The origin of COVID-19, “gain of function” research and the Anthropocene (IJE version)

Letter to the Editor (maximum length 700 words, 10 references, 2 figures) rejected by the International Journal of Epidemiology on May 12, 2023 (no review, no reason provided other than "too much competition"). This version has been expanded, with some links added and two new figures.

Note: from sometime in 2010 until early 2013 I worked closely with Dr Peter Daszak, as one of four co-editors of the journal EcoHealth, eg see "Global ecology, global health, ecohealth" https://link.springer.com/article/10.1007/s10393-011-0735-5 "EcoHealth and the influenza A/H5N1 dual use issue" https://link.springer.com/article/10.1007/s10393-012-0768-4 and "Nature, Gaia, Plagues, and People: Three Books on a Path to EcoHealth" (https://link.springer.com/article/10.1007/s10393-012-0797-z)

Key Words: virology, ethics, risk, planetary health, climate change, gain of function

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In 1975 Paul Berg, awarded the 1980 Nobel chemistry prize for his pioneering work recombining genetic material, warned, with colleagues, fresh from the Asilomar conference, of potential biohazards arising from the then novel technology which he and his colleagues were pioneering (1). Such recombinant genetic work is now sometimes called “gain of function” (GOF), because it can result in the acquisition of new phenotypic traits. However, GOF is imprecise, with potential risks and benefits. Sometimes, the dangerous pole of GOF is called “GOF of concern” or “dual use research of concern”. These names reflect awareness that the methods can be used for good or ill, including for bioweapons.

Around 2010 concern was growing that H5N1, a virus responsible for avian influenza, could develop the capacity to be transmitted between humans, and at the same time retain the high mortality known to be associated in diagnosed human cases. Researchers in the Netherlands and the US conducted experiments involving the use of “serial passage” involving ferrets to see if they could generate a form of H5N1 with enhanced mammalian transmission, potentially including among humans. This work generated intense controversy, leading to a brief moratorium on the manipulation of viruses considered to have pandemic potential (2).

In 2018 the Global Virome Project (GVP) was launched, with the ambitious goal of seeking to “discover the bulk of the projected remaining 1.67 million unknown viruses in animal reservoirs” and to characterize the majority of the 0.6 to 0.8 million considered to have “the highest zoonotic potential” (3). To assist this formidable task GVP supporters proposed to use “in vitro binding mechanisms coupled with in vivo models” (3). [Added after submission: see https://www.youtube.com/watch?v=IdYDL_RK--w where Peter Daszak boasts to Vincent Racaniello about the EcoHealth Alliance's capacity, via its partners, to manipulate viral characteristics; strikingly, neither express any recognition of the risks.] It is now evident that some of these techniques involved the deliberate manipulation of the genetic structure of viruses, including coronaviruses, and the exploration of their biological effects using chimeric, hybrid mammals such as “humanized mice” (4).

To non-virologists the existence of synthetic viruses may seem like science fiction, perhaps as fantastic as the relevance to human health of changes in the concentration of trace “greenhouse” gases once did. However, this is not science fiction. In 2017 researchers synthesised horsepox virus, from component fragments of RNA available by mail order. The lead author of this work later warned “any method that can be used to assemble horsepox virus could be used to construct variola, the virus that causes smallpox” (5). Thus, any emergence of smallpox, today, could be synthetic rather than the accidental or deliberate release from a known stockpile.

The possibility of laboratory enhanced viruses arising via GOF was recognised by the GVP (see figure 1) (6). There is now abundant documentation of links between one of the leading promoters of the GVP (Peter Daszak) and GOF involving coronaviruses, commissioned to be undertaken at the Wuhan Institute of Virology (WIV). This route is via the EcoHealth Alliance (EHA), which is led by Daszak. This organisation has received tens of millions of dollars from the US government, including the US Department of Defence (see below). Some of these funds have been used to fund work at the WIV which can arguably be defined as GOF, although the EHA later denied this (see figure 2). Though definitive evidence linking GOF with the emergence of SARS-Co-V-2 is still lacking, an increasingly number of scientists think that it is plausible (7).

