The Science in Society Review - Brown University [Fall 2011]

Fall 2011 | Brown University

The Mysterious Rise in Food AllergiesSpeaking in Code: Is Metaphorical Language Preventing the Public from Understanding Genetics? Pandamonium: The Politics Behind a Giant The Battle Over Gene Ownership

Neuromorphic Implants for Dissecting the Hard Problem of Consciousness

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EXECUTIVE MANAGEMENT TEAM Chief Executive Officer Jennifer Ong Chief of Global Affairs Jacob Parzen Executive Editor-In-Chief Dhruba Banerjee Chief Production Officer Darwin Chan Executive Director, E-Publishing Zain Pasha Executive Director, Internal Affairs Jennifer Yang Executive Director, Science Policy Faisal Rahimi Chief Marketing Officer Manisha Kaura Chief Financial Officer Robert Qi Chief Operating Officer, Europe Francesca Day Chief Operating Officer, Australia Madeleine Chan Chief Operating Officer, North America Mridula Nadamuni Chief Operating Officer, Asia Chin You Chuen INTERNATIONAL STAFF Senior Literary Editors Titas Banerjee Jefferson Chen Michael Graw Vicky Phan Harrison Specht Linda Xia Senior Production Editors Luna Chen, Cornell Jasmine Chuang, Cornell Hyo Jin Jessica Lee, Cornell Andrew Kam, UChicago Ai Ming Chow, Melbourne Cassie Yeh, Berkeley Senior E-Publishing Editors Anna Collins Edgar Pal Jae Kwan Jang John Lee Rahul Kishore

BOARD OF DIRECTORS Chairman Kevin Hwang Vice Chairman Erwin Wang Secretary Melissa Matarese Alumni Chair Joel Gabre Finance Chair Kalil Abdullah Board Members Manisha Bhattacharya Julia Piper James Shepherd TRIPLE HELIX CHAPTERS North America Chapters Arizona State University Brown University Carnegie Mellon University Cornell University Georgetown University Georgia Institute of Technology The Harker School Harvard University John Hopkins University University of California, Berkeley University of California, San Diego University of Chicago Yale University Europe Chapters Cambridge University Asia Chapters National University of Singapore Australia Chapters University of Melbourne

THE TRIPLE HELIXA global forum for science in societyThe Triple Helix, Inc. is the worlds 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 tomorrows 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!

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TABLE OF CONTENTS

094

Speaking in CodeMetaphorical language of genetics

Pandamonium

18

The politics behind a giant

20

Gene OwnershipPatents for genes

Cover ArticleThe Mysterious Rise in Food Allergies Natalie Christie, Cambridge

Local Articles6 9 Synthia - Venters Synthetic Cell Speaking in Code: Is Metaphorical Language Preventing the Public from Understanding Genetics? Neuromorphic Implants for Dissecting the Hard Problem of Consciousness Genetic Engineering and Xenotransplantation: Future Considerations and Regulations Pandamonium: The Politics Behind a Giant The Battle Over Gene Ownership Moving Forward? The Role of the State Hospital in the Mental Healthcare Recovery Movement Ending the Free Ride: A Two-Tiered Organ Donation Paradigm Examining the Prospects of Deep Brain Stimulation as Mood Disorder Treatment Shubha Jindal Marissa Palmor

12 15

William Schweitzer Cody Simmons

18 20 22

Hayley Sparks Gaurie Tilak Kyle Wemple

25 28

David Winer

Adela Wu

International Features31 Supermax Me? The Costs and Benefits of Long-Term Solidary Confinement Ethical Issues in Cancer Clinical Trials Mammography Screening Guidelines: A Lesson Yet to Be Learned Sex and Aging: The Social Stigma Big Change in Small Places: Development, Traditional Knowledge, and Womens Lives in the Peruvian Amazon

Doni Bloomfield, UChicago

34 37 40 42

Darius Borhan, UCSD

Sandra Hwang, Cornell

Jennifer Sung, UChicago Margo Elizabeth Johnson, ASU

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BROW BROWN R10/12/2011 12:01:39 AM

INSIDE TTH

Message from the Chapter PresidentWelcome Dear Reader! The start of another academic year brings with it a new issue of The Science in Society Review. This Fall, we are excited to present you with a diverse spectrum of articles. You will find our journal to be unique and interdisciplinary; our writers choose to investigate a wide variety of topics and address many different issues. The Triple Helix was originally founded in October 2004 as a single chapter at Cornell University. The Brown chapter began in 2005, and in the past six years TTH has grown into an international community of students, with chapters around the world. Collectively, we strive to study the connections between science, society and law. Or, more broadly, we examine the way in which sciences and humanities interact, overlap, and impact society at large. Our aim is to stimulate thoughtful discussion about these interactions and we hope the articles in following pages will encourage you to join this dialogue. As always, I would like to thank all students, faculty, and mentors who have played a role in the production of this journal. Moreover, we extend a special thanks to all members of our organization as well as to our readers. TTH would not exist without you. Please enjoy this edition! Sincerely, MariaLisa S.M. Itzoe President 2011-2012

STAFF AT BROWN 2011-2012 President MariaLisa Itzoe Editor-in-Chief Marissa Palmor Managing Editor Michael Spector Director of Science Policy Theresa Lii Assistant Directors 2012-2013 Lily Chan Shubha Jindal Director of Finance Connor Shinn Directors of Marketing Nicole Noronha Kyle Wemple Dan Meropol Website Manager Jovian Yu Faculty Review Board Andrea Megela Simmons Daniel Weinreich Gary Wessel Associate Editors Christine Bukowski Xianhan (Mary) Fei Chloe OConnell Rachel Occhiogrosso Mangala Patil Anthony Rivera Adam Shur Michael Spector Writers Shubha Jindal Marissa Palmor William Schweitzer Cody Simmons Hayley Sparks Gaurie Tilak Kyle Wemple David Winer Adela Wu

Message from the Outgoing Editor-in-ChiefThe Triple Helixs Science in Society Review is an extremely unique publication: we are an international journal of science, society, and lawand we are entirely student-run. Our literary staff work throughout the semester, engaging in in-depth research and careful reviewing, to create what you hold in your hands now. The Brown chapter journal includes all the articles written at Brown during the cycle and a selection of articles from other chapters around the world. All of the articles in this journal have one element in common: they address issues that resonate for the writers and that lie at some intersection of science, society, and law. And thats where the similarities end. We have published pieces written in the style of traditional scientific articles and pieces in the style of personal essays; our authors have written about deep brain stimulation, panda conservation, and problems with how information about genetics and genetic technologies is distributed to the public; our authors have performed extensive research ranging from using the library and online journal articles to traveling to Thailand to investigate advances in HIV prevention. What you hold in your hands represents a semesters worth of writing, editing, rewriting, and reediting by students like you who were inspired by developments in the worlds of science, society, and law to go beyond the classroom and explore those developments independently. I hope that this issue of The Science in Society Review will likewise inspire you. Enjoy! Catherine McCarthy Editor-in-Chief 2010-2011

2 THE TRIPLE HELIX Fall 2011Book 1.indb 2

2011, The Triple Helix, Inc. All rights reserved.

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INSIDE TTH

Message from the CEOOver the next few months, you will notice that things are changing. The TTH International Executive Management Team has been worked tirelessly to prepare divisional guidelines that not only improve internal communication between international and chapter leadership but also increase global recognition of The Triple Helix brand. We have plans to continue our science policy collaborations, develop student research opportunities that provide skills for post-graduate careers, utilize our advisory and alumni networks, and expand internationally. Our new website http://www.thetriplehelix.org reflects a huge component of that change our new updated logo. With a more refreshing color scheme as well as revised circular shape, the logo has now become a better representation of our international nature while keeping us in line with the 3-D trend moving forward. Yet all of these changes would not have happened without your feedback, because no matter how much we talk, no matter how much we plan, you, the members and chapter leaders, are ultimately what drive us onward. So we urge you to continue connecting with us: Like our new Facebook Page, Tweet your experiences at #thetriplehelix1 and #tthepub, join our TTH LinkedIn group, and even hangout with us on Google +. As we come to a close on the first cycle of our leadership terms, come forward and develop new ideas that will push each issue to the next level. We look forward to working with and getting to know each one of you in the upcoming year. Try for something bold, something new, something truly unique, and TTH will be there with you every step of the way. Cheers, Jennifer Ong Chief Executive Officer

