The Totality of the Circumstances surrounding SARS-CoV-2 emergence

We have probable cause to suspect a laboratory origin

The totality of evidence is more than the sum of its parts

Suppose you are a detective and you uncovered a letter proposing to commit a murder using a silver bullet in a very specific room of a very specific building. You go to that room and find a body with a silver bullet inside. Beside the body there is a gun with fingerprints on the gun matching the fingerprints on the letter. It’s not a stretch to deduce that a murder occurred, and the primary suspect may be whoever wrote the letter. The gun doesn’t need to be smoking for one to have probable cause that a crime has been committed.

We have a similar body of evidence laying before us on the origin of SARS-CoV-2.

I started off with a strongly zoonotic prior. I studied pathogen spillover from wildlife to people for years prior to COVID, pathogen spillover is common, and so for much of the pandemic I kept an open mind about a laboratory origin yet remained firmly entrenched in my prior belief of a zoonotic origin. However, as I examined the totality of evidence, especially as new evidence emerged, I began to see that the body of evidence supporting a lab origin of SARS-CoV-2 is overwhelming, far more so than most realize. The totality of evidence has completely changed my mind.

As I discussed this topic with very smart friends, I became aware that most people are not fully aware of the totality of the circumstances nor how strongly this body of evidence suggests SARS-CoV-2 arose from a lab. This article will cover the evidence that changed my mind. I am a quantitative biologist with a knack for betting, and there are deductive methods and probabilistic tricks I use to sharpen my own estimates and refine my own understanding. I thought about writing a formal paper on these probabilistic tricks (Bayes networks, sharp-penciled application of conditional probabilities instead of unconditional ones, all to get overwhelming Bayes factors in support of a laboratory origin), but I realized that anyone who could understand that mathspeak would probably already share my beliefs, provided they knew the totality of available evidence. This evidence needs to be popularized because it provides probable cause of a lab origin of a virus that killed 1 million Americans, and establishing probable cause may enable us to get the final pieces of evidence we need to fully understand what happened. This popularized version of my Bayesian reasoning is written as if I’m explaining the evidence to a judge or jury of peers.

In our society’s fast-paced news cycles and 240 character attention span, we often limit our focus to just a single piece of evidence at a time. We argue intensely about that outrageous evidence du jour, come to a strong opinion, and then move on. In so doing, we often move too quickly, treat every argument as independent, and, in our short attention spans and entrenched beliefs, we fail to see the bigger picture of how multiple pieces of evidence combine to produce a body of evidence stronger than the sum of the parts, a body of evidence that in its totality ought to change our beliefs.

The best analogy I can think of for seeing the big picture is to look at the photomosaic below. If you look closely at any one photo, you’ll see buildings, people, signs, fires, and other seemingly unrelated photos. Any one photo in a photomosaic is relatively meaningless by its own. One theory might look at the photomosaic and say all photos are independent and random and cast doubt on these photos being connected. Another theory will say we need to look at the totality of evidence to arrive at the correct conclusion about the photos and what they mean. When we zoom out to see the big picture, it’s clear that these photos were assembled in a clear & coherent way to yield the image of Vladimir Putin. The first theory encourages you to not see the likeness of Vladimir Putin in the figure below, whereas the other theory deduces these photos are connected, that the totality of evidence is greater than the sum of its parts.

Which theory do you believe?

A photomosaic illustrates why a body of evidence may be more informative than the mere sum of its parts. The totality of evidence on SARS-CoV-2 origins is similar.

The Evidence

Here are the most important photos of our SARS-CoV-2 origins photomosaic, the most important pieces of evidence that I believe need to be seen together as the connections between these pieces of evidence are pieces of evidence in and of themselves.

