E M Forster is a name you pretty well have to come across if you have ever been formally taught how to write better sentences, paragraphs and articles ---- and today that includes virtually all of us with a high school education or better.
Even senior scientists and academics. When those two deliberately ignore what they've been taught for decades, you should always expect foul play is afoot.
Showing posts with label merck. Show all posts
Showing posts with label merck. Show all posts
Wednesday, May 27, 2015
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 ...
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 ...
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 ....
Tuesday, August 12, 2014
Synthetic Howard Florey vs Natural Martin Henry Dawson
The untold scandal of the Anglo-American pharmaceuticals "CODE SLOWING" natural penicillin production in the crucial months before D-Day
Howard Florey seems to have contacted every major pharmaceutical firm and governmental scientific organization in the UK , Canada and America but clicked with only a very few.
Martin Henry Dawson's project was known by most of the same organizations - but he clicked with even fewer.
But both men eventually found institutional supporters of the same like mind as themselves - so it probably didn't matter how many rejected them.
Both men were relatively inflexible as to their ultimate objectives.
Florey sought a perfect chemical synthetic solution, no matter how long it took and was unwilling to settle for anything less .
By contrast, Dawson wanted any sort of solution to the penicillin supply issue - as long as it happened now ! - and that it provided an abundance of inexpensive wartime penicillin.
Florey found similarly chemically minded executives at Merck, ICI and in A. N. Richards the head of the medical division of the American OSRD (where the ultimate boss, Vannevar Bush was notorious for never ever hiring biologists.)
Dawson found a kindred soul in John L Smith of Pfizer (albeit prodded by his wife Mae) who decided to risk all by going the all-natural route when the industry consensus was to "Code Slow" natural penicillin production until perfect synthetic penicillin was invented.
And like Dawson, Smith's vision was for lots and lots and lots of penicillin - now !
Suddenly - a crucial month before D-Day - the race between the two competing visions was all over.
Not a drop of synth pen in the pipeline to Kansas City Kansas and then onto the waiting military hospital units in the south of England - instead tens of billions of units of natural penicillin were in that pipeline , almost all from Pfizer.
Florey stormed and the dying Dawson permitted himself a rare - wall-to-wall - grin .....
Sunday, July 27, 2014
Oxford Artificial versus Manhattan Natural
Howard Florey (along with Alexander Fleming and Winston Churchill's government) spend ten years before during and after WWII pursuing the chimera of totally artificial (patentable) penicillin --- to no avail.
As did Florey's supporters in America - Merck, Squibb and Vannevar Bush's all-powerful OSRD.
Set against then, on the opposite side of the Hudson River , was Dr Martin Henry Dawson and John l Smith , chemist and boss of Pfizer.
They saw possibilities in the fermentation of the (public domain - free for all to grow) natural penicillium to produce antibiotics.
This was despite its current yields being admittedly low: they felt as it was a totally new way of doing medicine , it might well improve drastically with more practise.
(I should mention that two other strong skeptics of the whole idea of the commercial viability of total synthesis of penicillin were also practising chemists : Glaxo boss Harry Jepcott and the WPB's penicillin czar Larry Elder.
It was chemist manques like Florey and the OSRD's Dr Richards who were the most likely to feel that of course man-made Chemistry was always bound to be superior to Mother Nature.)
Today of course, with penicillin being produced at 50,000 times the levels of Fleming for the same cost in time labour and materials, the case against oxford Artificial seems clear - but it wasn't so throughout the war and beyond.
Long Island scientist Miloslav Demerec deserves a lot more credit than he ever gets (which is none !) for his major role in making our wonderful world of relatively cheap abundant antibiotics ....
As did Florey's supporters in America - Merck, Squibb and Vannevar Bush's all-powerful OSRD.
Set against then, on the opposite side of the Hudson River , was Dr Martin Henry Dawson and John l Smith , chemist and boss of Pfizer.
They saw possibilities in the fermentation of the (public domain - free for all to grow) natural penicillium to produce antibiotics.
This was despite its current yields being admittedly low: they felt as it was a totally new way of doing medicine , it might well improve drastically with more practise.
(I should mention that two other strong skeptics of the whole idea of the commercial viability of total synthesis of penicillin were also practising chemists : Glaxo boss Harry Jepcott and the WPB's penicillin czar Larry Elder.
It was chemist manques like Florey and the OSRD's Dr Richards who were the most likely to feel that of course man-made Chemistry was always bound to be superior to Mother Nature.)
Today of course, with penicillin being produced at 50,000 times the levels of Fleming for the same cost in time labour and materials, the case against oxford Artificial seems clear - but it wasn't so throughout the war and beyond.
Long Island scientist Miloslav Demerec deserves a lot more credit than he ever gets (which is none !) for his major role in making our wonderful world of relatively cheap abundant antibiotics ....
Tuesday, November 19, 2013
WWII : the dogma of pure simplicity confounded by reality's mixed complexity
Llewellyn Park Refined versus Brooklyn Crude ...
Llewellyn Park New Jersey, home to Merck's CEO, George W Merck, along with many other rich people, was democratic America's first gated community, designed pure and simple to keep Reality out.
Unsurprisingly then that six foot four George Merck spent all of WWII failing to make pure simple synthetic penicillin --- despite mounting scientific evidence suggested it couldn't be done even at a financial loss.
By contrast, John l Smith, the five foot nothing tall vice president of operations at Pfizer, lived in the polyglot capital of the world, Brooklyn NYC, and spent his war quietly accepting that the only penicillin landing on the D-Day beaches and filling grateful civilian and soldiers' veins would be his firm's complexly impure natural penicillin.
Just two of the world's two billion people in the early 1940s, all who had to decide for themselves what to do and what to think when the reality of the war situation conflicted with their pre-1939 dogma about the nature of reality......
Sunday, February 10, 2013
Howard Florey saw potential enemies everywhere, but with "friends" like A N Richards and Robert Coghill, he hardly need bother looking any further
Howard Florey's correspondence twice notes that he has just received a higher yielding strain of penicillium from America.
The first, in November 1941 ,was obtained from Dr Rake at Squibb - a higher producing mutant from Fleming's original strain.
The second time in November 1943, some un-named strains were obtained from Robert Coghill of the NRRL , while he was visiting Oxford .
But in the two crucial years in between ?
I see bugger all evidence that Florey got the latest improvements in penicillium strains as they emerged at Peoria. (Prove me wrong, please) .
