Mea Culpa.
I admit it, I originally dissed Dr Wainwright's theory that much of the anti-Fleming abuse really came from a small group of Florey's Oxford post-docs, unable to accept that the world did not rise and set in Oxford.
But I have changed.
As I followed the letters of Florey and Heatley vetching for four years that all penicillin - to be worthy of the name penicillin - must measure up to the OXFORD STANDARD, my Canadian hackles rose.
My grandmother came from the suburbs of Manchester Lancashire and my granddad from Petley Bridge in Yorkshire -- they never spoke OXFORD ENGLISH and they promptly moved to a country where that sort of nonsense never mattered.
To read Florey telling A.N. Richards to keep secret any differences between Oxford and American penicillin - as if strep bacteria cared a toss - is to see a citizen of a nation who has lost the financial war still acting like they ruled the world, that George Washington had never won, and that they could still lay down the rules on how everyone was to speak and assay penicillin.
Read Milton Wainwright , particularly on Fleming - he says a lot of interesting things and raises a lot of interesting points...
Monday, September 6, 2010
Why HEATLEY rather than Fletcher,Chain or Jennings ?
The attempt to make Oxford penicillin the "Received Pronunciation" of world penicillin....
OXFORD :"First we take Manhattan, then we take Berlin, Paris and Cape Town..."
************
Fletcher could have accompanied Florey to America to remind Americans that Britons had also ,me-too, used penicillin to treat patients... after Dawson did it first in America.
Chain could be there, to say penicillin was his idea and that Florey only got interested after it got promising - and to admit, yes, his own chemical work was not yet as advanced as Meyer and the Schering Corp was in America.
Jennings could have gone along to say that Britain did the first animal protection test (which Fleming didn't do) but that, yes, Dawson did the first human protection test, in America.
But Heatley-the-invisible, he'd never steal any glory from Florey.
And he was the assay man - the man who would act like the schoolmaster he looked like - checking every American firms' penicillin sample to measure it against the Oxford Standard, and docking marks for any firm that failed to measure up.
For just as nobody anywhere else spoke as good an English as OXFORD ENGLISH , so too nobody's penicillin would ever quite measure up to to the Oxford Standard, the Received Pronunciation of penicillin, the only penicillin you could prescribe on the BBC or give to the King.
Two points: (1) the supposed standard, OXFORD PENICILLIN, was actually composed of 98% rubbish - and don't get me started about Oxford in general.
(2) There were in fact many many strains of penicillium producing many many different types of penicillin, depending on what they had to eat and how acidic their surroundings were etc. This is Reality at ground zero. But Florey spent the next 4 years denying and downplaying any existence of differences in types of penicillin.
His only chance at grasping the golden ring was to constantly maintain his claim that he was the first to purify penicillin - he couldn't have this claim disputed by people asking which of the twenty variants of penicillin did he ,ahem, first 'purify' exactly ?!
I don't know if Florey played chess - but he had the chess player's skill of always thinking six moves ahead of anyone he thought might possibly be his opponent as he clawed his way to the top of English Society.
And when he was a Baron and president of the Royal Society, you'd never guess he had been born in the Outback - his English was now far more RP than his penicillin ever became....
OXFORD :"First we take Manhattan, then we take Berlin, Paris and Cape Town..."
************
Fletcher could have accompanied Florey to America to remind Americans that Britons had also ,me-too, used penicillin to treat patients... after Dawson did it first in America.
Chain could be there, to say penicillin was his idea and that Florey only got interested after it got promising - and to admit, yes, his own chemical work was not yet as advanced as Meyer and the Schering Corp was in America.
Jennings could have gone along to say that Britain did the first animal protection test (which Fleming didn't do) but that, yes, Dawson did the first human protection test, in America.
But Heatley-the-invisible, he'd never steal any glory from Florey.
And he was the assay man - the man who would act like the schoolmaster he looked like - checking every American firms' penicillin sample to measure it against the Oxford Standard, and docking marks for any firm that failed to measure up.
For just as nobody anywhere else spoke as good an English as OXFORD ENGLISH , so too nobody's penicillin would ever quite measure up to to the Oxford Standard, the Received Pronunciation of penicillin, the only penicillin you could prescribe on the BBC or give to the King.
Two points: (1) the supposed standard, OXFORD PENICILLIN, was actually composed of 98% rubbish - and don't get me started about Oxford in general.
(2) There were in fact many many strains of penicillium producing many many different types of penicillin, depending on what they had to eat and how acidic their surroundings were etc. This is Reality at ground zero. But Florey spent the next 4 years denying and downplaying any existence of differences in types of penicillin.
