The recent appropriations bill passed by Congress this week has some good news for NIH and the biomedical research community. The Trump administration had proposed cutting the NIH budget by about 18% for the upcoming year, and stripping $1.8 billion from the current year, compounding more than a decade of funding declines. Support for NIH in general has been bipartisan over the years, but that has not shielded the agency from funding volatility over the last decade or so. As reported previously here, the Trump proposal to slash NIH funding was a pillar of the emerging March for Science movement, and a motivator for participation in the April 22 march.
The Congress has now rejected the Trump proposal:
Lawmakers increased the budget for the National Institutes of Health (NIH) in its bipartisan deal to fund the government, effectively ignoring the Trump administration’s proposal.
Congress bolstered funding by $2 billion over the next five months, securing $34.1 billion for the NIH. It's the biggest boost the NIH has received in more than a decade, higher than at any point during the Obama administration.
The explanation for the Congressional resistance is multi-layered, and certainly the visibility of the NIH proposal was very high and the resistance was very public. In addition, Democratic strategizing in the budget process negotiations played a key role. The recent 21st Century Cures Act (see here) which focuses on breakthrough projects (but was not explicitly funded; see here) is now specifically funded in this new bill. More funding fights loom, however, as the 2017-2018 fiscal year is not far away, and the future proposed cuts to NIH are not resolved. But it's fair to say that the collective resistance to this year's NIH cuts (followed by its success) demonstrated significant political muscle, likely to be exercised in the next round of annual negotiations.
The March for Science on April 22, 2017 focused national attention on a number of science-impacting developments under the Trump administration. The march heralds more of developing movement than a single event. For the biomedical research community, the immediate concern is a proposed cut to the National Institutes of Health (NIH) budget of about 18% which is quite radical, and is a sharp departure from the recent Congressional efforts to restore the NIH funding decline over the last decade (see factsheet). A commentary by Harold Varmus, Nobel Prize winner and former director of NIH, notes the national effects of reductions to the NIH budget:
To understand just how devastating a cut of less than 20 percent of an agency’s budget would be requires some understanding of how the N.I.H. operates. Very little of its typical annual budget is spent on the agency’s administration: The industrious, underpaid government scientists who manage the funding of the N.I.H.’s research programs consume less than 5 percent of its budget. Only a bit more, about 10 percent, supports the work of government scientists. In sharp contrast, over 80 percent of its resources are devoted to competitively reviewed biomedical research projects, training programs and science centers, affecting nearly every district in the country.
Ironically, at the close of the Obama administration, Congress passed the 21st Century Cures Act, which would add a new $6 billion to medical research; it received widespread bipartisan support. It was particularly welcomed by the NIH leadership as promoting several new frontier initiatives: Brain Research through Advancing Innovative Neurotechnologies (BRAIN) Initiative and the Precision Medicine Initiative (PMI).
So the NIH funding climate remains turbulent, which is not optimal for a funding agency that makes multi-year grants to researchers. The NIH budget proposal was a motivating factor for many march participants, including research scientists. The disconnect between the vitality of American biomedical science and the political vulnerability of federal support is readily apparent. Decades of investment in life science research has had a cumulative effect of integrating molecular biology into medical practice, with many prospects for precise and targeted interventions in disease processes. But it's more than that at stake; the generation of scientific knowledge as a public good is an enterprise worth funding and protecting.
In an effort to import more scientifically-based policy issues into the 2016 election, ScienceDebate.org, 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). ScienceDebate.org 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. ScienceDebate.org 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.
