacific Garbage Patch is, and how it has come to be of floating plastic to cover roughly the size of Texas.”2 The Garbage Patch, located in the central North Pacific Ocean, was revealed to have enormous amounts of plastic debris floating near the surface. The majority of the plastic found in the Garbage Patch is very small, typically being no larger than 5 mm in length. The Great Pacific Garbage Patch is located in an area where environmental and man-made factors have caused it to become the world’s largest landfill. The currents of the North Pacific Gyre create a vortex, leading to a convergence zone where nearly all matter caught in the currents becomes trapped. According to the Na- Stephen Jenkins studies Global Environmental Change and Sustainability at Johns Hopkins University. 23 JOHNS HOPKINS tional Oceanic and Atmospheric Administration, “80% of oceanic pollution originates from land. This is where humans come into play.”3 Improper waste disposal and negligence regarding the manufacturing of plastics are both significant contributors to oceanic debris. The natural currents of the Pacific Ocean in combination with societal factors have created the Great Pacific Garbage Patch. Previously, it was thought that plastics only broke down at very high temperatures over a long period of time. Contrary to this belief, in 2009 Japanese researchers found that “[plastic] degraded at temperatures of 86 degrees Fahrenheit”, and “breaks down…within a year of the trash hitting the water.”4 This creates problems for many reasons. The degradation of plastics is thought to release many potentially toxic chemicals into the ocean, THE SCIENCE IN SOCIETY REVIEW ∙ LENT 2015 them. These animals depend on the nutrition that the ocean provides and oftentimes cannot distinguish between plastic and food. About “44 percent of all seabirds eat plastic, sometimes with fatal effects. In total, an estimated 267 marine species are affected by plastic.”8 When large amounts of plastics are found within animals, the animals are not only being deprived of nutrients, but also faced with health problems such as digestive tract issues. According to the United Nations Environment Program, it is estimated that “1 million seabirds and 100,000 marine mammals and turtles die per year due to the ingestion of plastic.”9 These statistics help reveal the damage that plastic does to marine life. The issue of cleaning up the Great Pacific Garbage Patch has troubled scientists since its discovery. Fortunately, many non-profit organizations with the goal of The Great Pacific Garbage Patch is located in an area where environmental and man-made factors have caused it to become the world’s largest landfill. including bisphenol A. The release of BPA into the water is a danger to marine life and to humans as well. Research, titled the Lang Study, collected between the years 2003-2006 indicated that “exposure to BPA raises the chance of coronary heart disease in adults.”5 A similar study to replicate the results of the Lang study provided almost identical data; “adults who [had] the highest concentration of BPA within their urine had a 33% higher chance of suffering from coronary heart disease.”6 Other research has also been conducted on the potential dangers of BPA. A 2008 study that was published in the Proceedings of the National Academy of Sciences concluded that “BPA acts as an inhibitor of spinal synapse formation in the hippocampus and the prefrontal cortex.”7 Previous research had been done on this issue using mice, but the 2008 study used adult African Green Monkeys to show the probable harm that BPA could cause within humans. The researchers exposed the monkeys to 50 μg/kg of BPA per day. This number was selected because it falls within the daily safe limit as suggested by the EPA. Even at this recommended safe amount of exposure, research seems to indicate that it could have a harmful effect on primates. Although the exact effects are not completely understood, “alterations in patterns of synaptogenesis appear to play critical roles in neurologic disorders, including mental retardation and developmental disabilities, Alzheimer’s disease, schizophrenia, and mood disorders.”7 There lies another, more evident problem with the Great Pacific Garbage Patch. Birds of many species and other marine animals feed on whatever is available to 24 confronting this problem are becoming increasingly prominent in the world of environmental sustainability. One of these organizations is the Environmental Cleanup Coalition. Founded in 2008, this organization has brought together partners that promote the continuing health of our oceans. Project Kaisei is one such non-profit organization that is focused on increasing awareness of the scale of marine debris, its impact on our environment, and the solutions for both prevention and clean-up.10 