GeneWatch THE MAGAZINE OF THE COUNCIL FOR RESPONSIBLE GENETICS | ADVANCING THE PUBLIC INTEREST IN BIOTECHNOLOGY SINCE 1983
A look at the future of genetics and genomics, with an all-star cast: Cutting-edge researchers George Church James P. Evans Steven Salzberg Industry leaders Anne Wojcicki, 23andMe Joe Hammang, Pfizer Paul Billings, LifeTechnologies Policymakers Rep. Louise Slaughter Eric Green, NIH ISSN 0740-9737
Top bioethicists Arthur Caplan Henry T. Greely George Annas Science and policy experts Patricia Williams Dorothy Roberts Sheldon Krimsky Robert DeSalle Stuart Newman Emily Senay
Volume 25 Number 1-2 | January-February 2012
5 In Memoriam: Charlie Weiner By Sheldon Krimsky 6 We Are the 99% About 1% of us carry highly penetrant genetic mutations which we would greatly benefit from knowing about. For the rest of us, our whole genome sequence may not be particularly useful anytime soon. By Dr. James P. Evans 8 Interview: Eric Green Dr. Eric Green, Director of the National Human Genome Research Institute, spoke with GeneWatch about the future of genomic research. 10 At the Minnesota State Fair (in 2032) In 20 years, people head to the state fair to check out the cloned animals … and to sign up for the healthcare lottery. By George Annas 11 The Future of Consumer Genomics: Sharing is Caring An interview with Anne Wojcicki, co-founder and CEO of 23andMe 13 Unrequited Love: Reflections on Genomics, as Written in 2032 It’s the year 2032, and the only thing more surprising about what has happened in genomics in the last 20 years is what hasn’t happened. By Arthur L. Caplan 14 The $10 Genome Dr. Paul Billings of Life Technologies spoke with GeneWatch about the future of genomic medicine. 16 Deflated Expectations According to Gartner’s Hype Cycle Graph, genetic technologies currently fall into the “Trough of Disillusionment”—but on the bright side, next up is the “Slope of Enlightenment.” By Dr. Emily Senay 18 The Future of Genetic Nondiscrimination Legislation An interview with Congresswoman Louise Slaughter 19 Designer Eggs and Stem Cell Sausage Think genetics in 20 years is a brave new world? Look another 40 years down the road. By Henry T. Greely 20 Safe Bets: Priorities for Genetic Research Pfizer’s Joe Hammang spoke with GeneWatch about the future of medical genetic research.
22 Breaking the Bonds of Race and Genomics Genomic science is reinforcing misguided beliefs in intrinsic racial difference. Will genomics still be tethered to race twenty years from now? By Dorothy Roberts 23 Expect Changes: Genetics in 20 Years Whatever is coming in the field of genetics, we can be sure of one thing: it’s coming fast. By George Church 24 Some Assembly Required Computational biologist Steven Salzberg spoke with GeneWatch about the future of genome sequencing. 26 Toxicology in the Genome Scientists have found gene expression patterns that help to explain differences in how people react to drugs; why not do the same for industrial toxins? By Sheldon Krimsky 28 The Genomic Imaginary As the science of genomics reaches new heights over the next twenty years, it also presents new questions about inequality and privacy. By Patricia J. Williams 29 The Tree of Life Advances in genomics will lead to spectacular new ways to catalogue and analyze the millions of organisms living—and no longer living—on Earth. By Rob DeSalle 31 Meiogenics: Synthetic Biology Meets Transhumanism Some enthusiasts of synthetic biology envision technologies that would “improve” humans—and, perhaps, create useful “subhumans.” By Stuart A. Newman ** 33 Action Item: Labeling Genetically Engineered Foods in California By Pamm Larry 34 Developmental Science and the Role of Genes in Development A paper inspecting the fallacies of genetic reductionism. By Richard M. Lerner 37 Endnotes
Image: Árbol de la vida según Haeckel, E. H. P. A. (1866)
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GeneWatch January-February 2012 Volume 25 Number 1-2
Editor and Designer: Samuel W. Anderson Editorial Committee: Jeremy Gruber, Sheldon Krimsky, Ruth Hubbard GeneWatch is published by the Council for Responsible Genetics (CRG), a national, nonprofit, taxexempt organization. Founded in 1983, CRG’s mission is to foster public debate on the social, ethical, and environmental implications of new genetic technologies. The views expressed herein do not necessarily represent the views of the staff or the CRG Board of Directors. Address 5 Upland Road, Suite 3 Cambridge, MA 02140 Phone 617.868.0870 Fax 617.491.5344 www.councilforresponsiblegenetics.org
board of directors
Sheldon Krimsky, PhD, Board Chair Tufts University Peter Shorett, MPP Treasurer The Chartis Group Evan Balaban, PhD McGill University Paul Billings, MD, PhD Life Technologies Corporation Sujatha Byravan, Phd Centre for Development Finance, India Robert DeSalle, Phd American Museum of Natural History Robert Green, MD, MPH Harvard University Jeremy Gruber, JD Council for Responsible Genetics Rayna Rapp, PhD New York University Patricia Williams, JD Columbia University staff
Jeremy Gruber, President and Executive Director Sheila Sinclair, Manager of Operations Samuel Anderson, Editor of GeneWatch Andrew Thibedeau, Senior Fellow Magdalina Gugucheva, Fellow Editorial & Creative Consultant Grace Twesigye Unless otherwise noted, all material in this publication is protected by copyright by the Council for Responsible Genetics. All rights reserved. GeneWatch 25,1 0740-973
Samuel W. Anderson
Trying to predict where genetics and genomics will be in 20 years is a bit like filling out your “March Madness” bracket five years in advance. Nevertheless, we managed to convince seventeen experts to take a stab at it, perhaps sold partly on my promise to preface this issue with the acknowledgement that the assignment itself is unattainable, unreasonable, and perhaps even a touch absurd. All true. In fact, I’ll admit that when we first floated the idea, we were thinking “Genetics in 100 years,” with the possibility of being talked down to 50 years. Believe it or not, nobody wanted to take that on (well, almost nobody—thanks for being a sport, Hank Greely!). In retrospect, it’s easy to see why. Attempting to predict anything 50 or 100 years down the road is serious guesswork when you think about what has changed in the last 50 or 100 years; but forecasting a field as fast-moving as genetics that far into the future is truly outlandish. As some of the contributors on the following pages are quick to point out, 20 years is no easy task either. (“I feel like it would be sci-fi even if we were talking three to five years,” remarks Anne Wojcicki, founder and CEO of consumer genomics company 23andMe.) It has been only 12 years since Francis Collins announced the first rough draft of the human genome and nine years since the completion of the first “essentially complete” human genome. Since then, changes have come rapidly in genetic and genomic research and technologies. What can we expect in 2032? If you don’t find this question sufficiently daunting, imagine asking someone in 1992 about the future of personal computing. How many people would you have to ask before one of them would predict that nearly half of all Americans would own a personal computer (with a far faster processor and larger hard drive than anything in their time), telephone, camera, and music player all in one device about the size of a pack of gum? Don’t ask me what genetics and genomics’ smartphone equivalent will be in 20 years—we have experts for that. In fact, this is almost certainly our most illustrious cast of GeneWatch contributors yet: from Eric Green, Director of the National Human Genome Research Institute, to Congresswoman Louise Slaughter; from every major newspaper’s go-to bioethicists in Arthur Caplan, Hank Greely and George Annas, to esteemed researchers George Church, James P. Evans and Steven Salzberg; and representatives of the private sector, including Anne Wojcicki of 23andMe, Joe Hammang of Pfizer and Paul Billings of LifeTechnologies. This issue’s impressive cast came up with predictions falling all over the map. Quite a few of these responses raise truly novel possibilities, some particularly valiant in their boldness, and several capitalized on the invitation to take creative license. This issue is as appropriate a time as any to set aside conventions; whatever the method of forecasting the future of genetics and genomics, there is bound to be some madness in it. nnn
Write to (or for) GeneWatch GeneWatch welcomes article submissions, comments and letters to the editor. Please email email@example.com if you would like to submit a letter or with any other comments or queries, including proposals for article submissions. January-February 2012
In Memoriam: Charlie Weiner Charles Weiner, or Charlie, as he was fondly called, died peacefully, albeit unexpectedly for his legion of friends, of congestive heart failure on January 28, 2012 while he and his wife were at their winter retreat in West Cork, Ireland. Charlie made path breaking contributions to the oral history of science. He also was a strong advocate and facilitator in promoting citizen participation in policy and ethical decisions involving science. After receiving his Ph.D. from Case Institute of Technology in the History of Science and Technology, he became director of the Center for the History of Physics at the American Institute of Physics and served from 1965 to 1974. He produced a series of oral and transcribed interviews of physicists who played a key role in advancing nuclear physics and in the creation of the first atomic bomb. Among the many physicists he personally interviewed were Hans Bethe, George Gamow, Sten von Friesen, Wolfgang Panofsky, Philip Morrison, Sir James Chadwick and Stanley Livingston. These interviews are now available on line at the Niels Bohr Library & Archives of the American Institute of Physics. Charlie joined MIT in 1974 and served as director of the MIT Oral History Program from 1975 to 1986. At MIT Charlie embraced the newly developed analog videocassette technology (VHS) for capturing important events in the history of science. He applied the new technology to videotape Cambridge City Council hearings during the 1976 recombinant DNA controversy, which brought scientists and citizens into an unprecedented dialogue over the new laboratories developed for gene splicing research. Today, the black and white videos are classics in the history of science and have become part of the permanent collection of the Smithsonian Institution. He also generated scores of interviews of scientists and citizen non-scientists who were involved in the public debates over genetic research. He left a rich legacy of archival materials that have been used by countless scholars throughout the world. I was one of the first researchers to analyze the material and the background documents—spending two years at the MIT archives, until I completed Genetic Alchemy: The Social History of the Recombinant DNA Controversy. Charlie’s interest in science was in its human dimensions, both its social and ethical impacts and its affect on the life of individual scientists. Both Charlie and I were invited to the 25th anniversary of Asilomar (1975) in 2000 (an unprecedented meeting where leading scientists discussed the safety issues of new research before it was begun) at the Asilomar Conference Center in California. Charlie wrote a historical summary of what we should have learned from the early debates in recombinant DNA. It is hard to improve upon his eloquence. “Despite the success in improving the safety of research, the quasi self-regulation model developed in the recombinant DNA controversy is not adequate for expressing and enforcing societal and moral limits for potential genetic engineering applications such as human cloning or human Volume 25 Number 1-2
germ-line interventions. These potential applications are not inevitable, and they raise profound issues beyond laboratory and environmental safety and patients’ rights. They occur in a context of increasing genetic determinism, pervasive commercialization, and aggressive efforts to sell genetic intervention as a cure-all for medical and even social problems. Separation of the technical issues from the ethical issues, and the narrowing of ethical concerns to clinical biomedical ethics, limit meaningful public involvement and obscure the larger picture.” Charlie’s interest in science was in its social and ethical impact, not simply its pure form. He studied the schism among physicists over nuclear energy, the atomic bomb and the dangers of radiation. He never left that history but watched it evolve. He was an active member of Pugwash, an organization formed by Bertrand Russell after the signing of the Russell-Einstein Manifesto, dedicated to the elimination of nuclear weapons. The ethical questions about the atomic bomb, nuclear proliferation, and the dangers of atomic radiation provided the backdrop for his work on applied genetics. He wrote about the commercialization of science and the patenting of genes. He followed citizen movements, listened to their voices and brought their voices into the classroom. His writings on history of science were filled with passion, heart, and sensibility for those who struggle to see science and technology serve the common interests of humanity. While he held an appointment at one of the world’s most elite institution of higher learning, Charlie never allowed his moral compass to depart from the values he gained in his youth while an autoworker. He embraced the idea of “citizen science,” which became emblematic of his career as he explored the relationships between science and the public. At a plenary talk at the Tarrytown citizens’ biotechnology meeting in July 2011, Charlie recited, in a “WoodyGuthrie” style his original “Tarrytown Talking Blues.” I offer one of the 4 verses. “Suppose you’re starting college, tuition’s due, And they want a sample of your DNA too. They’ll study it, and find out what’s wrong with you. So first give them a swab of your DNA, Cause they know how to make it pay. They’ll swipe it, clone it, patent it, and own it.” Sheldon Krimsky Board Chair, Council for Responsible Genetics GeneWatch 5
We Are the Ninety-Nine Percent About 1% of us carry highly penetrant genetic mutations which we would greatly benefit from knowing about. For the rest of us, our whole genome sequence may not be particularly useful anytime soon. By James P. Evans
DNA sequencing is cheap and getting cheaper. A detailed elucidation of the sequence of one’s complete genome will soon be within the reach of all—patient, consumer and genomic thrill-seeker alike. But that doesn’t mean it will be useful (or indeed even mildly thrilling) for most of us anytime soon. The idea that your genome is likely to provide you, personally, with information of profound impact on your health is belied by the simple fact that the vast majority of maladies likely to affect you have many causes, of which genetics is almost always a minority component. Therefore, we will need to understand other factors, such as our environment, with far greater precision than we currently do before our genomic sequence provides meaningful health information to most of us. While your genetic code is (literally) a digital code and can thus be parsed and analyzed with
ease in this digital age, our environment remains messily analog, imprecise and chaotic. Until we can grasp our (ever-changing) environment with the kind of precision we now apply to our (static) genomes, knowledge of our genomic sequence will remain a dim and imprecise source of useful information. And understanding our environment, I suspect, is the work of more than 20 years. Thus for most of us—the 99%—I doubt that our whole genome sequence will be particularly useful or even interesting anytime soon. Rather, the near to mid-term promise of genomics lies in its application as simply another medical tool; useful to some and meaningless to most. But that should not be depressing (unless your business model hinges on selling everyone their whole genome sequence). After all, magnetic resonance imaging is exceedingly useful and indeed
revolutionary—but it doesn’t mean that most of us would benefit from a whole body MRI. The trick is to ignore hyperbolic claims about the universal benefits of genomics and think critically about where it is really likely to be of benefit. While for most of us our genomic sequence will be nothing more than a mild diversion, the situation is different for a small subset of us. For example, about 1/500 individuals in the U.S. carries a highly penetrant mutation in a Lynch Syndrome (LS) gene that confers a greater than 80% chance of colon cancer. Critically, once it is identified, that risk can be radically reduced through preventive measures currently available. While there are not many human genes which, when mutated, lead to a high risk of an eminently preventable disease, there are enough so that about 1% of us carry highly penetrant
mutations in one of them and would greatly benefit from knowing it. My prediction is that in the next 20 years we’ll see whole genome sequencing incorporated into medical care as a routine diagnostic tool which will be useful for those relatively unusual individuals who have a major medical condition explained primarily by an underlying genetic lesion. And perhaps most excitingly, we will finally see a productive fusion of genomics with public health. Ubiquitous, population-level sequencing of the handful of genes that actually matter to human health will identify those relatively rare individuals – the roughly 1% - who have mutations that strongly predispose to an eminently preventable disorder (e.g. various cancers or aneurysms). Thus, over the next 20 years, sequencing which is broadly applied to the asymptomatic population but targeted to focus on the handful of genes that really matter for preventing disease, has the potential to save lives and perhaps money (though we should be skeptical of claims that any new technology will actually reduce health care costs; they rarely do). The public health potential for robust sequencing will also likely be realized in the near-term as it is increasingly
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used to identify the severe recessive diseases for which prospective parents are both carriers. The application of genomics in public health contexts will inevitably create friction. When couples have ready knowledge of their carrier status for hundreds of severe recessive diseases, the most common use of this knowledge will be, as it is now, abortion of the affected fetus. And as more individuals undergo whole genome sequencing for legitimate healthcare purposes or in the rather silly pursuit of “recreational genomics,” some will inevitably find out things that they wish they’d never have discovered (like the fact that they have an exceedingly high risk for a truly awful and untreatable disorder). Such friction, unavoidable with the broad application of any new advance, makes it all the more important that we look with a critical eye upon what genomics really has to offer, apply it with care and don’t over-hype the benefits of this amazing new technology. nnn James P. Evans, MD, PhD, is Bryson Distinguished Professor of Genetics and Medicine at the University of North Carolina School of Medicine.
