junk science on the leading edge

Posted on Saturday 20 November 2010

Duke Scientist Under Investigation Resigns
Science Insider
American Association for the Advancement of Science
by Jennifer Couzin-Frankel
19 November 2010

A Duke University oncologist who had been the focus of a misconduct investigation has resigned from the university. Anil Potti had published papers in prominent journals identifying gene signatures in tumors that could predict how a patient would respond to treatment. But his work came under scrutiny after two biostatisticians at M.D. Anderson Cancer Center in Houston, Texas, spent years trying and failing to replicate it. The case broke wide open this summer when The Cancer Letter discovered that Potti had falsely claimed to have won a Rhodes scholarship. Duke placed Potti on administrative leave soon after.

Separately, the Journal of Clinical Oncology yesterday retracted one of the papers in question, by Potti and co-author Joseph Nevins, a cancer geneticist. “The authors wish to retract this article because they have been unable to reproduce the experiments,” the notice read. Duke said today that it has “initiated a process” to request retraction of another paper by Potti, which appeared in Nature Medicine.

The Duke case has also brought scrutiny to efforts to use tumor gene patterns to predict prognosis or response to treatment. Duke opened clinical trials that relied on Potti’s work even as others were expressing concerns about their accuracy. Those trials have since been halted, but the Institute of Medicine is setting up a panel to study clinical use of these gene signatures. That’s still in the works.
With the recent advances in genetics and DNA/Gene research, there’s a lot of excitement about the treatment possibilities that clinical research might bring. There’s a strong belief in the scientific community that there is a genetic component to the variable response to treatments in a variety of diseases, including cancer, and an earnest hope that identifying these genetic factors will radically improve our ability to treat a lot of conditions.

Unfortunately, it’s ripe for a lot of scientific skull-duggery. It’s an area where there is a lot of grant money available, and where there’s a lot of competition. From what I can read, Dr. Potti jumped the gun, falsely claiming to have found a genetic marker in breast tumors that might direct chemotherapy choices. I guess it’s like the "dot.com" bubble. When the Internet came on the stage, there were a jillion start-ups hoping to become the next Microsoft, or Google, or Amazon. Most failed.

It’s not lost on me that psychiatrist, Charles Nemeroff, already discredited for pushing fringy, unproven treatment programs and off-label uses of medications is drawn to this new area of research. In the paper I mentioned yesterday, he’s proposing some genetic mechanism in the transgenerational transmission of "trauma" [unique endophenotypes]. This summer, he was looking for genetic factors in medication responses in Depressive Illness [how’s your life…].

It’s actually how junk science works. Serious scientists develop some hypothesis based on an observation they or someone have made. They design a pilot study to see if it’s a fruitful idea to pursue. If it’s promising, they try to find a way to see if they can prove or disprove their hypothesis. The junk scientist stays on the leading edge of things looking for something to study, and isn’t particularly careful. Data is massaged. Graphs and statistics are massaged. And sometimes, that data is changed to support the unsupportable. It happens all too often. Fortunately, other scientists often repeat studies before trying to extend them. That’s what happened with Dr. Potti. And it’s not just medical science. Remember Marc Houser’s monkeys at Harvard [just not how things work…]?

In spite of what one sees on the news, real science creeps and plods. Breakthroughs are rare. Usually things don’t happen like that, but when they do, it’s a time for much celebration eg penicillin. Long ago when I was pursuing a research career, I went to lots of meetings and listened to hundreds of presentations. Some advanced what we knew by a micron or so. Many didn’t. But then one day, I was listening to a presenter who was studying amyloidosis – an obscure disorder where protein in deposited in the tissues. And as he talked, I realized [along with everyone else in the room] that he had nailed it. He showed us what amyloid protein really was, how it got there, what disease process was behind it, and suggested how it might be treated. It’s the only such presentation I’ve ever seen like that – a thing of beauty. After it was over, there weren’t the usual questions and challenges – just complements. That’s the thing most scientists dream of doing. Unfortunately, the junk scientists try to jump-start the process…

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