Explained: The Concept of Gain-of-Function Research

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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.

New 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.

A 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.

ABC 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 viruses.

Gain-of-function (GOF) Research

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 cause pandemics.

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 ; National Research Council ). ‘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. ), the artificial synthesis (via synthetic genomics) of a “live” polio virus from chemical components in 2002 (Cello et al. ), and the reconstruction (via synthetic genomics) of the 1918 “Spanish Flu” virus in 2005 (Tumpey et al. ).

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. ; Imai et al. ). 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).

 Controversy surrounding 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 ).

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 )—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 ).

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 ) 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:

  1. Review and summary of ethical literature on GOFR;
  2. 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
  3. 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).

In Next Part We will Publish Gain-of-Function Research Ethics

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