Tag: and Emerging Biotechnology

Today, NIH is releasing a Guide Notice on Clarifying NIH’s Priorities in Health Economics, demonstrating the importance NIH places on supporting research that examines “how scarce resources are allocated among alternative uses for the care of sickness and the promotion, maintenance, and improvement of health, including the study of how health care and health-related services, their costs and benefits, and health itself are distributed among individuals and groups in society.”  In other words, how economic models and methods can be used to support NIH’s mission to use fundamental knowledge to enhance health, lengthen life, and reduce illness and disability.

Health economics can provide rigorous tools for answering important questions about how new medical innovations are adopted and deployed; about how patients and doctors can make the best informed choices for treatment and prevention; and about how different ways of delivering health care can affect the health of individuals and populations.   Answering these sorts of questions is vital to our work here at NIH, and as of 2015, NIH funding has supported the work of five Nobel Laureates in Economic Sciences who made great advancements in our understanding of health and society.  In fact, health economics is only one example of the type of behavioral and social science research funded by NIH that is absolutely central to our ability to prevent and treat disability and disease.

Today’s Guide Notice clearly demonstrates the importance that NIH places on supporting health economics research in which health outcomes and health-related behaviors are the primary focus, and the connection between the subject(s) of the study and improved understanding of health are clear and explicit.  Health economics research that makes a strong, explicit tie to health and health-related outcomes is central to the NIH mission, and NIH believes that such studies are a worthy investment of taxpayer funds.  It is also true that an economic analysis is often included as one piece of a larger study and that such analysis is often part of understanding the real-world consequences of health interventions. Studies where the primary focus of the research is not health economics, but include such analyses as a secondary aim, continue to be a valued part of the NIH portfolio.

Some topics and approaches which are not necessarily NIH-wide priorities may still be priorities for the missions of individual Institutes and Centers. Principal Investigators (PIs) and potential PIs for NIH research grants should consult with NIH program officers in Institutes and Centers appropriate to their proposed topic if they have questions about whether their work will fit program priorities.

The Notice also identifies study topics outside the NIH mission, which will not be funded by the agency. These topics, although potentially valuable areas of research, do not connect clearly to NIH’s mission or priorities related to the understanding of health, and therefore may be a better fit at other organizations and agencies. This underscores NIH’s strong commitment to responsible stewardship of the taxpayer dollars and to transparency in setting priorities for the agency.

In biomedical research, scientists commonly perform experiments that involve enhancing or diminishing the function of a gene, which may change the observable characteristics of a model organism.  Such gain- and loss-of-function studies are a cornerstone of many fields of experimental biology and are routinely performed to help understand genetic pathways, infer the function of genes and proteins, and more.

Key to our understanding of what causes infectious disease, whether it’s influenza, HIV/AIDS, or the common cold, is figuring out the characteristics of what makes microorganisms cause disease. When applied to the study of infectious diseases, loss- and gain-of-function experiments can help identify determinants of virulence, pathogenesis, or other pathogen (disease-causing agents) characteristics.  These types of experiments aid in the discovery of potential targets or strategies for the development of vaccines or other medical countermeasures or inform disease surveillance efforts.

In recent years, there has been a lot of attention paid to certain types of gain-of-function studies resulting in pathogens with enhanced pathogenicity (ability to cause disease) or transmissibility (ability to be passed from one individual to another), especially in mammals.  These are what the popular press sometimes calls “superbugs,” and concerns have been raised about whether they might be intentionally or accidentally released.  Gain-of-function studies also present “dual use” concerns—that is, although the experiments are performed to provide insight into disease or to develop treatments, they may also generate research products or information that could be misused to harm public health or national security.  These biosafety and biosecurity issues are particularly acute with studies involving viruses, like influenza, that have a history of causing pandemics in humans. Indeed, some people have argued that certain gain-of-function studies should not be undertaken at all.

The U.S. government (USG) launched a deliberative process in October 2014 to re-evaluate the potential risks and benefits associated with gain-of-function research involving certain pathogens with the potential to cause a pandemic.  This process involves both the National Science Advisory Board for Biosecurity (NSABB), which will develop formal recommendations to the USG, and the National Academies, which in December 2014 hosted the first of two meetings to foster broad stakeholder discussions.  In addition, a risk-benefit assessment is being conducted by a private company, Gryphon Scientific, to inform the deliberations.  During this process, the USG has paused the release of new funding for gain-of-function studies that could enhance the pathogenicity or transmissibility of influenza, Middle East Respiratory Syndrome (MERS), or Severe Acute Respiratory Syndrome (SARS) viruses.

