What is gain-of-function research? – The Economist

Nov 1st 2021

DISQUIET IS growing about gain-of-function (GOF) research, a form of genetic manipulation on micro-organisms. Some anxiety stems from the idea that such work was responsible for creating SARS-CoV-2, the virus that causes covid-19. This remains unproven. But, more broadly, there is unease that Americas National Institutes of Health (NIH), which funds research, may have supported GOF work in China. Recently there was further controversy when the NIH said that a recipient of one of its grants, EcoHealth Alliance, failed to report its work in 2018 on making a mouse coronavirus more virulent. (EcoHealth Alliance says this information was reported.) Many have been alarmed to discover that, before 2019, Chinese and American researchers often genetically tinkered with SARS-like viruses. What exactly is gain-of-function research, and is it cause for alarm?

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Researchers have been modifying viruses for decadesand not always in benign ways. Twenty years ago Australian scientists changed a mousepox virus during an attempt to create a mouse contraceptive. The idea was to stimulate the production of antibodies against mouse eggs. But the gene that was inserted switched off the mouses immune system, making the virus more lethal.

In 2015 Ralph Baric and colleagues from the University of North Carolina in Chapel Hill took the virus that caused the first SARS outbreak and added a surface protein from another SARS-like virus, known as SHC014 and found in horseshoe bats. The newly created virus was able to infect human airway cells. This caused much alarm. The researchers themselves pointed out that their work showed, usefully, that the ingredients for future outbreaks of SARS-like viruses circulated in nature.

Some virus-tinkering is useful and no cause for worry, for example to create a covid-19 adenoviral vaccine, or to deliver a novel gene as a drug. But biosecurity experts worry when a pathogen has its ability to infect, or cause disease, enhanced. Agents of concern include Ebola, anthrax and respiratory viruses with the potential to cause pandemics, such as influenza and coronaviruses. A new term, gain-of-function research of concern (GOFROC), has emerged to distinguish this sort of work, although it is not widely used.

In July the debate about what constitutes GOF reached Americas Senate. Rand Paul, a Republican senator from Kentucky, tussled with Anthony Fauci, the director of the National Institute of Allergy and Infectious Diseases, which is part of the NIH. Mr Paul is angry that the research agency funded GOF work at the Wuhan Institute of Virology (close to where covid-19 was first spotted in late 2019). The results of the work were published in 2017. Spike proteinsthe parts of the virus that help it bind to its hostfrom eight different coronaviruses were put into the genome of another coronavirus called WIV1, and these new genetic innovations could infect human cells. Dr Fauci says the work does not qualify as GOF. The counter argument is that, although the work certainly invented new viruses, it did not enhance the ability of those viruses to infect humans because the original virus was also able to infect human cells. There is a bit of linguistic wriggling here. It may be true in technical terms that the NIH has not supported specific gain-of-function research, as it claims. But it remains possible that the work it funded ended up creating gains of function on agents of concern unintentionally.

It is still unclear whether SARS-CoV-2 originated from a petri dish or a pothole. But as more details emerge of the work that was done at the Wuhan Institute of Virology, there is growing unease about whether genetic tinkering with agents of concern should be done at all. One argument for continuing such research would be to predict the mutations in SARS-CoV-2 that might in future cause trouble for humans. An argument against this is that the virus will not necessarily behave in the wild as it does in the lab. The debate about GOF work will continue long after the interest in the origins of SARS-CoV-2 has subsided.

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What is gain-of-function research? - The Economist