June 30, 2012

AMA: Pre-Market Review, No Labels, for Genetically Engineered Food

The American Medical Association, a professional organization for physicians, again weighed into the debate over genetically engineered (GE) foods at its recent annual meeting. There are two prongs of the current policy debate over GE foods. One is whether genetically engineered foods need to undergo premarket testing and review for approval by the Food and Drug Administration (FDA). The FDA currently does not require premarket testing, in an official policy that dates back to 1992The other issue is whether genetically engineered foods should be labeled in order for consumers to know what they are buying. The FDA does not mandate labeling of GE foods, and legislative efforts at the state level have not succeeded (but note the upcoming California ballot initiative to require labels on GE food this fall). The AMA has now weighed in on both of these issues in a resolution on GE foods adopted at the recent annual meeting, following a report by its Council on Science and Public Health. The AMA recommends that pre-market testing of GE foods be required before the foods are sold to the public, but recommends against requiring the labeling of GE foods. This is an interesting hybrid of a position by the AMA, arguably advocating for the creation of a complicated regulatory apparatus at the FDA to review GE foods, while rejecting the more easily implemented labeling approach. This position reaffirms the AMA position against GE labeling that goes back at least to 2000, and reaffirms its more recent advocacy for pre-market testing. The import of this resolution is not clear, however, in the current labeling debates, such as the electoral showdown this fall in California, opponents of labeling can certainly point to the support by the AMA for their position. However, proponents of labeling can point to language in the AMA Council's report, noting "[t]o strengthen the FDA’s oversight, the Council recommended that pre-market safety testing be mandatory so that consumers are confident that the foods they eat are safe." The  implication that safety concerns remain about GE foods is an argument that labeling advocates can use.  Will other professional medical organizations jump into the fray? I think it’s unlikely (despite the health and safety concerns underpinning these debates), because these issues have been debated for two decades with little official wrangling by other organizations.  However, the adoption of an actual labeling regime in a state (e.g., California) could raise the profile of the issue and lead to calls for further official involvement by the medical community.

June 29, 2012

ACA Upheld; Focus on Preventive Care Includes Genetic Testing

This week's landmark Supreme Court decision to uphold the Affordable Care Act (ACA) has implications for the availability of genetic testing services that may become easier to get under the new law. The Court’s decision was based on a reading of the central mandate in the law as authorized by the taxing power of Congress; it characterized the mandate as an invalid exercise of its power under the Commerce Clause. The effect is to allow the law to stay in place and continue to roll out over the next few years (the widely discussed mandate does not kick in until 2014). One impact of the law is to change the insurance coverage for preventive care, including some aspects that involve genetic testing. In the U.S. newborns undergo mandatory screening for a panel of genetic and metabolic conditions – but the required list of screening tests varies according to state.  At the national level, the HHS Health Resources and Services Administration (HRSA) establishes a national “unform panel” - the Recommended Uniform Screening Panel - that currently covers 30 conditions, but the HRSA can add more tests as research warrants. In actual practice, then, each state has a different testing climate and none need follow the national guidelines. That now changes with the ACA. According to Section 2713 (a) of the ACA, insurance companies must allow payment when parents request coverage for any of the tests on the national uniform panel. Effectively, that will expand the testing options in the states. So, the effect of this provision will be to provide a national minimal screening panel to which which the states will supplement as desired. This expansion of coverage has been welcomed by patient advocates.  More broadly, this provision of the ACA tracks one of the themes in the legislation, which is to increase the visibility and availability of preventive care by mandating coverage for a wide number of relevant services in existing or newly-established health insurance policies.

June 27, 2012

CDC Establishes Influenza H5N1 Mutation Database

The Centers for Disease Control (CDC) has now published an online repository of influenza H5N1 mutations that have been catalogued around the world by public health authorities. The World Health Organization  has created an international network of public health centers to monitor the appearance of influenza virus strains around the world. So, although international surveillance of virus emergence is already mainstay of effective public health strategies today, this effort is notable because it follows on the recent controversy over the new influenza research on genetically altered and potentially dangerous H5N1 strains deliberately created by two laboratories (see here and here). Apprehension over the publication of key genetic changes that make a previously benign influenza virus into one that can spread quickly with severe clinical effects has been the driving force for the concern over whether this particular influenza research posed a unique and irreversible threat. However, the counter-argument has always been that if 5 or so mutations are so critical to the conversion of a relatively inert influenza virus into a dangerous strain, that knowledge needs to be disseminated and used. Such is the new CDC H5N1 database, the H5N1 Genetic Changes Inventorywhich attempts to create a central database for public health experts to track viral mutations on an international basis. The database will be updated "on a regular basis." Should virus isolates appear that exhibit the key genetic changes identified by the Kawaoka and Fouchier papers, that knowledge could be used to track their spread and respond with appropriate measures (such as increasing the availability of stockpiles of antiviral drugs; see here for information on the CDC stockpiling efforts).