The mycologists at the NRRL research centre in Peoria had steadily improved and improved and improved again Rake's variant and their final version, NRRL 1249.B21 produced - via surface cultivation - most of the world's wartime penicillin until quite late in the war.
At that point, submerged strain NRRL 832, from a non-Fleming strain first found in Belgium, took over.
I believe that Merck's chief consultant and OSRD medical chief ( giant conflict of interest alert !) A N Richards, supposedly Florey's second closest American friend, using as an excuse that America was now at war, deliberately held back the giving these improved strains to Florey.
All to further America's ( sorry ! Merck's) post-war commercial opportunities.
Nicolas Rasmussen, in his article "Of 'Small Men', Big Science and Bigger Business", looks much closer than most historians at the day to day workings of the medical wing of the famous OSRD.
He points to several examples where Richards authorizes the further spending of taxpayers' money, supposedly only for war weapons, on drug research that no longer had an obvious military use, because he claimed that keeping American's edge in their development would definitely benefit the nation.
If not in this war, or any war, how would the drug's successful development benefit a nation at war - supposedly the sole purpose of the OSRD, whose mandate was set up to expire the moment peace was declared ?
Richards doesn't say.
So let me suggest a more sinister purpose , because Rasmussen does not.
I note that the two examples that Rasmussen gives where the OSRD spends taxpayers money on projects that no longer seemed to have a military need were pet projects of Merck, the firm that Richards advised.
The first was the chemical synthesis work on penicillin , carried on well past the point (say June 1944) when biological penicillin was being produced en masse and cheaply.
The other was after mid 1943, when it was clear that cortisone would not help pilots fly higher longer - an important advantage for any nation's air force if proven so.
Merck got nothing for all the money it spent on synthetic penicillin but its finally successful efforts on cortisone was and is one of its biggest successes for both its scientific reputation and its pocketbook (the two of course being closely related).
First success with Cortisone would be an advantage to America as well as Merck, over European (Swiss) competitors --- but synthetic penicillin's success could only have come by crushing fellow American firm Pfizer and given the field to Merck.
How then would that serve America's interests, rather than merely Merck's?
Because Europe wasn't even in the running on biological penicillin in 1944.
Perhaps Richards, already a pensioner when he took on the job of heading the OSRD medical wing and with the rigidity of old age, still believed synthetic penicillin would better Pfizer's penicillin in price and yield.
Then Merck would beat their only European synthetic penicillin rival : Florey !
Normally, Vannevar Bush's OSRD - as in denying the British to atomic energy research - did a better job of using taxpayers' military-assigned money to screw America's European Allies' commercial chances after the war , without favouring any one American firm.
Richard's willingness to screw Pfizer and even his friend Florey, shows just how much further he was prepared to go to aid Merck.
But he needed pliant helpers to succeed.
Luckily for him, the NRRL's Robert Coghill seemed to have had a hard time accepting that research paid for by his employer , the US Department of Agriculture and ultimately the American public, belonged to the USDA.
And that this research shouldn't only go where a different agency's chief bureaucrat, A N Richards, wanted it to go - though he hadn't paid for it and had no statutory (legal) control over it.
However , I see Coghill, a misplaced chemist running a biological program, wanted in so badly on a "technically sweet" chemical problem (the synthesis of penicillin) that he sold out the farmers he had sworn to help.
Synthetic penicillin would only negate the ready market for hundreds of thousands of tons of farm waste corn steep liquor, farm waste whey and farm waste crude brown sugar, all used in the natural fermentation of penicillin and other antibiotics coming along in the pipeline.
Coghill did publicly announce that he was giving the top two commercial strains of penicillium (presumably NRRL 1249.B21 and 832) to the entire world in November 1943, about the same time as Florey first mentions having them.
Why ?
I can only suspect because they were about to become obsolete, as synthetic penicillin seemed only months away.
By April 1944, that no longer seemed so and Coghill was back on the side of the biological angels, publicly praising Pfizer's biological penicillin and modestly claiming a role in their success.
Coghill's talents seemed rather wasted in democratic America - I can see him as the ultimate bureaucratic survivor in Stalin's Russia, adroitly changing sides as the situation shifted, moment by moment.....
The first, in November 1941 ,was obtained from Dr Rake at Squibb - a higher producing mutant from Fleming's original strain.
The second time in November 1943, some un-named strains were obtained from Robert Coghill of the NRRL , while he was visiting Oxford .
But in the two crucial years in between ?
I see bugger all evidence that Florey got the latest improvements in penicillium strains as they emerged at Peoria. (Prove me wrong, please) .
The mycologists at the NRRL research centre in Peoria had steadily improved and improved and improved again Rake's variant and their final version, NRRL 1249.B21 produced - via surface cultivation - most of the world's wartime penicillin until quite late in the war.
At that point, submerged strain NRRL 832, from a non-Fleming strain first found in Belgium, took over.
I believe that Merck's chief consultant and OSRD medical chief ( giant conflict of interest alert !) A N Richards, supposedly Florey's second closest American friend, using as an excuse that America was now at war, deliberately held back the giving these improved strains to Florey.
All to further America's ( sorry ! Merck's) post-war commercial opportunities.
Nicolas Rasmussen, in his article "Of 'Small Men', Big Science and Bigger Business", looks much closer than most historians at the day to day workings of the medical wing of the famous OSRD.
He points to several examples where Richards authorizes the further spending of taxpayers' money, supposedly only for war weapons, on drug research that no longer had an obvious military use, because he claimed that keeping American's edge in their development would definitely benefit the nation.
If not in this war, or any war, how would the drug's successful development benefit a nation at war - supposedly the sole purpose of the OSRD, whose mandate was set up to expire the moment peace was declared ?
Richards doesn't say.
So let me suggest a more sinister purpose , because Rasmussen does not.
I note that the two examples that Rasmussen gives where the OSRD spends taxpayers money on projects that no longer seemed to have a military need were pet projects of Merck, the firm that Richards advised.
The first was the chemical synthesis work on penicillin , carried on well past the point (say June 1944) when biological penicillin was being produced en masse and cheaply.
The other was after mid 1943, when it was clear that cortisone would not help pilots fly higher longer - an important advantage for any nation's air force if proven so.
Merck got nothing for all the money it spent on synthetic penicillin but its finally successful efforts on cortisone was and is one of its biggest successes for both its scientific reputation and its pocketbook (the two of course being closely related).
