From Dispositive to Disposable:
How the Market Papers have Aged

Not right. Only the Worobey et al. preprint made geographical conclusions, and it was led both by me and by Kristian Andersen. That passage in quotes is indeed language from that preprint, yes. Importantly, though, since your questions below, combined with this statement, seem to imply otherwise, we were no less definitive in the peer-reviewed article in Science, whose very title notes that the Huanan market was the early epicenter of the pandemic, and whose Abstract states, unambiguously, that “our analyses show that the Huanan market was the epicenter of the COVID-19 pandemic”.

If the Senator’s commission’s report states or implies that the preprint and the Abstract differed in substance on this, then its authors and/or advisors are mistaken or they are being misleading or dishonest.

Now that this has been drawn to your attention, I hope you won’t imply in your article that the preprint differs from the published article on this crucial point since that would misinform your readers and perpetuate misinformation or disinformation that may be present in the report. (I should emphasize that I am responding to all of your questions knowing nothing of the reliability of the source from whom you say you received what you say are drafts of the report.)

Not quite right or complete. We found the home locations of 155 of the earliest known cases to be centered on (not “around”) the market to an extent that could not be explained by chance. But we also found them to lie much closer to the market than could be expected by chance, a separate and equally important analysis.

But even more importantly, we found the distance to, and centering on, the Huanan market of cases with no known epidemiological link to the Huanan market, to be particularly strong.

Not quite right. The analyses in our other paper (led by Jonathan Pekar and Joel Wertheim, as well as by Marc Suchard, Kristian Andersen and me) were blind to geography. It is the combination of (1) the geographical, within-market, and other analyses in Worobey et al. and (2) the genomic and epidemiological analyses in Pekar et al., which indicated a roughly 99.5% probability that there had been at least two separate introductions from a progenitor virus population that lead to overall conclusions about two jumps at the market.

Worobey et al. on its own shows that the Huanan market was the epicenter of the pandemic and that both lineage B (already known) but also lineage A are geographically associated with it.

Pekar et al. states:

“The presence of potential animal reservoirs, coupled with the timing of the lineage B primary case and the geographic clustering of early cases around the Huanan market (39), support the hypothesis that SARS-CoV-2 lineage B jumped into humans at the Huanan market in mid-November 2019.”

In a related study (39), we show that the two earliest lineage A cases are more closely positioned geographically to the Huanan market than expected compared with other COVID-19 cases in Wuhan in early 2020, despite having no known association with the market. This geographic proximity is consistent with a separate and subsequent origin of lineage A at the Huanan market in late November 2019. The presence of lineage A virus at the Huanan market was confirmed by Gao et al. (43) from a sample taken from discarded gloves.

It is of course an evidentiary gap, but, in light of the findings in our recent pair of Science papers, plus many other papers that have been published since the pandemic began, it is not significant. Our two recent papers establish that a natural zoonotic origin is the only plausible scenario for the origin of the pandemic. The Senator’s commission’s report cannot change the scientific evidence.

Moreover, this issue is discussed at length in Worobey et al.:

“Notably, none of the live (known to be susceptible) mammals from species we identify here as present at the Huanan market in November 2019 have been reported to have been tested for evidence of SARS-CoV-2 infection. The only live mammals ‘from’ the market among the 188 appear to have been animals such as stray cats, dogs, snakes, rabbits, and mice. Indeed, of the 188 animals tested, 167 were those species or hedgehogs, pigs, chickens, salamanders, crocodiles, turtles, fish or sheep (7). Only 21 individuals from traded mammalian species likely susceptible to SARS-CoV-2 infection were tested – but these were dead, of unknown procurement date, and refrigerated or frozen, and therefore unlikely to be a source of human infection: six “bamboo rat”, six “muntjac”, six “badger”, two “wild boar” and one “weasel” (7). Some of the wild mammals were screened (negative) for active SARS-CoV-2 infection by qRT-PCR, but a very low number have sampled from Hubei province (57).”

“In addition, bamboo rats, porcupines, and wild boar from farms in Hubei supplying the Huanan market, sampled during February and March 2020, also showed no sign of active infection (7). Unfortunately, to our knowledge, no serological testing was conducted on animals from within the market or from farms supplying it, nor on farm workers or animal traders in those supply chains. Indeed, both the Huanan market and the farms in Hubei province that supply it (48) were rapidly shut down before such sampling occurred. Hence, it is apparent that by the time the Huanan market was closed, and animal sampling at the market began, the SARS-CoV-2-susceptible live mammals that had been on sale there in the preceding months (Tables 1 and S5) were no longer present (7).”

