As part of its program, Berkeley offered students the option to participate in genetic testing for three common genetic variants relevant to the body’s ability to metabolize milk products, alcohol and folic acid. The University’s original plan was to allow students to elect to receive the results of their tests as part of the program. Two weeks ago, however, the California Department of Public Health (CDPH) ruled that if Berkeley wanted to return personalized genetic data to some of its freshmen, the testing must be conducted at the direction of a physician and performed by a licensed clinical laboratory. The significant logistical burden and cost of complying with the CDPH’s ruling forced Berkeley to modify its program. While some aspects of the program will go forward, no student will be able to access any personalized genetic information.

(CDPH’s ruling was unexpected. Berkeley’s Dean of Biological Sciences, Mark Schlissel, noted that the department’s ruling “relies on an interpretation of legal statutes that is entirely different from the interpretation of the same statutes by UC’s top lawyers.” The ruling itself has potentially significant implications for genetic research across the country, although that topic is the subject for a future post.)

The focus of this post is the rapid mobilization of critics of the Berkeley program and the power of public controversy to spur regulatory action and, ultimately, to force the University to adopt a fundamentally different approach to personal genomics education than originally intended. This in spite of a detailed internal review process that consumed substantial resources and required Berkeley’s Institutional Review Board (IRB) to approve the project. Examining how and why this happened is instructive for evaluating the future prospects of personal genomics research and innovation.

A Controversy Emerges. From the outset, a handful of bioethicists and public interest groups voiced hypothetical concerns about the risks of offering genetic testing to Berkeley’s freshmen. The Council for Responsible Genetics greeted the program’s launch with a letter to the University (pdf) that warned that genetic information “has the risk of being used out of context in ways that are contrary to the interests of the individual, perhaps even discriminatory and certainly privacy invasive.” Similarly, an article in The New York Times featured Boston University bioethicist George Annas, who posed the following hypothetical:

What if someone tests negative [for alcohol metabolization], and they don’t have the marker, so they think that means they can drink more? Like all genetic information, it’s potentially harmful.

Finally, the Center for Genetics and Society linked the Berkeley program to contemporaneous developments in direct-to-consumer (DTC) genetic testing, and warned that “students might think, ‘Berkeley gave it to us. It must be good. UC Berkeley would never be giving its incoming students anything bad or controversial.’”

In short order, what began as an innovative approach to introduce incoming students to genetics and personalized medicine by offering those students the opportunity to personalize their experience quickly became a controversy.

From Controversy to Regulation. Controversial educational initiatives are hardly new. Indeed, they are part of the mission of many institutions of higher education, including Berkeley. In responding to initial criticisms of the program (pdf), the University emphasized that “provoking a free and open discussion about issues surrounding genetic testing is an important aspect of educating our students to be informed citizens.”

Unquestionably, there is considerable value in subjecting all forms of innovation to close scrutiny. In fact, in any Common Rule-governed human subjects research, this is a requirement. Among the many criteria for IRB approval of a human subjects research project is the requirement that “risks to subjects are reasonable in relation to anticipated benefits.” The provision of informed consent is a separate, and similarly important, prerequisite to approval. Berkeley’s own IRB reviewed the University’s project, applied these and other statutory criteria, and ultimately approved the project.

Despite not being legally required to do so, Berkeley actively engaged with the program’s critics from the outset. A program that was vetted internally was now being vetted by the public, with the University’s active participation. In response to public feedback the University modified the project to clarify the project’s voluntary nature, the informed consent process and its separation from actual or perceived industry conflicts of interest.

Critics of the Berkeley program, however, were not satisfied. They continued to urge first the University and then California legislators to much more dramatically alter the program, or even to discontinue it entirely. The constant stream of criticism had an impact. Over the course of the summer, legislation was introduced that would have halted the program. That was followed by legislative hearings to debate the program’s merits and, ultimately, by the CDPH ruling that effectively ended the program in its originally-proposed form.

The rapid reaction of regulators to a debate that was largely driven, especially initially, by media reports, “expert” commentary and social media discourse was strikingly reminiscent of another mid-May personal genomics development.

The week before Berkeley’s program was announced, DTC genetic testing company Pathway Genomics and drugstore giant Walgreens announced a partnership that would have made Pathway’s consumer genetic test available through Walgreens’ stores. In Pathway’s case, the leap to controversy was even swifter: the initial story in The Washington Post describing the agreement warned of a “Pandora’s box of confusion, privacy violations, genetic discrimination and other issues.” Nonetheless, the end result was the same as regulators quickly stepped in and demanded changes. Rather than the CPDH demanding physician intervention and a clinical lab, in Pathway’s case it was the FDA declaring the product in question a medical device in need of a time-consuming and expensive medical device clearance or approval. In both cases, swift regulatory action effectively quashed the proposed activity.

