Re-reading Hotchkiss and Dubos's various 1940 era papers on their quick "small science" success at extracting, crystallizing and analyzing high yields of gramicidin, an early (unfortunately deadly) antibiotic exuded by microbes, one is struck by the apparent ease of the whole project.
By contrast, penicillin, another antibiotic exuded by another microbe, was extremely difficult to successfully handle - in every single aspect of it --- from growing the microbe to the ultimate failure to commercially synthesize penicillin itself.
This despite a multi-nation effort that eventually rivalled the Manhattan atomic Project for "Big Science" funding and skilled manpower levels.
But biochemist Dr Karl Meyer was not to know this in September 1940 when he recruited his co-worker, bacteriologist Dr Martin Henry Dawson, to "just" grow a little bit of the fungus microbe, for a "little while".
A seemingly small request, for a short period of time, that cost Dawson his life but also ended up changing our entire world, for the better, forever.
Showing posts with label karl meyer. Show all posts
Showing posts with label karl meyer. Show all posts
Saturday, September 26, 2015
Saturday, July 18, 2015
Dawson was, in fact, the THIRD (reluctant but duty bound) leader of the tiny Manhattan penicillin Project
In September 1940, fearing the internment of German Jewish refugee scientists - even possibly those with recent American citizenship - was bound to follow the panicky British Empire decision to most of its German refugees from Hitler, biochemist Dr Karl Meyer became the first leader of what was to become the four year long Manhattan penicillin Project.
Dr Meyer was determined to find some sort of way to prove to the American war machine that he was too valuable to intern.
And finally purifying a drug that could kill the few militarily important pathogen bacteria that the hot new Sulfa drugs could not, would do just that.
Purifying a natural substance is sometimes by far the most difficult step on the road to then synthetizing and patenting it.
Any clinical testing could wait until the substance was safely purified.
For now, what Meyer and his assistant Eleanor Chaffee needed most from their two microbiologists (doctors Dawson and Hobby) was their highly practised skills in growing microbes.
And then later, their other well honed skill in measuring the bacteria-killing powers of any substances Meyer's chemical skills threw up.
But all that changed in early October 1940, when new patient A. (Leroy) Alston heard of the project and in a very real sense, hijacked the leadership of the project.
Leroy was a young black man from Harlem, dying of then invariably fatal SBE (subacute bacterial endocarditis) the disease that made Rheumatic Fever the leading killer of young people until the 1960s.
Significantly most of those deaths occurred among the poor, immigrants and minorities.
And Leroy didn't like the idea of accepting a SBE death as inevitable, just the assigned fate for America's poor and minorities.
Didn't like it at all - not one bit.
And Leroy was just the sort of person - dying or not - to be able to make significant waves.
He was raised by a poor widow in Harlem who sometimes got waitressing work - but Leroy held down a middle class job at a white commercial insurance firm all through the Dirty Thirties.
A first class athlete in many different sports, he also founded and ran a pioneering track and field club made up of members from the Harlem's black working class.
That club, Harlem's Mercury Athletic Club, competed successfully, not just against the nation's top black (middle class) universities but also against the top white teams as well.
To Leroy, it was always much more than just athletic success - he self consciously sought out obstacles to the ability for blacks to compete on an equal terms with whites - and then challenged them.
In a word, Leroy was a fervent Civil Rights activist - from the Thirties era.
The reason for his unexpected success is best explained by going back to the High Schools that all of us have experienced.
The Jocks cum Preppies in my High School (and probably in your school as well) were indeed mostly made up of kids from the community's best off families - but by no means exclusively.
What they really held in common was not income or race but a winning combination of physical and social agility - they moved gracefully and persuaded gracefully.
By contrast I knew many kids in my high school, from the top families, with all the family resources in the world, were seemingly just born shy, awkward and socially inept.
Leroy was just one of High School Life's natural born leaders and orators.
And in this particular case, this natural born leader had an audience of just one person to persuade : Dr M (Henry) Dawson, senior of the two microbiologists on Meyer's tiny four person team.
Dawson was also the only member with clinical (ward) privileges - and at a relatively high level too.
He was the only one on the team with both the legal right and the practical ability within the hospital culture to inject new untested un-purified medicine to a patient without his superiors putting up (too) much of a fuss.
Even in the most research oriented teaching hospitals, the frontline ward doctor directing patient care stands far higher in the informal hierarchy than does the most senior of the supporting staff, such as the microbiologists and biochemists back in the labs.
And Dawson had just been elevated to associate attending physician status, with an entire admission ward under his direct control and yet he had never really exercised his new powers so far.
Leroy couldn't help noticing all the recent publicity and fundraising dollars devoted to Polio, which killed far less than did Rheumatic Fever/SBE, but affected predominantly white kids from the hyper-clean and spacious suburbs rather than ethnic minorities crowded into inner city tenements.
Rheumatic Fever, by contrast, by 1940 was getting far less attention and funding than had been traditionally the case.
This made him angry and as it happened, it made Dawson even angrier.
Dawson had long seen a long slow shift away from charity to self help cum narrow self interest in the world generally and his belief was well supported by the facts.
The case of polio was particularly instructive.
Usually the March of Dimes is seen as an example of progress in human affairs : the (usually middle class) families of patients with a particular disease banding together to act as a advocacy and fundraising group for their relatives's disease.
But in an earlier age, middle class people donated money freely to help people in need who they didn't even know - this sort of selfless (agape) giving is the true definition of charity - not something you do to help your nearest and dearest or to get a tax deduction.
Hospitals - like Columbia Presbyterian where Dawson worked - had once freely treated those in most need of help with the least funds to pay for it.
Now it only treated the poor if their cases were unique enough to teach the (mostly middle class) medical students well enough to ensure them of a lifetime high income and higher status.
Similarly nations had once went to war - heedless of the cost - to battle to defend the rights of the smallest,weakest nations like Belgium to survive.
Now nations stood silently, bystanders, as Belgium and other small nations got gobbled up, saying it wasn't in their nation's self interest to intervene.
And America's medical schools, like Columbia Presbyterian, in that Fall of 1940, were moving away from their increasingly weak efforts towards Social Medicine (medical research aiding the weakest members of society, regardless of their ability to pay).
Instead they were moving towards War Medicine (medical research oriented to aiding the most fit members in society - her soldiers.)
But Dawson's anger - though in keeping with his character he usually kept it carefully reined in and undercover - was also directed at his colleagues for dismissing his research into the ability of microbes to do many things that the most advanced human civilizations were incapable of.
Meyer in a sense was partially a mouthpiece for such conventional beliefs.
The idea that penicillin was not safe to inject into humans until it was purified by humans was hardly his alone - it was universal in the worldwide medical community since 1928.
But Dawson began to reason that the fungus had probably been making penicillin for hundreds of millions of years and had probably got it down to a science.
After all, he probably reminded Meyer, they already successfully made penicillin at normal atmospheric pressures and normal temperatures and without strong expensive toxic reagents - not something Meyer, even if he was to become totally successful, could ever likely claim.
Dawson had two hands - in his quiet passively aggressive way , on a day when no bosses were around - Draft Registration Day October 16 1940, he could give the world two fingers.
Reluctantly, quietly but firmly, Dawson became the third leader of the project.
On that day, Dawson would give the world's first ever penicillin injections, ushering the Age of Antibiotics.
And do so by using (a) a medicine made by conventional evolutionary biology's under-estimated underdogs (tiny penicillium cells) to aid (b) society's under-estimated underdogs - Jewish and black youths from NYC's working class ....
Dr Meyer was determined to find some sort of way to prove to the American war machine that he was too valuable to intern.
And finally purifying a drug that could kill the few militarily important pathogen bacteria that the hot new Sulfa drugs could not, would do just that.
Purifying a natural substance is sometimes by far the most difficult step on the road to then synthetizing and patenting it.
Any clinical testing could wait until the substance was safely purified.
For now, what Meyer and his assistant Eleanor Chaffee needed most from their two microbiologists (doctors Dawson and Hobby) was their highly practised skills in growing microbes.
And then later, their other well honed skill in measuring the bacteria-killing powers of any substances Meyer's chemical skills threw up.
But all that changed in early October 1940, when new patient A. (Leroy) Alston heard of the project and in a very real sense, hijacked the leadership of the project.
Leroy was a young black man from Harlem, dying of then invariably fatal SBE (subacute bacterial endocarditis) the disease that made Rheumatic Fever the leading killer of young people until the 1960s.
Significantly most of those deaths occurred among the poor, immigrants and minorities.
And Leroy didn't like the idea of accepting a SBE death as inevitable, just the assigned fate for America's poor and minorities.
Didn't like it at all - not one bit.
And Leroy was just the sort of person - dying or not - to be able to make significant waves.
He was raised by a poor widow in Harlem who sometimes got waitressing work - but Leroy held down a middle class job at a white commercial insurance firm all through the Dirty Thirties.
A first class athlete in many different sports, he also founded and ran a pioneering track and field club made up of members from the Harlem's black working class.
That club, Harlem's Mercury Athletic Club, competed successfully, not just against the nation's top black (middle class) universities but also against the top white teams as well.
To Leroy, it was always much more than just athletic success - he self consciously sought out obstacles to the ability for blacks to compete on an equal terms with whites - and then challenged them.
In a word, Leroy was a fervent Civil Rights activist - from the Thirties era.
The reason for his unexpected success is best explained by going back to the High Schools that all of us have experienced.
The Jocks cum Preppies in my High School (and probably in your school as well) were indeed mostly made up of kids from the community's best off families - but by no means exclusively.
What they really held in common was not income or race but a winning combination of physical and social agility - they moved gracefully and persuaded gracefully.
By contrast I knew many kids in my high school, from the top families, with all the family resources in the world, were seemingly just born shy, awkward and socially inept.
Leroy was just one of High School Life's natural born leaders and orators.
And in this particular case, this natural born leader had an audience of just one person to persuade : Dr M (Henry) Dawson, senior of the two microbiologists on Meyer's tiny four person team.
Dawson was also the only member with clinical (ward) privileges - and at a relatively high level too.
He was the only one on the team with both the legal right and the practical ability within the hospital culture to inject new untested un-purified medicine to a patient without his superiors putting up (too) much of a fuss.
Even in the most research oriented teaching hospitals, the frontline ward doctor directing patient care stands far higher in the informal hierarchy than does the most senior of the supporting staff, such as the microbiologists and biochemists back in the labs.
And Dawson had just been elevated to associate attending physician status, with an entire admission ward under his direct control and yet he had never really exercised his new powers so far.
Leroy couldn't help noticing all the recent publicity and fundraising dollars devoted to Polio, which killed far less than did Rheumatic Fever/SBE, but affected predominantly white kids from the hyper-clean and spacious suburbs rather than ethnic minorities crowded into inner city tenements.
Rheumatic Fever, by contrast, by 1940 was getting far less attention and funding than had been traditionally the case.
This made him angry and as it happened, it made Dawson even angrier.
Dawson had long seen a long slow shift away from charity to self help cum narrow self interest in the world generally and his belief was well supported by the facts.
The case of polio was particularly instructive.
Usually the March of Dimes is seen as an example of progress in human affairs : the (usually middle class) families of patients with a particular disease banding together to act as a advocacy and fundraising group for their relatives's disease.
But in an earlier age, middle class people donated money freely to help people in need who they didn't even know - this sort of selfless (agape) giving is the true definition of charity - not something you do to help your nearest and dearest or to get a tax deduction.
Hospitals - like Columbia Presbyterian where Dawson worked - had once freely treated those in most need of help with the least funds to pay for it.
Now it only treated the poor if their cases were unique enough to teach the (mostly middle class) medical students well enough to ensure them of a lifetime high income and higher status.
Similarly nations had once went to war - heedless of the cost - to battle to defend the rights of the smallest,weakest nations like Belgium to survive.
Now nations stood silently, bystanders, as Belgium and other small nations got gobbled up, saying it wasn't in their nation's self interest to intervene.
And America's medical schools, like Columbia Presbyterian, in that Fall of 1940, were moving away from their increasingly weak efforts towards Social Medicine (medical research aiding the weakest members of society, regardless of their ability to pay).
Instead they were moving towards War Medicine (medical research oriented to aiding the most fit members in society - her soldiers.)
But Dawson's anger - though in keeping with his character he usually kept it carefully reined in and undercover - was also directed at his colleagues for dismissing his research into the ability of microbes to do many things that the most advanced human civilizations were incapable of.
Meyer in a sense was partially a mouthpiece for such conventional beliefs.
The idea that penicillin was not safe to inject into humans until it was purified by humans was hardly his alone - it was universal in the worldwide medical community since 1928.
But Dawson began to reason that the fungus had probably been making penicillin for hundreds of millions of years and had probably got it down to a science.
After all, he probably reminded Meyer, they already successfully made penicillin at normal atmospheric pressures and normal temperatures and without strong expensive toxic reagents - not something Meyer, even if he was to become totally successful, could ever likely claim.
Dawson had two hands - in his quiet passively aggressive way , on a day when no bosses were around - Draft Registration Day October 16 1940, he could give the world two fingers.
Reluctantly, quietly but firmly, Dawson became the third leader of the project.
On that day, Dawson would give the world's first ever penicillin injections, ushering the Age of Antibiotics.
And do so by using (a) a medicine made by conventional evolutionary biology's under-estimated underdogs (tiny penicillium cells) to aid (b) society's under-estimated underdogs - Jewish and black youths from NYC's working class ....
Tuesday, June 23, 2015
(Synthetic) Penicillin - (NOT) meeting the Challenge : by Gladys Hobby (co-worker Karl Meyer)
It is a real pity that biochemist Karl Meyer left the writing of a real insider's account of wartime penicillin to his microbiologist co-worker Gladys Hobby.
