COVID-19, the WHO investigation, and Gain of Function research

COVID-19 may develop into the worst infectious disease crisis since “Spanish” flu, even worse than HIV/AIDS (if it evolves the capacity to outsmart vaccines, a worrying possibility, given recent South African data). In any case, it is a very unusual and disturbing event, several orders of magnitude worse than SARS or Ebola, if raw numbers of deaths and illnesses are considered.

Ascertaining the origin of COVID-19 is of utmost importance. Unlike almost all other recent “emergent” viral zoonoses, of which there are perhaps a score that are significant (e.g. Ebola, Hendra, Nipah, Lassa fever, Marburg and SARS) SARS-CoV-2 has a strongly developed “stealth capability”, i.e. the ability for significant asymptomatic transmission. MERS (also a coronavirus) also has stealth characteristics, but to date has proven far less contagious. (SARS lacks this capacity, hence it did not become a genuine pandemic, unless one uses a very low barrier for the definition of that term). 

HIV/AIDS, like many sexually transmitted infections, also has stealth characteristics, as it can be transmitted to people who are unaware they are at risk. Sometimes too, the person transmitting HIV is unaware of their illness. HIV/AIDS is a pandemic, using any definition, and its death toll still far exceeds that from COVID-19.

 

Could SARS-CoV-2 have been "engineered"?

The highly developed capacity of SARS-CoV-2 for such significant asymptomatic transmission struck me as extremely unusual, even in early 2020. However, initially, I put my unsettling thoughts (explained following) to the side, thinking that for reasons that I did not understand, nature, by itself (perhaps assisted by farmed or captured and traded species that are exotic in the West, but common in China, eg palm civets, raccoon dogs or pangolins) had evolved a viral "super-pathogen”. 

 

The leading British virologist John Oxford has, for almost two decades, published work postulating that "Spanish” flu was not entirely “natural", but had its characteristics “shaped’ by human factors associated with the Western Front in the Great War, especially the dense crowding together of ill troops, which (he argues) created a natural laboratory allowing a form of "serial passage” of the influenza virus (H1N1) among them. (See also here). Thus, Oxford postulates, evolution favoured the “honing” of a form of H1N1 which was unusually efficient at killing young people. Although Oxford’s theories on this topic are generally regarded as speculative, no one can deny that Spanish flu emerged in the closing period of the Great War; if the two events were not related then the world struck extraordinary bad luck. 

Because I have long been familiar with Oxford’s theory, including the principle of serial passage and other techniques used in “Gain of Function” research, it therefore crossed my mind, quite early, that SARS-CoV-2 might have been “engineered”. When I read the letter, published in The Lancet in February 2020 (Calisher et al), which we now know (thanks to US “Right to Know” which published relevant email correspondence concerning it) was conceived and driven by Dr Peter Daszak, head of the EcoHealth Alliance, I was dismayed with how the laboratory leak hypothesis had been dismissed. The letter even characterised such a view as “conspiracy”. 

 

In early 2020 the United Nations Environment Programme (UNEP) commissioned me to write a 15 page report (plus references) on the origin of SARS-CoV-2 and how future pandemics might be avoided. I thus started to read everything I could about this new virus, including via twitter. I thus gradually became aware of COVID-19 activists, several of whom are anonymous including a team called “D.R.A.S.T.I.C.". I also started to read, with great attention, statements by Professor Shi, director of the Wuhan Institute of Virology. 

 

"Gain of Function": a deadly euphemism? 

 

I soon realised that there were other troubling elements which gave plausibility to a laboratory leak hypothesis. One was that I became aware that Gain of Function (GOF) studies were being undertaken at the WIV, involving not only betacoronaviruses but chimeric creatures such as “humanised mice”. I also learned that these studies were (until suspended by the US administration headed by President Trump) being funded by the US National Institutes of Health, via the EcoHealth Alliance.  (Funding has apparently been restored, from a non-government source.)

GOF studies seek to answer questions such as what genetic sequences of a pathogen (generally a virus) impart characteristics, perhaps such as airborne transmission, or human to human transmission. Serial passage, using living animals, has long been a key technique of GOF, but is now complemented by cell lines, as well as animals with at least some characteristics of other species, eg humanised mice.

 

Two extreme examples of potential GOF experiments that should never be undertaken are: (1) could HIV be made transmissable by coughing? (2) Could a pathogen be engineered to target an ethnic minority? In my opinion, we collectively know far to little to conduct even simple, apparently "safe" GOF experiments. Of course, others differ. (See this debate in Nature Reviews Microbiology, published in 2015). But if GOF is to be conducted, surely we can agree that it needs strict safety protocols, transparent, accessible records (available for decades) and a strong "safety culture".

In fact, I think GOF studies warrant oversight similar to nuclear power, with teams of inspectors from neutral countries. In the film SARS COV2 – Identikit di un killer (Identikit of a killer), by Italian media organisation RAI, Canadian Professor of Public Health Amir Attaran likens GOF work to "playing with nuclear material to build a bomb" (approximately at the 54 minutes mark). Finally, GOF studies, to be safe, need to operate in countires with strong whistleblower protection, a quality clearly lacking not only in China, but many other nations.

