Let’s first clear up a technicality: it is not actually the origins of COVID-19 that is at the center of the debate. We know that COVID-19 is a disease that is caused by a virus named SARS-CoV-2 (an acronym for severe acute respiratory syndrome – coronavirus followed by the number 2 because the first severe acute respiratory syndrome caused by a coronavirus was identified in 2003. Now that we have identified another new SARS coronavirus, you will often see reference to the virus that caused an epidemic back in 2003 as SARS-CoV or SARS-CoV-1 to distinguish it from the newly recognized (or novel virus) SARS-CoV-2 that has caused the pandemic that was declared such on March 11, 2020.

The actual controversy is as to the origins of the SARS-CoV-2 virus itself.

If this were a presentation to physicians, public health experts or scientists, I would present the issues in a much more technical manner. But, this is intended for the public and assumes that the audience knows very little about virology, disease outbreak investigations, evolutionary biology, genetics, epidemiology, etc. Therefore, I am going to keep this at a high level. Of course, the trade-off is that I will necessarily oversimplify some matters and present some information that may have technical exceptions or other considerations – a level of complexity that we are not going to dive into, and frankly is not necessary for you to have a good general understanding of the issues. Despite the complexities, it is possible for the public to be informed, and I will do my best to do so.

Why is there so much uncertainty and controversy surrounding the question of the origin of SARS-CoV-2?

1. Politicization. As in most things these days, even this question, which can only be answered through scientific and forensic investigation and data, has become politicized. When an issue gets politicized, as this has, then we see many people align with their political tribes rather than following where the evidence takes them. In fact, many people who have dug in on one or the other hypothesis, cling to and defend that hypothesis with extremely limited understanding of what really is a complex matter. Unfortunately, when people of either side dig in and focus all of their energy on defending their party line, they are no longer objectively evaluating the evidence as we would have a jury do, but rather they become the equivalent of the prosecutor or defense attorney arguing their respective positions and trying to explain the evidence in a way that remains supportive of their side of the case in order to persuade the jury to their point of view.
2. The desire to attribute blame. Although there are likely many potential motives for why some people argue so fervently for a certain position and against the other, when something as sudden and unexpected and bad as this pandemic has been occurs, it is human nature to want to have someone to blame for it. A lab leak provides a more limited and identifiable number of organizations and people to direct blame at, whereas a zoonotic spillover event (infection transmitted from animals to humans) makes it far less clear who to blame and is far less satisfying.
3. The desire to avoid admitting vulnerability. Of course, the converse, assigning blame to a zoonotic spillover event can be uncomfortable in that it underscores our vulnerability to future such events that can turn our lives upside down with little notice, and begs the difficult question as to what our country plans to do to protect us from and respond to future such events.[1]
4. Loss of trust and credibility. Distrust has been amplified during the pandemic. Some prominent purveyors of disinformation as to other aspects of the pandemic – e.g., COVID is a hoax; COVID is no worse than the flu; ivermectin prevents and cures COVID-19; vaccines were causing cancers and hundreds of thousands of deaths, etc. – were early to insist that SARS-CoV-2 was the result of a lab-leak. I don’t rule out that possibility, however, when the loudest voices in support of lab-leak have already lost their credibility and have been known to lie about other related matters, unfortunately, it resulted in undermining the lab-leak hypothesis out of the gate, or worse, caused others to dig in against that possibility merely so as not to be associated with that group of people.
5. Conflicting government intelligence assessments. It also has been difficult to sort this all out because we have learned that our intelligence agencies are divided on which scenario they think is most likely, with some agencies favoring a zoonotic spillover event, others favoring a lab leak, and still others indicating that they don’t have enough evidence to offer any assessment, though almost all have indicated that their assessments are of “low confidence.” Only the FBI’s assessment (favoring a lab leak) was of “moderate confidence.” According to the Office of the Director of National Intelligence website:   https://www.dni.gov/nctc/jcat/jcat_ctguide/intel_guide.html site, the confidence levels are described as follows:

HIGH CONFIDENCE generally indicates that the judgments are based on high-quality information or that the nature of the issue makes it possible to develop a solid judgment.

MODERATE CONFIDENCE generally means that the information could be interpreted in various ways, that the intelligence community has alternative views, or that the information is credible and plausible but not corroborated sufficiently to justify a higher level of confidence.

LOW CONFIDENCE generally means that the information is scant, questionable, or very fragmented, so it is difficult to make solid analytic inferences; it could also mean that the intelligence community has significant concerns about or problems with the sources.

