Gain-of-function research (GoF research or GoFR) is
medical research
Medical research (or biomedical research), also known as experimental medicine, encompasses a wide array of research, extending from "basic research" (also called ''bench science'' or ''bench research''), – involving fundamental scientif ...
that genetically alters an organism in a way that may enhance the
biological functions of
gene product
A gene product is the biochemical material, either RNA or protein, resulting from expression of a gene. A measurement of the amount of gene product is sometimes used to infer how active a gene is. Abnormal amounts of gene product can be correlated ...
s. This may include an altered
pathogenesis
Pathogenesis is the process by which a disease or disorder develops. It can include factors which contribute not only to the onset of the disease or disorder, but also to its progression and maintenance. The word comes from Greek πάθος ''pat ...
,
transmissibility, or
host range
In biology and medicine, a host is a larger organism that harbours a smaller organism; whether a parasitic, a mutualistic, or a commensalist ''guest'' (symbiont). The guest is typically provided with nourishment and shelter. Examples include a ...
, i.e. the types of hosts that a
microorganism
A microorganism, or microbe,, ''mikros'', "small") and ''organism'' from the el, ὀργανισμός, ''organismós'', "organism"). It is usually written as a single word but is sometimes hyphenated (''micro-organism''), especially in olde ...
can infect. This research is intended to reveal targets to better predict
emerging infectious disease
An emerging infectious disease (EID) is an infectious disease whose incidence has increased recently (in the past 20 years), and could increase in the near future. The minority that are capable of developing efficient transmission between human ...
s and to develop
vaccines
A vaccine is a biological preparation that provides active acquired immunity
The adaptive immune system, also known as the acquired immune system, is a subsystem of the immune system that is composed of specialized, systemic cells and pro ...
and
therapeutics
A therapy or medical treatment (often abbreviated tx, Tx, or Tx) is the attempted remediation of a health problem, usually following a medical diagnosis.
As a rule, each therapy has indications and contraindications. There are many different ...
. For example,
influenza B
''Influenza B virus'' is the Monotypic taxon, only species in the genus ''Betainfluenzavirus'' in the virus family ''Orthomyxoviridae''.
Influenza B virus is known only to infect humans and Pinniped, seals. This limited host range is apparently ...
can infect only humans and harbor seals. Introducing
a mutation that would allow influenza B to infect rabbits in a controlled laboratory situation would be considered a gain-of-function experiment, as the virus did not previously have that function.
That type of experiment could then help reveal which parts of the virus's genome correspond to the species that it can infect, enabling the creation of antiviral medicines which block this function.
In
virology
Virology is the Scientific method, scientific study of biological viruses. It is a subfield of microbiology that focuses on their detection, structure, classification and evolution, their methods of infection and exploitation of host (biology), ...
, gain-of-function research is usually employed with the intention of better understanding current and future
pandemic
A pandemic () is an epidemic of an infectious disease that has spread across a large region, for instance multiple continents or worldwide, affecting a substantial number of individuals. A widespread endemic (epidemiology), endemic disease wi ...
s.
In vaccine development, gain-of-function research is conducted in the hope of gaining a head start on a virus and being able to develop a vaccine or therapeutic before it emerges.
The term "gain of function" is sometimes applied more narrowly to refer to "research which could enable a pandemic-potential pathogen to replicate more quickly or cause more harm in humans or other closely-related mammals."
Some forms of gain-of-function research (specifically work which involves certain
select agent
Under United States law, Biological select agents or toxins (BSATs) — or simply select agents for short — are bio-agents which (since 1997) have been declared by the U.S. Department of Health and Human Services (HHS) or by the U.S. Department ...
pathogens) carry inherent
biosafety
Biosafety is the prevention of large-scale loss of biological integrity, focusing both on ecology and human health.
These prevention mechanisms include conduction of regular reviews of the biosafety in laboratory settings, as well as strict guidel ...
and
biosecurity
Biosecurity refers to measures aimed at preventing the introduction and/or spread of harmful organisms (e.g. viruses, bacteria, etc.) to animals and plants in order to minimize the risk of transmission of infectious disease. In agriculture, thes ...
risks, and are thus also referred to as
dual use research of concern (DURC).
To mitigate these risks while allowing the benefits of such research, various governments have mandated that DURC experiments be regulated under additional oversight by institutions (so-called institutional "DURC" committees) and government agencies (such as the NIH's recombinant DNA advisory committee).
