When we say that Henry Dawson's vision of wartime penicillin was 'inclusive', while that of Howard Florey was 'exclusive' , we are really getting at the key issue that divided all the world during, before and after WWII.
" Just who do we include in ; just who do we exclude out of our civil society's blessings ?"
Florey never called his vision for wartime penicillin 'exclusive' , but he did much use another term that means the same thing and in any case , his definite actions spoke much louder than his unspoken assumptions.
The word he always used to describe his goals for penicillin was 'pure' , chemically pure.
A dose of penicillin that excludes everything else in the original penicillin juice, whether that be helpful, neutral or harmful.
A 100 gram Vitamin C rich orange not merely concentrated into Vitamin C rich orange juice but further purified until it is a mere 100 mg of 100% chemically pure Vitamin C powder ... with all that impure orange taste and texture safely removed.
If Calvinists ever become our leading chefs, this is what our food will look like : pure carbohydrate, protein, fat, vitamins and minerals in enormous pill form and worked down with many cups of sterile water.
Hitler wanted to exclude Jews, Romas, Queers, the chronically ill and the handicapped , socialists, Blacks - you name it - to make Germany one big pure homogeneous Aryan nation and race.
Left-leaning Social Medicine, of which Dawson was a proponent , wanted to see that Medicine helped all those sick : it was inclusive.
And not just by helping those American blacks, aboriginals and immigrants usually neglected under 'for-profit' medicine either.
Its proponents also wanted to intervene (medically and otherwise), overseas ,to help those under attack by Hitler, Stalin and Tojo.
By contrast, the conservatives behind the idea of "War Medicine" wanted to use the defence of America as an excuse to roll back the New Deal emphasis on Social Medicine by claiming that in a Total War lead-up, all precious resources had to shift away from the (generally poorer) 4Fs to the (generally better off) 1A citizens.
Just because they talked war did not mean they were pro intervention overseas, just the opposite.
Their vision not just excluded helping sick 4F Americans at home, it also excluded helping sick 4Fs overseas as well.
Florey and Fleming both wanted penicillin to be chemically 100% pure and synthetic before it was produced in big volumes.
They were also both in intimate lockstep with the War Medicine proponents at Britain's Ministry of Supply and America's OSRD who wanted to restrict civilian access to (and knowledge of) the miracle cure , all the better to make penicillin a weapon of war.
If it could be kept exclusively as a secret weapon of war, the Allies could return wounded troops to combat quicker than the Germans or Japanese could.
By contrast, Dawson felt that doctors should help the sick and wounded soldiers of both sides (including Allied POWS !) and help the civilians of all sides : Neutral , Axis and Allied.
And he wanted penicillin - whether synthetically pure or naturally impure* he didn't care - produced in mass levels now , not after the war was over.
(* His team never let the impurity of their self-proclaimed "crude penicillin" stop them from being the first in history to give it systemically, via needle, to save a life.
They later even published a journal article speculating crude penicillin had additional beneficial substances that made it a better medication than just pure penicillin itself...)
Dawson definitely did not want to see the medicine produced in tiny levels so as to render acceptable the rationing of it, to justify giving it only to those civilians who were useful because of their involvement in the war effort.
He felt even a person incapable of almost any work still deserved penicillin, a warm meal, a warm bed and a warm smile.
Dawson felt this sort of American medical establishment thinking was far too close to that of Hitler's Aktion T4 projects - where people judged non-useful were starved, denied warm shelter and medicine or killed outright.
He believed if the Allies were seen saving the lives of people most of the educated world saw as 'useless' - even during an all-out Total War - this would help defeat Hitler morally in the many many Neutral countries and also strengthen the resolve of those Allied frontline troops facing death to defeat him militarily.
If the OSRD and Florey used penicillin as a weapon, we need ask did Dawson use it as a weapon, as well ?
Yes he certainly did.
As a weapon in a moral battle.
Dawson's touting of the inclusive use of wartime medicine definitely did have a moral cum political/diplomatic impact, in addition to the extra patients it medically admitted to be saved.......
Showing posts with label howard florey. Show all posts
Showing posts with label howard florey. Show all posts
Wednesday, September 11, 2013
Tuesday, September 10, 2013
Despite Eric Lax, Howard Florey is still "Box Office Poison" to women readers
And as every book editor well knows , most readers of narrative fiction/non-fiction are women.
But in the Lax take on the wartime penicillin saga, the hero offered up is a man who leaves his deaf middle class wife to ride around on her bike in the rain collecting urine from penicillin patients while he 'has it off' with his aristocratic mistress in the luxurious bath and bedroom suite he had at his office in (never-Blitzed) Oxford England .
And this at a time when millions of Britons in the rest of the UK were being bombed out their homes by the Blitz and (barely) living in makeshift shelters.
Charming, really charming !
Just of the sort of hero women readers want to cuddle up to - Not.
The character - or lack of it - of Howard Florey is what made Eric Lax's recent biography such a flop among ordinary readers.
So, despite the fact that a survey of thousands of American women found they considered penicillin the most important news story of the entire 20th century , we still have never had a successful popular book or movie about the dramatic wartime history of penicillin.
What is missing in all past efforts is a focus on the one classical hero in the whole saga : the dying Dr Dawson and his unrelenting efforts to make penicillin inclusive not exclusive.
That and a too trusting reliance by previous writers upon the official histories rather than digging deeper into the primary records.
Because the people in Washington and London who wrote the official histories determined, above all, to cover up their very expensive and very time-wasting wartime flop : the synthetic penicillin project led by Florey and George Merck and paid for mostly by the taxpayers - as always.
So they tried to pretend that the stone these builders rejected had really been their idea all along. With Dawson prematurely dead at war's end and unable to set the record straight , it was - literally - dead simple.
Women, around the world , will buy a popular history about wartime penicillin by the tens of millions of copies - with the right set of heroes and villains laid out before them.
"The smallest Manhattan Project : the unexpected triumph of inclusive penicillin" will do just that .....
But in the Lax take on the wartime penicillin saga, the hero offered up is a man who leaves his deaf middle class wife to ride around on her bike in the rain collecting urine from penicillin patients while he 'has it off' with his aristocratic mistress in the luxurious bath and bedroom suite he had at his office in (never-Blitzed) Oxford England .
And this at a time when millions of Britons in the rest of the UK were being bombed out their homes by the Blitz and (barely) living in makeshift shelters.
Charming, really charming !
Just of the sort of hero women readers want to cuddle up to - Not.
The character - or lack of it - of Howard Florey is what made Eric Lax's recent biography such a flop among ordinary readers.
So, despite the fact that a survey of thousands of American women found they considered penicillin the most important news story of the entire 20th century , we still have never had a successful popular book or movie about the dramatic wartime history of penicillin.
What is missing in all past efforts is a focus on the one classical hero in the whole saga : the dying Dr Dawson and his unrelenting efforts to make penicillin inclusive not exclusive.
That and a too trusting reliance by previous writers upon the official histories rather than digging deeper into the primary records.
Because the people in Washington and London who wrote the official histories determined, above all, to cover up their very expensive and very time-wasting wartime flop : the synthetic penicillin project led by Florey and George Merck and paid for mostly by the taxpayers - as always.
So they tried to pretend that the stone these builders rejected had really been their idea all along. With Dawson prematurely dead at war's end and unable to set the record straight , it was - literally - dead simple.
Women, around the world , will buy a popular history about wartime penicillin by the tens of millions of copies - with the right set of heroes and villains laid out before them.
"The smallest Manhattan Project : the unexpected triumph of inclusive penicillin" will do just that .....
Sunday, August 25, 2013
Dawson's penicillin 1940-1945 : made in the Public Domain , FOR the Public Domain
Howard Florey's penicillin 1940-1945, by way of pointed contrast, was Pure penicillin for Purely military use only.
He believed that penicillium were tiny ancient life and so , by definition , linear progressive Evolution's "Yesterday's Men" .
He was sure civilized scientific Man was bound to make penicillin better and cheaper than some slimy mold in a sort of witch's caldron .
But, in fact , chemists actually needed hundreds of millions of dollars - in 1940s dollars - together with tens of thousands of tons of structural and stainless steel to make a whole series of chemical factories, just to get started on making penicillin.
All those big plants, together with lots of staff, a whole lot of energy and many corrosive solvents were Man's way of making penicillin.
They needed to be build expensively strong in order to safely apply high pressure and high & cold temperature over and over in many steps.
All this to replicate what a incredibly tiny fungus cell (sixty pico grams in mass) could produce at ordinary temperatures and ordinary pressures out of a little dirty water and a bit of decaying organic material.
That tiny fungus factory weighed about one billion trillion times less than all of the factories needed to make the basic chemicals that went into the final penicillin synthetic factory.
So if you thought that perhaps the tiny fungus could do the job better and cheaper, then you were with Dawson.
Now, just as how you viewed the possibility of the continuing viability of small beings coloured the type of penicillin factory you preferred, it seemed to also colour who you thought the penicillin should help.
So, Florey: big factory penicillin for big armies only ; Dawson : small factory penicillin for small people everywhere.....
He believed that penicillium were tiny ancient life and so , by definition , linear progressive Evolution's "Yesterday's Men" .
He was sure civilized scientific Man was bound to make penicillin better and cheaper than some slimy mold in a sort of witch's caldron .
But, in fact , chemists actually needed hundreds of millions of dollars - in 1940s dollars - together with tens of thousands of tons of structural and stainless steel to make a whole series of chemical factories, just to get started on making penicillin.
All those big plants, together with lots of staff, a whole lot of energy and many corrosive solvents were Man's way of making penicillin.
They needed to be build expensively strong in order to safely apply high pressure and high & cold temperature over and over in many steps.
All this to replicate what a incredibly tiny fungus cell (sixty pico grams in mass) could produce at ordinary temperatures and ordinary pressures out of a little dirty water and a bit of decaying organic material.
That tiny fungus factory weighed about one billion trillion times less than all of the factories needed to make the basic chemicals that went into the final penicillin synthetic factory.
So if you thought that perhaps the tiny fungus could do the job better and cheaper, then you were with Dawson.
Now, just as how you viewed the possibility of the continuing viability of small beings coloured the type of penicillin factory you preferred, it seemed to also colour who you thought the penicillin should help.
So, Florey: big factory penicillin for big armies only ; Dawson : small factory penicillin for small people everywhere.....
Crude Penicillin and Bacterial Transformation : two neologisms of Henry Dawson
Henry Dawson was far from a wordsmith but he did coin two neologisms that have survived in today's scientific and historical lexicon.
One was "bacterial transformation" (a form of HGT, horizontal gene transfer -- basically non-Darwinian inheritance) and the other was "crude penicillin".
To explain this latter term is is best to recognize it is really a term of scientific and political polemics.
Let us imagine a British Empire in the early 1940s, badly hurting a time of war because it had refused to accept a fact known for at least two centuries.
That fact was that the most natural , most versatile and cheapest way to solve the naval and merchant ship scurvy crisis was with a good supply of citrus fruit kept on board.
Marshalled against this fact discovered by James Lind was an array of louder, better educated and greedier voices.
What they were telling the government and the media and future historians was that Britain's dying sailors must simply be patient.
In its own sweet time an expensive synthetic vitamin C was sure to emerge, fully patented, from one of the nation's chemical firms.
One expensively patented , tasteless , pill would solve the human daily needs for vitamin C - as would other patented pills for all our daily food intake.
We needn't waste time away from our desks on meals when a glass of water and a big handful or two of pills would solve the problem.
Against this chemical boasting would be an array of people saying that they looked forward to meals - perhaps even more than sex and certainly far more than they looked forward to work.
Others would point out that citrus fruit and vitamin C rich vegetables are found world wide - are both cheap and abundant - a security of supply issue.
They would further point out that the deadly delay in solving this sea-going crisis for the Empire was simply down to greed and ambition.
The delay was down to some ambitious scientists seeking the glory for having synthesized something Mother Nature already provided and to some greedy chemical companies wanting a profitable patent to exploit.
These claims against patented vitamin C pills are so damning a master scientific polemist would be called upon to defend Chemistry.
A scientific polemist like Howard Florey because he, too, was a bit of a neologism creator : he was the first person to talk about impure and pure penicillin, for example.
An orange ,he could point out, could potentially be a dangerous source of vitamin C because it was an impure source of the needed vitamin (in the sense that vitamin C only made up a tiny fraction of one percent of the orange by weight).
In a 1940s culture where the middle class had more education than common sense, this would be effective arguing : everyone wanted cleanliness and purity.
Henry Dawson immediately caught onto this "Only I know how to make pure safe penicillin" line of attack from Florey's very first article on penicillin and quickly mounted a rebuttal.
And he did so in the august pages of the New York Times on May 6th 1941.
In effect, he said an orange can be one of four things, as regards to being an safe source of vitamin C.
It could be unsafe because both the orange and its vitamin C are potentially dangerous.
It could be safe because both the orange and its vitamin C are harmless to consume.
It could be unsafe because vitamin C is potentially dangerous, perhaps in larger quantities.
It could be unsafe because the orange itself was potentially toxic.
The only thing to do , as always , was less talk and more experiments.
He tested impure penicillin (penicillium juice) upon himself and upon some human patients and found it perfectly safe.
He boldly called his successful medicine "crude penicillin" --- naturally made penicillin happily bathing its its naturally produced impure bath.
it was a medicine made by microbes and offered up to all, free in the Public Domain : thus meeting Florey's subtle corporate agenda head-on.
Ironically, years later, it was revealed that pure penicillin itself was potentially unsafe (unlike the rest of the harmless penicillium juice) because when pure it can be given in large enough amounts to result in sudden penicillin allergy deaths !
Pure members of the aryan races might still believe they can only survive on pure penicillin and pure vitamin C but the rest of this polyglot world still likes to take its daily nourishment 'crude' , dining around the table with family and friends.
It hasn't seemed to harm the seven billions of us so far....
One was "bacterial transformation" (a form of HGT, horizontal gene transfer -- basically non-Darwinian inheritance) and the other was "crude penicillin".
To explain this latter term is is best to recognize it is really a term of scientific and political polemics.
Let us imagine a British Empire in the early 1940s, badly hurting a time of war because it had refused to accept a fact known for at least two centuries.
That fact was that the most natural , most versatile and cheapest way to solve the naval and merchant ship scurvy crisis was with a good supply of citrus fruit kept on board.
Marshalled against this fact discovered by James Lind was an array of louder, better educated and greedier voices.
What they were telling the government and the media and future historians was that Britain's dying sailors must simply be patient.
In its own sweet time an expensive synthetic vitamin C was sure to emerge, fully patented, from one of the nation's chemical firms.
One expensively patented , tasteless , pill would solve the human daily needs for vitamin C - as would other patented pills for all our daily food intake.
We needn't waste time away from our desks on meals when a glass of water and a big handful or two of pills would solve the problem.
Against this chemical boasting would be an array of people saying that they looked forward to meals - perhaps even more than sex and certainly far more than they looked forward to work.
Others would point out that citrus fruit and vitamin C rich vegetables are found world wide - are both cheap and abundant - a security of supply issue.
They would further point out that the deadly delay in solving this sea-going crisis for the Empire was simply down to greed and ambition.
The delay was down to some ambitious scientists seeking the glory for having synthesized something Mother Nature already provided and to some greedy chemical companies wanting a profitable patent to exploit.
These claims against patented vitamin C pills are so damning a master scientific polemist would be called upon to defend Chemistry.
A scientific polemist like Howard Florey because he, too, was a bit of a neologism creator : he was the first person to talk about impure and pure penicillin, for example.
An orange ,he could point out, could potentially be a dangerous source of vitamin C because it was an impure source of the needed vitamin (in the sense that vitamin C only made up a tiny fraction of one percent of the orange by weight).
In a 1940s culture where the middle class had more education than common sense, this would be effective arguing : everyone wanted cleanliness and purity.
Henry Dawson immediately caught onto this "Only I know how to make pure safe penicillin" line of attack from Florey's very first article on penicillin and quickly mounted a rebuttal.
And he did so in the august pages of the New York Times on May 6th 1941.
In effect, he said an orange can be one of four things, as regards to being an safe source of vitamin C.
It could be unsafe because both the orange and its vitamin C are potentially dangerous.
It could be safe because both the orange and its vitamin C are harmless to consume.
It could be unsafe because vitamin C is potentially dangerous, perhaps in larger quantities.
It could be unsafe because the orange itself was potentially toxic.
The only thing to do , as always , was less talk and more experiments.
He tested impure penicillin (penicillium juice) upon himself and upon some human patients and found it perfectly safe.
He boldly called his successful medicine "crude penicillin" --- naturally made penicillin happily bathing its its naturally produced impure bath.
it was a medicine made by microbes and offered up to all, free in the Public Domain : thus meeting Florey's subtle corporate agenda head-on.
Ironically, years later, it was revealed that pure penicillin itself was potentially unsafe (unlike the rest of the harmless penicillium juice) because when pure it can be given in large enough amounts to result in sudden penicillin allergy deaths !
Pure members of the aryan races might still believe they can only survive on pure penicillin and pure vitamin C but the rest of this polyglot world still likes to take its daily nourishment 'crude' , dining around the table with family and friends.
It hasn't seemed to harm the seven billions of us so far....
Tuesday, July 30, 2013
The world in September '39 : as divided as it had ever been, as divided as it had always been, as divided as it always would be
Seventy five years on, we still can see the differing value systems that divided modern liberal and conservative capitalist from modern communist and socialist from modern fascist and nazi.