We see people jump on whichever intelligence assessment is consistent with their preconceived views as evidence that their position is correct, when one can see from these confidence levels that low confidence is essentially no confidence and that even moderate confidence is far from certain.

• The bases for government intelligence assessments remain classified. For those, who like me, remain open to all possibilities, it is also difficult to come to a firm opinion on the origins because while much of the scientific evidence is published and publicly available, the intelligence assessments remain classified, so we don’t know what evidence any of those agencies might have that might impact our assessment. Before I would be willing to make a definitive opinion, I would want to know that I have seen all the relevant data and evidence.
• Lack of transparency and access for investigations on the part of China. The best and most helpful evidence for either a lab-leak or a zoonotic spillover event(s) (in other words transmission of infection from an animal to a human) is evidence that can only be gained in the region where the earliest cases were found – in this case, in Wuhan, China. While the World Health Organization (WHO) did conduct an initial investigation in Wuhan, the investigators were not given access to all areas and all the data that they requested. Obviously, these limitations limit the amount of data that disease outbreak investigators can gain that may provide us with answers. However, two points are worth making. First, even if investigators were granted unbridled access, it is possible that we might not be able to determine the animal source if it was a zoonotic spillover event. Second, many have pointed to China’s lack of transparency as evidence in support of a lab leak and China’s efforts to keep it from being discovered. And, while I am in no position to rule that possibility out, we should remember that China is not transparent about most things. In other words, if China was transparent about everything else, but secretive only about this outbreak, I think it would be much stronger evidence that the Chinese government felt it had something to hide in this regard. Further, I believe that China not only would want to conceal a lab leak if they believed that is what happened, but I think there is plenty of information to suggest that China was trying to conceal any evidence that the virus originated in China, including if the virus was spread in a wet market.

We should keep in mind that every modern-day president of the United States has also stated that he would not allow foreign government inspectors into U.S. research laboratories to conduct investigations of our laboratory operations. In addition, after the WHO conducted its first visit as part of its investigation, but before it returned for its second visit, President Trump stated that China should pay reparations of $10 trillion for its role in the pandemic. https://thehill.com/policy/international/china/557025-trump-demands-china-pay-reparations-for-role-in-coronavirus/. Of course, when a government starts making threats to another country and suggesting highly damaging penalties, it should not be surprising that any cooperation may come to an abrupt end.

My point here for this discussion is to acknowledge that China has not been transparent and has not been fully cooperative, but that in of itself is not strong evidence of a lab leak to the exclusion of all other possibilities. As an example, a finding that SARS-CoV-2 originated from the wet markets would still bring embarrassment and undesirable consequences to the Chinese President and government. Having been the source for two outbreaks with epidemic and now pandemic consequences would create tremendous pressure on China to halt its wet markets, a significant source of employment and economic activity, as well as a custom and tradition for many Chinese people, including some who consider some of the more exotic animals as a delicacy. It would not only embarrass the Chinese government, but feed into more anti-Chinese hate rhetoric and targeting, but also more calls for China to make huge reparations at a time when the Chinese economy is already facing strains. Further, there is mounting evidence that some animals were being sold at the markets illegally, which would further embarrass and bring criticism to the Chinese government for not diligently enforcing its laws.

As to the origins of SARS-CoV-2, we can consider 4 possible scenarios:

1. A zoonotic spillover event. SARS-CoV-2 evolved in nature and was transmitted by bats to animals that were subsequently transported to the wet markets for sale, that in turn transmitted the virus to humans.
2. Lab leak. SARS-CoV-2 had been obtained from samples taken in natural settings and the virus was transported to the Wuhan Institute of Virology for research purposes when through a lapse in safety procedures, the virus infected a lab worker who then transmitted the virus to others kicking off the pandemic.
3. Engineered virus. This is really a variation of number 2, which supposes that instead of the virus appearing in nature and then studied in the lab, the virus does not appear in nature, but instead was purposefully manipulated or engineered in the lab to create a virus with enhanced infectivity and/or virulence.
4. Bioweapon. SARS-CoV-2 was developed for purposes of biowarfare.

I think that the first two scenarios are the only serious considerations. Let’s explore why.

The Intelligence Community issued a statement on the origins of COVID-19 in 2020 and has reaffirmed in 2023 that its assessment in this regard has remained unchanged:

The Intelligence Community also concurs with the wide scientific consensus that the COVID-19 virus was not manmade or genetically modified.

