Florey and his many scientific supporters have always said that his interest in penicillin, beginning in early 1938, was the fact that it killed staph bacteria while the sulfa drugs did not.
Staph was not a big killer back then - not like strep bacteria - at least not in peacetime.
It tended to do its worst when it settled deep into big bones that weren't well supplied with blood - making it hard for white blood cells and sulfa molecules to get at the bacteria.
This condition is called acute or chronic osteomyelitis and it was rampant among the young children of the poor - in peacetime.
In wartime, surviving victims of war wounds - or the surviving wounded from the Blitz - often had huge deep wounds that involved their leg bones - a hard-to-get-at location that was ideal for staph bacteria to settle in for a long stay.
Patients affected went back and forth from convalescence bed to hospital bed while doctors and nurses strived to prevent the patient from getting worse in the hope the body would eventually seal off the infection without crippling the patient in the process.
Often they survived but were left crippled - other times the patient's resistance weakened and the staph spread widely till the patient died of general blood poisoning.
In war time, deep bone wounds infected by staph represented a massive cost to the military medical system - consuming resources for years while the affected soldier was unlikely to ever to return to full service. Blitz victims similarly taxed the overworked civilian medical system.
So Florey's business model for "war penicillin" - penicillin as a mere supplement for the sulfas, its wartime use to be strictly limited to healing military patients with deeply set staph infections of the bones and limbs - how did it sell ?
It didn't.
There is no record in all his biographies that any military medical types ever visited him until 1943 - nor is it recorded anywhere that he visited military doctors and was turned down.
Curious - the Navy, Air Force, 8th Army in North Africa, the Blitz victims - they had no end of deep staph infections of the bones to treat from September 2nd 1939 to September 2nd 1942 (three years - half of the entire war) but they avoided penicillin like it was plagued.
Florey was set up to supply an non-existent market.
By contrast,from 1940 to 1942, Dawson's main market had more customers than he could hope to fill.
Florey,Fleming, Heatley, Merck, Dawson of course, they all got requests (from around the world) for penicillin to treat SBE after Dawson announced that he had hopes to cure SBE with the new drug.
Dawson's business model for penicillin could not have been more different from Florey's.His Social Penicillinhe wanted to be made by a government factory and made available to all ( civilians and soldiers) in quantity and at a reasonable price - and made available like yesterday.
He thought penicillin could replace sulfa, not just supplement it, and used to kill all bacteria that was sensitive to it - not just staph.
Florey didn't directly treat any cases - he had no hospital rights unlike Dawson.
But the twenty serious systemic cases he
indirectly treated were almost all staph infected - so he kept to his business model in his own practise.
Similarly, Dawson had about 125 serious systemic cases that he directly dealt with and he too kept to his business model.
Those cases included all the types of bacteria that penicillin could kill---with about a third of them SBE cases.
Penicillin was promised to the military in mid-1943 after they finally decided that they wanted it ,by seeing it work well in military staph wounds in early 1943.
Score one for Florey.
But it only actually got delivered to the military and to the civilians when Dawson's
SBE success produced a patients' revolt across America and Canada ----inspiring Pfizer to go for broke.
Credit that to Dawson's business model--- and lets recall that by 1950 penicillin had completely replaced ,not supplemented, the mighty sulfas.....
Tuesday, October 12, 2010
Recombinant DNA and HGT's contribution to the penicillin saga
Where does one begin?
The beta-lactam molecular 'core' was originally created by bacteria and was only later was moved by HGT/ recombinant DNA into some fungi .
Those fungi then created the penicillin-variants of that very special fused beta-lactam ring .
But while this HGT operation was obviously fundamental to there being a penicillin saga to begin with, it had little direct impact on how the 1929-1944 penicillin saga actually unfolded.
But the four years of hard work and disappointments that Martin Henry Dawson endured between the Fall of 1926 and the Fall of 1930 working on HGT and recombinant DNA exchanges did make him the best qualified researcher in the world to put up with the temperamental penicillium between the Fall of 1940 and the Fall of 1944.
His pioneering work with R to S type (and S to S type) HGT exchanges between Strep pneumococcus bacteria made him eminently qualified to stand up to all the difficulties in growing penicillium to produce penicillin.
Dawson was the first in the world, together with Richard Sia, to successfully induce R to S pneumococcus HGT DNA exchanges in a test tube after most other researchers threw up their hands in despair and moved onto other research.
But he was no quitter and he pulled it off after years of failure.
Dawson then went on, with Agnes Warbasse, to do the same with S to S HGT DNA exchanges and this remains extremely difficult to do naturally, as Dawson did it.
He then went on to successfully grow colonies of M and L types of bacteria, all part of his effort over the roughly 15 years between 1926 and 1941 to establish that R,M,L were fully co-equal equivalents or alternatives to S types of bacteria - not defective or deficient versions of it.
This postmodernist notion naturally was seen as bizarre or worse in the strongly modernist atmosphere of medical research between the wars.
I see it as the bacterial equivalent of Dawson treating 4F civilians as the exact moral equivalent of 1A soldiers, not as defective 'useless mouth' variants, despite the reign of Total War Utilitarianism ruling western medicine between 1940 and 1945.
Dawson's pioneering HGT DNA/ Q-sensing work taught him ethics and it taught him technical skills - both which he called upon to get penicillin successfully launched......
The beta-lactam molecular 'core' was originally created by bacteria and was only later was moved by HGT/ recombinant DNA into some fungi .
Those fungi then created the penicillin-variants of that very special fused beta-lactam ring .
But while this HGT operation was obviously fundamental to there being a penicillin saga to begin with, it had little direct impact on how the 1929-1944 penicillin saga actually unfolded.
But the four years of hard work and disappointments that Martin Henry Dawson endured between the Fall of 1926 and the Fall of 1930 working on HGT and recombinant DNA exchanges did make him the best qualified researcher in the world to put up with the temperamental penicillium between the Fall of 1940 and the Fall of 1944.
His pioneering work with R to S type (and S to S type) HGT exchanges between Strep pneumococcus bacteria made him eminently qualified to stand up to all the difficulties in growing penicillium to produce penicillin.
Dawson was the first in the world, together with Richard Sia, to successfully induce R to S pneumococcus HGT DNA exchanges in a test tube after most other researchers threw up their hands in despair and moved onto other research.
But he was no quitter and he pulled it off after years of failure.
Dawson then went on, with Agnes Warbasse, to do the same with S to S HGT DNA exchanges and this remains extremely difficult to do naturally, as Dawson did it.
He then went on to successfully grow colonies of M and L types of bacteria, all part of his effort over the roughly 15 years between 1926 and 1941 to establish that R,M,L were fully co-equal equivalents or alternatives to S types of bacteria - not defective or deficient versions of it.
This postmodernist notion naturally was seen as bizarre or worse in the strongly modernist atmosphere of medical research between the wars.
I see it as the bacterial equivalent of Dawson treating 4F civilians as the exact moral equivalent of 1A soldiers, not as defective 'useless mouth' variants, despite the reign of Total War Utilitarianism ruling western medicine between 1940 and 1945.
Dawson's pioneering HGT DNA/ Q-sensing work taught him ethics and it taught him technical skills - both which he called upon to get penicillin successfully launched......
Leonard Colebrook is CENTRAL CASTING's penicillin hero
Time to wake up.
This isn't Hollywood.
"This Reality talking: Put your hands in the air and move slowly away from the World of Fiction".
In the World of Reality, Leonard Colebrook actually did bugger-all to advance the development of penicillin.
But Hollywood isn't totally wrong - he should have been the one to make penicillin a world wide success by 1932 or so.
He actually did do so in 1936 with a later - and lesser - 'miracle drug' : the sulfa family of drugs.
He did it by using some of the first commercially available sulfa to reduce childbed fever deaths to a very low figure - a feat that alone should have earned him immortality from grateful young mothers and families.
Childbed fever - actually commensal GAS strep bacteria (long term residents of the throats of the many attending doctors and nurses) settling in on the huge wound that is every new mother's uterus - is a particularly dreaded form of infectious death.
The death itself is often very painful. By definition the patient is relatively young (ie in her child-bearing years) . The death leaves a new born baby to be raised alone by a grieving young father and his young family.
Next Colebrook went on to pioneer new techniques to combat other forms of cross-infections that frequently develop in hospitals - starting with World War Two burn victims.