Why Debating Personal Genomics is Difficult. Recent developments suggest that innovation in personal genomics is an increasingly difficult undertaking. In addition to the Berkeley and Pathway cases, examples include the FDA’s increased oversight of DTC genetic testing companies (in addition to Pathway), the GAO’s report on the perils of DTC genetic testing and, most recently, criticism of the University of Minnesota’s attempt to bring genetic research to the State Fair. Collectively, this suggests the emergence of a disturbing trend: developments in the area of personal genomics that deserve serious public debate are shaped from the outset by commentators, policymakers and lawmakers more concerned with making a point than with advancing the conversation.

Of course, it is hardly news that emerging areas of science and controversy generate controversy. In recent weeks, the safety and desirability of human embryonic stem cell research has sparked a heated public debate, just as it has at regular intervals for the past decade. The new dynamic facing personal genomics is the rapidity and ease with which any initiative may be branded as “controversial,” combined with the willingness of lawmakers and regulators to intervene directly and rapidly in such “controversial” activities. This may be as much a function of new paradigms in media, politics and public discourse as it is a function of personal genomics itself, but whatever the reason the concern is that it is having a chilling effect on innovation throughout the field.

On the commercial side, the effects of increasing regulatory uncertainty are evident, as businesses and investors are considering abandoning personal genomics or moving their operations – and attendant jobs and capital – overseas. On the research side, similar confusion – particularly in light of the Berkeley program’s fate – continues to discourage researchers from exploring innovative approaches that might help to accelerate our attempts to decipher genetic complexity and, ultimately, provide us all with more effective, less expensive health care.

Whatever the context, there can be no substitute for careful, public and reasoned debate when it comes to evaluating the appropriateness of a new personal genomics proposal. Similarly, there is no substitute for fully informed consent; for ensuring that all individuals – whether they are students, patients or consumers – understand the full extent of the risks attached to a decision to participate in a personal genomics activity. Both are critical in assuring that personal genomics is conducted in a responsible fashion.

But public debate and informed consent require more than an ability to enumerate hypothetical risks. When it comes to evaluating innovative personal genomics proposals, all of us – participants, funders (including taxpayers), media and commentators and, especially, policymakers and regulators – owe a duty to be thoughtful and balanced in assessing their merits. To be blunt, it requires all of us to do more than throw darts at the easiest targets.

This means understanding that it is not enough to simply enable public debate between those with opposing views on the merits of a particular project. It means recognizing that all innovation – scientific, technological, commercial, research, educational, etc. – carries with it a measure of uncertainty, but that uncertainty alone is an insufficient reason to slam on the brakes. It means acknowledging the difference between hypothetical or low-probability risks and actual, documented harms, and recognizing that the first step should be determining which is which. And most importantly of all, it means considering the benefits of innovation in personal genomics that accrue in addition to – and often because of – its risks.

This is not an easy task. Particularly in a field such as personal genomics, which is driven by new and often untested scientific knowledge and technology, it is trivial to examine a new idea and find something that could conceivably go wrong. Is it possible that a freshman tested for a genetic variant associated with alcohol flush reaction could interpret a negative result as a license to consume alcohol in excess? Of course it is possible, for the bar of “possibility” is exceptionally low. It is much more difficult to convert hypothetical risks into actual data on behavior (i.e., do individuals act to their detriment as a result of non-clinical genetic testing in general, and specifically in the case of the alcohol flush variant?), and more difficult still to balance such risks against the benefits of the same activity.

Keeping Our Heads. Realizing the promise of personal genomics will be impossible unless our society is willing to accept some measure of uncertainty and, yes, risk-taking. Our challenge is to figure out not only when the benefits of personal genomics outweigh its risks, but also who should be permitted to make that frequently difficult and personal risk-benefit decision, and in what contexts.

For those who would place that decision in the hands of individuals, there can be no question that we must first provide those individuals with the necessary information and perspective to make an informed decision. But the process of informing personal genomics participants – of informed consent – no matter how thoughtful and comprehensive, can only take us so far. The information will never be complete, the perspective will never be perfect, and the decision will never be without risk.

It is true, too, that there are many situations where society examines the risks associated with a particular activity and decides that they are simply too high – whether to the individual or to society as a whole – to be assumed, even knowingly and voluntarily, by the individual. We do not, for instance, let teenagers consume alcohol. We place restrictions on the acquisition or use of all manner of technologies, from automobiles to firearms. We require regulatory approval and a doctor’s prescription for most pharmaceuticals.

But as a society we also evince a deep respect for autonomy, leaving many risky decisions in the hands of individuals. The decision to drink alcohol or drive a car in the first place (assuming one is of legal age), to become pregnant (and even to terminate a pregnancy) and to provide informed consent to participate in scientific research: all of these decisions we leave in the hands of individuals.

We have not yet determined whether personal genomics is more like the decision to conceive a child– a personal decision free from state intrusion – or the decision to undergo chemotherapy – a personal decision highly regulated by the state. In a field with a landscape as diverse and rapidly-changing as personal genomics, the answer will frequently depend on context. Some aspects of personal genomics (e.g., genetic testing to determine a proper therapeutic treatment) warrant a greater degree of societal intervention than others (e.g., genetic testing to determine geographic ancestry).

