Gain-of-function (GOF) research involves experimentation that aims or is expected to (and/or, perhaps, actually does) increase the transmissibility and/or virulence of pathogens.
Explained: The Concept of Gain-of-Function Research
Delhi (ABC Live India): Gain-of-Function Research :Amid Global Fight against
COVID-19, a serious debate is going on whether the virus evolved naturally or
was Coronavirus engineered in Wuhan laboratory.
lobby led by United States is confirming that Coronavirus virus is by-product
of Chinese Wuhan Laboratory, whereas China denied the allegation duly supported
by World Health Organization.
Research Team without siding with any of side trying to evaluate the case for
that publishing the scientific research theory which deals with laboratory made
Gain-of-function (GOF) research involves experimentation that aims
or is expected to (and/or, perhaps, actually does) increase the
transmissibility and/or virulence of pathogens. Such research, when conducted
by responsible scientists, usually aims to improve understanding of disease
causing agents, their interaction with human hosts, and/or their potential to
The ultimate objective of such research is to better inform public
health and preparedness efforts and/or development of medical countermeasures.
Despite these important potential benefits, GOF research (GOFR) can pose risks
regarding biosecurity and biosafety.
GOFR is a subset of “dual-use
research”—i.e., research that can be used for both beneficial and malevolent
purposes (Miller and Selgelid 2008; National Research Council 2004).
‘Dual-use research of concern’ (DURC) refers to dual-use research for which the
consequences of malevolent use would be exceptionally severe (whereas almost
any research might be considered “dual-use” broadly conceived—because almost
any research, or just about anything for that matter, can be used for some
malevolent purpose or other). Of particular concern in the context of life
science research is that advances in biotechnology may enable development and
use of a new generation of biological weapons of mass destruction.
DURC has thus been one of the
most hotly debated science policy issues during the 21st century, with
controversy surrounding a series of published experiments with potential
implications for biological weapons-making. Such studies include the genetic
engineering of a superstrain of the mousepox virus in 2001 (Jackson et al. 2001), the artificial synthesis (via synthetic
genomics) of a “live” polio virus from chemical components in 2002 (Cello et
al. 2002), and the
reconstruction (via synthetic genomics) of the 1918 “Spanish Flu” virus in 2005
(Tumpey et al. 2005).
Though all of these studies involved legitimate aims, critics
argued that they should not have been conducted and/or published. Some argued
that publishing studies like these in full detail provided “recipes” for
especially dangerous potential biological weapons agents to would-be
bioterrorists. Many who acknowledged such potential dangers, on the other hand,
argued that benefits of publication outweighed risks involved.
The most controversial dual-use
life science experiments to date involved the creation of highly pathogenic
H5N1 (avian) influenza virus strains that were airborne transmissible between
ferrets, which provide the best model for influenza in humans (Herfst et al. 2012; Imai et al. 2012). This research addressed an important
scientific question—i.e., Might it be possible for H5N1 to naturally evolve
into a human-to-human transmissible strain and thus result in a pandemic?—and
(purportedly) yielded an affirmative answer.
After the US National Science Advisory Board for Biosecurity
(NSABB) initially recommended that these studies should be published in a
redacted form (i.e., including key findings, while omitting detailed
description of materials and methods), it later approved publication of revised
versions in full, and the papers were published in 2012.
Advocates of these studies/publications
argued that they would improve surveillance of H5N1 in nature (facilitating
early identification of, and thus better response to, the emergence of
potential pandemic strains) and facilitate development of vaccines that might
be needed to protect against pandemic strains of the virus.
Critics questioned the validity of claims about such benefits and
argued that the studies might facilitate creation of biological weapons agents
that could kill millions, or possibly even billions, of people.
While the concern about the
biological weapons implications of this ferret H5N1 research pertains to
dangers of dual-use life science research as traditionally conceived, many of
the objections to this research additionally addressed the danger that the pathogens
created might have escaped from laboratories, and potential consequences
thereof—and there were particular concerns about the conditions under which
this research was conducted (e.g., the safety level of the laboratories where
this research was conducted).
these ferret H5N1 experiments has thus lead to a significant shift in debate
about dual-use research to framing in terms of “gain-of-function research”.
Whereas the dual-use debate largely focused on biosecurity dangers associated
with potential malevolent use of research, the GOFR debate has more explicitly
focused on risks involving both
biosecurity and biosafety—the point being that creation of
especially dangerous pathogens might pose highly significant biosafety risks
that are independent of, and perhaps more feasible to measure/assess than,
risks associated with malevolent use.
Since the first high-profile DURC
life science experiments were published in the early 2000s, much policy debate
has surrounded questions about how DURC should be governed.
Among other things, it has been argued that increased oversight of
research and/or publication of potentially dangerous discoveries may be
necessary, that codes of conduct for scientists (explicitly addressing dual use
issues) should be adopted, and/or that scientists should be further educated
about the dual use phenomenon and ethics; and relevant policies have been
implemented to varying degrees in different countries.
In light of the ferret H5N1 research controversy, furthermore,
influenza researchers imposed a voluntary moratorium on GOF studies from
January 2012 to February 2013; and the US Government developed/adopted policy
regarding the funding of GOF H5N1 studies in 2013 (Department of Health and
Human Services 2013).
Following more recent reports of biosafety mishaps involving
anthrax, smallpox, and H5N1 in government laboratories—and burgeoning debate
regarding biosafety risks of GOFR more generally (Kaiser 2014)—in 2014 the administration of US
President Barack Obama called for a “pause” on funding (and relevant research
with existing US Government funding) of GOF experiments involving influenza,
SARS, and MERS viruses in particular.
This pause applies specifically to experiments that “may be
reasonably anticipated to confer attributes … such that the virus would have
enhanced pathogenicity and/or transmissibility in mammals via the respiratory
route” (White House 2014).
With announcement of this pause, the US Government launched a
“deliberative process … to address key questions about the risks and benefits
of gain-of-function studies” (White House 2014)
to inform future funding decisions—and NSABB was tasked with making
recommendations to the US Government on this matter.
As part of this deliberative process, the National Institutes of
Health (NIH) commissioned this Ethical Analysis White Paper providing:
- Review and summary of ethical literature on GOFR;
- Identification and analysis of existing ethical and decision-making frameworks relevant to (i) the evaluation of risks and benefits of GOFR, (ii) decision-making about the conduct of GOF studies, and (iii) the development of US policy regarding GOFR (especially with respect to funding of GOFR); and
- Development of an ethical and decision-making framework that may be considered by NSABB when analyzing information provided by GOFR risk-benefit assessment, and when crafting its final recommendations (especially regarding GOFR funding policy decisions in particular).
Next Part We will Publish Gain-of-Function Research Ethics