Message from the EEiC and CPOPerhaps the most quintessential human--and indeed biological--necessity is food. But what if the body begins to reject the very nourishment it runs on? Could societal factors be responsible? In this Fall 2011 edition of the Science in Society Review, Natalie Christie discusses this growing problem in the cover story, The Mysterious Rise in Food Allergies. Greetings to the biannual journal of The Triple Helix! This is the first issue we have the privilege to share with you in our newly appointed positions. Whether you are a loyal reader or you have just picked this up for the first time, welcome to this unique forum for science, society, and law. You will find insightful and informative reporting from undergraduates across the world, united by a common understanding: We share the realization that science does not occur in a vacuum, but is integrated with the concerns and values of our time. In addition to the talented writers, the interdisciplinary goal of our organization is supported by leaders at both the individual chapter and international levels. Associate and managing editors at the chapter, and Senior Literary Editors comprising the International Editorial Board, work tirelessly to polish articles in preparation for publication. This journals layout and design is the work of production teams at Cornell, UChicago, and Berkeley. Laying out articles is important for incorporating written words into an aesthetically pleasing design that makes reading this issue an enjoyable experience. Design is an important aspect of our organization, as demonstrated by our new logo. The dynamic between the Literary and Production divisions cannot be understated, and it is this symbiotic relationship that makes this journal exist in your hands. Sincerely, Dhruba Banerjee and Darwin Chan Executive Editor-in-Chief and Chief Production Officer


THE TRIPLE HELIX Fall 2011 310/12/2011 12:01:40 AM

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CAMBRIDGE

The Mysterious Rise in Food AllergiesNatalie Christie

F

ood is vitally important for life, but for allergy sufferers it can be deadly. Over the last few decades, there has been a huge increase in the number of people with food allergies. Hospital admissions for children with food allergies have risen by five hundred percent since 1990, with 6-8 percent of children under the age of 3 affected [1]. An incredible forty percent of British children have suffered with an allergic problem at some stage of their life [2]. The question that we should be asking is: What is causing this dramatic increase? Simply put, an allergy is a hyperactive response from the sufferers immune system to certain substances foreign to our body. In the case of a food allergy, bodys immune system mistakes particular foods as harmful, producing antibodies known as IgEs which then try to attack the food, inciting the body to release chemicals. It is these chemicals which produce the symptoms of the allergy [3]. Food allergies encompass a whole range of symptoms, ranging from an itchy rash, sneezing, stomach cramps or mild fever to more severe symptoms such as asthma attacks, hypertension, and possible loss of consciousness. Common allergens include milk, eggs, peanuts, wheat or soya, but the list is extensive. Food allergies can have a severe impact on the life of the sufferer. For example, people with allergies have to keep a constant watch on everything they eat; one contaminated mouthful could have terrible consequences. This can cause eating to become very stressful, especially at social occasions and when eating out. Grocery shopping can take a long time, as every label must be read carefully. Labelling rules issued by the European Union have been extremely helpful for sufferers; it has now become a legal obligation to include 14 listed food allergens on all pre-packaged foods.

By far the most popular theory is the Hygiene Theory, formulated by epidemiologist David Strachan thirty years ago. Strachan first investigated hay fever, an allergic response to pollen. He discovered that increasing family size led to a reduced risk of developing hay fever and postulated that an increased exposure to infection during childhood prevented the development of the allergy. This theory has now been extended to include all allergies, especially food allergies, and nothing has, as of yet, been found to disprove it. Proponents of the theory believe that modern life has become too clean; children are exposed to so many cleaning detergents, antibacterial soaps and disinfectants that their immune systems cannot develop properly. The International Study of Asthma and Allergies in Childhood (ISAAC) has discovered that there are very few allergies in poorer countries the prevalence of allergies within a country increases in proportion to its affluence. It has been suggested that this is because children from poorer countries do not have access to such a standard of hygiene and thus live in dirtier environments [5]. Even though many scientists and medical doctors favour this hygiene theory, others are apprehensive as much of the theory is speculation at present. Maybe the increase in food allergies is the price that society has to pay for being free of some life-threatening diseases.Reproduced from [10]

Food allergies can have a severe impact on the life of the sufferer

However, the most important thing now is to find out why there has been such an increase in the number of allergy sufferers [4]. There has been a vast amount of research into why the allergy incidence has increased, and numerous correlations between allergies and other factors have been found. Although several theories are rather convincing and have a lot of support in the academic and medical world, a single decisive account has not emerged yet. The three most plausible theories are the hygiene theory, leaky gut syndrome and the vitamin D theory.

Secondly, there has been link discovered between childhood obesity and food allergies. Results from the National Health and Nutrition Examination Survey 2005-2006 (USA) show that with a rise in childhood obesity there has also been an increase in childhood food allergies [6]. Investigations of IgE responses have shown that children of average weight had no increase in IgE antibodies when tested with allergens, but there was a huge increase found in obese children. A further study by scientists at GlaxoSmithKline (a pharmaceutical company)



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CAMBRIDGEsought to find the reason of the correlation [7]. They suggest that bad diets high in sugar and fat whilst low in fibre disturb the gut, causing dysbiosis (an unhealthy gut environment), as well as obesity. A disturbed gut environment is thought to cause a leaky gut, wherein cells in the small intestine are weakened and structurally damaged. This means that food antigens, instead of entering these cells, can sneak past them and into the blood stream, setting off allergic reactions. As well as causing immune reactions, a leaky gut would increase the insulin resistance of body cells, thus promoting poor glucose control and, eventually, obesity. A healthy diet could, in many cases, trigger a decrease in food allergies and obesity. Alternatively, there are many other things that might cause a leaky gut. Infectious agents, such as yeasts, pathogenic bacteria like salmonella, or an overgrowth of bacteria can increase intestinal permeability, regardless of ones diet. Parasitic infections have become more frequent with imported foods and greater foreign travel, but they have also risen in close association with heavier use of antibiotics. Antibiotics kill off friendly bacteria within the gut, leaving it to be colonised by detrimental yeast and bacteria. Overuse of over-the-counter drugs, such as paracetamol, aspirin, and ibuprofen have also been found to increase gut permeability, which eventually could lead to food allergies [8]. Nevertheless, the idea of the leaky gut syndrome remains an area of slight controversy itself. The site of much research at present, the condition is felt by many scientists to fall somewhere between conventional and alternative medicine. Though regularly diagnosed by alterative practitioners, it is still not formally recognised as a medical condition. If it were assumed that leaky gut syndrome were a true medical disorder, the question as to why the number of food allergies has increased so much would be answered. Recently, there has been a huge rise in the use of paracetamol and other NSAID drugs, as well as antibiotics. Many children do not have healthy diets and eat too many processed foods high in additives and sugar. Babies are born with a higher intestinal permeability than those of adults. If a baby is introduced to cows milk and food solids too early on, then the milk will pass through into the blood stream, causing the production of IgE antibodies. This leads to a dairy allergy. If the leaky gut syndrome was found to be the answer, then it would solve the problem of increasing food allergies simply. Unfortunately, this explanation does not address all the issues. There is still yet another possible solution: vitamin D deficiency. Researchers at the Massachusetts General Hospital in Boston have found a link between food allergies and lack of vitamin D [9]. Over a study of 1002 patients, scientists found that winter babies are more prone to food allergies.References1. National Institute For Health and Clinical Excellence (NICE) 2. Dr A Fox. http://www.adamfox.co.uk/Expertise.html 3. British Allergy Foundation www.allergyuk.org 4. Food Standards Agency http://www.food.gov.uk/safereating/allergyintol/label/ 5. Ahuja A. Is our zeal for cleanliness making us ill? The Times 2008 May 5 6. Visness C et al. Association of obesity with IgE levels and allergy symptoms in children and adolescents: Results from the National Health and Nutrition Examination Survey 2005-2006. The Journal of Allergy and Clinical Immunology, Pages 1163-1169.e4, May 2009 7. Rong J et al. Adipose Mitochondrial Biogenesis Is Suppressed in db/db and HighFat DietFed Mice and Improved by Rosiglitazone. Diabetes Journal 2007. 8. Gallard L M.D Leaky gut syndrome, breaking the vicious cycle. Foundation for integrated medicine http://www.mdheal.org/leakygut.htm 9. M. F. Vassallo et el. Potential Mechanisms For The Hypothesized Link Between Sunshine, Vitamin D, and Food Allergy In Children. The Journal of Allergy and Clinical Immunology Volume 126, Issue 2 , Pages 217-222, August 2010 10. CC-BY-NC, Wellcome Images, N0032617. URL: http://images.wellcome.ac.uk 11. CC-BY-NC, Wellcome Images, C0022910. URL: http://images.wellcome.ac.uk

Vitamin D helps the body to fight infections and suppresses the bodys allergy cells, contributing to greater tolerance for allergens. A lack of vitamin D would conversely lead to an increase in allergy occurrences. It is possible that this coincides with the rise in awareness of skin cancer over the past twenty years and the subsequently increased use of sun creams on children, which in turn could lead to a vitamin D deficiency. However, although plausible, one would think that vitamin D deficiency would only account for a small number of food

Reproduced from [11]

allergies, rather than the huge amount actually seen. In conclusion, there is no final answer as to why there has been such an increase in food allergies. The research is still going on, and several plausible explanations and theories exist that could be the answer. However, we need more investigation especially as a large proportion of work falls in the controversial area between alternative and conventional medicine. Many scientists have not accepted the Leak Gut Syndrome, although the evidence is building up for it, and if it was found to be correct, it would answer many problems. At present, scientists are focusing on the bacteria found in the gut, working on the Human Microbiome Project to map all of the bacteria found within the body, which may provide some answers, and maybe help decrease the prevalence of food allergies in the future. Natalie Christie is a third year student at St Catharines College studying History and Philosophy of Science.