The challenge is knowing where to draw that line. The risks posed by automobiles, firearms and pharmaceuticals are well-documented whereas, at least for the moment, the risks of personal genomics remain largely hypothetical. In the absence of clear data, the recent trend to deemphasize the benefits of personal genomics while focusing on its risks, and to use those risks as  justifications to shift control away from the individual, should cause us all to question whether we are drawing that line in the proper place.

If personal genomics is ever to live up to its name, at some point we must allow individuals – including the future leaders of our society, as embodied by Berkeley’s incoming freshmen – to decide for themselves whether and how to participate. To do otherwise, and to continue to aggressively criticize and thereby discourage personal genomics innovation in our zeal to render it a riskless enterprise, would be a mistake.

The research began two decades ago, ostensibly to search for a genetic variant that might be contributing to the increasing rate of diabetes in the tribe. The diabetes research proved unfruitful, but the blood donated by the Havasupai tribe members, and the DNA extracted from it, led to a number of follow-on research projects, grants and publications. It was that research – including searching tribe members’ DNA for variants linked to schizophrenia, and inferring the likely ancestral origins of the tribe’s founders – that led to lawsuits, millions in legal fees and, ultimately, the settlement.

Implications of the Havasupai Settlement. Harmon’s article provides a concise background to the dispute, and briefly describes the $700,000 settlement between ASU and the tribe to “remedy the wrong that was done.” Harmon and unnamed “legal experts” suggest that the settlement is significant because “it implied that the rights of research subjects can be violated when they are not fully informed about how their DNA might be used.”

In some respects, this is a trivial conclusion. One of the most important and well-known elements of the Common Rule – the regulatory regime that governs federally-funded human subjects research – is that researchers must seek, and participants provide, informed consent. Participants that are uninformed cannot provide valid consent and, thus, their rights as subjects are violated. In that respect, at least, the Havasupai case tells us nothing new. (I have not seen the settlement, but I doubt that it will (a) be made public or (b) contain an express admission of guilt from ASU, both factors that will limit its relevance to future similar scenarios.)

But the Havasupai case and Harmon’s article shine light on an important, and difficult, problem that continues to face scientific researchers, particularly those exploring human genetic variation: what does it really mean to provide “fully informed” consent for genomic research?

Fully Informed Consent? Looking at the text of the Common Rule, there are requirements that the researchers describe the nature and purposes of the research (§ 46.116(a)(1)), as well as both reasonably foreseeable (§ 46.116(a)(2)) and unforeseeable (§ 46.116(b)(1)) risks of participation. But the standard of informed consent that must be achieved is not explicitly spelled out. Is it “reasonably informed,” “substantially informed,” “fully informed” or something else altogether? (Interestingly enough, the language that Harmon uses – “fully informed” – does appear, but only in sections regarding research on pregnant women and fetuses, which is not applicable in this case.) Even if a clearer standard were articulated, how would researchers demonstrate that it had been satisfied?

The requirement of informed consent is part of the bedrock of modern human subjects research in the United States, and it is not going anywhere. In fact, the story of the Havasupai, as well as the tale of Henrietta Lacks (told so remarkably well in Rebecca Skloot’s new book) and other past failures of informed consent, suggest the informed consent requirement is here to stay, as well it should be.

A Difficult Balance. Yet, as we push forward into an era of large-scale, personalized genomic research, it is impossible to ignore the difficulties – legal, ethical and practical – that informed consent requirements impose. For example, truly informed consent for genomic research might require participants to possess a deep – or at least working – understanding of the underlying science. That sets a very high bar, and finding sufficient numbers of participants capable of providing such consent could restrict important research.

Even more daunting, however, is the difficulty of fully informing participants of the benefits and risks of participation in genomic research – particularly where the resultant findings could conceivably be linked back to the individual or, as in the case of the Havasupai, the individual’s community – when the researchers themselves lack this understanding. What genetic information can tell us about disease and other traits, and how this information can be used or misused in the case of individuals, is an area of continuing uncertainty. With the publication of the draft human genome sequence a decade in the rearview mirror, we know more than ever before. But there is still much that we don’t know.

Thankfully, new research models and strategies for seeking informed consent are being developed and tested. For instance, the Personal Genome Project (PGP) – for which I am an advisor, including with respect to the informed consent protocol – employs a model of “open consent.” The PGP focuses on preemptive and extensive risk disclosure, along with rigorous participant pre-screening to ensure that the risks of participation are understood. More broadly, the difficulties of informed consent and genomic research is an issue that the NIH is studying on an ongoing basis, with multiple internal working groups looking at different dimensions of the problem. Nevertheless, informed consent for genomic research poses a considerable challenge for policymakers, funding bodies, researchers and participants, and it is unlikely that any of the existing models represent a perfect approach.