Intelligence Community Statement on Origins of COVID-19 (dni.gov).

Thus, while the intelligence community remains divided as to the question of whether SARS-CoV-2 precipitated a pandemic through a zoonotic spillover event or a lab leak, the intelligence agencies are in complete agreement that scenarios 3 and 4 above are not considerations. To explain how we would know that the virus was not engineered or manipulated, this is where I am going to have to oversimplify because things get very complicated and involve genetics and biochemistry, which I love, but I am going to assume you do not. It is important to start with the fact that science has not progressed to the point where the Chinese or anyone else could design and create a virus from scratch. The technology and knowledge do exist to be able to modify viruses, but in these cases, we have to start with an already existing virus. Further, while we can force certain changes to the virus through laboratory techniques or through infecting animals in the laboratory, the modified virus is not unrelated to the prior versions and the changes to the virus leave identifiable signs that can be tracked from the original form of the virus to the modified version.

Further, our sequencing technologies have significantly advanced to where we can readily pick up new mutations and even recombinations (where genetic material from two different viruses are swapped in creating a new virus). Further, often we can detect genetic material from an animal host in a viral specimen that can tell us what species of animal was infected with the virus. Finally, we sometimes see biochemical changes to samples that we can tell could not have occurred in cell cultures in a laboratory, but only by interaction with a host’s immune system (meaning that the virus had to infect and interact with some host rather than just existing in a test tube, so to speak).

The possibility that SARS-CoV-2 was developed by the Chinese as a bioweapon defies logic. First, Bioweapons 101 emphasizes that you do not release a bioweapon developed against foreign adversaries in your own country in a highly populated city and in Bioweapons 102 you learn that you should vaccinate your population and leaders before you release the bioweapon, not a year or two later. Second, Chinese scientists have done leading research on coronaviruses and would know that case fatality rates for coronaviruses range from < 1% to about 35%. An important life lesson for me (thanks, Dad!) was that when I decided that I was going to fight back against a bully, I needed to deliver an effective punch that would render the bully so much pain or bleeding from his nose that the fight would be over before my opponent could strike back. It makes no sense to release a bioweapon on another country that would only kill 1 – 2% of the population of that country, especially if that would consist mostly of elderly citizens and not the part of the population of the age of military service. With a novel virus like SARS-CoV-2, Chinese scientists likely would not be able to predict its mortality rate in advance of deploying the weapon and infecting people, but could not reasonably predict that its mortality rate would be higher than 40% at the very highest. There are many other choices of far more lethal viruses. If the Chinese intended to release a bioweapon on say the United States, they would act very differently:

1. Release the bioweapon in the U.S. not in China and then rely on people to transport the virus by being infected and travelling internationally.
2. Pick a far more lethal virus because if you release a bioweapon that is easily identifiable and traceable that doesn’t deal a crippling blow to the US, you have just entered into war with the U.S. and will pay a severe price for whatever gains you think you have achieved with the bioweapon.
3. Vaccinate your population before you release the bioweapon, not one – two years later.

So, let’s assume that you buy my arguments and agree that the two most likely considerations for where the virus came from are either a natural zoonotic event where an infected animal at the wet markets infected humans, who then spread the virus to other humans or a lab leak in which a laboratory worker was inadvertently infected and subsequently spread the infection to others precipitating a pandemic.

If the World Health Organization (WHO) or other disease outbreak scientists were to go about determining which was the actual cause, and were granted the authority to examine any records and collect any evidence, they would consider the following, among other things:

Lab Leak

1. What research was being conducted in the laboratory?
2. What viruses are kept in the laboratory? Are any of those viruses SARS-CoV-2 or closely related viruses?
3. What animals are in the laboratory?
4. What biosafety measures were in place? What safety training was provided for workers? Were there any safety lapses? Were there any safety audits or inspections?
5. Did any laboratory workers develop any unexplained illnesses? If so, did any receive any medical evaluation, testing or treatment?
6. Did any family members or contacts of laboratory workers develop unexplained illnesses? If so, did they receive any medical evaluation, testing or treatment?

Zoonotic transmission

1. What animals were sold in the market? In particular, were there animals on site known to be hosts for coronaviruses, such as palm civets, pangolins, prairie dogs or raccoon dogs?
2. Had any animals brought to the market been noted to be sick or died before sale?
3. Where were the animals brought from? Were they captured from the wild or grown on farms?
4. Were any swabs collected from any of those animals or from cages, walls, tables, chairs, butchering equipment, floors, drains, sinks, or other sources within the market that would allow examination for viral genetic material?
5. Have any samples of carcasses, tissues or blood from any of the animals been retained and frozen?

