Tiffany Zhou | October 24, 2022
In the summer of 2022, Matthew Schrag, a neuroscientist at Vanderbilt University, came forward with reports of potential research misconduct in a highly cited 2006 Alzheimer’s study that was published in Nature. The 2006 Alzheimer’s study argued that the Aβ*56 amyloid plaque subtypes are the main cause of the neurodegenerative disease. The results of the 2006 study had been significant; up to 2006, no scientist had been able to prove a direct causative link between amyloid oligomers and Alzheimer’s. The results from the seminal paper therefore became a keystone of the broader amyloid hypothesis, which connects Aβ brain deposits to Alzheimer’s, and inspired further funding for work on these proteins (Piller 2022).
Overall, scientific misconduct, which includes forms of fabrication, falsification, and plagiarism, has serious consequences for both the individual and their overall field of research. Fraud detected in NIH-funded research can result in debarment from future grants and committees, fines, and even imprisonment (NIH 2019). Most importantly, false data can damage the integrity of the scientific community and result in wasted time and resources for researchers years down the line. In the investigative report with Science that revealed his findings, Schrag explained the importance of being a whistleblower: “You can cheat to get a paper. You can cheat to get a degree. You can cheat to get a grant. You can’t cheat to cure a disease,” he says. “Biology doesn’t care” (Piller 2022).
How was the research misconduct discovered?
Dr. Schrag first came across the possible errors in the 2006 Alzheimer study on PubPeer, an online platform where scientists provide feedback on post-publication research. Experts in the field had previously raised concerns about the replicability of the study’s results (Grimes 2022). His attention was drawn to possible manipulations of Western Blot figures. Using image analysis techniques to investigate, he found that several of the Aβ*56 bands were nearly identical, suggesting a post-experimental modification of data to fit the proposed hypothesis (Piller 2022). Schrag then brought his findings to Science, which sparked a 6-month investigation by image analysts and top Alzheimer’s researchers. Their review corroborated his claims and found further evidence of tampering with other blots, with the caveat that misconduct could not be proven without raw data from the original source.
“You can’t cheat to cure a disease, biology doesn’t care.” – Dr. Matthew Schrag
What implications does the research misconduct in the 2006 study have on Alzheimer’s research and the broader scientific community?
The discreditation of this previously fundamental work deals a blow to years of research on Alzheimer’s that built on the findings of the study. However, many researchers still have faith in the general amyloid/oligomer hypothesis. Dennis Selkoe, a scientist at Harvard University, says on this topic, “I hope that people will not become faint hearted as a result of what really looks like a very egregious example of malfeasance that’s squarely in the Aβ oligomer field” (Piller 2022). Studies by Selkoe and other specialists around the world have shown strong evidence for the effects of oligomers on Alzheimer’s development. Furthermore, it is crucial to note that in the past few years, top research journals have developed tools to screen for data and image manipulation in submitted articles, likely reducing the amount of falsified results that are published.
Despite fears of fueling public distrust in scientific research, Selkoe underscores the importance of critically examining the work of peers. In addition, Charles Piller, the Science reporter who worked with Schrag to expose misconduct, shares this sentiment: “It’s hard to say if being forthright and self-examining and being willing to confront error and potential misconduct in your own ranks will really build trust [but] the alternative is to allow that sort of activity to have a […] pernicious effect on the very work that you’ve dedicated your life to” (Mogensen 2022).
“We need to declare these examples and warn the world.” – Dennis Selkoe, Ph.D
In today’s fast-paced and ruthlessly competitive scientific world, the pressure to publish ground-breaking data with high frequency falls heavily on researchers. For a community that is largely built on trust, evidence of scientific misconduct, such as with the 2006 Alzheimer study, stirs up future questions about validating results and highlights the importance of checking the work of fellow peers. Hazarding the possibility of encouraging scientific skepticism is inevitable; rather, Schrag’s work has shown the importance of fostering a mindset of accountability and willingness to correct errors before they accumulate in the field.
Grimes DR. 2022 Jul 29. What an Alzheimer’s Controversy Reveals About the Pressures of Academia. The Atlantic. https://www.theatlantic.com/science/archive/2022/07/alzheimers-disease-data-fraud-sylvain-lesne/670995/.
Mogensen JF. 2022 Aug 17. An explosive new report could upend more than a decade of Alzheimer’s research. How did this happen? Mother Jones. [accessed 2022 Oct 10]. https://www.motherjones.com/politics/2022/08/alzheimers-research-image-photo-tampering-science-investigation-research/.
Piller C. 2022 Jul 21. Potential fabrication in research images threatens key theory of Alzheimer’s disease. Science. https://www.science.org/content/article/potential-fabrication-research-images-threatens-key-theory-alzheimers-disease.
Research Misconduct – Overview | grants.nih.gov. 2019. NIH. [accessed 2022 Oct 10]. https://grants.nih.gov/policy/research_integrity/overview.htm.