First success with Cortisone would be an advantage to America as well as Merck, over European (Swiss) competitors --- but synthetic penicillin's success could only have come by crushing fellow American firm Pfizer and given the field to Merck.
How then would that serve America's interests, rather than merely Merck's?
Because Europe wasn't even in the running on biological penicillin in 1944.
Perhaps Richards, already a pensioner when he took on the job of heading the OSRD medical wing and with the rigidity of old age, still believed synthetic penicillin would better Pfizer's penicillin in price and yield.
Then Merck would beat their only European synthetic penicillin rival : Florey !
Normally, Vannevar Bush's OSRD - as in denying the British to atomic energy research - did a better job of using taxpayers' military-assigned money to screw America's European Allies' commercial chances after the war , without favouring any one American firm.
Richard's willingness to screw Pfizer and even his friend Florey, shows just how much further he was prepared to go to aid Merck.
But he needed pliant helpers to succeed.
Luckily for him, the NRRL's Robert Coghill seemed to have had a hard time accepting that research paid for by his employer , the US Department of Agriculture and ultimately the American public, belonged to the USDA.
And that this research shouldn't only go where a different agency's chief bureaucrat, A N Richards, wanted it to go - though he hadn't paid for it and had no statutory (legal) control over it.
However , I see Coghill, a misplaced chemist running a biological program, wanted in so badly on a "technically sweet" chemical problem (the synthesis of penicillin) that he sold out the farmers he had sworn to help.
Synthetic penicillin would only negate the ready market for hundreds of thousands of tons of farm waste corn steep liquor, farm waste whey and farm waste crude brown sugar, all used in the natural fermentation of penicillin and other antibiotics coming along in the pipeline.
Coghill did publicly announce that he was giving the top two commercial strains of penicillium (presumably NRRL 1249.B21 and 832) to the entire world in November 1943, about the same time as Florey first mentions having them.
Why ?
I can only suspect because they were about to become obsolete, as synthetic penicillin seemed only months away.
By April 1944, that no longer seemed so and Coghill was back on the side of the biological angels, publicly praising Pfizer's biological penicillin and modestly claiming a role in their success.
Coghill's talents seemed rather wasted in democratic America - I can see him as the ultimate bureaucratic survivor in Stalin's Russia, adroitly changing sides as the situation shifted, moment by moment.....
Wednesday, January 30, 2013
Fleming never saved Churchill, but Gladys Hobby saved Florey's sister when his own penicillin couldn't !
Howard Florey was never more sleazy than in his dealings with Henry Dawson's team, as he desperately fought to restore the family name that his father dis-honored, by trying to remain the sole "hero" of wartime penicillin.
Just try to imagine what an university ethics committee today might say about a professor using his main rival's unpublished paper, sent to him in secret by his close friend (the same government official who censored his rival's paper and forbade its release) to improve his own work that is about to be allowed to be freely published !
That is what full Professor Howard Florey and university vice president and full Professor A N Richards actually did to associate professor chemist Professor Karl Meyer of Dawson's team , in mid 1942.
(As they say, tenure is 'red in tooth and claw'.)
The multi-hatted Professor A Newton Richards was a Vice President of the University of Pennsylvania, head of the medical wing of the OSRD , chief consultant to Merck and one of Howard Florey's best friends.
Like Mayor Rob Ford, he also never met a conflict of interest he could resist.
(By contrast, when Norman Heatley met Meyer in January 1942, Heatley recorded that Meyer was willing to send his data to Florey, but Heatley boldly told his boss (Florey) he (Heatley) won't because it didn't seem right, not if Florey was about to publish and Meyer was forbidden to.)
However, Professor Richards was of a very different moral character and saw nothing wrong in sending Professor Meyer's embargoed chemical work on the structure of penicillin to his main academic rival, Professor Florey.
By contrast, Dawson bent over backwards to try and find a source of penicillin for Florey (even at places like Pfizer - a place Florey determinedly didn't want to visit), totally unaware of Florey's well known reputation in the UK for being an academic bush whacker and a magpie of other people's hard work.
Florey's real (if totally private) reason to come to America in 1941, was mainly to establish that he and Merck, not Dawson and Pfizer, was the real leader in the hunt for viable penicillin.
By late 1942, Florey felt sure that the dying Dawson and Pfizer (having joined Merck's cartel) was out of the race.
Sweet indeed then, when in August 1944, a sullen Howard Florey had to stand politely beside Dawson team member Gladys Hobby as she showed him the natural penicillin poring off the Pfizer lines, while Merck and Florey's team at Oxford had totally failed to produce any synthetic penicillin for the D Day beaches.
Florey had spurned both Pfizer and Glaxo, yet it was they who delivered most of the penicillin that landed on the Normandy beaches that day --- "the stone the builders rejected" indeed.
Asa series of letters in the Royal Society Archive reveal, in December 1952, Florey had to eat yet more humble pie, first begging and then thanking Hobby for sending her own latest antibiotic off to save the life of his sister (Hilda Gardner) in Australia when his own penicillin wouldn't work....
Just try to imagine what an university ethics committee today might say about a professor using his main rival's unpublished paper, sent to him in secret by his close friend (the same government official who censored his rival's paper and forbade its release) to improve his own work that is about to be allowed to be freely published !
That is what full Professor Howard Florey and university vice president and full Professor A N Richards actually did to associate professor chemist Professor Karl Meyer of Dawson's team , in mid 1942.
(As they say, tenure is 'red in tooth and claw'.)
The multi-hatted Professor A Newton Richards was a Vice President of the University of Pennsylvania, head of the medical wing of the OSRD , chief consultant to Merck and one of Howard Florey's best friends.
Like Mayor Rob Ford, he also never met a conflict of interest he could resist.
(By contrast, when Norman Heatley met Meyer in January 1942, Heatley recorded that Meyer was willing to send his data to Florey, but Heatley boldly told his boss (Florey) he (Heatley) won't because it didn't seem right, not if Florey was about to publish and Meyer was forbidden to.)
However, Professor Richards was of a very different moral character and saw nothing wrong in sending Professor Meyer's embargoed chemical work on the structure of penicillin to his main academic rival, Professor Florey.
By contrast, Dawson bent over backwards to try and find a source of penicillin for Florey (even at places like Pfizer - a place Florey determinedly didn't want to visit), totally unaware of Florey's well known reputation in the UK for being an academic bush whacker and a magpie of other people's hard work.
