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.....

Vitamin C pills vs oranges: a metaphor for the dueling penicillin of Aussie docs, Florey and Duhig

A nice big fresh juicy orange and a tiny white pill can both have the exact same amount of vitamin c in them : about 100 mg ,  just above the recommended daily intake of the vitamin for a adult.

The synthetic vitamin c pill (first invented in the 1930s) is of course  supposedly pure, but actually consists mostly of "harmless" filler . It is usually taken with a small glass of water.

The orange was - in the eyes of the Modernist 1930s - an impure source of vitamin c. The orange consisted mostly of harmless filler (pulp fibre and a great taste) and about the same amount of water as needed to fill a small glass.

Despite being "impure", a whole (100mg)  orange a day would actually be more healthy for you than taking half (50 mg) of a "pure" pill every day.

All the body craves is its fix of 100 mg of the "C" a day , not whether human minds consider that vitamin c to be pure or impure.

Unless the vitamin c is bound to something that renders it biologically inactive, the body considers it as fully pure and effective and dismisses what sort of filler and water it chanced to come bundled with.

It was exactly same with the human bodies our two wartime Aussie doctors Duhig and Florey had taken a sacred oath to protect.

Heroic penicillin at its best ...

From twelve one liter flasks growing penicillium fungus in his Brisbane hospital lab , in late 1943, Dr James Dunhig got 2500 cc of penicillin juice, averaging at best five biologically active units of penicillin per cc , or about 12,500 units in total.

This crude, impure, liquid was strained but not processed - only kept chilled.

It was almost immediately put into a 42 year dying mother, a patient of Dr Geaney, in various sizes of IV doses (some as large at 600 cc) over a number of days -- and yet this impure medicine saved her life and home she went to her grateful and astonished family.

Dr Florey,originally from Adelaide, from the same 2500 cc of starting penicillin juice grown in his Oxford university lab in late 1943, also started off with 12,500 units of crude, unprocessed, penicillin.

But he chose to refine it over and over and over and over again, losing and destroying most of the penicillin in the long process.

Finally he ended up with a very little pile of relatively pure powder : one tiny mg of dried penicillin,  assaying about 1250 units of biological activity.

But you can't inject dry powder - no matter how pure - into a patient, so some of that oh so expensively extracted water had to be mixed again with the dry penicillin,  if it was to be usefully injected  in a dying patient.

Non-heroic penicillin, at its worst ...

But it wasn't - it was given instead to chemists, to be deliberately destroyed , all to make a more accurate assessment of penicillin's structure by examining its various sub components.

Then (in the middle of a deadly world war)  public domain penicillin could finally - profitably -  be synthetically analogued and  patented.

Just as well that Florey wasn't moved to waste any of his preciously pure penicillin on a dying woman, because 1250 units of penicillin , no matter how pure, couldn't save most dying adults but 12,500 units of impure penicillin sometimes did.

It is as I say, a classic example of the old saying that 'an whole impure orange a day will keep the doctor away, but half a pill of pure little white pill will not' ...