SARS-CoV-2 has a very unusual feature: it is surprisingly good at infecting a particular type of cell that has what is known as an angiotensin-converting enzyme 2 receptor. Some other animals have ACE2 receptors, but SARS-CoV-2 works much better in human or human-like ACE2 receptors. The significance of this cannot be overemphasized.
SARS-CoV-2 needs four things to happen to infect a human. It must enter the body and it must attach to certain cells. It must be cleaved at precisely the correct spot by the victim’s cells. The remaining genetic piece must then enter and infect the cell. Every one of these four steps has a low probability of occurring by chance. The probability of all four of these unlikely events developing randomly through mutations is, therefore, very low.
Could SARS-CoV-2 have acquired its clever attributes from another coronavirus of the same family? Are there coronaviruses that exploit human-like ACE2 receptors? For this, we need to discuss the furin cleavage site, which is where the ACE2 receptor precisely cuts SARS-CoV-2, as described in step 3 above.
This is from Charles L. Hooper and David R. Henderson, “The Origin of SARS-CoV-2,” AIER, June 18, 2021.
Another excerpt:
Location, Location, Location
If camels infected humans in the Middle East, we wouldn’t expect to see the first cluster of cases in, say, Honolulu. Early cases typically happen where the virus first became contagious. And even if people travel, they are likely to become sick or infect others en route, leaving a trail of evidence.
There are nine Metro lines and 40 hospitals in Wuhan and yet all the patients treated for Covid-19 between 1 December 2019 and early January 2020 were cared for in hospitals close to the Metro Line 2 commuter line, connecting Wuhan and WIV. That’s highly unlikely by random chance alone.
Charley did all the research for this and almost all the writing. I edited it but he very generously gave me co-authorship.
Read the whole thing.
READER COMMENTS
Thomas Lee Hutcheson
Jun 20 2021 at 9:46am
Interesting, but not relevant to the issue of whether the virus was the result of again of function research and the role that NIH did or did not play in gain or function research at Wuhan.
And super irrelevant to the issue of whether a virus resulting from gain of function research was deliberately released or it it were and accident.
And likewise irrelevant to the optimal policy response by the US and other countries to the spread of the virus beyond Wuhan.
David Henderson
Jun 20 2021 at 4:14pm
Wow! In short, we wrote an article that says what the title says it would be about. But you would have rather we had written a different article.
You know, Thomas, no one is stopping you from writing your own blog.
Thomas Lee Hutcheson
Jun 20 2021 at 5:13pm
That is right I wished you had written a different article, one more directed at what I think is important for policy decisions, but I’m not sorry you wrote the one you did.
David Henderson
Jun 20 2021 at 5:17pm
Fair enough.
john hare
Jun 20 2021 at 6:47pm
I only learned the definition of steel manning in one of your recent articles. Unfortunately, it’s what occurs to me on these articles. I did annoy the author of a previous article on the subject, apologies to both of you. The origin is important, our response catastrophic (IMO of course).
mark
Jun 24 2021 at 2:12pm
I actually find none of your 3 urgent questions very relevant or particulary-hard-to-answer.
What does it matter, how one calls the type of experiment? As the articles published by Shi et al. before 2020 about SARS-research show, they did build virus-chimeras from a SARS-related Crona-virus, with new receptor-types that attach well to human ACE2-receptors and replicated well in human cell-tissue. That was not done as “gain-of-function”, one could claim (Shi surely does), but as “research in the evolution of SARS 1”. (A comment on Scott Sumner’s “the real story” has the link. Study edited by Prof. Christian Drosten, Charite Berlin, our own German Fauci – just better, as Drosten quickly developed the first working Covid-test. Till today Drosten refuses to accept the possibility of lab-leak.) – That the virus research happened in the one-and-only lab in China “qualified” to do so, is not really in question.
A deliberate release? No kidding? Why release it deliberately in your own metropolis? In an Uighur-camp, maybe, or Tibet. Better even Taiwan. Bombay. NYC.