Florey's real (if totally private) reason to come to America in 1941, was mainly to establish that he and Merck, not Dawson and Pfizer, was the real leader in the hunt for viable penicillin.
By late 1942, Florey felt sure that the dying Dawson and Pfizer (having joined Merck's cartel) was out of the race.
Sweet indeed then, when in August 1944, a sullen Howard Florey had to stand politely beside Dawson team member Gladys Hobby as she showed him the natural penicillin poring off the Pfizer lines, while Merck and Florey's team at Oxford had totally failed to produce any synthetic penicillin for the D Day beaches.
Florey had spurned both Pfizer and Glaxo, yet it was they who delivered most of the penicillin that landed on the Normandy beaches that day --- "the stone the builders rejected" indeed.
Gladys Hobby saves Howard Florey's own sister -- when he couldn't
Asa series of letters in the Royal Society Archive reveal, in December 1952, Florey had to eat yet more humble pie, first begging and then thanking Hobby for sending her own latest antibiotic off to save the life of his sister (Hilda Gardner) in Australia when his own penicillin wouldn't work....
Saturday, January 19, 2013
Florey quickly flees the biology of NRRL Peoria for the chemical comforts of Merck
Howard Florey probably spent no more than a few hours of his whole life in the labs of the NRRL at Peoria, Illinois where most of the fruitful work that gave us the antibiotics revolution was actually done.
Within hours, he had dumped his sidekick Norman Heatley there to toil on the rural farmer-like task of growing penicillin, because Florey preferred much more the urban chemistry-oriented approach of firms like Merck and Squibb and ICL.
Florey after all had wanted to be part of the then most glamorous part of science( chemistry) and only took up medicine as the easiest way for an Australian to get employment in scientific research (as a medical "doctor" , he hated dealing with patients and in fact, hated dealing with people in general.)
He remained a chemist-manque all his life.
Hence why he avoided doing any hands-on research at NRRL Peoria on increasing the biological yield of penicillin .
He much preferred the chemical synthesis approach of Merck and of its chief scientific consultant, A N Richards, new head of the war medicine section of the war weapon research organization, the OSRD....
Within hours, he had dumped his sidekick Norman Heatley there to toil on the rural farmer-like task of growing penicillin, because Florey preferred much more the urban chemistry-oriented approach of firms like Merck and Squibb and ICL.
Florey was no country hick and disdained 'farming' penicillin
Florey after all had wanted to be part of the then most glamorous part of science( chemistry) and only took up medicine as the easiest way for an Australian to get employment in scientific research (as a medical "doctor" , he hated dealing with patients and in fact, hated dealing with people in general.)
He remained a chemist-manque all his life.
Hence why he avoided doing any hands-on research at NRRL Peoria on increasing the biological yield of penicillin .
He much preferred the chemical synthesis approach of Merck and of its chief scientific consultant, A N Richards, new head of the war medicine section of the war weapon research organization, the OSRD....
Did Merck consultant A N Richards diss penicillin during the first two years of the war?
Read any "Pollyanna" history of wartime penicillin and you quickly garner the impression that wartime Washington's top medical research bureaucrat, AN Richards of the famous OSRD organization, first learned of penicillin when his former student Howard Florey dropped by in the Fall of 1941.
In my opinion : "Bullfeathers" !
Richards was the key outside consultant for Merck and had been so since 1931 , so key that he acted more like a trusted insider, rather than playing the traditional role of an external naysayer brought in to correct too much internal group-think.
Since November 1939, a full two years before Richards is traditionally described as first getting involved in "this 'ere pen-E- cil-in stuff", Merck had been working fitfully on trying to learn the structure of public domain natural penicillin with the hope its chemists could produce patentable, profitable "look alike" analogues.
Memo had flown back and forth and committee and board meetings had been called and minutes written.
Hard to believe that Richards the pharmaceutical expert consultant was not consulted formally and informally - ever - during those two years of internal Merck debate on the merits of seriously spending money on synthesizing penicillin.
But the silence from Merck and Richards on just what Richards said to Merck about the potential of penicillin between November 1939 and August 1941 is deafening.
It isn't at all like Richards or Merck to modestly not to claim credit for their early prescience on penicillin.
In fact Merck brass went to enormous length to do just so in the major article "Wartime Industrial Development of Penicillin in the United States", written and researched in the late 1970s (with exclusive access to secret Merck archives) by company senior executiveW H Helfand.
Mysteriously, Richards name is totally absent during this article's discussion of the two years of Merck debate about penicillin, before Florey arrives at Richards' doorstep in Philadelphia.
However Helfand's article quotes Merck executive Osgood Perkins recalling that despite a memo "from so-called experts urging Merck not to waste time on it", in 1940 the company top brass decided to grow penicillin with the aim of isolating its active ingredient.
Now Osgood Perkins was a famous actor of that era but he never worked for Merck.
However the equally famous Wall Street lawyer George W Perkins did - in fact he was the brother-in-law of the company president George W Merck and served as chief operating officer for several decades, including the war years.
(And like his brother in law, Perkins worked at the top of America's highly secret germ warfare program when America formally went to war but still kept a close eye on his company.)
But the quote is from Lennard Bickel's book on Howard Florey, Rise up to Life, and in it, Bickel says he quotes Merck executive Osgood Nichols (also referenced as Osgood Nicholls by Bickel) in conversation with AN Richards in the early 1960s.
(Osgood Nichols probably saw the memos while researching "By Their Fruits" , a book about Merck and Waksman.)
Now I have determined that Bickel did screw up names (but only slightly) in his book, so I feel certain we are looking at Nichols, not Perkins, for the source of this quote.
Richards is silent to Osgood as to who the so called experts might be (and surely he would know) but rushes to defend Florey.
Just exactly how Helfard screws all this so badly is hard to ken.
I suspect that those "so-called experts" included both the much honored Richards and the equally much-honored Columbia university medical researcher, Nobel prize winner and long time Merck consultant Dickinson Richards.
Dickinson worked literally next door to Henry Dawson, who did the most work on penicillin in North America between 1940 and 1941.
So this Dr Richards (no relation to AN Richards) saw the world's then most extensive penicillin efforts (microbiological production, chemical research and clinical efforts with the seriously ill) close up and personal every day.
Thus his opinion on penicillin , as a Merck medical consultant since 1935, between 1940 to 1941 had to be valuable to Merck - but what was it ?
