GeneWatch Vol. 25 No. 1-2

GeneWatchTHE MAGAZINE OF THE COUNCIL FOR RESPONSIBLE GENETICS | ADVANCING THE PUBLIC INTEREST IN BIOTECHNOLOGY SINCE 1983

Volume 25 Number 1-2 | JaNuary-February 2012ISSN 0740-9737

Cutting-edge researchersGeorge ChurchJames P. EvansSteven Salzberg

Industry leadersAnne Wojcicki, 23andMeJoe Hammang, PfizerPaul Billings, LifeTechnologies

PolicymakersRep. Louise SlaughterEric Green, NIH

Top bioethicistsArthur Caplan

Henry T. GreelyGeorge Annas

Science and policy experts

Patricia WilliamsDorothy RobertsSheldon Krimsky

Robert DeSalleStuart Newman

Emily Senay

A look at the future of genetics and genomics, with an all-star cast:

2 GeneWatch 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.

GeneWatch 3Volume 25 number 1-2

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)


GeneWatch is published by the Council for Responsible Genetics (CRG), a national, nonprofit, tax-exempt 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, PhdMcGill University

Paul billiNgs, md, PhdLife Technologies Corporation

suJatha byraVaN, Phd

Centre for Development Finance, India

robert desalle, Phd

American Museum of Natural History

robert greeN, md, mPhHarvard University

Jeremy gruber, JdCouncil for Responsible Genetics

rayNa raPP, PhdNew York University

Patricia Williams, JdColumbia University

staFF

Jeremy Gruber, President and Executive DirectorSheila Sinclair, Manager of Operations

Samuel Anderson, Editor of GeneWatchAndrew Thibedeau, Senior Fellow

Magdalina Gugucheva, Fellow

editorial & creatiVe coNsultaNt

Grace Twesigye

GeneWatchJanuary-February 2012Volume 25 number 1-2

editor aNd desigNer: Samuel W. Andersoneditorial committee: Jeremy Gruber, Sheldon Krimsky,

Ruth Hubbard

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

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 unat-tainable, 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 suffi-ciently 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 cer-tainly our most illustrious cast of GeneWatch contributors yet: from Eric Green, Director of the National Human Genome Research Insti-tute, to Congresswoman Louise Slaughter; from every major news-paper’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 pre-dictions 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; what-ever the method of forecasting the future of genetics and genomics, there is bound to be some madness in it. nnn

Editor’s NoteSamuel W. anderSon

Write to (or for) GeneWatchGeneWatch welcomes article submissions, comments and letters to the editor. Please email [email protected] if you would like to submit a letter or with any other comments or queries, including proposals for article submissions.


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 facili-tator in promoting citizen participation in policy and ethi-cal decisions involving science. After receiving his Ph.D. from Case Institute of Technology in the History of Sci-ence and Technology, he became director of the Center for the History of Physics at the American Institute of Phys-ics 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 & Ar-chives 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 videocas-sette 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 scien-tists and citizens into an unprecedented dialogue over the new laboratories developed for gene splicing research. To-day, 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 dimen-sions, 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 re-combinant 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 recombi-nant DNA controversy is not adequate for expressing and enforcing societal and moral limits for potential genetic engineering applications such as human cloning or human

germ-line interven-tions. These potential applications are not in-evitable, and they raise profound issues beyond laboratory and envi-ronmental safety and patients’ rights. They occur in a context of increasing genetic de-terminism, pervasive commercialization, and aggressive efforts to sell genetic intervention as a cure-all for medical and even social prob-lems. Separation of the technical issues from the ethical is-sues, and the narrowing of ethical concerns to clinical bio-medical 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 Pug-wash, an organization formed by Bertrand Russell after the signing of the Russell-Einstein Manifesto, dedicated to the elimination of nuclear weapons. The ethical ques-tions 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 commercial-ization 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’ biotechnol-ogy meeting in July 2011, Charlie recited, in a “Woody-Guthrie” style his original “Tarrytown Talking Blues.” I of-fer 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 KrimskyBoard Chair, Council for Responsible Genetics


DNA sequencing is cheap and get-ting cheaper. A detailed elucidation of the sequence of one’s complete ge-nome 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 any-time 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 pro-vides 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 environ-ment remains messily analog, impre-cise and chaotic. Until we can grasp our (ever-changing) environment with the kind of precision we now apply to our (static) genomes, knowl-edge of our genomic sequence will remain a dim and imprecise source of useful information. And understand-ing 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 interest-ing 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 busi-ness model hinges on selling every-one their whole genome sequence). After all, magnetic resonance imag-ing 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 re-ally likely to be of benefit.

While for most of us our genomic sequence will be nothing more than a mild diversion, the situation is dif-ferent 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 preven-tive measures currently available. While there are not many human genes which, when mutated, lead to a high risk of an eminently prevent-able disease, there are enough so that about 1% of us carry highly penetrant

We Are the Ninety-Nine PercentAbout 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


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 se-quencing incorporated into medi-cal care as a routine diagnostic tool which will be useful for those rela-tively 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 fu-sion of genomics with public health. Ubiquitous, population-level se-quencing of the handful of genes that actually matter to human health will identify those relatively rare indi-viduals – the roughly 1% - who have mutations that strongly predispose to an eminently preventable disor-der (e.g. various cancers or aneu-rysms). 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 prevent-ing 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 se-quencing will also likely be realized in the near-term as it is increasingly

used to identify the severe recessive diseases for which prospective par-ents are both carriers.

The application of genomics in public health contexts will inevitably create friction. When couples have ready knowledge of their carrier sta-tus 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 genom-ics,” 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 dis-order). 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 amaz-ing new technology. nnn

James P. Evans, MD, PhD, is Bryson Distinguished Professor of Genetics and Medicine at the University of North Car-olina 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.


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 repeated-ly 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 ge-nomics 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 ge-nome, and figuring out how it’s go-ing to be medically relevant, will slow down.

