...when four would feel oh so good?
In 1970,Lennard Bickel, using information from Gladys Hobby, says that Martin Henry Dawson and Karl Meyer used a sample of Alexander Fleming's penicillin-producing strain received from Roger Reid in Baltimore to deliver History's first jab of antibiotics October 16 1940, before a sample of Ernest Chain's strain of penicillin-producing mold arrived from England via the wartime postal service.
Chain's sample - if it even was penicillium notatum - turned red and gave off no penicillin.
This story was repeated by Hobby in her 1985 definitive book on the wartime development of penicillin ---- and by most penicillin authors ever since.
Reid had originally got his penicillin strain in November 1930 from Charles Thom, the world expert on penicillium strains.
Who had gotten his sample from Harold Raistrick who got his from Fleming who got it as a contaminant in the air drifting upwards from the lab of LaTouche who scrapped it off a basement wall of somebody very rich in Belgravia.
(Finally !
The idle rich do something useful.....)
On July 9th 1941, Howard Florey visited Charles Thom who says that HM Dawson ( ie MH Dawson) contacted him directly to get a sample of Fleming's strain, after Chain's strains arrived in late October 1941.
So Dawson contacted at least three people that Fall of 1940 for a good penicillin-producung strain of the mold : Chain, Reid, Thom.
Why not then Alexander Fleming ???
Why not go to the Source, the Mother Load ?
This might account for Fleming's boss (Dr Wright) knowing all about penicillin-making at New York's Columbia University in March 1941, as referenced in Dr John Hedley-Whyte's account.
Dawson had meet Fleming at least twice, for sure -- in 1936 and 1939 when both were high poo-pahs in International Microbiology Congresses.
Anyone got any opinions on this ??
Wednesday, August 11, 2010
The Crude and the Dignified, ...
....are two wildly different versions of the Saga of Penicillin Development during World War Two.
You know only too well the Dignified version, as propagated by the OSRD of Vannevar Bush and by just about every academic writer on penicillin (I think it is a requirement for them to retain tenure or something) - I call it the dignified rendition of "The Revenge of the Nerds".
Martin Henry Dawson's efforts to grow, purify and apply his own homegrown penicillin to
save patients dying from invariable fatal SBE - all the while fighting off his own hospital, his own government and his own (dying) body - is the most tasteless, the most over the top and the most crude Hollywood medical bio-pic imaginable ,since the days of the dying Marie Curie laboring long into the night over her radium ores ,in a tin shed with a leaky roof.
A Forties three hankie melodrama full bore, for sure.
Enough to make any modernist scientist recoil in distaste.
Fair enough - stone-heartedness is a disease -and they are more to be pitied than blamed, etc etc.
But the patients, the punters, the bums on the seat love it.
They like - nay - love and worship - the idea of doctors who care about them enough to be willing to die for them.
I'm telling the tale for them ---- and in hopes that a few modernist scientists and academics might re-think how they deal with the real people affected by their lab efforts....
You know only too well the Dignified version, as propagated by the OSRD of Vannevar Bush and by just about every academic writer on penicillin (I think it is a requirement for them to retain tenure or something) - I call it the dignified rendition of "The Revenge of the Nerds".
Martin Henry Dawson's efforts to grow, purify and apply his own homegrown penicillin to
save patients dying from invariable fatal SBE - all the while fighting off his own hospital, his own government and his own (dying) body - is the most tasteless, the most over the top and the most crude Hollywood medical bio-pic imaginable ,since the days of the dying Marie Curie laboring long into the night over her radium ores ,in a tin shed with a leaky roof.
A Forties three hankie melodrama full bore, for sure.
Enough to make any modernist scientist recoil in distaste.
Fair enough - stone-heartedness is a disease -and they are more to be pitied than blamed, etc etc.
But the patients, the punters, the bums on the seat love it.
They like - nay - love and worship - the idea of doctors who care about them enough to be willing to die for them.
I'm telling the tale for them ---- and in hopes that a few modernist scientists and academics might re-think how they deal with the real people affected by their lab efforts....
Australians give away British Store
Mark Oliphant flew to America in a bomber to beg them to make the Atomic Bomb after British scientists had pushed its development while the American government held back.
Howard Florey flew to America in a Clipper plane to do ditto with Penicillin, a British development that the American government had also put on the back burner.
For both Australians, they did this out of strong personal conviction that it was the right thing to do.
It is true that both also did it with approval from some mid to upper level bureaucrats within the British government.
But there hadn't been anything like a full debate at the top of the British government about the matter, before the Australians were allowed to give away the store.
If there had been, it might have led to very different decisions on what was to become so portentous to Britain's dismal post-war fate.
Try to imagine our world post-1945 if the British , not the Americans , held the whip hand in atomic bombs and penicillin.....
Howard Florey flew to America in a Clipper plane to do ditto with Penicillin, a British development that the American government had also put on the back burner.
For both Australians, they did this out of strong personal conviction that it was the right thing to do.
It is true that both also did it with approval from some mid to upper level bureaucrats within the British government.
But there hadn't been anything like a full debate at the top of the British government about the matter, before the Australians were allowed to give away the store.
If there had been, it might have led to very different decisions on what was to become so portentous to Britain's dismal post-war fate.
Try to imagine our world post-1945 if the British , not the Americans , held the whip hand in atomic bombs and penicillin.....
Monday, August 9, 2010
The NEEDLE that wasn't there....
.... changed History.
In the early 1940s ,a parent was bemoaning to a doctor that by the time he got his sick child to the New London hospital from his summer home in Stonington Connecticut a few miles away, the doctors told him it was too late and his sixteen year old daughter Mary Louise was dead from spinal meningitis.
The doctor lectured him, as was his want, that if every GP carried a needle and some penicillin G in their black bag and gave it to every suspected case of meningitis, without waiting to get the patient to hospital to have their spinal fluid tapped and typed, no child ever need die from meningitis.
But unfortunately, the doctor went on to say, drug company executives are still too slow off the mark and GPs have no penicillin to put into their bags, 15 years after its discovery....shooting a meaningful glance at the parent.
The parent went home and thought about it a while ---- God he hated that guy - always wanting more and always giving you a lecture instead of thanks for whatever you could give him ------- but he did think about it and probably even talked it over with his wife.
Who knows what happened that night. Did he tell his wife," I'd like to help Henry but you know me, I don't like to move quickly."
And perhaps his wife said softly, "I know" and then immediately wished she had never said it.
Perhaps they always agreed to never again talk about that awful night so long ago.
Who knows ?
What we do know, is that something totally unexpected happened, thanks to that parent.
True he was notoriously known as a very frugal and cautious man, but now that he actually decided to ' do something about it' , he worked like a whirling dervish.
His name was John Lawrence Smith and if you know his name at all, you know him as one of the owners of the famed Brooklyn Dodgers.
During June 1944, the Brooklyn Dodgers had one terrible road trip after another.
But John L's other Brooklyn team scored one knockout after another that June in 1944, in places like Omaha ............ Utah ...... Juno ...... Silver........ and Gold.
This is the true story of " How Omaha Got Its 'P' " - and the doctor's advice is still good today - doctors are still advised to carry and use a needleful of Pen G on every suspected case of meningitis, ASAP, if they want to save a life.
If your child's life has been saved by a prompt needleful of Penicillin G, aka benzylpenicillin , offer up thanks to that parent.
(John L Smith ,the head of Pfizer, when it produced most of the penicillin that landed on the D-Day beaches - British and Canadian beaches as well as the American ones.)
And of course to that ever nagging doctor ,Martin Henry Dawson...
In the early 1940s ,a parent was bemoaning to a doctor that by the time he got his sick child to the New London hospital from his summer home in Stonington Connecticut a few miles away, the doctors told him it was too late and his sixteen year old daughter Mary Louise was dead from spinal meningitis.
The doctor lectured him, as was his want, that if every GP carried a needle and some penicillin G in their black bag and gave it to every suspected case of meningitis, without waiting to get the patient to hospital to have their spinal fluid tapped and typed, no child ever need die from meningitis.
But unfortunately, the doctor went on to say, drug company executives are still too slow off the mark and GPs have no penicillin to put into their bags, 15 years after its discovery....shooting a meaningful glance at the parent.
The parent went home and thought about it a while ---- God he hated that guy - always wanting more and always giving you a lecture instead of thanks for whatever you could give him ------- but he did think about it and probably even talked it over with his wife.
Who knows what happened that night. Did he tell his wife," I'd like to help Henry but you know me, I don't like to move quickly."
And perhaps his wife said softly, "I know" and then immediately wished she had never said it.
Perhaps they always agreed to never again talk about that awful night so long ago.
Who knows ?
What we do know, is that something totally unexpected happened, thanks to that parent.
True he was notoriously known as a very frugal and cautious man, but now that he actually decided to ' do something about it' , he worked like a whirling dervish.
His name was John Lawrence Smith and if you know his name at all, you know him as one of the owners of the famed Brooklyn Dodgers.
During June 1944, the Brooklyn Dodgers had one terrible road trip after another.
But John L's other Brooklyn team scored one knockout after another that June in 1944, in places like Omaha ............ Utah ...... Juno ...... Silver........ and Gold.
This is the true story of " How Omaha Got Its 'P' " - and the doctor's advice is still good today - doctors are still advised to carry and use a needleful of Pen G on every suspected case of meningitis, ASAP, if they want to save a life.
If your child's life has been saved by a prompt needleful of Penicillin G, aka benzylpenicillin , offer up thanks to that parent.
(John L Smith ,the head of Pfizer, when it produced most of the penicillin that landed on the D-Day beaches - British and Canadian beaches as well as the American ones.)
And of course to that ever nagging doctor ,Martin Henry Dawson...
If you don't like NEEDLES....
.... here is the guy you don't like:
 |
| MARTIN HENRY DAWSON 1896-1945 On October 16th 1940, on the 8th floor male ward of New York's famous Columbia Presbyterian Hospital, Dr Dawson stuck the first ever needle of antibiotics (penicillin) into patient Charles Aronson, launching a billion needle jabs of antibiotics in the seventy years since. OUCH ! This Fall marks the 70th anniversary of the much feared/ much revered antibiotic needle - at New York City's CUMC. And if CUMC are true to form, they will totally ignore it: Plus ça change (plus c'est la même chose) |
Penicillin a sidebar to WWII
One of the major differences in my account of the development of penicillin from all the others, is that I don't plan to tell the 'exciting' story of penicillin, with World War Two merely as part of the backdrop.
The fact is that during the war penicillin was never more than a sidebar to the main story, even on both sides of September 1943 when it was a major news item for about eight weeks .
Events elsewhere in the war moved penicillin forwards or backwards in importance in the eyes of war planners and nothing anyone in the entire circumscribed world of penicillin development had anything like the impact upon penicillin development that changes on the war front did.
The Eisenhower-Marshall proposed dates for a major cross-channel invasion - in summer 1942 or March 1943 (Operation Sledgehammer and Operation Roundup) - meant the US Army accepted and indeed demanded mass quantities of so-so but available medical supplies now over the possibility of better medical supplies later.
Penicillin was put on the back burner - deliberately - even though its superior qualities to sulfa was sensed early on.
The decisions to take the British tack of delaying the cross-channel invasion till May 1944 (or later), allowed US Army planners, early in 1943, to admit that the sulfa drugs had always had a lot of problems and that they were increasing in intensity.
Sulfa faced growing and widespread bacterial resistance.
In addition, powdered sulfa had proven frequently deadly when used in 'real life' sun-baked combat areas where water is usually in short supply.
This, in my view, was the result of too many combat-shy senior doctors making assumptions about battlefield conditions, when they had actually avoided the battlefield as young men during World War One .
The existing Army Surgeon was sent into retirement in the Spring of 1943 and a less cautious general (Norman Kirk) replaced him --- this has not been recognized as one of the new key factor in penicillin's improved prospects in getting up to mass production in America in late 1943.
But above all, penicillin now gained the time it needed if it was to be to eased into the military medicine cabinet.
All because of the extra year of breathing room gained for war planners because of the revised dates for the cross channel invasion from 1943 to 1944.