I suspect one of the "the so-called experts" who dissed penicillin was Dickinson Richards.
Why ? Because Helfand does not mention Merck offering to help Dickinson Richards' floor mate Dawson in his penicillin efforts in this very long article tasked with detailing everything and anything positive that Merck had done on penicillin before Florey arrived.
(But we do know what a third outside consultant to Merck said about penicillin because Helfand does quote him extensively.)
Soon to be Nobel Prize winner Selman Waksman is recorded as being strongly in favour of working up penicillin.
I believe that Helfand's job in this article was to recall all the good news and elide any bad news on Merck and penicillin 1939-1941 and he did his job rather well.
I think it would have rather spoiled the seamless panty lines of the traditional "Pollyanna" version of wartime penicillin served up by academic historians, to have revealed that AN Richards knew all about Merck's dilatory efforts with penicillin for two years but did little to speed it along. (And may have even of dissed it.)
Much better is to say that as soon as Florey first told Richards about the wondrous penicillin, Richards leaps into patriotic action to help Britain (cue The Special Relationship) and soon the world has penicillin oozing out of its pores....
In my opinion : "Bullfeathers" !
Richards was the key outside consultant for Merck and had been so since 1931 , so key that he acted more like a trusted insider, rather than playing the traditional role of an external naysayer brought in to correct too much internal group-think.
Since November 1939, a full two years before Richards is traditionally described as first getting involved in "this 'ere pen-E- cil-in stuff", Merck had been working fitfully on trying to learn the structure of public domain natural penicillin with the hope its chemists could produce patentable, profitable "look alike" analogues.
Memo had flown back and forth and committee and board meetings had been called and minutes written.
Hard to believe that Richards the pharmaceutical expert consultant was not consulted formally and informally - ever - during those two years of internal Merck debate on the merits of seriously spending money on synthesizing penicillin.
But the silence from Merck and Richards on just what Richards said to Merck about the potential of penicillin between November 1939 and August 1941 is deafening.
It isn't at all like Richards or Merck to modestly not to claim credit for their early prescience on penicillin.
In fact Merck brass went to enormous length to do just so in the major article "Wartime Industrial Development of Penicillin in the United States", written and researched in the late 1970s (with exclusive access to secret Merck archives) by company senior executiveW H Helfand.
Mysteriously, Richards name is totally absent during this article's discussion of the two years of Merck debate about penicillin, before Florey arrives at Richards' doorstep in Philadelphia.
However Helfand's article quotes Merck executive Osgood Perkins recalling that despite a memo "from so-called experts urging Merck not to waste time on it", in 1940 the company top brass decided to grow penicillin with the aim of isolating its active ingredient.
Now Osgood Perkins was a famous actor of that era but he never worked for Merck.
However the equally famous Wall Street lawyer George W Perkins did - in fact he was the brother-in-law of the company president George W Merck and served as chief operating officer for several decades, including the war years.
(And like his brother in law, Perkins worked at the top of America's highly secret germ warfare program when America formally went to war but still kept a close eye on his company.)
But the quote is from Lennard Bickel's book on Howard Florey, Rise up to Life, and in it, Bickel says he quotes Merck executive Osgood Nichols (also referenced as Osgood Nicholls by Bickel) in conversation with AN Richards in the early 1960s.
(Osgood Nichols probably saw the memos while researching "By Their Fruits" , a book about Merck and Waksman.)
Now I have determined that Bickel did screw up names (but only slightly) in his book, so I feel certain we are looking at Nichols, not Perkins, for the source of this quote.
Richards is silent to Osgood as to who the so called experts might be (and surely he would know) but rushes to defend Florey.
Just exactly how Helfard screws all this so badly is hard to ken.
I suspect that those "so-called experts" included both the much honored Richards and the equally much-honored Columbia university medical researcher, Nobel prize winner and long time Merck consultant Dickinson Richards.
Dickinson worked literally next door to Henry Dawson, who did the most work on penicillin in North America between 1940 and 1941.
So this Dr Richards (no relation to AN Richards) saw the world's then most extensive penicillin efforts (microbiological production, chemical research and clinical efforts with the seriously ill) close up and personal every day.
Thus his opinion on penicillin , as a Merck medical consultant since 1935, between 1940 to 1941 had to be valuable to Merck - but what was it ?
I suspect one of the "the so-called experts" who dissed penicillin was Dickinson Richards.
Why ? Because Helfand does not mention Merck offering to help Dickinson Richards' floor mate Dawson in his penicillin efforts in this very long article tasked with detailing everything and anything positive that Merck had done on penicillin before Florey arrived.
(But we do know what a third outside consultant to Merck said about penicillin because Helfand does quote him extensively.)
Soon to be Nobel Prize winner Selman Waksman is recorded as being strongly in favour of working up penicillin.
I believe that Helfand's job in this article was to recall all the good news and elide any bad news on Merck and penicillin 1939-1941 and he did his job rather well.
I think it would have rather spoiled the seamless panty lines of the traditional "Pollyanna" version of wartime penicillin served up by academic historians, to have revealed that AN Richards knew all about Merck's dilatory efforts with penicillin for two years but did little to speed it along. (And may have even of dissed it.)
Much better is to say that as soon as Florey first told Richards about the wondrous penicillin, Richards leaps into patriotic action to help Britain (cue The Special Relationship) and soon the world has penicillin oozing out of its pores....
Friday, January 18, 2013
Merck has credible excuses for being beaten on D-Day penicillin by Pfizer - but none whatsoever for being crushed by Commercial Solvent
Merck, the OSRD, Florey's Oxford team (all part of the synthetic penicillin obsession) continue to have many defenders among academia.
Yes, one academic excuse goes, yes Merck failed to deliver much penicillin to the D-Day beaches - that was left to Pfizer, which had been a major partner of Merck and Squibb in the three year long effort to produce commercial amounts of penicillin.
But, the excuse went, Pfizer had 20 years of highly successful fermentation experience before late 1941and the commercial penicillin project's beginnings.
But how then to explain the huge success of Commercial Solvents in producing medical grade penicillin from a cold start in January 1944 to levels twice that of Merck in just four months and then levels six or seven times higher than Merck in just three more months after that?
True, Commercial Solvent had 30 years of success in industrial grade fermentation in making bulk acetone but had never done anything even remote to pharmaceutical levels of purity and cleanliness.
