Michael Worobey
@MichaelWorobey
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Viruses. Pandemics. Professor and Head of Ecology and Evolutionary Biology at the University of Arizona. Tweets mine.
Joined February 2014
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Here's a visual of the US H5N1 "Cattle clade", HA plus two internal genes.
Strongly suggests to me there was single origin, at least for these sequences.
Possibly in late 2023/early 2024.
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We have just released two preprints on the origin of SARS-CoV-2:
1. "The Huanan market was the epicenter of SARS-CoV-2 emergence"
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Dear
@KatherineEban
,
@jeffykao
and
@ProPublica
:
Your recent story misquotes me in multiple ways, including ones that I contacted you about multiple times.
Astonishingly, you managed to ignore my corrections AND quote my concerns that you might do so!
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SARS-CoV-2/COVID-19 in Italy in September 2019: the most important finding yet on the origin of the pandemic*.
(*or an error with big consequences.)
A thread. 1/24
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We need to talk about that human case of H5N1 in Texas...
Here is a bootstrapped (NJ) tree showing how the closest realtive of H5N1 sampled in cattle is a virus the infected an male individual who reportedly worked on a farm with cattle (dairy, I believe).
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🚨🚨🚨
Wow. Huge development. SARS-related CoVs in bats in Europe just one mutation away from a polybasic furin cleavage at S1/S2.
And these very bat samples might contain low-frequency variants *with* functional FCS.
1/
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I said: "OUR TWO RECENT PAPERS establish that a natural zoonotic origin is THE ONLY plausible scenario for the origin of the pandemic."
Now you and the readers of this thread can see exactly why I had concerns that you might ignore/filtert pertinent comments and misquote me.
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Our preprints on the origin of SARS-CoV-2...
have now been peer reviewed and published as a pair of Research Articles by
@ScienceMagazine
We have just released two preprints on the origin of SARS-CoV-2:
1. "The Huanan market was the epicenter of SARS-CoV-2 emergence"
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Here I explain why I (continue to) think that a zoonotic origin of SARS-CoV-2 is more likely than a lab leak scenario - even though I signed 'The Science Letter'. 1/
"There are lots of pieces to still fill in, but this report [from
@MichaelWorobey
and colleagues] ties a lot of the pieces together that say, 'There is a really credible story for an animal origin of SARS-CoV-2,'" says
@JHSPH_CHS
senior scholar
@GGronvall
.
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1 of 10: The B.1.1.529 (omicron) Spike looks a whole lot like a 'polymutant' Spike experimentally generated to evade antibody responses from infection or vaccination, as noted by
@theodora_nyc
.
What does this portend for its immune escape properties?
I wish I was as optimistic
@jbloom_lab
Our polymutant spike has 20 aa substitutions and is almost completely resistant to neutralization by almost all vaccinated and convalescent plasma we tested. This new one has more in overlapping regions.
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OK, I think we're close to decisive evidence that US bovine H5N1 had a single origin from birds, and that when related viruses from birds *have* been found, they are jumps from cattle back into birds.
Grackles, blackbirds, chickens all show mammalian adaptation like PB2 M631L.
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&
2. "SARS-CoV-2 emergence very likely resulted from at least two zoonotic events"
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So sad to see you of all people,
@RichardDawkins
, being taken in by and amplifying the antiscientific misinformation and disinformation put out by
@mattwridley
regarding the origin of
#SARSCoV2
.
1/
Just watched
@MattWRidley
fielding Zoom Qs about Viral book. Matt is SPECTACULARLY well-informed with detailed facts & figures. Also balanced & fair-minded. He’s an MP, why isn’t he Minister of Health? Wouldn’t need civil service briefing! Buy the book!
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Important update on metadata of H5N1 in cattle (and back to birds):
Thanks to the extraordinary detective skills of
@flodebarre
, we are pleased to be able to share this table containing locations and dates for several H5N1 cases in cattle and birds:
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My friend and fellow department head
@uarizona
, Professor Tom Meixner, was shot and killed in the line of duty Wednesday afternoon.
I'm heartbroken.