His only chance at grasping the golden ring was to constantly maintain his claim that he was the first to purify penicillin - he couldn't have this claim disputed by people asking which of the twenty variants of penicillin did he ,ahem, first 'purify' exactly ?!
I don't know if Florey played chess - but he had the chess player's skill of always thinking six moves ahead of anyone he thought might possibly be his opponent as he clawed his way to the top of English Society.
And when he was a Baron and president of the Royal Society, you'd never guess he had been born in the Outback - his English was now far more RP than his penicillin ever became....
Thanks to DOCTOR MOM, "he (and she) will be coming home!"
Most wartime GIs who drank too much Schenley whiskey and ran their jeeps off the road and woke up in the hospital with a penicillin drip in their arm, never realized that not only did Schenley sell them the bite of a snake but they also sold them the cure.
That wartime penicillin might have come from Schenley Labs.
Their whiskey is still here - but their penicillin is long gone.
But Schenley did have the satisfaction for having produced the most iconic image of the entire saga of early penicillin.
Printed in rich vivid glossy magazine color, this ad featured the realistic style painting of a medic putting penicillin in the arm of a wounded Marine in a place that looks to be Tawara, as photographed by Marine photographer Norman Hatch.
Seventy years later, Hatch's photos remain the gold standard of 'you are there' combat photography.
This famous island battle first brought home to America just how bloody this war was going to be - particularly because of the casualty count.
But mostly because Hatch's grim photographs were deliberately released, rather than censored, to toughen up Americans at home to the mounting death toll that lay ahead.
So the ad's painting immediately conjured up a grim backdrop to any magazine readers in 1943-1945.
But the cutline below was pure uplift : "Thanks to PENICILLIN...
he will come home !"
Often rendered in the retelling as "Thanks to Penicillin, he will be coming home !"
The combination of image and cutline basically assures home viewers worried about their relative overseas that "Despite the vicious fighting and the terrible jungle conditions, thanks to penicillin, he WILL be coming home !"
This ad went totally unremarked upon during the war.
But in the 65 years since, it has grown by leaps and bounds in importance as almost every scholar today finds it to be the best single wartime expression of the sheer hope that grew in a world (bone tired of 15 years of Depression and War) that something good must lie ahead.
Usually, their subtext when recalling this ad is "Thanks to Big Science bringing us Penicillin, he will be coming home !"
I don't think this is true at all.
I believe that if left to their own devices (along with scads of our tax dollars) it would have been 1946 or later before enough penicillin would had been produced to help the soldier at the front , let alone the patient back home.
I think there were two competing strategies to speed up the production of wartime penicillin.
One was develop scientific evidence on a very wide and deep front ("Big Science") to convince scientists in universities, hospitals, corporate research labs and in bureaucratic offices that a small shift in international wartime priorities was justified to produce large amounts of penicillin as a supplement to the sulfa drugs for illnesses resistant to sulfa like those caused by staph bacteria.
But that only enough penicillin needed to be produced to aid the fighting men, at least until the war was finally won.
I hope you sense the contrast between a massive effort of "means" to secure a limited "end".
This was Howard Florey and his supporters' thesis.
The other strategy was proposed by just one man - a soon-to-be dying man - in September 1940 and maintained by him until his death in April 1945.
Martin Henry Dawson.
He said penicillin had already been privately discovered, in 1928 by Fleming, but no one had been roused and no lives had been saved.
Penicillin had also been publicly discovered,( ie published in the scientific media) in 1929 by Fleming and again in 1940 by Florey but no one had really been roused and no lives had been saved.
Dawson proposed instead to have penicillin popularly discovered - by Doctor Mom.
It was a Man's World back in 1940 .
(It mostly still is, but not as bad as back then !)
But even in 1940 women voted, bought much of the family's purchases and they were the daughters, mothers, sisters and spouses of the prominent men who ultimately ran things.
If they got on the case of the men to bring them penicillin and they stayed on the case (as women are very good at doing - some dare call it 'persistent nagging') , even reluctant men will eventually give in and get moving.
So Dawson persuaded Meyer and Hobby and Chaffee, his entire team of 'little science', to refocus their primary aim of their newborn penicillin pilot project.
He said they should immediately and narrowly focus on curing a single disease, Rheumatic Fever-induced Subacute Bacterial Endocarditis.
This disease was the one that all parents in the western world regarded as a constant Sword of Damocles over their heads ,at least until all their children had gotten safely into their early twenties.
Tuberculous might be the disease feared more by the poorest families and Diphtheria and Scarlet Fever might have been feared more in grandma's day, but from about 1910 to 1960, Rheumatic Fever (RF) was the number one killer of school age kids .