But we now see something that they themselves could not see : just how united ,in so many ways, that these variants of High Modernity actually all were with each other.
If we want truly fundamental divisions, I am afraid that historians are daily revealing that we won't find it in what the socialists and nazis and capitalists of 1939 actually did , in practise, as opposed to what their high blown rhetoric claimed they believed they would do.
But a deep and enduring division did divide the world in 1939, as it does in 2013 and did in 1739 and will continue to do so till the End of Time.
The percentages of individuals on each side of this division probably remains roughly the same in each new generation.
But, more profoundly, the cumulative, collective, effects of the current strength of each individual's conviction does vary widely, depending on times and places and even upon immediate circumstances.
This varying strength gives rise to our habit of naming contrasting eras of human history to mark the varying strength on both sides of this Great Divide.
Age of Plato versus Age of Aristotle, Classicism versus Romanticism, High Modernity versus Post-Modernity.
Underlying each different era, I wish to argue, we can see the varying strength of the convictions held by collective humanity, each member holding one of two simple but profound assumptions.
Half of us believe that deep down, physical reality is much simpler and much more predictable than it currently appears to be.
The other half of us believes that deep down, physical reality is much more complex and dynamically unpredictable than it currently appears to be.
Now if I wanted to appear academic, I would at this point hasten to say that these two positions are but idealized extremes on a wide and subtly changing continuum of what real people actually believe.
But I won't say that because I don't believe it.
I believe that these two are the only positions held on this issue given that people hold them as deep, unconscious, 'gut' reactions rather than as something carefully and consciously thought out.
And what really matters is the intensity with which they hold one of these two positions at any particular time and place and on particular issues.
I believe that Henry Dawson always held that reality was more complex than it appeared, just as Howard Florey almost certainly believed that reality was much simpler than at first appeared.
The pair's different deep assumptions surfaced most famously in their fiercely held wartime support for either naturally-made penicillin or man-made penicillin.....
But we now see something that they themselves could not see : just how united ,in so many ways, that these variants of High Modernity actually all were with each other.
If we want truly fundamental divisions, I am afraid that historians are daily revealing that we won't find it in what the socialists and nazis and capitalists of 1939 actually did , in practise, as opposed to what their high blown rhetoric claimed they believed they would do.
But a deep and enduring division did divide the world in 1939, as it does in 2013 and did in 1739 and will continue to do so till the End of Time.
The percentages of individuals on each side of this division probably remains roughly the same in each new generation.
But, more profoundly, the cumulative, collective, effects of the current strength of each individual's conviction does vary widely, depending on times and places and even upon immediate circumstances.
This varying strength gives rise to our habit of naming contrasting eras of human history to mark the varying strength on both sides of this Great Divide.
Age of Plato versus Age of Aristotle, Classicism versus Romanticism, High Modernity versus Post-Modernity.
Underlying each different era, I wish to argue, we can see the varying strength of the convictions held by collective humanity, each member holding one of two simple but profound assumptions.
Half of us believe that deep down, physical reality is much simpler and much more predictable than it currently appears to be.
The other half of us believes that deep down, physical reality is much more complex and dynamically unpredictable than it currently appears to be.
Now if I wanted to appear academic, I would at this point hasten to say that these two positions are but idealized extremes on a wide and subtly changing continuum of what real people actually believe.
But I won't say that because I don't believe it.
I believe that these two are the only positions held on this issue given that people hold them as deep, unconscious, 'gut' reactions rather than as something carefully and consciously thought out.
And what really matters is the intensity with which they hold one of these two positions at any particular time and place and on particular issues.
I believe that Henry Dawson always held that reality was more complex than it appeared, just as Howard Florey almost certainly believed that reality was much simpler than at first appeared.
The pair's different deep assumptions surfaced most famously in their fiercely held wartime support for either naturally-made penicillin or man-made penicillin.....
Monday, March 25, 2013
1940 Penicillin : localized Gas Gangrene or systemic SBE ?
Within days of reading war-dodger Howard Florey's published conclusion that the as-yet-unproven penicillin was particularly suited to the military's most feared infection, gas gangrene, war-hero Henry Dawson defiantly decided - by pointed contrast - that penicillin was particularly well suited to defeat the ultimate in non-military infections, deadly subacute bacterial endocarditis, SBE.
The timing of Dawson's decision - during the most critical days of the expected Invasion of Britain - only heighten this highly unusual contrast between how we expect war-heroes and war-dodgers to behave and how these two examples actually did behave.
Florey had declined to serve his country when he was young but now was very eager to aid it (as a draft-proof middle ager) by steering the new penicillin towards use as as a local antiseptic for gas gangrene infections in frontline casualty tents.
For centuries, gas gangrene infections were the most dreaded and also the most uniquely wartime forms of death (rarely causing death in peacetime).
Any talk of the possibility of finally ending gas gangrene's terrors was acutely pitched to catch the ears of war's political, military and medical leadership.
By contrast, when on the day of America's first peacetime Draft Registration, a day dedicated to locating all of America's 1A youth, Dawson choose to instead try and save the lives of two SBE sufferers, one Black and one Jewish, he was focused on the most 4F imaginable of the unwanted 4Fs.
For no nation's military , no matter how hard pressed for manpower, was likely to regard SBEs as more than just a particularly costly burden for a wartime economy to bear.
It usually hit young adults , the prime category for draft boards and munition factories, but no matter what modern medicine threw at it, it always ended after months of expensive effort with the inevitable death of the patient.
In that Fall of 1940, the Medical School at Columbia University, which employed Dawson, had moved to reduce its offerings in Social medicine and up its offerings in War medicine, in response to the battle for civilization not taking place over the skies of Britain.
It certainly had no cause to expect any complaints from professor Dawson, he of all its employees.
He was, after all, from a Canadian family of five brothers, all who volunteered to fight in WWI, all who were wounded in the front lines - one who had paid the ultimate price and others who got medals for bravery and leadership under fire.
Dawson likely had more front line experience - in the medical corp, the infantry and in artillery - than any one else in the Medical School.
When he wasn't serving in hospitals dealing with wounded soldiers, he was in military hospitals himself as a patient - fighting off life-threatening infected war wounds he himself received.
Surely such a patriot and such a veteran of battlefront infections saw the sense on Howard Florey's proposal to focus penicillin research on battlefront wound infections and to agree with his university's decision to focus on war related medical research ?
But clearly he did not - and the mystery is to account for why he did not - but instead, precisely and perversely, did exactly the opposite.
Penicillin did not, in the end, reduce deaths due to gas gangrene - in fact penicillin pioneer ( and WWI veteran) RJV Pulvertaft found that the evidence suggested that the percentage of gas gangrene sufferers who died actually went up in WWII , compared to the results obtained in the last years of the previous war !
By contrast, in the end, penicillin proved to be the best medicine ever seen to stop deadly systemic (body-wide) infections like SBE and blood-poisoning.
Based on just the evidence, part of the mystery might therefore seemed to solve itself: the modest Dawson was simply a far better scientist than the very pushy and ambitious, but ultimately plodding, Florey.
But Dawson was also extremely patriotic in ways that Florey couldn't begin to imagine and we still must explain why he felt that his best way to personally aid the war effort was to come to the aid of Life's weakest members.
Saint Peter had only denied Christ's pleas three times, but between 1931 and 1941, America had denied pleas for help from smaller, weaker countries under attack over two dozen times, only deciding
to put the Greatest Generation Ever to work fighting the only Good War, after it itself was attacked.
Helping Life's weakest members is all very nice in theory said America - but what in the hell does it have to do with fighting WWII - which was all about one's own naked self interest ?
Perhaps Dawson was merely confused - was still fighting WWI - was still fighting for poor bleeding little Belgium.
Perhaps....
The timing of Dawson's decision - during the most critical days of the expected Invasion of Britain - only heighten this highly unusual contrast between how we expect war-heroes and war-dodgers to behave and how these two examples actually did behave.
Florey had declined to serve his country when he was young but now was very eager to aid it (as a draft-proof middle ager) by steering the new penicillin towards use as as a local antiseptic for gas gangrene infections in frontline casualty tents.
For centuries, gas gangrene infections were the most dreaded and also the most uniquely wartime forms of death (rarely causing death in peacetime).
Any talk of the possibility of finally ending gas gangrene's terrors was acutely pitched to catch the ears of war's political, military and medical leadership.
By contrast, when on the day of America's first peacetime Draft Registration, a day dedicated to locating all of America's 1A youth, Dawson choose to instead try and save the lives of two SBE sufferers, one Black and one Jewish, he was focused on the most 4F imaginable of the unwanted 4Fs.
The most 4F of all the 4Fs : the SBEs
For no nation's military , no matter how hard pressed for manpower, was likely to regard SBEs as more than just a particularly costly burden for a wartime economy to bear.
It usually hit young adults , the prime category for draft boards and munition factories, but no matter what modern medicine threw at it, it always ended after months of expensive effort with the inevitable death of the patient.
In that Fall of 1940, the Medical School at Columbia University, which employed Dawson, had moved to reduce its offerings in Social medicine and up its offerings in War medicine, in response to the battle for civilization not taking place over the skies of Britain.
It certainly had no cause to expect any complaints from professor Dawson, he of all its employees.
He was, after all, from a Canadian family of five brothers, all who volunteered to fight in WWI, all who were wounded in the front lines - one who had paid the ultimate price and others who got medals for bravery and leadership under fire.
Dawson likely had more front line experience - in the medical corp, the infantry and in artillery - than any one else in the Medical School.
When he wasn't serving in hospitals dealing with wounded soldiers, he was in military hospitals himself as a patient - fighting off life-threatening infected war wounds he himself received.
Surely such a patriot and such a veteran of battlefront infections saw the sense on Howard Florey's proposal to focus penicillin research on battlefront wound infections and to agree with his university's decision to focus on war related medical research ?
But clearly he did not - and the mystery is to account for why he did not - but instead, precisely and perversely, did exactly the opposite.
Penicillin did not, in the end, reduce deaths due to gas gangrene - in fact penicillin pioneer ( and WWI veteran) RJV Pulvertaft found that the evidence suggested that the percentage of gas gangrene sufferers who died actually went up in WWII , compared to the results obtained in the last years of the previous war !
By contrast, in the end, penicillin proved to be the best medicine ever seen to stop deadly systemic (body-wide) infections like SBE and blood-poisoning.
Explaining the mystery and the paradox
Based on just the evidence, part of the mystery might therefore seemed to solve itself: the modest Dawson was simply a far better scientist than the very pushy and ambitious, but ultimately plodding, Florey.
But Dawson was also extremely patriotic in ways that Florey couldn't begin to imagine and we still must explain why he felt that his best way to personally aid the war effort was to come to the aid of Life's weakest members.
Saint Peter had only denied Christ's pleas three times, but between 1931 and 1941, America had denied pleas for help from smaller, weaker countries under attack over two dozen times, only deciding
to put the Greatest Generation Ever to work fighting the only Good War, after it itself was attacked.
Helping Life's weakest members is all very nice in theory said America - but what in the hell does it have to do with fighting WWII - which was all about one's own naked self interest ?
Perhaps Dawson was merely confused - was still fighting WWI - was still fighting for poor bleeding little Belgium.
Perhaps....
Saturday, February 16, 2013
Penicillin's "Bengali Famine Years" : 1943-1944
It was not America and Britain, it was not even the British and American governments ,that made the momentous decision, between late 1942 and early 1943, not to divert tax money just a little away from bombs and towards penicillin production instead.
This decision led, over the period of 1943-1944, to a Bengali Famine-like situation among the Allies over shortages of live-saving drugs for civilians.
It was only one government agency in each country that made that decision ; albeit all-powerful agencies in the middle of a war.
But I do not believe they acted contrary to the informally expressed sentiments of their country's war cabinets.
Let the record note their names : Vannevar Bush's weapon-developing agency known as the OSRD in America and the Ministry of (Army) Supply (MoS) in Britain, with the common link urging them into this course being Sir Howard Florey.
By contrast, diverting even a tiny tiny amount of the government's war resources to the issuing of firm standing orders for penicillin purchases could have provided adequate semi-purified natural penicillin to treat all cases (civilian and military) of patients dying from blood poisoning that were resistant to the only life-saving alternative, the sulpha drugs.
Let me make it perfectly, morally, clear : the fundamental issue was not that penicillin was in short supply : it was that any method of saving those dying of sulpha-resistant blood poisoning was in desperately short supply.
These diverted resources , expressed as firm government orders for penicillin at currently profitably prices ,would have stimulated private capital to make good use of current technology and of idle rural factories that had closed because of the war , as well as unskilled rural labour also left idle because of the war.
As models that this could have and in fact did work in practise, one only needs, in the case of Britain, to point to Glaxo's first low tech but efficient penicillin factories cobbled out of bits of unused space in other people's factories.
And in the American case, to point to an enterprising rural mushroom farmer called Raymond Rettew who briefly became the world's biggest penicillin producer, in the late spring of 1943.
FDR's party did not lose the 1944 election over this issue , because another part of his American government (the WPB, War Production Board) chose to totally reversed this decision, and in spades.
But Churchill's party did ultimately pay the full price for this decision made by the MoS (led by his fellow Tory, Sir Andrew Duncan) not to push for enough penicillin production resources to help civilian as well as soldier, later in the war.
That was when his party overwhelmingly lost the general election it was supposed to romp home in, July 2nd 1945 .
Churchill's equally callous decision not to stop the wartime Bengali Famine in which four million people died ( "If there really is a famine, why hasn't Gandhi died?" he sneered) probably also sealed the chances of Churchill's Britain holding onto the Indian Empire.
If Florey had been even moderately left wing rather than very right wing, he might have gone to other more left wing oriented agencies of the British and American governments and the wartime penicillin story could have been very different .
If the wartime history of Civil War Era America was written as historians write the Pollyanna story of wartime penicillin, there would be only one America and one government ,with no sense at all of conflict between different parts of America.
My work on wartime penicillin will make it very clear that two agencies of the American government, the OSRD and the WPB were not in agreement on penicillin production levels and methods but in conflict.
Just as in the UK, Howard Florey/MoS and Harry Jephcott/Glaxo were not in agreement on these same issues but in conflict.
And I will make it clear that there were no technical reasons why civilians could not have penicillin in 1943-1944 , rather it was the result of a political and moral decision not to produce one less bomber squadron if that was the cost of bring penicillin to dying civilians.
For these were penicillin famines by government fiat : Bengal-on-the-Potomac and Bengal-on-the-Thames.....
This decision led, over the period of 1943-1944, to a Bengali Famine-like situation among the Allies over shortages of live-saving drugs for civilians.
It was only one government agency in each country that made that decision ; albeit all-powerful agencies in the middle of a war.
But I do not believe they acted contrary to the informally expressed sentiments of their country's war cabinets.
Let the record note their names : Vannevar Bush's weapon-developing agency known as the OSRD in America and the Ministry of (Army) Supply (MoS) in Britain, with the common link urging them into this course being Sir Howard Florey.
By contrast, diverting even a tiny tiny amount of the government's war resources to the issuing of firm standing orders for penicillin purchases could have provided adequate semi-purified natural penicillin to treat all cases (civilian and military) of patients dying from blood poisoning that were resistant to the only life-saving alternative, the sulpha drugs.
Let me make it perfectly, morally, clear : the fundamental issue was not that penicillin was in short supply : it was that any method of saving those dying of sulpha-resistant blood poisoning was in desperately short supply.
These diverted resources , expressed as firm government orders for penicillin at currently profitably prices ,would have stimulated private capital to make good use of current technology and of idle rural factories that had closed because of the war , as well as unskilled rural labour also left idle because of the war.
As models that this could have and in fact did work in practise, one only needs, in the case of Britain, to point to Glaxo's first low tech but efficient penicillin factories cobbled out of bits of unused space in other people's factories.
And in the American case, to point to an enterprising rural mushroom farmer called Raymond Rettew who briefly became the world's biggest penicillin producer, in the late spring of 1943.
FDR's party did not lose the 1944 election over this issue , because another part of his American government (the WPB, War Production Board) chose to totally reversed this decision, and in spades.
But Churchill's party did ultimately pay the full price for this decision made by the MoS (led by his fellow Tory, Sir Andrew Duncan) not to push for enough penicillin production resources to help civilian as well as soldier, later in the war.
That was when his party overwhelmingly lost the general election it was supposed to romp home in, July 2nd 1945 .
Churchill's equally callous decision not to stop the wartime Bengali Famine in which four million people died ( "If there really is a famine, why hasn't Gandhi died?" he sneered) probably also sealed the chances of Churchill's Britain holding onto the Indian Empire.
If Florey had been even moderately left wing rather than very right wing, he might have gone to other more left wing oriented agencies of the British and American governments and the wartime penicillin story could have been very different .
If the wartime history of Civil War Era America was written as historians write the Pollyanna story of wartime penicillin, there would be only one America and one government ,with no sense at all of conflict between different parts of America.
My work on wartime penicillin will make it very clear that two agencies of the American government, the OSRD and the WPB were not in agreement on penicillin production levels and methods but in conflict.
Just as in the UK, Howard Florey/MoS and Harry Jephcott/Glaxo were not in agreement on these same issues but in conflict.
And I will make it clear that there were no technical reasons why civilians could not have penicillin in 1943-1944 , rather it was the result of a political and moral decision not to produce one less bomber squadron if that was the cost of bring penicillin to dying civilians.
For these were penicillin famines by government fiat : Bengal-on-the-Potomac and Bengal-on-the-Thames.....