Genetic Justice: DNA Data Banks, Criminal Investigations, and Civil Liberties National DNA databanks were initially established to catalogue the identities of violent criminals and sex offenders. However, since the mid-1990s, forensic DNA databanks have in some cases expanded to include people merely arrested, regardless of whether they’ve been charged or convicted of a crime. The public is largely unaware of these changes and the advances that biotechnology and forensic DNA science have made possible. Yet many citizens are beginning to realize that the unfettered collection of DNA profiles might compromise our basic freedoms and rights. Two leading authors on medical ethics, science policy, and civil liberties take a hard look at how the United States has balanced the use of DNA technology, particularly the use of DNA databanks in criminal justice, with the privacy rights of its citizenry.
Sheldon Krimsky is a founding member of the CRG Board of Directors, Professor of urban and environmental policy and planning at Tufts University, and author of eight books and over 175 published essays and reviews. Tania Simoncelli is a former member of the CRG Board of Directors and Science Advisor at the American Civil Liberties Union. She currently works for the U.S. Food and Drug Administration.
Interview: Eric Green Dr. Eric Green, Director of the National Human Genome Research Institute, spoke with GeneWatch about the future of genomic research.
Eric Green, PhD, MD, is Director of the National Institutes of Health’s National Human Genome Research Institute. The following is excerpted from an interview. The pace of progress: One thing I’ve heard said repeatedly about genomics in the 22 years I’ve been involved with it is that we tend to overpredict where we’ll get in the short term, say three to five years, and we tend to underpredict where we’ll get in longer intervals, like ten years. I think that phenomenon has been described by someone else in another field, but it really applies to genomics. It seems that over and over again, we are way overly optimistic about what’s going to happen in three to five years, and yet every time we look back at what we’ve done in the last ten years, we’re shocked by how far we’ve come. I think that’s absolutely the case now, especially in terms of data generation and DNA sequencing technologies. There’s no evidence I can see that it’s going to slow down; I don’t think genomics is going to hit the wall. I think it has as much momentum now as it did a decade ago, and I would contend that ten and twenty years from now, we will be even more surprised than we thought we would be. So I guess one of my overarching comments is that I see no reason to think that the pace at which we are developing new technologies, understanding our genome, and figuring out how it’s going to be medically relevant, will slow down. Genome sequencing and analysis: One thing I would predict is that 8 GeneWatch
the technologies for generating data will create a situation where data generation is trivial and analyzing the data becomes the overwhelming challenge. I think genomics is going to become more and more an information science and less a technology science, and I think the great challenges are going to be in how we analyze and interpret data in creative and powerful ways; and every time we need to generate more data, that will be the least expensive part of the equation. Once upon a time, the Human Genome Project was all about data generation; now we already find ourselves in a situation where we have data abundance but an analysis restriction. That disparity between the amount of effort to generate data and the amount of effort to analyze it will only grow with time. I can imagine 20 years from now it might cost $500 or $100 to generate a genome sequence, but to fully interpret it might cost more than the sequencing costs. Discovering how DNA works: The second prediction I have—a very bold prediction—is that 20 years from now, we will still be discovering basic ways that DNA confers function. I do not believe 20 years from now we will have figured out every last way that DNA encodes biological information; I still think there are major surprises out there to be found. I think there are major mechanisms still to be discovered, and with that will be a continued need for strategic interpretation. I think there’s a lot of biological information encoded in DNA that we will still be discovering. I’m even
saying that we’re going to be discovering basic mechanisms in 10 or 20 years. Even if we say that we think we know all the promoters in the genome, I’m sure 20 years from now, we’ll still be discovering new promoters acting in ways that we didn’t know about. I always say that the human genome sequence is like a great novel. We’ll be spending dozens and dozens, maybe hundreds of years interpreting and re-interpreting it, just like a great historic novel. It’s naïve to think that even in 10 years or 20 years we’ll have a complete catalog of every functional sequence and any deep understanding of how it works. A revolution in evolutionary biology: My third prediction under the general research area is that we will see a completely new way of studying evolutionary biology that will be fully computational. I think 20 years from now, probably before then, we will have genome sequences of thousands and thousands of animal species. A 10th grade biology student’s laboratory exercise will not be confined to dissecting frogs or looking at a fossil; they’ll be sitting at a computer and will have tools in front of them to look at genome sequences of tens of thousands of different vertebrates, and their laboratory exercise will be to figure out how DNA changes have led to biological innovation. There will be almost an entirely new field, a subcomponent of evolutionary biology, that will be dominated by computational analyses. Yes, we’ll still be digging up fossils, we’ll still be doing imaging and biometrics, but we will also have in front of January-February 2012
us a database of tens of thousands of genome sequences from all different kinds of critters that walk and swim and fly on this earth. Just imagine the experiment where you can look at a given stretch of a genome and trace the evolutionary history of every little piece through tens of thousands of vertebrate genomes. It’s incredible, but it’s absolutely doable 20 years from now. Genomics in medicine: I believe that certainly 20 years from now, the use of genomic information about individual patients will be standard of care. I think when it comes to cancer, it will be pervasive; I think genomic-based analyses of cancers will become standard of care for many different kinds of cancer probably well before 20 years. For pharmacogenomics, it will be standard of care for dozens, if not hundreds, of different conditions for which we will use genomic information on patients as a guide for selecting and dosing medications. And I’m very confident that we will use genome sequencing as standard of care for diagnosing rare single-gene genetic diseases. Hand in hand with that, I can believe that the routine will be that you’ll have a genetic sequence of every patient. Now, we can start wondering what it will look like, whether that genome sequence is obtained as part of newborn screening shortly after birth … I realize there are still many complicated issues, but I think one can certainly envision that whole-genome sequences might be generated as part of newborn screening. I can’t believe that electronic health records won’t be standard of care in hopefully most places in the world; and I can’t believe that genomic information wouldn’t just flow into those electronic records. But, again, that is another area where there are lots of complexities and questions, and we’re doing research in that area to clarify Volume 25 Number 1-2
things. Where I’m less certain is what the role of genomic information will be for truly understanding the genetic basis of common complex diseases in terms of individual patients. I don’t know whether we’ll get to the point in 20 years where we can look at 100 different loci and say, ‘You are at a 42% greater likelihood of getting coronary artery disease, and this is what you should do.’ I think the jury is still out on what that’s going to look like, and I wouldn’t want to overstate that part. I think that’s going to be a question mark for now. Understanding interactions:
I believe we will gain a much more sophisticated view and understanding of gene-environment interactions. On the genomics side of that equation, the technology surge has really happened in the last decade and will probably continue over the next decade; but I think that we’re getting to the point where it’s going to become trivial to gather data about the genome. I think the surge to anticipate over the next 10 or 20 years will be technologies for doing environmental monitoring. I think that one of the reasons we’re ignorant in understanding the environmental basis of disease is that we just don’t have technologies for doing fine-scale measurements of environmental exposures. I’m not sure my field is going to have anything to do with it—I don’t think it’s genomics, I think it’s environmental science—but I think technologies are coming; and
with that would come much more powerful studies to capture data on the environmental side that’s just as powerful as the data we’re getting on the genomics side. Ethical, legal and social issues: Finally, I firmly believe that the societal issues that we are already starting to grapple with around genomics—the ethical, legal, and social issues—will continue to require significant attention, significant research, and significant debate. I don’t think these ethical issues are going to go away. With technological advances and increasing knowledge will come a continued need to wrestle with very hard questions. I don’t think the questions are going to become simpler; if anything, I think they will become more complex. We shouldn’t fool ourselves into thinking that we’ll eventually figure all this stuff out and the ethical dilemmas will go away. I just don’t think that’s true. It’s not that I’m pessimistic; I think we can deal with them—we just can’t ignore them. nnn
At the Minnesota State Fair (in 2032) In 20 years, people head to the state fair to check out the cloned animals … and to sign up for the healthcare lottery. By George Annas The Olsen family had been coming to the Minnesota State Fair for almost 3 decades, and they had seen some changes. Blue ribbon cows and pigs, for example, were now all clones, virtually identical to the previous year’s winners except for their markings. The lack of variety had reduced the number of contestants (and barns) to a mere handful. The food, including the pronto pups, cotton candy, snow cones, and walleye-on-a-stick was much the same as it had been before 9/11. What now drew most people to the fair was the lottery. That’s why Ollie Olsen continued to bring the family. All of the citizens of the state are eligible, not just those qualified for subsidized health insurance, and all of their names are automatically entered into the lottery. Only in its fifth year, the kinks were still being ironed out, but even Ollie Olsen (known more for his hard work on the farm than his intellect) understood the basic concept. Health care expenditures now made up more than 80% of the federal budget, forcing downsizing to all but a skeleton military made up mostly of robots, and the elimination of all federal agencies not directly involved in healthcare. Ollie’s son, Jon, was a big believer in the lottery as a way to reduce health expenditures on the elderly. He also liked the idea of doing national experiments at the state level. The idea was to try to cap (use of the word “rationing” was prohibited by law, as was the term “death panel”) the total number of Americans who 10 GeneWatch
used the most expensive treatments in medicine. Jon and his twenty-something sibling, Alice, had freely “donated” their DNA for banking at the fair in 2010, and knew exactly what “the most expensive treatments” meant. The great human genome adventure had succeeded far beyond anyone’s wildest dreams. Now when anyone was sick, the first thing federal physicians did was to have the patient’s genomes sequenced (or re-sequenced, if their genome was already in their EHR). Treatment would be entirely determined by the structure of the patient’s DNA; medical care was thus “personalized” (the preferred term to describe genomic medicine). Sequencing itself was dirt cheap, but analysis of the sequence could involve hundreds of physicians and mathematicians. No wonder it was so expensive, and multiple ways had already been tried to reduce costs. Perhaps the most promising was to task the National Security Agency, which already stored the medical records and genome sequences of every American and most of the world’s population, as well as their social networks, finances, and educational backgrounds, to take over all electronic health record storage for the country’s physicians, hospitals, and health plans. But even eliminating information generation and storage duplication could not reduce the average cost of personalized medicine to under $2 million per person per year ($4-5 million for cancer cases that required
multiple tumor sequencing, and the creation of individualized drugs). The lottery was the solution. One lucky person from each state would annually win the prize of a federal certificate good for a lifetime of personalized medicine. The certificate was good for any family member, but could also be sold (the going rate last year was $20 million). Once treatment began, the certificate could not be transferred. If two family members were sick, only one could have their treatment personalized. Waiting for the drawing, Ollie decided to get pronto pups for him and his wife, and elk jerky and Dr. Pepper for the kids. Then he remembered that his cousin had signed up on three waiting lists before he finally got a liver transplant. Shouldn’t he and his family be able to go to as many state fairs around the country as they could manage? There was obviously no constitutional right to medical care, but wasn’t there still a constitutional right to travel? nnn George J. Annas, JD, MPH is Chair of Health Law, Bioethics & Human Rights at Boston University School of Public Health. January-February 2012
The Future of Consumer Genomics: Sharing Is Caring An Interview
Anne Wojcicki is co-founder and CEO of 23andMe, one of the world’s largest personal genomics companies. GeneWatch: Where do you see consumer genomics in 20 years? Anne Wojcicki: Twenty years is an eternity in this business. I feel like it would be sci-fi even if we were talking three to five years, so twenty … I’ve never thought that far ahead in this business. I can barely keep track of the next six months. We started 2012 thinking maybe we would try to do something in sequencing, but it was still kind of expensive; and by the second week of January, it’s cheap! It’s cheap, it’s fast, and it’s here. It’s moving so fast. Twenty years is so exciting. I get chills just thinking about it. For one, the cost of sequencing is going down so much—everything is going to be sequenced, and you’re going to see sequencing being used all the time. What I’m most excited about is that in 20 years, we’ll really understand
Over the next 20 years, I see a spectacular amount of information coming out, so having a service that can keep you updated will be important. Volume 25 Number 1-2
your genome: your health risks, why you are the way you are, the environmental factors, the underlying causes of disease. It’s not just personalized medicine, but personalized health. What does the business model look like in the future for a company like 23andMe? Correct me if I’m wrong, but it seems to me like most people are only going to buy the genetic tests once. In our model, we’ve always pushed the envelope in driving down cost. We don’t look at just getting access to your genome as a high margin business for us, or even any significant margin. We want to enable access. What we’ve realized—and I think what everyone has realized— is that this ongoing interpretation is where we have to spend a pretty large amount of resources. That’s why we’ve really transitioned into a service business rather than just a testing business. It won’t necessarily just be 23andMe where you go and get your genome sequence. You might get it from your physician, you might get it from a clinical trial … you can get it a number of different ways, so getting access to it is no longer going to be the bottleneck. Interpreting it is going to be the challenge. I think that’s where we are as a business: making sure that anyone who wants to get access to their genome can get access, and then providing an ongoing service where we
can continually keep people updated. We keep you up to date on the health side if there are new developments that are potentially relevant to your genome. Over the next 20 years, I see a spectacular amount of information coming out, so having a service that can keep you updated will be important. Are you looking at whole genome sequencing? We launched an exome pilot at the end of last year. We’ve done some whole genome sequencing, but it’s just a matter of price point. It’s getting so cheap, it seems unreasonable for us not to consider it. Can you tell us about 23andMe’s Neanderthal lab? There were some discoveries about Neanderthals and being able to specifically identify the Neanderthal DNA in humans. This is one of the fun things: we created a lab tool GeneWatch 11
so that you can see how much Neanderthal is in your DNA. So I can share that information with a couple hundred people, and I can look to see who has the least Neanderthal and who has the most. It makes my DNA interactive, it makes it fun. People have an image in their minds of a Neanderthal; but the person that I share with who has the most Neanderthal (and who is OK with me using the info)—the person at the very top, in the 99th percentile, is Ivanka Trump! So it’s not always about health: there are a lot of fun things. Our whole human history is so interesting, and it’s in our DNA. It sounds like this is all going in the direction of social networking, but with your genes. It is social networking. One of the things that is really important to us, also, is disease research. What we hope to do eventually is introduce a new model for understanding health and disease. So instead of having research done in the traditional models, you can actually have consumerdriven research. We have a number of different disease communities where people come together and take surveys, and we’re able to do a mass amount of research on this. So it’s social networking with a very specific purpose. In terms of the disease risk aspects, do you see a line between what’s appropriate in a commercial versus clinical setting, and do you see that changing in the future as technologies change? That’s something we’ve really approached with caution. We believe the consumer should have access to information that is fundamentally theirs. If it’s about my health or 12 GeneWatch
about my body, there’s no reason a physician should stand in between that information and me. That said, we recognize that the medical community has their concerns, and I think we’ve tried to be very responsible about how we’re putting out information. For things like the BRCA report [for risk of breast cancer], and the APOE report [for risk of Alzheimer’s Disease]—for the APOE report, we actually have a video with Robert Green talking about what you are likely to learn, what happens if you are or aren’t a carrier, and we’ve had really positive feedback about that from physicians, genetic counselors, and consumers. As people take more control over their health, they want not just the information, but all the context around it. So you might want to talk to a genetic counselor or a physician, but we don’t necessarily believe that you have to. As we know, medicine is more of an art than a science, so being able to get multiple opinions will be really valuable for the whole field of medicine, as well as for the patient.
