Gain-of-Function Research and the COVID Origins Debate

While there is no formally agreed upon definition of GOF research, it broadly involves the deliberate modification of pathogens to enhance traits such as transmissibility, virulence, or ability to infect new species.

Its primary aim is to understand how viruses evolve naturally in order to develop more effective vaccines and therapeutics before high-risk variants emerge in the wild. The practice has gained attention, particularly after the COVID-19 pandemic, due to concerns about potential accidents or misuse.

Historical Background of GOF

GOF research has roots dating back over a century to Louis Pasteur's early work. Although the term "gain-of-function" is more modern, scientists have been modifying pathogens for decades. The development of live attenuated vaccines like the measles vaccine in the 1960s, for example, utilized techniques now classified as GOF.

Early 21st Century Developments

In the early 2000s, GOF techniques became more precise, affordable, and accessible. After the 2003 SARS outbreak, research on coronaviruses increased, with Dr. Ralph Baric's lab at the University of North Carolina emerging as a leader in this type of research. A significant breakthrough came in 2006 when scientists successfully inserted a synthetic "cutting spot" — called a furin cleavage site — into the SARS-CoV spike protein. This modification was crucial for understanding how coronaviruses could potentially adapt to infect humans more efficiently.

GOF Research Today

The COVID-19 pandemic brought increased attention to GOF due to the lab leak theory, which alleges that the SARS-CoV-2 virus might have accidentally escaped from a research facility — specifically the Wuhan Institute of Virology (WIV) — where studies on coronaviruses were being conducted. The Chinese government denies GOF was being conducted at the WIV.

Before 2014, U.S. funding mechanisms for viral research — including GOF studies — operated with relatively limited oversight.

Federal agencies such as the National Institutes of Health (NIH), National Science Foundation (NSF), and Department of Defense (DOD) were major funders of international virology projects. The Bayh-Dole Act of 1980 allowed researchers to patent government-funded inventions, potentially influencing research agendas and commercial incentives.

Early International Collaboration and U.S.-China Ties

International collaboration between U.S. and Chinese labs grew significantly after the 2003 SARS outbreak. Dr. Hugh Auchincloss, who would later serve as Dr. Fauci's temporary successor at the National Institute of Allergy and Infectious Diseases (NIAID), led efforts to expand collaborative research with Chinese institutions. In 2011, Auchincloss traveled to Beijing to sign an agreement with a Chinese military-linked science foundation that funded work on bat coronaviruses conducted by New York-based EcoHealth Alliance and the Wuhan Institute of Virology (WIV).

The WIV also collaborated with labs in Texas, France, and Canada, and received funding from EcoHealth, which itself received funding from the NIAID. Some observers have noted that these collaborations included research related to GOF techniques, and that Dr. Shi Zhengli — who conducted coronavirus research at WIV — received training at the University of North Carolina, where Dr. Ralph Baric led similar studies.

Scientific Advocacy vs. Security Concerns

In 2012, Dr. Anthony Fauci publicly defended GOF research, stating that the potential benefits in vaccine development and viral understanding often outweighed the risks. However, critics argued that using U.S. taxpayer funds to support such research — particularly in foreign high-containment labs — violated regulatory safeguards and posed national security risks.

Emerging Biosecurity Concerns

Despite the scientific advances, safety concerns began to intensify. Initial safety protocols were stringent, with experiments conducted in high-containment laboratories, but critics argued even strict oversight might not mitigate all risks.

The controversy peaked in 2012 when controversial studies on H5N1 avian flu conducted in high-security labs sparked heated debates about biosecurity risks. These studies involved manipulating wild viruses to study their potential to infect humans.

Regulatory and Diplomatic Red Flags

Fears of accidental release of enhanced pathogens became a central issue following the avian flu outbreak. The Government Accountability Office raised alarms, leading to congressional hearings on improving lab safety oversight. U.S. embassy officials in Beijing later warned about potential safety risks at WIV in 2017 and 2018.

