Gain-of-function research advances knowledge and saves lives

VSOngress envisions a massive overhaul of the country’s scientific enterprise, largely in the name of ensuring competitiveness with China and other nations that invest billions in research. Like the United States, these countries recognize the importance of the “bioeconomy” and the role of research and innovation in the 21st century.

Yet, despite all the opportunities that would be offered by these investments, some policy makers are using these measures to advance simplistic and misguided notions about the complexity of specific research techniques. Many of these concerns revolve around gain-of-function research. In this work, scientists modify an organism to give it new abilities. The gain in office is now being described by some in Congress and in the media as grim. Some have even called for a total end to gain-of-function studies without acknowledging that it is a widely accepted research technique used by scientists around the world.

To do that would be short-sighted.

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With the drive to negotiate and pass the U.S. Innovation and Competition Act, which includes language that would have detrimental ramifications on viral gain-of-function research, it is imperative that Congress amend the law before the research landscape will not change 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 some of the genetic material from SARS-CoV-2 to cells in the body, where it stimulates an immune response that protects people when infected with SARS-CoV-2. The 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.

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Gain-of-function experiments have been widely used to uncover fundamental new insights into biology. This is particularly the case for the study of microbes, which are exceptional organisms for exploring the fundamental mechanisms of physiology and evolution. A standard experimental approach to discovering new biology is to isolate microbial variants that naturally acquire new functions through mutation.

Here is a simple example. Suppose a research team wants to study a protein used by a pathogen to survive in the blood during an infection. If this 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 solve this problem, it is possible to isolate variants of the microbe which acquire the capacity to produce the protein under normal laboratory conditions. By studying this “gain-of-function” variant, the protein can be studied more easily. Additionally, 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 also been applied in other areas of biology.

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

Similar gain-of-function transgenic approaches will help scientists design plants that are resistant to drought or pests 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 hope to develop preventive or therapeutic approaches to defeat them. It’s not always obvious why one microbe contains horrific epidemic potential while a closely related microbe poses a far lesser public health threat. The microbe that caused bubonic plague and decimated much of Europe’s population in the 14th century is remarkably similar on every level to the pathogens that cause nasty but barely deadly food poisoning. Understanding why closely related microbes perform so differently in humans requires examining them with a full experimental toolkit, including gain-of-function approaches.

Certainly, some pathogen gain-of-function research requires a higher level of scrutiny given its ramifications for biosafety and biosecurity. Scientists and other relevant experts should provide open and careful oversight with gain-of-function research of concern. Clear justification should be required to perform such work, and it should only be performed under highly controlled containment conditions. Self-examination and transparency are essential.

But calling all gain-of-function research worrisome and in need of strict oversight is a mistake. This can lead to inappropriate limitations on important work that reveals fundamental cell mechanisms or helps create new technologies that save lives.

Victor DiRita is a 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.

Donald E. Patel