But there it was - passing an increasingly demanding FDA testing requirements with its tens of billions of units of injectable penicillin.
Clearly, the supposedly-arcane craft could be learned fairly quickly, if a corporate culture demanded it.
Even Squibb redeemed itself by well beating Merck's output, by late 1944 .
Merck lost the race for one reason only : hubris.
It thought that since it had synthesized a few 300 molecular weight molecules that all 300 weight biological molecules were a piece of cake.
Tell that to penicillin with a weight of 334 and still not commercially synthesized.
Or tell it to quinine , molecular weight 324, and 200 years after Man-The-Almighty first started to synthesize it, still without a commercially viable synthesis technique at hand....
Yes, one academic excuse goes, yes Merck failed to deliver much penicillin to the D-Day beaches - that was left to Pfizer, which had been a major partner of Merck and Squibb in the three year long effort to produce commercial amounts of penicillin.
But, the excuse went, Pfizer had 20 years of highly successful fermentation experience before late 1941and the commercial penicillin project's beginnings.
But how then to explain the huge success of Commercial Solvents in producing medical grade penicillin from a cold start in January 1944 to levels twice that of Merck in just four months and then levels six or seven times higher than Merck in just three more months after that?
True, Commercial Solvent had 30 years of success in industrial grade fermentation in making bulk acetone but had never done anything even remote to pharmaceutical levels of purity and cleanliness.
But there it was - passing an increasingly demanding FDA testing requirements with its tens of billions of units of injectable penicillin.
Clearly, the supposedly-arcane craft could be learned fairly quickly, if a corporate culture demanded it.
Even Squibb redeemed itself by well beating Merck's output, by late 1944 .
Merck lost the race for one reason only : hubris.
It thought that since it had synthesized a few 300 molecular weight molecules that all 300 weight biological molecules were a piece of cake.
Tell that to penicillin with a weight of 334 and still not commercially synthesized.
Or tell it to quinine , molecular weight 324, and 200 years after Man-The-Almighty first started to synthesize it, still without a commercially viable synthesis technique at hand....
Wednesday, January 16, 2013
Roy S Koch "shows me the money" on wartime penicillin
Then , overnight in August 1943, penicillin became one of those parenterally delivered biologicals and nothing was ever quite the same.
One of Koch's jobs was tallying the actual amounts, month by month, firm by firm, of medical grade penicillin that passed from the FDA's approval into the military or civilian supply chain.
In those excited anxious days with American families's sons, brothers and fathers dying left (Pacific) and right (Atlantic) in record numbers, all eyes and ears were on the progress reports on penicillin production.
Everyone, in their own way, was pitching in to help American industry finally deliver the goods, 15 years later but better late than never.
Above all the American taxpayer was working overtime to pay for that promise of expanded production.
Paying for the government building of private-firm-run buildings, paying through extra personal taxes for the shortfall caused by the writing off of excess corporate taxes, paying for military and civilian expeditors, paying to aid to university researchers who were in turn aiding corporate coffers - on and on and on.
So a corporate failure to make good on a public promise to deliver a lot of penicillin, with the help of lots of taxpayers' money, was going to seem tantamount to committing an act of treason.
Hence Koch's carefully collected figures had to remain a closely guarded secret : American corporations may fail to deliver all the time, but the American public is never ever to know.
But in 1958, about 55 years ago and almost 15 years after the figures were first collected, a muckraking US government inquiry into price-fixing in the antibiotic business did reveal the figures --- even put it in a public domain documents so all the world could quote them freely.
But I have never seen anyone do so and I have read an awful lot on wartime penicillin : so if I am wrong, please email me at my email on this blog.
Anyway, the figures are posted above and you can access the report ("Economic Report on Antibiotics Manufacture" ) online --- this chart is from the appendix, page 331.
In January 1944, the Hare side of the race to make - and define - wartime penicillin was feeling pretty good : Merck had produced some actual therapeutically-effective penicillin by human synthesis (take that you nasty mold !), a result soon confirmed by the Oxford Hares and by other American Hares.
Yields were much lower than the mold-made penicillin and the impurities both more abundant and much more lethal than in the naturally-made penicillin , but the chemists (hundreds of the best chemists in the world) were working on it.
Soon the pesky Tortoises of wartime penicillin, mostly obscure johnnies come lately, could be kissed off - their brand new plants just so yesterday, so very obsolete : growing mold like some rural farmer and then making things by fermentation.
In this Modern Age !
Really, the nerve !
Still, in January 1944, some of the leaders in the secret effort to make penicillin by synthesis are still putting up a good front in aiding the build-up of penicillin supplies for the widely expected opening of the Second Front (D-day) in the late spring or early summer.
Their production of natural penicillin was quite good - compared to even a few months earlier.
The all-mighty Merck (leader, along with Howard Florey in Oxford England, of the penicillin Hares) delivered 3.1 billion units that month, about as much as some obscure mushroom farmer (Reichel) did , buried somewhere out in the backwoods of rural Pennsylvania.
Merck wasn't going to really go all out to produce a lot of natural penicillin for the boys overseas, not when they were about to blow the world away with their very own "technically sweet" synthetic penicillin.
But the boss, George W Merck, was still determined to be patriotic none the less, "do his bit".
Pfizer, another part of the New York area Hare triad, led the production, just barely, with 3.98 billion units.
Squibb ,the third of that triad, was not pulling its weight - even the War Production Board could barely contain their anger , as the folks at Squibb laying back on the oars --- producing just .61 billion units.
The Mid-West group of Hares hadn't done as well, but they hadn't been at it as long : Abbott did .71 billion, Lilly .43 , Upjohn .07 , Parke Davis .03.
Let us jump to April 1944.
Synthetic penicillin yields are still so low that they were a joke - making even Fleming's small amounts that he produced in 1928 look enormous in comparison.
But almost everyone's natural penicillin output has improved --- it was getting close, after all, to make the deadline to get into the pipeline to Kansas City's big depot and then out again to Southern England for the D-Day medical supply loadings.
Every drug CEO wanted to boast later in ads that it was his firm's penicillin that had won the day in the invasion of Nazi Europe.
Reichel had fallen way back below its January output and Merck hadn't even doubled its output.
But Squibb had increased its supply by 10 times , albeit from a low base and Abbott had done almost as well.
(Commercial Solvents had increased its output by 300 times, from a very low base - but it was a real newcomer.)
