Why gain-of-function research matters

In February 2021, a World Health Organization team investigating the origins of COVID-19 visited the
Wuhan Institute of Virology in Wuhan, China. Hector Retamal/AFP via Getty Images

Due to unanswered questions into the origins of the coronavirus pandemic, both the U.S. government and scientists have called for a deeper examination into the validity of claims that a virus could have escaped from a lab in Wuhan, China.

Much of the discussion surrounds “gain-of-function” research. So The Conversation asked David Gillum and Rebecca Moritz, who work closely with virologists on a day-to-day basis to ensure the safety and security of the research, and Sam Weiss Evans and Megan Palmer, who are science and technology policy experts, to explain what this term means and why this kind of research is important.

What does gain of function mean?

Any organism can acquire a new ability or property, or “gain” a “function.” This can happen through natural selection or a researcher’s experiments. In research, many different types of experiments generate functions, and some pose certain safety and security concerns.

Scientists use a variety of techniques to modify organisms depending on the properties of the organism itself and the end goal. Some of these methods involve directly making changes at the level of genetic code. Others may involve placing organisms in environments that select for functions linked to genetic changes.

Gain of function can occur in an organism in either nature or the laboratory. Some lab examples include creating more salt- and drought-resistant plants or modifying disease vectors to produce mosquitoes that are resistant to transmitting dengue fever. Gain of function can also be useful for environmental reasons, such as modifying E. coli so that it can convert plastic waste into a valuable commodity.

In the current debate around SARS-CoV-2, the virus that causes COVID-19, gain of function has a much narrower meaning related to a virus becoming easier to move between humans, or becoming more lethal in humans. It is important to remember, though, that the term “gain of function” by itself covers much more than this type of research.

Why would researchers do gain-of-function work on potentially dangerous pathogens?

Gain-of-function experiments may help researchers test scientific theories, develop new technologies and find treatments for infectious diseases. For example, in 2003, when the original SARS-CoV outbreak occurred, researchers developed a method to study the virus in the laboratory. One of the experiments was to grow the virus in mice so they could study it. This work led to a model for researching the virus and testing potential vaccines and treatments.

Gain-of-function research that focuses on potential pandemic pathogens has been supported on the premise that it will help researchers better understand the evolving pathogenic landscape, be better prepared for a pandemic response and develop treatments and countermeasures.

But critics argue that this research to anticipate potential pandemic pathogens does not lead to substantial benefit and is not worth the potential risks. And they say getting out ahead of such threats can be achieved through other means – biological research and otherwise. For instance, the current pandemic has provided numerous lessons on the social and behavioral dynamics of disease prevention measures, which could lead to robust new research programs on the cultural aspects of pandemic preparedness. Understanding when the risks of gain-of-function research outweigh the potential benefits and alternatives, therefore, continues to be subject to debate.

What are some examples of gain-of-function research, and how risky is it?

Some potential outcomes of gain-of-function research may include the creation of organisms that are more transmissible or more virulent than the original organism or those that evade current detection methods and available treatments. Other examples include engineering organisms that can evade current detection methods and available treatments, or grow in another part of an organism, such as the ability to cross the blood-brain barrier.

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