In addition, the invariably fatal subacute bacterial endocarditis (SBE) it brought to many Rheumatic Fever 'survivors' was a big killer of youth and adults all along life's journey.
But the main point of the myth of The Sword of Damocles was not the pain of the instant the sword actually did fall and kill you but rather that the situation made you afraid all of your life, just waiting for the day the sword might fall.
Most parents never experienced their children getting RF or SBE but all dreaded it might happen someday.
RF starts with a child getting a sore throat or tonsillitis from strep bacteria.
Think about it - what child doesn't get tons of those, even today with antibiotics?
Before antibiotics, the kids might cure themselves.
But one attack did not bring immunity.Your children got them again and again - like the common cold they were common, endemic ,ubiquitous.
Always the fear was that this strep throat attack will lead to something worse. Many kinds of worse, but the deadliest and the most common was Rheumatic Fever (RF).
Most times, nothing happened. But like Russian Roulette, for no good reason one strep throat attack or tonsillitis attack could lead to RF.
Now RF could kill your child outright, during the very first attack.
But in most cases, the child lived, even emerged unharmed.
But again it did not bring immunity.
Far from it, one incident of RF made a child more vulnerable to another and more severe attack of RF and so on and so on, ever downhill.
Now suppose the child survived all those severe repeater attacks but with a damaged heart - particularly damaged heart valves.
Now in their teens, the child was less likely to see RF ever again, but instead they faced the fact that ordinarily harmless tooth bacteria, swept into their blood stream by a single vigorous tooth brushing, could settle in on their damaged heart valves and lead to an 'invariably fatal' case of SBE.
They might , nevertheless, fight off a single bout of SBE - as perhaps as many as 10 to 20% did.
(The near 100% death rate for SBE as normally reported, was biased by only counting cases sick enough to end up in hospitals. But autopsy work often revealed hints of healed SBE scars on the valves of young traffic accident victims.)
But again, and I know I am a broken record, one cure of SBE did not prevent those tooth bacteria from settling in again on your valves - and the second bout was fatal.
RF induced SBE was a chronic ,invariably fatal, disease.
Dawson treated patients as young as 10 and as old as 60. After penicillin, patients were found to dying of RF mediated SBE into their seventies - deaths often disguised as a 'stroke' .
More bad news : the kind of strep throat bacteria that gives you RF grow more virulent by being passed back and forth repeatedly between humans in close contact.
If you had lots of children, that meant that your chances that several would get RF and SBE was higher than the statistical average, even when corrected for the number of children you had.
That is if you had six kids and a small house, their chances that one
of them would get RF should be six times 3.3 per 100,000 ( ie 1 in 5,000) but in fact it was much higher than this - more like 1 in a 1,000.
Small houses and big families being more common among poorer families, they got hit the hardest, resulting in it being called The Polio of the Poor.
But no family was really immune.
Dawson knew that a report of a cure for either RF or SBE would grab the attention of every single DOCTOR MOM in the world.
And Doctor Mom, not Dad (in charge of the bread winning), was the person in charge of the entire family's health -- if she wanted penicillin , now, she would get it - or governments (even wartime governments) would tremble.
Drug companies would rush in to take her money.
This was Dawson's thesis.
He had a small crew - four people, no government or foundation funding, with curing a single disease as its sole thrust. But against those small 'means', look at its broad 'ends'.
Doctor Mom, said Dawson, would see to it that her entire family all got lots of penicillin, now, not after the war - penicillin enough for both Frank on the battlefield on Tarawa and for little Susie in the Rhemuatic Fever ward in America.
Was he right - or did Florey's view prevail?
I will 'tell all' - on October 16th this year - in my e-book "MO goes PO".....
That wartime penicillin might have come from Schenley Labs.
Their whiskey is still here - but their penicillin is long gone.
But Schenley did have the satisfaction for having produced the most iconic image of the entire saga of early penicillin.
Printed in rich vivid glossy magazine color, this ad featured the realistic style painting of a medic putting penicillin in the arm of a wounded Marine in a place that looks to be Tawara, as photographed by Marine photographer Norman Hatch.
Seventy years later, Hatch's photos remain the gold standard of 'you are there' combat photography.
This famous island battle first brought home to America just how bloody this war was going to be - particularly because of the casualty count.
But mostly because Hatch's grim photographs were deliberately released, rather than censored, to toughen up Americans at home to the mounting death toll that lay ahead.
So the ad's painting immediately conjured up a grim backdrop to any magazine readers in 1943-1945.
But the cutline below was pure uplift : "Thanks to PENICILLIN...
he will come home !"