Dual-Use Dilemma and Strategic Priorities

The dual-use nature of GOF research — offering both life-saving insights and potential biowarfare applications — posed a dilemma for regulators. The National Science Advisory Board for Biosecurity (NSABB) was assigned to weigh benefits and risks. Despite increasing recognition of pandemic threats as national security issues, the U.S. was criticized for underinvesting in domestic virology capacity before 2014.

Between 2014 and 2017, the United States underwent a significant shift in its approach to GOF research, with these changes becoming central to the COVID-19 origin debate.

In 2014, growing biosafety concerns prompted the U.S. Department of Health and Human Services (DHHS) to implement a moratorium on funding for certain types of GOF research. This pause specifically targeted studies involving potentially pandemic-causing pathogens like SARS and MERS coronaviruses, as scientists and policymakers warned that a laboratory accident could trigger a catastrophic outbreak. The NSABB was tasked with reviewing the issues and recommending new policies.

Moratorium Exemptions

Despite the moratorium, several GOF studies were allowed to proceed through NIH-approved exemptions deemed necessary for public health or national security. Among them was the controversial Baric-Shi study on chimeric coronaviruses — a collaboration between American and Chinese scientists that had begun prior to the moratorium and received approval to continue.

In total, the NIH identified 18 GOF projects affected by the moratorium, and seven of these were granted exemptions to continue. The moratorium also had international repercussions. Some research projects potentially shifted overseas, with U.S.-based organizations like EcoHealth Alliance partnering with the Wuhan Institute of Virology.

Revised Oversight and the P3CO Framework

By 2016, the NSABB had completed its review and recommended new safety guidelines for high-risk research to ensure it could resume with appropriate safeguards.

In 2017, after implementing the new Potential Pandemic Pathogen Care and Oversight (P3CO) framework, the DHHS lifted the funding pause. The new safety framework required additional checks and approvals for studies that might create more dangerous pathogens. Research institutions had to demonstrate both the safety and necessity of their work before receiving funding.

GOF entered the spotlight again following the COVID-19 pandemic due to the proximity of the WIV to the epicenter of the initial outbreak and the Chinese government’s response, which led some to hypothesize the pandemic may have been the result of a lab leak.

In the earliest days of the COVID-19 pandemic, global understanding was marked by uncertainty and delayed information. Chinese authorities reportedly detected unusual cases in Wuhan as early as November 2019, though this information wasn't widely known. By late December, doctors in Wuhan identified a cluster of pneumonia cases, with official reporting beginning on Dec. 31, 2019.

Chinese Response and Information Sharing

Chinese researchers sequenced the virus's genome on Dec. 27, 2019. However, information sharing was quickly restricted, with private labs ordered to stop testing on Dec. 30 and a national directive issued on Jan. 3, 2020, limiting information flow. That same day, China officially notified the World Health Organization (WHO) about the situation, as the agency had requested further information about an unusual pneumonia two days earlier.

Initial Case Links and Genome Release

Many early cases were linked to the Huanan Seafood Wholesale Market, which was closed on Jan. 1, 2020. However, some early cases had no connection to the market, complicating the virus's origin theories. Chinese officials confirmed the discovery of a novel coronavirus on Jan. 7, with the virus genome publicly released on Jan. 11, although it was shared by a Chinese researcher on a U.S. website, possibly without government approval.

Scientific Confirmation and Early Measures

By Jan. 6, the virus was isolated and identified as the cause of the pneumonia. Human-to-human transmission was confirmed by mid-January, and the severity became evident when Wuhan and Hubei province entered lockdown on Jan. 23.

Origins Debate and Initial Consensus

Early scientific assessments favored a natural origin theory, with the virus likely jumping from horseshoe bats to humans through an intermediate animal host. The Huanan Seafood Market was identified as an early hotspot, though the nearby WIV raised questions about a potential lab leak.

The investigation into COVID-19’s origins during 2020–2021 was shaped by both political dynamics and scientific uncertainty.

