August 31, 2016

Will the 2016 Presidential Candidates Debate Science and Technology Policy?

In an effort to import more scientifically-based policy issues into the 2016 election,, a coalition of science-based and academic organizations, has issued a challenge to the Presidential candidates regarding their views on policies impacting the science sector (broadly construed). is calling for a Presidential debate focused on science and technology issues, with an online petition in support of such an event posted on their site. This effort was also conducted in earlier Presidential elections (see 2012 initiative); to date, there have been no such debates. The official Presidential debates are managed by a somewhat ad hoc organization, the Commission on Presidential Debates. The official debates this election cycle do not have subject matter limits. has also posted a list of 20 questions, culled from submissions by the participating organizations, for the candidates (Clinton, Trump, Johnson, Stein), who are invited to submit answers. There are foundational questions that impact the science sector generally, related to innovation, research funding, education, immigration and regulations. The most prominent life science-related questions are the following: 
Biodiversity: Biological diversity provides food, fiber, medicines, clean water and many other products and services on which we depend every day. Scientists are finding that the variety and variability of life is diminishing at an alarming rate as a result of human activity. What steps will you take to protect biological diversity?
Food: Agriculture involves a complex balance of land and energy use, worker health and safety, water use and quality, and access to healthy and affordable food, all of which have inputs of objective knowledge from science. How would you manage the U.S. agricultural enterprise to our highest benefit in the most sustainable way?
Public Health: Public health efforts like smoking cessation, drunk driving laws, vaccination, and water fluoridation have improved health and productivity and save millions of lives. How would you improve federal research and our public health system to better protect Americans from emerging diseases and other public health threats, such as antibiotic resistant superbugs?
Vaccinations: Public health officials warn that we need to take more steps to prevent international epidemics from viruses such as Ebola and Zika. Meanwhile, measles is resurgent due to decreasing vaccination rates. How will your administration support vaccine science?
There are several questions related to mental health issues, and the epidemic of opioid abuse. The rest of the list poses specific questions related to energy, environment, space, and the Internet. 

It is likely that the campaigns will respond to the written questions. Probably the most conspicuous omission (relative to the volume of recent debate and controversy in the life science community) is the emerging issue of the management and uses of gene-editing technologies (see earlier posts here and here). Additionally, there is no explicit acknowledgment of dual-use research in the life sciences (see earlier posts here and here). Nonetheless, the organization does elevate the visibility of science-related policies as central aspects of 21st century governance, and implicitly suggests that any credible candidate in 2016 needs to exhibit some degree of scientific literacy.

July 23, 2016

Congressional Impasse on Zika Virus Funding Impacts Public Health Efforts in Peak Summer Months

The Zika virus outbreak is spreading in the U.S., according to local public health authorities and the federal Centers for Disease Control (CDC); international Zika virus cases are also increasing. Infection occurs because of a mosquito bite that transmits the virus, and most public health interventions to date concentrate on limiting exposure to the mosquito (Aedes aegypti). As of yet, there is no vaccine or specific treatment for the Zika virus. The discovery that Zika virus infection in pregnant women can lead to birth defects, including microcephaly, raised the alarm about the spread of the virus in this population (see earlier post here). To date, there are about 1400 reported cases in the U.S; there are about 400 cases of Zika infection in pregnant women. Most cases in the U.S. are traced to individuals traveling outside the country, returning with the infection; Puerto Rico, Brazil and other Caribbean and Latin American countries are some of the hotspots of transmission. Now, however, there  appear to be are several cases of local transmission of the Zika virus in Florida, which means that the virus is gaining a foothold in the U.S. itself. As in most public health crises, the government is tasked with providing increased support to local authorities, funding for treatment developments, and other activities. Congress has been in a stalemate over emergency Zika virus funding over the last month. President Obama sought $1.9 billion in new dedicated funding; the House of Representatives approved $1.1 billion. On to the Senate, where several provisions inserted into the funding bill encountered opposition; most notably, an explicit ban on Planned Parenthood as the recipient of any new funds. As discussed in an earlier post, because of the risk that Zika virus infection poses to pregnant women, who are at risk to give birth to babies with developmental disorders (and not all are known at this point), access to contraception and other reproductive services would appear to be a key ingredient in minimizing the birth of Zika-affected babies. That’s where the usual political conflict over reproductive and family planning funding entered the Zika funding legislation, and created an impasse. So to date, the Senate has not approved the funding that the House approved, and Congress has taken its usual lengthy summer break without acting on emergency funding for Zika virus research and support. The 7-week hiatus in the Zika funding battle has dismayed federal public health officials. The American Medical Association  (AMA) faulted Congress
At a time when concerns continue to mount about the nation's readiness to protect the public from the Zika virus, the AMA is disappointed by Congress' failure to pass legislation before adjourning for summer recess that would provide the resources necessary for our country to respond to this looming public health crisis. Without ensuring there are sufficient resources available for research, prevention, control and treatment of illnesses associated with the Zika virus, the United States will be ill-equipped to deploy the kind of public health response needed to keep our citizens safe and healthy—especially since the spread of mosquito-borne illness is accelerated during the summer months.
Editorials in some of the hardest hit areas of the country noted how the impasse would adversely affect their regions; here is the Palm Beach Post from Florida on the local impact: 
Congress has left the building. And in its dysfunctional wake, it leaves yet another failed effort at passing crucial emergency funding to fight the spread of the dreaded Zika virus. For at least the next seven weeks, Florida — which has distinguished itself as ground zero for cases of the mosquito-borne virus — will just have to hope that the worst part of the rainy storm season doesn’t translate into more infections. (Palm Beach County has seen about 12 cases of travel-related Zika.) It may be a long, hot summer. Mosquitoes that carry the Zika virus breed year-round here, and the number of infections in the continental United States is mounting. On Monday, the state Health Department reported 13 new cases of the Zika virus in Florida - the most reported cases of the virus in a single day. Moreover, federal officials say they will have to postpone a slew of anti-Zika actions. For example, the U.S. Centers for Disease Control and Prevention will have “limited capacity” to help with efforts to counter mosquito populations in the continental U.S. and territories. 
Yes, it should be noted that the CDC is now dispersing about 60 million dollars currently to localities to augment public health efforts, but these are “stopgap” awards that will not approach the scale of the demand. Congress returns on September 6th.

