Global Pandemics: Gain-of-Function Research of Concern

Global Pandemics: Gain-of-Function Research of Concern

Updated November 21, 2022
Global Pandemics: Gain-of-Function Research of Concern
Introduction
funded research projects and contracts; seven of them
Gain-of-Function (GOF) research is a broad area of
subsequently received exemptions from the pause.
scientific inquiry where an organism gains a new property
or an existing property is altered. The terms gain of function
Current Oversight Mechanisms
and loss of function refer to any genetic mutation in an
As part of the 2014 pause on GOF research, OSTP initiated
organism that either confers a new or enhanced ability or
a deliberative process to evaluate the risks and potential
causes the loss of an ability. Such changes often occur
benefits of GOF research with potential pandemic
naturally. Additionally, scientists can induce some changes
pathogens. In January 2017, OSTP released Recommended
to organisms through experimentation. A key area of GOF
Policy Guidance for Departmental Development of Review
research is the study of both naturally occurring and
Mechanisms for Potential Pandemic Pathogen Care and
experimentally induced changes in organisms to better
Oversight, [P3CO] which described attributes of federal
understand the transmission, infection, and pathogenesis of
agency review and reporting processes for the additional
viruses. Through such knowledge, scientists hope to
oversight of federally funded research that is anticipated to
improve our understanding of human-pathogen interactions,
create, transfer, or use enhanced pathogens with pandemic
aid in assessments of potential pandemic pathogens, and
potential. Agency implementation of a review and reporting
further public health preparedness. Some analysts have
process with the described attributes would allow an agency
raised concerns that studies designed to understand how
to support GOF, GOFROC, or PPP research.
viruses might evolve may have the potential to generate
pathogens that affect humans with the potential to cause a
Following the OSTP guidance, the Department of Health
pandemic. To focus attention on this small subset of
and Human Services (HHS) released Framework for
studies, the scientific and policy communities have begun
Guiding Funding Decisions about Proposed Research
to use the terms gain of function research of concern
Involving Enhanced Potential Pandemic Pathogens (P3CO)
(GOFROC) and enhanced potential pandemic pathogens
in December 2017. The HHS P3CO framework releases
(PPP). However, all three terms (GOF, GOFROC, PPP)
HHS from the 2014 GOF research pause. HHS appears to
have been used interchangeably in some public discussions
be the only agency that has developed a GOF review
and media.
process that addresses the 2017 OSTP GOF guidance, and
the only federal agency that has reported GOF research
Risks and Benefits
funding.
Scientists and the public have debated the risks and benefits
of GOF research. Some in the scientific community argue
Key Components of HHS P3CO Framework
that the research is needed to better understand how viruses
P3CO establishes an additional review process for research
evolve, in order to develop better medical countermeasures
proposals that have gone through the normal scientific
and surveillance regimes for emerging pathogens. Further,
review process, have been determined to be scientifically
they assert that this research can be conducted responsibly
sound, and are reasonably anticipated to create, transfer, or
with proper biosafety and security protocols. Others argue
use enhanced potential pandemic pathogens (PPPs), defined
that the risks outweigh any potential benefits and that
as PPPs resulting from the enhancement of the
alternative experiments should be considered.
transmissibility and/or virulence of a pathogen. To be
subject to this extra scrutiny, an enhanced PPP must satisfy
Concerns over GOF research first emerged in 2011-2012
two criteria:
around a set of studies funded by the National Institutes of
Health (NIH) on respiratory transmission of the highly
1. It is likely highly transmissible and likely
pathogenic avian influenza virus H5N1. At that time, the
capable of wide and uncontrollable spread
debate centered on the security risks of publishing the
in human populations; and
results of these studies and whether the research should
2. It is likely highly virulent and likely to
have been allowed to proceed considering the risk of
cause significant morbidity and/or
accidental release. These debates, along with a series of
mortality in humans.
government laboratory biosafety incidents, not associated
The P3CO review process examines what the experiment
with the H5N1 studies, led the White House Office of
will produce (an enhanced PPP). If a proposal meets these
Science and Technology Policy (OSTP) to issue U.S.
criteria, it is to go through an independent, HHS-level,
Government Gain-of-Function Deliberative Process and
multidisciplinary P3CO review committee to determine, in
Research Funding Pause on Selected Gain-of-Function
part, whether the research is scientifically sound; the
Research Involving Influenza, MERS, and SARS Viruses in
pathogen is considered to be a credible source of a potential
October 2014. This initial pause affected 18 federally
future human pandemic; the potential risks compared to the
potential benefits to society are justified; there is no feasible
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link to page 2 Global Pandemics: Gain-of-Function Research of Concern
alternative method to address the same question in a
