It is hard to find the time to post here. I’m getting lots of requests to help scanning papers for image problems, and am also traveling a lot to give talks and be in panels. So my ‘monthly’ digests have now turned into quarterly digests, hahaha.
These past months, I have traveled to Berlin to receive the Einstein Foundation Award, to Oxford for the FAIRS Meeting, participated in a workshop in Stockholm organized by the Royal Swedish Academy of Sciences about the Reformation of Science Publishing, a conference in London at the Royal Society about the Future of Science Publishing, and a gathering with other science detectives and journalists in Krakow, Poland. In between, I gave several talks at research institutions and medical schools. I am getting pretty good at packing suitcases!
Here is a round-up of some noteworthy articles about research integrity.
Apologies for not posting for a while. Fall 2024 was a busy time for me, with travel to give talks in Australia and Singapore and some events in the US. Instead of trying to catch up with everything that has happened since September, here are some highlights.
Einstein Foundation Award
I’m thrilled to have won the 2024 Einstein Foundation Award for Promoting Quality in Research. The Einstein Foundation Berlin selects three winners each year. The 2024 winners are:
Early Career Award: Helena Jambor and Christopher Schmied at PixelQuality – Best practices for publishing images. ‘PixelQuality has established guidelines and checklists for publishing clear and reproducible images. It now aims to disseminate and refine them to handle AI-assisted image generation and analysis.’ ‘Research images are the proof of scientific findings, not just visuals. PixelQuality has set new standards for their reproducibility and transparency.’
Institutional Award:PubPeer – ‘PubPeer has become an essential part of the research communication landscape, with over 300,000 comments logged so far. It is estimated that since 2012, 19 percent of all retractions of papers worldwide in all academic domains had a prior discussion on the site. Beyond identifying flaws and fraud, PubPeer functions as an important tool to jointly improve scientific publications through „liquid feedback“.’
Individual Award:Elisabeth Bik – ‘Elisabeth Bik’s work in uncovering manipulated images, fraudulent research data and publications has created enormous impact all over the world. Her work has led to heightened awareness of questionable research practices and generated widespread attention to responsible conduct of research in the scientific community.’
The award ceremony will take place in March 2025 in Berlin, Germany.
The Einstein Foundation Award trophy is a piece of chalk, created by Professor Axel Kufus at the Berlin University of the Arts to honor ‘a basic tool that has been used to bring knowledge into the world for as long as we can remember’. Source: https://award.einsteinfoundation.de/about
The Bik Fund
Instead of accepting the Einstein Foundation award money for myself, I’ve decided to put it into ‘The Elisabeth Bik Science Integrity Fund’ – where I hope to help other science sleuths with small grants for e.g., traveling to conferences, buying equipment or software, or training. Our type of work often does not fit into the hypothesis-driven model of government or charity funds, so I hope to help by filling this funding gap.
It is my hope that we can make this fund grow, so we can help more integrity warriors in the future – donations to the Bik fund are tax-deductible and very welcome.
The book describes how Matthew Schrag, a neuroscientist at Vanderbilt University and a fellow image-sleuth, discovered possibly altered images in a highly-cited paper about amyloid plaques in Alzheimer’s patients and in other papers connected to the biotech company Cassava Sciences (see also below). It also gives a disturbing insight into the amount of fraud in neuroscience and the lack of action by journals, institutions, and government agencies.
Matthew Schrag and other ‘science sleuths’—Kevin Patrick, Mu Yang, and I—worked for two years checking thousands of papers in Alzheimer’s research and related fields for the book, uncovering a concerning number of potential problems in papers by Sylvain Lesné, Berislav Zlokovic, Eliezer Masliah, and others.
Charles Piller (right) and I at a book signing event for ‘Doctored’ – February 2025 at the Commonwealth Club in San Francisco, CA
Cassava Sciences Phase 3 did not work
I have written in the past (here and here) about problematic images in papers by Dr. Hoau-Yan Wang and Cassava Sciences (NASDAQ: $SAVA), a biotech company testing a drug targeting Alzheimer’s disease. These concerns were first spotted by Matthew Schrag and published in a Citizen Petition, in an attempt to halt Cassava’s clinical trials. Despite the apparent problems, the FDA did not stop Cassava’s clinical trials of their Alzheimer’s drug, Simufilam. But Cassava’s stock dropped significantly, upsetting a lot of investors.
For three years, fans of the $SAVA stock harassed the Dr. Wang critics – including me – claiming that the drug would work fine; that all stockholders would be rich as long as they would HODL; and that all our concerns were FUD. They joined forces in a SAVAges Discord app, where they talked about how one day they would all buy Maseratis, Lamborghinis, and even a SAVA island — and how retarded and fraudulent the SAVA-critics were.
