In 1981 Harcourt Brace Jovanovich published "Treatment of Infective Endocarditis" ,edited by Alan L Bisno.
You can read it on the stacks at your closest medical school library.
I suppose the most cited article is the first, a "Review of Early Experiences in Treatment of Bacterial Endocarditis, 1940-1955", by David T Durack, M.B., D Phil.
I first read it very early in 2005.
Durack is from Australia, came to Oxford as a Rhodes Scholar, and was soon regarded as one of the best young doctors around anywhere.
He did a very through review of his chosen subject, reading through the early articles closely.
Quickly he saw something in Dawson's and Hunter's first article on SBE patients treated by penicillin that others writing about penicillin or endocarditis hadn't fully sensed .
The disease of endocarditis was in fact the very first disease to ever be treated by an antibiotic, in the modern sense of that word.
(And even perhaps cured by an antibiotic, if you want to go out on a limb - others have - but I hesitate.)
(In any case, an event that happened on October 16th 1940 - an anniversary seventy years old this year - hence my urgency in trying to finish this book as soon as I can.)
An antibiotic in the modern or common sense meaning of that word is a medication produced by microbes that is taken internally and that can save lives.
(By contrast, antiseptics are often man-made chemicals and are applied externally and are intended as a band-aid solutions for minor cuts and bruises.)
To doctors, this means an antibiotic is a systemic medication and in the case of the original penicillin (aka Penicillin G), one administrated by needle - ie parenterally.
All this fully met by Dawson's first needle of penicillin stuck into a dying patient seventy years ago next month.
Durack managed to personally contact the three key surviving members of Dawson's team and I feel he must have asked some very probing questions.
Hunter and Hobby added interesting tidbits to the historical record, but Karl Meyer dropped the biggest bombshell.
Well it was a bombshell to me anyway, because I have this thing (call me a stickler) for exact dates and figures.
Hobby and Hunter weren't at Columbia in early September 1940 when the decision to begin the penicillin project was taken and Dawson never publicly spoke how it came about.
Karl Meyer had never publicly spoke out about his motives either---- until 1981, when he was 83.
I rather doubt he ever told Dawson,Chaffee or Hobby about his motives back in 1940-1945.
His personal motives hardly seemed to mount a high moral plane that might bring others in help out.
Meyer had recently been incensed, says Durack, by an article from Ernst Chain on lysozyme that slighted Meyer's earlier work (in 1933-1936) on lysozyme.
Durack quotes Meyers as saying that when he read, in August 1940, the first Oxford article in LANCET on penicillin, he determined to quickly purify penicillin, before Chain could, to pay him back.
Durack then moves on to the matters more pertinent to the actual subject of his review.
I, on the other hand, had a much greater interest in this particular matter and as a result I had available a greater variety of other information to try and make sense of this 'claim' of Meyer.
First, I doubted that Meyer in New York could have read a copy of Lancet with a cover date of August 24th, much earlier than about September 7th in peacetime, let alone when Britain was at war.
Secondly, in an 1990s oral interview with Meyer's boss in 1940, (Phillips Thygeson), Dr. Thygeson describes Meyer as a rather typical type of chemist who is (rightfully) worried that others will steal their data.
In old fashioned mystery books circa 1880 to 1940s, the 'formula' stolen from the safe was always chemical--- not math or physics or biology.
Only in chemistry is something extremely valuable to the world outside Science reducible to a page or two of formulas and symbols.
The most famous modern chemist of them all, Robert Burns Woodward, liked to make public his total synthesis of yet another impossible-to-synthesis natural material in a brief announcement of not more than a page or two.
It was as a sort of 'guy thing' type bravado, common in male chemists involved in scientific pissing contests --- but it does mean than valuable chemical results are easily stealable.
I knew Meyer and Chain had known each other since their student days in Berlin and that both were young German Jewish emigres
very insecure about their ability to avoid a wartime internment camp --- very eager to garner citation credits, if only for the sakes of their families.