use research of concern (DURC) policies and the P3CO
manner that poses less risk; the investigators have
guidance.
demonstrated the capacity and commitment to conduct the
research safely and securely; research results are expected
Table 1. Select Policies for Life Science Research
to be responsibly communicated; the research will be
subject to ongoing federal oversight; and the research is
Federal Policy/Guidelines
Description
ethically justifiable.
NIH Guidelines for Research
Outlines science-based safety
Involving Recombinant or
practices for creating and
Based on this review, the P3CO review committee reports
Synthetic Nucleic Acid
handling recombinant and
to the HHS funding agency (i.e., NIH) whether the research
Molecules
synthetic nucleic acid
is acceptable, not acceptable, acceptable on the condition
molecules, and organisms and
that certain experiments are modified, or acceptable on the
viruses containing such
condition that certain risk mitigation measures are
molecules. Also articulates
employed at the federal and institutional level. The funding
responsibilities of institutions,
agency makes the final determination on whether or not the
investigators, and Institutional
project will be funded and must report its decision to HHS
Biosafety Committees.
and OSTP.
HHS Screening Framework
Aims to reduce the risk that
Since the implementation of the P3CO policy, three
Guidance for Providers of
synthetic DNA will be
research projects have been reviewed and approved. Two of
Synthetic Double-Stranded
deliberately misused to
these projects had originally been awarded in 2013 and
DNA
create dangerous organisms.
were subject to the 2014 pause. Those projects were
United States Government
Addresses institutional
subsequently reviewed in 2018 under the P3CO policy and
Policy for Institutional
oversight of DURC, which
were approved to continue. Both projects concluded in
Oversight of Life Sciences
includes policies, practices,
2019. The third project, while approved with additional risk
Dual Use Research of
and procedures to ensure the
mitigation measures, ultimately shifted to utilize alternative
Concern (DURC)
identification of DURC and
approaches that do not involve enhanced PPP research.
that risk mitigation measures
are implemented if needed.
CRS has not identified any publicly released data on how
many projects, if any, have been referred into P3CO review
Federal Select Agent Program Oversees the possession,
and subsequently retracted from consideration by their
(FSAP)
use, and transfer of biological
principal investigators. Such data might help policymakers
select agents and toxins that
understand whether, and how many, research projects do
have the potential to pose a
not go forward due to the requirements of the P3CO policy.
severe threat to public,
animal or plant health, or to
COVID-19 and GOF
animal or plant products.
The emergence of COVID-19 and debates on its origin
Source: HHS; U.S. Federal Select Agent Program.
have refocused attention on GOF. A particular focus has
been the NIH funding of the EcoHealth Alliance study,
NSABB is to review and provide recommendations
Understanding the Risk of Bat Coronavirus Emergence,
regarding the balance between security and transparency
which collaborated with scientists at the Wuhan Institute of
when sharing PPP research information. It should also
Virology. Some have argued this project should have been
recommend whether or how to incorporate the P3CO policy
captured by the 2014 pause on GOF research and reviewed
into DURC. In February 2022, NSABB’s charge was
under the HHS P3CO guidance. NIH asserts that the
updated to re-evaluate DURC definitions; support for
research project did not meet the criteria of either policy.
international ePPP research; and whether the P3CO
framework effectively balances the benefits, biosafety, and
Looking Ahead
biosecurity risks of ePPP research. In September 2022, the
In addition to P3CO, multiple federal policies and
NSABB issued preliminary draft findings and
guidelines governing the funding and oversight of life
recommendations (https://osp.od.nih.gov/wp-
sciences research could also capture components of GOF
content/uploads/NSABB_P3CO_WG_Preliminary_Draft_F
research (Table 1). These require certain biosafety and
indings_and_Recommendations.pdf). NSABB’s final
biosecurity protocols to be implemented at the institutions
recommendations are anticipated in late 2022 or early 2023.
where the research will be conducted. Several near-term
federal activities are examining how these federal
Section 19010 of the Coronavirus Aid, Relief, and
regulations, policies, and guidelines address oversight of
Economic Security (CARES) Act (P.L. 116-136) requires
GOF research and whether they produce duplicative
the Government Accountability Office to examine the
extent to which HHS oversight addresses biosafety and
requirements, inefficiencies, or coordination challenges.
biosecurity risks—including consideration of DURC,
In January 2020, the HHS Secretary charged the National
FSAP, and P3CO—and whether these programs are
Science Advisory Board for Biosecurity (NSABB), a
duplicative.
federal advisory committee that addresses issues related to
For additional information, see CRS Report R47114,
biosecurity and dual use research, with reviewing the dual
Oversight of Gain of Function Research with Pathogens:
Issues for Congress, by Todd Kuiken.
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Global Pandemics: Gain-of-Function Research of Concern

IF12021
Todd Kuiken, Analyst in Science and Technology Policy

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