Martin Henry Dawson's 'SBE and penicillin' work went on regardless of the war's ebb and flow and his first success with SBE patients in the Spring of 1943 had roused John L Smith of Pfizer and others and so we might have had abundant penicillin by early 1944 ,irregardless of the new military demand for it ---we will never know.
The two penicillin stories ran in parallel ,not in series, and their climax coming together during the Spring of 1943 was, in fact, a coincidence ....
The fact is that during the war penicillin was never more than a sidebar to the main story, even on both sides of September 1943 when it was a major news item for about eight weeks .
Events elsewhere in the war moved penicillin forwards or backwards in importance in the eyes of war planners and nothing anyone in the entire circumscribed world of penicillin development had anything like the impact upon penicillin development that changes on the war front did.
The Eisenhower-Marshall proposed dates for a major cross-channel invasion - in summer 1942 or March 1943 (Operation Sledgehammer and Operation Roundup) - meant the US Army accepted and indeed demanded mass quantities of so-so but available medical supplies now over the possibility of better medical supplies later.
Penicillin was put on the back burner - deliberately - even though its superior qualities to sulfa was sensed early on.
The decisions to take the British tack of delaying the cross-channel invasion till May 1944 (or later), allowed US Army planners, early in 1943, to admit that the sulfa drugs had always had a lot of problems and that they were increasing in intensity.
Sulfa faced growing and widespread bacterial resistance.
In addition, powdered sulfa had proven frequently deadly when used in 'real life' sun-baked combat areas where water is usually in short supply.
This, in my view, was the result of too many combat-shy senior doctors making assumptions about battlefield conditions, when they had actually avoided the battlefield as young men during World War One .
The existing Army Surgeon was sent into retirement in the Spring of 1943 and a less cautious general (Norman Kirk) replaced him --- this has not been recognized as one of the new key factor in penicillin's improved prospects in getting up to mass production in America in late 1943.
But above all, penicillin now gained the time it needed if it was to be to eased into the military medicine cabinet.
All because of the extra year of breathing room gained for war planners because of the revised dates for the cross channel invasion from 1943 to 1944.
Martin Henry Dawson's 'SBE and penicillin' work went on regardless of the war's ebb and flow and his first success with SBE patients in the Spring of 1943 had roused John L Smith of Pfizer and others and so we might have had abundant penicillin by early 1944 ,irregardless of the new military demand for it ---we will never know.
The two penicillin stories ran in parallel ,not in series, and their climax coming together during the Spring of 1943 was, in fact, a coincidence ....
Sunday, August 8, 2010
How to tell a lie - and prosper
On February 1st 1964, the journal NATURE ran a long feature article by Dr A N Richards, a foreign member of the Royal Society, a professor emeritus in pharmacology at the University of Pennsylvania and the head of the medical section of America's all powerful science agency, the OSRD......
(Blogger ate about 1000 words right about here - I'll re-type it when my temper cools down - I have learned to print my blog posts out as PDFs right away since this 'incident' - ARRRGH !!!!!!)
......Fulton had been out in Central California investigating aviation medicine for the military and had wandered into a lab where a fungi researcher was working with this fungi ,without proper modern precautions, and Fulton was soon stricken onto death.
(Or he simply got it during the days he spent on a military base deep in this valley - the more likely explanation but a lot less colorful story...)
The disease was worked up by the American Military during the Cold War to use as a possible Germ Warfare weapon but in fact it was usually not fatal even if not treated.
But if it spreads from your lungs to everywhere else in your body, it was and is usually fatal.
Fulton eventually knew he was very sick from this fungus but he also knew he was also getting the best possible care one of the best medical schools in the world would naturally give to one of its most senior doctors - he wasn't excessively worried.
Nor where his doctors, until they took a routine swab from a unrelated boil he had on his abdomen to type it for sulfa treatment. Unfortunately, to their shock, it was filled with the fungus --- it seemed he was a goner and all kinds of "heroic' ( ie risky, foolhardy) medical interventions were suggested, as he seemed likely to die anyway.
Fulton had been telling his main doctors that his very best friend Howard Florey was working with a totally new substance, penicillin ---- produced by another fungus --- and finding it could kill an ever-widening array of microbes.
These doctors decided not to tell Fulton that his boil meant he likely faced a painful death and instead enlisted him to pull strings to get some penicillin for a fellow patient, Anne Miller.
They secretly would divert a bit of it, to see if killed off rival fungus and so save Fulton.
This was good peacetime science - but in wartime, the medical establishment tended to say, if it isn't a common military disease, let the man die - we need the penicillin more elsewhere.
Luckily for Fulton, the military had lots of bases in this valley and military men were getting sick and dying from this fungus - so a military need could be evoked - in a stretch.
Merck, the OSRD,and the COC had all gotten pitiful pleas for penicillin before the phone calls from John Fulton---- and turned them all down.
The calls usually involved SBE, an almost always fatal form of endocarditis that - in those days - usually stricken young teens and young adults.
These kids were considered by the medical establishment as the $Fs of the $Fs, as people not worth wasting penicillin on during an all out total war.
Martin Henry Dawson had said since 1940 that he felt that penicillin could cure SBE - war or no war - and they should be saved.
No other doctor in the world believed strongly that they should - at the time.
Most still didn't feel SBEs could be cured or were a priority, even at the time of his death in 1945 - by which time he had about three dozen cures - some cured for as long as three years with a repeat bout.
Norman Heatley of Florey's Oxford University penicillin team was working for Merck and reporting everything back to Florey in England.
He had already recorded in his diary, in November 5 1941 and December 3 1941, receiving pleas to provide penicillin to individuals dying of SBE, while visiting labs in Canada, Dawson's home country.
Merck, the ORSD, the COC hadn't helped young Joan Murray with her SBE then, so why help Anne Miller now ?
(Heatley, not a medical doctor, seems to have felt in his 1942 diary that Miller might have SBE.)
Let us, for a moment, return to Richards.
The thesis of Richards and all the other medical bureaucrats in charge of wartime penicillin was simple - "give us lots of taxpayers' money, leave us alone away from taxpayer scruntiny, and we will produce penicillin quickly and cheaply and distribute it objectively and absolutely without favouritism."
In fact, the very first case the OSRD/COC and Merck was involved in was a blatant case of favoring the mighty and the wise over the weak and foolish.
Once it was secretly told to a very few people - perhaps only Richards - that the penicillin for Miller was also going to go to help save Fulton, it made it likely that penicillin would be forthcoming.
In his own right, Fulton was considered a valuable part of the medical brains that America felt it needed to husband if it was to win the war --- he and his own doctor, Francis Blake, were high up in the war medicine committees deciding American health priorities.
The scientists found that even the politicians, the military and the business elite (and perhaps the general public as well) agreed that healthy, fit 1A scientists shouldn't be drafted - too valuable to the war effort.
The same thinking said penicillin was wisely used if it saved Fulton --- unwisely used if it merely went to save 4F useless SBE kids..
More importantly, Fulton was the very best friend of Florey, a man with few really close friends.
The other closest friend that Florey had in America was Richards himself.
Richards and Merck needed Florey on their side if they were to convert a largely British effort into a profitable venture for Merck in America.
While Blake secretly pulled strings for Fulton and Fulton openly pulled strings for Miller, the key person, I believe, was Richards.
The OSRD and CMR, the COC ,the NRRL,the British MRC and TRC, Merck and other drug firms , the NRC-NAS, the military Surgeons General, basically every official and semi official body connected to wartime penicillin all reveal a long paper trail of documents showing they usually bowed to Richards' dictates.
Luckily for Fulton, while the penicillin didn't do anything for his strain of fungus, careful nursing care kept him alive till his own body pulled him through.
He apparently never knew how he had been 'used' to help save his own life.
Anne Miller's case was not the first one involving penicillin in North America.
Dawson and Meyer's homebrew penicillin and Pfizer penicillin had treated at least 15 cases by March 14th 1942, the day Anne Miller got her famous first needle.
One had gotten penicillin - in fact history's very first needle of penicillin - and been cured - but not by penicillin.
Some had been cured by Dawson's penicillin - but the penicillin hadn't been injected internally as an antibiotic only dropped into an eye as an antiseptic.
A few cases of Dawson's had already been treated by the first commercial penicillin used clinically in North America - Pfizer lot number 696, first injected March 5th 1942, according to his co-worker, Gladys Hobby,in her lab records and correspondence file, as recounted in her 1985 book, PENICILLIN - MEETING THE CHALLENGE.
Because Pfizer wasn't in the OSRD-COC-Merck-Squibb agreement, its commercial penicillin wasn't counted by Richards and the OSRD when it came to proclaiming Anne Miller the first patient cured by penicillin in America.
Nor was Abbott or Eli Lilly, both huge drug companies back then, soon to do their own independent-of-the-OSRD/COC clinical trials.
But interestingly, the OSRD/COC were glad to add Dawson's cases, produced from this invisible Pfizer penicillin, to their total of the first 100 cases treated by penicillin in America.
AND Hobby says that Richards knew and personally approved Pfizer sending this commercially-produced penicillin to Dawson to use clinicallly , though Pfizer was not bound to listen to Richards at all.
A few of the most careful historians today say that Anne Miller was the first person cured by penicillin provided by the OSRD and I think this is exactly right.
But there was a vast world of penicillin activity around the globe between 1938-1945 and much of it was not directed by the OSRD or any OSRD-bodies in other countries - it was the work of individuals who like Dawson merely thought they could do something right now, not perfect or big, that might help save a few lives around them.
Ironically once those agape scientists and amateurs got to Doctor Mom, she lit the fire under Richards' ass that finally got us penicillin en masse,overnight, 15 years after it was first discovered...
addendum : I just discovered that TV megastar Dr Gregory House did reference Fulton's rare fungus disease in one of his episodes....
(Blogger ate about 1000 words right about here - I'll re-type it when my temper cools down - I have learned to print my blog posts out as PDFs right away since this 'incident' - ARRRGH !!!!!!)
......Fulton had been out in Central California investigating aviation medicine for the military and had wandered into a lab where a fungi researcher was working with this fungi ,without proper modern precautions, and Fulton was soon stricken onto death.
(Or he simply got it during the days he spent on a military base deep in this valley - the more likely explanation but a lot less colorful story...)
The disease was worked up by the American Military during the Cold War to use as a possible Germ Warfare weapon but in fact it was usually not fatal even if not treated.
But if it spreads from your lungs to everywhere else in your body, it was and is usually fatal.
Fulton eventually knew he was very sick from this fungus but he also knew he was also getting the best possible care one of the best medical schools in the world would naturally give to one of its most senior doctors - he wasn't excessively worried.
Nor where his doctors, until they took a routine swab from a unrelated boil he had on his abdomen to type it for sulfa treatment. Unfortunately, to their shock, it was filled with the fungus --- it seemed he was a goner and all kinds of "heroic' ( ie risky, foolhardy) medical interventions were suggested, as he seemed likely to die anyway.
Fulton had been telling his main doctors that his very best friend Howard Florey was working with a totally new substance, penicillin ---- produced by another fungus --- and finding it could kill an ever-widening array of microbes.
These doctors decided not to tell Fulton that his boil meant he likely faced a painful death and instead enlisted him to pull strings to get some penicillin for a fellow patient, Anne Miller.
They secretly would divert a bit of it, to see if killed off rival fungus and so save Fulton.
This was good peacetime science - but in wartime, the medical establishment tended to say, if it isn't a common military disease, let the man die - we need the penicillin more elsewhere.
Luckily for Fulton, the military had lots of bases in this valley and military men were getting sick and dying from this fungus - so a military need could be evoked - in a stretch.
Merck, the OSRD,and the COC had all gotten pitiful pleas for penicillin before the phone calls from John Fulton---- and turned them all down.
The calls usually involved SBE, an almost always fatal form of endocarditis that - in those days - usually stricken young teens and young adults.
These kids were considered by the medical establishment as the $Fs of the $Fs, as people not worth wasting penicillin on during an all out total war.