And by mischance, both were interested in the same very ,very, very narrow area of science and so bound to trip over each others' feet.
A rivalry seemed a distinct possibility.
Only one problem ---a very very big one --- Chain only published one article on lysozyme, and it didn't even get submitted to the British editors till October 28th 1940, let alone get published and find it way to America.
The Columbia penicillin effort was begun about September 9th 1940, months before this ----so could Meyer read into the future?!
I had to put Meyer's 'claim' on the mental back burner.
Then in early 2010, I read Ronald Bentley's "Leslie A (Epstein) Falk, 1915-2004, and Penicillin production at Oxford", published in the JOURNAL OF MEDICAL BIOGRAPHY, Volume 15, May 2007.
Bentley mentions that in Chain's sole article on lysozyme (of which Epstein, not Chain, is the lead author), Epstein (LE) thanks "Dr K Meyer" for lab space and assistance.
So sometime between June 10th 1940 (Epstein's return to New York) and early October 1940, Epstein was in Meyer's lab and presumably mentioned (a) how Epstein planned to dis-credit Meyer's early work and (b) that Chain was now working on penicillin and that work was very,very fruitful and would soon be published.
Alerted and incensed about (a), Meyer was also alerted about (b) so as to watch all ports for an article---- and to start attracting Dawson and Hobby to see the virtues of penicillin as a research subject.
Meyer, Chaffee and Hobby would probably have remained content to just grow enough penicillin to try and purify it.
But Dawson saw its capabilities as a possible ABF agent (anti bio-filmic agent) and the rest...... is history.
Seven flasks became seven hundred flasks, etc....
Wednesday, September 1, 2010
Fleming proved penicillin "non toxic to animals, even in large doses", says Florey and Chain
Soldiers with guns. In our cities. We're not making this up.
Florey and Chain really did say that about Fleming, in their famous penicillin grant application to the British Medical Research Council in September 1939.
It hardly squares with their claim for a place in the eternal scientific sun for finally doing the animal tests that Fleming didn't do.
But it does explain why they didn't do any animal testing with penicillin between Spring 1938 to Spring 1940 - and only then over Florey's loudly protesting dead body.
Why bother?
"Fleming's already done that."
But if the tests had been done in Spring '38, we might have had plenty of commercial penicillin by September 1939.... saving many,many lives...
Florey and Chain really did say that about Fleming, in their famous penicillin grant application to the British Medical Research Council in September 1939.
It hardly squares with their claim for a place in the eternal scientific sun for finally doing the animal tests that Fleming didn't do.
But it does explain why they didn't do any animal testing with penicillin between Spring 1938 to Spring 1940 - and only then over Florey's loudly protesting dead body.
Why bother?
"Fleming's already done that."
But if the tests had been done in Spring '38, we might have had plenty of commercial penicillin by September 1939.... saving many,many lives...
Chain irks boss - puts snakes before lysozyme
When Ernst Chain was hired as the Dunn Pathology School's biochemist in the Spring of 1935, his new boss, Howard Florey only asked one specific thing of Chain.
Florey wanted him to determine the chemical action of Lysozyme, an enzyme that Florey thought might be the cause of ulcers (particularly his own ulcer!)
But Chain first turned to his own work on the chemical action of the enzyme that made some snake venoms so extraordinarily and so quickly lethal in truly tiny amounts.
But now, in early 1936, he was made aware that someone he knew of very well indeed, a fellow German Jewish biochemist emigre he had met earlier in Berlin, Karl Meyer, had been and done up Lysozyme already.
The papers had been submitted in late 1935 and a little research revealed that Meyer had already published on Lysozyme in the prestigious journal SCIENCE , based on work from 1933.
So Chain had to scramble - and from this date, he regarded Meyer as his biggest rival in studying lytic (dissolving) enzymes.
