The genetically-minded Moderns of the 1930s felt they were facing a grave demographic crisis : why where there so few Ubermensch and so many undermensch: why so few Cedars and so much hyssop ?
In other words, why on earth were there so many beetles, defectives and useless mouths ?
Not believing in a Supreme Being, at least not believing in any Being Superior to themselves, they had to blame the Iron Laws of Nature and Evolution for this un-natural natural fondness for things weak and foolish.
If in ancient times , the Cedars of Lebanon were the biggest, tallest living beings known, the hyssop growing through the cracks in Beth Nielsen Chapman's concrete were 'the lowest of the low', the plant kingdom's equivalent of being the 4Fs of the 4Fs.
Seemingly the useless hyssop's only purpose for being put on this earth was to form a home for an equally purposeless mold.
But then, of course, when Fleming found that mold stopped bacteria cold and Dawson stuck it into a patient's arm to save a life, the lowly hyssop was revealed to have had a supreme purpose after all ....
Showing posts with label alexander fleming. Show all posts
Showing posts with label alexander fleming. Show all posts
Sunday, April 14, 2013
Sunday, February 10, 2013
Penicillin : biologic 1929-1939 , chemotherapeutic 1939-1949
In 1944, Frank M Berger ( later creator of the post-war drug Miltown but then just a worker in a local municipal public health lab in the remotes of northern England) came up with an unique way of making and using penicillin.
On second thoughts, his method might well have been done first by Alexander Fleming's Wright-Fleming vaccine institute and their pharmaceutical distributor Parke-Davis about 15 years earlier : Penicillin the Biologic.
On further further reflection : should have been done first by Alec Fleming.
Berger's penicillin was only concentrated and purified to the point that not too much penicillin was lost or too much scarce labour and expensive equipment used to create and extract it.
This biological penicillin, Berger claimed, was safe, potent and cheap ---and liquid.
Liquid --- and stored cold in the hospital that made it, ( not usually stored more than a week at most), until the next life-threatening case of blood poisoning in that same hospital was cured by its systemic (ie by needle) application.
The immediate use of whole liquid blood (another biologic dismissed earlier in the war) right at the front lines of combat was/is vital for survival of the badly wounded soldier.
But immediately pouring penicillin or sulfa into the man's dirty wound (ie via "local" application) - counter-intutively - is not.
Quickly getting him back to a hospital-like setting where penicillin or sulfa can be given him systemically, and under more carefully monitored conditions, was still useful.
But, it proved not essential to do so immediately even there ; often the staff could afford to wait to first see if signs of systemic infection were present (usually via a temperature rise.)
Ie, Howard Florey's 1939 claim that penicillin was only useful if made into a dry powder that remained stable at room temperature for months at a time was totally in error --- if life-saving was to be its main (wartime) role.
Berger's efforts were merely the best thought out among the number of doctors advocating biologic penicillin, not by any means the first (Dawson) or the most stunning (Duhig) .
By contrast, Florey was the chief high priest of Penicillin the Chemotherapeutic, (pure,dry,powdery), from first to last its leading advocate....
On second thoughts, his method might well have been done first by Alexander Fleming's Wright-Fleming vaccine institute and their pharmaceutical distributor Parke-Davis about 15 years earlier : Penicillin the Biologic.
On further further reflection : should have been done first by Alec Fleming.
Berger's penicillin was only concentrated and purified to the point that not too much penicillin was lost or too much scarce labour and expensive equipment used to create and extract it.
This biological penicillin, Berger claimed, was safe, potent and cheap ---and liquid.
Liquid --- and stored cold in the hospital that made it, ( not usually stored more than a week at most), until the next life-threatening case of blood poisoning in that same hospital was cured by its systemic (ie by needle) application.
The immediate use of whole liquid blood (another biologic dismissed earlier in the war) right at the front lines of combat was/is vital for survival of the badly wounded soldier.
But immediately pouring penicillin or sulfa into the man's dirty wound (ie via "local" application) - counter-intutively - is not.
Quickly getting him back to a hospital-like setting where penicillin or sulfa can be given him systemically, and under more carefully monitored conditions, was still useful.
But, it proved not essential to do so immediately even there ; often the staff could afford to wait to first see if signs of systemic infection were present (usually via a temperature rise.)
Ie, Howard Florey's 1939 claim that penicillin was only useful if made into a dry powder that remained stable at room temperature for months at a time was totally in error --- if life-saving was to be its main (wartime) role.
Berger's efforts were merely the best thought out among the number of doctors advocating biologic penicillin, not by any means the first (Dawson) or the most stunning (Duhig) .
By contrast, Florey was the chief high priest of Penicillin the Chemotherapeutic, (pure,dry,powdery), from first to last its leading advocate....
Wednesday, February 6, 2013
OSRD /1942: did Manhattan Project type thinking bleed over and obstruct the Penicillin Project as well ?
It is crystal clear that Merck's top scientific advisor A N Richards was never a strong advocate for fast-paced penicillin development within Merck, as that drug company casually messed about with penicillin, from November 1939 till August 1941.
That is, Merck had 18 months of some sort of commercial and scientific activity around penicillin , before Howard Florey actually arrived on the scene.
But Florey eventually made Richards a strong convert to the idea of having Richards' military medical weapon oriented agency , the famous OSRD , use penicillin for secret military advantage over the Axis.
It is not clear that this would have extended - in practise - to denying penicillin to dying Axis POWs.
But keeping penicillin a secret from the Axis definitely would have denied penicillin to dying Allied POWs behind Axis lines : something that all of Florey's, Richards' and Fleming's present day defenders universally ignore.
Very much to his credit then that WWI vet and WWII military officer and doctor Robert Pulvertaft did dis-obey orders and shared the secrets of penicillin production with Axis-friendly Turkish doctors.
But imagining a Canadian dying of sulfa-resistant blood poisoning in a German POW camp and the Canadian POWs being told by the German doctor, 'we could save him , if only we had a bit of this Allied-invented penicillin that we've been hearing rumours of'.
When the Canadians ask why doesn't the doctor get some, the doctor says that if the Allies won't even share penicillin with their own dying civilians, how can they be expected to share it with the enemy ?
But could penicillin have really ever have been a potentially secret and successful medical weapon ?
Here I , following closely on Henry Dawson's thinking, definitely part company with Florey and his friend Richards.
Henry Dawson demonstrated - in just five weeks - and under conditions as fully primitive as Fleming's, that one could quickly make a lot of crude penicillin that was non-toxic when injected into humans.
If Fleming and Dawson could do so, (quickly, easily and cheaply, ) so too could the fired up Nazi war machine.
Not so, said Florey -and his side kick Richards.
The scientific characteristics of penicillin haven't changed at all since September 1928, but now , thanks to Florey, the scientific rhetoric totally had.
Florey tells his readers and listeners, to ignore completely what Fleming-the-author says is "penicillin".
To wit, 'a mixture of about two dozen unknown compounds in a slurry of water that is non-toxic even if injected in very large volumes internally, and yet has marked anti-bacterial affects'.
In my revision of the facts, says Florey in his first August 1940 article, "penicillin" is now actually just one of those compounds.
All the rest and all that water are just dirty, dank and dangerous.
Only if penicillin is first pure, dry and stable is it any good.
Because where it is really good , is in the front lines as a local antiseptic for open war wounds (here I do still agree with Fleming) ---- and that idea won't work if crude liquid penicillin must kept viable in portable electric refrigerators.
Who ever has heard of such things ?
But as Florey tells Richards how complex and difficult the purification process is, Richards grows despondent again, but never the less this information does go into the back of Richards brain.
Only to re-emerge in early 1942, when the forces of war censorship and secrecy can be employed in full bloom.
Because complex and expensive separation and purification processes had become very much a two-edged sword for American military science and industry.
Artificial rubber was vital to the war effort - it was easy to make but a real bugger to separate the good rubber from the bad.
Dried blood products held real promise at the front lines - but only if their separation wasn't so complex.
And the Atomic Bomb - a piece of cake to make it work - if only we could get enough pure U-235 separated.
At some point early in 1942, these problems suddenly became military and commercial opportunities in the minds of the OSRD's highest officers.
If only rich, un-bombed America could solve these complex purification problems - and then keep the details secret - this would give them a big military advantage over their poorer enemy opponents.
And give America a post-war commercial advantage as well over its smaller poorer Allied friends like Britain.
So just as we see an abrupt turn around , in mid 1942 , from the OSRD re sharing much atomic information with the British, we start to see the British also get less information from the OSRD about penicillin research as well.
Like synthetic rubber, synthetic quinine, dried blood products and U-235, the very expensive complexity of pure penicillin suddenly made it more, not less ,of an attraction to the military weapon-oriented OSRD.
The key was to keep secret from the American voters and taxpayers just how many miracle cures were happening with the current - relatively impure -penicillin.
Because if they knew that, the newspapers would be filled with it and the Germans and Japanese would hear about it via Neutral nation reporting.
They they too would also start curing their base hospital wounded with crude semi-purified penicillin ,largely negating the military advantage of fully dry stable pure penicillin.
But was there really ever an absolute need for dry stable penicillin to use it in the front lines ?
Poppycock !
Because it turned out that good old crude liquid blood was actually much better than the complex dried stuff at saving soldiers' lives and could just as easily be used even in combat : good old fashioned low tech American ingenuity (not from the OSRD high tech boys of course) came to the rescue.
Cheap, rugged, disposable, parachute-portable plywood ice boxes kept blood and penicillin cold, with refills of ice every couple of days........
That is, Merck had 18 months of some sort of commercial and scientific activity around penicillin , before Howard Florey actually arrived on the scene.
But Florey eventually made Richards a strong convert to the idea of having Richards' military medical weapon oriented agency , the famous OSRD , use penicillin for secret military advantage over the Axis.
It is not clear that this would have extended - in practise - to denying penicillin to dying Axis POWs.
But keeping penicillin a secret from the Axis definitely would have denied penicillin to dying Allied POWs behind Axis lines : something that all of Florey's, Richards' and Fleming's present day defenders universally ignore.
Very much to his credit then that WWI vet and WWII military officer and doctor Robert Pulvertaft did dis-obey orders and shared the secrets of penicillin production with Axis-friendly Turkish doctors.
But imagining a Canadian dying of sulfa-resistant blood poisoning in a German POW camp and the Canadian POWs being told by the German doctor, 'we could save him , if only we had a bit of this Allied-invented penicillin that we've been hearing rumours of'.
When the Canadians ask why doesn't the doctor get some, the doctor says that if the Allies won't even share penicillin with their own dying civilians, how can they be expected to share it with the enemy ?
But could penicillin have really ever have been a potentially secret and successful medical weapon ?
Here I , following closely on Henry Dawson's thinking, definitely part company with Florey and his friend Richards.