In investigating a potential lab leak, of critical importance is whether the lab was working with the virus that has appeared in the general population and what kind of research was being conducted. It is important to note that some laboratory investigations would pose extremely low, if any, risk because research techniques used for some research purposes would result in inactivated virus, incapable of infecting animals or humans. Many research projects would not require propagation of the virus. If not propagated, then the viral counts are generally low (decreasing the risk of infection even in the event of an accidental exposure) and less handling of the virus is generally involved (reducing the opportunities for accidental exposure). Even if there were efforts to culture and amplify the SARS-CoV-2 virus, the most widely used process for cell culture of viruses routinely results in the loss of the specific structure found in SARS-CoV-2 from human specimens that has been at the core of the argument of many insisting that its presence is evidence that the virus was engineered (the furin cleavage site). We do know that the Wuhan Institute of Virology (WIV) did a lot of research on coronaviruses. In fact, the head of that lab often attended and presented at international virology conferences and many scientific papers were published from that lab. So, even without full transparency, we know a lot about the viruses being studied at WIV and the techniques being used. The closest known virus being studied and for which studies have been published would still be too distant to have been the precursor virus to SARS-CoV-2.

Like many research laboratories, WIV was known to carry out experiments with viruses on mice (mice are selected in part because other research animals are considerably more expensive and often cost-prohibitive). And laboratory experts indicate that the process of repeatedly administering infectious virus to mice would likely be the highest risk laboratory activity to result in accidental infection of a laboratory worker if there was any breach in the safety protocols.  However, the wild type virus (the original virus responsible for the outbreak and earliest cases) was incapable of infecting mice. It was not until much later in the pandemic that the virus evolved to favor a specific mutation (N501Y) that allowed the virus to infect mice and other rodents, as we now know can happen in rats such as those recently sampled in NYC. If researchers aimed to make the virus more transmissible through repeated mutations in animal models (a number of persons promoting the lab leak scenario suggest that the biggest support for this hypothesis is how well adapted this virus was for human transmission from the onset of the pandemic as opposed to a natural transmission that would gain increased transmissibility over time (as in fact was what we observed), then the virus would likely have evolved to acquire this mutation in the same manner that it did naturally over the course of the pandemic, yet, this mutation was not seen in sequences of the virus from the beginning of the pandemic. Even if so-called gain of function research was being conducted, when wild type virus was used on mice by other researchers during the pandemic for which genetic changes are made to enable the mouse to be infected, the virus did not become more pathogenic or transmissible, adding evidence that even if covert research was taking place, it is unlikely researchers would have continued gain of function research on this virus after these disappointing results and this would have been even more reason not to consider this virus as an effective potential bioweapon.

In laboratories such as WIV, it is customary to collect and store blood samples from lab workers so that in the event of a question about accidental infection, we can go back to those prior samples and perform tests such as antibody testing to determine the time period in which the worker was last seronegative (without antibody evidence of prior infection) and then seroconverted (now shows evidence of antibodies signaling infection unless the worker was vaccinated against that particular pathogen). We are told that such samples were collected and that there was no evidence that any workers seroconverted prior to the onset of the pandemic. However, to the best of my knowledge, WHO investigators were not provided with those specimens for independent testing.

There were conflicting reports as to whether any lab workers had become ill. Although there were some reports indicating that one or more lab workers did become ill (as many as three), this was also during the time China was experiencing its cold and flu season and I am not aware of any medical records or testing results that have been made public that created suspicion that any of the lab workers had anything other than an infection with a circulating respiratory virus, though without testing we would be unable to make that determination.

As for investigating a potential zoonotic transmission, there were many reports and pictures providing evidence that the markets typically did have many animals known to be hosts for coronaviruses. Also, it is widely known that these animals are kept in cages in close proximity to each other, often stacked one upon another without solid bottoms to the cages such that urine, feces and secretions would likely contaminate other animal cages and animals.

