Last week we discussed the problem of how widespread cheating is in scientific research. This week we review a specific case that has been publicized for more than a decade.
Some people seem larger than life. Carlo Croce is such an individual. Personally, I have read and admired many of his research publications for years, and it was only in reading about cheating in research that I became aware of the scandal that has grown to envelop him and his work.
Croce was born in 1944 in Milan, Italy, and earned his MD at La Sapienza University in Rome in 1969. He emigrated to the U.S. and joined the staff at the Wistar Institute in Philadelphia, a well-known NCI-funded basic science cancer research facility. By 1980, he had risen to become its associate director. In 1988 he moved to Temple University and in 1991 he became director of the Kimmel Cancer Center at Thomas Jefferson Medical College.
His research has focused on the discovery of new genes that play a role in carcinogenesis. One important such gene was ALL-1, which is critical in the pathogenesis of acute leukemias. It is involved in at least 10% of acute myelogenous leukemia. His laboratory was also responsible for the discovery of the BCL-2 gene in 1984, which is responsible or plays a role in a number of malignancies, most prominently in B-cell malignancies. This gene is also important in various solid tumors, including colon cancer, lung cancer and breast cancer. Various efforts have been made to develop drugs to address this tumor suppressor gene, but none has yet achieved FDA approval.
Perhaps his best known discovery was the FHIT gene (fragile histidine triad diadenosine triphosphatase) in 1996 which plays a role in the regulation of apoptosis (regulation of cell death). This gene appears to be important in colorectal cancer, lung cancer and esophageal cancer.
Over the course of his research career Croce created an enormous laboratory devoted to gene discovery, which was highly successful in elucidating genes that had the potential to be relevant in possible future drug discovery. Over time, he received as much as $100 million in National Institutes of Health funding alone for this work and widespread honors and acclaim. Around 2000, the cancer center at Ohio State University (OSU) was seeking to expand and so it recruited Dr. Croce, who went there in 2004 with a team of 100 scientists and staff; he became the chair of the Department of Cancer Biology and Genetics. He received an enormous salary (ultimately reaching $850,000) and an endowed chair.
Questions were raised about Croce as early as 2007, but these did not relate to his research but to other possible improprieties. There was a grant application submitted in his name which was very similar to a grant previously submitted by one of his junior colleagues. It was also alleged he had improperly pressured colleagues for co-authorship attribution, and similar allegations. OSU launched an investigation into these complaints, but nothing came of them.
Questions regarding his research began in 2013 and were investigated internally at OSU but did not become public until publication of a New York Times article in 2017. As with other such claims, they involved Western blots (these are gel electrophoresis analyses performed in order to separate proteins in blood or other samples) where the figures were alleged to have been manipulated or the figures were reused inappropriately in more than one publication, and similar claims. In each instance, these “errors” involved junior members of the research teams. Investigation by OSU and outside agencies always concluded that Croce himself had never directly been fraudulent. He was, however, severely criticized for poor oversight, sloppiness in the laboratory, and poor mentoring of his underlings. Much of this was seen as the result of his heavy traveling and too-busy schedule and too large a lab with a lack of direct control. The outcome was that he was initially removed as chair of his department in 2018, and his endowed chair was rescinded in 2021. Altogether, 11 papers he co-authored have been retracted. Multiple others have had “corrections” submitted to the journals where they were published.
Croce himself is litigating against OSU regarding the removal of his chair. It is unclear whether The Office of Research Integrity will take further action.
Croce himself continues as a research professor at OSU.
Finally, it is worth mentioning as a further illustration of his total lack of concern for the establishment that in an era when no cancer researcher would deal directly with the tobacco industry or lobby, Croce served as an adviser on the scientific advisory board of the Council for Tobacco Research throughout the 1990s.
Alfred I. Neugut, MD, PhD, is a medical oncologist and cancer epidemiologist at Columbia University Irving Medical Center/New York Presbyterian and Mailman School of Public Health in New York. Email: [email protected].
This article is for educational purposes only and is not intended to be a substitute for professional medical advice, diagnosis, or treatment, and does not constitute medical or other professional advice. Always seek the advice of your qualified health provider with any questions you may have regarding a medical condition or treatment.
