The GenDG (pdf) took effect early this year and, until recently, little news of its impact on German law, policy or business has made its way across the Atlantic. Last week, however, several prestigious German scientific academies released a report entitled “Predictive Genetic Diagnostics as an Instrument of Disease Prevention.” The “Academy Group,” as the report’s authors refer to themselves, consists of the Leopoldina, the Berlin-Brandenburg Academy of Sciences and Humanities and the German Academy of Science and Engineering Acatech. Astoundingly, according to a recent editorial in the journal Nature, the report is the first from the group in its 350 year existence.

While the Academy Group’s report “discusses all aspects of genetic testing of healthy individuals to prevent disease, including the medical, ethical, economic and legal dimensions of the issue,” it takes particular issue with the GenDG. In a press release announcing its report, the Academy Group characterized the GenDG as “out of touch with the latest technology, almost impossible to implement in clinical practice” and “in desperate need of amendment.”  The complete report (pdf) is available only in German, but the Academy Group’s summary and twenty-two recommendations (pdf) addressing both genetic testing and the GenDG specifically are available in English.

Reviewing the Recommendations. The Academy Group’s recommendations are informed by a fundamental belief that genetic testing should be focused on helping people “to remain healthy, to regain their health or, at least, to alleviate the consequences of illness.” Although the Academy Group briefly notes, later, that genetic testing “can be advantageous for the life planning of a person,” the clear focus is on clinical utility. Apart from genetic research, no meaningful value is ascribed to other uses of genetic testing and data that appear to have gained much more traction in the United States, the United Kingdom and elsewhere, including ancestry testing, self-experimentation and testing for medical conditions that possess personal utility even if they do not rise to the level of current clinical utility.

An Excess of Information. Another theme that runs through the Academy Group’s recommendations is a concern about an “excess of genetic information” generated by the increasing proliferation of genetic testing and, in particular, whole-genome sequencing. Although some may consider there to be no such thing as too much genomic data, the group’s concern is at least consistent with its core belief that genetic data is valuable solely to the extent of its clinical utility. Given that certain genetic data is acknowledged to be of limited clinical value for many individuals, at least as of today, the Academy Group sees such “excesses” as likely.

Despite its underlying concern about excess genetic data, the Academy Group clearly thinks the GenDG’s nearly complete prohibition on the long-term storage of genetic information takes things a step too far. The problem lies with §12 of the GenDG which requires, with very limited exceptions, the “immediate” destruction of genetic information after 10 years. The Academy Group’s recommendations encourage the GenDG to “take into account the aspects of long-term storage and subsequent analysis of the excess of genetic information” and, if adopted, would specifically remove the flat prohibition on storage of genetic information beyond a decade.

The group’s primary recommendation is reasonable: individuals should be allowed to decide, in conjunction with an appropriate healthcare provider, whether to (a) use such excess information in a specific manner (although no examples are provided), (b) destroy the information or (c) “save [it] for the time being in an unused state.” This would, in effect, allow the individual and her healthcare provider to determine what constitutes “excess of genetic information”, rather than continue the GenDG’s approach of statutorily determining non-clinical genetic data to be excess and thus not valuable.

However, the Academy Group’s recommendation extends only to individuals competent to make such a decision. Children or temporarily incompetent adults should not, according to the Academy Group, be given the option to use or seek to interpret any excess genetic information “because this would take the option of ignorance away from the examined person.” The Academy Group recommends that the information be “saved in a restricted form” until “competency is bestowed”—in the case of a child, at her 18th birthday party—at which point the individual would be allowed to decide for herself.

While the Academy Group’s recommendation with respect to genetic testing of children is more permissive than what appears to be allowed under the current GenDG framework, it is still at odds with practices in other countries where the genetic testing of minors for non-clinical purposes is not expressly prohibited.

Genetic Screening and Unintended Consequences. Several other Academy Group recommendations concern genetic screening at various stages, from preconception (carrier testing) to prenatal to postnatal (newborn screening). The recommendations are consistent with the fundamental approach of requiring testing to be related to medical treatment. This leads to the curious consequence of recommending limitations on testing of an unborn child but, once the child is born, encouraging genetic testing.

While the Academy Group recognizes that “healthy people or couples can be interested in finding out whether they are genetic carriers of any recessive hereditary disease…to assess the health risk of their own child,” the group believes that such carrier screening is not yet ready for widespread medical or commercial use. The group recommends:

For the time being, systematic heterozygote examinations with regard to the health risks for the children of the examined people should only be carried out as part of research projects. They should be embedded in secondary medical, ethical and social research in order to gain experience about the personal and social effects.

While numerous carrier screening providers offer services outside of Germany—both directly to consumers and through licensed healthcare providers—the Academy Group appears to have no interest in seeing Germany following suit.

The group’s recommendation, if adopted, could have the unintended consequence of promoting a new form of “medical tourism,” with some German couples taking a quick trip abroad (e.g., to the United Kingdom) for preconception carrier testing.