Often rendered in the retelling as "Thanks to Penicillin, he will be coming home !"
The combination of image and cutline basically assures home viewers worried about their relative overseas that "Despite the vicious fighting and the terrible jungle conditions, thanks to penicillin, he WILL be coming home !"
This ad went totally unremarked upon during the war.
But in the 65 years since, it has grown by leaps and bounds in importance as almost every scholar today finds it to be the best single wartime expression of the sheer hope that grew in a world (bone tired of 15 years of Depression and War) that something good must lie ahead.
Usually, their subtext when recalling this ad is "Thanks to Big Science bringing us Penicillin, he will be coming home !"
I don't think this is true at all.
I believe that if left to their own devices (along with scads of our tax dollars) it would have been 1946 or later before enough penicillin would had been produced to help the soldier at the front , let alone the patient back home.
I think there were two competing strategies to speed up the production of wartime penicillin.
One was develop scientific evidence on a very wide and deep front ("Big Science") to convince scientists in universities, hospitals, corporate research labs and in bureaucratic offices that a small shift in international wartime priorities was justified to produce large amounts of penicillin as a supplement to the sulfa drugs for illnesses resistant to sulfa like those caused by staph bacteria.
But that only enough penicillin needed to be produced to aid the fighting men, at least until the war was finally won.
I hope you sense the contrast between a massive effort of "means" to secure a limited "end".
This was Howard Florey and his supporters' thesis.
The other strategy was proposed by just one man - a soon-to-be dying man - in September 1940 and maintained by him until his death in April 1945.
Martin Henry Dawson.
He said penicillin had already been privately discovered, in 1928 by Fleming, but no one had been roused and no lives had been saved.
Penicillin had also been publicly discovered,( ie published in the scientific media) in 1929 by Fleming and again in 1940 by Florey but no one had really been roused and no lives had been saved.
Dawson proposed instead to have penicillin popularly discovered - by Doctor Mom.
It was a Man's World back in 1940 .
(It mostly still is, but not as bad as back then !)
But even in 1940 women voted, bought much of the family's purchases and they were the daughters, mothers, sisters and spouses of the prominent men who ultimately ran things.
If they got on the case of the men to bring them penicillin and they stayed on the case (as women are very good at doing - some dare call it 'persistent nagging') , even reluctant men will eventually give in and get moving.
So Dawson persuaded Meyer and Hobby and Chaffee, his entire team of 'little science', to refocus their primary aim of their newborn penicillin pilot project.
He said they should immediately and narrowly focus on curing a single disease, Rheumatic Fever-induced Subacute Bacterial Endocarditis.
This disease was the one that all parents in the western world regarded as a constant Sword of Damocles over their heads ,at least until all their children had gotten safely into their early twenties.
Tuberculous might be the disease feared more by the poorest families and Diphtheria and Scarlet Fever might have been feared more in grandma's day, but from about 1910 to 1960, Rheumatic Fever (RF) was the number one killer of school age kids .
In addition, the invariably fatal subacute bacterial endocarditis (SBE) it brought to many Rheumatic Fever 'survivors' was a big killer of youth and adults all along life's journey.
But the main point of the myth of The Sword of Damocles was not the pain of the instant the sword actually did fall and kill you but rather that the situation made you afraid all of your life, just waiting for the day the sword might fall.
Most parents never experienced their children getting RF or SBE but all dreaded it might happen someday.
RF starts with a child getting a sore throat or tonsillitis from strep bacteria.
Think about it - what child doesn't get tons of those, even today with antibiotics?
Before antibiotics, the kids might cure themselves.
But one attack did not bring immunity.Your children got them again and again - like the common cold they were common, endemic ,ubiquitous.
Always the fear was that this strep throat attack will lead to something worse. Many kinds of worse, but the deadliest and the most common was Rheumatic Fever (RF).
Most times, nothing happened. But like Russian Roulette, for no good reason one strep throat attack or tonsillitis attack could lead to RF.
Now RF could kill your child outright, during the very first attack.
But in most cases, the child lived, even emerged unharmed.
But again it did not bring immunity.
Far from it, one incident of RF made a child more vulnerable to another and more severe attack of RF and so on and so on, ever downhill.
Now suppose the child survived all those severe repeater attacks but with a damaged heart - particularly damaged heart valves.
Now in their teens, the child was less likely to see RF ever again, but instead they faced the fact that ordinarily harmless tooth bacteria, swept into their blood stream by a single vigorous tooth brushing, could settle in on their damaged heart valves and lead to an 'invariably fatal' case of SBE.