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Synthia: Venters Synthetic CellShubha Jindal

W

ith the creation of a synthetic cell by Craig Venters team in May 2010, we have taken technology beyond our wildest dreams. Designing a computeran inanimate machinethat does all our work is one thing; manipulating a live cell to work according to our wishes is another. Since May of 2010, the headlines of numerous research journals such as Science and Cell have focused on Craig Venter and his teams ground-breaking accomplishment of designing Synthia, a synthetic cell that holds immense potential for future research in synthetic biology, genetics, and pharmaceuticals. His research is important because it shows promise in developing vaccines and drugs to cure diseases, creating biofuels and environmental clean-up agents, and helping researchers to gain a better understanding of how life forms operate. However, his lab faced a variety of hurdles in creating the synthetic cell and now faces several regulatory and ethical issues regarding the control of this technology, such as concerns about biosafety and bioterrorism. The scientific community has heralded this research as the first successful construction of a cell that performs all its functions according to the instructions of a synthetic genome chemically prepared in the laboratory. However, certain factions of the non-scientific community fear that humans are playing God by creating life. The Procedure Dr. Hamilton Smith, one member of Venters synthetic cell team, sums up the research as the successful development of new tools and techniques to dissect the genetic instruction set of a bacterial cell to see and understand how it really works [1]. Dr. Smiths statement is an indication that the creation of a synthetic cell is a stepping-stone in exploring how life functions. To make the cell we now know as Synthia, researchers at the J. Craig Venter Institute [JCVI] designed, synthesized, and assembled a 1.08-mega-base pair Mycoplasma mycoides JCVI-syn1.0 genome starting from digitized genome sequence information and transplanting it into a M. capricolum

recipient cell. This recipient cell replicated to create new M. mycoides cells controlled only by the synthetic chromosome [1]. Venters team selected the parasitic bacterium M. mycoides for two primary reasons: it grows quickly, and it consists of a relatively small genome. The selection of these two properties was instrumental in the success of the research as it made the bacterium easier to work with. Impediments in Creating Synthia The Venter team had to overcome several hurdles in transplanting and expressing a chemically synthesized chromosome in a recipient cell. First, Venters lab needed to improve methods for handling and manipulating intact chromosomes [1]. They also needed to synthesize a circular plasmid consisting of a million base pairs, which was over 20 times more than any that had been synthesized before [2]. Most chemical synthesis techniques stop working at a few thousand DNA letters [3]. This means that the researchers Reproduced From [14] could not synthesize a whole genome at oncethey would have to do it in parts. Venter and his colleagues eventually solved this problem by putting smaller fragments of synthesized DNA into bacterial cells first, where they assembled into large fragments, and then into yeast cells that had the machinery to stitch those fragments together. These researchers also needed to learn how to transplant these genomes into a recipient bacterium to establish a cell that not only functioned, but was also controlled entirely by a synthetic genome. Most importantly, they needed to know if they could transfer a working chromosome from one species of bacteria into another. After clearing these problems, the last hurdle was to make an exact copy of the M. mycoides genome in the lab and transfer that synthetic genome into M. capricolum [3]. Positive Implications Venters research was particularly groundbreaking because the synthetic genome was not physically derived in any way



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BROWNfrom preexisting genetic material and showed that it could be synthesized in the laboratory. Standard genetic engineering allows splicing of short synthetic sequences into existing, natural DNA sequences, but Venters Synthia genome was created from scratch. Venters team used a DNA synthesizer to piece together the A, G, C, and T bases to form novel building blocks, which they then stitched together into a single sequence [4]. definition of life. Scientists at the JCVI envision that the knowledge gained by constructing this first self-replicating synthetic cell, coupled with decreasing costs for DNA synthesis, will give rise to wider use of this powerful technology [5]. Synthetic bacteria with special genes can be constructed for use in the medical field to cure diseases like cancer and genetic birth defects. Synthetic bacteria can also be used as a scientific tool to create bacteria that synthesize new amino acids and to see how these bacteria evolve compared with bacteria that produce the usual suite of amino acids [7]. Another possibility for this technology is the creation of bacteria that digest oil from leaks and spills or that consume cholesterol and other potentially harmful substances in our bodies [8]. Negative Implications As with many discoveries of this magnitude, however, Venters cell has generated many concerns despite the potential benefits it appears to provide. A synthetic cell raises questions about biosafety, such as whether this technology could be used in bioterrorism to create a harmful pathogen as a biological weapon [9]. Even if measures are taken to prevent bioterrorism, small mistakes in labs working with synthetic bacteria could lead to the escape of these microbes into the environment where they could harm the ecosystem and the human population [10]. These ethical considerations also relate to the possibility of synthetic microbes mutating, converting a harmless bacterium into a pathogenic one. Professor Julian Savulescu, an Oxford University ethicist, is also concerned about whether we are playing God. Venter himself maintains that he has created not life but a synthetic cell, the difference being that he has used a pre-existing cell and has only inserted a synthetic chromosome into it [7]. Since the cell functions according to the inserted genome and the rules of synthetic life, it is synthetic [11].

Venter states that Synthia is the first synthetic cell whose genome is totally derived from a synthetic chromosome

The synthetic cell is proof of the principle that genomes can be designed in the computer, synthesized in the laboratory, and transplanted into recipient cells to produce a new selfreplicating cell controlled exclusively by the synthetic genome. It is not only the end product that is important, however; the tools and laboratory techniques that were developed as part of this research provide a means to piece apart a bacterial cells genetic information in order to understand its function [5]. Dr. Daniel Gibson, who played a critical role in this project, realizes this when he talks about working on their ultimate objective of synthesizing a minimal cell [1]. Such a cell would contain only the genes that are necessary to sustain life in its simplest form [5]. If researchers were able to create a minimal cell, it will help them better understand how cells function. As a cell is the basic and most fundamental unit of life, this could lead to an understanding of how life itself functions. Venter and his team have some preliminary ideas on how to achieve the goal of a minimal cell. The current proposed method is to take out small sequences from the synthetic genome and utilize their current transplantation methods. Small genomic sequences will be continually removed until the deletion of genes starts disrupting the cell and the genome is as small as possible. It is proposed that this minimal cell would be a platform to analyze the function of every essential gene in a cell [5]. Venter states that Synthia is the first synthetic cell whose genome is totally derived from a synthetic chromosome. He asserts that this is an important stepnot only scientifically, but also philosophicallyand claims that it has changed [his] views of the definitions of life and how life works [6]. Venters team created new life out of already existing life in the form of the synthetic DNA. One begins to wonder where to draw the line between creating life and creating artificial life. The use of a naturally occurring microbe as a host could constitute creating artificial life. However, the instructions of the cell are contained in its DNA, and this was synthetically created. In this way, Venters research challenges our 2011, The Triple Helix, Inc. All rights reserved.

Synthetic bacteria can also be used as a scientific tool to create bacteria that synthesize Reproduced From [14]. new amino acids and to see how these bacteria evolve, compared with bacteria that produce the usual suite of amino acidsJohn Sulston, a Nobel Laureate, has more practical concerns about the technology used in creating Synthia. He argues that Venter will obtain a monopoly on a range of genetic engineering techniques, which will restrict geneticists across the world from freely conducting their experiments. OthersTHE TRIPLE HELIX Fall 2011 710/12/2011 12:01:41 AM

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BROWNin the scientific community regard Venters research as less than promising because of the number of years it will take to be able to design new organisms from scratch. Moreover, they argue that conventional genetic engineering techniques have already enabled them to make progress in making biofuels and vaccines and that Venters research is therefore not really efficient in large-scale research [12]. Concerns regarding the synthetic cell are legitimate as any powerful technology has the potential to cause more harm than provide benefits. For example, terrorists could use the synthetic cell as a weapon while scientists could use it to create oxygen-evolving bacteria to explore the possibility of life on other planets. Conclusion Currently, Venter is collaborating with Exxon Mobil to produce biofuels from algae [7]. Producing biodiesel and other biofuels from algae is widely regarded as the most promising basis for large-scale biofuel production due to its resilient and fast-growing nature [13]. In the future, designer bacteria can help in the creation of vaccines for currently incurable diseases such as Parkinsons disease. The construction of synthetic bacteria that take in carbon dioxide can alleviate pollution problems. This shows that the synthetic cell has great potential in the imminent future as it will allow humans to manipulate synthetic organisms according to their needs. The benefits are far-reaching although more research is required to tap into the unexplored advantages of this technology. Shubha Jindal is a Biology concentrator at Brown University interested in genetics research and is currently modeling human neurodegenerative diseases in Drosophila. Shubha also enjoys reading about new scientific breakthroughs, especially those at the level of molecular biology.Reproduced From [15]

