In Memory of Rick J. Carlson (1940-2009)

Rick_Carlson

I will miss Rick J. Carlson. News of his sudden death has me twisted in knots. Although I met Rick only 5 years ago, during this time he became a friend to me and one of my most valued advisors. What I’ll miss most about Rick are the excited phone calls once or twice a year, when he and I would take turns dumping our brains out about the shifting landscape of genomics and health policy. At the end of every call, we would promise each other to talk more regularly.

Rick liked to think big thoughts about the future of health care — far enough in the future that current rules of the system applied only loosely and where he had more freedom to think creatively and imaginatively about opportunities to effect positive change. He also was an expert of the hard realities facing our current health system and the difficulty of having anything turn out like you hoped it would. After all, Rick was one of the principal architects of the Health Maintenance Organization (or “H.M.O.”). When introducing Rick to others, I would always lead with this distinction, just to provoke his good nature (as others did too, I see).

This year, Rick was going to be a guest blogger here at TPG, with occasional pieces related to genomics and health policy. Rick proposed calling this blog series: “Where the Rubber Meets the Sky” (a tribute to Clem Bezold).

Although we were still in the process of editing his first installment, the essay is far enough along that it might be useful for a budding policy wonk out there somewhere and that would have made Rick happy.

Personal Genomics: public policy at the frontier of consumer markets in health care. By Rick Carlson

Context:

I first got interested in the consumer perspectives about genetics, while working on a Government financed “policy” research project at the University of Washington in 2004 when “retail genetics” was in its infancy. The study was designed to survey and discuss the arising markets and services such as ancestry and nutri-genomics web sites, and fledgling start-up’s like Sciona, and Great Smoky Labs, and the far more clinically rigorous, DNA Direct.

In the ensuing 4 years, the field, or market space, has rapidly expanded—and, changed. With increasingly powerful computational technology available, and private and public capitol flowing, the research that results is throwing off granular risk/reward data on human health that is spiking consumer, regulatory and policy interests, (spurred, as well, by widespread promotion of the concept of “personalized medicine”). And all of this, in spite of the very unimpressive and limited clinical playbook this research has actually given us.

To a degree, the rise of personal genomics markets, generally, is an outgrowth of rising consumer activism in health care under the rubric of “consumer-directed health care (CDHC). The policy objective is to increase the consumer’s investment if time, commitment to healthy living, and, most all money, into the health care system, the latter through steadily expanding cost-sharing by employers and payers. The long-term expectation (hope?) is that an educated, motivated consumer with “skin-in-the-game” will be more parsimonious in the use of scare health care resources.

The rise of consumer markets in genetics, however, is primarily due to a discernable increase in consumer interest in genetic information——expressed in equal measures of fear, apprehension and fascination. It seems as if nary has a day gone by without two or three, often breathless, discoveries of presumed genetic health and disease gene associations are being reported for everything from restless leg syndrome to breast cancer. Entrepreneurialism is alive and well too, with companies large, Microsoft, Yahoo, Google, WebMD and Revolution Health launching portal and search capabilities, and start-ups like23 & me, and Navigenics and deCodeMe—promoted as “personal genomics” companies.

At the same time, the almost sudden emergence of the personal genomics field is causing concern in clinical and regulatory and oversight circles, already troubled by the proliferation of consumer oriented web sites with arguably over-reaching claims.
(see, in particular, Hunter, Khoury and Drazen, “Letting the Genome out of the Bottle—Will We Get Our Wish?”, NEJM, Jan. 10, 2008, pp. 105-107).

The policy framework is best presented from these four perspectives

—-An Overview of the “personal genomics’ field;

—-Business and marketplace issues;

—-Policy issues (including bioethical concerns);

—-What’s next: looking ahead.

Part 1: Personal Genomics Markets

First, a distinction: the raw “genetic” data that companies like 23&Me is drawn from the same pool of data as does the research community, except, and this is the predicate of their positioning, the customer is provided personalized data from the rendering of a portion of their own genome (about 1% accounting for 95% or more of the genetic variation among us). The significant differences arise from how those data are characterized and “used”. Aggregated genomic data from gene-wide association studies are used by researchers to identify SNP’s that explain a sufficiently actionable amount of the variation in humans associated with health and disease status, and then, based on clinically acceptable genetic testing when available, determine what a specific patients response and/or susceptibility to a specific drug or disease might be. By contrast, personal genomic companies are promoting a service that allows a customer to “see” their own genome, and then guided by interpretative information, infer their own health status and/or susceptibilities to disease and/or capabilities and “store” their data securely with the company. Then, as tests become available the customer can be alerted that there is test available to “confirm” their arguable susceptibility and/or capability. These companies specifically disclaim that they are providing a health care or clinical service, admonishing their customers that they should seek the advice of a physician before making any health-related decisions.