Martin Henry Dawson had said since 1940 that he felt that penicillin could cure SBE - war or no war - and they should be saved.
No other doctor in the world believed strongly that they should - at the time.
Most still didn't feel SBEs could be cured or were a priority, even at the time of his death in 1945 - by which time he had about three dozen cures - some cured for as long as three years with a repeat bout.
Norman Heatley of Florey's Oxford University penicillin team was working for Merck and reporting everything back to Florey in England.
He had already recorded in his diary, in November 5 1941 and December 3 1941, receiving pleas to provide penicillin to individuals dying of SBE, while visiting labs in Canada, Dawson's home country.
Merck, the ORSD, the COC hadn't helped young Joan Murray with her SBE then, so why help Anne Miller now ?
(Heatley, not a medical doctor, seems to have felt in his 1942 diary that Miller might have SBE.)
Let us, for a moment, return to Richards.
The thesis of Richards and all the other medical bureaucrats in charge of wartime penicillin was simple - "give us lots of taxpayers' money, leave us alone away from taxpayer scruntiny, and we will produce penicillin quickly and cheaply and distribute it objectively and absolutely without favouritism."
In fact, the very first case the OSRD/COC and Merck was involved in was a blatant case of favoring the mighty and the wise over the weak and foolish.
Once it was secretly told to a very few people - perhaps only Richards - that the penicillin for Miller was also going to go to help save Fulton, it made it likely that penicillin would be forthcoming.
In his own right, Fulton was considered a valuable part of the medical brains that America felt it needed to husband if it was to win the war --- he and his own doctor, Francis Blake, were high up in the war medicine committees deciding American health priorities.
The scientists found that even the politicians, the military and the business elite (and perhaps the general public as well) agreed that healthy, fit 1A scientists shouldn't be drafted - too valuable to the war effort.
The same thinking said penicillin was wisely used if it saved Fulton --- unwisely used if it merely went to save 4F useless SBE kids..
More importantly, Fulton was the very best friend of Florey, a man with few really close friends.
The other closest friend that Florey had in America was Richards himself.
Richards and Merck needed Florey on their side if they were to convert a largely British effort into a profitable venture for Merck in America.
While Blake secretly pulled strings for Fulton and Fulton openly pulled strings for Miller, the key person, I believe, was Richards.
The OSRD and CMR, the COC ,the NRRL,the British MRC and TRC, Merck and other drug firms , the NRC-NAS, the military Surgeons General, basically every official and semi official body connected to wartime penicillin all reveal a long paper trail of documents showing they usually bowed to Richards' dictates.
Luckily for Fulton, while the penicillin didn't do anything for his strain of fungus, careful nursing care kept him alive till his own body pulled him through.
He apparently never knew how he had been 'used' to help save his own life.
Anne Miller's case was not the first one involving penicillin in North America.
Dawson and Meyer's homebrew penicillin and Pfizer penicillin had treated at least 15 cases by March 14th 1942, the day Anne Miller got her famous first needle.
One had gotten penicillin - in fact history's very first needle of penicillin - and been cured - but not by penicillin.
Some had been cured by Dawson's penicillin - but the penicillin hadn't been injected internally as an antibiotic only dropped into an eye as an antiseptic.
A few cases of Dawson's had already been treated by the first commercial penicillin used clinically in North America - Pfizer lot number 696, first injected March 5th 1942, according to his co-worker, Gladys Hobby,in her lab records and correspondence file, as recounted in her 1985 book, PENICILLIN - MEETING THE CHALLENGE.
Because Pfizer wasn't in the OSRD-COC-Merck-Squibb agreement, its commercial penicillin wasn't counted by Richards and the OSRD when it came to proclaiming Anne Miller the first patient cured by penicillin in America.
Nor was Abbott or Eli Lilly, both huge drug companies back then, soon to do their own independent-of-the-OSRD/COC clinical trials.
But interestingly, the OSRD/COC were glad to add Dawson's cases, produced from this invisible Pfizer penicillin, to their total of the first 100 cases treated by penicillin in America.
AND Hobby says that Richards knew and personally approved Pfizer sending this commercially-produced penicillin to Dawson to use clinicallly , though Pfizer was not bound to listen to Richards at all.
A few of the most careful historians today say that Anne Miller was the first person cured by penicillin provided by the OSRD and I think this is exactly right.
But there was a vast world of penicillin activity around the globe between 1938-1945 and much of it was not directed by the OSRD or any OSRD-bodies in other countries - it was the work of individuals who like Dawson merely thought they could do something right now, not perfect or big, that might help save a few lives around them.
Ironically once those agape scientists and amateurs got to Doctor Mom, she lit the fire under Richards' ass that finally got us penicillin en masse,overnight, 15 years after it was first discovered...
addendum : I just discovered that TV megastar Dr Gregory House did reference Fulton's rare fungus disease in one of his episodes....
Friday, August 6, 2010
Roth Spots, eye doctors lead way with penicillin
All the many good claims to be "the first ever penicillin case" involved eye problems ---- even Martin Henry Dawson's SBE cases!
In this order:
Paine/Fleming ---- pen as an antiseptic.
Dawson/Fletcher ----------pen as an antibiotic.
Let us not forget that the first to "concentrate" penicillin was another eye doctor, young Doctor Ridley, under Fleming's watch back in 1929.
Karl Meyer was a biochemist in an Eye department and needed some thin excuse to go along with Dawson's plan to use penicillin to cure SBE --- a heart disease.
Dawson's excuse - even thinner - was that SBE was a sequel of Rheumatic Fever which had arthritis as one of its features and might be connected, somehow, to Rheumatoid Arthritis.
Most doctors till recently, felt the surest sign of SBE was Roth Spots, white spots, on the retina.
Curing SBE would also cure the Roth Spot eye problem....
In this order:
Paine/Fleming ---- pen as an antiseptic.
Dawson/Fletcher ----------pen as an antibiotic.
Let us not forget that the first to "concentrate" penicillin was another eye doctor, young Doctor Ridley, under Fleming's watch back in 1929.
Karl Meyer was a biochemist in an Eye department and needed some thin excuse to go along with Dawson's plan to use penicillin to cure SBE --- a heart disease.
Dawson's excuse - even thinner - was that SBE was a sequel of Rheumatic Fever which had arthritis as one of its features and might be connected, somehow, to Rheumatoid Arthritis.
Most doctors till recently, felt the surest sign of SBE was Roth Spots, white spots, on the retina.
Curing SBE would also cure the Roth Spot eye problem....
Working with the like-minded
Why didn't Martin Henry Dawson work with the biochemist (Michael Heidelberger) that his own Department already had among its staff?
Why did biochemist Karl Meyer work on penicillin with Dawson rather than with clinicians in his own department?
Dawson did work with Heidelberger - but only once - once in their entire 15 year career together in the Department of Medicine.
Meyer did get two clinicians in his own department of Ophthalmology to try penicillin - but they won't publish until penicillin had become respectable.
His own boss (Phillips Thygeson) pretty well admitted he couldn't get along with Meyer.
Dawson's boss (WW Palmer) didn't believe anything could permanently cure SBE --- he also was on the same chemically-oriented wavelength as Heidelberger - who he had personally hired.
Dawson was much more biologically - almost ecologically - oriented.
Beyond that, Dawson got on with Karl Meyer because Meyer was a very rare biochemist, at least in those days.
He actually wanted his biochemical work to have an immediate and direct
impact on the patients' well being.
Dawson, too, always put the individual patient before the dictates of
abstract Science.
Pulvertaft, Queen, Duhig were all in bacteriology departments - I think this is why their penicillin pilot plants, while less important than Dawson's pioneering effort, probably came off better - and with a lot less heartaches - because growing penicillin was a natural fit in such departments.
Life isn't always fair - you must deal with it as it comes - but I wonder would Dawson have gotten Myasthenia Gravis if his boss had been more in tune with Dawson's vision of the potential of penicillin?
Why did biochemist Karl Meyer work on penicillin with Dawson rather than with clinicians in his own department?
Dawson did work with Heidelberger - but only once - once in their entire 15 year career together in the Department of Medicine.
Meyer did get two clinicians in his own department of Ophthalmology to try penicillin - but they won't publish until penicillin had become respectable.
His own boss (Phillips Thygeson) pretty well admitted he couldn't get along with Meyer.
Dawson's boss (WW Palmer) didn't believe anything could permanently cure SBE --- he also was on the same chemically-oriented wavelength as Heidelberger - who he had personally hired.
Dawson was much more biologically - almost ecologically - oriented.
Beyond that, Dawson got on with Karl Meyer because Meyer was a very rare biochemist, at least in those days.
He actually wanted his biochemical work to have an immediate and direct
impact on the patients' well being.
Dawson, too, always put the individual patient before the dictates of
abstract Science.
Pulvertaft, Queen, Duhig were all in bacteriology departments - I think this is why their penicillin pilot plants, while less important than Dawson's pioneering effort, probably came off better - and with a lot less heartaches - because growing penicillin was a natural fit in such departments.
Life isn't always fair - you must deal with it as it comes - but I wonder would Dawson have gotten Myasthenia Gravis if his boss had been more in tune with Dawson's vision of the potential of penicillin?
Ignoring 'day jobs' at our peril
Historians may think they are telling a faster paced tale when they leave out the minutiae
of ordinary daily life to focus on the high points of their subject's life - reasoning that these dramatic episodes are why you are buying their book.
But real people - even larger-than-life heroic real people - are worn down each day by picking up baby nappies at the store, taking out the trash, dealing with colleagues and relatives, answering routine letters or phone calls.
Remembering Mother's Day cards -- trying to fix a bank overdraft.
Perhaps the events they are famous for only took up a small fraction of each day during the period in question - squeezed in between the rest of their life.
All the more credit then for changing diapers and changing the world - when most of us can barely get through our routine day.
Alexander Fleming was ,mostly, the manager of a very large Vaccine Factory -- he discovered penicillin in his spare time.
I will not be the first or the last to say that how he dealt with penicillin after he discovered it was highly colored by the need to keep his vaccine factory profitable - because it paid for the entire institute he worked for.
Florey's day job was even more demanding - he did his famous mouse experiment in Room 46 of the Dunn Institute of Pathology that he ran.
That room number alone should tell how truly huge the Dunn Pathology Building really was.
He could have a hundred people in and about that building - and because he didn't have a hugely profitable vaccine line to sustain it, he spent most of his time trying to secure long term grants to pay them and buy them supplies and equipment.
He always freely admitted that is why he got interested in life-saving penicillin--- as an easy way for an increasingly desperate Institute Director to secure a nice large long term grant.
An honest account of Florey and penicillin would also mention his personal research interests outside of penicillin - which ranged very widely.
His mistress/closest co-worker intimated in a famous postscript in a letter to Norman Heatley that not till early 1942, four years after the penicillin project got started at Florey's institute, did it become the top research interest of Florey himself !
So for the years 1938-1941, how much time did Florey really give each day to the only research work he is remembered for today?
And Alfred Newton Richards over at the OSRD CMR - how much time did he really give to penicillin on a day by day basis ?
Supposedly plenty to judge by the hagiographies he had commissioned.
But when I follow the actual money trail from the OSRD to penicillin researchers --- or rather the non-money trail ---- I am left feeling he did nothing for penicillin much of the time.
Most of the millions he dished out each year - when millions meant plenty - went elsewhere - and I trust the money trail far more than I trust the post-success spin doctors.
Martin Henry Dawson had a day job too.
He ran an Arthritis Clinic - and in those days, arthritis was a symptom, not a cluster of diseases - much as fever isn't a disease but a symptom of many diseases.
Arthritis occurs ,transiently, in many diseases, so trying to determine what unusual disease a person might mean dragging them over to Dawson to get his opinion.
This kept the job interesting but it meant that it couldn't be regarded as a routine affair that could be handed of to a junior member while Dawson engaged in his personal research interests.
He fitted in his penicillin work between the Clinic hours, teaching classes, marking papers, doing grand rounds, helping grad students, attending committee meetings - going to his Dad's funeral back in Nova Scotia - picking up a great Persian carpet cheap the day the World's Fair closed.