Genome sequencing and analysis:

One thing I would predict is that

the technologies for generating data will create a situation where data gen-eration is trivial and analyzing the data becomes the overwhelming chal-lenge. I think genomics is going to be-come 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 in-terpret data in creative and powerful ways; and every time we need to gen-erate 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 our-selves in a situation where we have data abundance but an analysis re-striction. 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 func-tion. I do not believe 20 years from now we will have figured out every last way that DNA encodes biologi-cal 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 discov-ering 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 ge-nome 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 understand-ing of how it works.

A revolution in evolutionary biology:

My third prediction under the gen-eral 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 labora-tory exercise will not be confined to dissecting frogs or looking at a fos-sil; 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 evo-lutionary biology, that will be domi-nated by computational analyses. Yes, we’ll still be digging up fossils, we’ll still be doing imaging and biomet-rics, but we will also have in front of

Interview: Eric GreenDr. Eric Green, Director of the National Human Genome Research Institute, spoke with GeneWatch about the future of genomic research.


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 infor-mation 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 can-cers will become standard of care for many different kinds of cancer prob-ably well before 20 years. For phar-macogenomics, 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 be-lieve that the routine will be that you’ll have a genetic sequence of every pa-tient. Now, we can start wondering what it will look like, whether that ge-nome sequence is obtained as part of newborn screening shortly after birth … I realize there are still many com-plicated 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 infor-mation 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

things.Where I’m less

certain is what the role of genomic in-formation 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 dif-ferent 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 gene-environment 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 envi-ronmental basis of disease is that we just don’t have technologies for doing fine-scale measurements of environ-mental 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 ge-nomics—the ethical, legal, and so-cial issues—will continue to require significant attention, significant re-search, 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 ques-tions are going to become simpler; if anything, I think they will become more complex. We shouldn’t fool our-selves into thinking that we’ll eventu-ally 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


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 per-sonalized medicine. The certificate was good for any family member, but could also be sold (the going rate last year was $20 million). Once treat-ment began, the certificate could not be transferred. If two family mem-bers were sick, only one could have their treatment personalized.

Waiting for the drawing, Ollie de-cided to get pronto pups for him and his wife, and elk jerky and Dr. Pep-per for the kids. Then he remem-bered that his cousin had signed up on three waiting lists before he fi-nally 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.

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 physi-cians did was to have the patient’s ge-nomes 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). Se-quencing itself was dirt cheap, but analysis of the sequence could in-volve 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 re-cords and genome sequences of ev-ery American and most of the world’s population, as well as their social networks, finances, and educational backgrounds, to take over all elec-tronic 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

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, vir-tually 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 insur-ance, and all of their names are au-tomatically entered into the lottery. Only in its fifth year, the kinks were still being ironed out, but even Ol-lie Olsen (known more for his hard work on the farm than his intel-lect) understood the basic concept. Health care expenditures now made up more than 80% of the federal bud-get, forcing downsizing to all but a skeleton military made up mostly of robots, and the elimination of all fed-eral agencies not directly involved in healthcare.

Ollie’s son, Jon, was a big believ-er in the lottery as a way to reduce health expenditures on the elderly. He also liked the idea of doing na-tional 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

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


Anne Wojcicki is co-founder and CEO of 23andMe, one of the world’s largest per-sonal 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 talk-ing 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

your genome: your health risks, why you are the way you are, the envi-ronmental 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 com-pany 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 signifi-cant margin. We want to enable ac-cess. 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 23an-dMe 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 get-ting 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 ge-nome can get access, and then pro-viding an ongoing service where we

can continually keep people updat-ed. We keep you up to date on the health side if there are new develop-ments 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 unrea-sonable 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 Neander-thal DNA in humans. This is one of the fun things: we created a lab tool

The Future of Consumer Genomics: Sharing Is Caringan IntervIeW WIth anne WoJcIckI, co-founder and ceo of 23andme

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.


about my body, there’s no reason a physician should stand in between that information and me. That said, we recognize that the medical com-munity has their concerns, and I think we’ve tried to be very respon-sible about how we’re putting out in-formation. For things like the BRCA report [for risk of breast cancer], and the APOE report [for risk of Al-zheimer’s Disease]—for the APOE report, we actually have a video with Robert Green talking about what you are likely to learn, what hap-pens if you are or aren’t a carrier, and we’ve had really positive feed-back about that from physicians, ge-netic counselors, and consumers. As people take more control over their health, they want not just the infor-mation, but all the context around it. So you might want to talk to a ge-netic 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 re-ally valuable for the whole field of medicine, as well as for the patient.

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 coun-selors, but we have a partnership. We thought it was important that we’re not the ones who are neces-sarily giving all the information to consumers, that there should be a divide. We are the ones providing the information, and there is a sepa-rate group that is actually giving the genetic counseling. So we have part-nered with an external group, and that is available to people for an ex-tra fee. I think that’s something that

we’ll continue to pursue. We recog-nize 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 do-ing things responsibly, and to make sure that customers have all the ac-cess 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

so that you can see how much Ne-anderthal 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 re-search done in the traditional mod-els, you can actually have consumer-driven 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 as-pects, 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 ap-proached with caution. We believe the consumer should have access to information that is fundamen-tally theirs. If it’s about my health or


before it took root, or to prevent it altogether.

Efforts by private companies to move personalized risk testing to the Internet quickly followed the pub-lication of the first genome map. A variety of companies in the decade after the Collins/Venter mapping an-nouncement jumped on the ‘spito-mics’ bandwagon, encouraging indi-viduals 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 con-ditions; to gain insight into the iden-tity 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

met with little public enthusiasm. The lack of standards about the accu-racy and sensitivity of genetic tests, the relative difficulty in using risk in-formation, and the absence of serious efforts to ensure competent counsel-ing 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

Genomic risk factor testing played only a minor role in health

care by the third decade of the 21st

century.

came to understand, despite the fas-cination of knowing your genes, you could diminish your risk of most diseases by losing weight, exercising more, reducing alcohol intake, get-ting 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 ge-nome was complex, hard to under-stand 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 con-troversial 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 cen-tury, 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 dis-ease resistant strains of fish, vegeta-bles and other plants and animals led to a green revolution in farming and fishing that both fed the world, en-riched corporations and helped re-duce the damage done to water, soil and the atmosphere by older meth-ods of creating food.

