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Biosafety at NIH and Beyond….A Shared Responsibility

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Co-Authored by Carrie Wolinetz and Deborah Wilson

Following this week’s release of the Office of Science and Technology Policy’s joint memo on biosafety and biosecurity, coming at the tail end of National Biosafety Stewardship Month, it seems like an excellent time to discuss how NIH helps ensure the research we conduct at our own facilities as well as the research we fund across the globe is done safely.

Here at NIH, the NIH Division of Occupational Health and Safety (DOHS) is responsible for overseeing the day-to-day operations of a large and diverse biosafety program. A committed team of biosafety professionals helps ensure that the vital research being carried out by NIH is being done safely. To manage the unique challenges associated with the NIH intramural program, DOHS must be flexible in order to adapt to the changing research landscape.  Recently, DOHS has instituted changes to NIH policies for working with and storing potentially hazardous biological agents including human, plant, and/or animal infectious agents, poisons and toxins. These are significant changes to the way NIH has been doing business for almost four decades. Although NIH registers, reviews, and approves all active work with human pathogens and research involving non-exempt recombinant nucleic acids, it became clear we also needed to re-evaluate and optimize the methods used for keeping track of all biological agents that might have been stored in laboratories or repositories. In addition to support received from senior NIH management, a plan for interactions and information sharing was developed.  A continuous, open dialogue with NIH’s safety committees, such as the institutional biosafety committee (IBC), was also essential to invoking changes to long-standing programs and processes.

In support of the biosafety programs of the institutions that NIH funds, the NIH Office of Science Policy (OSP) conducts an extensive program of outreach and education on topics related to biosafety.  One of the signature programs in OSP is our extramural site visit program for grantee institutions.   The aim of these educational visits is to enable NIH to have a face to face dialog with institutions and to assist IBCs with their programs of biosafety oversight.  The visit includes a review of the policies and procedures that the institution is implementing to ensure the safe conduct of recombinant or synthetic nucleic acid research.  To date, OSP has visited over 110 institutions, and a write up of the program received the 2015 Richard C. Knudsen Memorial Publication Award from the American Biological Safety Association.

OSP has also used the information we have gathered from our site visits to develop a body of information on best practices, in particular the IBC Self-Assessment tool which institutions can use to evaluate their own IBC program.  We encourage all institutions to use the self-assessment tool, which addresses all of the major requirements of the NIH Guidelines.

These are just of few examples NIH is doing to ensure essential biomedical research is conducted safely.  Biosafety is a shared responsibility for all those involved in the research enterprise.  The close and collaborative relationship between the DOHS and OSP help ensure that NIH is at the top of the class with respect to biosafety oversight.  To learn more about NIH’s intramural biosafety program, please visit http://www.ors.od.nih.gov/sr/dohs/Pages/default.aspx.  More information on how NIH engages our extramural grantee institutions with respect to biosafety can be found at: /office-biotechnology-activities

RADM Deborah Wilson, Dr.P.H., is the Director of the Division of Occupational Health and Safety at NIH

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Talkin’ About an Evolution (of research oversight, that is!)

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To many scientists, the name Asilomar is synonymous with an historic event in the regulation of biotechnology. In 1975, experts from around the globe convened at the Asilomar conference center in California to discuss the promise and potential perils of an exciting and emerging technique, recombinant DNA technology.  The discussion laid the foundation for the  NIH Guidelines for Research Involving Recombinant or Synthetic Nucleic Acid Molecules (NIH Guidelines) The NIH Guidelines, aimed at ensuring the safe conduct of this burgeoning area of research, also gave rise to the   Recombinant DNA Advisory Committee (known simply as “the RAC”), an expert group comprising scientists, ethicists, public health experts, biosafety officials, and more, charged with providing advice to the NIH on matters related to recombinant DNA technology. In the late 1980s, the RAC took on a new role: advising NIH on the promising but very new area of human gene transfer research.

Forty years after Asilomar, recombinant DNA technology is ubiquitous in both basic and clinical research settings. As scientific understanding of recombinant DNA technology has evolved, so have the requirements that govern its use.  With this in mind, NIH has been examining the current oversight system for human gene transfer experiments and whether the review processes can be streamlined. To help craft a policy that maximizes scientific advances while ensuring public safety and trust, NIH asked the Institute of Medicine (IOM) to assess the role of the RAC in the oversight of human gene transfer research.  The IOM noted in its report that the RAC has served a valuable role, but concluded that the current level of oversight over each individual human gene transfer protocol is no longer justifiable.  The NIH agreed with this assessment and began developing a proposal for revising the process.

I am delighted to announce that today the proposal to simplify the human gene transfer protocol review process has been published in the Federal Register for public comment.  In short, NIH is proposing that protocols should only be reviewed by the RAC if an institutional oversight body (such as an Institutional Review Board or an Institutional Biosafety Committee) requests review because the proposed research is sufficiently novel.

This change is in keeping with current practice, as these committees have played a large role in overseeing this research for decades and have the expertise needed to ensure research is conducted in accordance with the highest scientific, safety, and ethical standards.

I encourage research stakeholders to provide feedback on the proposal during the 45 day comment period. Once NIH has considered all input, a final notice outlining the changes will be posted. Until then, the current requirements are still applicable.  This represents an important science policy principle: As science evolves, so must the policies that govern it.

I look forward to hearing your comments.

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The Gain-of-Function Deliberative Process

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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 28th 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 [email protected].

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.

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Staying Ahead of the Curve on Chimeras

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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.

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