Because Hobby's book "Penicillin : Meeting the Challenge", one or two gentle digs aside, is decidedly all moral uplift and hands across the water, marking her as "The Pollyanna of Penicillin".
Hobby's book sometimes is more fascinating for what she chooses to leave out than what she puts in it --- and yet she added a great deal of rare, even unique, information.
Meyer only really made one "for publication" comment about his part in wartime penicillin but it was frank and astringent.
It makes a reader wish he had said more : much, much more.
The major reason he didn't was because Meyer knew his role in saving the lives of thousands of SBEs and jumpstarting the fabulous success of native penicillin was all very well, but he was a biochemist damn it and his original goal was to synthesize native penicillin and replace it - not guide it up to the winner's podium.
Meyer had failed, partly because all chemists in the world also failed at this synthesis task --- and partly because he was treated very unfairly by his more powerful scientific competitors - and who wants to research and write a long book about your successful life's one big failure ?
By the time Meyer felt free to make even those few comments, for a book published in 1981, he was over eighty and the key penicillin players had almost all died.
In particular, Ernst Chain had just died a few months earlier.
Inspired by the death of Chain's boss, Howard Florey, in 1968, the first truly multi-continent account of wartime penicillin had come out in 1973, researched and written by Australian journalist and author Leonard Bickel.
Bickel did enough interviewing of minor front line participants still alive to uncover many fascinating, important but unreported/un-Pollyanna aspects of the saga.
His "Rise up to Life" included information from Gladys Hobby that first brought to those interested in the history of penicillin the forgotten efforts of Dr Martin Henry Dawson.
She said Dawson had pushed the North American development of early penicillin in an ultimately successful attempt to cure then invariably fatal SBE , the endocarditis that made Rheumatic Fever the leading killer of school age kids for half a century, a disease she said he had long made his personal crusade.
None of this was true - and she half knew that to be so.
I have found no evidence what so ever that Dawson ever mentioned SBE at any of the many scientific meetings he attended or that he wrote articles on it or did research into it.
And Hobby was his closest co-worker for ten years : she too had said, written and done nothing on SBE.
So Dawson had done nothing on SBE --- least not before October 1940, when the penicillin project at his hospital had already been underway for 5 weeks.
Hobby freely admits that she herself was away on vacation when the project began and she returned after several hectic weeks into the effort - so she could only know of the project's origins from what Meyer, Chaffee and Dawson told her.
The agreed plan, by the time she arrived, was that the native penicillin would be grown mostly by Hobby.
Then after being purified and its chemical structure figured out, it would be synthesized artificially, all this mostly done by Meyer and Chaffee, tasks expected to be completed sometime early in the New Year.
Then, and only then, would clinician Henry Dawson reach centre stage - injecting the synthetic penicillin into patients whose care he controlled as the sole attending physician among the small four person team.
A few days before Draft Registration Day, October 16th 1940, Dawson suddenly decided to put a very little of the very weak and very impure native penicillin into two patients with SBE, a disease whose cure, virtually all doctors agreed, would require lots of medication every day for weeks and weeks on end.
Dawson's tiny injections might raise the dying pair's morale but could have had no direct physical impact on their disease.
And it rather upended the team's agreed upon project protocol.
As that chemically-oriented protocol suggests, Meyer the biochemist had actually started the project.
But he waited a half century, till just after the death of Ernst Chain, to say exactly why he had.
In 1980, Meyer was interviewed by a young endocarditis researcher, Australian born Dr David T Durack, who was writing an article on the early history of the conquest of endocarditis by antibiotics for a book, edited by Allan Bisno, on infective endocarditis.
Meyer told Durack that in the late summer of 1940 he was incensed by the assignment of priority given to Meyer's own pioneering work on lysozyme in articles by Ernst Chain.
(Meyer probably didn't mention it but he was possibly even more incensed by Chain jumping his priority on Meyer's much more exclusive pioneering work on hyaluronan.)
Chain had been a fellow biochemistry student with Meyer in Berlin and even more importantly, both were not-yet-established-German-Jewish-emigre-scientists in the wartime Anglo-American medical research world.
For either, scoring a significant scientific discovery might keep them out of an internment camp, while a rival stealing their credit might mean a hard bed in that same internment camp.
I think most biochemistry experts agree that Karl Meyer was a far, far better biochemist all his life than Chain.
So for whatever reason(s) , Meyer's pioneering work was always closely followed up by Chain.
Only this time, Meyer would turn the tables --- follow up on Chain's pioneering work for once.
Try to beat Chain to the goal of purifying native penicillin to the point when its structure could be determined and then it could made by artificial synthesis.
A great story --- but how true ?
Because Chain didn't even submit his co-authored articles on hyaluronan and lysozyme until late September 1940 and late October 1940 and they weren't even published in the UK till December 1940 and no one in America could have read them before January 1941.
Was Meyer clairvoyant then ?
No - and Professor Ronald Bentley provides the solution.
He got to know Professor Leslie (Epstein) Falk late in both their careers and learned that Epstein had not just done his PhD thesis on lysozyme under Chain's close supervision but had also informally helped Chain in the early Oxford work on penicillin.
The Fall of France had prompted the US & UK governments to agree to return all the American Rhode scholars posthaste, because America was still neutral.
So Epstein couldn't even stay long enough to dot the last "i"s on his thesis, but he was in Oxford when Florey first injected penicillin into mice and cured their fatal disease without harming the mice with side effects.
Epstein felt the sudden uprise of excitement in Florey's entire institute and the move to keep it all hush hush until it had secured a commercial sponsor and had been published.
Epstein was Jewish and a leftist - Florey didn't much like either.
Epstein probably felt he owed Florey no particular loyalty as a result.
So he spilt the beans on the penicillin project, including Chain's expected role, to Meyer while using Meyer's expertise in lysozyme together with Meyer's reagents and lab space to finish his PhD - sometime between June 10th and September 7th 1940.
Like Epstein (and Chain for that matter), Meyer was also Jewish and left-leaning.
I personally feel that Epstein really liked Chain and only inadvertently let slip Chain's 'off the cuff' dismissive comments about Meyer's work.
Probably while recounting some of the endless 'colourful stories' that Chain's very mercurial personality tended to throw up.
Because I see nothing too offensive in either of Chain's relatively cautious articles (on Lysozyme and Hyaluronan) and in any case, they came out months after Meyer began his penicillin project.
No, Meyer, forewarned by Epstein in person what journal would get the Florey,Chain et al penicillin article and what month it might come out, lay in wait for whatever tidbits of new information on penicillin's curative effects the article might have.
He needed that information to be good because he needed microbiologists (Hobby) and clinicians (Dawson) on side, if he was to pull off the synthesis of penicillin.
Because there was no chemical test to tell you that you have actually synthesized penicillin - that could only be established biologically by skilled workers.
Now Durack also interviewed Hobby and Dawson's last co-worker Thomas T Hunter for his article and told them they'd be in it and when and where it would come out.
Hobby read Durack's article when it came out in 1981, that I am sure , including Meyer's bombshell revelation, and went on to publish her own account of wartime penicillin in 1986.
But she choose not to alter in any way her earlier claim to Bickel that their pioneering penicillin effort was led from the start by Dawson and was set up to defeat SBE with penicillin.
Meyer's account rang true, but Hobby wanted nothing in her book to upset its thesis that good will and a lot of hard work among united allies gave us the miracle of wartime penicillin.
If her work sold far less copies than Watson's 1968 "The Double Helix" one need not search hard to find why.
Her account of the 'drama' of wartime penicillin left out all the drama .....
Because Hobby's book "Penicillin : Meeting the Challenge", one or two gentle digs aside, is decidedly all moral uplift and hands across the water, marking her as "The Pollyanna of Penicillin".
Hobby's book sometimes is more fascinating for what she chooses to leave out than what she puts in it --- and yet she added a great deal of rare, even unique, information.
Meyer only really made one "for publication" comment about his part in wartime penicillin but it was frank and astringent.
It makes a reader wish he had said more : much, much more.
The major reason he didn't was because Meyer knew his role in saving the lives of thousands of SBEs and jumpstarting the fabulous success of native penicillin was all very well, but he was a biochemist damn it and his original goal was to synthesize native penicillin and replace it - not guide it up to the winner's podium.
Meyer had failed, partly because all chemists in the world also failed at this synthesis task --- and partly because he was treated very unfairly by his more powerful scientific competitors - and who wants to research and write a long book about your successful life's one big failure ?
By the time Meyer felt free to make even those few comments, for a book published in 1981, he was over eighty and the key penicillin players had almost all died.
In particular, Ernst Chain had just died a few months earlier.
Inspired by the death of Chain's boss, Howard Florey, in 1968, the first truly multi-continent account of wartime penicillin had come out in 1973, researched and written by Australian journalist and author Leonard Bickel.
Bickel did enough interviewing of minor front line participants still alive to uncover many fascinating, important but unreported/un-Pollyanna aspects of the saga.
His "Rise up to Life" included information from Gladys Hobby that first brought to those interested in the history of penicillin the forgotten efforts of Dr Martin Henry Dawson.
She said Dawson had pushed the North American development of early penicillin in an ultimately successful attempt to cure then invariably fatal SBE , the endocarditis that made Rheumatic Fever the leading killer of school age kids for half a century, a disease she said he had long made his personal crusade.
None of this was true - and she half knew that to be so.
I have found no evidence what so ever that Dawson ever mentioned SBE at any of the many scientific meetings he attended or that he wrote articles on it or did research into it.
And Hobby was his closest co-worker for ten years : she too had said, written and done nothing on SBE.
So Dawson had done nothing on SBE --- least not before October 1940, when the penicillin project at his hospital had already been underway for 5 weeks.
Hobby freely admits that she herself was away on vacation when the project began and she returned after several hectic weeks into the effort - so she could only know of the project's origins from what Meyer, Chaffee and Dawson told her.
The agreed plan, by the time she arrived, was that the native penicillin would be grown mostly by Hobby.
Then after being purified and its chemical structure figured out, it would be synthesized artificially, all this mostly done by Meyer and Chaffee, tasks expected to be completed sometime early in the New Year.
Then, and only then, would clinician Henry Dawson reach centre stage - injecting the synthetic penicillin into patients whose care he controlled as the sole attending physician among the small four person team.
A few days before Draft Registration Day, October 16th 1940, Dawson suddenly decided to put a very little of the very weak and very impure native penicillin into two patients with SBE, a disease whose cure, virtually all doctors agreed, would require lots of medication every day for weeks and weeks on end.
Dawson's tiny injections might raise the dying pair's morale but could have had no direct physical impact on their disease.
And it rather upended the team's agreed upon project protocol.
As that chemically-oriented protocol suggests, Meyer the biochemist had actually started the project.
But he waited a half century, till just after the death of Ernst Chain, to say exactly why he had.
In 1980, Meyer was interviewed by a young endocarditis researcher, Australian born Dr David T Durack, who was writing an article on the early history of the conquest of endocarditis by antibiotics for a book, edited by Allan Bisno, on infective endocarditis.
Meyer told Durack that in the late summer of 1940 he was incensed by the assignment of priority given to Meyer's own pioneering work on lysozyme in articles by Ernst Chain.
(Meyer probably didn't mention it but he was possibly even more incensed by Chain jumping his priority on Meyer's much more exclusive pioneering work on hyaluronan.)
Chain had been a fellow biochemistry student with Meyer in Berlin and even more importantly, both were not-yet-established-German-Jewish-emigre-scientists in the wartime Anglo-American medical research world.
For either, scoring a significant scientific discovery might keep them out of an internment camp, while a rival stealing their credit might mean a hard bed in that same internment camp.
I think most biochemistry experts agree that Karl Meyer was a far, far better biochemist all his life than Chain.
So for whatever reason(s) , Meyer's pioneering work was always closely followed up by Chain.
Only this time, Meyer would turn the tables --- follow up on Chain's pioneering work for once.
Try to beat Chain to the goal of purifying native penicillin to the point when its structure could be determined and then it could made by artificial synthesis.
A great story --- but how true ?
Because Chain didn't even submit his co-authored articles on hyaluronan and lysozyme until late September 1940 and late October 1940 and they weren't even published in the UK till December 1940 and no one in America could have read them before January 1941.
Was Meyer clairvoyant then ?
No - and Professor Ronald Bentley provides the solution.
He got to know Professor Leslie (Epstein) Falk late in both their careers and learned that Epstein had not just done his PhD thesis on lysozyme under Chain's close supervision but had also informally helped Chain in the early Oxford work on penicillin.
The Fall of France had prompted the US & UK governments to agree to return all the American Rhode scholars posthaste, because America was still neutral.
So Epstein couldn't even stay long enough to dot the last "i"s on his thesis, but he was in Oxford when Florey first injected penicillin into mice and cured their fatal disease without harming the mice with side effects.
Epstein felt the sudden uprise of excitement in Florey's entire institute and the move to keep it all hush hush until it had secured a commercial sponsor and had been published.
Epstein was Jewish and a leftist - Florey didn't much like either.
Epstein probably felt he owed Florey no particular loyalty as a result.
So he spilt the beans on the penicillin project, including Chain's expected role, to Meyer while using Meyer's expertise in lysozyme together with Meyer's reagents and lab space to finish his PhD - sometime between June 10th and September 7th 1940.
Like Epstein (and Chain for that matter), Meyer was also Jewish and left-leaning.
I personally feel that Epstein really liked Chain and only inadvertently let slip Chain's 'off the cuff' dismissive comments about Meyer's work.
Probably while recounting some of the endless 'colourful stories' that Chain's very mercurial personality tended to throw up.
