1 Boring Old Man

Looking at the APA meeting currently going on in Honolulu, I ran across a few items of note. On the opening page, there are some upbeat videos, Outgoing President Carol Bernstein leads off, but the one I gravitated to was Tom Insel, Director of the NIMH. Since his poor showing in shepherding Dr, Nemeroff’s move to Miami, he’s been more on my radar screen, and I realize that I think of him more as a cheerleader than a scientist. In the 1960s, I had a friend who characterized himself as a breakthrough freak. He bought all the gadgets and pored over magazines for the newest science innovations [I’ll bet he’s had a field day with the modern phones].

I hadn’t thought of his term for decades until recently when I began to follow some of the goings-on in modern psychiatry. It’s an apt name for the group of people that bother me – always talking about what’s up ahead, the coming breakthroughs. Insel’s interview is in a casual, open-collar shirt setting – lots of awkward hand gestures and canned responses. He talked about the research track at the APA organized along the lines of the NIMH Strategic Plan – the "Four Ps": Pathophysiology, Predictive Medicine, Personalized Medicine, Public Health Impact. Catchy. Then he launched into a boilerplate recitation of the burden of middle illness. I remember when he was in Atlanta and didn’t get reappointed at Yerkes, Nemeroff got him an Emory job directing a Translational Science project – breakthrough promotion, previous version. This round it was Insel’s usual future-think…

Speaking of breakthrough freaks, Charlie Nemeroff is leading a symposium later this morning on his next great hope to catch a rising star – personalized medicine. Note that his title has two "Ps" – Predictors and Personalized Medicine. Charlie is the paradigmatic breakthrough freak. He rode the SSRIs and Atypicals through their cycles. He’s still dogging Treatment Resistant Depression and Augmentation. He goes for new stuff – Vagal Nerve Zappers, Lithium Patches, Schatzberg’s Mifepristone. Now, he’s teamed up with Brain Resources and a bevy of other breakthrough freaks [personalized medicine: the Brain Resources company II…] in the biomarker/biosignature races. He’s joined there by Alan Schatzberg of CORCEPT, and John Rush of TMAP, STAR*D, and CO-MED. Personalized Medicine has attracted the breakthrough types like flies. There is another breakthrough cell forming in Tarrytown New York [personalized medicine: and along the hudson…] including Eric Nestler formerly the Chairman from the Texas Department that brought us STAR*D and TMAP, Maurice Fava from Harvard and STAR*D and Jeffrey Lieberman. These breakthrough freaks are going the private laboratory route in spite of all having been previous heavy hitters on the NIMH grant circuit, but are out of favor after repeated scandals. On the other hand, Madhukar Trivedi has been a front-running breakthrough freak for years – TMAP, STAR*D, CO-MED – but has escaped scandal, so his Personalized Medicine outing is through an NIMH Grant [Godzilla vs. Ghidorah – the Three Headed Monster from Outer Space…], also including a long listing of fellow breakthroughers [some of whom are involved in the other studies]. By the way, I notice that Nemeroff could only attract people from his particular team.

I suspect that every scientific discipline has such people with very long résumés that move from topic to topic hoping to score [and don’t]. But we in Psychiatry have way more than our share and a very high tolerance for scandal and feeble to non-existent results. A complete listing of all people in the projects from the last paragraph would account for a sizeable chunk of the NIMH Grant outlay in the recent decades, a fair showing in the who’s who of high places in psychiatry, and a solid place in the annals of non-discovery and non-results in the world of solid science. In spite of repeated unrealized expectations, they stay on the circuit until unseated by loud but not quite terminal scandals – moving from fad to fad hoping to finally hit a lucky number. It’s fair to ask why we have such a high acceptance for the people who can talk the talk but can’t seem to walk the walk.

I hate to be Johnny one-note, but I think it’s a direct consequence of the DSM-III revolution. The system as defined needs an influx of biological interventions and new science to sustain itself, so these leading edge breakthrough freaks are tolerated because they’re filled with the promise of new discovery. Without their ongoing patter, particularly as the last generation breakthroughs enter stages of disillusionment, there’s not much new on the horizon. In a rational world, a breakthrough is an exciting moment and cause for celebration.  For the breakthrough freak, the celebration transcends the moment and sustains the movement – breakthrough or not. There have been a number of attempts to keep the dream alive with old-timer breakthroughs already – including STAR*D [sequencing] and CO-MED [piling on] – that came to nothing. I doubt that personalized medicine will change that pattern.