Henry Dawson demonstrated - in just five weeks - and under conditions as fully primitive as Fleming's, that one could quickly make a lot of crude penicillin that was non-toxic when injected into humans.
If Fleming and Dawson could do so, (quickly, easily and cheaply, ) so too could the fired up Nazi war machine.
Not so, said Florey -and his side kick Richards.
The scientific characteristics of penicillin haven't changed at all since September 1928, but now , thanks to Florey, the scientific rhetoric totally had.
Florey tells his readers and listeners, to ignore completely what Fleming-the-author says is "penicillin".
To wit, 'a mixture of about two dozen unknown compounds in a slurry of water that is non-toxic even if injected in very large volumes internally, and yet has marked anti-bacterial affects'.
In my revision of the facts, says Florey in his first August 1940 article, "penicillin" is now actually just one of those compounds.
All the rest and all that water are just dirty, dank and dangerous.
Only if penicillin is first pure, dry and stable is it any good.
Because where it is really good , is in the front lines as a local antiseptic for open war wounds (here I do still agree with Fleming) ---- and that idea won't work if crude liquid penicillin must kept viable in portable electric refrigerators.
Who ever has heard of such things ?
But as Florey tells Richards how complex and difficult the purification process is, Richards grows despondent again, but never the less this information does go into the back of Richards brain.
Only to re-emerge in early 1942, when the forces of war censorship and secrecy can be employed in full bloom.
Because complex and expensive separation and purification processes had become very much a two-edged sword for American military science and industry.
Artificial rubber was vital to the war effort - it was easy to make but a real bugger to separate the good rubber from the bad.
Dried blood products held real promise at the front lines - but only if their separation wasn't so complex.
And the Atomic Bomb - a piece of cake to make it work - if only we could get enough pure U-235 separated.
At some point early in 1942, these problems suddenly became military and commercial opportunities in the minds of the OSRD's highest officers.
If only rich, un-bombed America could solve these complex purification problems - and then keep the details secret - this would give them a big military advantage over their poorer enemy opponents.
And give America a post-war commercial advantage as well over its smaller poorer Allied friends like Britain.
So just as we see an abrupt turn around , in mid 1942 , from the OSRD re sharing much atomic information with the British, we start to see the British also get less information from the OSRD about penicillin research as well.
Like synthetic rubber, synthetic quinine, dried blood products and U-235, the very expensive complexity of pure penicillin suddenly made it more, not less ,of an attraction to the military weapon-oriented OSRD.
The key was to keep secret from the American voters and taxpayers just how many miracle cures were happening with the current - relatively impure -penicillin.
Because if they knew that, the newspapers would be filled with it and the Germans and Japanese would hear about it via Neutral nation reporting.
They they too would also start curing their base hospital wounded with crude semi-purified penicillin ,largely negating the military advantage of fully dry stable pure penicillin.
But was there really ever an absolute need for dry stable penicillin to use it in the front lines ?
Poppycock !
Because it turned out that good old crude liquid blood was actually much better than the complex dried stuff at saving soldiers' lives and could just as easily be used even in combat : good old fashioned low tech American ingenuity (not from the OSRD high tech boys of course) came to the rescue.
Cheap, rugged, disposable, parachute-portable plywood ice boxes kept blood and penicillin cold, with refills of ice every couple of days........
Spores and Wartime Secrecy : can they actually co-exist ?
You might think I am going to talk about Anthrax spores and asymmetrical terrorist germ warfare.
But you are wrong, wrong, wrong.
I want to talk instead about wartime penicillin, and a part of it that is never ever discussed.
Its inherently asymmetrical medical nature.
Which appropriately enough, then "drifts over" into its inherently asymmetrical military potential.
So lets start.
And lets start talking about just how the intellectually mis-guided (as well as seriously morally misguided) were the prolonged attempts by the medical establishment in both America and Britain to regard penicillium spores as something that really could remain Top Secret medical military weapons.
And not just the wartime medical establishment, for recently author Eric Lax and his publishers felt they had a real winner in an exciting clock and dagger title for their book on wartime penicillin : "The Mould in Doctor Florey's Coat".
There was always something faintly Walter Mittyesque about Florey anyway - never more so than in the incident that gave this book its title.
Dunkirk was underway just as Florey at long last accepted that ole Flem's penicillin just might be priceless after all.
But how to save penicillin for the rest of the Allied cause, if Britain fell to the Germans ?
'Let's all rub penicillium spores in the inner seams of our clothing - so even if only one of us gets away, the precious fire of penicillin research can still be re-lit elsewhere'.
But none of these Oxford naifs seemed to have dared ask the boss (Florey) just how they came to possess these incredible spores in the first place.
Henry Dawson's first big scientific effort was in promoting the concept of HGT (Horizontal Gene Transfer) ,the instant transfer of genes between different species and even different families of Life, when its initial discoverer seemed reluctant to even publish his work.
Today it is believed that soil bacteria created the first beta lactam antibiotics about ten million years ago and - via HGT - gave it to soil molds who modified it slightly and made it penicillin.
So, sometime in 1928, a particularly productive penicillin producer strain of penicillium mold blow into a fancy home in London.
Alexander Fleming's colleague John Freeman was an expert on allergies, with many rich and powerful patients.
In 1928, Freeman heard a Dutch specialist claim that basement mold spores were the cause of many allergies.
Freeman got his rich London patients (or more likely their scullery maids) to scrape molds off their basement walls to be tested by his most recent hire, Irish-born mycologist Charles La Touche, towards seeking ways to gradually desensitize the patients against their particular household mold allergens.
La Touche had no high tech ways to keep spores inside his lab alone - not that I think in the long run a spore or two doesn't get out of the most secure modern facility.
There are many more fungus than us and they have and will be on the Earth a lot longer than us primarily because of their spores.
Their spores are incredibly tiny examples of temporarily suspended Life - Dried-up Life - inside a very hardy and bumpy package.
Tiny is the key here - so tiny they float anywhere and everywhere on the gentlest of breezes - down the hall and around the world.
Being bumpy but tiny and light doesn't hurt either - they can cling to almost any surface - like a human and its luggage bound for Australia, for example.
However if that surface is the tiniest bit damp and the tiniest bit tasty (they seem willing to eat almost anything faintly organic), they spring back into active slimey life.
One of La Touche's spores drifted out of his room and along the stairs to Fleming open Petri dish.
The rest actually wouldn't have been "legend", if Fleming hadn't promptly taken a sub culture of the resulting "spoiled" petri dish, and carefully and correctly preserved it.
Fleming did little to promote the medical use of penicillin in curing disease but he did vigerously promote it as a useful way for busy hospital labs to easily isolate the so called flu bacteria (sic) .
Dozens of labs world wide got a sample from him - they then gave samples of their samples to at least dozens of others.
That is how Florey got his penicillium spores he was so busy stuffing down his coat - from a sub culture Fleming had sent to the previous director of Florey's Dunn Institute.
The Free World beyond Britain had lots of sub cultures of penicillium spores of the rare - right - type, even without Florey's belated act of charity.
In theory they didn't really need Fleming's spores, only his public article - but in practise, until 1943, they really did need his spores.
Examples of Fleming's spores were actually everywhere - some even better penicillium producers than his original un-mutated version as well.
But they could only be found by teams of researchers seeking hundreds of the right looking blue-green mold on walls and spoiled fruit, and then testing all for their possible anti-bacterial qualities.
Until miracle cures got rumoured about, no one in the world was willing to go to that much effort , just to test a troublesome possible antiseptic.
But by 1943, the miracle cure stories were out amongst the clinical doctors everywhere - and I do really mean everywhere.
Everywhere that Florey went, Egypt, Iran, Russia he had to endure local doctors thrusting excellent producing strains of penicillin molds in his face that they had found locally !
The Axis were just as quick off the mark - Japan got its strain by merely looking about locally.
And the clever Japanese correctly guessed - from one badly reproduced photo in an Egyptian picture magazine - just how best to produce the stuff !
The atomic bomb was effectively secret even if the US had proclaimed it was making one from the rooftops in 1942.
Uranium was everywhere - like penicillium spores - but a bomb from it takes the world's largest, most expensive, building ever built merely to get started on separating pure U-235 from the more abundant U-238.
And without 90% pure U-235, no working bomb. No nothing.
Tons and tons of scarce money, time and effort kept the A-Bomb an American secret, even from the British and Canadians , let alone the Axis and Neutrals.
But by late 1943, popular magazine articles cheekily showed how one could make penicillin at home, on a kitchen top, for about $5 in equipment and growth mediums.
One didn't even need to go out searching for those semi-rare penicillin-producing strains by then.
In a surprising - even shocking - total volt face, the NRRL's Coghill and Raper had released the top two strains of penicillium.
That's right, the top two strains that were then producing most of the Allies' military-bound penicillin - to the public American mold type collection in Washington where, as they told the readers of JAMA worldwide, "anyone" can get some at a "nominal charge".
!!!!!!!!
No word if Argentina's Washington DC based scientific attache quickly took a cab over, got some samples and sent them off to his friends in Germany.
Clearly, penicillin was never a viable secret military medical weapon - Florey and Richards were both , to put it kindly, completely deluded to ever think so.
Deluded by utopian visions of near-total purity.
Because unlike the Atomic Bomb and U-235, penicillin's starting material (the spores) were both common worldwide AND its production fully successful even in a highly impure (aka low tech) state.
This was what Fleming had discovered in 1928 but never acted upon - this was the key insight that Henry Dawson brought to the penicillin story, starting on October 16th 1940....
But you are wrong, wrong, wrong.
I want to talk instead about wartime penicillin, and a part of it that is never ever discussed.
Its inherently asymmetrical medical nature.
Which appropriately enough, then "drifts over" into its inherently asymmetrical military potential.
So lets start.
And lets start talking about just how the intellectually mis-guided (as well as seriously morally misguided) were the prolonged attempts by the medical establishment in both America and Britain to regard penicillium spores as something that really could remain Top Secret medical military weapons.
And not just the wartime medical establishment, for recently author Eric Lax and his publishers felt they had a real winner in an exciting clock and dagger title for their book on wartime penicillin : "The Mould in Doctor Florey's Coat".
There was always something faintly Walter Mittyesque about Florey anyway - never more so than in the incident that gave this book its title.
Dunkirk was underway just as Florey at long last accepted that ole Flem's penicillin just might be priceless after all.
But how to save penicillin for the rest of the Allied cause, if Britain fell to the Germans ?
'Let's all rub penicillium spores in the inner seams of our clothing - so even if only one of us gets away, the precious fire of penicillin research can still be re-lit elsewhere'.
But none of these Oxford naifs seemed to have dared ask the boss (Florey) just how they came to possess these incredible spores in the first place.
Henry Dawson's first big scientific effort was in promoting the concept of HGT (Horizontal Gene Transfer) ,the instant transfer of genes between different species and even different families of Life, when its initial discoverer seemed reluctant to even publish his work.