Because I see nothing too offensive in either of Chain's relatively cautious articles (on Lysozyme and Hyaluronan) and in any case, they came out months after Meyer began his penicillin project.
No, Meyer, forewarned by Epstein in person what journal would get the Florey,Chain et al penicillin article and what month it might come out, lay in wait for whatever tidbits of new information on penicillin's curative effects the article might have.
He needed that information to be good because he needed microbiologists (Hobby) and clinicians (Dawson) on side, if he was to pull off the synthesis of penicillin.
Because there was no chemical test to tell you that you have actually synthesized penicillin - that could only be established biologically by skilled workers.
Now Durack also interviewed Hobby and Dawson's last co-worker Thomas T Hunter for his article and told them they'd be in it and when and where it would come out.
Hobby read Durack's article when it came out in 1981, that I am sure , including Meyer's bombshell revelation, and went on to publish her own account of wartime penicillin in 1986.
But she choose not to alter in any way her earlier claim to Bickel that their pioneering penicillin effort was led from the start by Dawson and was set up to defeat SBE with penicillin.
Meyer's account rang true, but Hobby wanted nothing in her book to upset its thesis that good will and a lot of hard work among united allies gave us the miracle of wartime penicillin.
If her work sold far less copies than Watson's 1968 "The Double Helix" one need not search hard to find why.
Her account of the 'drama' of wartime penicillin left out all the drama .....
Friday, March 13, 2015
Was Martin Henry Dawson's sub clinical MG pushed into a severe MG case by his penicillin work ?
Thousands of deaths later, doctors have come to realize that many,many drugs can turn quietly sub clinical cases of Myasthenia Gravis (MG) into full blow cases.
Situations that turn ordinary people into lifelong patients who now require constant and closely monitored medical interventions for their very survival and well being.
If the full blown case happens unexpectedly while the patient is out for the count, during a routine surgery, it can even cause an unexpected respiratory failure that could prove quickly fatal.
MG is by the most common member of a sizeable group of diseases that hinder the vital transmission of nerve control signals from the stem of the brain though to the nerve ends and then across a gap to the special muscles that control things like breathing and swallowing.
Thankfully, mammal bodies have a huge redundancy in signal sending and signal receiving receptors at either end of that gap to cover most possible problems.
So these diseases are not a simple matter of either being full on or full off but rather exist in a fluctuating continuum depending on our general health and stress levels .
Many of us have conditions that interfere - somewhat - with that nerve transmission process but we don't even realize it - just that sometimes we feel sort of 'punk' and 'out of it'.
These large number of until recently unnoticed sub clinical cases of MG does produce an example of a common situation where we are basically lied to, when fundraisers for the treatment and cure of a disease insist a disease's survival rate is "way up".
Here is how it happens :
Often, a new disease is only 'noticed' when enough people with the most severe symptoms arrive at some big city research hospital and form the basis of an article.
Most - having such severe symptoms as to be readily obvious - naturally die at first.
The disease researchers then say that the disease is very rare --- and with a very high morbidity rate.
But then gradually some reliable and sensitive diagnostic tests emerge, tests that indicate the disease actually exists mildly in many more people than was ever imagined.
Now the new 'survival rates' much quoted are in fact spread over a vast number of people who were never ever going to die of the disease, with or without medical intervention.
I don't wish to deny that many people who used to die from MG are now kept alive thanks to over a hundred years of research on this disease.
Just to warn you that all disease fundraisers are past masters at 'lying with statistics' , all trying to do good by getting as much success stories into their PR as possible.
Now all kinds of stresses - external chemical ones (like drugs and bugs) as well as internal (mental) ones - can make a person's MG condition suddenly worsen.
'Worsen' can extend as far as a sudden failure to breath - the dreaded "MG Crisis" - a situation that can kill the MG patient in minutes.
Lists of drugs that have - on occasion and with particular MG patients - made their condition worse, temporarily or forever - are so long and extensive as to make depressing reading.
But some types of drugs do it more consistently than others.
Penicillin is one such drug, with the breakdown components of it even more deadly : D Penicillamine is one such sub-compound.
Today a useful if dangerous drug, in the early 1940s, it was just something that chemists produced regularly in their attempts to break down fungus-made natural penicillin into its chemical sub components.
They were hoping that analyzing the resulting smaller bits would help them to put it all together again - but via human chemical synthesis.
Penicillin work at Columbia Presbyterian had started out strictly as an effort by German Jewish emigre chemist Karl Meyer to quickly synthesize penicillin.
He hoped, if he succeeded, to prove himself valuable enough to the American defence establishment to allow him to avoid possible internment, in case of a shooting war with Germany.
He wanted his colleague and friend Dawson to merely test tiny amounts of the resulting compounds for biological activity on equally tiny samples of bacteria.
There was no real need at this time, Meyer felt, to 'waste' scarce penicillin by using it on real patients.
Instead almost all of the natural penicillin produced by the team with great difficulty was then quickly destroyed by Meyer in repeated chemical efforts to try to break it into its smallest building block compounds.
Dawson had naturally helped out and had probably absorbed some of these penicillin sub compounds while breathing in the hot moist fumes - the idea of proper effective fume hoods being routinely provided to all labs was something many decades into the future.
If he got his subclinical MG stimulated by such fumes, he'd hardly be alone - there are other cases of scientists showing MG symptoms from simply working in rooms that a number of years before had seen much penicillin activities!
I suspect by October 16th 1940 and the first injections of what small amounts of penicillin that Dawson could pry away from Meyer's chemical work, Dawson's latent or sub clinical MG had already been stimulated.
He had been, in a sense, a ticking time bomb, being in his fifth decade, which is still the decade when most serious cases of MG first become noticed in males.
Then the stress of dealing with the paperwork of his father's death in distant Nova Scotia, instead home at busy exam time in NYC, may have really moved his MG into high gear.
High enough to be seriously noticed and to send him to some specialists, sometime in late December 1940 ...
Situations that turn ordinary people into lifelong patients who now require constant and closely monitored medical interventions for their very survival and well being.
If the full blown case happens unexpectedly while the patient is out for the count, during a routine surgery, it can even cause an unexpected respiratory failure that could prove quickly fatal.
MG is by the most common member of a sizeable group of diseases that hinder the vital transmission of nerve control signals from the stem of the brain though to the nerve ends and then across a gap to the special muscles that control things like breathing and swallowing.
Thankfully, mammal bodies have a huge redundancy in signal sending and signal receiving receptors at either end of that gap to cover most possible problems.
So these diseases are not a simple matter of either being full on or full off but rather exist in a fluctuating continuum depending on our general health and stress levels .
Many of us have conditions that interfere - somewhat - with that nerve transmission process but we don't even realize it - just that sometimes we feel sort of 'punk' and 'out of it'.
These large number of until recently unnoticed sub clinical cases of MG does produce an example of a common situation where we are basically lied to, when fundraisers for the treatment and cure of a disease insist a disease's survival rate is "way up".
Here is how it happens :
Often, a new disease is only 'noticed' when enough people with the most severe symptoms arrive at some big city research hospital and form the basis of an article.
Most - having such severe symptoms as to be readily obvious - naturally die at first.
The disease researchers then say that the disease is very rare --- and with a very high morbidity rate.
But then gradually some reliable and sensitive diagnostic tests emerge, tests that indicate the disease actually exists mildly in many more people than was ever imagined.
Now the new 'survival rates' much quoted are in fact spread over a vast number of people who were never ever going to die of the disease, with or without medical intervention.
I don't wish to deny that many people who used to die from MG are now kept alive thanks to over a hundred years of research on this disease.
Just to warn you that all disease fundraisers are past masters at 'lying with statistics' , all trying to do good by getting as much success stories into their PR as possible.
Now all kinds of stresses - external chemical ones (like drugs and bugs) as well as internal (mental) ones - can make a person's MG condition suddenly worsen.
'Worsen' can extend as far as a sudden failure to breath - the dreaded "MG Crisis" - a situation that can kill the MG patient in minutes.
Lists of drugs that have - on occasion and with particular MG patients - made their condition worse, temporarily or forever - are so long and extensive as to make depressing reading.
But some types of drugs do it more consistently than others.
Penicillin is one such drug, with the breakdown components of it even more deadly : D Penicillamine is one such sub-compound.
Today a useful if dangerous drug, in the early 1940s, it was just something that chemists produced regularly in their attempts to break down fungus-made natural penicillin into its chemical sub components.
They were hoping that analyzing the resulting smaller bits would help them to put it all together again - but via human chemical synthesis.
Penicillin work at Columbia Presbyterian had started out strictly as an effort by German Jewish emigre chemist Karl Meyer to quickly synthesize penicillin.
He hoped, if he succeeded, to prove himself valuable enough to the American defence establishment to allow him to avoid possible internment, in case of a shooting war with Germany.
He wanted his colleague and friend Dawson to merely test tiny amounts of the resulting compounds for biological activity on equally tiny samples of bacteria.
There was no real need at this time, Meyer felt, to 'waste' scarce penicillin by using it on real patients.
Instead almost all of the natural penicillin produced by the team with great difficulty was then quickly destroyed by Meyer in repeated chemical efforts to try to break it into its smallest building block compounds.
Dawson had naturally helped out and had probably absorbed some of these penicillin sub compounds while breathing in the hot moist fumes - the idea of proper effective fume hoods being routinely provided to all labs was something many decades into the future.
If he got his subclinical MG stimulated by such fumes, he'd hardly be alone - there are other cases of scientists showing MG symptoms from simply working in rooms that a number of years before had seen much penicillin activities!
I suspect by October 16th 1940 and the first injections of what small amounts of penicillin that Dawson could pry away from Meyer's chemical work, Dawson's latent or sub clinical MG had already been stimulated.
He had been, in a sense, a ticking time bomb, being in his fifth decade, which is still the decade when most serious cases of MG first become noticed in males.
Then the stress of dealing with the paperwork of his father's death in distant Nova Scotia, instead home at busy exam time in NYC, may have really moved his MG into high gear.
High enough to be seriously noticed and to send him to some specialists, sometime in late December 1940 ...
Monday, March 2, 2015
Anne Fulcher Hunter passes -- one of the last adult eyewitnesses to birth of penicillin
Mrs Hunter was born in Wisconsin in 1916 and died in Virginia in 2014, aged 98.
After she had raised her five children she resumed her career as a doctor, now in psychiatry rather than in pediatrics.
She is in my blog today because while a medical resident at Columbia Presbyterian she learned first hand of Drs Dawson, Hobby and Meyer's pioneering work in saving SBE patients with their own hospital-brewed penicillin.
She learned much more about them when she met and married Dr Thomas H Hunter, also a resident there, who from 1943-1946 became Dawson's lead co-worker in this work.
Hunter also became Dawson's personal doctor in Dawson's final months just before VE Day 1945.
Dawson had held off his case of (then almost always fatal) MG (Myasthenia Gravis) for four and a half years, until he had completed his penicillin-for-all project successfully and the Nazis had been defeated.
Mrs Hunter thus had a ringside seat in the most dramatic years of the entire wartime penicillin saga.
But the time I knew more about her, she was in her late nineties and I was not eager to try and get her permission to interview her.
The only other adult eyewitness to wartime penicillin that I know of that who is still alive is Dr H Boyd Woodruff of Watchung NJ, who is 97 and still actively writing scholarly articles !
Perhaps Anne Hunter and her husband told their children a little of those early penicillin days - I sort of hope so.
If not, maybe my book will tell the Hunter grandkids and kids just what their grand/parents and great/uncle were up to during the war years....
After she had raised her five children she resumed her career as a doctor, now in psychiatry rather than in pediatrics.
She is in my blog today because while a medical resident at Columbia Presbyterian she learned first hand of Drs Dawson, Hobby and Meyer's pioneering work in saving SBE patients with their own hospital-brewed penicillin.
She learned much more about them when she met and married Dr Thomas H Hunter, also a resident there, who from 1943-1946 became Dawson's lead co-worker in this work.
Hunter also became Dawson's personal doctor in Dawson's final months just before VE Day 1945.
Dawson had held off his case of (then almost always fatal) MG (Myasthenia Gravis) for four and a half years, until he had completed his penicillin-for-all project successfully and the Nazis had been defeated.
Mrs Hunter thus had a ringside seat in the most dramatic years of the entire wartime penicillin saga.
But the time I knew more about her, she was in her late nineties and I was not eager to try and get her permission to interview her.
The only other adult eyewitness to wartime penicillin that I know of that who is still alive is Dr H Boyd Woodruff of Watchung NJ, who is 97 and still actively writing scholarly articles !
Perhaps Anne Hunter and her husband told their children a little of those early penicillin days - I sort of hope so.
If not, maybe my book will tell the Hunter grandkids and kids just what their grand/parents and great/uncle were up to during the war years....
Sunday, March 1, 2015
First injection of penicillin into patients : October 16th 1940 New York
The first penicillin needle into a patient, ushering in our present Era of Antibiotics, was one of the most signal events in all medical history and it happened exactly 75 years ago this Fall.
Yet, until this present article, even the barest of its bare facts have never been publicly reported accurately - not even by the three key team leaders that first performed them !
Here is how it went, based on cross-checking the various published report by the three team leaders against public records and newspaper accounts:
On October 15th 1940, after a hectic six weeks learning from scratch just where to find the right strain of penicillium and then how to coax the temperamental fungus to produce raw penicillin juice, the three key members of the tiny team at New York's Columbia Presbyterian Medical Centre were finally ready.
The team leader (Nova Scotia born and raised Dr Martin Henry Dawson) would inject the penicillin into himself, a healthy volunteer, to test whether the never-before injected drug was dangerous to human life once in the bloodstream.
