Adumbration: A History Lesson
Edward Shorter’s comment on Barry Blackwell’s essay

There is one error in the Blackwell piece:  It was Henry Ford II, the original Henry Ford’s grandson, who presided over the Ford Company at the time of the Edsel blunder.

Barry Blackwell’s exquisite reflections highlight one big problem today in psychopharmacology and open a window on three smaller problems.

The big problem is industry’s unwillingness to explore dangerous new side effects that do not show up in clinical trials at the time of registration.  The reason for this foot-dragging is perfectly obvious:  Companies may invest hundreds of millions of dollars in drug development, and the thought of this sum suddenly being erased because someone has a headache is simply too awful for executives to contemplate.  A company’s entire profitability may ride on one or two blockbuster drugs whose patents have not yet expired, and thousands of jobs may depend on keeping those agents selling.  This reaction is perfectly human, if contrary to public health.

A perfect example of industry foot-dragging surfaced in the 1960s, as Sandoz, a precursor company of Novartis, displayed active resistance to Thomas Ban’s discovery that the antipsychotic thioridazine (Mellaril) could cause sudden cardiac death by altering the Q-T interval.  Ban had seen several patients simply fall over and he blew the whistle, but Sandoz showed a studied indifference because Mellaril was such a big seller.  I told this story much later in: Shorter. inhn.org controversies 07.18.2013.

Earlier, Tom Ban and I had written an article about the thioridazine problem and attempted to get it published.  Several first-rank medical journals, clearly beholden to Novartis’ advertising, turned it down on vague grounds along the lines of “not feasible at this time.”  It was never even sent out to referees.  So, yeah, the problems that Barry Blackwell highlights are not uncommon.

Now, I would like to make several other observations of a less prosecutorial nature.  The story that Blackwell tells is a riveting one, and engagingly recounted.  It is all the more poignant because such a story would be highly unlikely today.  Consider some of the major turning points in his tale:

Blackwell initially blew the whistle on the cheese problem in a short note in the Lancet.  He simply gathered a few cases together, wrote them up, and sent them in -- to one of the world’s major medical journals.  I have a bridge I’d like to sell to anyone who thinks this is possible today.  Look at the pages of the American Journal of Psychiatry:  They are covered with numbers.  The letters section at the end, which might also harbor a space for such a contribution, is dominated by heavy hitters, and the editors have to cap the number of references at . . . what . . . 20?   Dr. Blackwell, as a resident (registrar) would you have been able to take off the four months required for such an exhaustive literature review?  And as for surviving the drumfire of the “referees,” who preen with their superior knowledge, good luck.

                      Blackwell describes the helpfulness of Gerald Samuels, the drug rep of Smith Kline and French, as it then was, who suggested looking at the composition of the cheese, a capital idea!  Might a drug rep today play such a key role in sending his employer’s favorite agent to the bottom?   I don’t think so.

                      Blackwell was able to investigate the tyrosine issue thoroughly once Aubrey Lewis, the professor at the Institute of Psychiatry and the most powerful figure in the discipline in England, simply decreed that Blackwell was to receive what must have been a coveted plum: a two-year fellowship in pharmacology!  In the great majority of institutions with which I am familiar today, this simply would not happen.  There are committees that determine the distribution of such fellowships and prizes.  Diversity and gender are considered at great length.   To be sure, such safeguards militate against the distorting influence of an “old boys’ network.”  That is the positive side of such procedural safeguards.  The negative side is that such clever singletons as Blackwell, without powerful sociological considerations as a tailwind, will simply be overlooked.

What we gain on the swings of fairness, we may lose on the roundabouts of brilliance.  It is a trade-off, but one that does not favor inspired intuitive investigation.

Blackwell’s tale should be required reading today for residents, who need to learn that they are being trained as scientists and not just as clinicians.  But of course it won’t be…

Edward Shorter

June 11, 2015