Investigation finds ‘egregious misconduct’ by CUNY scientist

In a report shared with Science in October 2023, a committee investigating allegations of misconduct by Dr. Hoau-Yan Wang, a professor at the City College of New York (CCNY, which falls under the City University of New York (CUNY)), found evidence that was ‘highly suggestive of deliberate scientific misconduct’. Dr. Wang has been a frequent collaborator with Cassava Sciences (Nasdaq: SAVA), a biotech company working on a drug called simufilam for the treatment of Alzheimer’s disease. Unfortunately, Dr. Wang was unable to provide the committee with any original data or notebooks that could have addressed concerns about his work. Although the suspicions of manipulated images could therefore not be proved, the investigation revealed “long-standing and egregious misconduct in data management and record keeping by Dr. Wang”.

I first wrote of concerns about Dr. Wang’s papers in August 2021 after a Citizen Petition (CP) was filed with the FDA seeking to halt clinical trials of Cassava Sciences’ experimental drug Simufilam. In my blog post ‘Cassava Sciences: Of stocks and blots‘, I wrote about several papers by Wang et al. with problematic Western blots and overlapping photos of tissue sections. I confirmed several concerns raised in the CP and also found five additional papers with similar issues. In a second blog post ‘Cassava Sciences: Of Posters and Spaghetti Plots‘ I discussed concerns about a conference poster in which some data points appeared to have been altered. The $SAVA stock had already dropped significantly after the CP was filed, but before my blog posts were published.

It is worth posting here again that I do not own – nor have ever owned – Cassava Sciences stocks or held short positions, nor any stocks or long positions on competing pharmaceutical companies. Although my general work is crowdfunded through Patreon, I was not paid by anyone to raise these specific concerns about Dr. Wang’s papers or Cassava Sciences.

As of today, 42 papers by Dr. Wang have earned PubPeer posts, seven papers have been retracted, and five have been marked with an Expression of Concern, as per the Retraction Watch database. See also Retraction Watch’s coverage here, here, here, and here.

A very long research misconduct investigation

I assumed that the people who filed the CP in August 2021 had already shared their concerns with CUNY. But because I found some additional problems in several of Dr. Wang’s papers, I wrote to CUNY to report my concerns in November 2021. The standard procedure at most US universities is that misconduct allegations – provided they are legitimate concerns – will first prompt a preliminary Inquiry phase, followed by an Investigation phase.

After receiving no updates from the university, I asked CUNY in April 2022 if the initial inquiry had moved forward to the investigation phase. The Associate Provost for Research wrote back that I was ‘not deemed the original Complainant for this research misconduct allegation‘ and that ‘no additional information may be provided at this time‘. This was unexpected since CUNY’s own research misconduct policy states that the complainant needs to be informed about the progress from the inquiry to the investigation phase. There is no wording that this should only apply to the very first complainant. In any case, my reporting had also raised additional issues not included in the Citizen Petition, so for some concerns I likely was the first complainant. From my end, it appeared that CUNY was not following its own guidelines, and it seemed to me that the university appeared reluctant to investigate this case.

That same CUNY policy states that the inquiry phase should be completed within 60 calendar days, and that the next phase, the Investigation, should be completed within 120 calendar days.

If we allow for some extra time between the two phases, it seemed reasonable to expect a final report one year after the initial concerns were raised, which would have been around August 2022. But CUNY provided no update for more than two years.

Lawsuits and insults

Obviously, everyone following this case – both $SAVA shareholders as well as people interested in science integrity – was getting anxious to hear an update from CUNY.

Despite the concerns about the preclinical work conducted in Dr. Wang’s lab, reports about an investigation into stock manipulation by the Securities and Exchange Commission (SEC), and a criminal probe of the company by the Department of Justice (DoJ), Cassava Sciences continued enrolling patients in its Phase II and III trials.

Cassava Sciences vehemently denied any allegations of wrongdoing. Instead, in November 2022 the company filed a defamation lawsuit against the ‘perpetrators of a ‘short and distort’ campaign‘. The defendants included the two people who originally filed the Citizen Petition to the FDA – and who shorted the stock – as well as four people who had set up a website listing all concerns about the papers by Cassava Sciences’ collaborator Dr. Wang. Although I was named in the suit, I was not one of the defendants.