References1. Gibson DG, Glass JI, Venter JC. et al., Creation of a Bacterial Cell Controlled by a Chemically Synthesized Genome, Science [serial on the Internet]. 20 May, 2010 [cited 2011 Mar 15]; 329. Available from: http://www.sciencemag.org/content/329/5987/52. full 2. Chow C. Scientific Clearing House: Venters synthetic cell. [homepage on the Internet]. 2010 [cited 2011 Mar 15]. Available from: http://sciencehouse.wordpress. com/2010/05/25/venters-synthetic-cell/ 3. Palca J. Scientists Reach Milestone On Way To Artificial Life, [homepage on the Internet]. 2010 [cited 2011 Mar 15]. Available from: http://www.npr.org/templates/ story/story.php?storyId=127010591 4. Amos M. Team Venters synthetic cell, explained, [homepage on the Internet]. 2010 [cited 2011 Mar 15]. Available from: http://martynamos.blogspot.com/2010/05/teamventers-synthetic-cell-explained.html 5. J. Craig Venter Institute. First Self-Replicating Synthetic Bacterial Cell: First Self-Replicating, Synthetic Bacterial Cell Constructed by J. Craig Venter Institute Researchers. [homepage on the Internet]. 2010 [cited 2011 Mar 15]. Available from: http://www.jcvi.org/cms/press/press-releases/full-text/article/first-self-replicatingsynthetic-bacterial-cell-constructed-by-j-craig-venter-institute-researcher/ 6. Caroll J. Venter team births worlds first synthetic cell. Fierce Biotech [serial on the Internet]. 2010 [cited 2011 Mar 15]. Available from: http://www.fiercebiotech.com/ story/venter-team-births-worlds-first-synthetic-cell/2010-05-21 7. Callaway E. Immaculate creation: birth of the first synthetic cell, NewScientist [serial on the Internet]. 2010 [cited 2011 Mar 15]. Available from: http://www. newscientist.com/article/dn18942-immaculate-creation-birth-of-the-first-syntheticcell.html 8. Samuel G. The perils of creating synthetic life. BioNews [serial on the Internet]. 2010 [cited 2011 Mar 15].;559 Available from: http://www.bionews.org.uk/ page_61626.asp 9. Macrae F. Scientist accused of playing God after creating artificial life by making designer microbe from scratch - but could it wipe out humanity? MailOnline [homepage on the Internet]. 2010 [cited 2011 Mar 15]. Available from: http://www. dailymail.co.uk/sciencetech/article-1279988/Artificial-life-created-Craig-Venter-wipe-humanity.html 10. Ward L. Craig Venter Boots up First Synthetic Cell. Popular Mechanics [homepage on the Internet]. 2010 [cited 2011 Mar 15]. Available from: http://www. popularmechanics.com/science/health/breakthroughs/synthetic-cell-breakthrough 11. Kaebnick G. Is the Synthetic Cell about Life?: A bioethicist explores the soul of Venters new life form and of his experiment, The Scientist [serial on the Internet]. 2010 [cited 2011 Mar 15].;24[7] Available from: http://www.the-scientist.com/article/ display/57523/ 12. Wade N. Researchers Say They Created a Synthetic Cell. The New York Times [homepage on the Internet]. 2010 [cited 2011 Mar 29]. Available from: http://www. nytimes.com/2010/05/21/science/21cell.html 13. Garrett J. First Synthetic Cell Holds Promise for Biodiesel and Green Heating Oil. [homepage on the Internet]. 2010 [cited 2011 Mar 29]. Available from: http://www. heatingoil.com/blog/first-synthetic-cell-holds-promise-for-biodiesel-and-greenheating-oil0523/ 14. Dillow C. Venter Institutes Synthetic Cell Genome Contains Hidden Messages. [homepage on the Internet]. 2010 [cited 2011 Apr 27]. Available from: http://www. popsci.com/science/article/2010-05/venter-institutes-synthetic-cell-genome-containshidden-messages-watermarks 15. Macrae F. Scientist accused of playing God after creating artificial life by making designer microbe from scratch - but could it wipe out humanity? Mail Online [homepage on the Internet]. 2010 [cited 2011 Apr 27]. Available from: http://www. dailymail.co.uk/sciencetech/article-1279988/Artificial-life-created-Craig-Venter-wipe-humanity.html



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Speaking in Code: Is Metaphorical Language Preventing the Public from Understanding Genetics?Marissa Palmor

F

or over a decade, it has been widely accepted that we are living in the age of the genome. Since the initiation of the Human Genome Project, genetics and genetic technologies have been eliciting excitement and fervent debate everywhere from classrooms to headlines and dinner tables alike. However, it is evident from this discourse that the public fails to understand many of these concepts beyond the simplistic and metaphorical explanations that have become essential to science curricula and journalism. As a result of not understanding the significance of the genomefrom single gene units to their multifaceted interactionsmembers of the public failReproduced From [6]

to understand the technologies available to them as patients and consumers. Yet, public expectations for these technologies are rising, along with the stakes. With new technologies such as direct-to-consumer genome screening and prenatal testing entering markets around the country, the public has a responsibility to make informed decisions regarding the use and regulation of these products that could greatly impact their lives. From the media to educational systems, the public must understand this relatively young field of research to have a say in the regulation and development of todays many burgeoning genetic technologies. The Roots of the Metaphor It was not until James Watson and Francis Crick published A Structure for Deoxyribose Nucleic Acid [1], the first paper to describe the double helix structure of DNA, that widespread genetic metaphors truly entered popular dialogue. Along with this first publication came the illustration of DNAs ATCG base system acting as a master molecule or code [2], one metaphor that has evolved into the many others still in use today. For decades, one could not discuss the genome without hearing it described as an instruction book, the book of life, a blueprint of the human race, and so on. Each of these exact phrases, in fact, were heard on the day that President Bill Clinton, Prime Minister Tony Blair, Dr. Francis S. Collins, and Dr. J. Craig Venter came together in the East Room of the White House to announce the first survey of the completion of the Human Genome Project [HGP] [3]. In one public announcement, all speakers but Venter used one of these metaphors to convey the importance of this scientific work. Beyond likening the genome to a great book that may be read off just as clearly and linearly as one could read the words on this page, several connections were drawn to the image of a holy book of life, describing this instruction book as previously known only to God, saying that today we are learning the language in which God created life [3]. Though these metaphors may have been effective vehicles for politicians and officials to generate excitement and discourse among the public, they completely fail to convey the millions of dollars and decades of laborious research that brought the HGP to this point. Furthermore, these metaphors also provided, and even encouraged, a gross oversimplification of the complicated interactions of genetics, epigenetics, and environmental factors that come together to create life as it is observed and understood by the nonscientific public.



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BROWNTeaching in Metaphor Though these religious metaphors seem to have quieted down in the public media in recent years, other reductionist metaphoric language derived from these first misconceptions reigns on in todays classrooms. Though more than 80 [percent] of middle and high school science standards adopted since 2003 include terminology on the Human Genome Project cloningand/or other biotechnology terminology that did not exist in previous versions of the standards [4], there is ample evidence that efforts to bring genetics into the classroom are failing to displace previous misinformed conclusions about failure of teachers to introduce interactive lessons that encourage a real examination of genetics principles, has hampered the ability of students to communicate about genetics in the classroom as well as in public. Doctors and Genomes As disappointing as it is to hear that schoolrooms are failing to adequately educate youth about genetics, it is even more disheartening that the American medical communitys knowledge is falling behind the latest genetic developments. Executive Vice President, CEO, and MD Michael Maves of the American Medical Association recently wrote to the Food and Drug Administration, the number of genetic tests available directly to consumers has proliferated rapidly, and several studies have reported that physicians find it difficult to keep up with the pace of genetic technology [5]. Written on behalf of the American Medical Association in response to recent public meetings regarding the possible regulations for directto-consumer genome screening, this letter simultaneously requested that doctors be solely responsible for handling genome screenings and consultations. As Mavess letter indicates, even the medical officials to whom the public turns as agents of science are not able to effectively communicate the implications and meaning of genetic technologies and screening to their patients. If doctors are unable to effectively communicate with their patients about the significance of and appropriate responses to genomic screens, that task may be left in the hands of for-profit companies that may be inclined to skew that information to their advantagepresenting the information