When the Academy Group turns to testing of newborns, it is critical of provisions of the GenDG that have the effect of discouraging or interfering with such testing:

The Gendiagnostikgesetz considers the newborn screening as a genetic survey. Accordingly, since the Gendiagnostikgesetz came into force, the parents must be provided with a genetic consultation before blood is taken. Baby nurses and midwives, who previously took the blood, are no longer allowed to do this on their own responsibility. There are already indications that this is leading to the newborn screening not being carried out for some newborn babies. This can lead to life-long disability, which could have been avoided with early diagnosis and appropriate treatment.

The Academy Group’s recommendation in response is sensible: the GenDG “should regulate the newborn screening separately” and, presumably, in a fashion that does not hinder the practice from occurring routinely.

Conflicting Duties. A consequence of the GenDG’s extremely patient-centered and protective approach to genetic testing is that, according to the Academy Group, “without exception” the GenDG “considers confidentiality for patients to be of a higher significance than the medical fiduciary duty towards relatives that have a high risk of developing” a genetic condition. Under the GenDG, doctors are strictly prohibited from discussing genetic information with a relative, even where doing so might have significant clinical utility.

The Academy Group recommends a change in the weighting of these competing duties, saying that “in cases of clear medical benefits” doctors be permitted to balance the importance of individual genetic privacy enshrined in the GenDG against the clinical utility of genetic information to an individual’s relatives. Interestingly, the Academy Group does not propose—as it does elsewhere—a specific modification to the GenDG to enable this exercise of physician discretion, and it remains unclear whether following the group’s recommendation would leave doctors on the wrong side of current law.

The difficulty of balancing the competing duties of individual confidentiality, particularly in the context of genetic information, and the broader utility of genetic information, particularly for an individual’s close relatives, is not a problem unique to Germany or the GenDG. The United Kingdom’s General Medical Council addressed this exact issue last year and reached a conclusion similar to that of Germany’s Academy Group. As this issue continues to show up in a variety of contexts, policymakers—and especially doctors—are likely to continue to struggle to strike the proper balance.

Direct-to-Consumer Testing. Unsurprisingly, the Academy Group’s recommendations also tackle the topic of direct-to-consumer (DTC) genetic testing, which remains one of the most hotly contested areas of genetic testing regulation and policy as we head into 2011.

As we noted last year, the GenDG arguably already prohibits all DTC genetic testing. Nevertheless, the Academy Group expresses concern about the “uncertain scientific basis” of DTC tests, as well as with the possibility of surreptitious testing. Seeking to make the GenDG’s likely DTC ban explicit, and consistent with the Academy Group’s emphasis on clinical utility in genetic testing, the group recommends that DTC tests “not be permitted because they do not fulfill the requirements of medical and ethically acceptable predictive genetic diagnostics.” (The Academy Group also offers a separate recommendation banning all DTC advertising for genetic tests.)

The unfavorable outlook of legislators and policymakers toward DTC genetic testing is hardly restricted to Germany. In the United States, a report issued by the Government Accountability Office (GAO) over the summer was sharply critical of DTC genetic tests—although critics of the GAO report’s methodology and conclusions abound—and the Food and Drug Administration (FDA) is preparing to regulate all laboratory developed tests (LDTs), including DTC genetic tests. (For a more complete overview see The Past, Present and Future of DTC Genetic Testing Regulation.)

A Global Perspective. Finally, the Academy Group exhibits at least a partial recognition that Germany’s approach to genetic testing may not be perfectly aligned with the rest of the world.

The Academy Group’s sixth recommendation acknowledges that German laboratories often receive samples from abroad and, were the GenDG to be strictly applied, it might operate to significantly curtail the foreign business of German companies in light of the substantial consenting requirements imposed by the GenDG (among its other provisions). In recognition of this issue, the Academy Group recommends that:

The genetic analysis of a sample acquired abroad by a German laboratory should be acceptable if the doctor that has sent the sample confirms that the person concerned has been provided with information about the being, scope and significance of the genetic examination in accordance with the legal regulations in the sample’s country of origin and the person concerned has subsequently granted his consent.

Quite sensibly, the recommendation appears to permit German laboratories to process samples for diagnostic testing if the submitting doctor verifies that the sample is being sent in compliance with the laws of the sample’s country of origin.

Note, however, that other restrictions imposed by the GenDG appear to remain in place. Given the broad limitations the GenDG imposes on genetic testing products and services, including on both the circumstances in which testing may occur and the type of analyses which may be conducted, it seems likely that, even if this particular recommendation is adopted, German laboratories and genetic testing providers will struggle to offer the same suite of products as their international competitors. If the Academy Group’s aim is to ensure that German laboratories remain competitive at the global level, its recommendations will likely need to be broadened.¹

Other Recommendations. The remainder of the Academy Group’s recommendations echo those made by the vast majority of policy groups to review the issues surrounding the development and adoption of genetic testing. These include a need for (a) more research into the genetic bases of complex traits and the cost-effectiveness of existing technologies and services, (b) more specialists in human genetics and more effective training in genetics for existing medical professionals, (c) a renewed focus on translational research and (d) improved public and educational outreach concerning the “possibilities and limits of genetic medicine.” All of these goals are laudable and, at this point, none are surprising.