The “optimal policy response” is a very strict international ban on virus-chimera-generation (or just in, say, 5 super-high-security-labs; as Sumner suggested: far away from any cities, with 2+ weeks quarantine before leaving.) Will happen this year or next. – Or anybody suggesting to nuke China? That is, if they do not pay 1 million US$ per Covid death (i.e. 3 trillion US$ and counting)? – That is not gonna happen, ever.
P.S. (Sure, one could still suspect, that the Covid-19 was created on purpose as a bio-weapon. I admit, that this would change my feelings somewhat – I prefer to assume incompentency/human nature, not evilness. In most cases, that assumption works well. The consequences remain the same.)
Jon Murphy
Jun 20 2021 at 12:32pm
The whole piece is interesting. However, I wonder if you are putting too much emphasis on some of the unlikely outcomes? For example, you write:
I agree that it’s highly unlikely by random chance alone, but why are we comparing the outcome to random chance? If there is an unknown outbreak, wouldn’t we expect cases to be clustered as officials and doctors attempt to stem the spread? After all, isn’t that what we saw in the US as some hospitals were busy and others empty? What’s more, is the particular hospital in question better equipped to deal with a respiratory infection than other hospitals? I’d think it likely would be given its proximity to a lab that specializes in respiratory research. If the hospital is better suited, then one would expect to see a cluster of cases at that facility, even if symptoms developed elsewhere (for example, there are major cancer hospitals in Boston, so we’d expect to see a cluster of cancer patients in Boston regardless of where the cancer was developed).
I think the lab leak hypothesis is increasing in credibility, I’m not sure the point about clusters in hospitals really helps the point.
Charley Hooper
Jun 20 2021 at 6:16pm
Jon,
I think a key aspect of the quote above is the dates. At that time, China hadn’t even recognized (or admitted?) that the disease could be transmitted between humans. Plus, I believe that patients at that time weren’t treated with anything that a regular hospital wouldn’t have. So, based on what we know, the Chinese health care system wouldn’t have had any reason to move the patients—the disease wasn’t yet recognized for its pandemic potential and the treatment wasn’t special. Also, I haven’t seen any evidence that patients were, in fact, moved.
I interpret the location data to mean the locations of presentation, not the locations to which the patients were moved to be treated.
Jon Murphy
Jun 20 2021 at 8:15pm
Ah, that makes sense. Thanks!
JFA
Jun 20 2021 at 2:28pm
I think there might be a bit too much emphasis on the gain of function research theory (which is just an add on to the theory that it was leaked from a lab). I’ve also heard a few virologists say that a virus that was the product of GoF research would show additions of chunks of genes rather than differences in the genetic sequence being randomly distributed. The latest More or Less from the BBC briefly covers the topic.
JFA
Jun 21 2021 at 8:35am
I’d also say that there is more innuendo rather than actual evidence in the AEIR article for the virus being the product of GoF research, Example, “No reservoirs of similar viruses have been found in bats and intermediate hosts.”
Just from my brief reading of the discussion, it took 14 years to discover the origin of SARS. Scientist have also not isolated the Ebola virus in an animal. Testing 80,000 animals honestly doesn’t sound that impressive when you start to think of how many animals there are.
Alan Goldhammer
Jun 20 2021 at 4:07pm
Lab leaks and accidents happen all the time as one happened to me. Back in the day I was working at NIH on a Bordetella pertussis (whooping cough) project and had five flasks of log phase growth that were ready to harvest. One of the flasks containing 250 ml of culture shattered as I was taking it off the shaker and I was doused with culture. I got some help from a lab mate to clean it up and we washed everything down with Wescodyne (an iodine sanitizer). I wasn’t worried too much about myself but we had a four month old at home who had not been vaccinated. When I got home, I went straight to the laundry room and threw all the clothes into the washer and then took what must have been the longest shower in my life.
