Wednesday, September 12, 2012

Sulfa's Alexander Fleming : Paul Gelmo, winner of 1939 medical Nobel for discovery of Sulfa

Sulfa the MIRACLE drug
Alas Paul Gelmo , discoverer of Sulfa, is not likely to ever be as famous as Alexander Fleming, the discoverer of Penicillin and it is a mystery worth investigating to ask why not.

(And in truth Paul Gelmo did not win the 1939 Nobel in Medicine for his discovery. Gerhard Domagk, the actual winner, deserved his Nobel for sulfa about as much as Ernst Chain did his Nobel for penicillin --- which is to say "still in doubt".)

Gelmo invented cum discovered  sulfanilamide in 1908 as part of his PhD in organic chemistry, doing what Germans of his generation did best : churn out endless synthetic variants of dyes.

It had no known uses, although 11 years later it was found to have some anti-bacterial quantities by American biochemist Michael Heidelberger.

Voices off, unheard  : the cries of the dying

But Heidelberger didn't feel any moral urgency to push to have it tested clinically, to see it it might actually save lives.

(Heidelberger, a later colleague of Martin Henry Dawson , similarly declined to assist Dawson in the development of penicillin - thus missing on the ground floor action of the century's two biggest lifesavers.

Cry not for Michael - he outlived Gelmo and Dawson and died showered in laurels, apparently for never uttering an unconventional thought over his long, long life : an all around, don't-rock-the-boat, team player.)

Domagk did two things with Gelmo's sulfa , one good one bad.

The good thing is that he did what Ernst Chain did ,but which Fleming refused to do : he tested the substance at hand "in living creatures ("in vivo") despite it have failed earlier test tube tests ( "in vitro tests").

Once inside animals, surprise, surprise, it did work and it did fight off the deadliest of infections.

The bad thing he did is that he went along with his employer, I G Farben, when it delayed telling the world about this life-saving drug (the only one available at the time, mark you) for years, while it sought to invent a patentable analog of it.

Neither I G Faben or Domagk felt any moral urgency to put the drug they did have at hand on the market at once, profitably-patentable or not.

The actual dye that Domagk was originally charged with testing consisted of two separate molecules ( one of them sulfa) loosely bonded together to form a beautiful ruby-red dye---- a totally new dye and hence very patentable.

Ie potentially very profitable as a dye - but not as a drug.

This was because "in vitro", bonded together inside a test tube, the two molecule "patentable" ensemble did nothing medically.

 But once in a living body,"in vivo", the body's enzymes quickly cleaved the bonds between the two molecules and the sulfa portion - once on its own, quickly brought bacteria growth to a stop.

Sulfa could and did save tens of millions of lives.

 But as sulfa was now Public Domain (PD) 25 years after its original discovery, it would make no real money (only worldwide gratitude and acclaim) for I G Faben, and so they stalled releasing this life-saving miracle.

But as they never could find an analogue for sulfa , I G Faben finally and reluctantly released the original 2 molecule dye without telling anyone that it cleaved apart in living bodies and the active ingredient was a dirt cheap, abundant (and PD) byproduct of many dyeing operations.

Domagk-the-hero has to be forever tainted for his part in this delay.

Fleming also never tested his penicillin in a living being with a disease - he just did "in vitro" testing that told him that penicillin killed bacteria slower than it was secreted out of the body - thus to the never-one-to-waste-a-motion Fleming it seemed so useless as a systemic that it was not even worth testing "in vivo".

He felt no moral urgency in "just double checking" his hunch.

When Howard Florey - pushed hard by Chain - did finally test penicillin almost 12 years after it had been first discovered , he found it did kill artificial infections inside animals - it did work , "in vivo" !

But while he was an editor of the journal that Fleming's original 1929 article appeared in and so could have demanded Fleming do the "in vivo" tests to double check Fleming's hunch, he never did so.

That he did so only 12 years later - and this when pushed hard by Chain - hardly displays any moral urgency on his part to test this potential life-saver.

Sulfa and penicillin - successes "in vivo", failures "in vitro".

Like I G Faben , though not because it could be profitably patentable as a result, Fleming and Florey put all their priorities to see penicillin made synthetically before it was given mass distribution.

Martin Henry Dawson was all alone in believing that natural penicillin was perfectly acceptable to be mass produced and put to work right away, because people all around were dying daily without it.

Dawson thus invented a moral reason why natural penicillin should be mass produced "today - if not sooner".

It was this 'moral urgency' that Dawson alone brought to its invention, that finally led to the development of mass produced life-saving systemic penicillin.

 A moral urgency that Fleming, Florey,Heidelberger and I G Faben all so obviously lacked.....

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