Tip Sheets

New recommendations for high-risk pathogen research: Resources for coverage

By Bara Vaida and Tara Haelle

A type of research in which scientists alter the genetic code of pathogens with pandemic potential to understand how they might become more dangerous will be in the political and scientific spotlight this year. It’s among what’s covered under new recommendations for tightening protocols around any kind of research involving pathogens that are potentially highly transmissible, including viruses like SARS-CoV-2. 

The recommendations, made by two biosecurity advisory groups, were approved in early February by the the National Science Advisory Board for Biosecurity (NSABB) and now the White House will decide whether to implement them or not.

The guidance, which had been explicitly requested long before 2020, was put on hold when the pandemic began. Federal officials directed theNSABB in February 2022 to return to the task, and the report was issued in mid-January with 13 recommendations. It focused on two broad categories: research with enhanced potential pandemic pathogens, defined as “likely highly transmissible and virulent, and capable of causing significant morbidity or mortality,” and Dual Use Research of Concern (DURC), which the World Health Organization refers to as “research that is intended to provide a clear benefit, but which could easily be misapplied to do harm.” 

The research under the most scrutiny, called gain-of-function, is conducted in biosecure labs with the aim of developing treatments and vaccines to prevent future pandemics. The research was controversial prior to the pandemic and has come under even greater scrutiny as scientists continue to investigate the origin of COVID-19. Though not limited in its scope to gain-of-function research, the report’s recommendations largely focus on gain of function.

A summary of the report’s recommendations is below, but first some political context: In February, congressional Republicans began a series of hearings on the origins of COVID-19 and the federal government’s response to the pandemic, including oversight of gain-of-function research. Republicans plan to use the hearings as an opportunity to grill former National Institute of Allergy and Infectious Diseases director Anthony Fauci, as well as probe the agency’s link to a Wuhan laboratory that conducts pathogen research. 

Without adequate evidence, some Republican lawmakers have charged that the Wuhan lab is the source of SARS-CoV-2, the virus that causes COVID-19. The majority of scientific evidence points to a natural source for the virus, probably caused by repeated contacts between animals and people. But the exact source remains undetermined.

Also in mid-January, the Government Accountability Office issued a report that found the U.S. Department of Health and Human Services could do more to increase oversight of research on pathogens of pandemic potential.

As the federal government evaluates its research rules and Republicans hold hearings, misinformation is likely to proliferate on social media. Here’s some background, context and resources to help you cover this complex topic:

Scientific background

Since the advent of genetic engineering, virologists have routinely studied how altering a pathogen’s genetic code might enable it to infect a new host, usually in petri dishes or animal models. Altering genes could result in the pathogen having a benign gain of function or result in it losing function.

It is when the research involves pathogens of pandemic potential that many scientists have  raised alarms. In 2011, two researchers, one in Wisconsin and another in the Netherlands, published research showing how they had manipulated an avian flu virus to make it more transmissible among ferrets, which are susceptible to human and avian respiratory viruses. Their work was meant to help researchers develop an avian flu vaccine if one were needed, but the research raised alarms that a laboratory staff member who was reckless or had malicious intent could unleash a dangerous pathogen on the public.

Such concerns aren’t unwarranted. In 2014, the Centers for Disease Control and Prevention published a report detailing how “sloppy handling” of anthrax at a CDC lab resulted in accidental exposure of workers and how a vial of a dangerous strain of avian flu had been accidentally sent to a Department of Agriculture research lab. That same year, the NIH found decades-old samples of live smallpox virus had been incorrectly stored. 

At the end of 2014, the U.S. imposed a three-year ban on gain-of-function research, while federal officials wrote new rules governing research on pathogens with pandemic potential. Gain-of-function research resumed at the end of 2017 with NIH support and new HHS guidance on funding decisions related to “enhanced potential pandemic pathogens” research. (A Nature story included a timeline showing when virologists started raising concerns about gain-of-function as well as a history of the controversy about the nature of the research.)

An example of the benefits of gain-of-function research is improved prediction of which flu strains to include in the annual influenza vaccine. Other examples include identifying high-risk regions for emergence of new pathogens so surveillance can be improved there. 

The following papers provide additional background reading and context on benefits and the ongoing discussion about oversight improvement: 

COVID-19 origin and NIH controversy

As that controversy was brewing, researchers at a lab in Wuhan were manipulating the genetic code of certain bat viruses found in the wild. In 2017, they published a study showing their altered viruses could infect human and monkey cells in a petri dish and that bats were likely  reservoirs for coronaviruses with pandemic potential. The research was funded with support by EcoHealth Alliance, a non-profit that had received funding from the NIH.