I want to offer my deepest condolences to his wife, Kathleen Cotter Meixner, and his sons, Sean and Brendan. 1/15
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15 minutes later I wrote you:
"I will follow up with typo fixes and more complete answers.
In particular I meant to say our papers established natural zoonosis as “the only” rather than “a” plausible hypothesis."
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Please correct your errors (or reverse your deliberate and unethical choice to misquote) me immediately.
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1/16 I recently gave a public lecture about SARS-CoV-2 origins that touched on some of the myths & misinformation promoted by some proponents of a lab leak origin (below).
But I'd like to discuss a couple others here that I didn't have time to get into.
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Mmmm...Some beautiful scientific writing here in Senator Burr's "Senate report" on COVID origins.
The scientific illiteracy in this report is in a league of its own. This makes the US Senate look like a laughingstock.
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At 6 pm ET on Oct 26 2022 I wrote you:
"Our two recent papers establish that a natural zoonotic origin is a plausible scenario for the origin of the pandemic."
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But you ignored and filtered them.
I did NOT point "to multiple papers, as well as [my] own, that support natural zoonotic origin as “a plausible scenario for the origin of the pandemic.”"
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6 and half hours later I wrote you, via the twitter communication you acknowledge in your article that you saw:
"Our two recent papers establish that a natural zoonotic origin is the only plausible scenario for the origin of the pandemic."
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@edwardcholmes
"Together, these analyses provide dispositive evidence for the emergence of SARS-CoV-2 via the live wildlife trade and identify the Huanan market as the unambiguous epicenter of the COVID-19 pandemic."
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My views on recent VF article % famous "deleted sequences" study by
@jbloom_lab
:
Neat sleuth work. But mostly ‘stolen valor’ & unsupported accusations of malfeasance, laundered by a compromised peer review process. Allow me to explain. 1/103
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So, *preliminary* molecular clock analyses indicate that the time of the most recent common ancestor (TMRCA) of the US cattle flu clade was late December.
TMRCA of that clade and the closest relatives in birds, mid-December.
If single intro, likely between those rough dates.
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My colleagues and I have just posted a
"Note about availability of
#H5N1
2.3.4.4b consensus sequences from cattle and other species"
@virological_org
.
Consensus genomes and metadata.
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I think it is important that we start testing asymptomatic cattle, both dairy and beef.
Important to start genomic surveillance in Mexico and Canada, the two largest export markets for US cattle (in that order).
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Twice now I've seen people tweet the following sentence from the introduction of our recent paper out of context:
"However, the observation that the preponderance of early cases were linked to the Huanan market does not establish that the pandemic originated there."
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Fantastic work from Mang Shi & colleagues:
"a novel recombinant SARS-like coronavirus...with only five amino acid differences between its receptor-binding domain sequence and that of the earliest sequences of SARS-CoV-2" in Yunnan, China.
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A couple of amazing statements by former CDC Director Robert Redfield at the Select Subcommittee Hearing COVID origins:
"SARS1 never learned how to go human to human."
"This didn't come from the market. We now know that there were infections all the way back in September."
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6: I speculate that a third dose of mRNA vaccines may afford similar or superior protection against polymutant Spike-bearing viruses as seen in 'infected-then-vaccinated' individuals in
@theodora_nyc
's experiments.
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More interestingly, when you look at *only those cases with no known link to the Huanan market* you still see this pattern. This is a clear indication that community transmission started at the market.
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My concern at the moment is that H5N1 might evolve at a different rate in cattle than in birds. And until we have the sampling dates for the cattle viruses, we won't know if it is faster or slower (or the same) in cattle and birds.
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1: A thread connecting the dots between:
(1)
@PeterDaszak
et al's fascinating recent preprint on the *many* SARS-related CoV infections in humans per year in Southeast Asia, and
(2) The furin cleavage site of SARS-CoV-2, and
(3) Why Wuhan?
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And in the very next sentence you state:
"Before this story ran, Worobey posted his comments to us, as well as additional ones, on Twitter, so they would not be “ignored or filtered,”"
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I want to share a roadmap of how recently-shared data from the Chinese CDC, from environmental samples taken at the Huanan market, can be used *right now* to try to track down its animal sources.