 

 

Figure 1. Source: slide 4 https://www.slideshare.net/SirTemplar/2017-0907-global-virome-project. Note the words “gain of function” and “novel”. See also slide 2 (Figure 5, below), which makes a similar point, without using the term "gain of function".

Figure 2. The EHA has repeatedly denied that any of the work it commissioned at the WIV or elsewhere is GOF. However, this is based on arbitrary definitional interpretation. Before the work of the EHA became highly controversial their enthusiastic support for GOF was clear, as shown by this email from the EHA president, dated July 2016, made available to the public using freedom of information legislation. Source https://americasbestpics.com/picture/email-from-peter-daszak-to-jenny-greer-on-getting-gain-IE4Uc9f39

 

Figure 3.  (Added) The question must be asked: is the EHA, effectively, a branch of the US military? Sources https://twitter.com/RTheyLying/status/1655895977008431105 and https://www.usaspending.gov/recipient/12d878d7-3cbe-c819-e51e-7891f98ae955-C/all

Figure 4.  (Added) As of today (May 14, 2023 in Australia) this website shows that that US Dept of Defence is, by far, the largest provider of funds to the EcoHealth Alliance. Source: https://www.usaspending.gov/recipient/12d878d7-3cbe-c819-e51e-7891f98ae955-C/all

 

Figure 5 (added).  Source: slide 2 https://www.slideshare.net/SirTemplar/2017-0907-global-virome-project. According to the Global Virome Project in 2017, the accidental and/or intentional release of "laboratory-enhanced variants" is increasing. Yet, in 2020, Peter Daszak (closely involved with the GVP) covertly co-ordinated an influential letter, published in The Lancet, which attempted to dismiss concerns of a laboratory source of the pandemic as "conspiracy". (e.g. see van Helden, Butler et al: https://www.thelancet.com/journals/lancet/article/PIIS0140-6736(21)02019-5/fulltext)

Irrespective of COVID-19’s cause, the entirely synthetic or human-modified viruses that GOF can produce can be conceptualised as “novel entities”, one of the “planetary boundaries”, a foundational concept for planetary health (8). It is 34 years since the world’s first editorial on climate change and health in a medical journal. At that time, the word “Anthropocene” (the human shaped era) had not been coined (9), and that concept probably would, in 1989, have seemed far-fetched to most epidemiologists. Yet, today, concepts such as planetary boundaries, the Anthropocene and climate change are broadly accepted as relevant to global population health (10).

The consequences of GOF could already be immense. In future, unchecked, they could rival the scale of climate change and even the intentional use of nuclear weapons. It is time for epidemiologists to again broaden their horizons, and consider the disturbing possibility that the Anthropocene has entered a dangerous new phase.

References

1. Berg P, Baltimore D, Brenner S, Roblin RO, Singer M. Summary statement of the Asilomar Conference on recombinant DNA molecules. Proceedings of the National Academy of Science (USA). 1975;72(6):1981-4.

2. Wain-Hobson S. H5N1 viral-engineering dangers will not go away. Nature. 2013;495:411.

3. Carroll D, Daszak P, Wolfe ND, et al. The Global Virome Project. Science. 2018;359:872–4.

4. Segreto R, Deigin Y. The genetic structure of SARS-CoV-2 does not rule out a laboratory origin. BioEssays. 2020;n/a(n/a):2000240.

5. Noyce RS, Evans DH. Synthetic horsepox viruses and the continuing debate about dual use research. PLOS Pathogens. 2018;14(10):e1007025.

6. Global Virome Project. The beginning of the end of the pandemic era https://www.slideshare.net/SirTemplar/2017-0907-global-virome-project (viewed 13 April, 2023). 2017.

7. Bahry D. Rational discourse on virology and pandemics. mBio. 2023. DOI: 10.1128/mbio.00313-23

8. Butler CD. Comparing and contrasting two United Nations Environment Programme reports on COVID-19. Science in One Health. 2022;1:100003

9. Crutzen PI, Stoermer EF. The "Anthropocene". IGBP Newsletter. 2000;41:12.

10. Whitmee S, Haines A, Beyrer C, et al. Safeguarding human health in the Anthropocene epoch: report of The Rockefeller Foundation–Lancet Commission on planetary health. The Lancet. 2015;386:1973–2028.