Friday, July 23, 2021

A litmus test for biologists

Like “where were you when 9-11 happened”, all biologists must now have formed an opinion on the question of whether the COVID-19 virus is of natural origin or lab made/leaked, presumably by WIV.  Nobody can hide any longer under the 50-50 cover or fake ignorance, because everybody’s scientific reputation, knowledge, and judgments must be on the line regarding the most scientifically and socially explosive issue since Jan 2020.  Were it not for politicization of the issue, it shouldn’t be something even lay people are talking about, but as now, even if scientists never say never, there can be no grey zone: it is high time that either you believe in one theory, or you believe in the other. 

Behind the natural origin theory are supports from the unequivocal, long human history and results of new, unbiased virus analyses. Behind the other, well, nothing, other than the fact that WIV is at the same city where COVID-19 was first discovered, with some scientists working on bat CoVs.  The lab made/leak theory is essentially one and the same, because for lab leak to occur, WIV must first have the virus.  Then how did the WIV get it?  One is of course WIV invented it, hence lab made.  The other is WIV collected it from the wild, before it escaped from WIV.  If so, Fauci put it well: “But that means it was in the wild to begin with. That's why I don't get what they're talking about [and] why I don't spend a lot of time going in on this circular argument.” (https://www.nationalgeographic.com/science/article/anthony-fauci-no-scientific-evidence-the-coronavirus-was-made-in-a-chinese-lab-cvd).  Mind you, no evidence WIV ever had it prior to Dec 30, 2019.  WIV reportedly has 10k bat samples collected from the wide, but it doesn’t mean WIV has or is growing 10k different CoVs.  Based on published work, many samples don’t have viruses, many samples have the same CoV (e.g., see https://www.biorxiv.org/content/10.1101/2021.05.21.445091v1).  Moreover, recovering CoVs from bat samples are notoriously hard, because CoVs are likely inactivated during storage/transport or present in too low a level.  So the actual number of CoVs at WIV is much, much smaller than 10k, and many or most have remained at freezers undisturbed anyway.  What is more, even Ralph Baric, who signed the Science letter (https://science.sciencemag.org/content/372/6543/694.1), admitted that no matter how many CoVs WIV has collected, natural CoVs outnumber them by many orders of magnitude.  The same conclusion by Peter Daszak: how matter how many times WIV collected CoVs, they are negligible compared to the natural, human infection events.  In fact, WIV would go to the countryside to collect samples only after told by the locals that bats were there.  So whatever CoVs WIV caught, if infecting WIV workers, must have infected the locals without WIV protective gears many times prior.  In essence, the lab leak theory, in its most benign form, still has zero evidence, is a non-issue and an exceedingly long shot simply based on real life numbers, even before considering WIV safety practices.  Consequently, we must view that lab leak is just a backdoor lab made.

In short, the lab theory has no evidence, despite the most intense scrutiny in scientific history, for the past 19 months.  Below lists some of the debunked “evidence” and, more importantly, why it can’t possibly be made by WIV.

1. Evidence that wasn’t

Not for the lack of trying, lab made “evidence” popped up immediately in Jan 2020.  A funny thing is, throughout scientific research, whenever a piece of evidence is disputed, it is rarely completely discredited right away.  Not in the case of lab made theory though: corpses of such “evidence” have piled up mile-high quickly.  For example, the virus is man made because of an HIV signature, furin sites, etc.  Or WIV was shut down due to a leak in 2019 (https://www.thedailybeast.com/pentagon-contractors-report-on-wuhan-lab-origins-of-coronavirus-is-bogus).   Or COVID-19 cases surged in the fall 2019 based on satellite images around Wuhan hospitals (6/10/2020 blog, https://dash.harvard.edu/bitstream/handle/1/42669767/Satellite_Images_Baidu_COVID19_manuscript_DASH.pdf?sequence=3&isAllowed=y).  Three WIV researchers got sick in Nov 2019?  What are their names?  What were they sick for?  Remember the Niger yellow cake in 2003?  Aluminum tubes?  Mobile labs?  The latest was from Jesse Bloom, who also signed the Science letter and then claimed to have recovered “lost” virus sequences, showing China is hiding whatever (https://www.biorxiv.org/content/10.1101/2021.06.18.449051v1).  Never mind the sequences were not from the earliest patients, the Small paper associated with the data amply explained and discussed their implications.  After widespread pushback (https://www.sciencemag.org/news/2021/06/claim-chinese-team-hid-early-sars-cov-2-sequences-stymie-origin-hunt-sparks-furor), Jesse Bloom had to backpedal and downplay the importance of his “discovery”.  It turned out that the raw data was originally deposited to NCBI, but when the linked paper, after being revised and accepted, lost the reference to NCBI, the authors asked NCBI to remove the data.  And now the raw data have been re-deposited elsewhere (https://live.baidu.com/m/media/pclive/pchome/live.html?room_id=4621124099&source=search).  Curious what Bloom will say now and do with this work, and whether the media reports hyping his work (some even crying “smoking gun”) will update the information?  Fat chance.

