Gain-of-Function Research Legislation: Clarity for Some or Research for All?

An essay by Lily Barna

While the SARS-CoV pandemic brought gain-of-function (GOF) research into the spotlight, scientists have been debating its uses since years before its name was known in conjunction with COVID-19. Gain-of-function (GOF) research, a term previously unknown to many outside the field of research, is a subtype of general virology research. Viruses often gain or lose function in their journey of becoming pathogenic. These gains or losses of function can increase the severity, lethality, or infectivity of a virus. GOF research focuses only on those viruses that, when they gain a function, become more pathogenic. The most common GOF viruses currently being researched include the common influenza, Severe Acute Respiratory Syndrome (SARS), Middle East Respiratory Syndrome (MERS), and coronaviruses. There is a wide range in the severity and lethality of viruses that gain functions, and research that encourages or brings about functions in these viruses often helps scientists develop vaccines and improve understanding of their core mechanisms.

Few seem to vehemently endorse GOF research, and all strongly endorse intense regulation of it. Still, more and more are deciding that rather than any sort of regulatory process, the research ought to be banned altogether. As a strong divide within the scientific community continues to build, those in favor of retaining GOF research cite vaccine development and pandemic preparation as crucial factors to keep projects going. Those opposed primarily point toward pandemics in theory versus reality for reasons why GOF research is ineffectual. For example, many look to the COVID-19 pandemic, stipulated by some to have resulted from a GOF lab outbreak in Wuhan China, as a primary reason to halt all future GOF work. While both sides use the pandemic to bolster their arguments, the debate goes back for years, with the first ban on GOF research coming into effect in October 2014.

?On October 17, 2014, the US Government halted funding for all new research that involved gain-of-function pathogens. This was sparked by worry and strife within the research community, who themselves put an internal halt on GOF research in 2012. Not long after the internal moratorium, a series of accidents occurred at the Centers for Disease Control in Atlanta occurred in June 2014; centered around mishandled pathogens, this further catalyzed the push towards GOF research regulation and banning.

Current research was put on pause when the ban went into effect, subsequently forced to undergo review and risk assessments, then resumed only if deemed necessary. People quickly realized that the ban itself was misleading; viruses are always mutating and changing, it can be difficult to discern what mutation may be beneficial to the virus (i.e., more dangerous to the public) and how that mutation came about. Inaccurate language and nonspecific language in the ban left researchers worried that the government might suspend research in which viruses mutated on their own accord, uninduced by researchers.

One key actor in this ongoing conversation is Dr. Yoshihiro Kawaoka, a virologist who runs an infamous lab at the University of Washington’s Influenza Research Center. A virologist for four decades, Dr. Kawaoka’s work on the avian flu, Ebola, and other flu strains has been stalled for ten of those years, since the ban in 2014. Dr. Kawaoaka is frequently cited as one reason for putting the ban in place; he genetically modified a strain of avian flu to make it transmissible by air between ferrets. This research was funded by the National Institutes of Health (NIH), a government entity, and it raised concerns for increased transmissibility among other mammals, such as humans. People feared, even prior to 2020, that if an enhanced pathogen like this were to escape the lab, it could be potentially pandemic inducing. While the cause of the COVID-19 outbreak has not be identified with any finality, many who oppose GOF research place the pandemic as a firm piece of evidence that, in theory, if one of these GOF viruses escapes the lab, it could be an entirely new pandemic. With the lack of vaccine research on some GOF viruses, it is not unrealistic to be fearful that we could face another pandemic for which no strong and long-present vaccine is developed and easily distributable.

