Science's faith-based belief in the non-toxicity of pure natural Penicillin

For an entire generation of scientists, doctors and science reporters (those working between 1929 and 1949), it was an article of absolute faith that pure penicillin was non-toxic.

But how did they know? How in the hell did they know ?

For during most of those years they had never seen anything like pure penicillin , let alone given it an extensive work-out down in the hospital wards.

When the ward doctors finally got their hands on lots of crystal clear 100% pure factory-made penicillin , a not-so-funny thing happened.

Some of the patients got the rigours and the shakes, as some patients had always done on receiving earlier "crude penicillin", but these shakes ended in their sudden and dramatic death from severe anaphylactic shock.

The earlier generation of penicillin researchers (with an extremely tiny handful of exceptions) seemed to stuff logic and reason in the kester, whenever they discussed crude penicillin's non-toxicity.

The evidence before their eyes was clear.

It said, repeatedly, that a crude mixture of one part natural penicillin to thirty thousand parts of its natural impurities and nine hundred and seventy thousand parts water was basically non-toxic, causing only minor and temporary temperature rises when injected into animals (or slightly modified, into humans).

But the mental conclusion they always drew from these visible facts, was logically unwarranted to the max times infinity.

They said - consistently - for twenty years - that pure natural penicillin was extremely non-toxic (it just had to be !) and that the natural impurities were the cause of any fever caused upon injection (it just had to be !)

A lack of undergraduate level logic caused a holocaust of needless deaths

A undergraduate course in Philosophic Logic would suggest that these researchers and science reporters had totally confounded non-toxicity with purity.

Because a logics professor like Rowland C Marshall would remind his students that a moment's reflection should suggest that pure poison is more , not less, toxic than less pure poison : non-toxicity and purity share no relationship.

There are in fact only three possible correct answers in this particular pop quiz :

(A ) The impurities are the sole cause of the temporary allergic fever. (B) The penicillin is the sole cause of the allergic fever. (C) Both can be the cause, varying on the particular set of circumstances and genetic nature of the patients involved.

The truth is, there was no way of knowing, at that time, what was the real cause for this minor temporary fever spike ---  particularly after administrating only weak doses of crude mixture 'penicillin'.

A much better test would come when a much stronger doses of pure penicillin were administered and we could see then if strong and pure penicillin doses alone can cause allergic shock or not.

But even that might not convince anybody who felt it just had to be some incredibly tiny fragment from the original natural fermentation process that somehow slipped into 100% pure penicillin and that was the true cause of the allergy.

(A big shout out to Dr Gordon Stewart who pursued this line of thinking, in the true bull-headed cum Sir Robert Robinson fashion.)

 Why not, said American chemist John Sheehan,  why not wait ?

Why not wait to test an extremely pure dose of  synthetic penicillin, which had never ever been near a natural fermentation process, to test it for possible allergy shocks ?

He did so - and finally found that pure chemically synthesized penicillin indeed could still cause allergic reactions in some people.

In the end, it turned out that answer (C) was the correct one , but that with weak doses of penicillin administered fairly slowly, the reaction does not appear to have killed anyone.

At least not before1946 and the issuing of abundant amounts of pure penicillin for use in non-hospital settings.

This twenty year bugaboo about crudity equalling , ipso facto , toxicity was a pure intellectual red herring.

It not only fooled the generation of idiots who uttered it, it was also the major reason why a whole holocaust of patients died needlessly for 15 years while researchers sought to purify a life-saver that already worked perfectly well in a crude mixture.

To his undying credit, Henry Dawson realized how absurd this thinking was in October 1940 when he said " let's just do it".

He then slipped a needle-full of  a crude mixture of natural penicillin and its natural impurities into a patient, confident that the crude mixture would only cause a minor and temporary temperature rise at worst.

His sense of charity and chivalry was admirable, but in this particular case, I would argue his Scottish sense of logic and reason were rarer and more admirable still.....

Wartime Penicillin was a race between a Tortoise and a Hare,unexpectedly the Tortoise won but the Hare got to phone-in the results...

People invariably find the story of wartime penicillin fascinating because 75 years after the earliest events, it still remains a real puzzler with lots of inexplicables and unanswered questions.

