Increasing calls from scientific community for transparent investigation of SARS-CoV-2 origins

An open letter was published this past week in the leading scientific journal Science by a leading group of scientists urging for a balanced and transparent data-based evaluation of the origin of the pandemic. This involves understanding where the virus SARS-CoV-2 came from, and how it entered the human population to spark the current pandemic. First, it is important to recognize that there is no direct evidence establishing the answer to these questions at this time. There is considerable uncertainty and much that is not known. They acknowledge this, but the key of the letter is to urge a thorough, transparent, and empirical investigation of this question, that they argue has not been investigated in a balanced manner, and which is important to try to prevent any future pandemics.

There are two primary theories that have been discussed:

1. Zoonotic spillover: Originating in bat coronaviruses, it somehow entered humans through another animal species, perhaps via the Wuhan wet market, after naturally evolving to obtain the ability to infect humans through mutations that randomly occurred during that process, either while in bats or in the intermediate species.

2. Laboratory escape: The virus entered humans by leaking out from bat coronavirus researchers, either out of a bat coronavirus research facility in Wuhan (Wuhan Institute of Virology) immediately adjacent to the wet market, or from a bat coronavirus researcher infected during field work. Under these hypothesis, the virus may have naturally acquired mutations necessary to infect humans within the bat, or some have speculated that the mutations may have been acquired via gain-of-function research.

A report was published after a joint study of the World Health Organization (WHO) and China on March 30, 2021, concluded that the zoonotic spillover hypothesis was "likely to very likely," but the laboratory incident hypothesis was "extremely unlikely" (page 9 of report). This fit the early assumptions of many scientists, based on the fact that both SARS-CoV-1 and MERS viruses, both coronaviruses originating in bats and producing human epidemics, had strong scientific evidence of spread to humans through an intermediate animal host, thought to be palm civets and raccoon dogs for SARS-CoV-1 and camels for MERS.

This report has generated considerable skepticism from various scientists, including the Science letter highlighted that the two theories were not given balanced consideration, with only 4/313 pages of the report addressing the possibility of a laboratory accident. This letter calls for a more detailed, balanced, and transparent investigation considering both possibilities be done, with data openly shared and evaluated by independent scientific experts. They also highlight that others are calling for this same further evaluation, including the Director-General of WHO, the governments of the USA, UK, Slovenia, South Korea, Norway, Lithuania, Latvia, Japan, Israel, Estonia, Denmark, Czechia, Canada and Australia, and the European Union.

Former CDC director Robert Redfield in an interview with CNN on March 26, stated that his opinion is that the laboratory accident hypothesis is most likely, an opinion for which he was broadly pilloried in the media and from many in the scientific community. His reasoning was that it takes a long time for viruses to evolve in intermediate species before they acquire the ability to infect humans and become efficient in human-to-human transmission, noting that no intermediate species has been identified or confirmed.

Nicholas Wade, a former scientific writer for Nature, Science and the New York Times, has written an article on Medium that was published in Bulletin of the Atomic Scientists discussing these two hypotheses in detail, making a clearly leading argument that he believes the laboratory escape hypothesis is more likely to be true, and also hinting he believes that gain-of-function research may have played a role in its development. Wade is a controversial figure for his writing on genetics, evolution, and human society that has been heavily criticized by many scientists and sociologists, so many will take his writings with a grain of salt, but he provides references and evidence for his narrative including references to publicly available NIH grants and interviews given on particular dates that that others can check for their veracity and completeness, and to evaluate his arguments.

The zoonotic spillover has been widely believed from the start, promoted by a group of scientists in a February 18, 2020 op-ed published in The Lancet that compared alternative theories with conspiracy theories that "create fear, rumors and prejudice that jeopardise our global collaboration in the fight against this virus." As a result, the open consideration of any laboratory escape hypothesis has been strongly discouraged and likened to promoting baseless conspiracy theories. A March 17, 2020 op-ed published in Nature Medicine claimed that it was "improbable" that the virus was the result of human manipulation, based on the fact that it did not seem to be constructed on the backbone of a known existing coronavirus that they presume would have to have been true if the result of research. These two op-eds played a large role in establishing the zoonotic spillover hypotheses over any laboratory escape hypothesis as the status quo in the scientific community.

Recently, it has become more apparent and accepted that there is considerable uncertainty about which of these hypothesis is true, or if both are false and there is some alternative explanation. Some are worried that consideration of the laboratory escape hypothesis will lead to anti-Asian bias or violence. Certainly, the increase of anti-Asian violence in the USA and other places during the pandemic is a serious concern driven by ignorance and prejudice, and everything must be done to combat these sentiments. Regardless of how the virus emerged, there is no reason for anyone to blame the Chinese people, and the vital contributions of Chinese scientists to biomedical research including during this pandemic is undeniable, including a brave Chinese scientist who was instrumental in public release of the preliminary SARS-CoV-2 sequence that was the basis for all of our efforts to devise tests, treatments, and vaccines against the virus, at high personal risk with knowledge that this release went against the wishes of the Chinese government. There is no doubt that we must do everything to protect our Asian members of our community and fight against prejudice and bias. But this does not mean we should dismiss plausible hypotheses about SARS-CoV-2 origins just because they might raise difficult questions and problems. Conspiracy theories arise and thrive in an environment of lack of transparency, cover-ups, and purposeful ignoring of plausible hypotheses. I support a vigorous, transparent, balanced investigation of evidence for the origin of the virus, openly searching for the truth, whatever it is. Such an investigation is the best way to combat baseless conspiracy theories and uncover evidence for what actually happened, and this knowledge can be put to work to effectively reduce the probability of future pandemics.

If we find the zoonotic spillover hypothesis is true, then it is important to evaluate how to ensure safe handling of wildlife and tracking of viruses. If we find a laboratory accident contributed to this emergence, then it is important for high risk infectious disease research centers be rigorously monitored and best practices ensured, perhaps with the aid of international scientific agencies. If we do find that gain-of-function research contributed to the escape of this virus then perhaps international scientific agencies need to evaluate the guidelines and restrictions for such research and robustness of enforcement to protect against any future accidents. Update 6/4/2021: Vanity Fair has published an article investigating more information relevant to assessing the hypotheses about the origin of the virus. Image from ABC