None of this should be taken to mean that informed consent for genomic research is impossible. To admit that would leave us with the unenviable choice of sacrificing either the informed consent of participants or the valuable scientific research they enable. What the case of the Havasupai tribe does underscore, however, is just how difficult a task this is. It is clear that the next generation of personal genomics research will require more than purely scientific breakthroughs. We also need to think creatively about the ethical and legal framework in which such research is conducted, to make sure that it continues to promote scientific progress while protecting the participants – no matter what their background – that make such research possible.

All of this may seem to have little direct relevance to companies outside of biotechnology. However, the development of genetic knowledge and technology already has spawned new laws, regulations and patent uncertainties that impact almost all businesses in some way.

Privacy and Nondiscrimination. The federal Genetic Information Nondiscrimination Act of 2008 (GINA) represents the most comprehensive effort to date to regulate the use of genetic information. GINA initially only prohibited health insurers and group health plans from using genetic information to deny coverage or set payment rates. Another section, which just became effective in November 2009, affects all private and public employers with more than 15 employees.

GINA now prohibits discrimination against all employees and job applicants based on genetic information, prohibits the use of genetic information in making employment decisions, and strictly limits employer disclosure of genetic information. The EEOC anti-discrimination poster that is required to be displayed by all employers has been updated to include GINA.

A potential compliance trap in GINA is that it also restricts the collection of genetic information by employers. Genetic information includes not only actual genetic test results, but also family medical history that might show links to inheritable diseases. This has raised particular concern around wellness programs, and there is a limited regulatory exception for such employer programs if offered on a voluntary basis and if other specific requirements are met. The regulations are new and there is not yet any substantial enforcement history, so employers should exercise great caution in this area.

Health Care and Research. Health care providers are already very familiar with the Health Insurance Portability and Accountability Act (HIPAA) requirements of strict privacy protections for “individually identifiable health information,” which includes genetic information.

Medical researchers who work with genetic information are often subject to HIPAA and must also comply with the federal “Common Rule” which regulates human subject research. Genetic information has presented some unique regulatory issues for researchers because it can be more difficult to “de-identify” than other health information and it raises complex issues around obtaining the required informed consent of subjects.

Intellectual Property. Fundamental questions are currently unresolved concerning the protection of genetic-related intellectual property – especially patents. The legal and policy arguments about gene patents can be quickly summarized. On one hand, human genes can be considered “products of nature” which by law cannot be patented, and there also may be a basic moral objection to any individual or firm obtaining a patent (which is a legal monopoly) on a human gene. On the other hand, the Patent Office and courts have long allowed patents on genes that are isolated from their natural environment in the body. Gene patent advocates argue that no company will have the necessary economic incentive to develop lifesaving tests and treatments if the intellectual property the company creates—including isolated genes–cannot be protected.

The issue of whether isolated genes are patentable is before the federal courts in the Myriad case, which was organized by the ACLU to challenge Myriad Pharmaceutical’s patents on certain breast cancer susceptibility genes. On March 29, 2010 a US District Court granted summary judgment in favor of the ACLU side and invalidated the Myriad patents. This ruling will be appealed to the federal appeals court and the legal battle will continue, perhaps to the Supreme Court. A final ruling is still years away.

Meanwhile, there are other patent cases in the federal courts that may affect a number of businesses, including biotechnology. The Bilski case is at the Supreme Court and deals with the patentability of business methods – specifically, a method of hedging commodities risks. The decision in Bilski may have far-reaching consequences for patents on methods of analysis, data interpretation, and performing certain tasks.

On the regulatory side, an advisory committee to the Department of Health and Human Services has approved recommendations on gene patenting and licensing that have generated heated debate. Stay tuned to see if Congress can long avoid jumping in with new laws that will affect genetics-related intellectual property rights.

Editor’s Note: A slightly modified version of this column appeared last Friday in the Charlotte Business Journal.

Contributed by

In late February, the state of Texas incinerated 5.3 million newborn bloodspots.

The background – the Genomics Law Report has had several posts (here and here) about the ongoing situation involving 5.3 million newborn bloodspots in a state biorepository in Texas. Often referred to as “residual” bloodspots, these are the tiny dried bloodspots left over after states conduct mandatory screening for specified diseases. State practices regarding retention of the residual bloodspots vary widely, with some destroying them promptly and others storing them indefinitely. Where post-screening use of the bloodspots occurs, the most common use is for quality assurance and quality control of the screening tests. Some states also permit the release of small sets of bloodspots for research.

Any such research must be done in compliance with the federal Common Rule applicable to clinical research and HIPAA, the federal medical privacy law. To simplify these laws’ complex requirements – what researchers must do depends on whether the samples or information will be made available in an identifiable or de-identified form. If a researcher receives identifiable information, then informed consents, privacy authorizations, and Institutional Review Board (IRB) reviews are mandatory. If the researcher receives only de-identified samples or information, no parental consent or privacy authorizations are required, although some states, including Texas, still insist on IRB review.

