November 27, 2011

Novel Deadly Flu Virus and Publication Controls on Dual-Use Research of Concern

Post 9/11, the assessment of bioterrorism risks has also encompassed considering whether the publication of scientific research that provides a road map for the creating of deadly pathogens should be constrained. It’s hard to ignore the increase in reports of laboratory research that has created a novel and deadly influenza virus that could pose a human influenza pandemic risk. For background, there are several strains of influenza, not all of which pose a threat to human health. H5N1 influenza virus has long been a most virulent (deadly) form of influenza, but largely found in birds (avian flu) – fortunately, it has not been capable of efficient transmission from animal to human or spread between humans. Thus, although the virus has a high mortality rate (around 60%), it is not readily contagious, a fact that has limited its potential threat to humans. Now there are reports of the laboratory creation of a deliberately mutated H5N1 virus that was developed by Ron Fourchier and colleagues at the Erasmus Medical Center in the Netherlands which they reported at an influenza virus conference in September - in which they discovered that only 5 genetic mutations were required for a relatively inert H5N1 to acquire the capability of efficient spread among ferrets, long used as an animal/mammalian model of human influenza. Here is the short news report from the conference proceedings. Thus, it is possible to extrapolate that this novel virus has the properties of high lethality and efficient transmissibility in humans. No scientific report has been published to date. But there is reaction from the U.S. National Science Advisory Board for Biosecurity (NSABB), a federal advisory body created post-9/11 and located under the auspices of the NIH.  The NSABB is charged with evaluating what is known as “dual-use” research of concern (DURC) – work that is motivated by scientific inquiry but also offers the possibility of adverse use if the results are used in a dangerous manner; the NSABB can recommend that scientific work not be published (but it cannot prevent it).  A prime example of NSABB concern would be the creation of a novel virus, in which researchers attempt to learn what genetic changes separate a benign from a deadly virus – but in order to do so, they create the deadly virus and publish the experimental details. To date, it is reported that the NSABB has been asked to evaluate the risk of publication of this influenza work.

Post-9/11, there was an effort to create more awareness of the dangers of publishing such dual-use research in the life sciences – possible bioterrorism applications were in mind. Earlier concerns attached to such publication as the artificially constructed poliovirus and research that dissected the smallpox virus to identify the genes that confer such lethality. Although there is no scientific paper by Fouchier and colleagues yet, it remains to be seen what the NSABB will recommend, and whether the details of the scientific work will be made public, either formally or informally. Should we know what 5 mutations will convert a benign flu virus to a malignant version? Pro: yes, because this is part of learning how to counter and monitor the already-existing biological threats to human health; nature could generate a mutant virus with pandemic risk, even without human intervention; the work required to engineer such a virus is high-tech and formidable, not readily undertaken by rogue actors. Con: the dangers of such knowledge (and production of viral stocks) outweigh the intellectual gain - there is no containment of knowledge. My own view is that a deeper understanding of the pathology of microorganisms is irresistible if we are to fully capture and integrate how the microbial world coexists with humans and continues to generate health risks. Further attention to this reported virus is likely to refocus efforts on what we have (or need) in vaccines and antivirals (which is hard to do in the absence of some perceived imminent risk). We'll watch to see what further details emerge.

