My Favorite Fraud

A paper I read more than 25 years ago taught me a lesson I'll never forget.

Sep 1, 2008
Steven Wiley

Last week I was at a scientific conference in which career development was a major topic. The audience included mostly scientists at an early stage in their careers, but also a few older scientists, like myself, who were to provide advice on how to manage laboratories and careers. Popular discussion topics included how to run lab meetings and deal with the egos of graduate students and postdocs. My particular advice included: Keep current with experimental technologies, and evaluate papers on a technical basis before trusting their conclusions.

I'm sure that this advice sounded to some like the musings of a compulsive technogeek, but it was prompted by an incident that happened when I was a postdoc.

I was a member of a weekly journal club that discussed the latest papers in the field of cell signaling and growth control. All presenters were to provide an assessment of the technical rigor as well as the importance of papers. In the summer of 1982, however, we encountered a paper that was far out of the ordinary.

The paper, by lead author Mark Spector, appeared in Cell and described a remarkable new protein kinase cascade that was proposed to be central to cancer.1 This was our area of research, and so it sounded particularly exciting. When we read the paper, however, we immediately judged it fraudulent. The scale of the work was impossibly large and yielded the kind of perfect data that we had never seen before. Plus, many aspects of the work made no technical sense. For example, following a six-step heroic purification process involving centrifugation, affinity chromatography, and isoelectric focusing, the researchers obtained 5.8 ųg of purified kinase from 10 preparations. However, in the first figure of the paper, they used 15 ųg of the purified kinase to show a single stained band on a gel. Huh? Who sacrifices 25 preparations of an enzyme just to show a band on a gel?

This was only one of many obvious problems with this paper. We termed the study "a graduate student fantasy." The senior author, however, was the renowned scientist Efraim Racker, so many scientists in the field assumed that the results must be reliable. Being skeptical young scientists, we were not so sure. At a scientific meeting we attended a month later, it was clear that many other investigators were extremely wary of the results.

It was only a couple of months before the news appeared that the paper was fraudulent. Enzymes that were supposed to be phosphorylated turned out to be molecular weight markers radiolabeled with iodine. In fact, all of the numerous findings and hypotheses that appeared in six papers Spector published with Racker were incorrect. Spector denied wrongdoing, but he was expelled from school, and the papers were retracted. Several years later, Racker published a lengthy description of his futile efforts to reproduce the results.2 History has shown that the results were indeed a fantasy.

Thankfully, fraud this outlandish is rare in biology. What fascinated me the most about the case, however, was the lack of recognition by Racker (and apparently the paper's reviewers) of the technical implausibility of what the authors were describing. Exciting ideas and Racker's past accomplishments apparently blinded him and many other people in the field. The harm to science was minimal, but the damage to Racker's distinguished career was severe. A recent controversy regarding an engineered enzyme in the Duke lab of Homme Hellinga shows that over-optimistic interpretation of experimental results is still a sure-fire way to cast a cloud over your reputation.3

Ever since the Spector incident, I always read the technical details of a paper before I evaluate its conclusions. I'm not looking for fraud, but instead am trying to understand how critical the authors are being in evaluating their own work. Rigor in the technical design of an experiment is an indication of good scientific judgment by the authors. This also requires that I keep current with experimental technologies, because if I cannot understand the technical basis of a study, I cannot judge its validity. The most important lesson that I have learned from the Spector incident, however, is that self-delusion is probably a greater danger in the laboratory than fraud.

Correction (posted September 15): When originally posted, the article misspelled Efraim Racker?s name. The mistake, which The Scientist regrets, has been corrected.

Steven Wiley is a Pacific Northwest National Laboratory Fellow and director of PNNL's Biomolecular Systems Initiative.

References

1. M. Spector et al., "A mouse homolog to the avian sarcoma virus src protein is a member of a protein kinase cascade," Cell, 25:9-21, 1981. 2. E. Racker, "The Warburg effect: two years later," Science, 222:232, 1983. 3. http://www.sciencemag.org/cgi/eletters/319/5863/569b