Showing posts with label may 1940. Show all posts
Showing posts with label may 1940. Show all posts

Saturday, January 26, 2013

Florey delays penicillin for three more years : powdering the sick mice, May 1940

Just imagine for a moment if Howard Florey had actually done in May 1940 what he claimed he did for the rest of his life.



The one small/simple experiment that Alexander Fleming never did in 1928 and the one small/simple experiment he absolutely needed to do , to become for all time, the fully respected "discoverer" of penicillin.

At least in the eyes of scientists, doctors, historians and knowledgable lay people.

That experiment was to inject some of his mouse juice again into a mouse - but this time a  mouse deliberately infected with massive amounts of bacteria, not a healthy mouse.

All to see if his penicillin juice could pricelessly save lives by working internally to root out massive infections, not to merely become another in a long line of antiseptics, to be dabbed on cuts  merely as an aid to hurry up their natural scaring and healing.

Fleming never did this experiment.

Crucially, neither did Florey.


Fleming would have to have slowly injected half a gram (cc/ml)  of penicillin juice into an acutely ill 20 gram mouse, and since each gram had about 4 units of antibacterial activity in it, that would have been only 2 units of antibacterial activity per dose.

He'd have to repeat this about every 16 hours for perhaps three days to cure the mouse.

By contrast, because Florey first concentrated that penicillin juice down to about one thousandth of its original volume by boiling the water away in a vacuum, he ended up with mere milligrams of a dry brown powder - each mg containing the same antibacterial units as a gram of the original penicillin juice.

But after all this hard work, he also LOST two thirds of the original penicillin activity.

(He'd be fired if he did that for long in a commercial industrial fermentation operation !)

He dissolved 10 of those mgs of dry penicillin powder into .3 cc of distilled water ( back to the future again !) and injected perhaps 20 to 40 units of antibacterial activity into another acutely sick 20 gm mouse, saving its life in one large intense dose.

Luckily his mice did not die of needle fever during that single big dose - Fleming's need to give weaker injections, repeated over a longer period of time, did at least reduce the chance of severe side affects.

Properly handled, Fleming's strain routinely actually will give at least 40 units per gram of juice.

Then one half gram of his juice would give the exact same effect as 10 mg of Florey's dried powder (10 units in both cases.)

So an alternative path to Florey's tiresome and loss-inducing concentrating and purifying of tiny amounts of antibacterial activity in the original juice was to fire the team chemist and hire instead an industrial mycologist (fungus fermentation specialist) who knew how to starve a mold into giving more , not less, penicillin !

Up till Florey, all those who had written scientific articles on penicillin had acted as if it would be used as a non-toxic and wholly natural liquid , much as natural liver extracts were used to save those with pernicious anemia.

Florey introduced a totally new - and totally bogus - wrinkle into the effort to put penicillin to work saving lives.

He suddenly claimed that penicillin juice was NOT non-toxic - unknown parts of it was toxic "impurities" and that only the fully pure penicillin was non-toxic.

Though how he knew this, well in advance of getting anywhere near full purification, I best leave to your wild imagination !

Particularly if you knew some healthy person who died suddenly  of anaphylactic shock after a routine dose of 100% pure penicillin.

I am afraid I can never forgive Florey for the wasted years and wasted diversion of effort into purifying penicillin juice instead of simply pouring it - NOW ! - into dying patients.....


Wednesday, August 25, 2010

May 1940: our two protagonists enter stage left

The Penicillin Story had been underway for almost twelve years when our two protagonists, Howard Florey and Henry Dawson, first seriously entered the story in May 1940, Mensis Horribilis, and changed the Story's direction completely.

It is true that Ernest Chain, Leslie Epstein, and Norman Heatley had been working with penicillin at the Dunn Pathology Institute at Oxford University for about two years by that point.

But only when it became intensely and personally important to the Dunn's director, Howard Florey, (when he injected the first therapeutic doses for some artificially infected mice),did it gain some real momentum for the side of the war time penicillin story that I will call "Chemistry".

Dawson's team (Karl Meyer specifically) didn't display any interest in penicillin still sometime between June 10th 1940 and September 7th 1940 when he first heard of it from Leslie Epstein, newly arrived from Oxford and the Dunn.

Dawson didn't become directly involved in penicillin until he first heard of Florey's published results from Meyer, sometime around September 9th 1940.

But he was emotionally ready for committing to penicillin as his ABF agent (Anti BioFilmic agent) since a series of New York area symposiums on Rheumatic Fever and Subacute Bacterial Endocarditis (SBE) in April and May 1940, that had just been published in article form in August 1940.

After the development of the Sulfa drugs, bacterial diseases seemed passe to the ambitious medical researcher.

As a result, it was becoming clear that the victims of (middle class) virus diseases like Polio would soon occupy the emotional and charitable space once occupied by (working class) Rheumatic Fever patients.

But Rheumatic Fever/SBE was still the major killer of school age children and young adults, killing far more than Polio by at least ten to one.

Dawson was not employed by his hospital and university to worry himself over SBE, to put it mildly.

Endocarditis was generally thought of as a disease for heart specialists, while Dawson operated a day clinic for chronic arthritis - in 1940, about as low as you could go on status
ladder in an acute-life-threatening-disease-oriented teaching hospital.

But it seems he stepped in, early in September 1940 when he found no heart specialists felt penicillin could be the long sought cure and he found no drug company willing to make clinical penicillin for such a disease.

His heart drew him in.

But his head kept him there.

His lifelong hobby or personal research focus, as opposed to his day job, had always been the commensenality shared between humans and their live-in microbes, a sort of uneasy co-existence or cold war as we and they struggled to survive against the activities of the other side.

His two previous developments ( HGT/Q-Sensing for s. pneumoniae and Molecular Mimicry for s. pyogenes)  had profound implications for all Biology, not just Medicine.

Unfortunately, they had no immediate application for fighting back these two sometimes-deadly bugs.

But his instant and intense conviction that penicillin's combination of non-toxicity and extreme diffusability made it the perfect ABF tool for penetrating SBE vegetations ((biofilmic colonies) on heart valves would let him get three bugs for the price of one.

This was because it was s. pyogenes that caused our bodies to attack its own heart valves - damaged areas that later were colonized by s. pneumoniae or s. viridans - leading to  fatal acute or subacute endocarditis.

I will call this side of the wartime penicillin story, "Commensality" ....