Sometimes people ask me if I think Henry Dawson should have gotten a Nobel Prize for his successful pushing of the wartime mass production of natural penicillin.
As is well known , the Nobel Prize went instead to Howard Florey (and Ernst Chain and Alexander Fleming) despite the abject failure of their alternative wartime synthetic penicillin effort.
(But because so many of Stockholm's Nobel choices have been equally flawed, you can at least praise them for consistency.)
I understand Dawson to be a modest and humble man and I believe he would have regarded his saving of lives as reward enough.
Besides, I explain, Britain really needed a consolation prize (the Nobel) to cheer it up in late 1945.
Showing posts with label ernst chain. Show all posts
Showing posts with label ernst chain. Show all posts
Jul 27, 2014
The Stone the Builders Rejected : how New York saved natural penicillin antibiotics from the British
In London in 1928 , Sir Alexander Fleming discovered natural penicillin as a potential antibiotic but then rejected it - saying it would only be useful if chemically synthesized and even then only as a external antiseptic.
Sir Howard Florey at Oxford, together with chemist Sir Ernst Chain, took up Fleming's challenge to chemically synthesize penicillin and for a decade - from the late 1930s to the late 1940s, his lab chased the chimera of totally synthesized commercial penicillin without any success.
All three men - and these three men alone - got the Nobel Prize for penicillin .
This despite the fact that the penicillin that actually saves lives is still natural in origin, not synthetic , and is a general antibiotic and not a external antiseptic --- never before or since has abject failure been so grandly rewarded !
That penicillin - the penicillin that saved millions of lives during and immediately after the war -is still the the basis of our huge family of related beta lactam antibiotics that remains our front line defence against bacterial death.
It was left to New York to pick up the stone the British builders rejected and make it into the cornerstone of our entire antibiotics industry.
New York (Manhattan) gave the first ever penicillin shots (October 16 1940) not Britain and the patient from Bronx , who was dying from then invariably fatal endocarditis , actually went home alive !
New York had the world's first pilot plant sized penicillin effort (Fall 1940).
New York gave the first ever shots of commercial penicillin
released for use on patients, made by Brooklyn-based Pfizer in March 1942 .
In August 1943, a dying baby from Queens got life-saving penicillin only after the flagship New York newspaper of the Hearst newspaper chain intervened - the story went world-wide and Doctor Mom for the first time started demanding penicillin from government and industry.
More importantly, her story morally inspired the boss of Pfizer to build the world's first serious penicillin plant - posthaste plus plus plus.
Fifteen years after natural penicillin was discovered and rejected , the world's public suddenly wanted tons of it - yesterday .
But virtually all of Big Pharma worldwide - like Fleming and Florey - still preferred to wait for (patentable) synthetic penicillin because natural penicillin could be produced by anyone and what industry really wants free enterprise if it means a lots of new competitors?
In the Fall of 1943, penicillin really got a boost when a Staten Island doctor announced that contrary to the medical consensus , it could cure syphilis quickly and safely.
A much-feared world-wide scourge for 500 years , far bigger than AIDS, suddenly almost a thing of the past - thanks to penicillin !
But natural penicillin was still costly to produce , in terms of units produced per dollar of feedstock , machinery and labour.
Then a scientist in Cold Spring Harbour Long Island was finally listened to - for years he had an idea to make the penicillium produce a lot more penicillin per dollar of effort.
Soon a hundred times as much penicillin was coming out for the same dollar of effort - using his technology today we get 50,000 times (no that is not a typo) per dollar of effort as the world got in the early 1940s.
As a result of inaction by the rest of Big Pharma , New York (read : Pfizer) was left to produce 80% of the penicillin landed on D-Day - and for the rest of the war, the biggest chunk of the entire world's penicillin came from its Marcy Avenue plant.
Even if Sweden's Nobel Committee didn't know all that New York did - and all that Fleming and Florey didn't do - I firmly believe that God only knows what New York had done and He is pleased ....
Sir Howard Florey at Oxford, together with chemist Sir Ernst Chain, took up Fleming's challenge to chemically synthesize penicillin and for a decade - from the late 1930s to the late 1940s, his lab chased the chimera of totally synthesized commercial penicillin without any success.
All three men - and these three men alone - got the Nobel Prize for penicillin .
This despite the fact that the penicillin that actually saves lives is still natural in origin, not synthetic , and is a general antibiotic and not a external antiseptic --- never before or since has abject failure been so grandly rewarded !
That penicillin - the penicillin that saved millions of lives during and immediately after the war -is still the the basis of our huge family of related beta lactam antibiotics that remains our front line defence against bacterial death.
It was left to New York to pick up the stone the British builders rejected and make it into the cornerstone of our entire antibiotics industry.
