Republican lawmakers propose banning ‘gain of function’ research

A group of Republican lawmakers are seeking to ban “gain of function” research, which involves increasing the potency of certain pathogens in a laboratory setting. The lawmakers’ bill comes in response to incidents at the University of Wisconsin-Madison and as Republicans across the country have targeted this type of research following controversy over the origins of COVID-19.

Bill co-authors — Sen. Andre Jacque (R-DePere), Reps. Elijah Behnke (R-Oconto) and Ty Bodden (R-Hilbert) — stated in a memo that the “risks of these dangerous [gain of function] experiments are not only catastrophic, they are unnecessary.” 

The University of Wisconsin-Madison has warned lawmakers against such a ban in a letter, saying it would stifle pathogen-related research and result in significant delays and uncertainty even for research that is not prohibited, including research being done to protect Wisconsin’s residents, crops and livestock.

“Viruses mutate very rapidly all by themselves; they do not require humans conducting genetic engineering experiments to make them more lethally infectious,” the lawmakers said. 

Defining gain of function research

The bill, SB-401, would prohibit higher education institutions in Wisconsin from conducting “gain of function” research on “potentially pandemic pathogens.” Institutions found to violate the prohibition would be at risk of losing state funding in the following fiscal year. 

The bill would also require a researcher to submit a report to the state Department of Health Services at least 90 days before beginning research on a potentially pandemic pathogen. The report would need to include information about the pathogen, where research will be conducted, the scope, nature and purpose of the research, funding sources, the potential impact the pathogen will have on the public if released into the general population and the measures that will be taken to ensure it is not released.

An article from Biosafety Now — an organization that advocates for strengthening biosafety, biosecurity and biorisk management for research on pathogens — which was sent to lawmakers alongside the memo — said the bill would primarily affect the research of one laboratory run by one faculty member and would not impede on the development of vaccines or disease treatments or harm the biotechnology sector. 

But UW-Madison spokesperson Kelly Tyrrell said in an email that the bill is more expansive than the federal definition of “potential pandemic pathogens,” and would put the university in the position of having to interpret what kinds of research would fall under the purview of the bill or risk severe penalty. 

The bill defines “gain of function research” as “research that may reasonably be anticipated to enhance the transmissibility or virulence of a potentially pandemic pathogen.”

“Potentially pandemic pathogens” is defined under the bill as any virus, bacteria, fungus, or eukaryotic parasite that is moderately or highly “transmissible and likely capable of wide and uncontrollable spread in human populations,” “virulent and likely to cause significant mortality and morbidity in human beings, and “likely to pose a severe threat to public health and safety, the capacity of public health systems, or the security of this state if allowed to spread within the general population.” 

Dr. Gigi Gronvall, an immunologist and senior scholar at the Johns Hopkins Center for Health Security, echoed the concerns of UW-Madison, saying that defining ‘gain of function’ research is challenging and could make complying with a law confusing. 

Gronvall says that the wording lawmakers have used “makes it sound like scientists are trying to create weapons.” However, Gronvall says much of “gain of function” research “is trying to figure out what causes things to be more pathogenic or more transmissible.

“If there’s a way that it could be predicted, or if viruses  — like flu — if there are certain mutations that are associated with potentially infecting humans or mammals, then we could see those mutations out in the wild and say, ‘Oh, it’s getting closer to being infectious for mammals’,” Gronvall says. That information could help with the development of potential vaccines or treatments. 

Another definition from the American Society for Microbiology said gain of function is “a broad term that can encompass almost any type of research aimed at understanding mechanisms and processes,” and that these techniques are used in research to “alter the function of an organism in such a way that it is able to do more than it used to do.”

According to the American Society for Microbiology, gain of function research has been used in the development of Johnson & Johnson’s COVID-19 vaccine, for insulin production for people with diabetes and to address agricultural challenges such as crop resiliency and crop yield.

The “fuzzy” meaning, Gronvall says, is a problem because “a lot of the research that could get consumed by this category is research that we need to develop vaccines and to better understand the viruses that are causing illness and death right now.”

“While it’s good that lawmakers here are trying to protect their citizens, it’s going about it the wrong way,” Gronvall says. “You have a bill here that outlaws gain of function research but what that will mean to the researchers is really up in the air.”

Tyrrell said that the bill could prevent UW-Madison researchers from studying emerging pathogens that pose potential risk to human, animal and plant health, and impede scientists’ ability to contribute to public health preparedness.

For example, Tyrrell said the bill could preempt efforts to study and prepare for strains of avian influenza each year. University researchers currently work to monitor the avian influenza, which is highly lethal to farmed poultry, and work with farms and wildlife managers to protect the state’s industries and animal populations.

There is no research being performed on UW-Madison’s campus that meets the federal criteria for the potential pandemic pathogen care and oversight framework, which provides oversight of this type of research, Tyrrell said.

UW-Madison’s letter to lawmakers said the bill could also result in Wisconsin needing to rely on researchers in other states, such as Minnesota, Iowa, and Illinois, and losing millions of dollars of federal grant funding that benefits the state and its taxpayers. 

“The proposed legislation would also hamstring the growth of the biotech and biomedical sectors of Wisconsin’s economy,” the letter said. 