Maybe while picking up baby food for the new baby because Marjorie was running late at her school.
Or maybe he did some penicillin work in between sitting down on a couch to recover his strength as his Myasthenia Gravis kicked in.
That is Real Life stuff.
And I intend to put Real Life back into my account of the Penicillin Saga.
of ordinary daily life to focus on the high points of their subject's life - reasoning that these dramatic episodes are why you are buying their book.
But real people - even larger-than-life heroic real people - are worn down each day by picking up baby nappies at the store, taking out the trash, dealing with colleagues and relatives, answering routine letters or phone calls.
Remembering Mother's Day cards -- trying to fix a bank overdraft.
Perhaps the events they are famous for only took up a small fraction of each day during the period in question - squeezed in between the rest of their life.
All the more credit then for changing diapers and changing the world - when most of us can barely get through our routine day.
Alexander Fleming was ,mostly, the manager of a very large Vaccine Factory -- he discovered penicillin in his spare time.
I will not be the first or the last to say that how he dealt with penicillin after he discovered it was highly colored by the need to keep his vaccine factory profitable - because it paid for the entire institute he worked for.
Florey's day job was even more demanding - he did his famous mouse experiment in Room 46 of the Dunn Institute of Pathology that he ran.
That room number alone should tell how truly huge the Dunn Pathology Building really was.
He could have a hundred people in and about that building - and because he didn't have a hugely profitable vaccine line to sustain it, he spent most of his time trying to secure long term grants to pay them and buy them supplies and equipment.
He always freely admitted that is why he got interested in life-saving penicillin--- as an easy way for an increasingly desperate Institute Director to secure a nice large long term grant.
An honest account of Florey and penicillin would also mention his personal research interests outside of penicillin - which ranged very widely.
His mistress/closest co-worker intimated in a famous postscript in a letter to Norman Heatley that not till early 1942, four years after the penicillin project got started at Florey's institute, did it become the top research interest of Florey himself !
So for the years 1938-1941, how much time did Florey really give each day to the only research work he is remembered for today?
And Alfred Newton Richards over at the OSRD CMR - how much time did he really give to penicillin on a day by day basis ?
Supposedly plenty to judge by the hagiographies he had commissioned.
But when I follow the actual money trail from the OSRD to penicillin researchers --- or rather the non-money trail ---- I am left feeling he did nothing for penicillin much of the time.
Most of the millions he dished out each year - when millions meant plenty - went elsewhere - and I trust the money trail far more than I trust the post-success spin doctors.
Martin Henry Dawson had a day job too.
He ran an Arthritis Clinic - and in those days, arthritis was a symptom, not a cluster of diseases - much as fever isn't a disease but a symptom of many diseases.
Arthritis occurs ,transiently, in many diseases, so trying to determine what unusual disease a person might mean dragging them over to Dawson to get his opinion.
This kept the job interesting but it meant that it couldn't be regarded as a routine affair that could be handed of to a junior member while Dawson engaged in his personal research interests.
He fitted in his penicillin work between the Clinic hours, teaching classes, marking papers, doing grand rounds, helping grad students, attending committee meetings - going to his Dad's funeral back in Nova Scotia - picking up a great Persian carpet cheap the day the World's Fair closed.
Maybe while picking up baby food for the new baby because Marjorie was running late at her school.
Or maybe he did some penicillin work in between sitting down on a couch to recover his strength as his Myasthenia Gravis kicked in.
That is Real Life stuff.
And I intend to put Real Life back into my account of the Penicillin Saga.
Thursday, August 5, 2010
Jack Frost Dark saved more lives ....
... than Al-Qaida will ever spend.
If you live in the Greater New York area, you don't need to be told that the Jack Frost brand of dark brown sugar, made in Yonkers, is good stuff.
Damn good stuff.
Your doctor might not agree though - so here is an argument that should appeal to their
medical 'sense of being': did they know that Jack Frost Dark led to the development of the greatest life-saver the world has ever known??!
I know, I know, I also said this about Vegamite, but both stories happen to be true.
Alexander Fleming got a lot of criticism over his use of ox heart medium to grow the first penicillin.
This abuse came from the first generation of penicillin authors -all sycophants of Howard Florey and all modernist to the core.
Ox heart medium is rich and complex and undefined - ie we don't know what all is in it or in what percentages.
As a result, chemists ( the modernist archetype ) hate it with a passion.
They prefer something like the all synthetic Czapek-Dox 'defined' medium - a bland mixture of water and salts you could just see Jeremy Bentham urging the British government to use to feed prisoners ,because it meant that they would remain alive while ensuring that they got no illict enjoyment from their food.
Unfortunately, the penicillium mold hates the stuff as much as prisoners do - it prefers the rich murk of the ox heart stew.
Fleming grew his mold juice in 4 to 5 days in ox heart stew while the chemists led by Raistrick took 15-20 days to get their mold juice on the sparse Quaker-approved diet.
(Interestingly, Fleming started his penicillium on a synthetic medium (Sabouraud's). He did know about them and used them ,despite what his hostile biographer, Ronald Hare, says.
But he found pre-digested extracts of spoiled meat made the penicillium produce faster AND was much much cheaper to buy. Engineers would approve on both counts - though chemists won't.)
Florey, being a chemist-manque, dismissed the ox heart brew and went for some Czapek-Dox synthetic purity instead. But it was so slooooow, and so he "modified" it.
In fact he modified it right back to Fleming's brew, more or less: he added brewer's yeast (the cast-offs from brewing beer - rich, dirty, complex, undefined, cheap.)
Vegamite is basically brewer's yeast.
Florey retained the concept of his all important 'purity' (in his own mind ,at least) while he got the speed of faster production from this dirty stew.
Coghill, out in Peoria at the NRRL, was a chemist, but a chemist-out-of-water, in charge of a biologically-oriented Fermentation Station.
He devoted much time and effort to try to first purify and then synthesise penicillin - when that failed, he fell back to raving about the use of corn steep liquors to speed production times and increase penicillin output.
Corn steep is another industry cast-off, the stuff left over after all the pure starch has been removed from corn.
It is complex, undefined, dirty and cheap.
Coghill and Merck and many others spent the entire war, trying to figure out what was the one ingredient in corn steep liquor that gave the much better results they got with it.
They planned to synthesis that one ingredient and then dump the corn steep like a used condom.
Others, like the Dawson team, just took the dirty complex stuff as a 'black box' and a gift - they wanted penicillin for patients ,not penicillin for academic papers and academic acclaim.
In the end, it was dozens of things in the corn steep or the dirty sugar that the mold loved - we still use this stuff today - as 'undefined' as ever.
Chalk one up for the post modernist way of thought.
Adorno, the German philosopher working on the Columbia campus in 1941 could explain (and did explain) this Modernist preference for inefficient and expensive defined growth mediums over cheap and efficient but undefined growth mediums.
(Or for that matter, the equally odd Modernist obsession of favoring toxic but defined drugs over drugs that are undefined but perfectly non-toxic. As a patient, I know which one I would prefer to have coursing through my veins !)
In his 1944 "DIALECTIC OF ENLIGHTENMENT", published at Columbia, (the seminal work that ushered in the post modernist era), he said that the Enlightenment's promise to lead us out of the darkness of ignorance was really an exaggerated fear of the unknown.
Not a sensible fear of the dangerous but an a priori fear of anything unknown, even ahead of things that are dangerous but known.
For penicillin read Dangerous= toxic.
Let us turn, finally, from Adorno to Meyer and Hobby and Chaffee and Dawson.
In 1942, they told the world of their secret food for their pilot penicillin plant: Jack Frost Dark.
Many others, Merck Inc among them, took up their idea, seeking the dirtiest, darkest, cheapest substitute they could find in their own local area --- if Jack Frost wasn't around.
The best brown sugar was natural or industrial brown sugar - sugar with lots of crude molasses's minerals and bio-organism waste products still in it.
It could be gotten directly from some sympathetic sugar factory chemist. Since so many industry chemists in the New York area were German or Jewish ( or both) in those days, Meyer wouldn't have found it hard to get a few hundred pound bags right off the boats from the West Indies.
It was dirt-cheap and because it was also dirty, it gave the best yield of penicillin .
You see 'defined' medium means we know exactly what the microbes like to eat, to make them produce what ever it is we want.
But using complex, un-defined ,industrial cast-off brews means we throw our hands up in the air and admit we really don't know Nature.
Instead we gave them everything and the kitchen sink and said "pick whatever you think suits you best".
I see the entire Penicillin development story 1940-1945 as a prime example and the most suitable metaphor of the shift from Modernity to Post Modernity.
So while I am making a little sport with Vegamite and Jack Frost Dark - I am also deadly serious .
Both of these common domestic foodstuffs did not just give us greater penicillin supplies when they were so badly needed.
They also represented some of the first examples of the green post-modernist way of viewing Man's relationship to Nature's creatures as being co-equals rather than Master and Slave --- when we feed penicillium Jack Frost or Vegamite, we say " maybe you are smarter than us" .
Pass the brown sugar won't you ?
If you live in the Greater New York area, you don't need to be told that the Jack Frost brand of dark brown sugar, made in Yonkers, is good stuff.
Damn good stuff.
Your doctor might not agree though - so here is an argument that should appeal to their
medical 'sense of being': did they know that Jack Frost Dark led to the development of the greatest life-saver the world has ever known??!
I know, I know, I also said this about Vegamite, but both stories happen to be true.
Alexander Fleming got a lot of criticism over his use of ox heart medium to grow the first penicillin.
This abuse came from the first generation of penicillin authors -all sycophants of Howard Florey and all modernist to the core.
Ox heart medium is rich and complex and undefined - ie we don't know what all is in it or in what percentages.
As a result, chemists ( the modernist archetype ) hate it with a passion.
They prefer something like the all synthetic Czapek-Dox 'defined' medium - a bland mixture of water and salts you could just see Jeremy Bentham urging the British government to use to feed prisoners ,because it meant that they would remain alive while ensuring that they got no illict enjoyment from their food.
Unfortunately, the penicillium mold hates the stuff as much as prisoners do - it prefers the rich murk of the ox heart stew.
Fleming grew his mold juice in 4 to 5 days in ox heart stew while the chemists led by Raistrick took 15-20 days to get their mold juice on the sparse Quaker-approved diet.
(Interestingly, Fleming started his penicillium on a synthetic medium (Sabouraud's). He did know about them and used them ,despite what his hostile biographer, Ronald Hare, says.
But he found pre-digested extracts of spoiled meat made the penicillium produce faster AND was much much cheaper to buy. Engineers would approve on both counts - though chemists won't.)
Florey, being a chemist-manque, dismissed the ox heart brew and went for some Czapek-Dox synthetic purity instead. But it was so slooooow, and so he "modified" it.
In fact he modified it right back to Fleming's brew, more or less: he added brewer's yeast (the cast-offs from brewing beer - rich, dirty, complex, undefined, cheap.)
Vegamite is basically brewer's yeast.
Florey retained the concept of his all important 'purity' (in his own mind ,at least) while he got the speed of faster production from this dirty stew.
Coghill, out in Peoria at the NRRL, was a chemist, but a chemist-out-of-water, in charge of a biologically-oriented Fermentation Station.
He devoted much time and effort to try to first purify and then synthesise penicillin - when that failed, he fell back to raving about the use of corn steep liquors to speed production times and increase penicillin output.
Corn steep is another industry cast-off, the stuff left over after all the pure starch has been removed from corn.
It is complex, undefined, dirty and cheap.
Coghill and Merck and many others spent the entire war, trying to figure out what was the one ingredient in corn steep liquor that gave the much better results they got with it.
They planned to synthesis that one ingredient and then dump the corn steep like a used condom.
Others, like the Dawson team, just took the dirty complex stuff as a 'black box' and a gift - they wanted penicillin for patients ,not penicillin for academic papers and academic acclaim.
In the end, it was dozens of things in the corn steep or the dirty sugar that the mold loved - we still use this stuff today - as 'undefined' as ever.
Chalk one up for the post modernist way of thought.
