The story so far: With the re-emergence of the lab-leak origin theory for the SARS-CoV-2 , questions are also being raised on what gain-of-function research is , and whether the benefits of conducting such research outweigh the risks of pathogens escaping from labs. The Wuhan Institute of Virology was said to have conducted gain-of-function research on coronaviruses.
What is gain-of-function research?
In virology, gain-of-function research involves deliberately altering an organism in the lab, altering a gene, or introducing a mutation in a pathogen to study its transmissibility, virulence and immunogenicity. It is believed that this allows researchers to study potential therapies, vaccine possibilities and ways to control the disease better in future. “Gain-of-function research involves manipulations that make certain pathogenic microbes more deadly or more transmissible. This is done by genetically engineering the virus and by allowing them to grow in different growth mediums, a technique called as serial passage,” says Abdul Ghafur, senior consultant, infectious diseases, Apollo Hospitals.
There is also ‘loss-of-function’ research, which involves inactivating mutations, resulting in a significant loss of original function, or no function to the pathogen. When mutations occur, they alter the structure of the virus that is being studied, resulting in altered functions. Some of these significant mutations might weaken the virus or enhance its function.
Some forms of gain-of-function research reportedly carry inherent biosafety and biosecurity risks and are thus referred to as ‘dual-use research of concern’ (DURC). This indicates that while the research may result in benefits for humanity, there is also the potential to cause harm — accidental or deliberate escape of these altered pathogens from labs may cause even pandemics.
Thomas Briese of Columbia University described gain-of-function research done in the laboratory as being a “proactive” approach to understand what will eventually happen in nature, during a 2014 seminar on ‘ Potential Risks and Benefits of Gain-of-Function Research ’. Kanta Subbarao, who was then with the Laboratory of Infectious Diseases at the National Institute of Allergy and Infectious Diseases (NIAID), U.S., said in the seminar that current medical countermeasures are often insufficient largely because of resistance mechanisms that lead to ‘escape mutants’, i.e., drug-resistant strains. There is, hence, a continual need to develop new antiviral drugs and additional options, such as immunotherapy, based on neutralising monoclonal antibodies. Ultimately, gain-of-function studies, which enhance viral yield and immunogenicity, are required for vaccine development.
What is the situation in India?
In India, all activities related to genetically engineered organisms or cells and hazardous microorganisms and products are regulated as per the “ Manufacture, Use, Import, Export and Storage of Hazardous Microorganisms/Genetically Engineered Organisms or Cells Rules, 1989 ”. Last year, the Department of Biotechnology issued guidelines for the establishment of containment facilities , called ‘Biosafety labs’, at levels two and three. The notification provides operational guidance on the containment of biohazards and levels of biosafety that all institutions involved in research, development and handling of these microorganisms must comply with.
Should research continue?
Scientists have differing opinions on the issue, particularly since the emergence of the COVID-19 pandemic. While those on the side of gain-of-function research say that it makes science and governments battle-ready for future pandemics, there have been a rising number of calls to suspend such research. Proponents of gain-of-function research believe that “nature is the ultimate bioterrorist and we need to do all we can to stay one step ahead”.
Dr. Ghafur, who thinks it is time to stop such research, says, “Unfortunately, scientists have crossed all boundaries and created monster chimeric viruses.” In the U.S., after COVID-19 struck, concerns were raised to ensure greater transparency about such research. In 2014, the country paused funding for three years for such research until steps could be taken to ensure the safety of the procedure. The Scientific American says in a report that science policymakers “must wrestle with defining the rare instances in which the benefits of experiments that enhance a virus’s capacity to survive and flourish in human hosts outweigh any risks.”
At the World Health Organization (WHO), the Science Division leads activities on DURC and responsible use of life sciences research, focusing on mitigation and prevention of biorisks and associated ethical issues. Soumya Swaminathan, chief scientist, WHO, says that in 2020, the Department organised three DURC Dialogues with academies and councils, science editors and publishers, and donors of life sciences research. Following these dialogues, stakeholders called on the WHO to develop a Global Guidance Framework for member states to follow. The organisation initiated the development of that Framework and organised a consultative meeting in March 2021. Work is on to address key topics as part of the Framework.