If he survived unharmed, the team planned to use the free time provided the next day by the university's registration of students and young staff in America's very first peacetime Draft to inject some penicillin into two young male patients dying of then invariably fatal SBE.
More formally known as subacute bacterial endocarditis, SBE was the then common disease that made Rheumatic Fever the leading killer of the young.
So only October 16th (in between the two dying boys being registered for the Draft) and once again on October 17th 1940, Dr Dawson injected some of the team's hospital brewed penicillin into the two young men.
One was a young black star athlete , Aaron Leroy Alston born 1910 and residing on St Nicholas Avenue in Harlem and the other was a deathly-sick-all-his-life young Jewish man, Charles Aronson, born 1913 and residing on Vyse Avenue in the Bronx.
Next, the two young men got a much longer and and a much larger regime of oral Sulfa drugs.
Unexpectedly, the Sulfa worked on the sickly Aronson and he went home apparently cured, on a maintenance dose of Sulfa, in late December.
His cure held and he survived alright for three and a half years until another bout of SBE brought him back to Dawson.
This time Dawson had plenty of penicillin to cure SBE reliably and he did so again with Aronson.
Unfortunately, star athlete Alston did not respond to Sulfa drugs (more accurately his particular strain of SBE-causing Viridans Strep didn't respond) and Dawson started him again on a larger and longer regime of stronger injected penicillin on December 31st 1940.
He died mid-treatment in mid January 1941 and his tragically short sports career was celebrated and mourned by many sports fans across the city.
The penicillin brewed for him but not used was given to a third patient, a young middle class salesman in his thirties from upstate New York - Middletown to be precise ; his name George Milton Conant.
He got at least one course of Dawson's penicillin in late January.
He died on May 31st 1941 -nearly a month after Dawson gave a cautious report May 5th on his treatment of four SBE patients with penicillin , delivered before a huge convention of medical researchers at Atlantic City and given extraordinary wide coverage in the news media.
I (and even the team itself) know nothing of the fourth patient - but Dawson's May 5th report specifically says four were treated ( thus treated between between October 16th 1940 and late April 1941).
(It is is worth remarking, given the canonical status and wide circulation of this newspaper, that The New York Times' science correspondent William L Laurence (who wrote the famous eye-witness account of the first atomic explosion ,"Dawn Over Zero") reported the next day that he had heard Dawson saying that he had treated 4 patients suffering from SBE with his penicillin.)
As of the May 5th date, we know for sure that only one patient had definitely died but Dawson refused to crow about his small successes ---- or give specifics of just when the first injections were given and to how many patients.
Dawson later referred , in his 1944 JAMA article, to treating five SBE patients with early hospital brewed penicillin, of a potency not stated.
This allows us to assume that the fifth patient was probably treated very early in the Fall of 1941.
Because that was before Dawson had been introduced, after a visit from Norman Heatley, to the idea of calibrating the biological activity of penicillin by using Oxford units - as we still do to this day.
(The team seems to have stopped making penicillin during the high summer months because the temperature in the hospital, anywhere than in a bottom basement room, was far too high to successfully grow penicillium that would give off penicillin juice.)
Later he and his fellow team mates bacteriologist Dr Gladys Hobby and chemist Dr Karl Meyer would all give partially accurate and incomplete public accounts of those early (clearly non-dramatic) days - so who could blame the lay press or science historians for repeating their errors and adding some of their own ?
Yet, until this present article, even the barest of its bare facts have never been publicly reported accurately - not even by the three key team leaders that first performed them !
Here is how it went, based on cross-checking the various published report by the three team leaders against public records and newspaper accounts:
On October 15th 1940, after a hectic six weeks learning from scratch just where to find the right strain of penicillium and then how to coax the temperamental fungus to produce raw penicillin juice, the three key members of the tiny team at New York's Columbia Presbyterian Medical Centre were finally ready.
The team leader (Nova Scotia born and raised Dr Martin Henry Dawson) would inject the penicillin into himself, a healthy volunteer, to test whether the never-before injected drug was dangerous to human life once in the bloodstream.
If he survived unharmed, the team planned to use the free time provided the next day by the university's registration of students and young staff in America's very first peacetime Draft to inject some penicillin into two young male patients dying of then invariably fatal SBE.
More formally known as subacute bacterial endocarditis, SBE was the then common disease that made Rheumatic Fever the leading killer of the young.
So only October 16th (in between the two dying boys being registered for the Draft) and once again on October 17th 1940, Dr Dawson injected some of the team's hospital brewed penicillin into the two young men.
One was a young black star athlete , Aaron Leroy Alston born 1910 and residing on St Nicholas Avenue in Harlem and the other was a deathly-sick-all-his-life young Jewish man, Charles Aronson, born 1913 and residing on Vyse Avenue in the Bronx.
Next, the two young men got a much longer and and a much larger regime of oral Sulfa drugs.
Unexpectedly, the Sulfa worked on the sickly Aronson and he went home apparently cured, on a maintenance dose of Sulfa, in late December.
His cure held and he survived alright for three and a half years until another bout of SBE brought him back to Dawson.
This time Dawson had plenty of penicillin to cure SBE reliably and he did so again with Aronson.
Unfortunately, star athlete Alston did not respond to Sulfa drugs (more accurately his particular strain of SBE-causing Viridans Strep didn't respond) and Dawson started him again on a larger and longer regime of stronger injected penicillin on December 31st 1940.
He died mid-treatment in mid January 1941 and his tragically short sports career was celebrated and mourned by many sports fans across the city.
The penicillin brewed for him but not used was given to a third patient, a young middle class salesman in his thirties from upstate New York - Middletown to be precise ; his name George Milton Conant.
He got at least one course of Dawson's penicillin in late January.
He died on May 31st 1941 -nearly a month after Dawson gave a cautious report May 5th on his treatment of four SBE patients with penicillin , delivered before a huge convention of medical researchers at Atlantic City and given extraordinary wide coverage in the news media.
I (and even the team itself) know nothing of the fourth patient - but Dawson's May 5th report specifically says four were treated ( thus treated between between October 16th 1940 and late April 1941).
(It is is worth remarking, given the canonical status and wide circulation of this newspaper, that The New York Times' science correspondent William L Laurence (who wrote the famous eye-witness account of the first atomic explosion ,"Dawn Over Zero") reported the next day that he had heard Dawson saying that he had treated 4 patients suffering from SBE with his penicillin.)
As of the May 5th date, we know for sure that only one patient had definitely died but Dawson refused to crow about his small successes ---- or give specifics of just when the first injections were given and to how many patients.
Dawson later referred , in his 1944 JAMA article, to treating five SBE patients with early hospital brewed penicillin, of a potency not stated.
This allows us to assume that the fifth patient was probably treated very early in the Fall of 1941.
Because that was before Dawson had been introduced, after a visit from Norman Heatley, to the idea of calibrating the biological activity of penicillin by using Oxford units - as we still do to this day.
(The team seems to have stopped making penicillin during the high summer months because the temperature in the hospital, anywhere than in a bottom basement room, was far too high to successfully grow penicillium that would give off penicillin juice.)
Later he and his fellow team mates bacteriologist Dr Gladys Hobby and chemist Dr Karl Meyer would all give partially accurate and incomplete public accounts of those early (clearly non-dramatic) days - so who could blame the lay press or science historians for repeating their errors and adding some of their own ?
Tuesday, February 24, 2015
First antibiotic penicillin patient : when did we learn his name?
How do we know what we know ?
I am very confident that the very first patient of the Antibiotic Era was a young black man named Aaron (Leroy) Alston and that he lived on St Nicholas Avenue in Harlem, New York City.
But when I was asked recently by one of Aaron's relatives (journalist Claude Jay) to demonstrate my proof, I was momentarily nonplussed.
That was when because I initially came across the statement that Aaron was the first systemic penicillin (penicillin-the-antibiotic) patient in history in early 2005, it was in about a dozen different books, all read at the exactly the same time.
(People who know what a bookworm I am, will not find that last statement at all incredible !)
I gradually assembled more information about that historic event and on Aaron himself , from scattered bits of evidence here and there - material I realized had never been assembled into a coherent and self-confirming whole.
My biggest breakthrough - discovering Aaron's death certificate - was quickly followed by my second biggest breakthrough , discovering Claude Jay himself.
That is because, outside of his medical records, Aaron was generally known to the world as Leroy, or more formally, as A. Leroy Alston.
Aaron Leroy Alston was a superb athlete -- not just someone who died to furnish a footnote to someone else's story
I had held a strong clue that could have led me/ should have led me to Leroy years earlier.
But I discounted the evidence : that an A. Alston had won some very big amateur races in the NYC area.
I mistakingly assumed that anyone who had had acute rheumatic fever leading to severe heart valve damage, as Leroy/Aaron had to have had, couldn't possibly go on to be a top runner.
Now that I knew Aaron was also a Leroy Alston or an A. Leroy Alston and a great athlete to boot, I quickly found a good deal more about Leroy from newspapers of the day.
So I spent last week trolling through my files and the books on penicillin and rheumatic heart disease at Dalhousie University's medical library, trying to establish a timeline as to when the world first knew that Aaron was Patient One of the penicillin-the-antibiotic era.
I found nothing that named Aaron in the books and medical reports and newspapers of the war years.
NY World-Telegram first to get it (partially) right
But on the premature death of Aaron's penicillin doctor Martin Henry Dawson in April 1945, one New York newspaper, the World-Telegram, did correctly mention that his first penicillin patient was a Negro, as well as claiming that Dawson was the first to treat a patient with penicillin in the USA.
But the story not only does not name that patient, it confuses his story with that of the other first penicillin patient of Dawson's, Charles Aronson !
(Yes, Aaron was the first patient selected to receive systemic penicillin, but as the fates would have it, on the day he first received it, a new fellow sufferer (Charles) also got it at the very same time.)
The story describes Aaron as being 27 and being cured - that age and fate correctly belongs to Charles because sadly Aaron died despite the penicillin.
Now Dawson and his closest fellow worker, his lab chief Dr Gladys Hobby, were modest to the point of giving me a stroke.
The pair knew, when they initially read Howard Florey's August 1941 article on his team's first clinical use of systemic penicillin in February 1941, that Dawson's team had beat him by four months in first using penicillin systemically.
But maddeningly, they still modestly claimed only to be the first to do so in North America , in any newspaper interviews or medical articles published during the war years.
Hobby, I sense, had no great memory.
This is because already by 1949 (only 8 years later) and after consulting her own personal records (!), Hobby writing in a report for her then employer, Pfizer, says the first injection only happened on January 11th in 1941 !
Reading her later - more accurate - accounting, I can only suggest that in 1949 she meant to say that January 11th marked the first day of intravenous injections.
This after a series, in the months earlier, of first intracutaneous injections, then sub -cutaneous and then intramuscular injections.
(As doctors will know, there are actually dozens of different forms of medical injections - varying by both site and method.)
Hobby went to her grave also convinced that Dawson gave the first penicillin shots on October 15th 1940 - a statement she repeatedly gave to fellow penicillin historians who dutifully spread it far and wide.
I don't believe it --- and neither should you.
For nowhere in her ultimately relatively detailed chronological account of the first days of penicillin-the-antibiotic does she indicate when the totally new drug was first tested on a healthy volunteer before being injected into the two severely ill patients for real.
Even in the relatively relaxed medical research atmosphere of the 1940s, that would never have happened.
Durack and Bentley provide more clues
Let us turn first to a little known medical paper by Dr David T Durack, who based his article in part on a personal conversation with the biochemist of Dawson's tiny four person team, a person moreover who started Columbia's pioneering penicillin effort even before Dawson joined it.
Around 1980, Durack contacted that biochemist Karl Meyer, a distinguished scientist then in his early fifties and in full control of his faculties and memory.
(Durack's article was published before Hobby published her definitive 1986 book on penicillin but was never mentioned by Hobby - signalling to me that Hobby and Meyer were hardly close after Dawson's death.)
Durack's article, "Review of Early Experience in treatment of bacterial Endocarditis, 1940-1955", I found in the book "Treatment of Infectious Endocarditis", edited by Alan L Bisno.
Meyer's story at first seemed incredible to me, but as I gathered up more information here and there, it was confirmed by an article by Ronald Bentley at various key points.
Meyer had gone to a Berlin medical school with his fellow (German) (Jewish) student Ernst Chain and I believe had taken a mild dislike to him, something very easy to do with the mercurial Chain.
Now in September 1940 he had learned (directly via Chain's former graduate student, Jewish American Leslie Epstein*) that Chain was taking credit for important work first done by Meyer on Lysozyme and that he was now trying to synthesize penicillin.
*Read Bentley's fascinating account of Leslie Epstein Falk struggling with Chain to grow a little penicillin in the Fall and Spring of 1939-1940 and when Epstein is ordered out of Oxford only months before finishing his PhD, how he completes it partly thanks to a stay with Meyer at Columbia.
For both Chain and Meyer, I believe an elbows- out attitude, even against fellow German Jewish emigre scientists, was morally right in 1940.
Both knew that if they didn't prove themselves quickly to be top scientists in some way, they would end up interned by the German-and-Jew-distrusting Anglo-Saxon government elites, stuck in miserable prison camps along side Nazi Germans.
Meyer and Chain both thought synthesizing a small (350 Dalton weight) molecule like penicillin would be a breeze.
Meyer simply involved Dawson to do the early biological activity tests and then to do the much later clinical trials, after the drug had been synthesized.
Dawson jumped Meyer's gun, insisting on testing the drug's efficacy inside the human body long before it was synthesized.
Why?
Partly to save the lives of two young men before him who he thought were being discarded by a medical establishment using the excuse that they were gearing up for total war.
