Digging Through The Science—And The Noise—On What Is Known About The Origin Of SARS CoV-2
Update: In a new post we find that Shi Zhingli of Wuhan Institute of Virology has provided convincing evidence to Scientific American that SARS CoV-2 is the result of a natural jump to humans from an animal host and was not accidentally released from her lab, which had no isolates of any viruses that match closely enough to be the outbreak virus.
Although it seems that all of this has been going on forever at this point, it’s important to realize that the COVID-19 pandemic outbreak probably began less than six months ago. In the context of how we develop an understanding of a disease like this one, and the virus that causes it, SARS CoV-2, that means that we really have only just begun our analysis. Nevertheless, because of the ongoing disastrous impact on global public health as well as the global economy, it is imperative that we learn as much as we can as fast as we can.
In this post, I want to take a deep dive into what virologists and epidemiologists have pieced together on the emergence of SARS CoV-2. The problem is that what might initially appear to be straightforward scientific and public health questions eventually get muddled by accusations of disinformation, accusations of hiding data and offerings of potential leaks of intelligence that also have a chance to be disinformation. These noisy battles relate to basic facts that have a direct bearing on our understanding of the virus’ origin.
As a result, it needs to be stated from the outset that because some of the needed basic information may be hidden or some of what we think we know might be wrong. Therefore, this analysis will be unable to come to a definite conclusion. With any luck, the discussion will help us to have a framework within which we can proceed as more facts become verified.
Overview Derived From SARS CoV-2 Genetic Sequence
I want to start with the science. The very helpful graphic below is lifted from this paper in Current Biology. It is in three sections. The section on the left illustrates what we know from the genetic sequence of the virus when that is compared to other known viruses. What it shows is that the closest overall relative to SARS CoV-2, with a sequence identity of 96%, is RaTG13, another coronovirus isolated from a bat:
Let’s move to this Nature Medicine article from March 17 and this Cell article from April 16 for the narrative on diving into the distinguishing features of SARS CoV-2 from its genetic sequence.
From the Nature Medicine article, we get a description of the features of SARS CoV-2 that distinguish it from other known viruses (these features are what the center and right panels of the graphic address):
Our comparison of alpha- and betacoronaviruses identifies two notable genomic features of SARS-CoV-2: (i) on the basis of structural studies and biochemical experiments, SARS-CoV-2 appears to be optimized for binding to the human receptor ACE2; and (ii) the spike protein of SARS-CoV-2 has a functional polybasic (furin) cleavage site at the S1–S2 boundary through the insertion of 12 nucleotides, which additionally led to the predicted acquisition of three O-linked glycans around the site.
To translate some of the terms and clarify a bit, there are four genera of coronaviruses, with alpha and beta infecting mammals and delta and gamma infecting birds. The genome is the genetic sequence of the virus. I would usually say the DNA sequence, but coronaviruses are RNA viruses. There has been much discussion of ACE2 on this blog in the comments, so for now let’s just say ACE stands for angiotensin converting enzyme and ACE2 is present on the surface of many cell types found in many different tissues within the body. So what stands out here is that the structure of the virus spike protein, as determined from its genetic sequence and tests in the lab, allows it to bind exceptionally well to ACE2 when compared to other coronaviruses.
The middle panel of the graphic shows us that although the overall sequence of SARS CoV-2 is very closely aligned to the bat virus, when we narrow it down to only compare the region where the spike protein binds to ACE2, it is a perfect match of that part of a pangolin virus, while it is very different from the bat virus. For the important stretch of the spike protein (these amino acids are not next to each other when the gene sequence is read from start to finish, but once the protein is assembled from amino acids, the amino acids are close to each other from the way the protein assumes its three dimensional structure), the gene encodes a string of five amino acids in the protein that matches exactly with the pangolin virus sequence but in only the first of the five positions on the bat virus sequence.
But that final panel and the second half of the Nature Medicine snippet goes further in what is different about this virus. The gene for the spike protein encodes two subunits, S1 and S2. Remarkably, SARS CoV-2 has acquired a site where the two subunits can be separated using a enzyme called furin that is found in mammalian cells. The right panel shows us that neither the bat sequence nor the pangolin sequence has a furin cleavage site.
The Cell paper tells us that a furin cleavage site has not been seen in the betacoronaviruses closely related to SARS CoV-2. It has been seen in other human coronaviruses, though. Of further significance is that a furin cleavage site also appears in the more pathogenic bird flu viruses.
Not A Lab Construct
From the Nature Medicine article, we get one of the most convincing arguments I’ve seen against the virus being created in a lab:
While the analyses above suggest that SARS-CoV-2 may bind human ACE2 with high affinity, computational analyses predict that the interaction is not ideal and that the RBD sequence is different from those shown in SARS-CoV to be optimal for receptor binding. Thus, the high-affinity binding of the SARS-CoV-2 spike protein to human ACE2 is most likely the result of natural selection on a human or human-like ACE2 that permits another optimal binding solution to arise. This is strong evidence that SARS-CoV-2 is not the product of purposeful manipulation.
So, in other words, if someone in the lab wanted to set out to make a virus with the best possible ACE2 binding site, this is not the sequence the computer or the literature would have given them. That suggests that this very good binding sequence is a product of natural evolution instead. The Nature Medicine article also further noted that the genetic sequence of SARS CoV-2 differs too much from that of any other known coronavirus sequence for one of the known viruses to have been used as a starting point in engineering this stronger pathogen.