• The DEFUSE Grant

• SARS-CoV-2 arose in Wuhan

• SARS-CoV-2 has a Furin cleavage site in its Spike protein

• SARS-CoV-2 has the restriction map of an infectious clone

Additional evidence exists and we can argue for days about each small piece, much like someone could point to a photo of a fire in the picture of Putin above and say “Putin doesn’t have a fire on his cheek, so therefore it’s conspiratorial to see the photomosaic as Putin”. I focus on these four major pieces of evidence listed above because they are the most critical pieces of evidence whose body is greater than the sum of the parts. In talking with friends & family over the past two weeks, I realized that these four pieces of evidence, their implications & their connections with one-another, are not commonly known. The magistrate & members of the jury must become familiar with these four pieces of evidence and the story one deduces from their totality.

Some additional evidence has to be dealt with immediately before we proceed. Zoonotic origin theories of SARS-CoV-2 point to the existence of two large lineages at the base of the SARS-CoV-2 evolutionary tree and see these lineages as evidence of two spillover events. However, there are many ways to generate large lineages in an evolutionary tree, and the two large lineages at the base of the SARS-CoV-2 tree are much more likely evidence of contact tracing and two superspreading events, such as one in the wet market and one elsewhere. Another piece of evidence commonly promoted by zoonotic origin theorists is the cluster of some early cases about the Huanan wet market thereby leading them to conclude the wet market was the epicenter of the SARS-CoV-2 pandemic. However, those cases from the wet market are not the earliest cases. Earlier cases lacked a connection to the wet market, and wet-market cases were ascertained by contact + location tracing that strongly biases our case ascertainment to produce a set of cases in the areas of Wuhan where people looked for cases. If I find fish in a hole & fish some more in that hole and catch additional fish, I’m wrong to conclude that all fish originated from that hole. If I find coins underneath a streetlamp, it doesn’t mean there are not coins elsewhere.

The four most important pieces of evidence that changed my mind from a zoonotic origin to a lab origin are these four listed here: the DEFUSE grant, the Wuhan emergence, the Furin cleavage site, and the restriction map of SARS-CoV-2.

Here’s why:

The DEFUSE Grant

Before the COVID-19 pandemic, I was working with a team that was funded by a DARPA PREEMPT grant. We were studying Henipaviruses like Nipah & Hendra with the goal of preempting pathogen spillover to prevent pandemics. A major research goal in this field was to understand whether some strains of viruses were more likely to emerge than others, studying so-called “genotype-to-phenotype” relationships. Which viral genotypes have the phenotype of enhanced human infectivity?

The lowest-risk genotype-to-phenotype studies one can conduct involve finding a wild virus, sequencing its genome and testing its phenotype in the lab (receptor-binding, cell-entry, replication, infectivity, lethality, etc.). However, it takes a lot of effort to find viruses in nature and the diversity of wild-caught viruses is a drop in the ocean of evolutionary possibilities. Testing the genotypes of wild type viruses gives us a very limited picture of the space of possible viruses and which genotypes might be at a higher risk of causing a pandemic. Consequently, there is a clear temptation to make new viruses, such as chimeric viruses or viruses passaged in human cells. If we made a virus more capable of infecting people, it might reveal the essence of human-infective viruses and help us prepare vaccines before a pandemic ever happens. That is the siren song of greatness, of saving lives by preempting pandemics, that may lure virologists to open Pandora’s box. Engineer and evolve a novel pandemic-capable virus to create a vaccine against the virus before it causes a pandemic, and you might win a Nobel Prize… provided nothing goes wrong.

In late March of 2018, EcoHealth Alliance, the Wuhan Institute of Virology (WIV), and other collaborators submitted the DEFUSE proposal to DARPA’s PREEMPT program. In their DEFUSE proposal, this international collaboration proposed to sample bat coronaviruses, assemble viruses in the lab with infectious clone technology, develop recombinant chimeric spike proteins including some with a Furin cleavage site, and test the infectivity of these chimeric viruses in bats at the Wuhan Institute of Virology. Find, engineer, and evolve human-infectious viruses capable of causing a pandemic, develop a vaccine against them, and preempt a pandemic… provided nothing goes wrong.