The SCRIPPS Institute based out of the University of California San Diego is another organization with goals similar to Project Kaisei. Working together, the two groups funded the SEAPLEX voyage. The goal of SEAPLEX is to survey the distribution of 1 million seabirds and 100,000 marine mammals and turtles die per year due to the ingestion of plastic. plastic in the area that the Pacific Garbage Patch comprises and discover the impact of plastic debris on local fauna. SEAPLEX was completed in August 2009 and saw the two organizations travel a distance of 1,700 miles into the Pacific Ocean from their starting point of San Diego. During this time “small plastic debris was found THE TRIPLE HELIX CAMBRIDGE in 130 out of 132 surface sample nets that were used for regular analysis over the course of the expedition.”11 This joint effort is the world’s largest attempt to collect crucial data on the Pacific Garbage Patch. All of their information has been passed on to the NOAA which is looking into the potential effects and harm that the plastic causes. Similarly, the Abundant Seas Foundation researches potential cleaning methods using environmental engineering. Partnering with the ECC, the Abundant Seas Foundation has done work on the Pod Project, an effort to launch the Pelagic Pod into polluted waters. The Pods used in the project are made of recycled plastic with a design similar to an ocean buoy. They are powered by solar panels that are outfitted on the exterior of the pod, while the inside draws plastic particles into the chamber and a proprietary mesh that entangles the particles for permanent removal. The design allows for small materials to be filtered through, while larger organisms, such as fish, are safe from being trapped. “Water is directed downward into the Pod’s internal chamber. Inside the Pod, a density separation process and a plastic micro-fiber scrubber will remove the plastic particles from the seawater.”12 In addition to filtering microplastics, the pods help restore the marine ecosystem by acting as an anchor point for biomass. Fertilization of the water will be achieved by two methods: first, by releasing iron into the water from its scrap metal ballast, and second by releasing nutrient rich biscuits that are made from sterilized and compressed bio-solid derivatives from terrestrial wastewater treatment systems. Although still in the prototype phase, it is likely that these pods will be able to collect JOHNS HOPKINS microplastic debris without disturbing the natural environment. Mass production of this tool will become essential as the biggest obstacle to cleanup efforts in the past has always been the potential damage to the natural ecosystem inhabiting the same area. Research and development is still in the infancy stage, there is hope for the future as more data becomes available. REPRODUCED FROM [13] It is commonly accepted that the Great Pacific Garbage Patch poses a problem to the environment, but the exact nature and enormity of the issue is difficult to ascertain. As a result, the Garbage Patch remains largely mysterious to researchers today. Due to the relatively small number of studies that have been conducted on the subject, it is difficult to determine long-term effects, as well as potential methods of cleanup. Luckily, the issue is gaining widespread notoriety and there are now many organizations that are looking to combat the problems that the Garbage Patch poses. references 1. Browne M., Crump P., Niven S., Teuten E., Tonkin A., Galloway T., et. al. Accumulation of Microplastic on Shorelines Woldwide: Sources and Sinks. ACS Publications [Internet]. 2011 [cited 2011 December 6]; [approx. 1 p.]. Available from: http://pubs. acs.org/doi/abs/10.1021/es201811s?prevSearch=%255BContrib%253A%2Bmark%2Bbrowne%255D&searchHistoryKey= 2. Greenpeace International (NL). The trash vortex [Internet]. Amsterdam (NL): Greenpeace International; [cited 2011 December 8]. Available from: http://www.greenpeace. org/international/en/campaigns/oceans/pollution/trash-vortex/ 3. National Oceanic and Atmospheric Administration (US). Most Ocean Pollution Begins on Land [Internet]. Silver Spring (MD): U S Department of Commerce; 2011[updated 2011 Nov 17; cited 2011 December 5]. Available from: http://oceanservice.noaa.gov/ facts/pollution.html 4. Barry C. National Geograpic Society (US). Plastic Breaks Down in Ocean, After All – and Fast [Internet]. Washington (DC): National Geographic Society; 2009 August 20 [cited 2011 December 6]. Available from: http://news.nationalgeographic.com/ news/2009/08/090820-plastic-decomposes-oceans-seas.html 5. Lang I. , PhD; Galloway T., PhD; Scarlett A., PhD; Henley W., PhD; Depledge M., PhD, DSc; Wallace R., MD; et. al. Association of Urinary Bisphenol A Concentration With Medical Disorders and Laboratory Abnormalities in Adults. JAMA [Internet]. 