The Species Jump
Perhaps the most important step in the emergence of SARS CoV-2 is the jump from its initial host species to humans. This could have happened directly, or as in the case of MERS CoV, which went from bats to camels to humans, with an intermediate host. Note that MERS still has not adapted to efficient human to human transmission, and so when we see it, it’s usually from multiple camel to human events.
The problem here is that we don’t have proof of the host from which humans were first infected with SARS CoV-2. In other words, no virus isolated from an animal so far is related closely enough at the sequence level to SARS CoV-2 that we can say this is where humans were first infected, as we can tell from the MERS jumps from camels to humans. As we will discuss below, and as you are well aware, early suspicion on the origin of human infection centered on the wet market in Wuhan. Remarkably, authors of the Cell paper visited the market and took these pictures in October 2014 because they were concerned that wet markets in general, and this one in particular, represent a particularly large risk for bringing humans into contact with less commonly encountered hosts of potentially deadly viruses:
The caption properly notes that many early cases are linked to the market, but we don’t yet have proof of where and how the first human infection(s) took place. In discussing the jump and subsequent outbreak, the Cell authors continue:
The emergence and rapid spread of COVID-19 signifies a perfect epidemiological storm. A respiratory pathogen of relatively high virulence from a virus family that has an unusual knack of jumping species boundaries, that emerged in a major population center and travel hub shortly before the biggest travel period of the year: the Chinese Spring Festival.
/snip/
While our past experience with coronaviruses suggests that evolution in animal hosts, both reservoirs and intermediates, is needed to explain the emergence of SARS-CoV-2 in humans, it cannot be excluded that the virus acquired some of its key mutations during a period of “cryptic” spread in humans prior to its first detection in December 2019. Specifically, it is possible that the virus emerged earlier in human populations than envisaged (perhaps not even in Wuhan) but was not detected because asymptomatic infections, those with mild respiratory symptoms, and even sporadic cases of pneumonia were not visible to the standard systems used for surveillance and pathogen identification. During this period of cryptic transmission, the virus could have gradually acquired the key mutations, perhaps including the RBD and furin cleavage site insertions, that enabled it to adapt fully to humans. It wasn’t until a cluster of pneumonia cases occurred that we were able to detect COVID-19 via the routine surveillance system. Obviously, retrospective serological or metagenomic studies of respiratory infection will go a long way to determining whether this scenario is correct, although such early cases may never be detected.
So, the sequence information comes to a dead end here until the details of the epidemiology are reconstructed. As the authors note, it likely will prove impossible to sample many of the most important animals and humans that would clarify the route and timing. It is further worth noting that the bat from which the RaTG13 sequence is derived was found in Yunnan province, a very long way from Wuhan.
Epidemiology
It appears that as of this writing, the earliest known infection may have been a shrimp seller in the wet market who first developed symptoms on November 17. Also, this Lancet article provides further details on some of the early studies showing a high concentration of cases affiliated with the market in December. The Lancet graphic suggests a case on December 1 not affiliated with the market and the start of the market cluster on the tenth, with 27 of the 41 early patients considered here being associated with the wet market. If that were indeed the earliest case, we might think we’ve seen the index case. But if the South China Post article is to be believed, the shrimp seller fell ill on November 17 and, according to the article, one to five people a day from that day forward had the disease. If we believe that information, then the virus appears to have already been circulating before the middle of November.
It is when we start getting into this information that accusations of hiding information are thrown about. Were there earlier cases that China suppressed or that simply went undetected? We have no way of knowing at this point.
A further point that comes from the Cell paper is that SARS CoV-2 has been circulating long enough that minor variations in the gene sequence are arising that don’t affect pathogenicity but allow for tracing of various lineages of the virus in its spread around the globe. They also note that the lineages allow them to go back in time over the evolution of those sequences and the diversity diminishes a lot as they get back to the early isolates from Wuhan. This is further confirmation for Wuhan being essential in the earliest part of the outbreak.
Accidental Release
It is here that the noise gets really loud. If we accept the really strong evidence that SARS CoV-2 was not deliberately made in a laboratory, there remains the possibility that the virus could have escaped from a laboratory that studies potential pandemic agents.
As long ago as 2004, Rutgers scientist Richard Ebright spoke out against the massive amount of funding that was funneled into research on bioweapons after the 2001 anthrax attacks. From the New York Times:
Dr. Ebright disagrees with much of the security community about how best to protect the nation from attacks with biological weapons.
The government and many security experts say one crucial step is to build more high-security laboratories, where scientists can explore the threats posed not only by deadly natural germs, but also by designer pathogens — genetically modified superbugs that could outdo natural viruses and bacteria in their killing power. To this end, the Bush administration has earmarked hundreds of millions of dollars to erect such laboratories in Boston; Galveston, Tex.; and Frederick, Md., among other places, increasing eightfold the overall space devoted to the high-technology buildings.
Dr. Ebright, on the other hand, views the plans as a recipe for catastrophe. The laboratories, called biosafety level 4, or BSL-4, are costly, unnecessary and dangerous, he says.
”I’m concerned about them from the standpoint of science, safety, security, public health and economics,” he added in an interview. ”They lose on all counts.”
Ebright continues:
The labs, Dr. Ebright says, are a perilous overreaction to an inflated threat and will do more harm than good.
Although the threat of biological warfare is real, the weapons used by terrorists are unlikely to be the next-generation agents that the high-security labs are intended to study, he says. Yet by increasing the availability of such pathogens, Dr. Ebright argues, the labs will ”bring that threat to fruition.”