we’ll continue to pursue. We recognize that there will always be people who will want that option, and they should have that option. And we will always continue to engage with genetic counselors and the medical community to make sure we are doing things responsibly, and to make sure that customers have all the access points if they want them. Do you have any thoughts about things that are unlikely to happen in 20 years? There are a lot of science fiction movies that involve genetics, and I am more skeptical about some of the science fiction scenarios. One, I have faith in humanity, that we’ll put in the appropriate regulations; and two, genetics is a hard problem. I think we’ll be able to make a lot of really fabulous discoveries, but it won’t be enough to solve everything. nnn
Is that something that could be built into 23andMe’s own business? For example, are there any genetic counselors on staff at 23andMe, or might there be in the future? We don’t have any genetic counselors, but we have a partnership. We thought it was important that we’re not the ones who are necessarily giving all the information to consumers, that there should be a divide. We are the ones providing the information, and there is a separate group that is actually giving the genetic counseling. So we have partnered with an external group, and that is available to people for an extra fee. I think that’s something that January-February 2012
Unrequited Love: Reflections on Genomics, as Written in 2032 It’s the year 2032, and the only thing more surprising about what has happened in genomics in the last 20 years is what hasn’t happened. By Arthur L. Caplan Humans love themselves. We really do. We think that the universe revolves around us, or at least we did for many centuries. In biology, the elevation of our species continues to endure. This extravagant, albeit unwarranted, narcissism is reflected in the fact that when it comes to genomics, no species’ genes could, in humanity’s view, possibly be more important, more worthy of analysis, more deserving of testing, more appropriate for engineering and alteration then ours. Ironically, it was the mapping of the human genome in 2000 that should have triggered the end of our biological self-aggrandizement. It took only thirty years, roughly up to the year 2030, from the time that the announcement was made that teams led by Francis Collins and J Craig Venter had jointly produced a very crude map of the human genome to demonstrate that nature had left our love of our own species unrequited. The drive to map genomics and indeed the drive to fund genomics in the USA and other nations was sold to the public, the media and other scientists in the 1990s with the promise that if we could unlock the instructions for building the members of our species, for understanding the very essence of our nature, then all sorts of good things would follow. We would head to the doctor armed with a printout of our DNA to receive personalized care based upon our risk profile for acquiring diseases. Better still, we would lower the cost of health care by using genetic analysis to catch disease early Volume 25 Number 1-2
before it took root, or to prevent it altogether. Efforts by private companies to move personalized risk testing to the Internet quickly followed the publication of the first genome map. A variety of companies in the decade after the Collins/Venter mapping announcement jumped on the ‘spitomics’ bandwagon, encouraging individuals to spit in a cup and send off their DNA to a lab in order to find out whether they were at risk for cancer, diabetes, Alzheimer’s and other conditions; to gain insight into the identity of their forebears; or to find out if their kids were likely to have food allergies or become star athletes. As it turned out, these activities
Genomic risk factor testing played only a minor role in health care by the third decade of the 21st century. met with little public enthusiasm. The lack of standards about the accuracy and sensitivity of genetic tests, the relative difficulty in using risk information, and the absence of serious efforts to ensure competent counseling undermined interest in genetic testing. Simply having information about risk without the prospect of an efficacious intervention that could alter that risk dimmed interest in personal genetic risk assessment. And as doctor and patient slowly
came to understand, despite the fascination of knowing your genes, you could diminish your risk of most diseases by losing weight, exercising more, reducing alcohol intake, getting enough rest, eating a balanced diet, not smoking and not engaging in risky sexual activity—no genetic test required. Genomic risk factor testing played only a minor role in health care by the third decade of the 21st century. By 2030, it was clear that our genome was complex, hard to understand with any real precision, and tricky to manipulate. It was much easier to analyze the genomes of animals, plants and microbes. These proved simpler, less ethically controversial to try to modify, and had as much bearing on our health and welfare as trying to understand and modify our own genomes. By the third decade of the 21st century, genomics had revolutionized agriculture. As the earth warmed and the human population grew, the only way to create sufficient food was to genetically engineer plants and microbes. The creation of drought resistant crops, microbes capable of creating edible proteins with little impact on the environment, and disease resistant strains of fish, vegetables and other plants and animals led to a green revolution in farming and fishing that both fed the world, enriched corporations and helped reduce the damage done to water, soil and the atmosphere by older methods of creating food. Genomics in the form of synthetic biology had also begun to GeneWatch 13
revolutionize medicine. Microbes could be disabled through genetic engineering and plagues such as malaria, HIV, TB, measles and lethal bacterial infections were diminishing through a variety of vector-targeted genetically-based interventions. Drug manufacturing was closely linked to genomics and synthetic biology with many more efficacious and safer drugs and vaccines being manufactured using modified
bacteria and microbes. While it is true that doctors paid attention by 2030 to individual responses to drugs based upon pharmacogenomics studies, the real impact of genetics was being felt outside the realm of human genomes. The self-conceit of earlier decades that human genes because they are in humans ought to occupy the attention of efforts to apply new genetic knowledge had collapsed. Understanding
and changing the genomes of other species proved far more productive in improving health and well-being. nnn Arthur L. Caplan, PhD, is the Emmanuel and Robert Hart Director of the Center for Bioethics and the Sydney D Caplan Professor of Bioethics at the University of Pennsylvania in Philadelphia. He writes a regular column on bioethics for MSNBC.com.
The $10 Genome Dr. Paul Billings spoke with GeneWatch about the future of genomic medicine. Paul Billings, MD, PhD, is Vice Chair of the Board of Directors of the Council for Responsible Genetics and Chief Medical Officer of Life Technologies, Corp. The following is excerpted from an interview and represents Dr. Billings’ own views rather than those of Life Technologies. Genomic medicine: To the extent that one’s genomic DNA is stable—and I believe that the vast proportion of anyone’s DNA at any particular time is in fact stable, and does in fact basically reflect what you inherited at the time of conception—the analysis of that over the next 20 years will become increasingly simple and very inexpensive. And to the extent that this information is a reliable, quantitative, and identifiable component of disease diagnosis, therapeutic selection, et cetera, I believe that information will become an integral part of everybody’s medical record, probably from conception and certainly from birth. 14 GeneWatch
Genomic DNA information has very distinct advantages: it is measurable, I believe it will be highly reliable, and it is for the most part stable. Epigenomics, post-translational variability and environmental influences can be important and do modify the genomic information. And of course disease states like cancer are characterized by finding more genomic mutations than in non-cancerous cell genomes. But the overall impact of the genome should be reliable and accessible. We’ll figure out how to use that over the next 20 years, along with environmental impacts and other kinds of more variable components of our biology, to make more accurate, more reliable diagnoses, and to make more biologically formed choices about treatments and prevention. The fundamental thing that will be different in 20 years is that our medical records will be built more significantly on genetic and genomic information, and will be verifiable in a way that our current medical systems are not. That is not to say that genetics
or genomics is the be-all and end-all of risk—it’s clearly not. Genetic risk is highly environmentally modifiable, and even though the genome is for the most part stable, mutation does occur and modification of the expression of mutation can be significant. The genomes of cancer cells are somatically mutated at an amazing rate, and clearly there are epigenomic effects and modifications that can influence the power of a particular germline-inherited pattern. You still have a certain set of genes at conception, and we can elucidate very accurately and cheaply what those genes are, along with many January-February 2012
other factors that make genome analysis more complex and add a more nuanced and personalized story. Much of that is cultural and environmental, but there’s still a big difference between asking questions about your family medical history and sequencing your genome to find out whether you have this gene or that gene. That will be a major and on the whole useful change. Today there are many kids who are born with syndromes, but we don’t have any idea what’s wrong. We know that there’s something wrong, but we really don’t know what the bases of many birth syndromes are. We’re going to find a lot of these in the genome. Not all of them, and some will be methylation or exposures to mutagens in utero, but we’re going to have a more concrete basis for building up that knowledge than we used to. There are a lot of kids who die in the first year of life from disorders which we’ll identify either in utero or at birth, and we will prevent many of those deaths. The $100 (and $10) genome: I see in the next 20 years the technology driving down the cost of genomic sequencing to being very inexpensive, and it’s dramatically going
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to continue to drop. The $100 genome will be available in 5 years, and the $10 genome in 20. And at $10 per person, almost everybody in the world can get it. That will be the cost of generating the raw sequence; interpreting it and making it useful to the individual will add costs, maybe substantial ones. Highly medicalized analysis will take more time and will be more expensive, but a gross, computerized look at your genome will be available for very little money. As we do more DNA sequencing and we have more ability to correlate people’s sequences or clinical information—as medical records get better and people begin to share more information, and get involved in registries and research projects—the ability to automate analysis goes up. This means that over 5 or 10 or 15 years, the automated analysis—I would call it the “gross analysis” of one’s genome—is going to get much better. You’ll still want to go to an expert, you may want multiple looks, and there will be lots of other things that will help modify the interpretation beyond a single computer algorithm; but the trend will be toward automated analysis, and with that the cost will go down.