Even in retirement he led yet another crusade to modify the ubiquitous space heater so they all had clothing guards installed by law. Until this law was in place, thousands of people a year - in the UK alone - got severely burned or died, when their night clothing got set alight when it got entangled on the bare heating element.
His parents had raised him to be a Non Conformist missionary and reformer. In the event,Colebrook did as many would-be missionaries did at the turn of the last century - he channelled his missionary impulses into the field of medicine.
His highly moral impulse remained as intense as ever in everything he did.
He joined the Territorial (Reserve) Army and when he was called up in 1914, was prepared to go to the front as an infantry officer, not as a doctor.
But he was judged too valuable as a medical researcher to remain on the front lines - he spent the rest of the war in the rear echelons, with Fleming and Wright.
But at least- and unlike Fleming or Florey - he was willing to go to the Front.
In World War Two, he was again at the front, in a medical military capacity - teaching medical teams how to use sulfa powder in new war wounds ( he knew little more they did !) - and as the Front Line dissolved and became meaningless in the Battle for France he had a number of very close escapes.
He was 57 years old - and still at the front, still in the thick of it, trying to save lives 'right here, right now'.
Colebrook was the near-perfect example of the type of doctor I call the ward-doctor type.
This type of doctor may suffer from EED (Empathy Excess Disorder), in that they care too much for the patient, feel too much of their pain.
When they see patients dying needlessly around them, they are inclined to throw themselves even deeper into the battle at the bedside level - trying to use any or all of the best available techniques as best they can, as hard as they can.
What they can not see themselves doing, is beating what they'd call 'a cowardly retreat' to the quiet of a laboratory to 'study' the disease at its most fundamental level, hoping to find a cure - 'sure ,in about 6 years time'.
JV Duhig, Robert Pulvertaft, RH Boots, Perrin Long, Frank C Queen and even Karl Meyer are all doctors in the penicillin saga that fit this type.
There is a totally different type of doctor I will call a lab doctor. They probably suffer, to some extent, from EDD (Empathy Deficiency Disorder).
They too find it very hard to see patients dying needlessly, but they reject 'simply' providing 'band aid' palliative care for those who are dying without a cure in sight.
They spend their careers in the laboratory seeking the fundamentals of a disease and its cure in the universalities of chemistry and physics - as far as possible away from living, breathing, capricious individual human beings.
They may serve - if they must - in the military but they contrive that it is done in the rear echelons.
However, once over draftable age, they frequently display a newly bellicose attitude to war service that one rarely find among the ex-veterans who actually faced death on the front lines.
I am thinking of Fleming, Florey, Keefer, Richards, and their ilk.
Now they may have something to offer society as scientists, despite the negative picture I paint of them.
They are no more quitters in the lab than the clinician doctors are on the ward.
They might have the skills to grow something as difficult as penicillium and the strength to hang in there when their first ten months of efforts are marked by nothing but failure.
One could see Florey and Colebrook as the perfect combination of two men who are incomplete as individuals, when it comes to successfully developing penicillin.
Colebrook would be too focused on 'saving this patient - today' to ever set aside the months of time needed for the effort in the lab to learn how to grow penicillin.
Florey ,on his own, would be too focused on purifying penicillin to 100% pure to remember that there is a war on and patients dying while he fiddles.
But Florey and Colebrook had nothing in common, in terms of their personalities---- I couldn't see it ever happening.
Colebrook, by contrast, had worked successfully for years with Fleming at St Mary's but the relationship had soured when Fleming moved to displace Colebrook in Wright's affections.
Colebrook regarded Wright as his second father and could never forgive Fleming for this.
Besides, Fleming clearly lacked the drive to do hard work for months on end, needed if a hospital lab was to produce enough penicillin for human trials.
Colebrook succeeded with sulfa where he failed with penicillin because sulfa was abundantly and cheaply available in a stable form, ready to have any nurse give the patient as a pill as scheduled.
Penicillin had to be grown by the doctor determined to use it - as no drug company was really that willing to help.
He or she would have to concentrate and purify it and then preserved this highly labile drug long enough for it to make it to the patient's arm. It had to be given IV, and hence by doctor,likely themselves in fact ,a needle every three hours around the clock for weeks at a time.
Few doctors - even of the heroic cast like Colebrook or his American counterpart Perrin Long - were up for this.
Only Martin Henry Dawson combined the rare strengths of Fleming/Florey and Colebrook /Long in just one person.
That is why 70 years ago this week ,it was he - and him alone - that gave that long awaited first ever needle of penicillin, that sent a young boy named Charles Aronson home from his expected deathbed.....
This isn't Hollywood.
"This Reality talking: Put your hands in the air and move slowly away from the World of Fiction".
In the World of Reality, Leonard Colebrook actually did bugger-all to advance the development of penicillin.
But Hollywood isn't totally wrong - he should have been the one to make penicillin a world wide success by 1932 or so.
He actually did do so in 1936 with a later - and lesser - 'miracle drug' : the sulfa family of drugs.
He did it by using some of the first commercially available sulfa to reduce childbed fever deaths to a very low figure - a feat that alone should have earned him immortality from grateful young mothers and families.
Childbed fever - actually commensal GAS strep bacteria (long term residents of the throats of the many attending doctors and nurses) settling in on the huge wound that is every new mother's uterus - is a particularly dreaded form of infectious death.
The death itself is often very painful. By definition the patient is relatively young (ie in her child-bearing years) . The death leaves a new born baby to be raised alone by a grieving young father and his young family.
Next Colebrook went on to pioneer new techniques to combat other forms of cross-infections that frequently develop in hospitals - starting with World War Two burn victims.
Even in retirement he led yet another crusade to modify the ubiquitous space heater so they all had clothing guards installed by law. Until this law was in place, thousands of people a year - in the UK alone - got severely burned or died, when their night clothing got set alight when it got entangled on the bare heating element.
His parents had raised him to be a Non Conformist missionary and reformer. In the event,Colebrook did as many would-be missionaries did at the turn of the last century - he channelled his missionary impulses into the field of medicine.
His highly moral impulse remained as intense as ever in everything he did.
He joined the Territorial (Reserve) Army and when he was called up in 1914, was prepared to go to the front as an infantry officer, not as a doctor.
But he was judged too valuable as a medical researcher to remain on the front lines - he spent the rest of the war in the rear echelons, with Fleming and Wright.
But at least- and unlike Fleming or Florey - he was willing to go to the Front.
In World War Two, he was again at the front, in a medical military capacity - teaching medical teams how to use sulfa powder in new war wounds ( he knew little more they did !) - and as the Front Line dissolved and became meaningless in the Battle for France he had a number of very close escapes.
He was 57 years old - and still at the front, still in the thick of it, trying to save lives 'right here, right now'.
Colebrook was the near-perfect example of the type of doctor I call the ward-doctor type.
This type of doctor may suffer from EED (Empathy Excess Disorder), in that they care too much for the patient, feel too much of their pain.
When they see patients dying needlessly around them, they are inclined to throw themselves even deeper into the battle at the bedside level - trying to use any or all of the best available techniques as best they can, as hard as they can.
What they can not see themselves doing, is beating what they'd call 'a cowardly retreat' to the quiet of a laboratory to 'study' the disease at its most fundamental level, hoping to find a cure - 'sure ,in about 6 years time'.
JV Duhig, Robert Pulvertaft, RH Boots, Perrin Long, Frank C Queen and even Karl Meyer are all doctors in the penicillin saga that fit this type.
There is a totally different type of doctor I will call a lab doctor. They probably suffer, to some extent, from EDD (Empathy Deficiency Disorder).
They too find it very hard to see patients dying needlessly, but they reject 'simply' providing 'band aid' palliative care for those who are dying without a cure in sight.
They spend their careers in the laboratory seeking the fundamentals of a disease and its cure in the universalities of chemistry and physics - as far as possible away from living, breathing, capricious individual human beings.
They may serve - if they must - in the military but they contrive that it is done in the rear echelons.
However, once over draftable age, they frequently display a newly bellicose attitude to war service that one rarely find among the ex-veterans who actually faced death on the front lines.
I am thinking of Fleming, Florey, Keefer, Richards, and their ilk.
Now they may have something to offer society as scientists, despite the negative picture I paint of them.
They are no more quitters in the lab than the clinician doctors are on the ward.
They might have the skills to grow something as difficult as penicillium and the strength to hang in there when their first ten months of efforts are marked by nothing but failure.