“While >80,000 animal samples were tested and no evidence was found for presence of, or exposure to, SARS-CoV-2 (7), this is far from conclusive evidence for most animals. The negative predictive value of the surveys depends on the assumed prevalence. For serology, for instance, if one assumes a reservoir host in which the virus is endemic, seroprevalence likely is high, but will depend on the age of the animals and infection dynamics in that particular species. In addition, China is a vast country, and the possible sources of animals could be over a long distance. Therefore, the catchment area for surveillance studies is huge (58). Therefore, tracking back along the market supply chain is crucial for a more targeted effort, as recommended in the WHO mission report (7). In addition, it is possible that a one-off spillover event occurred on a farm that supplied the market. Such events would be needles in a haystack that are virtually unresolvable.”

I asked for the report so that I could verify assertions about its content like this. You declined. I will wait with curiosity to see if it says precisely this. It is important, for example, for me to answer your question above, to know if the report actually says that it “acknowledges” that I and my co-authors are in a difficult position of trying to figure out which data to rely on.

If it does say that, it is spectacularly wrong. First, “the report” (which really means its advisors and writers) is in no position to “acknowledge” whether we feel that we were or are in a difficult position without asking us! As it happens, I can speak for myself here. With respect to the two papers that seem to be a focus of the report and your reporting, I was not put in a difficult position of trying to figure out which data to rely on due to lack of candor from China. Indeed, this is standard lab leak narrative that I have called out as dangerous nonsense in the past (“Chinese scientists and authorities are liars. We can’t trust the data and especially those natural spillover conclusions.”)

The fact is, the data used in both these studies are extremely reliable. A large sample of genomic data captures early events in the evolutionary history of an outbreak. Scientists have never had genomic data from every early case from a pandemic. It’s always a subsample, and the methods used are tailored to deal with that. And the genomic data required nothing less and nothing more than the quality control we and hundreds of other researchers do for any similar viral genomic epidemiology analysis.

And regarding the geographic and environmental sampling data in the Worobey et al. paper: the notion that Chinese authorities, who indeed are now pushing ridiculous claims that the pandemic originated outside of China when our results show that the pandemic’s epicenter was the Huanan market, would have cooked the books so that two and half years after collecting the data we would discover patterns like this?:

Which shows that the area with the highest probability of drawing a home address of one of the earliest COVID-19 cases in the world was a tiny area right around the Huanan market? It’s just silly. One needs only to think through how unfavourable to what Chinese authorities might wish the data looked like to see that the reliability of the data, and the integrity of the Chinese scientists who generated them, shine through like a beacon.

That is not to say that China is open about everything to do with COVID-19, not by a longshot. But it is a particular sort of nonsensical to imagine that China would frame itself for allowing a hugely embarrassing repeat of the market-based emergence of the original SARS to cause the biggest pandemic in a century.

We are aware of many of these comments, which are a cottage industry on Twitter. These comments are either intentionally misleading or are the result of honest misunderstandings, perhaps due to a failure to read our papers, which address these issues in great detail.

Let’s take the notion that “your dataset of cases may be incomplete”. Of course it is incomplete. No data set of early cases of a pandemic disease has ever been complete. And this particular pathogen only lands a small fraction of infectees in the hospital. Again, that has been discussed in my work extensively. But that doesn’t affect the analyses or conclusions.

Now regarding the ascertainment bias issue: if you have read our paper, you will have noticed that the really interesting part of the results involves not cases epidemiologically linked to the market, which could indeed have been affected to some degree by ascertainment bias, but cases who were interviewed and said they had no link. Didn’t work there, didn’t shop there, didn’t knowingly have contact with anyone who had. They have an even strong geographical association with the market than cases who worked there. (And we explain why this is, if you’d like to understand it, in the paper.) So this notion that our results were compromised by ascertainment bias is a complete canard.

