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![handle is hein.crs/govefdm0001 and id is 1 raw text is: January 19, 2022
Global Pandemics: Gain-of-Function Research of Concern
Introduction
Gain-of-Function (GOF)research is abroad areaof
scientific inquiry where an organismgains a new property
or an existing property is altered. The terms gainoffunction
and loss offunction refer to any genetic mutation in an
organismthat 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 ofGOF
research is the study of both naturally occurring and
experimentally induced changes in organisms to better
understand the transmis sion, infection, and p athogenesis of
viruses. Through such knowledge, scientists hopeto
improve our understanding ofhuman-pathogen interactions,
aid in assessments of potentialpandemic pathogens, and
further public health preparedness. Some analysts have
raised concerns thats tudies designed to understand how
viruses might evolve may have the potential to generate
pathogens that affecthumans with the potential to cause a
pandemic. To focus attentionon this small subset of
studies, the scientific andpolicy communities havebegun
to use the terms gainoffunction research ofconcern
(GOFROC) and enhancedpotential pandemicpathogens
(PPP). However, all three terms (GOF, GOFROC, PPP)
have beenused interchangeably in some public discussions
and media.
Risks and Benefits
Scientists and the public have debated the risks andbenefits
of GOF research. Some in the scientific community argue
that the research is needed to better understandhow viruses
evolve, in order to develop better medical countermeasures
and surveillance regimes for emerging pathogens. Further,
they as sert that this research can be conducted responsibly
with proper bios afety and s ecurity 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 transmissionofthe 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
accidentalrelease. 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-FunctionDeliberative Process and
Research Funding Pause on Selected Ga in-of-Function
Research Involving Influenza, MERS, and SARS Viruses in
October 2014. This initialpause affected 18 federally
https://crsrept
funded research projects andcontracts; seven of them
subsequently received exemptions fromthe pause.
Current Oversight Mechanisms
As part of the 2014 p aus e on GOF research, OSTP initiated
a deliberative process to evaluate therisks andpotential
benefits of GOF res earch with potential pandemic
p athogens. In January 2017, OSTP released Recommended
Policy GuidanceforDepartmental Develop mentofReview
Mechanisms forPotential PandemicPathogen Care and
Oversight, [P3CO] which described attributes of federal
agency review and reporting processes for the additional
oversight offederally funded research thatis 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 supportGOF, GOFROC, or PPP research.
Following the OSTP guidance, theDepartment of Health
and Human Services (HHS) releasedFramework for
Guiding Funding Decisions About ProposedResearch
Involving Enhanced PotentialPandemic 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 additionalreview process forresearch
proposals that have gone through the normalscientific
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 fromthe 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 andlikely to
cause significant morbidity and/or
mortality in humans.
The P3CO reviewprocess examines both what is being
experimented on (a PPP) and 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 theres earch is scientifically sound; the
p athogen is considered to be a credible s ource of a potential
future human pandemic; the potential risks compared to the
potentialbenefits to society are justified; there is no feasible
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