One could see Florey and Colebrook as the perfect combination of two men who are incomplete as individuals, when it comes to successfully developing penicillin.
Colebrook would be too focused on 'saving this patient - today' to ever set aside the months of time needed for the effort in the lab to learn how to grow penicillin.
Florey ,on his own, would be too focused on purifying penicillin to 100% pure to remember that there is a war on and patients dying while he fiddles.
But Florey and Colebrook had nothing in common, in terms of their personalities---- I couldn't see it ever happening.
Colebrook, by contrast, had worked successfully for years with Fleming at St Mary's but the relationship had soured when Fleming moved to displace Colebrook in Wright's affections.
Colebrook regarded Wright as his second father and could never forgive Fleming for this.
Besides, Fleming clearly lacked the drive to do hard work for months on end, needed if a hospital lab was to produce enough penicillin for human trials.
Colebrook succeeded with sulfa where he failed with penicillin because sulfa was abundantly and cheaply available in a stable form, ready to have any nurse give the patient as a pill as scheduled.
Penicillin had to be grown by the doctor determined to use it - as no drug company was really that willing to help.
He or she would have to concentrate and purify it and then preserved this highly labile drug long enough for it to make it to the patient's arm. It had to be given IV, and hence by doctor,likely themselves in fact ,a needle every three hours around the clock for weeks at a time.
Few doctors - even of the heroic cast like Colebrook or his American counterpart Perrin Long - were up for this.
Only Martin Henry Dawson combined the rare strengths of Fleming/Florey and Colebrook /Long in just one person.
That is why 70 years ago this week ,it was he - and him alone - that gave that long awaited first ever needle of penicillin, that sent a young boy named Charles Aronson home from his expected deathbed.....
The Mystery of Penicillin's 18 missing years
I believe that all of the penicillin books up to now - and there have been hundreds of them - have basically been a series of 100,000 word excuses - "the dog ate my penicillin homework".
Excuses to us - the lay public - on behalf of Science in general or on behalf of one or other early penicillin researchers in particular.
But eighty years later, we lay people still want to know why it was that the best life saving medicine this world will ever see took an eighteen year vacation (from September 1928 till about September 1946) before local doctors around the world could routinely prescribe it to save a life.
Whether they are from the pen of a medical historian seeking to defend all of Science/a particular team effort or the effort of a lay author defending an individual scientist they particularly admire, all those apologies basically come down to this:
(It will actually highly technical and highly accurate at times---- but only when needed to refute technical excuses and bromides.)
THE FIRST MORAL HISTORY OF PENICILLIN
Mine will be a Moral History of penicillin - it will lay out a thesis that it was moral failings, not technical difficulties, that delayed penicillin becoming popularly know and commonly prescribed during all those years of death and suffering that we now call The Great Depression and World War Two.
The two events caused an excess of 100 million premature deaths over what might have been expected in that 16 year period.
Even if we content to 'merely' reduce those excessive deaths and not seek to prevent many of the so-called normal infectious deaths, how millions might penicillin have saved if it was readily available by 1929-1930?
Or consider this: despite the new global threat from nuclear weapons, the Cold War period from 1945 till 1985 was actually an incredibly optimist period in world human history.
The promise of 1945's penicillin was sufficient, all by itself, to overcome the fear induced by 1945's A-Bomb.
For a generation, penicillin kept most of us buoyed up about ourselves and the world around us.
Could those good vibes - induced in 1928-1929 instead of twenty years later - have been enough, by themselves, to prevent the worst of the Great Depression and World War Two from even happening ?
We will never know.
But I believe these questions are still big enough,eighty years on, for it to be worthwhile to re-examine the early penicillin saga to see if there is another explanation for the delay. One that will finally convince most lay people - and hopefully - even convince a few of the scientists.
DUHIG IS PROSECUTION'S KEY WITNESS
In the Fall of 1943, in Brisbane Australia, 15 years after Fleming discovered penicillin, Dr J V Duhig saved the lives of a dozen seriously ill people using a form of penicillin juice no more sophisticated than what Fleming had on hand in November 1928.
This the single hard, hard, hard, hard ,hard, historical stone against which I am going to grind every author and every account that claims that there were 'technical complications' why the world had to wait 15 or more years to put the life-saving effects of penicillin to work.
Until and unless they can explain to everyone's satisfaction why Duhig could do this - but why Fleming/Florey and Dawson et all couldn't - I will not relent.....
Excuses to us - the lay public - on behalf of Science in general or on behalf of one or other early penicillin researchers in particular.
But eighty years later, we lay people still want to know why it was that the best life saving medicine this world will ever see took an eighteen year vacation (from September 1928 till about September 1946) before local doctors around the world could routinely prescribe it to save a life.
Whether they are from the pen of a medical historian seeking to defend all of Science/a particular team effort or the effort of a lay author defending an individual scientist they particularly admire, all those apologies basically come down to this:
The 18 year delay was due to technical difficulties, not moral failings - at least not the moral failings of my hero.My book, by contrast, is not going to be a technical book - at least in its intentions.
(It will actually highly technical and highly accurate at times---- but only when needed to refute technical excuses and bromides.)
THE FIRST MORAL HISTORY OF PENICILLIN
Mine will be a Moral History of penicillin - it will lay out a thesis that it was moral failings, not technical difficulties, that delayed penicillin becoming popularly know and commonly prescribed during all those years of death and suffering that we now call The Great Depression and World War Two.
The two events caused an excess of 100 million premature deaths over what might have been expected in that 16 year period.
Even if we content to 'merely' reduce those excessive deaths and not seek to prevent many of the so-called normal infectious deaths, how millions might penicillin have saved if it was readily available by 1929-1930?
Or consider this: despite the new global threat from nuclear weapons, the Cold War period from 1945 till 1985 was actually an incredibly optimist period in world human history.
The promise of 1945's penicillin was sufficient, all by itself, to overcome the fear induced by 1945's A-Bomb.
For a generation, penicillin kept most of us buoyed up about ourselves and the world around us.
Could those good vibes - induced in 1928-1929 instead of twenty years later - have been enough, by themselves, to prevent the worst of the Great Depression and World War Two from even happening ?
We will never know.
But I believe these questions are still big enough,eighty years on, for it to be worthwhile to re-examine the early penicillin saga to see if there is another explanation for the delay. One that will finally convince most lay people - and hopefully - even convince a few of the scientists.
DUHIG IS PROSECUTION'S KEY WITNESS
In the Fall of 1943, in Brisbane Australia, 15 years after Fleming discovered penicillin, Dr J V Duhig saved the lives of a dozen seriously ill people using a form of penicillin juice no more sophisticated than what Fleming had on hand in November 1928.
This the single hard, hard, hard, hard ,hard, historical stone against which I am going to grind every author and every account that claims that there were 'technical complications' why the world had to wait 15 or more years to put the life-saving effects of penicillin to work.
Until and unless they can explain to everyone's satisfaction why Duhig could do this - but why Fleming/Florey and Dawson et all couldn't - I will not relent.....
why MUCOID mattered: Henry Dawson and Rheumatic Fever
Recently having had a sore throat or tonsillitis - when it is caused by our normally throat and nose inhabiting (commensal) strep bacteria- is the only way you can get Rheumatic Fever.
There has never been a confirmed incident when huge life-threatening amounts of virulent strep bacteria rolling about in a gaping wound (the type of dramatic situation that makes strep the most feared word in the medical lexicon) has ever caused a single case of life-threatening Rheumatic Fever.
Rheumatic Fever (RF) is (and was) a very serious and very common disease, yet it begins with the quietest possible onset - one third of all its victims can't even remember having had a recent sore throat.
'Sore throat', undefined, is so common throughout all our lives, that we find it hard to tell those ones that were caused by strep bacteria from those that weren't.
The safest rule is if the sore throat hurts much and hangs on more than a day or two - run to a doctor and ask for a swab test.
If we are very unwell and have had endless rounds of sore throats and even previous bouts of RF, probably almost any strain of strep can cause another round of RF.
But for most of us that are healthy and well fed, being in an stressful new situation in an enclosed space for weeks at a time with a particularly virulent strain of strep running from person to person back to person, is our only way to get it.
I mean a wartime military recruit camp - the best possible natural laboratory we have ever had to see just how many people can get RF if the conditions are perfect.
The observed percentages are high enough, often enough, to put real fear into that doctors that do statistics and are paid to keep an eye on epidemics ---this despite the fact that RF is almost totally gone in the western world.