In 2017, GOF research was allowed to continue for federally funded studies, with the explicit permission of the government after intense review. The moratorium was lifted in response to a risk assessment performed by the National Science Advisory Board for Biosecurity (NSABB) in 2016, who outlined the new framework enabling the US Department of health and Human Services (HHS) to assess each research project with its own “pandemic potential” rating. Two opinions were present when the ban was lifted in 2017, and both seem eerie in the lens of hindsight. NSABB chair Samuel Stanley was happy it was allowed to continue in some capacity, stating: “Basic research on these agents by laboratories that have shown they can do this work safely is key to global security.” Stanley was worried that after the ban we would be behind in the general and unending research race, both against others and nature itself. He said, in 2017: “I believe nature is the ultimate bioterrorist and we need to do all we can to stay one step ahead.”? The benefits and deterrents of this way of staying ahead are imperative to consider. Marc Lipsitch, an epidemiologist at Harvard T.H. Chan School of Public Health and vocal opponent of GOF research, felt otherwise in 2017: “[GOF studies] have done almost nothing to improve our preparedness for pandemics — yet they risked creating an accidental pandemic”. Marc has opposed GOF studies since the start of the debate and the 2014 ban, and many echo his sentiment now.

An important distinction between the 2014 and 2024 bans is the level of partisanship displayed by those fighting for or against the continuation of this research. The first ban on GOF research in this new crop occurred at the state level in Florida, followed now by Wisconsin, and potentially soon after by Texas. While Florida’s ban is the only one to be officially in place, this bill is following a political trend seen in other COVID-related issues. In 2023, Wisconsin’s Republican lawmakers introduced both state and federal bans on what they call “pandemic pathogens.” Many of the politicians endorsing the bills are also staunchly anti-vaccine and anti-mask mandates. Andre Jacque, R- De Pere, was a lead author on the Wisconsin proposed bill. He was vocally against masks and shared his severe COVID experience publicly. This public association can cause this ban to be lumped in with other issues as general conservative, anti-science opinions. Scientific groups such as Biosafety Now, a nonprofit centered on environmental activism, want the world to know they are completely pro-science, but still support the ban. It seems that regardless of being pre- or post- pandemic, anti- or pro- science, there are many people out there who either vehemently support or protest GOF research. Most of those who support it do so with a bevy of caveats and assertions for rigorous safety protocols and reviews.

In the camp of allowing GOF research to continue, people stress how the research on actual potential pandemic pathogens constitutes less than 1% of all GOF research. The majority focuses on influenzas and other diseases that are highly unlikely, or theoretically impossible, to spread into a pandemic of COVID proportions. Additionally, the issues for many are not the banning of research on that 1%, but the fear that inconsistent and inaccurate wording in the policies put forth would halt other crucial and non-harmful work.

Wisconsin, Florida, and Congress itself use the terms “potential pandemic pathogens” (PPPs) and “enhanced potential pandemic pathogens” (ePPPs) in their legislation. Yet neither define them with enough specificity. Technically the common cold could infect enough people to be considered a pandemic, thereby fitting into the Wisconsin PPP definition. The Congress-proposed bill, led by the House of Representatives, aims to replace the review process with a ban on all federal funded research on any bacteria, viruses, and fungi deemed to be ePPPs. The proposal was scheduled to be completed by the end of 2023, but the ban is not yet completed, or not yet presented to the public.

Ultimately, consensus may be achievable for most, if focus is put into ensuring the upcoming policies have clear, specific definitions on what gain of function research truly means, and on what pandemic inducing pathogens explicitly are. This means consulting scientists from multiple labs, having them work with legislation makers to ensure accuracy is at the forefront of the proposals, rather than partisanship or any other possible factor. The proposals could, in theory, satisfy most if they allow for the continuation of research into common colds and flus. While it is unlikely to 2024 ban will include such updated language, science continues in the meantime.

On March 5th, 2024, the University of Wisconsin-Madison opened their Influenza Research Center for a tour. Everyone who enters the actual lab space must don two pairs of scrubs, a towel, and special shoes. Showers must be taken upon exiting, even if just to use the restroom. Dr. Kawaoka still runs his lab here, focusing on influenza as opposed to his prior work on Ebola and avian flu. Others in the virology department at UW study RSV, pneumonia, HPV, and other viruses (and their interactions). All this work could potentially be banned with Wisconsin’s current proposal. Even within the UW community, the overall consensus seems to understand that the most extreme research has merit to be stalled, but the less-virulent viruses still deserve investigation.

The sentiments found at UW seem echoed throughout the science field: GOF research can be dangerous and should be highly regulated. The language of GOF research bans need to be specific enough in language to accurately apply to the research being done, for it is in the vague and uniformed language that dispute continues.