To study genotype-to-phenotype relationships in coronaviruses, EcoHealth proposed to make new, chimeric coronaviruses at the WIV. They proposed to swap around Spike proteins using infectious clones from related viruses and insert Furin cleavage sites.

“… we will introduce appropriate human specific cleavage sites and evaluate growth potential in Vero and HAE (Human Airway Epithelial) cell cultures.”

The proposed research would take place in the Wuhan Institute of Virology.

The DEFUSE proposal was not accepted as DARPA saw major risks that the proposed recombinant viruses might gain functions like enhanced infectivity or lethality in humans. However, the grant reveals the clear desire of this group to conduct such research and the intention to make a very unusual set of SARS coronaviruses not found in nature. While their intentions were not funded by DARPA, the proposed research is relatively inexpensive and EcoHealth and the Wuhan Institute of Virology had funding from other sources that could finance their proposed work. Their alternative sources of funding include an NIAID biodefense grant proposing extremely similar S-gene chimeras made with infectious clones. In fact, the NIAID grant was cited as a funding source in the construction of a novel infectious clone at the Wuhan Institute of Virology, rWIV1. The DEFUSE grant proposed to make infectious clones with chimeric Spike genes, SARS coronaviruses with furin cleavage sites, all at the Wuhan Institute of Virology.

The motives and intentions to create such a virus did not die with the rejection of DEFUSE. While not funded by DARPA, similar research proposals were funded by NIAID and others prior to and during the emergence of SARS-CoV-2, and may easily have provided enough discretionary funding to support the inexpensive research proposed in DEFUSE. The DEFUSE grant is the letter proposing the crime: catch wild bat coronaviruses, send them to Wuhan, assemble infectious clones in vitro with a specific method, swap Spike genes and add Furin cleavage sites, all to find an extremely human-infectious coronavirus against which we could produce vaccines.

Wuhan

SARS-CoV-2 emerged in Wuhan in late 2019.

Wuhan is not where researchers studying pathogen spillover would expect coronaviruses to emerge. A recent study by EcoHealth Alliance and members of the Wuhan Institute of Virology estimated the risk of SARS coronavirus spillover using data on wildlife coronavirus reservoirs, where those reservoirs live, where humans live, and where people have evidence of SARS coronavirus exposure in their blood. They get the following map of (a) the species richness of bats and (b) the relative intensity of bat-human overlap across SE Asia.

(a) SARS coronavirus bat reservoir richness and (b) bat-human overlap. Source

Below is the map of bat-human overlap, with Wuhan indicated.

The estimated range of bat SARS coronaviruses spans SE Asia from India to Indonesia, with hotspots of bat-human overlap estimated in Laos, Vietnam, and Yunnan province, China. The distance from Wuhan to the hotspot of bat-human overlap in Yunnan is about 1,000 miles, or about the distance from NYC to Miami. While an alligator attack could occur in NYC, I expect an alligator attack is most likely to occur in Florida.

The ecology of animals and distribution of humans means that interactions between humans and animals have very regular geographic patterns, and these lead to very clear expectations of where such interactions are likely to occur. Similarly, they help us identify highly unusual events. If a person was attacked by a hippopotamus in Africa, I might expect the hippopotamus to be wild, whereas if a person was attacked by a hippo in New York City, I might expect the hippo to be in a zoo. The same logic applies to interactions between humans and bats that cause sarbecovirus spillovers.

While the true number of SARS coronavirus spillover events is up for debate, the map above does a good job showing an agreeable estimate of where coronaviruses are likely to spillover from bats to people. Wuhan is a tiny speck on a large map of possibilities for the natural spillover route. If I were to draw a random SARS coronavirus spillover event, there is a near-zero probability it would occur in Wuhan.