They might , nevertheless, fight off a single bout of SBE - as perhaps as many as 10 to 20% did.
(The near 100% death rate for SBE as normally reported, was biased by only counting cases sick enough to end up in hospitals. But autopsy work often revealed hints of healed SBE scars on the valves of young traffic accident victims.)
But again, and I know I am a broken record, one cure of SBE did not prevent those tooth bacteria from settling in again on your valves - and the second bout was fatal.
RF induced SBE was a chronic ,invariably fatal, disease.
Dawson treated patients as young as 10 and as old as 60. After penicillin, patients were found to dying of RF mediated SBE into their seventies - deaths often disguised as a 'stroke' .
More bad news : the kind of strep throat bacteria that gives you RF grow more virulent by being passed back and forth repeatedly between humans in close contact.
If you had lots of children, that meant that your chances that several would get RF and SBE was higher than the statistical average, even when corrected for the number of children you had.
That is if you had six kids and a small house, their chances that one
of them would get RF should be six times 3.3 per 100,000 ( ie 1 in 5,000) but in fact it was much higher than this - more like 1 in a 1,000.
Small houses and big families being more common among poorer families, they got hit the hardest, resulting in it being called The Polio of the Poor.
But no family was really immune.
Dawson knew that a report of a cure for either RF or SBE would grab the attention of every single DOCTOR MOM in the world.
And Doctor Mom, not Dad (in charge of the bread winning), was the person in charge of the entire family's health -- if she wanted penicillin , now, she would get it - or governments (even wartime governments) would tremble.
Drug companies would rush in to take her money.
This was Dawson's thesis.
He had a small crew - four people, no government or foundation funding, with curing a single disease as its sole thrust. But against those small 'means', look at its broad 'ends'.
Doctor Mom, said Dawson, would see to it that her entire family all got lots of penicillin, now, not after the war - penicillin enough for both Frank on the battlefield on Tarawa and for little Susie in the Rhemuatic Fever ward in America.
Was he right - or did Florey's view prevail?
I will 'tell all' - on October 16th this year - in my e-book "MO goes PO".....
Sunday, September 5, 2010
1941 penicillin:Porton Down GERM WARFARE yes, patients no
The Florey Archives at London's Royal Society has a Florey letter (HF/1/3/2/1/19 )(previously 98HF.35.1.19) that didn't get shredded but probably was intended to be.
Dated December 4th 1941, it is addressed to Doctor "Cameron" at "Porton" and mentions scientists "Courtice" and "Gaddum".
Florey says ICI penicillin is at Porton and he is glad that Gaddum wants lots and lots of penicillin.
In December 1941, no one had much penicillin - certainly no patients in UK got any - and only Dawson's patients in the USA.
This must be some of the very first ICI penicillin ever produced - not for patients - but for 'Porton' .
One of Florey's very closest of his (very few) friends was Paul Fildes, very near the top of Britain's WWII Germ Warfare effort, which was centred at Porton Down.
That place has been for a century Britain's leading gas and germ warfare centre - in fact one of the top centres in the world for this highly secret activity.
Florey's first biographer, Bickel, indicated that in 1939, Florey had been asked by the War Office if he would be a consultant in 'poison gas research' (probably because of his proven skill in doing lethal experiments on small animals and his middle-aged chickenhawk attitude to the upcoming war.)
Florey had agreed.
I have always wonder if Florey's mystery month , mid July-mid August 1941, was somehow connected with him having informal talks on germ and gas warfare with various American researchers.
Certainly, Florey go top clearance for his trip to America from US and British officials - penicillin ,alone, seemed too unproven to warrant this kind of assistance.
Now Penicillin and Porton is like Jeckyll and Hyde to British audiences - no wonder this letter has never been mentioned in all the hagiography on penicillin and Florey.....
GR - Gordon Roy- Cameron *
FC -Frederick Colin- Courtice *
JH -John Henry- Gaddum
* Part of Florey's power was his cultivation of a network among the sizable Aussie contingent working in the UK - these two are but a tiny part of this group. Florey also cultivated ex pat britons who had taught in Australia.
Dated December 4th 1941, it is addressed to Doctor "Cameron" at "Porton" and mentions scientists "Courtice" and "Gaddum".
Florey says ICI penicillin is at Porton and he is glad that Gaddum wants lots and lots of penicillin.
In December 1941, no one had much penicillin - certainly no patients in UK got any - and only Dawson's patients in the USA.
This must be some of the very first ICI penicillin ever produced - not for patients - but for 'Porton' .
One of Florey's very closest of his (very few) friends was Paul Fildes, very near the top of Britain's WWII Germ Warfare effort, which was centred at Porton Down.