Adorno, the German philosopher working on the Columbia campus in 1941 could explain (and did explain) this Modernist preference for inefficient and expensive defined growth mediums over cheap and efficient but undefined growth mediums.
(Or for that matter, the equally odd Modernist obsession of favoring toxic but defined drugs over drugs that are undefined but perfectly non-toxic. As a patient, I know which one I would prefer to have coursing through my veins !)
In his 1944 "DIALECTIC OF ENLIGHTENMENT", published at Columbia, (the seminal work that ushered in the post modernist era), he said that the Enlightenment's promise to lead us out of the darkness of ignorance was really an exaggerated fear of the unknown.
Not a sensible fear of the dangerous but an a priori fear of anything unknown, even ahead of things that are dangerous but known.
For penicillin read Dangerous= toxic.
Let us turn, finally, from Adorno to Meyer and Hobby and Chaffee and Dawson.
In 1942, they told the world of their secret food for their pilot penicillin plant: Jack Frost Dark.
Many others, Merck Inc among them, took up their idea, seeking the dirtiest, darkest, cheapest substitute they could find in their own local area --- if Jack Frost wasn't around.
The best brown sugar was natural or industrial brown sugar - sugar with lots of crude molasses's minerals and bio-organism waste products still in it.
It could be gotten directly from some sympathetic sugar factory chemist. Since so many industry chemists in the New York area were German or Jewish ( or both) in those days, Meyer wouldn't have found it hard to get a few hundred pound bags right off the boats from the West Indies.
It was dirt-cheap and because it was also dirty, it gave the best yield of penicillin .
You see 'defined' medium means we know exactly what the microbes like to eat, to make them produce what ever it is we want.
But using complex, un-defined ,industrial cast-off brews means we throw our hands up in the air and admit we really don't know Nature.
Instead we gave them everything and the kitchen sink and said "pick whatever you think suits you best".
I see the entire Penicillin development story 1940-1945 as a prime example and the most suitable metaphor of the shift from Modernity to Post Modernity.
So while I am making a little sport with Vegamite and Jack Frost Dark - I am also deadly serious .
Both of these common domestic foodstuffs did not just give us greater penicillin supplies when they were so badly needed.
They also represented some of the first examples of the green post-modernist way of viewing Man's relationship to Nature's creatures as being co-equals rather than Master and Slave --- when we feed penicillium Jack Frost or Vegamite, we say " maybe you are smarter than us" .
Pass the brown sugar won't you ?
Wednesday, August 4, 2010
Iron Ring to Martin Henry Dawson's kids
People sometimes ask if I think if Martin Henry Dawson deserves a Nobel Prize for all his efforts in medicine and science.
Nobel Prizes only go to living scientists -a maximum of three per prize - and more often than not the Nobel Committee gives it to the wrong living scientists !
No, I think we Canadians should honor our fellow Canadian Henry Dawson in our own Canadian way.
He was not - formally - an engineer, unlike his two brothers.
But I think he fully deserves the symbol of a true engineer - the famous iron ring.
Engineers don't usually invent something truly new and significant - that is the scientist's job.
But they are the people called in to scale it up from the lab bench to pilot plant, then to full scale production, so it can start doing some good for humanity.
The people who should have been ordering the engineers in to do this work in the case of penicillin - the owners and executives of the big and little pharma firms in the UK,USA and Canada - declined to do so.
So a dying doctor - Henry Dawson - did it all up instead.
The first patient cured back in 1931 (by Cecil Paine) with penicillin-the-antiseptic, a newborn baby facing a lifetime of blindness, needed only the equivalent of one microgram (mcg) of pure penicillin.
That is the amount found in a milliliter (ml) --- or an eyedropper's worth--- of the unprocessed penicillium juice.
(A microgram is a thousandth of a milligram or a millionth of
a gram or a billionth of a kilogram.)
A milliliter (ml) aka a cubic centimeter (cc) aka a gram (gm) of liquid penicillium juice was needed (during 1928-1941) to produce that microgram.
That is a extraction ratio of one to a million, solid from liquid.
In terms of solid out from solids in, it took about 100 grams of relatively expensive solid "food"/ medium to produce 1 mg of solid bioactivity -BEFORE the huge producing and purifying losses found in large scale operations run at routine competency.
I would say that only 10% of nominal penicillin producing capacity was actually converted to finished clinical penicillin, between 1940-1942 ,in the larger pilot plant operations, based on the numbers and type of patients treated.
That is, in plain english, a conversion ratio of 1 kg of solid food producing 1 mg of solid bioactivity - a million to one ratio.
With these sort of ratios, engineers can already see the difficulties that lie ahead - before I tell them about penicillin's extreme lability and fragility...
The smallest test tube we have available is all the factory needed to produce a mcg or two of penicillin.
Which is enough to save Paine's baby, or one of Howard Florey's famous baby mice, or provide the material needed for Fleming to do all his 1928-1929 initial research using his patented micro-slide cell approach.
Scale it up 1000 times, you would now need a half dozen 2 liter Ernlenmeyer flasks to grow 1000 mcg's ( ie one milligram) worth of penicillin - about as much as Duhig and Gray used to save lives with in Brisbane in 1943.
But Dawson wanted to scale the Mount Everest of infectious disease - green SBE - the most dreaded form of the dreadful endocarditis.
He had a few lucky patients who held a strain of green strep in their heart valves that was as sensitive to penicillin as ordinary pyogenes strep was - so he could cure them with just a million times as much penicillin as Pain's baby or Florey's mouse - ie a gram of the stuff.
But other patients of his had SBE from strains about one thousand times less sensitive than ordinary pyogenes strep.
For them, he needed a kilo of pure penicillin- one billion times as much as Paine's baby needed.
That means he and his tiny pilot plant on the eighth floor of Columbia P and S would need
to process a million liters of penicillium juice over a two or three month period - ie 10 production runs of 100,000 liters each.
(That is about 200,000 milk bottles a run. In a big city dairy setup, that means processing 1000 milk bottles an hour, every hour, 24/7 for eight days straight, for each run.)
He couldn't have done that in P and S , even if his bosses had been helpful - which they weren't--- to put it mildly.
But Columbia University is set in th verye heart of New York's dairy factory district - the university fathers could have leased a vacant dairy and produced this quantity of penicillin, (much as the University of Toronto did with insulin in 1922 when they had an opportunity to help humanity.)
Dawson wanted so badly to save any and all SBE patients, not just those who were relatively healthy and had sensitive strains of bacteria, but died in early 1945 before he could get his hands on the huge amounts of penicillin needed.
But his assistant Thomas H Hunter soon had enough penicillin to save anyone who had SBE, no matter how old and sick - Dawson's ultimate goal.
Dawson knew penicillin could do the job from the moment he first read about it back in September 1940 - he knew it didn't need more purifying and perfecting for years and years - just a swift application of the production engineer's "MORE button" .
His "Manhattan Pilot" had to be content with only producing between 50 Imperial gallons and 100 US gallons of penicillium juice per eight day run - with a 50% production loss, just enough to save one SBE patient (with a very sensitive green strep strain) every two months.
However, he never actually got that level out of his 700 two liter Erlenmeyer flasks pilot plant, because he never got the cool dark room (or two or three) he needed on a permanent basis, if his penicillium were to settle down and produce.
Columbia chose instead - because it did have a choice, as Brian Mulroney said - to perfect the process (gaseous diffusion) that produced most of the world's nuclear bombs ---- ironically in that same dairy district that was more suited to making life-saving penicillin...
Nobel Prizes only go to living scientists -a maximum of three per prize - and more often than not the Nobel Committee gives it to the wrong living scientists !
No, I think we Canadians should honor our fellow Canadian Henry Dawson in our own Canadian way.
He was not - formally - an engineer, unlike his two brothers.
But I think he fully deserves the symbol of a true engineer - the famous iron ring.
Engineers don't usually invent something truly new and significant - that is the scientist's job.
But they are the people called in to scale it up from the lab bench to pilot plant, then to full scale production, so it can start doing some good for humanity.
The people who should have been ordering the engineers in to do this work in the case of penicillin - the owners and executives of the big and little pharma firms in the UK,USA and Canada - declined to do so.
So a dying doctor - Henry Dawson - did it all up instead.
The first patient cured back in 1931 (by Cecil Paine) with penicillin-the-antiseptic, a newborn baby facing a lifetime of blindness, needed only the equivalent of one microgram (mcg) of pure penicillin.
That is the amount found in a milliliter (ml) --- or an eyedropper's worth--- of the unprocessed penicillium juice.
(A microgram is a thousandth of a milligram or a millionth of
a gram or a billionth of a kilogram.)
A milliliter (ml) aka a cubic centimeter (cc) aka a gram (gm) of liquid penicillium juice was needed (during 1928-1941) to produce that microgram.
That is a extraction ratio of one to a million, solid from liquid.
In terms of solid out from solids in, it took about 100 grams of relatively expensive solid "food"/ medium to produce 1 mg of solid bioactivity -BEFORE the huge producing and purifying losses found in large scale operations run at routine competency.
I would say that only 10% of nominal penicillin producing capacity was actually converted to finished clinical penicillin, between 1940-1942 ,in the larger pilot plant operations, based on the numbers and type of patients treated.
That is, in plain english, a conversion ratio of 1 kg of solid food producing 1 mg of solid bioactivity - a million to one ratio.
With these sort of ratios, engineers can already see the difficulties that lie ahead - before I tell them about penicillin's extreme lability and fragility...
The smallest test tube we have available is all the factory needed to produce a mcg or two of penicillin.
Which is enough to save Paine's baby, or one of Howard Florey's famous baby mice, or provide the material needed for Fleming to do all his 1928-1929 initial research using his patented micro-slide cell approach.
Scale it up 1000 times, you would now need a half dozen 2 liter Ernlenmeyer flasks to grow 1000 mcg's ( ie one milligram) worth of penicillin - about as much as Duhig and Gray used to save lives with in Brisbane in 1943.
But Dawson wanted to scale the Mount Everest of infectious disease - green SBE - the most dreaded form of the dreadful endocarditis.
He had a few lucky patients who held a strain of green strep in their heart valves that was as sensitive to penicillin as ordinary pyogenes strep was - so he could cure them with just a million times as much penicillin as Pain's baby or Florey's mouse - ie a gram of the stuff.
But other patients of his had SBE from strains about one thousand times less sensitive than ordinary pyogenes strep.
For them, he needed a kilo of pure penicillin- one billion times as much as Paine's baby needed.
That means he and his tiny pilot plant on the eighth floor of Columbia P and S would need
to process a million liters of penicillium juice over a two or three month period - ie 10 production runs of 100,000 liters each.
(That is about 200,000 milk bottles a run. In a big city dairy setup, that means processing 1000 milk bottles an hour, every hour, 24/7 for eight days straight, for each run.)
He couldn't have done that in P and S , even if his bosses had been helpful - which they weren't--- to put it mildly.
But Columbia University is set in th verye heart of New York's dairy factory district - the university fathers could have leased a vacant dairy and produced this quantity of penicillin, (much as the University of Toronto did with insulin in 1922 when they had an opportunity to help humanity.)
Dawson wanted so badly to save any and all SBE patients, not just those who were relatively healthy and had sensitive strains of bacteria, but died in early 1945 before he could get his hands on the huge amounts of penicillin needed.
But his assistant Thomas H Hunter soon had enough penicillin to save anyone who had SBE, no matter how old and sick - Dawson's ultimate goal.
Dawson knew penicillin could do the job from the moment he first read about it back in September 1940 - he knew it didn't need more purifying and perfecting for years and years - just a swift application of the production engineer's "MORE button" .
His "Manhattan Pilot" had to be content with only producing between 50 Imperial gallons and 100 US gallons of penicillium juice per eight day run - with a 50% production loss, just enough to save one SBE patient (with a very sensitive green strep strain) every two months.
However, he never actually got that level out of his 700 two liter Erlenmeyer flasks pilot plant, because he never got the cool dark room (or two or three) he needed on a permanent basis, if his penicillium were to settle down and produce.