Friday, February 15, 2013
"Weaponized" penicillin to be a frontline Army wound powder and hence the needs of the Navy, Air Force and Civilians are not relevant...
One of the most historic of meetings and dates in the whole extended penicillin saga occurred on September 25 1942 at Portland House in London England .
In fact one key participant at the meeting sensed this so greatly that he even whispered that history was going to view it that way, into the ear of the chairman as the meeting broke up.
In many ways, this meeting was very odd as well as being very historic.
Mostly because who called it and who it asked to attend.
It was called by one of the powerful of the many British wartime Ministries, the Ministry of Supply (MoS), which actually only supplied the Army (and perhaps in few things , the other two armed services as well) - but never ever supplied civilian needs.
Ronald Clark in his biography of Ernst Chain says this meeting was proceeded by the Ministers of (army) Supply and (civilian) Health, Sir Andrew Duncan and Ernest Brown, jointly "taking the idea of the immediate mass production of penicillin to the War Cabinet".
If so, it was possibly informally done via a Ministry "Minute" to the War Cabinet as neither gentlemen were ever members of the small War Cabinet : even in peacetime many many British politicians become ministers, without ever being becoming cabinet ministers.
And significantly, no one from Brown's civilian-oriented department was at this historical meeting.
This is a very important matter to resolve definitely, in part because the peculiar nature of this crucial meeting spelt the doom of Winston Churchill and his party in the election of June-July 1945.
How on earth did penicillin the universal lifesaver ever come be re-jigged as something only useful to the combat needs of the British Army ?
None of the drug firms summoned to this meeting (which did NOT include the very politically powerful firm of ICI ) had any real political or military influence - they didn't push for the meeting to take place but merely came when they were called.
But two of the four scientists had the meeting certainly did have good credentials with the Army ( but not Navy or Air Force) medical authorities and were of the correct Tory stamp: Howard Florey and Alec Fleming.
They had pushed for this meeting with the Army's supply department.
So, the army-oriented MoS was there in full force with six top officials along with two top officials from the Army Medical Branch charged with drug procurement for frontline casualties.
Missing in action at this meeting - by design - was the Navy, Air Force and any officials representing the Civilian interest in penicillin production.
Florey and Fleming both strongly saw penicillin as basically a useful supplement to the cheap abundant and systemically-oriented oral sulfas, with penicillin to be used primarily as in "local applications" for frontline combat wounds.
True, the Navy and Air force casualties were more often treated at large hospitals (and more often simply died in action) than in the case of the Army.
The Army had to deal with the fact that more of its casualties emerged as alive but wounded ,compared to the other services, which was the good news ---- but the bad news was that their wounds were usually about to get badly infected as a result of the primitive conditions at the front line.
A highly concentrated anti-bacterial drug with a long storage life and stable under almost any conditions as a dry powder (ie highly pure as well as highly concentrated) seemed essential.
Then and only then could it be suitable to sprinkle on open wounds immediately as they occurred on the front lines by barely trained medics or ordinary soldiers themselves.
Or for a busy front line doctor in am ambulance tent to inject, with a little sterile water, in or around those open wounds, within hours of the wounding.
Chemically, sulfa was born fulfilling these requirements - but penicillin didn't really meet them until after the six years of war was long over.
But unfortunately, no thorough controlled clinical trials of this claim that a frontline local application anti-bacterial medication would be essential for wounded survival was ever done.
At war's end, the general assessment was that, in fact, the frontline powders and needlefuls of these "local" penicillin and sulfa (ie applied directly into the wound) were not essential.
Instead, the wonderfully low rate of death from wounds (versus either the much worse record of WWI or of WWII Germany) was felt to be more due to the Allies' quick thorough debridement (removal) of dead wounded flesh , front line blood transfusions and policy of rapid evacuations of wounded soldiers to clean, quiet ,well equipped base hospitals .
That ---- and the general good health of wounded Allied troops, because they had been kept well fed and lived in warm sanitary conditions in the months before being wounded.
In the military base hospitals and civilian general hospitals, wartime sulfas and penicillin did prove to be reliable life savers when given as a systemic, if and when blood poisoning was suspected.
In fact, "crude" liquid penicillin (totally un-concentrated and totally un-purified) injected by needle and prepared in the hospital daily by Dr Duhig, saved lives as a systemic at a Brisbane general hospital --- and could have done so in the military equivalent.
Ooops ! It did do so, at Cairo's largest military hospital, where Dr Pulvertaft treated patients with liquid systemic crude penicillin he made daily in the hospital.
How did the Navy, RAF and the public, along with those politicians sworn to protect these groups of humans beings, react to the idea that penicillin was to be made under the control of the Army and for war casualties only ?
Seemingly with initial indifference - though by the Spring of 1943, a freelancing Navy Surgeon Commander had converted the Admiralty's under-producing vaccine operation to a huge penicillin factory supplying all of the Royal Navy's penicillin needs.
The Admiralty had always 'looked after its own', had always produced its own vaccines and serums so it didn't take long before the Navy medical brass had a look around at the penicillin factory and beam approval.
(Unlike the Army and Air Force, they had won the battle to retain the supplying of their needs by a naval units controlled directly by the Admiralty itself.)
For some rather sad reasons, the Air Force had relatively few wounded, for its size, and for other reasons, the treating of the wounded and returning them to battle was not an operational priority.
Over the course of the whole war, each of the British armed service got about one third of the money spent on the war. But in terms of manpower, of five people in uniform there were three in the army versus one in the RAF and one in the Navy/Merchant Marine.
This is because the RAF and RN/Merchant Marine had lots of big expensive machines that if "taken out of action" usually resulted in a 100% loss (aka "sunk" or "crashed"), while except in disastrous retreats, this rarely happened to the Army and its smaller cheaper machines.
The Allied Armies proved very much better, for example, at recovering even badly damaged tanks , as compared to the Germans.
In terms of personnel killed, the story is more complex.
Most of the RAF were never in real danger of dying but among those that flew, rather than maintained aircraft on the ground, the death rate was very high -often as much from operational accidents as enemy fire.
In Bomber Command, 55 of 100 fliers died before finishing their tour of duty.
Again there were relatively few wounded fliers versus a high rate of deaths - with the relatively few that survived their plane being hit only doing so by remaining out of the war, as German POWS.
People losses anyway and quite frankly , were not a big concern to the RAF : it never had a shortage of qualified recruits.
The RAF was seen as very glamorous to those determined to be very brave and seen a very secure place to spend the war to those with peacetime technical and engineering skills and no urge to be brave.
Manpower sustaining by speeding the recovery of the wounded was never a critical issue for any of WWII's air forces.
Replacing lost machines ( and frequently the training of new flier recruits) was always their obsession instead.
The world's navies were almost as attractive as the air forces, and rarely suffered from manpower worries and wounded recovery worries.
Instead, the sudden loss of entire town-sized machines (battleships or aircraft carriers) with all two thousand on board dead at one stroke, from a single torpedo or bomb, was their admirals more realistic nightmare.
In addition, while the Merchant Marine had particularly high losses of lives, against the relatively small number of its personnel, the merchant marine crews' relatively high pay and lack of onerous military discipline kept manpower replacement issues at bay.
When all factors are combined, at a gross figure level, the three armed services all lost about the same percentage of dead against the total number enlisted in each service, though as I have shown, the chance of death in service fell very unevenly.
In the case of the Army, it fell hardest on the infantry, followed by the tank crews and often the combat engineers.
Because almost no one wanted to join the infantry, it had few volunteers and generally the infantry got those conscripted recruits so totally lacking in useful education and technical skills that no other section of the Army wanted them.
To combine metaphors : incredibly enough, in all the Allied military , the very pointy end of the offensive stick came from the very bottom of the barrel.
In a nutshell, this is why the Germans and Japanese proved so very hard to defeat.
Over the whole war, the death rate varied greatly among the three services - the Navy death rate actually went down as the war progressed, the RAF's deaths peaked in 1943-1944, while in the case of the Army it was expected to rise suddenly and sharply to WWI Western Front levels, following the invasion of Europe.
The Army faced a short sharp period of potentially huge casualties - most wounded and infected but in Allied hands, not POWS.
If they weren't too badly wounded and the right anti-bacterial medication was at hand, the Army might be able to get most of the wounded back into battle formations before the war ended.
Just as well ,as there were no new men hustling to enter the infantry replacement pipeline at the other end.
At the very least, the thought that if and when they got wounded, the Army could heal most of them, would make the infantry less reluctant to rise up and advance against deadly Mortar and Machine Gun fire.
Or so the Army brass fondly believed.
I have tried to make the Fall of 1942 case for the British Army making penicillin just for itself seem as sensible as possible.
But in fact, it was a case going around with its nose full of Coke and Ecstasy.
In the fall of 1942, the really big medical story wasn't the rise of penicillin ; it was the decline of the previous wonder slash miracle drug : the Sulfas.
After five years of ever newer, better sulfas coming on market, that pipeline had died.
It was a double whammy of disaster, because now the current sulfas were proving less useful as more and more bacteria were becoming resistant to them.
Either a disease's bacteria totally failed to respond to sulfa and the patient died, or so large a dose need to be given that some patients again died from sulfa's toxicity at high dose levels.
This was not some sort of a Army front line versus RAF or Navy base hospital versus civilian home GP issue --- the stuff just didn't work as well as it used to ---- anywhere : in the UK , in battlefields world wide, in Germany and in Russia.
Full stop.
Sulfa's improved replacement - and it might be penicillin, who can tell ? - would face immense pressure to made in sufficient quantities to fulfill all needs all over the world, in civilian systemic use as well as front line local antiseptic use.
This was Florey and Fleming's greatest intellectual failure : the inability to see this.
Now neither of them were conceptual thinkers, as even their most ardent supporters admit in print - they were uniquely tied to the concrete and conventional here and now rather than to abstract speculation.
By contrast, Rene Dubos didn't have their success in finding a useful anti-bacterial medicine from microbes, (his luck was bad) but he could clearly see the Big Picture issues in ways those two could never hope to.
I do not know where Dawson stood for sure on this conceptual versus concrete issue since we have no personal papers of his - but the fact that Dubos always felt highly of him suggests a hint.
Certainly if deeds are better than mere words, Dawson never acted at all as if penicillin had to be first weaponized before it could become useful to humanity.
He was the first to give the world a patient successfully treated by a life-saving antibiotic because he saw semi-crude penicillin as more than good enough to inject safely into a human being : Dies Mirabilis, October 16th 1940.....
In fact one key participant at the meeting sensed this so greatly that he even whispered that history was going to view it that way, into the ear of the chairman as the meeting broke up.
In many ways, this meeting was very odd as well as being very historic.
Mostly because who called it and who it asked to attend.
It was called by one of the powerful of the many British wartime Ministries, the Ministry of Supply (MoS), which actually only supplied the Army (and perhaps in few things , the other two armed services as well) - but never ever supplied civilian needs.
Ronald Clark in his biography of Ernst Chain says this meeting was proceeded by the Ministers of (army) Supply and (civilian) Health, Sir Andrew Duncan and Ernest Brown, jointly "taking the idea of the immediate mass production of penicillin to the War Cabinet".
If so, it was possibly informally done via a Ministry "Minute" to the War Cabinet as neither gentlemen were ever members of the small War Cabinet : even in peacetime many many British politicians become ministers, without ever being becoming cabinet ministers.
And significantly, no one from Brown's civilian-oriented department was at this historical meeting.
This is a very important matter to resolve definitely, in part because the peculiar nature of this crucial meeting spelt the doom of Winston Churchill and his party in the election of June-July 1945.
How on earth did penicillin the universal lifesaver ever come be re-jigged as something only useful to the combat needs of the British Army ?
None of the drug firms summoned to this meeting (which did NOT include the very politically powerful firm of ICI ) had any real political or military influence - they didn't push for the meeting to take place but merely came when they were called.
But two of the four scientists had the meeting certainly did have good credentials with the Army ( but not Navy or Air Force) medical authorities and were of the correct Tory stamp: Howard Florey and Alec Fleming.
They had pushed for this meeting with the Army's supply department.
So, the army-oriented MoS was there in full force with six top officials along with two top officials from the Army Medical Branch charged with drug procurement for frontline casualties.
Missing in action at this meeting - by design - was the Navy, Air Force and any officials representing the Civilian interest in penicillin production.
Florey and Fleming both strongly saw penicillin as basically a useful supplement to the cheap abundant and systemically-oriented oral sulfas, with penicillin to be used primarily as in "local applications" for frontline combat wounds.
True, the Navy and Air force casualties were more often treated at large hospitals (and more often simply died in action) than in the case of the Army.
The Army had to deal with the fact that more of its casualties emerged as alive but wounded ,compared to the other services, which was the good news ---- but the bad news was that their wounds were usually about to get badly infected as a result of the primitive conditions at the front line.
A highly concentrated anti-bacterial drug with a long storage life and stable under almost any conditions as a dry powder (ie highly pure as well as highly concentrated) seemed essential.
Then and only then could it be suitable to sprinkle on open wounds immediately as they occurred on the front lines by barely trained medics or ordinary soldiers themselves.
Or for a busy front line doctor in am ambulance tent to inject, with a little sterile water, in or around those open wounds, within hours of the wounding.
Chemically, sulfa was born fulfilling these requirements - but penicillin didn't really meet them until after the six years of war was long over.
But unfortunately, no thorough controlled clinical trials of this claim that a frontline local application anti-bacterial medication would be essential for wounded survival was ever done.
At war's end, the general assessment was that, in fact, the frontline powders and needlefuls of these "local" penicillin and sulfa (ie applied directly into the wound) were not essential.
Instead, the wonderfully low rate of death from wounds (versus either the much worse record of WWI or of WWII Germany) was felt to be more due to the Allies' quick thorough debridement (removal) of dead wounded flesh , front line blood transfusions and policy of rapid evacuations of wounded soldiers to clean, quiet ,well equipped base hospitals .
That ---- and the general good health of wounded Allied troops, because they had been kept well fed and lived in warm sanitary conditions in the months before being wounded.
In the military base hospitals and civilian general hospitals, wartime sulfas and penicillin did prove to be reliable life savers when given as a systemic, if and when blood poisoning was suspected.
In fact, "crude" liquid penicillin (totally un-concentrated and totally un-purified) injected by needle and prepared in the hospital daily by Dr Duhig, saved lives as a systemic at a Brisbane general hospital --- and could have done so in the military equivalent.
Ooops ! It did do so, at Cairo's largest military hospital, where Dr Pulvertaft treated patients with liquid systemic crude penicillin he made daily in the hospital.
How did the Navy, RAF and the public, along with those politicians sworn to protect these groups of humans beings, react to the idea that penicillin was to be made under the control of the Army and for war casualties only ?
Seemingly with initial indifference - though by the Spring of 1943, a freelancing Navy Surgeon Commander had converted the Admiralty's under-producing vaccine operation to a huge penicillin factory supplying all of the Royal Navy's penicillin needs.
The Admiralty had always 'looked after its own', had always produced its own vaccines and serums so it didn't take long before the Navy medical brass had a look around at the penicillin factory and beam approval.
(Unlike the Army and Air Force, they had won the battle to retain the supplying of their needs by a naval units controlled directly by the Admiralty itself.)
For some rather sad reasons, the Air Force had relatively few wounded, for its size, and for other reasons, the treating of the wounded and returning them to battle was not an operational priority.
Over the course of the whole war, each of the British armed service got about one third of the money spent on the war. But in terms of manpower, of five people in uniform there were three in the army versus one in the RAF and one in the Navy/Merchant Marine.
This is because the RAF and RN/Merchant Marine had lots of big expensive machines that if "taken out of action" usually resulted in a 100% loss (aka "sunk" or "crashed"), while except in disastrous retreats, this rarely happened to the Army and its smaller cheaper machines.
The Allied Armies proved very much better, for example, at recovering even badly damaged tanks , as compared to the Germans.
In terms of personnel killed, the story is more complex.
Most of the RAF were never in real danger of dying but among those that flew, rather than maintained aircraft on the ground, the death rate was very high -often as much from operational accidents as enemy fire.
In Bomber Command, 55 of 100 fliers died before finishing their tour of duty.
Again there were relatively few wounded fliers versus a high rate of deaths - with the relatively few that survived their plane being hit only doing so by remaining out of the war, as German POWS.
People losses anyway and quite frankly , were not a big concern to the RAF : it never had a shortage of qualified recruits.
The RAF was seen as very glamorous to those determined to be very brave and seen a very secure place to spend the war to those with peacetime technical and engineering skills and no urge to be brave.
Manpower sustaining by speeding the recovery of the wounded was never a critical issue for any of WWII's air forces.
Replacing lost machines ( and frequently the training of new flier recruits) was always their obsession instead.
The world's navies were almost as attractive as the air forces, and rarely suffered from manpower worries and wounded recovery worries.
Instead, the sudden loss of entire town-sized machines (battleships or aircraft carriers) with all two thousand on board dead at one stroke, from a single torpedo or bomb, was their admirals more realistic nightmare.
In addition, while the Merchant Marine had particularly high losses of lives, against the relatively small number of its personnel, the merchant marine crews' relatively high pay and lack of onerous military discipline kept manpower replacement issues at bay.
When all factors are combined, at a gross figure level, the three armed services all lost about the same percentage of dead against the total number enlisted in each service, though as I have shown, the chance of death in service fell very unevenly.