”It’s arming our opponents,” he said.
In addition, he says, the laboratories could leak. They could put deadly pathogens into irresponsible hands and they will divert money from other worthy endeavors like public health and the frontiers of biology. Moreover, their many hundreds of new employees would become a pool of deadly expertise that could turn malevolent, unleashing lethal germs on an unsuspecting public.
Note the “leak” bit. The article goes on:
But Dr. Ebright noted that the deadly SARS virus recently escaped from BSL-4 and BSL-3 labs in Taiwan, Singapore and Beijing, in each case setting off minor epidemics that killed or sickened people.
This 2014 paper from the Center for Arms Control goes into detail on two separate escapes of SARS from the same laboratory in Beijing, along with four other documented cases of releases of possibly pandemic pathogens if you care to read further. Suffice it to say that Ebright was right that with the proliferation of these new labs, there would be leaks. So far, they’ve all been accidental instead of the type feared by Ebright where someone from inside a laboratory deliberately releases a pathogen.
With regard to the SARS CoV-2 outbreak, rumors from nearly the very beginning swirled about a lab in Wuhan. There is in fact a level 4 containment lab in Wuhan and there is also a level 2 lab as well, that I believe is very close to the wet market.
Should there have been an accidental release from either of these labs, at this point we would have to postulate that China has specifically quashed all information relating to this event and kept the laboratory personnel and any close family or other contacts who may have been infected out of the databases of patients.
But that hasn’t stopped the noise. Some aspects of the noise even begin to look to me like an information operation of sorts. Of course, since we don’t know the originator of the operation, we don’t know if it is actual intelligence being leaked or if it is disinformation being sown to add to the chaos.
At any rate, this April 2 column from David Ignatius put the idea of an accidental leak from a Wuhan lab into the Washington Post. Those who follow intelligence community news know that Ignatius is often thought of as a mouthpiece for information the CIA wants disseminated. Are they his source here? Was some other information operative his source?
Then things really heated up on April 15. Here is John Roberts of Fox News asking Trump a question during the April 15 “press conference”:
Wow. That’s an incredibly specific question. It assumes a female intern at the lab who infected a boyfriend and then she (or did he, not clear to me from Roberts’ phrasing) went to the market. Even though this was April 15, I’ve seen no further pushing of this specific version of the story.
But Trump’s response is a bit concerning. Note that he says they’re “hearing that story a lot”, but then makes a really big deal of the word “sources”. Given Trump’s history of spilling classified intelligence, and the constant warnings to him about such leaks compromising “sources and methods”, I almost wonder if that’s a genuine response of his lizard brain to all those warnings. We simply have no way of knowing that or knowing if perhaps those “sources” happen to lie outside the intelligence community and among circle of wingnuts who have the ears of Trump and Fox News and he’s really proud of them but doesn’t want to divulge them.
That same day, Josh Rogin put out a Washington Post column pushing the leak from a lab story, this time tying it directly to the State Department cables in 2018 about lax biosecurity protocols at the level 4 containment lab in Wuhan that Roberts mentioned. But Rogin didn’t include the specifics about the intern.
I’ve heard nothing further on the intern question, but the general idea of an escape from a Wuhan lab still gets tossed around. Ignatius returned to the idea of an accidental release on April 23. He even talked to Ebright:
“Science is not going to shift this from a ‘could have been’ to a ‘probably was,’ ” messaged Richard H. Ebright, a leading biosafety expert at Rutgers. “The question whether the outbreak virus entered humans through an accidental infection of a lab worker . . . can be answered only through a forensic investigation, not through scientific speculation.” Ebright told me the Chinese government should launch a forensic investigation by reviewing “facilities, samples, records, and personnel.”
Given Ebright’s history of predicting just such an accidental release, I find it very reassuring that he isn’t ready to say that’s what happened. As he rightfully points out, we can only know what happened when detailed information is assembled on the epidemiology of the earliest cases. Only Chinese medical investigators can know whether any laboratory personnel, and especially whether any family or other close contacts of them appear on the timeline of the early infections. It is also crucial to know where any such infections, if they exist, fall on the timeline in relation to cases affiliated with the wet market.
My gut feeling is that the evidence still very strongly points to the virus originating through the wet market, but I also think the index case there likely goes back even earlier than the November 17 case discussed above, since there are suggestions there were other cases appearing daily by then. Also, it’s hard to imagine that if the official intelligence community had a story as specific as the intern story and had evidence to back it up, that Trump wouldn’t be trumpeting it on a daily basis to deflect the criticism being heaped on his response to the outbreak.
Stay tuned. I suspect the story will take several more turns before we ever reach any level of certainty.
Thanks, Jim!
Thanks for all the work. About that Trump boondoggle at West Point. The considerable expense the Army will pay to transport, house, and quarantine the cadets (14 days, is it?), and all the hoopla and extra security – will all be reimbursed by Trump 2020 as a campaign expense, non? It isn’t a legitimate charge on the Army’s budget, that’s for sure.
Jim, Dr. Ebright is accessible on Twitter and would certainly talk to you. There are several main ideas within “accidental lab release” that should probably be treated differently. One would be a virus isolated and in a lab that was released. Another would be infection of research who was surveying bats for viruses (research that was in fact ongoing and is known to have safety lapses). The evidence for the former would exist in the form of hypothetically curated but unreleased and presumed quashed sequence information. The evidence for the latter would be difficult to obtain but early linked deaths or illnesses to lab workers would support that. Evidence for linkage to the market would be widespread sampling of animals in the market for potential intermediate hosts. I find it shocking that there was not such an investigation. This type of investigation could strongly support a market origin and I do not understand why it was not undertaken.