Republicans have pointed to that paper as evidence that an accidental leak from the Wuhan lab unleashed SARS-CoV-2 on the world. Wuhan was the city with the first cluster of COVID-19 cases. They also charge the NIH was at fault for funding the research during the three-year gain-of-function ban. However, scientists say the Wuhan researchers proved cells could be infected in a petri dish but not humans and, therefore, was not gain-of-function research. What happens in a petri dish doesn’t necessarily translate to what happens in live humans, with complex immune systems. China also has denied that there was any lab leak in Wuhan.

A preponderance of evidence regarding the origins of SARS-CoV-2 still points to a spillover event, where an animal was a reservoir of the virus. 

The recommended changes to oversight rules

Gain-of-function research comprises a big chunk of the type of research addressed by the new recommendations, but they reach beyond gain-of-function research. That’s one of the criticisms from biosecurity experts. Some say the new guidance is too broad and runs the risk of shutting down wide swaths of virology research, including animal model development and vaccine research. 

The recommendations even “broadened the scope to include plants and animals,” explained biosecurity expert Gigi Gronvall, a senior scholar at the Johns Hopkins Center for Health Security. “Good luck to the plant researcher who finds their stuff in line with vaccine development studies for a disease that’s killing people,” Gronvall said.

The 13 key findings and corresponding 13 recommendations are summarized in the executive summary, starting on page 1, of the report, but here are a few key takeaways:  

  • The advisory groups found that the definition of a “potential pandemic pathogen” and “enhanced PPP (ePPP)” are too narrow because of an overemphasis on “highly” transmissible and “highly” virulent, which “could result in overlooking some research involving the creation, transfer, or use of pathogens with enhanced potential to cause a pandemic.” They recommend expanding the definitions to include “likely moderately or highly transmissible and likely capable of wide and uncontrollable spread in human populations; and/or likely moderately or highly virulent and likely to cause significant morbidity and/or mortality in humans.” 

  • The advisory group recommends removing automatic exclusions from guidelines for gain-of-function research related to surveillance and vaccine development.

  • Increase transparency at federal and local levels regarding the review process for gain-of-function research. 

  • Consider developing similar oversight policies for plant and animal research into pathogens that could threaten human health.

  • Any gain-of-function research in other countries that’s fully or partly funded, directly or indirectly, by the U.S. government must be subject to the same review and oversight procedures as those used in the U.S.

Tips for coverage

When covering gain-of-function research and/or recommended improvements to oversight, consider the following:

  • Clearly explain what “gain-of-function” means since this term has become polarizing and has been frequently misused in political discussions and hearings. 

  • Clearly explain and distinguish between the genuine risks that can exist with this type of research and the genuine potential benefits that can come from it; rely on experts to give relatable examples of both.

  • Avoid going too far down the rabbit hole of SARS-CoV-2 origins since this issue predates the pandemic and applies to a far broader range of pathogens, including viruses, bacteria, and fungi. 

  • Consider seeking expert comments from a range of different fields, not just virology and biosecurity but also immunology, vaccinology, basic science researchers, etc. 

For reporters looking for experts to talk about gain of function research and policy: 

  • Thomas Inglesby, director of the Center for Health Security of the Johns Hopkins Bloomberg School of Public Health. Reach him through Margaret Miller: margaret.miller@jhu.edu

  • Gigi Gronvall, senior scholar and association professor of immunology at the Johns Hopkins Center for Health Security, @ggronvall

  • Marc Lipsitch, professor of epidemiology, Harvard T. H. Chan School of Public Health, mlipsitc@hsph.harvard.edu

  • Juliette Morrison, assistant professor, microbiology and plant pathology, University of California, Riverside, juliet.morrison@ucr.edu 

  • Benjamin Neuman, a virologist and professor in the department of biology at Texas A&M University’s College of Science, bneuman@tamut.edu

  • Angela Rasmussen, Ph.D., a virologist at the Vaccine and Infectious Disease Organization at the University of Saskatchewan in Canada. You can contact her via https://angelarasmussen.org/contact

  • David Relman, professor of microbiology and immunology, Stanford Medicine, relman@stanford.edu

  • Jaime Yassif, vice president for global biological policy and programs at the nonprofit organization Nuclear Threat Initiative, Reach her via Cathy Gwin: gwin@nti.org