Because Wuhan is such an improbable place for bat-human overlap, the zoonotic origin hypothesis relies entirely on the Huanan wet market and the broader animal trade as the source of animals from which zoonosis occurred. Indeed, the animal trade is believed to be responsible for the 2002 SARS outbreak. A cluster of COVID-19 cases from late December 2019 was centered around the Huanan wet market, but there were credible reports of earlier cases tracing back to mid-November 2019 with no connection to the wet market and, unlike every natural SARS or MERS spillover event, the reservoir has not been found. Additionally, the most recent common ancestor of circulating SARS-CoV-2 strains in Wuhan dated back to October-November 2019, suggesting the cluster of cases around the wet market in late December 2019 was unlikely to represent the earliest cases and more likely caused by a human-to-human superspreading event.

To be clear, animal trade can cause outbreaks. However, animal trade outbreaks look a lot different from SARS-CoV-2 emergence. SARS-CoV-1 is more widely believed (by myself, too) to have originated from a civet. The animal-trade outbreak of SARS-CoV-1 left a trail of cases across Guangdong province shown in the figure below from this paper. While the animal trade and Huanan wet market are proposed as the proximal origins of SARS-CoV-2 under the zoonotic theory, the earliest cases may not have been associated with the wet market and SARS-CoV-2 lacks a broader geographic fingerprint characteristic of our prior experience with SARS-CoV outbreaks caused by animal trade networks.

SARS-CoV-1 arose from the animal trade and left a trail of cases across Guangdong Province. There is no such trail of animal trade cases for SARS-CoV-2.

To summarize, Wuhan is not a hotspot of bat-human overlap nor are there signs of a broader outbreak in animal trade networks. Altogether, this geographic evidence makes Wuhan a highly unlikely site for a SARS coronavirus zoonosis.

Wuhan is, however, a global hotspot of coronavirus research and the leading coronavirus researcher at the WIV, Shi Zheng-Li, was a PI on the DEFUSE proposal. After the SARS-CoV-1 outbreak in 2002, there were 6 other documented SARS outbreaks - two of them in Beijing, and all of them caused by laboratory accidents. Laboratory accidents are far more common than many members of the public realize. Even absent the DEFUSE proposal, the emergence of SARS-CoV-2 in Wuhan with a geographic pattern inconsistent with animal trade emergence ought to tilt the scales towards a laboratory origin. With the DEFUSE proposal and a lab origin theory, we might further hypothesize the virus emerging in Wuhan to have unusual genomic features characteristic of a laboratory origin.

The coronavirus research at the Wuhan Institute of Virology included making recombinant coronaviruses like rWIV1, swapping spike genes to assess the human-infectivity of novel bat coronaviruses brought in from Laos, Vietnam, and Yunnan province. Leading coronavirus researchers in the Wuhan Institute of Virology proposed to insert a Furin cleavage site into a SARS coronavirus. Under a lab origin theory, we might expect, then, that the SARS-CoV-2 appears like a chimeric coronavirus with an unusual spike gene, and possibly even a furin cleavage site as proposed in DEFUSE.

The Furin Cleavage Site

SARS-CoV-2 has a Furin cleavage site (FCS), and it is the only SARS coronavirus with one. Furin cleavage sites are not common. Prior to SARS-CoV-2, we had discovered as many Furin cleavage sites in SARS coronaviruses as we had discovered winged primates or flying penguins: zero. Other mammals have wings (bats) and other birds fly, but the lineages of interest don’t. Similarly, despite extensive wildlife sampling, SARS coronaviruses were not known to have Furin cleavage sites. The exact FCS of SARS-CoV-2 is not found in any other coronavirus and in fact it contains specific RNA sequences - CGG CGG - that are almost nonexistent in bats but are optimized for humans. Not only are FCS’s nonexistent in other SARS coronaviruses, but this specific FCS is particularly anomalous in its optimization for humans. From an evolutionary standpoint, the FCS is a massive anomaly in nature, yet it is exactly what was proposed in the DEFUSE grant.

Recall the language of the DEFUSE grant:

“… we will introduce appropriate human specific cleavage sites and evaluate growth potential in Vero and HAE (Human Airway Epithelial) cell cultures.”