The personal genomics market leaders deny that they are just selling “curiosity” to the affluent and worried well, arguing that individuals fortified with personalized data will be motivated to address and minimize controllable risk factors and hence prevent or at least slow the onset or progression of chronic disease. This is a provocative and promising premise, and may be right, but to date we have very little evidence to support it, acknowledging at the same time that we haven’t had enough experience with highly personalized risk information to know the likely answer.

2. Business and Marketplace Issues

Positioned in between conventionally available genetic testing through labs and physicians and the personal genomics frontier, are companies like DNA Direct. DNA Direct, as the exemplar in this sector, serves as a virtual delivery model for a set of genetic tests that have at least threshold evidence of clinical utility. The company provides consultation with genetic counselors, and focuses on developing proprietary tools for the interpretation of genetic risk data to the consumer. Though started as a pure direct-to-consumer offering, DNA Direct, and other companies in this business category increasingly look to a variety of payment models including referrals from physicians and genetic counselors, as well as third party reimbursement when available. This distinguishes these existing businesses from personal genomics companies, though; as the latter evolve they may compete in providing testing services.

Details aren’t yet available to accurately peg the business model for the personal genomics market. As it evolves, however, it appears to be premised on securing enough subscribing customers in order to develop or outsource a genetic testing service, and, further, by aggregating data serve as a data warehouse to which access would be “sold”. Beyond this, these companies intend to utilize their customer base, presumably on an opt-in model, to create social networking relationships, with the sites either supported by subscriptions or advertising, or both. These businesses have only recently been launched and they appear to be well financed with buy-in from tried and tested venture capital groups and, in the case of 23&Me, Google. But, to date there is little if any, marketplace data to support their business models.

Naturally, in any new market there are fundamental factors related to the success and prosperity of any type of business, but, of those, there are a few related to business of health care and the science of Genomics that are unique.

The health care community, particularly researchers and providers have already voiced criticism and will be highly skeptical. Public oversight and regulatory agencies will also be alerted. Some part of this is reflexive: many providers simply discount the ability of patients and consumers to either understand their health care needs or act responsibly when they claim to, and, sadly, perhaps we consumers haven’t given them good reasons to change their views. That said, a distinct business risk arises because the dim views of too many doctors can suppress the market.

Then there is the vexing nature of the underlying science and technology. To use a thin analogy, when selling a financial service the complexity lies in the instruments and tools based on tested marketplace and economic fundamentals, with the rewards going to those who execute effectively on those fundamentals. Conversely, in health care, and exceptionally so in Genomics, the complexity lies in the underlying fundamentals of the science—-and the science is a fast and moving target as Genomics health care further evolves. This dynamic creates at least two business risks: betting on the science to confirm the first impressions upon which the businesses depend, and understanding that good health is ultimately far more valued as a public good than financial rewards, and therefore, more protected.

Finally, there is the issue of whether pushback from payers and providers about driving inappropriate and unnecessary demand. Usually a solid sign of business success is the ability to prime markets and produce demand. In health care, however, driving demand is often when viewed as problematic, even superficial, or neurotic (except as practiced by physicians, when it’s called “medicalization”). If personal genomics company customers start showing up with their “genome chip” or print-outs in physician offices in any real numbers, the green eyeshade cost-containing forces will be aligned against them, and they can also count on Congressional hearings.

3. Policy Issues.

“The potential to discover what contributes to red hair, freckles, pudginess, or a love of chocolate—-let alone quantifying one’s genetic risk for cancer, asthma or diabetes—-is both exhilarating and terrifying. It comes not only with great promise for improving health through personalized medicine and understanding our individuality but also with risks for discrimination and loss of privacy.”, Science, Vol. 318, 21 December 2007, p1842.

The policy issues can be organized into four categories: clinical, bio-ethical/legal, regulatory and social.

Clinical: to clinicians, information that doesn’t lead to known and effective treatments and good outcomes of care lacks prima facie clinical utility, and could also cause mischief and misinterpretation through an unholy mix of slick marketing and gullible consumers. In particular, physicians are concerned about “false negatives”, especially worrisome if a consumer’s genetic profile inaccurately posits low risks for life-threatening and compromising conditions. This concern was recently heightened when a study of the reliability of lab results showed wide variation on reported testing results. (2006, Genentech)

A related concern is that for many consumers if their lab results do not appear to show them to be at elevated risk for a given condition they might falsely assume that they have “no” risk, and hence can neglect healthy behaviors .