A mirrored approach can be seen in the
European Union
The European Union (EU) is a supranational political and economic union of member states that are located primarily in Europe. The union has a total area of and an estimated total population of about 447million. The EU has often been des ...
's Dual Use Coordination Group (DUCG).
Importantly, the US and EU regulations both mandate that an unaffiliated member of the public (or several) be "active participants" in the oversight process. Significant debate has taken place in the scientific community on how to assess the risks and benefit of gain-of-function research, how to publish such research responsibly, and how to engage the public in an open and honest review.
In January 2020, the
National Science Advisory Board for Biosecurity
The National Science Advisory Board for Biosecurity (NSABB) is a panel of experts that reports to the Secretary of the United States Department of Health and Human Services. It is tasked with recommending policies on such questions as how to preve ...
convened an expert panel to revisit the rules for gain-of-function research and provide more clarity in how such experiments are approved, and when they should be disclosed to the public.
Experiments that have been referred to as "gain-of-function"
In early 2011, two groups were investigating how flu viruses specific to birds could possibly cross over and create pandemics in humans: one led by
Yoshihiro Kawaoka
is a virologist specializing in the study of the influenza and Ebola viruses. He holds a professorship in virology in the Department of Pathobiological Sciences at the University of Wisconsin-Madison, USA, and at the University of Tokyo, Japan.
...
at the
University of Wisconsin–Madison
A university () is an educational institution, institution of higher education, higher (or Tertiary education, tertiary) education and research which awards academic degrees in several Discipline (academia), academic disciplines. Universities ty ...
in Madison, Wisconsin and another led by
Ron Fouchier Ronaldus (Ron) Adrianus Maria Fouchier (born 13 October 1966) is a Dutch virologist who is Deputy head of the Erasmus MC Department of Viroscience, headed by Prof. Marion Koopmans.
Notability
Fouchier is notable for his research on respiratory vir ...
at
Erasmus University Medical Center
Erasmus University Medical Center (Erasmus MC or EMC) based in Rotterdam, Netherlands, affiliated with Erasmus University and home to its faculty of medicine, is the largest and one of the most authoritative scientific University Medical Centers in ...
in the Netherlands.
Both groups had both
serially passaged H5N1 avian influenza in ferrets, manually taking the virus from one ferret to another, until it was capable of spreading via
respiratory droplets
A respiratory droplet is a small aqueous droplet produced by exhalation, consisting of saliva or mucus and other matter derived from respiratory tract surfaces. Respiratory droplets are produced naturally as a result of breathing, speaking, snee ...
. The normally bird-specific virus, through replication over time in the ferrets' lungs, had adopted several amino acid changes that enabled it to replicate in the mammalian lungs, which are notably colder than those found in birds. This small change also allowed the virus to transmit via droplets in the air made when the ferrets' coughed or sneezed.
Proponents of the Kawaoka and Fouchier experiments cited several benefits: these answered the question of how a virus like H5N1 could possibly become airborne in humans, allowed other researchers to develop vaccines and therapeutics which specifically targeted these amino acid changes, and also demonstrated that there was a linkage between transmissibility in avian viruses and lethality: while the virus had become more transmissible, it had also become significantly less deadly.
Various critics of the research (including members of Congress) responded to the publications with alarm. Others called the experiments an "engineered doomsday." Questions were raised by other scientists including Marc Lipsitch of the
T. H. Chan School of Public Health at
Harvard University
Harvard University is a private Ivy League research university in Cambridge, Massachusetts. Founded in 1636 as Harvard College and named for its first benefactor, the Puritan clergyman John Harvard, it is the oldest institution of higher le ...
about the relative risks and benefits of this research.
In May 2013, a group led by
Hualan Chen
Chen Hualan (; born March 1969) is a Chinese people, Chinese Veterinary virology, veterinary virologist best known for researching animal epidemic diseases. She is a member of the World Organisation for Animal Health (OIE) and a member of the Foo ...
, director of
China
China, officially the People's Republic of China (PRC), is a country in East Asia. It is the world's most populous country, with a population exceeding 1.4 billion, slightly ahead of India. China spans the equivalent of five time zones and ...
's
National Avian Influenza Reference Laboratory, published several experiments they had conducted at the
BSL3+ laboratory of the
Harbin Veterinary Research Institute Harbin Veterinary Research Institute (HVRI) is a Chinese biological research institute located in Harbin, China. It is under the supervision of the Chinese Academy of Agricultural Sciences (CAAS).
HVRI was created in 1948 and is the first veterinar ...