I’m not a virologist and cannot comment on gain of function experimentation. It is clear that there are lots of corona viruses out in nature that we have not seen yet as they may not be pathogenic or that the clinical symptoms are very mild. I’m of the mind that we do need to have a better understanding of the safety practices at the Wuhan facility and better research into this class of viruses in general.
I would take issue with the section in the article on bioweapons. I have some expertise in this area having served on a Congressional Office of Technology Assessment advisory panel on ‘Weapons of Mass Destruction’ and was an advisor to the Department of State as they were preparing for the 3rd Review Conference of the Bioweapons Convention. I was also involved in a site review of the Army’s Fort Dietrick facility. President Nixon terminated the US offensive program, research only continued on defensive measures. This involves maintaining cultures of anthrax and other pathogens so they can study potential drug and vaccine therapies. At the time of my site visit (1994 IIRC) they had an active program on anthrax biodefense. It should be noted that anthrax is still potent animal pathogen and it’s not uncommon to find anthrax spores in cattle feed lots. Mr. Hooper’s alarm about this is misplaced.
Finally, to conclude this length post, there continue to be lots of viral and bacterial pathogens in nature that cause disease and death. Richard Preston’s ‘The Hot Zone’ is illuminating reading about the Reston Virginia incident.
Fred
Jun 20 2021 at 10:30pm
What can we do to rapidly control pathogens before they breakout and cause worldwide illness? I don’t think that we can stop a deliberate attack by a state or by a lone malicious actor like the anthrax spreader twenty years ago; it is just too easy to disseminate a virus or bacteria. There are nearly eight billion people each one a potential incubator of disease. Genetic manipulation of living organisms is getting easier every day. There are lots of good reasons for many governments to operate research labs, and failures of safeguards happen, and, yes, governments often believe in CYA above all. Is it possible to establish an early warning system? Will an early warning system have lots of false alarms that will be costly? I see big problems without easy solutions.
Ken P
Jun 20 2021 at 10:39pm
Great article! The article is very thorough and is the first article I’ve seen that raises the issue of transgenic mice expressing human ACE2 receptor in lung tissue. I’m sure the mice are a great tool but also could have been used to increase infectiousness in humans. It’s important to think about the fact there may have been live animals infected with a BLS3 organism. That’s much trickier to deal with than passing some tissue culture flasks in a biocontainment hood.
To me, the policy response by China is very suspicious. They are known for clamping down, but they are also clearly trying to have the highest economic output possible. There is no good explanation for them to clamp down so hard when, as your article points out, the official statement was that it was not known to pass from human to human.
Mark C
Jun 21 2021 at 1:22am
Looking at probability after something happens is a mistake that many people make, and David sure makes a lot of it in one article. It’s similar to attributing the marriage to your current spouse as the will of God because there are billions of people in this worl , can’t be coincidence that I met my current spouse.
There are billions, if not trillions of virus that ppl are exposed to every year, given enough time, you’re bound to come across some viruses that’s particularly infective of human.
The so called Furin cleavage is particularly weird, from what I read, many ‘real experts’ think this is one feature that actually shows covid19 is not engineered. Because previous known works always result to failure. Unless of course the Chinese discover a new technic that others are not aware.
“If camels infected humans in the Middle East, we wouldn’t expect to see the first cluster of cases in, say, Honolulu.”
You do realize SARS start in Guangzhou and HK which is also far away from the bats in South western China right?
On your answer to Jon,
“I think a key aspect of the quote above is the dates. At that time, China hadn’t even recognized (or admitted?) that the disease could be transmitted between humans. .. So, based on what we know, the Chinese health care system wouldn’t have had any reason to move the patients”
That’s not entirely true also, although they might not have sequenced the genome, a quick examination under microscope could have shown this virus is similar to influenza or family of coronavirus that tend to infect lungs , that’s enough reason to be sent to the hospital near the lab.