Lastly, as the utility of genetic testing increases, especially with the rapid pace of diagnostic development underway, clinicians may sense competition and intensify calls for more stringent regulation. Physicians, among all health care professionals, can most effectively incite regulatory zeal.

Bio-Ethical/legal: a range of concerns arise for the bioethics community, from paternalistic—–harms outweigh benefits—- to dismissive—-can’t hurt/ variations on caveat emptor. The most frequently expressed concerns arise from fears that consumers at increased risk for a serious disease will either become fatalistic because they fail to apprehend that genetic data are inherently probabilistic (except for a few highly penetrant condition such as HD), or, conversely, may become neglectful of their health if their genomic profile is seemingly benign

Legal issues include, of course discrimination by employers and insurers on the basis of definable risk, an ever growing concern in the absence of Federal legislation, and related concerns about privacy if the information, There is to date, very little settled law with respect to the uses genetic information because the issues had only raised marginal concerns until just recently. One case, Abigail Alliance vs. FDA that addressed the rights of consumers to treatments even if experimental might have provided some clarity on these issues, but, on appeal to the Supreme Court, the Court declined to hear the appeal from the Circuit Court upholding the FDA’s position that the plaintiff’s did not have a right to access to unproven, un-approved medications.

Regulatory: Though there is on-going debate and discussion at the Federal level about strengthening the regulation of genetic testing, there isn’t yet a clear consensus. At root, the question is which model of oversight applies: will personal genomics markets be regulated as clinical services and hence fall under the scrutiny of the FDA, and state licensure requirements, or as a commercial concern regulated as a consumer information business like financial services where the issues of full and fair disclosure, protections again fraud and truth-in-advertising apply.

Social: genetic discrimination can be practiced by communities, and social systems, not just by employers and insurance companies, though its forms are different. Stigmatization has occurred because of presumed genetic defects and disorders, and is likely to intensify. Communities of the disabled are increasingly apprehensive about “biological” stratifications. And, finally, it is now being appreciated that much of our accumulating genetic information could lead us down one of the slipperiest of slopes if it becomes the fodder for engineering human perfection. (A very thoughtful and balanced discussion of many of these issues can be found in, Michel Sandel, The Case Against Perfection: Ethics in an Age of Genetic Engineering, Belknap/Harvard, 2007)

Ultimately genetic data alter our sense and that of others about our identities. These technologies are more culturally and socially disruptive than they are disruptive to business and economic models. Hence, personal genomics markets are fundamentally marked by uncertainty because of the disruptive nature of the products offered. Still, all the evidence points to a niche market, albeit a potentially lucrative one. Even if the price point for rendering a customers genome comes down, as predicted, to a $1000.00 in ten, or even five, years personal genomics markets are indisputably elite markets.

On the other hand, there may be social and health benefits may be worth waiting for—– —will giving people data personalized to their specific risks and capacities have a strong enough motivational effect to actually reduce their risk factors through lifestyle practices? We don’t have these answers yet because we haven’t studied the subject enough; in fact, hardly at all. But, if positive outcomes can be achieved through the use of highly granular and individualized data, it would be of even greater significance if those outcomes could counter, even offset, the heavy tolls of the diseases of civilization, as Dubos called them——-Diabetes, Obesity, cardiovascular conditions and Cancer—afflicting the developed world, and increasingly, the developing world..

4. A look ahead:

The prospect ahead for Genomics technologies is illustrates why Genomic has been called a “terrible gift” (Carlson and Stimeling, The Terrible Gift: The Brave New World of Genetic Medicine, Public Affairs, Perseus Books, 2003) The potential benefits are exciting and immense, but along the way, society will have to digest a stew of disruptive social, cultural and economic uncertainties. The opportunities for improved public health are increasingly evident. But, our social uncertainties are deep and linked to a fear of genies let out of bottles by excessive entrepreneurialism. Our economic uncertainties, on the other hand, arise out of the complexity of the underlying science and how to scale demand for first generation genetic service technologies that can only reach a short ways now, but, guided by cogent public policy, could eventually reach far.

Following the rise of personal genomics markets will start to give us some answers to these uncertainties.

