Blepharitis , a chronic inflammation of the eyelids, remains one of the world's most common eye problems.
Much of the time it is caused by staph bacteria and at the start of world war two, staph was one of the few common pathogen bacteria not killed by the various sulfa drugs - the 'antibiotics' of the day.
This was a big problem for the military of all the combatant nations of that war.
They regarded aviation as the alpha and the omega of modern warfare and so gave inordinate attention to the brand new field of "aviation medicine".
One only has to recall the moral panic the Allies fell into on mere rumours that the Germans had discovered the Viagra of aviation - a cortisone that let their pilots fly higher faster longer, well you get the picture.
Meyer had a consultancy with Schering Corp America - an German-owned company - involving ,among other things, attempts to create stable esters of penicillin.
Fears that Schering's work on cortisone was at the behest of the Nazis, ( it was not) rendered Schering totally suspect in the eyes of British and American intelligence circles.
Anyone connected with Schering - like Karl Meyer and his penicillin efforts - went into a little black book of "no-nos".
Aircrews and Blepharitis
An existing, generally intractable, case of blepharitis kept a lot of potential air crews out of the various air forces right at the recruiting office - that was problem A.
Problem B was that a lot of crews seemed to get blepharitis, either after they had been through training or while out on active service .
This was perhaps due to the strain of operating in the air of five miles up, behind an oxygen mask for hours.
It doesn't directly worsen your vision but it gives you blurry eyes which comes much to the same thing.
It also needlessly worried aircrews, who feared it meant worse things than it did.
Not just pilots or gunners are hit by its effects - engineers, navigation officers and bomb setters all had to look at lots of crucial numbers on lots of dials in very dim light - one pair of blurred eyes at the wrong moment could be terminal for the entire plane and crew.
Karl Meyer ,as a German Jewish emigre, had an easier relationship with Dr Ludwig Von Sallmann, who also was in exile --- from his native Austria because his wive was Jewish.
But even Sallmann only seemed to want to put Meyer's semi-purified penicillin into animals and then didn't publish anything on the results till a few years later (in 1943 - at least 2 years after the first experiments).
Typically of many,many doctors, he published freely on his early work with penicillin only after Baby Patty Malone made penicillin world famous, safe and respectable.
At least Dr Phillips Thygeson did put the crude penicillin into the eyes of 8 patients with chronic blepharitis caused by (sulfa-resistant) staph bacteria, between the late Fall of 1940 and the early Spring of 1941, with some very good results.
But he refused to publish on this success (adding his name to Fleming and Paine et al in England who also refused to publish their spectacular early successes with crude penicillin and eye diseases.)
The history of penicillin might have been much different if these doctors had crowed just a little.
Thygeson finally published on bleparitis and penicillin - in 1945 - noting its key military importance !
I think an oral history interview with Thygeson late in life suggests what happened:
I don't think he could stand Meyer much.
He accused him of being a constant paranoid about his work--- and having a gutteral accent that no student could understand.He said nothing about Sallmann's accent - though Sallmann had arrived in America about 8 years after Meyer.
Now a young student had heard all of these stories, feared dealing with Meyer but found him soft spoken and kind and stuck with him throughout his career long enough to write his affectionate obit - so opinions clearly differed on Meyer's manner and personality.
Dawson hung in with him for almost 10 years, so he couldn't have been impossible to work with.
In fact, Meyer gradually transferred himself from the eye clinic to the internal medicine department where Dawson worked.
Thygeson chose not to help out Meyer, Dawson or the fate of penicillin by publishing in an area sure to advance penicillin's importance in the eyes of the military-oriented OSRD of Vannevar Bush.
Instead he stuck to publishing on his results with sulfa drugs - these were totally pure, came via the highly conventional route of a commercial drug company - and didn't work and had potential toxic side effects.
But they didn't come from the home brew lab of Karl Meyer and that might have been a big point in their favour...
@MichaelMarshallMogoesPo
Showing posts with label thygeson. Show all posts
Showing posts with label thygeson. Show all posts
Thursday, July 1, 2010
Wednesday, June 30, 2010
Dawson had been set to be the "invisible man", the Charles Fletcher of The Manhattan Pilot
I believe that for two critical weeks at the very beginning of the The Manhattan Project, Martin Henry Dawson was not set to be the team leader/senior investigator - in fact he was not expected to be involved at all.
The team was supposed to be led by the biochemist Karl Meyer, with someone (anyone) acting as the microbiologist to test the 'in vitro' activity of the penicillin produced , again with some doctor (anyone) from Columbia Presbyterian's eye clinic in the clinician's job (the nominal job of Dawson on the final Pilot team) .
The penicillin pilot's aim, at that point, was simply (!) to purify and then synthesize penicillin - most of the small amounts of crude penicillin produced would have to be destroyed in crystallization (purification) experiments.
Only tiny, tiny amounts could be spared to show the resulting penicillin still retained the needed biological activity against bacteria on a glass slide or against bacteria on/in a human.
These were expected to be merely subordinate activities to the main show - "making penicillin".
These were expected to be merely subordinate activities to the main show - "making penicillin".
Now any drug, not just penicillin, needs to be first proven safe for humans when taking internally and be available in huge amounts, before it can be injected into the body as a 'systemic' --- versus simply being dropping a bit of it into the restricted/external area around the eyeball as an 'antiseptic'.
Penicillin, in particular, quickly slips out of the body and so needs even larger amounts than most drugs to work successfully as a systemic.
This is why penicillin's first successes in Britain during the 1930 (but tragically for humanity never published), were in removing deadly bacteria from the area around the eyes.
Meyer ,working in an eye clinic ,knew these truths better than most. In fact, he did involve two doctors from his clinic to use some of his penicillin with their patients but both doctors (Von Sallmann and Thygeson) seemed dubious about its usefulness around and in the eyes (as well they should have been).
The results were not spectacular and were published a few years later.
Eyes were saved in the early 1930s from a lifetime of blindness with treatments of diluted crude penicillin that in total must have consisted of only 1.6 Oxford units of biological activity (that is equal to one millionth of a gram of pure penicillin).


By contrast, Dawson's disease of choice to test penicillin upon, SBE, subacute bacterial endocarditis, may today require 1.6 billion units of penicillin to cure.
That is one kilogram of pure penicillin - one billion times as much penicillin.
It was known in 1940 that SBE would need an extraordinary large amount of whatever drug that could kill the bacteria in its vegetations because of the unique location of the lesions and the poor blood supply of the heart valves they rested upon- that is the problem in fact that still makes SBE the 'gold standard' of intractable infections.
All drugs to date, as of 1940, had to be used in such large amounts to kill the bacteria that they killed the patient first - because even a relatively "non-toxic" drug is deadly if used by the shovelful !
It was Dawson's genius to see that penicillin's strength was not what the popular books on it still proclaim - its ability to kill bacteria - but rather its ability not to kill the patients, even when used in extraordinarily high amounts for months at a time.
And SBE proved to be just the disease to demonstrate that fact....
@MichaelMarshallMogoesPo
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