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Gain of function research since you brought it up.

What is ‘gain of function’? Why scientists are divided about the risk and benefits of experimenting with deadly viruses. What is ‘gain of function’?

Why scientists are divided about the risk and benefits of experimenting with deadly viruses

by Cynthia McCormick Hibbert
January 30, 2025

As the Trump administration reportedly considers halting so-called “gain of function” research that can make viruses more dangerous or contagious, scientists remain divided about the risk versus benefits of this type of experimentation.

Northeastern University experts say the debate about the use of “gain of function” goes back years — and several presidential administrations — but intelligence reports linking COVID-19 to a possible lab leak in China have brought it to public attention like never before.

Jared Auclair, a Northeastern expert in chemical biology, says proponents argue that the research allows scientists to get a jumpstart on pandemic preparedness, while opponents warn about the dangers of labs unleashing hyper-virulent diseases on an unsuspecting populace.

“The division is all based on risk,” Auclair says, including the possibility of “essentially creating a superbug that if you released it into the world could be catastrophic.”

“From my perspective, this is not a science question anymore. This is a policy question,” says Samuel Scarpino, an expert in pathogen surveillance and director of Northeastern’s AI + Life Sciences.

“We know that we have learned things from these experiments. We know that they are potentially risky,” he says. “The question is whether what we learn is valuable enough to offset the risks. That’s a question the policymakers we elect have to answer.”

Increasing transmissibility and virulence
In a broad sense, gain of function experimentation has been practiced by humans for tens of thousands of years in the cultivation of plants and breeding of animals, Scarpino says.

“Most of the time, when you hear someone say ‘gain of function,’ they mean an effort on the part of researchers to select for the increased ability of a pathogen — a bacteria, virus or microorganism — to infect a host that it previously could not,” he says.

“So we might try to select for increased transmissibility. We might select for increased virulence. We might try to select for host switching of the microorganism such that it selects a host it previously couldn’t,” Scarpino says.

Gain of function literally means harnessing molecular and cell biology approaches to genetically enhance the function of a virus, Auclair says.

The idea is to better comprehend what a virus looks like so that scientists can respond with therapies, vaccines or even further genetic manipulation to deprive it of a dangerous function, Auclair says.

“You understand what a gain of function mutation might do, and how we might prevent it,” he says. “It’s essentially like war gaming. What is the worst thing we can think of and make? Then can we make an antidote to that thing?”

Debate over safety, efficacy and lab leaks
“There are two kinds of debates over gain of function, and one of them is whether we should be doing them from a safety perspective,” Scarpino says.

“If you’re running these gain of function experiments, they typically have pretty stringent requirements around laboratory safety,” he says.

Related: Northeastern receives $17.5 million from CDC to launch infectious disease prediction center
But despite precautions, what happens in the lab doesn’t always stay in the lab.

“We know empirically that there are laboratory leaks all over the world. We heard about one in Australia last year,” Scarpino says. In that case, hundreds of vials of deadly virus were lost in what the media called a “biosecurity bungle.”

“We know that there’s no way we can guarantee that these things won’t ever be released, no matter what level of protection we take,” Scarpino says.

A group of international scientists called the Cambridge Working Group pointed to incidents in top U.S. laboratories involving smallpox, anthrax and bird flu in a July 2014 declaration expressing concern over the release of potential pandemic pathogens in gain of function experiments.

In October of that year the Obama administration put a temporary halt to gain of function studies of SARS, MERS and influenza over the objections of another group of researchers called Scientists for Science.

The moratorium was lifted under the first Trump administration about three years later with the release of new federal guidelines on funding decisions about proposed research on pathogens that have the enhanced potential for creating pandemics.

Unique benefit of gain of function
The second debate over gain of function experiments is “whether we learn anything uniquely valuable from them,” Scarpino says.

Scientists who favor the experimentation point out that an organism’s phenotype “emerges from the complicated interaction of genes and the transcripts that they generate, and the proteins and the environment,” he says.

“As a result, you can’t really take a reductionist approach to try and identify and isolate individual contributors. Instead you have to look at the whole organism,” and how it reacts to changes in function, Scarpino says.

One example of a discovery from gain of function involved research with ferrets that revealed what the flu needs to transmit readily from person to person, he says. “So there’s at least one example we can point to where there was a mutation that was not on our radar that we now know is important,” he says.

“We of course can never know if the other camps that were working on this would have discovered it independently with their own methods” without increasing transmissibility in the animals, Scarpino says.

The Wall Street Journal’s exclusive report says Trump’s team is working out details on a halt to federal funding of gain of function research.

“The question in my mind is whether research (not involving gain of function) is enough to give us the early warning signals we need without the risk of running the gain of function experiments,” Scarpino says.

“Is that added degree of certainty worth the risk of a highly pathogenic virus escaping from the lab?”

Cynthia McCormick Hibbert is a Northeastern Global News reporter. Email her at c.hibbert@northeastern.edu or contact her on X/Twitter @HibbertCynthia.

https://news.northeastern.edu/2025/01/30/what-is-gain-of-function/#:~:text=%E2%80%9CMost%20of%20the%20time%2C%20when,could%20not%2C%E2%80%9D%20he%20says.

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