2008 [cited 2011 December 8];300(11):1303-1310. Available from: http://jama.ama-assn.org/ content/300/11/1303.full 6. Melzer D., Rice N., Lewis C., Henley W., Galloway T. Association of Urinary Bisphenol A Concentration with Heart Disease: Evidence from NHANES 2003/06. PLoS ONE [Internet]. 2010 January [cited 2011 December 8];5(1):1-9. Available from: http://www.plosone.org/article/fetchObjectAttachment.action?uri=info%3Adoi%2F10.1371%2Fjournal.pone.0008673&representation=PDF 7. Leranth C., Hajszan T., Szigeti-Buck K., Bober J., MacLusky N. Bisphenol A prevents the synaptogenic response to estradiol in hippocampus and prefrontal cortex of ovariectomized nonhuman primates. PNAS [Internet]. 2008 Sep [cited 2011 December 10];105(37) [approx 4 p.]. Available from: http://www.ncbi.nlm.nih.gov/pmc/articles/ PMC2544599/?tool=pmcentrez#__sec6 8. Greenpeace International (NL). Plastic Debris in the World’s Oceans [Internet] Amsterdam (NL): Greenpeace International; [cited 2011 December 7]. Available from: http://www.greenpeace.org/austria/Global/austria/dokumente/Studien/meere_Plastic_Debris_Study_2006.pdf 9. Gjerde K., Ecosystems and Biodiversity in Deep Waters and High Seas. UNEP [Internet]. 2006 [cited 2011 December 8]; 178: 54. Available from: http://www.unep.org/pdf/ EcosystemBiodiversity_DeepWaters_20060616.pdf 10. Project Kaisei (US). Kaisei History [Internet] San Francisco (CA): Project Kaisei; [cited 2011 December 9]. Available from: http://www.projectkaisei.org/kaisei_history.aspx 11. Scripps Institution of Oceanography (US). SEAPLEX [Internet] San Diego (CA): Scripps Institution of Oceanography; 2009 [cited 2011 December 9]. Available from: http://sio.ucsd.edu/Expeditions/Seaplex/Science/ 12. Abundant Seas Foundation (US). Pod Project [Internet] Gig Harbor (WA): Abundant Seas Foundation; 2009 [cited 2011 December 9]. Available from: http://abundantseas. org/pod_project 13. http://nerdswithoutborders.net/index.php?title=File:Hawaii_turtle_2.JPG 25 REPRODUCED FROM [7] THE SCIENCE IN SOCIETY REVIEW ∙ LENT 2015 CORNELL The New “Black Gold”: Biochar Jennifer Sun as battles over greenhouse gas emissions, renewable energy technologies, climate change, land degradation, and a host of other environmental issues continue, researchers and policy makers have begun to look towards more aggressive approaches for developing sustainable practices. In recent years, one new technology has emerged as a promising method of not only sequestering carbon, but also simultaneously improving agricultural soil fertility and producing energy. Biochar, or a charcoal formed during the slow burning of woody biomass, has been used for hundreds and thousands of years in nutrient-poor soils in the Amazon Basin and more recently in Japan as a fertilizer in nutrient-poor soils in these regions.5 Within in the past few years, however, biochar has risen to international attention as a potential carbon-capture and soil amendment technology that can be used on both local and industrial scales. Biochar, or “black carbon,” is a concentrated carbon product derived from the slow pyrolysis of biomass. This process of biochar production builds upon the concept of burning biomass instead of fossil fuels for energy, which reduces carbon emissions by recycling carbon between recently grown biomass and fuel combustion, rather than releasing carbon from a long-term carbon pool. Instead of combusting biomass to produce heat, however, in pyrolysis woody biomass is burned at low temperatures with little or no oxygen. This process produces bio-oils and drives off gases such as carbon monoxide and hydrogen, which can be captured and either burned to produce heat or further processed to produce other forms of energy.5 What is left behind is biochar, or a charcoal in which carbon has been concentrated to twice its original levels.1,3 This concentrated carbon product can either be burned to produce more electricity, or added to agricultural fields as a soil addition. 26 Jennifer Sun studies the Science of Natural and Environmental Systems, with a concentration in Environmental Biology, at Cornell University. It is through this use as an agricultural amendment that biochar truly distinguishes itself from other carbon-capture technologies.5 While the gas products of pyrolysis can still be captured to offset the energy needed to produce the biochar, the remaining carbon in the char will be sequestered underground. Furthermore, biochar application dramatically reduces methane and nitrous oxide emissions from microorganisms in soil, both of which are even more potent greenhouse gases than carbon dioxide.4 As a result, biochar can be classified as a net carbon-negative process under the Kyoto Protocal standards.4 As an organic product, biochar also helps improve soil quality and fertility, improving agricultural production and helping to