What had happened was that both men, unaware of each other's interest, had settled on this same narrow area of science to base their life's work upon !
And since both men, plus plenty of others, mistakenly regarded penicillin as a lytic enzyme, a showdown was sure to come one day.
For both men, this 'guy thing' dueling over citation credit in a obscure backwater of science got badly away from them when it turned out penicillin had more than academic importance.
In the case of Meyer, he gave up the control of his penicillin project to his colleague Martin Henry Dawson.
He did so, when it became clear that powerful elements of the American and British governments were determined to see that Meyer was to play no role in the chemistry of penicillin.
They indicated this by engaging in repeated acts of censorship of his publications and by firing his colleagues from the Schering Corporation of America.
Chain also lost his penicillin project to his boss Florey, when the animal studies of the substance suddenly got interesting.
(Florey was well known for letting you do all the heavy lifting on a project that you and him were supposedly jointly involved in, only to have him steal it from under you if something promising turned up.
He got away with it, technically, because he was the senior investigator - but it hardly made him popular.
And it explains why the lazy but likable Fleming got most of the credit for the Oxford team's work.)
But Florey had no interest in the clinical side of penicillin and quickly became just the administrator of the overall Oxford penicillin project, away from England almost more than he was home.
Now Chain could regain some control, by throwing himself into the
work to purify and then totally synthesize penicillin - something Chain and the Oxford team did in February 1944.
But it turned out the yield was terrible and the process long , difficult and very expensive.
Meanwhile, Dawson had gotten his chosen corporate partner, Pfizer, morally committed to producing as much penicillin as possible as soon as possible.
That meant NATURAL (microbe-made) penicillin - the way we still produce all the various penicillins and beta lactam antibiotics.
In the end, Nature batted last and it batted long.
The supposedly simple, unchanging, (etc) creatures in the Domain of microbes vanquished the efforts of all the best PhDs in the human Domain of Chemistry.
Chain never returned to Lysozyme - penicillin , even his failed
synthetic efforts, still gave him a knighthood and a Nobel prize.
Why bother?
Meyer got no personal gain out of his four years of penicillin efforts - just personal heartaches.
But he had the quiet satisfaction that his personal efforts to save a few lives had moved Pfizer, the company that finally gave us the mass penicillin that saved millions of lives.
In 1946, the war over, Meyer turned back to Lysozyme, with his wartime research assistant on penicillin, Eleanor Chaffee ( now Hahnel) helping him.
Meyer kept up his work on Lysozyme and other lytic enzymes long past his formal retirement.
By then Chain, noticeably mellowing in his later years, had died.
Meyer , too, finally revealed his secret, the one he never told Chaffee, Dawson or Gladys Hobby.
He had originally embarked on penicillin merely to get back at Chain for failing to adequately credit him on his own Lysozyme work from way back in 1936.
This is truly Operatic Science - the way that Science all too often really works, if scientists would only admit it .....
Florey wanted him to determine the chemical action of Lysozyme, an enzyme that Florey thought might be the cause of ulcers (particularly his own ulcer!)
But Chain first turned to his own work on the chemical action of the enzyme that made some snake venoms so extraordinarily and so quickly lethal in truly tiny amounts.
But now, in early 1936, he was made aware that someone he knew of very well indeed, a fellow German Jewish biochemist emigre he had met earlier in Berlin, Karl Meyer, had been and done up Lysozyme already.
The papers had been submitted in late 1935 and a little research revealed that Meyer had already published on Lysozyme in the prestigious journal SCIENCE , based on work from 1933.
So Chain had to scramble - and from this date, he regarded Meyer as his biggest rival in studying lytic (dissolving) enzymes.
What had happened was that both men, unaware of each other's interest, had settled on this same narrow area of science to base their life's work upon !
And since both men, plus plenty of others, mistakenly regarded penicillin as a lytic enzyme, a showdown was sure to come one day.