The Trump administration initially downplayed the threat and delayed measures like widespread testing and contact tracing. As the pandemic progressed, Trump and Secretary of State Pompeo publicly suggested that the virus may have originated at WIV, contradicting the official statements made by U.S. intelligence officials and health expert.

In July 2020, the administration announced that the United States would withdraw from the WHO, accusing it of mishandling the pandemic and aiding China in covering up COVID-19's origins. The administration also allegedly pressured scientific agencies like the CDC to align with political messaging.

Scientific Debate on Origins

The debate over COVID-19's origins intensified during this period. Initially, most scientists publicly favored a natural origin, citing similarities between SARS-CoV-2 and bat coronaviruses, and early cases' connection to the Huanan Market. However, the inability to find an intermediate host and the presence of a unique furin cleavage site in SARS-CoV-2 raised questions. The lab leak theory gained attention in 2021, partly due to articles by British science writer Nicholas Wade highlighting the WIV's location and coronavirus research.

Proximal Origin Controversy

Nature Medicine published a paper titled the "Proximal Origin of SARS-CoV-2" in March 2020, which generated criticism from some prominent scientists, in particular Richard H. Ebright, a Board of Governors Professor of Chemistry and Chemical Biology at Rutgers University. The paper argued that SARS-CoV-2 most likely originated from natural zoonotic transmission rather than a lab leak, with the media and public health figures frequently citing it to refute the lab leak theory.

Ebright, who called the paper "scientific fraud," detailed his criticisms through public statements, X posts, and interviews, focusing on allegations of scientific misconduct, misrepresentation of data, and the need for the paper's retraction.

Ebright highlighted internal messages between the paper's authors — which were later confirmed by the Intercept — demonstrating the authors' doubts about the natural-origin hypothesis and that they considered a lab origin plausible. Ebright inferred that the paper's conclusions were influenced by the authors' ties to funding agencies and institutions with stakes in downplaying the lab leak theory, noting that some authors received funding from the NIH.

Though Ebright's criticisms of the natural origin theory were not outright dismissed, many prominent scientists downplayed the possibility of the lab leak theory or said it was unlikely.

Response to Ebright

In 2024, around a dozen scientists filed a formal complaint with Rutgers alleging that Ebright and microbiologist Bryce Nickels violated the university's policies on free expression by posting "provably false" comments they said were defamatory and threatened the scientists' safety. Ebright said the complaint was "a crude effort to silence their opponents."

In 2025, the second Trump administration published a paper supporting Ebright's claims. The White House echoed many of Ebright's initial criticisms of the "Proximal Origins" paper, alleging that the Biden administration resorted to "outright censorship—coercing and colluding with the world's largest social media companies to censor all COVID-19-related dissent."

WHO Investigation and Access Challenges

The WHO faced significant challenges investigating the origins. In early 2021, the WHO conducted a brief two-week investigation in Wuhan, intended as the first phase of a longer process. Team members reported difficulties obtaining necessary information, with political tensions complicating collaborative efforts.

Fauci’s Role and Public Controversy

Dr. Anthony Fauci, as NIAID Director, played a prominent role in public communications regarding COVID-19 and its origins. He consistently emphasized the virus's risks, sometimes conflicting with the Trump administration's more optimistic messaging. In April 2020, Fauci's public statements aligned with mainstream scientific claims supporting a natural origin, backed by U.S. intelligence agencies concluding the virus was not "man-made or genetically modified."

However, Fauci's role became controversial when allegations emerged about his involvement in funding research at the WIV. Rep. Mike Turner claimed Fauci made public statements unsupported by intelligence. Fauci later denied these accusations, stating his testimony about COVID-19's origin had been "seriously distorted."

Concerns about transparency and safety at the WIV were amplified by whistleblower reports and retrospective scrutiny.

In late 2019, Chinese physician Dr. Li Wenliang raised early warnings about a novel virus, which were subsequently suppressed by local authorities. In 2020, reports emerged suggesting that several scientists who publicly dismissed the lab-origin hypothesis had undisclosed ties to WIV research, raising questions about potential conflicts of interest.

