“Gain of Function”: a poorly understood element of the Anthropocene

Colin D Butler

When I proposed a short essay on “gain of function” (GoF) and its relevance to the Anthropocene (the human-dominated geological era) the theory that COVID-19 could have originated from a laboratory accident (or, less likely, was deliberately released) was still largely dismissed as a “conspiracy”. In recent weeks that has changed; many newspapers and magazines are giving the possibility serious attention, including some on the political left, such as The Guardian and the New York Times. Among top journals, Science has broken ranks, publishing a letter, suggesting that the theory is plausible. My editorial, published in December 2020, which foreshadowed these changes, no longer looks so isolated.

In early 2020 I was commissioned, by the United Nations Environment Programme, to write approximately 10,000 words on the origin of SARS-CoV-2 and its relevance to environmental change in the Asia-Pacific. My starting position was that the origin of COVID-19 would echo that of SARS, which emerged from the farming (possibly intensively) of species exotic to most Australians, such as raccoon dogs and palm civets. However, I soon learned that GoF had been postulated as an underlying factor for the pandemic. At that time I did not recognise the term, although I was aware of a precursor ,“dual use”, as I had co-authored an editorial, in relation to controversial work done to manipulate influenza viruses.

Succinctly, GoF has been defined, by its critics, as “research to increase the pathogenicity, transmissibility, or alter the host range of highly pathogenic microbes with pandemic potential, including, but not limited to influenza A viruses”. GoF techniques include the deliberate “editing” of the genome of pathogens such as viruses (for example by gene splicing) and the use of “serial passage” to alter the host range. Because this is an inexact science, GoF needs to be undertaken in high security laboratories.

As I explored the GoF literature I became increasingly disturbed, not because I could prove GoF is the root of COVID-19 (as yet, no one can) but because there is a convincing argument that it could. Furthermore, even if COVID-19 originated outside a laboratory, it appears possible that “SARS-3” might occur via GoF and a laboratory leak. One such warning came from Canadian professor of public health Amir Attaran. In the video “SARS COV2 – Identikit di un killer”, produced by Italian state media, RAI, Prof Attaran compares GoF research, today, to atomic weapons research in the 1940s. At the 54 minute mark he states that GoF “is like playing with nuclear material to build a bomb”. Another warning is from Professor Simon Wain-Hobson, who points out that hypothetical work to convert HIV to an airborne pathogen should never be contemplated (61 mins 30 secs).

I learned that the Cambridge Working Group, had, in 2014, issued a “Consensus statement on the creation of potential pandemic pathogens”. After reminding the reader of some of the many laboratory accidents that have occurred, and by pointing out that these escapes are increasing in frequency, they stress that public health is risked not only via the escape of known pathogens, but also newly created “potential pandemic pathogens”. They state that it is possible to create, in a laboratory, “highly transmissible, novel strains of dangerous viruses”. They conclude by arguing that “expected net benefits should outweigh the risks”.

I also heard an interview with Pulitzer Prize-winning author, Lawrence Wright, whose novel “The End of October” describes a pandemic that starts in Asia and sweeps the world. Wright recounts a visit to Fort Detrick, the acknowledged centre for U.S. biological warfare research (some of it defensive, e.g. for vaccines). In the 41st minute he describes an interview with an unnamed US intelligence expert who warns that, soon, teenagers will be able to make novel viruses in their bedrooms. The interviewer (Claire Nichols) remarks she is terrified. I am too.

What can be done? 

In recent days US National Institute of Allergy and Infectious Diseases Director Anthony Fauci has explicitly denied that a grant that he authorised to the EcoHealth Alliance (which in turn was partly used to fund work at Wuhan Institute of Virology, in China, involving coronaviruses) was used for “gain of function” work. Others have argued that Dr Fauci is hairsplitting. Less transparently, the EcoHealth Alliance has also received funds (perhaps its majority) from the US Department of Defence.

Some GoF supporters argue it will bring great benefits, perhaps including vaccines needed to fight the current pandemic. Others argue that researchers overstate the benefits and understate the risks. In any case, this field cannot be left to self-regulate; an exemplary ethical environment, as far as possible, is required. This is obviously lacking in some settings today. Increased awareness of Gain of Function work is highly relevant to public health, and multidisciplinary oversight of it is clearly justified.


Colin D. Butler is an Honorary Professor at the National Centre for Epidemiology and Population Health, Australian National University. He is an expert in Public Health And Health Services, Epidemiology and Environmental Science. He was awarded the Public Health Association of Australia Tony McMichael award for public health, ecology and environment in 2018.  



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