Hardly dueling Scots, though.
Fleming's Cheadle Prize winning medical essay "DIAGNOSIS OF ACUTE BACTERIAL INFECTIONS" (the only time I know of that he seriously engaged the subject of endocarditis) was written in 1909 and published in the ST MARYS HOSPITAL GAZETTE (volume15 , pages 67-69,72-77).
Most biographers of Fleming felt this early essay nevertheless set out the course of his life's work - which extended for another 45 years - so it is well worth a close reading.
Dawson confounded the essay's conclusions on intravenous injections to treat endocarditis in March 1942, with his first success in reducing bacterial colonies in endocarditis patient's blood.
Critics of vaccines said endocarditis's constant shedding of small amounts of bacteria directly into the bloodstream should lead to a natural immunity against them but instead actually only led to death.
Fleming dosed himself with a staphylococcic vaccine via an intravenous injection directly into the bloodstream.
(Staph was then a far less virulent bacteria than it is today.)
He lived, having only a slight headache and fever, but gained no increased resistance to staph.
Intravenous injections of vaccines gave maximum infectious effects and minimal increases in natural antibodies said Fleming.
Despite the fact that all of Fleming's considerable wealth came from his great skill in injecting the very dangerous drug Salvarsan directly into veins, he seemed dubious on 'systemic' or intravenous medications in general.
I think this is partially why he never tested penicillin as a systemic medicine in humans - or animals.
Not till 1940 did Dawson do so for humans and Florey for animals...
Sunday, September 5, 2010
Thursday, September 2, 2010
Dawson, Florey and the multiple suppliers
Dawson first turned down Pfizer and then a month later accepted their offer of penicillin extracts, at the same time his co-worker Meyer was working with a potential competitor of Pfizer called Schering and Co, while at same time Dawson, Meyer, Hobby and Chaffee were producing their very own penicillin !
This was not unique.
Florey produced his own penicillin and was willing to ask for penicillin from any commercial firm and got commercial supllies from at least Merck, ICI and Kimball and Bishops, the latter two on a regular basis.
Why ?
And how were conflict of interests avoided?
I believe none of the commercial firms had a problem if a doctor wished to stick their penicillin (and that of all their competitors,) into patients.
Even if the doctor(s) first concentrated the commercial liquid
extracts up to a minimal level necessary for therapy - say to a dried state of 30-50 units per mg.
None of this would affect the commercial interests of the firms.
But it would be unfair if a doctor used commercial extracts to improve extraction processes or to do chemical synthesis work on the firms' offerings.
The firms were spending lots of money on these sorts of activities and hoped to eventually profit from it.
They won't want the doctor get to the patent office first or pass on the information on to their favorite commercial firm.
So Dawson, who cared not for the chemical synthesis of penicillin, could treat patients with Pfizer penicillin, while Meyer the chemist used his own penicillin or that of Schering to do chemical studies.
Everybody happy.
Florey did likewise - using mostly ICI penicillin on his famous second series of treatments of patients but not using any of it for chemical studies, while his own team's penicillin mostly went to the team chemists to be destroyed in chemical studies.
It hardly jibs with the heroic image of either group now does it?
I can only say that very quickly, Meyer dropped synthesis studies and shifted to chemically altering penicillin into an ester so it worked better (ie worked slooooower) inside patients.
Morally, it is hard to fault this sort of chemical work.
Oxford claimed (ala LADs' PEN) that it produced 500 litres of penicillin a week between the Fall of 1940 till May 1944.
That is 400 million units of useful, injectable penicillin, in Duhig Units.
I feel sure than Duhig's first reaction would be the same as mine: "Bull feathers".
I bet a check of the published records will show that only 4 million units of Oxford-created penicillin ended up being used for patients in that period.
(To keep things in perspective, in 2010, 4 million units - 4 MegaUnits - is what you might receive as a daily dose, for an average serious infection. But in 1942, it should be enough to treat 40 patients with life-threatening illnesses.)
Gladys Hobby, quoting a ICI report on Oxford's efforts, says in 1941 they were producing 2 grams a week at 16-32 units a mg, ie 15,000 to 30,000 units a week or a maximum of 1 to 2 million units a penicillin a year at the outside best.
I have seen an estimated figure of 13 million units produced in total between 1938 till 1944, coming - it seems - from Norman Heatley, and that seems to match this report fairly well.
Trevor I Williams, in probably the best single book on the Oxford team ,"HOWARD FLOREY", says that even in 1942, half of the final Oxford penicillin went to the chemists.
I believe all, or almost all, went to the chemists from 1943 onwards.
Doctor Mom has a right to be skeptical about the Lads....
This was not unique.
Florey produced his own penicillin and was willing to ask for penicillin from any commercial firm and got commercial supllies from at least Merck, ICI and Kimball and Bishops, the latter two on a regular basis.
Why ?
And how were conflict of interests avoided?
I believe none of the commercial firms had a problem if a doctor wished to stick their penicillin (and that of all their competitors,) into patients.
Even if the doctor(s) first concentrated the commercial liquid
extracts up to a minimal level necessary for therapy - say to a dried state of 30-50 units per mg.
None of this would affect the commercial interests of the firms.
But it would be unfair if a doctor used commercial extracts to improve extraction processes or to do chemical synthesis work on the firms' offerings.
The firms were spending lots of money on these sorts of activities and hoped to eventually profit from it.
They won't want the doctor get to the patent office first or pass on the information on to their favorite commercial firm.
So Dawson, who cared not for the chemical synthesis of penicillin, could treat patients with Pfizer penicillin, while Meyer the chemist used his own penicillin or that of Schering to do chemical studies.
Everybody happy.