Genomics in the form of syn-thetic biology had also begun to

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 mem-bers of our species, for understand-ing 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 ge-netic analysis to catch disease early

Unrequited Love: Reflections on Genomics, as Written in 2032It’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


and changing the genomes of other species proved far more productive in improving health and well-being. nnn

Arthur L. Caplan, PhD, is the Em-manuel and Robert Hart Director of the Center for Bioethics and the Syd-ney D Caplan Professor of Bioethics at the University of Pennsylvania in Philadelphia. He writes a regular col-umn on bioethics for MSNBC.com.

revolutionize medicine. Microbes could be disabled through genetic engineering and plagues such as ma-laria, HIV, TB, measles and lethal bacterial infections were diminishing through a variety of vector-target-ed genetically-based interventions. Drug manufacturing was closely linked to genomics and synthetic biology with many more efficacious and safer drugs and vaccines be-ing manufactured using modified

bacteria and microbes. While it is true that doctors paid

attention by 2030 to individual re-sponses to drugs based upon phar-macogenomics studies, the real im-pact of genetics was being felt outside the realm of human genomes. The self-conceit of earlier decades that human genes because they are in hu-mans ought to occupy the attention of efforts to apply new genetic knowl-edge had collapsed. Understanding

The $10 Genome Dr. Paul Billings spoke with GeneWatch about the future of genomic medicine.

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 ex-pression of mutation can be signifi-cant. The genomes of cancer cells are somatically mutated at an amazing rate, and clearly there are epigenom-ic 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

Genomic DNA information has very distinct advantages: it is mea-surable, I believe it will be highly reli-able, and it is for the most part stable. Epigenomics, post-translational vari-ability and environmental influences can be important and do modify the genomic information. And of course disease states like cancer are charac-terized by finding more genomic mu-tations than in non-cancerous cell ge-nomes. But the overall impact of the genome should be reliable and acces-sible. We’ll figure out how to use that over the next 20 years, along with en-vironmental 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 medi-cal records will be built more signifi-cantly on genetic and genomic infor-mation, and will be verifiable in a way that our current medical systems are not. That is not to say that genetics

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 concep-tion—the analysis of that over the next 20 years will become increasing-ly simple and very inexpensive. And to the extent that this information is a reliable, quantitative, and identifi-able component of disease diagno-sis, therapeutic selection, et cetera, I believe that information will become an integral part of everybody’s medi-cal record, probably from conception and certainly from birth.


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 ge-netics about what kind of manifesta-tion 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 in-fectious agent? In some conditions, the kind of microbes that reside in your gut, and the proteins they pro-duce, may interact with your body (and there may be some genetics to this) to cause illness or modify sever-ity of conditions like autoimmune disorders.

In many cases, your gene combi-nations might only confer moderate risk for a disease, and it’s the environ-ment around you that matters more. But even if it’s just a small percent of the population that has powerful ge-netic determinants, to help that small percent is really a major deal. nnn

to continue to drop. The $100 ge-nome 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; in-terpreting 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 ex-pensive, 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 automat-ed 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 mul-tiple looks, and there will be lots of other things that will help modify the interpretation beyond a single com-puter algorithm; but the trend will be toward automated analysis, and with that the cost will go down.

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 expo-sures 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 pre-vent many of those deaths.

The $100 (and $10) genome:

I see in the next 20 years the tech-nology driving down the cost of ge-nomic sequencing to being very in-expensive, and it’s dramatically going


available products, most of them un-anticipated in the initial hype phase. Everybody is surprised but pretty soon forgets their earlier skepticism and readily adopts the new prod-ucts. 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

are currently in the trough of disil-lusionment. 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 no-where to go but up. It is during this phase that the few stalwart innova-tors toil away in obscurity creating early versions of what will eventually

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.

be the next big thing that really will deliver. So before too long we could be experiencing an explosion of in-novation in genetics and genomics.

But will this explosion include a cure for big problems like cancer? Two great minds think so: Jim Wat-son, co-discoverer of DNA, and Al-bert Brooks, comedian and author. Writing in Cancer Discovery in No-vember 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 can-cers, all comers, 100% cured. Unfor-tunately 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 Wat-son has predicted a cancer cure and Brooks is famous for his overly neg-ative outlook. Secondly, a cure for cancer would be the most obvious thing to predict, and according to the hype cycle it’s usually stuff no-body 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 incre-mental, 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

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 dev-astating diseases such as Alzheim-er’s, Parkinson’s and cancer. Those promises were wildly overblown, but nevertheless made it into the zeitgeist, leaving many discour-aged. 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 mak-ing 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 un-derstand how technology matures, Gartner’s Hype Cycle begins with the emergence of an important new technology that captures popu-lar imagination and promises to change everything. The new tech-nology is then over-hyped by sci-entists, 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 at-tention anymore, the new technol-ogy begins to yield innovative and

Deflated ExpectationsAccording 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


bigger way than currently antici-pated and will be driven not by sci-entists but average folks. I base this prediction on nothing more than re-cent 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 Parkin-son’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 adopt-ers. 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,

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 go-ing 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 long-lost 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.


identification of BRCA1 and BRCA2 came about because of the extraor-dinary 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 chanc-es that additional genetic priva-cy 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 aston-ishing 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 phy-sician. Over here [in the House of Representatives], we had commit-tee chairs who bottled it up at some group’s request.

Do you expect any future expan-sion of GINA’s protections—for ex-ample, 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 chang-ing medicine and healthcare in the next 20 years?