In the case of the Army, it fell hardest on the infantry, followed by the tank crews and often the combat engineers.
Because almost no one wanted to join the infantry, it had few volunteers and generally the infantry got those conscripted recruits so totally lacking in useful education and technical skills that no other section of the Army wanted them.
To combine metaphors : incredibly enough, in all the Allied military , the very pointy end of the offensive stick came from the very bottom of the barrel.
In a nutshell, this is why the Germans and Japanese proved so very hard to defeat.
Over the whole war, the death rate varied greatly among the three services - the Navy death rate actually went down as the war progressed, the RAF's deaths peaked in 1943-1944, while in the case of the Army it was expected to rise suddenly and sharply to WWI Western Front levels, following the invasion of Europe.
The Army faced a short sharp period of potentially huge casualties - most wounded and infected but in Allied hands, not POWS.
If they weren't too badly wounded and the right anti-bacterial medication was at hand, the Army might be able to get most of the wounded back into battle formations before the war ended.
Just as well ,as there were no new men hustling to enter the infantry replacement pipeline at the other end.
At the very least, the thought that if and when they got wounded, the Army could heal most of them, would make the infantry less reluctant to rise up and advance against deadly Mortar and Machine Gun fire.
Or so the Army brass fondly believed.
I have tried to make the Fall of 1942 case for the British Army making penicillin just for itself seem as sensible as possible.
But in fact, it was a case going around with its nose full of Coke and Ecstasy.
In the fall of 1942, the really big medical story wasn't the rise of penicillin ; it was the decline of the previous wonder slash miracle drug : the Sulfas.
After five years of ever newer, better sulfas coming on market, that pipeline had died.
It was a double whammy of disaster, because now the current sulfas were proving less useful as more and more bacteria were becoming resistant to them.
Either a disease's bacteria totally failed to respond to sulfa and the patient died, or so large a dose need to be given that some patients again died from sulfa's toxicity at high dose levels.
This was not some sort of a Army front line versus RAF or Navy base hospital versus civilian home GP issue --- the stuff just didn't work as well as it used to ---- anywhere : in the UK , in battlefields world wide, in Germany and in Russia.
Full stop.
Sulfa's improved replacement - and it might be penicillin, who can tell ? - would face immense pressure to made in sufficient quantities to fulfill all needs all over the world, in civilian systemic use as well as front line local antiseptic use.
This was Florey and Fleming's greatest intellectual failure : the inability to see this.
Now neither of them were conceptual thinkers, as even their most ardent supporters admit in print - they were uniquely tied to the concrete and conventional here and now rather than to abstract speculation.
By contrast, Rene Dubos didn't have their success in finding a useful anti-bacterial medicine from microbes, (his luck was bad) but he could clearly see the Big Picture issues in ways those two could never hope to.
I do not know where Dawson stood for sure on this conceptual versus concrete issue since we have no personal papers of his - but the fact that Dubos always felt highly of him suggests a hint.
Certainly if deeds are better than mere words, Dawson never acted at all as if penicillin had to be first weaponized before it could become useful to humanity.
He was the first to give the world a patient successfully treated by a life-saving antibiotic because he saw semi-crude penicillin as more than good enough to inject safely into a human being : Dies Mirabilis, October 16th 1940.....
Wednesday, February 13, 2013
The first - and internally fatal - Tory response to the Beveridge Report : the Ministry of Supply takes over Penicillin ...
To make sense of this claim, we need to clear as to what the role of Britain's powerful wartime Ministry of Supply actually was.
The Ministry of Supply (the MoS) was never the British equivalent of the American War Production Board (WPB), no matter how many times this claim is offered up.
In fact, it was very much closer in spirit to Vannevar Bush's powerful Office of Scientific Research and Development (the OSRD) per the role set out for both under statute , than it was to the statutory role set out for the WPB.
Britain's Ministry of Supply strived to supply the military's needs - period. Unlike the WPB, it did not try to arbitrate between the conflicting demands of civilian and military claims upon scarce material and manpower.
Equally, the OSRD did NOT deal with all of America's wartime science and research efforts , a point that no doubt Jesus Christ himself will have to repeat again and again to academics on Judgement Day and on into all Eternity.
It only dealt with that amount of science and research that involved the designing of (but not the production of) new weapons that could come into use, during the current war.
Bush was very very careful to sharply limit the parameters of his organization, all to make it more dominant within its narrow but vital sphere.
So when Howard Florey went to both the OSRD and to the Ministry of Supply to help in the production of penicillin - rather than going instead to ask help from the American Public Health Service and the British Ministry of Health, he had already made it very clear where his penicillin priority lay.
He wanted additional penicillin production yes --- but only sufficient to supply the armed forces, period.
Florey was strongly conservative, as were all the key individuals within the Minister of Supply and the OSRD : Big Government to them was abhorrent.
Thus the sudden willingness, eagerness even, of the Ministry of Supply in the Fall of 1942 to go all out and seize control of all of the British commercial penicillin production has to be seen as ideologically surprising.
Unless it can (and should) be seen as the opening conservative counter-attack against the rumoured radical notions of the Beveridge Report.
A preemptive move to ensure that the Ministry of Health (also run by a Tory minister but with wider than just military responsibilities) didn't dominate penicillin production.
If is often claimed that the Ministry of Supply took over all of penicillin production because the Scottish-born minister was an old pal of fellow Scot, Alec Fleming, who asked him to do so.
Politicians - grant us at least this - do not spontaneously fall upon old friends and their requests with open arms --- not unless it suits us.
In September and October 1942, Fleming's request much suited Duncan and the British Tories.
In late September and October 1942, the tenor of the Beveridge report, though as yet unreleased, was well known within the top officials of Whitehall.
It called for a placing the values of equality and egalitarianism at the core of the British government - a notion intensely hostile to Tory values.
For penicillin, all this Beveridge "equality" talk could only mean one of two things.
It might mean divvying inadequate amounts of penicillin equally between dying civilians and dying soldiers - when Tories felt the most vital hope of penicillin was that it would help maintain current front line troop levels without the need to "call up" middle class men (their voters) now at home engaged in war work.
Or it might mean diverting the cost of one additional Lancaster squadron (three million pounds) away from the all-out bombing of civilian Germany , towards creating more penicillin factories on the successful Glaxo model.
Glaxo had taken up space in bits of idle factories and by using local cheap and plentiful unskilled labour,( aka women) , had cheaply but efficiently produced a lot of penicillin with current low technology methods and equipment.
(Basically making penicillin as if it was a milk product , using the very abundant modern dairy equipment existing everywhere thanks to the 1920s civilized world's mania over pure milk.)
A lot of similar factories could be quickly brought up to speed, supplying a good deal of penicillin, without requiring too much vital material like stainless steel, already in desperately short supply.
If all this sounds very familiar, that is because this solution is what Britain in the end was forced to do - but very late and only under intense public pressure.
If it had been done wholeheartedly in the Fall of 1942, there would have been no highly public late 1944 civilian penicillin famine crisis.
But the Conservative bits and bob of the Coalition Government wanted no part of equality and penicillin was just the first of many counterattacks against the threat of Beveridge.
They were unsuccessful in the extreme, blowing what had to seem to them (and to Labour !), a sure electoral victory at war's end.
"Unfair distribution of a vital commodity in short supply" , to quote The Times (of all people !) referencing an earlier debate over Hugh Dalton's fuel rationing proposals , was totally anathema to the British public.
In June 1945, what little polling type information we have suggests it was the unfair rationing of medical services that moved people to Labour .
The most current example of that unfair medical rationing had to be rationing difficulties with life saving penicillin.
Let me repeat that : "life saving". This was not just temporary unfairness in allocating housing or clothing : this was the unfair allocation of life itself.
You can't get a more "vital commodity" than life itself : to switch from the specialized language of the economist to that of the political scientist trying to account for a surprise pattern of vote changing, "life" is a very salient issue.
If so, the unexpected and total defeat of Churchill's Tories in June 1945 can be seen as having its origins in the Fall of 1942, when the Ministry of Supply (and Howard Florey) successfully re-defined the shortage of penicillin (contra Beveridge), as a shortage of military penicillin, civilians be damned.....
The Ministry of Supply (the MoS) was never the British equivalent of the American War Production Board (WPB), no matter how many times this claim is offered up.
In fact, it was very much closer in spirit to Vannevar Bush's powerful Office of Scientific Research and Development (the OSRD) per the role set out for both under statute , than it was to the statutory role set out for the WPB.
Britain's Ministry of Supply strived to supply the military's needs - period. Unlike the WPB, it did not try to arbitrate between the conflicting demands of civilian and military claims upon scarce material and manpower.
Equally, the OSRD did NOT deal with all of America's wartime science and research efforts , a point that no doubt Jesus Christ himself will have to repeat again and again to academics on Judgement Day and on into all Eternity.
It only dealt with that amount of science and research that involved the designing of (but not the production of) new weapons that could come into use, during the current war.
Bush was very very careful to sharply limit the parameters of his organization, all to make it more dominant within its narrow but vital sphere.
So when Howard Florey went to both the OSRD and to the Ministry of Supply to help in the production of penicillin - rather than going instead to ask help from the American Public Health Service and the British Ministry of Health, he had already made it very clear where his penicillin priority lay.
He wanted additional penicillin production yes --- but only sufficient to supply the armed forces, period.
Florey was strongly conservative, as were all the key individuals within the Minister of Supply and the OSRD : Big Government to them was abhorrent.
Thus the sudden willingness, eagerness even, of the Ministry of Supply in the Fall of 1942 to go all out and seize control of all of the British commercial penicillin production has to be seen as ideologically surprising.
Unless it can (and should) be seen as the opening conservative counter-attack against the rumoured radical notions of the Beveridge Report.
A preemptive move to ensure that the Ministry of Health (also run by a Tory minister but with wider than just military responsibilities) didn't dominate penicillin production.
If is often claimed that the Ministry of Supply took over all of penicillin production because the Scottish-born minister was an old pal of fellow Scot, Alec Fleming, who asked him to do so.
Politicians - grant us at least this - do not spontaneously fall upon old friends and their requests with open arms --- not unless it suits us.
In September and October 1942, Fleming's request much suited Duncan and the British Tories.
In late September and October 1942, the tenor of the Beveridge report, though as yet unreleased, was well known within the top officials of Whitehall.
It called for a placing the values of equality and egalitarianism at the core of the British government - a notion intensely hostile to Tory values.
For penicillin, all this Beveridge "equality" talk could only mean one of two things.
It might mean divvying inadequate amounts of penicillin equally between dying civilians and dying soldiers - when Tories felt the most vital hope of penicillin was that it would help maintain current front line troop levels without the need to "call up" middle class men (their voters) now at home engaged in war work.
Or it might mean diverting the cost of one additional Lancaster squadron (three million pounds) away from the all-out bombing of civilian Germany , towards creating more penicillin factories on the successful Glaxo model.
Glaxo had taken up space in bits of idle factories and by using local cheap and plentiful unskilled labour,( aka women) , had cheaply but efficiently produced a lot of penicillin with current low technology methods and equipment.
(Basically making penicillin as if it was a milk product , using the very abundant modern dairy equipment existing everywhere thanks to the 1920s civilized world's mania over pure milk.)
A lot of similar factories could be quickly brought up to speed, supplying a good deal of penicillin, without requiring too much vital material like stainless steel, already in desperately short supply.
If all this sounds very familiar, that is because this solution is what Britain in the end was forced to do - but very late and only under intense public pressure.
If it had been done wholeheartedly in the Fall of 1942, there would have been no highly public late 1944 civilian penicillin famine crisis.
But the Conservative bits and bob of the Coalition Government wanted no part of equality and penicillin was just the first of many counterattacks against the threat of Beveridge.
They were unsuccessful in the extreme, blowing what had to seem to them (and to Labour !), a sure electoral victory at war's end.
"Unfair distribution of a vital commodity in short supply" , to quote The Times (of all people !) referencing an earlier debate over Hugh Dalton's fuel rationing proposals , was totally anathema to the British public.
In June 1945, what little polling type information we have suggests it was the unfair rationing of medical services that moved people to Labour .
The most current example of that unfair medical rationing had to be rationing difficulties with life saving penicillin.
Let me repeat that : "life saving". This was not just temporary unfairness in allocating housing or clothing : this was the unfair allocation of life itself.
You can't get a more "vital commodity" than life itself : to switch from the specialized language of the economist to that of the political scientist trying to account for a surprise pattern of vote changing, "life" is a very salient issue.
If so, the unexpected and total defeat of Churchill's Tories in June 1945 can be seen as having its origins in the Fall of 1942, when the Ministry of Supply (and Howard Florey) successfully re-defined the shortage of penicillin (contra Beveridge), as a shortage of military penicillin, civilians be damned.....
Sunday, February 10, 2013
Penicillin : biologic 1929-1939 , chemotherapeutic 1939-1949
In 1944, Frank M Berger ( later creator of the post-war drug Miltown but then just a worker in a local municipal public health lab in the remotes of northern England) came up with an unique way of making and using penicillin.
On second thoughts, his method might well have been done first by Alexander Fleming's Wright-Fleming vaccine institute and their pharmaceutical distributor Parke-Davis about 15 years earlier : Penicillin the Biologic.
On further further reflection : should have been done first by Alec Fleming.
Berger's penicillin was only concentrated and purified to the point that not too much penicillin was lost or too much scarce labour and expensive equipment used to create and extract it.
This biological penicillin, Berger claimed, was safe, potent and cheap ---and liquid.
Liquid --- and stored cold in the hospital that made it, ( not usually stored more than a week at most), until the next life-threatening case of blood poisoning in that same hospital was cured by its systemic (ie by needle) application.
The immediate use of whole liquid blood (another biologic dismissed earlier in the war) right at the front lines of combat was/is vital for survival of the badly wounded soldier.
But immediately pouring penicillin or sulfa into the man's dirty wound (ie via "local" application) - counter-intutively - is not.
Quickly getting him back to a hospital-like setting where penicillin or sulfa can be given him systemically, and under more carefully monitored conditions, was still useful.
But, it proved not essential to do so immediately even there ; often the staff could afford to wait to first see if signs of systemic infection were present (usually via a temperature rise.)
Ie, Howard Florey's 1939 claim that penicillin was only useful if made into a dry powder that remained stable at room temperature for months at a time was totally in error --- if life-saving was to be its main (wartime) role.
Berger's efforts were merely the best thought out among the number of doctors advocating biologic penicillin, not by any means the first (Dawson) or the most stunning (Duhig) .
By contrast, Florey was the chief high priest of Penicillin the Chemotherapeutic, (pure,dry,powdery), from first to last its leading advocate....
On second thoughts, his method might well have been done first by Alexander Fleming's Wright-Fleming vaccine institute and their pharmaceutical distributor Parke-Davis about 15 years earlier : Penicillin the Biologic.
On further further reflection : should have been done first by Alec Fleming.
Berger's penicillin was only concentrated and purified to the point that not too much penicillin was lost or too much scarce labour and expensive equipment used to create and extract it.
This biological penicillin, Berger claimed, was safe, potent and cheap ---and liquid.
Liquid --- and stored cold in the hospital that made it, ( not usually stored more than a week at most), until the next life-threatening case of blood poisoning in that same hospital was cured by its systemic (ie by needle) application.
The immediate use of whole liquid blood (another biologic dismissed earlier in the war) right at the front lines of combat was/is vital for survival of the badly wounded soldier.
But immediately pouring penicillin or sulfa into the man's dirty wound (ie via "local" application) - counter-intutively - is not.
Quickly getting him back to a hospital-like setting where penicillin or sulfa can be given him systemically, and under more carefully monitored conditions, was still useful.
But, it proved not essential to do so immediately even there ; often the staff could afford to wait to first see if signs of systemic infection were present (usually via a temperature rise.)
Ie, Howard Florey's 1939 claim that penicillin was only useful if made into a dry powder that remained stable at room temperature for months at a time was totally in error --- if life-saving was to be its main (wartime) role.
Berger's efforts were merely the best thought out among the number of doctors advocating biologic penicillin, not by any means the first (Dawson) or the most stunning (Duhig) .
By contrast, Florey was the chief high priest of Penicillin the Chemotherapeutic, (pure,dry,powdery), from first to last its leading advocate....
Howard Florey saw potential enemies everywhere, but with "friends" like A N Richards and Robert Coghill, he hardly need bother looking any further
Howard Florey's correspondence twice notes that he has just received a higher yielding strain of penicillium from America.
The first, in November 1941 ,was obtained from Dr Rake at Squibb - a higher producing mutant from Fleming's original strain.
The second time in November 1943, some un-named strains were obtained from Robert Coghill of the NRRL , while he was visiting Oxford .
But in the two crucial years in between ?
I see bugger all evidence that Florey got the latest improvements in penicillium strains as they emerged at Peoria. (Prove me wrong, please) .
The mycologists at the NRRL research centre in Peoria had steadily improved and improved and improved again Rake's variant and their final version, NRRL 1249.B21 produced - via surface cultivation - most of the world's wartime penicillin until quite late in the war.
At that point, submerged strain NRRL 832, from a non-Fleming strain first found in Belgium, took over.
I believe that Merck's chief consultant and OSRD medical chief ( giant conflict of interest alert !) A N Richards, supposedly Florey's second closest American friend, using as an excuse that America was now at war, deliberately held back the giving these improved strains to Florey.
All to further America's ( sorry ! Merck's) post-war commercial opportunities.
