The following post was written by a former research fellow in the lab of Piero Anversa to whom we’ve promised confidentiality. Anversa has previously told us that he cannot comment because of an ongoing investigation.
Regular readers of Retraction Watch will note the recent news regarding the work conducted in the laboratory of Piero Anversa at Brigham and Women’s Hospital, a Harvard Medical School affiliate. In the early 2000s, his laboratory published a series of papers regarding the regenerative qualities of bone marrow-derived and cardiac-resident “stem cells.”
Those initial findings, as well as the research conducted since those early studies, have always been surrounded by controversy, as many have been unsuccessful in efforts to replicate their results. Controversy among competitors is not uncommon in our profession, but this particular one has blossomed into a formal investigation of their findings, and has, to date, led to the retraction of one paper and an expression of concern about another.
I think that most scientists, perhaps with the exception of the most lucky or most dishonest, have personal experience with failure in science—experiments that are unreproducible, hypotheses that are fundamentally incorrect. Generally, we sigh, we alter hypotheses, we develop new methods, we move on. It is the data that should guide the science.
In the Anversa group, a model with much less intellectual flexibility was applied. The “Hypothesis” was that c-kit (cd117) positive cells in the heart (or bone marrow if you read their earlier studies) were cardiac progenitors that could: 1) repair a scarred heart post-myocardial infarction, and: 2) supply the cells necessary for cardiomyocyte turnover in the normal heart.
This central theme was that which supplied the lab with upwards of $50 million worth of public funding over a decade, a number which would be much higher if one considers collaborating labs that worked on related subjects.
In theory, this hypothesis would be elegant in its simplicity and amenable to testing in current model systems. In practice, all data that did not point to the “truth” of the hypothesis were considered wrong, and experiments which would definitively show if this hypothesis was incorrect were never performed (lineage tracing e.g.).
Further, controls that suggested that the data might be artifactual were ignored or not conducted. However, I challenge the readers to determine any of this information from the published manuscripts. So how does this slip through the cracks for years? The fault for this can likely be attributed to multiple sources although a conspicuous lack of stringency in the peer review process of the journals in which they were published come to mind.
Beyond the science, ironically, a certain braggadocio also existed surrounding this hypothesis. Anyone who attended the pertinent sessions at the American Heart Association Scientific Sessions could attest to this. In essence, to Dr. Anversa all investigators who questioned the hypothesis were“morons,” a word he used frequently at lab meetings. For one within the group to dare question the central hypothesis, or the methods used to support it, was a quick ticket to dismissal from your position.
Information Segregation + Machiavellian Principles = Successful Lab
The day to day operation of the lab was conducted under a severe information embargo. The lab had Piero Anversa at the head with group leaders Annarosa Leri, Jan Kajstura and Marcello Rota immediately supervising experimentation. Below that was a group of around 25 instructors, research fellows, graduate students and technicians. Information flowed one way, which was up, and conversation between working groups was generally discouraged and often forbidden.
Raw data left one’s hands, went to the immediate superior (one of the three named above) and the next time it was seen would be in a manuscript or grant. What happened to that data in the intervening period is unclear.
A side effect of this information embargo was the limitation of the average worker to determine what was really going on in a research project. It would also effectively limit the ability of an average worker to make allegations regarding specific data/experiments, a requirement for a formal investigation.
The general game plan of the lab was to use two methods to control the workforce: Reward those who would play along and create a general environment of fear for everyone else. The incentive was upward mobility within the lab should you stick to message. As ridiculous as it sounds to the average academic scientist, I was personally promised money and fame should I continue to perform the type of work they desired there. There was also the draw of financial security/job stability that comes with working in a very well-funded lab.
On the other hand, I am not overstating when I say that there was a pervasive feeling of fear in the laboratory. Although individually-tailored stated and unstated threats were present for lab members, the plight of many of us who were international fellows was especially harrowing. Many were technically and educationally underqualified compared to what might be considered average research fellows in the United States. Many also originated in Italy where Dr. Anversa continues to wield considerable influence over biomedical research.
This combination of being undesirable to many other labs should they leave their position due to lack of experience/training, dependent upon employment for U.S. visa status, and under constant threat of career suicide in your home country should you leave, was enough to make many people play along.
Even so, I witnessed several people question the findings during their time in the lab. These people and working groups were subsequently fired or resigned. I would like to note that this lab is not unique in this type of exploitative practice, but that does not make it ethically sound and certainly does not create an environment for creative, collaborative, or honest science.
So what, if anything, did I learn from spending a period of my life in my scientific nightmare? The conditions I have written about are not unique, although the particulars of how the misconduct happened may be. The simplest explanation is that, in spite of the efforts of ethical watchdogs, these are behaviors that science is selecting for with its current funding and publication mechanisms. I was glad to learn of the investigation regarding this lab but without vigilance and alterations to current structures, newer, more careful versions of Piero Anversa will undoubtedly move in to take his place.