restore degraded soils for agricultural use.1 For example, biochar helps retain water and associated nutrients in soil, while reducing soil erosion and general soil degradation. This not only increases crop yields, but also reduces the need for additional chemical fertilizers, which not only reduces energy and production costs, but also reduces nutrient leaching and associated water pollution that can cause algal blooms and fish kills.1,6 By maintaining soil quality and fertility over a longer period of time, biochar will help agricultural areas support growth for longer, slowing the process of deforestation for agricultural expansion in many developing nations.1 Because biochar is an organic product, it is acknowledged that it will eventually decompose and release carbon back into the atmosphere. Once buried in soil, however, biochar is estimated to remain stable for hundreds, or potentially thousands, of years.2,3 On the timescale THE TRIPLE HELIX CAMBRIDGE of carbon-capture and storage, this is considered to be a long-term sequestration technology: in comparison, other carbon storage methods such as afforestation or no-tillage agriculture have storage capacities only on the order of a few years to decades.1 As a result, this net carbon-negative product has generated considerable interest as a potential carbon-offset technology, which can help generate revenue through the carbon trade market to help maintain the cost of biochar production. At least 150 current biochar projects have been identified in 43 countries As with any energy—or emissions—reduction technology, the level of success and economic viability of biochar depends on a variety of factors, including the availability of cheap feedstocks and a market for the bioenergy and carbon credits produced by biochar production.1, 4 Dr. Johannes Lehmann, Chairman of the International Biochar Initiative Board and Associate Professor in the Department of Crop and Soil Sciences at Cornell, estimates that the use of forest residues, crop residues, or fast-growing vegetation grown on currently idle cropland in the US to produce biochar could sequester 10% of current US carbon emissions.1 However, though the development large-scale production of biochar may still encounter some economic barriers, one great benefit of biochar over other technologies is that the pyrolysis process is already well developed, having been used previously for energy production. The process is also very flexible and can utilize a wide variety of biomass feedstocks, including agricultural and forestry wastes, urban wastes, and crop residues in addition to purposefully grown biomass such as corn stover and miscanthus, a species of perennial grass. As a result, small-scale production of biochar is ideal for use in developing countries, particularly in the tropics where nutrient content in soils is relatively low.1,6 Recently, Cornell University and the International Biochar Initiative have been working with the World Bank to identify potential new target regions that may be able to benefit from biochar application. So far at least 150 current biochar projects have been identified in 43 countries, including Chile, Uganda, Kenya, Sri Lanka, and many others.6 Though the concept of biochar has been known for a few decades, biochar has only recently been seriously recognized as a potential carbon-capture technology in the past 5 or 6 years.5 Since then, a number of energy bills that have been introduced to the Senate have included provisions for the funding of biochar research and its inclusion as an approved carbon-offset technol- CORNELL ogy, including the Water Efficiency via Carbon Harvesting and Restoration (WECHAR) Act of 2009, which was specifically aimed at funding biochar research and projects.6 Industrial-scale biochar production has also begun to grow rapidly, with new plants being produced in Brazil, Japan, and China within the past couple of years.5 Finding the resources, political support and funding to develop biochar production and sequestration still present a major challenge towards developing biochar to its full potential. Proponents of the technology do not attempt to claim that it will be the panacea for our climate change challenges, but at least in the near-term it is likely to play an increasingly important role in providing a variety of benefits—energy production, improved soil quality and carbon capture—in localized regions worldwide. Indeed, the lack of need for new technology or synthetic chemicals, the ability to utilize a variety of biomass feedstocks, and the myriad of ecological and economic benefits offered in addition to carbon capture make biochar a particularly attractive technology. Though ultimately carbon sequestration may only be moderate-term solution, improved soil fertility can be relied upon. Whether for short- or long-term environmental benefits, biochar as a multi-use technology will likely play a role in combating greenhouse gas emissions and soil degradation in both developed and developing nations in coming years. REPRODUCED FROM [8] references 1. Lehmann J. A handful of carbon. Nature. 