Targeting UW-Madison following three research incidents

Lawmakers cited three incidents, which occurred in the last 14 years at UW-Madison, as reasoning for the bill. 

“Incidents at the University of Wisconsin-Madison have raised questions as to whether UW researchers followed federal guidelines and timely reported two biosecurity breaches during [gain of function] experiment,” lawmakers said in a memo.

Jacque added in an email to the Wisconsin Examiner that he has also had “concerns over UW faculty blurring ethical boundaries or dismissing ethical concerns in various ways from my time as a student forward, so I see this as a responsible guardrail to put in place.”

UW-Madison said the lawmakers mischaracterized aspects of the incidents in their memo to lawmakers, and that the university takes the incidents “extremely seriously.” 

“While there are risks inherent in studying viruses, bacteria, and other pathogens, such risks are considered and balanced at both the federal and institutional level,” the memo stated.

The most recent incident happened in 2019 when a researcher in training was observing two senior scientists who were collecting nasal samples from ferrets involved in a transmission experiment of H5N1 avian influenza virus. During the research, a respirator hose was disconnected for seconds before it was reconnected. 

According to UW-Madison, researchers followed the lab’s emergency response procedure, by informing the university and the Federal Select Agent Program. The university was asked to file an incident report to the National Institutes of Health Office of Science Policy (NIH-OSP), which later characterized the actions taken as appropriate.

The second incident that happened in 2013 involved a researcher who was working with influenza virus and was accidentally stuck with a needle. The university followed its reporting obligations by sharing the incident with federal agencies and followed its protocols for managing a low-risk exposure. 

The final incident occurred in 2009 when members of a UW-Madison research laboratory introduced antibiotic resistance genes into strains of Brucella without the knowledge of the UW–Madison Institutional Biosafety Committee or the Office of Biological Safety, which oversees biological research at UW–Madison. 

When the university discovered what the researchers had done, the laboratory was instructed to cease work and destroy the strains. The university was fined $40,000 and worked with federal regulators to implement corrective measures, including developing mandatory training and strengthening the Office of Biological Safety. 

Tyrrell said the fine reflects the oversight system working as it is meant to and added that the researcher who led the lab is also no longer affiliated with UW-Madison.

Gain of function research is more regulated than it once was. 

The federal National Institutes of Health (NIH) implemented a moratorium against that type of experiment on influenza, SARS, and MERS viruses in 2014. The pause was lifted in 2017 after the U.S. Department of Health and Human Services released a formalized framework for oversight of federally funded research with enhanced pathogens of pandemic potential. That framework is just one way that “gain of function” research is regulated on a federal and institutional level. 

“This research is highly regulated at the federal level; the federal laws, regulations and guidelines all aim to balance the risk of this research with its benefits for protecting human and animal health,” UW-Madison stated in a letter.

Wisconsin bill follows concerns over COVID-19 origins 

Concerns about “gain of function” date back to before the COVID-19 pandemic, but interest in regulating and banning “gain of function” research has been renewed in recent years at a federal and state level as a result of theories about the origins of COVID-19. 

The authors of the Wisconsin bill said gain of function research has “the potential for disproportionately disastrous consequences resulting from lapses in biosecurity, and the U.S. government recently identified ‘gain of function research of concern’ funded by U.S. agencies at the Wuhan Institute of Virology in violation of funding stipulations.”

Gronvall, who has studied the origins of COVID-19, says this points back to concerns about activities in Wuhan and conspiracy theories about the origin of SARS-COV-2.  The majority of scientists, including Gronvall, say that COVID-19 likely originated from human-animal contact. 

“There’s a lot of evidence now, more than for most diseases that have emerged from nature, that SARS-COV-2 came from an animal market in Wuhan because that’s how a lot of diseases come into humans because of contact between sick animals and people,” Gronvall says. 

Despite this, the “lab leak” theory, that the virus occurred as a result of work in a Chinese lab, has gained traction in the political realm, mostly among Republicans, and resulted in an increased focus on “gain of function” research.

Wisconsin U.S. Rep. Mike Gallagher introduced a bill in March that would ban federal money from funding gain-of-function research for five years with the aim of providing time to evaluate the risks of the research and for proper safety standards and protocols to be implemented. 

Florida became the first state to ban gain of function research after Gov. Ron DeSantis signed a bill in March of this year. Texas introduced a similar bill in March. 

The Wisconsin bill so far only has Republican cosponsors including Sen. Steve Nass (R-Whitewater), Reps. Janel Brandtjen (R-Menomonee Falls), Rep. Dave Murphy (R-Greenville) and Chuck Wichgers (R-Muskego).

Gronvall says that “nature’s got a huge laboratory,” and there is the potential for people to encounter something worse than SARS-COV-2 in the future.

“Biosafety is super important and we need to pay attention to that, however, that’s not what this bill does and without defining what is or is not allowed, a cautious person may decide that their work is too close to the line and they don’t want to get in trouble with the law,” Gronvall says. “Lawmakers need to be a little bit careful about where they set these lines because we do need this research and there’s some pretty stellar virus research that goes on in Wisconsin.”