What we want for this bill is to cut down on hospital stays and unneces-sary surgeries. Since we all have dif-ferent genes, we need individualized medicine, so doctors can find what treatments we will personally re-spond 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 sci-ence 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 work-ing so well. nnn

U.S. Rep. Louise Slaughter, D-N.Y., first introduced genetic privacy legislation in Congress in 1995 and went on to cham-pion the bill that would become the Ge-netic 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 test-ed for BRCA1 and BRCA2 genes—it flies in the face of what we were try-ing 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 over-turning 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 for-ward and patented those genes. The

The Future of Genetic Nondiscrimination Legislationan IntervIeW WIth conGreSSWoman louISe SlauGhter


GeneWatch has asked me, and others, to predict the future of ge-netics 20 years out; but, question-ing authority, I am going to disobey and instead predict it 60 years out. This is, of course, madness. The lon-ger 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 em-barrassed in 60 years, while my sur-vival 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 rem-nant of humanity struggles to survive in the aftermath of the nuclear holo-caust of 2027 or a non-computerized

humanity abandons serious science after the Butlerian Jihad, also known as the Fifth Great Awakening. As-sume general continuity with today’s world (an assumption that seems unlikely but at least gives us a frame-work 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 con-ceived through in vitro fertilization so that preimplantation genetic diag-nosis can be used to select the genet-ic traits of the next generation. The key development here will be making human eggs from induced pluripo-tent stem cells, freeing IVF from the unpleasant, expensive, and risky pro-cess 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 di-rect attack on their molecular weak-nesses or by improving the ways our immune systems respond to them. Major non-infectious diseases, in-cluding cancer and heart disease, will also be greatly reduced by more effective prevention and more effec-tive treatments, for cancer probably through precise targeting of tumor cells. Stem cell transplants, as disso-ciated 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 per-haps especially their brains, will just wear out.

Third, the non-human biological world will have been engineered, the better to serve, and amuse, human-ity. Most people will eat lots of nutri-tious and (fairly) tasty meat derived from stem cells, which will be cheap-er, much greener, and more humane. (The rich will still eat dead steers, at a high price and with a frisson of sin-fulness akin to what may lead some to smoke cigars.) Crop shortages will disappear as genetically modified crops make their own fertilizers, in-crease yields, and adjust to the envi-ronment of a climate-changed world. The carbon dioxide levels of the at-mosphere will begin, slowly, to come down through a combination of ge-netically 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

Designer Eggs and Stem Cell SausageThink genetics in 20 years is a brave new world? Look another 40 years down the road. By henry t. Greely


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.

saber-toothed cat will roam again in animal parks; a few spots will feature vaguely disappointing “best guesses” at recreated dinosaurs.

Does this sound disappoint-ingly positive, even Pollyannaish? It shouldn’t. The technologies can be used in good ways or in ways dysto-pian 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 cre-ate 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 medi-cine 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 biofu-el 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 pain-ridden 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

Safe Bets: Priorities for Genetic ResearchJoe Hammang of Pfizer, Inc. spoke with GeneWatch about the future of medical genetic research.

level and at the private level, in the biotechnology and biopharmaceu-tical areas. I think what happened was that we saw a very strong draw towards developing therapies—that

Joe Hammang, PhD, is Senior Direc-tor of Worldwide Science Policy at Pfizer, Inc. The following is excerpted from an interview.

The unpredictable rate of change:

When I read about these tech-nologies 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 tech-nologies. People will say something’s going to happen tomorrow or next year, and it’s inevitably much slower. Technologies don’t advance as quick-ly as we want, because we’re human beings, we’re impatient. We want to

see advances, and we want to make medicines to help people, but the tra-jectory is always very difficult to pre-dict. 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


of disease in cancer has led to in-credible advances. We are now actu-ally 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 under-stand 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 medi-cine aren’t going to come as quickly there. We aren’t going to see the rev-olutionary 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 understand-ing today. If we don’t have that, it’s very hard to see these advances com-ing 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 mas-sive public health problems here and throughout the world, are going to be greatly aided by next generation vaccines, vaccines which can be tar-geted against multiple strains of bac-teria. It’s going to revolutionize pub-lic health treatment here in the U.S. and abroad. One can see particular advantage abroad, in places where medical structure is nil or nonex-istent. These technologies, I think, are going to advance greatly over the next decade or two. This idea of be-ing able to allow an individual to fight infection before it becomes infection is extraordinarily powerful. nnn

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 medi-cines 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 dol-lars in making new medicines against those targets, something that the bi-opharmaceutical 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 dis-ease is just over half a billion dollars, so less than a tenth of the NCI spend-ing. That may have a significant role to play in the fact that this very com-plicated disease is very poorly under-stood 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 go-ing to require much more significant investments at both the government and the biopharmaceutical level. The stakes are so high, and the cost to so-ciety with Alzheimer’s disease is go-ing to be so great, especially as the population ages.

Personalized medicine for cancer, Alzheimer’s, and pathogens:

Our understanding of the genetics

is, cell replacement therapies—and not enough towards tool develop-ment, 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 technolo-gies have been slow to come, now I believe there is a much greater em-phasis on tool development. And the great news is that this tool develop-ment—what we learn from it, and the investments that the biopharmaceu-tical industry makes in tool develop-ment 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 repro-ducible from one batch to the next, and what makes them decide to be-come 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 discov-eries 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 re-placement for the continued invest-ment in research.

Investment priorities:

You can look at the National Can-cer Institute investment over time, contrasted with an area like the Na-tional Institutes of Aging and the National Institutes for Neurological Diseases, which provide the primary amount of Alzheimer’s disease fund-ing in the U.S. If you look at the NCI’s investments from the 1960s to pres-ent, the cumulative total is about $90


Twenty years ago it appeared that mainstream science finally was abandoning the concept of biologi-cal human races. From 18th century typologists to 20th century eugeni-cists, 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 re-place 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 origi-nally 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 sys-tem, the science that emerged from sequencing the human genome has been shaped by a resurgence of inter-est in race-based genetic variation. Some scientists claim that clusters of genetic similarity detected with nov-el genomic theories and computer technologies correspond to antiquat-ed racial classifications and prove that human racial differences are real and significant. Others are search-ing for genetic differences between races that could explain staggering inequalities in health and disease as

well as variations in drug response, with the biotechnology and phar-maceutical industries poised to con-vert the new racial science into race-specific products. As we wait for the promise of gene-tailored medicine to materialize, race has become an avenue for turning the vision of to-morrow’s personalized medicines into today’s profit making commodi-ties. While uncritically importing antiquated racial categories into re-search, 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 in-trinsic 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 so-cial inequality affects people’s health, not because race is hardwired in our genes.