2007; 447: 143-144 2. Ammontte J, Lehmann J., and Joseph S. Terrestrial Carbon Sequestration with Biochar: A Preliminary Assessment of its Global Potential. American Geophiysical Union. 2007. Abstract. 3. Gaunt JL, Lehmann J. Energy Balance and Emissions Associated with Biochar Sequestration and Pyrolysis Bioenergy Production. Environ. Sci. Technol. 2008, 42 (11): 4152-4158. 4. Gaskin JW, Steiner C, Harris K, Das KC, Bibens B. Effect of Low-Temperature Pyrolysis Conditions of Biochar for Agricultural Use. 5. Lehmann, J. Personal communication. 21 Oct 2011. 6. International Biochar Initiative [Internet]. [cited 21 Oct 2011]. Available from: http://www.biochar-international.org/ 7. http://commons.wikimedia.org/wiki/File:Charcoal2.jpg 8. http://spin-project.eu/img/12043_Ecoera_biochar_ladybug.JPG 27 THE SCIENCE IN SOCIETY REVIEW ∙ LENT 2015 CORNELL Reading Reinvented: How Computers and the Internet are Influencing our Society Latha Panchap in the mind of the average computer user, the internet has the answers to almost all of life’s questions. Between the search engines and the millions of constantly updated webpages, the internet gives users the ability to know everything that has happened, is happening, and might happen, all at their fingertips. This is the internet’s greatest gift: unlimited information. However, recent discoveries about the internet’s effect on Americans’ reading skills show that such technology may have significant repercussions on society and today’s youth. A 2010 study from the Pew Research Center shows that Americans spend an average of 60 hours a month on the Internet. American internet users spend 42% of this time viewing internet content, such as blogs and articles.1 The growing concern among parents and teachers, however, is that this time spent surfing Fanfiction. net or Tumblr could be used to do something more intellectually stimulating.2 A study released in 2004 by the National Endowment of the Arts (NEA) indicates that the decrease in the number of novels read by teenagers may be a crucial reason for the drop in standardized 28 Latha Panchap is studying Biological Engineering and Business at Cornell University. reading test scores.3 Chairman of the NEA, Dan Gioia, believes that the Internet and its many distractions may be one of the main sources of this decline, signified by his statement “[The benefits of newer electronic media] provide no measurable substitute for the intellectual and personal development initiated and sustained by frequent reading.”2 Gioia’s claim brings up an interesting point: What exactly is the difference between reading in print and reading online? In their book The Myth of the Paperless Office, cognitive psychologist Dr. Abigail Sellen and researcher Richard Harper come to the conclusion that navigating a webpage requires more brain power than turning the pages of a novel. Furthermore, the light-producing screens of computers force our eyes to constantly focus and refocus.4 This difficulty alone causes users to read 25% slower on screen than on paper.5 In addition, the many distractions of the internet cause readers to lose ‘flow’, a term used by psychology professor Dr. Mihaly Csikszentmihalyi to describe “a deep but effortless involvement that removes from awareness the worries and frustrations of everyday life.” Paper novel enthusiasts can identify with this familiar feeling: becoming immersed in a novel and losing all sense of time. This state of full absorption in reading is difficult to achieve with a computer. Instant messages, emails, music, and pop-up ads distract us and cause frequent breaks in our ‘flow’.4 Attention blindness is a crucial part of achieving ‘flow’. Cognitively, this can be explained through the actions of neurons. Neurons fire off in pathways to complete certain actions, such as reading. As these pathways are repeated more often, the neurons link together, and the actions are performed more efficiently. Eventually, these actions become automatic reflexes that pass undetected under our radar of attention. This is known as attention blindness. Reading is an automatic reflex, meaning that our neurons are already wired together in efficient pathways to do this task. Because of this, we are subject to attention blindness while reading. Profes- THE TRIPLE HELIX CAMBRIDGE sor Cathy Davidson feels that people pay attention to actions, responses, and ideas for which their neurons have not formed pathways. Therefore, when pop-ups or instant messages appear on the screen, we automatically pay more attention to these distractions than to