In the case of Texas, newborn bloodspots were collected and retained since 2002, building up a repository from 5.3 million children. Between 2002 and 2009, the Department of State Health Service (DSHS) provided 8350 de-identified samples to researchers – 0.16% of the total samples available. DSHS did not obtain parental consent for the distribution of these 8350 samples, as it was not required for de-identified use, although it did conduct an IRB review for each project. The research projects included studying the genetic causes of deafness to investigating inherited immune disorders, as listed on a DSHS web page describing research disclosures and uses. In the very small number of cases where identifiable research was conducted (200 out of 5.3 million), the state obtained prior consent from the parents, as required by research and privacy laws.

As Adam Doerr discussed in a post on February 2, the Texas Civil Rights Project brought a class action against the state in March 2009 on federal constitutional grounds, alleging that the retention and use of the samples without parental knowledge or consent was an illegal search and seizure. The plaintiffs did not allege privacy law violations. Meanwhile, the state legislature passed a bill enacting an opt-out program applicable to babies born after May 2009. After the state failed to win a motion to dismiss, it settled the case with the plaintiffs in December 2009, agreeing, among other things, to destroy all bloodspots collected before the new opt-out law.

Allison Williams Dobson’s post on March 1 updated readers on the ensuing developments. A Texas news site reported that 800 samples had been sent to a federal Armed Forces mitochondrial DNA database used to help categorize the ethnicity of missing persons’ remains. Department emails revealed that the state had considered publicizing its agreement witha state university for the long-term storage of the bloodspots, but chose not to do so out of concerns about public sensitivity. The plaintiffs’ attorney, Jim Harrington, was furious, a key state legislator felt he had been misled by the omission, and sharp criticisms were traded among the attorneys on both sides.

The bottom line – the destruction of the bloodspots proceeded on schedule.

This unfortunate outcome represents an incalculable loss to the research community and, through their work, to the individuals and families who are waiting for breakthrough treatments for diseases. Realizing what a loss this would be if it couldn’t be prevented, an ad hoc coalition came together in January to try to reach a compromise solution and save the bloodspots. Genetic Alliance, a national nonprofit dedicated to advancing health through genetics, for which I serve as Senior Counsel, brought together privacy advocates, University of Texas researchers, prominent Texans, and technology companies that offer online consent management and biospecimen management services, to try to quickly craft a solution whereby the bloodspots could be saved and parents could be offered meaningful consent options. We fashioned a coordinated program involving not only parental consent tools but also public education on the medical advances that could be achieved if parents allowed their children’s blood to be used in research. The coalition was seeking outside philanthropic funding so that the state would bear no additional cost.

Somewhat surprisingly, we quickly succeeded in reaching preliminary agreement with the plaintiff’s attorney, who was amenable to amending the settlement to postpone the destruction of the bloodspots if progress was being made on a parental consent mechanism. Our team also had numerous encouraging conversations with key legislators who hoped for such a compromise. DSHS, however, declined to open the settlement and postpone the destruction, citing their concern that any further disruption might jeopardize the viability of the newborn screening program intended to protect babies’ immediate health. We were, frankly, hopeful that we might be able to persuade DHSH to change its mind.

But then the story about 800 bloodspots being sent to the federal forensics database ran online. Even though those samples were de-identified and sending them was thus permissible under privacy and research laws, the uproar that followed poisoned the atmosphere in Texas. Tempers flared, accusations flew, the blogosphere of people suspicious of government exploded, and in the words of state Senator Duell, “if there was any way the bloodspots were going to be saved, the whole thing fell apart at that point.”

What can we learn from this highly unfortunate outcome? Among the lessons is that when angry and anxious parents confront state health departments who are trying to run public health programs, we should not be surprised that the long-term interests of research and scientific advances are ignored altogether. Neither parents who would have wanted their children’s bloodspots to be saved and used in research, nor countless parents who are eagerly waiting for the discovery of tests and treatments for their children’s conditions, had any voice whatsoever in the litigation or the public policy decision-making. Likewise, researchers who could have defended the tremendous medical benefits expected from their research played no part. Decisions were made under pressure and stress that simply did not reflect a broad spectrum of society’s interests. In addition, this sad case reveals that the status quo of widespread public ignorance about newborn screening and residual bloodspot uses has a high potential for erupting into acrimony and ill-advised decisions. Ignoring parents’ desires for more knowledge and decision-making will continue to put these bloodspot biorepositories – a national treasure trove for research advances – at peril. Surely, we can do better than this.

As we discussed in A Closer Look at Biobanking of Newborn Blood Spots, states collect blood samples from most infants born in the United States each year, with the goal of detecting and treating a variety of potentially serious conditions. The Texas Department of State Health Services (DSHS) has been collecting newborn blood samples from babies born within the state since the 1960s. Texas currently tests for conditions including cystic fibrosis, endocrine disorders, fatty acid disorders, and others—28 disorders in all (pdf). At least some of the samples are apparently subjected to genetic testing for hemoglobinopathy, phenylketonuria, and galactosemia.