“Several observations suggest that the geographic association of early COVID-19 cases with the Huanan market is unlikely to have been the result of ascertainment bias (see the supplementary text and tables S2 and S3) (39). These include (i) few, if any, cases among Huanan market–unlinked individuals are likely to have been detected by active searching in the neighborhoods around the market, only in hospitals, because all of the cases analyzed here were hospitalized (7); (ii) public health officials simultaneously became aware of Huanan-linked cases both near and far from the Huanan market, not just the ones near it (fig. S11) (5); (iii) Huanan market–unlinked cases would not be expected to live significantly closer to the market than linked cases if they had been ascertained as contacts traced from those market-linked cases; and (iv) seroprevalence in Wuhan was highest in the districts around the market (40, 41). It is also noteworthy that the December 2019 COVID-19 cases that we consider here were identified based on reviews of clinical signs and symptoms, not epidemiological factors such as where they resided or links to the Huanan market (7), and that excess deaths from pneumonia rose first in the districts surrounding the market (42). Moreover, the spatial relationship with the Huanan market remains after removing the two-thirds of the unlinked cases residing nearest the market.”

With further details in the supplement.

First, this is not exactly breaking news. The same animal data were reported in the joint WHO-China study report on the origin of the COVID-19 “China Part”, cited in and discussed at length in the Worobey et al. paper in Science. Moreover, we discuss in great detail that no relevant live animals from the market were tested.

As my colleague Jonathan Pekar notes “The dominance of lineage B simply suggests that lineage B was introduced into humans before lineage A. If the animals in the Huanan market were infected with SARS-CoV-2 or its progenitor, there was likely limited genetic diversity among these viruses. In fact, multiple introductions resolve why lineage B predominated the early pandemic. Additionally, the Gao preprint indicates that lineage A was also at the market, thereby supporting the introduction of both lineages at the market.”

I would add that if the report really says that, then its authors and advisors cannot have read and/or understood Pekar et al. and Worobey et al. Or they are not being honest.

The article appeared on page A4 not on the front page! For goodness sake. And as you well know, you should be asking the NYTimes for insights into their editorial decisions, not me. Though I believe the word “dispositive” played no role in their decisions.

context

Editorial note, added retrospectively

"Not on the front page" is technically correct but understates the placement.

The Times's "Today's Headlines" digest for Sunday, 27 February 2022 — the morning after the preprints and the NYT feature dropped — listed "New Research Points to Wuhan Market as Pandemic Origin" as the lead item under Editors' Picks, immediately following the day's three Top News stories, all on Russia's invasion of Ukraine (which had begun three days earlier). On a Sunday when the war legitimately dominated every top slot, the market-origin piece was still the most prominently featured non-Ukraine story the paper ran.

Since this is a well-worn talking point on lab leak Twitter, it does make me wonder about the extent to which your reporting will simply regurgitate, uncritically, such talking points. Given that you have “given” me very little time to respond to your queries, and I am assuming that you have not actually approached the NYTimes reporters/editors themselves about this since you wouldn’t be asking me if you had, this comes across as a deeply unserious effort at reporting the facts. While this comes as no surprise from Katherine and Vanity Fair, I’m genuinely shocked and dismayed to see such a journalistic practice from ProPublica, who I have admired.

You mention that you have seen “drafts”, plural, of the report. Did you really need to leave me less than 22 hours to respond to your queries? Did you really need to write your characterizations of issues pertaining to my work and then ask me to correct their inaccuracies, rather than seeking my input instead of writing inaccurate text?

That is correct. The entire paper changed quite a bit, not least because the preprint was not written in the style, format or length of a Science Research Article. It is true that the word “dispositive” did not appear in the published paper. That was a choice we made ourselves in part because the word is a legal one we realized is not best suited, or well-defined, for a scientific audience. Nevertheless we used similar language in the Science paper: “our analyses indicate that the emergence of SARS-CoV-2 occurred through the live wildlife trade in China”.

Most importantly of all, none of our results were weakened in the peer-reviewed papers compared to the preprints. Indeed, they were vastly strengthened.

As Jonathan notes: “There have been repeated introductions of other viruses too, including several coronaviruses. MERS-CoV spills over into humans regularly, and there have been dozens of introductions. SARS-CoV spilled over into humans multiple times. Even recently, there were two separate introductions of porcine deltacoronavirus in Haiti. The animals in the Huanan market were not independent: they were from the same area of the market, with SARS-CoV-2 likely circulating among them and other animals there. Additionally, after humans exposed and infected mink with SARS-CoV-2, the virus rapidly spread through mink farms and then was introduced back into the human population dozens of times. The rare evolutionary events (e.g., developing the ability to bind to ACE2, developing the ability to replicate in humans, spilling over from bats to an intermediate host) all happened beforehand. As evidenced by SARS-CoV-2 itself and other viruses, once a virus is able to infect and transmit among humans, repeated introductions into the human population when humans are in consistent contact with the source—here, animals at the Huanan market—is not unlikely.”