/END

Interview with Robert Green about Presidential DNA

robert_green_headshot

Last week I featured a recent NEJM article by Robert Green and George Annas about presidential DNA and its role in public elections. Co-author Robert Green (pictured right) agreed to share more about his views on the issue, in the following Q&A:

TPG: Both presidential candidates released information about their personal medical history during the recent election. Why do you believe genetic information should be treated differently? Why is DNA exceptional?

RG: There is a great deal of debate about whether DNA information warrants the ‘exceptionalism’ that has attached to it. The risk information provided by most genetic tests is currently less specific than family history and other risk factors can provide, putting it squarely into the domains of disease risk that health workers regularly communicate to patients. When discussing common diseases, the “exceptionalism” of genetic testing is amplified by the incorrect public perception that most genetic markers provide highly predictive information, when in fact, this is true for only a few.
Yet for some situations, there are undeniably special features to genetic testing. DNA is a highly specific identifier for forensic purposes and the occasional revelation of non-paternity can create upheaval in families. Genetic tests for highly penetrant diseases may provide reliable predictive information far in advance of symptoms, and providing such information to one family member may inadvertantly provide it to another who does not wish to receive it. And in situations where highly penetrant disease information is available far in advance of symptoms, there is greater potential for both prevention and for discrimination or unnecessary psychological distress.
Since much of the aura of ‘exceptionalism’ surrounding genetic testing is a byproduct of misunderstood notions of determinism, some of it should fade and normalize as the population learns more about genetics in the coming decade.

TPG: Both Obama and McCain have potentially serious conditions in their family medical histories (prostate cancer and heart disease, respectively). Do you believe genetic information could have helped voters in the last election evaluate the health status of the candidates?

RG: Most of us would agree that health information is relevant to a candidate’s fitness for office, particularly an office like the Presidency. Therefore, health information that could affect fitness for office seems undeniably relevant to voter decisions. So while the public does not have a right to know every detail of a candidate’s medical history, those facts relevant to fitness should be public information. Health information related to fitness may be misunderstood, exaggerated or minimized and therein lies the problem. The public is not particularly skilled or rational at sorting out the probabilities associated with health risks from whatever source… be it prior illness, lifestyle habits like smoking, cholesterol levels, family history information or genetic testing results. In the last election, I do not believe that any genetic information currently available woudl have been sufficiently predictive to warrant sharing with voters. However, if a highly predictive genetic test for recurrence of melanoma were available, that would arguably have been relevant and thus, would warrant dislosure to voters.

TPG: In your article you argued that the fierce political environment that surrounds elections, combined with our limited ability to understand genetic information, might lead to “genetic McCarthyism”. Is this a temporary circumstance?

RG: As we pointed out, there is a clear potential that someone might try to use genetic markers to smear another candidate, particularly in the realm of behavioral of psychiatric genetics. Certain conditions, such as mental illnesses, are so psychologically loaded that such smears might even be effective, even if quickly countered by experts explaining the predictive limitations of the science. But as your question suggests, as the general population becomes more familiar with genetic information and the limitations and complexities of such information, there should be less of a potential for distortion. Whether you call it “Genetic McCarthyism” or “Genetic Swiftboating”, and whether it occurs in presidential politics or in other contentious situations (lesser elections, custody cases), all of us in genetics should be prepared for it and prepared to combat it when it occurs.


Green, Robert C., Annas, George J. The Genetic Privacy of Presidential Candidates. N Engl J Med 2008 359: 2192-2193.

Dr. Robert Green is a professor in the Departments of Neurology, Medicine (Genetics), and Epidemiology at the Boston University Schools of Medicine and Public Health.

Presidential DNA: Don’t Ask, Don’t Tell?

Millions of individuals in the United States will know something about their own DNA by 2012. Whole genome sequencing will no longer be the exotic luxury item it is today. Genome scans like those available now for a few hundred dollars will be dirt cheap, if not free. By almost all accounts, genetic information will be more accessible to more people in 2012 than it is today.

The next presidential candidates will face an electorate that is radically more conversant in and curious about DNA than ever before. We should reasonably expect that the presidential election of 2012 will include, for the first time, requests for candidates to make their genetic information part of the public record.

Should the candidates heed these requests?

In an article published today in the New England Journal of Medicine, Robert Green and George Annas advocate for the next presidential candidates to honor a “Don’t Ask, Don’t Tell” policy for DNA. If genetic information is invoked by either candidate, the authors argue, the outcome will almost surely be one of exaggerated claims:

“…in the world of inflammatory accusations and smears that characterize presidential politics, it would be easy to engage in what might be called “genetic McCarthyism” by implying that an increased risk of disease is more substantial than it really is.”