The data have been around since very early 2020...
1/
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Your story states:
"Worobey pointed to multiple papers, as well as his own, that support natural zoonotic origin as “a plausible scenario for the origin of the pandemic.”
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I wrote this Opinion piece for the
@latimes
on last week's evidence-free news cycle on COVID origins.
It covers my own scientific journey: started closer to
@jonstewart
, with whom I sympathize, but ended far, far away.
Thx
@JoshGohlke
, super-editor!
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I wrote this article in
@ForeignPolicy
with
@angie_rasmussen
.
In it, I describe why I decided it was not wise to engage with a "Lancet Commission" chair, Jeffrey Sachs, who is not competent to lead an evaluation of the origin of the COVID-19 pandemic.
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And the lineage A likely postdated lineage B even though it is likely more similar to the bat progenitor virus. And the earliest jump (likely but not certainly B) was probably in LATE November and NO EARLIER than November.
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We now know that this individual was a dairy farm worker who worked in a geographical area with cattle with symptoms consistent with H5N1...but it appears that no samples were collected (!) from cattle from the farm where he worked:
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There was a key, overlooked, finding in our recent preprint.
Skeptical the pandemic started at the Huanan market? The strong evidence that lineage A, not just B, is geographically associated with the market needs your attention.
Long 🧵
We have just released two preprints on the origin of SARS-CoV-2:
1. "The Huanan market was the epicenter of SARS-CoV-2 emergence"
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7: If so, it further underscores the *urgent* need to get serious about vaccine equity worldwide, with so many people still at 0 doses, let alone 3.
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And they allowed us to look at the density of cases in Wuhan early in the pandemic. Even though there is some noise in the location data, Huanan market sits right in the highest density region.
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Paper 1: Given that the Huanan market is the only location in Wuhan for which prior epidemiological and geographic evidence exists that it might have been the site of origin of the epidemic, we set out to test this hypothesis statistically.
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We show that, contrary to what some may have believed, wished to believe or asserted, live mammals susceptible to SARS-CoV-2 were present at the Huanan market in the crucial months of November and December 2019.
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Here is a link to 239 consensus genome sequences, assembled by
@xrayfoo
, from sequencing reads of 2.3.4.4b H5N1 influenza A virus from cattle and other species.
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Into the weeds:
One reason it is particularly frustrating that full metadata has not been shared for genome sequences my colleagues and I have assembled from raw sequence read data released by
@USDA
/
@USDA_APHIS
, is that without those dates...
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1: We have just posted a study suggesting there may be no real
#SARSCoV2
genomes that are transitional between lineages A and B. Arcane, right?
But stick with me - this stuff is *absolutely* crucial to figuring out how the pandemic got started.
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11 of 10: Important to add that T cell immunity and non-neutralization antibody responses are likely to provide considerable protection against severe disease and death even if omicron turns out to be a very serious neutralizing antibody escape variant.
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We found that cases in December were both nearer to, and more centered on, the Huanan market than could be expected given either the population density distribution of Wuhan, or the spatial distribution of COVID cases later in the the epidemic. Its epicenter was at the market
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This strongly suggests that BOTH lineage B and lineage A arose at the Huanan market and began spreading into the Wuhan residential community from there. More on that in a bit.
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@hholdenthorp
So, so sorry.
And the trivialization that COVID mostly kills "just" old people: 😡
Your mom's life cut short by 5 years? Or even just 1? Same for 100s of 1000s like her? It leaves us so impoverished.
Memories, wisdom, love that stretched back nearly century lost too soon.
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Very good thread on the current crescendo of disinformation and misinformation on the origins of the COVID-19 pandemic.
“The real opposition is the media. And the way to deal with them is to flood the zone with shit.”
Steve Bannon’s quote explains everything about why these increasingly deranged “intel” about the origin of COVID are coming out now, prior to declassification of actual intel.
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@PeacockFlu
was the first person I know of who homed in on how interesting this human's virus was, in the context of the cattle H5N1 outbreak, in this piece by
@HelenBranswell
.