Typically, absence of evidence is not evidence of absence.  But in any research endeavor, if you have a hypothesis and have tried many different ways to test it, and you come up empty every time-what is more, however you test it, you get the results refuting your hypothesis-you’ve got to question your hypothesis seriously.  A beautiful theory slain by ugly facts, nothing unusual about that.  But what is uglier is clinging to a theory disputed by all the facts while supported by none, which is exactly what the lab theory adherents do.  How can they do this, even when all their hard-earned “evidence” had blown up in their faces?  The fig leaf, of course, is China not being transparent!  But what does it even mean?  As an example, in early 2020, China was also accused of being not transparent, e.g., hiding the case and death numbers, right?  Now, over one year later, can everybody testify China’s numbers or undercounting being any different from those from other countries?  If anything, China’s official fatality number is closer to the truth (https://doi.org/10.1136/bmj.n415) than most countries’ (http://www.healthdata.org/special-analysis/estimation-excess-mortality-due-covid-19-and-scalars-reported-covid-19-deaths). But has the West admitted that China had indeed been as good as others in reporting COVID-19 cases and deaths?  Hell no!

In all truthfulness, it is not China being not transparent, it is that some people simply won’t take no for an answer, and don’t believe a word out of China.  More transparency?  WIV is a research institute not unlike other universities and institutes around the world.  WIV works openly with international collaborators.  WIV publishes in scientific journals for all to see.  You can’t be more transparent than that.  Anyone can pool WIV’s papers over the years to see if there is any hint, even remotely, on COVID-19 virus work prior to 2020.  Answer: absolutely nil.  There is no probable cause for any “investigation”-indeed, no cause at all, 19 months later.  Think WIV opening up everything will shut up the diehard?  One can easily imagine that if they still don’t get the answer they want, they will question whether WIV has hid something, or cooked the book, or maybe another place at Wuhan or even China made the virus.  This is a bottomless pit.  Besides, has such “transparency” been demanded for or achieved by anybody else in the world?  How did it work up for Iraq in 2002?

2. Why WIV couldn’t have possibly made the virus (also 5/27/21 and 6/5/21 blogs)

RNA sequence analyses have shown that the virus has no sign of human manipulation.  Humans can’t possibly design viruses with a desired feature from scratch as simply as typing computer codes, so the only way to make a virus that passes bioinformatics detection, in theory, is to propagate a precursor CoV, without or with prior random mutagenesis, in Vero cells, or mice, or ACE2 transgenic mice, while selecting for a certain property.  There are so many obstacles in this GOF that the chance of success is dismally slim, with unknown and never certain outcomes.  (A variation is to recombine CoVs in cells or mice, but its complexity will shoot up exponentially.)  How many cells will be needed?  How many mice?  How long for the propagation and selection?  How and what to select for?  What is the end point?  Are results in cells in vitro or in mice even applicable in humans, a major deal breaker?  Any scientists who have an iota of idea what this experiment entails know how impractical the task is.  Oh, one more thing: what might the precursor CoV be?  Shi Zhengli at WIV has said before 2020 they had grown only 3 CoVs, all closely related to SARS, 80% identical to COVID-19 virus (scim.ag/ShiZhengli). Starting from SARS would have been nuts, because there is no scientific question to speak of, SARS is so far off to COVID-19 and more deadly already.  The WSJ and DRASTIC favorite (6/5/2021 blog), RaTG13 virus, is 96.2% identical, but it doesn’t bind human ACE2 well, meaning it is only weakly infectious if at all (https://www.biorxiv.org/content/10.1101/2021.05.21.445091v1), so it would have been tough to establish infection to begin with.  And, did I mention Shi never even had the virus (scim.ag/ShiZhengli)?  Thus, this supposed GOF has no head: don’t have/know the starting CoV, no tail: no idea how the final CoV will act on humans, and a body that may or may not work.  No success, even a tiny and remote one, of such GOF, has ever been reported for CoV.  Why would WIV, by all means a normal research institute, want to do that? 

