Saturday, January 26, 2013

Fleming's seminal 1929 article on penicillin is missing two words : impurities and crude

Fleming, in this extremely famous article, defines his "penicillin" as consisting of  one or more soluble solid active ingredients in a liquid nutritional  broth, no more and no less.

He makes it clear that "penicillin" is merely a useful shorthand for that cumbersome longer phrase.

He never once uses the word impurities or impure or crude: to him his active ingredient is perhaps ALL  of the soluble solids left behind when the water is evaporated .

Fleming says that this (mixture) of soluble solids and nutritional broth is non-toxic to the extent that it can be injected in a mass of one fortieth of body weight without harm.

(That is, this liquid mixture appears to be safely injectable in a mouse and a rabbit to the equivalent of  a single bolus of 1500 to 2000 cc into an average adult human.)

And Fleming isn't the only one never to use impurities or crude in describing penicillin in a scientific report, in the twelve years between 1928 and 1940.

Clutterbuck & Raistrick in 1932 do not use the words impurities or crude, nor does Roger Reid in 1934, or Elizabeth Pickering at Squibb in 1937 or Siegbert Bornstein in 1939.

But Howard Florey, the chemist manque , the anti-clinician, he sure does in 1940.

He might even ask his potential readers, "Purity : how many ways do you want it ?"

Despite being a very short article - almost more of a scientific note  in the style of letters to the journal Nature - Florey manages to inject the words "purify" , "not a pure substance", "impure" and "impurities" and talks constantly of his "penicillin preparations" as if they are something quite different and advanced from Fleming's liquid penicillin.

But, in fact, Florey has merely concentrated all the soluble solids by evaporating away the water, so that 4 tiny units of anti-bacterial activity are no longer in a gram of water and solubles, but in a milligram of solubles.

But two thirds of the scarce anti-bacterial activity has been lost in this totally unnecessary and expensive and complex effort : and in any case, this dry powder has to have water added back into it, to inject it for use !

Dawson, Pulvertaft, Duhig, Yermolieva , Berger (among a mere handful of all the world's doctors ---- maybe just .01% of them  thought this way) seemed to have picked up on Fleming's crucial point.

A point he quickly missed, because he publicly always said that the substance would have to be synthesized pure by chemists before it might be a useful antiseptic .

But his original point was true, nevertheless.

It was this : that regardless of whatever was the compound(s) with that mixture of soluble solids that had the anti-bacterial powers, the water and other solids had no harmful effect and needn't be laboriously purified out - or even concentrated by evaporation - at a tremendous loss of the anti-bacterial matter.

Dawson is at pains to introduce the word "crude" repeatedly in his 1941 article, but with a much different point that Florey's article a few months earlier.

Dawson wants to hammer home that despite the crudity of this mixture of the anti-bacterial activity and the other soluble solids, it was still non-toxic even when injected ( finally) into the human blood stream : life-saving does not have to wait until the chemist's apple has been polished to a 't' .

Dawson is , in a sense , "The James Lind of Penicillin".

Put in another way, James Lind said we don't know which compound (later determined to be vitamin c) it is in limes that prevents scurvy but that shouldn't stop us from using it - NOW ! - to save lives.

Almost two hundred years later, another Scottish (Canadian) doctor (Henry Dawson) said pretty much the same thing.

The lesson might be this : chemists, let the sleeping dogs of chemical perfection lie -----  while we clinicians get on with saving lives.....

No comments:

Post a Comment