Gain-of-function (GoF) research involves modifying microorganisms, such as viruses, to alter their characteristics. This research aims to understand how pathogens might evolve, for example, by becoming more transmissible or virulent. The goal is to anticipate how pathogens change and to help prepare for future pandemics.
The Scientific Purpose and Process
Scientists conduct gain-of-function research to understand the evolutionary pathways of pathogens. By introducing genetic changes or exposing viruses to new environments, researchers observe how these microorganisms adapt. This allows for monitoring wild viruses for similar mutations that could pose a threat to human health.
This research also aims to accelerate the development of countermeasures like vaccines and antiviral drugs. Creating a more potent or transmissible virus in a controlled laboratory setting enables scientists to test potential treatments against a challenging target. This proactive approach provides a head start in developing effective interventions before a natural outbreak.
The general laboratory process for gain-of-function research can involve several techniques. One method is serial passage, where a virus is repeatedly transferred through different hosts, such as laboratory animals or cell cultures, to encourage adaptation and changes in its characteristics. Another approach is reverse genetics, which involves directly editing the viral genome to introduce specific mutations. These controlled modifications allow researchers to pinpoint the genetic changes responsible for altered viral functions.
The Dual-Use Dilemma and Associated Dangers
Gain-of-function research presents a “dual-use dilemma,” meaning it yields information or products with both beneficial and harmful applications. While the research aims to advance public health, the knowledge or engineered pathogens could be misused for purposes like bioterrorism. This underscores the complex ethical considerations.
One primary danger is the accidental release of an engineered pathogen from a laboratory. Despite rigorous safety protocols, human error, equipment malfunction, or unforeseen events can occur. Such an escape could lead to an outbreak, potentially initiating a pandemic with a virus that has enhanced virulence or transmissibility.
Concerns also exist that this research could inadvertently create a pathogen more dangerous than any naturally occurring strain. By enhancing specific characteristics, scientists might engineer a virus with unprecedented transmissibility, pathogenicity, or resistance to existing treatments. If such a modified pathogen were to escape, it could pose a severe threat to global public health, potentially overwhelming healthcare systems.
Oversight and Safety Protocols
To manage the dangers of gain-of-function research, several layers of oversight and safety protocols are in place. In the United States, the Potential Pandemic Pathogen Care and Oversight (P3CO) Framework serves as a governmental regulatory structure. This framework requires a specialized review process for research proposals that create, transfer, or use enhanced potential pandemic pathogens, ensuring thorough scrutiny before approval.
Physical containment measures are also paramount in mitigating risks, implemented through various Biosafety Levels (BSLs). For gain-of-function studies involving highly dangerous pathogens, BSL-3 and BSL-4 laboratories are utilized. BSL-3 labs feature controlled air pressure and restricted access, while BSL-4 labs represent the highest level of containment, often requiring researchers to wear full-body, positive-pressure suits and work within sealed environments with multiple layers of security.
Institutional Biosafety Committees (IBCs) play a significant role at the local level within universities and research institutions. These committees provide an additional layer of review and oversight for research involving recombinant DNA and infectious agents, including gain-of-function studies. IBCs ensure that all research adheres to established safety guidelines and ethical considerations before experiments commence.
Notable Research and Public Scrutiny
Gain-of-function research has periodically come under intense public scrutiny, notably following high-profile experiments. A significant controversy arose around 2011 and 2012 when two separate laboratories successfully engineered the H5N1 avian influenza virus to become transmissible between ferrets through airborne droplets. This sparked a global debate among scientists, policymakers, and the public regarding the risks, leading to a temporary moratorium on this research in the U.S.
The origins of the COVID-19 pandemic also brought gain-of-function research into the public spotlight. While the precise origin of SARS-CoV-2 remains a subject of ongoing scientific debate, the existence of a high-security virology laboratory in Wuhan, China, that conducted research on coronaviruses, fueled discussions about a potential laboratory-related incident. This highlighted the public interest in understanding potential connections between laboratory activities and emerging infectious diseases, irrespective of definitive conclusions.