Back at the start of the 1940s, two highly skilled biochemists (Karl Meyer and Ernst Chain) both confidently expected to quickly synthesize artificial penicillin, as they knew natural penicillin was a relatively small biological molecule of only about 350 Daltons.
After 100 weeks of hearing this reoccurring promise of quick results from Chain, his imperious boss, Howard Florey, reluctantly decided to inject his first human patients in February 12th 1941 with still-impure natural penicillin.
Henry Dawson, normally the most diffident of men, changed his mind about waiting till co-worker Meyer's synthetic penicillin arrived in January 1941, and after only five weeks into their joint penicillin efforts and without so much as a backward glance, injected his first patients with impure natural penicillin on October 16th 1940.
Showing posts with label synthetic penicillin. Show all posts
Showing posts with label synthetic penicillin. Show all posts
Friday, May 29, 2015
Thursday, February 26, 2015
1945: 380 years of the Synthetic Autarky Project vs 3.8 billion years of the microbial synthesis project...
In 1945, Modern Scientism (1875-1965 , long may it rest in peace) was always convinced it was the smartest bunch of guys in the universe : it could do anything and everything Mother Nature could do, only better, faster, cheaper, cleaner.
After all, it had 380 years of experience behind it in the science of chemical synthesis - and almost 50 years experience in atomic synthesis.
After all, it had 380 years of experience behind it in the science of chemical synthesis - and almost 50 years experience in atomic synthesis.
Wednesday, February 25, 2015
At Columbia-Cornell Medicial, pre-war modernity ain't dead yet
The website for New York City's Columbia-Cornell medical centre is finally touting the two famous universities' involvement in the triumph of wartime's natural penicillin.
So of course, the collective minds at C-C Medical choose to emphasize the project that quietly failed at their institute, not the one that succeeded beyond all measure.
For what they are really marking is wartime Cornell's failure to produce synthetic penicillin at commercial prices and in commercial grade purity.
So of course, the collective minds at C-C Medical choose to emphasize the project that quietly failed at their institute, not the one that succeeded beyond all measure.
For what they are really marking is wartime Cornell's failure to produce synthetic penicillin at commercial prices and in commercial grade purity.
Friday, January 23, 2015
WWII Columbia filters natural penicillin AND natural uranium
It is easy to see how Columbia University's two wartime Manhattan Projects differed : after all one saved countless thousands of lives while the other one caused countless thousands of deaths.
But it never hurts to consider how much they had in common - together - set against other parts of the Allied wartime nuclear and antibiotics effort.
But it never hurts to consider how much they had in common - together - set against other parts of the Allied wartime nuclear and antibiotics effort.
Monday, September 22, 2014
Merck's conflict of interest : planning to use molds as poisons of war makes it hard to see molds as lifesavers...
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| George W Merck (with big cigar) with Chemical Warfare officer at a drug trade conference (!) |
George W Merck spent most of WWII dividing his time between heading the biological weapons effort of the US government (which including researching molds as deadly poisons) and trying to create a synthetic version of the lifesaving penicillium mold.
Mentally that must have made it hard for Merck, head of Merck Drugs, to give a fair hearing to the possibility that the penicillium mold - all by itself, 'as is' - might be able to save lives...
Saturday, September 13, 2014
"The 'Cillium is a Roan that's never been rid , though thousands of chemists once claimed they did "
The title is a snatch of a song about the penicillium chrysogenum , with apologies to Curley Fletcher and his rather better known tale of the Strawberry Roan that also was never successfully rode.
To justify the expense of the Manhattan Project , America's military research bosses at the OSRD saw to it that A-bombs were dropped on Hiroshima and Nagasaki and then credited (wrongly) with being the sole cause for ending WWII.
To justify all the OSRD money wasted on not synthesizing penicillin, particularly when their rival WPB-OPRD spent far less to quickly make natural penicillin a resounding success, the OSRD bosses faked a synthetic success (about penicillin) to release to the gullible scientific media.
For Vincent du Vigneaud's team at Cornell Medical in NYC did indeed produce a little biologically active penicillin in the course of their efforts to synthesize penicillin.
So thousands of the world's top chemists got to take a public bow for yet another signal triumph in modern - BIG - science's endless progress ever upward.
But privately most knew that du Vigneaud synthetic goal was towards a molecule shape that did not match the necessary shape of biologically-active natural penicillin.
So this tiny amount of real penicillin must have been an accidental impurity of a mis-conceived theoretical approach !
More than 85 years after it was discovered, chemists have still not commercially synthesized a better or cheaper base penicillin molecule than what the tiny weak fungi can do on its own ...
To justify the expense of the Manhattan Project , America's military research bosses at the OSRD saw to it that A-bombs were dropped on Hiroshima and Nagasaki and then credited (wrongly) with being the sole cause for ending WWII.
To justify all the OSRD money wasted on not synthesizing penicillin, particularly when their rival WPB-OPRD spent far less to quickly make natural penicillin a resounding success, the OSRD bosses faked a synthetic success (about penicillin) to release to the gullible scientific media.
du Vigneaud's synthetic success (read synthetic = fake)
For Vincent du Vigneaud's team at Cornell Medical in NYC did indeed produce a little biologically active penicillin in the course of their efforts to synthesize penicillin.
So thousands of the world's top chemists got to take a public bow for yet another signal triumph in modern - BIG - science's endless progress ever upward.
But privately most knew that du Vigneaud synthetic goal was towards a molecule shape that did not match the necessary shape of biologically-active natural penicillin.
So this tiny amount of real penicillin must have been an accidental impurity of a mis-conceived theoretical approach !
More than 85 years after it was discovered, chemists have still not commercially synthesized a better or cheaper base penicillin molecule than what the tiny weak fungi can do on its own ...
Monday, September 8, 2014
WWII's paradigm shift - at least publicly , modern scientists forced to repress their Id fears about natural penicillin's slime monsters
We have long been taught that 1950s science fiction movies with all their red-colored Blob taking over and consuming little towns were really just a stand in for the dreaded red Russian commies taking over.
But this does those wonderfully slimy monsters a big disservice.
They do symbolize real fears but those fears are much deeper and far more profound than jus fearingt some opposing political party.
The values of the Modern Age (now called (big M) Modernity) were an unconscious (Id-induced) reaction to the events of late Victorian (small m) modernization (now more usually called globalization) that was both consciously welcomed and unconsciously feared.
Modernization brought not just an overwhelming plenitude of new physical goods and experiences but a plenitude of new and bewildering mental experiences as late Victorian era academics greatly and quickly expanded our sense of the vast size, age and complexity of our universe and this planet within it.
Things and ideas no longer seemed to remain in their traditional stable corners but intermingled in many destabilizing ways.
But Progress and Modernness was good , was it not ? - so how to release all those fears about all its unintended consequences without seeming as hopelessly old-fashioned as grandma ?
Slime creatures are the visually physical embodiment of these mental notions of instability - always living in the littoral regions between solid earth and fluid water, their very bodies were halfway between wet and dry, between solid and jelly-like.
When - much to almost everyone in science's total surprise - synthetic penicillin failed and natural penicillin triumphed, all scientists had to make the best of a scary situation - at least in public.
Deep tank penicillin with all its reassuring huge stainless steel tanks run by stern faced men in white coats behind mountains of dials and knobs was one way, the best way, to deny that the pee and poop of tiny slime molds was soon going to surge into the temple of the human body.
Once again, the iconography tells the tale the Id can't publicly speak about : no more shots of women (never ever men) tending their tiny poop and pee charges inside the transparently walled flasks of penicillium mold .
Poop and pee is still there but concealed behind the stainless steel wall so men (and it is always and only men now) can now safely stand close to the little unruly darlings.
You'd almost confuse it with a synthetic penicillin fctory - and that is the whole intent.....
But this does those wonderfully slimy monsters a big disservice.
They do symbolize real fears but those fears are much deeper and far more profound than jus fearingt some opposing political party.
The values of the Modern Age (now called (big M) Modernity) were an unconscious (Id-induced) reaction to the events of late Victorian (small m) modernization (now more usually called globalization) that was both consciously welcomed and unconsciously feared.
Modernization brought not just an overwhelming plenitude of new physical goods and experiences but a plenitude of new and bewildering mental experiences as late Victorian era academics greatly and quickly expanded our sense of the vast size, age and complexity of our universe and this planet within it.
Things and ideas no longer seemed to remain in their traditional stable corners but intermingled in many destabilizing ways.
But Progress and Modernness was good , was it not ? - so how to release all those fears about all its unintended consequences without seeming as hopelessly old-fashioned as grandma ?