Pfizer switches sides and kills Modernity ...
But Pfizer wasn't playing fair, for it had turned from being a Hare into a Tortoise : it had increased its natural penicillin output by 10 times, from a very high base and doubled it again in May : producing more than the entire world's penicillin plants combined.
By July, Merck was almost producing less than it had in January, while Pfizer was producing 25 times as much as it had in January.
Still no early sign of synthetic penicillin production and Pfizer was on its way to producing enough penicillin for the entire world,naturally, with or without Merck's 'technically sweet" synthetic stuff .
Modernity had just taken a fatal shot to the base of the neck and deep down, everyone knew it....
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.
Thursday, July 29, 2010
Foster, Woodruff & McDaniel: is it true?
More precisely, was it all of the truth - or was it published by the bosses of Merck as a deliberate half-truth?
I have a real "moral" problem with an scientific article from 1943.
1943?
Like 68 years ago?
Exactly - and one of the junior authors (Dr Boyd Woodruff) is still alive and active, albeit as active as any 94 year old scientist can be!
And he seems a very nice man from an interview or two I have read of his.
The article comes from "the research lab" of Merck, so I suppose Merck's production staff on the factory floor can always offer up a 'plausible deniability' of the article's claims.
It was submitted for publication on May 28 1943, and published in November 1943.
Most journals ,even then, let you add short addendums till very near the actual date of printing.
It is entitled :
"MICROBIOLOGICAL ASPECTS OF PENICILLIN, III - PRODUCTION OF PENICILLIN IN SURFACE CULTURES OF PENICILLIUM NOTATUM
Now it was no secret, then or now, that the Florey team in Oxford, along with his funders at the MRC and the Rockefeller Foundation,along with his friend John Fulton at Yale, together with the OSRD, the CMR, the chemical chief at NRRL (formerly from Yale), and the COC were all extremely close to George W Merck and Merck inc.
The head of the OSRD and its chief legal counsel, along with the head of the CMR and the head of the COC all ended up on the board or acting as consultants to Merck.
Their real bond was that almost all were chemist-manques --- or as we'd say today, chemist wannabes.
The prestige of chemists never shined brighter than the years of their growing up and adulthood and so they worshipped at its fountain only a little more fervently than the average educated person did.
Florey wanted to be a research chemist - his parents said being a medical doctor was more practical.
Richards ,the head of the CMR, was an indifferent student until he fell under the spell of a chemist - he ended up teaching the new subject of pharmacology - a very chemically-oriented area of expertise.
Merck had wanted to be a research chemist - his father's early death made him the head of his (very,very) chemically-oriented drug company.
Remind me to tell you a very funny story sometime on just how chemically-oriented Merck Inc was back in the 1930s.
Robert Coghill headed up the very biologically-oriented Fermentation Division at the NRRL, but he had been a chemist and longed to do real chemistry work - ie synthesize things.
Richards at the CMR really controlled penicillin in North America, to the extent anyone did.
This article won't have come out, unless Richards was 100% happy with it.
I re-stumbled on this article (I had read it many times before) when I had problems documenting a frequently made claim of other authors on early penicillin : that the chemistry of penicillin was the only area that was censored during the war years.
I found that articles on the general and specific chemistry of penicillin were extremely abundant from 1928-1943.
I found that for the period August 1941 to about January 1943, it was actually articles on the clinical use of penicillin that were totally non-existent, and on both sides of the Atlantic.
No where would 'Doctor Mom' finds reports in her local newspaper of people snatched from the jaws of death by penicillin during that crucial 18 month period - I think these good news stories were deliberately discouraged and held back until the drug companies and the government could produce a rabbit out of their hats.
And I found no mention anywhere, until Raper and Coghill's articles in May 1944 (when the penicillin crisis had ended in a sudden and unexpected total triumph) about the new productive sub-strains of Fleming's original feeble penicillium mold developed at the NRRL from January 1942 onward.
(NRRL 1249 ,1249.B , 1249.B21)
Or of the way that production soared with the subsitution of corn steep liquor and lactose for sucrose and yeast extract,something the NRRL (and the OSRD/Richards) knew back in December 1941.
I got the distinct impression that nobody (except maybe Florey himself) knew about the real significance of lactose/corn liquor combo and not even Florey got access to these distinctly better sub-strains of penicillium.
Since Florey and Dawson (and lots of others) were struggling to produce their own penicillin until 1943-1944, ie from 2 years after these discoveries, news of all of this would have meant they would have got 10 to 20 times the yield from their existing equipment and staff effort.
They would no longer be beholden to the drug companies or the OSRD and Richards - which just might have been the point.
This article would have been read by the entire microbiology world - it was published in the Journal of Bacteriology (ASM), the leading microbiology journal in the Americas - a vast agriculturally advanced part of the world and so a hotbed of microbiological research of the practical sort.
The impression for a professional microbiologist reading this article , back in 1943, is that Merck Inc ,itself, in mid-1943, had tested a few substrains of penicillium, finding some better and some worse than Fleming's original....all pretty ho hum.
And that it found the best medium to grow penicillin on was Dawson's dirty (cheap-impure-complex) brown sugar. Again the formula was publicly available and not really a great help for a hospital lab trying to produce enough penicillin to cure one extremely ill patient a month.
(I think the average teaching hospital laboratory department needed to produce about one million units of clinical penicillin a month without extraordinary requirements of staff, space or effort if it was to feel it was worthwhile continuing working on clinical penicillin trials ,independent of what the drug companies and government would provide , ON THEIR TERMS.)
The Merck researchers said that they had tried lactose and found it no better than dirty brown sugar. No mention of corn steep liquor at all.
So was Merck using Fleming's old strain, and a dirty brown sugar medium to make all of its commercial penicillin in the Fall of 1943?
I do not believe so - and I will not believe so till I see dated photographs and hear eye witnesses under oath.
I accept that ,during war, firms and institutions will not tell their own citizens all what they are doing.
If you can't tell the truth about something, better to remain silent.
But I do not accept that you spread deliberate disinformation - which is what I think this article did - and still does.
I think it deliberately low-balled the state of the art, circa Fall 1943, of Merck's effort to increase the yield of penicillin juice produced by the mold, before the chemists stepped in to increase the yield of clinical penicillin concentrated from that juice.
This article feels like it was written in about March 1942, not in May or November 1943.
If that is so,who was it designed to mislead by being released ?