, investigating what would happen if a 2009 H1N1 circulating in humans infected the same cell as an avian influenza H5N1.
Importantly, the experiments had been conducted before a research pause on H5N1 experiments had been agreed upon by the greater virologist community.
They used these experiments to determine that certain genes, if reassorted in such a dual-infection scenario in the wild, would allow transmission of the H5N1 virus more easily in mammals (notably guinea pigs as a
model organism
A model organism (often shortened to model) is a non-human species that is extensively studied to understand particular biological phenomena, with the expectation that discoveries made in the model organism will provide insight into the workin ...
for rodent species), proving that certain agricultural scenarios carry the risk of allowing H5N1 to cross over into mammals. As in the Fouchier and Kawaoka experiments above, the viruses in this study were also significantly less lethal after the modification.
Critics of the 2013 Chen group study (including
Simon Wain-Hobson Simon Wain-Hobson (born 25 May 1953) is a British/French microbiologist, professor of molecular retrovirology at the Pasteur Institute in Paris, director of the French National HPV Reference Laboratory, and board chairman of the Foundation for Vacc ...
of the
Pasteur Institute
The Pasteur Institute (french: Institut Pasteur) is a French non-profit private foundation dedicated to the study of biology, micro-organisms, diseases, and vaccines. It is named after Louis Pasteur, who invented pasteurization and vaccines f ...
and former
Royal Society
The Royal Society, formally The Royal Society of London for Improving Natural Knowledge, is a learned society and the United Kingdom's national academy of sciences. The society fulfils a number of roles: promoting science and its benefits, re ...
President
Robert May) decried this as an unsafe experiment that was unnecessary to prove the intended conclusions, calling Chen's work "appallingly irresponsible" and also raising concerns about the biosafety of the laboratory itself.
Others (including the Director of the WHO Collaborating Centre on Influenza in Tokyo, Masato Tashiro) praised Chen's laboratory as "state of the art." Jeremy Farrar, director of the
Oxford University
Oxford () is a city in England. It is the county town and only city of Oxfordshire. In 2020, its population was estimated at 151,584. It is north-west of London, south-east of Birmingham and north-east of Bristol. The city is home to the ...
Clinical Research Unit in Ho Chi Minh City, described the work as "remarkable" and said that it demonstrated the "very real threat" that "continued circulation of H5N1 strains in Asia and Egypt" poses.
A preprint by
Boston University
Boston University (BU) is a private research university in Boston, Massachusetts. The university is nonsectarian, but has a historical affiliation with the United Methodist Church. It was founded in 1839 by Methodists with its original campu ...
researchers, published on 14 October 2022, described their experiments splicing the
SARS-CoV-2 BA.1 Omicron's spike protein into an ancestral SARS-CoV-2 variant isolated in the early days of the pandemic, creating a new
chimeric version of the virus. All of the six mice exposed to the ancestral variant died; eight of the ten mice exposed to the chimeric variant died; and none of the ten mice exposed to Omicron died. This suggests that "mutations outside of spike are major determinants of the attenuated pathogenicity of Omicron 209 in K18-hACE2 mice". According to the preprint, the work was supported by grants from various branches of the NIH. (However, the NIH later denied funding the experiments. The researchers later stated the NIH did not fund the experiments directly.)
On 17 October, the ''
Daily Mail
The ''Daily Mail'' is a British daily middle-market tabloid newspaper and news websitePeter Wilb"Paul Dacre of the Daily Mail: The man who hates liberal Britain", ''New Statesman'', 19 December 2013 (online version: 2 January 2014) publish ...
'' ran the headline "Boston University CREATES a new COVID strain that has an 80% kill rate — echoing dangerous experiments feared to have started the pandemic". (The headline was later flagged "as part of Facebook's efforts to combat false news and misinformation". ''
PolitiFact
PolitiFact.com is an American nonprofit project operated by the Poynter Institute in St. Petersburg, Florida, with offices there and in Washington, D.C. It began in 2007 as a project of the ''Tampa Bay Times'' (then the ''St. Petersburg Times'' ...
'' noted the "lab leak" theory was unproven, and also stated "citing the 80% figure alone leaves out key context, including that the resulting strain was less fatal than the original, which killed 100% of mice. Experts say this kind of research is not unusual and the experiment was conducted in accordance with accepted safety procedures.") All research funded by the NIH that can make COVID more virulent or transmissible must undergo an extra gain-of-function review. Critics charged that, because the chimera may have combined Omicron's high transmissibility with the ancestral strain's lethality, the experiment should have undergone the extra review. The researchers deny that the research was funded by the NIH, and also deny that the experiment qualified as gain-of-function in the first place.