In 2016, the National Science Advisory Board for Biosecurity (NSABB) has returned to reconsider the issues regarding the approval, funding and oversight of experiments on pathogens that are engineered to contain mutations conferring elevated transmissibility in mammals and/or enhanced pathogenicity (virulence). This line of research has been called gain-of-function research (GOF). Such pathogens are studied to determine which genetic changes in a virus or bacterium confer attributes which create a more dangerous pathogen. Knowledge that a specific genetic mutation could confer a higher risk profile could theoretically allow more precise and knowledgeable public health surveillance of naturally occurring mutations. In addition, therapeutic countermeasures could be developed in advance of an actual strain appearing in the population. Nonetheless, these experiments could produce what have been called potentially pandemic pathogens (PPP) and are therefore controversial because of the possible release of a dangerous microbe, either by accident (biosafety) or design (biosecurity). The NSABB is charged with advising the federal government on bioterrorism-related scientific matters, the panel being created post-9/11. In the wake of controversial experiments published in 2011 and 2012 describing the creation of GOF H5N1 influenza viruses with enhanced transmissibility in humans, the NSABB has been working on formalizing a risk-benefit framework for determining whether certain experiments should be restricted or their funding limited. In 2014, a federal moratorium on the funding of GOF studies was imposed following a series of biosafety incidents at federal laboratories (some GOF studies have been allowed to resume, involving Middle East respiratory syndrome coronavirus (MERS-CoV) and influenza). The NSABB is now conducting public meetings as the next stage in the deliberative process it outlined in 2015. The NSABB commissioned a formal risk and benefit assessment (RBA) from an outside contractor to provide the board with qualitative and quantitative information about the risks and benefits of conducting certain scientific studies. The NSABB also commissioned a formal study of the ethical frameworks that could be relevant to the formulation of official policy. In addition, a working group of the NSABB has published their review of the current issues. Their findings are as follows:
Key Finding 1: There are many types of GOF studies and not all of them have the same level of risks. Only a small subset of GOF studies - GOF studies of concern - entail risks that are potentially significant enough to warrant additional oversight.
Key Finding 2. The U.S. government has effective policy frameworks in place for managing risks associated with life sciences research. There are several points throughout the research life cycle where, if the policies are implemented effectively, risks can be managed and oversight of GOF studies could be applied.
Key Finding 3. Oversight policies vary in scope and applicability, therefore, current oversight is not sufficient for all GOF studies that raise concern.
Key Finding 4. There are life sciences research studies that should not be conducted on ethical or public health grounds if the potential risks associated with the study are not justified by the potential benefits. Decisions about whether GOF studies of concern should be permitted will entail an assessment of the potential risks and anticipated benefits associated with the individual experiment in question. The scientific merit of a study is a central consideration during the review of proposed studies but other considerations and values are also important.
Key Finding 5. The biosafety and biosecurity issues associated with GOF studies are similar to those issues associated with all high containment research, but a small subset of GOF studies have the potential to generate strains with high and potentially unknown risks (emphasis added). Managing risks associated with all high containment research requires Federal-level oversight, institutional awareness and compliance, and a commitment by all stakeholders to safety and security. Biosafety and biosecurity are international issues requiring global engagement.
Last month, the NSABB held an public committee meeting to review all of these recently commissioned reports, with the purpose of making progress in developing a formal roadmap for the federal government to use in deciding whether and/or how to support GOF experiments. The NSABB also invited public comments on the studies cited above. Criticism from other scientists include critiques of the GOF definition itself, objections to the comparatives used in the RBA assessment (e.g., 1918 pandemic influenza virus), a call for more clinician involvement in the process, as well as general objections to a lack of avenues for more public participation in the debate. As this deliberative process plays out over the next several months, the fate of the government-imposed moratorium will also be a consequence of the NSABB conclusions. The deliberative process continues: the second public National Academies of Sciences Symposium on GOF research will be held on March 10 & 11, 2016 and will include a discussion of the RBA study as well as NSABB’s preliminary findings and draft recommendations (the first symposium was held in 2014, see here). There will be an opportunity for the public to participate in the event as well as to submit questions online.