Clearly not Squibb,Pfizer,Withrop,Abbott etc - those firms that had been working with penicillin for a few years and had a pretty good idea of the state of the art of natural penicillin production in mid to late 1943.
But hundreds of other firms might want to 'try their hand' at penicillin (175 firms did apply to do just that, just after this article was submitted).
Giving them just enough information to try their hand and then to retire discouraged might just be what the Merck leadership had in mind....
I have a real "moral" problem with an scientific article from 1943.
1943?
Like 68 years ago?
Exactly - and one of the junior authors (Dr Boyd Woodruff) is still alive and active, albeit as active as any 94 year old scientist can be!
And he seems a very nice man from an interview or two I have read of his.
The article comes from "the research lab" of Merck, so I suppose Merck's production staff on the factory floor can always offer up a 'plausible deniability' of the article's claims.
It was submitted for publication on May 28 1943, and published in November 1943.
Most journals ,even then, let you add short addendums till very near the actual date of printing.
It is entitled :
"MICROBIOLOGICAL ASPECTS OF PENICILLIN, III - PRODUCTION OF PENICILLIN IN SURFACE CULTURES OF PENICILLIUM NOTATUM
Now it was no secret, then or now, that the Florey team in Oxford, along with his funders at the MRC and the Rockefeller Foundation,along with his friend John Fulton at Yale, together with the OSRD, the CMR, the chemical chief at NRRL (formerly from Yale), and the COC were all extremely close to George W Merck and Merck inc.
The head of the OSRD and its chief legal counsel, along with the head of the CMR and the head of the COC all ended up on the board or acting as consultants to Merck.
Their real bond was that almost all were chemist-manques --- or as we'd say today, chemist wannabes.
The prestige of chemists never shined brighter than the years of their growing up and adulthood and so they worshipped at its fountain only a little more fervently than the average educated person did.
Florey wanted to be a research chemist - his parents said being a medical doctor was more practical.
Richards ,the head of the CMR, was an indifferent student until he fell under the spell of a chemist - he ended up teaching the new subject of pharmacology - a very chemically-oriented area of expertise.
Merck had wanted to be a research chemist - his father's early death made him the head of his (very,very) chemically-oriented drug company.
Remind me to tell you a very funny story sometime on just how chemically-oriented Merck Inc was back in the 1930s.
Robert Coghill headed up the very biologically-oriented Fermentation Division at the NRRL, but he had been a chemist and longed to do real chemistry work - ie synthesize things.
Richards at the CMR really controlled penicillin in North America, to the extent anyone did.
This article won't have come out, unless Richards was 100% happy with it.
I re-stumbled on this article (I had read it many times before) when I had problems documenting a frequently made claim of other authors on early penicillin : that the chemistry of penicillin was the only area that was censored during the war years.
I found that articles on the general and specific chemistry of penicillin were extremely abundant from 1928-1943.
I found that for the period August 1941 to about January 1943, it was actually articles on the clinical use of penicillin that were totally non-existent, and on both sides of the Atlantic.
No where would 'Doctor Mom' finds reports in her local newspaper of people snatched from the jaws of death by penicillin during that crucial 18 month period - I think these good news stories were deliberately discouraged and held back until the drug companies and the government could produce a rabbit out of their hats.
And I found no mention anywhere, until Raper and Coghill's articles in May 1944 (when the penicillin crisis had ended in a sudden and unexpected total triumph) about the new productive sub-strains of Fleming's original feeble penicillium mold developed at the NRRL from January 1942 onward.
(NRRL 1249 ,1249.B , 1249.B21)
Or of the way that production soared with the subsitution of corn steep liquor and lactose for sucrose and yeast extract,something the NRRL (and the OSRD/Richards) knew back in December 1941.
I got the distinct impression that nobody (except maybe Florey himself) knew about the real significance of lactose/corn liquor combo and not even Florey got access to these distinctly better sub-strains of penicillium.
Since Florey and Dawson (and lots of others) were struggling to produce their own penicillin until 1943-1944, ie from 2 years after these discoveries, news of all of this would have meant they would have got 10 to 20 times the yield from their existing equipment and staff effort.
They would no longer be beholden to the drug companies or the OSRD and Richards - which just might have been the point.
This article would have been read by the entire microbiology world - it was published in the Journal of Bacteriology (ASM), the leading microbiology journal in the Americas - a vast agriculturally advanced part of the world and so a hotbed of microbiological research of the practical sort.
The impression for a professional microbiologist reading this article , back in 1943, is that Merck Inc ,itself, in mid-1943, had tested a few substrains of penicillium, finding some better and some worse than Fleming's original....all pretty ho hum.
And that it found the best medium to grow penicillin on was Dawson's dirty (cheap-impure-complex) brown sugar. Again the formula was publicly available and not really a great help for a hospital lab trying to produce enough penicillin to cure one extremely ill patient a month.
(I think the average teaching hospital laboratory department needed to produce about one million units of clinical penicillin a month without extraordinary requirements of staff, space or effort if it was to feel it was worthwhile continuing working on clinical penicillin trials ,independent of what the drug companies and government would provide , ON THEIR TERMS.)
The Merck researchers said that they had tried lactose and found it no better than dirty brown sugar. No mention of corn steep liquor at all.
So was Merck using Fleming's old strain, and a dirty brown sugar medium to make all of its commercial penicillin in the Fall of 1943?
I do not believe so - and I will not believe so till I see dated photographs and hear eye witnesses under oath.
I accept that ,during war, firms and institutions will not tell their own citizens all what they are doing.
If you can't tell the truth about something, better to remain silent.
But I do not accept that you spread deliberate disinformation - which is what I think this article did - and still does.
I think it deliberately low-balled the state of the art, circa Fall 1943, of Merck's effort to increase the yield of penicillin juice produced by the mold, before the chemists stepped in to increase the yield of clinical penicillin concentrated from that juice.
This article feels like it was written in about March 1942, not in May or November 1943.
If that is so,who was it designed to mislead by being released ?
Clearly not Squibb,Pfizer,Withrop,Abbott etc - those firms that had been working with penicillin for a few years and had a pretty good idea of the state of the art of natural penicillin production in mid to late 1943.
But hundreds of other firms might want to 'try their hand' at penicillin (175 firms did apply to do just that, just after this article was submitted).
Giving them just enough information to try their hand and then to retire discouraged might just be what the Merck leadership had in mind....
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