Will genomics still be tethered to race twenty years from now? De-spite the disturbing revival of bio-logical 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 so-ciologists, 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 bio-logical races. Antiracist, disability, economic, gender, reproductive, and environmental justice groups are re-alizing that they all have a stake in contesting the emerging racial sci-ence based in genetics. This social movement rejects the view that hu-man beings are naturally divided into races at the molecular level and re-fuses to look to genomic science and technology to bridge the enduring chasm between racial groups. Rather, we should affirm our shared human-ity by working to end the social ineq-uities preserved by the political sys-tem of race. Instead of hamstringing scientists, discarding the folklore of biological races would liberate them to focus on more fruitful lines of re-search—to study how genes function in human beings and to locate, un-derstand, 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.

Breaking the Bonds of Race and GenomicsGenomic science is reinforcing misguided beliefs in intrinsic racial difference. Will genomics still be tethered to race twenty years from now? By dorothy roBertS


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 de-creased 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 acceler-ations, we have to be especially cau-tious 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 fea-tures. Only as transportation tech-nology matured did we see seat belts, airbags, licenses and radar speed-monitors. The analogs for genetic en-gineering are organisms which can’t exchange functional genetic material with the environment, plus licensing and computer surveillance of all syn-thetic genomics components—from chemicals and machines to genes and genomes. Gene therapy is transition-ing from the train wreck of random

viral delivery (with immune and can-cer consequences) to precise homol-ogous 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 out-comes 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 ge-nomes safely takes pressure off the manipulation of the germline and encourages us to embrace and man-age our diversity, rather than overly medicalize, suppress or eliminate di-versity. Tiny effect sizes and “missing heritability” doesn’t limit us if we con-tinue to find—or invent—rare, highly protective alleles, not just for viral resistance (above), but for less break-able 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, nar-colepsy). 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 cost-effective tools that enable us to han-dle N=1. We increasingly embrace the interrelations among genomes, environments, traits and cohorts. This emphatically includes educa-tion 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, aller-gens, foods, immune function, thera-pies, and transplants.

Sharing:

Research subjects and consum-ers 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 educa-tion (e.g. PGEd.org)? Once we can freely access such data, will our per-sonal genomes be like our faces and voices, which we expose? Faces and voices reveal large parts of our cul-ture, ancestry, health, age, emotions, and education. These are often the basis of life-altering decisions by oth-ers about us. Nevertheless, we tend to share them. For research, several groups have noted the disingenuous nature of implying anonymity to re-search subjects (even in “controlled-access” or “authorized-access” da-tabases). Such closed-access and proprietary datasets also restrict col-laborations, international grassroots participation and out-of-the-box ex-plorations. Arguments that people will not volunteer without mislead-ing assurances are becoming far less convincing as we watch the volunteer lists for fully open-access human re-search projects rapidly grow. nnn

George Church, PhD, is Professor of Ge-netics at Harvard Medical School, Di-rector of the Center for Computational Genetics, and founder of the Personal Genome Project.

Expect Changes: Genetics in 20 YearsWhatever is coming in the field of genetics, we can be sure of one thing: it’s coming fast. By GeorGe church


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 differ-ent than they were 20 years ago. Most of the changes have been in-cremental, 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 chromo-some structure is. That’s true of nearly every genome out there, and in fact there are still gaps in the hu-man genome.

The advent of next-generation sequencing has dramatically sped

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 togeth-er. That process has various labo-ratory steps and very complicated computational steps that are imper-fect, so you don’t get the whole ge-nome 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 break-throughs lately, but somehow we’ve got to get there, and hopefully with-in the next 20 years we will. If we come up with better technology to help us sequence the genome, hope-fully we’ll be able to sequence more genomes even faster—and they’ll be complete instead of drafts.

Discovering new genes:

We use a lot of indirect methods to try to figure out which parts of the

genome are the genes, so we’re con-stantly discovering new functional parts of genomes that are either genes or regulatory sequences that control genes; but it’s very piece-meal. 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 bet-ter 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 num-ber of human genes. So sometime, maybe in the next 20 years, we’ll ac-tually 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.

Some Assembly RequiredComputational biologist Steven Salzberg spoke with GeneWatch about the future of genome sequencing.


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 treat-ments 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

very quickly. And I don’t know how you do that—nobody knows.

Personalized medicine:

I think that individualized ge-nome sequencing and individual-ized 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

some extent. Whether it will be our whole genome or just parts of our genomes, we will have our own ge-nomes sequenced, and we will see that information used by our own health care providers.

I think it’s actually inevitable—20

When the Europeans first landed on the shores of North America, you can extrapolate: well, eventu-ally, 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.

Sequencing breakthroughs:

Whether we’ll be able to se-quence a new genome with a tech-nology 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 thou-sand base pairs at a time. If you had a thousandfold increase in that ca-pability, that would let you sequence and assemble a complete genome

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.


“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 chemi-cals 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 revo-lution. Our sequenced DNA was thought to hold the key to under-standing the onset of disease. Why are some children afflicted with autism? Why do some adults stop producing enough insulin? Why do some otherwise healthy individu-als 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 sequenc-ing will change medicine by reveal-ing the existence of a disease years before its onset or by introducing new therapies with the tools of mo-lecular medicine and stem cells.

The terms “gene-environment in-teraction” and “epigenetics” are now recognized as the clue to many dis-ease 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 ex-pression, 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.

On the website of the National In-stitute 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 environ-mental 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 fo-cused on the mechanisms operating at the molecular level. Thus, there is much discussion about sequenc-ing the epigenome to gain an un-derstanding of the genetic switches or to probe deeply into non-coding DNA for discovery of RNA sequenc-es 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 car-pets or plastic. The detoxification mechanisms of people vary widely. Without a sufficient quantity of en-zyme production, our bodies can-not break down certain chemicals fast enough before experiencing harm. If we expect to make any ma-jor 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 envi-ronmental agents. What we need is a massive effort to unravel the “gene-environment” interaction in disease causation. We have over 100,000 chemicals in current industrial use. Many of these chemicals were intro-duced into commerce without much toxicological evaluation. It takes be-tween 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 cost-benefit analyses before a chemical is removed from the marketplace.

The one area where there have been major contributions in deci-phering the gene-environment in-teraction is in the study of the ge-netic 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 chemi-cals have differential effects on dif-ferent genomes? How can we detect the detoxification potential of each individual toward a chemical? The

Toxicology in the GenomeScientists 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


associated with sensitivity and/or resistance to chemotherapy may be used to help provide more effective treatment.