For decades, one could not discuss the genome without hearing it described as an instruction book, the book of life, a blueprint of the human racegenetic science. A study conducted by the American Society of Human Genetics [ASHG] in 2008 analyzing the results of a high school essay contest regarding the techniques and ethics of modern genetic science concluded that misconceptions derived from the media or over-simplified teaching goals are not effectively corrected in high school classrooms, in spite of well-intended statewide standards for science curricula and the teachers implementing them [4]. Five hundred essays submitted to this contest were analyzed in depth for these misconceptions, and they demonstrated such examples in areas ranging from genetic technology to patterns of inheritance; the deterministic nature of genes and the genetic basis of disease; and the nature of genetic materials, research, and reproductive technology. Although this study intentionally separated these categories, it is clear that each of these elements is integral to effective communication regarding genetics and the genetic technologies making headlines today. Many of the essays were in ways that reflect the strength of the popular genome as a book metaphor, suggesting that the content of genetic information could be simply read off with direct meanings and consequences. This is due to the popular one gene, one phenotype paradigm that is derived from the patterns of Mendelian genetics, the simplest of genetics models that also receives the most attention in classrooms. Rather than emphasize the complex non-Mendelian and polygenic models of inheritance that are more frequently at work in phenotypes of interest, most state standards [seventeen of twenty] require only the explanation of this clear model that most directly feeds into one gene, one phenotype assumptions about genetics [4]. Though it may seem a great step forward that genetics lessons have entered the classroom en masse, the oversimplification of much of this teaching, as well as the 10 THE TRIPLE HELIX Fall 2011Book 1.indb 10

misconceptions derived from the media or oversimplified teaching goals are not effectively corrected in high school classrooms, in spite of well-intended statewide standards for Reproduced From [14]. science curricula and the teachers implementing them

as certain to increase hype and dramatize personal anecdotes. The debate continues as to whether returning screening results with detailed explanations of the genetic data and its potential consequences, or lack thereof, is enough to ensure appropriate interpretation of this information. This concern is well-founded, since much of media coverage regarding the genes reported in such screens follow the gene for X modelsaying that a gene for this or that downstream phenotype has been discovered by new research. While screening companies like 23andMe do 2011, The Triple Helix, Inc. All rights reserved.

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BROWNlook for single nucleotide polymorphisms [SNPs] that seem to hold direct relationships to diseases, in reality, these genes are just one of hundreds that contribute to disease and other characteristics of interest to the public. For this reason, data needs to be returned with detailed explanations of what it may and may not suggest, without allowing for any quick conclusions. As such, the question still stands whether, like the metaphorical analogy of the human genome to a book, people reading their own reports will seek prescriptions, answers, and categorizations, or if they will take the time to fully comprehend the nuanced explanations and uncertainties involved in interpreting this raw data. Changing Metaphors, Shifting Paradigms As debates about genetic technologies continue, and as the public pushes to delve further into headline-making scientific breakthroughs, it is time to critically analyze the way that this information is understood and propagated. Rather than accept the current metaphorical language and consequent misconceptions of genetics in popular discourse, real advancements must be made to increase the accuracy of such discoursespreading awareness and promoting the exchange of unaltered facts. To do so, policymakers, educators, doctors, researchers, and journalists need to make effective changes in their fields to spread scientific knowledge earlier and further. By bringing an awareness of actual genetic science to classrooms as early as possible, and ensuring that the popular media do not use faulty metaphors as a linguistic crutch or a marketing tool, those who publicize and regulate science could give the American public the means to better understand this developing field. The medical community must in turn strive to stay abreast of technological advancements and the subsequent concerns and needs of their patients, and the researchers providing this data must be held from exaggerating or making inaccessible the results of their work. With enough collaboration and cooperation, the public could easily be made more aware of this complex yet critical field. A real understanding of genetics is indispensible for the publics acceptance and effective utilization of genetic technologies in an informed and appropriate manner as these technologies continue to fascinate and affect us. Marissa Palmor 12 is a Human Biology concentrator with an interest in bioethics and reproductive health. She may be reached at [email protected].

Reproduced From [7]

References1. Watson JD and Crick FHC, A Structure for Deoxyribose Nucleic Acid. Nature 1953; 171:737-738. 2. Hedgecoe A, Transforming genes: metaphors of information in modern genetics. Science as Culture 1999; 8:209-228. 3. Office of the Press Secretary of the White House. Remarks by the President, Prime Minister Tony Blair of England [via Satellite], Dr. Francis Collins, Director of the National Human Genome Research Institute, and Dr. Craig Venter, President and Chief Scientific Officer, Celera Genomics Corporation, on the Completion of the First Survey of the Entire Human Genome Project [press release]. Washington, D.C: The White House; 2000 June 26.

4. Shaw KM, Van Horne K, Zhang H, Boughman J. Essay Contest Reveals Misconceptions of High School Students in Genetics Content. Genetics 2008; 11571168 5. Maves MD. Re: Molecular and Clinical Genetics Panel of the Medical Devices Advisory Committee, Notice of Meeting [Docket No. FDA-2011-N-0066] [letter]. Chicago, IL; 2011 February 23. 6. Original Watson and Crick Model Picture [Image on the Internet]. 2007 [cited 10 May 2011]. Available from: http://www.farooqhussain.org/projects/ dnamodelreconstruction. 7. 23andMe Genome-Testing Kits Picture [Image on the Internet]. 2010 [cited 10 May 2011]. Available from: http://www.flickr.com/photos/nosha/4668325959/.



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Neuromorphic Implants for Dissecting the Hard Problem of ConsciousnessWilliam S. SchweitzerWhat is the Hard Problem of Consciousness? eople dont agree about what consciousness is. Notions of self-awareness or meta-cognition as criteria for consciousness emerge in some philosophical, cognitive science, and machine-engineering scholarship. Consciousness may one day join attention, memory, and perception as something we explain in terms of neural connections and firing patterns. Hypothetically, a robot could copy these to implement all of the cognitive operations that make us think of ourselves as selves and even to convince people it is an intelligent being. Still, we wouldnt be able to tell whether such a robot really experiences. Reproduced From [20] A more direct definition of consciousness is any minimal trace of subjective experience, or qualia. A quale is, for example, the greenness our mind imposes on light of a certain wavelength hitting the retina. Nothing outside ones head is intrinsically green, or savory, or shrill, or aromatic. Pupil dilations, knee-jerk reflexes, and salivation are automatic responses to certain stimuli, but they are not phenomenological and therefore not qualia. We may consider qualia, these phenomenological building blocks, and the interactions between them identical with experience, and with consciousness. Understanding how experience exists and functions is commonly known as the Hard Problem of consciousness [1]. There is a growing interdisciplinary scientific interest in this ancient mystery. At the annual Towards a Science of Consciousness conference, one can encounter philosophers, psychologists, cognitive scientists, neuroscientists, biologists, quantum physicists, and even spiritual writers. Along with the journals Consciousness and Cognition and Journal of Consciousness, this conference includes among its chief goals the furthering of understanding of what makes experience happen. of neurons [2,3] to electromagnetic fields that emerge from and unite organic information-processing architecture [4,5,6] to special arrangements of pure causal information [7,8]. Once the NCCs are isolated, a second question remains as to how conscious states relate to physical states. One popular account of consciousness treats experience as a fundamental entity of the world, alongside matter, energy, and space-time [7]. By casting experience and the physical world as dual facets of the same thinginformationthis view presents organizational invariance, the panpsychic claim that any object that conveys causal information shares an identity with some minute trace of experience [7]. According to this viewpoint, two brains with identical connectivity processing the same thing would have identical qualia. It doesnt matter whether one is made of silicon, or is the size of a mainframe computer, or relies on a central processing unit; as long as it processes the same essential information as a biological brain, it would have the same experience. If we can establish fundamental principles about the relationship between the shared physical world and private phenomenology, we are then able to test a third set of more elaborate theories. Perhaps the most mathematical and empirically testable theory of how and why a quale can result from causal information is Integrated Information Theory [IIT], which builds on organizational invariance [8]. This theory assigns a value, [phi], to the information a system can realize above and beyond its parts. Although a digital screen may convey complex information, it has a very small because it performs no discrimination between any causal signals beyond the OFF/ ON state of its component diodes. Our minds, however, can discriminate between countless input states composed of integrated information from each sensenot just the two inputs, ON or OFF [8]. According to this theory, any quale can be graphed as a geometric shape carved out by causally related points, each marking a set of probabilities, each probability corresponding to a certain information state in the brain [8]. Why the Hard Problem Is Not Easy The problem is these hard problems are hard because we

P

Unpacking the Hard Problem The Hard Problem can be broken down into several smaller problems. The primary question is, What are the minimal events and structures [the neural correlates of consciousness, or NCC] that must be present for consciousness to happen? The necessary correlates, according to competing accounts, range from patterns of quantum leaps within the microtubules 12 THE TRIPLE HELIX Fall 2011Book 1.indb 12


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BROWNcan only observe our own experience, and no one elses. Experience is inherently private [9]. As Nagel argued, we could exhaustively visualize the functional processes by which a bat uses echolocation to perceive its surroundingsthis is public information. But without any echolocation of our own, we cannot possibly imagine what the experience is like for a bat. An explanatory gap persists between the two ways of knowing [9]. In fact, you cant really know whether a bat, or Turing machine, or anyone other than yourself, is conscious at all [10]. Of course, we assume awake and dreaming humans are conscious. An advantage of this assumption is that it lets us begin to correlate some brain states with experience [unlike machines, we trust they really are conscious] and others with its absence. Whether we correlate changes in brain activity with the mind-altering effects of LSD or the spawning of two consciousnesses within a split-brain patient [1], studies on humans at least allow for third-person [but not direct] access to information from a subjects private experience. We are less disposed to assume a Turing machine is conscious. Still, an advantage of working with machines is that we design them ourselves and can take them apart to isolate exactly what interests us. Neuroimaging cannot nearly catch such detail in living patients. Even if it could, one cannot fiddle with real brains the way one can with machinery. Human studies allow access to private information but do not allow much control over the neural circuitry; machine studies allow for this control but can never satisfy the need for private information. All components of the hard problem are caught between machine and human studies in that they require both private information and control of the physical components to isolate the neural correlates of consciousness. Neuromorphic Implants: A Plausible Solution A methodology combining the best of both worlds may be on the horizon. In the last decade, a spate of ambitious projects have been launched around the globe to artificially imitate brains [11]. DARPAs SyNAPSE Program aims to develop electronic neuromorphic machine technology that scales to biological levels [12]. DARPA started this initiative in the hope that directly mimicking neural structures in hardware would afford computational advantages over traditional computer chips. And so it has: Kwabena Boahens Brains in Silicon program at Stanford is harnessing the brains parallel processing architecture to rival the Blue Gene supercomputers serial-processing performance with a million times less energy [13]. The group is one of several contributors to silicon replicas of retinas, whose increasing energy and size efficiency is pav-

Reproduced From [14].