Charley Hooper
Jun 27 2021 at 1:31am
Consider Occam’s razor. Which is more likely to occur, a tiny probability of natural evolution or a large probability of laboratory alteration? The lab manipulation theory has a probability close to one, for reasons enumerated in the article, and the natural evolution theory has a probability close to zero, as explained in the article.
We make that very point in our article.
Scientists have known for almost 30 years how to add a furin cleavage site. Why do you think that all of these attempts have failed?
You haven’t presented any evidence that the patients were moved. Your point is speculation. We should ask why hospitals would move patients closer to a virus lab. The virus lab doesn’t treat patients, it does basic research. Even if a sample from a patient was sent to the virus lab, that sample could be sent from thousands of miles away just as easily as from across town. These patients were showing up with what is known as “influenza-like illness.” Hospitals treat this type of patient every day. It is perfectly normal for a hospital to treat such a patient and not try to move them. Generally, treatments for ILI focus on the symptoms. To sequence a virus, you need more than a microscope; hospitals rarely even do diagnostic tests to see specifically what the culprit is. It is not very common for a hospital to sequence a virus in a patient being treated for ILI.
Mark C
Jun 28 2021 at 11:53pm
Hi Charles, first of all, I like the book you wrote with David, Making Great Decisions in Life and Business. That being said, let’s get back to our debate:
“Consider Occam’s razor. Which is more likely to occur, a tiny probability of natural evolution or a large probability of laboratory alteration? The lab manipulation theory has a probability close to one, for reasons enumerated in the article, and the natural evolution theory has a probability close to zero, as explained in the article.”
For me Occam’s razor points toward natural evolution. Also I can see why you think chance of lab alteration is large, if the evidence is so damning, wouldn’t more scientists come out and say all that Furin Cleavage (more on this later), ACE2 receptors are not likely to happen without human intervention? The fact is they can all happen in nature, and relatively common, and by Occam’s razor, they probably emerged in nature.
“Scientists have known for almost 30 years how to add a furin cleavage site. Why do you think that all of these attempts have failed?”
Scientist can add FCS no doubt, but from what I read, artificially added FCS will get deleted in the end. Also, it’s not just Covid19 has FCS, MERS-Cov and many other Coronavirus do have them. I really not sure who propagates that FCS somehow is a damning evidence for lab manipulation.
“You haven’t presented any evidence that the patients were moved. Your point is speculation. We should ask why hospitals would move patients closer to a virus lab. The virus lab doesn’t treat patients, it does basic research. Even if a sample from a patient was sent to the virus lab, that sample could be sent from thousands of miles away just as easily as from across town. These patients were showing up with what is known as “influenza-like illness.” Hospitals treat this type of patient every day. It is perfectly normal for a hospital to treat such a patient and not try to move them. Generally, treatments for ILI focus on the symptoms. To sequence a virus, you need more than a microscope; hospitals rarely even do diagnostic tests to see specifically what the culprit is. It is not very common for a hospital to sequence a virus in a patient being treated for ILI”
By your argument, they wouldn’t need to transfer the patients if it was a lab-leak either, they just need to make sure the patients are under very strict quarantine. Not sure why you think “influenza-like illness” is trivial, in my place you will probably get quarantined if it’s influenza.
KevinDC
Jun 22 2021 at 9:58am
The lab-leak hypothesis is a topic about which I’ve been decidedly agnostic, mostly because I’m no virologist or epidemiologist and I don’t have any illusions that I’d be a good judge here. I think it’s an underrated virtue to have no opinion on topics you don’t know well.
That said, there is a sort of weak heuristic I use when at least considering initial probabilities. When there’s some topic under dispute, with people on both sides who seem (to my outside view) to be about equally well informed and credentialed and smart, but one side seems excessively concerned with policing the discourse and trying to prevent any debate or discussion on the topic from taking place, I assume that side is probably wrong. And it’s definitely seemed to me that the advocates of the natural origins hypothesis fit that description. As I said, it’s a weak heuristic – it only has the effect of making the lab-leak hypothesis seem marginally more plausible to me, at least on initial consideration.
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