For both men, this 'guy thing' dueling over citation credit in a obscure backwater of science got badly away from them when it turned out penicillin had more than academic importance.
In the case of Meyer, he gave up the control of his penicillin project to his colleague Martin Henry Dawson.
He did so, when it became clear that powerful elements of the American and British governments were determined to see that Meyer was to play no role in the chemistry of penicillin.
They indicated this by engaging in repeated acts of censorship of his publications and by firing his colleagues from the Schering Corporation of America.
Chain also lost his penicillin project to his boss Florey, when the animal studies of the substance suddenly got interesting.
(Florey was well known for letting you do all the heavy lifting on a project that you and him were supposedly jointly involved in, only to have him steal it from under you if something promising turned up.
He got away with it, technically, because he was the senior investigator - but it hardly made him popular.
And it explains why the lazy but likable Fleming got most of the credit for the Oxford team's work.)
But Florey had no interest in the clinical side of penicillin and quickly became just the administrator of the overall Oxford penicillin project, away from England almost more than he was home.
Now Chain could regain some control, by throwing himself into the
work to purify and then totally synthesize penicillin - something Chain and the Oxford team did in February 1944.
But it turned out the yield was terrible and the process long , difficult and very expensive.
Meanwhile, Dawson had gotten his chosen corporate partner, Pfizer, morally committed to producing as much penicillin as possible as soon as possible.
That meant NATURAL (microbe-made) penicillin - the way we still produce all the various penicillins and beta lactam antibiotics.
In the end, Nature batted last and it batted long.
The supposedly simple, unchanging, (etc) creatures in the Domain of microbes vanquished the efforts of all the best PhDs in the human Domain of Chemistry.
Chain never returned to Lysozyme - penicillin , even his failed
synthetic efforts, still gave him a knighthood and a Nobel prize.
Why bother?
Meyer got no personal gain out of his four years of penicillin efforts - just personal heartaches.
But he had the quiet satisfaction that his personal efforts to save a few lives had moved Pfizer, the company that finally gave us the mass penicillin that saved millions of lives.
In 1946, the war over, Meyer turned back to Lysozyme, with his wartime research assistant on penicillin, Eleanor Chaffee ( now Hahnel) helping him.
Meyer kept up his work on Lysozyme and other lytic enzymes long past his formal retirement.
By then Chain, noticeably mellowing in his later years, had died.
Meyer , too, finally revealed his secret, the one he never told Chaffee, Dawson or Gladys Hobby.
He had originally embarked on penicillin merely to get back at Chain for failing to adequately credit him on his own Lysozyme work from way back in 1936.
This is truly Operatic Science - the way that Science all too often really works, if scientists would only admit it .....
how I got into this 'penicillin thing'
People are frequently curious how I got involved in this penicillin book.
They ask "do you have a medical or science degree or something?"
I don't - particularly the 'something' .
All I can say is that all my life I have been badly bitten by the curiosity bug.
I have always been intensely curious - about anything and everything.
Like a dog with a bone.
Here , for example, is a picture taken on Vancouver's English Bay Beach in the Fall of 1960.
My parents treasure it :
I have just turned nine and while all other kids are running around playing in the sand, there I am sitting and reading a newspaper that some adult had thoughtfully/thoughtlessly left behind.
I don't know whether this curiosity is a gift from God or a curse from God, but there it is....
Michael Marshall, penicillin researcher, age nine, relaxing on beach...
They ask "do you have a medical or science degree or something?"
I don't - particularly the 'something' .
All I can say is that all my life I have been badly bitten by the curiosity bug.
I have always been intensely curious - about anything and everything.
Like a dog with a bone.
Here , for example, is a picture taken on Vancouver's English Bay Beach in the Fall of 1960.
My parents treasure it :
I have just turned nine and while all other kids are running around playing in the sand, there I am sitting and reading a newspaper that some adult had thoughtfully/thoughtlessly left behind.
I don't know whether this curiosity is a gift from God or a curse from God, but there it is....