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Tremendous team effort:
Paper 1.
Led by
@K_G_Andersen
and me:
@josh__levy
@LrnM9
@acritschristoph
@jepekar
@stgoldst
@Angie
Rasmussen
@MOUGK
@WildCRU_Ox
@MarionKoopmans
@suchard_group
Joel Wertheim
@LemeyLab
@robertson_lab
Bob Garry
@edwardcholmes
@arambaut
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Striking contrast with cases from later in the epidemic, when the virus was more widespread in Wuhan. In early 2020, you see cases all through central Wuhan, on both sides of the Yangtze.
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It happened to be a stall that one of us,
@edwardcholmes
, had visited 5 years before the pandemic, and where he had taken this photo of a raccoon dog.
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And that means the outbreak could be somewhat older or younger than our current estimates.
We want to be able to understand, ASAP, how this cattle outbreak originated and what is full consequences might be.
And we have at least one hand tied behind our back at the moment.
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We used the maps in the WHO mission's report on the origin of SARS-CoV-2 to extract latitude and longitude for most of the known COVID-19 cases from Wuhan with symptom onset in December 2019.
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The differences suggest that the individual was either infected in a separate event — maybe not via a cow, but through contact with infected wild birds — or that there might have been another line of viruses in cattle early on and it has since died out.
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“It’s basically too distant a cousin to be connected directly to this outbreak, which either means it’s a second spillover or there was an early bifurcation of the cattle sequences,” Peacock said.
<End text from Helen's article:>
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While there are caveats we mention in the preprint (please read it) and neither this preprint nor the other have been published post peer review, the location of stalls selling live mammals was highly predictive of where environmental positives were located.
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"is that that means likely that person became infected through a herd that we did not receive any samples from for testing,"
"There were herds that had clinical signs in that geographic area before we had the first herd that we had positive H5N1 test results in.
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I believe the combined evidence (especially that this person likely became infected from cattle) points strongly in favour of the hypothesis that the human virus and the current sample of cattle virus are descendents of a single jump of H5N1 from birds into cattle.
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Hard to believe the level of idiocy/dishonesty that could lead to such distortions...but it is of course no longer hard to believe! Good for a laugh, though. And the history books.
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On origin of
#SARSCoV2
It is sad, and fundamentally anti-science, to spin a conspiracy theory out of scientists changing their views when they learn something they hadn't previously known.
“When the facts change, I change my mind - what do you do, sir?”
-John Maynard Keynes (?)
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This is a great thread on how disinformation on the origin of COVID-19 can snowball into a media storm of misinformation.
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Combining the findings of the two papers, we thus concluded that these two cross-species transmission events happened at the Huanan market (more on what we learned about within the market in a bit).
And we suspected that it was because A happened perhaps a week or two....
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Surprisingly, uses cases for which we could link a location and genome sequence - and this is one of *the* most important findings in this paper - we found that so-called lineage A viruses (the ones that had not been found at the market)....
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@jeffykao
and
@KatherineEban
. Because you have not given me sufficient time to respond fully to your queries about
@SenatorBurr
's upcoming commission report on the origin of COVID-19, nor made it clear that you would incorporate the additional information...
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Nice 🧵from
@adriancjr
: viruses that have not become less virulent over time.
One correction: the M group of HIV-1 emerged ~1910, not in the 1960s...so it has maintained its virulence for ~century.
If most transmission occurs before illness, little selection for low virulence.
This 🧵is a layman's understanding regarding virus pathogenicity and evolution: science only says that viruses which kill all their hosts will disappear. That's all. From this, it doesn't follow that viruses have an "inner desire" not to kill their hosts or to become milder.
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Great article from Eddie Holmes on many of the key scientific, political and social aspects of this question.
In science we can't prove things, so I wouldn't have chosen the title. But our studies *should* lay to rest "lab leak" origins (multiple).
1/n
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I feel I must reply to a comment from
@DavidRelman
in a recent
@nytimes
article on a piece of mine in
@ScienceMagazine
on why a careful analysis of the earliest known cases in Wuhan indicate that the pandemic started at the Huanan Market.