Today it is believed that soil bacteria created the first beta lactam antibiotics about ten million years ago and - via HGT - gave it to soil molds who modified it slightly and made it penicillin.
So, sometime in 1928, a particularly productive penicillin producer strain of penicillium mold blow into a fancy home in London.
Alexander Fleming's colleague John Freeman was an expert on allergies, with many rich and powerful patients.
In 1928, Freeman heard a Dutch specialist claim that basement mold spores were the cause of many allergies.
Freeman got his rich London patients (or more likely their scullery maids) to scrape molds off their basement walls to be tested by his most recent hire, Irish-born mycologist Charles La Touche, towards seeking ways to gradually desensitize the patients against their particular household mold allergens.
La Touche had no high tech ways to keep spores inside his lab alone - not that I think in the long run a spore or two doesn't get out of the most secure modern facility.
There are many more fungus than us and they have and will be on the Earth a lot longer than us primarily because of their spores.
Their spores are incredibly tiny examples of temporarily suspended Life - Dried-up Life - inside a very hardy and bumpy package.
Tiny is the key here - so tiny they float anywhere and everywhere on the gentlest of breezes - down the hall and around the world.
Being bumpy but tiny and light doesn't hurt either - they can cling to almost any surface - like a human and its luggage bound for Australia, for example.
However if that surface is the tiniest bit damp and the tiniest bit tasty (they seem willing to eat almost anything faintly organic), they spring back into active slimey life.
One of La Touche's spores drifted out of his room and along the stairs to Fleming open Petri dish.
The rest actually wouldn't have been "legend", if Fleming hadn't promptly taken a sub culture of the resulting "spoiled" petri dish, and carefully and correctly preserved it.
Fleming did little to promote the medical use of penicillin in curing disease but he did vigerously promote it as a useful way for busy hospital labs to easily isolate the so called flu bacteria (sic) .
Dozens of labs world wide got a sample from him - they then gave samples of their samples to at least dozens of others.
That is how Florey got his penicillium spores he was so busy stuffing down his coat - from a sub culture Fleming had sent to the previous director of Florey's Dunn Institute.
The Free World beyond Britain had lots of sub cultures of penicillium spores of the rare - right - type, even without Florey's belated act of charity.
In theory they didn't really need Fleming's spores, only his public article - but in practise, until 1943, they really did need his spores.
Examples of Fleming's spores were actually everywhere - some even better penicillium producers than his original un-mutated version as well.
But they could only be found by teams of researchers seeking hundreds of the right looking blue-green mold on walls and spoiled fruit, and then testing all for their possible anti-bacterial qualities.
Until miracle cures got rumoured about, no one in the world was willing to go to that much effort , just to test a troublesome possible antiseptic.
But by 1943, the miracle cure stories were out amongst the clinical doctors everywhere - and I do really mean everywhere.
Everywhere that Florey went, Egypt, Iran, Russia he had to endure local doctors thrusting excellent producing strains of penicillin molds in his face that they had found locally !
The Axis were just as quick off the mark - Japan got its strain by merely looking about locally.
And the clever Japanese correctly guessed - from one badly reproduced photo in an Egyptian picture magazine - just how best to produce the stuff !
The atomic bomb was effectively secret even if the US had proclaimed it was making one from the rooftops in 1942.
Uranium was everywhere - like penicillium spores - but a bomb from it takes the world's largest, most expensive, building ever built merely to get started on separating pure U-235 from the more abundant U-238.
And without 90% pure U-235, no working bomb. No nothing.
Tons and tons of scarce money, time and effort kept the A-Bomb an American secret, even from the British and Canadians , let alone the Axis and Neutrals.
But by late 1943, popular magazine articles cheekily showed how one could make penicillin at home, on a kitchen top, for about $5 in equipment and growth mediums.
One didn't even need to go out searching for those semi-rare penicillin-producing strains by then.
In a surprising - even shocking - total volt face, the NRRL's Coghill and Raper had released the top two strains of penicillium.
That's right, the top two strains that were then producing most of the Allies' military-bound penicillin - to the public American mold type collection in Washington where, as they told the readers of JAMA worldwide, "anyone" can get some at a "nominal charge".
!!!!!!!!
Didn't they know there was a war on ?
No word if Argentina's Washington DC based scientific attache quickly took a cab over, got some samples and sent them off to his friends in Germany.
Clearly, penicillin was never a viable secret military medical weapon - Florey and Richards were both , to put it kindly, completely deluded to ever think so.
Deluded by utopian visions of near-total purity.
Because unlike the Atomic Bomb and U-235, penicillin's starting material (the spores) were both common worldwide AND its production fully successful even in a highly impure (aka low tech) state.
This was what Fleming had discovered in 1928 but never acted upon - this was the key insight that Henry Dawson brought to the penicillin story, starting on October 16th 1940....
Saturday, January 26, 2013
Florey delays penicillin for three more years : powdering the sick mice, May 1940
Just imagine for a moment if Howard Florey had actually done in May 1940 what he claimed he did for the rest of his life.
The one small/simple experiment that Alexander Fleming never did in 1928 and the one small/simple experiment he absolutely needed to do , to become for all time, the fully respected "discoverer" of penicillin.
At least in the eyes of scientists, doctors, historians and knowledgable lay people.
That experiment was to inject some of his mouse juice again into a mouse - but this time a mouse deliberately infected with massive amounts of bacteria, not a healthy mouse.
All to see if his penicillin juice could pricelessly save lives by working internally to root out massive infections, not to merely become another in a long line of antiseptics, to be dabbed on cuts merely as an aid to hurry up their natural scaring and healing.
Fleming never did this experiment.
Fleming would have to have slowly injected half a gram (cc/ml) of penicillin juice into an acutely ill 20 gram mouse, and since each gram had about 4 units of antibacterial activity in it, that would have been only 2 units of antibacterial activity per dose.
He'd have to repeat this about every 16 hours for perhaps three days to cure the mouse.
By contrast, because Florey first concentrated that penicillin juice down to about one thousandth of its original volume by boiling the water away in a vacuum, he ended up with mere milligrams of a dry brown powder - each mg containing the same antibacterial units as a gram of the original penicillin juice.
But after all this hard work, he also LOST two thirds of the original penicillin activity.
(He'd be fired if he did that for long in a commercial industrial fermentation operation !)
He dissolved 10 of those mgs of dry penicillin powder into .3 cc of distilled water ( back to the future again !) and injected perhaps 20 to 40 units of antibacterial activity into another acutely sick 20 gm mouse, saving its life in one large intense dose.
Luckily his mice did not die of needle fever during that single big dose - Fleming's need to give weaker injections, repeated over a longer period of time, did at least reduce the chance of severe side affects.
Properly handled, Fleming's strain routinely actually will give at least 40 units per gram of juice.
Then one half gram of his juice would give the exact same effect as 10 mg of Florey's dried powder (10 units in both cases.)
So an alternative path to Florey's tiresome and loss-inducing concentrating and purifying of tiny amounts of antibacterial activity in the original juice was to fire the team chemist and hire instead an industrial mycologist (fungus fermentation specialist) who knew how to starve a mold into giving more , not less, penicillin !
Up till Florey, all those who had written scientific articles on penicillin had acted as if it would be used as a non-toxic and wholly natural liquid , much as natural liver extracts were used to save those with pernicious anemia.
Florey introduced a totally new - and totally bogus - wrinkle into the effort to put penicillin to work saving lives.
He suddenly claimed that penicillin juice was NOT non-toxic - unknown parts of it was toxic "impurities" and that only the fully pure penicillin was non-toxic.
Though how he knew this, well in advance of getting anywhere near full purification, I best leave to your wild imagination !
Particularly if you knew some healthy person who died suddenly of anaphylactic shock after a routine dose of 100% pure penicillin.
I am afraid I can never forgive Florey for the wasted years and wasted diversion of effort into purifying penicillin juice instead of simply pouring it - NOW ! - into dying patients.....
The one small/simple experiment that Alexander Fleming never did in 1928 and the one small/simple experiment he absolutely needed to do , to become for all time, the fully respected "discoverer" of penicillin.
At least in the eyes of scientists, doctors, historians and knowledgable lay people.
That experiment was to inject some of his mouse juice again into a mouse - but this time a mouse deliberately infected with massive amounts of bacteria, not a healthy mouse.
All to see if his penicillin juice could pricelessly save lives by working internally to root out massive infections, not to merely become another in a long line of antiseptics, to be dabbed on cuts merely as an aid to hurry up their natural scaring and healing.
Fleming never did this experiment.
Crucially, neither did Florey.
Fleming would have to have slowly injected half a gram (cc/ml) of penicillin juice into an acutely ill 20 gram mouse, and since each gram had about 4 units of antibacterial activity in it, that would have been only 2 units of antibacterial activity per dose.
He'd have to repeat this about every 16 hours for perhaps three days to cure the mouse.
By contrast, because Florey first concentrated that penicillin juice down to about one thousandth of its original volume by boiling the water away in a vacuum, he ended up with mere milligrams of a dry brown powder - each mg containing the same antibacterial units as a gram of the original penicillin juice.
But after all this hard work, he also LOST two thirds of the original penicillin activity.
(He'd be fired if he did that for long in a commercial industrial fermentation operation !)
He dissolved 10 of those mgs of dry penicillin powder into .3 cc of distilled water ( back to the future again !) and injected perhaps 20 to 40 units of antibacterial activity into another acutely sick 20 gm mouse, saving its life in one large intense dose.
Luckily his mice did not die of needle fever during that single big dose - Fleming's need to give weaker injections, repeated over a longer period of time, did at least reduce the chance of severe side affects.
Properly handled, Fleming's strain routinely actually will give at least 40 units per gram of juice.
Then one half gram of his juice would give the exact same effect as 10 mg of Florey's dried powder (10 units in both cases.)
So an alternative path to Florey's tiresome and loss-inducing concentrating and purifying of tiny amounts of antibacterial activity in the original juice was to fire the team chemist and hire instead an industrial mycologist (fungus fermentation specialist) who knew how to starve a mold into giving more , not less, penicillin !
Up till Florey, all those who had written scientific articles on penicillin had acted as if it would be used as a non-toxic and wholly natural liquid , much as natural liver extracts were used to save those with pernicious anemia.
Florey introduced a totally new - and totally bogus - wrinkle into the effort to put penicillin to work saving lives.
He suddenly claimed that penicillin juice was NOT non-toxic - unknown parts of it was toxic "impurities" and that only the fully pure penicillin was non-toxic.
Though how he knew this, well in advance of getting anywhere near full purification, I best leave to your wild imagination !
Particularly if you knew some healthy person who died suddenly of anaphylactic shock after a routine dose of 100% pure penicillin.