EcoHealth Alliance and GOF Research Partnerships

Additional attention focused on the role of EcoHealth Alliance, a U.S. organization that facilitated international research partnerships, including collaborations between the WIV and Dr. Ralph Baric’s lab at the University of North Carolina.

By 2018, EcoHealth Alliance received up to $15 million annually from various U.S. government agencies, some of which flowed to the WIV. Dr. Shi Zhengli's records indicate that between 2014 and 2019, the WIV received over $1.2 million in U.S. grants.

Meanwhile, critics argued that GOF studies on coronaviruses were conducted at the WIV in collaboration with Baric's lab. Some researchers contended that studies involving the insertion of human-pathogenic spike proteins into viral backbones from 2017 to 2019 qualified as GOF work, while others disagreed, noting the experiments may not have met the NIH’s technical definition.

The NIAID continued to approve experiments at the WIV despite the 2014 DHHS moratorium on GOF research.

Reassessment of WIV Laboratory Safety

Long-standing safety concerns about the WIV were also revisited. France warned U.S. officials about inadequate safety protocols at the lab, while in 2018, U.S. embassy officials raised alarms about safety protocols at the WIV, noting the institute's inexperience in operating high-containment laboratories. The lab's location in a densely populated area was also criticized as unsuitable for high-risk research.

Multiple safety audits reportedly revealed lapses without subsequent corrective action. Some reports alleged that certain experiments were conducted under BSL-2 (biosafety level 2) conditions rather than the more secure BSL-4, despite internal and external warnings.

During the early stages of the pandemic, the Chinese government tightly controlled public discourse on COVID-19 origins.

Authorities allegedly censored social media posts, removed research from university websites, and restricted publication of findings related to the WIV unless approved in advance. At the same time, Chinese officials publicly rejected the lab leak theory and promoted alternative narratives, including the idea that the virus may have originated outside of China.

In the United States, public health leaders also took steps to discourage speculation about a lab-based origin. Emails from early 2020 show top officials like Fauci and Dr. Francis Collins discussing efforts to combat what they called a "destructive conspiracy." A State Department investigation into the origins was reportedly discontinued in early 2021 due to questions about its methodology and credibility.

The official position in 2020 aligned with the mainstream scientific claims: that COVID-19 most likely emerged from natural zoonotic spillover. However, by May 2021, U.S. President Joe Biden ordered a renewed intelligence review into the lab leak possibility.

Social Media Moderation

Social media platforms initially treated the lab leak theory as misinformation. In February 2021, Facebook explicitly banned posts claiming COVID-19 was man-made, citing guidance from health authorities. Twitter removed or down-ranked similar claims and suspended accounts like markets blogger Zero Hedge after it published unverified lab leak allegations. YouTube also removed videos that contradicted WHO and CDC guidance.

Internal communications and court records — such as those disclosed in the Missouri v. Biden case — later indicated that some of these moderation decisions were influenced by informal communications between public officials and tech companies. By mid-2021, following renewed calls for investigation, platforms began updating their policies. Facebook lifted its ban on lab-origin discussions in May 2021, and other companies followed suit.

Scientific Communication

In early 2020, leading scientific journals published high-profile statements dismissing the lab leak theory. A February 2020 letter in The Lancet, later found to have been organized by EcoHealth Alliance's Peter Daszak, condemned "conspiracy theories" about non-natural origins. A March 2020 Nature Medicine article further reinforced this by concluding that SARS-CoV-2 was not engineered and a lab origin was unlikely.

These publications became widely cited as evidence that the lab leak theory had been debunked. Privately, however, some authors initially suspected a lab accident before aligning publicly with a natural origin. Other scientists who proposed lab-origin hypotheses reported difficulty publishing their work or facing professional backlash. It wasn’t until May 2021 that a turning point came, when Science published an open letter from 18 prominent scientists calling for a serious investigation into all origin possibilities, including a lab leak.