the text.6 The internet’s negative effects go much deeper than distracting and taxing the user. In his article “Is Google Making Us Stupid?” Nicholas Carr voices the worry that Instant messages, emails, music, and popup ads distract us and cause frequent breaks in our ‘flow’ many readers now have— that the internet is influencing the way we process information. According to Carr, we no longer possess the focus and thought to deeply understand what we are reading, only the ability to skim and superficially grasp the meaning of the text.7 Dr. Jakob Nielsen, who holds a degree in human-computer interactions, claims that humans’ method of reading has actually changed— our new reading pattern consists of web searches and scanning, paying attention to CORNELL small paragraphs, bolded words, headings, and lists.8 His eyetracking study, which observed the eye movements of 232 users, showed that people scan websites using a rough F-pattern, reading the first two paragraphs and then scanning the left side of the page.9 Nielson’s conclusion is that computer users have become ‘information foragers’. Like jungle animals scavenging for food, we’ve learned to scan websites for information, find what we need, and move on to the next website.10 Search engines like Google and Bing have encouraged this process by organizing pertinent webpages into one list and giving snippets of text to summarize the contents of each site. Google’s desire to create “the perfect search engine” consequently takes all the work out of actively searching for information and discourages people from exhausting a single source before finding another.7 Proponents of this internet revolution argue that the benefits of the internet far outweigh the aforementioned repercussions. Experts in early childhood development claim that the interactive interface of the internet promotes the development of literacy and problem-solving skills, as well as the ability to synthesize information from multiple sources.11 Educators supporting the use of the web as a reading medium believe that it can also provide many different perspectives and a wider, more comprehensive view of a subject. Computer-based reading’s strong influence on American children caused literacy experts to advocate the addition of a computer component to the Nation’s Report Card, an annual study 29 THE SCIENCE IN SOCIETY REVIEW ∙ LENT 2015 CORNELL conducted to measure the proficiency of the nation’s youth in a variety of subject areas.2 Mr. Jonathan Senchyne, a doctoral candidate in English at Cornell University, believes that the ability to REPRODUCED FROM [13] instantly share and edit information is another huge advantage of internet reading (J. Senchyne, personal communication, October 27, 2011). The invention of blogs and other types of self-publish sites has granted everyone the ability to express their opinion to the world at large. Wikis, for example, have become a popular way for people to share the information that they have and learn from what others have posted. Although this content may not always come from a reliable source, studies show that the collaboration of many individuals on one subject’s Wiki page can lead to very accurate content. Wikipedia, for example, was found to have an error rate close to that of Encyclopedia Britannica, a highly-regarded scholarly encyclopedia. However, Wikipedia differs from Encyclopedia Britannica in that if found, these errors can be fixed immediately by anybody with internet access.12 Senchyne believes that this type of instant sharing and editing has allowed computer users, especially students and younger children, to become “social readers” who now read the article, then discuss it in forums with one another. Access to unlimited information and multiple perspectives makes the internet an invaluable source for young Americans in the process of developing synthesis and problem-solving skills. However, the internet’s many distractions and its complicated interface can cause us to lose focus on what we are reading. Over the years, our brains have learned to overcome these challenges by skimming articles for answers instead of gaining a deep understanding of the text. As the influence of the internet continues to grow, the differences between reading paper text and reading online will become more pronounced, as will the effects of web-based reading on the way we read, write, think, and communicate. During this revolution, we must stay aware of these differences and either learn to adapt our daily lives to this new system of thinking or find a way to control the degree to which the internet influences our daily lives. references 1. Smith C. Internet Usage Statistics: How We Spend Our Time Online (INFOGRAPHIC). Huffington Post [Internet]. [homepage on the Internet]. 