Gain-of-function research of concern
Significant debate has taken place in the scientific community on how to assess risk-benefit of gain-of-function research, and how to engage the public in deliberations for policymaking. These concerns encompass
biosafety
Biosafety is the prevention of large-scale loss of biological integrity, focusing both on ecology and human health.
These prevention mechanisms include conduction of regular reviews of the biosafety in laboratory settings, as well as strict guidel ...
, relating to the accidental release of a pathogen into the population,
biosecurity
Biosecurity refers to measures aimed at preventing the introduction and/or spread of harmful organisms (e.g. viruses, bacteria, etc.) to animals and plants in order to minimize the risk of transmission of infectious disease. In agriculture, thes ...
relating to the intentional release of a pathogen into the population, and
bioethics
Bioethics is both a field of study and professional practice, interested in ethical issues related to health (primarily focused on the human, but also increasingly includes animal ethics), including those emerging from advances in biology, med ...
, the principles of biorisk management and research review procedures.
Academic symposia
Gain-of-Function Research: A Symposium
In December 2014, the
National Research Council National Research Council may refer to:
* National Research Council (Canada), sponsoring research and development
* National Research Council (Italy), scientific and technological research, Rome
* National Research Council (United States), part of ...
and the
Institute of Medicine
The National Academy of Medicine (NAM), formerly called the Institute of Medicine (IoM) until 2015, is an American nonprofit, non-governmental organization. The National Academy of Medicine is a part of the National Academies of Sciences, E ...
organized a two-day symposium to discuss the potential risks and benefits of gain-of-function research. The event was attended by scientists from around the world, including
George Gao,
Gabriel Leung
Gabriel Matthew Leung (, born 6 November 1972) is the executive director (Charities and Community) of the Hong Kong Jockey Club. From 2013 to 2022, he was the longest-serving Dean of Medicine at the University of Hong Kong, where he was also ...
and
Michael Selgelid
Michael J. Selgelid is a bioethicist and moral philosopher who has written on ethics and public health, biotechnology, and infectious diseases. He is the current director of the Centre for Human Bioethics at Monash University and of the World ...
,
Baruch Fischhoff,
Alta Charo
Robin Alta Charo (born 1958) is the Warren P. Knowles Professor of Law and Bioethics at the University of Wisconsin–Madison and a leading American authority on bioethics. She holds appointments in both Wisconsin's law school and medical school. ...
,
Harvey Fineberg,
Jonathan Moreno,
Ralph Cicerone
Ralph John Cicerone (May 2, 1943 – November 5, 2016) was an American atmospheric scientist and administrator. From 1998 to 2005, he was the chancellor of the University of California, Irvine. From 2005 to 2016, he was the president of the Unit ...
,
Margaret Hamburg
Margaret Ann "Peggy" Hamburg (born July 12, 1955, Chicago, Illinois) is an American physician and public health administrator, who is serving as the chair of the board of the American Association for the Advancement of Science (AAAS) and co-chair ...
,
Jo Handelsman
Jo Emily Handelsman (born March 19, 1959 in New York City) is the Director of the Wisconsin Institute for Discovery at University of Wisconsin–Madison. She is also a Vilas Research Professor and a Howard Hughes Medical Institute Professor. Dr. H ...
,
Samuel Stanley,
Kenneth Berns
Kenneth Ira Berns is an American virologist who is currently a distinguished professor emeritus at the department of Molecular Genetics and Microbiology at the University of Florida College of Medicine. He is primarily known for his work on adeno- ...
,
Ralph Baric,
Robert Lamb,
Silja Vöneky,
Keiji Fukuda
is a Japanese-American physician and epidemiologist, specializing in influenza epidemiology. He was an Assistant Director-General of the World Health Organization (WHO) from 2009 to 2016, and the Director of the School of Public Health at th ...
,
David Relman
David Arnold Relman is an American microbiologist and the Thomas C. and Joan M. Merigan Professor in Medicine, and in Microbiology & Immunology at the Stanford University School of Medicine. His research focuses on the human microbiome and mic ...
, and
Marc Lipsitch. Shortly thereafter, the US government granted exceptions to the GoFR moratorium to 7 out of 18 research projects that had been affected.