Nicolas Rasmussen, in his article "Of 'Small Men', Big Science and Bigger Business", looks much closer than most historians at the day to day workings of the medical wing of the famous OSRD.
He points to several examples where Richards authorizes the further spending of taxpayers' money, supposedly only for war weapons, on drug research that no longer had an obvious military use, because he claimed that keeping American's edge in their development would definitely benefit the nation.
If not in this war, or any war, how would the drug's successful development benefit a nation at war - supposedly the sole purpose of the OSRD, whose mandate was set up to expire the moment peace was declared ?
Richards doesn't say.
So let me suggest a more sinister purpose , because Rasmussen does not.
I note that the two examples that Rasmussen gives where the OSRD spends taxpayers money on projects that no longer seemed to have a military need were pet projects of Merck, the firm that Richards advised.
The first was the chemical synthesis work on penicillin , carried on well past the point (say June 1944) when biological penicillin was being produced en masse and cheaply.
The other was after mid 1943, when it was clear that cortisone would not help pilots fly higher longer - an important advantage for any nation's air force if proven so.
Merck got nothing for all the money it spent on synthetic penicillin but its finally successful efforts on cortisone was and is one of its biggest successes for both its scientific reputation and its pocketbook (the two of course being closely related).
First success with Cortisone would be an advantage to America as well as Merck, over European (Swiss) competitors --- but synthetic penicillin's success could only have come by crushing fellow American firm Pfizer and given the field to Merck.
How then would that serve America's interests, rather than merely Merck's?
Because Europe wasn't even in the running on biological penicillin in 1944.
Perhaps Richards, already a pensioner when he took on the job of heading the OSRD medical wing and with the rigidity of old age, still believed synthetic penicillin would better Pfizer's penicillin in price and yield.
Then Merck would beat their only European synthetic penicillin rival : Florey !
Normally, Vannevar Bush's OSRD - as in denying the British to atomic energy research - did a better job of using taxpayers' military-assigned money to screw America's European Allies' commercial chances after the war , without favouring any one American firm.
Richard's willingness to screw Pfizer and even his friend Florey, shows just how much further he was prepared to go to aid Merck.
But he needed pliant helpers to succeed.
Luckily for him, the NRRL's Robert Coghill seemed to have had a hard time accepting that research paid for by his employer , the US Department of Agriculture and ultimately the American public, belonged to the USDA.
And that this research shouldn't only go where a different agency's chief bureaucrat, A N Richards, wanted it to go - though he hadn't paid for it and had no statutory (legal) control over it.
However , I see Coghill, a misplaced chemist running a biological program, wanted in so badly on a "technically sweet" chemical problem (the synthesis of penicillin) that he sold out the farmers he had sworn to help.
Synthetic penicillin would only negate the ready market for hundreds of thousands of tons of farm waste corn steep liquor, farm waste whey and farm waste crude brown sugar, all used in the natural fermentation of penicillin and other antibiotics coming along in the pipeline.
Coghill did publicly announce that he was giving the top two commercial strains of penicillium (presumably NRRL 1249.B21 and 832) to the entire world in November 1943, about the same time as Florey first mentions having them.
Why ?
I can only suspect because they were about to become obsolete, as synthetic penicillin seemed only months away.
By April 1944, that no longer seemed so and Coghill was back on the side of the biological angels, publicly praising Pfizer's biological penicillin and modestly claiming a role in their success.
Coghill's talents seemed rather wasted in democratic America - I can see him as the ultimate bureaucratic survivor in Stalin's Russia, adroitly changing sides as the situation shifted, moment by moment.....
The first, in November 1941 ,was obtained from Dr Rake at Squibb - a higher producing mutant from Fleming's original strain.
The second time in November 1943, some un-named strains were obtained from Robert Coghill of the NRRL , while he was visiting Oxford .
But in the two crucial years in between ?
I see bugger all evidence that Florey got the latest improvements in penicillium strains as they emerged at Peoria. (Prove me wrong, please) .
The mycologists at the NRRL research centre in Peoria had steadily improved and improved and improved again Rake's variant and their final version, NRRL 1249.B21 produced - via surface cultivation - most of the world's wartime penicillin until quite late in the war.
At that point, submerged strain NRRL 832, from a non-Fleming strain first found in Belgium, took over.
I believe that Merck's chief consultant and OSRD medical chief ( giant conflict of interest alert !) A N Richards, supposedly Florey's second closest American friend, using as an excuse that America was now at war, deliberately held back the giving these improved strains to Florey.
All to further America's ( sorry ! Merck's) post-war commercial opportunities.
Nicolas Rasmussen, in his article "Of 'Small Men', Big Science and Bigger Business", looks much closer than most historians at the day to day workings of the medical wing of the famous OSRD.
He points to several examples where Richards authorizes the further spending of taxpayers' money, supposedly only for war weapons, on drug research that no longer had an obvious military use, because he claimed that keeping American's edge in their development would definitely benefit the nation.
If not in this war, or any war, how would the drug's successful development benefit a nation at war - supposedly the sole purpose of the OSRD, whose mandate was set up to expire the moment peace was declared ?
Richards doesn't say.
So let me suggest a more sinister purpose , because Rasmussen does not.
I note that the two examples that Rasmussen gives where the OSRD spends taxpayers money on projects that no longer seemed to have a military need were pet projects of Merck, the firm that Richards advised.
The first was the chemical synthesis work on penicillin , carried on well past the point (say June 1944) when biological penicillin was being produced en masse and cheaply.
The other was after mid 1943, when it was clear that cortisone would not help pilots fly higher longer - an important advantage for any nation's air force if proven so.
Merck got nothing for all the money it spent on synthetic penicillin but its finally successful efforts on cortisone was and is one of its biggest successes for both its scientific reputation and its pocketbook (the two of course being closely related).
First success with Cortisone would be an advantage to America as well as Merck, over European (Swiss) competitors --- but synthetic penicillin's success could only have come by crushing fellow American firm Pfizer and given the field to Merck.
How then would that serve America's interests, rather than merely Merck's?
Because Europe wasn't even in the running on biological penicillin in 1944.
Perhaps Richards, already a pensioner when he took on the job of heading the OSRD medical wing and with the rigidity of old age, still believed synthetic penicillin would better Pfizer's penicillin in price and yield.
Then Merck would beat their only European synthetic penicillin rival : Florey !
Normally, Vannevar Bush's OSRD - as in denying the British to atomic energy research - did a better job of using taxpayers' military-assigned money to screw America's European Allies' commercial chances after the war , without favouring any one American firm.
Richard's willingness to screw Pfizer and even his friend Florey, shows just how much further he was prepared to go to aid Merck.
But he needed pliant helpers to succeed.
Luckily for him, the NRRL's Robert Coghill seemed to have had a hard time accepting that research paid for by his employer , the US Department of Agriculture and ultimately the American public, belonged to the USDA.
And that this research shouldn't only go where a different agency's chief bureaucrat, A N Richards, wanted it to go - though he hadn't paid for it and had no statutory (legal) control over it.
However , I see Coghill, a misplaced chemist running a biological program, wanted in so badly on a "technically sweet" chemical problem (the synthesis of penicillin) that he sold out the farmers he had sworn to help.
Synthetic penicillin would only negate the ready market for hundreds of thousands of tons of farm waste corn steep liquor, farm waste whey and farm waste crude brown sugar, all used in the natural fermentation of penicillin and other antibiotics coming along in the pipeline.
Coghill did publicly announce that he was giving the top two commercial strains of penicillium (presumably NRRL 1249.B21 and 832) to the entire world in November 1943, about the same time as Florey first mentions having them.
Why ?
I can only suspect because they were about to become obsolete, as synthetic penicillin seemed only months away.
By April 1944, that no longer seemed so and Coghill was back on the side of the biological angels, publicly praising Pfizer's biological penicillin and modestly claiming a role in their success.
Coghill's talents seemed rather wasted in democratic America - I can see him as the ultimate bureaucratic survivor in Stalin's Russia, adroitly changing sides as the situation shifted, moment by moment.....
Wednesday, February 6, 2013
OSRD /1942: did Manhattan Project type thinking bleed over and obstruct the Penicillin Project as well ?
It is crystal clear that Merck's top scientific advisor A N Richards was never a strong advocate for fast-paced penicillin development within Merck, as that drug company casually messed about with penicillin, from November 1939 till August 1941.
That is, Merck had 18 months of some sort of commercial and scientific activity around penicillin , before Howard Florey actually arrived on the scene.
But Florey eventually made Richards a strong convert to the idea of having Richards' military medical weapon oriented agency , the famous OSRD , use penicillin for secret military advantage over the Axis.
It is not clear that this would have extended - in practise - to denying penicillin to dying Axis POWs.
But keeping penicillin a secret from the Axis definitely would have denied penicillin to dying Allied POWs behind Axis lines : something that all of Florey's, Richards' and Fleming's present day defenders universally ignore.
Very much to his credit then that WWI vet and WWII military officer and doctor Robert Pulvertaft did dis-obey orders and shared the secrets of penicillin production with Axis-friendly Turkish doctors.
But imagining a Canadian dying of sulfa-resistant blood poisoning in a German POW camp and the Canadian POWs being told by the German doctor, 'we could save him , if only we had a bit of this Allied-invented penicillin that we've been hearing rumours of'.
When the Canadians ask why doesn't the doctor get some, the doctor says that if the Allies won't even share penicillin with their own dying civilians, how can they be expected to share it with the enemy ?
But could penicillin have really ever have been a potentially secret and successful medical weapon ?
Here I , following closely on Henry Dawson's thinking, definitely part company with Florey and his friend Richards.
Henry Dawson demonstrated - in just five weeks - and under conditions as fully primitive as Fleming's, that one could quickly make a lot of crude penicillin that was non-toxic when injected into humans.
If Fleming and Dawson could do so, (quickly, easily and cheaply, ) so too could the fired up Nazi war machine.
Not so, said Florey -and his side kick Richards.
The scientific characteristics of penicillin haven't changed at all since September 1928, but now , thanks to Florey, the scientific rhetoric totally had.
Florey tells his readers and listeners, to ignore completely what Fleming-the-author says is "penicillin".
To wit, 'a mixture of about two dozen unknown compounds in a slurry of water that is non-toxic even if injected in very large volumes internally, and yet has marked anti-bacterial affects'.
In my revision of the facts, says Florey in his first August 1940 article, "penicillin" is now actually just one of those compounds.
All the rest and all that water are just dirty, dank and dangerous.
Only if penicillin is first pure, dry and stable is it any good.
Because where it is really good , is in the front lines as a local antiseptic for open war wounds (here I do still agree with Fleming) ---- and that idea won't work if crude liquid penicillin must kept viable in portable electric refrigerators.
Who ever has heard of such things ?
But as Florey tells Richards how complex and difficult the purification process is, Richards grows despondent again, but never the less this information does go into the back of Richards brain.
Only to re-emerge in early 1942, when the forces of war censorship and secrecy can be employed in full bloom.
Because complex and expensive separation and purification processes had become very much a two-edged sword for American military science and industry.
Artificial rubber was vital to the war effort - it was easy to make but a real bugger to separate the good rubber from the bad.
Dried blood products held real promise at the front lines - but only if their separation wasn't so complex.
And the Atomic Bomb - a piece of cake to make it work - if only we could get enough pure U-235 separated.
At some point early in 1942, these problems suddenly became military and commercial opportunities in the minds of the OSRD's highest officers.
If only rich, un-bombed America could solve these complex purification problems - and then keep the details secret - this would give them a big military advantage over their poorer enemy opponents.
And give America a post-war commercial advantage as well over its smaller poorer Allied friends like Britain.
So just as we see an abrupt turn around , in mid 1942 , from the OSRD re sharing much atomic information with the British, we start to see the British also get less information from the OSRD about penicillin research as well.
Like synthetic rubber, synthetic quinine, dried blood products and U-235, the very expensive complexity of pure penicillin suddenly made it more, not less ,of an attraction to the military weapon-oriented OSRD.
The key was to keep secret from the American voters and taxpayers just how many miracle cures were happening with the current - relatively impure -penicillin.
Because if they knew that, the newspapers would be filled with it and the Germans and Japanese would hear about it via Neutral nation reporting.
They they too would also start curing their base hospital wounded with crude semi-purified penicillin ,largely negating the military advantage of fully dry stable pure penicillin.
But was there really ever an absolute need for dry stable penicillin to use it in the front lines ?
Poppycock !
Because it turned out that good old crude liquid blood was actually much better than the complex dried stuff at saving soldiers' lives and could just as easily be used even in combat : good old fashioned low tech American ingenuity (not from the OSRD high tech boys of course) came to the rescue.
Cheap, rugged, disposable, parachute-portable plywood ice boxes kept blood and penicillin cold, with refills of ice every couple of days........
That is, Merck had 18 months of some sort of commercial and scientific activity around penicillin , before Howard Florey actually arrived on the scene.
But Florey eventually made Richards a strong convert to the idea of having Richards' military medical weapon oriented agency , the famous OSRD , use penicillin for secret military advantage over the Axis.
It is not clear that this would have extended - in practise - to denying penicillin to dying Axis POWs.
But keeping penicillin a secret from the Axis definitely would have denied penicillin to dying Allied POWs behind Axis lines : something that all of Florey's, Richards' and Fleming's present day defenders universally ignore.
Very much to his credit then that WWI vet and WWII military officer and doctor Robert Pulvertaft did dis-obey orders and shared the secrets of penicillin production with Axis-friendly Turkish doctors.
But imagining a Canadian dying of sulfa-resistant blood poisoning in a German POW camp and the Canadian POWs being told by the German doctor, 'we could save him , if only we had a bit of this Allied-invented penicillin that we've been hearing rumours of'.
When the Canadians ask why doesn't the doctor get some, the doctor says that if the Allies won't even share penicillin with their own dying civilians, how can they be expected to share it with the enemy ?
But could penicillin have really ever have been a potentially secret and successful medical weapon ?
Here I , following closely on Henry Dawson's thinking, definitely part company with Florey and his friend Richards.
Henry Dawson demonstrated - in just five weeks - and under conditions as fully primitive as Fleming's, that one could quickly make a lot of crude penicillin that was non-toxic when injected into humans.
If Fleming and Dawson could do so, (quickly, easily and cheaply, ) so too could the fired up Nazi war machine.
Not so, said Florey -and his side kick Richards.
The scientific characteristics of penicillin haven't changed at all since September 1928, but now , thanks to Florey, the scientific rhetoric totally had.
Florey tells his readers and listeners, to ignore completely what Fleming-the-author says is "penicillin".
To wit, 'a mixture of about two dozen unknown compounds in a slurry of water that is non-toxic even if injected in very large volumes internally, and yet has marked anti-bacterial affects'.
In my revision of the facts, says Florey in his first August 1940 article, "penicillin" is now actually just one of those compounds.
All the rest and all that water are just dirty, dank and dangerous.
Only if penicillin is first pure, dry and stable is it any good.
Because where it is really good , is in the front lines as a local antiseptic for open war wounds (here I do still agree with Fleming) ---- and that idea won't work if crude liquid penicillin must kept viable in portable electric refrigerators.
Who ever has heard of such things ?
But as Florey tells Richards how complex and difficult the purification process is, Richards grows despondent again, but never the less this information does go into the back of Richards brain.
Only to re-emerge in early 1942, when the forces of war censorship and secrecy can be employed in full bloom.
Because complex and expensive separation and purification processes had become very much a two-edged sword for American military science and industry.
Artificial rubber was vital to the war effort - it was easy to make but a real bugger to separate the good rubber from the bad.
Dried blood products held real promise at the front lines - but only if their separation wasn't so complex.
And the Atomic Bomb - a piece of cake to make it work - if only we could get enough pure U-235 separated.
At some point early in 1942, these problems suddenly became military and commercial opportunities in the minds of the OSRD's highest officers.
If only rich, un-bombed America could solve these complex purification problems - and then keep the details secret - this would give them a big military advantage over their poorer enemy opponents.
And give America a post-war commercial advantage as well over its smaller poorer Allied friends like Britain.
So just as we see an abrupt turn around , in mid 1942 , from the OSRD re sharing much atomic information with the British, we start to see the British also get less information from the OSRD about penicillin research as well.
Like synthetic rubber, synthetic quinine, dried blood products and U-235, the very expensive complexity of pure penicillin suddenly made it more, not less ,of an attraction to the military weapon-oriented OSRD.
The key was to keep secret from the American voters and taxpayers just how many miracle cures were happening with the current - relatively impure -penicillin.
Because if they knew that, the newspapers would be filled with it and the Germans and Japanese would hear about it via Neutral nation reporting.
They they too would also start curing their base hospital wounded with crude semi-purified penicillin ,largely negating the military advantage of fully dry stable pure penicillin.
But was there really ever an absolute need for dry stable penicillin to use it in the front lines ?
Poppycock !
Because it turned out that good old crude liquid blood was actually much better than the complex dried stuff at saving soldiers' lives and could just as easily be used even in combat : good old fashioned low tech American ingenuity (not from the OSRD high tech boys of course) came to the rescue.
Cheap, rugged, disposable, parachute-portable plywood ice boxes kept blood and penicillin cold, with refills of ice every couple of days........
Spores and Wartime Secrecy : can they actually co-exist ?
You might think I am going to talk about Anthrax spores and asymmetrical terrorist germ warfare.
But you are wrong, wrong, wrong.
I want to talk instead about wartime penicillin, and a part of it that is never ever discussed.
Its inherently asymmetrical medical nature.
