Wednesday, December 5, 2012

Did Phillips Thygeson fumble Penicillin in 1940?

Of course he did - but he was hardly alone.

Between 1930 and 1940 a series of unbroken successes with semi-purified penicillin in the treatment of very serious eye infections were unreported by the eye doctors who performed them.

If these striking successes with serious eye infections had been reported, penicillin would have gone into commercial production before the war and saved millions of lives world wide.

Dr Fred Ridley, future eye specialist, was the first to semi-purify penicillin in 1929 while working for Alexander Fleming and he witnessed most of the beginnings of penicillin , including its earliest (unsuccessful) clinical uses.

So he also probably knew of Fleming's only clinical success with his penicillin.

It involved a severe case of pneumococcal conjunctivitis and happened in 1932, according to the patient (Dr Keith Bernard Rogers) or in 1929, according to Fleming's biographer Gwyn MacFarlane.)

I think 1932 more likely by far.

There is a good explanation why Fleming chose not to published this great success : it revealed far too much of his own character.

Though Fleming was the director of a large medical cum commercial enterprise, in many ways he displayed the work ethos of a classic 'lifer'.

 He gave a rigid, dutiful, 9-5, Monday to Friday output, but nothing more. No 'heroic medicine' for Fleming.

What he really lived for was in playing - and winning   -competitive games ---- after work hours.

He is perhaps the best example we have (outside perhaps of president George W Bush and Mayor Rob Ford) of the dangers society faces when sports-obscessed teenage boys fail to grow up and mature.

When it seemed his all-important rifle team might lose a critical match because its star shot had an eye infection, Fleming dropped everything to cure him with his penicillin and win the match.

(Perhaps if Fleming's brother John, dying of pneumonia, had been about to be involved in an important game, Fleming might have worked equally hard to save his life with penicillin.)

Now, as is well known, Fleming loved messing about and 'playing soldier' with real war rifles; it was equally well known that he  disliked the thought of being a real soldier.

This fact was well enough known to be a source of minor comedy to his colleagues.

The outer medical world, reading a published article, might not connect Dr Rogers' marvelous cure with 'Flem' winning his all important rifle shot.

But, soon, potentially all 10,000 or so doctors and nurses in the greater London area would, as the local medical gossip mill ground into overtime, having another joke at Flem's expense.

Earlier,beginning in 1930,just after Fleming's only major penicillin paper was released, another student of his, Dr Cecil G Paine, had a series of successes with his own hospital-made (totally unpurified) penicillin in eye inflections.

Together with eye doctor Albert Nutt, he saved seven newborns from going blind from gnorreal inflections in the eye.

 His eighth case involved an almost certain lose of an eyeball (or possible death from general infection) -- a coal mine manager with a fragment of rock having penetrated the eye, allowed colonies of bacteria to form at the site.

(This is a situation very similar to SBE : like eyeballs, heart valves are smooth and bacteria free, unless roughed up by physical damage.)

The pneumococcal bacteria were cleared up by crude penicillin filtrate washes and the foreign object removed. The eye was basically unscarred in healing.

It should have been - to experienced eye doctors anyway- an obvious miracle.

To other doctors, Rogers and the mine manger cures of pneumococcal infections would have suggested that perhaps injected penicillin might cure lobar pneumonia.

In the 1930s, lobar pneumonia was a leading cause of death in people of relatively young age and otherwise good health : the equivalent contemporary emotional effect of such deaths today might be the loss to breast cancer of young mothers in their thirties leaving behind very young children.

In the 1930s, it was the loss of middle aged fathers in one income families, leaving behind teenage children.

Pneumonia deaths were often devastating and totally unexpected.

But neither Fleming or Paine or Nutt published their successes.

Paine told of his success to both Howard Florey and to Leonard Coldbrook no long afterwards, both both men, neither of them shrinking violets to put it mildly, did not seize this particular nettle.

I suggest a reason why when I try to account for Thygeson's similar reluctant to get into penicillin at the ground floor.

We are left then with Henry Dawson, who proved far more willing to publish his relative failures with penicillin than many others were willing to publish their clearcut successes !