Thanks for the tip on Ebright. I should make sure that i at least follow him.
Yes, the idea of a virus in the lab being released would mean that lab was very early in the process of working on a virus for which they had not yet published a sequence.
And the idea that someone surveying bats or other animals getting infected would only loosely fall into the idea of lab accidentally releasing it.
Why there isn’t yet information on surveys of the market is one of the biggest mysteries. It does seem like the first thing that should have been done. We have no way of knowing if it was done, and if so, why the information hasn’t been released.
Welcome to the blog. Please come back often.
Thanks, Jim. I agree that research survey-related would be loosely related to the main line of conspiracy thinking on viral origins, but I think its plausibility is such that I would advocate shutting down any viral survey research of that kind just as strongly as advocating for closing of animal markets. I don’t want to traffic in too base of speculation, but one reason why animal market survey might not have been considered important is if authorities *knew* the origin were due to any research-related reason (either escape or survey-related). Meaning, if reason known they would not waste manpower or resources in the middle of an exploding pandemic on a moot point (whereas to us this seems obvious place to look if we are unclear on where the zoonosis originated). Another place where I would wonder about a lemma would be that there are documented projects to survey bats that *have* been surveying bats. If we don’t see data for work that we know was done for these projects, that also becomes a concern.
craig kaplan-
you don’t “shut down research”, whether survey or other form. you evaluate it once it is published for its flaws and value, and then publish that evaluation.
Not really, most negative studies go unpublished
tough to get “negative results” published in peer-reviewed journals. hell, it’s tough to get any results published in peer-reviewed journals . . .
Very interesting reading, Jim. I have been reading everything I can get my hands on about this novel coronavirus and viruses, in general, since this pandemic began. I think the notion that this virus was “manufactured” or “engineered” in a lab is nonsense and not supported by any known facts and is based on speculation only. Here is an enlightening article about one of the main virus researchers in China and she doesn’t think it was made in or escaped from a lab in China:
https://www.scientificamerican.com/article/how-chinas-bat-woman-hunted-down-viruses-from-sars-to-the-new-coronavirus1/
If you want to read about a real scary virus, do a little reading about the Nipha virus. America, as a nation, needs to stop wasting billions on military weapon systems and starting focusing on the real risks to human extinction: climate change and viruses!
This isn’t an engineered virus – not by humans, anyway – but it’s *thoroughly* nasty, worse than either SARS or MERS. The woman who died on Feb 6, in Santa Clara county, had a healthy heart before the virus, and she died of a massive heart attack – the report is that her heart ruptured. The strokes in people who were barely showing symptoms, the blood clots, the liver and kidney problems, the lung problems…you DO NOT want to get this.
on the woman who died:
https://www.sfgate.com/bayarea/article/Coronavirus-updates-COVID-19-Bay-Area-deaths-cases-15225947.php
There are also the reports of micro-clots causing 30- and 40-somethings to have strokes normally seen in septuagenarians. IIRC that was one of the ways fictional Andromeda Strain killed in the book by attacking cell walls (leading to clotting) and later the polymer seals.
We already knew early on that this one (unlike the usual seasonal flu) leaves permanent scarring and other nasty side effects so the idiots going to church today in LA for “Pastor” Spell will learn the hard way that plagues are God’s lesson of choice.
Nipah: scary indeed — fever, headache, drowsiness, disorientation, frequently leading to coma in 24–48 hours. The most recent outbreak (in Kerala, India, as were two earlier ones, in 2001 and 2007) was recognized May 2, 2018, contained, and declared over on June 10 of the same year(!) Nineteen cases, seventeen deaths; population, 33.4 million.
The interesting thing here is that a Covid-19 outbreak in Kerala which began in late-January seems to have been handled with the same community-centered competence and dispatch evident in its treatment of Nipah. Which included immediate, complete lock down (well before any other part of India), extended periods of quarantine, and widespread use of “…the centrally procured real-time polymerase chain reaction (PCR) testing kits…[as well as] rapid test kits from the Pune-based Mylab.”
Nine out of ten of those infected were under sixty years of age; total number of deaths, three.
(good story here: https://www.theguardian.com/commentisfree/2020/apr/21/kerala-indian-state-flattened-coronavirus-curve)
Well,, I was in India at the time,, came home,, and well,, spent two months in the hospital,, venus sinus thrombosis,, liver infection, Pneumonia,, (weeks coughing up blood),, lungs filled with fluid, 1 week in a coma,, ect,, Yes,, I can attest that if this is what I caught,, was not pleasant. I just pulled a record,, and was meeting with a Hematologist in July 2007,,, as a result of this,, so,, back it back 2-3 months,, don’t know,, but was in the right area.
What really did strike me about this was the disorientation, as yes, had the fever, headache, (actually the headache was the very first symptom), diarrhea, vomiting, but the thing that sticks out was the inability to concentrate on the flight back, (worst of my life, even in business class), and well,, apparently I was having a seizure when my wife called the paramedics (same day I got back,, less than 72hrs from first symptom). I came to when the cold air hit me as they took me out of the building, and I remember them asking me if I knew where I was,, I answered “don’t know,, china?”,, as was my next scheduled trip destination, I still remember thinking why don’t I know where I am, they mentioned we were approaching the Peter Laugheed,, so I asked,, if we are going there,, that means we are in Calgary, well, remember the paramedic took note I figured that out, then nothing for 3 weeks.
