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![handle is hein.crs/govejlu0001 and id is 1 raw text is: Congressional Research Servic
Informing the legisiative debate since 1914
Updated November 21, 2022
Global Pandemics: Gain-of-Function Research of Concern
Introduction
Gain-of-Function (GOF) research is a broad area of
scientific inquiry where an organism gains a new property
or an existing property is altered. The terms gain offunction
and loss offunction refer to any genetic mutation in an
organism that either confers a new or enhanced ability or
causes the loss of an ability. Such changes often occur
naturally. Additionally, scientists can induce some changes
to organisms through experimentation. A key area of GOF
research is the study of both naturally occurring and
experimentally induced changes in organisms to better
understand the transmission, infection, and pathogenesis of
viruses. Through such knowledge, scientists hope to
improve our understanding of human-pathogen interactions,
aid in assessments of potential pandemic pathogens, and
further public health preparedness. Some analysts have
raised concerns that studies designed to understand how
viruses might evolve may have the potential to generate
pathogens that affect humans with the potential to cause a
pandemic. To focus attention on this small subset of
studies, the scientific and policy communities have begun
to use the terms gain offunction research of concern
(GOFROC) and enhanced potential pandemic pathogens
(PPP). However, all three terms (GOF, GOFROC, PPP)
have been used interchangeably in some public discussions
and media.
Risks and Benefits
Scientists and the public have debated the risks and benefits
of GOF research. Some in the scientific community argue
that the research is needed to better understand how viruses
evolve, in order to develop better medical countermeasures
and surveillance regimes for emerging pathogens. Further,
they assert that this research can be conducted responsibly
with proper biosafety and security protocols. Others argue
that the risks outweigh any potential benefits and that
alternative experiments should be considered.
Concerns over GOF research first emerged in 2011-2012
around a set of studies funded by the National Institutes of
Health (NIH) on respiratory transmission of the highly
pathogenic avian influenza virus H5N1. At that time, the
debate centered on the security risks of publishing the
results of these studies and whether the research should
have been allowed to proceed considering the risk of
accidental release. These debates, along with a series of
government laboratory biosafety incidents, not associated
with the H5N1 studies, led the White House Office of
Science and Technology Policy (OSTP) to issue U.S.
Government Gain-of-Function Deliberative Process and
Research Funding Pause on Selected Gain-of-Function
Research Involving Influenza, MERS, and SARS Viruses in
October 2014. This initial pause affected 18 federally
funded research projects and contracts; seven of them
subsequently received exemptions from the pause.
Current Oversight Mechanisms
As part of the 2014 pause on GOF research, OSTP initiated
a deliberative process to evaluate the risks and potential
benefits of GOF research with potential pandemic
pathogens. In January 2017, OSTP released Recommended
Policy Guidance for Departmental Development of Review
Mechanisms for Potential Pandemic Pathogen Care and
Oversight, [P3CO] which described attributes of federal
agency review and reporting processes for the additional
oversight of federally funded research that is anticipated to
create, transfer, or use enhanced pathogens with pandemic
potential. Agency implementation of a review and reporting
process with the described attributes would allow an agency
to support GOF, GOFROC, or PPP research.
Following the OSTP guidance, the Department of Health
and Human Services (HHS) released Framework for
Guiding Funding Decisions about Proposed Research
Involving Enhanced Potential Pandemic Pathogens (P3CO)
in December 2017. The HHS P3CO framework releases
HHS from the 2014 GOF research pause. HHS appears to
be the only agency that has developed a GOF review
process that addresses the 2017 OSTP GOF guidance, and
the only federal agency that has reported GOF research
funding.
Key Components of HHS P3CO Framework
P3CO establishes an additional review process for research
proposals that have gone through the normal scientific
review process, have been determined to be scientifically
sound, and are reasonably anticipated to create, transfer, or
use enhanced potential pandemic pathogens (PPPs), defined
as PPPs resulting from the enhancement of the
transmissibility and/or virulence of a pathogen. To be
subject to this extra scrutiny, an enhanced PPP must satisfy
two criteria:
1. It is likely highly transmissible and likely
capable of wide and uncontrollable spread
in human populations; and
2. It is likely highly virulent and likely to
cause significant morbidity and/or
mortality in humans.
The P3CO review process examines what the experiment
will produce (an enhanced PPP). If a proposal meets these
criteria, it is to go through an independent, HHS-level,
multidisciplinary P3CO review committee to determine, in
part, whether the research is scientifically sound; the
pathogen is considered to be a credible source of a potential
future human pandemic; the potential risks compared to the
potential benefits to society are justified; there is no feasible](ViewImageLocal?handle=hein.crs/govejlu0001&div=1&collection=&method=preview&ext=.png&size=3)