That place has been for a century Britain's leading gas and germ warfare centre - in fact one of the top centres in the world for this highly secret activity.
Florey's first biographer, Bickel, indicated that in 1939, Florey had been asked by the War Office if he would be a consultant in 'poison gas research' (probably because of his proven skill in doing lethal experiments on small animals and his middle-aged chickenhawk attitude to the upcoming war.)
Florey had agreed.
I have always wonder if Florey's mystery month , mid July-mid August 1941, was somehow connected with him having informal talks on germ and gas warfare with various American researchers.
Certainly, Florey go top clearance for his trip to America from US and British officials - penicillin ,alone, seemed too unproven to warrant this kind of assistance.
Now Penicillin and Porton is like Jeckyll and Hyde to British audiences - no wonder this letter has never been mentioned in all the hagiography on penicillin and Florey.....
GR - Gordon Roy- Cameron *
FC -Frederick Colin- Courtice *
JH -John Henry- Gaddum
* Part of Florey's power was his cultivation of a network among the sizable Aussie contingent working in the UK - these two are but a tiny part of this group. Florey also cultivated ex pat britons who had taught in Australia.
Fleming versus Dawson on Endocarditis
Hardly dueling Scots, though.
Fleming's Cheadle Prize winning medical essay "DIAGNOSIS OF ACUTE BACTERIAL INFECTIONS" (the only time I know of that he seriously engaged the subject of endocarditis) was written in 1909 and published in the ST MARYS HOSPITAL GAZETTE (volume15 , pages 67-69,72-77).
Most biographers of Fleming felt this early essay nevertheless set out the course of his life's work - which extended for another 45 years - so it is well worth a close reading.
Dawson confounded the essay's conclusions on intravenous injections to treat endocarditis in March 1942, with his first success in reducing bacterial colonies in endocarditis patient's blood.
Critics of vaccines said endocarditis's constant shedding of small amounts of bacteria directly into the bloodstream should lead to a natural immunity against them but instead actually only led to death.
Fleming dosed himself with a staphylococcic vaccine via an intravenous injection directly into the bloodstream.
(Staph was then a far less virulent bacteria than it is today.)
He lived, having only a slight headache and fever, but gained no increased resistance to staph.
Intravenous injections of vaccines gave maximum infectious effects and minimal increases in natural antibodies said Fleming.
Despite the fact that all of Fleming's considerable wealth came from his great skill in injecting the very dangerous drug Salvarsan directly into veins, he seemed dubious on 'systemic' or intravenous medications in general.
I think this is partially why he never tested penicillin as a systemic medicine in humans - or animals.
Not till 1940 did Dawson do so for humans and Florey for animals...
Fleming's Cheadle Prize winning medical essay "DIAGNOSIS OF ACUTE BACTERIAL INFECTIONS" (the only time I know of that he seriously engaged the subject of endocarditis) was written in 1909 and published in the ST MARYS HOSPITAL GAZETTE (volume15 , pages 67-69,72-77).
Most biographers of Fleming felt this early essay nevertheless set out the course of his life's work - which extended for another 45 years - so it is well worth a close reading.
Dawson confounded the essay's conclusions on intravenous injections to treat endocarditis in March 1942, with his first success in reducing bacterial colonies in endocarditis patient's blood.
Critics of vaccines said endocarditis's constant shedding of small amounts of bacteria directly into the bloodstream should lead to a natural immunity against them but instead actually only led to death.
Fleming dosed himself with a staphylococcic vaccine via an intravenous injection directly into the bloodstream.
(Staph was then a far less virulent bacteria than it is today.)
He lived, having only a slight headache and fever, but gained no increased resistance to staph.
Intravenous injections of vaccines gave maximum infectious effects and minimal increases in natural antibodies said Fleming.
Despite the fact that all of Fleming's considerable wealth came from his great skill in injecting the very dangerous drug Salvarsan directly into veins, he seemed dubious on 'systemic' or intravenous medications in general.
I think this is partially why he never tested penicillin as a systemic medicine in humans - or animals.
Not till 1940 did Dawson do so for humans and Florey for animals...
Thursday, September 2, 2010
Dawson, Florey and the multiple suppliers
Dawson first turned down Pfizer and then a month later accepted their offer of penicillin extracts, at the same time his co-worker Meyer was working with a potential competitor of Pfizer called Schering and Co, while at same time Dawson, Meyer, Hobby and Chaffee were producing their very own penicillin !
This was not unique.
Florey produced his own penicillin and was willing to ask for penicillin from any commercial firm and got commercial supllies from at least Merck, ICI and Kimball and Bishops, the latter two on a regular basis.