What’s Next for Germany? It remains to be seen whether some or all of the Academy Group’s recommendations will be adopted by German lawmakers. Of particular interest are those recommendations that require, explicitly or implicitly, revisions to Germany’s just-passed GenDG legislation.

However, even if all of the group’s recommendations are adopted, GenDG will continue to stand as one of the most restrictive and, yes, paternalistic pieces of genetic legislation passed by any country to date. As other countries continue to grapple with how to appropriately regulate genetic technologies, including genetic diagnostic products, Germany’s experience with the GenDG may serve as a test case for one approach.

_________________________

¹ We are unaware of the effect, if any, that the GenDG is currently having on German biotechnology companies, entrepreneurs and investors, but would welcome feedback from our readers on this point.

We should first disclose that one of us (John) has a dog in this fight, albeit a small one. In 2003, (along with biologist and patent lawyer Roberte Makowski), John published an article in the Journal of the Patent and Trademark Office Society entitled Back to the Future: Rethinking the Product of Nature Doctrine as a Barrier to Biotechnology Patents (pdf). In that article, Roberte and John laid out an argument for challenging Myriad-style patents on “isolated” genes as claiming products that are only trivially different from the naturally-occurring versions. Judge Sweet cited this article and, in several parts of his opinion, followed the roadmap it created. So, if you oppose the Myriad patents, you’re welcome; if you like them, we’re sorry.

What Summary Judgment Means. As Dan noted, and John first wrote last fall, it is rare for plaintiffs to win on summary judgment. For either side to receive summary judgment, it must show that there are no disputed issues of fact that require a trial to resolve, and that, on the undisputed facts, the law mandates judgment in its favor. This standard is especially hard for a plaintiff to meet, since it bears the burden of proof at trial. At the summary judgment stage, a defendant can usually create an issue of fact and thereby avoid summary judgment just by saying “they have the burden of proof at trial, and a jury might not believe them.” Although this is an unusual case in that the basic facts—most notably Myriad’s patent claims and the fundamental biology and genetics that makes possible those claims—really are not in dispute, a summary judgment ruling for the plaintiffs nonetheless sends a clear message about how strong this particular judge thought their case was—and how weak he thought Myriad’s was.

The Road to Invalidation. The court broke Myriad’s patent claims into two major groups: (i) those claiming isolated DNA sequences and (ii) those claiming methods for comparing or analyzing gene sequences to identify the presence of mutations corresponding to a predisposition to breast or ovarian cancer (p. 2). Both sets of patents were rejected under Section 101 of the Patent Act, which enumerates the permissible categories of patentable subject matter: processes, machines, manufactures, and compositions of matter. As the judge noted, a long history of cases forbids claims on laws of nature, abstract ideas, and natural phenomena, which include products of nature.

Isolated DNA Sequences. The claims to DNA sequences in isolation were held to be insufficiently distinct from naturally occurring genes in the body—the product of nature version. This conclusion embodied several critical steps. First, the court emphasized that whether a patent applicant claims patentable subject matter is a free-standing inquiry, separate from the determination of whether the invention also satisfies the standards of novelty, utility, and non-obviousness. In other words (and contrary to arguments often made by patent lawyers), you cannot prove that something is a patent-eligible, human-made invention—and not a product of nature—by showing how new and useful it is. It either is patentable subject matter or it isn’t.

Having established this principle, the court went to assess just how different an “isolated” gene would have to be to avoid characterization as a product of nature. Myriad defined “isolated” in its patents as “substantially separated from other cellular components which naturally accompany a native human sequence [such as] human genome sequences and proteins” (p. 92). Myriad relied heavily on some cases going back to the early twentieth century—especially one involving purified adrenaline—to argue that this was enough of a difference.

The judge disagreed, strongly. He went back even further, to nineteenth-century cases involving line fibers and wood pulp, as well as later cases involving such things as pure tungsten, and concluded that “purification of a product of nature, without more, cannot transform it into patentable subject matter. Rather, the purified product must possess ‘markedly different characteristics’ in order to satisfy the requirements” (p. 121).

Not Markedly Different. Myriad’s isolated genes failed this test. In his search for “markedly different characteristics,” Judge Sweet focused—and this is the most radical part of the opinion—on the critical functional property of a gene, whether in the body or in isolation: its ability to carry the information sufficient and necessary to code for a protein.

DNA represents the physical embodiment of biological information, distinct in its essential characteristics from any other chemical found in nature. It is concluded that DNA’s existence in an ‘isolated’ form alters neither this fundamental quality as it exists in the body nor the information it encodes (pp. 3-4).