(It is still common in third world countries that until fairly recently historically never saw a case of it.)
We still don't know enough about it, to be terribly confident that it will remain beaten here in the western world.
Currently, the biggest focus of research effort is something that Martin Henry Dawson would not have found surprising : it is the fact that it is the most heavily mucoid of hemo strep colonies that seem to cause RF among populations normally felt to be at least risk.
Mucoid heavy strains of hemo strep turn RF from a social disease affecting the poor mostly, to something that could kill any or all of us.
A deep interest in raising the awareness of the virulence of Mucoid colonies of GAS strep generally (along with his pioneer use of penicillin to cure RF's final effect, SBE) was Dawson's particular contribution to the world wide effort to explain and prevent RF from the 1920s to the 1960s.
I do not believe that Dawson had actually pinpointed mucoid strains of hemolytic strep as the leading agents of the most deadly versions of RF - he simply knew that mucoid colonies were usually the most deadly agents in all of the dozens of serious diseases that strep deals out to us humans - and in the 1930s, RF was the most important hemo strep disease around.
Having his thesis proven in the case of acute RF wouldn't have surprised Dawson - but it would have pleased him.
His 1930s mucoid work, sandwiched as it was between his pioneering work on recombinant DNA in the 1920s and his pioneering penicillin work in the 1940s has naturally been overshadowed by these two, the two biggest medical stories of the entire 20th century and beyond.
But to explain how in 1940 that an arthritis 'aspirin doctor' ended up in the area of endocarditis, today the domain of heart surgeons, we need to see this intellectual connection between mucoid hemo strep causing RF, which in turn led to SBE.......
There has never been a confirmed incident when huge life-threatening amounts of virulent strep bacteria rolling about in a gaping wound (the type of dramatic situation that makes strep the most feared word in the medical lexicon) has ever caused a single case of life-threatening Rheumatic Fever.
Rheumatic Fever (RF) is (and was) a very serious and very common disease, yet it begins with the quietest possible onset - one third of all its victims can't even remember having had a recent sore throat.
'Sore throat', undefined, is so common throughout all our lives, that we find it hard to tell those ones that were caused by strep bacteria from those that weren't.
The safest rule is if the sore throat hurts much and hangs on more than a day or two - run to a doctor and ask for a swab test.
If we are very unwell and have had endless rounds of sore throats and even previous bouts of RF, probably almost any strain of strep can cause another round of RF.
But for most of us that are healthy and well fed, being in an stressful new situation in an enclosed space for weeks at a time with a particularly virulent strain of strep running from person to person back to person, is our only way to get it.
I mean a wartime military recruit camp - the best possible natural laboratory we have ever had to see just how many people can get RF if the conditions are perfect.
The observed percentages are high enough, often enough, to put real fear into that doctors that do statistics and are paid to keep an eye on epidemics ---this despite the fact that RF is almost totally gone in the western world.
(It is still common in third world countries that until fairly recently historically never saw a case of it.)
We still don't know enough about it, to be terribly confident that it will remain beaten here in the western world.
Currently, the biggest focus of research effort is something that Martin Henry Dawson would not have found surprising : it is the fact that it is the most heavily mucoid of hemo strep colonies that seem to cause RF among populations normally felt to be at least risk.
Mucoid heavy strains of hemo strep turn RF from a social disease affecting the poor mostly, to something that could kill any or all of us.
A deep interest in raising the awareness of the virulence of Mucoid colonies of GAS strep generally (along with his pioneer use of penicillin to cure RF's final effect, SBE) was Dawson's particular contribution to the world wide effort to explain and prevent RF from the 1920s to the 1960s.
I do not believe that Dawson had actually pinpointed mucoid strains of hemolytic strep as the leading agents of the most deadly versions of RF - he simply knew that mucoid colonies were usually the most deadly agents in all of the dozens of serious diseases that strep deals out to us humans - and in the 1930s, RF was the most important hemo strep disease around.
Having his thesis proven in the case of acute RF wouldn't have surprised Dawson - but it would have pleased him.
His 1930s mucoid work, sandwiched as it was between his pioneering work on recombinant DNA in the 1920s and his pioneering penicillin work in the 1940s has naturally been overshadowed by these two, the two biggest medical stories of the entire 20th century and beyond.
But to explain how in 1940 that an arthritis 'aspirin doctor' ended up in the area of endocarditis, today the domain of heart surgeons, we need to see this intellectual connection between mucoid hemo strep causing RF, which in turn led to SBE.......
Friday, October 8, 2010
Sir Robertson's curious letter and curiouser claim
Late August and early September 1942 saw a furious burst of letters to the editor directed at The Times of London, provoked by an August 27th editorial in paper concerning penicillin.
The three hundred word effort echoed an earlier editorial from The Lancet , and supported their claim that the drug was non toxic and more active than sulfa drugs and that its production should be greatly expanded and quickly.
Since penicillin looked to be a real comer with much 'moral capital' accruing to the companies or institutions that best claimed the laurels for first developing it, naturally all the major bodies involved had to elbow their way forward to stake their claim - the current 'all-for-one' war effort not withstanding.
(A note to errant historians and authors: the drug companies' penicillin research arm, the TRC,were actually the first to gave themselves credit. Only then did St Mary's Hospital step in to also seek some glory.)
Sir Robert Robertson, the world famous Oxford chemist , spoke for the Oxford team.
Some of what he claimed were mere weasel words.
Dawson published the results of his treatment of 12 patients by May 1941, Florey his results on ten patients in August 1941.
Both were admirably cautious in assessing what if anything penicillin had done for their patients.
Dawson was actually the first to treat a patient and see that patient go home from his deathbed --- so Robertson was content to use weasel words that Florey was the first to "demonstrate the value
(of penicillin) clinically."
'Demonstrate' is a subjective term - in the eyes of the beholder - and Robertson knew it.
So, he had as well admitted that Fleming discovered penicillin and that Dawson had been the first to use it clinically as a life-saving systemic antibiotic.
What credit left for Oxford?
Robertson then told the bare-faced lie that toxic materials were produced by the penicillium mold, along with penicillin.
Florey was therefore to be praised for being the first to separate the unsafe impurities from the safe pure penicillin so that it could be at last safely used on humans. (But wasn't, not by Florey - at least not right away ...!)
Nobody who ever worked with penicillin-producing penicillium , starting with Fleming in 1928 and carrying right on through twenty years later, ever saw enough of anything harmful, at levels enough to be toxic.
All made a point to note that the raw penicillin juice was not toxic even when injected in huge quantities by normal medical standards.
Foremost among these supporters of the use of semi-purified or raw penicillin was one Howard Florey.
He publicly marveled that in hundreds of IM injections, no damage was ever seen at the site of the needle - not even in babies. The impure preparations he rated at 10% pure at the max (actually 3% pure) yet their impurities ( 97% of the dose) were non toxic - even when given in huge dosages.
It is hard to imagine a better test for proving the impurities were NOT toxic --- I can not,myself, imagine one.
What was going on then - in the mind of Professor Robertson and his chemist-manque Dr Florey ?
If Robertson and Florey had made any headway on synthesizing penicillin, I am sure this would have been their sole claim to glory.
But they hadn't.
So what can chemists do?
They can separate substances, even if they can't synthesize them, and even if the substances didn't need separating !
A nice meal does not improve when a chemist burns it all and then pours acid over the remains, to separate it into its constitute elements.
Penicillin juice - as Australian Dr James Vincent Duhig demonstrated in Brisbane in the Fall of 1943, doesn't need to be separated from its impurities at all, in order to save lives safely.
When it comes to questions of health, trust Duhig,MD over chemist Robertson PhD.
I don't expect Oxford University's academics to ever set the scholastic record straight about what Oxford did and didn't do with penicillin.
Claiming a leading role in developing the best lifesaver the world will ever know is simply too much of a money spinner for Oxford and the entire Thames Valley community.....
The three hundred word effort echoed an earlier editorial from The Lancet , and supported their claim that the drug was non toxic and more active than sulfa drugs and that its production should be greatly expanded and quickly.
Since penicillin looked to be a real comer with much 'moral capital' accruing to the companies or institutions that best claimed the laurels for first developing it, naturally all the major bodies involved had to elbow their way forward to stake their claim - the current 'all-for-one' war effort not withstanding.