According to the complaint (pdf) filed in federal court in March 2009 by the Texas Civil Rights Project, the state began to retain the samples for research use in 2002. The five plaintiffs in the lawsuit were parents of children born in Texas, including one woman who was pregnant when the suit was filed. The defendants in the suit were the DSHS and its commissioner, along with Texas A&M University and several university administrators.

In response to the suit, the Texas legislature quickly enacted a law governing the collection of newborn blood samples. The new law, which went into effect in May 2009, provides that the DSHS “may retain for use by the department or laboratory genetic material used to conduct the newborn screening tests.” Parents are given the opportunity to opt out—they can ensure that the samples taken from their child are destroyed by filling out a “Destruction Directive” form (pdf). The new law also provides for de-identification of samples provided to researchers and oversight by an institutional review board.

The defendants claimed that these changes to Texas law made the suit moot—that the case no longer presented a valid legal dispute. In its order (pdf), the court rejected this argument because the new law did not address the blood spots already collected by the DSHS, including those allegedly collected from the plaintiffs’ children.

Having rejected the argument that the changes in the law meant that the suit should be dismissed, the court turned to the interesting question of whether the parents had the right to sue. To sue in federal court, a plaintiff must show “standing”—that he or she is the right person to argue the dispute before the court. Courts analyzing this issue focus on the question of injury—has the defendant caused an injury to the plaintiff that the court has the power to remedy? The question of injury often comes up in public interest cases, and especially in civil rights and environmental litigation. Here, the state claimed that the parents did not meet the injury requirement because the injury they claimed was “only conjectural and hypothetical,” relating only to the “potential for misuse of the blood specimens or ‘medical and genetic’ information contained in them.”

If the court had accepted this argument, it could have set a precedent¹ that would limit future litigation—it would be very difficult for a plaintiff in this sort of case to conclusively show that he or she was directly injured by a misused sample. The court rejected this argument, however, stating that there is “reasonable fear of the potential for misuse because of the continued storage of the samples.” If other courts adopt this standard, a plaintiff suing a laboratory or researcher would not necessarily have to show that his own sample was misused, only that his sample was part of the group of samples subject to misuse. With newborn blood spots—where state policy often requires sample collection from all infants born in the state—this requirement will be easy to meet.

Next, the court addressed the Fourth Amendment of the U.S. Constitution, the first of two federal constitutional theories argued by the plaintiffs. In general terms, the Fourth Amendment protects against “unreasonable searches and seizures” by the government. In their response to the defendant’s motion to dismiss (pdf), the plaintiffs argued that they did not “object to the state’s mandated newborn screening program so long as safeguards are in place to destroy an infant’s samples within a reasonable period of time.” What they objected to, they said, was “the secret seizure of the initial [newborn blood spot] collection as a continuing deprivation of rights” because the state did not have “consent to draw infants’ blood for indefinite storage and undisclosed research, and did so deceptively.”² Although the court did not fully resolve this issue, it did refuse to grant the defendants’ motion to dismiss the lawsuit, a decision that likely precipitated the settlement.

Plaintiffs’ second constitutional argument was based on their right to privacy and liberty under the Fourteenth Amendment. The court found that the plaintiffs stated a claim under the Fourteenth Amendment, assuming that the facts they claimed were true. Specifically, the court noted that the plaintiffs claimed that the blood spots “contain deeply private medical and genetic information, and were expropriated without knowledge or consent,” a claim that the court viewed as involving “bodily integrity.”³ The court also referred to plaintiffs’ claims that the protocols used by the Texas researchers were not consistent with federal protections for human research subjects under the Common Rule, including its requirements for informed consent. Like the Fourth Amendment decision, the court’s recognition that samples of genetic material involves privacy and liberty interests protected by the Fourteenth Amendment could be significant in future cases, possibly providing a form of constitutional protection in situations where the Common Rule may not apply.

Finally, the case is interesting for what it reveals about the interests at stake in civil rights litigation over genetic issues. Here, the plaintiffs and their civil rights lawyer sought to vindicate privacy interests related to their genetic information. They viewed the retention of the samples as government overreaching, as indicated by references to “Big Brother” and “the specter of a DNA data bank” in the Texas Civil Rights Project’s press release announcing the suit. By contrast, the state’s primary interest was continuing its work of screening newborn infants for treatable conditions. As the DSHS stated in its press release announcing the settlement, “settling this lawsuit is in the best interest of this program’s core mission to screen all newborn babies in Texas for life-threatening disorders.” Much to the regret of many researchers, neither party in the case had the primary goal of protecting the millions of samples scheduled for destruction for use in ongoing and future research.⁴

In July 2009, the American College of Medical Genetics released its Position Statement on Importance of Residual Newborn Screening Dried Blood Spots (pdf). In the statement, the ACMG describes opponents of research using retained newborn blood spots as “a very small but very vocal minority” with “arguments based on unsubstantiated and highly exaggerated privacy concerns.” As noted above, federal courts require parties to litigation to demonstrate an “injury”—a real stake in the outcome of a case. In future cases involving newborn blood spots, it will be interesting to see whether individual researchers or groups like the ACMG become more directly involved in such litigation. The result in this case—the destruction of millions of samples pursuant to a settlement agreement between two parties, neither of which was primarily interested in research goals—could well help support such involvement.