Gain-of-Function Research: A Second Symposium
On March 10–11, 2016, the
National Academies of Sciences, Engineering, and Medicine
The National Academies of Sciences, Engineering, and Medicine (also known as NASEM or the National Academies) are the collective scientific national academy of the United States. The name is used interchangeably in two senses: (1) as an umbrell ...
held its second public symposium to discuss potential U.S. government policies for the oversight of gain-of-function (GOF) research. The symposium was held at the request of the U.S. government to provide a mechanism to engage the life sciences community and the broader public and solicit feedback on optimal approaches to ensure effective federal oversight of GOF research as part of a broader U.S. government deliberative process.
Academic advocacy groups
Cambridge Working Group
The Cambridge Working Group was formed by Harvard epidemiologist
Marc Lipsitch with fellow scientists at a meeting held in Cambridge, Massachusetts, following a "trifecta" of biosecurity incidents involving the
CDC
The Centers for Disease Control and Prevention (CDC) is the national public health agency of the United States. It is a United States federal agency, under the Department of Health and Human Services, and is headquartered in Atlanta, Georgi ...
, including the accidental exposure of viable anthrax to personnel at CDC's Roybal Campus, the discovery of six vials containing viable smallpox from the 1950s, labeled as Variola but in a box with other samples poorly labeled, at the FDA's White Oak campus, and the accidental shipping of H9N2 vials contaminated with H5N1 from the CDC lab to a USDA lab.
On July 14, 2014, the group published a Consensus Statement authored by 18 founding members, including
Amir Attaran
Amir Attaran ( fa, امیر عطاران) is an American and Canadian professor in both the Faculty of Law and the School of Epidemiology, Public Health and Community Medicine at the University of Ottawa.
Early life and education
Attaran was bor ...
,
Barry Bloom
Barry R. Bloom is Harvard University Distinguished Service Professor and Joan L. and Julius H. Jacobson Professor of Public Health in the Department of Immunology and Infectious Diseases and Department of Global Health and Population in the Harv ...
,
Arturo Casadevall,
Richard H. Ebright,
Alison Galvani, Edward Hammond,
Thomas Inglesby
Thomas James Campbell Inglesby (19 September 1832 – 18 July 1889) was a South African building contractor, public official and Mayor of Cape Town.
Biography
Inglesby was the son of Jane Wilson and Thomas Inglesby, who was a master craftsman at ...
,
Michael Osterholm
Michael Thomas Osterholm (born March 10, 1953) is an American epidemiologist, Regents Professor, and Director of the Center for Infectious Disease Research and Policy at the University of Minnesota.
On November 9, 2020, Osterholm was named to ...
,
David Relman
David Arnold Relman is an American microbiologist and the Thomas C. and Joan M. Merigan Professor in Medicine, and in Microbiology & Immunology at the Stanford University School of Medicine. His research focuses on the human microbiome and mic ...
,
Richard Roberts,
Marcel Salathé and
Silja Vöneky. Since its initial publication, over 300 scientists, academics, and physicians have added their signature.
The statement advocates for all work involving potential pandemic pathogens to be halted until a quantitative and objective assessment of the risks has been undertaken. It then argues that alternative approaches that do not involve such risks should be used instead.
The group engaged in public advocacy, influencing the US government's decision in December 2014 to suspend funding of research that would create certain types of novel potential pandemic pathogens.
Scientists for Science
Shortly after the Cambridge Working Group released its position statement, Scientists for Science was formed by 37 signatories taking an alternative position, that "biomedical research on potentially dangerous pathogens can be performed safely and is essential for a comprehensive understanding of microbial disease pathogenesis, prevention and treatment." Since its publication, the SfS statement has received 200+ signatures from working scientists, academics, and biosafety professionals.
One of the group's founding members,
University of Pittsburgh
The University of Pittsburgh (Pitt) is a public state-related research university in Pittsburgh, Pennsylvania. The university is composed of 17 undergraduate and graduate schools and colleges at its urban Pittsburgh campus, home to the universit ...
virologist
W. Paul Duprex, has argued () that the then-recent few events were exceptions to an overall good record of lab safety, and that these exceptions should not have been a reason for shutting down experiments that may have been of tangible benefit to public health.
He and other SfS signatories have argued that these pathogens are already subject to extensive regulations and that it would be more advantageous and effective to focus on improving lab safety and oversight, ensuring that experiments are conducted in the public interest.
Notable signatories are
Constance Cepko
Constance Louise Cepko is a developmental biologist and geneticist in Harvard Medical School.