The election results are in, with consequences for several high-profile biotechnology issues at stake. Voters rejected California's Proposition 37, which would have required the labeling of genetically engineered (GE) foods in the state (see here). A vigorous campaign occurred in the state, of which opponents outspent supporters by about 5 to 1. An effective source of opposition to the measure was based on arguments that this new law would have adverse economic consequences - for consumers (higher prices), businesses (compliance) and a cash-strapped state (administrative costs). The final vote was 53% opposed, 46% in favor; this would have been the first state to enact such a law. The movement to label GE foods continues, with upcoming efforts on deck in Washington and Oregon. In a separate issue, the reelection of President Obama cements his policy of allowing federal funds to be used for embryonic stem cell research (see here), so this biotechnology sector has stability for at least several years. At a meta-level, impacting the major life science agencies such as NIH and the FDA, neither house of Congress changed hands (keeping committee leaderships in place), so that leadership of key committees in the House, such as the Committee on Science, Space and Technology, remains a GOP preserve, while the Democrats retain control of the Senate and its Committee on Health, Education, Labor and Pensions (HELP). The Obama reelection also locks in the Affordable Care Act (see here). Lastly, Charles Darwin received 4,00 write-in votes in a Georgia congressional election where the incumbent Rep. Paul Broun (R), a member of the House Committee on Science, Space and Technology, is an outspoken opponent of the theories of evolution, embryology, and Big Bang cosmology. Broun was reelected.
A preview of the biotechnology-related election issues on the November 6 ballot illustrates both direct and indirect implications of the upcoming vote. Two areas of biotechnology and the law will be clearly impacted by the results of state and national elections - the partial regulation of genetically engineered food through labeling, and the federal funding of embryonic stem cell research. The most directly consequential measure (yes/no) is in California. There is a state ballot initiative to require the labeling of genetically engineered (GE) foods in California, Prop 37; if adopted, it would be the first such state mandate to be imposed (see here). Thus, on November 7th, California could be looking at implementing a regime of mandatory labeling for GE foods, and we could expect legal challenges to follow with likely First Amendment challenges to the labeling, where the contours of the commercial speech doctrine would be at issue (e.g., somewhat analogous to International Dairy Foods Association v. Amestoy (2nd. Cir. 1996), where the 2nd Circuit invalidated a Vermont measure requiring hormone-related labeling of dairy products).
It is also foreseeable that the outcome of the Presidential election will indirectly (but seriously) affect the status of stem cell research in the U.S. – specifically the ongoing controversy over the federal funding of embryonic stem cell research (see here). In 2009, President Obama reversed the Bush-era policy of disallowing the use of federal funds for the derivation of new embryonic stem cell lines; as a result, the National Institutes of Health (NIH) is allowed to award grants for such research. The Romney website contains a policy on stem cell research; while not directly addressing the use of federal funds for embryonic stem cell research, the statement is written to focus on alternatives: “Adult stem cell research and alternative methods to derive pluripotent stem cells, such as altered nuclear transfer and direct reprogramming, are scientific paths that carry much promise and avoid raising ethical concerns.” Governor Romney vetoed a Massachusetts bill in 2005 that would have allowed “therapeutic cloning” – the creation of a cloned embryo to derive genetically compatible embryonic stem cells (this debate was extant in federal legislative battles at that time, with Democrats and Republicans having opposing positions). The 2012 campaign site contains this statement: “When confronted with the issue of stem cell research as governor of Massachusetts, Mitt Romney chose to support life by vetoing a bill that would have allowed the cloning of human embryos.” Actually, this is a veto more grounded in a rejection of deliberate embryo creation rather than the stem cell research itself. Thus, this statement does not address whether Romney would allow the funding to derive embryonic stem cells from leftover or discarded embryos that were created not for research, but in the process of assisted reproductive technologies (e.g., at fertility clinics). However, from all available evidence, it can be inferred that the Romney position will be to undo the Obama policy of federal funding for new stem cell lines from unused embryos. Thus, on November 7th, the stem cell community wil either encounter the status quo (Obama) or the possible elimination of federal funds for embryonic stem cell research (Romney); a Romney win would also obviate the current legal challenges to the Obama policy. On a final note, the larger specter of federal support for scientific research is implicated in the national race, particularly as questions of government scope and resources have factored in so highly. A group of 68 Nobel Prize winners endorsed President Obama recently, largely based on their view that Obama “delivered on his promise to renew our faith in science-based decision making and has championed investment in science and technology,” while concluding that Romney would “devastate a long tradition of support for public research and investment in science.”