Columbia chose instead - because it did have a choice, as Brian Mulroney said - to perfect the process (gaseous diffusion) that produced most of the world's nuclear bombs ---- ironically in that same dairy district that was more suited to making life-saving penicillin...
Friday, July 30, 2010
MedStudents Save Lives Sitting On Ass
If you think Columbia university medical students do good work on their feet, consider this:
Seventy years ago this Fall, they did some of their best life-saving work, while sitting on their buns and probably nodding off !
It happened this way:
Dr Dawson's Manhattan Pilot project to grow 700 2-litre flasks worth of penicillium medium required a lot of permanent space; permanent space his practical and commonsensical bosses were unwilling to allocate to him.
Eventually he found if he put the flasks under the seats at Columbia P&S's famous teaching amphitheatre , the butts of the (mostly male) med students would provide enough heat to allow the penicillium mold to "hatch".
The thought of all those highly competitive, testosterone-driven studmuffins acting as brood hens , to birth the Era of Antibiotics seems an unlikely tale - but as in much of the Dawson saga, its all true....
Seventy years ago this Fall, they did some of their best life-saving work, while sitting on their buns and probably nodding off !
It happened this way:
Dr Dawson's Manhattan Pilot project to grow 700 2-litre flasks worth of penicillium medium required a lot of permanent space; permanent space his practical and commonsensical bosses were unwilling to allocate to him.
Eventually he found if he put the flasks under the seats at Columbia P&S's famous teaching amphitheatre , the butts of the (mostly male) med students would provide enough heat to allow the penicillium mold to "hatch".
The thought of all those highly competitive, testosterone-driven studmuffins acting as brood hens , to birth the Era of Antibiotics seems an unlikely tale - but as in much of the Dawson saga, its all true....
"PHOTO OF MARTIN HENRY DAWSON"
Thursday, July 29, 2010
Foster, Woodruff & McDaniel: is it true?
More precisely, was it all of the truth - or was it published by the bosses of Merck as a deliberate half-truth?
I have a real "moral" problem with an scientific article from 1943.
1943?
Like 68 years ago?
Exactly - and one of the junior authors (Dr Boyd Woodruff) is still alive and active, albeit as active as any 94 year old scientist can be!
And he seems a very nice man from an interview or two I have read of his.
The article comes from "the research lab" of Merck, so I suppose Merck's production staff on the factory floor can always offer up a 'plausible deniability' of the article's claims.
It was submitted for publication on May 28 1943, and published in November 1943.
Most journals ,even then, let you add short addendums till very near the actual date of printing.
It is entitled :
"MICROBIOLOGICAL ASPECTS OF PENICILLIN, III - PRODUCTION OF PENICILLIN IN SURFACE CULTURES OF PENICILLIUM NOTATUM
Now it was no secret, then or now, that the Florey team in Oxford, along with his funders at the MRC and the Rockefeller Foundation,along with his friend John Fulton at Yale, together with the OSRD, the CMR, the chemical chief at NRRL (formerly from Yale), and the COC were all extremely close to George W Merck and Merck inc.
The head of the OSRD and its chief legal counsel, along with the head of the CMR and the head of the COC all ended up on the board or acting as consultants to Merck.
Their real bond was that almost all were chemist-manques --- or as we'd say today, chemist wannabes.
The prestige of chemists never shined brighter than the years of their growing up and adulthood and so they worshipped at its fountain only a little more fervently than the average educated person did.
Florey wanted to be a research chemist - his parents said being a medical doctor was more practical.
Richards ,the head of the CMR, was an indifferent student until he fell under the spell of a chemist - he ended up teaching the new subject of pharmacology - a very chemically-oriented area of expertise.
Merck had wanted to be a research chemist - his father's early death made him the head of his (very,very) chemically-oriented drug company.
Remind me to tell you a very funny story sometime on just how chemically-oriented Merck Inc was back in the 1930s.
Robert Coghill headed up the very biologically-oriented Fermentation Division at the NRRL, but he had been a chemist and longed to do real chemistry work - ie synthesize things.
Richards at the CMR really controlled penicillin in North America, to the extent anyone did.
This article won't have come out, unless Richards was 100% happy with it.
I re-stumbled on this article (I had read it many times before) when I had problems documenting a frequently made claim of other authors on early penicillin : that the chemistry of penicillin was the only area that was censored during the war years.
I found that articles on the general and specific chemistry of penicillin were extremely abundant from 1928-1943.
I found that for the period August 1941 to about January 1943, it was actually articles on the clinical use of penicillin that were totally non-existent, and on both sides of the Atlantic.
No where would 'Doctor Mom' finds reports in her local newspaper of people snatched from the jaws of death by penicillin during that crucial 18 month period - I think these good news stories were deliberately discouraged and held back until the drug companies and the government could produce a rabbit out of their hats.
And I found no mention anywhere, until Raper and Coghill's articles in May 1944 (when the penicillin crisis had ended in a sudden and unexpected total triumph) about the new productive sub-strains of Fleming's original feeble penicillium mold developed at the NRRL from January 1942 onward.
(NRRL 1249 ,1249.B , 1249.B21)
Or of the way that production soared with the subsitution of corn steep liquor and lactose for sucrose and yeast extract,something the NRRL (and the OSRD/Richards) knew back in December 1941.
I got the distinct impression that nobody (except maybe Florey himself) knew about the real significance of lactose/corn liquor combo and not even Florey got access to these distinctly better sub-strains of penicillium.
Since Florey and Dawson (and lots of others) were struggling to produce their own penicillin until 1943-1944, ie from 2 years after these discoveries, news of all of this would have meant they would have got 10 to 20 times the yield from their existing equipment and staff effort.
They would no longer be beholden to the drug companies or the OSRD and Richards - which just might have been the point.
This article would have been read by the entire microbiology world - it was published in the Journal of Bacteriology (ASM), the leading microbiology journal in the Americas - a vast agriculturally advanced part of the world and so a hotbed of microbiological research of the practical sort.
The impression for a professional microbiologist reading this article , back in 1943, is that Merck Inc ,itself, in mid-1943, had tested a few substrains of penicillium, finding some better and some worse than Fleming's original....all pretty ho hum.
And that it found the best medium to grow penicillin on was Dawson's dirty (cheap-impure-complex) brown sugar. Again the formula was publicly available and not really a great help for a hospital lab trying to produce enough penicillin to cure one extremely ill patient a month.
(I think the average teaching hospital laboratory department needed to produce about one million units of clinical penicillin a month without extraordinary requirements of staff, space or effort if it was to feel it was worthwhile continuing working on clinical penicillin trials ,independent of what the drug companies and government would provide , ON THEIR TERMS.)
The Merck researchers said that they had tried lactose and found it no better than dirty brown sugar. No mention of corn steep liquor at all.
So was Merck using Fleming's old strain, and a dirty brown sugar medium to make all of its commercial penicillin in the Fall of 1943?
I do not believe so - and I will not believe so till I see dated photographs and hear eye witnesses under oath.
I accept that ,during war, firms and institutions will not tell their own citizens all what they are doing.
If you can't tell the truth about something, better to remain silent.
But I do not accept that you spread deliberate disinformation - which is what I think this article did - and still does.
I think it deliberately low-balled the state of the art, circa Fall 1943, of Merck's effort to increase the yield of penicillin juice produced by the mold, before the chemists stepped in to increase the yield of clinical penicillin concentrated from that juice.
This article feels like it was written in about March 1942, not in May or November 1943.
If that is so,who was it designed to mislead by being released ?
Clearly not Squibb,Pfizer,Withrop,Abbott etc - those firms that had been working with penicillin for a few years and had a pretty good idea of the state of the art of natural penicillin production in mid to late 1943.
But hundreds of other firms might want to 'try their hand' at penicillin (175 firms did apply to do just that, just after this article was submitted).
Giving them just enough information to try their hand and then to retire discouraged might just be what the Merck leadership had in mind....
I have a real "moral" problem with an scientific article from 1943.
1943?
Like 68 years ago?
Exactly - and one of the junior authors (Dr Boyd Woodruff) is still alive and active, albeit as active as any 94 year old scientist can be!
And he seems a very nice man from an interview or two I have read of his.
The article comes from "the research lab" of Merck, so I suppose Merck's production staff on the factory floor can always offer up a 'plausible deniability' of the article's claims.
It was submitted for publication on May 28 1943, and published in November 1943.
Most journals ,even then, let you add short addendums till very near the actual date of printing.
It is entitled :
"MICROBIOLOGICAL ASPECTS OF PENICILLIN, III - PRODUCTION OF PENICILLIN IN SURFACE CULTURES OF PENICILLIUM NOTATUM
Now it was no secret, then or now, that the Florey team in Oxford, along with his funders at the MRC and the Rockefeller Foundation,along with his friend John Fulton at Yale, together with the OSRD, the CMR, the chemical chief at NRRL (formerly from Yale), and the COC were all extremely close to George W Merck and Merck inc.
The head of the OSRD and its chief legal counsel, along with the head of the CMR and the head of the COC all ended up on the board or acting as consultants to Merck.
Their real bond was that almost all were chemist-manques --- or as we'd say today, chemist wannabes.
The prestige of chemists never shined brighter than the years of their growing up and adulthood and so they worshipped at its fountain only a little more fervently than the average educated person did.
Florey wanted to be a research chemist - his parents said being a medical doctor was more practical.
Richards ,the head of the CMR, was an indifferent student until he fell under the spell of a chemist - he ended up teaching the new subject of pharmacology - a very chemically-oriented area of expertise.
Merck had wanted to be a research chemist - his father's early death made him the head of his (very,very) chemically-oriented drug company.
Remind me to tell you a very funny story sometime on just how chemically-oriented Merck Inc was back in the 1930s.
Robert Coghill headed up the very biologically-oriented Fermentation Division at the NRRL, but he had been a chemist and longed to do real chemistry work - ie synthesize things.
Richards at the CMR really controlled penicillin in North America, to the extent anyone did.
This article won't have come out, unless Richards was 100% happy with it.
I re-stumbled on this article (I had read it many times before) when I had problems documenting a frequently made claim of other authors on early penicillin : that the chemistry of penicillin was the only area that was censored during the war years.
I found that articles on the general and specific chemistry of penicillin were extremely abundant from 1928-1943.
I found that for the period August 1941 to about January 1943, it was actually articles on the clinical use of penicillin that were totally non-existent, and on both sides of the Atlantic.
No where would 'Doctor Mom' finds reports in her local newspaper of people snatched from the jaws of death by penicillin during that crucial 18 month period - I think these good news stories were deliberately discouraged and held back until the drug companies and the government could produce a rabbit out of their hats.
And I found no mention anywhere, until Raper and Coghill's articles in May 1944 (when the penicillin crisis had ended in a sudden and unexpected total triumph) about the new productive sub-strains of Fleming's original feeble penicillium mold developed at the NRRL from January 1942 onward.
(NRRL 1249 ,1249.B , 1249.B21)
Or of the way that production soared with the subsitution of corn steep liquor and lactose for sucrose and yeast extract,something the NRRL (and the OSRD/Richards) knew back in December 1941.
I got the distinct impression that nobody (except maybe Florey himself) knew about the real significance of lactose/corn liquor combo and not even Florey got access to these distinctly better sub-strains of penicillium.
Since Florey and Dawson (and lots of others) were struggling to produce their own penicillin until 1943-1944, ie from 2 years after these discoveries, news of all of this would have meant they would have got 10 to 20 times the yield from their existing equipment and staff effort.
They would no longer be beholden to the drug companies or the OSRD and Richards - which just might have been the point.
This article would have been read by the entire microbiology world - it was published in the Journal of Bacteriology (ASM), the leading microbiology journal in the Americas - a vast agriculturally advanced part of the world and so a hotbed of microbiological research of the practical sort.
The impression for a professional microbiologist reading this article , back in 1943, is that Merck Inc ,itself, in mid-1943, had tested a few substrains of penicillium, finding some better and some worse than Fleming's original....all pretty ho hum.