July 17, 2016

Congress Passes Federal Labeling Requirement for Genetically Engineered Foods; State Labeling Laws Would Be Preempted

Vermont enacted the first state law that requires the manufacturers of food products with genetically engineered (GE) ingredients to label their food products accordingly. Its Act 120 became law on July 1, 2016. However, for decades, there has been an ongoing battle at the federal level over whether a national labeling scheme should be enacted (the term GMO/genetically modified organism is also used). (See earlier posts for more background). So, after the Vermont bill became effective, there was a flurry of activity in Congress again to address the issue of a federal labeling scheme for GE food products. (The FDA has not required labels on food products with GE ingredients, in a policy that dates back to 1992). The Senate recently passed a bill, S. 764, that would mandate a particular federal labeling scheme for GE ingredients, and would also preempt any state labeling laws. The federal bill uses the term "bioengineering" to describe the products covered by the law: 
[F]ood - (A) that contains genetic material that has been modified through in vitro recombinant [DNA] techniques; and (B) for which the modification could not otherwise be obtained through conventional breeding or found in nature. 
There is an explicit statement of the preemption achieved by this legislation: 
No State or a political subdivision of a State may directly or indirectly establish under any authority or continue in effect as to any food or seed in interstate commerce any requirement relating to the labeling of whether a food (including food served in a restaurant or similar establishment) or seed is genetically engineered (which  shall  include such other similar terms as determined by the Secretary of Agriculture) or was developed or produced using genetic engineering, including any requirement for claims that a food or seed is or contains an ingredient that was developed or produced using genetic engineering.
This last provision is aimed at the recent Vermont law, as well as other initiatives in Connecticut, Maine and Alaska. Since its enactment in 2014, the Vermont law had already impacted the food and restaurant industries, with some major players declaring that they would provide labels in anticipation of the law (see here). It was apparent that the Vermont law had immediate national impact, as food manufacturers faced compliance with the statute or avoidance of Vermont’s market (practically unworkable). Now, the House of Representatives has passed a version of the recent Senate bill, and it goes to President Obama for signing; it appears that he will sign it. The clear effect of the federal bill is to preempt the long-sought state labeling laws. However, does this bill actually require a label? The bill departs from other labeling proposals over the years (state and federal) in that it contains no explicit requirement to provide a “GMO” or other GE-related name on the main label of the product. The actual labeling scheme in the new federal law is quite elastic, describing the format of the labeling as follows: 
[T]he form of a food disclosure under this section be a text, symbol, or electronic or digital link. 
Thus, a consumer could use a smartphone to read a QR code, or utilize a provided link to access information, or read whatever disclosure material the manufacturer has chosen to provide. The forms of the notification could be arguably obscure, and indirect. In other words, at least so far, there will be no uniformity of disclosure. Already, there are allegations that the bill is discriminatory in that it will make it harder for some consumers to pursue the informational references; access to digitally formatted information is not universal. The USDA has two years to make the law operational, and may refine the labeling formats in that period, subject to public input.