Slime creatures are the visually physical embodiment of these mental notions of instability - always living in the littoral regions between solid earth and fluid water, their very bodies were halfway between wet and dry, between solid and jelly-like.
When - much to almost everyone in science's total surprise - synthetic penicillin failed and natural penicillin triumphed, all scientists had to make the best of a scary situation - at least in public.
Deep tank penicillin with all its reassuring huge stainless steel tanks run by stern faced men in white coats behind mountains of dials and knobs was one way, the best way, to deny that the pee and poop of tiny slime molds was soon going to surge into the temple of the human body.
Once again, the iconography tells the tale the Id can't publicly speak about : no more shots of women (never ever men) tending their tiny poop and pee charges inside the transparently walled flasks of penicillium mold .
Poop and pee is still there but concealed behind the stainless steel wall so men (and it is always and only men now) can now safely stand close to the little unruly darlings.
You'd almost confuse it with a synthetic penicillin fctory - and that is the whole intent.....
Sunday, September 7, 2014
In Howard Florey's Dunn , nurturing penicillium was women's work . REAL men didn't change diapers or penicillin vessels...
No women were ever allowed to be lab technicians at Howard Florey's Dunn Institute on the conservative campus of Oxford University*.
Tech work was way over their pretty little heads.
But then suddenly, because raw natural penicillin juice is basically the piss and poop of the stinky, slinky, slippery penicillium slime , no man - at least no real man - ever wanted to touch the stuff the Dunn was forced to grow for the chemists to destroy analytically.
(In those days, no real man ever changed a diaper or had anything else to do with all those dark damp dank things , you know, "down there".)
So enter ,stage left : Ruth Callow and Clare Inayat Khan. Pioneering "penicillin girls" aka Dunn lab techs.
(Memo to Twin Tower terrorist Ramzi Yousef: lifesaving penicillin pioneer Claire was a Moslem, just like yourself - only she did good, not evil.)
But the indignity of having to deal with the unpredictable penicillium was hated by all the men at the Dunn , not something to be proud of.
So as soon as possible all the elaborate equipment used to grow and extract natural penicillin was dumped - without ceremony - into the nearest rubbish pile.
Nothing was retained to serve as historical evidence for this supposedly noble effort.
Because the real show was all in the chemistry section, trying to synthesis patentable artificial penicillin analogues.
And there - need I say more - the workers were all men.
Real men ...
* As reported by David Wilson in his book "Penicillin in perspective ",1976 - page 176.
The STRAWBERRY ROAN of Synthetic Chemistry : natural un-patented lifesaving penicillin
A thousand chemists tried and a thousand chemists died (at least in academic embarrassment) failing to break natural penicillin's bouncing bronco at the height of WWII - when they really should have been doing something far more useful - like fighting Hitler , instead of restraining the natural miracle's ability to save lives....
Natural penicillin's unexpected triumph --- against Synthetics' 1939-1945 war against Nature
Big Science - Synthetic Science - had a lot of triumphs during WWII, the war that its promises , not Hitler's megalomania, actually started.
Synthetic Oil, Synthetic Rubber, Synthetic Silk, Synthetic Quinine , Synthetic Man , Synthetic Penicillin all sought to replace 'unreliable' natural products with new improved Man-perfected 'predictable' substitutes.
Synthetic Plutonium (sic) , Synthetic DDT, Synthetic Zyklon-B , Synthetic Freon, and Synthetic Napalm went one step further when Man was considered to have created new products that Nature could never have dreamed up.
Thank God for Nature then !
And as for Man-made predictability , it is worth recalling that human chemists only make a tiny minority of all chemical compounds.
Chemists usually stumble on a compound with useful properties and then go to work on replacing its side chains until even better properties emerge.
But so too the environment and biological beings do the same to the sidechains of Man-made chemical compounds such as Freon and DDT.
In the process Nature created massive un-natural disasters Scientific Man could never have predicted precisely but human humility might have considered a distinct possibility .
The German chemical world's promise that in the very near future total synthetic autarky was possible allowed enough otherwise sensible adult Germans to go along with Hitler's megalomania talk of endless wars of conquest to get the whole ball of wax started.
Sensible adult Germans who should have personally remembered the failure of WWI's ersatz synthetics to feed and heat a starving , freezing nation under total blockade.
Synthetic Oil, Synthetic Rubber, Synthetic Silk, Synthetic Quinine , Synthetic Man , Synthetic Penicillin all sought to replace 'unreliable' natural products with new improved Man-perfected 'predictable' substitutes.
Synthetic Plutonium (sic) , Synthetic DDT, Synthetic Zyklon-B , Synthetic Freon, and Synthetic Napalm went one step further when Man was considered to have created new products that Nature could never have dreamed up.
Thank God for Nature then !
And as for Man-made predictability , it is worth recalling that human chemists only make a tiny minority of all chemical compounds.
Chemists usually stumble on a compound with useful properties and then go to work on replacing its side chains until even better properties emerge.
But so too the environment and biological beings do the same to the sidechains of Man-made chemical compounds such as Freon and DDT.
In the process Nature created massive un-natural disasters Scientific Man could never have predicted precisely but human humility might have considered a distinct possibility .
The German chemical world's promise that in the very near future total synthetic autarky was possible allowed enough otherwise sensible adult Germans to go along with Hitler's megalomania talk of endless wars of conquest to get the whole ball of wax started.
Sensible adult Germans who should have personally remembered the failure of WWI's ersatz synthetics to feed and heat a starving , freezing nation under total blockade.
Auschwitz to help birth the Perfect Man , Man-Made Man, Synthetic Man
During WWII, Germans killed tens of millions of Slavs, Jews, Romas and Aryan 'unfits' , all part of a huge (scientific) war within a smaller (military) war .
That scientific war , a deadly serious war that both proceeded and succeeded WWII's nominally important military war, sought to replace Nature's messy plenitude of many imperfect natural types with one Man-made perfect , perfectly static , type.
The synthesis-minded, Nature's breakers , were going to tame these unruly bucking natural broncos.
Just as the Victorian Era pornographers had virtually tamed similar bucking uppity feminist women with stirrups* in their texts and images.
(*Victorian male doctors read pornography as much as other Victorian men did and they later renamed the foot rests for their female patients as "stirrups".)
The stinky,slinky, slimy , constantly mutating fungal molds existing in an unstable, unpredictable world midway between the solid/dry and the wet/flowing , were a particular bete noire to Modern Man , as a glance at that era's most feared monsters ( H P Lovecraft anyone ?) will readily attest.
This is the real, if largely unconscious , reason why 1939-1945's synthetic chemists warred against the penicillium mold (and not the enemy) and why doctors of that period declined to use perfectly safe, effective natural penicillin to save the dying.
But the penicillium was (and remains) one bucking bronco these chemical breakers never could break.
Hitler and the synthetic chemists thought they were good - but then Hitler and the chemists had never tangled with the Strawberry Roan ...
Tuesday, August 26, 2014
Abundant Penicillin by 1942 - only if Howard Florey didn't come to America ?
When ,in April 1941, Howard Florey learned that his best shot at world acclaim (as the only begetter of systemic penicillin) was at risk because Henry Dawson had got there first, the old claim jumper boot scooted over to America to shake a little dust.
Unfortunately, while in America he met and bonded with an old friend, A Newton Richards, the chief medical advisor (sans MD degree !) to both Merck and the US government's war science research arm , Vannevar Bush's OSRD.
Together the pair agreed that most of the wartime penicillin effort should go into first synthesizing it - rather than merely scaling up existing natural penicillin fermentation technology and getting penicillin to the military and civilian patients dying for lack of it - now.
Richards (who never met a conflict of interest he didn't like) was mindful that Merck's cross harbour rival, Pfizer, was likely to be the big winner if natural fermentation - and not Merck's strength artificial synthesis - was used to produce this priceless new drug.
Left alone, Pfizer (with Henry Dawson's team assisting) was already on the way, during that Fall in 1941 , to producing enough penicillin to get the show on the road.
A pity then that Florey had to spoil the show ...
Unfortunately, while in America he met and bonded with an old friend, A Newton Richards, the chief medical advisor (sans MD degree !) to both Merck and the US government's war science research arm , Vannevar Bush's OSRD.
Together the pair agreed that most of the wartime penicillin effort should go into first synthesizing it - rather than merely scaling up existing natural penicillin fermentation technology and getting penicillin to the military and civilian patients dying for lack of it - now.
Richards (who never met a conflict of interest he didn't like) was mindful that Merck's cross harbour rival, Pfizer, was likely to be the big winner if natural fermentation - and not Merck's strength artificial synthesis - was used to produce this priceless new drug.
Left alone, Pfizer (with Henry Dawson's team assisting) was already on the way, during that Fall in 1941 , to producing enough penicillin to get the show on the road.