Thanks Jim.
While I don’t necessarily think SARS-Cov-2 was specifically bioengineered to be a bioweapon, I wouldn’t be surprised if it was a human cell line adapted bat coronavirus that may be a recombinant with the Pangolin virus. The Wuhan labs may have been trying to develop a SARS like virus to better understand the pathogenesis of SARS and had no idea what they created.
My biggest question mark is the furin cleavage site which is a 12 nt insertion. Where the heck did that come from?
That’s not clear. What we do know is that one mechanism of change for these sorts of viruses is recombination, where a patch of information from one virus gets exchanged for the analogous patch in another when different viruses are in the same host. We also know that this junction between S1 and S2 is already known to be an exchange site for other events. The authors of the Cell paper suggest that if a progenitor virus without the insertion was circulating in humans prior to the outbreak, it may have gained that function through such an exchange with another virus.
That’s the best supposition I’ve had for how the particular combination of SARS-CoV-2 features could come about quickly* — makes the most sense to me, a series of recombinatorial (~hotspot, in the case of the furin cleavage site insertion site) events between viral soups within person-hosts. I haven’t had time to read that Cell paper yet but agree with that of which you’ve excerpted in the post and added in this comment.
Besides cryptic human-to-human transmission, it seems a zoonosis (or two) must have repeatedly passed before reservoiring in (e.g.) wet market workers for some time. And then a garden-variety human non-SARS-type CoV (or yet another zoonosis) perhaps supplied the furin cleavage package (I assume that change is what made it more readily transmissible between humans; if so, I’d bet that that change maybe preceded the one conferring greater ACE2 affinity, such that it spread and swilled a little before the acuity of illness . But now that I’m thinking aloud I’m kind of back-and-forthing it all…). [I also have my suspicions that limited numbers of travelers brought it to the US by the fall as well.]
Too bad there are likely not old samples from last fall or summer to test for CoV with sequence homologies to, say, bat and pangolin versions concurrently.
What I’d like to see is antibody testing in humans (in geographically & culturally relevant areas) for e.g. bat and pangolin coronaviruses. Anybody working on that? While we can suppose that their absence would be unreliable, _presence_ would be informative, if open to interpretation.
Also, I recall Ebright’s arguments from that time and agreed with him then.
Adding: none of (the parts of) these options are incompatible with, say, what viget and accidental lab leakers propose — there’d just be fewer steps taking place in the wild — though I do see spread and swilling and shifting around and amongst wet market workers and users as perhaps more parsimonious and ecologically valid. Unless it all happened _really_* fast. Last I knew there were those (~handful of) initial cases not tied to the market, but that could just indicate degrees of separation in community spread.
*All timescales being relative.
some things that are worrisome to me is that sars-cov-2 shares some similarities to the deadly mers disease in the sars family:
https://link.springer.com/article/10.1007/s10389-020-01258-3
further, it is polymorphic which i think implies (assumption on my part) that this version of a sars infection can change its characteristics.
two reported apparent genetic changes relative to prior sars infections that can be quite deadly are (1) unusual blood clotting and (2) alveoli (tiny sacs in the bottom of the lungs) that do not register ordinary symptoms of loss of ability to exchange carbon dioxide and oxygen until oxygen levels are so low the patient has little chance too recover.
re polymorphism and the plasticity of this nasty, shape-shifting virus we’re running from:
from harpie at 8:25 am below:
https://nymag.com/intelligencer/2020/04/we-still-dont-know-how-the-coronavirus-is-killing-us.html
Thanks for actual science rather than what passes for “science” reporting in most media outlets. A lab leak is certainly possible, and the Chinese government covering it up is too. That’s what governments do with dreadful mistakes. It’s what the US government would do if it could as well. But possible and probable are different with it all being relatively immaterial to the current situation. The idea that China should have known more sooner and passed information out when talking about a novel virus is just the wailing of a dying empire led by toddlers. The genetic sequence was published in January. Every misstep since then is a failure that has nothing to do with China.
I agree, Trump owns the response. The response is way too little way too late. Interesting that Red Dawn email chain had guessed the vector by 3 February though they also can’t confirm. They had also outlined what the response should be, not what it became to be, too bad no one listened.
Thank you Jim, was up late reading most of the links.
” The idea that China should have known more sooner and passed information out when talking about a novel virus is just the wailing of a dying empire led by toddlers. ”
My understanding is that the central Chinese government is very dissatisfied with how the leaders of Hubei province responded to the virus early on.
https://www.straitstimes.com/asia/east-asia/coronavirus-china-sacks-hubei-party-chief-xinhua-reports
I doubt that Xi Jinping and the central committee would agree that PRC is a dying empire led by toddlers.
When Lex said a “Dying Empire led by toddlers,” I think Lex was referring to the U.S.
Thank you Jim.
Dr. Peter Daszak, a zoologist. “He’s a disease ecologist, the president of EcoHealth Alliance, a nonprofit that works globally to identify and study our vulnerabilities to emerging infectious disease.”
“Pure Baloney”: Zoologist Debunks Trump’s COVID-19 Origin Theory, Explains Animal-Human Transmission
https://www.democracynow.org/2020/4/16/peter_daszak_coronavirus
I have deleted a comment from a previously unregistered commenter that linked to a Medium article with exhaustive information supporting a lab leak hypothesis. I deleted because the article was written by an MBA “serial entrepreneur” who has been affiliated with biotech but appears to not have any science degrees. Also the author of the Medium piece now is promoting companies with what appears to be anti-aging quackery and happens to be Russian.