And that it found the best medium to grow penicillin on was Dawson's dirty (cheap-impure-complex) brown sugar. Again the formula was publicly available and not really a great help for a hospital lab trying to produce enough penicillin to cure one extremely ill patient a month.
(I think the average teaching hospital laboratory department needed to produce about one million units of clinical penicillin a month without extraordinary requirements of staff, space or effort if it was to feel it was worthwhile continuing working on clinical penicillin trials ,independent of what the drug companies and government would provide , ON THEIR TERMS.)
The Merck researchers said that they had tried lactose and found it no better than dirty brown sugar. No mention of corn steep liquor at all.
So was Merck using Fleming's old strain, and a dirty brown sugar medium to make all of its commercial penicillin in the Fall of 1943?
I do not believe so - and I will not believe so till I see dated photographs and hear eye witnesses under oath.
I accept that ,during war, firms and institutions will not tell their own citizens all what they are doing.
If you can't tell the truth about something, better to remain silent.
But I do not accept that you spread deliberate disinformation - which is what I think this article did - and still does.
I think it deliberately low-balled the state of the art, circa Fall 1943, of Merck's effort to increase the yield of penicillin juice produced by the mold, before the chemists stepped in to increase the yield of clinical penicillin concentrated from that juice.
This article feels like it was written in about March 1942, not in May or November 1943.
If that is so,who was it designed to mislead by being released ?
Clearly not Squibb,Pfizer,Withrop,Abbott etc - those firms that had been working with penicillin for a few years and had a pretty good idea of the state of the art of natural penicillin production in mid to late 1943.
But hundreds of other firms might want to 'try their hand' at penicillin (175 firms did apply to do just that, just after this article was submitted).
Giving them just enough information to try their hand and then to retire discouraged might just be what the Merck leadership had in mind....
Coghill like Eisenhower had two speeches
It is well known that Eisenhower always prepared two speeches before each new amphibious landing.
The official one spoke of the day's success and gave all the credit to the brave boys who died to achieve it.
The unofficial one, prepared on a scrap of paper in pencil, also lauded the brave boys who died but it announced that the landing had failed and that Eisenhower took all the blame for the lack of success.
After every landing but one, he promptly tore up the scrap of paper and threw it away.
He called it his "In Case of Failure" speech.
But in the rush and excitement of D-Day, June 6th 1944, he clean forgot about tearing up this version of the speech.
On July 11th 1944, Eisenhower found the scrap of paper in a jacket pocket and showed it to his Naval aide, Captain Harry C Butcher,while preparing to tear it up like he had always done before.
Butcher begged Eisenhower to let him keep it instead.
Reluctantly, the General gave it to him.
Fragile with the passage of time upon a piece of cheap acidic paper, it is now one of the most precious relics in the Eisenhower Museum.
I thought of this touching story when I read Robert D Coghill's famous public speech of May 1944 that he gave (with OSRD's full approval), just after watching vials of 100,000 units of NATURAL penicillin pouring off the line at Pfizer's Marcy Avenue plant faster than he could count.
That penicillin was destined for its first ever mass clinical trial --- on the bloody beaches of Normandy on June 6th 1944.
NATURAL penicillin had both won the race to supply sufficient military penicillin vials before D-Day and had surprised everyone in the world of chemistry by beating man-made penicillin to the gate.
In the speech, Coghill, for the first time ,gave the details in a soon-to-be-cliched story of
how his NRRL facility in Peoria (a branch of the US Department of Agriculture) had made the success of NATURAL penicillin all possible.
Charged with finding a use for thousands of tons of a farm waste product, the dank murky corn steep liquor left over from the wet conversion of corn into cornstarch, his NRRL staff had tried it as food on penicillin and presto,it turned out to be the one secret ingredient that neither Britain or Germany had and the only ingredient that made NATURAL penicillin production viable.
Cue happy smiling children recovering thanks to penicillin from Peoria - cue the happy Mid-West farmers & voters in Republican states thanking the Roosevelt administration for getting a good price for what was once a useless waste product they had to get rid of.
Cue Coghill's very happy bosses at USDA and the White House.
But Coghill had another speech ready, just in case what he had actually hoped for, had come about.
You see Coghill was a chemist ,not a biologist, and he was secretly hoping for the Nirvana of every chemist in those days - the full synthesis of some difficult yet important molecule.
On August 3rd 1943, when babies (cue the sobbing mothers) were dying because there was not enough clinical penicillin to give to most seriously ill civilians, Coghill and the NRRL bought 5 million units of clinical penicillin from the only firm actually making the stuff in any quantity (four years into a bloody war) - Reichel Labs, a backwoods mushroom farm ( I-Am-Not-Making-This-Up !!!!).
Coghill was not a medical doctor and the NRRL had no patients.
Actually, he and the NRRL staff were about to destroy the precious life-granting stuff, all in an attempt to synthesize it from ordinary industrial chemicals.
And if they had succeeded?
All those $$$$$ sales of their clients' corn steep liquor would have disappeared overnight.
But Coghill-the-survivor would have had his speech already prepared, making sure that the public and Congress knew the role he and the NRRL had had in creating the world's first SYNTHETIC penicillin.
Yessiree-bob!
Coghill, in his chilling way, convinces me that he could have survived - even flourished - in the Stalinist Politburo during the worst of the bureaucratic infighting - somehow that man's bread always managed to land butter side up....
The official one spoke of the day's success and gave all the credit to the brave boys who died to achieve it.
The unofficial one, prepared on a scrap of paper in pencil, also lauded the brave boys who died but it announced that the landing had failed and that Eisenhower took all the blame for the lack of success.
After every landing but one, he promptly tore up the scrap of paper and threw it away.
He called it his "In Case of Failure" speech.
But in the rush and excitement of D-Day, June 6th 1944, he clean forgot about tearing up this version of the speech.
On July 11th 1944, Eisenhower found the scrap of paper in a jacket pocket and showed it to his Naval aide, Captain Harry C Butcher,while preparing to tear it up like he had always done before.
Butcher begged Eisenhower to let him keep it instead.
Reluctantly, the General gave it to him.
Fragile with the passage of time upon a piece of cheap acidic paper, it is now one of the most precious relics in the Eisenhower Museum.
I thought of this touching story when I read Robert D Coghill's famous public speech of May 1944 that he gave (with OSRD's full approval), just after watching vials of 100,000 units of NATURAL penicillin pouring off the line at Pfizer's Marcy Avenue plant faster than he could count.
That penicillin was destined for its first ever mass clinical trial --- on the bloody beaches of Normandy on June 6th 1944.
NATURAL penicillin had both won the race to supply sufficient military penicillin vials before D-Day and had surprised everyone in the world of chemistry by beating man-made penicillin to the gate.
In the speech, Coghill, for the first time ,gave the details in a soon-to-be-cliched story of
how his NRRL facility in Peoria (a branch of the US Department of Agriculture) had made the success of NATURAL penicillin all possible.
Charged with finding a use for thousands of tons of a farm waste product, the dank murky corn steep liquor left over from the wet conversion of corn into cornstarch, his NRRL staff had tried it as food on penicillin and presto,it turned out to be the one secret ingredient that neither Britain or Germany had and the only ingredient that made NATURAL penicillin production viable.
Cue happy smiling children recovering thanks to penicillin from Peoria - cue the happy Mid-West farmers & voters in Republican states thanking the Roosevelt administration for getting a good price for what was once a useless waste product they had to get rid of.
Cue Coghill's very happy bosses at USDA and the White House.
But Coghill had another speech ready, just in case what he had actually hoped for, had come about.
You see Coghill was a chemist ,not a biologist, and he was secretly hoping for the Nirvana of every chemist in those days - the full synthesis of some difficult yet important molecule.
On August 3rd 1943, when babies (cue the sobbing mothers) were dying because there was not enough clinical penicillin to give to most seriously ill civilians, Coghill and the NRRL bought 5 million units of clinical penicillin from the only firm actually making the stuff in any quantity (four years into a bloody war) - Reichel Labs, a backwoods mushroom farm ( I-Am-Not-Making-This-Up !!!!).
Coghill was not a medical doctor and the NRRL had no patients.
Actually, he and the NRRL staff were about to destroy the precious life-granting stuff, all in an attempt to synthesize it from ordinary industrial chemicals.
And if they had succeeded?
All those $$$$$ sales of their clients' corn steep liquor would have disappeared overnight.
But Coghill-the-survivor would have had his speech already prepared, making sure that the public and Congress knew the role he and the NRRL had had in creating the world's first SYNTHETIC penicillin.
Yessiree-bob!
Coghill, in his chilling way, convinces me that he could have survived - even flourished - in the Stalinist Politburo during the worst of the bureaucratic infighting - somehow that man's bread always managed to land butter side up....
Physics,Chemistry break 1940 promises
At the time of the New York World's Fair, with its theme of a learned gaze into the crystal ball to reveal the America of the 1960s, Big Physics and Big Chemistry made two firm promises:
Physics promised that with nuclear fission newly achieved, by 1960 your family home would be heated and lit by electricity '"too cheap to meter", made by atomic energy.
It also said that this war would be a clean quick war, hitting only military targets, as B-17 bombers, with precision Norden bombsights, would be able to drop a bomb into a pickle barrel ,from 15,000 feet.
Chemistry pledged that your family would be disease free by the 1960s, "with hospitals no longer used for infectious diseases", thanks to pure,defined, man-made chemicals like the growing family of sulfa drugs.
But in 1945, atomic energy was used only to destroy homes (and the families inside).
(And with a bomb that powerful there was no need to aim, which was just as well ,as the Norden bombsights turned out to be useless.)
True, diseases were being held at bay, but not conquered, by 1945.
But not by the toxic and increasingly ineffective sulfa drugs.
Rather the success was due to penicillin - an impure,undefined mixture made by Nature and grown on an impure, undefined mixture of nutritional mediums also made by Nature.
And it was the humble science of biology that helped make it all work - while chemists only got in the way.
World War Two was NOT a triumph of nerdy,weedy scientists in spectacles winning the war when the stud muffin /BMOC /football captains of America proved unable to best the visiting German and Japanese teams out on the field.
This was the official take on World War Two Science, as produced by the leading science bureaucrats in their official and semi-official histories.
Because this 'revenge of the nerds' is so self-flattering to academics, even normally skeptical historians have lapped up the 'official version' like it was mother's milk.
In truth, Science suffered as many defeats to its ego during WWII as any over-confident general ever did.
In 1940, Man may have batted first, but by 1945 it was Nature that bats last: and Nature bats last and Nature bats long ....
It would perhaps be a bit much to ask today's historians to turn their sights on their colleagues and themselves and ask have they probed the truth of the penicillin saga or , to paraphrase Donald J McGraw,("On Leaving the Mine ", 1991) have they been content to merely uncritically retell tales already told too often ?
Physics promised that with nuclear fission newly achieved, by 1960 your family home would be heated and lit by electricity '"too cheap to meter", made by atomic energy.
It also said that this war would be a clean quick war, hitting only military targets, as B-17 bombers, with precision Norden bombsights, would be able to drop a bomb into a pickle barrel ,from 15,000 feet.
Chemistry pledged that your family would be disease free by the 1960s, "with hospitals no longer used for infectious diseases", thanks to pure,defined, man-made chemicals like the growing family of sulfa drugs.
But in 1945, atomic energy was used only to destroy homes (and the families inside).
(And with a bomb that powerful there was no need to aim, which was just as well ,as the Norden bombsights turned out to be useless.)
True, diseases were being held at bay, but not conquered, by 1945.
But not by the toxic and increasingly ineffective sulfa drugs.
Rather the success was due to penicillin - an impure,undefined mixture made by Nature and grown on an impure, undefined mixture of nutritional mediums also made by Nature.
And it was the humble science of biology that helped make it all work - while chemists only got in the way.
World War Two was NOT a triumph of nerdy,weedy scientists in spectacles winning the war when the stud muffin /BMOC /football captains of America proved unable to best the visiting German and Japanese teams out on the field.
This was the official take on World War Two Science, as produced by the leading science bureaucrats in their official and semi-official histories.
Because this 'revenge of the nerds' is so self-flattering to academics, even normally skeptical historians have lapped up the 'official version' like it was mother's milk.