I am afraid I can never forgive Florey for the wasted years and wasted diversion of effort into purifying penicillin juice instead of simply pouring it - NOW ! - into dying patients.....
Thursday, January 24, 2013
Nobel prize merely for concentrating penicillin into a SOLID for therapeutic use ?
Gloria T Sanders (in her 1986 book on amputations of the lower limbs) mentions in passing that Howard Florey was the first to concentrate penicillin into a solid, so it could finally be used in human therapy.
This has become a commonplace in recent years, as a Google search on "Florey" and "concentrated" will quickly reveal, replacing earlier claims that he was the first to "purify" penicillin.
But since the solid penicillin was in fact not a whit more stable than Fleming's original liquid penicillin, if both were properly stored, it offered no advantages to Fleming's wet stuff and a whole lot of disadvantages.
Florey's team had to do a great deal of expensive and labour-intensive chemical work to reduce 3 grams of watery penicillin (containing about 6 to 12 units of biological activity in total) to one milligram of solid penicillin containing about 2 to 4 units in total.
So now, instead of saving three dying patients, only one could be selected to live and the other two had to be triaged to die prematurely.
Remind me again how this was a therapeutic improvement !
And in addition, since life-saving penicillin had to be injected not swallowed, that dry milligram of penicillin had to be dissolved back into three grams of water, to put into the human body.
It seemed a long and wasteful effort, only to end up right back where you began.
The view that anything dried was inevitably better ,"more modern", than its fresh and juicy original was common in the era between the two world wars, particularly in Florey's Britain.
British cooking in the 1920s can be practically defined by the sudden availability year around of abundant and cheap dried fruits from all over the Empire.
Even today, Britain remain far and away the most avid consumers of packaged foods.
But it is not so in medicine that dry is invariably better than wet , along the road of progress.
WWII started with the military medical services of the Allies happily separating the plasma from the red cells of volunteer blood, throwing away the perfectly good and valuable red cells and then shipping the dried plasma to the combat-front to deal with fatal shock from massive wounds.
Later they realized that while the plasma did prevent immediate death from shock, a badly wounded serviceman who had lots of plasma but not enough red cells was truly over-stressing his already badly stressed heart and lungs needlessly, making survival still touch and go.
So a relatively minor administrative change (providing low tech disposable iceboxes and making liquid blood by plane transport a very top priority) allowed liquid blood to flow to the front-lines in the last year of the war - saving more lives than dry plasma could.
Concentration ,let me remind you, did not separate the tiny amounts ( ppm) of penicillin from the roughly 3% of solute solids (aka impurities) in the original gram of penicillin juice - it merely removed all the (sterile by definition) water.
But since those impurities were basically non-toxic, they were no more (and no less) harmful evaporated temporarily solid or remaining dissolved in water until they were injected.
Dignified, if alpha-male-ish, scientists do not going around saying my penis is longer than yours but they did going around saving my penicillin is purer than yours.
Which is to say, instead of concentrating penicillin purposelessly only to lose two thirds of it, they truly did purify it to a point of being between 15% to 90% pure, but at an even higher cost in terms of chemicals and labour - and penicillin - lost in the process.
But it did not save lives - it cost lives : hardly something those fine folks in Stockholm should be rewarding ....
This has become a commonplace in recent years, as a Google search on "Florey" and "concentrated" will quickly reveal, replacing earlier claims that he was the first to "purify" penicillin.
But since the solid penicillin was in fact not a whit more stable than Fleming's original liquid penicillin, if both were properly stored, it offered no advantages to Fleming's wet stuff and a whole lot of disadvantages.
Florey's team had to do a great deal of expensive and labour-intensive chemical work to reduce 3 grams of watery penicillin (containing about 6 to 12 units of biological activity in total) to one milligram of solid penicillin containing about 2 to 4 units in total.
So now, instead of saving three dying patients, only one could be selected to live and the other two had to be triaged to die prematurely.
Remind me again how this was a therapeutic improvement !
And in addition, since life-saving penicillin had to be injected not swallowed, that dry milligram of penicillin had to be dissolved back into three grams of water, to put into the human body.
It seemed a long and wasteful effort, only to end up right back where you began.
The view that anything dried was inevitably better ,"more modern", than its fresh and juicy original was common in the era between the two world wars, particularly in Florey's Britain.
British cooking in the 1920s can be practically defined by the sudden availability year around of abundant and cheap dried fruits from all over the Empire.
Even today, Britain remain far and away the most avid consumers of packaged foods.
But it is not so in medicine that dry is invariably better than wet , along the road of progress.
Unlike penicillin, WWII combat blood goes from dry back to wet ...
WWII started with the military medical services of the Allies happily separating the plasma from the red cells of volunteer blood, throwing away the perfectly good and valuable red cells and then shipping the dried plasma to the combat-front to deal with fatal shock from massive wounds.
Later they realized that while the plasma did prevent immediate death from shock, a badly wounded serviceman who had lots of plasma but not enough red cells was truly over-stressing his already badly stressed heart and lungs needlessly, making survival still touch and go.
So a relatively minor administrative change (providing low tech disposable iceboxes and making liquid blood by plane transport a very top priority) allowed liquid blood to flow to the front-lines in the last year of the war - saving more lives than dry plasma could.
Concentration ,let me remind you, did not separate the tiny amounts ( ppm) of penicillin from the roughly 3% of solute solids (aka impurities) in the original gram of penicillin juice - it merely removed all the (sterile by definition) water.
But since those impurities were basically non-toxic, they were no more (and no less) harmful evaporated temporarily solid or remaining dissolved in water until they were injected.
Dignified, if alpha-male-ish, scientists do not going around saying my penis is longer than yours but they did going around saving my penicillin is purer than yours.
Which is to say, instead of concentrating penicillin purposelessly only to lose two thirds of it, they truly did purify it to a point of being between 15% to 90% pure, but at an even higher cost in terms of chemicals and labour - and penicillin - lost in the process.
But it did not save lives - it cost lives : hardly something those fine folks in Stockholm should be rewarding ....
Sunday, January 20, 2013
Wartime penicillin's biggest secret was "hidden in plain sight", on the pages of the very first article on penicillin
The real reason why the tortoise Henry Dawson, despite starting almost three years late, beat the hare Howard Florey to become the first ever to put an injection of an antibiotic into a human patient, is to be found inside wartime penicillin's biggest secret.
Unexpectedly, wartime penicillin's biggest secret was not stamped "TOP SECRET" and was not buried under lock and key in some government cabinet in Washington or London.
Instead, Henry Dawson discovered it in October 1940, incredibly enough "hidden in plain sight" , on the pages of Alexander Fleming's very first article on penicillin from back in 1929.
Hidden from even its own author for all those years ; remaining hidden to almost everyone ever since - except for a very few caring and observant wartime doctors.
The great secret is all about non-toxicity and natural penicillin.
No, no , no, ---- don't jump the gun.
Its not that penicillin is non-toxic (because in some crucial ways it is not).
Rather more surprising, the great secret turns on the lucky fact that natural penicillin's natural impurities are so relatively non-toxic.
Back to 1928.
After about ten days of activity, and after a good straining through a lab filter to remove all solids, a gram of Fleming's 1928 penicillium liquid medium contained one part per million of penicillin -- one microgram of penicillin , ie about 1.6 units of bacteria killing activity .
97% of that gram was pure water and the remaining 3% were natural impurities - mostly organic acids.
We humans eat organic acids all the time - particularly in preference to their alkaline opposites, the bases.
Unfortunately, in a the world obsessed with eugenic purity, the good news ended with this particular penicillium strain's thankful lack of general toxicity.
The Age of Modernity liked things to be distinct and separate, not buried together in mixtures : it demanded purity in everything, from the German race to the Allied brand of penicillin.
Unfortunately for this obsession with purity, those various natural acids produced by the penicillium were so much like penicillin chemically (though not at all in anti-bacterial activity) that they were almost impossible to separate from penicillin without either destroying it and or losing it along the way.
In September 1940, at the start of their teaching hospital's first term, Henry Dawson had agreed to restrain his instinct to try and save lives.
Restrain himself, until his fellow team member, chemist Karl Meyer, had purified their penicillin (that the tiny team was home- growing) to a point where it was judged 'pure' enough to inject safely in a human body.
The projected launch date was the start of next school term, in early January 1941: ironically the exact same time Howard Florey's team was scheduled to start injecting their 'purified' penicillin into humans ! Dawson's team didn't know this, how close they came to be 'also-rans' .
Florey thought his team so far ahead he felt no particular urgency to rush into saving lives ; purity and not humanity, was always more his 'thing' anyway.
But ultimately Dawson couldn't stand to stand idly by as two young boys died needlessly from the dreaded and invariably fatal SBE (subacute bacterial endocarditis).
Not when he was convinced that penicillin's unique combination of non-toxicity, potency and diffusibility could save them.
He had not much literature on penicillin to read and re-read while waiting for the difficult process of purification to succeed , not in October 1940: only five articles .
Suddenly he realized that there was a possible solution to his moral dilemma , in that literature and right there under his nose all the time.
All five authors, beginning with Fleming, had mentioned that natural penicillin's natural impurities were not really toxic - at worse, a minor irritant.
So why continue to purify and purify penicillin - at an enormous cost in labour and in penicillin losses?
Why labour to purify it past the point where it could be concentrated (like orange juice), just enough to have a useful therapeutic effect without literally drowning the body in excess water ?
At that time, Dawson team was often making penicillin brew so weak that pouring it directly into a human body (by IV drip) would require putting a kilo of water into the blood stream for every 1000 units of penicillin activity !
But one go around of initial concentration cum purification might result in a little dirty brown powder that assayed 8 units per mg (one thousands of a gram) - 50 mgs of this powder dissolved in a gram of a suitable liquid, 3 times a day, would give the patient 1200 units of penicillin --- without the risk of drowning them internally.
And so on October 16th 1940, Henry Dawson jumped the gun and launched the Age of Antibiotics three months ahead of schedule.
Later on, by mid 1942, the raw penicillin juice made in hospitals assayed at around 40 units per ml of medium (about 25 times as pure) and it no longer needed to be even concentrated like orange juice (because even that resulted in heavy losses and needless additions of chemical contaminants).
It could simply be strained of solids, bottled and stored in a cold dark refrigerator until injected into a patient (and not merely dabbed into the patient's open wound, which was as far as most other penicillin pioneers were willing to go with non drug-company made penicillin.)
This is what a few brave penicillin pioneers (salute their heroic efforts please !) did : Robert Pulvertaft, James Duhig, and Zinaida Yermolieva.
Admittedly ,the first two did save lives by injecting raw penicillin into patients' blood supply, while still expressing some reluctance to do so - by contrast, the soviet team led by Ms Yermolieva did so routinely - all the more praise to them !
If only crude raw penicillin had been used to save lives, starting in 1928, millions of people would not have needlessly died world wide , in a totally unnecessary holocaust bigger than anything Hitler had planned for the Jews .....