A pity then that Florey had to spoil the show ...
Wartime Oxford : the planned capital of a racially pure Nazi Britain ---- and of chemically pure penicillin
Hitler never seriously tried to bomb Oxford England , despite its very militarily important engineering works.
The often made claim that Howard Florey had to give penicillin away to America because he was bombed out of Oxford by the Blitz is made only by his American fans - even his most ardent British fans weren't ever that thick.
After all , they had survived life in British cities enduring the various Nazi bombing efforts and at the time had greatly envied Oxford's well known gilded wartime immunity.
The story is that Hitler saw Oxford as having successfully taught the Anglo-Saxon cum Aryan elite racial truths for almost a millennium (it may in fact be the world's oldest surviving university) and so it seemed to him to be the one place in Britain that most held aloft his biological political values.
Britain's elite vigorously resented Hitler's high opinion of Oxford University in his vision of the world back then - and continue to do ever since.
(Rarely do they ask why working class Britons also view Oxford as the very essence of pure Anglo Saxon privilege.)
By contrast, he clearly viewed becoming a full Oxford Professor of a named chair and director of an Oxford institute as meaning he had reached the near top of the Anglo Saxon intellectual ladder.
This is indicated by the fact that as soon as his position was secure, he felt he could finally return with his head held high to the Australia he had fled 15 years earlier - after his father had disgraced the family name.
So, on an ancient site where students had been taught for almost a millennium , his dreams of a chemical penicillin tomorrow first soared.
And it was here - amidst Oxford University's fabled green splendor - that his visions of the man-made, the artificial and of the synthetic pure flourished the most extravagantly.
Oxford Refined - clearly for Florey - and for Hitler - more than just an accent ...
The often made claim that Howard Florey had to give penicillin away to America because he was bombed out of Oxford by the Blitz is made only by his American fans - even his most ardent British fans weren't ever that thick.
After all , they had survived life in British cities enduring the various Nazi bombing efforts and at the time had greatly envied Oxford's well known gilded wartime immunity.
The story is that Hitler saw Oxford as having successfully taught the Anglo-Saxon cum Aryan elite racial truths for almost a millennium (it may in fact be the world's oldest surviving university) and so it seemed to him to be the one place in Britain that most held aloft his biological political values.
Britain's elite vigorously resented Hitler's high opinion of Oxford University in his vision of the world back then - and continue to do ever since.
(Rarely do they ask why working class Britons also view Oxford as the very essence of pure Anglo Saxon privilege.)
Florey and purity - racial and chemical
Howard Florey won't have taken even a top job at NYC's Columbia University - no matter how big the salary and how big the size of his lab.
He hated Manhattan with a passion - he saw its concrete jungle as dirty, noisy, crowded and filled with Jews, catholic Italians and blacks.
By contrast, he clearly viewed becoming a full Oxford Professor of a named chair and director of an Oxford institute as meaning he had reached the near top of the Anglo Saxon intellectual ladder.
This is indicated by the fact that as soon as his position was secure, he felt he could finally return with his head held high to the Australia he had fled 15 years earlier - after his father had disgraced the family name.
So, on an ancient site where students had been taught for almost a millennium , his dreams of a chemical penicillin tomorrow first soared.
And it was here - amidst Oxford University's fabled green splendor - that his visions of the man-made, the artificial and of the synthetic pure flourished the most extravagantly.
Oxford Refined - clearly for Florey - and for Hitler - more than just an accent ...
Connecting New York's PENICILLIN dots ...
Some authors are content to merely describe a long series of coincidental dots ---- other authors like to investigate to see if anything connects all those coincidental dots.
I am one of the latter : as many a TV police detective is fond of saying , my motto is "I don't believe in coincidences."
When I fell upon the story of Henry Dawson and wartime penicillin, I noticed that most of the twenty or so full length accounts of wartime penicillin always included the awkward fact that he (and not their hero Howard Florey) was the one to give history's first ever penicillin shots.
They briefly described that first needle in a sentence or paragraph or page or two --- and then always go on quickly to say that Dawson himself was dying of a terminal illness - 'so necessarily passes out of our story'.
The rest of their three hundred or page accounts have nothing further about Dawson's team.
Clearly they mentally needed a way to dispose of Dawson (his convenient terminal illness) without seriously engaging his team's more than five years of involvement with penicillin.
They already had a preconceived shape to their biography of Florey and so they mentally hardly wanted to investigate Dawson's story any further --- less it ruined their story's trim panty lines.
Dawson did indeed die from his illness - but that was only at the end of April 1945 , while his team effort can be said to have begun when team member Karl Meyer learned firsthand of Florey's successful curing of infected mice in the early summer of 1940 from Florey ex-team member Leslie Epstein (Falk).
Dawson in fact kept very active in pioneering penicillin work right up to his death.
His team - in particular Gladys Hobby at Pfizer and Thomas hunter at Columbia - continued to do important work with penicillin for a few more years , even after the war's end.
Now what struck me with the force of a hammer in the first few days of my research - even back ten years ago when I knew almost nothing about wartime penicillin - was the amazing number of truly significant events in the penicillin story that had happened in the New York City area.
And that they all seemed to be of a similar type - let us simply describe them as all taking a similarly non-conventional approach to solving the penicillin supply issue.
Set against the relatively inactivity of a similar nature from the other 1990 million other human beings on earth in 1940 , they certainly seemed statistically odd beyond measure to be unconnected.
Since Dawson was both the first and the most active of these NYC inside agitators , I began seeking out possible links between him (or his team members) and these other New York penicillin efforts.
I quickly found many, many direct connections - and am still doing so.
Who - just for a minor example - would have ever thought that Dr Anne Fulcher Hunter had both a husband (Thomas Hunter) working with Dawson at the heart of the natural penicillin effort at Columbia and a half brother (Donald Melville) working at the heart of the opposing synthetic penicillin effort with Vincent du Vigneaud at Cornell ?
Heatedly interesting discussions indeed around her family dinner table !
My book will make the case that Dawson's passion inspired many New York scientists and businessmen to step out of their conventional skins for once in their lives to try something very risky and yet very morally worthy.
Most of these people would probably freely admit that their wartime Dawson-inspired penicillin adventures were the high points of their careers and indeed of their entire lives.
So I will fully structure my book around Dawson and NYC, but unlike previous books, I will not damn contrasting efforts by a single sentence-paragraph-page of faint praise.
Florey, Fleming, the OSRD and Merck will all get plenty of space to make their case for limiting wartime penicillin use to frontline Allied soldiers only - and that only after it had been first perfected as a patentable synthetic analogue.
I will leave it to the reader (and to God) to decide which side made the better moral case ...
I am one of the latter : as many a TV police detective is fond of saying , my motto is "I don't believe in coincidences."
When I fell upon the story of Henry Dawson and wartime penicillin, I noticed that most of the twenty or so full length accounts of wartime penicillin always included the awkward fact that he (and not their hero Howard Florey) was the one to give history's first ever penicillin shots.
They briefly described that first needle in a sentence or paragraph or page or two --- and then always go on quickly to say that Dawson himself was dying of a terminal illness - 'so necessarily passes out of our story'.
The rest of their three hundred or page accounts have nothing further about Dawson's team.
Clearly they mentally needed a way to dispose of Dawson (his convenient terminal illness) without seriously engaging his team's more than five years of involvement with penicillin.
They already had a preconceived shape to their biography of Florey and so they mentally hardly wanted to investigate Dawson's story any further --- less it ruined their story's trim panty lines.
Dawson did indeed die from his illness - but that was only at the end of April 1945 , while his team effort can be said to have begun when team member Karl Meyer learned firsthand of Florey's successful curing of infected mice in the early summer of 1940 from Florey ex-team member Leslie Epstein (Falk).
Dawson in fact kept very active in pioneering penicillin work right up to his death.
His team - in particular Gladys Hobby at Pfizer and Thomas hunter at Columbia - continued to do important work with penicillin for a few more years , even after the war's end.
Now what struck me with the force of a hammer in the first few days of my research - even back ten years ago when I knew almost nothing about wartime penicillin - was the amazing number of truly significant events in the penicillin story that had happened in the New York City area.
And that they all seemed to be of a similar type - let us simply describe them as all taking a similarly non-conventional approach to solving the penicillin supply issue.
Set against the relatively inactivity of a similar nature from the other 1990 million other human beings on earth in 1940 , they certainly seemed statistically odd beyond measure to be unconnected.
Since Dawson was both the first and the most active of these NYC inside agitators , I began seeking out possible links between him (or his team members) and these other New York penicillin efforts.
