Clinician researchers meet the physician scientists

Recently our department of medicine grand rounds was on the subject of asthma.  It began with a clinical vignette about a child with asthma, lasting three minutes, and, was followed by 47 more of intracellular cascades.  The talk was like many others this year, and the speaker, who was introduced as a physician scientist, lived up to the part.

As someone who works in an academic hospital, I know many physician-scientists.  They are physicians by virtue of completing medical school, residency, fellowship, and, often, from years of seeing patients. And, they are scientists by the narrow definition of science that seems to be favored these days.  Namely, they work in or manage a laboratory that utilizes molecular, biochemical, cellular or systems biology methods to describe the workings of the human body (or parts thereof) in health and disease.  The goal of ‘science,’ so defined, is to identify therapeutic targets, which can be exploited for clinical gains, or, at a minimum, to create a pathophysiological foundation so that others may someday do so.  At least, this is what I’ve gathered.

I call this definition of science, narrow, because it is not:  one who utilizes the scientific method, i.e. the generation of testable hypotheses that are empirically studied.  Many physicians are scientists by this mark, though the words most often used instead to describe them are: clinician researchers. I conclude then that research, as opposed to science, concerns events that are visible to the naked eye, such as mortality (a dead body), morbidity (an injured body), the use of medical therapies (pills, surgical instruments, etc.), and the cost effectiveness of such therapies (dollar bills). At least, this is how the words are being used colloquially.  Clinician researchers and physician scientists do have one thing in common presumably, and that is the clinician-physician part.  I have deduced that this part (clinician, physician) means the same thing, viz. a person who takes care of patients, or, alternatively, doctor.

There are other activities clinician researchers and physician scientists share in academic hospitals: committees, administrative responsibilities, and a host of conferences include both.  In terms of conferences, we have:  morning report, grand rounds, case conferences, and a few others.  I wish to submit (and admittedly this is purely subjective) that, in recent years, there has been a steady growth of ‘scientist topics’ into the content of these discussions.  Grand rounds begins, as this did, with a three minute vignette regarding a child with asthma followed by nearly an hour of intracellular cascades. Morning report spends the first ten minutes discussing a patient with diabetes, and the next forty on the mechanism of a new class of drugs (though oddly it omits mentions of their lack of hard endpoint data).  Entirely new conferences have been created. The molecular medicine series began this year in my hospital, for instance.  Thus, I estimate that at least a third of my ‘conference time’ is spent squinting at cartoon molecular cascades.  Having visited many other academic institutions over the last four years, I contend this is a global phenomenon.

I could argue about the relevance and implications of learning and relearning all this ‘science’ for clinical practice, but I have done so elsewhere and at length.  Here, instead, I wish to articulate the feeling that these talks evoke in me, a feeling I suspect is shared among countless clinician researchers and even some, yes, if you’ll believe it, physician scientists, who might admit this only in private.  That feeling is:  “Nooooooooooooooo.  Please stop.  Dear God.  Please.  Stop.  I beg you.”  Or, alternatively, “Please don’t fall asleep, please don’t fall asleep …” if I am tired, or have skipped coffee.  When the appointed time for the conference expires, and the speaker continues to go through slides without realization of his or her intrusion, my heart quickens.  If a talk runs ten minutes over, I am on the verge of a panic attack.

Listening to an hour long talk that ends in someone getting a drug to a phase one or two study, would be like me putting down ‘Applied to Harvard’ on my curriculum vitae.  With a 3.4 percent admission rate, and a 1% chance of garnering FDA approval (let alone the still lower percentage of drugs that are actually useful), both should be similarly dismissed with, ‘so what?’   I’m glad someone finds these topics interesting, and devotes their life to it, though—with MSTPs and grant funding used to defer clinical responsibilities—the incentives to do so are immense, but can we, at least, admit that such topics may not be appropriate (or interesting) in mixed company.

Let’s say I do tune in for five or ten minutes of the molecular talk.  Inevitably, such an act is met with immense frustration.  The Speaker:  “So, our hypothesis was that ‘unpronounceable molecular bit x’ or UPMBX is necessary for constitutive expression of the ‘acronym you hear all the time’ or AY-HATT pathway.  Fortunately, Juan Calderon who is now at Rockefeller, formerly in Boston, and Rick Jeffries, who is at Cold Spring, had worked in concert with Novartis to develop a kinase inhibitor, which Yuan Li at the Beijing Institute had shown also binds UPMBX, and inhibits its ability to phosphorylate.”  The speaker’s voice rising, suggesting intrigue.

The story continues, but I’ll summarize.  They get the drug. They test it in cell lines.  It doesn’t work.  Then post-doc y in principle investigator z’s lab makes the observation that it only worked in cell lines that were mutant for ‘other molecular bit’ or OMB, but not in those that were wild type, therefore it would make sense … But, this is where my first of many questions begins.  What makes you think this is a real finding?  A post-hoc analysis of an experiment with an n of ten.  Should this part be replicated before you go on…whoops, too late. Since the story ends in a phase two trial with results pending, I know that the speaker won’t ultimately be able to allay my doubts, and I’ll feel annoyed by his/her unconditional optimism.

Many dispute whether or not basic science is clinically relevant, but that few doubt that it teaches one to be a better critical thinker.  I would argue, blasphemously perhaps, that it does this only if one defines ‘critical’ in the loosest of ways, as each link of the experimental saga provokes countless doubts, alternative explanations, and wiggle room, which go largely unmentioned, at least in such forums. But, no matter whether you think of molecular medicine as salvation or self-promotion, can we at least agree that the talks are boring?  They bore the clinician-physician in all of us who is concerned with how people live in sickness and health and what medicine does, can do, and should do to help them.  The asthmatic boy is no more relevant to an hour of putative pathogenesis than any patient or no patient, and thus the talk fails to connect to the doctor within us.  It is at once unmoored and misleading.

Vinay Prasad is an internal medicine physician.

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