And again:

In light of DNA’s unique qualities as a physical embodiment of information, none of the structural and functional differences cited by Myriad between native BRCA1/2 DNA and the isolated BRCA1/2 DNA claimed in the patents-in-suit render the claimed DNA ‘markedly different.’ This conclusion is driven by the overriding importance of DNA’s nucleotide sequence to both its natural biological function as well as the utility associated with DNA in its isolated form. The preservation of this defining characteristic of DNA in its native and isolated forms mandates the conclusion that the challenged composition claims are directed to unpatentable products of nature. (p. 125).

Why is this so radical? Since the inception of gene patenting a generation ago, patent lawyers have taken the position that genes are just chemicals. Their information-carrying function is irrelevant to their patentability, the lawyers say. Because genes are chemically different in isolation, at least in a literal sense, they can’t be considered products of nature. The USPTO and the courts, including the Federal Circuit (the patent court of appeals), have uniformly acquiesced. Now a federal court has said that, no, genes aren’t just chemicals—precisely because they carry information. Genetic exceptionalism has become a principle of law, at least in Judge Sweet’s court.

Next Go the Process Claims. Myriad’s process claims got even less respect. In just a few pages, out of 156 in total, the court concluded that they all failed the Federal Circuit’s “machine or transformation” test for method claims. (This test comes from the recent Bilski case. Although the Supreme Court will soon issue its own opinion in Bilski, the machine or transformation test is the law unless and until the Supremes order otherwise.) Judge Sweet found that none of the methods were tied to any particular machine, nor did they bring about a tangible transformation of anything. Rather, “because the claimed comparisons of DNA sequences are abstract mental processes, they also constitute unpatentable subject matter” (p. 4).

Judge Sweet also added that, even if the claims were construed in such a way that they constituted “physical transformations associated with isolating and sequencing DNA, they would still fail the ‘machine or transformation’ test under §101 for subject matter patentability.” (p. 147).

Taking it to the Next Level. Where do we go from here? Myriad will surely appeal to the Federal Circuit (it has a right to that appeal), a process that could take a year or more. It is possible that the District Court’s judgment invalidating the Myriad patents will be stayed, or suspended, during that appeal. Judge Sweet’s order will not affect any patents not directly involved in the case, nor be binding on any other court, and it is highly unlikely that the USPTO will change its gene patent examination standards just because of this decision.

Then it will be up to the Federal Circuit. Our initial guess is that the court will end up affirming Judge Sweet on some or all of the process claims, but will cut way back on his broad attack on gene patents. But that decision is way down the road and, of course, will be informed by what the Supreme Court decides to do with Bilski. Even farther down the road is an appeal from the Federal Circuit to the Supreme Court, where all bets would be off.

To summarize, as breathtaking as this opinion may be, its legal effect is currently very limited. Another federal district judge would be free reach exactly the opposite conclusion tomorrow (if another comparable case were pending, which it isn’t). Things won’t get serious (legally) until the Federal Circuit rules, since its opinion will bind all federal courts except the Supreme Court.

Practical Implications. With the decision only hours old, the headlines are already starting to roll in. “The End of Gene Patenting?” “Judge Rejects Patents on Genes.” “Judge Nullifies Gene Patents.” While it is clear that this decision is headline news, it is equally important not to overstate either its legal significance or its likely practical effect. The limited legal reach of the opinion—unless and until it is upheld by a higher court—has been discussed above. Less certain is its practical effect, including how businesses, clinicians and patients may change their behavior in response to the ruling.

As a recent report on gene patents (pdf) from the Secretary’s Advisory Committee on Genetics, Health and Society (SACGHS) emphasized, the existing gene patent landscape has created considerable uncertainty as to how and by whom many genetic and other diagnostic tests may be performed. That uncertainty prompted SACGHS to recommend a pair of exemptions from patent infringement liability: one for genetic testing for “patient care purposes” and another for the “use of patent-protected genes in the pursuit of research.”

It would, of course, be incredibly risky to rely on the SACGHS recommendations—which are only recommendations, and not binding law—to justify otherwise infringing activities for, as we wrote last month, there is a very long road from advisory committee recommendation to Congressional legislation. Similarly, it would be mistake to view a District Court decision as paving the way to ignore all of Myriad’s BRCA patents, let alone providing the ability to disregard gene patents more broadly. This opinion may stick, but it is at least as likely that it won’t.

Of course, just because something would be risky, legally speaking, does mean that it won’t happen. It’s within the realm of possibility that commercial or even non-commercial (e.g., academic or research) laboratories could take Judge Sweet’s opinion as an invitation to challenge Myriad’s monopoly of BRCA1/2 testing head on. (Isaac Ro and Jeff Ares, of equity research firm Leerink Swann, however, think that a commercial challenge would be unlikely to succeed (pdf) given the combined strength of Myriad’s current commercial position and its remaining, unchallenged BRCA patent portfolio.) Risky or not, there is a possibility that Judge Sweet’s opinion will prove in time to have let the gene patent horse out of the barn in a way that cannot easily be undone, even by a subsequent reversal at a higher court. For the moment, however, we do not foresee this decision producing any radical changes in commercial, clinical or other activity surrounding Myriad’s BRCA patents, or gene patents more broadly.