I quickly found many, many direct connections - and am still doing so.
Who - just for a minor example - would have ever thought that Dr Anne Fulcher Hunter had both a husband (Thomas Hunter) working with Dawson at the heart of the natural penicillin effort at Columbia and a half brother (Donald Melville) working at the heart of the opposing synthetic penicillin effort with Vincent du Vigneaud at Cornell ?
Heatedly interesting discussions indeed around her family dinner table !
My book will make the case that Dawson's passion inspired many New York scientists and businessmen to step out of their conventional skins for once in their lives to try something very risky and yet very morally worthy.
Most of these people would probably freely admit that their wartime Dawson-inspired penicillin adventures were the high points of their careers and indeed of their entire lives.
So I will fully structure my book around Dawson and NYC, but unlike previous books, I will not damn contrasting efforts by a single sentence-paragraph-page of faint praise.
Florey, Fleming, the OSRD and Merck will all get plenty of space to make their case for limiting wartime penicillin use to frontline Allied soldiers only - and that only after it had been first perfected as a patentable synthetic analogue.
I will leave it to the reader (and to God) to decide which side made the better moral case ...
Monday, August 25, 2014
Chemistry PhD = Hubris ?
As penicillium mold spores drift about through the air, the fortunate ones land on a suitably moist food supply.
The spores almost need the moisture more than the food , as they can feed on almost any organic matter.
But when they get stressed, usually when the food supply runs low , they may respond by producing the antibiotics we rather loosely call by the single word 'penicillin' , to keep at bay bacterial competitors for that same food.
Note I said antibiotics in the plural, because, depending on the particular food source at hand, each penicillin produced might be in fact ever so slightly different.
Technically, the key part of the penicillin molecule - the famous strained beta lactam ring - must always be there , for it to work as a antibiotic .
But the extra bit on the side of that key component - the side chain - can vary widely and will tend to produce various kinds and strengths of antibiotics.
Many of them offer different - useful - qualities - from the original penicillin (type G).
Now, in Nature , all these marvellous variants are mere happy accidents induced by the chance of varying wind currents and drifting spores.
In the Lab, biologists and chemists feed the penicillium spores all sorts of extra food treats , (fancied up ,the technical word for these humble food supplements is precursors) hoping to see a useful variant emerge.
When the new improved variants do emerge , the chemists tend to glorify this 'brute force' approach to the discovery of new chemicals by daring to call the results "semi-synthetic" penicillin.
But this just hubris and hooey.
It is merely a way for human chemists - who tried and failed to make penicillin from scratch* like the tiny mold spores so readilyand so easily did - to regain some lost luster for their profession.
(*To chemists , this is their holy grail of "total synthesis".)
Because it is really no different than the ancient practise of farmers trying out plants on differing soil mixtures and cultivation techniques and running with the methods that gave the best yields.
The chemists, rather like the British , lost really big in WWII.
Partly to physics (the A-Bomb) and partly to biology (natural penicillin triumphing over the chemists' failure to make synthetic penicillin) .
And like the British, they've been trying to re-write the history of WWII ever since ....
The spores almost need the moisture more than the food , as they can feed on almost any organic matter.
But when they get stressed, usually when the food supply runs low , they may respond by producing the antibiotics we rather loosely call by the single word 'penicillin' , to keep at bay bacterial competitors for that same food.
Note I said antibiotics in the plural, because, depending on the particular food source at hand, each penicillin produced might be in fact ever so slightly different.
Technically, the key part of the penicillin molecule - the famous strained beta lactam ring - must always be there , for it to work as a antibiotic .
But the extra bit on the side of that key component - the side chain - can vary widely and will tend to produce various kinds and strengths of antibiotics.
Many of them offer different - useful - qualities - from the original penicillin (type G).
Now, in Nature , all these marvellous variants are mere happy accidents induced by the chance of varying wind currents and drifting spores.
In the Lab, biologists and chemists feed the penicillium spores all sorts of extra food treats , (fancied up ,the technical word for these humble food supplements is precursors) hoping to see a useful variant emerge.
When the new improved variants do emerge , the chemists tend to glorify this 'brute force' approach to the discovery of new chemicals by daring to call the results "semi-synthetic" penicillin.
But this just hubris and hooey.
It is merely a way for human chemists - who tried and failed to make penicillin from scratch* like the tiny mold spores so readilyand so easily did - to regain some lost luster for their profession.
(*To chemists , this is their holy grail of "total synthesis".)
Because it is really no different than the ancient practise of farmers trying out plants on differing soil mixtures and cultivation techniques and running with the methods that gave the best yields.
The chemists, rather like the British , lost really big in WWII.
Partly to physics (the A-Bomb) and partly to biology (natural penicillin triumphing over the chemists' failure to make synthetic penicillin) .
And like the British, they've been trying to re-write the history of WWII ever since ....
Sunday, August 24, 2014
Time to end the much-told cover-up of UNSUCCESSFUL wartime penicillin and tell the untold tale of SUCCESSFUL wartime penicillin
Against about fifty previous books about wartime penicillin , I want my penicillin book to do something wildly different --- I want to celebrate success, not cover-up failure.
If the wartime deployment of penicillin was ultimately successful (and everybody seems to agree it was) what exactly did this successful penicillin look like?
It turns out it actually was :
(a) naturally made penicillin - not man made.
(b) and (via exports of massive amounts of American penicillin under Lend-Lease and other programs), it was made available to all in the wartime world dying from any and all diseases it could cure - not just reserved for a relatively small number of frontline Allied soldiers judged capable of returning to immediate combat, if given penicillin.
Ie , what successful wartime penicillin definitely was not, was synthesized and weaponized.
I am writing this book because I believe , 75 years after the start of wartime penicillin , it is overdue time to finally have a long, hard and brutally honest look at the actual record of the people and institutions universally regarded as the heroes of wartime penicillin.
Chief among them - by general consensus - are Fleming, Florey along with the MRC and the Ministry of Supply in Britain.
In America : the OSRD-CMR, NRRL chief Coghill , Merck Inc and the NAS-COC .
Yet all these heroes spent the entire war stridently opposed both to (a) the immediate mass production of naturally made penicillin and (b) its wartime production in quantities sufficient for all dying for lack of it in the world .
If they be the 'heroes' of wartime penicillin , it hardly needed villains !
By contrast , institutions like the British Royal Navy, Glaxo , Pfizer , the WPB and people like Dawson , Demerec , Pulvertaft and Duhig rate a paragraph (or at best , a page or two) in even lengthy accounts of wartime penicillin.
Yet these people and institutions strongly promoted the immediate wartime mass production of naturally produced penicillin for all - and then set out and did it - they made the successful version of wartime penicillin.
They did not advocate holding off on the wartime production of badly needed penicillin until it had been totally synthesized at commercial prices (something that hasn't happened yet).
Nor did they advocate that wartime penicillin be only used for those who were moderately injured, among the frontline Allied troops.
All these people and institutions shared one more thing in common (besides achieving the only universally popular scientific success of WWII).
They were not part of the Anglo-American medical-scientific establishment.
Thus they did not have privileged access (during the crucial years of 1944-1948) to information still labelled secret and only released - on a highly selective basis - in self-serving official histories that successfully polished the turd that was the total failure of weaponized synthetic penicillin.
It was not until 1972, with Lennard Bickel's invaluable book "RISE UP TO LIFE" , that many of the secrets of wartime penicillin began to be revealed - at least to the majority of the world that looked to British-oriented authors to explain penicillin.
Bickel was actually merely trying to boost credit to Howard Florey over that given to Alexander Fleming, but his book was just late enough to avoid the strictures of wartime secrecy and just early enough to interview many penicillin pioneers before they died.
And his account tried very hard to balance the British-oriented accounts published to date with information about lesser known but very important penicillin efforts around the world.
But Bickel , like all others to date, did not set WPB-Pfizer-Glaxo natural penicillin in total opposition to OSRD-Merck-Oxford synthetic penicillin.
Rather, like all accounts of the atomic Manhattan Project, he sees them as being equally funded, equally ardently pushed parallel efforts towards a common (time-sensitive) goal.
But in the case of the atomic bomb , the documentary record is very clear - almost any and all ways that might help to make enough nuclear material for even a few bombs before the war's end were massively funded and whipped into a flurry of activity by General Groves .
So for example, a trillion dollar (in 2014 dollars) gaseous diffusion production plant were built as fast as possible , before any pilot plant had even shown that particular process might work !
Even so, America only got enough weapon material for just two small bombs a scant month before Japan surrendered.
By contrast, natural penicillin's breakthrough technology ( a repeated process of selecting the best natural mutations of the penicillium mold, radiating them to produce more mutations and so on) only required a few biologists working a few months at a cost of a few thousands of dollars.