The issue of presidential DNA and who gets access to it, is here to stay. 2012 presidential hopefuls have a few years to work out their talking points.

What would your talking points be? Would requests for disclosure of genetic information affect your decision to run for public office? Could you imagine scenarios where genetic information might influence your decision to vote for one candidate over another?

This week I’ll be interviewing Robert Green to learn more about his views on the future role, or absence, of genetics in political campaigns. Comments are open.

Green, Robert C., Annas, George J. The Genetic Privacy of Presidential Candidates. N Engl J Med 2008 359: 2192-2193.

Parallel Dataverses: Doppelgangers in Medicine and Recreation

Dr. Egon Spengler: There’s something very important I forgot to tell you.
Dr. Peter Venkman: What?
Dr. Egon Spengler: Don’t cross the streams.
Dr. Peter Venkman: Why?
Dr. Egon Spengler: It would be bad.

Some regulatory regimes in the United States, like those in the state of New York, require laboratories that receive and analyze any tissue specimen for any purpose to adhere to standards of clinical medicine. The laboratories are, for example, required to follow quality measures defined by the Clinical Laboratory Improvement Amendments (CLIA). Furthermore, individual citizens are prohibited from ordering laboratory services directly. They must, instead, work through a state-appointed and licensed physician if they seek to obtain personal biological data.

This restriction does not depend on the intended use of the data. An individual who wants to have the DNA in their saliva analyzed for recreational purposes, like genealogy or ancestry or education, still must work through a physician.

This has resulted in the paradoxical situation of non-clinical, clinical genetic testing. “Don’t cross the streams,” Dr. Egon Spengler would say. Well, the streams are already crossed and its time, I think, to uncross them. Biological data for non-medical purposes needs a paradigm distinct from the medical domain.

Here are a few reasons why this proposal should be strongly considered:

(1) Physicians are overburdened as it is, there is no need from them to be involved in recreational activities like genetic genealogy.

(2) Ditto for governmental regulatory bodies that are charged with ensuring the quality and safety of medical products and practices.

(3) Autonomy of individuals is being restricted unjustly.

(4) Enforcing clinical standards on non-clinical activities puts an unfair burden on individuals who may want to specifically avoid clinical implications of genetic sequence data, which might include the discovery of a medically relevant genotype (e.g., male infertility and genealogy testing) and health insurance liabilities.

So, what do you think? Should uncrossing the streams be an initiative we support? What are other reasons why this may or may not be a good idea?

Disintermediation: Why Genomics is More Like Insulin Injections than Napster

Some are comparing the shake-up of business models in the genomics industry by DTC companies with the disruption of the music industry via P2P services like Napster, who radically changed how music was distributed. Seemingly overnight, the music industry felt they had been bamboozled and marginalized. Their role as the primary distributors, gatekeepers, and fee collectors of music had been challenged — and by a teenager! This made them very unhappy, to say the least.

Like Napster, the consumer genomics industry is a force of disintermediation. Access to personal genetic data no longer requires a trip to a clinic, or any face-to-face interactions with physicians or genetic counselors, as they have in the past. This makes the traditional medical genetics community very unhappy. Like the music industry, they do not want to be marginalized as distributors, gatekeepers, and fee collectors of genetic knowledge.

Some would argue that the analogy goes further: the ultimate fate of Napster will be the fate of consumer genomics companies. Napster was shut-down by court order, and later re-emerged with a more traditional model of distribution that re-inserted the intermediaries they famously had marginalized via P2P. Some believe its only a matter of time before consumer genomics companies are shut-down and are required to re-insert physicians and face-to-face counseling.

I disagree. The future of the consumer genomics industry is more likely to follow the path of insulin injections, than music. The reason is purely economic. To be sure, if diabetics needed insulin injections only once a year, rather than several times a day, physicians would still be in control of the syringe.

Insulin is both life-sustaining and life-threatening, depending on the dose. The risk that a diabetic patient might inadvertently kill themselves with the wrong dose of insulin is real. However, the fact that diabetics need injections on a regular basis, even several times a day for some, meant that doctors were out-of-the-picture. Self-injection of insulin by diabetics is so commonplace today, its easy to forget just how radical the practice of self-injection is, provided the dangers to the patient and the well-intended desire of the medical establishment to protect them.