In the broader policy debate surrounding gene and biotechnology patents, however, this decision is the latest, unmistakable shot across the bow of gene patent holders, particularly those such as Myriad Genetics that have developed businesses around patent-protected genetic tests supported by exclusive rights in underlying gene patents. As we wrote last summer, and as the SACGHS report pointed out in detail, there is a coming crisis at the intersection of multiplex genetic testing and whole-genome sequencing and biotechnology patents, particularly gene patents. This decision is sure to intensify the public policy discussion surrounding the appropriateness of gene patents, and ratchet up the media and public attention paid to the issue.

But to what practical effect? It seems unlikely that this decision, at least for the moment, will make Congress any more likely to take up the Supreme Court’s longstanding invitation—recently reiterated by SACGHS—to sort out the whole biotech patent area. In fact, it might make legislators even more reluctant to act, on the (erroneous) assumption that the courts have everything under control. Biotechnology businesses and investors are similarly unlikely to use this decision as the basis for significant departures from their current approaches with respect to gene patents.

What everybody will undoubtedly be doing is waiting and watching, closely, to see what comes next. The patentability of genes—as well as the broader issues of biotechnology commerce and access to and development of genetic tests that today’s opinion touches upon—is an issue that has long demanded a clearer resolution. To that chorus of voices we can now add Judge Sweet in the Southern District of New York. This is an important step—but only a step—along the road to resolving that issue. Next stop, in all likelihood: the Supreme Court’s decision in Bilski.

For better or worse, that’s where the instructions ended. The invited contributors identified the ELSI of their choice and discussed (or not) their rationale for so selecting as they saw fit. In addition to refraining from substantive editing, we intentionally avoided coordinating commentaries. Although we encouraged independent submissions from a variety of contributors and deprived them of any advance knowledge of what others in the series would say, one of our hopes was that consensus would begin to form around certain key ethical, legal and social issues.

To some degree this occurred. In collecting the series for the convenience of readers who would like to have all of the contributions in one place (pdf), we have ultimately settled on six broad topic headings for the commentaries, which are preceded by Jason Bobe’s call to arms for a new generation of “genomic astronauts.” It’s Mine! focuses on the privacy, ownership and access questions that continue to swirl around genomic information. Personalized Medicine in the Real World is wide-ranging, with commentaries that examine existing societal, scientific and governmental barriers to the implementation of personalized medicine, and several that propose specific solutions designed to eliminate certain of those barriers. In Too Much Information, the commentaries return to data and consider how individuals, clinicians, researchers and, ultimately, society will assimilate the coming deluge of personal genomic information. Back to School features several commentaries that make the case that improved educational models are the key to realizing the potential of genomics and personalized medicine. The commentaries in No _______ Need Apply focus on one of the most oft-discussed risks associated with personal genomic information―genetic discrimination. Finally, our commentators take a look to the future in Testing the Limits?, examining issues of genetic testing, modification and exceptionalism.

Although we have presented the series using these broad headings, as we undertook the task of gathering the commentaries and attempted to identify cross-cutting themes and trends, we came to appreciate even more the value of the series. That is, the commentaries simply do not fit into neat boxes. That was probably to be expected, given the variety and thoughtfulness of our contributors and the breadth and uncertainty that continues to surround the fields of genomics and personalized medicine.

Despite our organizational efforts, each of our contributors could easily have his or her own topic heading. And more than anything else, the diversity of ideas and opinions expressed in What ELSI is New? is its most significant contribution. After all, our other hope for the series was that the broad range of contributors would hold up seemingly familiar issues in new lights and see new connections. They sure did.

Dan Vorhaus

Editor, Genomics Law Report

December 2009

Today brings word, via ScienceInsider, that the Border Agency is pulling back on its plans to use DNA and isotope analysis to evaluate the nationality of asylum seekers attempting to enter the U.K. According to ScienceInsider:

In a statement released this afternoon by the Home Office, which oversees the Border Agency, the department’s Chief Scientific Advisor Paul Wiles now says such evidence will be collected for later analysis of its potential but will not currently be used for individual case decisions.

As Daniel MacArthur points out at Genetic Future, while some of the initial outrage over the Border Agency’s policy may have been overstated, “the initial policy was still grossly premature” and the “Border Agency’s decision to take a step back and consider the implications before wading into the morass of genetic ancestry testing” is a welcome development.