Scientists have used genetic test-ing 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 metabo-lizes warfarin, and the Vitamin K epoxide reductase gene (VKORC1), has enabled more accurate dosing that takes account of the genome of an individual. Genotyping vari-ants in genes encoding Cytochrome P450 enzymes (CYP2D6, CYP2C19, and CYP2C9), which metabolize an-tipsychotic medications, have been used to improve drug response and reduce side-effects. Pain killers like codeine affect people differently. Tests for certain enzymes (P450-2D6) can determine whether some-one will be an ultra-rapid metabo-lizer of codeine, which could induce life-threatening toxicity.

If we can understand through cer-tain enzyme pathways that individu-als react differently to drugs and that some of us cannot efficiently metab-olize certain chemicals, why couldn’t we do the same for industrial toxins within the next 20 years? Once we learn that many people cannot de-toxify a chemical that bioaccumu-lates in their body, it provides new grounds for finding a substitute for that chemical rather than waiting a quarter century to complete hun-dreds 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.

with the human genome may have unintended consequences. Instead of banning the chemical, it may re-sult in a genetic classification of people—those hypersensitive to chemical X, those with peanut aller-gies, 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 mecha-nism 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 regu-latory mechanism for removing the chemicals from the environment.

Biomedical scientists have been able to titrate chemotherapy agents to individuals based on genomic in-formation. Gene expression patterns

differences in people’s ability to de-toxify a chemical may be the result of shorter genes coding for the rel-evant 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 noth-ing in direct-to-consumer testing kits that reveals the cause of any dis-ease 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 Cana-van’s disease.

Of course, a massive effort to determine how chemicals interact


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 includ-ing medicine, engineering, biology, anthropology and journalism. At the beginning of every semester I do a silly little exercise as a way of put-ting on the table all the romantic im-ages 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 ge-netics, whatever they draw is almost always relentlessly pre-modern: little men scurrying about with messen-ger bags; “a womb inside each cell”; mini-drones circulating just beneath the skin; “a golden fully-formed-but-microscopic Me, floating in the tho-rax”; 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 secu-larly 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 fil-ters 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 taxono-mies will chart through the genetic

forest, the mind-maps their nomina-tions 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 mira-cles. We will have access to our far-thest ancestral links. Governments, schools, employers and corporations will have access to our farthest ances-tral links as well. Recombinant and synthetic biology will revolutionize our conception of reproduction and the life cycle itself.

That said, the little gallery of draw-ings 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 possibili-ties will give new meaning to the ex-pression “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-as-product will be vexed; for if medi-cal research is ostensibly the driver of many recent genomic discoveries, the designated funding behind that research surely exists in ambiguous tension with corporatized pharma-ceutical 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 hu-manity 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, hu-bristic risk disguised as “progress,” mutilation masquerading as “im-provement,” or eugenics doing busi-ness 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.”

The Genomic ImaginaryAs 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


The Tree of LifeAdvances 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 biol-ogy 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 di-rectly benefit from the advancing tech-nology. 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 infor-matic 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 foun-dation for all of biological science.

Officially, there are 1.7 million spe-cies of organisms on this planet. By of-ficially I mean “named”. A named spe-cies 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 arthro-pods (insects, crustaceans, spiders etc) would be the most speciose group of living things on the planet, strengthen-ing 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 mil-lions 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 per-spective if we looked at the diversity of


American Museum of Natural His-tory to have its genome sequenced as part of the process of accession-ing. My colleagues at the AMNH might think me crazy, but the reality is this goal will most likely be a real-ity in two decades. And in many cas-es 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 mu-seum 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 spe-cies. This is a daunting task that will be made simpler by the ability to se-quence whole genomes quickly and cheaply. While a DNA barcode sys-tem may not be in the cards in the future, The Tree of Life will be a real-ity 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 capabili-ties 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 co-director of its molecular laboratories and a member of CRG’s Board of Directors.

“New techniques and new approach-es 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 at-tempt 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 real-ity, and that human variety does indeed have biological underpinnings, it is im-portant to realize that those biologi-cal foundations are both transitory and epiphenomenal. Despite cultural barri-ers 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 con-structs ever more at odds with real-ity. Increasingly, it seems, we are simply who we think we are.”

- from Race? Debunking a

Scientific MythBy 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.

Race? Debunking a Scientific Myth

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 ex-tinct, the immensity of this diversity should be more than evident.

To demonstrate the utility of a DNA based approach to classify-ing 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 mitochondri-al genome for the past decade. This project, while seemingly simple in its design, is an important one. Mostly because it will gather together tis-sues, 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 bio-logical, forensic and conservation re-search. Many initiatives have strived toward a centralized repository for the biodiversity of this planet and have failed. One of the major suc-cesses of CBoL doesn’t concern the progress they have made (they have close to 1,500,000 reference sequenc-es in their databases and this covers about 150,000 named species), nor that the DNA barcode sequences will be useful, but rather they have dem-onstrated that the infrastructure for such an initiative is possible and nec-essary for its utility.

What the advances in genetic technology also mean is that any specimen collected or used by a sci-entist 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 sci-entist to see every specimen that is accessioned into our collection at the


Synthetic biology is a collection of techniques, and research and busi-ness agendas, that includes the con-struction of DNA sequences that encode protein or RNA molecules which assemble into macromolecu-lar complexes, biochemical circuits and networks with known or novel functions; the substitution of chemi-cally synthesized DNA or DNA ana-logues for their natural counterparts in order to change cell behavior and/or produce novel products; and at-tempts to define and construct basic living systems from minimal sets of molecules.1 Synthetic biology has been termed “extreme genetic engi-neering” 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 in-dividual genes.

Although production of new kinds of fuels and foods are the best-known, and potentially most lucra-tive, programmatic objectives of syn-thetic biology, the field’s visionaries and front men also have ambitions that have landed them in the pre-cincts 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 reen-gineer 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

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 eugen-ic 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 improve-ment. 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 riski-ness 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 organ-isms 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 improve-ments are more directed toward util-ity 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 ge-nome, 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 dis-posable 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 imple-menting such programs fall aside. Ex-isting 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 meta-phoric “lemonade” salvaged from the lemons of transhumanist experimen-tation. It is not clear who will make the cut of being human, who will not, and who will decide. But if begin-ning- and end-of-life controversies have been among the most divisive social issues up to the present, the implementation of the synthetic bi-ologists’ 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.