Why ?
And how were conflict of interests avoided?
I believe none of the commercial firms had a problem if a doctor wished to stick their penicillin (and that of all their competitors,) into patients.
Even if the doctor(s) first concentrated the commercial liquid
extracts up to a minimal level necessary for therapy - say to a dried state of 30-50 units per mg.
None of this would affect the commercial interests of the firms.
But it would be unfair if a doctor used commercial extracts to improve extraction processes or to do chemical synthesis work on the firms' offerings.
The firms were spending lots of money on these sorts of activities and hoped to eventually profit from it.
They won't want the doctor get to the patent office first or pass on the information on to their favorite commercial firm.
So Dawson, who cared not for the chemical synthesis of penicillin, could treat patients with Pfizer penicillin, while Meyer the chemist used his own penicillin or that of Schering to do chemical studies.
Everybody happy.
Florey did likewise - using mostly ICI penicillin on his famous second series of treatments of patients but not using any of it for chemical studies, while his own team's penicillin mostly went to the team chemists to be destroyed in chemical studies.
It hardly jibs with the heroic image of either group now does it?
I can only say that very quickly, Meyer dropped synthesis studies and shifted to chemically altering penicillin into an ester so it worked better (ie worked slooooower) inside patients.
Morally, it is hard to fault this sort of chemical work.
Oxford claimed (ala LADs' PEN) that it produced 500 litres of penicillin a week between the Fall of 1940 till May 1944.
That is 400 million units of useful, injectable penicillin, in Duhig Units.
I feel sure than Duhig's first reaction would be the same as mine: "Bull feathers".
I bet a check of the published records will show that only 4 million units of Oxford-created penicillin ended up being used for patients in that period.
(To keep things in perspective, in 2010, 4 million units - 4 MegaUnits - is what you might receive as a daily dose, for an average serious infection. But in 1942, it should be enough to treat 40 patients with life-threatening illnesses.)
Gladys Hobby, quoting a ICI report on Oxford's efforts, says in 1941 they were producing 2 grams a week at 16-32 units a mg, ie 15,000 to 30,000 units a week or a maximum of 1 to 2 million units a penicillin a year at the outside best.
I have seen an estimated figure of 13 million units produced in total between 1938 till 1944, coming - it seems - from Norman Heatley, and that seems to match this report fairly well.
Trevor I Williams, in probably the best single book on the Oxford team ,"HOWARD FLOREY", says that even in 1942, half of the final Oxford penicillin went to the chemists.
I believe all, or almost all, went to the chemists from 1943 onwards.
Doctor Mom has a right to be skeptical about the Lads....
This was not unique.
Florey produced his own penicillin and was willing to ask for penicillin from any commercial firm and got commercial supllies from at least Merck, ICI and Kimball and Bishops, the latter two on a regular basis.
Why ?
And how were conflict of interests avoided?
I believe none of the commercial firms had a problem if a doctor wished to stick their penicillin (and that of all their competitors,) into patients.
Even if the doctor(s) first concentrated the commercial liquid
extracts up to a minimal level necessary for therapy - say to a dried state of 30-50 units per mg.
None of this would affect the commercial interests of the firms.
But it would be unfair if a doctor used commercial extracts to improve extraction processes or to do chemical synthesis work on the firms' offerings.
The firms were spending lots of money on these sorts of activities and hoped to eventually profit from it.
They won't want the doctor get to the patent office first or pass on the information on to their favorite commercial firm.
So Dawson, who cared not for the chemical synthesis of penicillin, could treat patients with Pfizer penicillin, while Meyer the chemist used his own penicillin or that of Schering to do chemical studies.
Everybody happy.
Florey did likewise - using mostly ICI penicillin on his famous second series of treatments of patients but not using any of it for chemical studies, while his own team's penicillin mostly went to the team chemists to be destroyed in chemical studies.
It hardly jibs with the heroic image of either group now does it?
I can only say that very quickly, Meyer dropped synthesis studies and shifted to chemically altering penicillin into an ester so it worked better (ie worked slooooower) inside patients.
Morally, it is hard to fault this sort of chemical work.
Oxford claimed (ala LADs' PEN) that it produced 500 litres of penicillin a week between the Fall of 1940 till May 1944.
That is 400 million units of useful, injectable penicillin, in Duhig Units.
 |
| J V (James Vincent) DUHIG |
I bet a check of the published records will show that only 4 million units of Oxford-created penicillin ended up being used for patients in that period.
(To keep things in perspective, in 2010, 4 million units - 4 MegaUnits - is what you might receive as a daily dose, for an average serious infection. But in 1942, it should be enough to treat 40 patients with life-threatening illnesses.)