New York (Manhattan) gave the first ever penicillin shots (October 16 1940) not Britain and the patient from Bronx , who was dying from then invariably fatal endocarditis , actually went home alive !
New York had the world's first pilot plant sized penicillin effort (Fall 1940).
New York gave the first ever shots of commercial penicillin
released for use on patients, made by Brooklyn-based Pfizer in March 1942 .
In August 1943, a dying baby from Queens got life-saving penicillin only after the flagship New York newspaper of the Hearst newspaper chain intervened - the story went world-wide and Doctor Mom for the first time started demanding penicillin from government and industry.
More importantly, her story morally inspired the boss of Pfizer to build the world's first serious penicillin plant - posthaste plus plus plus.
Fifteen years after natural penicillin was discovered and rejected , the world's public suddenly wanted tons of it - yesterday .
But virtually all of Big Pharma worldwide - like Fleming and Florey - still preferred to wait for (patentable) synthetic penicillin because natural penicillin could be produced by anyone and what industry really wants free enterprise if it means a lots of new competitors?
In the Fall of 1943, penicillin really got a boost when a Staten Island doctor announced that contrary to the medical consensus , it could cure syphilis quickly and safely.
A much-feared world-wide scourge for 500 years , far bigger than AIDS, suddenly almost a thing of the past - thanks to penicillin !
But natural penicillin was still costly to produce , in terms of units produced per dollar of feedstock , machinery and labour.
Then a scientist in Cold Spring Harbour Long Island was finally listened to - for years he had an idea to make the penicillium produce a lot more penicillin per dollar of effort.
Soon a hundred times as much penicillin was coming out for the same dollar of effort - using his technology today we get 50,000 times (no that is not a typo) per dollar of effort as the world got in the early 1940s.
As a result of inaction by the rest of Big Pharma , New York (read : Pfizer) was left to produce 80% of the penicillin landed on D-Day - and for the rest of the war, the biggest chunk of the entire world's penicillin came from its Marcy Avenue plant.
Even if Sweden's Nobel Committee didn't know all that New York did - and all that Fleming and Florey didn't do - I firmly believe that God only knows what New York had done and He is pleased ....
Sep 3, 2012
Former OXFORD UNIVERSITY chemist found - in National Portrait Gallery !
 |
| its all about this gold |
The world famous photographer turned 100 this month !
And the missing chemist?
He is Wilson Baker, a former Oxford University chemist associated with Big Science's highly expensive failure to synthesis penicillin during WWII.
He went missing from one of science's iconic of all photos, after he rather 'blotted his Oxford copybook' by daring to go off to work at another university.
Iit all began back in 1944 when photographer Suschitzky took a series of still photos ,to accompany an ICL-sponsored motion film on the triumph of wartime penicillin.
The film was actually a form of a rear guard action to regain some of the "life-saving penicillin" glory for Britain, after the American soda pop supplier, Charles Pfizer and Sons, became the first firm in the world to truly mass produce penicillin.
They did it the natural way, as long advocated by their associate, Dr Martin Henry Dawson.It is still the way we produce penicillin.
In the most famous shot in the penicillin still series (NPG P562) , a group of four of Oxford's best wartime chemists pose around a table.
They include Nobel prize winners Sir Robert Robinson and Sir Ernst Chain and Sir Edward Abraham (a co-developer of our most used family of antibiotics, a close relative of penicillin).
And then Wilson Baker himself, who had to settle for a FRS instead of a knighthood, perhaps because he was a committed Quaker and pacifist during WWII.
"The Chemist Vanishes...."
But ,as recounted earlier in SVE's earlier rendering, sometime after Baker 'left the family firm' , the Oxford University's copy of this famous image was butchered.
Butchered seemingly by the same high quality photo re-touchers who butchered similar photos for Stalin, after this or that former Commissar was 'liquidated', like Bain closing a factory, and had to be removed from all historical photos .
Out went Wilson and in went a cutout image of Oxford's most famous bio-tech son , Sir Howard Florey .
Florey came in via a photo scissored out crudely from another famous post-event re-staged photo : Florey and his faithful retainer needling some poor little mouse in a cage.
The resulting image never looked to be designed to avoid detection.
The fame of the mousing photo, together with the crudity of the inked backfilling to help to the final photo "jell" , ensured that anyone at all familiar with the history of penicillin would quickly detect it.
However Britain's notorious libel laws - even more favorable to the rich and powerful than those of Hitler's Germany, together with Oxford University's deep pockets for big libel law firms - ensures that no one, least of all Skygods vs earthlings , would ever call this a case of plagiarism.
Yes plagiarism , albeit allegedly done by a university itself instead of one of its young students.
Since Oxford won't do the right thing, it is very nice that the National Portrait Gallery made the original photo - with the original Wilson Baker back in - its featured photo of the month....
Aug 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....
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