Speaking of quackery, just saw this on CBS Sunday morning.
Quackery: A history of fake medicine and cure-alls
How does one treat a COVID-19 infection? If someone tells you “Drink bleach,” or tries to sell you a “coronavirus prevention pill,” run away! Correspondent Mo Rocca talks with “Quackery” co-author Dr. Lydia Kang, and with Dr. Stephen Barrett (who runs the Quackwatch website), about the history of quack medicine, and of charlatans and snake oil salesmen who use fears about medical conditions to separate fools from their money with almost surgical precision.
https://www.cbsnews.com/video/quackery-a-history-of-fake-medicine-and-cure-alls/
While con-artists and fake healers are dangers to public health, the biggest quacks and the greatest danger to public health, in terms of numbers killed and injured, have been medical professionals.
Medical “Quackwatchers” seem utterly oblivious to the scale of the ongoing damage done to humans by their colleagues.
Quackery and hackery.
skua, this may be tangential to your point but I think it’s relevant. I hadn’t heard anyone I know espouse the Covid-as-Bioweapon (that is, deliberately engineered and released by the Chinese) theory until I “saw”–via telemedicine—my clinician for an appointment two weeks ago; she invoked it unbidden. Most likely it is the prevailing view of the practice, run by an opinionated anesthesiologist who shares his views freely. As an MD, he naturally radiates authority. Even I found myself wondering if my doctors had inside information–or, somehow, clearer heads than mine.
First question that comes to mind is, why would the Chinese want to kill off so many of their customers?
Tom, my first question was: Why would China knowingly kill thousands of Chinese citizens? My doctor said, “Communists don’t care about their own people.” So there’s that.
Well, I don’t know, Ginevra. Your MD sounds like one of those people who naturally radiate authority who people should be wary of, and their beliefs.
Of course, Tom, you’re right. People should be wary of self-arrogated authority. But as our current president exemplifies, most are not.
Jim, thanks for all your work. Medium has always been a suspect source for me. This from Media Bias/Fact Check: “Founded in 2012, Medium is an online publishing platform developed by Twitter co-founder Evan Williams. Medium considers their platform as social journalism, having a hybrid collection of amateur and professional people and publications, or exclusive blogs or publishers. Basically, they are a blog host.”
i think the josh rogin report noted here and posted elsewhere at emptywheel deserves more than passing mention:
https://www.washingtonpost.com/opinions/2020/04/14/state-department-cables-warned-safety-issues-wuhan-lab-studying-bat-coronaviruse/
“… In january 2018, the U.S. Embassy in Beijing took the unusual step of repeatedly sending U.S. science diplomats to the Wuhan Institute of Virology (WIV), which had in 2015 become China’s first laboratory to achieve the highest level of international bioresearch safety (known as BSL-4). WIV issued a news release in English about the last of these visits, which occurred on March 27, 2018. The U.S. delegation was led by Jamison Fouss, the consul general in Wuhan, and Rick Switzer, the embassy’s counselor of environment, science, technology and health…
“… What the U.S. officials learned during their visits concerned them so much that they dispatched two diplomatic cables categorized as Sensitive But Unclassified back to Washington. The cables warned about safety and management weaknesses at the WIV lab and proposed more attention and help. The first cable, which I obtained, also warns that the lab’s work on bat coronaviruses and their potential human transmission represented a risk of a new SARS-like pandemic.
“… During interactions with scientists at the WIV laboratory, they noted the new lab has a serious shortage of appropriately trained technicians and investigators needed to safely operate this high-containment laboratory,” states the Jan. 19, 2018, cable, which was drafted by two officials from the embassy’s environment, science and health sections who met with the WIV scientists. (The State Department declined to comment on this and other details of the story.) …
“…As the cable noted, the U.S. visitors met with Shi Zhengli, the head of the research project, who had been publishing studies related to bat coronaviruses for many years. In November 2017, just before the U.S. officials’ visit, Shi’s team had published research showing that horseshoe bats they had collected from a cave in Yunnan province were very likely from the same bat population that spawned the SARS coronavirus in 2003…
“… Most importantly,” the cable states, “the researchers also showed that various SARS-like coronaviruses can interact with ACE2, the human receptor identified for SARS-coronavirus. This finding strongly suggests that SARS-like coronaviruses from bats can be transmitted to humans to cause SARS-like diseases. From a public health perspective, this makes the continued surveillance of SARS-like coronaviruses in bats and study of the animal-human interface critical to future emerging coronavirus outbreak prediction and prevention.”
“… The research was designed to prevent the next SARS-like pandemic by anticipating how it might emerge. But even in 2015, other scientists questioned whether Shi’s team was taking unnecessary risks. In October 2014, the U.S. government had imposed a moratorium on funding of any research that makes a virus more deadly or contagious, known as “gain-of-function” experiments…”
“… As many have pointed out there is no evidence that the virus now plaguing the world was engineered; scientists largely agree it came from animals. But that is not the same as saying it didn’t come from the lab, which spent years testing bat coronaviruses in animals, said Xiao Qiang, a research scientist at the School of Information at the University of California at Berkeley…”
orion highlights:
— serious safety and management issues
– serious shortage of appropriately trained technicians and investigators
–
This is exactly my worry. See my comment upthread. They could had taken RaTG13 as a backbone and recombined the RBD from the Pangolin viruses to serially passage in human cell lines in order to better study SARS like viruses and how they cause diseases. Of course if such a virus escapes, as the US intelligence community apparently worried…..