Meanwhile a group of disappointed $SAVA shareholders filed a class action lawsuit against Cassava Sciences accusing them of securities fraud, since they lost a lot of money when the stock price crashed after the CP was released in August 2021.

Emotions also ran high on social media, with jokes turning into insults and conspiracy theories. One large shareholder even accused critics of Dr. Wang’s papers of ‘genocide‘ because he claimed the concerns were preventing the drug from being approved by the FDA for use in Alzheimer’s patients.

A CUNY report obtained by Science

Finally, in October 2023, more than two years after the initial concerns about Dr. Wang’s papers had been shared with CUNY, there was an update on the CUNY investigative committee’s findings. This was not in the form of an official report published by the university, but in a report obtained by the journal Science. In an October 12 Science article, Charles Piller shared excerpts from the 50-page report, which states:

‘The commitee has found evidence highly suggestive of deliberate scientific misconduct by Dr. Wang for 14 of the 31 allegations. However, we were unable to objectively assess the merit of the allegations due to the failure of Dr. Wang to provide underlying, original data or research records and the low quality of the published images that had to be examined in their place.’

‘… our investigation has revealed long-standing and egregious misconduct in data management and record keeping by Dr. Wang. It appears likely that no primary data and no research notebooks pertaining to the 31 allegations exist.’

‘This is a source of deep frustration to the committee, which spent the better part of a year actively attempting to provide an objective investigation into these serious charges against Dr. Wang.’

Source: https://www.science.org/do/10.1126/science.adl3444/full/cuny_wang_final_report-1698701360173.pdf

The committee agreed that several papers authored by Wang et al. appeared to contain manipulated photos. But instead of addressing these concerns by providing the investigators with original, high-resolution films, scans, or notebooks, Wang gave them hundreds of image files, none of which appeared to contain originals matching the allegations investigated by the committee. Although the suspicions of manipulated images could therefore not be proven, the investigation revealed “long-standing and egregious misconduct in data management and record keeping by Dr. Wang.”

Dr. Wang also stated that many boxes with research records were thrown away ‘in response to a request from CCNY to clean the lab during the COVID-19 pandemic’, but it appeared that such a request was never sent. He also said that a hard drive was destroyed by IT services when they sequestered data from his lab.

The committee also found that Professor Wang had been running gels and blots himself, a practice that is highly unusual in most labs, where grad students, post-docs, and research assistants typically conduct almost all the lab work.

Although the investigation was already completed in May 2023 and the report was shared with the Office of Research Integrity (ORI), CUNY never published it nor did it take any steps regarding Dr. Wang. The final report was shared with Science by an anonymous person.

The report also mentions an independent image consultant hired by CUNY, who withdrew their services ‘citing legal risks to themselves and their business‘. I want to specifically state here that this consultant was not me. I am not independent in this case, since I was one of the persons reporting the initial allegations to CUNY.

Outrage by the SAVAges

Not surprisingly the $SAVA stock price dropped after the Science article was published on October 12, 2023, but quickly recovered in the following weeks. This may have been partially caused by angry social media posts by some Cassava Sciences stockholders, who started dismissing the report by stating that there was no evidence of misconduct (here, here, and here) and accusing the investigating committee of colluding with ‘the shorts’, Science, STAT News, The New York Times, with me, and whoever else they could think of, presumably to reinstate confidence in the stock (here, here, here, here, and here). They also sent threatening and racist tweets to the CUNY professor who was leading the investigation (here, here, here, here, here, here, and here).

A day after the Science article came out, Cassava Sciences released a statement from its CFO emphasizing that the report ‘makes no findings of data manipulation‘. Instead of dismissing the findings of the report (e.g. by sharing research data or original films), the press release appears to suggest that short-sellers might have played a role in ‘the leak‘. This seems to be a recurrent theme: blaming ‘the shorts’.

Two days later Cassava’s legal counsel Chris Cook sent a letter to CUNY with many concerns about the investigative report.