Thanks to this breakthrough, most countries outside of the USA successfully provide much of their wartime penicillin needs with a scaled up version of the primitive technology that Fleming first used - and rejected - way back in 1928 !
Only a political and moral unwillingness to create more of these primitive factories kept the UK, Canada and Australia from supplying all possible needs with scaled up 1928 technology.
It was the WPB's totally unknown OPRD , a latecomer to the penicillin effort , that quickly and cheaply made penicillin production with mutated natural penicillin such a success that we still produce all the world's antibiotics the same way to this day.
It was clear in the case of penicillin that almost everyone (outside our valiant few) from government ministers to newspaper reporters to ordinary GP doctors to Big Pharma, felt that penicillin was going to have to be first made synthetically to make enough for a wartime world and that this event was going to be quickly achieved.
(At the same time, I should say that most of the synthetic advocates generally didn't know the full extent of the intention to weaponize penicillin and that thankfully many seemed to oppose that idea when its morally repugnant nature was made clearer.)
Efforts to synthesize penicillin were fully backed by the British and American medical scientific establishment while efforts to push natural penicillin production that came from people like Cold Spring Harbour Lab chief Miloslav Demerec and Glaxo's boss Harry Jephcott were rebuffed by that same elite.
Spurred by the efforts of Dr Dawson , Dr Dante Colitti got he Hearst media empire to rouse the Dr Moms of the world with the plight of baby Patty Malone.
Even the powerful men running the Anglo-American medical-scientific establishment (& Big Pharma) momentarily quailed before the uproar from Dr Mom , but soon they returned to pushing for perfected synthetic penicillin before seeking any all-out production.
But Big Pharma was not totally united - one man within its ranks differed - and sometimes one individual is more than enough to change a whole world.
John L Smith, boss of Pfizer, was prompted by his own Dr Mom - his wife - to connect Patty Malone to the death of his own daughter - a death that Fleming could have helped prevent if only he had promoted - rather than negating - penicillin by needle.
As an ordinary patriotic American , Smith also knew D-Day was due soon. Unlike ordinary Americans, he also knew that only penicillin could prevent the war deaths by infection the sulfa drugs were no longer effective against.
Like General Groves on steroids, Smith whipped Pfizer employees to produce tons of penicillin - now ! - for D-Day and civilian patients.
In a surprisingly few months ( by the Spring of 1944) - Smith - thanks admittedly greatly to the timely efforts of Miloslav Demerec - had solved the world's penicillin crisis.
But the Anglo-American medical scientific establishment - as always with bureaucrats spending other peoples' money - kept pushing hard on synthetic penicillin for two more wasted years.
Their Plan B ( eventually employed) was to push the Big Half Truth that they were always fully behind natural penicillin from 1939 onward and were merely held up by the pesky penicillium spores themselves.
In fact, the only way they could think to totally synthesize artificial penicillin was to repeatedly destroy massive amounts of natural penicillin and then examine the resulting entrails.
Thus they did in fact support the limited production of natural penicillin - all through the war - but mostly for their chemists to destroy and then analysis - not to give to any and every patient dying for lack of it.
Shamefully, academic historians have let them get away with this particular Big Half Truth ever since ....
If the wartime deployment of penicillin was ultimately successful (and everybody seems to agree it was) what exactly did this successful penicillin look like?
It turns out it actually was :
(a) naturally made penicillin - not man made.
(b) and (via exports of massive amounts of American penicillin under Lend-Lease and other programs), it was made available to all in the wartime world dying from any and all diseases it could cure - not just reserved for a relatively small number of frontline Allied soldiers judged capable of returning to immediate combat, if given penicillin.
Ie , what successful wartime penicillin definitely was not, was synthesized and weaponized.
I am writing this book because I believe , 75 years after the start of wartime penicillin , it is overdue time to finally have a long, hard and brutally honest look at the actual record of the people and institutions universally regarded as the heroes of wartime penicillin.
Chief among them - by general consensus - are Fleming, Florey along with the MRC and the Ministry of Supply in Britain.
In America : the OSRD-CMR, NRRL chief Coghill , Merck Inc and the NAS-COC .
Yet all these heroes spent the entire war stridently opposed both to (a) the immediate mass production of naturally made penicillin and (b) its wartime production in quantities sufficient for all dying for lack of it in the world .
If they be the 'heroes' of wartime penicillin , it hardly needed villains !
By contrast , institutions like the British Royal Navy, Glaxo , Pfizer , the WPB and people like Dawson , Demerec , Pulvertaft and Duhig rate a paragraph (or at best , a page or two) in even lengthy accounts of wartime penicillin.
Yet these people and institutions strongly promoted the immediate wartime mass production of naturally produced penicillin for all - and then set out and did it - they made the successful version of wartime penicillin.
They did not advocate holding off on the wartime production of badly needed penicillin until it had been totally synthesized at commercial prices (something that hasn't happened yet).
Nor did they advocate that wartime penicillin be only used for those who were moderately injured, among the frontline Allied troops.
All these people and institutions shared one more thing in common (besides achieving the only universally popular scientific success of WWII).
They were not part of the Anglo-American medical-scientific establishment.
Thus they did not have privileged access (during the crucial years of 1944-1948) to information still labelled secret and only released - on a highly selective basis - in self-serving official histories that successfully polished the turd that was the total failure of weaponized synthetic penicillin.
It was not until 1972, with Lennard Bickel's invaluable book "RISE UP TO LIFE" , that many of the secrets of wartime penicillin began to be revealed - at least to the majority of the world that looked to British-oriented authors to explain penicillin.
Bickel was actually merely trying to boost credit to Howard Florey over that given to Alexander Fleming, but his book was just late enough to avoid the strictures of wartime secrecy and just early enough to interview many penicillin pioneers before they died.
And his account tried very hard to balance the British-oriented accounts published to date with information about lesser known but very important penicillin efforts around the world.
But Bickel , like all others to date, did not set WPB-Pfizer-Glaxo natural penicillin in total opposition to OSRD-Merck-Oxford synthetic penicillin.
Rather, like all accounts of the atomic Manhattan Project, he sees them as being equally funded, equally ardently pushed parallel efforts towards a common (time-sensitive) goal.
But in the case of the atomic bomb , the documentary record is very clear - almost any and all ways that might help to make enough nuclear material for even a few bombs before the war's end were massively funded and whipped into a flurry of activity by General Groves .
So for example, a trillion dollar (in 2014 dollars) gaseous diffusion production plant were built as fast as possible , before any pilot plant had even shown that particular process might work !
Even so, America only got enough weapon material for just two small bombs a scant month before Japan surrendered.
By contrast, natural penicillin's breakthrough technology ( a repeated process of selecting the best natural mutations of the penicillium mold, radiating them to produce more mutations and so on) only required a few biologists working a few months at a cost of a few thousands of dollars.
Thanks to this breakthrough, most countries outside of the USA successfully provide much of their wartime penicillin needs with a scaled up version of the primitive technology that Fleming first used - and rejected - way back in 1928 !
Only a political and moral unwillingness to create more of these primitive factories kept the UK, Canada and Australia from supplying all possible needs with scaled up 1928 technology.
It was the WPB's totally unknown OPRD , a latecomer to the penicillin effort , that quickly and cheaply made penicillin production with mutated natural penicillin such a success that we still produce all the world's antibiotics the same way to this day.
It was clear in the case of penicillin that almost everyone (outside our valiant few) from government ministers to newspaper reporters to ordinary GP doctors to Big Pharma, felt that penicillin was going to have to be first made synthetically to make enough for a wartime world and that this event was going to be quickly achieved.
(At the same time, I should say that most of the synthetic advocates generally didn't know the full extent of the intention to weaponize penicillin and that thankfully many seemed to oppose that idea when its morally repugnant nature was made clearer.)
Efforts to synthesize penicillin were fully backed by the British and American medical scientific establishment while efforts to push natural penicillin production that came from people like Cold Spring Harbour Lab chief Miloslav Demerec and Glaxo's boss Harry Jephcott were rebuffed by that same elite.
Spurred by the efforts of Dr Dawson , Dr Dante Colitti got he Hearst media empire to rouse the Dr Moms of the world with the plight of baby Patty Malone.
Even the powerful men running the Anglo-American medical-scientific establishment (& Big Pharma) momentarily quailed before the uproar from Dr Mom , but soon they returned to pushing for perfected synthetic penicillin before seeking any all-out production.
But Big Pharma was not totally united - one man within its ranks differed - and sometimes one individual is more than enough to change a whole world.