Florey did likewise - using mostly ICI penicillin on his famous second series of treatments of patients but not using any of it for chemical studies, while his own team's penicillin mostly went to the team chemists to be destroyed in chemical studies.
It hardly jibs with the heroic image of either group now does it?
I can only say that very quickly, Meyer dropped synthesis studies and shifted to chemically altering penicillin into an ester so it worked better (ie worked slooooower) inside patients.
Morally, it is hard to fault this sort of chemical work.
Oxford claimed (ala LADs' PEN) that it produced 500 litres of penicillin a week between the Fall of 1940 till May 1944.
That is 400 million units of useful, injectable penicillin, in Duhig Units.
 |
| J V (James Vincent) DUHIG |
I bet a check of the published records will show that only 4 million units of Oxford-created penicillin ended up being used for patients in that period.
(To keep things in perspective, in 2010, 4 million units - 4 MegaUnits - is what you might receive as a daily dose, for an average serious infection. But in 1942, it should be enough to treat 40 patients with life-threatening illnesses.)
Gladys Hobby, quoting a ICI report on Oxford's efforts, says in 1941 they were producing 2 grams a week at 16-32 units a mg, ie 15,000 to 30,000 units a week or a maximum of 1 to 2 million units a penicillin a year at the outside best.
I have seen an estimated figure of 13 million units produced in total between 1938 till 1944, coming - it seems - from Norman Heatley, and that seems to match this report fairly well.
Trevor I Williams, in probably the best single book on the Oxford team ,"HOWARD FLOREY", says that even in 1942, half of the final Oxford penicillin went to the chemists.
I believe all, or almost all, went to the chemists from 1943 onwards.
Doctor Mom has a right to be skeptical about the Lads....
MARJORIE DAWSON ,
still in widow's weeds in 1946, at a film industry meeting
Mom's penicillin versus Lads' penicillin
That's 'DOCTOR MOM' by the way, and 'LADS' as in British Lad's magazines (a weak rendering in North American terms might be "its a guy thing" - a stronger rendering would be that Connie Kaldor song about "Jerks" .)
I have tried out various names for what I am now calling Doctor Mom's penicillin: pragmatic penicillin, patients' penicillin --- all share a common drive - to save lives , now.
Lads' penicillin can also be usefully be called prestige penicillin, purified penicillin, priority penicillin, scientific paper penicillin, scientific penicillin ,scientists' penicillin.
The goal here is "who can get 100% pure, stable, colorless penicillin crystals first - dam the poor yield and dam the poor patients, forget that there is a War on."
(And by the way I almost never call it "penicillin" when I am thinking about it or even when I talk about it - I call it simply
"PEN" rather as the British chemists called their reports, the PEN reports, and just as the paper tags on patients undergoing penicillin treatment during the war were also labelled PEN.)
I have tried out various names for what I am now calling Doctor Mom's penicillin: pragmatic penicillin, patients' penicillin --- all share a common drive - to save lives , now.
Lads' penicillin can also be usefully be called prestige penicillin, purified penicillin, priority penicillin, scientific paper penicillin, scientific penicillin ,scientists' penicillin.
The goal here is "who can get 100% pure, stable, colorless penicillin crystals first - dam the poor yield and dam the poor patients, forget that there is a War on."
(And by the way I almost never call it "penicillin" when I am thinking about it or even when I talk about it - I call it simply
"PEN" rather as the British chemists called their reports, the PEN reports, and just as the paper tags on patients undergoing penicillin treatment during the war were also labelled PEN.)
(Yellowcake uranium (easily mistaken for early dried penicillin powder or dried mustard) together with the wartime 'products' derived from it, were also given prominent labels with black letters and symbols on a bright mustard yellow background.)
Mom's pen is expressed in a ratio of units of penicillin actually ready for use in human patients over a period of time.
As in :"Pfizer released 500 mg of dry penicillin, (the famous Lot #696) assaying at 50 units a mg, for Dawson to use on his patients in March 2nd 1942 - a total of 25,000 units of therapeutic penicillin."
Or : "Starting in October 1941,Pfizer released to Dawson a 5 gallon carboy of non-concentrated penicillin juice every week, the juice assayed at an average of 2 units a ml, so if injected immediately into a patient in the form of a drip IV, that was 160,000 units of therapeutic penicillin a month ."
Lads' penicillin can be found described - ad nausem - throughout almost any account about penicillin.
Its boastful vagueness stands in for the most basic of basic arithmetic.
Here is one example, picked at random from the recent book on early penicillin:
We are told that the Royal Navy set up a 'small' production unit in 1942. Even if you follow the penicillin saga closely, this might be the first time you have read of this effort - it must have been small potatoes.
Apparently not so, for in the very next sentence we are told their weekly production was 200 million units.
To put this in context, Pfizer - the world's largest drug firm and a company you have heard of , said it produced 400,000 units of penicillin in March 1942.
(If you have a good memory, you will recall that not all of this ended up in patients' veins - Dawson seems to have only got 25,000 units and he was Pfizer's only clinician at this point.
Most of this semi-purified dry penicillin was probably destroyed by Pfizer chemists trying to degrade it enough to guess at the building blocks of its assembly by the penicillium.)
In early 1943, it took two months for the entire American pharameutical industry to produce as much penicillin as the Royal Navy's little operation at Clevedon produced in a week.
Count me more skeptical of this story than Robert Bud is.
Another example, from Macfarlane's biography of Howard Florey.
It is the claim that production at Oxford had been 500 litres a week for a few months by January 1941.
Wednesday, September 1, 2010
Meyer to Durack: I started penicillin to get back at Chain
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....
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....
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...
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