Education
She was born in Laurel, Maryland. She received her B.S. in biochemistry and microbiology at the University of Maryland College of Computer ...
,
Dickson Despommier
Dickson D. Despommier (June 5, 1940) is an emeritus professor of microbiology and Public Health at Columbia University. From 1971 to 2009, he conducted research on intracellular parasitism and taught courses on parasitic diseases, medical ecology ...
,
Erica Ollmann Saphire,
Geoffrey Smith,
Karla Kirkegaard
Karla Kirkegaard (born 1954) is the Violetta L. Horton Research Professor of genetics at the Stanford University School of Medicine. She was the chair of the Department of Microbiology and Immunology from 2006 to 2010. She is an elected member of ...
,
Sean Whelan,
Vincent Racaniello
Vincent R. Racaniello (born January 2, 1953) is a Higgins Professor in the Department of Microbiology and Immunology at Columbia University's College of Physicians and Surgeons. He is a co-author of a textbook on virology, ''Principles of Virolo ...
and
Yoshihiro Kawaoka
is a virologist specializing in the study of the influenza and Ebola viruses. He holds a professorship in virology in the Department of Pathobiological Sciences at the University of Wisconsin-Madison, USA, and at the University of Tokyo, Japan.
...
. Columbia University virologist
Ian Lipkin
Walter Ian Lipkin (born November 18, 1952) is the John Snow Professor of Epidemiology at the Mailman School of Public Health at Columbia University and a professor of Neurology and Pathology at the College of Physicians and Surgeons at Columbia ...
, who signed both statements, said "there has to be a coming together of what should be done".
Founders of both groups published a series of letters detailing their discussions and viewpoints.
All authors, however, agreed that more education of the public and open discussion of the risks and benefits was necessary. Several also wrote that sensationalized headlines and framings of the ongoing process as a "debate" with "opposing sides" had negatively affected the process, while the reality is much more collegial.
International policies and regulations
International outlook and engagement on gain-of-function research policy and regulation vary by country and region. Due to the potential effect on the global community at large, the ethical acceptability of such experiments depends on the extent to which it is accepted internationally. In 2010, the
World Health Organization
The World Health Organization (WHO) is a specialized agency of the United Nations responsible for international public health. The WHO Constitution states its main objective as "the attainment by all peoples of the highest possible level of h ...
developed a non-binding guidance document for DURC, summarizing the positions of many different nations as "self-governing" and others as strictly following oversight based on the International Health Regulations, the
Biological and Toxin Weapons Convention (BTWC), and the Center for International Security Studies' Biological Research Security System. The document also recommended the aforementioned as potential resources for countries to develop their own policies and procedures for DURC.
European Union
The European Academies Science Advisory Council has formed a working group to examine the issues raised by gain-of-function research and to make recommendations for the management of such research and its outputs.
The possibility for developing common approaches between the United States and Europe has been explored.
In May 2014, the German National Ethics Council presented a report to the
Bundestag
The Bundestag (, "Federal Diet") is the German federal parliament. It is the only federal representative body that is directly elected by the German people. It is comparable to the United States House of Representatives or the House of Commons ...
on proposed guidance for governance of GoFR. The report called for national legislation on DURC. As of May 2021, the German government has not passed the endorsed legislation.
The NEC also proposed a national code-of-conduct for researchers to consent, endorsing which experiments qualify as misconduct and which do not, based on founding principles of public benefit. The German Research Foundation and German National Academy of Sciences made a joint suggestion to expand the role of existing research ethics committees to also evaluate proposals of DURC.
United States
Gain-of-function research moratorium
From 2014 to 2017, the
White House
The White House is the official residence and workplace of the president of the United States. It is located at 1600 Pennsylvania Avenue NW in Washington, D.C., and has been the residence of every U.S. president since John Adams in 1800. ...
Office of Science and Technology Policy
An office is a space where an organization's employees perform administrative work in order to support and realize objects and goals of the organization. The word "office" may also denote a position within an organization with specific dut ...
and the
Department of Health and Human Services
The United States Department of Health and Human Services (HHS) is a cabinet-level executive branch department of the U.S. federal government created to protect the health of all Americans and providing essential human services. Its motto is " ...
instituted a gain-of-function research moratorium and funding pause on any dual-use research into specific pandemic-potential pathogens (
influenza
Influenza, commonly known as "the flu", is an infectious disease caused by influenza viruses. Symptoms range from mild to severe and often include fever, runny nose, sore throat, muscle pain, headache, coughing, and fatigue. These symptoms ...