The evolutionary anomaly of the FCS must be impressed upon the lay reader, so I’ll repeat it here. The FCS of SARS-CoV-2 is the first FCS of any SARS coronavirus. It is an uncommonly human-specific cleavage site for what’s otherwise a lineage of bat coronaviruses. The SARS-CoV-2 FCS has not one but two CGG codons appropriate for humans and it mimics a particular protein (ENaC) found in humans.

We’ve sampled many SARS coronaviruses over the past few decades. Not a single SARS coronavirus had an FCS. The entire evolutionary tree of SARS coronaviruses spans hundreds to thousands of years of viral evolution, the equivalent of millions of years of evolutionary time in humans, and in all that natural evolution there was not a single FCS to be found prior to SARS-CoV-2. The branch separating SARS-CoV-2 from its closest relative covers a brief ~19 years of evolution, or about 0.6% of the SARS coronavirus evolutionary tree. Hundreds to thousands of years of evolution failed to produce an FCS until suddenly, less than 2 years after the DEFUSE grant was proposed, a human-specific Furin cleavage site with human-optimized codons appeared in a SARS coronavirus in Wuhan, exactly as proposed in DEFUSE.

In the context of the DEFUSE grant and a Wuhan emergence lacking the geographic fingerprint of an animal trade outbreak, the human-specific FCS of SARS-CoV-2 is not an independent piece of evidence with an unquantifiable probability of occurring in nature. To call the first ever FCS in a sarbecovirus an independent piece of evidence would be like calling a silver bullet independent of both the gun and the letter proposing to use a silver bullet in that exact gun. Under a zoonotic origin theory, the FCS is an astonishingly low-probability event that is independent of the Wuhan origin and independent of the DEFUSE grant. Under the most compelling lab origin theory, these pieces of evidence are all dependent by being so clearly linked to a well-defined research program.

Are there any other pieces of evidence that can corroborate the lab origin theory?

Until recently, all we had was the DEFUSE grant, the Wuhan origin, the highly suspect FCS, and unusual behavior from the researchers in question & those who funded them. It seemed like the SARS-CoV-2 origins question was at a stalemate.

Then, we looked closely at the methods of viral assembly proposed the DEFUSE grant.

The BsaI/BsmBI Restriction Map

The DEFUSE grant proposed to make chimeric coronaviruses with furin cleavage sites in their Spike protein. The easiest way to insert a Furin cleavage site and make chimeric coronaviruses would involve assembling a DNA clone. There is one extremely common way to assemble a DNA clone for a coronavirus, a method that was specifically cited in DEFUSE and other grants from this group of collaborators proposing to make chimeric coronaviruses in Wuhan.

The specific method of assembly was published by none other than one of the collaborators on the DEFUSE grant in his seminal paper: “Efficient Reverse Genetic Systems for Rapid Genetic Manipulation of Emergent and Preemergent Infectious Coronaviruses”. The method involves looking at the viral genome, modifying it slightly with silent mutations to add/remove special cutting/pasting sites (“type II restriction sites”), and then using the corresponding cutting/pasting enzymes (‘restriction enzymes’) to assemble the full-length DNA clone.

Valentin Bruttel, Tony VanDongen and I examined all infectious clones of coronaviruses made from 2000-2019 by type II directional assembly. We found that 8 out of 10 infectious clones, including the single CoV infectious clone made in the Wuhan Institute of Virology, used the specific type II directional assembly method cited in the DEFUSE grant. We uncovered a fingerprint of this particular method of in vitro viral assembly: due to bioengineering constraints, the cutting/pasting sites researchers choose end up being unusually regularly spaced compared to the random spacing of cutting/pasting sites in non-engineered viruses.

SARS-CoV-2 has that exact fingerprint. In our preprint, we examined a wide range of other coronaviruses and SARS-CoV-2 has the most extreme infectious-clone-like type II restriction map of all the natural coronaviruses we analyzed. The FCS of SARS-CoV-2 is anomalous among sarbecoviruses, and the type II restriction map of SARS-CoV-2 is the most extreme type II restriction map of any coronavirus we analyzed.