November 25, 2011

FDA Revokes Avastin Approval as Breast Cancer Treatment

The FDA has finally pulled the plug on approval of the biotech drug Avastin for treating advanced breast cancer. Avastin is a monoclonal antibody which works by targeting and shrinking the blood vessels required for tumor growth.  What was interesting about this drug was that it was approved on the FDA fast track in 2008 at a time when it looked to be a promising therapy for the treatment of advanced breast cancer.  In June, an FDA advisory committee recommended that the FDA remove its endorsement for use in metastatic breast cancer, citing studies in which Avastin had shown very little effect on survival time. What is important about this whole episode from the regulatory perspective are several facets: the use of a fast track FDA approval process to capture a promising lead on a biotech drug while minimizing delay in clinical studies, hence the initial approval in 2008; the promise to condition final approval on studies which more thoroughly teased out whether the drug did significantly lengthen survival time (the studies did not support the promised effect) and the extensive public scrutiny of the FDA decision by a powerful patient constituency (pro-approval petition by some breast cancer advocates) and a biotech company (Genentech) which surely did not want to lose its FDA imprimatur and actively campaigned to keep drug approval. But Commissioner Margaret Hamburg sided with the advisory committee in ending the FDA approval, publishing a lengthy document which outlines the reasoning for the decision. Of course, physicians may continue to prescribe Avastin off-label for treatment of breast cancer, but the drug can no longer be legally advertised for such use. Notably, not all breast cancer advocates opposed the FDA's decision; the National Breast Cancer Coalition expressed support. Of most immediate concern for breast cancer patients who still want to receive Avastin is that the lack of FDA endorsement will cause most insurance plans to not cover the cost of the drug (about $88,000 per year). What's also interesting about Avastin (and potentially other biotech drugs which target the support system for cancer cells) is that its mechanism would appear to have wide applicability (be able to generally limit tumor growth) but in actual clinical trials, the effects may be quite heterogeneous (Avastin retains FDA approval for use in treating colon, lung, kidney, and brain cancers).

November 14, 2011

Stem Cell Protagonists in Wisconsin Senate Race

The Wisconsin 2012 Senate race is featuring a particularly sharp contrast between the leading candidates regarding stem cell research, whether the stem cells are derived from existing adult cells or from embryos. The issue of embryonic stem cell research remains controversial as it requires the use of (and possible deliberate creation of) an embryo. Many “pro-life” advocates include an opposition to embryonic stem cell research as part of a platform which opposes the right to abortion. In the Wisconsin 2012 Senate race, former governor Tommy Thompson is the current frontrunner for the GOP nomination to run against Democrat Rep. Tammy Baldwin. Thompson has become not only an advocate, but a sponsor, of recent efforts to increase adult stem research. This was illustrated by his appearance last week at the adult stem cell conference convened by the Vatican, which has entered the stem cell debate through a 5-year, $1 million partnership with NeoStem, Inc., a New York-based adult stem cell biotech company. His remarks took aim at embryonic stem cell research in favor of promoting adult stem cell research: "That’s what I love about adult stem cells – we’re using the divine wisdom inside of us to supercharge our bodies and wipe away disease.  And as we do this, not one single human embryo is destroyed. " Here's an eyewitness report from Art Caplan of the University of Pennsylvania on the dubious scientific merits of the conference. Thompson has also called for a federal commission to be established that would specifically advance adult stem cell research.  Wisconsin Democrats have criticized Thompson's overt association with Vatican venture. Rep. Baldwin has been an advocate for embryonic stem cell research; of note is that one of the first successful efforts in isolating embryonic stem cells took place at the University of Wisconsin in 1998 and that Wisconsin has had a significant stem cell sector ever since. If Thompson secures the GOP nomination and Senate race is between Baldwin and Thompson, the stage could be set for a fairly explicit referendum on official policies toward adult vs. embryonic stem cell research. With Thompson standing with the Vatican efforts to elevate adult stem cell work and Baldwin being a firm proponent of embryonic stem cell research, this race would recast the stem cell debate in a novel and idiosyncratic context. Beyond the politics, what's important to remember is that research into both sources of stem cells is worth conducting and funding, but the scientific merits of each (and funding decisions to follow) may be interpreted through ideological filters which distort actual results. Thus, the relative merits of each may not emerge for years.