In 2012 I co-authored an editorial with the editor and other co-editors of the journal EcoHealth that discussed some of the pros and cons of “dual use” technologies with regard to influenza viruses. The term “dual use” (in relation to virus research) has fallen from use, replaced by “Gain of Function”. I formed the opinion, in 2012, that these studies could be very dangerous. Indeed a moratorium on such studies was applied for several years, but has since been relaxed. For more information on the risks of Gain of Function, see: http://www.cambridgeworkinggroup.org/

 

See, also, this essay by Dylan Housman, called "Why Aren’t We Talking More About China’s ‘Gain Of Function’ Coronavirus Research?"

 

Strange comments by Professor Shi 

 

In mid-2020 I learned, initially via the activists on Twitter, of illnesses of six mine workers, exposed to large quantities of bat guano from their work clearing a mine shaft in Yunnan, China, in 2012. At first, I was incredulous, wondering if the Master's thesis which described the clinical course of these workers (of whom three died, despite aggressive treatment), could be an elaborate hoax. I wondered why these cases had not been brought to international attention far earlier. Why, for example, had the EcoHealth Alliance, whose self-described mission is to alert the world to new viruses, had not known of them? 

 

Although fragmentary evidence of these illnesses was released in 2014 (see http://dx.doi.org/10.3201/eid2006.131022), a more complete story was not confirmed until an Addendum was published in Nature in November 2020, written by Professor Shi and others at the Wuhan Institute of Virology. More recently Professor Shi has also commented on this thesis, to John Sudworth of the BBC. Her comments about this thesis were oddly disparaging.

 

In December 2020 I published an editorial in The Journal of Human Security documenting some of Professor Shi’s inconsistencies and belated, piecemeal, revelations. In that essay, I argued that the laboratory leak was a plausible hypothesis. 

A story from George Orwell?

 

Now I come to the recent WHO-associated investigation into the origins of COVID-19. This involved scientists screened by China. I am unaware of whether members of the team were considered whose selection was later vetoed by China. I certainly was not invited.

 

A report by this team is to follow, and there was a press conference lasting over two hours, to which I have not listened. However, there appears to be an impression, widely circulated, that there was consensus among the team that the virus was not from a laboratory. The evidence stated in favour of this appears to boil down to something like “we spent 3 hours at the Wuhan Institute of Virology, we talked to the people there, and we formed the opinion that they are honest and competent. When they said the virus had not leaked we believed them”. Even if I am over-simplifying the evidence which they found, my opinion is that this conclusion is based on flimsy evidence. For a start, at least one of the participants, (who has, at least in one interview I have seen on Chinese media called Prof Shi a “friend”) has an obvious conflict of interest. The credibility of this team is reduced by including this person in the team, as was pointed out in the recent open letter "Call for a Full and Unrestricted International Forensic Investigation into the Origins of COVID-19" (to which I contributed).

This scientist is also involved in The Lancet, “commission” about the origins of SARS-CoV-2. I will try to write more about that in future; suffice to say, at this point, the attempt that I and others (including some of the authors of the recent open letter) recently made to publish on this topic, in that journal, was rejected.

 

More convincing evidence to refute the laboratory leak hypothesis would require the release of detailed laboratory records, perhaps going back for a decade or more, and answers to many of the questions posed by the “D.R.A.S.T.I.C.” twitter team. Were the Wuhan Institute of Virology (WIV) transparent, such records and answers would not require a visit to China, and they would long ago have been provided. The release of such records would restore some trust and goodwill, in a way that this recent visit has not. Importantly, however, even if the WIV were more forthcoming, evidence of a laboratory leak could still be hidden. That is, while WIV could confirm a leak, they could also hide it, even if one occurred. However, the release of such detailed records (even if screened by WIV) might provide clues which forensic investigation could uncover. From the point of view of China, this is a risk not worth taking, if they have something to hide. And, even if the pandemic did not involved Gain of Function work done in Wuhan, it is virtually certain that other work by the WIV would be scientifically valuable, with potential for good or ill (ie “dual use”) and it would be naive to expect transparency.

 

Alternatively, however, if a virus of 99.9% similarity to SARS-CoV-2 were found in a bat or an intermediary species (eg a ferret-badger), and investigators could be confident that it was authentic, then the laboratory leak hypothesis for SARS-CoV-2 could be confidently excluded. Though it would not exclude the chance of a leak in future.

In summary, the WHO-associated team’s dismissal of the laboratory leak theory could have been provided in a novel by George Orwell. It is absurd to think this reassurance should be taken seriously, and it is depressing that the team appear to think it will be taken seriously. Curiously, however, WHO Director General Tedros Adhanom has since appeared to indicate that the laboratory leak hypothesis should not be dismissed.