(A note to errant historians and authors: the drug companies' penicillin research arm, the TRC,were actually the first to gave themselves credit. Only then did St Mary's Hospital step in to also seek some glory.)
Sir Robert Robertson, the world famous Oxford chemist , spoke for the Oxford team.
Some of what he claimed were mere weasel words.
Dawson published the results of his treatment of 12 patients by May 1941, Florey his results on ten patients in August 1941.
Both were admirably cautious in assessing what if anything penicillin had done for their patients.
Dawson was actually the first to treat a patient and see that patient go home from his deathbed --- so Robertson was content to use weasel words that Florey was the first to "demonstrate the value
(of penicillin) clinically."
'Demonstrate' is a subjective term - in the eyes of the beholder - and Robertson knew it.
So, he had as well admitted that Fleming discovered penicillin and that Dawson had been the first to use it clinically as a life-saving systemic antibiotic.
What credit left for Oxford?
Robertson then told the bare-faced lie that toxic materials were produced by the penicillium mold, along with penicillin.
Florey was therefore to be praised for being the first to separate the unsafe impurities from the safe pure penicillin so that it could be at last safely used on humans. (But wasn't, not by Florey - at least not right away ...!)
Nobody who ever worked with penicillin-producing penicillium , starting with Fleming in 1928 and carrying right on through twenty years later, ever saw enough of anything harmful, at levels enough to be toxic.
All made a point to note that the raw penicillin juice was not toxic even when injected in huge quantities by normal medical standards.
Foremost among these supporters of the use of semi-purified or raw penicillin was one Howard Florey.
He publicly marveled that in hundreds of IM injections, no damage was ever seen at the site of the needle - not even in babies. The impure preparations he rated at 10% pure at the max (actually 3% pure) yet their impurities ( 97% of the dose) were non toxic - even when given in huge dosages.
It is hard to imagine a better test for proving the impurities were NOT toxic --- I can not,myself, imagine one.
What was going on then - in the mind of Professor Robertson and his chemist-manque Dr Florey ?
If Robertson and Florey had made any headway on synthesizing penicillin, I am sure this would have been their sole claim to glory.
But they hadn't.
So what can chemists do?
They can separate substances, even if they can't synthesize them, and even if the substances didn't need separating !
A nice meal does not improve when a chemist burns it all and then pours acid over the remains, to separate it into its constitute elements.
Penicillin juice - as Australian Dr James Vincent Duhig demonstrated in Brisbane in the Fall of 1943, doesn't need to be separated from its impurities at all, in order to save lives safely.
When it comes to questions of health, trust Duhig,MD over chemist Robertson PhD.
I don't expect Oxford University's academics to ever set the scholastic record straight about what Oxford did and didn't do with penicillin.
Claiming a leading role in developing the best lifesaver the world will ever know is simply too much of a money spinner for Oxford and the entire Thames Valley community.....
CRITICAL biography of Norman Heatley long, long overdue
I don't think Norman Heatley (1911-2004) did as much to advance penicillin as he thought he did.
I think a more balanced collective biography of the entire Oxford team might better spread the credit (and blame) about.
It seems to me that Glister and Sanders did far more, and Heatley far less ,to get penicillin production actually working and producing.
Norman himself conveyed to the world his view that he felt he was no longer a key member of the Oxford penicillin team after 1943 - as the historical blue plaque on his home so indicates.
(He even tried to apply for a job at a drug firm far far from the Dunn in 1944 !)
The Oxford team kept up their penicillin work up to the war's end in 1945 and beyond -I am curious to know what it was that Heatley felt he was doing at the Dunn between 1943 and 1946, if it didn't involve penicillin.
Sanders and Glister and all the rest - except Florey and Heatley -were never very interested to tell their part in the penicillin saga at Oxford.
So in this land of the blind, the one-eyed Heatley became king - particularly in the 36 years after Florey's death.
Heatley grew ever bolder in his claims ,as more and more of
'the old gang' passed on beyond the point of rebuttals via 'letters to the editor', directed at The Times.
The Oxford community, still unable to understand how credit for penicillin was taken up by a Scotsman (Alexander Fleming) and a parvenu American soda pop company (Pfizer), fully supported Heatley in this effort.
I don't expect my biography of another penicillin pioneer, close associate of Pfizer, and a Scotman, Martin Henry Dawson, to be any more popular in Oxford.....
I think a more balanced collective biography of the entire Oxford team might better spread the credit (and blame) about.
It seems to me that Glister and Sanders did far more, and Heatley far less ,to get penicillin production actually working and producing.
Norman himself conveyed to the world his view that he felt he was no longer a key member of the Oxford penicillin team after 1943 - as the historical blue plaque on his home so indicates.
(He even tried to apply for a job at a drug firm far far from the Dunn in 1944 !)
The Oxford team kept up their penicillin work up to the war's end in 1945 and beyond -I am curious to know what it was that Heatley felt he was doing at the Dunn between 1943 and 1946, if it didn't involve penicillin.
Sanders and Glister and all the rest - except Florey and Heatley -were never very interested to tell their part in the penicillin saga at Oxford.
So in this land of the blind, the one-eyed Heatley became king - particularly in the 36 years after Florey's death.
Heatley grew ever bolder in his claims ,as more and more of
'the old gang' passed on beyond the point of rebuttals via 'letters to the editor', directed at The Times.
The Oxford community, still unable to understand how credit for penicillin was taken up by a Scotsman (Alexander Fleming) and a parvenu American soda pop company (Pfizer), fully supported Heatley in this effort.
I don't expect my biography of another penicillin pioneer, close associate of Pfizer, and a Scotman, Martin Henry Dawson, to be any more popular in Oxford.....
Thursday, October 7, 2010
it was the patients' MOMS who brought penicillin to the DOCTORS
The private discovery of penicillin happened in September 1928, the public discovery in June 1929 when it was published in an important, peer-reviewed scientific journal.
But then it just sat there for twelve to fifteen years.
So your great grandfather or great aunt died needlessly because the doctors and the scientists did nothing with penicillin, after that public discovery.
In August and September 1943, however, your grandmother "popularly" discovered penicillin when she read about Baby Patricia in some newspaper articles in some of the Hearst publications.
Now the fur really flew, as your grandmother demanded to know why your uncle, off wounded in a hospital in the South Pacific, wasn't getting any of this penicillin.
Her Mom-like anger and urgency finally got the men moving and before long her doctor and every other doctor had penicillin to treat patients.
So don't go tell me that doctors bring penicillin to patients.
Publication in a scientific journal (aka making something public as the scientists say) is not the be all and end all of effective science, as satisfying as it is to scientific egos.
The most influential scientific publication of Doctor Martin Henry Dawson was an oral, not printed, account of the first human cases ever treated with systemic penicillin, given at an Annual Meeting of the Society of Clinical Investigators in May 1941 in front of hundreds of the world's leading medical scientists from all over the world.
Did he publicize his work with penicillin ? We laypeople might think so.
Howard Florey, however, sensed a loophole.
He chose to regard an oral presentation of a paper at an conference, and subsequently published on paper in July 1941, as 'not a scientific publication' and ignored all mention of Dawson's breakthrough in his own references to his subsequent August 1941 paper on penicillin.
Thankfully, Dawson's work got written up in the New York Times ---near the business section --- not a scientific publication, admittedly.
However when the people in charge of the chequebook at Pfizer read it, they saw to it that their Brooklyn Crude penicillin was there to save the wounded on the D-Day beaches and ever after, until the war's end.
Florey continued to publish scientifically on his synthetic penicillin (Oxford Pure)---- but he never actually delivered any.
Pfizer never did publish on its safe, effective Brooklyn Crude.
They just delivered to the beaches, on time, and in quantity.
If you were a soldier in the Princess Louise Regiment (PLF) regiment lying on the Gothic Line, wounded, which would you prefer: British published talk or unpublished American walk ?
Well I was a (post war) member of the PLF and I bloody well know which one I'd prefer.
"OXFORD talks, but BROOKLYN walks..."
But then it just sat there for twelve to fifteen years.
So your great grandfather or great aunt died needlessly because the doctors and the scientists did nothing with penicillin, after that public discovery.
In August and September 1943, however, your grandmother "popularly" discovered penicillin when she read about Baby Patricia in some newspaper articles in some of the Hearst publications.
Now the fur really flew, as your grandmother demanded to know why your uncle, off wounded in a hospital in the South Pacific, wasn't getting any of this penicillin.
