Gain-of-function research advances knowledge and saves lives

Congress is considering a massive overhaul of the nation’s scientific enterprise, much of it in the name of ensuring competitiveness with China and other nations that are pouring billions into research. Like the U.S., these countries recognize the importance of the “bioeconomy” and the role of research and innovation in the 21st century.

Yet for all the opportunity that would be afforded by these investments, a few policymakers are using these measures to advance simplistic and misguided notions regarding the complexities of specific research techniques. Many of these concerns center around gain-of-function research. In this work, scientists alter an organism to give it new abilities. Gain of function is now being depicted by some in Congress and in the media as sinister. Some have even called for an end to gain-of-function studies altogether without recognition that it is a widely accepted research technique employed by scientists around the globe.

Doing that would be short-sighted.

With the push to negotiate and pass the U.S. Innovation and Competition Act, which includes language that would have harmful ramifications on viral gain-of-function research, it is imperative that Congress modifies the act before the landscape of research is altered for decades to come.

Gain-of-function research has enabled innovation for the development of life-saving drugs and vaccines. Johnson & Johnson’s Covid-19 vaccine is a gain-of-function approach. It uses a type of virus called an adenovirus to deliver a portion of the SARS-CoV-2 genetic material to the body’s cells, where it stimulates an immune response that protects people when they become infected by SARS-CoV-2. Adenovirus does not naturally produce this genetic material: It was engineered to do so through gain-of-function research. This general approach is not unique to the SARS-CoV-2 vaccine; vaccine production has long been supported by similar gain-of-function approaches.

Gain-of-function experiments have been widely used to uncover foundational new knowledge about biology. This is particularly the case with the study of microbes, which are outstanding organisms for exploring basic mechanisms of physiology and evolution. A standard experimental approach for discovering new biology is to isolate microbial variants that naturally gain new functions through mutation.

Here’s a simple example. Say a research team wants to study a protein used by a pathogen to survive in the bloodstream during infection. If that protein is made naturally by the microbe only when it resides in the bloodstream, it can be very difficult to study in the laboratory. To address this problem, it is possible to isolate variants of the microbe that gain the ability to produce the protein under normal laboratory conditions. By studying this “gain-of-function” variant, the protein can be studied more readily. What’s more, the biological processes that control its production are also revealed by understanding the mutation that led to the gain of function.

Approaches like this have been used throughout the history of microbial genetics and have been applied in other fields of biology as well.

In the 1970s and 1980s, the pharmaceutical and biomedical science industries were transformed by the recombinant-DNA revolution that relied on the manipulation of microbes and gain-of-function experiments. This powerful technology has made it possible to solve daunting problems. For example, it allowed production and purification of massive amounts of insulin produced in bacteria or yeast with reliably consistent potency, reducing the risks of using insulin extracted from animals and providing a safe alternative to inefficient insulin production from animal pancreas cells.

Similar transgenic gain-of-function approaches will help scientists engineer plants for drought or pest resistance, and ultimately feed more people in a warming world.

These are just a few of the many examples in which scientists have creatively applied gain-of-function approaches to discover new biology or create beneficial products.

Research on pathogens is essential if we are to have any hope of developing preventive or therapeutic approaches to defeat them. It is not always evident why one microbe contains within it horrific epidemic potential while a closely related one poses a far smaller public health threat. The microbe that caused bubonic plague and decimated much of Europe’s population in the 14th century is remarkably similar at every level to pathogens that cause unpleasant but hardly life-threatening food-poisoning. Answering why closely related microbes have such different outcomes in people requires examining them with a full experimental toolbox, including gain-of-function approaches.

To be sure, some gain-of-function research on pathogens requires a higher level of review given its ramifications for biosafety and biosecurity. Scientists and other relevant experts must ensure open and careful oversight with gain-of-function research of concern. Clear justification should be required for carrying out such work, and it should be done only under highly controlled containment conditions. Self-scrutiny and transparency are essential.

But to label all gain-of-function research as worrisome and requiring stringent oversight is misguided. Doing so may lead to inappropriate limitations on important work that reveals fundamental mechanisms of the cell or helps create new technologies that save lives.

Victor DiRita is professor and chair of microbiology and molecular genetics at Michigan State University and past president of the American Society for Microbiology. Stefano Bertuzzi is CEO of the American Society for Microbiology.