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¹Because this case was before a federal district court, it would not bind other federal courts in the same way that a decision in the U.S. Supreme Court or the Circuit Courts can. Nevertheless, district court decisions can be highly influential on other courts, especially when they deal with relatively unexplored legal issues, as this one did.

²The state also argued that all samples were de-identified of any connection to the donor before being used for research purposes. Although this point could impact the legal analysis, including requiring a court to opine on the effectiveness of de-identification as a technique for ensuring privacy, the proceedings never got far enough for it to be relevant.

³The right to bodily integrity, grounded in the Fourteenth Amendment, was a key part of the holding in the 1942 Supreme Court decision in Skinner v. Oklahoma. In Skinner, the Supreme Court held unconstitutional an Oklahoma law that permitted the involuntary sterilization of certain “habitual criminals.” (In the process, it also overturned the result in the infamous case of Buck v. Bell, which we previously discussed on the GLR.) In rejecting the Oklahoma law, the Court held that the power to sterilize can have “subtle, far-reaching and devastating effects,” especially in “evil or reckless hands,” where it could cause “races or types which are inimical to the dominant group to wither and disappear.” Accordingly, the court noted, a person sterilized by the state is a person “forever deprived of a basic liberty.” With this language, Skinner was the first step in the line of cases that eventually led to Roe v. Wade.

⁴Press reports do indicate, however, that the 10,000 to 12,000 bloodspots already released to some 35 different research projects can continue to be used under the terms of the settlement. The court’s docket does not contain a copy of the settlement agreement.

As the cost of generating genetic data continued to decline new companies brought new commercial offerings to the table, including whole-genome sequencing from Knome and, more recently, Illumina, and an increasing focus on the genetics underlying complex diseases and traits.

Recruiting Customers as Research Subjects

Even more recently a new dimension to the field of DTC genetics has emerged: Direct-to-Consumer research.  In May of 2008 23andMe’s founders laid out their vision for customer-driven research.  23andWe, as the company’s research arm is known, launched its first significant project in March of this year when, aided by financial support from Sergey Brin, the co-founder of Google and the husband of 23andMe co-founder Anne Wojcicki, 23andMe announced a large-scale study aimed at the genetic bases of Parkinson’s disease.  The study aims to recruit 10,000 patients with Parkinson’s disease to enroll.  Participants in the study will receive 23andMe’s services for $25, a steep discount from the going rate of $399.

And on Tuesday, 23andMe announced what it is terming the “Research Revolution, a community outreach program that empowers people to drive the direction of genetic research.”  In some ways this Research Revolution is genomic research meets American Idol, with the general public invited to vote by participating in the project and choosing from a list of 10 diseases to support.  (Participation costs $99 for a stripped-down version of 23andMe’s service that does not include several key features, including ancestry information, carrier testing and access to the underlying raw genetic data).

In return, 23andMe pledges to do research on any disease that enrolls enough patients to ensure a productive study.  23andMe scientists will collaborate with outside researchers who have expertise in the particular topics being studied.

Not to be outdone, several weeks ago TruGenetics entered the DTC genomics space for the low, low price of $0.  The catch?  Signing up to receive the free genome scan requires participation in the TruGenetics research database.  From the TruGenetics Terms and Conditions:

Research

Your questionnaire responses and genetic information will be used for genetic research. One of the main goals of TruGenetics^TM is to develop a unique research database for conducting genetic studies. Your decision to use TruGenetics’^TM services indicates that you are willing to contribute your questionnaire responses and genetic information to the TruGenetics^TM research database. This research database will be free of any information that can be used to trace this data to you. All of the data in the research database will be anonymized and analyzed in aggregate (as a group) so that no single individual can be identified through the research database. TruGenetics^TM may conduct this research, or may partner with another organization, including non-profit and commercial entities, to conduct research. TruGenetics^TM may charge a fee for conducting research using this database. This research may lead to publications that reveal the findings. These publications will not contain any information that can be used to identify you.

You will not benefit directly from contributing your information to the research database. However, important discoveries might be made through this research, and this might significantly help other people. If these discoveries are validated and accepted by the scientific community, we will provide you with this information as it pertains to your genes. This research may also lead to the development of a commercial product. You will not receive any payments if this occurs.

Existing Regulation of Human Subjects Research

Is soliciting consumers in an attempt to build an attractive or novel research database a viable business model for these companies?  Daniel MacArthur at Genetic Future has tackled this question several times (see here, here, here and here) and thinks that it just may be.  Viable or not, however, this emerging model — in which research and commercial activities are hybridized to the point where it may be difficult at times to distinguish profit-seeking from knowledge-seeking activities — is almost certain to attract to the attention of legislators and regulators if it persists.