Meiogenics: Synthetic Biology Meets TranshumanismSome enthusiasts of synthetic biology envision technologies that would “improve” humans—and, perhaps, create useful “subhumans.” By Stuart a. neWman


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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 Com-mittee … 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 indus-try. 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

us the labeling that 80+% of the popu-lation 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 com-mitted to organizing and educating their communities.

Although we started as a grass-roots 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, farm-ers, activist organic companies, par-ent 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 pos-sibility of the company being sued. Within the last few months, Con-necticut and Washington have newly introduced labeling legislation. Den-nis Kucinich (D-Ohio), re-introduced three GE bills: H.R. 6636, the Geneti-cally Engineered Food Right to Know Act, H.R. 6635, the Genetically En-gineered Food Safety Act and H.R. 6637, the Genetically Engineered Technology Farmer Protection Act.

Things look promising, but in or-der for anything to be enacted, we need all hands on deck. One easy yet powerful thing to do is to leave a com-ment 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, al-though 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.

Labeling Genetically Engineered Foods in CaliforniaA grassroots call to action. By Pamm larry

Action item:


The key point of this article is that concepts reflecting, theories of, and methods purporting to provide support for genetic reductionism are egregiously flawed, counterfac-tual, and unequivocal reflections of scholarly failures. Evidence derived from evolutionary and developmen-tal biology, as well as from my own field, the study of human develop-ment 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 pro-vide 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 stud-ied was developmental psychology. This field was embedded in a Carte-sian world view. As a consequence, the field held as its core conceptual issue split conceptions of the world, such as continuity versus disconti-nuity, stability versus instability, and of course nature versus nurture, with

the latter issue cast in many ways, e.g., heredity versus environment, maturation versus learning, or na-tivism versus empiricism.1 The fact that these split conceptions were re-garded as reflecting the fundamen-tal conceptual issues of the field le-gitimated genetic reductionist ideas and rationalized as plausible theo-ries or approaches (e.g., behavior ge-netics, sociobiology, or evolutionary psychology) that claimed to explain how genes provided the fundamen-tal material bases of human behavior and development, and did so inde-pendent of fusions with the ecology or context of human development.2

However, today, developmental psychology has been transformed into developmental science. As rich-ly 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 de-velopment has evolved from being either a biogenic or a psychogenic approach to conceptualizing and studying the life span to a multi-disciplinary approach that seeks to integrate variables from biological through cultural and historical lev-els of organization into a synthetic, co-actional system.5 As such, re-ductionist accounts of development that adhere to a Cartesian dualism, and that pull apart facets of the in-tegrated developmental system, are rejected by proponents of relational developmental systems theories6 and, as well, by evolutionary biolo-gists who embrace integrative, biol-ogy-context ideas as pertaining to

both phylogeny and ontogeny.7 For instance, while gene structure, func-tion, and selection constitute one dimension of evolution, epigenesis, the behavioral actions of organisms, and culture represent three addi-tional 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 multi-dimensional and integrative view of ontogeny as being constituted by four integrated dimensions. That is, and reflecting a new way of concep-tualizing the links between ontoge-ny and phylogeny,9 there is evidence that gene structure and function across ontogeny involve mutually influential relations with a cultural-ly- 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 cogniz-ing 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 (epi-genetic) characteristics over the life span and across generations.

Genes within the Developmental System

Reflecting this four-dimensional view of ontogenetic change, Char-ney points to how the contemporary scientific study of genetics is signal-ing not only a non-split approach to developmental science but, as well,

Developmental Science and the Role of Genes in Development: Ontogeny in Four DimensionsBy rIchard m. lerner

Academic paper:


differences in their overall content and genomic distribution of 5-meth-ylcytosine DNA and histone acetyla-tion, 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 epigen-esis and human development are provided by Lickliter and Honeyc-utt (2010). They note that evidence from developmental biology, neu-roscience, and developmental psy-chology contradict the ideas that “instructions for building organisms

reside in their genes, that genes are the exclusive vehicles by which these instruc-tions are transmitted from one generation to the next, and that there is no meaning-ful feedback from the environment to the genes.”12

Together, the evi-dence presented by Lickliter Honeycutt (2010), and by Char-ney (in press) and Fraga, et al. (2005),

among others13 create the basis for a true Kuhnian paradigmatic revo-lution.14 The findings presented by these scholars constitute anoma-lies (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 develop-mental systems theory and, consis-tent with Kuhn’s discussion of sci-entific revolutions, the very findings that are anomalies in (falsifications of ) genetic reductionist models (and

and third, they appear to play a critical role in development dur-ing the perinatal period, and in enabling phenotypic plasticity in offspring in particular.10

One striking example of the trans-formative role of epigenetic process-es in the development across the life span of phenotypic plasticity among siblings exists in regard to monozy-gotic (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 char-acteristics). Fraga et al. suggest that epigenetic differences between MZs may account for these instances of divergence across development. Ac-cordingly, Fraga and colleagues as-sessed global and locus-specific dif-ferences 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 epi-genetically indistinguishable during the early years of life, older mono-zygous twins exhibited remarkable

is tolling a death knell for genetic reductionist approaches such as be-havioral genetics. He says that:

The science of genetics is un-dergoing a paradigm shift. Re-cent discoveries, including the activity of retrotransposons, the extent of copy number varia-tions, somatic and chromosom-al mosaicism, and the nature of the epigenome as a regulator of DNA expressivity, are challeng-ing a series of dogmas concern-ing the nature of the genome and the relationship between genotype and phe-notype. DNA, once held to be the un-changing tem-plate of heredity, now appears sub-ject 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 mo-saicism is the nor-mal human condi-tion; and treated as the sole biological agent of heritability, we now know that the epigenome, which regulates gene expressivity, can be in-herited via the germline. These developments are particularly significant for behavior genet-ics 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 be-havior; second, they have im-portant implications for the va-lidity of heritability and gene association studies, the meth-odologies that largely define the discipline of behavior genetics;


emotion, ability, physiology, or tem-perament); 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. character-istics); in relation to what character-istics of the context (e.g., under what conditions of the family, the neigh-borhood, social policy, the economy, or history); are likely to be associat-ed with what facets of adaptive func-tioning (e.g., maintenance of health and of active, positive contributions to family, community, and civil soci-ety)? These multiple, nested sets of conditions indicate that each person should be studied as a unique indi-vidual, an idea that has been cou-pled with relational developmental systems theory-predicated method-ological innovations.22

