New Delhi: The term ‘gain of function research’ has recently cropped up in the debate about the origins of the Covid-19 pandemic, which has killed over 34 lakh people worldwide.
ThePrint explains what the term means, and why it has once again rekindled the question of whether the SARS-CoV-2 spread was a result of a laboratory accident in China.
What is gain of function research?
‘Gain of function’ is a field of research focused on growing generations of microorganisms, under conditions that cause mutations in a virus.
These experiments are termed ‘gain of function’ because they involve manipulating pathogens in a way that they gain an advantage in or through a function, such as increased transmissibility.
Such experiments allow scientists to better predict emerging infectious diseases, and to develop vaccines and therapeutics.
Gain of function research may use genetic engineering or serial passaging.
Genetic engineering involves ‘editing’ the genetic code to modify the virus in a way predetermined by the scientists.
Meanwhile, serial passaging involves allowing the pathogen to grow under different circumstances and then observing the changes. For example, the pathogen may first be grown in one environment, and then a portion of it may be taken and allowed to grow in different sets of controlled environments. The process is continuously repeated, and the final product is compared to the original pathogen to understand how the microbe changed its genetic code.
Why US temporarily paused funding it
The issue of gain of function research came under scrutiny in 2012, when a team of Japanese scientists in the US published a paper that helped show how the avian flu H5N1 may have transmitted to humans.
The group had altered the virus in a way that allowed it to reproduce in mammal lungs, which are a bit colder than bird lungs. This change allowed the virus to be transmitted via coughing and sneezing in ferrets.
Although the research helped explain how H5N1 could become airborne in humans, it created an outcry in the US, with The New York Times stating in an editorial opinion “that the research should never have been undertaken”.
Within the next two years, the Barack Obama administration in the US paused the funding of gain of function studies, particularly those anticipated to confer attributes to influenza, MERS, or SARS viruses — which have the potential to cause pandemics.
The plan was to initiate a deliberative process to determine the risks and benefits of such experiments, and to develop a US policy for approving new studies.
This moratorium was lifted under the Donald Trump administration in 2017 with a new policy framework to assess proposed research that would create pathogens with pandemic potential.
Relevance to Covid-19 pandemic
The discussion around gain of function research came back to focus recently, after a report argued that the possibility of the virus accidentally leaking out of the Wuhan Institute of Virology could not be entirely dismissed.
While scientists had earlier ruled out the possibility of the virus being ‘genetically engineered’, the report by senior journalist Nicholas Wade said serial passaging may have led to the evolution of the virus during an ongoing gain of function research project in the Chinese city.
Wade’s report alleged that the US’ National Institute of Allergy and Infectious Diseases (NIAID) had funded a gain of function research at the Wuhan Institute. However, Dr Anthony Fauci, the director of NIAID and most prominent face in the US’s efforts against the pandemic, denied this.
Since the report was published, there have been fresh calls from scientists across the world to thoroughly investigate the origins of the SARS-CoV-2 virus — taking hypotheses about both natural and laboratory spillovers seriously until there is sufficient data.
WHO Director General Tedros Adhanom Ghebreyesus had stated in March there will be a further investigation into whether an ‘accidental leak’ from the Wuhan institute led to the Covid-19 pandemic.
Ethics related to gain of function research
As mentioned above, the idea behind allowing mutant viruses to grow in a lab is to understand the risks of future pandemics.
Even before the H5N1 research created an outcry in the US, the World Health Organization in 2010 developed a ‘guidance document’ for Dual Use Research of Concern (DURC) in the life sciences.
DURC refers to technology that was developed for peaceful purposes, but could be used for military aims.
By 2014, there was a shift in the concerns, as pointed out by bioethics professor Michael J. Selgelid. Instead of deliberate misuse to cause harm, the concerns were around biosafety — that is, “a devastating pandemic could potentially result from a laboratory accident involving an especially dangerous pathogen created via GOFR (gain of function research)”.
Selgelid also noted that even if GOFR has been adequately safe so far, similar future research might be conducted in countries or institutions with weaker infrastructure, where research oversight may occur.
In an article written in 2012, Dr Fauci stated that the “benefits of such experiments and the resulting knowledge outweigh the risks”.
“It is more likely that a pandemic would occur in nature, and the need to stay ahead of such a threat is a primary reason for performing an experiment that might appear to be risky,” Fauci had written.
However, he too pointed out that a gain of function experiment involving a virus with serious pandemic potential, performed in a world-class laboratory by experienced investigators, could be replicated by another scientist who does not have the same training and facilities.
Ideally, research that involves risky, infectious pathogens that can spread via aerosols are conducted in Biosafety Safety Level-4 labs — considered the most secure for working with viral samples. Biosafety level is a set of precautions required to isolate dangerous biological agents in a laboratory, and the levels of containment range from 1 (the lowest) to 4.
Fauci argued that the scientist in his example, working in a lab lower than Level 4, could become infected with the virus, in turn leading to an outbreak that would ultimately trigger a pandemic.
After the outbreak of Covid-19, scientists from the US called for rethinking gain of function experiments. They proposed an important criterion for proceeding with such experiments — that there be a compelling medical reason to do so.
“One should not be performing GOF experiments simply to ‘see what would happen’ without strong evidence that it could happen naturally,” the researchers wrote. “In other words, just because an experiment can be done does not mean that it should be done.”
(Edited by Shreyas Sharma)
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