Unexpectedly, wartime penicillin's biggest secret was not stamped "TOP SECRET" and was not buried under lock and key in some government cabinet in Washington or London.
Instead, Henry Dawson discovered it in October 1940, incredibly enough "hidden in plain sight" , on the pages of Alexander Fleming's very first article on penicillin from back in 1929.
Hidden from even its own author for all those years ; remaining hidden to almost everyone ever since - except for a very few caring and observant wartime doctors.
The great secret is all about non-toxicity and natural penicillin.
No, no , no, ---- don't jump the gun.
Its not that penicillin is non-toxic (because in some crucial ways it is not).
Rather more surprising, the great secret turns on the lucky fact that natural penicillin's natural impurities are so relatively non-toxic.
Fungus are very much a mixed bag on the toxicity front. Lots of them are so non-toxic that we love to eat them as our daily food : bread, beer, cheese, mushrooms, tofu and treated milk products.
Others release tiny amounts of toxins (mycotoxins) so toxic they rate up there with the most deadly poisons we know, by weight.
Back to 1928.
After about ten days of activity, and after a good straining through a lab filter to remove all solids, a gram of Fleming's 1928 penicillium liquid medium contained one part per million of penicillin -- one microgram of penicillin , ie about 1.6 units of bacteria killing activity .
97% of that gram was pure water and the remaining 3% were natural impurities - mostly organic acids.
We humans eat organic acids all the time - particularly in preference to their alkaline opposites, the bases.
Unfortunately, in a the world obsessed with eugenic purity, the good news ended with this particular penicillium strain's thankful lack of general toxicity.
The Age of Modernity liked things to be distinct and separate, not buried together in mixtures : it demanded purity in everything, from the German race to the Allied brand of penicillin.
Unfortunately for this obsession with purity, those various natural acids produced by the penicillium were so much like penicillin chemically (though not at all in anti-bacterial activity) that they were almost impossible to separate from penicillin without either destroying it and or losing it along the way.
In September 1940, at the start of their teaching hospital's first term, Henry Dawson had agreed to restrain his instinct to try and save lives.
Restrain himself, until his fellow team member, chemist Karl Meyer, had purified their penicillin (that the tiny team was home- growing) to a point where it was judged 'pure' enough to inject safely in a human body.
The projected launch date was the start of next school term, in early January 1941: ironically the exact same time Howard Florey's team was scheduled to start injecting their 'purified' penicillin into humans ! Dawson's team didn't know this, how close they came to be 'also-rans' .
Florey thought his team so far ahead he felt no particular urgency to rush into saving lives ; purity and not humanity, was always more his 'thing' anyway.
But ultimately Dawson couldn't stand to stand idly by as two young boys died needlessly from the dreaded and invariably fatal SBE (subacute bacterial endocarditis).
Not when he was convinced that penicillin's unique combination of non-toxicity, potency and diffusibility could save them.
He had not much literature on penicillin to read and re-read while waiting for the difficult process of purification to succeed , not in October 1940: only five articles .
Suddenly he realized that there was a possible solution to his moral dilemma , in that literature and right there under his nose all the time.
All five authors, beginning with Fleming, had mentioned that natural penicillin's natural impurities were not really toxic - at worse, a minor irritant.
So why continue to purify and purify penicillin - at an enormous cost in labour and in penicillin losses?
Why labour to purify it past the point where it could be concentrated (like orange juice), just enough to have a useful therapeutic effect without literally drowning the body in excess water ?
At that time, Dawson team was often making penicillin brew so weak that pouring it directly into a human body (by IV drip) would require putting a kilo of water into the blood stream for every 1000 units of penicillin activity !
But one go around of initial concentration cum purification might result in a little dirty brown powder that assayed 8 units per mg (one thousands of a gram) - 50 mgs of this powder dissolved in a gram of a suitable liquid, 3 times a day, would give the patient 1200 units of penicillin --- without the risk of drowning them internally.
And so on October 16th 1940, Henry Dawson jumped the gun and launched the Age of Antibiotics three months ahead of schedule.
Later on, by mid 1942, the raw penicillin juice made in hospitals assayed at around 40 units per ml of medium (about 25 times as pure) and it no longer needed to be even concentrated like orange juice (because even that resulted in heavy losses and needless additions of chemical contaminants).
It could simply be strained of solids, bottled and stored in a cold dark refrigerator until injected into a patient (and not merely dabbed into the patient's open wound, which was as far as most other penicillin pioneers were willing to go with non drug-company made penicillin.)
This is what a few brave penicillin pioneers (salute their heroic efforts please !) did : Robert Pulvertaft, James Duhig, and Zinaida Yermolieva.
Admittedly ,the first two did save lives by injecting raw penicillin into patients' blood supply, while still expressing some reluctance to do so - by contrast, the soviet team led by Ms Yermolieva did so routinely - all the more praise to them !
An unnecessary penicillin holocaust ...
If only crude raw penicillin had been used to save lives, starting in 1928, millions of people would not have needlessly died world wide , in a totally unnecessary holocaust bigger than anything Hitler had planned for the Jews .....
Friday, January 18, 2013
Like Admiral Byng, but in reverse, AlexanderFleming was given a Nobel prize "pour encourager les autres"
Alexander Fleming pursued, preserved and publicized a foolish observation that turned out to be.... not so foolish after all.
His personal Nobel Prize was really to encourage other future scientists to also publicize their oddball observations because they too might be all important.
New scientific breakthroughs are often delayed because the scientifically powerful are older and no longer open to an new ideas any newer than the new breakthroughs of their youth.
A person bold enough to bring forth oddball ideas is likely to face a lot of bricks and catcalls from these powerful personages who control grants and tenure and publication in big journals. (Big shout out to Dr Milton Wainwright !)
So the thought that a possible future Nobel Prize might lay in the offing if one faces the bricks and the catcalls , does tend to give all of us a little dutch courage.
Fleming was badly wrong about penicillin on two key counts.
It did not need to be synthetic to be useful and it was not limited to only local antiseptic use, but he argued these points from a reasoned position and did not attempt to weasel away from these positions when he was proven badly wrong by the mid-1940s.
And when I say wrong, I mean being highly visible wrong (as Fleming had become the most famous single person on earth).
Wrong ,wrong, wrong before the eyes of every single scientist in the world.
That took more than a little courage --- it is a pity than none of the rest of the penicillin pioneers who also advocated synthetic penicillin research to well past its due date were not as open in admitting their similar error......
His personal Nobel Prize was really to encourage other future scientists to also publicize their oddball observations because they too might be all important.
New scientific breakthroughs are often delayed because the scientifically powerful are older and no longer open to an new ideas any newer than the new breakthroughs of their youth.
A person bold enough to bring forth oddball ideas is likely to face a lot of bricks and catcalls from these powerful personages who control grants and tenure and publication in big journals. (Big shout out to Dr Milton Wainwright !)
So the thought that a possible future Nobel Prize might lay in the offing if one faces the bricks and the catcalls , does tend to give all of us a little dutch courage.
Fleming was badly wrong about penicillin on two key counts.
It did not need to be synthetic to be useful and it was not limited to only local antiseptic use, but he argued these points from a reasoned position and did not attempt to weasel away from these positions when he was proven badly wrong by the mid-1940s.
And when I say wrong, I mean being highly visible wrong (as Fleming had become the most famous single person on earth).
Wrong ,wrong, wrong before the eyes of every single scientist in the world.
Fleming accepted he had been wrong and didn't fudge it
That took more than a little courage --- it is a pity than none of the rest of the penicillin pioneers who also advocated synthetic penicillin research to well past its due date were not as open in admitting their similar error......
Tuesday, January 15, 2013
Penicillin's four most famous patients shouldn't have been PATIENTS... according to the research protocol
When anal-retentive children grow up, if indeed they ever grow up, they either became clients of Madame X the Dominatrix... or they become medical research scientists devoted to extremely strict and rigid clinical trials with firm protocols and hard-fast deadlines.
So it was with wartime penicillin and a group of such anally-oriented researchers swore to devote whatever scarce natural penicillin they could produce to test on cases of staph (and gas gangrene) infections.
After all, the various patented and chemically synthesized sulfa drugs could be relied upon to look after the far more common and more deadly strep infections, couldn't they ?
Or maybe not.
Let us look at those famous four early cases.
By chronology , the first was Charles Aronson ,dying of SBE (subacute bacterial endocarditis) caused by strep viridans in October 1940.
Dr Henry Dawson gave him a tiny amount of penicillin (to boost his morale) and a whole lot of sulfa to help his body defences and he unexpectedly survived this invariably fatal disease.
Case One : success one.
(About his fellow SBE patient, Aaron Alston, little is known for certain, only that he received the exactly same tiny dosage of penicillin as Aronson at first and later got some additional slightly larger doses of penicillin.
It is implied that he died of his disease early in 1941: but then this is also said to be true of Aronson and that claim is definitely wrong.)
Case Two.
That famous policeman dying from the prick of a rose : Albert Alexander of Oxford would have lived, should have lived, if only Howard Florey hadn't polished the apple so long testing penicillin on healthy animals (his forte) rather than on dying humans.
That and stopping the course of antibiotics too soon (today a widely known elementary error but something I can't really blame Florey's team for back in February 1941.)
Alexander had a mixed infection of strep and staph that had gradually consumed most of his face and was now threatening his brain. At the stage of his disease when he first met penicillin, conventional wisdom was that he was a definite goner.
It was second miracle that he recovered from this --- until the penicillin needed to totally clear up his infection was given to someone else who were not dying of their infection.
Case Three : Anne Miller.
The OSRD/CMR and the NAS/COC (the medical war lords of Washington, to adapt Bruce Catton's famous phrase) had agreed, along with the only two (out of over 200) drug companies in America that agreed to join in their restrictive government effort on penicillin, that the first priority on investigating the healing powers of penicillin was to look at staph infections.
In addition the two drug companies, Merck and Squibb , felt would be at least mid-1942 before any of this government-sanctioned penicillin would be released for clinical trials.
But strings were pulled to save the live of Florey's best friend, John Fulton, a top member of America's medical research elite --- by claiming the badly needed penicillin was actually for his fellow patient Anne Miller, dying of strep infection after a miscarriage.
So in March 1942, her life, too, was saved, in a dramatic fashion and post-the-awkward-fact that this totally broke all the agreed-upon protocols, the OSRD and NAS began touted Miller as the first patient treated in America.
(Obviously not true, but "embedded historians", ie historians who do most of their research in the lush gardens of the self-selected "official" archives of the OSRD and NAS, have generally fallen for this hook and sinker.)
Case Four : Harry Lambert.
Lambert was an employee of Fleming Brothers, a very successful optical wholesale firm run by Alexander Fleming's family.