It has been reported that animals were frequently transported from southern parts of China to the various wet markets. There are extensive bat caves and bat populations in the southern regions of China. Bats have long been known to be hosts to numerous coronaviruses and bat caves have often been sampled to detect new or novel strains of coronaviruses and other viruses since 2003. So, here again, there is a need to clarify some of the language being used. For those who state that the origins of SARS-CoV-2 are the Huanan wet market in Wuhan, that does not seem the most likely scenario to me, and I don’t think that is exactly what they mean. Rather, Wuhan, and the wet markets there do seem likely to be the site of the spillover, but many of these animals were transported from other areas of China to Wuhan, infected already, I would suspect, and of course, the reason they are referred to as intermediary hosts is that they are in a chain of transmission that begins with bats, and those bats are more likely to be located in the southern regions of China. Further confusing this whole issue is that, as we describe in our book, the first outbreak can be the first cases of infection, however, it is not necessarily so. An outbreak that leads to a large number of cases, some of whom get very sick alerts us to a disease outbreak and a potential novel virus. However, there could have been isolated cases that preceded the first known outbreak that because they were isolated, did not arouse attention or concern and went undetected, perhaps attributed to a cold or the flu. In fact, one report studying the earliest sequences available suggests that in fact, the sequences obtained from the market may be further down (i.e., evolved later in time) the phylogenic tree (in essence the family tree for a virus) than some sequences obtained outside of Wuhan, such as Guangdong Province, the same province from which both HCoV-HKU1 and SARS-CoV-1 are thought to have originated, or at least where they were first identified.

The strongest evidence for zoonotic transmission would be if animals at the market had been tested for the virus and had turned up positive. However, officials moved in quickly when news of the disease outbreak first appeared and removed the animals. It is unknown whether the Chinese government conducted any testing of these animals. The next strongest evidence would be if we knew where the animals came from and we could identify the virus in the same kind of animals in those areas. Other evidence would be if animals and people living nearby where these animals for the wet markets were obtained tested positive for antibodies for SARS-CoV-2 before the pandemic had first manifested in that area.

Some prominent virologists, geneticists and evolutionary biologists presented findings at the WHO’s Scientific Advisory Group for the Origins of Novel Pathogens in March from the analysis of genetic sequences of the virus obtained from swabs at the wet market that were just publicly released by scientists at the Chinese CDC.

As noted above, when a virus’ genetic material is recovered after it has caused infection, genetic material from the host animal may sometimes be combined with the virus genetic material. Some of the sequences just made available show genetic material consistent with raccoon dogs, animals known to be hosts for coronaviruses, and in large enough amounts that experts think contamination is unlikely an explanation. While this discovery is of limited significance because it was not collected until 1/12/20, and does not prove that a raccoon dog was infected with SARS-CoV-2 or that an infected raccoon dog was the intermediary host and source of the spillover events, together with the fact that many swabs from carts, animal-processing equipment, sewage wells and water drains at the market revealed genetic material of the virus, is certainly evidence that raccoon dogs were there at the market and raises the possibility that raccoon dogs may have played a role in the transmission of infection. Of course, animals of all kinds were kept in very close proximity. it is certainly possible that another species infected the raccoon dogs, or the raccoon dogs infected another species that in turn spilled over to humans, if raccoon dogs were infected at all. We simply can’t say for sure.

Wildlife and bat surveillance for novel organisms, and in this case, in search of a SARS-CoV-2 host or an animal species that harbors a progenitor virus candidate is challenging due to the vast number of hosts of coronaviruses, the vast geography over which these animals can be found, and the fact that the SARS-CoV-2 accumulates mutations rapidly with forward transmission and especially with cross-species transmission, as well as the fact that high rates of recombination (the swapping of segments of genetic material between viruses) occur in nature.

Today, in murder cases, for example, we like to have a body, the murder weapon, a convincing motive, fingerprints and DNA that put the suspect at the murder scene along with eye witnesses and cell phone data that establish the time of the crime and overcome any alibis the accused may have. Of course, none of these are required for a conviction, and in fact, many cases are brought and convictions obtained based on circumstantial evidence.

This is likely where we find ourselves with respect to the origins of SARS-CoV-2. Given the time that has passed, and the lack of cooperation and access from China, we likely will never know the origin with 100% certainty. To continue my legal analogies, we don’t require juries to make decisions with 100% certainty in their review of the evidence. For civil matters, juries are to decide cases based on whether the plaintiff has proved their case by a preponderance of the evidence – in other words, is their version of the case more likely than not. In criminal matters, juries are to decide cases on the basis of whether the prosecution has proved their case beyond a reasonable doubt – in other words, the prosecution has presented the case such that the juror has no reasonable doubt as to the defendant’s guilt and none of the defendant’s witness testimony, defenses or explanations are enough to create a reasonable amount of doubt as to the defendant’s guilt relating to the offense that is being charged.