The limits of genomics: Now, there are a lot of things that the genome won’t be that important for. I remember when there was talk about the genetics of leprosy. There is an element of genetics to leprosy, as it turns out, but it’s essentially an infectious disease. There may be genetics about what kind of manifestation you have or how severe a case you get, but the bottom line is that you have to have “the bug around” to get leprosy. There are going to be a lot of diseases where the major risk factor will always be, do you live in an environment that harbors the infectious agent? In some conditions, the kind of microbes that reside in your gut, and the proteins they produce, may interact with your body (and there may be some genetics to this) to cause illness or modify severity of conditions like autoimmune disorders. In many cases, your gene combinations might only confer moderate risk for a disease, and it’s the environment around you that matters more. But even if it’s just a small percent of the population that has powerful genetic determinants, to help that small percent is really a major deal. nnn
Deflated Expectations According to Gartner’s Hype Cycle Graph, genetic technologies currently fall into the “Trough of Disillusionment”—but on the bright side, next up is the “Slope of Enlightenment.” By Emily Senay
The ten year anniversary of the completion of the Human Genome Project reminded us that genetic and genomic research has yet to fulfill the promise of cures for devastating diseases such as Alzheimer’s, Parkinson’s and cancer. Those promises were wildly overblown, but nevertheless made it into the zeitgeist, leaving many discouraged. If the past is the best predictor of the future, what does this mean for genetic technology 20 years on? Will the big breakthroughs come? Will genetic technologies emerge that surprise us all? To help in making somewhat accurate predictions about the future I thought it might be wise to consult the Ouija board of new technologies: Gartner’s Hype Cycle Graph. Developed to help investors understand how technology matures, Gartner’s Hype Cycle begins with the emergence of an important new technology that captures popular imagination and promises to change everything. The new technology is then over-hyped by scientists, journalists and investors, creating the first phase: the peak of inflated expectations. When those expectations are not quickly met, disappointment sets in and the new technology is declared a bust—the trough of disillusionment phase. Then while nobody is paying attention anymore, the new technology begins to yield innovative and 16 GeneWatch
available products, most of them unanticipated in the initial hype phase. Everybody is surprised but pretty soon forgets their earlier skepticism and readily adopts the new products. The new thing becomes old hat and the technology enters the phase of the hype cycle know as the slope of enlightenment. So where is genetic technology on the hype cycle graph? Plotting events since the completion of the Human Genome Map, it is clear we
It is during this phase that the few stalwart innovators toil away in obscurity creating early versions of what will eventually be the next big thing. are currently in the trough of disillusionment. Bummer, I know. But if you trust the Hype Cycle Graph, this could actually be good news. If we are in the trough then there is nowhere to go but up. It is during this phase that the few stalwart innovators toil away in obscurity creating early versions of what will eventually
be the next big thing that really will deliver. So before too long we could be experiencing an explosion of innovation in genetics and genomics. But will this explosion include a cure for big problems like cancer? Two great minds think so: Jim Watson, co-discoverer of DNA, and Albert Brooks, comedian and author. Writing in Cancer Discovery in November 2011, Watson prophesies that with hard work scientists will be able to use RNAi to selectively block cancer genes leading to a cure for many cancers within the next 5 to 10 years. Brooks also predicts a cure in his new novel 2030–all cancers, all comers, 100% cured. Unfortunately the resulting dystopia is not so appealing. Old people don’t die, debt balloons, and a generational war breaks out when the “olds” suck all the resources. Personally, I don’t think either scenario is likely. For starters, this isn’t the first time Watson has predicted a cancer cure and Brooks is famous for his overly negative outlook. Secondly, a cure for cancer would be the most obvious thing to predict, and according to the hype cycle it’s usually stuff nobody sees coming that emerges first and takes off. So I expect that curing cancer, Parkinson’s or Alzheimer’s is going to be tougher, more incremental, and slower than we all want. So what will emerge? Going out on a limb, I predict “social genetics” will take off much sooner and in a January-February 2012
bigger way than currently anticipated and will be driven not by scientists but average folks. I base this prediction on nothing more than recent random conversations with two friends: both educated and savvy. For no particular reason each had their genes mapped by one of those new personal genetic companies. They weren’t worried about Parkinson’s or breast cancer. In fact they couldn’t really articulate why they spent a couple hundred bucks and sent their spit to California. Maybe they’re weird or just early adopters. No matter, though they learned nothing of real medical utility they couldn’t have been more thrilled to share with me their risk of restless leg syndrome, excessive earwax, Volume 25 Number 1-2
abdominal aortic aneurysm, etc. It all seemed like TMI, even a little creepy; at best, a novelty. Then it hit me: that’s just what I thought when I first heard about a lot of things like the Internet, email, Google, and Facebook. The genetic genie is out of the bottle! Everybody is going to want their codes cracked— and they then are going to want to share that info with you. Imagine a website called GeneticConnections. com. Upload your code, find longlost relatives, make common variant friends, or find your perfect genetic mate! Nah. Forget it. It’ll never work. I’m sure I’m wrong and Jim Watson is right. I really hope so … even if Albert Brooks is right too! nnn
Emily Senay, MD, MPH, is currently the medical correspondent for PBS Need to Know. She is also an Assistant Professor of Preventive Medicine and a course instructor in the Masters of Public Health Program at Mount Sinai School of Medicine. Prior to joining PBS she was a medical correspondent for CBS News for 15 years.
The Future of Genetic Nondiscrimination Legislation An
Congresswoman Louise Slaughter
U.S. Rep. Louise Slaughter, D-N.Y., first introduced genetic privacy legislation in Congress in 1995 and went on to champion the bill that would become the Genetic Information Nondiscrimination Act (GINA). GeneWatch: After GINA’s passage, do you see continuing problems with the way genetic information is regulated? Do you think new laws will be needed in the near future? Rep. Slaughter: I’m not so sure. I think we did a pretty thorough job [with GINA] on ownership of your genes—of making sure that you own them. The remaining difficulty might be, I think, inhibition of research. The fact that 20% of the genes are under patent to companies—who can charge $2,600 anytime anyone with breast cancer wants to get tested for BRCA1 and BRCA2 genes—it flies in the face of what we were trying to do: to make it much easier to identify cancer as early as we could. We want to identify those people who are more likely to get breast and ovarian cancer, and suddenly we find that they have to go through this company that charges what I think is a fairly exorbitant price. I’m looking forward to the Supreme Court overturning this, because genes should not be patented. That was the biggest surprise to us as we were working to get the bill passed. This company came forward and patented those genes. The 18 GeneWatch
identification of BRCA1 and BRCA2 came about because of the extraordinary generosity of the Ashkenazi Jews who gave their blood so they could be tested. I think it’s an affront to them, and to all women, that a product of that should be patented and not in the public domain. What do you think are the chances that additional genetic privacy legislation could be passed in Congress? You know, it took me thirteen and a half years to get this passed. I imagine that we would be able to pass further legislation, but with this Congress, we don’t know. I hope that the promise of genomics will not be stymied by what we dealt with trying to pass GINA. There were a number of people who had thought we were talking about cloning—but when the time came for the vote, they all voted for it, which was really astonishing after what we’d been through. As you know, the Senate passed our bill unanimously twice, which I think was because Senator Frist was a physician. Over here [in the House of Representatives], we had committee chairs who bottled it up at some group’s request. Do you expect any future expansion of GINA’s protections—for example, to cover life insurance? Life insurance is really not a part of the bill. One thing we can change
is that right now it does not cover military personnel; that’s something we’re working on. How do you envision GINA changing medicine and healthcare in the next 20 years? What we want for this bill is to cut down on hospital stays and unnecessary surgeries. Since we all have different genes, we need individualized medicine, so doctors can find what treatments we will personally respond to. It’s happening, and that’s a remarkable achievement. For the first time in our history, science and politics should go hand in hand. Research is growing by leaps and bounds, and I do believe this science is limitless. It’s going to change a lot of the scourges of mankind. As so often happens in legislation, nobody has heard about the bill … but we’re very pleased that it’s working so well. nnn
Designer Eggs and Stem Cell Sausage Think genetics in 20 years is a brave new world? Look another 40 years down the road. By Henry T. Greely GeneWatch has asked me, and others, to predict the future of genetics 20 years out; but, questioning authority, I am going to disobey and instead predict it 60 years out. This is, of course, madness. The longer the reach, the greater the hubris, both because of the greater chance of truly unexpected “black swan” events—having a 1 in 10,000 event happen in 60 years is three times as likely as having one happen in 20 years—as well as the greater effect of a small deviation at the beginning over three times as many years. On the other hand, the great advantage of a 60-year prediction is that there is no chance I’ll be around to be embarrassed in 60 years, while my survival for 20 more years is (I hope) plausible. So, what will genetics, or more broadly, the biosciences, look like in the year 2072? Let’s leave some of the possibilities to one side—a small remnant of humanity struggles to survive in the aftermath of the nuclear holocaust of 2027 or a non-computerized
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humanity abandons serious science after the Butlerian Jihad, also known as the Fifth Great Awakening. Assume general continuity with today’s world (an assumption that seems unlikely but at least gives us a framework for discussion). In that case, I predict three major consequences of the biosciences revolution, driven by, but extending beyond, genetics. First, human reproduction will be much more selective. Most children, except for the poorest inhabitants of the poorest nations, will be conceived through in vitro fertilization so that preimplantation genetic diagnosis can be used to select the genetic traits of the next generation. The key development here will be making human eggs from induced pluripotent stem cells, freeing IVF from the unpleasant, expensive, and risky process of egg retrieval. Second, human medicine will be greatly improved, largely by our greater ability to intervene in both pathogens and human cells at the molecular level. Infectious diseases
will be nearly conquered either by direct attack on their molecular weaknesses or by improving the ways our immune systems respond to them. Major non-infectious diseases, including cancer and heart disease, will also be greatly reduced by more effective prevention and more effective treatments, for cancer probably through precise targeting of tumor cells. Stem cell transplants, as dissociated cells, as tissues, and as whole solid organs, will play an important role in treating some conditions; so (finally) will gene therapy. People will still die, but rarely of illness; they will often live until their 90s or 100s, at which point their bodies, and perhaps especially their brains, will just wear out. Third, the non-human biological world will have been engineered, the better to serve, and amuse, humanity. Most people will eat lots of nutritious and (fairly) tasty meat derived from stem cells, which will be cheaper, much greener, and more humane. (The rich will still eat dead steers, at a high price and with a frisson of sinfulness akin to what may lead some to smoke cigars.) Crop shortages will disappear as genetically modified crops make their own fertilizers, increase yields, and adjust to the environment of a climate-changed world. The carbon dioxide levels of the atmosphere will begin, slowly, to come down through a combination of genetically engineered, carbon-neutral biofuels and specially engineered “remediation” organisms that suck CO2 and other greenhouse gases out of the air. The passenger pigeon, the dodo, the mammoth, and the GeneWatch 19
saber-toothed cat will roam again in animal parks; a few spots will feature vaguely disappointing “best guesses” at recreated dinosaurs. Does this sound disappointingly positive, even Pollyannaish? It shouldn’t. The technologies can be used in good ways or in ways dystopian enough for the most dedicated bioluddite. Many of us would view control over human reproduction as a good thing if it allowed parents to prevent the births of children with serious genetic diseases, but few of us would be happy with governments forcing parents to have children with, or without, particular genetic traits. No doubt, some people will try to create genetic super-beings, with risks to the rest of society and, even more likely, unforeseen physical or mental problems for the new “super” men
and women. Deeply genetic medicine could end up creating a geriatric overclass, as parents, grandparents, and great grandparents stick around and increasingly monopolize wealth (thanks to early investments) and power (thanks to both high wealth and strong voter participation). In a worst case, medical advances may keep (rich) old bodies alive, at high cost, while not being able to prevent those old brains from deteriorating. For every algal source of green biofuel there is likely to be a novel kudzu, wreaking unforeseen havoc; for every healthy mammoth in a theme park in Alaska there will be some painridden pet unicorn, suffering with an engineered body that just doesn’t work. And governments, terrorists, and bored teenaged hackers will have used biological weapons– and might
use them again. I strongly suspect that the one part of the biosphere that will not change much is the human mind, individual and collective. We will still rise to breathtaking moral heights and sink to appalling depths. We will still make brilliant leaps and behave with stunning ineptitude. When people are concerned, all solutions are just introductions to new problems. My own guess is that we will use these vast new tools of control over biology both wisely and foolishly and that, on balance, we will muddle through. But it will not be dull. nnn Henry T. Greely, JD, is Director of the Center for Law and the Biosciences at Stanford University.