When his strep infection wasn't helped by sulfa, Alexander was pressured by his family to try some of his wonderful penicillin on the case.
Awkward that : cause Fleming claimed he didn't have any and never did have any of his miracle drug.
Fact was, Fleming was still totally repugnant to putting his own "crude" penicillin into the temple of a human body. So he went cap in hand to Florey to get some "refined" penicillin.
Florey, to his credit, gave him as much as he had - pulled from experiments in purification and synthesis of penicillin.
(Florey's penicillin was still 75% junk, just as Fleming's penicillin was 99% junk , but it had been manipulated by a real live chemist, so that made it alright to put in a body !)
Lambert's life was saved, partly by Florey's penicillin and partially by Fleming's surgeon manque skill in injecting it into Lambert's spine.
As a result, Fleming overnight became a true believer in his own medicine's systemic healing powers ,14 years after he first discovered it.
Four cases, among many, where the first wonder drug , the sulfa family of medicines, were not working and where only penicillin saved a life.
But still a great reluctance (except from Henry Dawson) to say this aloud in front of the customers : that a mold-medicine was beaten the pants off a man-made synthetic and was not merely a supplement to sulfa for frontline staph wounds, but an all-around better life-saver and needed to be mass produced, like yesterday.....
So it was with wartime penicillin and a group of such anally-oriented researchers swore to devote whatever scarce natural penicillin they could produce to test on cases of staph (and gas gangrene) infections.
After all, the various patented and chemically synthesized sulfa drugs could be relied upon to look after the far more common and more deadly strep infections, couldn't they ?
Or maybe not.
Let us look at those famous four early cases.
By chronology , the first was Charles Aronson ,dying of SBE (subacute bacterial endocarditis) caused by strep viridans in October 1940.
Dr Henry Dawson gave him a tiny amount of penicillin (to boost his morale) and a whole lot of sulfa to help his body defences and he unexpectedly survived this invariably fatal disease.
Case One : success one.
(About his fellow SBE patient, Aaron Alston, little is known for certain, only that he received the exactly same tiny dosage of penicillin as Aronson at first and later got some additional slightly larger doses of penicillin.
It is implied that he died of his disease early in 1941: but then this is also said to be true of Aronson and that claim is definitely wrong.)
Case Two.
That famous policeman dying from the prick of a rose : Albert Alexander of Oxford would have lived, should have lived, if only Howard Florey hadn't polished the apple so long testing penicillin on healthy animals (his forte) rather than on dying humans.
That and stopping the course of antibiotics too soon (today a widely known elementary error but something I can't really blame Florey's team for back in February 1941.)
Alexander had a mixed infection of strep and staph that had gradually consumed most of his face and was now threatening his brain. At the stage of his disease when he first met penicillin, conventional wisdom was that he was a definite goner.
It was second miracle that he recovered from this --- until the penicillin needed to totally clear up his infection was given to someone else who were not dying of their infection.
Case Three : Anne Miller.
The OSRD/CMR and the NAS/COC (the medical war lords of Washington, to adapt Bruce Catton's famous phrase) had agreed, along with the only two (out of over 200) drug companies in America that agreed to join in their restrictive government effort on penicillin, that the first priority on investigating the healing powers of penicillin was to look at staph infections.
In addition the two drug companies, Merck and Squibb , felt would be at least mid-1942 before any of this government-sanctioned penicillin would be released for clinical trials.
But strings were pulled to save the live of Florey's best friend, John Fulton, a top member of America's medical research elite --- by claiming the badly needed penicillin was actually for his fellow patient Anne Miller, dying of strep infection after a miscarriage.
So in March 1942, her life, too, was saved, in a dramatic fashion and post-the-awkward-fact that this totally broke all the agreed-upon protocols, the OSRD and NAS began touted Miller as the first patient treated in America.
(Obviously not true, but "embedded historians", ie historians who do most of their research in the lush gardens of the self-selected "official" archives of the OSRD and NAS, have generally fallen for this hook and sinker.)
Case Four : Harry Lambert.
Lambert was an employee of Fleming Brothers, a very successful optical wholesale firm run by Alexander Fleming's family.
When his strep infection wasn't helped by sulfa, Alexander was pressured by his family to try some of his wonderful penicillin on the case.
Awkward that : cause Fleming claimed he didn't have any and never did have any of his miracle drug.
Fact was, Fleming was still totally repugnant to putting his own "crude" penicillin into the temple of a human body. So he went cap in hand to Florey to get some "refined" penicillin.
Florey, to his credit, gave him as much as he had - pulled from experiments in purification and synthesis of penicillin.
(Florey's penicillin was still 75% junk, just as Fleming's penicillin was 99% junk , but it had been manipulated by a real live chemist, so that made it alright to put in a body !)
Lambert's life was saved, partly by Florey's penicillin and partially by Fleming's surgeon manque skill in injecting it into Lambert's spine.
As a result, Fleming overnight became a true believer in his own medicine's systemic healing powers ,14 years after he first discovered it.
Sulfa-resistant strep was a leading cause of death by 1942...
Four cases, among many, where the first wonder drug , the sulfa family of medicines, were not working and where only penicillin saved a life.
But still a great reluctance (except from Henry Dawson) to say this aloud in front of the customers : that a mold-medicine was beaten the pants off a man-made synthetic and was not merely a supplement to sulfa for frontline staph wounds, but an all-around better life-saver and needed to be mass produced, like yesterday.....
Friday, January 4, 2013
Penicillin : a bunch of biologists who put all their faith in chemistry vs two chemists who put all their faith in biology
In the Alice Through the Looking Glass world of wartime penicillin it should hardly be surprising that about the only strong supporters of natural ,biological, penicillin in the upper echelons of the overall enterprise were two professional chemists : Larry Elder of the American Office for Production Research and Development (the OPRD) and Harry Jephcott of the British drug company, Glaxo.
Or that the group most strongly bewitched by the thought of synthetic penicillin were a bunch of medical doctors with Howard Florey and Alexander Fleming leading the charge (with the OSRD and MRC close behind): the sort of scientists who might have been thought would normally occupy a place at the biological end of hard science.....
Or that the group most strongly bewitched by the thought of synthetic penicillin were a bunch of medical doctors with Howard Florey and Alexander Fleming leading the charge (with the OSRD and MRC close behind): the sort of scientists who might have been thought would normally occupy a place at the biological end of hard science.....
Thursday, December 20, 2012
Fleming vs Wright 1929: local surgeon vs general immunologist ?
It is not generally accepted that Alexander Fleming actually did fight hard with his nominal boss, Sir Almroth Wright, to ensure the inclusion of a brief paragraph in his 1929 article that introduced penicillin to the world - the one that said it might have antiseptic applications.
Many researchers are skeptical about the idea of an undocumented fight.
They fear Fleming and his supporters are merely using it as an excuse to shift the blame onto Wright for Fleming's 15 year failure to put the world's best ever germ killer to work saving lives.
I do think there was a fight and that the disagreement , in a sense, flatters Wright and diminishes a part of Fleming's current reputation (though I haste to add , Fleming himself never ever fostered this part of his reputation.)
Fleming trained as a surgeon, but never practised (supposedly).
But I think he did act and think like a surgeon, and this surgeon manque side of him coloured his whole medical career.
A surgeon's personality is drawn to the concrete and the here and now : it is specific and local by nature.
This patient is dying because of a lesion right here, not there or there or 'we don't know where or why' : let me cut it out - now ! - and they will live.
By contrast, an intellectual like Wright was a generalist, a universalizer and systematizer.
In his medical career, he focused on giving body-wide vaccines : general systemics .
He was an immunologist.
We don't ordinarily think of getting a needle in the arm of BG vaccine to prevent TB as protecting us throughout our whole body : TB hits the only lungs doesn't it ?
But TB actually hits the whole body and a vaccine against it does protect the entire body.
Fleming made his living - a very good living indeed - running Wright's highly profitably vaccine factory, but his personal scientific interests certainly display a life-long interest in locally (directly) applied antiseptics for locally-situated diseases.
His needle or sprayer he welded like a surgeon welds a scalpel.
So, back to 1929.
Perhaps Wright was merely skeptical that anything delivered merely locally to an infection will have enough oomph to kill the germs : the whole body needs to push its weight.
Wright doesn't oppose penicillin as a possible antiseptic : he merely questions the worth of any antiseptic !
(And Penicillin did turn out to be most effective as a general systemic, though simultaneous local application and even local surgery often helped as well.)
Fleming has an exalted (aka surgically-minded) and very interventionist sense of how to use antiseptics : one does not dab it gingerly around the outer edges of a wound : one gets a big needleful and drills down into the lesion just below the surface, to deliver the germ killer directly.
So in 1929, he feels penicillin might work not just by being applied to areas with germs but also may have to be injected into those areas to do its work.
One of Fleming's main competitors, Howard Florey, had wanted to be a chemist, but ended up a physiologist : he spent his entire life cutting into and cutting up animals.
It is noteworthy that he, too, found delivering penicillin as a general systemic incredibly boring and always drifted to penicillin cases where there was a surgical aspect to grab his attention.
Similarly, fifteen years later when Fleming does start using penicillin to save lives, it is this sort of work that holds his interest - not merely the putting of a needle ,every four hours, into a patient's butt to deliver a general systemic .
By way of final contrast, Fleming's second main competitor, Henry Dawson, was going to be a law professor but ended up as a bacteriologist (though his main day job was as a rheumatologist ).
He was actually that rarity : a clinical investigator.
While Fleming and Florey generally never went near a patient if they could help it, Dawson was an internist, an attending physician at a big general teaching hospital.
He spent half of his day in a back room lab, like Florey and Fleming, but the other half of each day was spent on the wards, dealing with real life people with real life medical conditions.
An internist aka clinician is less focused on specific diseases as fundamental researchers tend to be.
She or he must deal with real patients who do have a specific disease, but along with this, they have a whole pile of other medical or mental conditions that greatly reduce or increase the impact of the specific disease.
Internist are biased to general systemics (and biased against locally-minded surgeons ?) such as maintaining the overall morale of the patient (aka 'a good bedside manner') and tend to view systemic medications like penicillin as perfectly in keeping with the internist's craft.
I suggest that the differing attitudes between Florey/Fleming and Dawson regarding the urgency to use penicillin as a general systemic might have been predicted from their career-long proclivities......
Many researchers are skeptical about the idea of an undocumented fight.
They fear Fleming and his supporters are merely using it as an excuse to shift the blame onto Wright for Fleming's 15 year failure to put the world's best ever germ killer to work saving lives.
I do think there was a fight and that the disagreement , in a sense, flatters Wright and diminishes a part of Fleming's current reputation (though I haste to add , Fleming himself never ever fostered this part of his reputation.)
Fleming trained as a surgeon, but never practised (supposedly).
But I think he did act and think like a surgeon, and this surgeon manque side of him coloured his whole medical career.