Gladys Hobby, quoting a ICI report on Oxford's efforts, says in 1941 they were producing 2 grams a week at 16-32 units a mg, ie 15,000 to 30,000 units a week or a maximum of 1 to 2 million units a penicillin a year at the outside best.
I have seen an estimated figure of 13 million units produced in total between 1938 till 1944, coming - it seems - from Norman Heatley, and that seems to match this report fairly well.
Trevor I Williams, in probably the best single book on the Oxford team ,"HOWARD FLOREY", says that even in 1942, half of the final Oxford penicillin went to the chemists.
I believe all, or almost all, went to the chemists from 1943 onwards.
Doctor Mom has a right to be skeptical about the Lads....
MARJORIE DAWSON ,
still in widow's weeds in 1946, at a film industry meeting
Mom's penicillin versus Lads' penicillin
That's 'DOCTOR MOM' by the way, and 'LADS' as in British Lad's magazines (a weak rendering in North American terms might be "its a guy thing" - a stronger rendering would be that Connie Kaldor song about "Jerks" .)
I have tried out various names for what I am now calling Doctor Mom's penicillin: pragmatic penicillin, patients' penicillin --- all share a common drive - to save lives , now.
Lads' penicillin can also be usefully be called prestige penicillin, purified penicillin, priority penicillin, scientific paper penicillin, scientific penicillin ,scientists' penicillin.
The goal here is "who can get 100% pure, stable, colorless penicillin crystals first - dam the poor yield and dam the poor patients, forget that there is a War on."
(And by the way I almost never call it "penicillin" when I am thinking about it or even when I talk about it - I call it simply
"PEN" rather as the British chemists called their reports, the PEN reports, and just as the paper tags on patients undergoing penicillin treatment during the war were also labelled PEN.)
I have tried out various names for what I am now calling Doctor Mom's penicillin: pragmatic penicillin, patients' penicillin --- all share a common drive - to save lives , now.
Lads' penicillin can also be usefully be called prestige penicillin, purified penicillin, priority penicillin, scientific paper penicillin, scientific penicillin ,scientists' penicillin.
The goal here is "who can get 100% pure, stable, colorless penicillin crystals first - dam the poor yield and dam the poor patients, forget that there is a War on."
(And by the way I almost never call it "penicillin" when I am thinking about it or even when I talk about it - I call it simply
"PEN" rather as the British chemists called their reports, the PEN reports, and just as the paper tags on patients undergoing penicillin treatment during the war were also labelled PEN.)
(Yellowcake uranium (easily mistaken for early dried penicillin powder or dried mustard) together with the wartime 'products' derived from it, were also given prominent labels with black letters and symbols on a bright mustard yellow background.)
Mom's pen is expressed in a ratio of units of penicillin actually ready for use in human patients over a period of time.
As in :"Pfizer released 500 mg of dry penicillin, (the famous Lot #696) assaying at 50 units a mg, for Dawson to use on his patients in March 2nd 1942 - a total of 25,000 units of therapeutic penicillin."
Or : "Starting in October 1941,Pfizer released to Dawson a 5 gallon carboy of non-concentrated penicillin juice every week, the juice assayed at an average of 2 units a ml, so if injected immediately into a patient in the form of a drip IV, that was 160,000 units of therapeutic penicillin a month ."
Lads' penicillin can be found described - ad nausem - throughout almost any account about penicillin.
Its boastful vagueness stands in for the most basic of basic arithmetic.
Here is one example, picked at random from the recent book on early penicillin:
We are told that the Royal Navy set up a 'small' production unit in 1942. Even if you follow the penicillin saga closely, this might be the first time you have read of this effort - it must have been small potatoes.
Apparently not so, for in the very next sentence we are told their weekly production was 200 million units.
To put this in context, Pfizer - the world's largest drug firm and a company you have heard of , said it produced 400,000 units of penicillin in March 1942.
(If you have a good memory, you will recall that not all of this ended up in patients' veins - Dawson seems to have only got 25,000 units and he was Pfizer's only clinician at this point.
Most of this semi-purified dry penicillin was probably destroyed by Pfizer chemists trying to degrade it enough to guess at the building blocks of its assembly by the penicillium.)
In early 1943, it took two months for the entire American pharameutical industry to produce as much penicillin as the Royal Navy's little operation at Clevedon produced in a week.
Count me more skeptical of this story than Robert Bud is.
Another example, from Macfarlane's biography of Howard Florey.
It is the claim that production at Oxford had been 500 litres a week for a few months by January 1941.
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