Reproduced From [21]



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BROWNing the way for implantation in the blind [14]. Besides this, the group is starting on blueprints for neuromorphic replicas of the cochlea, the cerebellum, the basal ganglia, part of the thalamus, and eventually the cortex [13]. Other important aspects of neural computation are being selected and copied as well. The Neuromorphics Laboratory at Boston University aims to solve the prohibitive energy demands of combining information from separate memory and processing centers in digital computer architecture. Their answer to this is the memristor, a kind of transistor with the unique sical conditioning of motor response circuitry to restore motor learning in aged rats [16, 17]. Finally, large-scale simulations of the mammalian brain on computers push the limit on what can be copied on software, if not hardware. These include the Blue Brain Project, the IBM Blue Gene supercomputers cat brain simulation [11], and the Integrate and Fire Array Transceiver at Johns Hopkins [11]. Neuromorphic engineers are still working hard just to build replicas of the most peripheral neural circuits that can actually replace damaged tissue. However, it is not inconceivable that increasingly integrative partshigh- partsof the brain may follow suit [13, 18]. The march of computational neuroscience and neuromorphic engineering points toward a medical future in which a silicon chip helps an aging or Alzheimers patient compensate for memory loss or fills the literal and figurative holes in the quality of life of a stroke victim. Such an implant would be unprecedented because it would give trusted, human consciousness private access to hardware we engineered ourselves. If a neuromorphic implant can restore experience in some way, its designers will have virtually isolated the neural correlates of consciousness. If not, a failure still provides useful feedback. Whats more, an implant that produces the exact same experience when it conveys the same information would support the principle of organizational invariance; if the experience did not correlate with the information, one could ask what other physical factors affect experience. Finally, the relationship between phenomenology and information on an implant may support or contradict IIT theory and its competitors. As a neuroscience major with an interest in biomedical engineering, William finds the intersection between the brain and philosophy especially interesting, which is what led him to write about the mind body problem, and how technology can help.

By casting experience and the physical world as dual facets of the same thing informationthis view presents organizational invariance, the panpsychic claim that any object that conveys causal information shares an identity with some minute trace of experience

property of retaining information about its own stimulation history in its resistive state, somewhat like a synapse [15]. Another group aims to develop a rehabilitative nanochip, or ReNaChip, that can interface with the brain and bridge processing gaps left by aging, or perhaps stroke. The group is currently working on a chip that copies the cerebellums clasRefernces1. Pinker S. The Brain: The Mystery of Consciousness. Time Magazine [serial online]. 2007 Jan 19 [Cited 2011 Mar 16]; Available from http://www.time.com/time/ magazine/article/0,9171,1580394,00.html 2. Hameroff SR, Penrose R. Conscious events as orchestrated space-time selections. Journal of Consciousness Studies. 1996; 3 [1]: 36-53. 3. Hameroff S. The conscious pilotdendritic synchrony moves through the brain to mediate consciousness. J Biol Phys. 2010 April 2;3:71-93. 4. Pockett S. Initiation of Intentional Actions and the Electromagnetic Field Theory of Consciousness. Humana Mente. 2011 Jan; 15:159-175. 5. McFadden, J. The Hard Problem Made Easy? Journal of Consciousness Studies. 2002; 9[8]:45-60. 6. Lorenz S, Ames H, Versace M. Consciousness and Neuromorphic Chips: A Case for Embodiment. Paper presented at: Interdisciplinary graduate conference on consciousness; April 2010. Available at http://www.neurdon.com/2010/12/07/ moneta_and_the_c_word/ 7. Chalmers D. Facing Up to the Problem of Consciousness. Journal of Consciousness Studies. 1995; 2[3]:200-19. 8. Tononi, G. Consciousness as Integrated Information: a Provisional Manifesto. Biol. Bull. 2008 Dec; 215: 216242. 9. Nagel, T. What is it like to be a bat? The Philosophical Review. 1974 Oct; 83[4]:43550. 10. Descartes R. Meditations on First Philosophy. 11. Versace M, Chandler B. The brain of a new machine. Spectrum, IEEE. 2010 Dec; 47[12]:30-37. doi: 10.1109/MSPEC.2010.5644776 12. Systems of Neuromorphic Adaptive Plastic Scalable Electronics [SyNAPSE]

[Internet]. DARPA; [cited 2011 Mar 16]. [one screen], Available from: http://webext2. darpa.mil/Our_Work/DSO/Programs/Systems_of_Neuromorphic_Adaptive_Plastic_ Scalable_Electronics_%28SYNAPSE%29.aspx 13. Brains in Silicon [homepage on the Internet]. Stanford: Leland Stanford Jr. Board of Trustees; c2006 [cited 2011 Mar 16]. Sect, People; [about 6 screens] Available from http://www.stanford.edu/group/brainsinsilicon/people.html 14. Koch C, Mathur B. Neuromorphic vision chips. Spectrum, IEEE. 1996 May; 33[5]:38-46 doi: 10.1109/6.490055 15. Livitz G, Versace M, Gorchetchnikov A, Ames H, Leveille J, Chandler B, et al. Adaptive, brain-like systems give robots complex behaviors. Institute of Neuromorphic Engineering; c2011. Doi: 10.2417/1201101.003500 16. Renachip [homepage on the Internet]. Newcastle University; c2008 [cited 2011 Mar 16]. Sec, Objectives; [one screen] Available from http://www.renachip.org/ objectives.aspx 17. Welsh J, Schwarz C, Garbourg Y. The cerebellum as a neuronal prosthesis machine. Progress in Brain Research. 2002. doi:10.1016/S0079-6123[01]30020-1 Kurzweil R. The Singularity is Near. Viking Adult; 2005. 18. Jackson A, Mavoori J, Eberhard E. Long-term motor cortex plasticity induced by an electronic neural implant. Nature. 2006 Nov 2; 444. doi:10.1038/nature05226. 19. Sandberg, A, Bostrom, N. Whole Brain Emulation: A Roadmap, Technical Report. Oxford: Future of Humanity Institute; 2008. 20. Web, Revol. Alan-turing. Digital Image. Flickr.com. 5 October 2009. Web. June 18, 2011. http://www.flickr.com/photos/revolweb/3984345157/ 21. Electronica, Ars. Retina implantat. Digital Image. Flickr.com. 15 March 2011. Web. June 18, 2011. http://www.flickr.com/photos/arselectronica/5529172444/



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Genetic Engineering and Xenotransplantation: Future Considerations and RegulationsCody Vance Simmons

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any are familiar with the ethical dilemmas posed by tissue harvesting, animal testing, and genetic engineering. These scientific areas all relate to another field that has yet to receive the same level of ethical scrutiny: xenotransplantation. According to the U.S. Food and Drug Administration (FDA), xenotransplantation is any procedure that involves the transplantation, implantation or infusion into a human recipient of either (a) live cells, tissues, or organs from a nonhuman animal source, or (b) human body fluids, cells, tissues or organs that have had ex vivo contact with live nonhuman animal cells, tissues or organs (1). Recent breakthroughs in genetic engineering have led to promising advances in overcoming the scientific barriers to xenotransplantation. However, the implications of fast-progressing mammalian genetic engineering and tissue harvesting have not been fully considered in an ethical and regulatory context, making it necessary to address and implement clearer distinctions, terminology, and limits so that such progress does not unacceptably outpace regulation. Xenotransplantation: Background The FDA estimates that 10 Americans die every day waiting to receive life-saving organ transplants (1). Such a drastic organ demand has led several European nations, including France, Austria, and Spain, to institute a presumed consent system in which citizens are presumed to be organ donors unless otherwise specified, which has resulted in increased organ availability (2). Some ethicists have even begun to question the necessity of a patient being dead before initiating transplant surgery (3). In addition to organ replacement, xenotransplantation could also lead to treatments for conditions like diabetes, neurodegenerative disorders, and chronic pain control (4). The first nonhuman primates considered as a potential source for human xenotransplants were chimpanzees, due to their similar size, similar genome sequence, and compatible


blood type. However, given that this primate is endangered and has shown an increased risk of disease transmission, a porcine (pig) organ source is currently thought to be preferable over chimpanzees and other potential animal sources (5). Pigs reproduce rapidly and have comparably sized organs, and they show a decreased risk of disease transmission due to their phylogenetic distance from humans and to the many centuries over which pigs and humans have been in close contact (5). However, several significant physiological challenges remain with the utilization of porcine organs and tissues:THE TRIPLE HELIX Fall 2011 1510/12/2011 12:01:42 AM