Human genomic research regulation, as with all human subjects research, is informed by the societal response to the universally condemned research atrocities of the early 20^th century.  From Nazi Germany to the Tuskegee syphilis study, abuses of human research subjects led to the Nuremberg Code, the Declaration of Helsinki and ultimately the publication of the Belmont Report in 1978, which continues to serve today as the foundation for modern human subject research protections in the United States.  In 1991, more than a dozen Federal departments and agencies joined with the Department of Health and Human Services in adopting a uniform set of regulations known colloquially as the “Common Rule.”

Among many other functions, the Common Rule — as implemented and enforced by the Office for Human Research Protections (OHRP) — sets out guidelines for the review of human research projects by Institutional Review Boards (IRBs), including guidelines for determining which individuals should serve on IRBs, what types of research should (and should not) be approved for public participation and how to achieve informed consent from research participants prior to enrollment.

The activities of at least partially publicly funded genomic research projects such as the Personal Genome Project (PGP) or the Coriell Personalized Medicine Collaborative (CPMC) — which invite members of the general public to enroll in large-scale research studies that address many of the same questions as those posed by 23andWe and TruGenetics — are covered by the Common Rule, commercial genomic research projects such as those outlined by 23andMe and TruGenetics are not similarly covered.  (Research conducted by pharmaceutical, medical device and other companies subject to FDA regulation is subject to FDA human subject protection regulations that closely track the Common Rule).

That does not imply anything untoward about these emerging DTC genomic research projects.  23andMe provides a detailed Privacy Policy, Consent and Legal Agreement and Terms of Service that, collectively, serve many of the same functions that an informed consent agreement would serve in the academic research context.  In the Consent and Legal Agreement, 23andMe spells out its research framework:

Collaborative Research: 23andMe may enter into partnerships with other investigators and organizations — non-profit and/or commercial — that conduct scientific research. Prior to embarking on any such projects, 23andMe will establish a research advisory committee to guide such collaborations. 23andMe may grant researchers associated with partner organizations access to aggregated data from our database of genetic and other contributed personal information for specific research queries. 23andMe will only provide individual level data to external researchers upon individual consent from each customer. In addition, we will ensure that such research partners obtain clearance from institutional review boards, as appropriate, and agree to maintain confidentiality consistent with our privacy statement. Once information is shared with research partners, we cannot guarantee that it will be destroyed upon request.

The Terms and Conditions provided by TruGenetics serve a similar role, although they are not (as of this writing) as specific as those provided by 23andMe.

But as self-regulating entities, commercial DTC companies do not conduct their research with the same degree of transparency required of academic or governmental genomic research.  The composition of a “research advisory committee” or the specific nature of “partner organizations” (or other providers of research funding) is not necessarily public information, as would be required of more traditional research projects.

On the other hand, as businesses that routinely deal directly with consumers, research conducted by DTC companies may prove to have several distinct advantages over traditional research models, including a greater ability and desire to return research results to participants.  As Genetic Future puts it:

In order for academic consortia to pursue the 23andMe model, they need to be in a position to return comprehensive results from genome scans to their patients and controls. However, providing such complex information to a lay audience is extremely difficult, and probably beyond the means of most academic groups. That means (as I noted back in March) there’s a potentially massive possible market for 23andMe here in providing a mediation service for returning research data to patients, and for providing the resources required to keep participants engaged actively in the research community.

But regardless of whether companies like 23andMe end up being physically involved in this mediation process, I’d suggest that academics need to take heed of the model the company is pursuing. It’s likely that over the next few years the current model for returning research data to participants —  i.e. don’t — will become increasingly unpopular with potential research subjects, and indeed I’d argue that this model has always bordered on the unethical. Finding realistic ways of presenting large-scale genetic data to research participants is something that academic researchers will need to sort out soon, one way or another — and those that do it well, I suspect, will find it much easier to recruit and maintain their research cohorts.

Although regulated research projects like the PGP and CPMC have already begun to buck the trend by returning research results directly to participants (and in the case of the PGP, placing those results in the public domain as well), it seems likely that consumer-focused companies such as 23andMe will continue to be more adept at mediating the transfer of information between researchers and participants than the researchers themselves.  There are indeed good reasons to believe that DTC genomic research may be a key contributor to a “research revolution.”

The Future (Regulation) of DTC Genomic Research?

So what does all of this mean for the future of DTC genomic research?  Although the past twelve to eighteen months have seen legislators and regulators alike begin to turn their attention to the commerce of genetic testing and genomic sequencing, those discussions have typically focused on whether and how to regulate the provision of commercial services.  Comparatively little attention, if any, has been paid to the research efforts of DTC companies.

It’s certainly possible that companies like TruGenetics and 23andMe can build large customer-supplied research databases and contribute meaningful scientific research to the public at large while simultaneously policing themselves to ensure that, for example, participants provide adequate informed consent, research results are not compromised by conflicts of interest and research programs and models are vetted for scientific and ethical appropriateness and merit. 

But one thing is certain: if this new model of DTC genomic research persists and succeeds, it will draw considerably more attention from legislators and regulators in the not-too-distant future.