Perhaps as a result of this legal warning from Cassava (which really should not be mingling with institutional investigations IMO), CUNY released a statement saying that it will not comment on the accuracy of the investigation, and that it will stay (pause) the underlying inquiry, and investigate the process.

A mysterious lab notebook

In the midst of all these statements, Matt Nachtrab, a substantial $SAVA investor (he owns over 1 million shares) posted a surprising exhibit on X (previously Twitter): a photo of a lab notebook, with Dr. Wang’s name written on the front. In his post, Nachtrab writes: ‘I have seen some of these notebooks and pages, and I see no harm in sharing the attached image as evidence that there are notebooks that exist that were in the lab the whole time.‘

This tweet is surprising for two reasons.

First, it is surprising that Cassava Sciences shares lab notebooks with one of its largest private investors. If a company shares non-public information such as lab notebooks with a shareholder, one could imagine that the company might also share non-public information information about an upcoming bankruptcy, clinical trial failure, or SEC investigation with that shareholder. In this hypothetical scenario, said shareholder might then sell their shares before the bad news is made public and the stock drops, to prevent their losses. This is called ‘insider trading‘ and it is illegal. This is not saying that Nachtrab has been doing anything illegal now, but his tweet gives some insight into his intimate relationship with the company, casting doubt when he makes a future buy or sale of its shares.

Second, the existence of this lab notebook appears to contradict the CUNY investigative report’s statement: ‘the lab did not employ notebooks to record the details of the preparation or execution of the western blot experiments performed in the lab‘. Of course, the notebook could be empty (Nachtrab only showed its cover) or it might have contained notes irrelevant to the published Western blots.

Absence of evidence is not evidence of absence

So where are we now, after concerns about the CUNY papers were first reported in August 2021? More than two years later, it is clear that the CUNY investigative committee agreed that the images in Dr. Wang’s papers looked manipulated, but that they were unable to confirm or dismiss these concerns because Dr. Wang could not share a single film or notebook related to these images. Dr. Wang also stated that most of these lab data were tossed out. Therefore, the committee could not prove that those published images had been manipulated.

But as the saying goes, ‘the absence of evidence is not evidence of absence’. The lack of original data does not mean that the concerns about misconduct are actually false.

Dr. Wang should not have tossed his lab data. The Office of Research Integrity states that the intentional destruction of research records or refusal to share can be considered misconduct: ‘The destruction, absence of, or respondent’s failure to provide research records adequately documenting the questioned research is evidence of research misconduct.’

Some have argued that the allegations were about papers more than 6 years old, and that older data should not be investigated. But 16 of the 31 allegations refer to papers published in 2015-2021, so falling under the ORI six-year limitation since the concerns were raised in 2021. In addition, ORI has exceptions to this rule, and one of them is the “Subsequent use exception”, related to potential misconduct that is cited or used in newer publications or grants. So if one of the papers-under-investigation is older than 6 years, but is cited in a newer paper by the respondent(s), that paper might actually be included in research misconduct investigation – if I interpret this correctly.

Stating that papers older than 6 years will not be considered in research misconduct investigations may therefore not always be correct. Simply halting a research misconduct investigation because of a leaked report or legal threats by a company also appears to not be serving scientific integrity.

CUNY investigation in the news

I am sure there will be more news about this case in the future. Meanwhile, some other recent news articles about this case:

• Scientists Investigating Alzheimer’s Drug Faulted in Leaked Report – Apoorva Mandavilli – The New York Times
• CUNY Halts Investigation of Alzheimer’s Researcher – Apoorva Mandavilli – The New York Times
• Cassava implies ‘short-sellers’ to blame for leaking CUNY report alleging scientific misconduct – Max Bayer – Fierce Biotech
• Cassava Sciences: Update Following Leaked CUNY Report, Fundamentals Remain Unchanged – Seeking Alpha
• $500m Alzheimer’s drug scandal: NY scientist behind NIH-funded therapy busted for allegedly manipulating data in 20 research papers – now there are calls for trials to be cut off – Caitlin Tilley – Daily Mail