In truth, Science suffered as many defeats to its ego during WWII as any over-confident general ever did.
In 1940, Man may have batted first, but by 1945 it was Nature that bats last: and Nature bats last and Nature bats long ....
It would perhaps be a bit much to ask today's historians to turn their sights on their colleagues and themselves and ask have they probed the truth of the penicillin saga or , to paraphrase Donald J McGraw,("On Leaving the Mine ", 1991) have they been content to merely uncritically retell tales already told too often ?
Tuesday, July 27, 2010
"Remember Mercy", Hollywood 'High Concept'
In the Fall of 1940, Nazi bombers rained death and suffering down on Britain as a preliminary to a planned invasion and all Civilization trembled.
In this time of Wrath, a dying doctor forgot his own troubles to Remember Mercy... and ushered in the Age of Life-Saving Antibiotics.
In this time of Wrath, a dying doctor forgot his own troubles to Remember Mercy... and ushered in the Age of Life-Saving Antibiotics.
Baby Patricia & Penicillin in Comic Book
In 1944, True Heroes Comic Books featured the inspiring story of Dr Dante Colitti saving the life of two year old baby Patricia Malone, August 11th 1943, with some penicillin that he, the child's father and the Hearst media empire had wheedled out of a hard-nosed American medical establishment.
This was the event that made penicillin known world wide, virtually over night after 15 years of being ignored.
Colitti's hospital and Dr Dawson's hospital shared the same catchment area for patients, being only a mile apart.
News of Dawson's cures, that Spring, of a number of women with the incurable disease of SBE had spread like wildfire among the patients and staff of both hospitals , leading to Colitti trying the stuff on his dying young patient...
This was the event that made penicillin known world wide, virtually over night after 15 years of being ignored.
Colitti's hospital and Dr Dawson's hospital shared the same catchment area for patients, being only a mile apart.
News of Dawson's cures, that Spring, of a number of women with the incurable disease of SBE had spread like wildfire among the patients and staff of both hospitals , leading to Colitti trying the stuff on his dying young patient...
Sunday, July 25, 2010
outline for "Remember Mercy, Manhattan's OTHER Project,1940-1945"
As always, subject to changes, and changes back, and forth....
The cover will feature a group of the main characters clustered around a hospital bed, in mid August 1944, Presbyterian Hospital, New York City.
Clustered, as if posing for a photograph.
I don't know if any happy friend or relative of a family brought back from the brink of
death by Dr Dawson ever did take such a celebratory snapshot.
But I would be very surprised if none ever did.
The artwork painting is a vignette. A half circle of light emerald green paint ( aka institutional green) swirls across the top.
In huge hand lettering around that half circle of green, is Remember Mercy, letters so big they threatened to burst out beyond the edges of the paper.
From across a bookstore, those two words should be all that you can distinctly see or read.
Below the clustered figures and the hospital bed, in much smaller hand writing, is Manhattan's other Project, 1940-1945. Those words now curves upwards at either end, to symbolically complete the circle with the words above.
Below the words, the green emerald paint vignettes off.
This is the cover 'teaser' copy.
On the inside title page, the actual subtitle is simply Mo goes Po ,beneath Remember Mercy.
Also on the title page, I mention this book is dedicated to the memory of Judith Hamel, "who like Dawson, was much too willing to step into the breach, when she was needed..." and indicate that I wrote it to inspire young people, considering a vocation in the Health Science...
Now back to the figures clustered around the hospital bed.
I don't know the name of the young mother in the bed, with her happy soldier husband and her new baby at her breast, only her age and her initials and the key dates and medical details.
G.L. was 21 in 1944, born 1923 +/- , had had a child on March 5 1944, despite a history of Rheumatic Fever leading to serious heart problems.
I can only imagine many saying her getting pregnancy-induced terminal SBE served her right.
Dawson didn't agree.
On July 22nd he started her on Penicillin and in three days her blood was sterile of SBE bacterial colonies. On August 19th she went home to be with her husband, who had been granted leave, presumably to bury his wife and put his new child up for adoption.
Seen in 1945-1946 she remained a picture of perfect health .
But the date I am photographing is a little earlier, August 15th 1944, it is the day that the very starts of the story effectively take leave of the story.
I see GL having an IM drip of bright glowing yellow white penicillin flowing into her arm and the yellow glow of the fluid bag on high dominates the entire image.
But back to the two departing starts to this culmination scene.
Start #1 is Charlie Aronson, Patient One of the Age of Antibiotics, has been cured a second time of SBE by Dawson and penicillin.
He is almost certainly in a wheelchair, has had a stroke,perhaps is on a IV fluids bag, but he is a survivor,has beaten much worse.
Sure enough,Charlie, the patient with nine or more lives, is still around, when last checked in upon, in March 1946.
In another wheelchair, perhaps, is Start #2 , Dr Martin Henry Dawson, for whom August 1944 is also wrap in many senses.
Curing GL and Charlie is a wonderful end to this run of patients . JAMA's editor Morris Fishbein, head of the national medical censorship forces, has agreed to publish a long article from Dawson on his SBE successes since September 1940, in early 1945, so the article has to get started right away.
Since his own doctors and Dawson himself privately wonder if Dawson will be alive in early 1945, the earlier the publication the better: as a fitting culmination to a life well lived and a symbol of his triumph over the resistant of the medical elite, Fishbein among them, to his vision of what penicillin can do for SBE.
Dawson's name is on one or two more papers, but perhaps more in tribute, he is getting more and more life-threatening MG 'incidents' where his lung muscles suddenly stop working - ambulances, emergency care, oxygen
tanks, stays at home in enforced bed rest while he frets about his patients.
Perhaps Dawson has an oxygen tank with him this day, attached to his wheelchair, like Charlie.
Both Charlie and Dawson, frankly, look deathly ill. But they are grinning ,ear to ear, their two arms feebily locked in a victory clasp.
beside them is Marjorie, with her cane, for her bad days with her hip - here to take her husband off to celebrate.
Meyer & Chaffee are off busy with their hydraluronic acid work and Hobby is working at Pfizer - so the rest of the Mercy Project aren't available for this historic photo.
But Floyd Odlum is here, in his crutches and so is Dr Tom Hunter in his crutches.
The weak and the foolish, pause, for a photo shot, to mark their victory over the mighty and the wise....
The cover will feature a group of the main characters clustered around a hospital bed, in mid August 1944, Presbyterian Hospital, New York City.
Clustered, as if posing for a photograph.
I don't know if any happy friend or relative of a family brought back from the brink of
death by Dr Dawson ever did take such a celebratory snapshot.
But I would be very surprised if none ever did.
The artwork painting is a vignette. A half circle of light emerald green paint ( aka institutional green) swirls across the top.
In huge hand lettering around that half circle of green, is Remember Mercy, letters so big they threatened to burst out beyond the edges of the paper.
From across a bookstore, those two words should be all that you can distinctly see or read.
Below the clustered figures and the hospital bed, in much smaller hand writing, is Manhattan's other Project, 1940-1945. Those words now curves upwards at either end, to symbolically complete the circle with the words above.
Below the words, the green emerald paint vignettes off.
This is the cover 'teaser' copy.
On the inside title page, the actual subtitle is simply Mo goes Po ,beneath Remember Mercy.
Also on the title page, I mention this book is dedicated to the memory of Judith Hamel, "who like Dawson, was much too willing to step into the breach, when she was needed..." and indicate that I wrote it to inspire young people, considering a vocation in the Health Science...
Now back to the figures clustered around the hospital bed.
I don't know the name of the young mother in the bed, with her happy soldier husband and her new baby at her breast, only her age and her initials and the key dates and medical details.
G.L. was 21 in 1944, born 1923 +/- , had had a child on March 5 1944, despite a history of Rheumatic Fever leading to serious heart problems.
I can only imagine many saying her getting pregnancy-induced terminal SBE served her right.
Dawson didn't agree.
On July 22nd he started her on Penicillin and in three days her blood was sterile of SBE bacterial colonies. On August 19th she went home to be with her husband, who had been granted leave, presumably to bury his wife and put his new child up for adoption.
Seen in 1945-1946 she remained a picture of perfect health .
But the date I am photographing is a little earlier, August 15th 1944, it is the day that the very starts of the story effectively take leave of the story.
I see GL having an IM drip of bright glowing yellow white penicillin flowing into her arm and the yellow glow of the fluid bag on high dominates the entire image.
But back to the two departing starts to this culmination scene.
Start #1 is Charlie Aronson, Patient One of the Age of Antibiotics, has been cured a second time of SBE by Dawson and penicillin.
He is almost certainly in a wheelchair, has had a stroke,perhaps is on a IV fluids bag, but he is a survivor,has beaten much worse.
Sure enough,Charlie, the patient with nine or more lives, is still around, when last checked in upon, in March 1946.
In another wheelchair, perhaps, is Start #2 , Dr Martin Henry Dawson, for whom August 1944 is also wrap in many senses.
Curing GL and Charlie is a wonderful end to this run of patients . JAMA's editor Morris Fishbein, head of the national medical censorship forces, has agreed to publish a long article from Dawson on his SBE successes since September 1940, in early 1945, so the article has to get started right away.
Since his own doctors and Dawson himself privately wonder if Dawson will be alive in early 1945, the earlier the publication the better: as a fitting culmination to a life well lived and a symbol of his triumph over the resistant of the medical elite, Fishbein among them, to his vision of what penicillin can do for SBE.
Dawson's name is on one or two more papers, but perhaps more in tribute, he is getting more and more life-threatening MG 'incidents' where his lung muscles suddenly stop working - ambulances, emergency care, oxygen
tanks, stays at home in enforced bed rest while he frets about his patients.
Perhaps Dawson has an oxygen tank with him this day, attached to his wheelchair, like Charlie.
Both Charlie and Dawson, frankly, look deathly ill. But they are grinning ,ear to ear, their two arms feebily locked in a victory clasp.
beside them is Marjorie, with her cane, for her bad days with her hip - here to take her husband off to celebrate.
Meyer & Chaffee are off busy with their hydraluronic acid work and Hobby is working at Pfizer - so the rest of the Mercy Project aren't available for this historic photo.
But Floyd Odlum is here, in his crutches and so is Dr Tom Hunter in his crutches.
The weak and the foolish, pause, for a photo shot, to mark their victory over the mighty and the wise....
Friday, July 23, 2010
Only now its "Les douze ans perdu"
People sometimes ask ,"how is my book on life in Canada's new frontier towns of the 1950s going?"
The book was called "Les dix ans trouve" --- all about the postwar determination to make up for the years lost to the Great Depression AND World War One.
That's right WW One - not WW Two .
Well I have abandoned that book, permanently I fear - for my new project on Martin Henry Dawson.
But do I look like a guy who wastes anything ?
Let alone someone who ever wastes research or literary scribbles.
Much of the earlier book's themes are still alive in the Dawson project - only now the heroine is Ms Penicillin and her Great Depression lasts from the Fall of 1928 to the Fall of 1940.
In a tribute to the Broadfoot Depression classic "The Ten Lost Years" , her travails I call "The Twelve years Lost"....
read more about it over at the blog "Mo goes Po" .
(And check out that blog's fantastic collection of Martin Henry Dawson photos at "Mo goes Po" .)
The book was called "Les dix ans trouve" --- all about the postwar determination to make up for the years lost to the Great Depression AND World War One.
That's right WW One - not WW Two .
Well I have abandoned that book, permanently I fear - for my new project on Martin Henry Dawson.
But do I look like a guy who wastes anything ?
Let alone someone who ever wastes research or literary scribbles.
Much of the earlier book's themes are still alive in the Dawson project - only now the heroine is Ms Penicillin and her Great Depression lasts from the Fall of 1928 to the Fall of 1940.
In a tribute to the Broadfoot Depression classic "The Ten Lost Years" , her travails I call "The Twelve years Lost"....
read more about it over at the blog "Mo goes Po" .
(And check out that blog's fantastic collection of Martin Henry Dawson photos at "Mo goes Po" .)
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