John L Smith, boss of Pfizer, was prompted by his own Dr Mom - his wife - to connect Patty Malone to the death of his own daughter - a death that Fleming could have helped prevent if only he had promoted - rather than negating - penicillin by needle.
As an ordinary patriotic American , Smith also knew D-Day was due soon. Unlike ordinary Americans, he also knew that only penicillin could prevent the war deaths by infection the sulfa drugs were no longer effective against.
Like General Groves on steroids, Smith whipped Pfizer employees to produce tons of penicillin - now ! - for D-Day and civilian patients.
In a surprisingly few months ( by the Spring of 1944) - Smith - thanks admittedly greatly to the timely efforts of Miloslav Demerec - had solved the world's penicillin crisis.
But the Anglo-American medical scientific establishment - as always with bureaucrats spending other peoples' money - kept pushing hard on synthetic penicillin for two more wasted years.
Their Plan B ( eventually employed) was to push the Big Half Truth that they were always fully behind natural penicillin from 1939 onward and were merely held up by the pesky penicillium spores themselves.
In fact, the only way they could think to totally synthesize artificial penicillin was to repeatedly destroy massive amounts of natural penicillin and then examine the resulting entrails.
Thus they did in fact support the limited production of natural penicillin - all through the war - but mostly for their chemists to destroy and then analysis - not to give to any and every patient dying for lack of it.
Shamefully, academic historians have let them get away with this particular Big Half Truth ever since ....
Thursday, August 14, 2014
Penicillin for patients : stable ? pure ? or just 'safe enough' ? -- the essential disagreement between Fleming, Florey and Dawson
Alexander Fleming was famously known for his frugality : in speech, in the use of materials and in his physical exertions on his paid job.
Being too self confident in his own intellectual abilities (and perhaps also being too frugal cum lazy in the physical exertion department ?) fatally led him to avoid doing the needed series of experiments to prove up his claim that penicillin would never have time to do its work inside the body.
So he misled himself - and more importantly , the entire world, for 14 years that penicillin would only work on the body, never in the body - and tens of millions died premature deaths that could have/ should have been avoided.
However, because Fleming saw penicillin as only working outside the body he had no need for Howard Florey's delusions about penicillin having to be highly purified to work safely inside the body.
Fleming merely want the chemists to make penicillin as a stable powder in a bottle any doctor could readily buy from a near by druggist, store on an unrefrigerated shelf for years and still expect to work as an external antiseptic at 100% efficiency when needed.
Call this 'lazy man medicine' or call it normalcy.
Because only one doctor in ten thousand world wide ever tried making homemade penicillin even after it was proclaimed a life-saving miracle.
They all preferred to simply patiently wait until this miracle came to them as a stable and certified safe powder in a bottle from Big Pharma.
(I am not sure all their dying patients were as patient.)
Howard Florey - to his credit - seemed to have never bought Fleming's tale that penicillin would never work inside the body - as had every other medical scientist in the world .
But because he thought it had to be purified first and that purification would be very difficult , if not impossible , he did nothing until he got a competent full time chemist on staff together with a large long term grant to sustain the effort.
Meanwhile ten wasted years (1929-1939) went by.
Clearly Florey was no medical crusader, burning to save lives NOW!
And he , too , had too much faith in his own intellectual powers.
In 1939 he requested grant money for his co-worker Ernst Chain's work on three bacteria-killing chemicals produced by living microbes against other living microbes (what scientists call antibiosis).
One was penicillin and one key phrase in the grant request reveals his thinking and his fatal flaw.
He believed that penicillin , if it can be purified, will prove safe and effective inside the body (eventually and hopeful inside the bodies of infected human patients).
But he just assumes this , again just like Fleming .
Without actually doing any of the needed experiments to prove his contention, one simply can not say that penicillin is non toxic inside the body and it is the impurities that will be unsafe inside the body.
Actually there are always - in advance of the actual experiments - a range of possibilities sliding between three poles (that represent absolutes rather than real world situations.)
The three poles are (a) only the main product is toxic (b) only the impurities are toxic (c) both are equally toxic or equally non toxic.
Let us get concrete with a few examples.
You are a chemical firm making the poison prussic acid. You discover impurities in the resulting mix (impurities being anything that isn't prussic acid).
Prussic acid is almost uniquely toxic and it is the main product - any impurities thrown up may or maybe not toxic but are unlikely to be anywhere as toxic as prussic acid.
But in this case, you are seeking pure toxicity - impure non-toxicity is the problem , not the solution.
Grapefruit are a so so source of pure vitamin C . A 500 gram fruit might hold only 50 mg of vitamin C - one bit in 10,000 is pure vitamin C and the rest is - technically - impurities.
So why do we bother ?
Well they are very tasty , providing lots of water, fibre, sugar and various other minerals and vitamins - as well as some of the tasteless vitamin C we could get from a pill.
(And surprise surprise, that pill , when taken with the needed glass of water, is also mostly dross and a tiny amount, often only 100 mg, of vitamin C !)
And all those grapefruit 'impurities 'are safe - we eat them without any danger and in fact with a great deal of enjoyment.
All our food mostly consists of a vast bulk of relatively safe impurities and tiny amounts of pure vitamins and minerals.
But some foods - some very tasty mushrooms - consist of mostly nice food and tiny amounts of impurities called toxins that kill us.
So it all depends.
First we must define what is the main product we want from a mixture before we can define its 'impurities'.
Do grapefruits consist of 90% food (discarding only the skin and seeds) or do they consist of .001 % vitamin C and 99.99% dross ?
Then we need to do the experiments before drawing any conclusions.
Because sometimes , as with weak impure penicillin juice versus pure strong penicillin powder , it turns out that penicillin allergy deaths only began with massive amounts of the 100% pure stuff !
By sheer good luck, in this particular mushroom (this strain of the sometimes dangerous penicillium mold), the impurities were non-toxic as was the penicillin .
But for a relatively large percent of people, if given large amounts of pure penicillin direct into a vein by careless doctors, it can kill on the spot in a severe allergy reaction.
The safe solution is to go on using pure penicillin but to test new patients with tiny amounts - just beneath the skin - first.
Florey spent more than ten years - from the late 1930s to the late 1940s seeking ever purer penicillin to increase the safety of this injectable drug.
His obsession was scientifically wrong, logically deluded and it delayed the wartime introduction of mass produced penicillin for years.
Florey was an eugenicist and a racist from his youth and I believe this sort of racial purity thinking leaked over into the science side of his brain - he saw penicillin as the Anglo Saxons and the impurities as the Blacks.
Blood that was 99% Anglo Saxon and 1% Black was impure and defiled - and much the same applied to pure versus impure penicillin.
In Florey's twisted mind.
Another problem was that both Fleming and Florey were far more lab doctors than ward doctors - while Martin Henry Dawson divided his time equally between both.
Sheltered university chemists quickly lose their delusions about the academic awards for obtaining 100% total synthesis ,regardless of expense or yield, once on the factory floor of a profit-seeking chemical firm.
So too with busy ward doctors balancing a dying patient versus a very dangerous drug that might injure them as well as save their life.
My mother , in her early thirties, was saved from certain infectious death by a single course of streptomycin .
It left her deaf in one ear - by that time, in 1962 , this was a well known risk of high doses of that drug.
She didn't complain then and she never ever did .
She told how grateful she was to lose her hearing to gain her life just three days before she suffered her fatal stroke - when she was in her eighties, a half century later.
So call me prejudiced - I like doctors who take chances to save patients' lives.
I like Martin Henry Dawson.
He saw two patients about to die from invariably fatal endocarditis.
All other known medical solutions had failed.
He knew penicillin seemed non toxic in various animals and in human blood - from his own research and that of Fleming and Florey.
He tested a small amount of penicillin that he suspected to be probably very weak , on himself, injected just under his skin.
No toxic results.
He did the same on the two patients - not toxic.
He gradually and slowly upped the amounts and also moving gradually to injection methods that introduced the penicillin far quicker into the blood and hence was far more potentially dangerous.
Only local pain at the injection site and a temporary fever and shakes was noted - routine for most injected drugs then.
All Dawson sought from penicillin was that it was relatively safe - and effective.
He used the penicillin he made himself with hours or days - he wasn't afraid of hard work, unlike Fleming - so stability was an non-issue to him.
Like the food that Dawson ate and enjoyed, his crude penicillin was hardly pure - but so what - it was basically safe.
Safer in fact - even in crude form - than the 100% pure sulfa drugs that were then routinely saving many lives while also making many people very very sick in the process.
Like a chemist on the shop floor ( think Smith, Elder and Jephcott ) Dawson saw life as full of compromises and the job was determining what was really Job One.
For all of them , it was saving as many patients as they could - NOW !
And God Bless 'Em for that...