I like to say that I am “origins agnostic,” meaning that I have no vested interest in either scenario and neither finding would alter my work or approach to this pandemic. That doesn’t mean that the origins answer doesn’t make any difference. It does with regards to our nation’s international relationship with China and what steps our country and other countries might take to ensure China’s cooperation in making sure it takes steps to prevent a similar event in the future.

But, as far as I am concerned, the fact that both scenarios are considered to be realistic possibilities, means that we need countries to come together to discuss ways to mitigate both risks. Experts in virology and laboratory operations need to come together to identify the vulnerabilities in our current system that could lead to a lab leak, and determine new standards that can mitigate these risks, along with some politically acceptable manner in which compliance with safety measures can be assured. At the same time, we must come to grips with the growing number of zoonotic infections and measures to reduce opportunities for spillover events, research directed at rapid detection of novel viruses, improved infection control measures for wet markets and animal exports/imports, improved speed and effectiveness of disease outbreak investigations, research directed at new antivirals and other therapeutics, research into more effective and rapidly deployable vaccines, more focus on the elimination or at least control of outbreaks with viruses already identified as having high pandemic potential, and more research into the biology, transmission, virulence and pathogenesis of disease of novel viruses with high mortality rates and high pandemic potential.

So, what would be my verdict if I was a juror? I simply could not reach the level of “beyond a reasonable doubt,” when I know that our government’s intelligence community is coming to different conclusions as to which scenario is more likely and they are as of yet keeping their evidence classified, even though their confidence levels suggest that evidence is not high quality or reliable. Of concern, I don’t even know that these intelligence agencies have shared their evidence and data with each other. Nevertheless, I would want the opportunity to review all the evidence for myself before coming to a verdict beyond a reasonable doubt.

However, I could reach a verdict based on the preponderance of the evidence, with that evidence being all of the evidence that is in the public realm as of the time of this writing. I would find in favor of a zoonotic spillover event. Here is why:

1. Lab leaks have certainly occurred, but the overwhelming majority of these occurred prior to the adoption of the current biosafety lab standards. No lab leak has ever resulted in sustained transmission, let alone an epidemic or pandemic.
2. While China has not allowed independent verification, the only evidence we have from the WIV is evidence that the lab was not conducting research on SARS-CoV-2 or a virus sufficiently closely related that could have served as the progenitor of SARS-CoV-2 and that serologic testing of laboratory workers’ blood samples prior to the onset of the pandemic failed to demonstrate any SARS-CoV-2 infections. This is not conclusive, but for purposes of my jury analogy, the prosecution has not provided any evidence to contradict these representations.
3. I give little weight to the argument that the WIV is in Wuhan, the outbreak was in Wuhan, therefore, the WIV must have been the source of the virus. First, our CDC has laboratories in Atlanta, Georgia. If we had a disease outbreak in Atlanta, my first thought would not be that it must be a lab leak from the CDC, but rather that Atlanta is an international air hub and a traveler from outside of Atlanta may have brought the disease there (e.g. this is what happened when a man with Ebola showed up to a Dallas hospital). Wuhan is a very large city (population > 11 million) with a large international airport. It would be very easy for an infection to be brought into the city and for a novel virus outbreak to be distributed throughout the globe so long as the virus does not make people very sick at the same time that they become infectious. Further, as suspicious as the location of the WIV is for an outbreak in Wuhan, I find it even more suspicious that Wuhan is the location for wet markets (at least four that we know of), sites that we have been able to establish as the origins for other zoonotic outbreaks, including SARS-CoV-1. In fact, epidemiological case contact tracing shows more connection of cases of COVID-19 to the markets than to the lab. Two of the three earliest known cases of COVID-19 have been linked to the Huanan market (where the swabs I referenced above were collected). Of all the cases identified in December of 2019 in China, 55% of the cases had a connection to a wet market (28% to the Huanan market) in Wuhan, however, I would also point out that there are contradictory reports that suggest that most cases in the first week of the outbreak did not have contacts with the markets. Note, given that SARS-CoV-2 is highly transmissible to close contacts and family members, you would not expect every case to have a direct connection (work or visit) to the markets if that was the site of the outbreak. My conclusion on this point is that WIV is no more suspicious as the site of origin than the Huanan market is as both are located in the city of the first known outbreak, but the epidemiologic contact tracing studies, while inconclusive, are certainly stronger in favor of the market than the lab.
4. Zoonotic transmissions account for approximately 75% of outbreaks with novel viruses (e.g., pandemic influenza viruses, monkeypox virus, Ebola virus, human immunodeficiency virus, hantavirus, SARS-CoV-1, MERS-CoV, Lassa virus, Nipah virus, rabies virus, and Marburg virus).
5. SARS-Co-V (2003) resulted from a zoonotic spillover event from palm civets in wet markets in China.
6. MERS-CoV (2012), another novel coronavirus that caused a large outbreak was a zoonotic transmission to humans from camels.
7. HCoV-HKU1, a coronavirus that is endemic and is largely thought of as a common cold virus, was first described in a large Chinese city (Shenzhen, Guangdong) in the winter of 2004, the result of a zoonotic transmission for which we still have ben unable to identify the intermediary host. (This is important because one of the arguments for lab leak is the assertion that a particular structure of the SARS-CoV-2 (the so-called furin cleavage site within the spike protein) is not naturally occurring and thus favors an engineered virus. However, the HCoV-HKU1 has this same structure.)
8. The recent sequencing data that I mentioned above is certainly not proof beyond a reasonable doubt, but I would place it in the category of a preponderance of the evidence when considered in light of all of the above, including the possibility that raccoon dogs may very well have been the intermediary host (i.e., bats [natural host] -> raccoon dogs [intermediary host] -> humans) or alternatively may have spread the infection to the animal that served as the intermediary host or may have been infected by that intermediary host.
9. There were two lineages of SARS-CoV-2 circulating at the same time in China during the outbreak. Lineage B, which is the lineage that became dominant globally in 2020 and ever since was linked to the Huanan market. Lineage A, which no longer circulates, was tied to other wet markets in Wuhan. Two lineages don’t make much sense for a lab leak, but provide additional support for zoonotic spillover events, notably more than one. The animals supplied to the wet markets were often transported together from the southern part of China and then distributed to the various wet markets. It is very plausible that an infected animal could have transmitted the virus to other animals, including other species of animals, given the close contact in which animals were caged and transported. With repeated transmissions and with infections in different animal species, one would expect some mutations to occur giving rise to the two separate lineages.
10. In my mind, there is scientific evidence in support of a zoonotic transmission, even though it is not enough to prove it beyond a reasonable doubt. On the other hand, unless our intelligence agencies have evidence that remains concealed from the public, there is no evidence for a lab leak. This doesn’t rule out a lab leak, it just means that in my mind, the evidence available to date weighs far greater on the side of a zoonotic transmission.

I want to again point out that there is no publicly known “smoking gun” here. We don’t have the swab of an animal at the wet market at the beginning or just prior to the outbreak with the recovery of infectious SARS-CoV-2 that is an identical sequence to the virus infecting the earliest known cases in humans. On the other hand, neither do we have evidence that WIV or any other laboratory in China had SARS-CoV-2 specimens in the laboratory or any other coronavirus close enough to be the progenitor of SARS-CoV-2 with seroconversion (a + antibody test to SARS-CoV-2) in a laboratory worker prior to the outbreak, nor evidence that a lab worker from a lab working with SARS-CoV-2 was ill prior to the outbreak and SARS-CoV-2 was recovered from that lab worker.

As I said, I do not have enough evidence to reach a verdict beyond a reasonable doubt. If I were to find out that the FBI has sworn statements from a lab worker who is a credible witness and provided authenticated copies of laboratory records evidencing that the lab was secretly working on SARS-CoV-2 and hiding it from the public and/or had blood specimens from lab animals or a lab worker with evidence of SARS-CoV-2 infection prior to the outbreak and that the FBI had signals intelligence that indicated that this research was indeed occurring prior to November of 2019, that might completely change my verdict. Of course, I would want to understand why the FBI only attributed moderate level of confidence to that evidence.

Unless some scientist or government has definitive evidence that they are currently keeping a secret, but later makes public or that evidence is somehow leaked (pardon the pun), my guess is that we will never know the origins of this virus beyond a reasonable doubt.

My purpose in writing this blog piece is not to convince you of one hypothesis over the other, because I am not convinced. I am persuaded towards the view of this being a zoonotic transmission and I have shared my current thinking, but I don’t conduct research with viruses and I am definitely not an evolutionary biologist, and I could certainly be wrong. Rather, my point in writing this was to merely help the lay public (non-scientists) understand the issues, the complexity and nuances to this debate, and provide you with enough information that you can think for yourself and come to your own conclusion without taking a position merely because your friends, family or social network has a particular point of view. In that same vein, please feel free to read the published articles for yourself. I have included a list of articles (I have included a couple of articles from the lay press for those who don’t enjoy reading scientific studies as much as I do!) that include both articles supporting a zoonotic spillover event and some supporting the lab leak hypothesis.