Partly to secure Meyer's flank, because the biochemist was working after all in a hospital, a workplace oriented strongly to instantly applied science, not in a more leisurely basic research lab.
So Meyer tells Durack, on October 15th 1940, penicillin was indeed injected for the very first time, as Hobby (and all those after her) claimed.
But not injected into a patient.
Injected instead by Dawson into Dawson acting as the human guinea pig to test it for human toxicity - Dawson believing it was better that he the doctor died than the patient doing so.
(Entirely typical of the decorated war hero Dawson, as was entirely typical the decision of war shirker Sir Howard Florey not to risk his 'valuable' life testing his penicillin on himself !)
But Durack reports (indirectly - no names are used) that Dawson only injected Charles Alston, not on Charles and Aaron.
This could be because he also interviewed Dr Thomas T Hunter.
Hunter was a later member of Dawson's team, who never met Aaron but who did meet Charles many, many times.
He first met him in the Spring of 1944 when he came back with a second attack of endocarditis and was cured by Dawson yet again, this time by penicillin alone instead of with a little penicillin and a lot of sulfa drugs.
Hunter did further checkups on the health of Charles until early 1946 at least - so his story naturally stuck in Hunter's mind years later.
Hobby was not on the team - but still in close touch - when Charles returned in the Spring of 1944 - maybe why she remembered him much less.
This raises a significant point - why do almost all writers choose to mention just Aaron or just Charles instead mentioning both ?
Penicillin writers and their hidden agendas
Because most writers have a not so hidden agenda.
(Mine is that I think Dawson got a raw deal from history for his pioneering HGT and Penicillin work.)
To date, most others writing about wartime penicillin have sought, above all else, to exalt Howard Florey over the man who they feel wrongly gets the credit for penicillin-the-antibiotic, Sir Alexander Fleming.
They are equally worried that the real credit should not slip off of Fleming's mantle only to fall onto that of the colonial Henry Dawson.
Like Florey, and unlike Dawson and Hobby , they realize Dawson was the first to ever give a needle of penicillin-the-antibiotic and hence it was he who ushered in our Age of Antibiotics.
Further they know that Dawson championed natural penicillin (and it is worth noting that most of our current antibiotics are still based on the original natural penicillin), to be made by Pfizer and others.
Florey and Fleming, by pointed contrast, strongly championed synthetic penicillin, to be made by ICI (Imperial Chemical Industries) and others.
ICI never made a single commercial drop of the synthetic stuff - no one ever has - and 80% of all the penicillin landed on D-Day and there after came from Pfizer alone.
Seemingly hard then not give Dawson the lion's share of the wartime penicillin glory - but it can be done, if you work at it.
So these agenda-driven writers dutifully note, in almost footnote fashion, that Dawson indeed gave history' first (very small) penicillin injection.
They then decide to focus on just one of the two initial patients (Aaron), the one that died.
Next they note that Dawson quickly got Myasthenia Gravis and that he also died.
All half truths, but enough truth in them so they feel they needn't cover his four further years* of clinical penicillin activities between April 1941 and April 1945.
*Dawson had much, much longer period of clinical involvement with wartime penicillin than did either Florey or Fleming.
Hunter and Durack, by contrast, want to see Dawson's first medical glass as half full.
So they focus on Charles (the other one of the original pair, the one who lived) as the first patient to ever receive penicillin.
Someone, they imply, as a result went on to survive a hitherto invariably fatal disease.
The truth is that two low status young men - one a black and another a Jew - got history's first penicillin shots basically out of the agape concern of a doctor who wasn't even their lead doctor or a specialist in their disease.
One patient, Aaron, was extensively treated with penicillin but still died, while the other patient Charles was responsive to sulfa (unlike Aaron) and lived.
The little penicillin Charles got had almost no effect clinically but it sure boosted his morale and that might have helped save him as much as the massive sulfa doses.
Bickel to the rescue
Now we move ahead in time to about 1970, when Australian write Lennard Bickel decides to write a biography* of Australian born penicillin pioneer Sir Howard Florey, who had just died in 1968.
"Rise up to Life", first published in 1972.
He interviews anyone who he can find who was there at the time to talk about wartime penicillin, tracking down people in America, Britain and Australia.
Many buried names and stories only survive today because of his fine journalistic efforts.
Bickel wanted to exalt his fellow countryman of that there is no doubt, but he did not wish to bury Dawson - in fact he exhumed him from the grave of human forgetfulness.
I do not believe that Hobby would have even written her seminal account of wartime penicillin without Bickel .
His book and the reaction to it, finally convinced her, almost 25 years after the fact, that Dawson had indeed been the first in the world to inject systemic penicillin and hence held a story worth recalling.
Because we know she told Bickel in circa 1970 interviews for his book that she was still convinced that Dawson was merely the first to treat patients in the USA alone with penicillin.
And she - citing her notes - claimed he had treated only one patient on that historic day, which she said was October 15th 1940 - and that the patient died.
But at least and finally, she brought forth his name : Aaron Alston.
And she talks forthrightly about Dawson's fatal Myasthenia Gravis.
But she - and Bickel - make it clear that if he worked less as a result of this crippling disease, he still worked full out on penicillin till his death in the spring of 1945.
Since Bickel became the key - almost primary source level - "go to source" for most of the academic accounts of wartime penicillin, it is remarkable how this clear statement of his four more years of penicillin activities could be so twisted and ignored.
Flash forward to 1985, Hobby has retired after a modestly successful paid career working at at Pfizer on new antibiotics and a Veterans' hospital working on TB and a more successful volunteer career as a editor of various scientific society journals.
She has gotten to know everybody who was anybody in early penicillin in both North America and in Britain.
Yale University* Press, her publisher was admirably demanding and so Hobby trolled deep to firm up her claims - even consulting a Miss Louise Good for her lab records of the early use of Dawson's penicillin.
If only Yale was as demanding upon its own staff, who persist in claiming that their University was the first place to use penicillin in America.
Dawson was their first and was also the first to see cures with local (topical) use of penicillin to treat staph eye infections.
But Yale can rightfully claim a first, for inn March-April 1942, they successfully treated a case and saved a life with the systemic use of penicillin alone.
Charles Aronson's life was saved too, and much earlier - in December 1940 - but by lots of sulfa and perhaps a little contribution from pioneering penicillin.
Good's work
Good seems to be the sole source in Hobby's 1985 book "Penicillin : Meeting the Challenge" of Hobby's new information on Aaron and on who she calls Charles Aronson, his fellow needle pioneer on October 16th and 17th 1940.
Now I could reliably confirm the relatively detailed information on patient C.A. found in Dawson and Hunter's 1945 JAMA article on their clinically successful use of systemic penicillin in curing subacute bacterial endocarditis.
Dawson and Hunter's C.A. had to be Good and Hobby's Charles Aronson, born in 1913 and thus highly likely to be a young Jewish-American man with that name from the Bronx found in the 1940 US Census.
Similarly, it seemed clear from Good's information that Aaron had died in the Columbia-Presbyterian Hospital, in the Borough of Manhattan, in the days around January 18th 1941.
So I could then overcome a problem unique to the New York City death certificate of that era.
They are easy to obtain and quite detailed - but do not give the cause of death, unlike those of most other jurisdictions - that information is given to the city government alone in another document.
So in a city that big, and when one seeks someone with an ethnically common name, one needs the borough the death was registered in and the exact day of death to safely match death certificate of a particular Aaron Alston with the unique penicillin/endocarditis Aaron Alston.
Thanks to Claude, I could now find newspaper accounts of Aaron Leroy Alston getting sick and then dying in the time periods that Hobby and Good address - both sets of data confirming each other.
So there you have it - Aaron Alston , the very first to receive penicillin-the-antibiotic is never directly named in any of a dozen or so clinical medical articles published during or just after the war years at the time that do reference him but indirectly.
His name and his connection to the first ever use of penicillin-the-antibiotic is mentioned in dozens of more recent medical history oriented academic articles, all dating after Bickel's pioneering book of 1972.
In addition, Aaron's story is mentioned in least one wire service story from Warren Leary, the AP science reporter.
In early October 1978, Leary reported that the longstanding belief that the British had been the first to inject penicillin into a patient was wrong.
Leary based his claim on a recent report in the Journal Chemistry from Dr George Kauffman that talked of Dawson's pioneering work.
One suspects Kauffman in turn had recently read Bickel's new book !
Aaron's story is still distorted
Gladys Hobby's penicillin book is probably found in every first class medical research library in the world and she gives the most detail about Aaron Alston - my blog aside.
Problems persist : author and wartime penicillin pioneer John C Sheehan, in a MIT Press* published book, "The Enchanted Ring" , confusingly thinks Aaron Alston is the doctor giving that very first needle to some unnamed patient.
He even regards Dawson's team, operating in the same hospital, as totally separate from 'Dr Alston' and his team !
*New Yorker magazine stories are throughly fact-checked, scientific journal articles a little, university press books by distinguished scholars from the same university as is publishing their book ? Not so much.
Okay, now for the biggest and serious problem : the near universal inclination for all sorts of researchers, even historians who really should know better, to read into Dawson's 1941 claim that he treated four SBE patients with penicillin all unsuccessfully, as meaning they all died.
Yes, SBE was then 99% fatal on its first presentation, but Charles Aronson was in that 1%, cured by sulfa, a little penicillin, God's grace and his own documented ability to survive more lives than a cat.
I know for certain the names of three of Dawson's first five SBE patients, that they were all five clinical failures re treatment with penicillin, that two Aaron Leroy Alston and George M Conant) died for sure, one lived for sure (Charles Aronson).
The other two I know nothing about, except that they were likely young men from the greater NYC area and that their likely months of admission were April 1941 and October 1941.
All the team members that treated them are dead and the hospital records from that time destroyed - we will likely never know more unless some family member remembers a relative dying of SBE around those dates at Columbia Presbyterian.
We have good information on the two dozen later SBEs that Dawson subsequently treated - but only have three full names provided by Hobby's book all which have so far produced dead ends.
What we need most for Aaaron is a picture of him.
I recall much of the fifty year mystery of blue singer Robert Johnson wasn't lack of reliable data about his life, but rather a lack of an ability to put a human face on a terribly interesting individual.
I feel the same about the fascinating Aaron Leroy Alston 1910-1941...
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 ...... !
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....
Monday, January 21, 2013
Thanks to SAMJ (the SOUTH AFRICAN MEDICAL JOURNAL), we can learn of first published guess as to penicillin's chemical structure
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| SAMJ : the South African Medical Journal |
But that is not so, thanks to the South African medical journal SAMJ and its enterprise at putting all of its over 100 years of back issues online and free to access.
It is little known that Karl Meyer, the chemist on the tiny pioneering Columbia university team ( the first ever to use penicillin as an antibiotic), contributed an unique intellectual portion to Henry Dawson's first presentation on penicillin.
This presentation was delivered in Atlantic City, at the 33rd annual meeting of the American Society for Clinical Investigation, ( the famous "Young Turks" ) May 5th 1941 --- attended by top medical researchers from all over the world and covered by the scientific and popular media.
To add to the journalistic fun, their more senior and sober counterparts, the American Association of Physicians, met the very next day in the same place - and the two generations of doctors didn't always agree on everything, naturally .
Most penicillin historians seemed to have limited their knowledge of this seminal event to the New York Times report on it, easily available anywhere on microfilm.
But the official abstract of Dawson's presentation , formally published in the Journal of the Society in July 1941, mentions - in passing - two important subject areas that all the popular media left out in describing Dawson's paper.
His presentation talked of the methods of preparation ( and importantly made it clear this took place in Dawson and Meyer's hospital lab and not in some drug company lab), without saying anything more.
Fortunately later articles do amplify on the earliest methods of growing and extraction in great detail.
But the precis also indicates that information as then known of penicillin's chemical nature , ie known as of late 1940-early 1941 , was discussed --- without saying what was speculated.
This speculation is NOT repeated in any later article, because this early speculation was not even close to penicillin's final chemical structure, as found with the help of hundreds of chemists, five long gruelling years later.
But, while I am not a chemist, I think I can say it wasn't a bad guess for what was known - almost by sight and smell - about the earliest dry penicillin powder.
Thanks to SAMJ, the South African Medical Journal
But back to SAMJ - because it was all down to one of their most enterprising correspondents , H O Hofmeyr, that we know anything at all about the earliest chemistry of penicillin.
Hofmeyr came from a very politically powerful Afrikaner family and so it is not surprising he was sent abroad, during WWII, to be South Africa's scientific eyes and ears in places like Washington DC.
He wrote a very complete diary of his visit to the Clinical Investigators annual meeting and it was published, in full ,in the September 1941 monthly issue of SAMJ.
I think I remain the only one to ever cite Hofmeyr's eyewitness report on the opening of the Age of Antibiotics.
I have always treasured his report on Dawson's paper , partly for his slightly snide tone relating that this particular paper caught the imagination of ("sniff") the ("popular") press who gave it ("lurid") headlines like 'Giant Germicide Yielded by Mold'.
But in addition, Dr HO ( as everyone called him) correctly noted in 1941 what current historians always, always miss : that Dawson's use of penicillin on subacute bacterial endocarditis, the dreaded SBE, was in some ways, highly conventional.
Hofmeyr said it still remained in 1941, the absolute "acid test" for the claims of every new potential chemotherapeutic agent.
But buried in middle of the paragraph, Hofmeyr indicates that the Columbia team is willing to speculate publicly that penicillin seems related to the hydroquinones.
The hydroquinones are a big family best known for their use in photo developing and skin whitening, but one in particular, paraquinone ,strikes me as looking, smelling and acting rather like early penicillin powder.