A surgeon's personality is drawn to the concrete and the here and now : it is specific and local by nature.
This patient is dying because of a lesion right here, not there or there or 'we don't know where or why' : let me cut it out - now ! - and they will live.
By contrast, an intellectual like Wright was a generalist, a universalizer and systematizer.
In his medical career, he focused on giving body-wide vaccines : general systemics .
He was an immunologist.
We don't ordinarily think of getting a needle in the arm of BG vaccine to prevent TB as protecting us throughout our whole body : TB hits the only lungs doesn't it ?
But TB actually hits the whole body and a vaccine against it does protect the entire body.
Fleming made his living - a very good living indeed - running Wright's highly profitably vaccine factory, but his personal scientific interests certainly display a life-long interest in locally (directly) applied antiseptics for locally-situated diseases.
His needle or sprayer he welded like a surgeon welds a scalpel.
So, back to 1929.
Perhaps Wright was merely skeptical that anything delivered merely locally to an infection will have enough oomph to kill the germs : the whole body needs to push its weight.
Wright doesn't oppose penicillin as a possible antiseptic : he merely questions the worth of any antiseptic !
(And Penicillin did turn out to be most effective as a general systemic, though simultaneous local application and even local surgery often helped as well.)
Fleming has an exalted (aka surgically-minded) and very interventionist sense of how to use antiseptics : one does not dab it gingerly around the outer edges of a wound : one gets a big needleful and drills down into the lesion just below the surface, to deliver the germ killer directly.
So in 1929, he feels penicillin might work not just by being applied to areas with germs but also may have to be injected into those areas to do its work.
One of Fleming's main competitors, Howard Florey, had wanted to be a chemist, but ended up a physiologist : he spent his entire life cutting into and cutting up animals.
It is noteworthy that he, too, found delivering penicillin as a general systemic incredibly boring and always drifted to penicillin cases where there was a surgical aspect to grab his attention.
Similarly, fifteen years later when Fleming does start using penicillin to save lives, it is this sort of work that holds his interest - not merely the putting of a needle ,every four hours, into a patient's butt to deliver a general systemic .
general internist vs local surgeons
By way of final contrast, Fleming's second main competitor, Henry Dawson, was going to be a law professor but ended up as a bacteriologist (though his main day job was as a rheumatologist ).
He was actually that rarity : a clinical investigator.
While Fleming and Florey generally never went near a patient if they could help it, Dawson was an internist, an attending physician at a big general teaching hospital.
He spent half of his day in a back room lab, like Florey and Fleming, but the other half of each day was spent on the wards, dealing with real life people with real life medical conditions.
An internist aka clinician is less focused on specific diseases as fundamental researchers tend to be.
She or he must deal with real patients who do have a specific disease, but along with this, they have a whole pile of other medical or mental conditions that greatly reduce or increase the impact of the specific disease.
Internist are biased to general systemics (and biased against locally-minded surgeons ?) such as maintaining the overall morale of the patient (aka 'a good bedside manner') and tend to view systemic medications like penicillin as perfectly in keeping with the internist's craft.
I suggest that the differing attitudes between Florey/Fleming and Dawson regarding the urgency to use penicillin as a general systemic might have been predicted from their career-long proclivities......
Tuesday, December 18, 2012
Fleming's non-toxic antiseptic was useless (and was called penicillin)
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| Toxic - but effective - antiseptic |
And highly valuable, even priceless, whenever our body faces massive body-wide infections that can kill us.
By contrast, what Alexander Fleming claimed to offer between the Fall of 1928 and the Fall of 1942, was a slow acting, non-toxic, wide-spectrum antiseptic (externally applied) germ-killer that was in very short supply and very unstable.
Forget, for the moment, most of Fleming's 'claims'.
The main point his listeners would take away was that this was a non-toxic antiseptic and as such, not particularly valuable.
Non-toxic and yet not particularly valuable ??!!
Yes, even fairly toxic systemics can sometimes be useful.
And as for antiseptic use, even very toxic substances can still be totally useful.
This confusion comes about because even doctors are frequently far too loose as to what they actually mean when they say a drug is toxic.
Toxic usually means - when you dig into the subject - it kills tender cells, in our interiors , and when delivered via the blood supply.
But toxic chemicals poured into body cavities and wounds without access to the internal blood supply (aka antiseptics) can end up doing very little damage in the overall scheme of things.
Even if they kill our body's cells at lower levels of the drug than the level needed to kill bacteria cells, they still can be useful : the wound at first might be a mess of already dead human cells acting as a food source for deadly bacteria.
Later after the bacteria are dead and the dead human cells are flushed away, the toxic antiseptic can be withdrawn before it starts killing new living human cells.
So antiseptics don't really need to be non-toxic, to be effective.
But they do need to be cheap, abundant, have long term stability and non-complicated storage requirements : everything that Fleming's offering (Penicillin) lacked.
Limited visions indeed : comparing penicillin to gramicidin
Something that Gramicidin, its chief rival from 1939 to 1943, did offer in spades. (Gramicidin was highly dangerous if taken internally but quite useful if poured into open wounds.)
But even the act of medically comparing penicillin to gramicidin , as many medical researchers did in those years, gives us a rare insight into their personal 'war aims'.
They saw the many different sulfa drugs as essential for all forms of infections, internal and external, military and civilian : and so scarce resources must be diverted to their mass production.
But the fact that they only saw penicillin as an antiseptic , meant they saw its use limited to wound-type infections - ie mostly for military personnel and even there, only for trauma infections.
This limited estimation of the worth of penicillin contrasts vividly with penicillin's biggest booster, Henry Dawson.
Quite simply, he said in 1941 that he saw penicillin has having "unlimited possibilities" and that "the government" should mass produce it for all , rather than wait for Big Pharma to get its act together.
If Dawson saw it first and foremost as a systemic (and most deadly infections are systemic), Fleming had spent the last dozen years flatly telling all his face-to-face listeners that penicillin would never ever work as a systemic.
He said this beginning in 1928 and he clung to this fatally incorrect "belief" until at least 1942 or 1943.
Yes, Alexander Fleming should be honoured as the father of penicillin, but he should also be condemned as the father who also trying his hardest to kill his own child for 15 years....
Tuesday, December 4, 2012
Scots wha hae wartime penicillin : chase Fleming's synthetic chimera or save lives with Dawson's shovel-ready ?
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| Dawson vs Fleming decided wartime PENICILLIN |
By unlikely coincidence , our two Scots, Alexander Fleming and Henry Dawson, were both born on August 6th, albeit 15 years apart (1881 and 1896).
Fleming was 18 when the Boer War broke out but refused to go and fight - he loved being in the London Scottish Rifles and was a keen marksman but was not really up for dying and discomfort and all that real chivalry stuff.
Dawson was also 18 when WWI broke out but only joined up in October 1915, after nurse Edith Cavell was murdered by the Germans in Belgium.
Dawson started off in the medical corps as a private and orderly but became a junior officer in the infantry and trench mortar artillery, was wounded twice and got the MC with citation for displaying bravery, chivalry and command despite being badly wounded.
Now it is widely claimed that Modernity repudiated Chivalry, after the horrors of the battles of Somme and Arras during World War One.
Modernity repudiates Chivalry : Chivalry repudiates Modernity right back
But a few writers - like Raymond Chandler and Howard Koch - claim that in World War Two, Chivalry repudiated Modernity and this is a thesis that I also hold - pointing to the Henry Dawson and Patty Malone stories as my prime examples of proof.
Fleming and his ilk : Florey, the NAS/OSRD/MRC et al , were seemingly contend between 1928 and 1945 to keep on polishing a turd, to still chase the chimera of synthetic penicillin for a few years more, while the world all around them burned.
Dawson passionately believed that if impure natural penicillin could save lives now , he had a moral duty to do so - Now !
His penicillin might be quick and dirty and a pain in the butt* for doctors and hospitals to keep in supply but it was shovel-ready, with its sleeves rolled up, ready to save lives : anyone, anywhere, anytime.
Fleming's synthetic chimera won all the early innings but Dawson's shovel-ready came from behind to win the race , in the late months of 1943.
Just as Chandler's Big Sleep had proved an unexpectedly massive hit with the general public and voters, so had Howard Koch's Casablanca and Henry Dawson's shovel-ready attitude of using existing natural - albeit impure - penicillin to save lives of 4F civilians today !
Chivalry - it turns out - was far from dead....
* and often , a literal 'pain the butt' for the patients too !
Friday, November 30, 2012
Would penicillin have been available for patients in 1930, if Fleming had produced his '29 paper - and then died ?
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| If only pneumonia had killed Alec, not John.... |
It is, he says (translated into today's medical terminology) a wide spectrum totally non-toxic anti-bacterial agent , the only one he as ever seen that doesn't harm the natural healing powers of the body's blood.
It is, Fleming says with great force , simply a great lab clearing agent for vaccine studies and potentially a useful antiseptic...
....And ? AND ?! You wait for the other shoe to drop, somewhat impatiently : how is it as a systemic, for saving those dying from bacterial infections ?
Oh that, says Fleming indifferently , its useless for that.
And, he adds brutally honestly , as an antiseptic it is slow acting and is so unstable that it will only be useful if the chemists can synthesize it - but they haven't so far.
For fourteen years , I believe only one man stood between penicillin the potential life-saver for millions and penicillin the actual life saver for millions and that man was - unfortunately - Alexander Fleming.
The history of penicillin might have been quite different if only he and not his brother John had died of the pneumonia that Fleming's 1928 imperfect penicillin would have cured.
I can not believe that Fleming could offer such frequent public build-ups of his wonderful penicillin without someone in the audience venturing : well how do you rate its life-saving systemic qualities then ?
Fleming in his honest (but incorrect) way , would have had to say in public what he deliberately omitted from his published articles : 'as a systemic, I believe that penicillin is useless'.
This - more than anything someone else did or didn't do - dammed penicillin to wander useless in the desert for 15 years : its own discoverer damning it with the very faintest of praise ....
Wednesday, November 28, 2012
How Parke-Davis could have made a fortune in 1929 from the ultimate in generic drugs : natural penicillin
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| Parke-Davis, as seen from my folks' homes |
Penicillin - in theory - is one such 'ultimate generic drug' , but was it in fact, in 1929 ?
Many strains of various bacteria and molds make penicillin-like beta-lactam materials but most do so in such small quantities that it takes very sensitive testing to discover their existence.
As such, St Mary's hospital in 1929 had the only two known strains of microbes known to make sufficient penicillin to be useful to man.
The original mold had been gathered as part of John Freeman's pioneering studies in allergies.
(Freeman's researches were the only part of the entire Wright-Fleming money-making empire that had any longterm scientific validity - as evidenced by being the only part of the Institute that a drug company, Beecham, was actually willing to part good money for in the 1950s after Fleming and Wright were safely in their graves.)