The initial task of the NSABB was to advise on the design and conduct of the risk-benefit assessment.  In May, the Board approved its Framework for Guiding Risk and Benefit Assessments of Gain-of-Function Studies.  This framework outlines principles that should guide the risk-benefit assessment, describes the types of risks and benefits that should be analyzed, and makes recommendations on the types of pathogens, pathogen characteristics, and types of gain-of-function studies that should be analyzed.  The National Institutes of Health (NIH) and Gryphon Scientific are using this framework to guide the analysis of the risks and benefits.

The NSABB’s second task is to develop recommendations to the USG on a conceptual framework for evaluating research proposals involving gain-of-function studies that raise concerns.  The Board will convene on September 28^th at the NIH campus in Bethesda, Maryland to discuss its progress and continue its deliberations.  This meeting will also include an update on the risk-benefit assessment and a panel discussion of the ethical, legal, and policy issues associated with the gain-of-function issue.  The meeting is open to the public and will also be webcast live.  Additional information, including links to the pre-registration website and meeting agenda, can be found on the NSABB meeting webpage.

The results of the risk-benefit assessment are anticipated this fall and the Board’s draft recommendations are anticipated in early 2016.  These draft recommendations will then be discussed at a second National Academies meeting next spring before being finalized. The USG will consider the Board’s recommendations as it develops policy for the funding and oversight of gain-of-function studies and expects to revisit the funding pause at that time as well.

Public input is key to this process.  NSABB meetings, as well as those hosted by the National Academies, are free and open to the public.  Public participation is encouraged and all NSABB meetings include time for members of the public to provide comments.  Written comments can be submitted to the Board at any time at NSABB@od.nih.gov.

The debate about gain-of-function studies involving pathogens with pandemic potential are related to broader ongoing discussions about laboratory safety and security.  However, even more broadly, the gain-of-function debate is about public trust in the scientific enterprise.  The life sciences are rapidly evolving and we have the ability to manipulate biological systems in ways that were not possible, even 10 years ago.  New discoveries and emerging technologies hold immense promise but they will also continue to test our policy frameworks.  It is an exciting time, but also a sobering one for those in science policy.  It is our job to help ensure that science can advance rapidly as well as safely, ethically, and responsibly.

One of the truisms of science policy is that developments are often reactive, in response to external events or breakthrough leaps forward in science and technology.  Thoughtful, deliberative policymaking on emerging fields of science and biotechnologies is challenging, particularly since unpredictability is inherent in the very nature of scientific discover.  Simply put, the wheels of science often turn faster than the wheels of policy.

Today, NIH published a notice in the NIH Guide for Grants and Contracts announcing the agency would “not fund research in which human pluripotent cells are introduced into non-human vertebrate animal pre-gastrulation stage embryos” while we consider a possible policy revision in this area.   As described in the Guide notice, this is an exciting area of science that is rapidly progressing, but in which ethical and animal welfare considerations might merit additional guidance to move forward.  This is a unique opportunity to take a deep breath, look at the state of the science, and think about current policies and consider whether any additional policies are needed to promote the responsible conduct of this promising science.

Of course, thinking about the ethical considerations related to the formation of these types of animal-human chimeras is not new.   In 2005, the National Academies Guidelines for Research on Human Embryonic Stem Cells urged caution for experiments in which human embryonic stem cells were introduced into non-human embryos, suggesting both restrictions and additional consideration might be necessary.  NIH adopted several of those provisions in the 2009 NIH Guidelines for Human Stem Cell Research. While the Academies report pre-dated the discovery of the ability to create induced pluripotent stem cells, the ethical considerations raised remain resonant.   Advances in cellular technologies and gene editing present opportunities to address interesting scientific questions and propel progress in regenerative medicine.  They also illustrate that the time is ripe to proactively consider whether additional ethical considerations should be put into place to guide the science moving forward.

Moving forward, NIH will bring together experts in the field to discuss the state of the science: what are the aims of research involving early stage chimeras and what are the advances on the horizon?  This discussion will help serve as a foundation to consider policy needs going forward.  In other words, thoughtful, deliberative policymaking at its best.