Her Mom-like anger and urgency finally got the men moving and before long her doctor and every other doctor had penicillin to treat patients.
So don't go tell me that doctors bring penicillin to patients.
Publication in a scientific journal (aka making something public as the scientists say) is not the be all and end all of effective science, as satisfying as it is to scientific egos.
The most influential scientific publication of Doctor Martin Henry Dawson was an oral, not printed, account of the first human cases ever treated with systemic penicillin, given at an Annual Meeting of the Society of Clinical Investigators in May 1941 in front of hundreds of the world's leading medical scientists from all over the world.
Did he publicize his work with penicillin ? We laypeople might think so.
Howard Florey, however, sensed a loophole.
He chose to regard an oral presentation of a paper at an conference, and subsequently published on paper in July 1941, as 'not a scientific publication' and ignored all mention of Dawson's breakthrough in his own references to his subsequent August 1941 paper on penicillin.
Thankfully, Dawson's work got written up in the New York Times ---near the business section --- not a scientific publication, admittedly.
However when the people in charge of the chequebook at Pfizer read it, they saw to it that their Brooklyn Crude penicillin was there to save the wounded on the D-Day beaches and ever after, until the war's end.
Florey continued to publish scientifically on his synthetic penicillin (Oxford Pure)---- but he never actually delivered any.
Pfizer never did publish on its safe, effective Brooklyn Crude.
They just delivered to the beaches, on time, and in quantity.
If you were a soldier in the Princess Louise Regiment (PLF) regiment lying on the Gothic Line, wounded, which would you prefer: British published talk or unpublished American walk ?
Well I was a (post war) member of the PLF and I bloody well know which one I'd prefer.
"OXFORD talks, but BROOKLYN walks..."
Tuesday, October 5, 2010
Oct 16 1940 : the disease was MODERNITY
A marvellously effective drug lay on a British shelf, unused, for twelve long years --- 'a miracle cure in search of a disease' --- on October 16th 1940 in a Manhattan hospital it finally found it : the disease was MODERNITY and the cure was penicillin.
The nominal disease Dr Martin Henry Dawson was seeking to cure that day (almost exactly 70 years ago) with the first ever needleful of the antibiotic penicillin was SBE, an invariably fatal calcination of the heart valves.
However the real disease he was seeking to heal was modern utilitarianism, aka stone-heartedness.
Neither Fleming or Florey - to put it mildly - were up for this job.
In a few weeks,Dawson discovered he himself was dying as well but he felt duty-bound to carry on helping the helpless and the hopeless, despite a 'Total War' atmosphere which assigned 'useless mouths' like the SBEs to baneful neglect --- or worse.
The nominal disease Dr Martin Henry Dawson was seeking to cure that day (almost exactly 70 years ago) with the first ever needleful of the antibiotic penicillin was SBE, an invariably fatal calcination of the heart valves.
However the real disease he was seeking to heal was modern utilitarianism, aka stone-heartedness.
Neither Fleming or Florey - to put it mildly - were up for this job.
In a few weeks,Dawson discovered he himself was dying as well but he felt duty-bound to carry on helping the helpless and the hopeless, despite a 'Total War' atmosphere which assigned 'useless mouths' like the SBEs to baneful neglect --- or worse.
Sunday, October 3, 2010
Dying Doctor goes 'Over the Top' in WWII to save his patients
This is the plot of "MO goes PO" in "Hollywood High Concept", with the movie retitled as
"Penicillin Stat! : Dying Doctor goes 'Over the Top' in WWII to save his Patients."
As his skeptical medical critics saw the situation , Henry Dawson went completely 'Over the Top' in 1940, in his quest to save terminally ill SBE patients with his penicillium juice.
But then he had gone already 'Over the Top' in 1917 - and again in 1918 (while, by contrast, they had sat out the war ambitiously pushing ahead amid the deleted numbers of wartime grad school) so I suppose he earned the right to do the same in WWII.....
"Penicillin Stat! : Dying Doctor goes 'Over the Top' in WWII to save his Patients."
As his skeptical medical critics saw the situation , Henry Dawson went completely 'Over the Top' in 1940, in his quest to save terminally ill SBE patients with his penicillium juice.
But then he had gone already 'Over the Top' in 1917 - and again in 1918 (while, by contrast, they had sat out the war ambitiously pushing ahead amid the deleted numbers of wartime grad school) so I suppose he earned the right to do the same in WWII.....
Friday, October 1, 2010
Florey: if patents fail, try trademarks
By March 1941, Howard Florey ( the son of an industrialist who made his fortune through his knowledge of patents, trade secrets and trademarks ,as both a buyer and a seller ) knew that no drug firm was likely to take out a license on his penicillin purification process, even if he did get Oxford University or the MRC to patent it.
Taking it as a given that no one applies for a patent for a process that does not work at all, the usual delay and expense is over determining whether the process is truly novel.
The question as to whether it is truly commercial is left to the market.
A process that costs more to yield less product than an existing process, is not going to find any licensees even if the fees were pennies per annum.
Pfizer had citric acid, Florey had COKE
But Florey had basically kept his (highly inefficient) process highly secret - and an inefficient process that remains a trade secret, combined with a lot of chutzpah and legwork, can still make for a perfectly viable and profitable trade mark.
You simply claim that your product is superior than anyone else's because of your secret formula ,kept in a bank vault, ( Coke anyone?) and so is worth a superior price.
You simply substitute the power of saturation advertising when saturation catalyst chemistry fails to produce the expected yield.
This is what Florey commenced to do on his trip to America - insist that only Oxford University brand penicillin was the one and only true penicillin - just as the world had gotten used to being told that Oxford had the only real English bible and the only real English dictionary and the only real English accent.
I couldn't see this going down a ton in Plymouth,UK, a Royalist stronghold in the (English) Civil War, but at Yale and Harvard USA where the American rebels had fought and won a revolution against Oxford imposing its religious and cultural values on other faiths, this sort of stuff was a big hit.
I am sorry to say this - but when it comes to truly sucking up to any and every aristocrat - our American friends are suckers of the first water.
The chimera of penicillin
'Penicillin' doesn't actually exist - at least not as a single entity : rather it is the overall name for a large sub family of an even bigger family of antibiotics called the beta-lactams.
Almost all of these penicillins are defined as being hydrophobic (ie having non-polar side chains) antibiotics produced by fungi ,not bacteria ,that act mostly on gram positive bacteria and contain at their core the vital beta-lactam structure.
Reverse most of this, but leave the beta-lactam core and you have the cephalosporins antibiotic sub family.
Florey would rant at anyone who produced different results (like his long suffering friends at Merck) that their penicillin couldn't possibly be the real penicillin if it wasn't like his.
But it could be and was - different food mediums and conditions produced different types of beta-lactams and also differing amounts of antiobiotics that were not beta-lactams, from the same strain of penicillium.
In addition the penicillium frequently and rapidly mutated into different strains that could produce differing amounts of different penicillins in response to a fixed /standard set of conditions and food mediums.
Aaaaarrrgh !!!!!
In real life, outside the lab, reality was often as messy and untidy as real Australia was from its citizens' visions of a pure white only Australia.
Florey was a purity-wonk
Unfortunately, unlike his pragmatic Dad, Florey's main motif throughout his life was to seek out purity in all its forms - moral as well as chemical - we see this repeatedly referenced in his letters to his future wife Ethel from the 1920s.
I think Florey's barnstorming of America worked - he couldn't claim he had been the first in anything important in penicillin beyond the mouse test - Fleming, Paine and Dawson saw to that - but he could at least claim he had the purest penicillin on Earth.
To save lives, penicillin dose size, not quality, matters more...
I'll say it again - pure is a relative term, a percentage term - bacteria die and people's lives are saved only by large absolute amounts of penicillin - regardless of their relative purity.
Florey's all out pursuit of purity quality over penicillin quantity was a moral failing of the highest possible order.
In the war against Hitler and his racist purity views, to work full out, from 1938 to 1945, on finding an all-white penicillin was as obscene as as seeking to preserve an all-white Australia --- or an all-white Germany......
Taking it as a given that no one applies for a patent for a process that does not work at all, the usual delay and expense is over determining whether the process is truly novel.
The question as to whether it is truly commercial is left to the market.
A process that costs more to yield less product than an existing process, is not going to find any licensees even if the fees were pennies per annum.