Safe Bets: Priorities for Genetic Research Joe Hammang of Pfizer, Inc. spoke with GeneWatch about the future of medical genetic research. Joe Hammang, PhD, is Senior Director of Worldwide Science Policy at Pfizer, Inc. The following is excerpted from an interview. The unpredictable rate of change: When I read about these technologies and think back on these last couple decades, I’m always struck by one thing: It’s incredibly hard to project the trajectory of new technologies. People will say something’s going to happen tomorrow or next year, and it’s inevitably much slower. Technologies don’t advance as quickly as we want, because we’re human beings, we’re impatient. We want to 20 GeneWatch
see advances, and we want to make medicines to help people, but the trajectory is always very difficult to predict. Something you think is a reality very soon can actually be very far off. A really good example is gene therapy, a technology that in the ‘90s we thought would have rapid uptake, but had a massive setback. Another example is stem cell technology. When human embryonic stem cells were first identified, there were those who thought the technology would be ready within a couple of years. That’s clearly not the case, and what we found is that in order to bring safe and effective products into the marketplace, massive investments are needed both at the governmental
level and at the private level, in the biotechnology and biopharmaceutical areas. I think what happened was that we saw a very strong draw towards developing therapies—that
is, cell replacement therapies—and not enough towards tool development, to use those incredible cell technologies to screen medicines and to learn about the behavior of the cells, to learn about cell cultures and cell processes. That took a bit of a backseat to therapies. Today I believe that is reversed; because technologies have been slow to come, now I believe there is a much greater emphasis on tool development. And the great news is that this tool development—what we learn from it, and the investments that the biopharmaceutical industry makes in tool development and drug screening—will have direct benefits down the road for cell therapies. The same information is required: what makes cells safe and effective, what makes them reproducible from one batch to the next, and what makes them decide to become different cells of the body. I think another important point is that not only do we need massive investments over time at both the government and industry level, but there’s also a lot of luck involved. It’s serendipity sometimes when discoveries are made, and when the right people have that information and are able to synthesize it and understand what these advances really mean. Sometimes the advances we see are very revolutionary and things change quickly overnight, but there’s no replacement for the continued investment in research. Investment priorities: You can look at the National Cancer Institute investment over time, contrasted with an area like the National Institutes of Aging and the National Institutes for Neurological Diseases, which provide the primary amount of Alzheimer’s disease funding in the U.S. If you look at the NCI’s investments from the 1960s to present, the cumulative total is about $90 Volume 25 Number 1-2
billion to date. We now have a much greater understanding of the genetics of the disease. We know that cancer is not one disease, like science thought when President Nixon declared war on cancer. That’s allowed us to hone in on very specific mutations so that we can develop very specific medicines tailored to these mutations, and that will certainly continue over time. What it means, though, is that the investment made by the federal government—it’s critical, but it’s just the start. There’s more and more work that needs to be done to take that basic information and continue to invest hundreds of billions of dollars in making new medicines against those targets, something that the biopharmaceutical industry does very well. In contrast, when you look at the National Institutes of Aging budget— considering that today’s NCI spends about $5 or $6 billion annually— what we spend on Alzheimer’s disease is just over half a billion dollars, so less than a tenth of the NCI spending. That may have a significant role to play in the fact that this very complicated disease is very poorly understood today. We’ve made significant advances, but there’s so much more that needs to be understood there. Imaging technologies are needed, biomarkers are desperately needed, and continued investment is going to be required. My point is that if we hope to crack a huge problem like Alzheimer’s disease, it’s probably going to require much more significant investments at both the government and the biopharmaceutical level. The stakes are so high, and the cost to society with Alzheimer’s disease is going to be so great, especially as the population ages. Personalized medicine for cancer, Alzheimer’s, and pathogens:
of disease in cancer has led to incredible advances. We are now actually treating people with cancer with specific medicines that are tailored to these segments of the population. The more of those medicines that are developed, and the more we understand about how those drugs work— and about why those drugs don’t work in specific patients—I think it’s going to push the field of oncology forward very quickly in comparison to other areas. Alzheimer’s disease appears to be a much more complex problem, so the advances of personalized medicine aren’t going to come as quickly there. We aren’t going to see the revolutionary changes there as quickly. I have faith that it will come, that we will understand the genetics of Alzheimer’s disease, but the point is that we don’t have that understanding today. If we don’t have that, it’s very hard to see these advances coming as quickly. I think that our understanding of genetics allows companies like ours, and the entire biopharmaceutical industry, to get huge advantages in the area of vaccines. Our abilities to create vaccines that are specific to bacterial populations, emerging pathogens which are creating massive public health problems here and throughout the world, are going to be greatly aided by next generation vaccines, vaccines which can be targeted against multiple strains of bacteria. It’s going to revolutionize public health treatment here in the U.S. and abroad. One can see particular advantage abroad, in places where medical structure is nil or nonexistent. These technologies, I think, are going to advance greatly over the next decade or two. This idea of being able to allow an individual to fight infection before it becomes infection is extraordinarily powerful. nnn
Our understanding of the genetics GeneWatch 21
Breaking the Bonds of Race and Genomics Genomic science is reinforcing misguided beliefs in intrinsic racial difference. Will genomics still be tethered to race twenty years from now? By Dorothy Roberts Twenty years ago it appeared that mainstream science finally was abandoning the concept of biological human races. From 18th century typologists to 20th century eugenicists, scientists have always been instrumental in justifying the myth that the human species is naturally divided by race. But the rejection of eugenics after World War II and discoveries by human evolutionary biologists in subsequent decades brought hope that a new science of human genetic diversity would replace the old racial science. In 2000, the Human Genome Project, which mapped the entire human genetic code, confirmed the genetic unity of the human species and the futility of identifying discrete racial groups in the remaining genetic difference. Biologically, there is only one human race. Race applied to human beings is a social grouping; it is a system originally devised in the 1700s to support slavery and colonialism that classifies people into a social hierarchy based on invented biological, cultural, and legal demarcations. But instead of hammering the last nail in the coffin of an obsolete system, the science that emerged from sequencing the human genome has been shaped by a resurgence of interest in race-based genetic variation. Some scientists claim that clusters of genetic similarity detected with novel genomic theories and computer technologies correspond to antiquated racial classifications and prove that human racial differences are real and significant. Others are searching for genetic differences between races that could explain staggering inequalities in health and disease as 22 GeneWatch
well as variations in drug response, with the biotechnology and pharmaceutical industries poised to convert the new racial science into racespecific products. As we wait for the promise of gene-tailored medicine to materialize, race has become an avenue for turning the vision of tomorrow’s personalized medicines into today’s profit making commodities. While uncritically importing antiquated racial categories into research, the emerging racial science has a new twist—it claims to measure biological distinctions across races and “admixed” populations with more accurate precision, and without social bias. At the same time, many Americans believe that the election of Barack Obama as president ushered in a new “post racial” society of equality, harmony, and opportunity. Genomic science is reinforcing the belief in intrinsic racial difference even as most Americans ignore the devastating effects of racism on our society and the seemingly colorblind regime of unequal wealth, health, education, and imprisonment. Race does have medical significance—because social inequality affects people’s health, not because race is hardwired in our genes. Will genomics still be tethered to race twenty years from now? Despite the disturbing revival of biological concepts of race, there is also renewed hope that this is a last gasp of racial thinking in science. Many evolutionary biologists, genomic scientists, anthropologists and sociologists, historians of science, and legal scholars are pointing out the errors and biases in recent claims
of race-based genetic difference. A competing field of health research is revealing compelling evidence of the biological pathways through which racial inequality gets “embodied,” including the unhealthy effects of everyday racial discrimination. But it will take a political movement to undo the centuries-old myth of biological races. Antiracist, disability, economic, gender, reproductive, and environmental justice groups are realizing that they all have a stake in contesting the emerging racial science based in genetics. This social movement rejects the view that human beings are naturally divided into races at the molecular level and refuses to look to genomic science and technology to bridge the enduring chasm between racial groups. Rather, we should affirm our shared humanity by working to end the social inequities preserved by the political system of race. Instead of hamstringing scientists, discarding the folklore of biological races would liberate them to focus on more fruitful lines of research—to study how genes function in human beings and to locate, understand, and eliminate the effects of racism on health. nnn Dorothy E. Roberts, JD, is Kirkland & Ellis Professor of Law at Northwestern University School of Law.
Expect Changes: Genetics in 20 Years Whatever is coming in the field of genetics, we can be sure of one thing: it’s coming fast. By George Church Pace: Advances in genetic research and technologies will continue at not only a faster pace than twenty years ago, but exponentially so. The costs of reading and writing genomes decreased by 1.5-fold per year in the 1980s and 10-fold per year in the past 6 years, with no evidence of limits to this exponential shift over the next few years. When we see such accelerations, we have to be especially cautious that our humanity keeps pace with our technology. Safety and security: As genome engineering becomes a mature engineering field, it begins to follow the path of (and possibly outdo) other engineering disciplines in developing safety and security features. Only as transportation technology matured did we see seat belts, airbags, licenses and radar speedmonitors. The analogs for genetic engineering are organisms which can’t exchange functional genetic material with the environment, plus licensing and computer surveillance of all synthetic genomics components—from chemicals and machines to genes and genomes. Gene therapy is transitioning from the train wreck of random
Volume 25 Number 1-2
viral delivery (with immune and cancer consequences) to precise homologous recombination. For example, Phase 1 clinical trials on Zn finger knockouts of both copies of the HIV receptor gene (CCR5) in one’s own blood cells presents a much-needed AIDS cure, with encouraging outcomes so far. Even more profound is the idea that a very tiny proportion of the population has this protective genetic state naturally. Diversity: The ability to change our adult genomes safely takes pressure off the manipulation of the germline and encourages us to embrace and manage our diversity, rather than overly medicalize, suppress or eliminate diversity. Tiny effect sizes and “missing heritability” doesn’t limit us if we continue to find—or invent—rare, highly protective alleles, not just for viral resistance (above), but for less breakable bones (e.g. rare LRP5 alleles), for radically lower LDL-cholesterol (via rare PCSK9 alleles), for slow aging, and especially for neural diversity (ADHD, dyslexia, OCD, bipolar, narcolepsy). The push of big pharma and genome-wide association studies to lump us together into giant cohorts is giving way to the prospect that each of us is an N=1 cohort. Hence serious efforts arise to develop costeffective tools that enable us to handle N=1. We increasingly embrace the interrelations among genomes, environments, traits and cohorts. This emphatically includes education as part of our environment and cohort, and epigenomes bridging all of these. The super-exponential cost
drop of genetic technologies not only impacts our ability to measure (and alter) our human genomes, but also our environment -- microbes, allergens, foods, immune function, therapies, and transplants. Sharing: Research subjects and consumers increasingly demand access to their data. How and why would we paternalistically protect them from such data? Will we only allow the wealthy to access their own data, or will we swiftly implement education (e.g. PGEd.org)? Once we can freely access such data, will our personal genomes be like our faces and voices, which we expose? Faces and voices reveal large parts of our culture, ancestry, health, age, emotions, and education. These are often the basis of life-altering decisions by others about us. Nevertheless, we tend to share them. For research, several groups have noted the disingenuous nature of implying anonymity to research subjects (even in “controlledaccess” or “authorized-access” databases). Such closed-access and proprietary datasets also restrict collaborations, international grassroots participation and out-of-the-box explorations. Arguments that people will not volunteer without misleading assurances are becoming far less convincing as we watch the volunteer lists for fully open-access human research projects rapidly grow. nnn George Church, PhD, is Professor of Genetics at Harvard Medical School, Director of the Center for Computational Genetics, and founder of the Personal Genome Project. GeneWatch 23
Some Assembly Required Computational biologist Steven Salzberg spoke with GeneWatch about the future of genome sequencing.
Steven Salzberg, PhD, is a Professor of Medicine in the McKusick-Nathans Institute of Genetic Medicine at Johns Hopkins University. Genome sequencing in 20 years: Certainly things are very different than they were 20 years ago. Most of the changes have been incremental, but adding things up, it’s been quite dramatic. Extrapolating forward, I don’t know if there will be any revolutionary changes; but even with steady progress, 20 years is a long time, and things will look very different from the way they look now. One thing that we need to solve, and something I’ve worked on, is the assembly of genomes. I’d like to think that in less than 20 years we’ll have either solved it, or there will be such dramatic progress that it won’t be a problem anymore. We have sequenced thousands of species. Almost all of them, with the exception of some bacteria, are draft genomes. That means there are gaps in the sequence, and there are parts of the sequence that aren’t really positioned correctly, they’re not lined up along chromosomes; so we can stitch them together, but we don’t know what the chromosome structure is. That’s true of nearly every genome out there, and in fact there are still gaps in the human genome. The advent of next-generation sequencing has dramatically sped 24 GeneWatch
up the rate at which we’re tackling new species, but they remain draft genomes; in fact, the quality of draft genomes has probably gone down a little bit with next generation sequencing. How we sequence the genome today (and tomorrow): We break it into a very large number of pieces, and we sequence those pieces in very short reads of 100 base pairs or so. Then we use a program, like the programs my group develops, to put it all together. That process has various laboratory steps and very complicated computational steps that are imperfect, so you don’t get the whole genome reconstructed at the end. A better way to do it would be to just grab a chromosome and read it from one end to the other. You wouldn’t have to assemble it; you’d just have the chromosome sequence at the end. And there are people who are working on ways to read longer and longer stretches of DNA—without any big breakthroughs lately, but somehow we’ve got to get there, and hopefully within the next 20 years we will. If we come up with better technology to help us sequence the genome, hopefully we’ll be able to sequence more genomes even faster—and they’ll be complete instead of drafts.
genome are the genes, so we’re constantly discovering new functional parts of genomes that are either genes or regulatory sequences that control genes; but it’s very piecemeal. In a way, that makes it more exciting, because you never know what you’re going to find—even looking at well studied genomes you can find lots of new things—but I’m hoping we’ll develop new and better methods for figuring out which parts of the genome are important to the organism. For humans, I would like to be able to see a full catalog of all the genes. We don’t have a catalog of all the human genes yet. In fact, we don’t even know the precise number of human genes. So sometime, maybe in the next 20 years, we’ll actually be able to say that we have the complete list of human genes—that is, all the protein coding genes and all the RNA genes.
Discovering new genes: We use a lot of indirect methods to try to figure out which parts of the January-February 2012
When the Europeans first landed on the shores of North America, you can extrapolate: well, eventually, they’ll explore the whole thing. I would say that at the rate we’re going, in 20 years there’s a good chance we will have a catalog of all of the human genes. It’s not certain, because it’s very hard to pin them down, but there’s a good chance.
very quickly. And I don’t know how you do that—nobody knows.
I would say that at the rate we’re going, in 20 years there’s a good chance we will have a catalog of all of the human genes.