Being too self confident in his own intellectual abilities (and perhaps also being too frugal cum lazy in the physical exertion department ?) fatally led him to avoid doing the needed series of experiments to prove up his claim that penicillin would never have time to do its work inside the body.
So he misled himself - and more importantly , the entire world, for 14 years that penicillin would only work on the body, never in the body - and tens of millions died premature deaths that could have/ should have been avoided.
Howard Florey's fatal flaw
However, because Fleming saw penicillin as only working outside the body he had no need for Howard Florey's delusions about penicillin having to be highly purified to work safely inside the body.
Fleming merely want the chemists to make penicillin as a stable powder in a bottle any doctor could readily buy from a near by druggist, store on an unrefrigerated shelf for years and still expect to work as an external antiseptic at 100% efficiency when needed.
Call this 'lazy man medicine' or call it normalcy.
Because only one doctor in ten thousand world wide ever tried making homemade penicillin even after it was proclaimed a life-saving miracle.
They all preferred to simply patiently wait until this miracle came to them as a stable and certified safe powder in a bottle from Big Pharma.
(I am not sure all their dying patients were as patient.)
Florey's great insight
Howard Florey - to his credit - seemed to have never bought Fleming's tale that penicillin would never work inside the body - as had every other medical scientist in the world .
But because he thought it had to be purified first and that purification would be very difficult , if not impossible , he did nothing until he got a competent full time chemist on staff together with a large long term grant to sustain the effort.
Meanwhile ten wasted years (1929-1939) went by.
Clearly Florey was no medical crusader, burning to save lives NOW!
And he , too , had too much faith in his own intellectual powers.
In 1939 he requested grant money for his co-worker Ernst Chain's work on three bacteria-killing chemicals produced by living microbes against other living microbes (what scientists call antibiosis).
One was penicillin and one key phrase in the grant request reveals his thinking and his fatal flaw.
He believed that penicillin , if it can be purified, will prove safe and effective inside the body (eventually and hopeful inside the bodies of infected human patients).
But he just assumes this , again just like Fleming .
Without actually doing any of the needed experiments to prove his contention, one simply can not say that penicillin is non toxic inside the body and it is the impurities that will be unsafe inside the body.
Actually there are always - in advance of the actual experiments - a range of possibilities sliding between three poles (that represent absolutes rather than real world situations.)
The three poles are (a) only the main product is toxic (b) only the impurities are toxic (c) both are equally toxic or equally non toxic.
Let us get concrete with a few examples.
You are a chemical firm making the poison prussic acid. You discover impurities in the resulting mix (impurities being anything that isn't prussic acid).
Prussic acid is almost uniquely toxic and it is the main product - any impurities thrown up may or maybe not toxic but are unlikely to be anywhere as toxic as prussic acid.
But in this case, you are seeking pure toxicity - impure non-toxicity is the problem , not the solution.
Grapefruit are 99.99% impure of vitamin C - thanks be to God
Grapefruit are a so so source of pure vitamin C . A 500 gram fruit might hold only 50 mg of vitamin C - one bit in 10,000 is pure vitamin C and the rest is - technically - impurities.
So why do we bother ?
Well they are very tasty , providing lots of water, fibre, sugar and various other minerals and vitamins - as well as some of the tasteless vitamin C we could get from a pill.
(And surprise surprise, that pill , when taken with the needed glass of water, is also mostly dross and a tiny amount, often only 100 mg, of vitamin C !)
And all those grapefruit 'impurities 'are safe - we eat them without any danger and in fact with a great deal of enjoyment.
All our food mostly consists of a vast bulk of relatively safe impurities and tiny amounts of pure vitamins and minerals.
But some foods - some very tasty mushrooms - consist of mostly nice food and tiny amounts of impurities called toxins that kill us.
So it all depends.
First we must define what is the main product we want from a mixture before we can define its 'impurities'.
Do grapefruits consist of 90% food (discarding only the skin and seeds) or do they consist of .001 % vitamin C and 99.99% dross ?
Then we need to do the experiments before drawing any conclusions.
Because sometimes , as with weak impure penicillin juice versus pure strong penicillin powder , it turns out that penicillin allergy deaths only began with massive amounts of the 100% pure stuff !
By sheer good luck, in this particular mushroom (this strain of the sometimes dangerous penicillium mold), the impurities were non-toxic as was the penicillin .
But for a relatively large percent of people, if given large amounts of pure penicillin direct into a vein by careless doctors, it can kill on the spot in a severe allergy reaction.
The safe solution is to go on using pure penicillin but to test new patients with tiny amounts - just beneath the skin - first.
Florey spent more than ten years - from the late 1930s to the late 1940s seeking ever purer penicillin to increase the safety of this injectable drug.
His obsession was scientifically wrong, logically deluded and it delayed the wartime introduction of mass produced penicillin for years.
Florey was a racist
Florey was an eugenicist and a racist from his youth and I believe this sort of racial purity thinking leaked over into the science side of his brain - he saw penicillin as the Anglo Saxons and the impurities as the Blacks.
Blood that was 99% Anglo Saxon and 1% Black was impure and defiled - and much the same applied to pure versus impure penicillin.
In Florey's twisted mind.
Ward doctors are like shop floor chemists - they hold few illusions
Another problem was that both Fleming and Florey were far more lab doctors than ward doctors - while Martin Henry Dawson divided his time equally between both.
Sheltered university chemists quickly lose their delusions about the academic awards for obtaining 100% total synthesis ,regardless of expense or yield, once on the factory floor of a profit-seeking chemical firm.
So too with busy ward doctors balancing a dying patient versus a very dangerous drug that might injure them as well as save their life.
My mother would have backed Martin Henry Dawson 110%
My mother , in her early thirties, was saved from certain infectious death by a single course of streptomycin .
It left her deaf in one ear - by that time, in 1962 , this was a well known risk of high doses of that drug.
She didn't complain then and she never ever did .
She told how grateful she was to lose her hearing to gain her life just three days before she suffered her fatal stroke - when she was in her eighties, a half century later.
So call me prejudiced - I like doctors who take chances to save patients' lives.
I like Martin Henry Dawson.
He saw two patients about to die from invariably fatal endocarditis.
All other known medical solutions had failed.
He knew penicillin seemed non toxic in various animals and in human blood - from his own research and that of Fleming and Florey.
He tested a small amount of penicillin that he suspected to be probably very weak , on himself, injected just under his skin.
No toxic results.
He did the same on the two patients - not toxic.
He gradually and slowly upped the amounts and also moving gradually to injection methods that introduced the penicillin far quicker into the blood and hence was far more potentially dangerous.
Only local pain at the injection site and a temporary fever and shakes was noted - routine for most injected drugs then.
All Dawson sought from penicillin was that it was relatively safe - and effective.
He used the penicillin he made himself with hours or days - he wasn't afraid of hard work, unlike Fleming - so stability was an non-issue to him.
Like the food that Dawson ate and enjoyed, his crude penicillin was hardly pure - but so what - it was basically safe.
Safer in fact - even in crude form - than the 100% pure sulfa drugs that were then routinely saving many lives while also making many people very very sick in the process.
Like a chemist on the shop floor ( think Smith, Elder and Jephcott ) Dawson saw life as full of compromises and the job was determining what was really Job One.
For all of them , it was saving as many patients as they could - NOW !
And God Bless 'Em for that...
Monday, July 28, 2014
Oxford University Artificial Penicillin totally fails to deliver - morally as well as technically
It goes without saying that Oxford University's wartime chimera of totally synthesized artificial penicillin was an abject failure.
75 years on, we still start the production of all the penicillin and beta lactam antibiotics with natural fermentation.
So ---- just a minor technical failing ?
Few go on to consider the moral failings behind the Conservative Party-led British government's wartime penicillin decisions.
The (New Deal-oriented) American WPB (War Production Board) had greatly upped the penicillin amounts originally proposed by Oxford's American ally , Vannevar Bush's OSRD.
The WPB wanted not just enough penicillin produced to satisfy the life-saving demands of the American military, with some left for certain civilian conditions.
They wanted levels that meant all American lifesaving situations were met.
With plenty left over to fill all the unmet demands among the other Allies, with still more left for neutral nations, liberated Europe and even Axis POWs.
The WPB fulfilled Dr Martin Henry Dawson's dream of cheap abundant penicillin for all in the war world - in spades !
By contrast, Churchill's government was unwilling to divert enough resources away from yet more heavy bombers to cure all of Britain's military and civilian life-threatening bacterial infections - let alone to meet the needs of its own colonies.
And as for the rest of the world ? The could all whistle for their penicillin , as far as Churchill was concerned.