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BROWN Protein differencesMolecular incompatibility of some proteins make successful xenotransplantation less likely to succeed due to malfunction of regulatory processes (5). Antibody-mediated rejectionHyperacute rejection often occurs due to activation of the inflammatory response, which leads to clotting, endothelial damage, and ultimately graft rejection within minutes (6). Cell-mediated rejectionStudies have shown that human T cells can directly recognize porcine antigens and histocompatibility complex through various path ways, complicating efforts to neutralize the damage caused by natural killer cells and macrophages (6). SizeNot all recipients are potential candidates due to differences in organ sizes. LongevityThe lifespan of a pig is approximately 15 years so the longevity of a porcine xenotransplant is unknown. TemperatureThe average body temperature of pigs is 39C, 2C above the average human body temperature, which could affect the activity of important enzymes if transplanted into humans (5). Genetic Engineering: Background The World Health Organization defines genetically modified organisms as organisms in which the genetic material (DNA) has been altered in a way that does not occur naturally (7). The first step in genetic engineering is isolating the gene of interest, a process that usually involves multiplication using polymerase chain reaction (PCR). Following isolation, the gene can be modified and combined with other sequences (such as a promoter and terminator region) in order to function correctly, which usually entails techniques such as restriction enzyme digests, molecular cloning, and DNA ligations (8). A selectable marker is then used to help transform cells with the new DNA, and various tests can be conducted to determine if the DNA is indeed present in the cells. While the challenges to xenotransplantation are not to be underestimated, genetic engineering has already enabled scientists to overcome some of these challenges. The U.S. Company AquaBounty has already produced genetically modified salmon that grow to their full size in half the normal time, and they recently announced that the FDA was close to granting approval for their consumption, despite the concern that the salmon would quickly outcompete and cause extinction of wild salmon if they were ever set loose in the wild (9). In addition, in August of 2010 an investigation by the Food Standards Agency in Britain revealed that milk from a cloned cow had already been put on sale for public consumption (10). Genetic Engineering and Xenotransplantation: Progress and Applications Overcoming challenges to transplantation at a genetic and molecular level has led to significant improvements in the quest to develop xenotransplants from bench to bedside. For example, the deactivation of a gene (specifically the galtransferase gene) in donor pigs coupled with the addition of key human genes involved in regulating immune response has been shown to potentially reduce the risk of rejection and to allow tissue recipients to receive much lower doses of immunosuppressive drugs (11). Further research suggests that a combination of genetically engineered xenograft tissue with tolerance conditioning of the recipient using genetically engineered bone marrow will further help in overcoming rejection (4). Such improvements in xenotransplant efficacy through genetic engineering are expected to continue to improve the immune characteristics and efficiency, and therefore longevity, of these organs and their human hosts. The efficacy of genetically engineered animal products has already been accepted by scientists and the government, even though few regulatory lines have been drawn. On February 6, 2009, the FDA approved the first human biological product produced by GE animals in the United States (12). The product, ATryn, consists of the human antithrombin that was engineered to be produced in goats milk and is used as an anticoagulant to prevent blood clots in patients with hereditary AT deficiency (12). However, the U.S. government has drawn the ethical line with regard to certain areas of research, which forced some projects to move to China that involved the growth of rabbit embryos that had nuclei from human somatic cells (13). In 2004, one investigator discovered that injecting human stem cells into a pig embryo created a fetus with intermingled cellular and genetic components of both pig and human origin (13). Genetically Engineered Animals and Xenotransplantation: Future Research and Ethical Implications Xenotransplantation, compared to most fields of science, is relatively young (4). It has recently received significant attention due to its potential to alleviate the dire shortage of organs and tissue needed for transplantationnot only does xenotransplantation bypass many of the ethical and logistical challenges involved with making human transplants more readily available, but it could make transplants readily available

Given the controversy genetic engineering has already given rise to, imagine the ethical dilemmas if human-animal chimeras are capable of being brought to term and harvested for their organs.

on a wide scale. However, all of the current treatments used to extend xenograft survival involve significant immune suppression; this could result in novel infections by animal-borne pathogens as well as newly emerged infectious agents (6). As described earlier, researchers have already begun to explore developing embryos comprised of genetic material



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BROWNfrom both humans and animals. While the current state of xenotransplantation research involves tissues and organs that are of distinctly animal origin, history has taught us not to underestimate the rate of scientific progress. The capability of producing organs such as muscles, bones, uteri, and neural tissue in animals that mimic, and perhaps are even identical to, those of humans could come sooner than one might think. Given the controversy genetic engineering has already given rise to, imagine the ethical dilemmas if human-animal chimeras are capable of being brought to term and harvested will bring has not been considered to its full scientific, ethical, and regulatory extent. Clearer distinctions, terminology, and limits must be set with regard to the extent of genetic engineering, the species involved and what constitutes said species, and the types of organs and tissues to be harvested. Cody Vance Simmons, a student studying Biology at Brown, has significant interest in the life sciences as well as the commercialization and processes to bring value-add products and treatments to patients. The promising advances and opportunities relating to genetic engineering as well as xenotransplantation, along with the various ethical concerns that have arisen in both of these fields, made this topic a natural choice.

Does an embryo that was humanderived but whose genome is part chimpanzee deserve human rights once born?for their organs. Does an embryo that was human-derived but whose genome is part chimpanzee deserve human rights once born? And why could one not make a clone of oneself devoid of consciousness, pain, and self-awareness so that any organs needed would be readily accessible? Perhaps more ethically realistic, animals might be genetically engineered to have tissues, and even organs, with completely different functions, functions drastically different than the current human physiology allows. Imagine muscles with altered contractile properties or an engineered organ that requires significantly more energy and could serve as a weight loss mechanism. The future state that progressive mammalian genetic engineering and tissue harvestingReferences1. Vaccines, Blood, & Biologics Xenotransplantation [Online]. 2010 Feb [cited September 24th, 2010]; Available from: URL: http://www.fda.gov/BiologicsBloodVaccines/Xenotransplantation/default.htm 2. Organ donation: An opt-out policy? [Online]. 2010 June [cited September 24th, 2010]; Available from: URL: http://www.usatoday.com/news/health/2010-06-29-organ-donors_N.htm 3. When Does Life Belong to the Living? [Online]. 2010 Sept [cited September 25th, 2010]; Available from: URL: http://www.scientificamerican.com/article.cfm?id=when-does-life-belong 5. Dooldeniya M, Warrens A. Xenotransplantation: where are we today? J R Soc Med 2003. 96: 11-117. 6. Mohiuddin MM. Clinical Xenotransplantation of Organs: Why Arent We There Yet? PLoS Med 2007. 4(3): e75. 7. 20 Questions on Genetically Modified (GM) Foods [Online]. 2010 [cited September 26th, 2010]; Available from: URL: http://www.who.int/foodsafety/publications/biotech/en/20questions_en.pdf 8. Berg P, Mertz J. Personal reflections on the origins and emergence of recombinant DNA technology. Genetics 2010. 184 (1): 917.