Whether we’ll be able to sequence a new genome with a technology that lets us assemble it with no gaps—that will require some breakthroughs. Incremental steps will not get us there. There are different ways it could happen, some probably that I can’t envision. If you can come up with a sequencing technology that lets you read chromosomes in extremely long fragments—say a million base pairs at a time—that would be a breakthrough. Right now the best you can do is read one or two thousand base pairs at a time. If you had a thousandfold increase in that capability, that would let you sequence and assemble a complete genome Volume 25 Number 1-2
Personalized medicine: I think that individualized genome sequencing and individualized medicine is going to happen, and I think it will happen in less than 20 years. I think we will all be getting our DNA sequenced, to
years is maybe a little short, but I think it’s inevitable that everyone will have his or her entire genome on their computer at home, and their physician will have it, and they will regularly turn to it to look things up. When you go to a new doctor, you should be able to walk in with your genome on a thumb drive. Your risk for future diseases and your responsiveness to various treatments is very much affected by your genome, and we’re in a large scale enterprise right now to collect all of that information and figure it out: how your genome predicts whether you’ll respond well to a drug, how it predicts your risk of a disease … this is all useful information for someone who is trying to take some action about their own health. So I think it will translate into the clinic pretty quickly. nnn
some extent. Whether it will be our whole genome or just parts of our genomes, we will have our own genomes sequenced, and we will see that information used by our own health care providers. I think it’s actually inevitable—20 GeneWatch 25
Toxicology in the Genome Scientists have found gene expression patterns that help to explain differences in how people react to drugs; why not do the same for industrial toxins? By Sheldon Krimsky “Have you ever passed a nail salon gasping from the chemicals seeping through the open door, while a dozen women patrons and their handlers are breathing in those same chemicals without a trace of discomfort?” There was a time shortly before the human genome was sequenced that many believed genetic science was on the cusp of a medical revolution. Our sequenced DNA was thought to hold the key to understanding the onset of disease. Why are some children afflicted with autism? Why do some adults stop producing enough insulin? Why do some otherwise healthy individuals who reach their senior years lose mental functions and memory? Ten years after the human genome was sequenced, biomedical scientists have become more cautious in their optimism about how DNA sequencing will change medicine by revealing the existence of a disease years before its onset or by introducing new therapies with the tools of molecular medicine and stem cells. The terms “gene-environment interaction” and “epigenetics” are now recognized as the clue to many disease conditions. The switches that turn genes on and off may be more important in understanding clinical pathology than mutations in coding sequences of DNA. These switches, which may stop or modify gene expression, are in the form of protein complexes that overlay the DNA code, such as histones or methyl groups, or the RNA interference molecules that reside in the genome. 26 GeneWatch
On the website of the National Institute of General Medical Sciences we find the following statement: “A good part of who we are is ‘written in our genes,’ inherited from Mom and Dad. Many traits, like red or brown hair, body shape and even some personality quirks, are passed on from parent to offspring. But genes are not the whole story. Where we live, how much we exercise, what we eat: These and many other environmental factors can all affect how our genes get expressed.” Despite the growing awareness that environmental factors interact with and affect the human genome, most of the research remains focused on the mechanisms operating at the molecular level. Thus, there is much discussion about sequencing the epigenome to gain an understanding of the genetic switches or to probe deeply into non-coding DNA for discovery of RNA sequences that interfere or modulate gene expression. Meanwhile, we know that around 100,000 people die from adverse drug reactions. Some people are highly sensitive to chemicals in perfumes or outgassing from carpets or plastic. The detoxification mechanisms of people vary widely. Without a sufficient quantity of enzyme production, our bodies cannot break down certain chemicals fast enough before experiencing harm. If we expect to make any major inroads into preventing the many environmentally-induced diseases, each of which may affect a small percentage of the population, then
we must use the human genome and the epigenome to acquire an understanding of why some people are more adversely affected by environmental agents. What we need is a massive effort to unravel the “geneenvironment” interaction in disease causation. We have over 100,000 chemicals in current industrial use. Many of these chemicals were introduced into commerce without much toxicological evaluation. It takes between 25-50 years to regulate or ban a chemical that has been shown to be harmful to humans. The United States has only banned about a half dozen chemicals over half a century. In part this is because the regulatory system is geared toward industrial interests. The government requires very minimal safety studies to permit a chemical into industrial use, but demands an extraordinary body of replicable scientific studies and costbenefit analyses before a chemical is removed from the marketplace. The one area where there have been major contributions in deciphering the gene-environment interaction is in the study of the genetic effects of ionizing radiation. Perhaps radiation effects on health is the low hanging fruit because of the mutations the radiation produces, although low level radiation effects remains highly controversial. How can we learn what chemicals are adversely affecting the healthy human genome and what chemicals have differential effects on different genomes? How can we detect the detoxification potential of each individual toward a chemical? The January-February 2012
differences in people’s ability to detoxify a chemical may be the result of shorter genes coding for the relevant detoxifying enzymes, or the enzyme-producing gene is switched off. Most of the commercial interest in the sequenced human genome has been focused on risk factors for certain diseases that are read from the individual’s DNA. There is nothing in direct-to-consumer testing kits that reveals the cause of any disease other than what is encrypted in the code itself. And there are only a small number of illnesses where there is a one-to-one correlation between having a particular form of a gene and a disease, such as cystic fibrosis, sickle cell anemia and Canavan’s disease. Of course, a massive effort to determine how chemicals interact
with the human genome may have unintended consequences. Instead of banning the chemical, it may result in a genetic classification of people—those hypersensitive to chemical X, those with peanut allergies, etc.—putting the onus on them about how to navigate through life. Many people have figured out they are hypersensitive to new carpets, latex or perfumes and learn how to keep away. But if we had a mechanism that showed us these people were not psychologically challenged but rather had a normal genome with less capacity to metabolize chemical toxins, we would have a new regulatory mechanism for removing the chemicals from the environment. Biomedical scientists have been able to titrate chemotherapy agents to individuals based on genomic information. Gene expression patterns
associated with sensitivity and/or resistance to chemotherapy may be used to help provide more effective treatment. Scientists have used genetic testing to identify patients at high risk of bleeding from the drug warfarin. Two genes account for most of the risk. Recently, genetic variants in the gene encoding Cytochrome P450 enzyme CYP2C9, which metabolizes warfarin, and the Vitamin K epoxide reductase gene (VKORC1), has enabled more accurate dosing that takes account of the genome of an individual. Genotyping variants in genes encoding Cytochrome P450 enzymes (CYP2D6, CYP2C19, and CYP2C9), which metabolize antipsychotic medications, have been used to improve drug response and reduce side-effects. Pain killers like codeine affect people differently. Tests for certain enzymes (P4502D6) can determine whether someone will be an ultra-rapid metabolizer of codeine, which could induce life-threatening toxicity. If we can understand through certain enzyme pathways that individuals react differently to drugs and that some of us cannot efficiently metabolize certain chemicals, why couldn’t we do the same for industrial toxins within the next 20 years? Once we learn that many people cannot detoxify a chemical that bioaccumulates in their body, it provides new grounds for finding a substitute for that chemical rather than waiting a quarter century to complete hundreds of studies with mixed results. nnn Sheldon Krimsky, PhD, is Chair of the Board of Directors and a founder of the Council for Responsible Genetics. He is a Professor of Urban and Environmental Policy and Planning at Tufts University.
Volume 25 Number 1-2
The Genomic Imaginary As the science of genomics reaches new heights over the next twenty years, it also presents new questions about inequality and privacy. By Patricia J. Williams I teach a Justice and Bioethics class that, over the years, has attracted not only law students, but students from a grand variety of disciplines including medicine, engineering, biology, anthropology and journalism. At the beginning of every semester I do a silly little exercise as a way of putting on the table all the romantic images they might be harboring: I ask them to draw a cartoon depicting the DNA in their own bodies. Very few draw molecular topology. Indeed, no matter how sophisticated their backgrounds in biochemistry or genetics, whatever they draw is almost always relentlessly pre-modern: little men scurrying about with messenger bags; “a womb inside each cell”; mini-drones circulating just beneath the skin; “a golden fully-formed-butmicroscopic Me, floating in the thorax”; a Harvard beanie; Da Vinci’s Vitruvian Man; a “biological Torah in the Ark of the body.” The symbolism embedded in these framing metaphors and tropes—as delivered up by even the most secularly scientific minds—is intriguing. These are images of faith and karma and alchemy, of holy text and of the resurrection of the body—as well as of entitlement and preordination. While I ask my students to do this exercise as a way of externalizing what might otherwise remain fairly unconscious associations, these filters are persistent. They remain on the table, they do not go away. When I contemplate the next few decades of genetic technology and research, I think of those students and what roads their chosen taxonomies will chart through the genetic 28 GeneWatch
forest, the mind-maps their nominations will impose upon our collective understanding. In twenty years, I have no doubt that the actual science of genomics will have continued to expand explosively. I have no doubt that we will have medicines that at present we would think of as miracles. We will have access to our farthest ancestral links. Governments, schools, employers and corporations will have access to our farthest ancestral links as well. Recombinant and synthetic biology will revolutionize our conception of reproduction and the life cycle itself. That said, the little gallery of drawings I keep convinces me that the most important questions we face now and will then are age-old: how will we distribute the benefits of new knowledge? Will this sudden source of power and wealth be translated into public health benefits, or hoarded by elites? Will biologized notions of “endowment” displace or supersede
notions of political equality? The ability to read DNA quickly and cheaply, moreover, will put big holes in much of what we presently consider private as a matter of right. Similarly, the surveillance possibilities will give new meaning to the expression “You can run, but you can’t hide.” Finally, the delicate conceptual and jurisprudential relation between the historic sanctity or inalienability of human bodies and the body-asproduct will be vexed; for if medical research is ostensibly the driver of many recent genomic discoveries, the designated funding behind that research surely exists in ambiguous tension with corporatized pharmaceutical interests. What I hope we will have refined by then is our sense of urgency about the social justice issues presented by genomics. I hope that we will have embraced this science for what it teaches us about our common humanity and our interdependence with all other life forms. I hope that we will be guided by respect for the dignity of organisms and caution about unintended consequence, rather than by commercial profit, magical thinking, predestination, hubristic risk disguised as “progress,” mutilation masquerading as “improvement,” or eugenics doing business as…usual. This is what I hope. But that is also what I fear. nnn Patricia J. Williams, JD, is a Professor of Law at Columbia University and a member of CRG’s Board of Directors. She writes a monthly column for The Nation called “Diary of a Mad Law Professor.” January-February 2012
The Tree of Life Advances in genomics will lead to spectacular new ways to catalogue and analyze the millions of organisms living—and no longer living—on Earth. By Rob DeSalle Advances in DNA sequencing and genomics offer to enhance not only human health and human based biology but also offer to open doors for the characterization of the biodiversity on our planet. There are two major areas in modern biodiversity studies that will directly benefit from the advancing technology. The first and perhaps the most important concerns aiding the simple cataloguing of diversity on our planet. This aspect of genomics information will utilize genomic data as an informatic anchor for organizing the biology of a species. The second concerns using genome level information to create a “Tree of Life” that could serve as a foundation for all of biological science. Officially, there are 1.7 million species of organisms on this planet. By officially I mean “named”. A named species is important because it has been recognized as a species by experts in an area of organismal diversity (such as botany or zoology or mycology) using the methods outlined by Carl von Linne over 250 years ago. If we take just these 1.7 million named species, then arthropods (insects, crustaceans, spiders etc) would be the most speciose group of living things on the planet, strengthening the famous geneticist JBS Haldane’s statement that “God has an inordinate fondness of beetles”. And from those same 1.7 million species only 6,000 would be bacteria. On the other hand, we know from several studies that this number is off by at least three, perhaps four orders of magnitude, meaning that there are more than likely tens of millions of microbial species we have yet to discover. On the other hand, there are many fewer vertebrate species for us to discover anew. So from this perspective if we looked at the diversity of Volume 25 Number 1-2
Race? Debunking a Scientific Myth
“New techniques and new approaches can and will tell us an enormous amount about the biological history of our species; but they also teach us that this history was a very complex one that is very inaccurately – indeed, distortingly – summed up by any attempt to classify human variety on the basis of discrete races. While we can acknowledge that our ideas of race do in some sense reflect a historical reality, and that human variety does indeed have biological underpinnings, it is important to realize that those biological foundations are both transitory and epiphenomenal. Despite cultural barriers that uniquely help slow the process down in our species, the reintegration of Homo sapiens is proceeding apace. And this places the notion of “races” as anything other than sociocultural constructs ever more at odds with reality. Increasingly, it seems, we are simply who we think we are.” - from Race? Debunking a Scientific Myth By Ian Tattersall and CRG Board member Rob DeSalle
Available from Texas A&M University Press. Order by calling 800-826-8911, or visit www.tamupress.com.
