Showing posts with label allergy. Show all posts
Showing posts with label allergy. Show all posts

Monday, January 21, 2013

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.....

Wednesday, November 28, 2012

How Parke-Davis could have made a fortune in 1929 from the ultimate in generic drugs : natural penicillin

Parke-Davis, as seen from my folks' homes
A medication made by some natural being out in Nature is the 'ultimate generic drug'  ---- being PD (Public Domain) from its birth, which possibly occurred hundreds of millions of years before Humanity first noticed it.

Penicillin - in theory - is one such 'ultimate generic drug' , but was it in fact, in 1929 ?


Many strains of various bacteria and molds make penicillin-like beta-lactam materials but most do so in such small quantities that it takes very sensitive testing to discover their existence.

As such, St Mary's hospital in 1929 had the only two known strains of  microbes known to make sufficient penicillin to be useful to man.

The original mold had been gathered as part of John Freeman's pioneering studies in allergies.

 (Freeman's researches were the only part of the entire Wright-Fleming money-making empire that had any longterm scientific validity - as evidenced by being the only part of the Institute that a drug company, Beecham, was actually willing to part good money for in the 1950s after Fleming and Wright were safely in their graves.)

Spores from Freeman's unique mold had drifted up to Fleming's lab and so the hospital now controlled two copies of the same unique strain of mold.

Parke-Davis lost its chance to remain the world's biggest drug company


The Institute had a close contractual relationship with what was then the world's biggest and best research-oriented drug company - Detroit's Parke-Davis.

 (Their enormous ( for their day) research labs were/are clearly visible right across the river from both my parents' home in Windsor Ontario.)

Patents were impossible for natural drugs but hardly needed, for St Mary's/Parke-Davis controlled the only source of the vital reagent needed to make penicillin : their unique strain of penicillium.

Keep that strain in-house and they could have a profitable monopoly forever.

Think this wildly unlikely ?

How do you think today's real penicillin makers still act ?

They develop in-house strains of penicillium and never patent them or share them.

The down-stream techniques after the penicillium express the penicillin juice are/were patented and hence public, for a fee.

But they are useless without a stable, high producing penicillium strain : one can afford to be quite cavalier with one's chemical engineering efficiencies when your unique strain out-produces all your competitors by an order or two of magnitude !

Trade Secrets rather than patents remain the most profitably business method in the biological drug business - now in 2012 as in 1928 .

When Fleming, after he too-quickly dismissed penicillin for systemic use, started freely giving away penicillium spores as a low value lab clearing agent, he ruined any hopes that Parke-Davis and St Mary's might put heavy money in penicillin production and promotion.

Ironically when he thus destroyed the early commercial hopes for penicillin production, his spores out there in the wider medical world, successfully kept the MRC/NAS/OSRD triad from delaying wartime penicillin any longer than they already did....