Michael Marshall, penicillin researcher, age nine, relaxing on beach...
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....
Monday, August 30, 2010
Brotzu 'does the clinical' that Florey and Fleming didn't
You know the mantra if you have ever read a taxpayer-funded article from an academic historian about post-war science.
It was 1945's Manhattan Project and the Synthesis of Penicillin that led to the birth of Big Science.
(All bow down and worship.)
It now takes lashings of taxpayers' money and large teams of scientists to lead to big breakthroughs these days, particularly in drug research.
Hard then to explain the actions of Giuseppe Brotzu, full time mayor and part time medical scientist of Cagliari Sardinia during the hot summer days of July 1945.
Sardinia was not then and is not today a hotbed of scientific research - in a word, it was as Non-U as a place could be.
Not the sort of place to attract the big money and big teams of Big Science.
Nevertheless, world-shaking research starts with big ideas, not big money or big name scientists.
Brotzu's big idea begins when he wonders if the relative resistance that his citizens display to endemic typhoid fever is because of something in the harbour water - specifically something in the water near the raw sewer outflow into that harbour.
His big idea pays off and he discovers the first of the (ever-expanding) cephalosporin family of antibiotics - a trillion dollar industry - even bigger than the original penicillin .
Our mayor gets turned down by the big scientists in Rome - wrong party, wrong ideas.
So he grows some of his sewer fungi by using boiled placentas- from the maternity ward - as his medium, this is wartime Italy after all.
He then injects some of the raw liquid given off by this fungus into patients and finds it brings relief to people with typhoid fever.
Ie Brotzu does in 1945 what Fleming in 1928 and Florey in 1938 failed to do - he tests his discovery promptly , first via animal protection tests and then on real human patients.
Still no interest, so he creates a fake medical journal and gets a copy to Britain.
Florey's team, to its credit, is interested.
This, appropriately enough for a story set in Southern Italy, is truly "Operatic" Science and is not at all "Dignified" Science.
But our mayor's obvious agape love of his citizens led him to do some heroic things and he ended up helping to save millions of lives in the years since.
I think Martin Henry Dawson would have admired him very much....
(All bow down and worship.)
It now takes lashings of taxpayers' money and large teams of scientists to lead to big breakthroughs these days, particularly in drug research.
Hard then to explain the actions of Giuseppe Brotzu, full time mayor and part time medical scientist of Cagliari Sardinia during the hot summer days of July 1945.
Sardinia was not then and is not today a hotbed of scientific research - in a word, it was as Non-U as a place could be.
Not the sort of place to attract the big money and big teams of Big Science.
Nevertheless, world-shaking research starts with big ideas, not big money or big name scientists.
Brotzu's big idea begins when he wonders if the relative resistance that his citizens display to endemic typhoid fever is because of something in the harbour water - specifically something in the water near the raw sewer outflow into that harbour.
His big idea pays off and he discovers the first of the (ever-expanding) cephalosporin family of antibiotics - a trillion dollar industry - even bigger than the original penicillin .
Our mayor gets turned down by the big scientists in Rome - wrong party, wrong ideas.
So he grows some of his sewer fungi by using boiled placentas- from the maternity ward - as his medium, this is wartime Italy after all.
He then injects some of the raw liquid given off by this fungus into patients and finds it brings relief to people with typhoid fever.
Ie Brotzu does in 1945 what Fleming in 1928 and Florey in 1938 failed to do - he tests his discovery promptly , first via animal protection tests and then on real human patients.
Still no interest, so he creates a fake medical journal and gets a copy to Britain.
Florey's team, to its credit, is interested.
This, appropriately enough for a story set in Southern Italy, is truly "Operatic" Science and is not at all "Dignified" Science.
But our mayor's obvious agape love of his citizens led him to do some heroic things and he ended up helping to save millions of lives in the years since.
I think Martin Henry Dawson would have admired him very much....
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