November 8, 2011

Litigation Continues to Challenge Planting of GE Crops in Wildlife Refuges

A coalition of plaintiffs continues a series of lawsuits that challenge the practice of granting permission for the planting of genetically engineered (GE) crops, including soybeans and corn, in the federal wildlife refuges (see complaint). The current lawsuit alleges that the U.S. Fish and Wildlife Service has allowed the planting of GE crops in 66 Midwestern refuges without conducting an Environmental Impact Statement (EIS) as required by the National Environmental Policy Act (NEPA). These plantings have occurred as part of a FWS program which designates a portion of a refuge for agricultural purposes. NEPA, passed in 1970, requires that any action undertaken by a federal agency that may have environmental consequences be thoroughly evaluated by conducting a rigorous environmental review of possible impacts and consideration of alternatives. NEPA effectively allows for citizen challenges to a broad range of federal actions that pose environmental risk through the use of a procedural objection, as exemplified by this lawsuit. No EIS was prepared here; this pattern has been followed by FWS in granting permissions for GE crops is refuges across the U.S. To date, the plaintiffs have won rulings in earlier challenges to the planting of GE crops in the refuges, where the courts have ordered FWS to conduct the requisite EIS (earlier this year, the U.S. District Court in Delaware ordered a halt to such plantings, pending the completion of an EIS). One might guess that the FWS would decide as a matter of national policy to prepare an EIS for any proposed designation of refuge property for GE plantings. The FWS, however, has been unwilling to establish such a national policy that would routinely institutionalize EIS preparation - instead, the individual lawsuits must seek adjudication to get an EIS prepared, and any GE plantings underway halted (one estimate is that GE crops are planted in 75 national wildlife refuges). This lawsuit is the fourth such legal action, and it is likely that courts will continue to conclude that the planting of any GE crop on land that is designed to house and maintain natural habitats is exactly the kind of intervention that demands the strictest legal review.

November 6, 2011

Precision Medicine: The Patient as Data Repository

The era of defining the human patient as a data repository continues; this recharacterization represents the convergence of massive molecular (including genetic) data with digital information capacities (electronic medical records), creating an era of “precision medicine.” At the request of the National Institutes of Health, the National Academy of Sciences was tasked to develop an entirely new view of human disease, less informed by a collection of symptoms and a general description of malfunction and centered instead on a molecular-driven profile of a patient.  They have issued a report, Toward Precision Medicine: Building a Knowledge Network for Biomedical Research and a New Taxonomy of Disease that proposes a new disease classification system that is informed by the collection of genetic, proteomic, microbial and other biological states – the end result is to more sharply define disease states and allow for treatment that is more personalized, with a higher likelihood of success. As part of this effort, the report calls for the use of existing patient data to build an information commons which provides the intellectual foundation for reunderstanding human medical processes.  But how to get there?

The evolving imperative is to integrate patient care and data collection into a giant information commons, where every patient, if you will, is part of the ongoing “clinical trial” that becomes the modern medical enterprise. Of course, actual clinical trials, in which an individual agrees to become a research subject for scientific/medical investigation, are a well-established pillar of medical science and they are conducted using norms of consent, transparency, and privacy; an overview here). What does this mean for the law? The report does note a need to "initiate a process within appropriate federal agencies to assess the privacy issues."  Existing legal privacy protections are several (HIPAA, regarding the privacy of medical records, GINA, regarding does provide some assistance as Title I addresses unfair uses of genetic information by health insurers regarding premiums, etc.).The upshot is that rewriting human disease in molecular language is intellectually appealing, but the conversion of patients into information subjects has obvious privacy implications.  Treatment consequences include a kind of adverse typecasting with consequences for receiving medical care (or insurance for).  The proposed federal initiative is now new. An example of a private effort to integrate patient records into a genetics research program is underway by Kaiser Permanente in California, in which insured patients can consent to having their deidentified patient records entered into their genetic research program. The program provides formal privacy guarantees, and has its own internal Institutional Review Board (IRB) which reviews protocols. As the era of molecular medicine redefines the patient as a data repository, the law must supply the requisite human norms of privacy, risk, and choice to accompany such a transformation.