Past laboratory leaks

 

I think the tide is turning, in the sense that consideration that the virus may have been a laboratory leak is no longer automatically considered as evidence of conspiracy thinking. There have been many such leaks in the past; here is a partial list: smallpox (1966, 1972, 1978, all in the UK), SARS (2002, Singapore; 2004 Taiwan, 2004, China), anthrax (1979 USSR), Yersinia pestis (2009, USA), Ebola (2004, Russia, 2009 Germany), Marburg, Neisseria meningitis, Venezuelan equine encephalitis, foot and mouth disease (2009, UK), H5N1 influenza (2014, USA) and H1N1 influenza c1976 (China or USSR). 

 

In the absence of genuine and complete co-operation from China, getting to the truth is very difficult. But, on the balance of probability, the theory of a lab leak is becomes increasingly plausible. Although supporters claim Gain of Function studies can do great good, such studies can, obviously, do great harm, at least in theory. At a minimum, such studies need to be managed by people with great integrity and scrupulous attention to detail. My opinion of Prof Shi is that she either lacks the qualities needed for this (shown by her own documented inconsistencies), or, more charitably, is working in a milieu, in a totalitarian society, where such qualities are impossible to display. 

 

Trying to explain Professor Shi's inconsistencies 

It is perhaps possible that Prof Shi’s inconsistencies are a result of Chinese security policy and officials, who greatly restrict her freedom of speech. This could explain otherwise inexplicable errors (for such a senior person) such as her attribution of the miners’ deaths to fungal infection, her mis-reporting of the number of sick miners who died (she says two*, to Jane Qiu in Scientific American). Richard Ebright  described some of Prof Shi's responses as "formulaic, almost robotic, reiterations of statements previously made by Chinese authorities and state media”.

 

Her inconsistencies and occasionally facile comments (eg concerning the Master's thesis) might be because Prof Shi is too frightened to speak out (and has long been constrained in what she could write and speak). In a way that would be encouraging, as it could indicate that, in fact, she is a person of great integrity, as Dr Peter Daszak has long argued. It could signify that she is in danger, although it's hard to see how even the Chinese state could risk making her "disappear" at this stage, without raising far even more questions. 

 

The alternative explanation (that Prof Shi is, to put it kindly, rather simple) is perhaps better for Prof Shi's safety, but even more unsettling for the world.

I honestly don't know which explanation is more plausible, but I am confident that Gain of Function research needs strong regulation, and also that independent journalists and analysists need to press on, trying to uncover the truth. I am dismayed that top journals such as Nature and The Lancet are not more penetrating; I wonder to what extent they too are influenced by Chinese censorship and money. Back in 2007 we argued that journals also have conflicts of interest, which journals should periodically declare.

 

Gain of Function studies are probably being undertaken in many countries. Because they are not banned, there is likely to be an "arms race" underway. Banning them might not stop this race, but it would dampen it. WHO should speak out strongly about GOF research, irrespective of the origin of COVID-19, such experiments could go wrong, with devastating consequences. The relationship between the Anthropocene and infectious diseases is far more complicated than deforestation, climate change and landuse change; it also includes medical proceedures and laboratory research, and - yes - the possibility of a laboratory escape.

* It is not only Prof Shi who presents alternative numbers regarding the miners' deaths. The original report, by a different Chinese team, from 2014, incorrectly says that there were three cases, all of whom died (See: http://dx.doi.org/10.3201/eid2006.131022). In fact there were six, of whom half died (that is, if the Master's thesis is correct).

This blog was slightly updated on March 7, 2021

Some key references on laboratory leaks:

Brault, A.C., et al., Potential sources of the 1995 Venezuelan equine encephalitis subtype IC epidemic. Journal of virology, 2001. 75(13): p. 5823-32.

Branswell, H., Bio-unsafety level 3: could the next lab accident result in a pandemic? Scientic American, 2014

Enserink, M., Reports blame lab for foot-and-mouth fiasco. Science, 2007.

Heymann, D.L., R.B. Aylward, and C. Wolff, Dangerous pathogens in the laboratory: from smallpox to today’s SARS setbacks and tomorrow's polio-free world. The Lancet, 2004. 363: p. 1566-68.

Meselson, M., et al., The Sverdlovsk anthrax outbreak of 1979. Science, 1994. 266: p. 1202-1208.

Silver, S., Laboratory-acquired lethal infections by potential bioweapons pathogens including Ebola in 2014. FEMS Microbiology Letters, 2014. 362: p. 1–6.

 

Some key references on medical procedures and epidemics

 

Bookchin, D. and Schumacher, J. (2004) The Virus and the Vaccine, St Martins Griffin, New York.

Jain, S.L. (2020) The WetNet: What the oral polio vaccine hypothesis exposes about globalized interspecies fluid bonds. Medical Anthropology Quarterly, n/a. https://doi.org/10.1111/maq.12587.

Pépin, J. (2013) The origins of AIDS: from patient zero to ground zero. Journal of Epidemiology and Community Health, 67, 473-475. 10.1136/jech-2012-201423.