If It is Too Good to Be True . . .

The February 12, 2012, CBS 60 Minutes covered a story that has sparked a great deal of interest among cancer patients and medical professionals. The topic was an investigator named Anil Poti who, while working at Duke University developed a laboratory platform for the study of human lung cancer.

Using molecular profiling, Dr. Poti and his collaborators, reported their capacity to distinguish responding and non-responding cancer patients, providing survival curves that were nothing short of astonishing. I recall attending the original lectures given by these investigators at the American Association of Cancer Research meeting several years ago.

As an investigator in the field of drug response prediction, working in lung cancer I had a particular interest in their platform and I was extremely impressed by the outcomes they reported. At the time, I wondered how the static measurement of gene profiles could possibly characterize the nuances of human biology, to encompass the epigenetic, siRNA, pseudogene, non-coding DNA and protein kinetics that ultimately characterize the human phenotype. Nonetheless, with such compelling data I was prepared to be convinced.

That is until a relatively unheralded report in the Cancer Letter raised concerns by several biostatisticians regarding the reproducibility of Dr. Poti’s findings. And then more comments were followed by a full NIH investigation. A panel of biostatisticians was convened and a formal report provided the explanation for Dr. Poti’s excellent results.

They had been invented. The clinical outcomes were not real results. The findings had been retrofitted to match the patient responses and this was the subject of the 60 Minutes report.

What the 60 Minutes report did not address however, was the real problem. That being the inability of contemporary genetic profiling to truly define human biology. For all the reasons enumerated above, siRNA, non-coding DNA, etc., the simple measurement of gene sequences cannot accurately predict biological behavior. This is what the 60 Minutes reporters and the physicians they interviewed, never discussed. The problem at hand is not an errant investigator but an errant scientific community. Our love affair with the gene that began in 1953 (Watson and Crick) has now been confronted by a most heartbreaking example of infidelity (pun intended).

Genes do not make us what we are; they only (sometimes) permit us to become what we are, with the vagaries of transcription and translation lying between.

This leads us to the reasons I find this so critically important:

  1. I cannot stress strongly enough that this is NOT what I do. Genomic analysis (their work) and functional analysis (our work) are distinctly different platforms.
  2. I strenuously resist any attempt on the part of anyone to tar me or my work with this brush.
  3. It is precisely because genomic analysis cannot accurately predict cancer patient outcomes, that these investigators found it necessary to invent their data.
  4. Despite this, functional analyses can and do provide these types of predictive results in lung cancers and other diseases as we have reported in numerous publications.
  5. Finally, while imitation is the sincerest form of flattery, this is one instance in which I would prefer to decline the compliment.