(A) The BsaI/BsmBI restriction maps of CoVs, with the unusual even-spacing of SARS-CoV-2 BsaI/BsmBi sites in vertical dashed lines. (B) In the number of fragments & length of the longest fragment, SARS-CoV-2 is right within the idealized range of the proposed efficient reverse genetic system. (C) The BsaI/BsmBI map of SARS-CoV-2 is an anomaly among natural coronaviruses and a midpoint of engineered coronaviruses.

If ever there was a coronavirus engineered in the lab but not declared as such, it would be SARS-CoV-2. We estimated well under 0.07% chance of observing such an idealized reverse genetic system in a wild coronavirus, and we further showed that the specific mutations generating this unusual restriction map appear to be exactly the kinds of mutations bioengineers would use. All mutations modifying this restriction map are the “silent” mutations bioengineers use, and there is a significantly higher concentration of silent mutations within these restriction sites than in the rest of the viral genome. Every way we looked at it, SARS-CoV-2 looked like an infectious clone from a reverse genetic system assembled exactly as proposed in the DEFUSE grant.

Under the zoonotic origin theory, the restriction map of SARS-CoV-2 and the exact mutations bioengineers use to make it is another independent coincidence added to our now very long list of extremely unlikely coincidences. By our estimate, this coincidence has well under 0.07% chance of occurring in nature. Zoonotic origin proponents hypothesize that the restriction map of SARS-CoV-2 may have been caused by recombination and indeed we cannot reject their hypothesis with existing data. However, as with the FCS, their theory requires an increasingly unlikely combination of evolutionary events in such a short time. With the restriction map, they are now saying 3-5 additional recombination events must have occurred in the tiny branch of evolutionary time since SARS-CoV-2 deviated from the common ancestor of its closest relative. These recombination events produced the first-ever FCS in a sarbecovirus, they produced the most engineered-looking restriction map of any coronavirus, and this highly unlikely set of evolutionary events occurred in a coronavirus that emerged in Wuhan far from the hotspot of coronavirus diversity and with no geographic trail of animal-trade infections.

Under the lab origin theory, the restriction map was exactly what we would expect from a coronavirus made under the DEFUSE grant. The underlying method for making an infectious clone was practiced by very few labs in the world, and 2 of the maybe 4-5 labs in the world utilizing this method were on the DEFUSE grant. This method was used by the WIV to make a recombinant bat coronavirus in 2016 and it is the method proposed for making chimeric viruses in both the DEFUSE grant as well as the funded NIAID grant. The restriction map we found would make it very easy to insert an FCS.

The Totality of the Circumstances

The DEFUSE grant proposed to make chimeric bat coronaviruses with recombinant spike proteins and a Furin cleavage site, all using a peculiar method for assembling infectious clones.

SARS-CoV-2 arose under two years later in Wuhan appearing like a chimeric bat coronavirus with a recombinant spike protein and a Furin cleavage site, and the most striking evidence of that exact, peculiar method for making infectious clones found in any coronavirus. Under the zoonotic origin theory, all of these anomalies are coincidences.

In general, scientific paradigms shift because of an increasingly large stack of anomalies. The anomalies explained as coincidences or accounted for by increasingly contrived explanations under the old theory all make perfect parsimonious sense under the new theory.

One could find a body on the ground with a silver bullet and a gun and a letter to use the gun and silver bullet in precisely that room, and one could say “huh, what a bunch of independent coincidences”. The letter wasn’t funded so therefore the intentions did not continue. The gun isn’t smoking. Silver bullets might be uncommonly rare, but anything is possible with evolution. The fingerprint might be the most significant fingerprint in the history of fingerprints, but blots of ink and oil can also give rise to this pattern by chance.