Spores from Freeman's unique mold had drifted up to Fleming's lab and so the hospital now controlled two copies of the same unique strain of mold.
Parke-Davis lost its chance to remain the world's biggest drug company
The Institute had a close contractual relationship with what was then the world's biggest and best research-oriented drug company - Detroit's Parke-Davis.
(Their enormous ( for their day) research labs were/are clearly visible right across the river from both my parents' home in Windsor Ontario.)
Patents were impossible for natural drugs but hardly needed, for St Mary's/Parke-Davis controlled the only source of the vital reagent needed to make penicillin : their unique strain of penicillium.
Keep that strain in-house and they could have a profitable monopoly forever.
Think this wildly unlikely ?
How do you think today's real penicillin makers still act ?
They develop in-house strains of penicillium and never patent them or share them.
The down-stream techniques after the penicillium express the penicillin juice are/were patented and hence public, for a fee.
But they are useless without a stable, high producing penicillium strain : one can afford to be quite cavalier with one's chemical engineering efficiencies when your unique strain out-produces all your competitors by an order or two of magnitude !
Trade Secrets rather than patents remain the most profitably business method in the biological drug business - now in 2012 as in 1928 .
When Fleming, after he too-quickly dismissed penicillin for systemic use, started freely giving away penicillium spores as a low value lab clearing agent, he ruined any hopes that Parke-Davis and St Mary's might put heavy money in penicillin production and promotion.
Ironically when he thus destroyed the early commercial hopes for penicillin production, his spores out there in the wider medical world, successfully kept the MRC/NAS/OSRD triad from delaying wartime penicillin any longer than they already did....
Wednesday, October 3, 2012
Duhig's Penicillin saved lives where Alexander Fleming failed - because of - not in spite of - "poorer" technology !
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| GLAXO's moral lowpoint: April '43 |
Briefly , Glaxo was the world's largest producer of what little penicillin the world produced, 15 long years after its first discovery. But none of that penicillin - zero - went to directly helping World War Two's sick and the dying.
Instead it was all destroyed by Glaxo chemists, as part of in the war-long futile contest to see what drug company would be the first to see MAN make penicillin, instead of some slimey slime.
Much of the story of wartime penicillin was that sordid story.
The dark dirty story of an contest between alpha male chemists and CEOs and chemists manques (in particular), to see who could get the Nobel prize and the glory and the profit for the patentable total synthesis of penicillin --- rather than submerging all that testosterone in an all out attempt to aid the sick and dying now and fuss over the glory later.
95 % of the wartime penicillin story was shabby beyond belief, but 5% was truly heroic medicine at its best
It is a truly shabby tale ---- as shabby as the war itself.
Alexander Fleming was part of that shabby tale : he never deflected from his 14 year old belief that penicillin might be a good antiseptic ( ie not to be taken internally, as life-saving drugs must be), if and only the chemists learned to synthesize it.
Jim Duhig --- once he had learned how people like Henry Dawson had grown their own clinical penicillin and injected it in a semi-purified state into their patients without killing them - went a further step.
He "downmarketed" his technological requirements and didn't bother to even semi-purify his home-owned penicillin.
The penicillin he injected into dying patients in 1943-1944 was cruder than even the semi-purified penicillin that Fleming dabbed around the open wounds of patients in 1928-1929, 15 years earlier.
Fleming reported mostly failures with his semi-purified penicillin while Duhig's totally unpurified penicillin saved the lives of patients all doctors had placed 'beyond hope' !
How on Earth ?!
All attempts at purifying, concentrating or crystallizing penicillin came at great costs: the harsh chemical techniques destroyed most of the delicate penicillin, the efforts wore out the overworked wartime staff and introduced deadly chemicals into the penicillin (when removing deadly chemicals was the original point of the whole exercise ! )
Duhig focussed his tiny overworked crew into merely making more and more raw penicillin - ie in upping raw production - and then in carefully preserving that delicate lifesaver, until it could be quickly poured into the bodies of dying patients.
Per person-hour of effort, I suspect that Duhig got 10 to100 times as much clinical penicillin as Dawson, Fleming , Glaxo, Merck, Florey et all got for all their hard work.
(Dawson being at the 10x end and Florey at the 100x end.)
Only Robert Pulvertaft, despite working in the desert heat (!) of wartime Egypt, probably did as well in turning raw penicillin juice into saved lives , with the minimum of human effort.
The unconscious, untested, assumption had always been that the other materials in raw penicillin juice would cause a deadly allergic reaction in patients unless purified away.
Never considered - except by Henry Dawson's team - was the idea that raw penicillin's other unknown materials might actually help penicillin work - as they certainly rarely seemed to harm the patient.
The jury is still out on that idea --- but un-purified penicillin did in fact rarely, if ever, harm the patients.
But converting penicillin from a weak acid to a salt ( to stabilize it for longterm commercial storage and sales) does bring the well known dangers of introducing too much salts into the delicate balance of salts in the heart-blood system.
(Since Duhig's totally un-purified penicillin remained a weak acid and not a salt, he could pump simply tremendous amounts of penicillin liquid into patients' blood without killing them.)
And it was only once penicillin was totally purified and given in high doses did some people - a very few people - start dying from an allergic reaction to ------- to PURE penicillin !
Call it groupthink or tunnel vision, but *eugenics' powers over mid century doctors and scientists was so strong, they never asked the most basic of all science questions.
They never asked themselves, " if a mixture of penicillin and impurities sometimes causes a sharp spike in temperature in some patients, is it caused by (a) those particular patients's body chemistry (b) the impurities (c) or the penicillin itself ?"
If only they had, millions of people might have lived out their full lives, starting in 1928.....
* Eugenics was merely the leading edge of a middle class culture obsessed with purity and a hatred of dirt that went beyond all bounds of rationality : only a Mary Douglas could begin to assess what was really going on in the middle class mind in the mid 20th century.
Saturday, September 29, 2012
Aside from VEGEMITE, what did Aussies Gray & Duhig have that Alexander Fleming totally lacked ? (Moral Fervour)
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| 6 million might have lived |
Aussie "Men at Work" , under tough wartime conditions
"They came from a land down under" - working in fact in then remote Brisbane Australia , under severe wartime shortage of staff and materials, their methods displayed NO technical improvements over what Fleming and his two young assistants had managed 15 years earlier.
Unfortunately, Altruism was never Alexander Fleming's long suit...
The key difference was that they had the moral fervour ( that Fleming totally lacked) to try almost anything to save people who were certain to die in days if not hours , by pumping extraordinary amounts of impure ("crude") penicillin water into their bodies.
Even at that late stage in penicillin's development, when the whole middle class world was talking up the miracle of penicillin, most doctors would rather see a patient die, than publicly admit that they injected an impure natural substance into a human being's bloodstream.
(It, after all, was an age of eugenics, and pure breeds, families of good blood and evil half bloods , pure-blooded Indians, when 1/32 or even one drop of black blood made you legally black and when the American Red Cross would not allow the mixing of black and white blood in transfusions : pureness and blood had a quasi-scientific, almost mystical , quality in those years .)
Nothing impure went into such a symbol of purity as human blood.
So even in late 1943, only a few doctors let the two pioneers, Duhig and Gray, inject raw penicillin juice into their patients - and even they, only when their patient seemed at death's door.
So these were not average very sick patients - they were gravely weakened patients given up for dead - so their recovery was all the more remarkable.
Penicillin's Holocaust
If Fleming had displayed any of their moral fervour in the 12 peacetime years when he had penicillin virtually to himself, an estimated six millions lives might have been saved.
Including - tragically - his own favourite brother John in 1937 - whose pneumonia case was easily curable by even modest amounts of crude penicillin water - if only Alexander Fleming had tried.
Instead it was left to the moral fervour of another Scot, Nova Scotian born Martin Henry Dawson, to first put impure penicillin into a patient's bloodstream, in 1940.
Fewer doctors than you can count on your hands followed Dawson's moral fervour when it came to fighting for the right of impure - natural - penicillin's to save lives, in those all important years between October 1940 and May 1944....
* They used Vegemite in the making of their penicillin juice , as a growth stimulant
If Penicillin was a Scottish DETECTIVE MURDER MYSTERY ....
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| Alexander FLEMING |
But Henry Dawson would be the Scottish copper who finds the murderer .
Tuesday, September 25, 2012
Needed : a MORAL history of Wartime Penicillin
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| SBE fatal to heart valves |
Not impossible to write such histories - dozens of historians have already done so.
Just not possible to do the job --- with any faithfulness to the actual contemporary record --- through those prisms.
Penicillin History has been Whig History....
By artfully cutting and pasting bits of the contemporary primary record it is possible to recast everything, even from that day in September 1928 when Fleming first saw that funny mold in his petri dish, as moving steadily and inevitably forward to the time when billions of units of natural produced systemic penicillin daily rolled off the line at Pfizer in the early Spring of 1944 - with natural (microbe produced) antibiotics being the norm to this day.
But in fact, most of the early1940s scientific, medical and commercial establishment was stunned into silence when penicillin ended up (a) suddenly proven up as the world's best-ever systemic life-saver and (b) being produced cheaply, abundantly and reliably - and produced only thanks to microbes to boot.
The 15 years up to 1944 had seen no new scientific advances or new commercial reasons to suddenly turn to penicillin as a systemic/lifesaver or to favour its production by natural (microbial) means ---- over the situation as Alexander Fleming had described it in his first paper of June 1929.
Only the moral situation had changed.
All the scientific, medical and commercial reasons were still valid against Henry Dawson for staking his life to cure invariably fatal SBE with natural systemic penicillin and against "John L" Smith of Pfizer for staking his company to help him.
But their personal moral reasons for doing so were overwhelming to these two men and so they attempted and achieved the impossible.
Monday, September 24, 2012
Calling his voyages "out-sourcing to India", Romney and Ryan veto any more government money to 47%er Christopher Columbus
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| Columbus also never paid federal taxes |
For first 15 years, (1928-1943), Alexander Fleming was also thought to have merely discovered another useless systemic drug, not the best known, best loved, most priceless medication ever.
Penicillin and the Americas : who would have ever thought that they shared a common fate : discovered to be one (relatively useless) thing by one person, only to re-evaluated by another person as something far more marvellous altogether ?
Well that is the danger of voting and thinking like a Republican ; thinking that the world is a static place and that everything is either always useful ("makers") and or always useless ("takers").
If Ryan and Romney were sitting on the throne in Spain in the late 1490s, they would have tossed off Columbus and his requests for more government aid for sea voyages as just another waster from the useless 47% set.
When did Columbus ever pay federal income taxes ?
But if the King of Spain had taken that modern, social darwinistic, attitude there'd be no historical Columbus , no America , no Romney, no Ryan and no Republican party.
And won't that be a great loss to humanity .......
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