We now accept the disintermediation of insulin injections without a second thought. Could it really be any other way? The same will be true of genomics. Although self-examination of biological data presents many risks to individuals, the expense of forcing people to go through gatekeepers and censoring data in the interest of protecting individuals from themselves will be too burdensome. An editorial in this month’s issue of Nature Biotechnology, sums this up nicely:

Faced with this huge expansion of data on ‘my’ health, it will simply not be affordable to maintain our dependence on medical gatekeepers, whether they are physicians or genetic counselors, without individuals taking a much greater responsibility for their own wellbeing. Whether the medical establishment likes it or not, it will be too cumbersome and too expensive to conduct personalized medicine if all diagnostic-to-therapeutic decisions depend on doctors…For personal genomics not to be stillborn, the medical community and regulators thus need to reevaluate their role as gatekeepers. Clearly, they need to be involved in the medical actions that might follow as a consequence of genetic or other diagnostic testing…But simply shutting down the whole direct-to-consumer gene testing enterprise because it departs from the traditional genetic testing paradigm of doctor ordered test will both retard progress and stifle investment in more advanced whole-genome sequencing technologies—technologies that have the potential to ultimately deliver the promise of genome-directed medicine.

Risks and responsibilities associated with self-management of genomic data will increasingly be transferred from physicians to individuals, as they were with insulin injections (and home pregnancy tests). The medical community and regulators will play incredibly important roles in genomics, but serving as gatekeepers to biological data is not one of them.

Editorial. “In need of counseling?Nature Biotechnology. 26(7):716. July, 2008.

Biocensorship for the Biocentury?

The freedom to explore one’s own biology, all the way down to the molecular level, should be among the freedoms we hold dear as individuals. I’m agitated that the censorship of personal biological data is being advocated as a reasonable course of action to reign-in the nascent consumer genomics industry. Self-examination should not require permission from any authority. We should protect the autonomy and integrity of individuals.

For most of human history, the ability of an individual to learn about their own body through self-examination was limited to little more than the five senses: sight, touch, hearing, taste, and smell. Modern technological advances have extended these natural abilities dramatically. Devices allow us now to see details about ourselves that were once low resolution, out-of-sight, or even unimaginable. Keychain widgets can dispense data on blood-alcohol levels. Joggers can monitor fluctuations in heart rate plotted against GPS-gathered data about their path, elevation, and pace. Diabetics can obtain instant glucose readings. Video games can track longitudinal BMI scores. Alarm clocks can monitor REM cycles and promise to wake their owners at a time when they are the most well-rested, the least sluggish, and still able to be on-time for the morning appointment.

The ability of individuals to obtain vast quantities of data about their own biology and environments is a new frontier. Most people are hardly aware the frontier exists at all. Only a handful of explorers have set-off into the deep data wilderness. Individuals who have access to biological data about themselves face certain risks. For example, the data might be cause for confusion or lead to actions that are regrettable. These risks are not unique to biological data. All data have the potential to be dangerous to those who choose to consume it. Restricting access to personal biological data under the premise that “data are dangerous” and people need blanket protection from misunderstandings they may encounter is tantamount to censorship.

The only reason more people are not outraged about this new species of censorship — biocensorship — is because the ability of individuals to obtain vast quantities of cheap data about personal biology and their environments is a new phenomenon. The introduction now of gatekeepers to “protect you” from your personal biological data would go largely unnoticed, at least for a few more years. Regulatory oversight of personalized medicine ain’t all bad. But, we should be careful not to hamstring the biocentury with biocensorship and be sure to protect the freedoms of individuals to examine their molecular selves.

See also, posts by Rob Carlson, Daniel MacArthur.

Free Personal Genome Activism goes International

Today GTO pointed to a new website advocating the $0 Genome Project. A WhoIs look-up shows the administrative contact for the various websites associated with this project to be the Korean Bioinformation Center (KOBIC).

The last major bid for a free genome project was made from California in September of 2004 under the banner of the CUVIGS Initiative, or Californians for Universal Voluntary Individual Genome Sequencing.

Without surprise, CUVIGS supporters looked to George Church for feedback (interview still available here). Snip from their news release:

Professor Church believes that the emergence of Californians for Universal Voluntary Individual Genomic Sequencing, which is trying to place an initiative on the California ballot that would provide public funding to increase the availability and lower the unit cost of doing individual genomic sequencing, “sounds like a wonderful initiative, very visionary of California to think of such a thing….If the people spoke out like that, it would be a historic moment.” He added that “it needs to be phased in carefully with lots of oversight.” He also supported competition between Massachusetts and California to see who could pass such an initiative first.