June 24, 2012

Federal Court Rejects Claim by Guatemalan Victims of U.S. Medical Experiments

A federal district court has rejected a legal claim by individuals in Guatamala who asserted their right to compensation for the unethical medical experimentation that was carried out by U.S. researchers in the 1940’s (Garcia v. Sebelius, Dist. D.C., 2012). The researchers from the U.S. Public Health Service exposed the plaintiffs to sexually transmitted diseases (syphilis, gonorrhea) to create research subjects. No informed consent or bioethical standards were used to conduct these studies; the participants were institutionalized (prisons, hospitals, etc.) and had little control over the conditions of their confinement. The legal claim was filed under the Alien Tort Statute, which provides a mechanism for aliens to file legal claims for violations of international law or treaties in U.S. courts. The statute has been used extensively to assert human rights claims in a variety of international settings; nonetheless, the scope of the statute is still hotly contested (see upcoming Kiobel v. Royal Dutch Petroleum, to be heard in the Fall 2012 term). The specific legal issue in the Guatamala case was whether the government, would face liability under the Federal Tort Claims Act (FTCA), which does expose government employees to liability when their acts are which ordinarily concedes a waiver of sovereign immunity by virtue of the existence of the statute for caused by the negligent or wrongful act or omission of any employee of the Government while acting within the scope of his office or employment, nonetheless would escape lliability due to an exception for activities conducted in a foreign country. Although the plaintiffs asked the court to carve out an exception to that clause in this case, the court rejected that argument: “Here, the plaintiffs' Alien Tort Statute claims all arise out of injuries suffered in Guatemala, and the claims are thus barred by the FTCA's foreign country exception.”  The court further noted, that despite its inability to grant relief, the U.S. government has conceded the severe injustices of this case and has declared its intention to provide redress.  Indeed, the State Department issued an official apology in 2010: “We deeply regret that it happened, and we apologize to all the individuals who were affected by such abhorrent research practices.” The Presidential Commission on Bioethical Issues also issued a report (discussed here). No official compensation scheme has been announced by the U.S. government.

June 22, 2012

Gene Patent Litigation Returns to Federal Circuit After Remand

The high-profile gene patent litigation is back in court this summer. The Supreme Court responded to a petition for certiorari in AMP v. USPTO (involving the Myriad Genetics patents on the BRCA1 and BRCA2 breast and ovarian cancer genes) by granting, vacating and remanding the case for reconsideration by the Federal Circuit in view of the recent Mayo v. Prometheus case. The plaintiffs have challenged the patents as invalid for lack of patentable subject matter under 35 U.S.C. 101. In Mayo, the Supreme Court unanimously invalidated a patent for a method of optimizing drug dosage by making use of a natural correlation between a drug metabolite and effectiveness. The Court decided that the patent claims essentially claimed the underlying natural correlation for exclusive use, a result that it contrary to the norm in patent law that patents not issue for “laws of nature, natural phenomena and abstract ideas.” Note the language of Mayo: “And so there is a danger that the grant of patents that tie up their use will inhibit future innovation premised upon them, a danger that becomes acute when a patented process amounts to no more than an instruction to ‘apply the natural law,’ or otherwise forecloses more future invention than the underlying discovery could reasonably justify.” However, Mayo involved a method patent.  In AMP, the plaintiffs challenged both the DNA/gene patent claims as well as the genetic testing method claims. After the trial court invalidated both types, the Federal Circuit affirmed the method claim decision but reversed on the DNA claims. That result was then appealed to the Supreme Court. So the case is now focused chiefly on the DNA claims (and one method claim for a drug screening technique). All parties have now filed their briefs at the Federal Circuit for the rehearing on July 20 (ACLU heading the plaintiffs' coalition here; Myriad Genetics here). I filed an amicus brief last week in support of the plaintiffs; I argue that the Mayo decision is quite emphatic in its insistence that products or laws of nature not be encompassed by  patent claims – with the result that the isolated DNA claims in the patents very clearly cover naturally occurring genes and naturally occurring mutated genes (which have deleterious consequences for breast and ovarian cancer patients). My view is that Mayo strengthens the challenge to the DNA patent claims because it looks closely at patent claims which relate to “natural” subject matter and asks whether an inventive contribution has occurred to justify a patent. Furthermore, Mayo also posed the inquiry this way: “[T]he underlying functional concern here is a relative one: how much future innovation is foreclosed relative to the contribution of the inventor.” There is little doubt that the Myriad patents have cast a severe chill on the development of the genetic testing field for BRCA1 and BRCA2, and since these patent claims provide minimal inventive enhancement to the basic scientific subject matter, the patent claims would appear to be invalidated by Mayo. The oral argument at the Federal Circuit is on July 20.