Realizing that we don’t know for sure and may never know with 100% certainty, my hope is that we take both possibilities seriously and embark on planning on how to reduce the risk of either origin for a future pandemic. Unfortunately, I suspect that the chances that even our own government, let alone the countries of the world, will undertake serious efforts to mitigate these risks is even less the chances we will ultimately know with certainty the origins of SARS-CoV-2.

 References and Further Reading:

1.      The Origin and Prevention of Pandemics – PMC (nih.gov)

2.      Ten years after SARS: where was the virus from? https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3747529/.

3.      Bat cave solves mystery of deadly SARS virus — and suggests new outbreak could occur https://www.nature.com/articles/d41586-017-07766-9.

4.      Exposure to diverse sarbecoviruses indicates frequent zoonotic spillover in human communities interacting with wildlife – PMC (nih.gov)

5.      Identification of coronaviruses in farmed wild animals reveals their evolutionary origins in Guangdong, southern China | Virus Evolution | Oxford Academic (oup.com)

• Animal sales from Wuhan wet markets immediately prior to the COVID-19 pandemic | Scientific Reports (nature.com)

• SAGO statement on newly released SARS-CoV-2 metagenomics data from China CDC on GISAID (who.int)

• https://www.nytimes.com/2023/03/17/health/covid-origins-who.html?smid=nytcore-ios-share&referringSource=articleShare

• The Strongest Evidence Yet That an Animal Started the Pandemic – The Atlantic

1. Bat coronaviruses related to SARS-CoV-2 and infectious for human cells | Nature

1. Closest known relatives of virus behind COVID-19 found in Laos (nature.com)

1. A comprehensive survey of bat sarbecoviruses across China for the origin tracing of SARS-CoV and SARS-CoV-2 | Research Square

1. Surveillance of SARS-CoV-2 in the environment and animal samples of the Huanan Seafood Market | Research Square

1. Exploring the Natural Origins of SARS-CoV-2 in the Light of Recombination – PMC (nih.gov)

1. A Novel Potentially Recombinant Rodent Coronavirus with a Polybasic Cleavage Site in the Spike Protein | Journal of Virology (asm.org)

1. Did the coronavirus jump from animals to people twice? (nature.com)

1. The molecular epidemiology of multiple zoonotic origins of SARS-CoV-2 | Science

1. SARS-CoV-2 emergence very likely resulted from at least two zoonotic events | Zenodo

1. Breaches of safety regulations are probable cause of recent SARS outbreak, WHO says – PMC (nih.gov)

• Early Transmission Dynamics in Wuhan, China, of Novel Coronavirus–Infected Pneumonia | NEJM

• The Huanan Seafood Wholesale Market in Wuhan was the early epicenter of the COVID-19 pandemic | Science

• A critical analysis of the evidence for the SARS-CoV-2 origin hypotheses | mSphere (asm.org)

• The origins of SARS-CoV-2: A critical review – ScienceDirect

• Clinical features of patients infected with 2019 novel coronavirus in Wuhan, China – ScienceDirect

• Recovery of Deleted Deep Sequencing Data Sheds More Light on the Early Wuhan SARS-CoV-2 Epidemic | Molecular Biology and Evolution | Oxford Academic (oup.com)

• Ban on gain-of-function studies ends – The Lancet Infectious Diseases

• Genomic determinants of Furin cleavage in diverse European SARS-related bat coronaviruses | bioRxiv

• Unearthed genetic sequences from China market may point to animal origin of COVID-19 | Science | AAAS

• Pandemic origins and a One Health approach to preparedness and prevention: Solutions based on SARS-CoV-2 and other RNA viruses | PNAS

• A strategy to assess spillover risk of bat SARS-related coronaviruses in Southeast Asia | Nature Communications

• Virome characterization of game animals in China reveals a spectrum of emerging pathogens – PMC (nih.gov)

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[1] This was the question that prompted Dr. Ted Epperly and I to write our new book, Preparing for the Next Global Outbreak: A Guide to Planning from the Schoolhouse to the White House. The book is available for preorder Browse All | Hopkins Press (jhu.edu) and is available on April 18.