The story of wartime penicillin is actually quite clear.... but it is its history that seems so full of holes and silences.

A great Russian poet once voiced the thought that lovers only sing love songs when they are far apart --- when they are together they have much better things to do.

So too with the winners in the race  to define and provide wartime penicillin.

The selfless nature of the objectives of those who won the race suggests that they might be equally self-effacing in the moment of triumph : just glad that penicillin was being made available to all, at a reasonable price, and before the six year long war ended.

The losers in the penicillin race were grasping and ambitious and  lost so dramatically and so unexpectedly , and so it would seem natural for them to seek a form of physic revenge by re-writing the history of wartime history.

The losers were, in part, from the government side of the race and they had lots of taxpayers money to write and publish huge official histories.

Even after that, they held most of the solid documentation (which they thoughtfully marked as "secret" during the war) in their official archives.

The same governments that , after the war, offered to generously fund all academic researchers and research projects - that they approved of .

The losers were also Big Pharma , who held much of the unpleasant details in their closely guarded archives but who were willing to fund researchers and open their archives in a limited fashion to them, provided the drug executives had reason to feel the researchers were sympathetic to their view point.

And all the secondary researchers ever since have had to scramble from pillar to post to get any sort of firm information about the winning side of the race for penicillin , while information from the losers comes at them by the trainload in war friendly well light archives in Washington and London.

How balanced an account can we expect even the most dispassionate author to provide under those circumstances ?

My job , as I see it , is not to be dispassionate but rather a partisan for the winning side : but not to be a partisan for anybody on the winning side.

I will seek to establish a firm , fact-based chronology when things did happen (and more importantly, did not happen) and try to follow the money trail : ignoring talk and claims and promises for cold hard cash (and again : more importantly, lack of evidence of cold hard cash.)

I will review all contemporary claims of penicillin yields to judge if they were credible-- and few were.

Above all, I will separate clearly when the contemporary numbers refer to absolute amounts and when they refer to relative amounts of penicillin : for this is one of the widest failings in all accounts about penicillin and one that is at the very core of the muddle about wartime penicillin.

The winning side wanted larger and larger absolute amounts of penicillin --- to help those dying of infection, in all countries, as soon as possible.

The relative purity of those absolute units of therapeutic penicillin interested them not in the slightest : greater and greater production of absolute units of therapeutic penicillin was their only concern.

Four daily injections of 500 cc of crude penicillin juice , with about 2 units of penicillin per filtered ml of medium, (4000 units of absolute penicillin per day , in total) was judged useful to Australian Jimmy Duhig because it saves a mother's live , even though that material (in relative terms of purity) was only 1 part per million of the medium !

 By way of pointed contrast, his fellow Australian Howard Florey was very proud in getting a single milligram of solid penicillin from the same amount and strength of penicillin juice, because it assayed at 450 units per mg, ie 25% pure.

Duhig's yield of therapeutic penicillin was 100% because he lost nothing trying to purify it - and the impurities in his penicillin juice caused his patient no more than temporary discomfort.

Florey's yield was 12% , because his repeated attempts to purify his penicillin juice resulted in huge losses and huge destruction of the basic penicillin ---- and it introduced toxic chemical contaminants worse than the natural impurities it sought to get rid of !

A patient receiving this material as medicine would get much less penicillin and probably find it more painful to boot.

But thankfully , patients didn't usually get this sort of penicillin from Florey.

His patient-directed penicillin was only purified to about 40 units per mg, and while nominally 'dirtier' , was actually probably safer than the early 'pure' variety : and certainly the yield was much higher and so the patient got more absolute units of germ killing power.

(Bacteria are only killed by absolute amounts of penicillin not by its relative purity : after all, the greatest diluter of penicillin - by far - is not the original pint of medium fluid but rather the quarts of blood fluid in the human body !)

No, the "pure" (high relative purity) penicillin was a holy grail sought for only one reason : we need pure penicillin to determine its chemical nature for then Man can hope to artificially synthesize it and push Mother Nature out of the picture entirely.

Millions of patients died, needlessly, during the 15 plus years of this fruitless quest.

Wouldn't you also want to cover your tracks in this shameful episode of your life....