organisms based on “true” numbers, the overwhelming winner would be bacteria and rather, God would have an inordinate fondness of microbes. When we add to the fray that 99.9% of the life on this planet has gone extinct, the immensity of this diversity should be more than evident. To demonstrate the utility of a DNA based approach to classifying and discovering diversity, I want to mention an initiative called the Consortium for the Barcode of Life (CBoL). This initiative has quietly been churning away at obtaining a short sequence for a 600 base pair reference region of the mitochondrial genome for the past decade. This project, while seemingly simple in its design, is an important one. Mostly because it will gather together tissues, taxonomic data, biogeographic data, and other data specific to the 1.7 million species on this planet. The DNA sequences themselves can serve as identifiers for future biological, forensic and conservation research. Many initiatives have strived toward a centralized repository for the biodiversity of this planet and have failed. One of the major successes of CBoL doesn’t concern the progress they have made (they have close to 1,500,000 reference sequences in their databases and this covers about 150,000 named species), nor that the DNA barcode sequences will be useful, but rather they have demonstrated that the infrastructure for such an initiative is possible and necessary for its utility. What the advances in genetic technology also mean is that any specimen collected or used by a scientist can and more than likely will have its genome sequenced. We will be able to use billions of base pairs as a DNA barcode in the future. Indeed it is one of my goals as a museum scientist to see every specimen that is accessioned into our collection at the
American Museum of Natural History to have its genome sequenced as part of the process of accessioning. My colleagues at the AMNH might think me crazy, but the reality is this goal will most likely be a reality in two decades. And in many cases DNA sequences are all we have to recognize new species such as with bacteria, archaea and some fungi. As an example, recently an entirely new phylum of fungi was discovered directly as a result of the advancing modern technology. It’s one thing to find, name, store and catalogue species as most museum scientists do. It’s another to figure out how species are related to each other and this is the purview of a sub discipline of biology called systematics. For the past decade the National Science Foundation (NSF) has supported and promoted a large multi-institutional project called the Tree of Life (ToL). This project hopes to construct THE branching diagram for all of the 1.7 million named species. This is a daunting task that will be made simpler by the ability to sequence whole genomes quickly and cheaply. While a DNA barcode system may not be in the cards in the future, The Tree of Life will be a reality as a result of the influx of whole genome sequencing. And The Tree of Life can serve as a cornerstone for modern biology. Why? Because a branching diagram is a very efficient way to store information. Couple the unique information storage capabilities with the idea that the branching order reflects evolutionary history, and we are in for some bizarre but overall pleasant surprises about life on this planet other than ourselves in the near future. nnn Rob DeSalle, PhD, is a curator in the American Museum of Natural History’s Division of Invertebrate Zoology and codirector of its molecular laboratories and a member of CRG’s Board of Directors. January-February 2012
Meiogenics: Synthetic Biology Meets Transhumanism Some enthusiasts of synthetic biology envision technologies that would “improve” humans—and, perhaps, create useful “subhumans.” By Stuart A. Newman Synthetic biology is a collection of techniques, and research and business agendas, that includes the construction of DNA sequences that encode protein or RNA molecules which assemble into macromolecular complexes, biochemical circuits and networks with known or novel functions; the substitution of chemically synthesized DNA or DNA analogues for their natural counterparts in order to change cell behavior and/ or produce novel products; and attempts to define and construct basic living systems from minimal sets of molecules.1 Synthetic biology has been termed “extreme genetic engineering” by the Erosion Technology and Concentration (ETC) Group2, in contrast to earlier recombinant DNA techniques that sought mainly to modify and refine existing types of organisms by altering or inserting individual genes. Although production of new kinds of fuels and foods are the bestknown, and potentially most lucrative, programmatic objectives of synthetic biology, the field’s visionaries and front men also have ambitions that have landed them in the precincts of transhumanism, a eugenic cultural movement concerned with the production of “better” humans.3 Thus, the Harvard researcher George Church confided to a reporter for Science magazine, “I wouldn’t mind being virus-free,” which elicited the comment: “It may be too late to reengineer all of his own cells to prevent viral infections, but Church doesn’t rule out the possibility of rewiring the genome of a human embryo to be Volume 25 Number 1-2
virus-proof.”4 In a similar vein, Drew Endy, a synthetic biology researcher formerly at MIT and now at Stanford, asked rhetorically in an interview with a New Yorker reporter, “What if we could liberate ourselves from the tyranny of evolution by being able to design our own offspring?”5 One difference from earlier eugenic fantasies is that synthetic biologists now know enough to realize that it would be hundreds of times more likely to botch an embryo’s genome by gene manipulation techniques than to come up with an improvement. The prospect of trying these techniques on their own prospective offspring thus fails to arouse much enthusiasm, despite the promotion of a supposed right of “procreative liberty” by transhumanism-friendly legal theorists.6 The inherent riskiness of embryo genetic manipulation has also become generally known, precluding significant numbers of the general public from offering up their embryos for such experiments. If we think of human-type organisms not as anybody’s children (or parents), but rather as sources of transplantable tissues and organs, experimental subjects, or crash test dummies and land mine defusers, eugenics takes on a whole new set of meanings, in which the improvements are more directed toward utility rather than enhanced success as members of the human community. In Drew Endy’s words, “If you look at human beings as we are today, one would have to ask how much of our own design is constrained by the fact that we have to be able to reproduce…
If you could complement evolution with a secondary path, decode a genome, take it off-line to the level of information…we can then design whatever we want, and recompile it…At that point, you can make disposable biological systems that don’t have to produce offspring.”7 With the objective thus being “meiogenics” (from the Greek μείον: less), that is, the creation of useful subhumans, many barriers to implementing such programs fall aside. Existing regulatory regimes on human experimentation pertain to what are agreed-upon humans; other, more permissive experimental regimes, cover vertebrate animals. If synthetic biologists can calibrate and titrate biological humanity and its animal consciousness by taking the human genome offline and recompiling it, we may be faced, in 20 years, with all manner of humanoid organisms, serving various practical purposes. Some may even represent metaphoric “lemonade” salvaged from the lemons of transhumanist experimentation. It is not clear who will make the cut of being human, who will not, and who will decide. But if beginning- and end-of-life controversies have been among the most divisive social issues up to the present, the implementation of the synthetic biologists’ meiogenic future may even further erode a shared sense of humanness. nnn Stuart A. Newman, PhD, is Professor of Cell Biology and Anatomy at New York Medical College. He was a founding member of the Council for Responsible Genetics. GeneWatch 31
FGPI is a collaboration of the following organizations:
Labeling Genetically Engineered Foods in California A grassroots call to action. By Pamm Larry Less than an hour ago, I got word that AB 88, a California Bill that would require labeling of genetically engineered fish, got voted down in the Assembly Appropriations Committee … again. California has tried to get GE foods labeling regulations a number of times before this. The last time was in 2010 when the California State Grange “shopped” a version and no legislator would touch it. Because our elected officials will not enact laws to give us the right to know what’s in our foods, a year ago this month, I, a grandmother with no managerial campaign experience, decided that it was my job to get this issue on the ballot so the people of the State of California could vote on it. I started out with no knowledge of the logistics of this process. I had no funding, no support from the leading GMO organizations (aside from the Organic Consumers Association) and no support from the organic industry. The only people who lit up were the people I started to share my crazy idea with. They all KNEW that this was the game changer that would get
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us the labeling that 80+% of the population repeatedly say they want in poll after poll. I am happy to say that through our tenacity and commitment, we have grown from one person to over 115 leaders throughout the state, all committed to organizing and educating their communities. Although we started as a grassroots movement and continue to have that as a crucial arm of our campaign, we realize that for us to win, we need everyone onboard, large and small, in order to win this. We have been joined by major organizations, health groups, environmental groups, farmers, activist organic companies, parent groups and faith based groups to create a solid, broad base coalition that continues to grow exponentially. We now have a professional campaign manager and are gearing up to gather 850,000 signatures mid-February to Earth Day in April. We are confident we will get this on the ballot, then win in November. We have other bright spots on the GE labeling front. In November 2011,
a court ruled that GE canola could not be labeled “natural” without the possibility of the company being sued. Within the last few months, Connecticut and Washington have newly introduced labeling legislation. Dennis Kucinich (D-Ohio), re-introduced three GE bills: H.R. 6636, the Genetically Engineered Food Right to Know Act, H.R. 6635, the Genetically Engineered Food Safety Act and H.R. 6637, the Genetically Engineered Technology Farmer Protection Act. Things look promising, but in order for anything to be enacted, we need all hands on deck. One easy yet powerful thing to do is to leave a comment for the national formal petition to the FDA written by the Center for Food Safety, at www.justlabelit.org. It’s clear that in order for us to get labeling, voting with our dollars, although vital, is not enough. There are increasing numbers of GE foods up for deregulation. The time for labeling is now. Please join us! nnn Pamm Larry is founder of LabelGMOs.org.
Developmental Science and the Role of Genes in Development: Ontogeny in Four Dimensions By Richard M. Lerner The key point of this article is that concepts reflecting, theories of, and methods purporting to provide support for genetic reductionism are egregiously flawed, counterfactual, and unequivocal reflections of scholarly failures. Evidence derived from evolutionary and developmental biology, as well as from my own field, the study of human development across the life span, not only destroy any remaining enthusiasm for genetic reductionism but also provide an alternative, relational developmental systems model for understanding the role of genes in human life. In addition, relational developmental systems ideas provide reason for optimism about the potential success of programs and policies aimed at enhancing the lives of diverse individuals. There are many ways to explain the nature of the support for the key point of this article. However, I will focus on a discussion of the ways in which the contemporary study of human development provides this support. A Brief History of Developmental Science Across much of its history, the major disciplinary frame within which the human life span was studied was developmental psychology. This field was embedded in a Cartesian world view. As a consequence, the field held as its core conceptual issue split conceptions of the world, such as continuity versus discontinuity, stability versus instability, and of course nature versus nurture, with 34 GeneWatch
the latter issue cast in many ways, e.g., heredity versus environment, maturation versus learning, or nativism versus empiricism.1 The fact that these split conceptions were regarded as reflecting the fundamental conceptual issues of the field legitimated genetic reductionist ideas and rationalized as plausible theories or approaches (e.g., behavior genetics, sociobiology, or evolutionary psychology) that claimed to explain how genes provided the fundamental material bases of human behavior and development, and did so independent of fusions with the ecology or context of human development.2 However, today, developmental psychology has been transformed into developmental science. As richly illustrated by the chapters across the four volumes of the Handbook of Child Psychology, 6th edition,3 as well as in other major publications in the field,4 the study of human development has evolved from being either a biogenic or a psychogenic approach to conceptualizing and studying the life span to a multidisciplinary approach that seeks to integrate variables from biological through cultural and historical levels of organization into a synthetic, co-actional system.5 As such, reductionist accounts of development that adhere to a Cartesian dualism, and that pull apart facets of the integrated developmental system, are rejected by proponents of relational developmental systems theories6 and, as well, by evolutionary biologists who embrace integrative, biology-context ideas as pertaining to
both phylogeny and ontogeny.7 For instance, while gene structure, function, and selection constitute one dimension of evolution, epigenesis, the behavioral actions of organisms, and culture represent three additional dimensions of evolution that are integrated with genes to foster evolutionary change.8 Indeed, this multidimensional and integrative view of evolution directly involves a similarly multidimensional and integrative view of ontogeny as being constituted by four integrated dimensions. That is, and reflecting a new way of conceptualizing the links between ontogeny and phylogeny,9 there is evidence that gene structure and function across ontogeny involve mutually influential relations with a culturally- and historically-textured ecology of human development. This context is both a product and a producer of the intentional self-regulations of humans (e.g., involving the cognizing of their purposes, their selection and management of goals, and their executive functioning, strategic thinking, resource recruitment, and attentional and emotional control), actions that create emergent (epigenetic) characteristics over the life span and across generations. Genes within the Developmental System Reflecting this four-dimensional view of ontogenetic change, Charney points to how the contemporary scientific study of genetics is signaling not only a non-split approach to developmental science but, as well, January-February 2012
is tolling a death knell for genetic reductionist approaches such as behavioral genetics. He says that: The science of genetics is undergoing a paradigm shift. Recent discoveries, including the activity of retrotransposons, the extent of copy number variations, somatic and chromosomal mosaicism, and the nature of the epigenome as a regulator of DNA expressivity, are challenging a series of dogmas concerning the nature of the genome and the relationship between genotype and phenotype. DNA, once held to be the unchanging template of heredity, now appears subject to a good deal of environmental change; considered to be identical in all cells and tissues of the body, there is growing evidence that somatic mosaicism is the normal human condition; and treated as the sole biological agent of heritability, we now know that the epigenome, which regulates gene expressivity, can be inherited via the germline. These developments are particularly significant for behavior genetics for at least three reasons: First, these phenomena appear to be particularly prevalent in the human brain, and likely are involved in much of human behavior; second, they have important implications for the validity of heritability and gene association studies, the methodologies that largely define the discipline of behavior genetics; Volume 25 Number 1-2
and third, they appear to play a critical role in development during the perinatal period, and in enabling phenotypic plasticity in offspring in particular.10 One striking example of the transformative role of epigenetic processes in the development across the life span of phenotypic plasticity among siblings exists in regard to monozygotic (MZ) twins. Fraga, Ballestar, Paz, Ropero, Setien, et al. (2005) note that, although MZ twins share a common genotype, most MZ twins are not identical, in that many types
of phenotypic differences exist (e.g., in regard to susceptibility to disease and several anthropomorphic characteristics). Fraga et al. suggest that epigenetic differences between MZs may account for these instances of divergence across development. Accordingly, Fraga and colleagues assessed global and locus-specific differences in DNA methylation and histone acetylation among a group of white MZ twins from Spain (N = 80; 62.5% female; mean age = 30.6 years, SD = 14.2 years). Fraga et al. found that “although twins are epigenetically indistinguishable during the early years of life, older monozygous twins exhibited remarkable
differences in their overall content and genomic distribution of 5-methylcytosine DNA and histone acetylation, affecting the gene-expression portrait.”11 Indeed, 35% of the 80 MZ pairs had significant differences in their DNA methylation and histone acetylation profiles. Other examples that link epigenesis and human development are provided by Lickliter and Honeycutt (2010). They note that evidence from developmental biology, neuroscience, and developmental psychology contradict the ideas that “instructions for building organisms reside in their genes, that genes are the exclusive vehicles by which these instructions are transmitted from one generation to the next, and that there is no meaningful feedback from the environment to the genes.”12 Together, the evidence presented by Lickliter Honeycutt (2010), and by Charney (in press) and Fraga, et al. (2005), among others13 create the basis for a true Kuhnian paradigmatic revolution.14 The findings presented by these scholars constitute anomalies (in effect, falsifications) of the “old,” genetic reductionist paradigm. These anomalies result in a crisis for the reductionist paradigm and, critically, a basis for science (and for working scientists) to turn toward an available, alternative paradigm. This new paradigm is relational developmental systems theory and, consistent with Kuhn’s discussion of scientific revolutions, the very findings that are anomalies in (falsifications of ) genetic reductionist models (and GeneWatch 35
methods) are integrated within the now dominant paradigm.15 Relational Developmental Systems Theory Given the evidence about the role of genes in the developmental system that I have summarized, the contemporary study of human development eschews Cartesian, split conceptualizations and, in turn, favors post- postmodern, relational metatheories that stress the integration of different levels of organization as a means to understand and to study life-span human development.16 Thus, the conceptual emphasis of relational developmental systems theory, which today is at the cutting-edge of theory and research within developmental science, is placed on the nature of mutually influential relations between individuals and contexts, represented as “individual/context” relations.17 That is, in such theory, the focus is on the “rules,” the processes that govern exchanges between individuals and their contexts. Brandtstädter (1998) terms these relations “developmental regulations” and notes that where developmental regulations involve mutually beneficial individual/context relations, they constitute adaptive developmental regulations.18 The possibility of adaptive developmental relations between individuals and their contexts, and the potential plasticity of human development that is a defining feature of ontogenetic change within the relational developmental system, are distinctive features of this approach to human development. As well, the core features of developmental systems models provide a rationale for making a set of methodological choices that differ in design, measurement, sampling, and data 36 GeneWatch
analytic techniques from selections made by researchers using split or reductionist approaches to developmental science. Moreover, the emphasis on how the individual acts on the context to contribute to the plastic relations with it fosters an interest in person-centered (as compared to variable-centered) approaches to the study of human development.19 Furthermore, the array of individual and contextual variables involved in these relations constitutes a virtually open set. Estimates are that the odds of two genetically identical genotypes arising in the human population is about one in 6.3 billion, and each of these potential human genotypes may be coupled across life with an even larger number of life course trajectories of social experiences.20 Thus, the number of human phenotypes that can exist is fundamentally equivalent to being infinite, and the diversity of development becomes a prime, substantive focus for developmental science. This diversity may be approached with the expectation that positive changes can be promoted across all instances of variation, as a consequence of health-supportive alignments between people and settings. With this stance, diversity becomes the necessary subject of inquiry in developmental science. That is, to understand the bases of and, in turn, to promote individual/context relations that may be characterized as healthy, positive, adaptive, or resilient – which are relations reflecting the maintenance or enhancement of links that are mutually beneficial to individuals and context – scholars must ask a complex, multi-part question.21 They must ascertain: what fundamental attributes of individuals (e.g., what features of biology and physiology, cognition, motivation,
emotion, ability, physiology, or temperament); among individuals of what status attributes (e.g., people at what portions of the life span, and of what sex, race, ethnic, religious, geographic location, etc. characteristics); in relation to what characteristics of the context (e.g., under what conditions of the family, the neighborhood, social policy, the economy, or history); are likely to be associated with what facets of adaptive functioning (e.g., maintenance of health and of active, positive contributions to family, community, and civil society)? These multiple, nested sets of conditions indicate that each person should be studied as a unique individual, an idea that has been coupled with relational developmental systems theory-predicated methodological innovations.22 The emergence of such methodological advances is important, given that addressing such a set of interrelated questions requires a systematic program of developmental research elucidating trajectories across life of individual/context relations within the developmental system. Moreover, the linkage between the ideas of plasticity and diversity that gave rise to this set of questions provides a basis for extending relational developmental systems thinking to form an optimistic view of the potential to apply developmental science to promote person/context exchanges that may reflect and/or promote health and positive, successful development. Accordingly, employing a relational developmental systems frame for the application of developmental science affords a basis for forging a new, strengthbased vision of and vocabulary for the nature of human development and for specifying the set of individual and ecological conditions
that, together, may reflect a positive, strength-based perspective about human development.23 Conclusions Quite simply, genes are not the to-be-reduced-to entities that provide any “blueprint” for behavior or development, nor do they function as a “master molecule;” they are not the context-independent governors of the “lumbering robots”24 housing them; and they are not the fixed material basis of the grand synthesis of heredity and Darwinism found in the neo-Darwinian model.25 Instead, and consistent with the four-dimensional, and neo-Lamarckian system involved in evolution,26 genes are a plastic feature of the four-dimensional, epigenetic, action-oriented,
and cultural and historical ontogenetic system that constitutes the fundamental process of human development across the life span. Given the plasticity of the relational developmental system within which genes are embedded, a final split between basic and applied science may be overcome. We may be optimistic that the future of genetic research will be marked by new information about how we can promote epigenetic changes that enhance the probability of more positive development among all individuals across the life course. nnn
The writing of this article was supported in part by grants from the John Templeton Foundation, the Thrive Foundation for Youth, and the National 4-H Council. I am grateful to G. John Geldhof, Gary Greenberg, Jacqueline V. Lerner, Jarrett M. Lerner, Peter C. M. Molenaar, Megan Kiely Mueller, Willis F. Overton, and Kristina L. Schmid for their comments. Richard M. Lerner may be contacted at firstname.lastname@example.org.