Yellow , arid penetrating smell, very sensitive to acids and bases, yes it sure does look, smell and act like early penicillin.
But paraquinone has only has about one third the molecular weight and number of atoms that penicillin has (and was thought to have in 1941) so it would have to be quite an elaborated version to fit the known facts.
WE have to wait to 1942 and the much better known journals such as NATURE and SCIENCE to find the next set of informed guesses as to penicillin's structural nature, but thanks to SAMJ, we have recovered an important fragment of medical history .....
Sunday, January 20, 2013
Henry Dawson "jump-started" The Age of Antibiotics because, almost alone in the medical world, he wasn't obsessed with 'purity' but rather with 'charity'
We have the records of only a few contemporary reactions to Henry Dawson's surprise decision to dramatically kick-start The Age of Antibiotics, 12 years after it should have begun but three months before it was scheduled to begin , but they are suggestive.
Gladys Hobby, his assistant, entered the Meyer-Hobby penicillin project a few weeks into it, after taking a late summer vacation.
She returned, she told penicillin author Leonard Bickel just 20 years later, to "an air of excitement filling the Dawson-Meyer lab" , Dawson had "immediately begun to work on this new project" and she "was at once caught up in his eager search".
Dawson was willing to wait "only eight days" after Meyer began purifying his first ever brew of penicillin before, "full of excitement" he injected this just-begun-being-purified material into two dying patients .
One patient died, one went home cured - Dawson refused to credit his small amount of "extremely low potency" penicillin with this cure, but he was "heartened" by the "low toxicity" of this "extremely crude" preparation. "No serious toxic effects observed."
Hobby later wrote in her own book on penicillin, that Dawson had "recognized immediately that penicillin .... might be effective in the treatment of ...subacute bacterial endocarditis in particular". The product used on October 16th 1940, she admits, was "crude" , "slightly purified (concentrated)" , even "extremely crude" .
At first, only the "low toxicity" of the "crude and impure" penicillin was noteworthy , not its curing ability.
On May 5th 1941, Dawson addressed hundreds of the world's top research doctors in Atlantic City, an event traditionally well covered by the popular media.
So we learn - via the New York Time's famous Atomic Bill Lawrence that Dawson admitted to the audience that despite his "crude" penicillin not being "pure", "no serious toxic effects were observed."
Via science journalist Steven Spencer, writing in America's largest evening paper, the Philadelphia Evening Bulletin, we learn that Dawson said that his penicillin was not toxic even when given in doses far beyond those dosages needed to clear up infections -- a distinct advantage over the sulfas, which are toxic to some people."
He said, reports Spencer, that penicillin had "unlimited possibilities."
Finally, an opponent of Dawson, Stanhope Bayne-Jones tells Howard Florey in strict confidence in July 1941, that Dawson is "quite honest" but "uncritically enthusiastic" .
I think I have demonstrated what was Dawson's key insight into penicillin, the insight that drove his excitement and his passion.
It was that he realized that even a crude mix of hospital-made natural penicillin with all its natural impurities still in it was both potent AND non toxic (in fact more potent and much less toxic than drug-company-made PURE sulfa drugs).
So morally, a doctor could not wait for 100% pure natural penicillin or for 100% pure synthetic penicillin, before starting to use penicillin to save the dying by systemic injections.
He had discovered unrefined natural penicillin's big secret....
Gladys Hobby, his assistant, entered the Meyer-Hobby penicillin project a few weeks into it, after taking a late summer vacation.
She returned, she told penicillin author Leonard Bickel just 20 years later, to "an air of excitement filling the Dawson-Meyer lab" , Dawson had "immediately begun to work on this new project" and she "was at once caught up in his eager search".
Dawson was willing to wait "only eight days" after Meyer began purifying his first ever brew of penicillin before, "full of excitement" he injected this just-begun-being-purified material into two dying patients .
One patient died, one went home cured - Dawson refused to credit his small amount of "extremely low potency" penicillin with this cure, but he was "heartened" by the "low toxicity" of this "extremely crude" preparation. "No serious toxic effects observed."
Hobby later wrote in her own book on penicillin, that Dawson had "recognized immediately that penicillin .... might be effective in the treatment of ...subacute bacterial endocarditis in particular". The product used on October 16th 1940, she admits, was "crude" , "slightly purified (concentrated)" , even "extremely crude" .
At first, only the "low toxicity" of the "crude and impure" penicillin was noteworthy , not its curing ability.
On May 5th 1941, Dawson addressed hundreds of the world's top research doctors in Atlantic City, an event traditionally well covered by the popular media.
So we learn - via the New York Time's famous Atomic Bill Lawrence that Dawson admitted to the audience that despite his "crude" penicillin not being "pure", "no serious toxic effects were observed."
Via science journalist Steven Spencer, writing in America's largest evening paper, the Philadelphia Evening Bulletin, we learn that Dawson said that his penicillin was not toxic even when given in doses far beyond those dosages needed to clear up infections -- a distinct advantage over the sulfas, which are toxic to some people."
He said, reports Spencer, that penicillin had "unlimited possibilities."
Finally, an opponent of Dawson, Stanhope Bayne-Jones tells Howard Florey in strict confidence in July 1941, that Dawson is "quite honest" but "uncritically enthusiastic" .
I think I have demonstrated what was Dawson's key insight into penicillin, the insight that drove his excitement and his passion.
It was that he realized that even a crude mix of hospital-made natural penicillin with all its natural impurities still in it was both potent AND non toxic (in fact more potent and much less toxic than drug-company-made PURE sulfa drugs).
So morally, a doctor could not wait for 100% pure natural penicillin or for 100% pure synthetic penicillin, before starting to use penicillin to save the dying by systemic injections.
He had discovered unrefined natural penicillin's big secret....
Tuesday, August 31, 2010
The Duel begins: October 1940
By October 1940, Ernst Chain knew he was in the race of his lifetime over penicillin - and while he had a MD colleague who plodded, his rival's MD colleague obviously moved like greased lightning.
By that October, Chain had a copy of Leslie Epstein's finished paper on the Lysozyme work that Epstein had done with Chain at Oxford.
The paper thanked Karl Meyer at Columbia University for the help and the lab space that Epstein had received from him.
Meyer had done similar research on Lysozyme (an enzyme that dissolves certain bacteria) - but 4 years earlier - so attribution of priority was going to be a touchy issue for all three individuals.
In fact, incensed by Epstein informing him that Chain did not plan to properly credit Meyer's earlier work, Karl Meyer was determined to extract revenge by purifying penicillin before his rival did !
Chain and Meyer, both Germans and Jews and both biochemists interested in enzymes that dissolve substrates, had known each other back in Berlin biochemical circles in the mid 1920s.
They had become serious rivals in the mid-1930s , both publishing on lysozyme and on the 'spreading factor' that dissolved hydraluronic acid, (including the hydraluronic acid found as part of some bacteria).
Each new published article became like another dueling scar on the cheeks of rival german students.
Now penicillin also looked to be another enzyme that dissolved bacteria - a new point of rivalry.
Both unlike the earlier two, it seemed to have the potential to cure life-threatening diseases - and bring world fame to the biochemist connected to the first team that did so.
Now Meyer's MD colleague,Martin Henry Dawson, had written Chain, asking for some penicillin spores (enclosing a $5 international money order) and informing Chain he planned to use it on SBE,endocarditis, the Mount Everest of infectious disease.
Serious stuff --- clearly Meyer's team had been fully informed about Chain's two and half years of work on penicillin by Leslie Epstein.
Meanwhile Chain's MD colleague, Howard Florey, hadn't yet even started scaling up to the pilot plant size of production needed to treat human patients.
Chain did send some penicillin spores - eventually - spores that never produced penicillin.
Perhaps an accident - perhaps deliberate.
Too late - Dawson mailed him a letter on October 28th 1940 : Dawson had already gotten Fleming's spores from an American researcher , grown it, tested it and injected concentrated penicillin into two SBE patients on October 16th 1940.
Beaten to the punch.
All Chain could hope to do was to avoid being blamed for Epstein telling Meyer about the secret penicillin project, by not telling anyone about the Dawson letters
That and then try to light a fire under Florey to 'do the clinical' as soon as possible.
Unfortunately, Chain had come to realize that Florey never did anything quickly......
By that October, Chain had a copy of Leslie Epstein's finished paper on the Lysozyme work that Epstein had done with Chain at Oxford.
The paper thanked Karl Meyer at Columbia University for the help and the lab space that Epstein had received from him.
Meyer had done similar research on Lysozyme (an enzyme that dissolves certain bacteria) - but 4 years earlier - so attribution of priority was going to be a touchy issue for all three individuals.
In fact, incensed by Epstein informing him that Chain did not plan to properly credit Meyer's earlier work, Karl Meyer was determined to extract revenge by purifying penicillin before his rival did !
Chain and Meyer, both Germans and Jews and both biochemists interested in enzymes that dissolve substrates, had known each other back in Berlin biochemical circles in the mid 1920s.
They had become serious rivals in the mid-1930s , both publishing on lysozyme and on the 'spreading factor' that dissolved hydraluronic acid, (including the hydraluronic acid found as part of some bacteria).
Each new published article became like another dueling scar on the cheeks of rival german students.
Now penicillin also looked to be another enzyme that dissolved bacteria - a new point of rivalry.
Both unlike the earlier two, it seemed to have the potential to cure life-threatening diseases - and bring world fame to the biochemist connected to the first team that did so.
Now Meyer's MD colleague,Martin Henry Dawson, had written Chain, asking for some penicillin spores (enclosing a $5 international money order) and informing Chain he planned to use it on SBE,endocarditis, the Mount Everest of infectious disease.
Serious stuff --- clearly Meyer's team had been fully informed about Chain's two and half years of work on penicillin by Leslie Epstein.
Meanwhile Chain's MD colleague, Howard Florey, hadn't yet even started scaling up to the pilot plant size of production needed to treat human patients.
Chain did send some penicillin spores - eventually - spores that never produced penicillin.
Perhaps an accident - perhaps deliberate.
Too late - Dawson mailed him a letter on October 28th 1940 : Dawson had already gotten Fleming's spores from an American researcher , grown it, tested it and injected concentrated penicillin into two SBE patients on October 16th 1940.
Beaten to the punch.
All Chain could hope to do was to avoid being blamed for Epstein telling Meyer about the secret penicillin project, by not telling anyone about the Dawson letters
That and then try to light a fire under Florey to 'do the clinical' as soon as possible.
Unfortunately, Chain had come to realize that Florey never did anything quickly......
Florey's "Unfinished": the unfaithful Vassal #2
In 2002, Milton Wainwright published "Fleming's Unfinished" .
Fleming was not some obscure Scottish composer and the "Unfinished" was not a musical work cobbled together from unpublished musical sketches after the composer's death and based on a close study of his mature style.
In fact a famous composer is rather undone if no one cares enough about them to find something that can be hacked into shape, published and performed to acclaim.
Now Fleming ,that is Sir Alexander Fleming, as one of the most famous names of all, is hardly thought of as someone badly done by in the "fame" department .
But among scientists, he is damned by faint praise - faulted for dropping penicillin almost as soon as he picked it up - leaving millions to die needlessly.
Milton Wainwright (and Ronald Hare, Gynn Macfarlane and Kevin Brown) have all pointed to Fleming's extensive notes on penicillin from the Fall of 1928 to the Fall of 1940 as proof he didn't quickly give up totally on penicillin as an antiseptic agent.
Wainwright goes much further and claims that Fleming had hopes for penicillin as an antibiotic in the common sense - something taken internally to cure life-threatening diseases.
I, and almost every one else, disagrees that Fleming did see it that way... until August 1942 - making him penicillin's biggest Doubting Thomas.
Anyway, Wainwright implies that Fleming was just about to wrap up his 12 years of research on penicillin, when the Florey team's first article rendered it all moot. So Wainwright was going to try to finish it for him anyway.
My belief is that Fleming had good cause to doubt penicillin's efficacy as a systemic, based on his lab work.
Fleming ,and the institute that he worked at, was never inclined 'to do the clinical' anymore than his nemesis, Howard Florey, was.
Both men avoided the wards, "preferring the deep,deep sleep of the laboratory bench to the hurly-burly of the hospital bed".
(And don't think that I haven't waited my whole life for a chance to misuse that quote in my writing...)
Florey's father and his business was betrayed ,the Florey family claims, by an unfaithful servant - an accountant.
Certainly, Florey was notorious for acting like he trusted none of the scientists directly under his employ, while giving an unusually free hand to any researcher merely 'renting space' at his Institute.
Once bitten, twice shy, I guess.
Unfaithful Vassal #1, Ernst Chain, actually saved Florey's plodding bacon, when Chain broke ranks and broke protocol on the wide front/ slow moving penicillin project in March 1940.
This is because Unfaithful vassal #2, Leslie Epstein, didn't keep silent about the penicillin project when he returned to New York on June 10th 1940.
He talked it up to Dawson's teammate Karl Meyer that summer, along with the more unpleasant news that Chain meant to dish Meyer of some credit for the chemical meaning of Lysozyme.
(This, the first big discovery of Fleming tied together Fleming and Florey and Chain and Epstein and Meyer and Dawson and Hobby.
All, for different reasons, were keenly interested in its bacteria-dissolving nature and in anything (like penicillin) that looked to be similar.)
Now Chain and Meyer were both Jewish, German and unknown scientifically.
These two young bio-chemists knew they would soon end up in alien internment camps (as thousands like them eventually did) if they couldn't soon establish scientific reputations.
Every bit of citation credit helped - well worth fighting dirty over.
Meyer resolved to get revenge by beating Chain to the punch on the purification of penicillin - Chain's private baby.