2010 Jun 22 [cited 2011 Oct 3]; Tech: [about 2 screens]. Available from: http://http://www.huffingtonpost. com/2010/06/22/internet-usage-statistics_n_620946.html 2. Rich M. The Future of Reading - Literacy Debate - Online, R U Really Reading?. The New York Times [Internet]. 2008 Jul 27 [cited 2011 Oct 07]; Arts [about 10 screens]. Available from: http://www.nytimes.com/2008/07/27/books/27reading.html?pagewanted=all 3. Rich M. Study Links Drop in Test Scores to a Decline in Time Spent Reading. The New York Times [Internet]. 2007 Nov 19 [cited 2011 Oct 02]; Arts [about 3 screens]. Available from: http://www.nytimes.com/2007/11/19/arts/19nea.html?adxnnl=1&ref=books&adxnnlx=1326294343-Nkr+Fh/sP757DBsEwL2+sQ 4. Powers W. Hamlet’s Blackberry: Why Paper is Eternal. Joan Shorenstein Center on the Press, Politics and Public Policy Discussion Paper Series. Cambridge: Harvard College; 2007. p. 1-74. 5. Nielsen J. Useit.com: Jakob Nielsen’s Website. [homepage on the Internet]. 1997 [cited 2011 Sep 30]. Why Users Scan Instead of Read; [2 screens] Available from: http:// www.useit.com/alertbox/whyscanning.html 6. Davidson C. Now You See It: How the Brain Science of Attention Will Transform the Way We Live, Work, and Learn. New York: Viking; 2011. 7. Carr N. Is Google Making Us Stupid?. The Atlantic [Internet]. 2008 [cited 2011 Oct 30 02]; Magazine: [about 8 screens]. Available from: http://www.theatlantic.com/magazine/archive/2008/07/is-google-making-us-stupid/6868/ 8. Nielsen J. Useit.com: Jakob Nielsen’s Website. [homepage on the Internet]. 1997 [cited 2011 Sep 30]. How Users Read on the Web; [3 screens] Available from: http://www. useit.com/alertbox/9710a.html 9. Nielsen J. Useit.com: Jakob Nielsen’s Website. [homepage on the Internet]. 2006 [cited 2011 Sep 30]. F-Shaped Pattern For Reading Web Content; [3 screens] Available from: http://www.useit.com/alertbox/reading_pattern.html 10. Nielsen J. Useit.com: Jakob Nielsen’s Website. [homepage on the Internet]. 2003 [cited 2011 Sep 30]. Information Foraging: Why Google Makes People Leave Your Site Faster; [4 screens] Available from: http://www.useit.com/alertbox/20030630.html 11. Johnson G. Internet Use and Cognitive Development: a Theoretical Framework. E-Learning Digital Media. 2006 [cited 2011 Oct 25] 3(4): [8 pages]. Available from: http://www.wwwords.co.uk/pdf/freetoview.asp?j=elea&vol=3&issue=4&year=2006&article=7_Johnson_ELEA_3_4_web 12. Shu W, Chuang Y. The Behavior of Wiki Users. Soc Behav Personal [serial on the Internet]. 2011 [cited 2011 October 25]; 39(6): [14 pages] Available from: http:// web.ebscohost.com/ehost/detail?sid=b1debc69-81bf-4fb4-a76a-01113140993%40 sessionmgr110&vid=4&hid=112&bdata=JnNpdGU9ZWhvc3QtbGl2ZQ%3d%3d#db=aph&AN=62718753 13. http://commons.wikimedia.org/wiki/File:Great_Books.jpg THE TRIPLE HELIX CAMBRIDGE ACKNOWLEDGEMENTS The Triple Helix Cambridge would like to thank the following colleges and groups for their generous continued support. The Cavendish Laboratory Gonville and Caius The University Chemical Laboratory Major Sponsor The School of the Biological Sciences The School of Clinical Medecine Homerton Queens’ The Department of History and Philosophy of Science The Societies Syndicate The Cambridge Philosophical Society Christ’s Newnham St. John’s Magdalene cambridge philosophical society – lent 2015 Lighting the Future: Next generation LED lighting to save energy and improve our health Monday, 9 February 6 p.m. – 7 p.m. Professor Sir Colin Humphreys CBE FREng FRS, Department of Materials Science www.cambridgephilosophicalsociety.org [email protected] 01223 334743 a v hill lecture Science and the quiet art revisited Between rock and a hard place: soil, the ambiguous material Monday, 23 February 6 p.m. – 7 p.m. Monday, 9 March 6 p.m. – 7 p.m. Professor Sir David Weatherall Professor Malcolm Bolton Institute of Molecular Medicine, University of Oxford All events are in the Bristol-Myers Squibb Lecture Theatre, Department of Chemistry. Lectures are open to all who are interested. If you are interested in supporting The Triple Helix’s mission financially or otherwise, please contact us at [email protected] © 2015 The Triple Helix, Inc. All rights reserved. FREng, Department of Engineering The Triple Helix Cambridge is an independent chapter of The Triple Helix, Inc., an educational 501(c)3 non-profit corporation. The Science in Society Review is published once per term by the Triple Helix Cambridge and is available free of charge. Its sponsors, advisors, and the University of Cambridge are not responsible for its contents. The views expressed in this journal are solely those of the respective authors. the triple helix cambridge Get involved! We’re committed to making science a greater part of society. WRITE FOR US [email protected] Make your voice heard across the world. Have an idea for an article? Get in touch! 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