Pfizer had citric acid, Florey had COKE
But Florey had basically kept his (highly inefficient) process highly secret - and an inefficient process that remains a trade secret, combined with a lot of chutzpah and legwork, can still make for a perfectly viable and profitable trade mark.
You simply claim that your product is superior than anyone else's because of your secret formula ,kept in a bank vault, ( Coke anyone?) and so is worth a superior price.
You simply substitute the power of saturation advertising when saturation catalyst chemistry fails to produce the expected yield.
This is what Florey commenced to do on his trip to America - insist that only Oxford University brand penicillin was the one and only true penicillin - just as the world had gotten used to being told that Oxford had the only real English bible and the only real English dictionary and the only real English accent.
I couldn't see this going down a ton in Plymouth,UK, a Royalist stronghold in the (English) Civil War, but at Yale and Harvard USA where the American rebels had fought and won a revolution against Oxford imposing its religious and cultural values on other faiths, this sort of stuff was a big hit.
I am sorry to say this - but when it comes to truly sucking up to any and every aristocrat - our American friends are suckers of the first water.
The chimera of penicillin
'Penicillin' doesn't actually exist - at least not as a single entity : rather it is the overall name for a large sub family of an even bigger family of antibiotics called the beta-lactams.
Almost all of these penicillins are defined as being hydrophobic (ie having non-polar side chains) antibiotics produced by fungi ,not bacteria ,that act mostly on gram positive bacteria and contain at their core the vital beta-lactam structure.
Reverse most of this, but leave the beta-lactam core and you have the cephalosporins antibiotic sub family.
Florey would rant at anyone who produced different results (like his long suffering friends at Merck) that their penicillin couldn't possibly be the real penicillin if it wasn't like his.
But it could be and was - different food mediums and conditions produced different types of beta-lactams and also differing amounts of antiobiotics that were not beta-lactams, from the same strain of penicillium.
In addition the penicillium frequently and rapidly mutated into different strains that could produce differing amounts of different penicillins in response to a fixed /standard set of conditions and food mediums.
Aaaaarrrgh !!!!!
In real life, outside the lab, reality was often as messy and untidy as real Australia was from its citizens' visions of a pure white only Australia.
Florey was a purity-wonk
Unfortunately, unlike his pragmatic Dad, Florey's main motif throughout his life was to seek out purity in all its forms - moral as well as chemical - we see this repeatedly referenced in his letters to his future wife Ethel from the 1920s.
I think Florey's barnstorming of America worked - he couldn't claim he had been the first in anything important in penicillin beyond the mouse test - Fleming, Paine and Dawson saw to that - but he could at least claim he had the purest penicillin on Earth.
To save lives, penicillin dose size, not quality, matters more...
I'll say it again - pure is a relative term, a percentage term - bacteria die and people's lives are saved only by large absolute amounts of penicillin - regardless of their relative purity.
Florey's all out pursuit of purity quality over penicillin quantity was a moral failing of the highest possible order.
In the war against Hitler and his racist purity views, to work full out, from 1938 to 1945, on finding an all-white penicillin was as obscene as as seeking to preserve an all-white Australia --- or an all-white Germany......
Thursday, September 30, 2010
"Manhattan Clearing #7":undignified and unprofessional,HEROIC, science
Henry Dawson probably surprised himself as much as he surprised the rest of his battalion, maybe even surprised his hometown community, when he revealed a talent for 'heat of the crisis' gifted improvisation and leadership during the events that led to him winning a Military Cross and Citation for Bravery.
That same talent came to the fore perhaps only two more times in his life - during his work on HGT and again in his efforts with penicillin - both times with high stakes outcomes.
He never was an emergency ward doctor or wartime clearing station doctor but he may have had the talent to excel at it.
He most clearly showed this talent in the hectic five weeks leading up to giving that needle of penicillin to Charlie Aronson, seventy years ago, on October 16th 1940.
Neither Fleming or Florey could have done this work - it simply wasn't in their character. Both were all too aware of the constant need to maintain the public image of dignity and certitude for medical scientists.
Both men also lacked that personal empathy for patients as people that led Dawson to forget his professional dignity as he literally ran about with a needle of penicillin - STAT - in his efforts to save lives....
That same talent came to the fore perhaps only two more times in his life - during his work on HGT and again in his efforts with penicillin - both times with high stakes outcomes.
He never was an emergency ward doctor or wartime clearing station doctor but he may have had the talent to excel at it.
He most clearly showed this talent in the hectic five weeks leading up to giving that needle of penicillin to Charlie Aronson, seventy years ago, on October 16th 1940.
Neither Fleming or Florey could have done this work - it simply wasn't in their character. Both were all too aware of the constant need to maintain the public image of dignity and certitude for medical scientists.
Both men also lacked that personal empathy for patients as people that led Dawson to forget his professional dignity as he literally ran about with a needle of penicillin - STAT - in his efforts to save lives....
for Dawson, Penicillin came with only one possible modifier: "STAT!"
I have said before that the Fall of 1918 was the life-defining moment for both Henry Dawson and Howard Florey.
In September 1918, Florey's family literally tumbled down the social scale.
Down, down, down from wealthy socially prominent Upper Mitcham - sliding quickly back down the social scale to a little cottage in the lower suburbs near the city centre (Fullarton Estates in South Adelaide) rather like the humble cottage where the family had begun its life in Adelaide only 35 years earlier.
No more big mansion, no more grand summer home, no more grand automobile, no more factory and firm, no more money for school fees - all gone in the bankruptcy following his dad's sudden death.
Like Charles Dickens never forgiving his mother from not rescuing him from the blacking factory, Howard Florey never forgave his father for bringing the family firm and name to ruin by not keeping a proper watch on his subordinate employees - the event that the family claimed led to the firm's collapse.
For Dawson,September 1918 meant he was wounded once again - even more seriously this time.
Once more he had months in hospitals recovering and once again he had to endure the yells and smells of the young boys needlessly dying beside him from relatively minor wounds that had become grossly infected with bacteria.
This time, thousands of soldiers were also dying from the bacterial diseases that followed upon the infamous Spanish Flu.
Sometime during those months spent recovering, Dawson stopped referring to himself as a soldier planning to return to an Arts Degree, instead become someone planning to become a doctor.
He became a bacteria specialist in fact.
In 1940, both men got an unexpected opportunity to re-live (and more importantly, to re-do and un-do ) those traumatic events.
Florey turned his Department's entire building at Oxford University into what he called the Dunn "PENICILLIN FACTORY", run by Florey like a factory-operating Victorian paterfamilas, just as his own father had done in the family's halcyon days before the firm became a publicly traded company.
Woe to any member of the Florey family firm at the Dunn, like Norman Heatley, who dared even think of leaving the Dunn factory if Florey didn't want him to.
Leonard Bickel recounts this incident in his "Rise Up to Life" biography of Florey and when I first read it six years ago, I thought how feudal it all sounded - like the way minor Nova Scotia lumber
barons still treat their employees in backwoods communities where their mill is the only source of work.
About the only thing missing were the annual Florey 'factory family' picnics.
For Dawson, he turned his tiny lab, together with the nearby corridor and ward, into what I call his own "MANHATTAN
CLEARING # 7" , a sort of civilian casualty clearing post or station rather like the many that Dawson had served in or suffered in during the Great War.
(His lab was was on the Floor G at the Presbyterian Hospital in Manhattan, and G is the seventh letter of the alphabet. As he had also started his medical career in 1915, as a private
(orderly) in the Canadian #7 Stationary Hospital (organized by Dalhousie University's Medical School) - I gave his effort this particular name.)
Unlike a stationary or base hospital much of the time, a Casualty Clearing Station really operates at only one tempo ---- STAT.
This medical term means 'as fast as possible', 'immediately', 'its a clinical life-threatening emergency', all words that aptly describes the type of patients a CCS or CCP got after earlier medical posts sorted out the less wounded.
Florey and Chain openly admit they crafted their penicillin project to be a broad long term investigation on the entire topic of microbial antagonism - designed to bring in lots of work for staff and lots of grants for equipment -- to help make the Dunn into a world class research institution.
This they achieved - penicillin was only one of hundreds of antibiotics they investigated in WWII.
By contrast, Dawson strictly focused, from day one, on saving as many Juvenis Interruptus (SBE) patients as possible, as quick as possible, with penicillin.
STAT was his byword in all things penicillin and in just five weeks he had grown, concentrated, tested and now was saving lives with a substance about almost nothing was known - a record probably no other doctor has excelled.
