Enhanced Potential Pandemic Research: To Do or Not To Do?

Weighing a Way Forward for Controversial Research

BY SEPPIDEH SAMI, CC

The topic of gain-of-function research (GOFR) has garnered much discussion recently in the popular press and also in the scientific literature. How can we accurately weigh the risks and benefits of certain types of GOFR? Can we realistically expect regulatory policies to be fully implemented and adhered to…globally?

World-renowned infectious disease expert Marc Lipsitch began raising such questions long before the COVID-19 pandemic. He thinks that, with a bit of work and lots of open discussion, we can find an effective means to conduct GOFR.

Lipsitch, a Professor of Epidemiology and Director of the Center for Communicable Disease Dynamics at the Harvard T.H. Chan School of Public Health (Boston), presented his thoughts on this topic at an NIH–FDA COVID-19 Scientific Interest Group lecture titled “Toward a Reasonable Middle Ground for Oversight for Enhanced Potential Pandemic Pathogen Research” at the Lipsett Amphitheater on June 30.

“COVID-19 brings new salience to the need to prevent accidental pandemics,” said Lipsitch. “Now is the time to act.” A reasonable middle ground in the scientific community is needed, he said, to ensure that regulation is effective in enabling science that is both informative and safe.

GOFR, where a pathogen is genetically modified to change its function, is largely considered safe, and indeed necessary, to better understand viruses and develop new vaccines. However, a small subset of GOFR, known as GOF research of concern (GOFROC), is far more controversial.

Ideally conducted under strict oversight and biosecurity measures, GOFROC involves creating enhanced potential pandemic pathogens (ePPP)—microorganisms that are capable of wide, uncontrollable spread in human populations and have been made more virulent or transmissible than their naturally occurring counterparts.

Supporters of GOFROC argue that such work is necessary to assess the pandemic potential of newly emerging viruses and inform public health and preparedness efforts for the next pandemic. Opponents express deep concern that ePPPs, more contagious and deadly than naturally occurring strains, pose significant risks to the public safety and health of millions of people if accidentally released into the environment. They also note that this type of GOFROC does not lead to vaccine development and argue that nearly all of the public health benefits of GOFROC can be achieved in ways that do not increase the risk of an accidental or malicious pandemic.

In his talk, Lipsitch presented compelling reasons why more robust oversight of GOFROC is necessary and shared a set of reasonable considerations and recommendations that could serve to develop a regulatory framework.

For example, he advocated for a standardized scientific process to review all GOFROC proposals and identify pathogens with the potential to cause a pandemic. That review would be followed by a risk-benefit evaluation of whether to move forward with the research. According to Lipsitch, if the work creates a specific public health benefit that cannot be achieved by safer means, and that public health benefit is large enough to outweigh the risk it creates and is scientifically sound, then it should be approved. “Harm reduction works,” Lipsitch said, adding that such risk evaluation is challenging but not impossible if based on carefully considered and valid criteria. “Perfection is a luxury but we can massively reduce the risks while preserving public health benefits.”

Those beyond the scientific community, such as ethicists, public representatives, and policymakers, should also be involved in the conversation about the risks of research with ePPPs, Lipsitch said. He noted that Congress is currently discussing the issue. “Scientists understandably get concerned when politicians interfere [in] details of research. But politicians have a responsibility for safeguarding public safety…[and] a societal discussion must occur,” he told the Catalyst.

“As scientists we have a public trust to do work that is as beneficial as possible and strongly respects [the] public’s concerns about safety,” Lipsitch said. “We need to be very cautious about the work we do and the risks we take, especially when there are more effective ways to reach the same scientific goals as well as public health goals, while maintaining safety.”

Lipsitch's NIH lecture was serendipitous and not part of the COVID-19 SIG's lecture schedule. He happened to be speaking on a panel in downtown Washington, D.C., hosted by the American Enterprise Institute to discuss the lessons learned from the COVID-19 pandemic. Joining him as a panelist was Emily Ricotta, who leads the Epidemiology and Data Management Unit at the National Institute of Allergy and Infectious Diseases and is part of the COVID-19 SIG.

“We had the panel discussion on Friday morning, drove up from D.C. on an extremely hot day, then hurried from the NIH Gateway Center to the Lipsett Amphitheater and made it just in time,” Ricotta said. “It was all very last minute but a great and rare opportunity for the NIH.”

Ricotta added that she hoped to raise awareness about the diversity of expertise necessary to contribute to considerations of GOFROC and a pandemic response.

The lecture drew hundreds of viewers despite being restricted to the HHS intranet. View the archive (HHS-only) at https://videocast.nih.gov/watch=49969. 

Watch the June 30 American Enterprise Institute panel discussion “Health Scholars on the Impact of COVID-19” at https://www.c-span.org/video/?529065-2/health-scholars-impact-covid-19.

Seppideh Sami, making her Catalyst feature debut, is a Training Coordinator in the Patient Support Services Department at the NIH Clinical Center. In her spare time, she enjoys studying the conservation and preservation of the natural world, especially plants.