We’ve found out that the Santa Clara county cases go back even further than what they thought based on autopsies and there are a number of cases still pending. Earliest for the county so far is Feb 6 which is a few weeks before what they originally thought. So can we go further back with the Chinese than November 17? If as the SCCounty Supervisor has stated,
““We’ll never, ever know how many people contracted the coronavirus in San Clara County or California or the U.S. That ship has sailed. Even self-reporting would be inherently inaccurate or impossible,” Santa Clara County Supervisor Dave Cortese said. “Our only hope of getting a decent history of it is by counting the dead. I’m really disappointed that coroners all over the country haven’t done a better job. They’ve been signing death certificates as strokes or heart attacks or natural causes.”
If true, for us then sorting it out in China may be nothing more than a political exercise in assigning blame and the Ignatius and Rogin articles are simply the US leaking in its own interest. There are two broad categories, either accident or design. Scientists seem to be ruling out design, so accident is most likely the culprit.
The US took 7 years to reach a conclusion on the anthrax attacks of 2001 so there is no reason to believe at this point that the Chinese are any more efficient than us. Looking for the smoking gun is certainly compelling both on the biological front as portrayed here and in culpability.
Uhm.
You left out naturally jumping species to spread, which remains the most likely explanation by far.
And if you’ve been a reader of this blog for very long, the “conclusion” reached on anthrax is not on a sound scientific or forensic basis.
Nope, brand new, and I did leave it out, thanks appreciate the correction.
Thanks, Jim! I shared the following a few days ago (although with a different selection of excerpts at that time.) And, even though it doesn’t relate directly to our current virus predicament, it does contemplate the possibility of simultaneity of events occurring naturally in our earthly environment. Or, as the author/scientist says, “We think evolution struck twice, and so this biology must be important…” To me, this suggests similar possibilities for current virus spread.
“How an Ancient Virus Spread the Ability to Remember” | MedPage Today, 12/13/19 (access video and transcript in url at bottom)
“…..Shepherd discovered that, at a biological level, the process of memory storage strongly replicates that of viral transmission.”
…..
“We also know that a whole new gene program gets turned on when you learn, leading to protein synthesis that turns experiences into physical changes in the brain, so the structure of your brain is literally changing as you learn.”
…..
“We think that ARC gene came from an ancient viral infection or retrotransposon insertion over 400 million years ago in an ancestor, and maybe this chance event led to the evolution of brains that allowed land animals to adapt to every niche on earth.”
“But there’s one more thing that’s puzzling about ARC. There’s also a fly gene. Our analysis showed that actually the fly gene was repurposed and evolved from a different retrotransposon, but the fly protein, the ARC protein, can still form a capsid and has similar biology to the mammalian gene.”
“We think evolution struck twice, and so this biology must be important, but like any paradigm shift in science, we’re now left with more questions than answers. Why would you need a viral-like mechanism in your brain? What else is ARC transferring cell to cell, and what happens to those cells that are infected? Why would you need this for memory storage in the first place?”
“While we don’t have the answers yet, there are some immediate implications. We know that ARC is only made in the cells that are incorporated into that specific circuit that encodes the memory, and maybe when ARC is released, it tells the other neighboring cells not to be incorporated into that memory so they can be saved for later memories.”
…..
“It’s fascinating to think that some of the most complex processes in the brain may have been the result of an ancient viral infection.”
https://www.medpagetoday.com/tedmed/tedmed/83872
More thinking outside of the box… A good candidate for an intermediate host may be the domestic cat or felinidae in general. We know both house cats and other exotic cats are susceptible to SARS-CoV-2. Domestic cats can also be infected by FeCoV, a coronavirus that can be quite severe in cats, but usually isn’t . It also has a furin cleavage site in the Spike S1/S2 boundary. It’s an alphacoronavirus, not a Betacoronavirus like SARS-COV-2, so not sure if the homology is high enough to support a recombination event. But I’d bet there are lots of felines (exotic and otherwise) in the area of the wet market for sure.
If you are thinking in terms of feline vectors, you might start with a species of palm civet. I’m seeing animals that look like these in pictures of “wet markets”. This was one possible source for the first SARS.
I don’t know why Chinese feel the need to eat these, but in Southeast Asia there is a saying that “Chinese will eat anything that moves with its back to the sky.”
civets aren’t felines. their classification family is viverridae.
Apology for the OT, but anyone ever try that civet-shat coffee?
Wasn’t thinking in strict taxonomy, more in terms of habits and diet. The term “cat-like” is applicable. These are omnivores rather than strict carnivores, and they occupy the right habitats.
Pangolins are insectivores who are more likely to acquire infections directly from insects, in which case they would likely have less sequence similarity.
I’m also thinking in terms of SARS, which had many similarities.
The Guardian has a piece today on covid-19 origins:
https://www.theguardian.com/world/2020/apr/28/how-did-the-coronavirus-start-where-did-it-come-from-how-did-it-spread-humans-was-it-really-bats-pangolins-wuhan-animal-market
Sounds a little like the sayng about science-fiction fans: ‘will eat anything that doesn’t move faster than them’. Or “everything but the table’.
Just to add a note regarding possibilities, the wet market is very near the Hankou train station. It is one of the main inter-regional train stations in Wuhan, and could have been a transmission route of a virus carrier from the south or west of Hubei (Yunnan anyone?).
