Over two years since the first cases started appearing in Wuhan, China, there is much we don’t know about the origins of SARS-CoV-2, the virus causing COVID-19. However, scientists can quickly resolve this question by finding bats in caves somewhere in China and southeast Asia. They could trace the chain that led to the COVID-19 epidemic in Wuhan. The reality is that it’s unlikely this would happen soon based upon recent history. It was 14 years between the first identification of HIV virus as the cause of AIDS, and the demonstration that it has been transferred to human beings from a particular group of chimpanzees. However, this possibility had been predicted many years before. A decade passed between the outbreak of SARS in 2003-2004 and the identification of its cause. It was seven years before it was discovered that the 2009-10 pandemic of influenza had originated from Mexican swine. The alternative possibility to a natural origin—a laboratory leak—will be difficult to definitively prove or disprove.
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Importantly, the focus on origins raises the question of whether there were significant changes in research or health policy for prior pandemics. For example, HIV. We learned that chimps to humans transmitted HIV in rain forests. However, we didn’t interrupt human lives or visits in these rain forests. HIV was likely to have reached cities as a result of increased prostitution and population movements. It then spread worldwide through frequent travel and large numbers of sexual contacts and medical uses. IV drug addiction and high blood pressure also played a role. Public policy did not change much, it is obvious. We now know that SARS was not the original cause, but SARS-CoV-2. Although the great influenza pandemic was thought to have started in WW I, we went on to WW II without stopping soldiers from being stationed in barracks. Knowing, in short. Origins made little difference in how we treated and dealt with the disease—in most if not all cases.
Yet the World Health Organization (and much of the scientific community) initially agreed with the Trump Administration’s claim that understanding the origin of SARS-CoV-2 was of vital immediate importance. The administration’s concern was, plausibly, less a matter of dispassionate interest in science but more an effort to open a new front in the U.S. response to a rising China, or an effort to divert attention from a delayed and chaotic U.S. response to the pandemic. A large effort should be made to determine the source of SARS CoV-2. This would allow for public and public health policies that are based on this knowledge. How can we counter Omicron, or Delta, by better understanding SARS-CoV-2’s origin? The knowledge of origins can help scientists understand the science behind SARS-CoV-2 and close off political disputes. But, it is unlikely that our knowledge about origins will change any decisions regarding how to respond to SARS-CoV-2 or what we do in preparation for the next pandemic. You can assume that one hypothesis, nature or laboratory leak, could prove to be true.
This is the place where we stand now in our origins debate: There was one idea that bats came from nature directly, or indirectly through another animal. One alternative is that it was due to research error. The possibility that scientists studying bats on the ground have been infected or brought infected bats back from the lab is possible. Inadvertent release of the virus then spread. It is also possible that “gain-of-function” research could have created SARS-CoV-2, followed by its accidental release. Early expression of support for the gain-of-function hypothesis concerned CGG, one of the codons specifying the amino acid arginine for its insertion into the virus’s newly forming spike protein thereby enabling a human protease (furin) to more efficiently cut the coronavirus spike protein which can facilitate infection. Nobel Laureate David Baltimore had previously suggested that CGG Codon for Arginaine (CGG) was unusual and would suggest man-made origins. But, it is unconvincing. The CGG codon is present in other coronaviruses such as those that cause the common cold. However, it’s only limited to the beta subgroup of SARS-CoV-2.
The President gave the U.S. intelligence agency (IC) 90-days to determine if natural causes or research error were more likely. They reported their results in August. Although one agency found research error more likely than another, the other four agencies believed that natural causes were the most probable. However, the National Intelligence Council’s summary concluded in favor of natural origins although each agency and the NIC only placed low to moderate confidence. The declassified version of the IC report also pointed to the Chinese government’s “…frustration [that] the international community is using the issue to exert political pressure on China…” as a reason why further Chinese cooperation in establishing origins remains unlikely. We doubt that there will ever be a definitive answer to this question, even though research errors remain a possibility. The evidence is increasingly supporting the natural origins hypothesis. Earlier assessments which pointed to a laboratory leakage, such as that discussed in the furin hypothesis above, are now weakening with increased scrutiny.
The question is how important it really matters. Each scenario is unique and we know the best way to address it. Each situation has its own unique set of circumstances, which makes it difficult to decide what direction you should take. Prudence suggests that every option be considered.
- Surveillance of diseases. Clearly, investment in diseases surveillance at the human–wildlife interface and in preventing potential spillovers of virus infection from animal to person should be prioritized. This is true even if SARS-Cov-2 was a result of research error.
- Research safety. Laboratory research with dangerous pathogens must be safer. Inadvertent releases of dangerous pathogens from labs in every part of the globe have been documented in numerous instances over decades. Also, safety protocols should be improved for specimen management and field research. For any given type of pathogenic virus it is necessary to have better standards for training. It is important to weigh the benefits of research funding against the potential dangers associated with studying microbes.
- Research on gain-of-function. This phrase is used by most virologists to indicate research to find out if certain genetic modifications made to a virus in a laboratory can increase the virus’ ability to infect cells. This refers to human coronaviruses having a higher capacity to infect humans. It is our goal to improve protection against these viruses, which could cause serious epidemics or human pandemics. This goal, which would allow the medical community to have better knowledge of how to diagnose and develop vaccines for such viruses, is no doubt worthy. It is important to weigh the risks and benefits. It is possible for viruses to be escaped from research labs, as virologists understand. Every experiment should be evaluated for the potential risk and reward. These points are now being reviewed by experienced virologists. However, we have to admit that most scientists will be tempted not only because they believe that their capabilities and that they control the environment in the laboratory well enough. Scientists will be eager to move forward. Positive reviews will increase the likelihood that such research will be funded by NIH. However, their reviews can sometimes not be very transparent. Perhaps we could learn from the Asilomar meeting of molecular biologists. There were detailed discussions about the ethics and possible dangers of certain types of gene-cloning experiments. The discussions resulted in guidelines for acceptable and unacceptable. We believe that it is a good idea to have non-specialists (even scientists) as part of the process of reviewing the grant application. This will allow for independent oversight of research funding.
The origin of SARS CoV-2 has attracted a lot scientific attention. And, let’s be honest, it would be nice to know. But knowing where the origins are may be a limitation to how we address Omicron, Delta, and any other future threats. It may not be possible to avoid the distractions of politicized attempts to evaluate origins, but instead invest in long-term, international collaboration endeavors on SARS CoV-2, and preparations for potential pandemics.