Suppose WIV did embark on such experiments, a lot of people must be involved and know about it.  Grant agencies, staff and reviewers, grant abstracts searchable, because it would need tons of money.  NIH’s $600K is peanut.  You can’t do it alone in your basement.  It will take a long time (years), using a large lab space and resources.  It will involve a lot of researchers.  WIV is a close-knit community, only several hundred workers, along with many domestic and foreign collaborators.  WIV-associated people travel and reside around the world.  There may be 1000 people over the years that would have an idea, even if grapevine, of what was going on.  Yet, after the loudest clamor and maybe $10 million reward (proposed by David Asher, an anonymous DOS source for the VF article https://www.vanityfair.com/news/2021/06/the-lab-leak-theory-inside-the-fight-to-uncover-covid-19s-origins) for 19 months, exactly zero person has come out of WIV.  On the contrary, whoever has spoken, Chinese or non-Chinese, in China or outside, all denied GOF or any knowledge, or anything unusual at WIV (https://www.bloomberg.com/news/features/2021-06-27/did-covid-come-from-a-lab-scientist-at-wuhan-institute-speaks-out).  Generally a negative is less telling, but in this case, it speaks volume.  Either no GOF, or a conspiracy theory on par of 9-11 being an inside job.    

3. Why bothers?

What did WIV want to achieve anyway?  Showing CoVs can evolve?  Already knew that.  CoVs can be deadly?  Knew that too, with SARS and MERS.   What is left, and what the lab theory people really want to lead to, is that COVID-19 is a Chinese bioweapon.   But if the Chinese are evil and crazy enough to do it, COVID-19 is truly an odd product.  It kills no more than 0.5% of the infected, with most of the dead the elderly.  Shouldn’t a bioweapon aim at young people, with a much higher kill rate?  Bird flu is much “better” than CoV in this regard: flu viruses mutate and recombine faster, and some already have high mortality rates for the broad population.  Here lies a paradox for the lab theory: the Chinese must be the best scientists, making the most difficult GOF ever by far to work, yet at the same time the worst scientists, choosing/making a wimpy virus instead of an easier and much more deadly bird flu.  Which is it?

4.  All biologists’ professional honor at stake

Most officials, media, public in the West subscribe to the lab theory.  Media reported that two US intel agencies leaned towards the natural origin, while one the lab theory.  But didn’t all 18 believed in Iraq WMD in 2002?  A slam dunk, right? 

To be fair, a vast majority of scientists have consistently sided with natural origin.  A small dissenting voice, preferably amplified by the media, comes from scientists with little bench experience with modern viruses/molecular biology/mammalian screening, and those who did their last experiments 20 years ago or earlier.  Jesse Bloom seems to equate making a new virus to playing computers.  He sounds agonistic once in a while, yet the hype in the media about his “discovery” must have come largely from him.  Alina Chan, an MIT postdoc, is also now computation-oriented.  She is among most vocal lab made theory proponents, yet all her claims, along with DRASTIC’s, including her newest tweets of Bloom’s “discovery”, have invariably fizzled.  How many times can one be wrong before not being taken seriously?  Well, in the US, as many as possible.  

Richard Ebright, a Rutgers professor, is squarely in the lab made camp early on, even though he, like Bloom, occasionally tries to appear 50-50.  He knows bacterial RNAP X-rays, but does he know mammalian systems and virus-host interactions?  Luc Montagnier, a Nobel prize winner for discovering HIV, has waded deep into wackiness in this century, if not before.  He thought the COVID-19 virus was made towards an HIV vaccine.  Considering every possible way to make HIV vaccines has been tried and failed for the past 40 years, while there are now good treatments, one has to really wonder WTF would everybody want to make an HIV vaccine out of a CoV?  Has any CoV ever been used in a vaccine?  What are the advantages of CoV over other, existing vectors?  Then there is David Baltimore, another Nobel prize winner for discovering reverse transcription.  His claim of “smoking gun” gave much credence to Nicholas Wade’s piece, which was as widely distributed as mistake-laden (https://thebulletin.org/2021/05/the-origin-of-covid-did-people-or-nature-open-pandoras-box-at-wuhan/).   Baltimore later regretted his words and tried to backtrack by saying he just wanted more research, but the damage has been done.  Besides, more research is indeed needed to test early human sera and more animal samples around the world, but not wasted on something that runs counter to established knowledge and common sense.

Some of these people, like Baltimore, should have known better.  But they have now ventured into conspiracy theories.  What they are doing comes with no cost to them, since it is simply opening their mouth, while ignoring all "evidence" debunked and existing research.  On the other hand, refuting their claims or satisfying their demands is energy draining, impractical, and never ending, for they will simply move on to invent new questions.  They claim they simply want to know, to ask questions.  But they are not interested in getting answers they dislike, no matter how irrational, farcical, and fantasy their favorite answers are.

There is no middle ground, no 50-50.   All biologists, particularly the lab made/leak people, with your professional life on the line, must answer these simple and fundamental questions: how do you think WIV got the virus?  How do you think WIV made the virus?  What evidence is there WIV had or made the virus?  If you even waver a second in answering those questions, then you must realize the lab theory is toast.  Don’t hide behind the China-not-transparent crap.  Many more scientists arrive at the opposite conclusion even though China is no more or less transparent to them.   

Everybody must stake his/her professional honor and credential on this litmus test.