We would be poor investigators to neglect the likely connections between the evidence on the scene. It’s very reasonable - and, in fact, it’s excellent investigative work - to deduce a clear and parsimonious theory that explains the entire set of evidence without relying on a stack of improbable coincidences. Laboratory accidents are tragically common, as are murders, and so the wise detective would seriously consider this theory from the very beginning.

While the zoonotic origin theory relies on explaining the most critical evidence as a series of anomalies, the alternative theory is that SARS-CoV-2 was engineered in a lab. The most likely lab-origin theory is that SARS-CoV-2 was created exactly as stated in the DEFUSE grant and escaped from a lab in Wuhan, most likely the Wuhan Institute of Virology and was most likely an accident. I deduce it is most likely an accident because someone eager to commit an act of bioterrorism who had the sophistication to genetically engineer CoVs would also endeavor to cover their tracks by using alternative methods of assembly that do not leave obvious fingerprints in the restriction maps of infectious clones. Furthermore, the restriction map we observe on SARS-CoV-2 seems like it may be very useful to assemble chimeric bat coronaviruses in the lineage around SARS-CoV-2, and that was a common and relatively innocent research objective pre-COVID.

This particular lab origin theory relies on the research intentions stated in the DEFUSE grant. From that starting point, one doesn’t need to explain away the most remarkable features of SARS-CoV-2 with anomalies but rather one can predict them with reason. One can easily explain why SARS-CoV-2 arose in Wuhan with no broader animal-trade outbreak. One can explain why SARS-CoV-2 has a human-specific FCS, complete with human-optimized codons, and a restriction map that is anomalous in nature yet consistent with infectious clones produced by collaborators on the DEFUSE grant, cited specifically in both the DEFUSE and NIH grants. It was this simple deductive process with the totality of evidence that led me to change my mind from overwhelming belief in a zoonotic origin of SARS-CoV-2 to overwhelming belief in a research-related origin.

With this theory in mind, a lot of additional circumstantial evidence begins to make sense. First, a US intelligence report claims that several members of the Wuhan Institute of Virology were sick in November 2019 - while we don’t know the basis or reliability of that intelligence, November 2019 is exactly the time when SARS-CoV-2 is estimated to have emerged. Second, the WIV and EcoHealth have refused to share not only their coronavirus databases that would exonerate them if a natural origin were true, but the president of EcoHealth and one of their major funders organized a letter to The Lancet calling lab origin hypotheses “conspiracy theories”. NIH and NIAID, which used US biodefense funds to support DEFUSE-like research of EcoHealth, have similarly shown a remarkable lack of transparency, redacting communications in which managers deliberated the early origins of SARS-CoV-2 and, apparently, Fauci + Collins lead an effort to claim a laboratory origin is implausible in the Proximal Origin paper.

Under the zoonotic origin theory, this unusually poor transparency, failure to disclose COIs, and additional circumstantial evidence gets added to the towering stack of coincidences. Under the lab origin theory, the behavior of researchers and the funders who funded them can all be viewed as either consciousness of guilt or even just the fear of possible guilt without explicit knowledge. Someone could fire a silver bullet in the air and hear on the news that a silver bullet fell from the sky and killed someone - that alone could trigger efforts to avoid investigations and cover tracks. They wouldn’t need to know for a fact that it was their bullet to fear potential liability.

The totality of the circumstances around the emergence of SARS-CoV-2 ought to give authorities probable cause to obtain additional information. While a laboratory accident is not malicious, accidents that result in the loss of human life may still be considered manslaughter. Manslaughter is a crime. There is probable cause to suspect a crime may have occurred in a laboratory accident leading to the emergence of SARS-CoV-2, an accident that proceeded to kill 1 million Americans and over 18 million people worldwide in the COVID-19 pandemic. Additional injury exists in the persistent symptoms of “Long COVID” and the political, economic, educational, and other harms resulting from the pandemic.