He didn't start right away, but he planned to - even if Florey's team hadn't of published in August 1940.
Meyer had to wait till his team re-assembled in September 1940 after family vacations - he absolutely needed the services of a microbiologist and a clinician if he hoped to purify penicillin.
My version of Florey's "Unfinished" looks at what would have happened if Unfaithful Vassal #1, that is Chain, hadn't broke protocol on March 18th 1940 and had some of his penicillin powder stuck into two mice by the obliging Doctor John Barnes.
Florey hated doing anything twice - freely admitted hated doing routine clinical work.
(When you and I are dying of perfectly regular lobar pneumonia caused by perfectly regular Type II s. pneumococcus, that is "routine clinical work" to Florey - though possibly not to you and I !!!)
He always wanted to be the person to do something the first time - whether or not it had any meaning outside of that feat - the athlete of science.
I take some of that back - many things he disdained doing ever - first or otherwise.
He probably never ever gave a human a needle of penicillin - he had no privileges to do so but he didn't seek them either.
He was first and last a good animal experimenter.
Putting penicillin into mice was his job, not Chain's.
And Chain had agreed to it.
But to Chain , more than to Florey, penicillin was his project - a project to purify penicillin chemically.
The proof of any success he might think he had in purifying penicillin was dependent on demonstrating the material had biological activity.
For that, as Florey (and Fleming et al) could point out, testing it against bacteria in a petri dish was all that was needed - and Chain could do that, without having to gain a hard-to-get animal testing license.
The plan, the protocol, that Fleming and Chain had sold to the MRC and to the Rockefeller Foundation called for a methodical, through, step-by-step study of penicillin.
No rush - the Rockefeller grant was intended - unofficially - to run for years and the first payment wasn't even due till March 1st 1940.
So Florey might have felt that any animal testing was way too premature and could be held off till the Fall of 1940, when he might be less busy with his current, more important, research on shock and when Chain might be further along on the chemical side.
So animal protection tests on November 25th 1940, and publication in Lancet three months later, as planned - ie in late February 1941.
Too late to learn that Dawson has already announced his results at a public lecture at the NEW SCHOOL FOR SOCIAL RESEARCH on February 12th 1941 !
The wartime story of penicillin would then look very different.
If Florey's father was ruined by an unfaithful Vassal, Howard Florey can only be thankful that he was saved by an unfaithful Vassal....
Fleming was not some obscure Scottish composer and the "Unfinished" was not a musical work cobbled together from unpublished musical sketches after the composer's death and based on a close study of his mature style.
In fact a famous composer is rather undone if no one cares enough about them to find something that can be hacked into shape, published and performed to acclaim.
Now Fleming ,that is Sir Alexander Fleming, as one of the most famous names of all, is hardly thought of as someone badly done by in the "fame" department .
But among scientists, he is damned by faint praise - faulted for dropping penicillin almost as soon as he picked it up - leaving millions to die needlessly.
Milton Wainwright (and Ronald Hare, Gynn Macfarlane and Kevin Brown) have all pointed to Fleming's extensive notes on penicillin from the Fall of 1928 to the Fall of 1940 as proof he didn't quickly give up totally on penicillin as an antiseptic agent.
Wainwright goes much further and claims that Fleming had hopes for penicillin as an antibiotic in the common sense - something taken internally to cure life-threatening diseases.
I, and almost every one else, disagrees that Fleming did see it that way... until August 1942 - making him penicillin's biggest Doubting Thomas.
Anyway, Wainwright implies that Fleming was just about to wrap up his 12 years of research on penicillin, when the Florey team's first article rendered it all moot. So Wainwright was going to try to finish it for him anyway.
My belief is that Fleming had good cause to doubt penicillin's efficacy as a systemic, based on his lab work.
Fleming ,and the institute that he worked at, was never inclined 'to do the clinical' anymore than his nemesis, Howard Florey, was.
Both men avoided the wards, "preferring the deep,deep sleep of the laboratory bench to the hurly-burly of the hospital bed".
(And don't think that I haven't waited my whole life for a chance to misuse that quote in my writing...)
Florey's father and his business was betrayed ,the Florey family claims, by an unfaithful servant - an accountant.
Certainly, Florey was notorious for acting like he trusted none of the scientists directly under his employ, while giving an unusually free hand to any researcher merely 'renting space' at his Institute.
Once bitten, twice shy, I guess.
Unfaithful Vassal #1, Ernst Chain, actually saved Florey's plodding bacon, when Chain broke ranks and broke protocol on the wide front/ slow moving penicillin project in March 1940.
This is because Unfaithful vassal #2, Leslie Epstein, didn't keep silent about the penicillin project when he returned to New York on June 10th 1940.
He talked it up to Dawson's teammate Karl Meyer that summer, along with the more unpleasant news that Chain meant to dish Meyer of some credit for the chemical meaning of Lysozyme.
(This, the first big discovery of Fleming tied together Fleming and Florey and Chain and Epstein and Meyer and Dawson and Hobby.
All, for different reasons, were keenly interested in its bacteria-dissolving nature and in anything (like penicillin) that looked to be similar.)
Now Chain and Meyer were both Jewish, German and unknown scientifically.
These two young bio-chemists knew they would soon end up in alien internment camps (as thousands like them eventually did) if they couldn't soon establish scientific reputations.
Every bit of citation credit helped - well worth fighting dirty over.
Meyer resolved to get revenge by beating Chain to the punch on the purification of penicillin - Chain's private baby.
He didn't start right away, but he planned to - even if Florey's team hadn't of published in August 1940.
Meyer had to wait till his team re-assembled in September 1940 after family vacations - he absolutely needed the services of a microbiologist and a clinician if he hoped to purify penicillin.
My version of Florey's "Unfinished" looks at what would have happened if Unfaithful Vassal #1, that is Chain, hadn't broke protocol on March 18th 1940 and had some of his penicillin powder stuck into two mice by the obliging Doctor John Barnes.
Florey hated doing anything twice - freely admitted hated doing routine clinical work.
(When you and I are dying of perfectly regular lobar pneumonia caused by perfectly regular Type II s. pneumococcus, that is "routine clinical work" to Florey - though possibly not to you and I !!!)
He always wanted to be the person to do something the first time - whether or not it had any meaning outside of that feat - the athlete of science.
I take some of that back - many things he disdained doing ever - first or otherwise.
He probably never ever gave a human a needle of penicillin - he had no privileges to do so but he didn't seek them either.
He was first and last a good animal experimenter.
Putting penicillin into mice was his job, not Chain's.
And Chain had agreed to it.
But to Chain , more than to Florey, penicillin was his project - a project to purify penicillin chemically.
The proof of any success he might think he had in purifying penicillin was dependent on demonstrating the material had biological activity.
For that, as Florey (and Fleming et al) could point out, testing it against bacteria in a petri dish was all that was needed - and Chain could do that, without having to gain a hard-to-get animal testing license.
The plan, the protocol, that Fleming and Chain had sold to the MRC and to the Rockefeller Foundation called for a methodical, through, step-by-step study of penicillin.
No rush - the Rockefeller grant was intended - unofficially - to run for years and the first payment wasn't even due till March 1st 1940.
So Florey might have felt that any animal testing was way too premature and could be held off till the Fall of 1940, when he might be less busy with his current, more important, research on shock and when Chain might be further along on the chemical side.
So animal protection tests on November 25th 1940, and publication in Lancet three months later, as planned - ie in late February 1941.
Too late to learn that Dawson has already announced his results at a public lecture at the NEW SCHOOL FOR SOCIAL RESEARCH on February 12th 1941 !
The wartime story of penicillin would then look very different.
If Florey's father was ruined by an unfaithful Vassal, Howard Florey can only be thankful that he was saved by an unfaithful Vassal....
Friday, August 20, 2010
Hobby finally gets her due
Today the best known member, at least among the general public, of the tiny Columbia University team that did the most to bring penicillin to the public as soon as possible (and did so over Columbia's dead body) is Gladys Hobby.
It is a fame she never enjoyed while still active in antibiotics.
The terminally ill Henry Dawson gets most of the credit for providing the moral energy and drive to the Columbia penicillin effort - something that Hobby and Meyer were always forthright in reminding people.
Karl Meyer lived the longest of the main foursome and lived long enough to see his lifelong scientific interest, hyaluronic acid, become a virtual growth industry.
The fourth member ,Eleanor Evelyn Chaffee (aka Mrs Eleanor Hahnel?), will emerge from the shadows, if it is the very last thing I do.
Thomas Hunter first saw fame for finishing Dawson's proof that penicillin could cure the incurable - SBE. Then he became a medical school dean best known for promoting medical education in the third world.
The fairy godfather of the team, Floyd Odlum, is probably best known today for displacing Howard Hughes at RKO.
Miriam Olmstead is today best known as a former girlfriend of the Rocket man, not Elton John, but rather Robert Goddard.
There were a few others, not as invisible as Chaffee ,but rarely connected today to this pioneering penicillin effort.
Hobby after penicillin went on to discover and prove up other big antibiotics and then take leadership roles in science organizations when few women were permitted to do so.
As a result we get many bare bones bios of her - celebrating what she did but not why.
The best - by far - of these is Elizabeth Moot O'Hern's "WOMEN SCIENTISTS" .
It is based on a 1977 interview with Hobby and includes some rare photos of Hobby - most other accounts re-cycle the photograph of Hobby shepherding Fleming about on his tour of South America.
{{What I really want is a photo of Hobby without her pearls - she always wore them - particularly at work in the lab - she was someone that people of my mother's generation would call a 'looker' because of her sharp dress and make-up.
Perhaps this was a survival technique for daring to work above her station in a very male-dominated world.
But those pearls ----I bet the woman wore them in the bath and to bed !
Perhaps not to church though - a true 'old skool' Presbyterian...}}
But O'Hern's admirable account fails to explain the 'why' in Hobby's four year struggle to bring penicillin to the public, over the opposition of many powerful forces.
I think Professor Jeremy Greene, from Harvard's History of Science Department, does a great job with the 'why' in his brief bio of Hobby in "NOTABLE AMERICAN WOMEN" edited by Susan Ware et al.
He focuses on her very first articles to explain how she came to hold a unique bridge role between the biological and chemical approaches to defeating bacterial infections.
Greene says she defends the validity of studying non-pathogenic bacteria .
(This was a real career-loser between 1870 and 1960 in medical science.)
Dawson's entire career - again opposed to his day job - was also devoted to exploring non- pathogens and pathogens as equally interesting and equally viable ways for commensal bacteria to survive in the human body.
This bonded Hobby to Dawson.
A deep commitment to seeing new research put to work saving lives, even if it hadn't been all explained in scientific terms, was what bonded Meyer to Hobby.
Meyer was the rarest of 1930s biochemists - he was clinically oriented.... aka he was face to face people-oriented.
Dawson's team was very small and not well supported by his university --- but having two such unusual people to work with him (Hobby and Meyer) helped make up for this....
 |
| GLADYS LOUNSBURY HOBBY Nov 19 1910 -July 4 1993 |
It is a fame she never enjoyed while still active in antibiotics.
The terminally ill Henry Dawson gets most of the credit for providing the moral energy and drive to the Columbia penicillin effort - something that Hobby and Meyer were always forthright in reminding people.
Karl Meyer lived the longest of the main foursome and lived long enough to see his lifelong scientific interest, hyaluronic acid, become a virtual growth industry.
The fourth member ,Eleanor Evelyn Chaffee (aka Mrs Eleanor Hahnel?), will emerge from the shadows, if it is the very last thing I do.
Thomas Hunter first saw fame for finishing Dawson's proof that penicillin could cure the incurable - SBE. Then he became a medical school dean best known for promoting medical education in the third world.
The fairy godfather of the team, Floyd Odlum, is probably best known today for displacing Howard Hughes at RKO.
Miriam Olmstead is today best known as a former girlfriend of the Rocket man, not Elton John, but rather Robert Goddard.
There were a few others, not as invisible as Chaffee ,but rarely connected today to this pioneering penicillin effort.
Hobby after penicillin went on to discover and prove up other big antibiotics and then take leadership roles in science organizations when few women were permitted to do so.
As a result we get many bare bones bios of her - celebrating what she did but not why.
The best - by far - of these is Elizabeth Moot O'Hern's "WOMEN SCIENTISTS" .
It is based on a 1977 interview with Hobby and includes some rare photos of Hobby - most other accounts re-cycle the photograph of Hobby shepherding Fleming about on his tour of South America.
{{What I really want is a photo of Hobby without her pearls - she always wore them - particularly at work in the lab - she was someone that people of my mother's generation would call a 'looker' because of her sharp dress and make-up.
 |
| Note the pearls .... |
Perhaps this was a survival technique for daring to work above her station in a very male-dominated world.
But those pearls ----I bet the woman wore them in the bath and to bed !
Perhaps not to church though - a true 'old skool' Presbyterian...}}
But O'Hern's admirable account fails to explain the 'why' in Hobby's four year struggle to bring penicillin to the public, over the opposition of many powerful forces.
I think Professor Jeremy Greene, from Harvard's History of Science Department, does a great job with the 'why' in his brief bio of Hobby in "NOTABLE AMERICAN WOMEN" edited by Susan Ware et al.
He focuses on her very first articles to explain how she came to hold a unique bridge role between the biological and chemical approaches to defeating bacterial infections.
Greene says she defends the validity of studying non-pathogenic bacteria .
(This was a real career-loser between 1870 and 1960 in medical science.)
Dawson's entire career - again opposed to his day job - was also devoted to exploring non- pathogens and pathogens as equally interesting and equally viable ways for commensal bacteria to survive in the human body.
This bonded Hobby to Dawson.