As to the virus going undetected for a while, it is not unreasonable to consider that visits to doctors in China are very short, and not focused on looking for novel diseases. That it was discerned as early as it was may be the most surprising result.
7.6B people create a lot of chances for a virus that had been spreading safely to make the jump to a deadly form.
Your post supports the inference that this will not be a one of kind occurrence.
Thank you for the informative post!
It made me remember an article written March 30, a few days before Ignatius.
https://thebulletin.org/2020/03/experts-know-the-new-coronavirus-is-not-a-bioweapon-they-disagree-on-whether-it-could-have-leaked-from-a-research-lab/
They also have a few other recent articles that resonate with your arguments:
https://thebulletin.org/2020/03/hot-zone-in-the-heartland/
https://thebulletin.org/2020/04/on-biolabs-and-pandemic-risk-listen-to-scientific-americans-interview-with-editor-elisabeth-eaves/
The Bulletin are the guys with the famous Doomsday Clock, btw.
Thanks. Those are wonderful links.
Thanks, Jim.
The timeline of COVID19 cases in Wuhan in the Lancet article (published Jan 24, 2020) in your post caught my eye. I had not heard about a Dec. 1, 2019 case before.
Instead, I was familiar with the timeline of COVID19 cases in Wuhan from the New England Journal of Medicine article (published Jan 29, 2020). Figure 1 from the NEJM article shows the first case on Dec 7.
There are about 42 to 44 cases accounted for by Jan 2, 2020, so perhaps the two articles are referencing the same patients but picking a different date for onset of symptoms?
https://www.nejm.org/doi/full/10.1056/NEJMoa2001316
In any case, the Figure 1 in the above NEJM article states that an investigation of the wet market was started on Jan 2, 2020 (as well as other investigations on that date). So as you said, where is the data now that we’re at the end of April 2020?
(or started Jan 3, 2020)
Via Laura Rozen:
https://twitter.com/dwallacewells/status/1254444837186740225
12:18 PM · Apr 26, 2020
Links to:
We Still Don’t Know How the Coronavirus Is Killing Us
https://nymag.com/intelligencer/2020/04/we-still-dont-know-how-the-coronavirus-is-killing-us.html
David Wallace-Wells 4/26/20
Also posted on Rayne’s post.
New info on the vaccine front:
In Race for a Coronavirus Vaccine, an Oxford Group Leaps Ahead
As scientists at the Jenner Institute prepare for mass clinical trials, new tests show their vaccine to be effective in monkeys.
https://www.nytimes.com/2020/04/27/world/europe/coronavirus-vaccine-update-oxford.html
April 27, 2020, 1:51 p.m.
Correct me if I’m wrong but wasn’t David Ignatius one of the columnists who beat the drums loudly and irresponsibly for W’s Iraq war? If so, why does he still have a column from which he can generate more evil nonsense?
Oh right, that’s exactly why he still has a column. These people never go away and never apologize for their active stupidity.
The analogy and graphs in this article helped me get a better grasp of how the virus mutates and spreads:
“The coronavirus genome is like a shipping label that lets epidemiologists track where it’s been” – April 27, 2020
Bert Ely, Taylor Carter, University of South Carolina
https://theconversation.com/the-coronavirus-genome-is-like-a-shipping-label-that-lets-epidemiologists-track-where-its-been-136826
The first COVID-19 patients whose RNA was sequenced in December 2019 showed that three strains of SARS-CoV-2 existed in late December and all three strains have spread around the world. Based on the mutation rate, scientists have estimated that a common ancestor to these three stains existed in November 2019. (I read several scientific publication on this subject, but failed to find them amid the exploding literature.) Earlier strains that were less transmissible could have existed in November, but would be difficult to find today. The patients with the initial three strains were all linked to the Seafood Market and came down with the illness in the second half of December, but the first publication reported earlier cases and some that weren’t linked to the Seafood Market. It seems absurd to suggest that the 49 known cases identified at the end of December were all, or even a majority of the cases that existed then, so the unconfirmed story you linked from the South China Morning Mail makes sense to me.
If a laboratory virus escaped from a Wuhan laboratory in early November 2019, it shouldn’t have taken until the end of December 2019 to recognize the problem. By then, hundreds of medical professionals would have been unnecessarily exposed to a known. At least three Chinese doctors reprimanded for spreading rumors via social media about the sequencing of SARS-COV-2 in late December, so it is logical to assume that the escape of a virus from a Wuhan research laboratory would have been hard to keep secret.
Re the possible November 2019 “start”, maybe these are helpful?
ht tps://www.nature.com/articles/s41591-020-0820-9
ht tps://pubmed.ncbi.nlm.nih.gov/32104911/
ht tps://nextstrain.org/narratives/ncov/sit-rep/2020-01-30?n=12
Throwing this your way, Jim. Compelling argument that the transition goes through the raccoon dog
https://www.theguardian.com/world/2020/apr/26/virologist-christian-drosten-germany-coronavirus-expert-interview
Q: What do we know about that intermediate host – is it the “poor pangolin”, as it’s come to be known?
A: I don’t see any reason to assume that the virus passed through pangolins on its way to humans. There is an interesting piece of information from the old Sars literature. That virus was found in civet cats, but also in raccoon dogs – something the media overlooked. Raccoon dogs are a massive industry in China, where they are bred on farms and caught in the wild for their fur. If somebody gave me a few hundred thousand bucks and free access to China to find the source of the virus, I would look in places where raccoon dogs are bred.