Which appropriately enough, then "drifts over" into its inherently asymmetrical military potential.
So lets start.
And lets start talking about just how the intellectually mis-guided (as well as seriously morally misguided) were the prolonged attempts by the medical establishment in both America and Britain to regard penicillium spores as something that really could remain Top Secret medical military weapons.
And not just the wartime medical establishment, for recently author Eric Lax and his publishers felt they had a real winner in an exciting clock and dagger title for their book on wartime penicillin : "The Mould in Doctor Florey's Coat".
There was always something faintly Walter Mittyesque about Florey anyway - never more so than in the incident that gave this book its title.
Dunkirk was underway just as Florey at long last accepted that ole Flem's penicillin just might be priceless after all.
But how to save penicillin for the rest of the Allied cause, if Britain fell to the Germans ?
'Let's all rub penicillium spores in the inner seams of our clothing - so even if only one of us gets away, the precious fire of penicillin research can still be re-lit elsewhere'.
But none of these Oxford naifs seemed to have dared ask the boss (Florey) just how they came to possess these incredible spores in the first place.
Henry Dawson's first big scientific effort was in promoting the concept of HGT (Horizontal Gene Transfer) ,the instant transfer of genes between different species and even different families of Life, when its initial discoverer seemed reluctant to even publish his work.
Today it is believed that soil bacteria created the first beta lactam antibiotics about ten million years ago and - via HGT - gave it to soil molds who modified it slightly and made it penicillin.
So, sometime in 1928, a particularly productive penicillin producer strain of penicillium mold blow into a fancy home in London.
Alexander Fleming's colleague John Freeman was an expert on allergies, with many rich and powerful patients.
In 1928, Freeman heard a Dutch specialist claim that basement mold spores were the cause of many allergies.
Freeman got his rich London patients (or more likely their scullery maids) to scrape molds off their basement walls to be tested by his most recent hire, Irish-born mycologist Charles La Touche, towards seeking ways to gradually desensitize the patients against their particular household mold allergens.
La Touche had no high tech ways to keep spores inside his lab alone - not that I think in the long run a spore or two doesn't get out of the most secure modern facility.
There are many more fungus than us and they have and will be on the Earth a lot longer than us primarily because of their spores.
Their spores are incredibly tiny examples of temporarily suspended Life - Dried-up Life - inside a very hardy and bumpy package.
Tiny is the key here - so tiny they float anywhere and everywhere on the gentlest of breezes - down the hall and around the world.
Being bumpy but tiny and light doesn't hurt either - they can cling to almost any surface - like a human and its luggage bound for Australia, for example.
However if that surface is the tiniest bit damp and the tiniest bit tasty (they seem willing to eat almost anything faintly organic), they spring back into active slimey life.
One of La Touche's spores drifted out of his room and along the stairs to Fleming open Petri dish.
The rest actually wouldn't have been "legend", if Fleming hadn't promptly taken a sub culture of the resulting "spoiled" petri dish, and carefully and correctly preserved it.
Fleming did little to promote the medical use of penicillin in curing disease but he did vigerously promote it as a useful way for busy hospital labs to easily isolate the so called flu bacteria (sic) .
Dozens of labs world wide got a sample from him - they then gave samples of their samples to at least dozens of others.
That is how Florey got his penicillium spores he was so busy stuffing down his coat - from a sub culture Fleming had sent to the previous director of Florey's Dunn Institute.
The Free World beyond Britain had lots of sub cultures of penicillium spores of the rare - right - type, even without Florey's belated act of charity.
In theory they didn't really need Fleming's spores, only his public article - but in practise, until 1943, they really did need his spores.
Examples of Fleming's spores were actually everywhere - some even better penicillium producers than his original un-mutated version as well.
But they could only be found by teams of researchers seeking hundreds of the right looking blue-green mold on walls and spoiled fruit, and then testing all for their possible anti-bacterial qualities.
Until miracle cures got rumoured about, no one in the world was willing to go to that much effort , just to test a troublesome possible antiseptic.
But by 1943, the miracle cure stories were out amongst the clinical doctors everywhere - and I do really mean everywhere.
Everywhere that Florey went, Egypt, Iran, Russia he had to endure local doctors thrusting excellent producing strains of penicillin molds in his face that they had found locally !
The Axis were just as quick off the mark - Japan got its strain by merely looking about locally.
And the clever Japanese correctly guessed - from one badly reproduced photo in an Egyptian picture magazine - just how best to produce the stuff !
The atomic bomb was effectively secret even if the US had proclaimed it was making one from the rooftops in 1942.
Uranium was everywhere - like penicillium spores - but a bomb from it takes the world's largest, most expensive, building ever built merely to get started on separating pure U-235 from the more abundant U-238.
And without 90% pure U-235, no working bomb. No nothing.
Tons and tons of scarce money, time and effort kept the A-Bomb an American secret, even from the British and Canadians , let alone the Axis and Neutrals.
But by late 1943, popular magazine articles cheekily showed how one could make penicillin at home, on a kitchen top, for about $5 in equipment and growth mediums.
One didn't even need to go out searching for those semi-rare penicillin-producing strains by then.
In a surprising - even shocking - total volt face, the NRRL's Coghill and Raper had released the top two strains of penicillium.
That's right, the top two strains that were then producing most of the Allies' military-bound penicillin - to the public American mold type collection in Washington where, as they told the readers of JAMA worldwide, "anyone" can get some at a "nominal charge".
!!!!!!!!
No word if Argentina's Washington DC based scientific attache quickly took a cab over, got some samples and sent them off to his friends in Germany.
Clearly, penicillin was never a viable secret military medical weapon - Florey and Richards were both , to put it kindly, completely deluded to ever think so.
Deluded by utopian visions of near-total purity.
Because unlike the Atomic Bomb and U-235, penicillin's starting material (the spores) were both common worldwide AND its production fully successful even in a highly impure (aka low tech) state.
This was what Fleming had discovered in 1928 but never acted upon - this was the key insight that Henry Dawson brought to the penicillin story, starting on October 16th 1940....
But you are wrong, wrong, wrong.
I want to talk instead about wartime penicillin, and a part of it that is never ever discussed.
Its inherently asymmetrical medical nature.
Which appropriately enough, then "drifts over" into its inherently asymmetrical military potential.
So lets start.
And lets start talking about just how the intellectually mis-guided (as well as seriously morally misguided) were the prolonged attempts by the medical establishment in both America and Britain to regard penicillium spores as something that really could remain Top Secret medical military weapons.
And not just the wartime medical establishment, for recently author Eric Lax and his publishers felt they had a real winner in an exciting clock and dagger title for their book on wartime penicillin : "The Mould in Doctor Florey's Coat".
There was always something faintly Walter Mittyesque about Florey anyway - never more so than in the incident that gave this book its title.
Dunkirk was underway just as Florey at long last accepted that ole Flem's penicillin just might be priceless after all.
But how to save penicillin for the rest of the Allied cause, if Britain fell to the Germans ?
'Let's all rub penicillium spores in the inner seams of our clothing - so even if only one of us gets away, the precious fire of penicillin research can still be re-lit elsewhere'.
But none of these Oxford naifs seemed to have dared ask the boss (Florey) just how they came to possess these incredible spores in the first place.
Henry Dawson's first big scientific effort was in promoting the concept of HGT (Horizontal Gene Transfer) ,the instant transfer of genes between different species and even different families of Life, when its initial discoverer seemed reluctant to even publish his work.
Today it is believed that soil bacteria created the first beta lactam antibiotics about ten million years ago and - via HGT - gave it to soil molds who modified it slightly and made it penicillin.
So, sometime in 1928, a particularly productive penicillin producer strain of penicillium mold blow into a fancy home in London.
Alexander Fleming's colleague John Freeman was an expert on allergies, with many rich and powerful patients.
In 1928, Freeman heard a Dutch specialist claim that basement mold spores were the cause of many allergies.
Freeman got his rich London patients (or more likely their scullery maids) to scrape molds off their basement walls to be tested by his most recent hire, Irish-born mycologist Charles La Touche, towards seeking ways to gradually desensitize the patients against their particular household mold allergens.
La Touche had no high tech ways to keep spores inside his lab alone - not that I think in the long run a spore or two doesn't get out of the most secure modern facility.
There are many more fungus than us and they have and will be on the Earth a lot longer than us primarily because of their spores.
Their spores are incredibly tiny examples of temporarily suspended Life - Dried-up Life - inside a very hardy and bumpy package.
Tiny is the key here - so tiny they float anywhere and everywhere on the gentlest of breezes - down the hall and around the world.
Being bumpy but tiny and light doesn't hurt either - they can cling to almost any surface - like a human and its luggage bound for Australia, for example.
However if that surface is the tiniest bit damp and the tiniest bit tasty (they seem willing to eat almost anything faintly organic), they spring back into active slimey life.
One of La Touche's spores drifted out of his room and along the stairs to Fleming open Petri dish.
The rest actually wouldn't have been "legend", if Fleming hadn't promptly taken a sub culture of the resulting "spoiled" petri dish, and carefully and correctly preserved it.
Fleming did little to promote the medical use of penicillin in curing disease but he did vigerously promote it as a useful way for busy hospital labs to easily isolate the so called flu bacteria (sic) .
Dozens of labs world wide got a sample from him - they then gave samples of their samples to at least dozens of others.
That is how Florey got his penicillium spores he was so busy stuffing down his coat - from a sub culture Fleming had sent to the previous director of Florey's Dunn Institute.
The Free World beyond Britain had lots of sub cultures of penicillium spores of the rare - right - type, even without Florey's belated act of charity.
In theory they didn't really need Fleming's spores, only his public article - but in practise, until 1943, they really did need his spores.
Examples of Fleming's spores were actually everywhere - some even better penicillium producers than his original un-mutated version as well.
But they could only be found by teams of researchers seeking hundreds of the right looking blue-green mold on walls and spoiled fruit, and then testing all for their possible anti-bacterial qualities.
Until miracle cures got rumoured about, no one in the world was willing to go to that much effort , just to test a troublesome possible antiseptic.
But by 1943, the miracle cure stories were out amongst the clinical doctors everywhere - and I do really mean everywhere.
Everywhere that Florey went, Egypt, Iran, Russia he had to endure local doctors thrusting excellent producing strains of penicillin molds in his face that they had found locally !
The Axis were just as quick off the mark - Japan got its strain by merely looking about locally.
And the clever Japanese correctly guessed - from one badly reproduced photo in an Egyptian picture magazine - just how best to produce the stuff !
The atomic bomb was effectively secret even if the US had proclaimed it was making one from the rooftops in 1942.
Uranium was everywhere - like penicillium spores - but a bomb from it takes the world's largest, most expensive, building ever built merely to get started on separating pure U-235 from the more abundant U-238.
And without 90% pure U-235, no working bomb. No nothing.
Tons and tons of scarce money, time and effort kept the A-Bomb an American secret, even from the British and Canadians , let alone the Axis and Neutrals.
But by late 1943, popular magazine articles cheekily showed how one could make penicillin at home, on a kitchen top, for about $5 in equipment and growth mediums.
One didn't even need to go out searching for those semi-rare penicillin-producing strains by then.
In a surprising - even shocking - total volt face, the NRRL's Coghill and Raper had released the top two strains of penicillium.
That's right, the top two strains that were then producing most of the Allies' military-bound penicillin - to the public American mold type collection in Washington where, as they told the readers of JAMA worldwide, "anyone" can get some at a "nominal charge".
!!!!!!!!
Didn't they know there was a war on ?
No word if Argentina's Washington DC based scientific attache quickly took a cab over, got some samples and sent them off to his friends in Germany.
Clearly, penicillin was never a viable secret military medical weapon - Florey and Richards were both , to put it kindly, completely deluded to ever think so.
Deluded by utopian visions of near-total purity.
Because unlike the Atomic Bomb and U-235, penicillin's starting material (the spores) were both common worldwide AND its production fully successful even in a highly impure (aka low tech) state.
This was what Fleming had discovered in 1928 but never acted upon - this was the key insight that Henry Dawson brought to the penicillin story, starting on October 16th 1940....
Tuesday, February 5, 2013
Wartime Penicillin's coke-addled Janus Month : March 1943
In March 1943 (midway through the war) , for the very first time in WWII, a part of wartime penicillin research that had been hitherto public was finally and effectively put under official government censorship : anything involving the chemistry of penicillin.
At the very same time, other (hitherto effectively secret) parts of the penicillin story were about to become globally publicized in official government propaganda !
"I am not making this up", as Canada's Liberal Party is wont to say.
The chemical nature of penicillin was about to become Top Secret and there was to be no more public articles by Howard Florey's or Henry Dawson's team, in journals like NATURE and SCIENCE, all about the chemical structure of penicillin to aid German or Japanese chemists on how to synthesize penicillin themselves.
But given the wide availability of all the previous chemistry structure-oriented articles in these two, the biggest of all general science journals in the world, the Axis might not need much further help.
Because back issues of these two journals were still easily available to the scientific diplomatic attaches of the many still-neutral nations in capital cities like London, Ottawa and Washington, the Axis chemists may not have needed to employ spies, to seek out the newest secret research .
But the Top Secret classification reflected a new found confidence at Merck, Oxford and the ORSD that the penicillin molecule had finally been cracked and the chemistry of the molecule was a commercial and possibly military secret well worth keeping.
Even Robert Coghill, the penicillin czar at the fermenatation-oriented NRRL labs, was about to turn his coat to the side of synthesis.
What better time then to hand the hated finicky biological approach to penicillin production to the War Production Board, (the WPB) ?
Who cared if the WPB and the normally-secretive US Army seemed determined to widely publicize , to Allied, Axis and neutral nation alike, just how good this new fangled penicillin really was for military medicine ?
Yes.
Because for the first time in the war, parts of penicillin other that its chemistry (such as its clinical miracle cures which had been hitherto in America effectively if unofficially censored) were going to become the focus of official government propaganda and broadcast to the heavens.
In an variant on "the first shall be last and the last first", what had been public was about to become secret and what had been secret was about to become public.
In January 1943, Karl Meyer, the chemist of Dawson's team, could still publish the team's latest best guess on the chemical formula for penicillin, but the team still couldn't discuss their results on treating patients since October 1940.
By January 1944, Dawson could publish his success with patients and penicillin to the world via JAMA, but later that same year, Meyer's harmless paper on biological products of penicillin written to be delivered at a conference, was forced to be withdrawn at the last minute, for fear he'd say something chemical and hence secret.
Bizarre but true ...... !
At the very same time, other (hitherto effectively secret) parts of the penicillin story were about to become globally publicized in official government propaganda !
"I am not making this up", as Canada's Liberal Party is wont to say.
The chemical nature of penicillin was about to become Top Secret and there was to be no more public articles by Howard Florey's or Henry Dawson's team, in journals like NATURE and SCIENCE, all about the chemical structure of penicillin to aid German or Japanese chemists on how to synthesize penicillin themselves.
But given the wide availability of all the previous chemistry structure-oriented articles in these two, the biggest of all general science journals in the world, the Axis might not need much further help.
Because back issues of these two journals were still easily available to the scientific diplomatic attaches of the many still-neutral nations in capital cities like London, Ottawa and Washington, the Axis chemists may not have needed to employ spies, to seek out the newest secret research .
But the Top Secret classification reflected a new found confidence at Merck, Oxford and the ORSD that the penicillin molecule had finally been cracked and the chemistry of the molecule was a commercial and possibly military secret well worth keeping.
Even Robert Coghill, the penicillin czar at the fermenatation-oriented NRRL labs, was about to turn his coat to the side of synthesis.
What better time then to hand the hated finicky biological approach to penicillin production to the War Production Board, (the WPB) ?
Who cared if the WPB and the normally-secretive US Army seemed determined to widely publicize , to Allied, Axis and neutral nation alike, just how good this new fangled penicillin really was for military medicine ?
Yes.
Because for the first time in the war, parts of penicillin other that its chemistry (such as its clinical miracle cures which had been hitherto in America effectively if unofficially censored) were going to become the focus of official government propaganda and broadcast to the heavens.
Janus month indeed.
In an variant on "the first shall be last and the last first", what had been public was about to become secret and what had been secret was about to become public.
In January 1943, Karl Meyer, the chemist of Dawson's team, could still publish the team's latest best guess on the chemical formula for penicillin, but the team still couldn't discuss their results on treating patients since October 1940.
By January 1944, Dawson could publish his success with patients and penicillin to the world via JAMA, but later that same year, Meyer's harmless paper on biological products of penicillin written to be delivered at a conference, was forced to be withdrawn at the last minute, for fear he'd say something chemical and hence secret.
Bizarre but true ...... !
Thursday, January 31, 2013
If wartime penicillin was a wah pedal ....
Imagine the Nobel prize winner for medicine , Baron Howard Florey, being pulled off his efforts to discover new antibiotics in the late 1940s by an impatient Leo Fender.
Leo pleads, "Howard,make me a wah pedal, and make it quick ; I need something unique for my new guitar and amp line".
Howard takes his time, and delivers the pedal years late. But it is beautiful finished and has a high fidelity electronic circuit that is so pure that it delivers vanishingly small amounts of harmonic distortion (albeit at the cost of an anemic output).
I can already hear guitar players going "Oh, goody !"
Luckily for humanity, Leo has also telepathed the spirit of penicillin pioneer Henry Dawson back to earth and given him the same assignment.
Early next morning, Henry has the job all done : a crude but workable bread-board design, with screamingly high distortion impurities, but with a low battery drain design and the effect level preset on 11 on a scale of one to ten (aka ("stun").