The authorities begged to differ, however. In March 2024, Science reported that FDA inspectors had found many problems in Dr. Wang’s lab, ranging from uncalibrated instruments, lack of control samples, and stored data files, to leaving out outliers based on subjective criteria. Another report by the City University of New York (CUNY) to the Office of Research Integrity (ORI), leaked to Science, described ‘egregious misconduct’ in Dr. Wang’s lab. In June last year the Department of Justice announced that Professor Wang had been charged with operating a ‘Multimillion-Dollar Grant Fraud Scheme’.
Meanwhile, lawsuits were filed back-and-forth. Cassava Sciences was suing the people who filed the FDA citizen petition and who set up the website CassavaFraud.com, while stockholders were suing Cassava in a class-action lawsuit for misrepresenting the quality of the experiments performed by Dr. Wang. The Securities and Exchange Commission (SEC) charged Cassava with misrepresenting clinical trials result, and later settled for $40M. And CUNY, instead of officially announcing their misconduct findings, was investigating who leaked their misconduct investigation report to Science.
Finally, last December the biotech company announced that the Phase 3 trial did not meet the anticipated endpoints. In other words, Simufilam did not halt or improve Alzheimer’s disease. The Cassava Sciences stock immediately dropped to $2-3 dollars, and the SAVAges Discord became a valley of despair. No more SAVA island.
Didier Raoult enters the Retraction Watch Leaderboard
As I’ve written previously, many papers from Professor Didier Raoult, the former director of the IHU Méditerranée Infection in Marseille, France, are problematic.
Some appear to contain manipulated images, while others describe research conducted without proper ethical permits. A number of Raoult’s studies were performed on vulnerable populations, such as homeless people, or on study participants in the Global South, which I [gasp!] dared to label neocolonial science.
As described in this paper by Fabrice Frank et al, the IHU-MI produced a set of 248 studies all with the same IRB approval number, 09–022. Despite sharing the same permit, the publications varied in terms of sample type, demographics, and countries. Other ‘multi-use’ IRB numbers were found too. Typically, an IRB approves one particular study, and researchers are not allowed to reuse this permit for other, unrelated, studies. Dr. Raoult appears to have cared little for such rules, however.
After raising our concerns on PubPeer and social media, and also writing to journal editors, several journals have started to issue Expressions of Concern and retractions.
In fact, Raoult has now earned so many retractions (32 as of today) that he has entered the Retraction Watch Leaderboard. The most significant of them is the retraction of the paper that claimed that Hydroxychloroquine could treat COVID-19. I criticized this paper in my blog post in April 2020, days after its publication. It took more than four years to get it retracted.
With over 600 of his papers on PubPeer and 225 EoCs, it seems safe to assume that for Raoult’s position on the Retraction Watch Leaderboard list, the only way is up.
Over the last week I’ve been analyzing a set of papers from a research group at Brigham and Women’s Hospital, which falls under the Harvard Medical School. The papers have the usual image problems we unfortunately encounter so often, such as duplicated photos of mice and overlapping Western blots.
But this set also includes a 2022 paper that appears to have copied/pasted several figure panels from other researchers and even from scientific vendors. Most of these problems were found with ImageTwin or reverse image searches.
Quick links [the spreadsheet and slide have been updated with an additional problem found on Feb 2, 2024]:
spreadsheet with the 28 29 papers found with PubPeer links [Excel file]
slide deck with the 58 59 image problems found in the 28 29 papers [PDF].
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”.
This blog post expresses my personal opinion and is not an accusation of misconduct.
An exciting new paper about STAT3
The STAT (“signal transducer and activator of transcription“) protein family consists of proteins involved in many important aspects of cellular function, such as growth, differentiation, and apoptosis (programmed cell death). These transcription activators are activated themselves if other molecules bind to them, and they act as messengers that transfer changes outside of a cell to inside the nucleus, by binding to promoters and determining which genes are switched on or off. One of STAT proteins, STAT3, in particular has been the topic of many studies, because it might play a role in cancer. Simply put, the continuous activation of STAT3 might induce cancer, and STAT3 might be a target for new anti-cancer drugs.
A recent study, published on 28 August 2019 in Nature by authors from Harvard Medical School and the Dana Farber Cancer Institute, therefore gained quite some attention. It reported on one of the ways by which STAT3 can be activated, through the binding of fatty acids in a process called palmitoylation.