,
MERS
Middle East respiratory syndrome (MERS) is a viral respiratory infection caused by ''Middle East respiratory syndrome–related coronavirus'' (MERS-CoV). Symptoms may range from none, to mild, to severe. Typical symptoms include fever, cough, ...
, and
SARS
Severe acute respiratory syndrome (SARS) is a viral respiratory disease of zoonotic origin caused by the severe acute respiratory syndrome coronavirus (SARS-CoV or SARS-CoV-1), the first identified strain of the SARS coronavirus species, ''sever ...
) while the regulatory environment and review process were reconsidered and overhauled.
Under the moratorium, any laboratory who conducted such research would put their future funding (for any project, not just the indicated pathogens) in jeopardy.
The NIH has said 18 studies were affected by the moratorium.
The moratorium was a response to
laboratory biosecurity incidents that occurred in 2014, including not properly inactivating
anthrax
Anthrax is an infection caused by the bacterium ''Bacillus anthracis''. It can occur in four forms: skin, lungs, intestinal, and injection. Symptom onset occurs between one day and more than two months after the infection is contracted. The sk ...
samples, the discovery of unlogged
smallpox
Smallpox was an infectious disease caused by variola virus (often called smallpox virus) which belongs to the genus Orthopoxvirus. The last naturally occurring case was diagnosed in October 1977, and the World Health Organization (WHO) c ...
samples, and injecting a chicken with the wrong strain of
influenza
Influenza, commonly known as "the flu", is an infectious disease caused by influenza viruses. Symptoms range from mild to severe and often include fever, runny nose, sore throat, muscle pain, headache, coughing, and fatigue. These symptoms ...
. These incidents were not related to gain-of-function research. One of the goals of the moratorium was to reduce the handling of dangerous pathogens by all laboratories until safety procedures were evaluated and improved.
Subsequently, symposia and expert panels were convened by the
National Science Advisory Board for Biosecurity
The National Science Advisory Board for Biosecurity (NSABB) is a panel of experts that reports to the Secretary of the United States Department of Health and Human Services. It is tasked with recommending policies on such questions as how to preve ...
(NSABB) and
National Research Council National Research Council may refer to:
* National Research Council (Canada), sponsoring research and development
* National Research Council (Italy), scientific and technological research, Rome
* National Research Council (United States), part of ...
(NRC).
In May 2016,
[ the NSABB published "Recommendations for the Evaluation and Oversight of Proposed Gain-of-Function Research".] On 9 January 2017, the HHS published the "Recommended Policy Guidance for Departmental Development of Review Mechanisms for Potential Pandemic Pathogen Care and Oversight" (P3CO). This report sets out how "pandemic potential pathogens" should be regulated, funded, stored, and researched to minimize threats to public health and safety.
On 19 December 2017, the NIH
The National Institutes of Health, commonly referred to as NIH (with each letter pronounced individually), is the primary agency of the United States government responsible for biomedical and public health research. It was founded in the late ...
lifted the moratorium because gain-of-function research was deemed "important in helping us identify, understand, and develop strategies and effective countermeasures against rapidly evolving pathogens that pose a threat to public health
Public health is "the science and art of preventing disease, prolonging life and promoting health through the organized efforts and informed choices of society, organizations, public and private, communities and individuals". Analyzing the det ...
."
COVID-19 pandemic
During the COVID-19 pandemic
The COVID-19 pandemic, also known as the coronavirus pandemic, is an ongoing global pandemic of coronavirus disease 2019 (COVID-19) caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). The novel virus was first identif ...
a number of highly speculative theories spread about the origin of the SARS-CoV-2
Severe acute respiratory syndrome coronavirus 2 (SARS‑CoV‑2) is a strain of coronavirus that causes COVID-19 (coronavirus disease 2019), the respiratory illness responsible for the ongoing COVID-19 pandemic. The virus previously had a ...
virus and links to gain-of-function research. In January 2021, University of Saskatchewan
A university () is an institution of higher (or tertiary) education and research which awards academic degrees in several academic disciplines. Universities typically offer both undergraduate and postgraduate programs. In the United States, t ...
virologist Angela Rasmussen
Angela Lynn Rasmussen is an American virologist at the Vaccine and Infectious Disease Organization at the University of Saskatchewan in Canada.
