Sunday, August 29, 2010

was I too harsh on Eric Lax ?

Some have worried that I was.

But I don't agree and I hope that even Eric Lax will see why I argued as I did.

Almost anyone reading Lax's book on penicillin, "The Mold in Dr Florey's Coat", is struck by the fact that the emotional climax of the book is well forward in the overall Penicillin Saga - occurring in May 1940.

 I would have set the emotional climax much later - in August/September 1943 or in May/August 1944.

Lax's book builds steadily up to the (supposedly) crucial animal protection tests that Lax and almost all other penicillin authors chide Fleming for failing to perform in the Fall of 1928.

A check of Lax's own indexing confirms the large number of pages (in a shortish book) that are devoted to animal testing and the mouse protection tests.

He is also that rarity among the many penicillin authors in deciding to quote at length from John Fulton's letter to the Nobel Committee ,in which Fulton says that Florey deserves the Nobel because of his animal experiments with penicillin.

Surely an, ahem, unique viewpoint.

But in a perverse sort of way it does show some truth - Fulton and Florey loved to experiment on the bodies of animals far more than they did anything else in life.

Lax sets up the animal protection tests of May 1940 as the moral high ground of the entire penicillin story.

He even highlights the story of the Florey team deciding to smear their coats with the most widely available 'rare' mold on Planet Earth (thanks to Fleming !), all to keep it from the Nazis.

I merely say that what is good for the goose is even better for the gander.

Yes, Fleming should have needled the mouse back in '28, but why didn't Florey do the bog simple mouse test in early 1938, when peacetime drug firms might have been able to produce commercial penicillin, even before Hitler overran Poland ?

The usual biographer's apology for Florey waiting from Spring 1938 till Spring 1940 to test penicillin against an artificial illness (and until Spring 1941 before testing against a real human illness) is that he needed purified dry penicillin before he could do an injection.

Fleming's rebuttal would be "that since I never obtained any dry purified penicillin - according to Florey" - "then I was under no moral obligation to do the mouse protection test".

"Or if I should have done so anyway with wet penicillin in 1928,then Florey should have done ditto in 1938."

Duhig from Brisbane could also chime in with that blunt Australian manner, with "Look, Florey, I saved large adults from terminal illnesses with injections of weak,wet, penicillin - surely you could cure a diseased mouse with some of your 1938 wet penicillin if you had only tried ..."

In support of Duhig, Heatley says that the first penicillin used by Chain in March 1940 ( in a sort of toxicity test) had between 2 to 5 units of anti-bacterial activity per mg and that
a 20 gram mouse got 40 mgs - that is about 4,000 to 10,000 units per kg of body weight.

For a 80 kg adult human male that is the equivalent of a single dose of 320,000 to 800,000 units of injected penicillin - even today that is 'heroic medicine'  -and as a single dose in a series for animal protection it is about one hundred times too big.

But is also the liquid penicillin you would obtain, even in 1928 or 1938, from a single medium sized lab flask  - not exactly hard work to gather up.

But it is 40 mls of liquid penicillin to inject into a mouse - far too much even if done as a slow drip.

However, injecting .5 or 1.0 ml of raw crude wet penicillin at a time into a twenty gram mouse, as part of a series of injections, would be perfectly safe.

It would give , in human adult male equivalent terms, a single dose of about 4,000 to 16,000 units - which is about what a wartime adult male penicillin patient did get in a single dose in a series of shots (usually receiving 4 to 8 such shots in a twenty four hour day).

The technical claims against using crude wet penicillin in animal protection tests fails to stand up - but fails for Florey as well as for Fleming.

In talking about (Duhig's) raw, totally non-concentrated penicillin as being suitable for animal protection tests, I am deliberately worsening the case against Fleming.

In fact, while in 1940 Florey had a dry brown powder with 2-5 units of activity per mg, in 1929, Fleming had a brown gooey toffee with 2-5 units of activity per mg - once re-wetted with distilled water to inject into a mouse, both were as equal as can be.

 Neither were pure.

But both had been concentrated successfully enough to be highly useful therapeutic penicillin - if only that pair had had the guts to 'do the clinical' .

That was something that Dawson did , and did in a ' New York minute' .

Harsh on Eric Lax ?

I don't think so...

No comments:

Post a Comment