The prime minister of the nation that had given the world the discovery and early development of the world's first and best lifesaver thus threw all that global goodwill away - just for a handful of more bombs.
With that one - unbelievably heartless and stupid - decision , Churchill ensured that the Pax Britannica became the Pax Americana .....
75 years on, we still start the production of all the penicillin and beta lactam antibiotics with natural fermentation.
So ---- just a minor technical failing ?
Few go on to consider the moral failings behind the Conservative Party-led British government's wartime penicillin decisions.
The (New Deal-oriented) American WPB (War Production Board) had greatly upped the penicillin amounts originally proposed by Oxford's American ally , Vannevar Bush's OSRD.
The WPB wanted not just enough penicillin produced to satisfy the life-saving demands of the American military, with some left for certain civilian conditions.
They wanted levels that meant all American lifesaving situations were met.
With plenty left over to fill all the unmet demands among the other Allies, with still more left for neutral nations, liberated Europe and even Axis POWs.
The WPB fulfilled Dr Martin Henry Dawson's dream of cheap abundant penicillin for all in the war world - in spades !
By contrast, Churchill's government was unwilling to divert enough resources away from yet more heavy bombers to cure all of Britain's military and civilian life-threatening bacterial infections - let alone to meet the needs of its own colonies.
And as for the rest of the world ? The could all whistle for their penicillin , as far as Churchill was concerned.
The prime minister of the nation that had given the world the discovery and early development of the world's first and best lifesaver thus threw all that global goodwill away - just for a handful of more bombs.
With that one - unbelievably heartless and stupid - decision , Churchill ensured that the Pax Britannica became the Pax Americana .....
Monday, January 21, 2013
Dawson's DIY penicillin a postmodernist "shot across the bow" of Modernist Big Pharma
Two hundred years from now, only the first of the Dawson team's many articles on wartime penicillin will still be cited and still considered seminal.
This, despite the fact that Nova Scotia-born Henry Dawson's last penicillin article told a surprised world that invariable fatal subacute bacterial endocarditis (the much dreaded SBE) had finally been cured - by his penicillin method that he had pioneered 5 years earlier.
But instead it is Dawson's first penicillin first article, the "impure but non toxic" article of May 5th 1941, that had (and continues to have) ramifications beyond any one disease, ramifications indeed beyond even medicine and science itself.
In that article, delivered before a large group of international medical researchers in Atlantic City and widely reported by the popular and scientific media from The New York Times to the South Africa Medical Journal, Dawson deliberately paired and then contrasted two oxymoronic phrases.
But first, recall that Dawson chose to appear in front of all his peers to praise his new drug to the heavens AND announce that it had no therapeutic effect on a series of four SBE cases in a row.
Trust me on this one : normally scientists do not rush to the biggest conference in town to proudly announce repeated failure.
But it wasn't the lack of therapeutic success from his impure natural penicillin that Dawson was really so eager to announce.
Rather it was the lack of toxic effects from his crude homemade mixture of natural penicillin and its natural impurities that he was so proud (and perhaps amazed) to announce.
(In a sort of 'reverse Ivory Soap', his starting penicillin brew was far less than 99 and 44 100th percent impure : pure penicillin made up only one part per million of his mixture !)
It could have had - perhaps even should have had - a highly deadly mycotoxin poison buried somewhere in that fungus mix, but God took pity on Humanity and it did not.
We do not have a complete version of Dawson's report and ad lib comments , only various precis. But assembled together, I believe we can garner Dawson's actual words and phrases used to prescribe his main intent behind this article.
He described how his tiny team made their hospital-grown crude (impure) and natural penicillin, calling it both more potent and much less toxic than the factory-made chemically pure synthetic sulfa drugs, less potent and more toxic, made by Big Pharma .
His takeaway line, as the CBC's Don Connolly likes to say, is that "despite being impure, homemade natural penicillin was actually less toxic and much more potent than factory-made pure synthetic sulfa drugs."
Today, in this postmodern age, this statement might hardly seem controversial ; but in 1940, at the apogee of Modernity, to diss the Du Pont slogan of "living better chemically" was to indulge in sheer heresy.
At the same university as Dawson (Columbia) and at the exact same time, famed German-scholars-in-exile Adorno and Horkheimer were busy dismantling 500 years of Modernity, brick by brick, and patiently reassembling them as Postmodernity.
Perhaps posthumously, their fellow university colleague Henry Dawson can lay claim to being among Postmodernity's first scientific converts.....
This, despite the fact that Nova Scotia-born Henry Dawson's last penicillin article told a surprised world that invariable fatal subacute bacterial endocarditis (the much dreaded SBE) had finally been cured - by his penicillin method that he had pioneered 5 years earlier.
But instead it is Dawson's first penicillin first article, the "impure but non toxic" article of May 5th 1941, that had (and continues to have) ramifications beyond any one disease, ramifications indeed beyond even medicine and science itself.
In that article, delivered before a large group of international medical researchers in Atlantic City and widely reported by the popular and scientific media from The New York Times to the South Africa Medical Journal, Dawson deliberately paired and then contrasted two oxymoronic phrases.
But first, recall that Dawson chose to appear in front of all his peers to praise his new drug to the heavens AND announce that it had no therapeutic effect on a series of four SBE cases in a row.
Trust me on this one : normally scientists do not rush to the biggest conference in town to proudly announce repeated failure.
But it wasn't the lack of therapeutic success from his impure natural penicillin that Dawson was really so eager to announce.
Rather it was the lack of toxic effects from his crude homemade mixture of natural penicillin and its natural impurities that he was so proud (and perhaps amazed) to announce.
(In a sort of 'reverse Ivory Soap', his starting penicillin brew was far less than 99 and 44 100th percent impure : pure penicillin made up only one part per million of his mixture !)
It could have had - perhaps even should have had - a highly deadly mycotoxin poison buried somewhere in that fungus mix, but God took pity on Humanity and it did not.
We do not have a complete version of Dawson's report and ad lib comments , only various precis. But assembled together, I believe we can garner Dawson's actual words and phrases used to prescribe his main intent behind this article.
He described how his tiny team made their hospital-grown crude (impure) and natural penicillin, calling it both more potent and much less toxic than the factory-made chemically pure synthetic sulfa drugs, less potent and more toxic, made by Big Pharma .
His takeaway line, as the CBC's Don Connolly likes to say, is that "despite being impure, homemade natural penicillin was actually less toxic and much more potent than factory-made pure synthetic sulfa drugs."
"Living better chemically ?"
Today, in this postmodern age, this statement might hardly seem controversial ; but in 1940, at the apogee of Modernity, to diss the Du Pont slogan of "living better chemically" was to indulge in sheer heresy.
At the same university as Dawson (Columbia) and at the exact same time, famed German-scholars-in-exile Adorno and Horkheimer were busy dismantling 500 years of Modernity, brick by brick, and patiently reassembling them as Postmodernity.
Perhaps posthumously, their fellow university colleague Henry Dawson can lay claim to being among Postmodernity's first scientific converts.....
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......
Sunday, January 13, 2013
Most of the penicillin grown in its first 15 years, was wasted on useless attempts at synthesis, not used to save the dying
If my claim be wrong : show me the money !
Open all the archives on university, hospital and corporate penicillin files.
Show us the size and number of penicillin production runs, month by month, from September 1928 to September 1943 ( ie including the first four years of the war).
Then shows us the amount of penicillin units actually released for therapeutic use on human patients suffering from infections suspected of being defeatable by penicillin, during that same time period.
I have never seen any published accounts where the responsible authorities complained about all the precious potentially life-saving penicillin that was being wasted ---- during an all-out Total War ! ----on a futile 20 year long effort to synthesize patentable profitable penicillin from PD (public domain) natural penicillin.
But there are plenty of complaints from the higher-ups about all the penicillin being wasted on saving the lives of ("useless feeders") young people dying from hitherto invariably fatal SBE (endocarditis)......
Open all the archives on university, hospital and corporate penicillin files.
Show us the size and number of penicillin production runs, month by month, from September 1928 to September 1943 ( ie including the first four years of the war).
Then shows us the amount of penicillin units actually released for therapeutic use on human patients suffering from infections suspected of being defeatable by penicillin, during that same time period.
Patents, Profits and Patriotism : pick two out of the three...
I have never seen any published accounts where the responsible authorities complained about all the precious potentially life-saving penicillin that was being wasted ---- during an all-out Total War ! ----on a futile 20 year long effort to synthesize patentable profitable penicillin from PD (public domain) natural penicillin.
But there are plenty of complaints from the higher-ups about all the penicillin being wasted on saving the lives of ("useless feeders") young people dying from hitherto invariably fatal SBE (endocarditis)......
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