On the one hand, the Border Agency’s rapid course correction demonstrates that not all government agencies are deaf to public criticism and that not all misguided uses of genomic data are malevolent or require a formal regulatory or legislative response. Still, it seems unlikely that this is the last that will be heard about the Human Provenance project, and even in the rear-view mirror this was an unfortunate episode. And it seems to me that the conclusion to last week’s article is as relevant today as it was then:

The coming weeks will likely see further focus on the details of the Human Provenance pilot project, and we hope that the project is quickly brought in line with scientific realities and rendered consistent with important ethical, legal and social principles. But over the longer term we hope that in responding to this unfortunate example of genomic data usage, legislators hold in check their tendencies toward paternalism and genetic exceptionalism and that law- and policy-makers continue to advance a pragmatic and measured discussion that recognizes equally both the risks and benefits of genomic data availability and that leaves open a path for genomic research and personalized medicine to move forward.

Science

Scientists are greeting with surprise and dismay a project to use DNA and isotope analysis of tissue from asylum seekers to evaluate their nationality and help decide who can enter the United Kingdom. “Horrifying,” “naïve,” and “flawed” are among the adjectives geneticists and isotope specialists have used to describe the “Human Provenance pilot project,” launched quietly in mid-September by the U.K. Border Agency. Their consensus: The project is not scientifically valid—or even sensible.

In addition to the feature article, ScienceInsider has also published a FAQ describing what is now known about the program as well as links to the underlying documents and expanded reactions from leading geneticists and isotope specialists.

The project is, as the name indicates, a pilot project, and one spokesperson described it as being “in its baby stages.” Still, as reported by ScienceInsider, the scientific community’s reaction to the program appears to be swift, unanimous and extraordinarily critical. Daniel MacArthur of Genetic Future has a slightly more measured take, expressing skepticism about the ability of the government agency to identify precisely an individual’s geographic ancestry based on genomic data and rightly pointing out that the “crucial issue is that it must be shown that the data are used in appropriate ways, and not given undue weight in making serious decisions about a person’s future.” That’s an issue that cannot be resolved until the Border Agency provides additional details on both its scientific methods and its utilization of the collected DNA and isotope data.

The near-uniform scientific skepticism that has greeted the announcement of the Human Provenance project suggests that we should not be surprised to see the pilot project substantially revised, or even scrapped altogether. But has damage already been done?

The issues of granting political asylum and the use of genomic data are both politically and socially delicate. So it is especially unfortunate when such hot-button policy issues arise in the context of a project that is scientifically so questionable. If those were the only dynamics at play the Human Provenance project would likely generate outsized social and media commentary, and quite possibly a significant legislative or regulatory response. But the timing is such that this development comes at a crucial moment for the field of genomics. At present, a delicate balance exists between genomic science—including the emerging fields of DTC genomics and personalized medicine—and the developing legislative and policy framework that will guide and govern the development and application of that science. And with so much genomic science and policy yet to be written, even minor developments produce outsized effects, which makes the potential consequences of the Border Agency’s project so worrisome.

To illustrate this point consider an editorial published this month in the journal Nature Biotechnology which argues that a greater balance is needed in the policy discussion surrounding the use and availability of genomic data; one that acknowledges the benefits and societal importance of such data alongside its inherent risks:

On its own, the sequence of letters in a human genome is uninformative. Its power for good arises only from associations with medical histories, behavioral characteristics, physical descriptions and environmental influences. Likewise, its capacity for ill derives only from the genome’s potential for providing pointers to human qualities that serve as the basis for discrimination and defamation already prevalent in our societies—sex and sexual orientation, societally defined ‘race’, age, physical and mental health, aptitude or suitability for athleticism or employment, and eligibility for health, disability and life insurance.

No one doubts that there are risks. But thus far discussion of the risks has dominated the debate over the use of DNA data. It is time for the debate to refocus on the benefits of data availability.

The question that should be asked is not “How can things go wrong and how can we prevent that?” [Answer: “in a myriad of ways” and “only with a great deal of contortion”] but “What is a necessary goal and how can we achieve it?”

To the list of iniquitous uses we may now add “national origin.” By appropriating genomic technologies in a questionable attempt at border control, the Human Provenance project has shifted the conversation from a prospective discussion of risk avoidance and mitigation to a present debate over whether the Border Agency’s use of genomic and isotope data analysis is ethically or legally appropriate, let alone scientifically valid.

On the one hand, actual misuses of genomic data provide an important reminder that the risks associated with that data are not always hypothetical. Informed consent agreements, for example, often provide detailed lists of potential risks that attach to genomic data, but for seriously considering such risks there is likely no substitute for seeing the data actually misused.

At the same time, there is real reason to worry that highly publicized controversial uses of genomic data will result in reactionary and protective legal, regulatory or policy responses, quite possibly to the detriment of clearly legitimate uses of genomic data. Moreover, programs such as the Human Provenance project serve to refocus the discussion of genomic data policy away from the benefits of data availability—or at least the balanced “discussion of the risks to an individual with discussion of how an individual might benefit” that the Nature Biotechnology editorial proposes—to a discussion focused solely on the risks and dangers.