He was too old and too 'previously wounded' to end up again the the combat front lines, but he was 'still on the job', still saving young lives anyway he could.....
In September 1918, Florey's family literally tumbled down the social scale.
Down, down, down from wealthy socially prominent Upper Mitcham - sliding quickly back down the social scale to a little cottage in the lower suburbs near the city centre (Fullarton Estates in South Adelaide) rather like the humble cottage where the family had begun its life in Adelaide only 35 years earlier.
No more big mansion, no more grand summer home, no more grand automobile, no more factory and firm, no more money for school fees - all gone in the bankruptcy following his dad's sudden death.
Like Charles Dickens never forgiving his mother from not rescuing him from the blacking factory, Howard Florey never forgave his father for bringing the family firm and name to ruin by not keeping a proper watch on his subordinate employees - the event that the family claimed led to the firm's collapse.
For Dawson,September 1918 meant he was wounded once again - even more seriously this time.
Once more he had months in hospitals recovering and once again he had to endure the yells and smells of the young boys needlessly dying beside him from relatively minor wounds that had become grossly infected with bacteria.
This time, thousands of soldiers were also dying from the bacterial diseases that followed upon the infamous Spanish Flu.
Sometime during those months spent recovering, Dawson stopped referring to himself as a soldier planning to return to an Arts Degree, instead become someone planning to become a doctor.
He became a bacteria specialist in fact.
In 1940, both men got an unexpected opportunity to re-live (and more importantly, to re-do and un-do ) those traumatic events.
Florey turned his Department's entire building at Oxford University into what he called the Dunn "PENICILLIN FACTORY", run by Florey like a factory-operating Victorian paterfamilas, just as his own father had done in the family's halcyon days before the firm became a publicly traded company.
Woe to any member of the Florey family firm at the Dunn, like Norman Heatley, who dared even think of leaving the Dunn factory if Florey didn't want him to.
Leonard Bickel recounts this incident in his "Rise Up to Life" biography of Florey and when I first read it six years ago, I thought how feudal it all sounded - like the way minor Nova Scotia lumber
barons still treat their employees in backwoods communities where their mill is the only source of work.
About the only thing missing were the annual Florey 'factory family' picnics.
For Dawson, he turned his tiny lab, together with the nearby corridor and ward, into what I call his own "MANHATTAN
CLEARING # 7" , a sort of civilian casualty clearing post or station rather like the many that Dawson had served in or suffered in during the Great War.
(His lab was was on the Floor G at the Presbyterian Hospital in Manhattan, and G is the seventh letter of the alphabet. As he had also started his medical career in 1915, as a private
(orderly) in the Canadian #7 Stationary Hospital (organized by Dalhousie University's Medical School) - I gave his effort this particular name.)
Unlike a stationary or base hospital much of the time, a Casualty Clearing Station really operates at only one tempo ---- STAT.
This medical term means 'as fast as possible', 'immediately', 'its a clinical life-threatening emergency', all words that aptly describes the type of patients a CCS or CCP got after earlier medical posts sorted out the less wounded.
Florey and Chain openly admit they crafted their penicillin project to be a broad long term investigation on the entire topic of microbial antagonism - designed to bring in lots of work for staff and lots of grants for equipment -- to help make the Dunn into a world class research institution.
This they achieved - penicillin was only one of hundreds of antibiotics they investigated in WWII.
By contrast, Dawson strictly focused, from day one, on saving as many Juvenis Interruptus (SBE) patients as possible, as quick as possible, with penicillin.
STAT was his byword in all things penicillin and in just five weeks he had grown, concentrated, tested and now was saving lives with a substance about almost nothing was known - a record probably no other doctor has excelled.
He was too old and too 'previously wounded' to end up again the the combat front lines, but he was 'still on the job', still saving young lives anyway he could.....
Tuesday, September 28, 2010
Boots to Bombsights and back to Boots again !
Howard Florey's father won a massive government contact to supply boots to Australia's Reserve Army in the run up to World War One.
(Under the circumstances, how could he also spare his only son to actually wear one of those pairs of boots?)
Boots, along with shovels, were a big part of World War One, as millions of infantry armed with rifles and shovels were the key to a nation's continued survival and its hopes of ultimate victory.
But by 1940, low tech boots were so yesterday (along with the riflemen who wore them), as high tech bombsights - the Norden in particular - were seen as the key to survival.
In the US military, the infantry were the leftovers after all the other sections of the Army, along with the Navy and Marines, cherry-picked the best and the brightest.
By 1943, a survey revealed that not only were the MOS 745s (the frontline riflemen) less educated and less skilled than anyone else in the entire Military, they were also smaller and lighter.
Remember, these are the guys we all expected to pack on 75 pounds in extra gear and ammo and then run up hill full tilt under enemy fire, with only a millimeter of cotton twill to protect them !
Meanwhile, late in 1943, the rear echlon thumb suckers in Washington finally realized two very important things:
(1) The ultra modern Norden, together with the bomber attached to it, was as useless as a senior Congressman's mouth, when it came to actually making Germany surrender.
It was going to take old fashioned boots and shovels - lots of them - actually astride German soil, to make the Krauts to quit.
(2) There weren't enough infantry riflemen, period - let along top grade riflemen - to do the job. And as the wet, cold Fall 1943 campaign up the Italian Boot revealed, even the American boot wasn't up to the game.
Tens of thousands of the infantrymen already in desperately short supply in Italy were out of action, in hospitals with non-battlefield conditions.
Yes, some were in hospitals to be cured of VD ( much of it self- inflicted to get them out of the never-ending American meatgrinder system of Divisional combat - far worse than anything any army experienced in WWI).
This was well publicized - blaming the victim, in effect.
Less well known was the tens of thousands of foot soldiers in hospital with Trench Foot, produced by poor quality American footwear for wet winter combat conditions .
The nation that later boasted it was the first to put a pair of boots on the Moon, had more problems putting proper boots on its frontline dogfaces in WWII.
Less attention to making the plump perfect Norden mechanical bombsight and a bit more attention making better boot uppers might have been a better application of the vaunted American knowhow.
Perhaps Howard Florey should have given up penicillin and taken up his dad's trade, if he really wanted to aid America....
(Under the circumstances, how could he also spare his only son to actually wear one of those pairs of boots?)
Boots, along with shovels, were a big part of World War One, as millions of infantry armed with rifles and shovels were the key to a nation's continued survival and its hopes of ultimate victory.
But by 1940, low tech boots were so yesterday (along with the riflemen who wore them), as high tech bombsights - the Norden in particular - were seen as the key to survival.
In the US military, the infantry were the leftovers after all the other sections of the Army, along with the Navy and Marines, cherry-picked the best and the brightest.
By 1943, a survey revealed that not only were the MOS 745s (the frontline riflemen) less educated and less skilled than anyone else in the entire Military, they were also smaller and lighter.
Remember, these are the guys we all expected to pack on 75 pounds in extra gear and ammo and then run up hill full tilt under enemy fire, with only a millimeter of cotton twill to protect them !
Meanwhile, late in 1943, the rear echlon thumb suckers in Washington finally realized two very important things:
(1) The ultra modern Norden, together with the bomber attached to it, was as useless as a senior Congressman's mouth, when it came to actually making Germany surrender.
It was going to take old fashioned boots and shovels - lots of them - actually astride German soil, to make the Krauts to quit.
(2) There weren't enough infantry riflemen, period - let along top grade riflemen - to do the job. And as the wet, cold Fall 1943 campaign up the Italian Boot revealed, even the American boot wasn't up to the game.
Tens of thousands of the infantrymen already in desperately short supply in Italy were out of action, in hospitals with non-battlefield conditions.
Yes, some were in hospitals to be cured of VD ( much of it self- inflicted to get them out of the never-ending American meatgrinder system of Divisional combat - far worse than anything any army experienced in WWI).
This was well publicized - blaming the victim, in effect.
Less well known was the tens of thousands of foot soldiers in hospital with Trench Foot, produced by poor quality American footwear for wet winter combat conditions .
The nation that later boasted it was the first to put a pair of boots on the Moon, had more problems putting proper boots on its frontline dogfaces in WWII.
Less attention to making the plump perfect Norden mechanical bombsight and a bit more attention making better boot uppers might have been a better application of the vaunted American knowhow.
Perhaps Howard Florey should have given up penicillin and taken up his dad's trade, if he really wanted to aid America....
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