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The genetic sequence from the human case, which occurred on an unidentified farm in Texas, is sufficiently different from the cattle sequences that it can’t be easily linked to them, he said.
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Paper 2.
Led by
@jepekar
,
@suchard_group
,
@K_G_Andersen
, me, and Joel Wertheim:
@afmagee42
,
@EdythParker
,
@niemasd
,
@gkay92
,
@TanyaVasylyeva
,
@acritschristoph
,
@josh__levy
,
@LrnM9
,
@suchard_group
,
@edwardcholmes
,
@arambaut
,
@akaEscapePlan
,
@KatherineIz
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One striking (to us at least) finding: one stall had 5 environmental positive samples for very animal-centric surfaces, including a "metal cage in a back room". And the was one of the stalls we know was selling live mammals illegally in late 2019. But, there's more...
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Cats, chickens, blackbirds and grackles on farms with sick cattle are all getting infected by spillback. This human is no different, likely.
I suspect that we will find, as the number of sequenced cattle viruses grows, ones on the same branch of the tree that led to this human.
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@edwardcholmes
Coda: As we were doing the final quality checks on these papers yesterday, this preprint by George Gao et al posted.
And it found that lineage A was indeed found at the Huanan market, in a swab from a glove (sample A20).
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<Start text from Helen's article:>
“If you look at all the cattle sequences together, they all cluster, as do the cats and the chickens and the grackles and stuff.”
“The thing that doesn’t fit that picture is the human case,”
he said.
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Terrific reporting from
@sciencecohen
.
I'm quoted saying testing (only) cows crossing state lines is a "drop in the bucket".
But at least it is a start, sampling asymptomatic cattle, which will yield important insights even if it might not stop spread.
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@EricTopol
@USDA
@CDCgov
Welcome developments. Important correction, however:
"—First bird->cow transmission likely in Texas late 2023"
Our analyses indeed indicate late 2023 origin. But the viruses in Texas cattle are clearly "derived", and not the first in cattle.
Jump happened elsewhere.
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showed an extremely strong geographical association with the Huanan market (bottom of the table):
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One last thing - this suggests, but does not prove, that the common ancestor of both the main, and putative minor, bovine H5N1 lineages existed in Texas.
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8: Lots of speculation in this thread. Caveat emptor.
But the cool thing is that within days we will have data on phenotypic properties like neutralization titers with this newly discovered variant.
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...from December 2019 up until mid February of 2020. About 1/3 are lineage A and 2/3 lineage B. We find that the were very likely at least *two* origins SARS-CoV-2 - one for lineage A and one for lineage B. The patterns in the phylogeny are the giveaway.
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Digging deeper, we found a report from the China CDC, who had done testing of environmental samples (swabs of surfaces) in the market, that provided details missing in the WHO report. Like, if a stall was "positive", how many samples were positive there...
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🚨🚨🚨
Well here's one I missed since May 24 by Chang et al.
Thanks to SAGO report for the tip-off!
43,850 samples from 32,484 blood donors in Wuhan Sept to Dec 31, 2019.
*0* positive for SARS-CoV-2 by the definitive assay, neutralization titers. 1/
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I want to comment on this exchange. One person is wrong and one is right. There is, in fact, strong physical evidence suggesting an origin of this pandemic at the Huanan market in Wuhan.
A quick 🧵
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But it looks to me like a strong possiblity that this has been circulating in cattle for months under our noses, even before the first inkling there might be something new in February.
This reveals massive gaps in our pathogen surveillance and detection systems.
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I admit I can't explain their negative results in negative controls. But my money is on the positives being false positives.
The Chinese government is keen to assert that the pandemic started outside China. I fear this study will play right into that narrative. 24/24
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And what surface were they from? We also were able to go through business registries and things like record of fines for the sales of illegal wildlife, to show that more businesses that realized during the WHO study had been selling live mammals in late 2019...
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Congratulations
@edwardcholmes
!
The science of viral genomic epidemiology stands on the shoulders of this guy👇.
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