The emergence of such meth-odological advances is important, given that addressing such a set of interrelated questions requires a systematic program of developmen-tal research elucidating trajectories across life of individual/context rela-tions within the developmental sys-tem. Moreover, the linkage between the ideas of plasticity and diversity that gave rise to this set of questions provides a basis for extending rela-tional developmental systems think-ing 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, suc-cessful development. Accordingly, employing a relational developmen-tal systems frame for the application of developmental science affords a basis for forging a new, strength-based vision of and vocabulary for the nature of human development and for specifying the set of indi-vidual and ecological conditions

analytic techniques from selections made by researchers using split or reductionist approaches to develop-mental science. Moreover, the em-phasis on how the individual acts on the context to contribute to the plas-tic relations with it fosters an inter-est in person-centered (as compared to variable-centered) approaches to the study of human development.19

Furthermore, the array of indi-vidual and contextual variables in-volved in these relations constitutes a virtually open set. Estimates are that the odds of two genetically iden-tical genotypes arising in the human population is about one in 6.3 bil-lion, and each of these potential human genotypes may be coupled across life with an even larger num-ber of life course trajectories of so-cial experiences.20 Thus, the number of human phenotypes that can exist is fundamentally equivalent to being infinite, and the diversity of develop-ment 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 conse-quence of health-supportive align-ments 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 rela-tions that may be characterized as healthy, positive, adaptive, or resil-ient – 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 ques-tion.21 They must ascertain: what fundamental attributes of individu-als (e.g., what features of biology and physiology, cognition, motivation,

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 de-velopment eschews Cartesian, split conceptualizations and, in turn, fa-vors post- postmodern, relational metatheories that stress the integra-tion of different levels of organiza-tion as a means to understand and to study life-span human develop-ment.16 Thus, the conceptual em-phasis 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 in-fluential relations between individu-als and contexts, represented as “in-dividual/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 “developmen-tal regulations” and notes that where developmental regulations involve mutually beneficial individual/con-text relations, they constitute adap-tive developmental regulations.18

The possibility of adaptive devel-opmental relations between indi-viduals and their contexts, and the potential plasticity of human de-velopment that is a defining feature of ontogenetic change within the relational developmental system, are distinctive features of this ap-proach to human development. As well, the core features of develop-mental systems models provide a ra-tionale for making a set of method-ological choices that differ in design, measurement, sampling, and data


The writing of this article was supported in part by grants from the John Temple-ton Foundation, the Thrive Foundation for Youth, and the National 4-H Coun-cil. 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 com-ments. Richard M. Lerner may be con-tacted at [email protected].

and cultural and historical onto-genetic system that constitutes the fundamental process of human de-velopment across the life span.

Given the plasticity of the rela-tional developmental system within which genes are embedded, a fi-nal split between basic and applied science may be overcome. We may be optimistic that the future of ge-netic research will be marked by new information about how we can promote epigenetic changes that enhance the probability of more positive development among all in-dividuals across the life course. nnn

Richard M. Lerner, PhD, is Bergstrom Chair in Applied Developmental Sci-ence and the Director of the Institute for Applied Research in Youth Develop-ment at Tufts University.

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 pro-vide 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 hous-ing 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-dimen-sional, and neo-Lamarckian system involved in evolution,26 genes are a plastic feature of the four-dimen-sional, epigenetic, action-oriented,

Stuart Newman, p. 31

1. Newman, S.A. 2012. Synthetic biol-ogy: Life as app store. Capitalism Nature Socialism, in press.

2. ETC Group. 2010. The new biomassters: Synthetic biology and the next as-sault on biodiversity and livelihoods. ETC Group Communiqué 104.

3. Newman, S.A. 2010. The trans-humanism 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

Richard M. Lerner, p. 34

1. For reviews, see: Lerner, R. M. (2002). Concepts

and theories of human develop-ment (3rd ed.). Mahwah, NJ: Lawrence Erlbaum Associates.

Overton, W. F. (2006). Developmental psy-chology: Philosophy, concepts, methodol-ogy. In R. M. Lerner (Ed.), Handbook of child psychology, vol. 1: Theoretical models of human development (6th ed., pp. 18-88). Editors-in-chief: W. Damon & R. M. Lerner. Hoboken, NJ: John Wiley & Sons.

Overton, W. F. (2010b). Life-span de-velopment: 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:

Greenberg, F. (2011). The failure of biogene-tic analysis in psychology: Why psychol-ogy is not a biological science. Research in Human Development, 8(3-4), 173-191.

Gottlieb, G. (1998). Normally occurring environmental and behavioral influ-ences on gene activity: From central dogma to probabilistic epigenesis. Psychological Review, 105, 792-802.

Overton, W. F. (2011). Relational de-velopmental systems and quantita-tive 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.

Endnotes


Lamb, M. E., & Freund, A. M. (Eds.) Handbook of life-span development, Volume 2: Social and emotional de-velopment (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 developmen-tal 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 varia-tion. 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 identi-ties: 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 sym-bolic 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 con-struction. 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 per-spectives 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 classi-cal 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 life-span development. Editor in chief: R. M. Lerner. (pp. 30-54). Hoboken, NJ: Wiley.

20. Hirsch, J. (2004). Uniqueness, diversity, similarity, repeatability, and heritabil-ity. In C. Garcia Cole, E. Bearer, & R. M. Lerner (Eds.), Nature and nurture: The complex interplay of genetic and environmental influences on hu-man 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, phi-losophies, 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, 198426. e.g., Gissis & Jablonka, 2011


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GeneWatch Vol. 25 No. 1-2