A deep commitment to seeing new research put to work saving lives, even if it hadn't been all explained in scientific terms, was what bonded Meyer to Hobby.
Meyer was the rarest of 1930s biochemists - he was clinically oriented.... aka he was face to face people-oriented.
Dawson's team was very small and not well supported by his university --- but having two such unusual people to work with him (Hobby and Meyer) helped make up for this....
Friday, August 6, 2010
Working with the like-minded
Why didn't Martin Henry Dawson work with the biochemist (Michael Heidelberger) that his own Department already had among its staff?
Why did biochemist Karl Meyer work on penicillin with Dawson rather than with clinicians in his own department?
Dawson did work with Heidelberger - but only once - once in their entire 15 year career together in the Department of Medicine.
Meyer did get two clinicians in his own department of Ophthalmology to try penicillin - but they won't publish until penicillin had become respectable.
His own boss (Phillips Thygeson) pretty well admitted he couldn't get along with Meyer.
Dawson's boss (WW Palmer) didn't believe anything could permanently cure SBE --- he also was on the same chemically-oriented wavelength as Heidelberger - who he had personally hired.
Dawson was much more biologically - almost ecologically - oriented.
Beyond that, Dawson got on with Karl Meyer because Meyer was a very rare biochemist, at least in those days.
He actually wanted his biochemical work to have an immediate and direct
impact on the patients' well being.
Dawson, too, always put the individual patient before the dictates of
abstract Science.
Pulvertaft, Queen, Duhig were all in bacteriology departments - I think this is why their penicillin pilot plants, while less important than Dawson's pioneering effort, probably came off better - and with a lot less heartaches - because growing penicillin was a natural fit in such departments.
Life isn't always fair - you must deal with it as it comes - but I wonder would Dawson have gotten Myasthenia Gravis if his boss had been more in tune with Dawson's vision of the potential of penicillin?
Why did biochemist Karl Meyer work on penicillin with Dawson rather than with clinicians in his own department?
Dawson did work with Heidelberger - but only once - once in their entire 15 year career together in the Department of Medicine.
Meyer did get two clinicians in his own department of Ophthalmology to try penicillin - but they won't publish until penicillin had become respectable.
His own boss (Phillips Thygeson) pretty well admitted he couldn't get along with Meyer.
Dawson's boss (WW Palmer) didn't believe anything could permanently cure SBE --- he also was on the same chemically-oriented wavelength as Heidelberger - who he had personally hired.
Dawson was much more biologically - almost ecologically - oriented.
Beyond that, Dawson got on with Karl Meyer because Meyer was a very rare biochemist, at least in those days.
He actually wanted his biochemical work to have an immediate and direct
impact on the patients' well being.
Dawson, too, always put the individual patient before the dictates of
abstract Science.
Pulvertaft, Queen, Duhig were all in bacteriology departments - I think this is why their penicillin pilot plants, while less important than Dawson's pioneering effort, probably came off better - and with a lot less heartaches - because growing penicillin was a natural fit in such departments.
Life isn't always fair - you must deal with it as it comes - but I wonder would Dawson have gotten Myasthenia Gravis if his boss had been more in tune with Dawson's vision of the potential of penicillin?
Thursday, July 1, 2010
Personal animosities at Columbia Eye Institute pushed Meyer into Dawson's arms on penicillin?
Blepharitis , a chronic inflammation of the eyelids, remains one of the world's most common eye problems.
Much of the time it is caused by staph bacteria and at the start of world war two, staph was one of the few common pathogen bacteria not killed by the various sulfa drugs - the 'antibiotics' of the day.
This was a big problem for the military of all the combatant nations of that war.
They regarded aviation as the alpha and the omega of modern warfare and so gave inordinate attention to the brand new field of "aviation medicine".
One only has to recall the moral panic the Allies fell into on mere rumours that the Germans had discovered the Viagra of aviation - a cortisone that let their pilots fly higher faster longer, well you get the picture.
Meyer had a consultancy with Schering Corp America - an German-owned company - involving ,among other things, attempts to create stable esters of penicillin.
Fears that Schering's work on cortisone was at the behest of the Nazis, ( it was not) rendered Schering totally suspect in the eyes of British and American intelligence circles.
Anyone connected with Schering - like Karl Meyer and his penicillin efforts - went into a little black book of "no-nos".
Aircrews and Blepharitis
An existing, generally intractable, case of blepharitis kept a lot of potential air crews out of the various air forces right at the recruiting office - that was problem A.
Problem B was that a lot of crews seemed to get blepharitis, either after they had been through training or while out on active service .
This was perhaps due to the strain of operating in the air of five miles up, behind an oxygen mask for hours.
It doesn't directly worsen your vision but it gives you blurry eyes which comes much to the same thing.
It also needlessly worried aircrews, who feared it meant worse things than it did.
Not just pilots or gunners are hit by its effects - engineers, navigation officers and bomb setters all had to look at lots of crucial numbers on lots of dials in very dim light - one pair of blurred eyes at the wrong moment could be terminal for the entire plane and crew.
Karl Meyer ,as a German Jewish emigre, had an easier relationship with Dr Ludwig Von Sallmann, who also was in exile --- from his native Austria because his wive was Jewish.
But even Sallmann only seemed to want to put Meyer's semi-purified penicillin into animals and then didn't publish anything on the results till a few years later (in 1943 - at least 2 years after the first experiments).
Typically of many,many doctors, he published freely on his early work with penicillin only after Baby Patty Malone made penicillin world famous, safe and respectable.
At least Dr Phillips Thygeson did put the crude penicillin into the eyes of 8 patients with chronic blepharitis caused by (sulfa-resistant) staph bacteria, between the late Fall of 1940 and the early Spring of 1941, with some very good results.
But he refused to publish on this success (adding his name to Fleming and Paine et al in England who also refused to publish their spectacular early successes with crude penicillin and eye diseases.)
The history of penicillin might have been much different if these doctors had crowed just a little.
Thygeson finally published on bleparitis and penicillin - in 1945 - noting its key military importance !
I think an oral history interview with Thygeson late in life suggests what happened:
I don't think he could stand Meyer much.
He accused him of being a constant paranoid about his work--- and having a gutteral accent that no student could understand.He said nothing about Sallmann's accent - though Sallmann had arrived in America about 8 years after Meyer.
Now a young student had heard all of these stories, feared dealing with Meyer but found him soft spoken and kind and stuck with him throughout his career long enough to write his affectionate obit - so opinions clearly differed on Meyer's manner and personality.
Dawson hung in with him for almost 10 years, so he couldn't have been impossible to work with.
In fact, Meyer gradually transferred himself from the eye clinic to the internal medicine department where Dawson worked.
Thygeson chose not to help out Meyer, Dawson or the fate of penicillin by publishing in an area sure to advance penicillin's importance in the eyes of the military-oriented OSRD of Vannevar Bush.
Instead he stuck to publishing on his results with sulfa drugs - these were totally pure, came via the highly conventional route of a commercial drug company - and didn't work and had potential toxic side effects.
But they didn't come from the home brew lab of Karl Meyer and that might have been a big point in their favour...
@MichaelMarshallMogoesPo
Much of the time it is caused by staph bacteria and at the start of world war two, staph was one of the few common pathogen bacteria not killed by the various sulfa drugs - the 'antibiotics' of the day.
This was a big problem for the military of all the combatant nations of that war.
They regarded aviation as the alpha and the omega of modern warfare and so gave inordinate attention to the brand new field of "aviation medicine".
One only has to recall the moral panic the Allies fell into on mere rumours that the Germans had discovered the Viagra of aviation - a cortisone that let their pilots fly higher faster longer, well you get the picture.
Meyer had a consultancy with Schering Corp America - an German-owned company - involving ,among other things, attempts to create stable esters of penicillin.
Fears that Schering's work on cortisone was at the behest of the Nazis, ( it was not) rendered Schering totally suspect in the eyes of British and American intelligence circles.
Anyone connected with Schering - like Karl Meyer and his penicillin efforts - went into a little black book of "no-nos".
Aircrews and Blepharitis
An existing, generally intractable, case of blepharitis kept a lot of potential air crews out of the various air forces right at the recruiting office - that was problem A.
Problem B was that a lot of crews seemed to get blepharitis, either after they had been through training or while out on active service .
This was perhaps due to the strain of operating in the air of five miles up, behind an oxygen mask for hours.
It doesn't directly worsen your vision but it gives you blurry eyes which comes much to the same thing.
It also needlessly worried aircrews, who feared it meant worse things than it did.
Not just pilots or gunners are hit by its effects - engineers, navigation officers and bomb setters all had to look at lots of crucial numbers on lots of dials in very dim light - one pair of blurred eyes at the wrong moment could be terminal for the entire plane and crew.
Karl Meyer ,as a German Jewish emigre, had an easier relationship with Dr Ludwig Von Sallmann, who also was in exile --- from his native Austria because his wive was Jewish.
But even Sallmann only seemed to want to put Meyer's semi-purified penicillin into animals and then didn't publish anything on the results till a few years later (in 1943 - at least 2 years after the first experiments).
Typically of many,many doctors, he published freely on his early work with penicillin only after Baby Patty Malone made penicillin world famous, safe and respectable.
At least Dr Phillips Thygeson did put the crude penicillin into the eyes of 8 patients with chronic blepharitis caused by (sulfa-resistant) staph bacteria, between the late Fall of 1940 and the early Spring of 1941, with some very good results.
But he refused to publish on this success (adding his name to Fleming and Paine et al in England who also refused to publish their spectacular early successes with crude penicillin and eye diseases.)
The history of penicillin might have been much different if these doctors had crowed just a little.
Thygeson finally published on bleparitis and penicillin - in 1945 - noting its key military importance !
I think an oral history interview with Thygeson late in life suggests what happened:
I don't think he could stand Meyer much.
He accused him of being a constant paranoid about his work--- and having a gutteral accent that no student could understand.He said nothing about Sallmann's accent - though Sallmann had arrived in America about 8 years after Meyer.
Now a young student had heard all of these stories, feared dealing with Meyer but found him soft spoken and kind and stuck with him throughout his career long enough to write his affectionate obit - so opinions clearly differed on Meyer's manner and personality.
In fact, Meyer gradually transferred himself from the eye clinic to the internal medicine department where Dawson worked.
Thygeson chose not to help out Meyer, Dawson or the fate of penicillin by publishing in an area sure to advance penicillin's importance in the eyes of the military-oriented OSRD of Vannevar Bush.
Instead he stuck to publishing on his results with sulfa drugs - these were totally pure, came via the highly conventional route of a commercial drug company - and didn't work and had potential toxic side effects.
But they didn't come from the home brew lab of Karl Meyer and that might have been a big point in their favour...
@MichaelMarshallMogoesPo
Wednesday, June 30, 2010
Dawson had been set to be the "invisible man", the Charles Fletcher of The Manhattan Pilot
I believe that for two critical weeks at the very beginning of the The Manhattan Project, Martin Henry Dawson was not set to be the team leader/senior investigator - in fact he was not expected to be involved at all.
The team was supposed to be led by the biochemist Karl Meyer, with someone (anyone) acting as the microbiologist to test the 'in vitro' activity of the penicillin produced , again with some doctor (anyone) from Columbia Presbyterian's eye clinic in the clinician's job (the nominal job of Dawson on the final Pilot team) .
The penicillin pilot's aim, at that point, was simply (!) to purify and then synthesize penicillin - most of the small amounts of crude penicillin produced would have to be destroyed in crystallization (purification) experiments.
Only tiny, tiny amounts could be spared to show the resulting penicillin still retained the needed biological activity against bacteria on a glass slide or against bacteria on/in a human.
These were expected to be merely subordinate activities to the main show - "making penicillin".
These were expected to be merely subordinate activities to the main show - "making penicillin".
Now any drug, not just penicillin, needs to be first proven safe for humans when taking internally and be available in huge amounts, before it can be injected into the body as a 'systemic' --- versus simply being dropping a bit of it into the restricted/external area around the eyeball as an 'antiseptic'.
Penicillin, in particular, quickly slips out of the body and so needs even larger amounts than most drugs to work successfully as a systemic.
This is why penicillin's first successes in Britain during the 1930 (but tragically for humanity never published), were in removing deadly bacteria from the area around the eyes.
Meyer ,working in an eye clinic ,knew these truths better than most. In fact, he did involve two doctors from his clinic to use some of his penicillin with their patients but both doctors (Von Sallmann and Thygeson) seemed dubious about its usefulness around and in the eyes (as well they should have been).
The results were not spectacular and were published a few years later.
Eyes were saved in the early 1930s from a lifetime of blindness with treatments of diluted crude penicillin that in total must have consisted of only 1.6 Oxford units of biological activity (that is equal to one millionth of a gram of pure penicillin).
By contrast, Dawson's disease of choice to test penicillin upon, SBE, subacute bacterial endocarditis, may today require 1.6 billion units of penicillin to cure.
That is one kilogram of pure penicillin - one billion times as much penicillin.
It was known in 1940 that SBE would need an extraordinary large amount of whatever drug that could kill the bacteria in its vegetations because of the unique location of the lesions and the poor blood supply of the heart valves they rested upon- that is the problem in fact that still makes SBE the 'gold standard' of intractable infections.
All drugs to date, as of 1940, had to be used in such large amounts to kill the bacteria that they killed the patient first - because even a relatively "non-toxic" drug is deadly if used by the shovelful !
It was Dawson's genius to see that penicillin's strength was not what the popular books on it still proclaim - its ability to kill bacteria - but rather its ability not to kill the patients, even when used in extraordinarily high amounts for months at a time.
And SBE proved to be just the disease to demonstrate that fact....
@MichaelMarshallMogoesPo
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