June 21, 2012

H5N1 Influenza Research Published After Controversy

After many months, the research that details the deliberate creation of a genetically altered H5N1 avian influenza virus has been published this week; this is the second of two papers that caused an outcry earlier this year when it was disclosed that novel H5N1 viruses which exhibited pandemic potential were about to be published (see here, here and here). Great efforts to delay and monitor publication ensued, with the U.S. government advisory committee (NSABB) recommending against publication; later, this was modified in the face of developing information and adverse reaction to the prospect of government-initiated publication restraints (however voluntary). This new paper by Ron Fouchier and colleagues in the Netherlands details the 5 mutations it identified to convert a minimally transmissible virus into a readily transmissible, airborne version in a mammalian model – an attribute that is most likely to make a virus with high mortality but inefficient spread characteristics into a immediate public health threat. The novel viruses were not lethal, but it is thought that the acquisition of transmissibility has been a firewall keeping many lethal viruses in check; thus, the import of this work is clear. The research by Fouchier et al. used the technique of passaging the virus through ferrets in order to produce the novel strain; this method somewhat approximates natural biological processes, as opposed to laboratory-chosen mutations. A team of statisticians assess the likelihood that such a virus could arise naturally (possible and worrisome, through mutations over time). This week's special issue of Science also published many (free) commentaries on this H5N1 publication; notably, whether, from a cyber perspective, any “publication bans” can be meaningful given the likelihood that any computer system can be hacked into; whether the government’s recently announced DURC policy will be effective (this was the attempt to shore up how the government accounts for life science research capable of both benign and malicious uses); and whether the continuing self-imposed moratorium on H5N1 research will continue. Of note is the fact that this novel virus was sensitive to Tamiflu, one of the stock antivirals available in an outbreak. That vulnerability can’t be taken for granted, however. The import of this research is to reveal how a truly pandemic influenza is possibly several mutations away from a natural appearance.

June 6, 2012

Mapping the Synthetic Biology Field: An International Overview

A scholarly survey of the emerging field of synthetic biology has been published by a team of researchers from the UK and Japan, and published in the open-access journal, PLOS One. This is a timely overview of this field, international in scope. The authors detail the language problems that can attach to new fields, where different practitioners or commenters use disparate terms to describe this work. For example, synthetic biology is a field that combines engineering with biology, but in this respect, it overlaps with the established field of genetic engineering, which has been around now since the 1970’s. So what accounts for the difference? Some of it is in the ambition of the field, where declarations of the goal to create entirely new organisms are routine; in contrast, genetic engineering usually relies on genetic manipulation of existing organisms (microbes, plants) to add useful phenotypes. Synthetic biology is also associated with the imperative to unravel biological mechanisms with the goal of establishing a catalogue of modular “parts” that can be used to design new biological circuits and new organisms (see, e.g., the Biobricks initiative which does just that). For legal purposes, this article locates the field against the backdrop of relevant international instruments which have bearing on this field (the Convention on Biological Diversity, relating to equitable sharing of genetic resources) and the Cartagena Protocol on Biosafety (relating to guidelines for the use and transport of living modified organisms). With respect to the U.S., the most authoritative consideration of the legal issues raised by synthetic biology was undertaken by the Presidential Commission for the Study of Bioethical Issues (PCBSI), which published its 2010 study of synthetic biology and issued recommendations for continuing vigilance (noting serious issues of risk assessment and management that could attend the design and release of novel organisms), but no calls for either a moratorium or specific regulation at that time (in fact, noting categorizing its approach as “regulatory parsimony”). More generally, the PCBSI defined a framework for “five ethical principles relevant to considering the social implications of emerging technologies: (1) public beneficence, (2) responsible stewardship, (3) intellectual freedom and responsibility, (4) democratic deliberation, and (5) justice and fairness.” What’s also interesting is a follow-on effort started this year by the Woodrow Wilson International Center for Scholars to track how the recommendations of the PCBSI are implemented. For example, their Synthetic Biology Project scorecard documents no federal activity pursuant to various recommendations relating to risk assessment, where there was federal activity related to ethics and public education. In sum, this new scholarly work on synthetic biology is a necessary prerequisite to any serious international oversight of the field, in that such an effort must be rooted in empirical knowledge of the scope of the field and its practitioners.