9. GM food battle moves to fish as super-salmon nears US approval [Online]. Sept 2010 [cited September 28th, 2010]; Available from: URL: http://www.guardian.co.uk/environment/2010/sep/26/gm-food-battle-salmon 10. Meat from cloned cow offspring in food chain [Online]. Aug 2010 [cited September 28th, 2010]; Available from: URL: http://www.theaustralian.com.au/news/executive-lifestyle/meat-from-clonedcow-offspring-in-food-chain/story-e6frg8jo-1225901519056 11. Xenotransplantation: A Pig Issue [Online]. June 2010 [cited September 29th, 2010]; Available from: URL: http://www.abc.net.au/science/articles/2010/06/23/2933487.htm 12. U.S. Food and Drug Administration. FDA Approves First Human Biologic Produced by GE Animals. FDA Veterinarian Newsletter 2008 Volume XXIII, No VI. 13. Background: Cloned and Genetically Modified Animals [Online]. Apr 2005 [cited September 29th, 2010]; Available from: URL: http://www.geneticsandsociety.org/article.php?id=386 14. M.D. Lemonick, A. Dorfman, What Makes us Different? Time Magazine. Sunday, Oct. 1, 2006. 15. https://intramural.nhlbi.nih.gov/Offices/OCD/CSRP/PublishingImages/ Cardiac%20Xenotransplantation%20surgery.jpg



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Pandamonium: The Politics Behind a GiantHayley Sparks

F

orget the elephant in the room. The conservation movement has another charismatic mammal that makes experts uncomfortable: the panda bear. Lethargic and adorable, giant pandas have long been emblematic of efforts to protect endangered species. However, in recent years, many question why we devote so much to an animal with which we have had so little success. In fact, the causes of the difficulties with panda protection strike at the heart of what is wrong with conservation today and raise a frightening question: when should we let a species go extinct? Panda Past The giant panda (Ailuropoda melanoleuca) once ranged from eastern China to Myanmar and Vietnam. Bamboo, the pandas main source of food, was plentiful, and the bears had virtually no natural predators. However, in the 20th century, pandas became the victim of human expansion and urbanization. Habitat destruction and poaching reduced the population rapidly. But the pandas decline did not go unnoticed. In 1961, the World Wildlife Fund (WWF) chose the panda to symbolize the newly founded organization dedicated to preserving the worlds biodiversity (1). As a result of WWF, pandas benefited from a kind of visibility on the world stage virtually unparalleled by that of any other endangered species. They appeared on shirts, bags, mugs, and WWF literature. In 1972, the Peoples Republic of China even gave two pandas to the United States as a diplomatic gesture after Richard Nixon visited the country. When the two pandas came to the National Zoo, every day hundreds of people, several rows deep, flocked to catch glimpses of Ling-Ling and Hsing-Hsing (2). Even today, visitor numbers skyrocket when a zoo places a panda on exhibit, reflecting their popularity with the public (1). The public adoration of pandas contributed to an approach to endangered species protection called single-species conservation, which still plays a major role in conservation initiatives today. This model argues that monitoring the health of one species with a specific role in the ecosystem indirectly protects that ecosystem as whole. However, scientists disagree on what this exact role should be. Some support species chosen because of large habitat requirements that encompass the habitats of the other animals; this animal is known as an umbrella species because other animals are within that species protected habitat umbrella. Popular examples include

the northern spotted owl and the California gnatcatcher (3). Others espouse the idea that the single species must be a charismatic megafauna (4). This means that the animal generates interest and sympathy from the public, often becoming the target of anthropomorphism. These species are flagship species. The panda is a perfect example. With a small and scattered range, they cannot be thought of as a species with an expansive habitat umbrella. However, people like pandas and will donate money to protect them because, experts believe, their round faces and big eyes remind us of human babies and trigger parenting instincts (5). This, proponents argue, makes them equally valuable to conserving the entire ecosystem. Unsurprisingly, the vast majority of species that receive this flagship designation are large mammals. Examples include the African elephant, lion, Reproduced from [10] and orangutan. Like the giant panda, these animals fall into this category of charismatic megafauna. China has set aside no fewer than 50 reserves, summing to 10,400 km2 (over twice the size of Rhode Island) to specifically protect pandas (1). These reserves, in theory, should protect all of the inhabitants of the panda habitat, although a recent study has suggested that the health of a flagship species does not reflect the health of other species. (6). Indeed, many scientists now believe that there is no sound ecological reason to expect that a species charisma will enable it to function as an umbrella (4). Increasingly, panda conservation and the flagship movement as a whole have been criticized as deleterious to the original goal of conservation: the promotion of biodiversity. Panda Present To understand this harsh criticism of panda conservation, we must first examine the problems that face panda conservation efforts today and why many now see the panda problem as an insurmountable one. Currently, roughly 1,600 panda bears are thought to live in the wild, spread between remote patches of temperate forest in the mountain ranges of southwestern China (6). The giant pandas, like other bears, have evolved with a digestive system designed for meat, not the bamboo that comprises the vast majority of their diet. As a result, the average panda must spend around twelve hours munching on anywhere between 20 to 40 pounds of bamboo every day. To compare, a polar bear, with a similar digestive system and larger body mass, needs only 4.4 pounds of meat a day to survive (7). Even with that huge intake, because bamboo



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BROWNhas a nutritional value compathe planets biodiversity. Singlerable to that of cardboard, the species conservation hopes for a panda must conserve energy trickle-down effect of ecological Increasingly, panda and refrains from unnecessary stability to preserve biodiversity movement. This explains its (1). But the key is that preserving conservation and the characteristic lethargy and the an ecosystem is often at odds with flagship movement description of the panda as an preserving one species. Take, for evolutionary dead end by Chris example, the artificial inseminaas a whole have been Packham, the President of the tion of pandas mentioned earlier. criticized as deleterious London Wildlife Trust and the Although millions of dollars have Bat Conservation Trust (8). Even been spent on developing this to the original goal without human interference, betechnique and implementing it of conservation: the cause of the pandas inflexible in zoos, the only possible bendiet, it remains extremely vuleficiaries are the panda bears. promotion of biodiversity nerable to the natural phenomThis is only one example of how enon of bamboo die-out, during the interests of a flagship species which bamboo unpredictably, as often oppose the needs of the the name suggests, dies. During these periods, pandas can larger ecosystem for which it is supposed to raise awareness. starve by the hundreds (6). Furthermore, in Preliminary Assessment of the Flagship However, even more crucially, there remains the ques- Species Concept at a Small Scale, Caro et al. suggest that tion of reproduction. Simply, pandas do not copulate (or even flagship species are not even a good indicator of the health show an inclination to do so) very often. The only time male of other organisms within their ecosystem. That is, flagship and female pandas interact is the one time per year when the speciesdo not protect disproportionately high numbers female ovulates. Yet scientists have observed that even then, of species or high species abundances at a small ecological these attempts often end in failure, with one member of the scale (9). This suggests that flagship species density does not pair losing interest before the male can inseminate the female reflect the density of other animal populations in the region (6). To counter this, the process of artificial insemination is and that there is little value in giving that species priority in now used in many captive breeding situations and has had conservation funding and initiatives. success. However, although artificial insemination produces This examination of the failings of the flagship singlepanda cubs, they are often ill equipped to survive outside species model, especially as it relates to pandas, brings us of captivity, despite breeders best efforts to minimize hu- back to the original question: when should we let a species man interaction and prepare the cubs for life in the wild. For go extinct? The marketability of an endangered species is not example, Xiangxiang, a panda born at the Wolong National something to ignore. The Chinese River Dolphin pinpoints the Nature Reserve in China, inexplicably died less than a year effect that the popularity of an animal with the public can have. after his release into the wild even after years of preparation Slimy and fleshy pink, the dolphin could never be considered (6). In light of the difficulties mentioned above, it is easy to a charismatic megafauna. Unlike the panda, who lives in the understand why conservationists feel at a loss. Resources are same habitat, the dolphin quietly disappeared and went extinct finite, and panda conservation is hugely expensive. However, over the last decade. The flagship species model, despite all this is not a reflection on panda conservation efforts so much of its failings, at least generates public awareness, preventing as on the efficacy as the flagship model as a whole. an animal from going extinct without public knowledge or interest. Clamoring over the failings of a model for which we Panda Future have no better option might merely create pandamonium. Ninety-nine percent of species that have lived on the earth have gone extinct. The trend has certainly accelerated in recent Hayley Sparks 14 is a biology concentrator from Washington, D.C. years, almost definitely as a result of human expansion (1). She has worked at the Smithsonian National Zoo for the past five For this reason, we must support conservation efforts to save years, and especially enjoys working at the panda enclosures.References1.World Wildlife Fund. Species fact sheet: Giant Pandas. WWF Worldwide; [updated 2011]Available From: http://www.worldwildlife.org/species/finder/giantpanda/ panda.html 2. Byron J. Pat Nixon and Panda Diplomacy. The New Nixon Blog [Internet]. The New Nixon. 2011 Feb - [cited 2011 May 1]. Available from:http://blog. nixonfoundation.org/2011/02/pat-nixon-and-panda-diplomacy/ 3. Blair, R.,Fleishman, E., Murphy, D. Selecting Effective Umbrella Species. Conservation Magazine. 2001. 2(2) Blair, R.,Fleishman, E., Murphy, D. Selecting Effective Umbrella Species. Conservation Magazine. 2001. 2(2) 4. Simberloff, D. Flagships, umbrellas, and keystones: is single-species management passe in the landscape era?. Biological Conservation. 1998; 83 (3): 247-257. 5. Verhovek, SH. So why are pandas so cute? The Washington Post.[Internet]. Published: May 11,1987 (cited 2011 May 1). Available from: http://www.nytimes. com/1987/05/11/nyregion/so-why-are-pandas-so-cute.html 6 .Du, B., Ran, J., Yue, B. Conservation of the endangered giant panda ailuropoda melanoleuca in China: successes and challenges . Fauna & Flora International. 2009. 43(2):176-178. 6. Caro, T., Engilis, A. , Fitzherbert, E., Gardner, T. Preliminary assessment of the flagship species concept at a small scale. Animal Conservation. 2004: 63-70. 7. SeaWorld Adventure Parks. Polar Bears:Diet &

The Science in Society Review - Brown University [Fall 2011]

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