It is very basic looking , with just one big button, set in the very middle of the sturdy front panel of the wah pedal.
Henry's genius is that this button simply says one word : MORE !
And that my friends, is the essential kernel of the conflict between these two giants of wartime penicillin....
Leo pleads, "Howard,make me a wah pedal, and make it quick ; I need something unique for my new guitar and amp line".
Howard takes his time, and delivers the pedal years late. But it is beautiful finished and has a high fidelity electronic circuit that is so pure that it delivers vanishingly small amounts of harmonic distortion (albeit at the cost of an anemic output).
I can already hear guitar players going "Oh, goody !"
Luckily for humanity, Leo has also telepathed the spirit of penicillin pioneer Henry Dawson back to earth and given him the same assignment.
Early next morning, Henry has the job all done : a crude but workable bread-board design, with screamingly high distortion impurities, but with a low battery drain design and the effect level preset on 11 on a scale of one to ten (aka ("stun").
It is very basic looking , with just one big button, set in the very middle of the sturdy front panel of the wah pedal.
Henry's genius is that this button simply says one word : MORE !
And that my friends, is the essential kernel of the conflict between these two giants of wartime penicillin....
Wednesday, January 30, 2013
Fleming never saved Churchill, but Gladys Hobby saved Florey's sister when his own penicillin couldn't !
Howard Florey was never more sleazy than in his dealings with Henry Dawson's team, as he desperately fought to restore the family name that his father dis-honored, by trying to remain the sole "hero" of wartime penicillin.
Just try to imagine what an university ethics committee today might say about a professor using his main rival's unpublished paper, sent to him in secret by his close friend (the same government official who censored his rival's paper and forbade its release) to improve his own work that is about to be allowed to be freely published !
That is what full Professor Howard Florey and university vice president and full Professor A N Richards actually did to associate professor chemist Professor Karl Meyer of Dawson's team , in mid 1942.
(As they say, tenure is 'red in tooth and claw'.)
The multi-hatted Professor A Newton Richards was a Vice President of the University of Pennsylvania, head of the medical wing of the OSRD , chief consultant to Merck and one of Howard Florey's best friends.
Like Mayor Rob Ford, he also never met a conflict of interest he could resist.
(By contrast, when Norman Heatley met Meyer in January 1942, Heatley recorded that Meyer was willing to send his data to Florey, but Heatley boldly told his boss (Florey) he (Heatley) won't because it didn't seem right, not if Florey was about to publish and Meyer was forbidden to.)
However, Professor Richards was of a very different moral character and saw nothing wrong in sending Professor Meyer's embargoed chemical work on the structure of penicillin to his main academic rival, Professor Florey.
By contrast, Dawson bent over backwards to try and find a source of penicillin for Florey (even at places like Pfizer - a place Florey determinedly didn't want to visit), totally unaware of Florey's well known reputation in the UK for being an academic bush whacker and a magpie of other people's hard work.
Florey's real (if totally private) reason to come to America in 1941, was mainly to establish that he and Merck, not Dawson and Pfizer, was the real leader in the hunt for viable penicillin.
By late 1942, Florey felt sure that the dying Dawson and Pfizer (having joined Merck's cartel) was out of the race.
Sweet indeed then, when in August 1944, a sullen Howard Florey had to stand politely beside Dawson team member Gladys Hobby as she showed him the natural penicillin poring off the Pfizer lines, while Merck and Florey's team at Oxford had totally failed to produce any synthetic penicillin for the D Day beaches.
Florey had spurned both Pfizer and Glaxo, yet it was they who delivered most of the penicillin that landed on the Normandy beaches that day --- "the stone the builders rejected" indeed.
Asa series of letters in the Royal Society Archive reveal, in December 1952, Florey had to eat yet more humble pie, first begging and then thanking Hobby for sending her own latest antibiotic off to save the life of his sister (Hilda Gardner) in Australia when his own penicillin wouldn't work....
Just try to imagine what an university ethics committee today might say about a professor using his main rival's unpublished paper, sent to him in secret by his close friend (the same government official who censored his rival's paper and forbade its release) to improve his own work that is about to be allowed to be freely published !
That is what full Professor Howard Florey and university vice president and full Professor A N Richards actually did to associate professor chemist Professor Karl Meyer of Dawson's team , in mid 1942.
(As they say, tenure is 'red in tooth and claw'.)
The multi-hatted Professor A Newton Richards was a Vice President of the University of Pennsylvania, head of the medical wing of the OSRD , chief consultant to Merck and one of Howard Florey's best friends.
Like Mayor Rob Ford, he also never met a conflict of interest he could resist.
(By contrast, when Norman Heatley met Meyer in January 1942, Heatley recorded that Meyer was willing to send his data to Florey, but Heatley boldly told his boss (Florey) he (Heatley) won't because it didn't seem right, not if Florey was about to publish and Meyer was forbidden to.)
However, Professor Richards was of a very different moral character and saw nothing wrong in sending Professor Meyer's embargoed chemical work on the structure of penicillin to his main academic rival, Professor Florey.
By contrast, Dawson bent over backwards to try and find a source of penicillin for Florey (even at places like Pfizer - a place Florey determinedly didn't want to visit), totally unaware of Florey's well known reputation in the UK for being an academic bush whacker and a magpie of other people's hard work.
Florey's real (if totally private) reason to come to America in 1941, was mainly to establish that he and Merck, not Dawson and Pfizer, was the real leader in the hunt for viable penicillin.
By late 1942, Florey felt sure that the dying Dawson and Pfizer (having joined Merck's cartel) was out of the race.
Sweet indeed then, when in August 1944, a sullen Howard Florey had to stand politely beside Dawson team member Gladys Hobby as she showed him the natural penicillin poring off the Pfizer lines, while Merck and Florey's team at Oxford had totally failed to produce any synthetic penicillin for the D Day beaches.
Florey had spurned both Pfizer and Glaxo, yet it was they who delivered most of the penicillin that landed on the Normandy beaches that day --- "the stone the builders rejected" indeed.
Gladys Hobby saves Howard Florey's own sister -- when he couldn't
Asa series of letters in the Royal Society Archive reveal, in December 1952, Florey had to eat yet more humble pie, first begging and then thanking Hobby for sending her own latest antibiotic off to save the life of his sister (Hilda Gardner) in Australia when his own penicillin wouldn't work....
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.
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.....
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.....
Thursday, January 24, 2013
Nobel prize merely for concentrating penicillin into a SOLID for therapeutic use ?
Gloria T Sanders (in her 1986 book on amputations of the lower limbs) mentions in passing that Howard Florey was the first to concentrate penicillin into a solid, so it could finally be used in human therapy.
This has become a commonplace in recent years, as a Google search on "Florey" and "concentrated" will quickly reveal, replacing earlier claims that he was the first to "purify" penicillin.
But since the solid penicillin was in fact not a whit more stable than Fleming's original liquid penicillin, if both were properly stored, it offered no advantages to Fleming's wet stuff and a whole lot of disadvantages.
Florey's team had to do a great deal of expensive and labour-intensive chemical work to reduce 3 grams of watery penicillin (containing about 6 to 12 units of biological activity in total) to one milligram of solid penicillin containing about 2 to 4 units in total.
So now, instead of saving three dying patients, only one could be selected to live and the other two had to be triaged to die prematurely.
Remind me again how this was a therapeutic improvement !
And in addition, since life-saving penicillin had to be injected not swallowed, that dry milligram of penicillin had to be dissolved back into three grams of water, to put into the human body.
It seemed a long and wasteful effort, only to end up right back where you began.
The view that anything dried was inevitably better ,"more modern", than its fresh and juicy original was common in the era between the two world wars, particularly in Florey's Britain.
British cooking in the 1920s can be practically defined by the sudden availability year around of abundant and cheap dried fruits from all over the Empire.
Even today, Britain remain far and away the most avid consumers of packaged foods.
But it is not so in medicine that dry is invariably better than wet , along the road of progress.
WWII started with the military medical services of the Allies happily separating the plasma from the red cells of volunteer blood, throwing away the perfectly good and valuable red cells and then shipping the dried plasma to the combat-front to deal with fatal shock from massive wounds.
Later they realized that while the plasma did prevent immediate death from shock, a badly wounded serviceman who had lots of plasma but not enough red cells was truly over-stressing his already badly stressed heart and lungs needlessly, making survival still touch and go.
So a relatively minor administrative change (providing low tech disposable iceboxes and making liquid blood by plane transport a very top priority) allowed liquid blood to flow to the front-lines in the last year of the war - saving more lives than dry plasma could.
Concentration ,let me remind you, did not separate the tiny amounts ( ppm) of penicillin from the roughly 3% of solute solids (aka impurities) in the original gram of penicillin juice - it merely removed all the (sterile by definition) water.
But since those impurities were basically non-toxic, they were no more (and no less) harmful evaporated temporarily solid or remaining dissolved in water until they were injected.
Dignified, if alpha-male-ish, scientists do not going around saying my penis is longer than yours but they did going around saving my penicillin is purer than yours.
Which is to say, instead of concentrating penicillin purposelessly only to lose two thirds of it, they truly did purify it to a point of being between 15% to 90% pure, but at an even higher cost in terms of chemicals and labour - and penicillin - lost in the process.
But it did not save lives - it cost lives : hardly something those fine folks in Stockholm should be rewarding ....
This has become a commonplace in recent years, as a Google search on "Florey" and "concentrated" will quickly reveal, replacing earlier claims that he was the first to "purify" penicillin.
But since the solid penicillin was in fact not a whit more stable than Fleming's original liquid penicillin, if both were properly stored, it offered no advantages to Fleming's wet stuff and a whole lot of disadvantages.
Florey's team had to do a great deal of expensive and labour-intensive chemical work to reduce 3 grams of watery penicillin (containing about 6 to 12 units of biological activity in total) to one milligram of solid penicillin containing about 2 to 4 units in total.
So now, instead of saving three dying patients, only one could be selected to live and the other two had to be triaged to die prematurely.
Remind me again how this was a therapeutic improvement !
And in addition, since life-saving penicillin had to be injected not swallowed, that dry milligram of penicillin had to be dissolved back into three grams of water, to put into the human body.
It seemed a long and wasteful effort, only to end up right back where you began.
The view that anything dried was inevitably better ,"more modern", than its fresh and juicy original was common in the era between the two world wars, particularly in Florey's Britain.
British cooking in the 1920s can be practically defined by the sudden availability year around of abundant and cheap dried fruits from all over the Empire.
Even today, Britain remain far and away the most avid consumers of packaged foods.
But it is not so in medicine that dry is invariably better than wet , along the road of progress.
Unlike penicillin, WWII combat blood goes from dry back to wet ...
WWII started with the military medical services of the Allies happily separating the plasma from the red cells of volunteer blood, throwing away the perfectly good and valuable red cells and then shipping the dried plasma to the combat-front to deal with fatal shock from massive wounds.
Later they realized that while the plasma did prevent immediate death from shock, a badly wounded serviceman who had lots of plasma but not enough red cells was truly over-stressing his already badly stressed heart and lungs needlessly, making survival still touch and go.
So a relatively minor administrative change (providing low tech disposable iceboxes and making liquid blood by plane transport a very top priority) allowed liquid blood to flow to the front-lines in the last year of the war - saving more lives than dry plasma could.
Concentration ,let me remind you, did not separate the tiny amounts ( ppm) of penicillin from the roughly 3% of solute solids (aka impurities) in the original gram of penicillin juice - it merely removed all the (sterile by definition) water.
But since those impurities were basically non-toxic, they were no more (and no less) harmful evaporated temporarily solid or remaining dissolved in water until they were injected.
Dignified, if alpha-male-ish, scientists do not going around saying my penis is longer than yours but they did going around saving my penicillin is purer than yours.
Which is to say, instead of concentrating penicillin purposelessly only to lose two thirds of it, they truly did purify it to a point of being between 15% to 90% pure, but at an even higher cost in terms of chemicals and labour - and penicillin - lost in the process.
But it did not save lives - it cost lives : hardly something those fine folks in Stockholm should be rewarding ....
Wednesday, January 23, 2013
James Baxter's Pulitzer Prize winning nonsense about wartime penicillin
As part of OSRD's campaign to spin its considerable successes and many failures, William College president and historian James Phinney Baxter III was hired in mid war (1943) to assemble a bewitching mixture of hitherto-secret facts and sheer blarney, called "Scientists Against Time".
It sure fooled the 1947 Pulitzer Committee, but it shouldn't continue to fool us.
In mid 1943, reports of the consistent creation of crystal pure penicillin began to came in from various laboratories - the final necessary difficult perquisite to beginning the 'easy' chemical synthesis of penicillin.
In what appeared to be a very astute move (at the time!), the OSRD moved to hand off the Congressional blame for the wasting tens of millions of 1940s taxpayers dollars on a failed expansion of biological penicillin production to an inferior Washington bureaucratical competitor (the War Production Board's OPRD).
The OSRD wanted to focus on garnering in all the certain glory coming to the Washington agency that was seen as funding and running the program that led to the synthesis of cheap and abundant artificial penicillin.
But the OSRD lost its gamble.
Instead it was the lowly OPRD that won, in a highly dramatic and timely fashion just in time for D-Day, while high-and-mighty OSRD had to eat millions of taxpayers' dollars spent generating not one nickel of therapeutic synthetic penicillin.
Baxter's job, in the chapter devoted to the OSRD's penicillin efforts, was to spin these awkward facts otherwise.
He was helped by the failure of the underfunded OPRD not to have the money needed to pay for its own tame house historian.
Baxter's job was to convert the biological success of the latecomers OPRD into being just a minor part of the final success of the long time efforts of OSRD-funded chemists to "purify" penicillin.
He sought to tie together the "chemical" ( his words - page 342 of his book) success of in natural penicillin production) as somehow coming out of the 16 years wasted on the "chemical" synthesis of the antibiotic.
The chemical "Purification" of the "crude" mixture of biological penicillin and its biological impurities was to provide that intellectual bridge.
But in fact, the body could care less about purification - it does worry about toxicity, but regards neutral fillers and water as largely irrelevant.
Quite rightly, it only regards the absolute amounts of biological activity (measured in "Units") of soluble penicillin as being important to cure an infection.
It cares not at all about their original relative degree of dryness (concentration), the amount of neutral bulk filler that comes bundled with them, or the amount of water that penicillin comes dissolved in.
After all, the human body is between 50% to 75% water and it quickly dilutes all drugs to incredibly small concentrations.
Now just to remind readers, one gram of water (mass) is one cc (cm3) of water (cubic area) is one ml (volume) --- and a gram of penicillium juice holding 3% of dissolved solids isn't going to fundamentally change this formula much.
James Duhig got 400 to 800 units of biological activity from each one litre flask (containing 200 grams of penicillin liquid) that he grew in his Brisbane lab in 1943-1944, using the exact same strain of penicillium and the exact same low level of technology that Alexander Fleming had in 1928.
That is he got 2 to 4 units per ml/cc/ gm of penicillium medium, the exact same as Fleming got way back in the Fall of 1928.
Basically Duhig and Fleming got about one microgram of active penicillin per gram of water : one part per million, one ppm.
You don't have to be a rocket scientist to know that is not much of a ratio of useful to useless !
But even when Fleming diluted that 1 ppm in a lot more sterile water - down to the level of one part per billion -, a tiny drop of extremely diluted stuff could still kill deadly bacteria.
But Duhig didn't dilute his stuff any further. Instead he chilled his penicillin liquid, only running it through a filter to remove solid solids.
It still contained its 3% of soluble solids "impurities", along with its 97% pure water. It was still as 'crude' as the day it was born.
Then Dr Duhig injected that liquid straight into a woman's blood stream in 300 to 600 gram amounts (aka 300 to 600 ml/cc of solution). (A thousand or two units of biological activity per injection.)
And incredibly (considering that today we would use millions not thousands of units per injection) Duhig's crude penicillin pulled a dying woman almost literally out of her grave.
He finally did in remote Queensland Australia in 1943 what Alexander Fleming in 1928 London - and every single doctor in the world after him - criminally failed to do : use the original penicillin , entirely untouched by the hands of the chemists, to save lives.
But it is another Australian-born doctor, Howard Florey (originally from Adelaide) now operating out of Oxford University, who scientists and historians (including our Dr Baxter) give all the credit for making Fleming's crude "novelty-only" penicillin into a refined/purified life saver, in a famous experiment in May 1940.
But does he - and this famous "mouse" experiment - deserve that credit?
By Florey's own words, he doesn't think so.
Its all there in Florey's second penicillin article, "Further Observations on Penicillin" ,LANCET, August 1941.
(This incredibly detailed article should have been sufficient, in and of itself, for any competent hospital or multinational drug company anywhere in the world of WWII to make life saving penicillin --- provided they could get their hands on Fleming's strain of penicillium, or one like it.)
In this article, Florey does indicate that his March 1941 human therapeutic penicillin has 40 units per mg of powder (page 178).
But on the next page (page 179) he clearly indicates that the powder used in the May 1940 mouse experiment probably had less than 1/10 the biological activity of the current human therapeutic penicillin.
So that powder had 2 to 4 units per mg , compared to the 2 to 4 units per gram of original crude fluid.
That is , we have gone from having penicillin consisting of about one part per million of liquid to consisting one part per thousand of dry powder.
Since all the water is gone, what is in the other 999 parts of that milligram ? Yep, its the same 3% of soluble biological impurities that were in the original crude watery mixture of Fleming.