Now, it seems, we can add South Korea to the competition for free personal genomes.

If they were to exist, “free genomes” would be more equivalent to “free kittens” than “free beer” in terms of the responsibility needed. Free beer requires very little commitment, there are virtually no instructions for its proper use and it can just be poured down the sink if it is doesn’t meet expectations. George’s recommendation for careful oversight of any such project, would be essential.

Compelled Disclosure, Richard Nixon and your genetic information

In addition to the three general modes of sharing genetic information I described yesterday, there is another type of disclosure individuals considering personal genome sequencing should be aware of: compelled disclosure by subpoena.

For genetic sequence data to be useful, it will need to be shared with individuals, companies, or organizations. These individuals might take extraordinary care to maintain the confidentiality of this information and to be good data stewards. But, they might receive a subpoena that requests confidential records to be made available for a court proceeding. For individuals who are concerned about the confidentiality of their genetic information, compelled disclosure by subpoena should be considered a risk.

The good news is that subpoenas of medical research data about individuals who were promised confidentiality is uncommon. There are a few famous cases, one involved lawyers hired by tobacco companies to go looking for data about asbestos raising the chances of lung cancer in smokers. A subpoena allowed them to gain access to the confidential files of a Dr. Irving Selikoff, although the files were redacted to protect identities of research participants prior to (compelled) disclosure (a few details here).

Don’t get Dicked Richard’ed
So, what does Richard Nixon have to do with compelled disclosure? Interesting trivia mainly. The Supreme Court case United States vs. Nixon is typically cited by the courts as the precedent for supporting compelled disclosure by subpoena.

Endote: Boo Hoo
Incidentally, there is a very nice article in the New England Journal of Medicine about scientific researchers who get subpoenaed. The article is not open access, unfortunately, so you probably can’t read it without paying $10.

It has been at least a few months since my last mention of frustration about the lack of access to quality information for Joe Schmoes, like myself.

I get frustrated most when articles deal with issues that are of direct relevance to the general public and they are not accessible, like the article about subpoenas above. Clearly, this article should be of interest to researchers. But what about research participants? It is, after all, their data that is potentially at risk. Research participants should not be treated like cows and keeping them outside the tent of good scholarly work on matters such as this does just that. I say this with the utmost sincerity, I’m not a dogmatic jerk in real life.

My favorite example in the last few years was an article published in Science with a title that included language about the “need for public dialogue“. If you click on the link, you’ll see that the article is trapped behind a firewall. For public dialogue to occur, the public needs access to the article. No?

One of the things I look forward to the most over the next 10 years or so, and one of the reasons I’m so happy to be a part of the Personal Genome Project with its open-access and open source ethos, is increased public access to science and the scientists who produce it. Support open access.

This month I am doing an extended meditation about the risks of obtaining and sharing personal genome sequences. This exercise will be cathartic for me. Beyond that, I hope it may help to reorient the conversation about risks into something that one day might resemble practical guidance for individuals considering obtaining and sharing personal genetic information.

Expectation setting about the risks of obtaining and sharing genetic information

Imagine being given the job of writing a manual that describes the risks associated with driving. All new drivers will be required to read this manual before they get behind the wheel.

The publisher wants a manual that is both comprehensive and concise. So, great care will need to be taken about the number of words dedicated to each risk. Spend too much time writing about flat tires, potentially more significant risks may get glossed over.

By the way, the year is 1908 and the Model-T is just beginning to roll off the assembly lines. Few people in the world actually own their own vehicles, but expectations are that many people will want to learn to drive even if its only recreational. They may even own vehicles themselves one day (heck, there might even be a system of interconnecting roads one day).


Model T


 

Foreseeing the potential mass appeal of vehicular transport, the publisher has requested that the manual take into account not only risks that exist today, but treatment should also be given to potential future risks that may arise.

The value of this manual will depend on how well the author is able to match the content with the driving situations readers are likely to face. Are they driving in the mountains of Coroico or in conditions similar to those I’m facing here in Boston, which look something like this:

dangerous roads
(Photo by Shuck)

 

The value of the manual will also depend on the drivers themselves: their experiences, their level of knowledge, their particular type of vehicle, and their expected behavior on the road. Are they risk-takers?

risky drivers
(photo by zerega)

 

Risks may even depend on an individual’s belief system:

amish drivers
(photo by cindy47452)

 

Setting reasonable expectations about risk
What is obvious to us now is that any manual produced in 1908 about the risks of driving very likely would be completely irrelevant today, except for those of us who find historical minutiae to be of great entertainment value.