The “totality of the circumstances” criteria for establishing probable cause is a more recent legal development that critics say relaxes the requirements for probable cause. However, the evidence suggesting a lab origin of SARS-CoV-2 even meets the criteria for older, more stringent bright-line rules like the Aguilar-Spinelli test for probable cause that still exist in some states like New York. The information presented here is reliable. The DEFUSE grant is on record. The Wuhan emergence is clear. There is no dispute about the original SARS-CoV-2 genome containing the FCS, only that perhaps that occurred by chance. There is no dispute that the restriction map of SARS-CoV-2 is characteristic of an infectious clone, only that perhaps that, too, occurred by chance. The reasons to support the conclusion of a laboratory origin from this information are laid out here by a credible source - I am a quantitative ecology & epidemiology researcher with a PhD from Princeton who studied pathogen spillover from bats to people for years prior to the COVID-19 pandemic. The underlying circumstances are also evident and easy to corroborate - EcoHealth alliance proposed to insert an FCS into an infectious clone, they were collecting coronaviruses and sending them to the Wuhan Institute of Virology, they collaborated on the production of chimeric bat coronaviruses pre-COVID and continued collaborations post-COVID. The researchers in question - and perhaps even some of the agency heads who funded them - have obstructed scientific investigation into their research by claiming a zoonotic origin was indisputable, calling lab origin hypotheses “conspiracy theories”, and refusing to release their databases to the world. Even the DEFUSE grant was not released by EcoHealth, but rather released following its acquisition by a team of independent investigators. Even under the strictest legal requirements in a few US states, the evidence of a laboratory origin of SARS-CoV-2 meets the standards of probable cause.

Scientific deductions & the totality of evidence

When we isolate every piece of evidence by itself, there is nothing to deduce because by definition deduction involves connecting facts to a larger theory. The letter and the room and the gun and the fingerprint and the bullet are all independent coincidences in the mind of someone lacking deductive capabilities or fearful of the obvious results of deduction. However, a skilled investigator deduces a murderer not by observing the murder itself & seeing a smoking gun in the hands of a murderer, but often by a fingerprint, a bullet, a cold gun, and a letter related to the scene of a crime. The DEFUSE grant is the letter, the closed doors and sealed lips of the Wuhan Institute of Virology are a cold gun gone quiet, the FCS is the silver bullet proposed in the letter, and the restriction map we found recently the fingerprint of a very small set of bioengineers in the world.

Yes, all of these may just be bizarre coincidences. Further investigation may find no additional evidence to prove a laboratory origin beyond reasonable doubt. Further investigation may even find data that rejects the lab origin theory outlined here. However, we don’t solve mysteries by treating every piece of evidence as an independent coincidence, nor do we advance science by serially atomizing every anomalous fact that conflicts with our cherished theory of virological innocence.

As a scientist, I can’t tell you how badly I want scientists to have not opened Pandora’s Box. It took enormous amounts of self-examination and self-criticism to question my own cherished belief in the theory of a zoonotic origin. While people say that all evidence on lab origin is weak and every statement is merely a reflection of our prior beliefs, I strongly dissent. The totality of evidence and the process of deduction described here convinced me to change my mind. As a statistician on the paper fleshing out one of these pieces of evidence, I even designed our analysis of the BsaI/BsmBI restriction map in hopes that it would reject the synthetic origin hypothesis and soothe my scientist-loving soul, only to find the hypothesis weathered a series of strong tests & graduated from a hypothesis to the level of scientific theory.

Now, the world is the jury. I leave these deductions with you all in hopes they may provide investigators with probable cause to obtain information that helps us understand the cause of over 18 million deaths and the historic political and economic turmoil that resulted from the pandemic. I encourage the acquisition of more information regardless of whether that information corroborates or disproves the theory presented here. I hope these deductions may inspire a greater level of scientific rigor in our information system and encourage additional detectives to look closer at the evidence and existing theories, construct their own hypotheses, procure new data, test their most cherished theories, and share their results with the world.

The totality of the circumstances around the emergence of SARS-CoV-2 gives probable cause for a laboratory origin.

I rest my case.