As the United States government is urged to tighten oversight of gain-of-function research, scientists have differing views on whether such studies are necessary and could help to prepare for future pandemics.
Last October, the National Institutes of Health (NIH) officials launched a research inquiry the institute partly funded. In the study — which has not been peer-reviewed — Boston University scientists created a synthetic form of the SARS-CoV-2 virus, which killed 80% of lab mice, while the then-dominant Omicron variant caused only non-lethal disease.
The research sparked controversy in the media, while the study authors said that the findings of the research were taken out of context because the new virus was less dangerous than the original Wuhan strain. Moreover, the findings couldn't be applied to humans.
The Boston University researchers claimed this wasn't a gain-of-function (GOF) research, which is characterized as altering organisms to enhance their biological functions, including making them more dangerous or contagious. However, the research fueled fears about the spillover of dangerous pathogens used or created in this type of study.
Concerns over 'discrediting virology'
Last year, the Senate started hearings on the origin of SARS-CoV-2 and whether gain-of-function research financed by U.S. taxpayers money could have led to the virus spread.
The recent report from the Department of Energy concluded that the pandemic was caused by a laboratory leak in Wuhan but also acknowledged that these findings are of "low confidence," according to media reports. Thus far, the increasing evidence shows that the virus jumped to humans from bats.
In January, 150 scientists expressed concern that such hearings could discredit virology and virologists and add fuel to an "anti-science, fear-based movement."
David Wessner, Ph.D., a professor of biology at Davidson College, says that the argument is worth considering. However, scientists should also better communicate the importance of these kinds of experiments.
"I think that the scientific process is at risk of being politicized and turned into sound bites that don't really serve the endeavor particularly well," he tells Healthnews.
In their commentary, the scientists explained that gain-of-function approaches are essential to the research because they are "powerful genetic tools in the laboratory." For example, using these approaches, some oncolytic viruses have been endowed with new properties that kill tumors. At least two FDA-approved products resulted from enhancing viruses with new functions.
Wessner says that while gain-of-function research may be interpreted as scary, it allows scientists to see what happens if the virus mutates in a certain way.
"It gives us insight into what might happen and allows us to think about how we could potentially control the pathogen in the future."-David Wessner, Ph.D.
Some disagree with this kind of argument. Johns Hopkins computational biologist Steven Salzberg, Ph.D., argues that viruses created in the lab are not natural and will not look like the viruses that appear in nature.
In the University's blog post, "It's Time to Stop Creating 'Superbugs' in the Labs," Salzberg explains that "there is a non-zero risk of a lab leak," despite the best scientists' efforts, and urges to shut down all gain-of-function in the U.S. immediately.
More oversight could be problematic
In their draft recommendations, two National Science Advisory Board for Biosecurity working groups called for better government oversight over gain-of-function research.
Wessner says some suggested changes are reasonable and should be implemented. For example, expanding oversight to privately funded research, as well as the research done outside the U.S. but with American funding.
"They proposed to expand the infectious agents that would be subject to review. It could be problematic to open the door to have this increased level of oversight for a whole host of different infectious agents," Wessner says.
Gain-of-function research is supervised by the Department of Health and Human Services (HHS). But the policy that the HHS developed in 2017 "does not fully meet the key elements of effective oversight identified in past work," according to a report by the Government Accountability Office, a governmental watchdog. It says that the policy allows subjective and potentially inconsistent interpretations of what is "reasonably anticipated" research.
Foreseeing risks is not always possible
Is it always possible to predict the outcomes of the study? Ram Duriseti, Ph.D., M.D., a clinical associate professor at Stanford University, says that there are unknown variables and known uncertainties in every research, and that can be controlled and arranged in a sensitivity analysis.
"But in any experiment, there are hidden variables that you don't understand. There could be the primary reason for a particular correlation or even a causal effect that you don't know," he tells Healthnews.
Because scientists ultimately need to have ecological or real-world evidence to actually test any hypothesis, there needs to be a "very high level of accountability," Duriseti says. And there is a good reason why gain-of-function was outlawed. In 2014, the NIH announced it was pausing funding for gain-of-function research, which was resumed three years later after developing a framework for guiding funding decisions.
The NIH said that this type of research is important in helping to develop strategies and effective countermeasures against pathogens that pose risks to public health.
But there have been cases of dangerous pathogens escaping the lab. In 2014, the CDC investigated the possible exposure of 75 employees to anthrax, a severe infectious disease that may cause death. This was a result of the lab making activated anthrax samples by mistake.
Nevertheless, gain-of-function research has already proved to benefit the public. One of the most recent examples is Johnson & Johnson's COVID-19 vaccine, which was created by altering adenoviruses. And if predictions about the increasing risk of extreme pandemics are accurate, the discussions about GOF benefits may continue.
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