From the Genetic Information Nondiscrimination Act (GINA) in the United States to the EU’s Directive 95/46/EC on data protection to Germany’s recently enacted Human Genetic Examination Act, where governments have tackled the issue of genomic data availability and usage, the results to date have typically been restrictive and proscriptive. This is a trend that, if allowed to proceed unchecked, threatens the future of genomic research and one which many scientists and policymakers vigorously oppose.

Which is why it is so surprising and disappointing to see the United Kingdom—the same country whose House of Lords delivered, mere months ago, a potentially seminal report on genomic medicine that advocated patience, improved educational initiatives and a wait-and-see regulatory approach to many aspects of genomic data use and research (including with respect to DTC genetic testing regulation and genetic discrimination)—jump the gun with a project as misguided and unscientific as the Human Provenance program.

As the Nature Biotechnology editorial concludes, “when it comes to exploring the basis of being human and moving toward the goal of genomic medicine, society needs to do more to provide personal incentives to those who choose to disclose their data, despite the risks.” A worthy and much needed call. But by evidencing such a lack of understanding of or respect for genomic data, the Human Provenance program thrusts the risks of genomic data—particularly its misuse by those in positions of authority—back into the spotlight and casts a deep shadow over the substantial benefits of improving genomic data availability.

The coming weeks will likely see further focus on the details of the Human Provenance pilot project, and we hope that the project is quickly brought in line with scientific realities and rendered consistent with important ethical, legal and social principles. But over the longer term we hope that in responding to this unfortunate example of genomic data usage, legislators hold in check their tendencies toward paternalism and genetic exceptionalism and that law- and policy-makers continue to advance a pragmatic and measured discussion that recognizes equally both the risks and benefits of genomic data availability and that leaves open a path for genomic research and personalized medicine to move forward.

There’s no need for me to dissect and evaluate the arguments against DTC genomics made in the article. That task has been ably carried out by Daniel MacArthur, Blaine Bettinger and Jens McCabe. And it’s worth mentioning that the Times’ DTC genomics coverage has been relatively rich and varied (see, e.g., the now infamous “spit party” coverage, 23andMe co-founder Anne Wojicki’s Q&A on the Freakonomics blog or Steven Pinker’s excellent piece in the Times magazine, “My Genome, My Self”).

I do want to weigh in, however, on the potential consequence of the paternalistic medical establishment viewpoint that is advanced in the Times article, which paints DTC genomics as an industry lacking in analytic validity, clinical validity, clinical utility and (in what was a new concept for me) “ethical validity.” In failing to acknowledge any of the benefits provided by DTC genomics (which MacArthur, Bettinger and McCabe all highlight), the Times article invites readers (including legislators) to plausibly conclude that a legitimate solution might be simplyto restrict the business of genomic interpretation to traditional medical professionals. This is, in fact, exactly what Germany is proposing to do on a national level, but this type of genetic paternalism—largely a byproduct of a genetic exceptionalism perspective—is an extreme position, with most legislators taking a more measured approach, at least to date.

There’s no doubt that there are substantial limitations to the services provided by DTC genomics providers, and it is important that those limitations be identified and presented to consumers, ideally by the companies themselves but, if need be, as mandated by regulation. But the services also have the potential to provide benefits to individuals, including the various forms of “personal utility” highlighted by the joint NIH-CDC workshop I reported on last month. Failing to recognize both that potential and the power of new technologies and business models to realize it risks turning our backs on just the kind of leading edge innovation that has created the potential in the first place. Regrettably, in assessing an issue that is all about the future, the Times’ prescription is entirely backward-looking.

Strict Regulation of Genetic Examinations

The Act employs the terms “genetic examination” and “genetic analysis” in most of its provisions and defines these terms so broadly (§ 3) as to admit some uncertainty as to what would or would not constitute a genetic examination or genetic analysis. The vagueness of the definitions is mitigated to a degree by other defined terms that clarify that the Act’s provisions on genetic examinations and genetic analyses apply, in fact, to such examinations and analyses for medical purposes or for determining descent. The Act requires that “diagnostic” or “predictive” genetic examinations be ordered and interpreted by medical doctors having appropriate training and conducted only by institutions having the appropriate accreditation (§ 7). Such genetic examinations and genetic analyses may be conducted only upon the express, written and informed consent of the patient (§ 8).

In seeking informed consent (§ 9), doctors conducting a genetic examination must offer the patient counseling services (§ 10) that include an explanation of possible medical, psychological and social risks of conducting, or not conducting, a genetic examination. Patients also have a right to elect not to know the results. Consent may be withdrawn at any time, including orally, and a patient may require that the results of his or her genetic examination, including an tissue samples, be destroyed (§ 12, 13).

Prenatal genetic examinations (§ 15) are limited to identifying treatable medical conditions “according to the generally accepted status of science and technology.” However, no prenatal genetic testing is permitted for medical conditions or illness that do not “break out” until after the age of 18. What constitutes the “generally accepted status of science and technology” (§ 23) will be determined using guidelines supplied by the 13-member “Genetic Diagnostic Commission.”