June 30, 2016

Supreme Court Denies Certiorari in Sequenom v. Ariosa

The Supreme Court has denied certiorari for the appeal in Sequenom v. Ariosa (Fed. Cir. 2015). There has been widespread interest in this case, which invalidated patent claims to a method of performing prenatal diagnosis using cell-free fetal DNA (cffDNA) collected from a maternal blood sample (see earlier post here). The method has been critical to the development of non-invasive prenatal testing (NIPT). NIPT testing can be used to identify chromosomal abnormalities or other genetic aberrations, and it offers an alternative to the invasive techniques of amniocentesis or chorionic villi sampling, both of which carry some risk to the fetus. Sequenom would have followed a sequence of recent Supreme Court decisions, AMP v. Myriad (2013) and Mayo v. Prometheus (2012) (Mayo) that each invalidated patent claims in the life sciences for a lack of patentable subject matter. The most controversy has followed the Mayo decision, which was then followed by a software-related patent case, Alice v. CLS (2014). The Mayo/Alice pair has distilled an analytic framework for determining when method patent claims impermissibly read on a law of nature or a natural phenomenon. The framework has been criticized for being overly broad, and for having a deleterious impact on the viability of method patent claims in the life sciences, particularly in the diagnostic testing sector. In the Federal Circuit decision in Sequenom last year, the concurrence by Judge Linn also took direct issue with the Court’s recent dictates in these method patent cases. But the Court did not take the invitation to focus on its own recently developed test. So in deciding not to take the case, the Court will not - for now - review its Mayo/Alice roadmap. One example of continuing influence of the Court's current paradigm is Cleveland Clinic v. True Health Diagnostics (N.D. Ohio 2016), invalidating the method patent claims on a method of detecting cardiovascular disease by detecting the elevation of specific enzyme levels (see earlier post here).

June 22, 2016

RAC Approves First Use of CRISPR Gene-Editing Protocol in Humans

Yesterday, the Recombinant DNA Advisory Committee (RAC), a federal advisory committee to the NIH, held a public meeting to consider the first submission for approval to use a CRISPR/Cas9-based (CRISPR) study protocol with human patients. CRISPR is a technique that allows genes to be edited; it has swept through biomedical science in the last few years as a breakthrough technology. The RAC committee has provided oversight for the field of gene transfer therapies for decades (and supplements FDA and local institutional oversight by IRBs and IBCs). As an advisory committee to NIH, first constituted in 1974, RAC's regulatory portfolio for human experiments began with reviewing gene transfer studies pursuant to the NIH Guidelines for Research Involving Recombinant or Synthetic Nucleic Acid Molecules. The field of "gene therapy" has largely been comprised of studies involving gene transfer into patients to correct, replace, or diminish gene activity relevant to various clinical conditions; to date, several thousand gene therapy clinical trials worldwide have been conducted. RAC's jurisdiction extends to the use of gene-editing protocols, as well as other gene-altering technologies such as RNA interference. Now, a collaborative effort from the University of Pennsylvania (Penn), M.D. Anderson Cancer Center, and the University of California, San Francisco produced a proposed study protocol involving CRISPR gene-editing that was discussed and evaluated by the RAC this week at its meeting. The protocol involves an ex vivo technology where T cells of cancer patients will be removed and subject to gene-editing to alter several cell receptors before the cells are infused back into the patient. The goal is to engineer the T cells of the immune system so that they target and destroy cancer cells; this initial study is to identify any safety issues that might emerge. The recruited patients have either myeloma, melanoma, or sarcomas and would be those for which conventional therapies are not available or effective. During the meeting, questions were raised about potential conflicts of interest due to financial interests of some investigators, as well as the involvement of Penn, as it was the site of the now well-known 1999 gene therapy trial that resulted in the death of Jesse Gelsinger; that trial had notable flaws involving the transparency of preclinical testing and of competing financial interests. After public review and discussion of the protocol, the committee voted to approve the protocol. Yesterday's approval marks the first RAC-sanctioned use of CRISPR technology in human patients.

This is the first study protocol submitted to RAC that uses CRISPR in humans, but it is not the first gene-editing human protocol that RAC has considered. Sangamo BioSciences received approval to use its zinc-finger gene-editing technology (ZFN) in two different human trials: an ex vivo protocol approved in 2007, and an in vivo protocol approved in 2015. In what appeared to be a coincidence, yesterday's meeting also considered the first proposed gene therapy trial to treat Ornithine Transcarbamylase (OTC) Deficiency since the 1999 Gelsinger trial. Several discussants referenced the Gelsinger incident in their comments. The committee held a discussion of whether preclinical trials for the gene transfer method in non-human primates were necessary before approval (only mice studies were provided); RAC then voted an approval with stipulated conditions

As gene transfer studies have become more routine over the last several decades, the scope and need for continued RAC oversight has been questioned. A recent study of RAC that was conducted by the Institute of Medicine examined whether gene transfer oversight by RAC continued to be necessary; the report concluded that only new protocols presenting novel vectors or technical approaches needed to be evaluated by RAC. However, the IOM committee explored whether the RAC model of a public advisory committee could be utilized more generically for other emerging biotechnologies. including, for example, protocols from the field of nanobiotechnology or synthetic biology, for example. The IOM report endorsed consideration of an expanded scope for RAC or an advisory committee with similar attributes to provide the kind of oversight for new technologies as RAC has provided for decades in the field of gene therapy.