Several items regarding the federal funding of life science research are worth noting because they illustrate the tensions over how the government funds science and what the public may or may not receive in the form of benefit. As a general matter, the federal government allocates approximately 10% of its discretionary funding to research and development, a percentage that has declined from about 25% in the mid-1990's. One point of contention in science funding debates is that the government funds useless research that appears to have no link to human improvement. That charge resonates with some of the parameters of basic research in molecular biology, where by definition, scientists have used seemingly obscure organisms as models (e.g., fuitfly, yeast, nematode, fish) for studying molecular processes, and the argument for such research has been that such work reveals universal biological processes that apply to humans. Now, in recognition of the fact that wild-card research observations could have great relevance for human benefit (including health), a Golden Goose Award has been established by a coalition of universities, think tanks, and businesseses for the purpose of “highlighting examples of seemingly obscure studies that have led to major breakthroughs and resulted in significant societal impact.” In a ceremony this week, one of the awards was for the research on the green fluorescent protein from jellyfish - which first explained why some jellyfish glow - but then the isolation of the gene allowed it to be used as a portable flashlight attached to genetic switching molecules, providing a means to track how gene expression occurs in any cell; such a technique has been used in HIV and cancer research. Other awards this week recognized analogous work in radiation physics and material science. So that is all to the good, but such efforts occur against real funding instability for federal science research. In a related but unfortunate linkage, the ongoing federal budget politics have produced a sequestration deal that ended the budget standoff last August but then embedded automatic cuts in federal spending that occur in January 2013. There's no progress in Washington on avoiding such an outcome. As a result, the current projection is for an 8.2 percent cut in federal science funding, with a specific loss of at least $2.5 billion for NIH alone. That would (and already has) greatly impact existing grant programs and plans for upcoming research in biomedicine; e.g., see a Mayo Clinic analysis. All of this is worth remembering as the political season produces a lot of verbiage regarding the criticality of American science, but a peek behind the words reveals mathematical truths that will undermine how much research can get done.
Science and technology policy has been recognized as an integral component of the Presidential election cycle for the past several elections. The organization Sciencedebate.org has managed to place a set of science policy questions before the presidential candidates in 2008 and again this year; President Obama and Governor Romney have answered the questions here. It’s clear that the major political parties, based on ideological and process preferences, differ on how the (federal) government should be involved in the operation of American science operates and in how its emerging technologies should be regulated by government. One policy lever is fiscal: the decision to authorize spending on “big science” (e.g., space exploration or the Human Genome Project) or to calibrate annual funding levels for the major federal research agencies (in the case of life sciences, the National Institutes of Health and the National Science Foundation are closely watched). Those decisions are on the input side. On the output side, what happens to the technologies produced with the help of federal monies? Here are such critical issues of regulation as those governing genetically engineered food and crops, genetic testing, nanotechnologies, and stem cell research. Although Obama and Romney provide general remarks to the set of general question, there is an absence of any details regarding some critical and pressing issues in the biotech-related life sciences:, e.g., authorization of (embryonic) stem cell research, labeling of genetically engineered (GE) food, or how the government manages dual-use research and disclosure with bioterrorist potential For example, the 2008 questionnaire specifically asked about genetics research and embryonic stem cell research. Obama's policies are evident from his record (e.g., yes to embryonic stem cell research, no to regulation or mandatory labeling of GE food). The current set of questions did not require either candidate to be specific on those issues. In general, with respect to the formation of government policy for the life sciences, the president has an Office of Science and Technology Policy (since 1976), and the last several presidents have created their own bioethics-related advisory panels (Obama's is here) to study current controversies. Despite that, this election-year project to focus the (major) presidential candidates on the role of science in today’s government portfolio is useful, but more explicit questioning on the actual issues confronting regulatory agencies and legislatures would place the very real policy differences between the candidates in sharper focus.