Florey has not purified his penicillin at all, merely concentrated it (that is merely removed its water ; we make orange or milk powder from their watery originals in the same way, by evaporation).
My essential point is that Fleming's 1928 mixture of natural penicillin and biological impurities was safe to inject, with or without its sterile water being removed.
(And remember, Florey had to put water back into his powder to get it into his patients ; if it was to go in as a slow IV drip, it could be as diluted as it was in the original brew, before all that expensive concentrating.)
That concentration process took not just an awful lot of human energy to perform ; it also destroyed two thirds of the available penicillin.
Concentrated penicillin didn't save more patients ; criminally it actually saved two thirds less.
By late 1942 - early 1943, biological improvements in growing penicillin now gave us raw penicillin brew that gave 40 units per cc of liquid.
The Russians, logically enough, felt there was no need to waste human energy and expensive scarce equipment merely to destroy two thirds of this life-saving liquid, just so they could falsely claim to "purify" it, aka 'concentrate' it.
The other Allies might well have followed their example and then we would have had no mid-war penicillin famine.
Life saving did not require purified penicillin - in fact, the wartime purification of penicillin tended to reduce the amount of penicillin of penicillin available for the dying in figures varying from two thirds to infinity.
Yes infinity : in the Spring of 1943 Glaxo was - briefly - the world's largest penicillin producer.
Incredibly, in the middle of a bloody war, none of that penicillin went to save human lives. It all went to the Glaxo chemists to destroy, trying to get it to go into crystal so they could synthesis it, analogue it and profitably patent it.
Purification, inessential to life-saving, was crucial to the efforts to synthesis penicillin.
Enough penicillin to save millions would have come years earlier if universities and drug companies had released their chemists to the Draft Boards and hired mycologists instead.
But Baxter doesn't play it that way.
Florey had merely evaporated Fleming's penicillin and had thus obtained penicillin that was relatively 1000 times stronger than Fleming.
However, in absolute terms of therapeutic penicillin per flask of penicillin brew, it was actually three times less strong (and remember our bodies and their germs only care about absolute amounts, not relative amounts.)
But Baxter (who wasn't at the experiment) deliberately ignores Florey's own words (and Florey was at the experiment) to confidently and falsely claim that the mouse experiment penicillin was 3% pure.
Actually it was .3% pure , as Florey himself admitted in 1941,the same as Fleming's 1928 crude mixture.
Fleming deserves a lot of credit for making penicillin available - but also a lot of blame as well, when he failed to confirm his failed micro experiment on the possible systemic use of his crude penicillin - by trying it again on a variety of animals and humans.
Florey, similarly, deserved much credit for pushing penicillin to the front of scientific attention - but also a lot of blame for his obsessive need to put make purified crystal penicillin for chemical synthesis.
Worse, he mis-used his scientific authority to actively brow-beated many other decent doctors into stopping their production of "good enough" penicillin, merely to try to save lives in the middle of a savage war.
If they saved lives with crude penicillin, he saw his sole claim to scientific fame disappearing.
Florey readily admitted that he wasn't the first to discover penicillin (Fleming) and tried not to admit that he was not the first to put it into a patient (Dawson) ,but he wanted very much to claim that he was the first to purify it, so it could be injected into humans.
Duhig would dismiss that claim.
As would Dawson, who was at great pains (in his May 1941 article on penicillin) to publicly emphasize that his first human injections were taken from crude, concentrated "not purified, yet non-toxic" penicillin.
And so should have Dr Baxter......
It sure fooled the 1947 Pulitzer Committee, but it shouldn't continue to fool us.
In mid 1943, reports of the consistent creation of crystal pure penicillin began to came in from various laboratories - the final necessary difficult perquisite to beginning the 'easy' chemical synthesis of penicillin.
In what appeared to be a very astute move (at the time!), the OSRD moved to hand off the Congressional blame for the wasting tens of millions of 1940s taxpayers dollars on a failed expansion of biological penicillin production to an inferior Washington bureaucratical competitor (the War Production Board's OPRD).
The OSRD wanted to focus on garnering in all the certain glory coming to the Washington agency that was seen as funding and running the program that led to the synthesis of cheap and abundant artificial penicillin.
But the OSRD lost its gamble.
Instead it was the lowly OPRD that won, in a highly dramatic and timely fashion just in time for D-Day, while high-and-mighty OSRD had to eat millions of taxpayers' dollars spent generating not one nickel of therapeutic synthetic penicillin.
Baxter's job, in the chapter devoted to the OSRD's penicillin efforts, was to spin these awkward facts otherwise.
He was helped by the failure of the underfunded OPRD not to have the money needed to pay for its own tame house historian.
Baxter's job was to convert the biological success of the latecomers OPRD into being just a minor part of the final success of the long time efforts of OSRD-funded chemists to "purify" penicillin.
He sought to tie together the "chemical" ( his words - page 342 of his book) success of in natural penicillin production) as somehow coming out of the 16 years wasted on the "chemical" synthesis of the antibiotic.
The chemical "Purification" of the "crude" mixture of biological penicillin and its biological impurities was to provide that intellectual bridge.
But in fact, the body could care less about purification - it does worry about toxicity, but regards neutral fillers and water as largely irrelevant.
Quite rightly, it only regards the absolute amounts of biological activity (measured in "Units") of soluble penicillin as being important to cure an infection.
It cares not at all about their original relative degree of dryness (concentration), the amount of neutral bulk filler that comes bundled with them, or the amount of water that penicillin comes dissolved in.
After all, the human body is between 50% to 75% water and it quickly dilutes all drugs to incredibly small concentrations.
Now just to remind readers, one gram of water (mass) is one cc (cm3) of water (cubic area) is one ml (volume) --- and a gram of penicillium juice holding 3% of dissolved solids isn't going to fundamentally change this formula much.
James Duhig got 400 to 800 units of biological activity from each one litre flask (containing 200 grams of penicillin liquid) that he grew in his Brisbane lab in 1943-1944, using the exact same strain of penicillium and the exact same low level of technology that Alexander Fleming had in 1928.
That is he got 2 to 4 units per ml/cc/ gm of penicillium medium, the exact same as Fleming got way back in the Fall of 1928.
Basically Duhig and Fleming got about one microgram of active penicillin per gram of water : one part per million, one ppm.
You don't have to be a rocket scientist to know that is not much of a ratio of useful to useless !
But even when Fleming diluted that 1 ppm in a lot more sterile water - down to the level of one part per billion -, a tiny drop of extremely diluted stuff could still kill deadly bacteria.
But Duhig didn't dilute his stuff any further. Instead he chilled his penicillin liquid, only running it through a filter to remove solid solids.
It still contained its 3% of soluble solids "impurities", along with its 97% pure water. It was still as 'crude' as the day it was born.
Then Dr Duhig injected that liquid straight into a woman's blood stream in 300 to 600 gram amounts (aka 300 to 600 ml/cc of solution). (A thousand or two units of biological activity per injection.)
And incredibly (considering that today we would use millions not thousands of units per injection) Duhig's crude penicillin pulled a dying woman almost literally out of her grave.
He finally did in remote Queensland Australia in 1943 what Alexander Fleming in 1928 London - and every single doctor in the world after him - criminally failed to do : use the original penicillin , entirely untouched by the hands of the chemists, to save lives.
But it is another Australian-born doctor, Howard Florey (originally from Adelaide) now operating out of Oxford University, who scientists and historians (including our Dr Baxter) give all the credit for making Fleming's crude "novelty-only" penicillin into a refined/purified life saver, in a famous experiment in May 1940.
But does he - and this famous "mouse" experiment - deserve that credit?
By Florey's own words, he doesn't think so.
And incredibly, Baxter had Florey's actual words in front of him, when he wrote his own account just after the war's end.
Its all there in Florey's second penicillin article, "Further Observations on Penicillin" ,LANCET, August 1941.
(This incredibly detailed article should have been sufficient, in and of itself, for any competent hospital or multinational drug company anywhere in the world of WWII to make life saving penicillin --- provided they could get their hands on Fleming's strain of penicillium, or one like it.)
In this article, Florey does indicate that his March 1941 human therapeutic penicillin has 40 units per mg of powder (page 178).
But on the next page (page 179) he clearly indicates that the powder used in the May 1940 mouse experiment probably had less than 1/10 the biological activity of the current human therapeutic penicillin.
So that powder had 2 to 4 units per mg , compared to the 2 to 4 units per gram of original crude fluid.
That is , we have gone from having penicillin consisting of about one part per million of liquid to consisting one part per thousand of dry powder.
Since all the water is gone, what is in the other 999 parts of that milligram ? Yep, its the same 3% of soluble biological impurities that were in the original crude watery mixture of Fleming.
Florey has not purified his penicillin at all, merely concentrated it (that is merely removed its water ; we make orange or milk powder from their watery originals in the same way, by evaporation).
My essential point is that Fleming's 1928 mixture of natural penicillin and biological impurities was safe to inject, with or without its sterile water being removed.
(And remember, Florey had to put water back into his powder to get it into his patients ; if it was to go in as a slow IV drip, it could be as diluted as it was in the original brew, before all that expensive concentrating.)
That concentration process took not just an awful lot of human energy to perform ; it also destroyed two thirds of the available penicillin.
Concentrated penicillin didn't save more patients ; criminally it actually saved two thirds less.
By late 1942 - early 1943, biological improvements in growing penicillin now gave us raw penicillin brew that gave 40 units per cc of liquid.
The Russians, logically enough, felt there was no need to waste human energy and expensive scarce equipment merely to destroy two thirds of this life-saving liquid, just so they could falsely claim to "purify" it, aka 'concentrate' it.
The other Allies might well have followed their example and then we would have had no mid-war penicillin famine.
Life saving did not require purified penicillin - in fact, the wartime purification of penicillin tended to reduce the amount of penicillin of penicillin available for the dying in figures varying from two thirds to infinity.
Yes infinity : in the Spring of 1943 Glaxo was - briefly - the world's largest penicillin producer.
Incredibly, in the middle of a bloody war, none of that penicillin went to save human lives. It all went to the Glaxo chemists to destroy, trying to get it to go into crystal so they could synthesis it, analogue it and profitably patent it.
Purification, inessential to life-saving, was crucial to the efforts to synthesis penicillin.
Enough penicillin to save millions would have come years earlier if universities and drug companies had released their chemists to the Draft Boards and hired mycologists instead.
But Baxter doesn't play it that way.
Florey had merely evaporated Fleming's penicillin and had thus obtained penicillin that was relatively 1000 times stronger than Fleming.
However, in absolute terms of therapeutic penicillin per flask of penicillin brew, it was actually three times less strong (and remember our bodies and their germs only care about absolute amounts, not relative amounts.)
But Baxter (who wasn't at the experiment) deliberately ignores Florey's own words (and Florey was at the experiment) to confidently and falsely claim that the mouse experiment penicillin was 3% pure.
Actually it was .3% pure , as Florey himself admitted in 1941,the same as Fleming's 1928 crude mixture.
Fleming deserves a lot of credit for making penicillin available - but also a lot of blame as well, when he failed to confirm his failed micro experiment on the possible systemic use of his crude penicillin - by trying it again on a variety of animals and humans.
Florey, similarly, deserved much credit for pushing penicillin to the front of scientific attention - but also a lot of blame for his obsessive need to put make purified crystal penicillin for chemical synthesis.
Worse, he mis-used his scientific authority to actively brow-beated many other decent doctors into stopping their production of "good enough" penicillin, merely to try to save lives in the middle of a savage war.
If they saved lives with crude penicillin, he saw his sole claim to scientific fame disappearing.
Florey readily admitted that he wasn't the first to discover penicillin (Fleming) and tried not to admit that he was not the first to put it into a patient (Dawson) ,but he wanted very much to claim that he was the first to purify it, so it could be injected into humans.
Duhig would dismiss that claim.
As would Dawson, who was at great pains (in his May 1941 article on penicillin) to publicly emphasize that his first human injections were taken from crude, concentrated "not purified, yet non-toxic" penicillin.
And so should have Dr Baxter......
Monday, January 21, 2013
Vitamin C pills vs oranges: a metaphor for the dueling penicillin of Aussie docs, Florey and Duhig
A nice big fresh juicy orange and a tiny white pill can both have the exact same amount of vitamin c in them : about 100 mg , just above the recommended daily intake of the vitamin for a adult.
The synthetic vitamin c pill (first invented in the 1930s) is of course supposedly pure, but actually consists mostly of "harmless" filler . It is usually taken with a small glass of water.
The orange was - in the eyes of the Modernist 1930s - an impure source of vitamin c. The orange consisted mostly of harmless filler (pulp fibre and a great taste) and about the same amount of water as needed to fill a small glass.
Despite being "impure", a whole (100mg) orange a day would actually be more healthy for you than taking half (50 mg) of a "pure" pill every day.
All the body craves is its fix of 100 mg of the "C" a day , not whether human minds consider that vitamin c to be pure or impure.
Unless the vitamin c is bound to something that renders it biologically inactive, the body considers it as fully pure and effective and dismisses what sort of filler and water it chanced to come bundled with.
It was exactly same with the human bodies our two wartime Aussie doctors Duhig and Florey had taken a sacred oath to protect.
From twelve one liter flasks growing penicillium fungus in his Brisbane hospital lab , in late 1943, Dr James Dunhig got 2500 cc of penicillin juice, averaging at best five biologically active units of penicillin per cc , or about 12,500 units in total.
This crude, impure, liquid was strained but not processed - only kept chilled.
It was almost immediately put into a 42 year dying mother, a patient of Dr Geaney, in various sizes of IV doses (some as large at 600 cc) over a number of days -- and yet this impure medicine saved her life and home she went to her grateful and astonished family.
Dr Florey,originally from Adelaide, from the same 2500 cc of starting penicillin juice grown in his Oxford university lab in late 1943, also started off with 12,500 units of crude, unprocessed, penicillin.
But he chose to refine it over and over and over and over again, losing and destroying most of the penicillin in the long process.
Finally he ended up with a very little pile of relatively pure powder : one tiny mg of dried penicillin, assaying about 1250 units of biological activity.
But you can't inject dry powder - no matter how pure - into a patient, so some of that oh so expensively extracted water had to be mixed again with the dry penicillin, if it was to be usefully injected in a dying patient.
But it wasn't - it was given instead to chemists, to be deliberately destroyed , all to make a more accurate assessment of penicillin's structure by examining its various sub components.
Then (in the middle of a deadly world war) public domain penicillin could finally - profitably - be synthetically analogued and patented.
Just as well that Florey wasn't moved to waste any of his preciously pure penicillin on a dying woman, because 1250 units of penicillin , no matter how pure, couldn't save most dying adults but 12,500 units of impure penicillin sometimes did.
It is as I say, a classic example of the old saying that 'an whole impure orange a day will keep the doctor away, but half a pill of pure little white pill will not' ...
The synthetic vitamin c pill (first invented in the 1930s) is of course supposedly pure, but actually consists mostly of "harmless" filler . It is usually taken with a small glass of water.
The orange was - in the eyes of the Modernist 1930s - an impure source of vitamin c. The orange consisted mostly of harmless filler (pulp fibre and a great taste) and about the same amount of water as needed to fill a small glass.
Despite being "impure", a whole (100mg) orange a day would actually be more healthy for you than taking half (50 mg) of a "pure" pill every day.
All the body craves is its fix of 100 mg of the "C" a day , not whether human minds consider that vitamin c to be pure or impure.
Unless the vitamin c is bound to something that renders it biologically inactive, the body considers it as fully pure and effective and dismisses what sort of filler and water it chanced to come bundled with.
It was exactly same with the human bodies our two wartime Aussie doctors Duhig and Florey had taken a sacred oath to protect.
Heroic penicillin at its best ...
From twelve one liter flasks growing penicillium fungus in his Brisbane hospital lab , in late 1943, Dr James Dunhig got 2500 cc of penicillin juice, averaging at best five biologically active units of penicillin per cc , or about 12,500 units in total.
This crude, impure, liquid was strained but not processed - only kept chilled.
It was almost immediately put into a 42 year dying mother, a patient of Dr Geaney, in various sizes of IV doses (some as large at 600 cc) over a number of days -- and yet this impure medicine saved her life and home she went to her grateful and astonished family.
Dr Florey,originally from Adelaide, from the same 2500 cc of starting penicillin juice grown in his Oxford university lab in late 1943, also started off with 12,500 units of crude, unprocessed, penicillin.
But he chose to refine it over and over and over and over again, losing and destroying most of the penicillin in the long process.
Finally he ended up with a very little pile of relatively pure powder : one tiny mg of dried penicillin, assaying about 1250 units of biological activity.
But you can't inject dry powder - no matter how pure - into a patient, so some of that oh so expensively extracted water had to be mixed again with the dry penicillin, if it was to be usefully injected in a dying patient.
Non-heroic penicillin, at its worst ...
But it wasn't - it was given instead to chemists, to be deliberately destroyed , all to make a more accurate assessment of penicillin's structure by examining its various sub components.
Then (in the middle of a deadly world war) public domain penicillin could finally - profitably - be synthetically analogued and patented.
Just as well that Florey wasn't moved to waste any of his preciously pure penicillin on a dying woman, because 1250 units of penicillin , no matter how pure, couldn't save most dying adults but 12,500 units of impure penicillin sometimes did.
It is as I say, a classic example of the old saying that 'an whole impure orange a day will keep the doctor away, but half a pill of pure little white pill will not' ...
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