It might be that people like Rodley and Nutt who choose to become eye specialists are retiring types and not likely to stick their necks out.

Above all, unlikely to admit in print that they un-dignified the medical profession by daring to use "home made bread" rather than drug "store bought bread" to cure a patient.

But Phillips Thygeson hardly seemed this type of eye doctor : he had a long career in advanced eye research and his own biographers admit he had a fearsome , explosive temper when crossed.

He, too, had early success with penicillin - treating eight cases of
chronic staphylococcal blepharitis "satisfactory" with  natural penicillin semi-purified by Karl Meyer. One case in particular that was resistant to all sulfas showed a prompt respond to penicillin.

We know all of this, only because of Dawson breaking protocol on several occasions to talk up Thygeson's work in public and print, perhaps hoping by doing so to get Thygeson to commit his work to paper. (No luck !)

Thygeson did not like Karl Meyer at all and thought him a paranoid - though many others had no such problem with him.

We know Leonard Colebrook had the strongest possible reasons to dislike Fleming.

He believed that Fleming had deliberately manipulated Colebrook out of the affections of the only 'real' father Colebrook felt he had - his and Fleming's boss, Dr A. Wright.

I don't think I am alone in thinking this is why the crusading doctor Colebrook overlooked using Fleming's penicillin to cure childbirth fever deaths, in the eight long years before sulfa drugs arrived.

Meyer also worked with the eminent eye specialist Ludwig Von Sallman , using penicillin semi-purified by Meyer.

I do not know the time this happened, but am inclined to think it happened after Thygeson left Columbia University.

It probably happened in mid 1942 , while Dawson was away having a serious operation and recovering and was published as soon as the medical censors would allow it - ie from late 1943 onward.

But when did Thygeson's pioneering penicillin work happen ?

My educated guess may surprise penicillin history specialists and is the subject of another blog.

But for now, let me note that Dr John Hedley-Whyte, in his fascinating article, "Lobar Pneumonia treated by Musgrave Park physicians", notes a few other eye related cases that involved pioneering use of early penicillin - and that these were reported (and as a result, we finally got penicillin for all.)

The famous policeman dying in Oxford had seen a minor rosebud scratch infection, over the months of ineffective treatment , go into his eye socket and then into his skull.

SBE, a classic disease of the innermost body ( it affects heart valves)  can be detected by many outwardly visible signs, one of them the famous Roth spots in the eyes.

Hedley-Whyte's powerful insight into Florey's behavior in April 1941

Hedley-Whyte's point and it both unique to him and powerfully insightful, is that penicillin for ten years was an eye doctor's tool and that an informal wash of communications about it, via personal contact and personal letters , went back and forth across the Atlantic from 1929 to 1941.

Hedley-Whyte  says this is how Fleming and Florey knew about Dawson's as yet unpublished work with treating SBE in New York in March 1941.

I know his case to be partly true because most printed claims about penicillin being "alway censored during World War Two" is loose historian's bosh.

For example, Leonard Colebrook in Britain  in 1940-41, is careful to disguise the word sulfa so as to get past the censors when responding to Perrin Long in America, but has no trouble using the full word penicillin.

Very little about penicillin was actually censored and even this was internal semi-voluntary censorship by editors at the largest scientific journals, acting patriotically under informal pressure from the scientific elites.

 All mention of serious chemical synthesis work on penicillin after about late 1942 was withheld by the relatively few teams engaged in this work.

But reporting chemical work to merely semi-purify penicillin at a crude level went uncensored: this is how Duhig in remote Brisbane learned how to make crude penicillin stable enough and safe enough to inject straight into dying patients.

True - that in America and due to the odious, unctuous Morris Fishbein - almost ALL mention of penicillin was withheld from the larger journals and the popular media from the Fall of 1941 till about the Fall of 1943.

Most effected were cases of treatments by semi-purified natural penicillin : Fishbein's committee's apparent hope was that if the public didn't hear about these efforts, pressure to actually make natural penicillin in commercial amounts could be held off until Science laid the marvelous egg of man-made penicillin....

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