Do you think this manual would have included “road rage” or the dangers of text messaging while driving? (BTW, in 1908, the Western Electric number 317 magneto wall phone did not even have an interface for dialing numbers, let alone text…calls required a voice-based interaction with an operator)

So, any manual developed today about the risks of obtaining and sharing a genome sequence will have a limited shelf-life. A few risks may come to be recognized more or less as “eternal truths” that go hand-in-hand with genome sequencing, while others are destined to become historical artifacts.

To get started with this meditation about risks, I’m going to state the obvious. Talking about the risks of obtaining and sharing genetic information is difficult to do in absolute terms for at least three reasons:

1) Risks are contextual
2) Risk-taking preferences vary widely
3) Many risks are poorly understood or are non-obvious

This month I am doing an extended meditation about the risks of obtaining and sharing personal genome sequences. This exercise will be cathartic for me. Beyond that, I hope it may help to reorient the conversation about risks into something that one day might resemble practical guidance for individuals considering obtaining and sharing personal genetic information.

Risks of obtaining and sharing your genome sequence

The era of personal genomics will transform our notions of risk in many ways. In the realm of health and medicine, we will soon have much more specific information about our baseline risk for a health outcome, such as a disease or a pharmaceutical drug response, and how it is influenced by our DNA and modulated by other factors like physiology, lifestyle, and environment. At some point, we will have health risk profiles that prioritize and sort risks according to severity, immediacy, and whether effective strategies are available for managing them with pharmaceuticals, lifestyle modifications, or other medical interventions. There might even be a richter scale for genomics one day. This vision of the future is often referred to as “personalized medicine”.

Genome sequences are an important source of fuel for powering the engine of translational medicine and driving the transformation of how we understand and manage health risks. But before anyone can step on the accelerator toward personalized medicine, people need to be willing to actually obtain and share personal genome sequences. Without this willingness, personalized medicine faces an energy crisis – a shortage of genomic fuel – and may putter or stall. Where will this willingness come from?

Roadmap to Willingness
Unlike personalized medicine, which has a coterie of visionaries and an abundance of roadmaps, each with their own devotees, no “roadmap to willingness” exists as far as I can tell. So, how do we build one? What are the ingredients of a roadmap?

The same three ingredients are needed to get nearly any enterprise off the ground, as I heard recently in a wonderful talk by Doug Solomon of IDEO (here). They are feasibility, desirability, and viability. And you really need all three, having just one or two doesn’t cut it.

To get to willingness, personal genomics needs to be cheap (feasible), useful (desirable), and safe (viable). As far as I’m concerned, two out of three ingredients are in the bag. There are tremendously productive forces working to make genomes both cheap and useful. While personal genomics may not be fantastically cheap or fantastically useful at this moment, we’re on a clear path to get there (and quickly).

Google Chart API Venn diagram of the three ingredients for making personal genomics a smashing success
 

The ingredient that could use some serious inspiration is safety. After all, what should be sought is not a “roadmap to willingness” that is just blinky lights and siren songs, but a “roadmap for informed willingness” that includes well-marked signs, off-ramps, and rest areas (for slow drivers with small bladders).

Where the rubber meets the road
Some influential policy-wonks are still spending their energy questioning whether or not we *should* as a society be pursuing personal genomics at all. Then there are those who have gotten past that and take for granted, as they should, that large numbers of people will desire and seek personal genome sequencing. Yet, I still have the overwhelming sense that we are very much stuck in a stage of facile hand-wringing about the implications of obtaining and sharing personal genome sequences and that these activities tend to be more oriented toward sending people into some sort of existential apoplexy than they are a potential source of pragmatic guidance.

We are at the point in history where the rubber is about to meet the road for personal genome sequencing. So, I would like to advocate that we spend more time rounding out this roadmap. We should begin with a meditation about risk and consider the calculus an individual would need in order to weigh the tradeoffs between taking the personal genomics plunge right now or standing on the sidelines for another day.

The month of December I plan to focus my blogging efforts, nearing one blog post per day (assuming I’m not paralyzed by some existential crisis, fingers crossed), on my thoughts about the risks of obtaining and sharing personal genetic information. I hope you’ll join me.

P.S. The Venn diagram above was created on the fly via the recently released Google Chart API — an incredibly easy-to-use way to add graphic bling to any blog. Here is the coded URL, in case you want to play with the Venn Diagram on your own.

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