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Thursday, August 14, 2014

Penicillin for patients : stable ? pure ? or just 'safe enough' ? -- the essential disagreement between Fleming, Florey and Dawson

Alexander Fleming was famously known for his frugality : in speech, in the use of materials and in his physical exertions on his paid job.

Being too self confident in his own intellectual abilities (and perhaps also being too frugal cum lazy in the physical exertion department ?) fatally led him to avoid doing the needed series of experiments to prove up his claim that penicillin would never have time to do its work inside the body.

So he misled himself - and more importantly , the entire world,  for 14 years that penicillin would only work on the body,  never in the body - and tens of millions died premature deaths that could have/ should have been avoided.


Howard Florey's fatal flaw


However, because Fleming saw penicillin as only working outside the body he had no need for Howard Florey's delusions about penicillin having to be highly purified to work safely inside the body.

Fleming merely want the chemists to make penicillin as a stable powder in a bottle any doctor could readily buy from a near by druggist, store on an unrefrigerated shelf for years and still expect to work as an external antiseptic at 100% efficiency when needed.

Call this 'lazy man medicine'  or call it normalcy.

Because only one doctor in ten thousand world wide ever tried making homemade penicillin even after it was proclaimed a life-saving miracle.

They all preferred to simply patiently wait until this miracle came to them as a stable and certified safe powder in a bottle from Big Pharma.

(I am not sure all their dying patients were as patient.)

Florey's great insight


Howard Florey - to his credit - seemed to have never bought Fleming's tale that penicillin would never work inside the body - as had every other medical scientist in the world .

But because he thought it had to be purified first and that purification would be very difficult , if not impossible , he did nothing until he got a competent full time chemist on staff together with a large long term grant to sustain the effort.

Meanwhile ten wasted years (1929-1939) went by.

Clearly Florey was no medical crusader, burning to save lives NOW!

And he , too , had too much faith in his own intellectual powers.

In 1939 he requested grant money for his co-worker Ernst Chain's work on three bacteria-killing chemicals produced by living microbes against other living microbes (what scientists call antibiosis).

One was penicillin and one key phrase in the grant request reveals his thinking and his fatal flaw.

He believed that penicillin , if it can be purified, will prove safe and effective inside the body (eventually and hopeful inside the bodies of infected human patients).

But he just assumes this , again just like Fleming .

Without actually doing any of the needed experiments to prove his contention, one simply can not say that penicillin is non toxic inside the body and it is the impurities that will be unsafe inside the body.

Actually there are always - in advance of the actual experiments - a range of possibilities sliding between three poles (that represent absolutes rather than real world situations.)

The three poles are (a) only the main product is toxic (b) only the impurities are toxic (c) both are equally toxic or equally non toxic.

Let us get concrete with a few examples.

You are a chemical firm making the poison prussic acid. You discover impurities in the resulting mix (impurities being anything that isn't prussic acid).

Prussic acid is almost uniquely toxic and it is the main product - any impurities thrown up may or maybe not toxic but are unlikely to be anywhere as toxic as prussic acid.

But in this case, you are seeking pure toxicity - impure non-toxicity is the problem , not the solution.

Grapefruit are 99.99% impure of vitamin C - thanks be to God


Grapefruit are a so so source of pure vitamin C . A 500 gram fruit might hold only 50 mg of vitamin C - one bit in 10,000 is pure vitamin C and the rest is - technically - impurities.

So why do we bother ?

Well they are very tasty , providing lots of water, fibre, sugar and various other minerals and vitamins - as well as some of the tasteless vitamin C we could get from a pill.

(And surprise surprise, that pill , when taken with the needed glass of water, is also mostly dross and a tiny amount, often only 100 mg, of vitamin C !)

And all those grapefruit 'impurities 'are safe - we eat them without any danger and in fact with a great deal of enjoyment.

All our food mostly consists of a vast bulk of relatively safe impurities and tiny amounts of pure vitamins and minerals.

But some foods - some very tasty mushrooms - consist of mostly nice food and tiny amounts of impurities called toxins that kill us.

So it all depends.

First we must define what is the main product we want from a mixture before we can define its 'impurities'.

Do grapefruits consist of 90% food (discarding only the skin and seeds) or do they consist of .001 % vitamin C and 99.99% dross ?

Then we need to do the experiments before drawing any conclusions.

Because sometimes , as with weak impure penicillin juice versus pure strong penicillin powder , it turns out that penicillin allergy deaths only began with massive amounts of the 100% pure stuff !

By sheer good luck, in this particular mushroom (this strain of the sometimes dangerous penicillium mold), the impurities were non-toxic as was the penicillin .

But for a relatively large percent of people, if given large amounts of pure penicillin direct into a vein by careless doctors, it can kill on the spot in a severe allergy reaction.

The safe solution is to go on using pure penicillin but to test new patients with tiny amounts - just beneath the skin - first.

Florey spent more than ten years - from the late 1930s to the late 1940s seeking ever purer penicillin to increase the safety of this injectable drug.

His obsession was scientifically wrong, logically deluded and it delayed the wartime introduction of mass produced penicillin for years.

Florey was a racist


Florey was an eugenicist and a racist from his youth and I believe this sort of racial purity thinking leaked over into the science side of his brain - he saw penicillin as the Anglo Saxons and the impurities as the Blacks.

Blood that was 99% Anglo Saxon and 1% Black was impure and defiled - and much the same applied to pure versus impure penicillin.

In Florey's twisted mind.

Ward doctors are like shop floor chemists - they hold few illusions 


Another problem was that both Fleming and Florey were far more lab doctors than ward doctors - while Martin Henry Dawson divided his time equally between both.

Sheltered university chemists quickly lose their delusions about the academic awards for obtaining 100% total synthesis ,regardless of expense or yield, once on the factory floor of a profit-seeking chemical firm.

So too with busy ward doctors balancing a dying patient versus a very dangerous drug that might injure them as well as save their life.

My mother would have backed Martin Henry Dawson 110%


My mother , in her early thirties, was saved from certain infectious death by a single course of streptomycin .

It left her deaf in one ear - by that time, in 1962 , this was a well known risk of high doses of that drug.

She didn't complain then and she never ever did .

She told how grateful she was to lose her hearing to gain her life just three days before she suffered her fatal stroke - when she was in her eighties, a half century later.

So call me prejudiced - I like doctors who take chances to save patients' lives.

I like Martin Henry Dawson.

He saw two patients about to die from invariably fatal endocarditis.

All other known medical solutions had failed.

He knew penicillin seemed non toxic in various animals and in human blood - from his own research and that of Fleming and Florey.

He tested a small amount of penicillin  that he suspected to be probably very weak , on himself, injected just under his skin.

No toxic results.

He did the same on the two patients - not toxic.

He gradually and slowly upped the amounts and also moving gradually to injection methods that introduced the penicillin far quicker into the blood and hence was far more potentially dangerous.

Only local pain at the injection site and a temporary fever and shakes was noted - routine for most injected drugs then.

All Dawson sought from penicillin was that it was relatively safe - and effective.

He used the penicillin he made himself with hours or days - he wasn't afraid of hard work, unlike Fleming - so stability was an non-issue to him.

Like the food that Dawson ate and enjoyed, his crude penicillin was hardly pure - but so what - it was basically safe.

Safer in fact - even in crude form - than the 100% pure sulfa drugs that were then routinely saving many lives while also making many people very very sick in the process.

Like a chemist on the shop floor ( think Smith, Elder and Jephcott ) Dawson saw life as full of compromises and the job was determining what was really Job One.

For all of them , it was saving as many patients as they could - NOW !

And God Bless 'Em for that...

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