On July 11, I received a letter from the National Institutes of Health ordering me to stop my research on Mycobacterium tuberculosis, the bacterium that causes tuberculosis, because the work was deemed too “dangerous.” Surely this must be a mistake, I thought, since my lab has been operating safely for more than a decade.
I am an associate professor of molecular and cell biology at University of California, Berkeley, where I study TB. I’m also a principal investigator on two grants from the NIH in which experiments using routine techniques were abruptly flagged as possible “dangerous gain-of-function research.” My work isn’t dangerous, but stopping research that could lead to cures could be.
In wealthy countries, people think TB is a disease of the past. Advances in medicine and public health have virtually eradicated it from the U.S. and western Europe. Yet globally, TB kills more people than any other infectious disease and is also becoming more difficult to treat as drug resistance increases. If we lose the ability to treat TB with existing drugs, the whole world, including the United States, is at risk.
Researchers in my lab and many others across the country are striving to perform research that is essential for the discovery of new drugs to eradicate TB and prevent its worldwide resurgence. The 2024-25 TB outbreak in Kansas City — more than 100 cases, making it the largest in the U.S. in decades — is a clear reminder that the risk is not just theoretical.
Technically, my work on TB does involve gain of function, a category of research that has been both politicized and widely misunderstood.
“Gain of function” is a broad category of research that involves genetically altering an organism to give it new abilities. Gain-of-function experiments have been crucial for increasing our understanding of bacteria like M. tuberculosis in the pursuit of discovering new treatments. These techniques have also been essential in developing new therapies for cancer, new vaccines, and treatments to improve crop resiliency and animal health. Gain-of-function research has provided enormous benefits for clinical therapies, including the hepatitis B vaccine, CAR T-cells for cancer, and modified adenoviruses used in gene therapies for muscular dystrophy.
The NIH letter terminating my research cited a May executive order in which the president ordered a stop to “dangerous gain-of-function research.” That is a very small subset of gain-of-function research, in which a potentially disease-causing organism is made more virulent, more transmissible, or more capable of infecting new hosts. Because this type of research can be risky, I fully support requiring robust safety measures to ensure it is conducted responsibly. Decisions designating research as “dangerous” must be transparent, deliberative, and scientifically informed. This approach is vital to prevent the unwarranted curtailment of safe research that serves the public good.
My grants were flagged as “dangerous” by NIH officials for two common practices in TB research that have been used safely for decades. First, to pinpoint the weaknesses of M. tuberculosis, we create genetic mutations that disable specific genes. These mutations actually make the bacterium less virulent — the opposite goal of gain-of-function research. Second, we often use resistance to kanamycin, an antibiotic not used to treat humans because of severe side effects, to isolate mutated strains. The kanamycin kills all of the bacteria except for that which is resistant. We use kanamycin resistance as a molecular marker — like a genetic ID badge — that allows us to identify and isolate the small percentage of bacteria in a population that we have successfully modified, since only these bacteria can survive when exposed to the antibiotic kanamycin. Our kanamycin-resistant strains are fully treatable by all clinically used antibiotics and cannot spread drug resistance to other strains, so they pose no risk to the public. The use of kanamycin has not been considered dangerous by any reasonable definition, and that has been true for decades.
Our techniques are essential to lifesaving TB research. Yet my colleagues across the country have also received letters targeting practices that have been proven safe over decades and remain crucial to finding new drugs and treatments.
Much of the TB research targeted by the NIH uses standard approaches that adhere to very strict laboratory guidelines and that have been reviewed by institutional committees of scientists, biosafety experts, and members of the public. My work is conducted in a Biosafety Level 3 facility with stringent requirements: personal protective equipment, including protective clothing and respiratory protection; only working with live bacteria within biosafety cabinets that prevent release of organisms into the environment; and using rooms with specialized ventilation to provide an additional layer of containment.
Limiting dangerous gain-of-function research is an important goal. But effective oversight must utilize scientific knowledge to distinguish between low-risk and actual, demonstrable threats so that we do not impede progress against deadly diseases for no real safety benefit. An overly broad approach, with the resulting ramifications for lifesaving research we’re already seeing, could be exacerbated by the recently proposed “Risky Research Review Act.” Without clear definitions, scientific expertise, and streamlined review processes, lifesaving research could be stopped. This would be an even bigger threat to public health than the broad, misinformed definition of “dangerous” that is being applied here.
Sarah Stanley, Ph.D., is an associate professor and Richard and Rhoda Goldman distinguished chair in the biological sciences as well as faculty director for the Alliance for Global Health and Science at the University of California, Berkeley.
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