Richard M. Lerner, PhD, is Bergstrom Chair in Applied Developmental Science and the Director of the Institute for Applied Research in Youth Development at Tufts University.
Stuart Newman, p. 31
Richard M. Lerner, p. 34
1. Newman, S.A. 2012. Synthetic biology: Life as app store. Capitalism Nature Socialism, in press. 2. ETC Group. 2010. The new biomassters: Synthetic biology and the next assault on biodiversity and livelihoods. ETC Group Communiqué 104. 3. Newman, S.A. 2010. The transhumanism bubble. Capitalism Nature Socialism 21 (2): 29-42. 4. Bohannon, J. 2011. The life hacker. Science 333 (6047): 1236-1237 5. Specter, M. 2009. A life of its own. Where will synthetic biology lead us? The New Yorker. September 28: 61. 6. Robertson, J. A. “Procreative Liberty in the Era of Genomics.” Am J Law Med 29, no. 4 (2003): 439-87. 7. Specter, op. cit., p. 62
1. For reviews, see: Lerner, R. M. (2002). Concepts and theories of human development (3rd ed.). Mahwah, NJ: Lawrence Erlbaum Associates. Overton, W. F. (2006). Developmental psychology: Philosophy, concepts, methodology. In R. M. Lerner (Ed.), Handbook of child psychology, vol. 1: Theoretical models of human development (6th ed., pp. 1888). Editors-in-chief: W. Damon & R. M. Lerner. Hoboken, NJ: John Wiley & Sons. Overton, W. F. (2010b). Life-span development: Concepts and issues. In W. R. Overton (Ed.), Cognition, biology, and methods across the life span: Vol. 1, Handbook of life-span development. Editor in chief: R. M. Lerner. Hoboken, NJ: Wiley. 2. For critiques, see:
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Greenberg, F. (2011). The failure of biogenetic analysis in psychology: Why psychology is not a biological science. Research in Human Development, 8(3-4), 173-191. Gottlieb, G. (1998). Normally occurring environmental and behavioral influences on gene activity: From central dogma to probabilistic epigenesis. Psychological Review, 105, 792-802. Overton, W. F. (2011). Relational developmental systems and quantitative behavior genetics: Alternative of parallel methodologies. Research in Human Development, 8(3-4), 258-263. 3. Damon, W., & Lerner, R. M. (Eds.). (2006). Handbook of Child Psychology (6th edition). Hoboken, NJ: Wiley & Sons. 4. Bornstein, M. H., & Lamb, M. E. (Eds.). (2010). Developmental science: An advanced textbook (6th edition). New York: Taylor and Francis.
Lamb, M. E., & Freund, A. M. (Eds.) Handbook of life-span development, Volume 2: Social and emotional development (Editor-in-Chief: R. M. Lerner). Hoboken, NJ: Wiley, 2010. Overton, W. (Vol. Ed.), (2010a). Cognition, Biology, Methods. Volume 1 of The Handbook of Life-span Development (Editor-in-Chief: R. M. Lerner). (pp. 1-29). Hoboken, NJ: Wiley. 5. Elder, G. H., Jr. (1998). The life course and human development. In R. M. Lerner (Vol. Ed.) & W. Damon (Ed.), Handbook of child psychology: Vol. 1 Theoretical models of human development (5th ed., pp. 939-991). New York: John Wiley. Gottlieb, G. (1997). Synthesizing nature-nurture: Prenatal roots of instinctive behavior. Mahwah, NJ: Lawrence Erlbaum Associates, Inc. Hood, K. E., Halpern, C. T., Greenberg, G., & Lerner, R. M. (Eds.). (2010). The handbook of developmental science, behavior and genetics. Malden, MA: Wiley Blackwell. Molenaar, P. C. M. (2010). On the limits of standard quantitative genetic modeling of inter-individual variation: Extensions, ergodic conditions and a new genetic factor model of intra-individual variation. In K. E. Hood, C. T. Halpern, G. Greenberg, & R. M. Lerner (Eds.). Handbook of developmental systems, behavior and genetics. (pp. 626-648). Malden, MA: Wiley Blackwell. 6. Mistry, J., & Wu, J. (2010). Navigating cultural worlds and negotiating identities: A conceptual model. Human Development, 53, 5-25; Overton, 2010b. 7. Ho, M. W. (2010). Development and evolution revisited. In K. E. Hood, C. T. Halpern, G. Greenberg, & R. M. Lerner (Eds.). Handbook of developmental systems, behavior and genetics. (pp. 61-109). Malden, MA: Wiley Blackwell. Ho, M. W., & Saunders, P. T. (Eds.). (1984). Beyond neo-Darwinism: Introduction to the new evolutionary paradigm. London: Academic Press. Gissis, S. B., & Jablonka, E. (Eds.). (2011). Transformations of Lamarckism: From subtle fluids to molecular biology. Cambridge, MA: The MIT Press. Jablonka, E., & Lamb, M. J. (2005). Evolution in four dimensions: Genetic, epigenetic, behavioral, and symbolic variation in the history of life. Cambridge, MA: MIT Press. 8. Jablonka & Lamb, 2005
9. e.g., see Gould, S. J. (1977). Ontogeny and phylogeny. Cambridge, MA: Harvard University Press. 10. Charney, E. (in press). Behavior genetics and post genomics. Behavioral and Brain Sciences. 11. Fraga, M. F., Ballestar, E., Paz, M. F., Ropero, S., Setien, F., Ballestar, M. L., Heine-Sun, D., Cigudosa, J. C., Urioste, M., Benitez, J., Boix-Chornet, M., Sanchez-Aguilera, A., Ling, C., Carlsson, E., Poulsen, P., Vaag, A., Stephan, Z., Spector, T. D. Wu, Y., Plass, C., & Esteller, M. (2005). Epigenetic differences arise during the lifetime of monozygotic twins. Proceedings of the National Academy of Sciences, USA, 102, 10604-10609; p. 10604. 12. Lickliter, R. & Honeycutt, H. (2010). Rethinking epigenesis and evolution in light of developmental science. In M.S. Blumberg, J.H. Freeman, & S.R. Robinson (Eds.), Oxford handbook of developmental behavioral neuroscience. Oxford: Oxford University Press, pp. 30-47; p. 33. 13. e.g., Ho, 2010; Ho & Saunders, 1984; Greenberg, 2011; Gisses & Jablonka, 2011; Hood, et al., 2010; Jablonka & Lamb, 2006; Molenaar, 2010 14. Kuhn, T. S. (1962). The structure of scientific revolutions. Chicago: University of Chicago Press. 15. Overton, W. F. (in press). Evolving scientific paradigms: Retrospective and prospective. In L. L’Abate (Ed.). The role of paradigms in theory construction. New York: Springer. 16. Overton, 2010b; Overton, in press; Overton, W. F., & Müller, U. (In press). Meta-theories, theories, and concepts in the study of development. In R. M. Lerner, M A. Easterbrooks, & J. Mistry (Eds.) (2011). Comprehensive Handbook of Psychology: Developmental Psychology (Volume 6). Editor-in-Chief: Irving B. Weiner. New York: Wiley. 17. e.g., see the two volumes of the Handbook of Life-Span Development; Lamb & Freund, 2010; Overton, 2010a 18. Brandtstädter, J. (1998). Action perspectives on human development. In R. M. Lerner (Ed.), Theoretical models of human development. Volume 1 of the Handbook of child psychology (5th ed., pp. 807-863), Editor-in-chief: W. Damon. New York: Wiley. 19. e.g., see Molenaar, P C. M. (2007). On the implications of the classical ergodic theorems: Analysis of
developmental processes has to focus on intra-individual variation. Developmental Psychobiology, 50, 60-69. Nesselroade, J. R., & Molenaar, P. C. M. (2010). Emphasizing intraindividual variability in the study of development over the lifespan. In W. R. Overton (Ed.), Cognition, biology, and methods across the life span: Vol. 1, Handbook of lifespan development. Editor in chief: R. M. Lerner. (pp. 30-54). Hoboken, NJ: Wiley. 20. Hirsch, J. (2004). Uniqueness, diversity, similarity, repeatability, and heritability. In C. Garcia Cole, E. Bearer, & R. M. Lerner (Eds.), Nature and nurture: The complex interplay of genetic and environmental influences on human behavior and development (pp. 127–138). Mahwah, NJ: Erlbaum. 21. Lerner, R. M., Agans, J. P., Arbeit, M. R., Chase, P. A., Weiner, M. B., Schmid, K. L., & Warren, A. E. A. (In press). Resilience and positive youth development: A relational developmental systems model. In. S. Goldstein and R. Brooks (Eds.), Handbook of Resilience in Children (2nd Ed.).New York: Springer Publications. Lerner, R. M., Schmid, K. L., Weiner, M. B., Arbeit, M. R., Chase, P. A., Agans, J. P., & Warren, A. E. A. (In press). Resilience across the lifespan. In B. Hayslip Jr. & G. C. Smith (Eds.). Emerging Perspectives on Resilience in Adulthood and Later Life. New York, NY: Springer Publications. 22. e.g., Nesselroade & Molenaar, 2010; Molenaar, 2007, 2010 23. Lerner, J. V., Bowers, E. P., Minor, K., Lewin-Bizan, S., Boyd, M. J., Mueller, M. K., Schmid, K. L., Napolitano, C. M., & Lerner, R. M. (In press). Positive youth development: Processes, philosophies, and programs. In R. M. Lerner, M. A., Easterbrooks, & J. Mistry (Eds.), Handbook of Psychology, Volume 6: Developmental Psychology (2nd edition). Editor-in-chief: I. B. Weiner. Hoboken, NJ: Wiley. 24. Dawkins, R. (1976). The selfish gene. New York: Oxford University. 25. e.g., Ho, 2010; Ho & Saunders, 1984 26. e.g., Gissis & Jablonka, 2011
Race and the Genetic Revolution
Science, Myth, and Culture
Edited by Sheldon Krimsky and Kathleen Sloan
“I can hardly wait for this book to begin circulation. It should be read and taught as widely as possible.” —Adolph Reed, Jr., University of Pennsylvania Divided into six major categories, the collection begins with the historical origins and current uses of the concept of “race” in science. It follows with an analysis of the role of race in DNA databanks and its reflection of racial disparities in the criminal justice system. Essays then consider the rise of recreational genetics in the form of for-profit testing of genetic ancestry and the introduction of racialized medicine, specifically through an FDA-approved heart drug called BiDil, marketed to African American men. Concluding sections discuss the contradictions between our scientific and cultural understandings of race and the continuing significance of race in educational and criminal justice policy, not to mention the ongoing project of a society that has no use for racial stereotypes. SHELDON KRIMSKY is professor of urban and environmental policy and planning and adjunct professor of public health and community medicine at Tufts University. He is the author of Science in the Private Interest: Has the Lure of Profit Corrupted Biomedical Research? KATHLEEN SLOAN is a human rights advocate specializing in global feminism. She has run nonprofit organizations for more than twenty years and has directed communications and public relations functions for multinational corporations and nonprofits.
CO LU M B I A U NIVE R S ITY PRE S S Tel: 800-343-4499 Fax: 800-351-5073 cup.columbia.edu Volume 25 Number 1-2
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“Novel and forward thinking, this book will be a valuable addition to a literature that needs to be brought up to speed.” —David Rosner, Columbia University and Mailman School of Public Health
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Support from people like you makes CRG’s work possible. Much of our income comes from individuals. Your support helps keep our programs free of the restrictions that come with funding from pharmaceutical and health care companies or government sources. We are the watchdogs for accurate and unbiased information about biotechnology, even when the truth doesn’t suit current political or commercial agendas. And we depend on you to be able to do what we do. There are many ways you can help CRG. You can become a donor: an annual gift in quarterly installments of $25, $50 or $100 gives us a wonderful and predictable support with a minimal shock to your budget. You may also be able to designate CRG through your workplace giving program, including the Combined Federal Campaign. Many companies will actually match or even double-match your donation. Check with your employer about its matching gift program. You might also consider making an investment in a future where biotechnology is properly used by remembering CRG in your will with a bequest or charitable trust gift. To learn more about helping CRG, please call us at 617.868.0870. You may also write the Council for Responsible Genetics at 5 Upland Road, Suite 3, Cambridge MA 02140, or visit www.councilforresponsiblegenetics.org.