Education and early career
During graduate school, Rasmussen worked in the laboratory of Vincent ...
wrote that one version of the information invoked previous gain-of-function work on coronaviruses to promulgate the idea that the virus was of laboratory origin. Rasmussen stated that this was unlikely, due to the intense scrutiny and government oversight to which GoFR is subject, and it is improbable that research on hard-to-obtain coronaviruses could occur under the radar.
In a congressional hearing on May 11, 2021, about Anthony Fauci
Anthony Stephen Fauci (; born December 24, 1940) is an American physician-scientist and immunologist serving as the director of the National Institute of Allergy and Infectious Diseases (NIAID) and the chief medical advisor to the president. ...
's role as the Chief Medical Advisor to the United States Office of the President, senator Rand Paul
Randal Howard Paul (born January 7, 1963) is an American physician and politician serving as the junior U.S. senator from Kentucky since 2011. A member of the Republican Party, he is a son of former three-time presidential candidate and 12 ...
stated that "the U.S. has been collaborating with Shi Zhengli of the Wuhan Virology Institute, sharing discoveries about how to create super viruses. This gain-of-function research has been funded by the NIH." Fauci responded "with all due respect, you are entirely and completely incorrect...the NIH has not ever and does not now fund gain-of-function research onducted atthe Wuhan Institute of Virology." ''The Washington Post
''The Washington Post'' (also known as the ''Post'' and, informally, ''WaPo'') is an American daily newspaper published in Washington, D.C. It is the most widely circulated newspaper within the Washington metropolitan area and has a large nati ...
'' fact-checking team later rated Paul's statements as containing "significant omissions and/or exaggerations". NIH funding to the EcoHealth Alliance
EcoHealth Alliance is a US-based non-governmental organization with a stated mission of protecting people, animals, and the environment from emerging infectious diseases. The nonprofit is focused on research that aims to prevent pandemics and p ...
and later sub-contracted to the Wuhan Institute of Virology
The Wuhan Institute of Virology, Chinese Academy of Sciences (WIV; ) is a research institute on virology administered by the Chinese Academy of Sciences (CAS), which reports to the State Council of the People's Republic of China. The institute ...
was not to support gain-of-function experiments, but instead to enable the collection of bat samples in the wild. EcoHealth Alliance spokesperson Robert Kessler has also categorically denied the accusation.
''The Washington Post'' also quoted Rutgers University
Rutgers University (; RU), officially Rutgers, The State University of New Jersey, is a Public university, public land-grant research university consisting of four campuses in New Jersey. Chartered in 1766, Rutgers was originally called Queen's ...
biosecurity expert Richard Ebright's dissenting opinion about Fauci's testimony, demonstrating that there is disagreement about what qualifies as "gain of function" research. Ebright asserted that experiments conducted under the EcoHealth grant "met the definition for gain-of-function research of concern under the 2014 Pause." MIT
The Massachusetts Institute of Technology (MIT) is a private land-grant research university in Cambridge, Massachusetts. Established in 1861, MIT has played a key role in the development of modern technology and science, and is one of the m ...
molecular biologist Alina Chan
Alina Chan is a Canadian molecular biologist specializing in gene therapy and cell engineering at the Broad Institute of MIT and Harvard, where she is a postdoctoral fellow. During the COVID-19 pandemic she became known for questioning the prevail ...
has argued that these experiments would not have been affected by the 2014 moratorium, because the experiments involved "naturally-occurring viruses" adding that the moratorium had "no teeth".
Several scientists have criticized the US government's GoFR regulations as having serious shortcomings (especially with regards to the NIH's funding of the EcoHealth Alliance grant proposal). Ebright has remarked that the process is not applied to all experiments which are implicated in the government's policies, while virologists David Relman
David Arnold Relman is an American microbiologist and the Thomas C. and Joan M. Merigan Professor in Medicine, and in Microbiology & Immunology at the Stanford University School of Medicine. His research focuses on the human microbiome and mic ...
and Angela Rasmussen have cited a worrying lack of transparency from oversight panels.
See also
* Biotechnology risk
* Directed evolution
Directed evolution (DE) is a method used in protein engineering that mimics the process of natural selection to steer proteins or nucleic acids toward a user-defined goal. It consists of subjecting a gene to iterative rounds of mutagenesis (cre ...
* Dual-use technology
In politics, diplomacy and export control, dual-use items refers to goods, software and technology that can be used for both civilian and military applications.
* Global Virome Project
References
{{Reflist
Further reading
* European Academies' Science Advisory Council: Gain of function: experimental applications relating to potentially pandemic pathogens
Report
Virology
Zoonoses