Non-Discrimination

With limited exceptions, the Act prohibits insurers (§ 18) and employers (§ 19) from demanding a genetic examination or the results of any previously conducted medical genetic examination. Insurers may request the results of previously conducted exams in the case of life, disability or pension insurance policies exceeding EUR 300,000 or that provide an annuity exceeding EUR 30,000 per year. The Act also provides an exception for occupational medical exams needed to assess genetic traits responsible for severe work-related health conditions (a provision that needs further regulatory clarification) (§ 20). The Act reinforces the prohibitions on requesting or obtaining genetic tests with a blanket prohibition on genetic discrimination by employers (§ 21). The Act contains an even more comprehensive prohibition (§ 4) providing that no person may be discriminated against or disadvantaged on account of genetic characteristics, or the genetic characteristics of a genetically related person, identified by a genetic examination. This latter prohibition is so broad as to be almost incomprehensible—taken at face value it seems to prohibit any genetic information from being used by any person in any detrimental fashion—and will require further elaboration by courts or regulators.

Direct-to-Consumer (DTC) Provisions

The requirement that any “diagnostic” or “predictive” genetic examinations be ordered and interpreted by medical doctors (§ 7), and the results disclosed to the individual only by the ordering physician (§11), means that any would-be providers of DTC genetic services will need to convince German regulatory authorities that they are supplying educational or informational products, and not clinical or medical services. One of the many uncertainties in reading the Act is whether whole-genome sequencing, which can yield both clinical and non-clinical information, would be prohibited unless ordered and interpreted by a medical doctor. Given the general tenor of the Act, prohibition seems likely.

Complicating matters further is a somewhat cryptic (either as written or as translated) provision of the Act (§ 6) that authorizes the Federal Health Ministry to restrict access to “genetic study materials” (an undefined term) for the conduct of genetic examinations to persons and institutions authorized to conduct such examinations. Possible restrictions could bar German residents from receiving or returning DTC sample collection kits or accessing information concerning genetic testing and genetic conditions directly from DTC companies such as 23andMe, Navigenics or Pathway Genomics.

Research and Other Exceptions

The Act does not apply to “genetic examinations and genetic analyses or the handling of genetic samples or genetic data conducted for research purposes.” Although the term “research purposes” is not defined, the exception (§ 2) appears to protect pure research and is reinforced by the fact that most substantive provisions of the Act apply to genetic testing for medical purposes. Similarly excepted are genetic analyses for authorized criminal procedures and in accordance with the Infection Protection Act.

Penalties, Future Regulations and Delayed Effectiveness

The Act contemplates that it will be fleshed out by future regulatory actions. It establishes a Genetics Diagnostics Commission that, in conjunction with the Robert Koch Institute (a German analog of the Center for Disease Control) will develop the regulations (§ 23). In addition, the Act becomes effective only in gradual steps (§ 27) that defer the effective date of most provisions until October 2009, 2010 or 2011. Interestingly, Section 6 of the Act, which authorizes the Federal Health Ministry to restrict access to “genetic study material” and appears targeted at DTC genetic testing services, is one of the few provisions given immediate effect. Depending on the violation, the Act provides for penalties of imprisonment up to two years and fines of up to 300,000 EUR per violation (§ 26).

An Extreme of the Spectrum

Germany’s Human Genetic Examination Act exists at a paternalistic extreme of the spectrum with respect to the regulation of genetic services and information, sharing that space with the similarly restrictive Norwegian Biotechnology in Human Medicine Act (pdf), both of which seem influenced by the Council of Europe’s Convention on Human Rights and Biomedicine. Elsewhere on the spectrum, the most comprehensive piece of U.S. federal genetic legislation, the Genetic Information Nondiscrimination Act (GINA), restricts use of genetic information by insurers and employers but leaves individuals free to use genetic testing services as they choose. Similarly, in the United Kingdom, the recent and widely-discussed House of Lords Report on Genomic Medicine advises the DTC genetic testing industry to adopt a voluntary code of conduct for assessing the clinical utility of its services and the need for associated genetic counseling.

The German Act, on the other hand, adopts an extremely protective, even fearful, view of genetic information as something so dangerous and private that the generation and disclosure of genomic data must be mediated solely through specially trained physicians, accompanied by psychological and social counseling, and subject to destruction of the data at any time upon the request of the subject individual. In addition to tightly regulating the doctor/patient relationship, the Act appears intended to outlaw (or at least highly restrict) DTC genetic testing services. One of the laudable purposes of the act, “to protect human dignity and to ensure the individual right to self-determination via sufficient information,” is belied by provisions of the Act that restrict the ability of individuals to access their own genetic information directly.

Assuming the legislation is enacted, there will be plenty of international observers tracking the consequences of Germany’s attempt to tightly control its citizens’ access to and use of their genetic information. Will DTC companies cease sending spit kits to German residents? Will German citizens seek genetic testing in less restrictive climes? Will Germany’s example prompt other countries to follow a similar policy of genetic exceptionalism enforced by paternalistic regulation?