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....

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.

Rather 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....

Monday, September 27, 2010

Dawson,Florey: wildly different colonial Edwardians

Howard Florey and Henry Dawson were both born in the mid 1890s and grew up in roughly similar upper/middle class circumstances in two small outposts of the Edwardian Era British Empire.

But both took wildly variant approaches to almost every major decision affecting people born in the Edwardian Era.

Most famously, these two Edwardian colonials differed wildly over the best way to quickly get penicillin into wide use during World War Two.

We abuse history if we read too much into the generalities of a particular era and not enough into the particularities of the individuals living in the era.

 People, not eras, after all make the choices and do the actions.

If Florey was highly 'typical' of his Era, Dawson definitely was not 'typical' at all : however he still remained, someone from that Era -
a fact we must confront head on.....

50 years separate Leaders at top and Teen riflemen at bottom

In every war, the top national leadership are usually in their sixties.

My definition of national leader goes well beyond prime ministers and generals to include the unseen, semi-retired, powers behind the throne: the newspaper owners, the chief shareholders of the largest corporations, the professors emeritus etc.

By contrast, the men at the pointiest end of the stick, the infantry dogfaces armed only with a rifle and a shovel, are often in their teens.

Fifty years, a very long half century, usually separates the men who run the war from those who merely did as they are told.

So a historical approach which focuses too much on the memories of youngest veterans, the ones who survive the longest on civilian street, can seriously distort the historical record.

Yes they actually fought the battles and this makes for dramatic stories.

But, but, but - a focus on their experience comes at a high price.

Babies may experience history but they certainly didn't form it.

We need always to remember that the men who caused World War I -  and who led it -  had their formative experience of their life in the Pre-Modern Era ( back in 1850s and 1860s).

But their front line teenage soldiers were children of the Modern Era at its most florid - the worldwide Wheat and Rail Boom that led into the Edwardian Era.

So there was a disconnect.

In the Viet Nam War, the leaders were fully from the Modern Era but the teens fighting it were of the Post-Modern Era.

Another disconnect.

However in World War II,our only fully MODERN WAR , both its leaders and its teen soldiers were both fully in the same Modern Era ----albeit up to a point.

After all its leaders grew up in the booming Edwardian Era and the kids fighting in its front lines grew up in the depths of the Great Depression.

Probing further, we can see that the Edwardian Era was one where people were both, at almost the same instant, extremely optimistic and extremely pessimistic.

Progress and Degeneracy were their two bywords.

Most Edwardian Era adults held both views but still leaned consistently more to one side or other side.

I would, for an example, place Howard Florey on the optimistic side and Henry Dawson on the pessimistic side of the Edwardian Era estimation of Man's ability to favourably affect Reality.

My book on the wartime Penicillin Saga will not shortchange the leaders of the various wars it covers.

 I will highlight the fact that for most of us, our definitive values-forming experiences occur in our mid teens.

And I will then focus on the paradox that we
only get full rein to impose those teen age values on those younger than us when we are about 50 years older and our victims are themselves in their own mid-teens !

WW II leaders and their populace generally were
less convinced about the effectiveness of War elan and were more convinced of the effectiveness of War Science, in comparison to Great War populations.

This was partly due to the effect of recent experience - elan hadn't worked too well against machine guns in Flanders' Fields.

But it also reflected the intense belief in the 'Power of Science' held by Edwardian Era teenagers who were now running the Second World War at the very top of the food chain...

Saturday, September 25, 2010

War hospital stays made Dawson bacteriologist not surgeon

Not until February 1919, when the war was over, and Henry Dawson was back in Canada facing discharge, did he say that his civilian occupation was to be a MEDICAL student.

Until then, he was just an Arts student.

With his excellent marks, if in 1915 he had told military recruiters that he was intending to go into med school, he would have been almost 'ordered' to remain in school and become a doctor, as they were so desperately needed .

He spent a year in military hospitals as a buck private orderly, dealing with the severely injured and severely infected wounded coming off the battlefields.

Many other patients ,less dramatically, were
nevertheless dying from diseases they had picked up in other places than from a battlefield wound.

Then he was wounded,once as a infantry officer and then once as an artillery officer, both times fairly severely, and spent long periods in various hospitals.

The only heroes in these wound-oriented hospitals were the surgeons - they saved lives by their skill with a good eye and a steady hand.

The nursing staff might save lives by attention to detail in keeping wounds clean.

But regular (clinician) doctors contributed little towards a cure - they could diagnose but didn't have any medicine to save a patient if severe blood poisoning set in.

Bacteria were more dangerous than German bullets.

Interesting, there is no evidence Dawson decided to try and become a surgeon like all the surgeon-heroes he had met in the hospitals, once he was at McGill's Med School.

Instead Dawson quickly became a bacteriologist-pathologist and remained so all his life.

I think he felt that too many of the healthy young boys around him in his stays in hospital had survived their battlefield wound and had survived the surgery , only to die of bacterial infection.

This, he felt, was medicine's weakest link.

He wasn't seeking to emulate his medical heroes, but rather seeking to reform medicine from within.

 I believe he set out with a critical attitude to the existing medical practise - he felt it didn't give enough attention to the successful bacteria's secrets.

I think he saw too many young boys needlessly die who had never danced or ever been kissed...

Florey family and PATENTS :ducks and water

In the reverential biographies of  Howard Florey ( he has never had a critical biography - I hope to inspire one of them though), he is always played as the anti-patent guy on penicillin.

By contrast, Ernst Chain is always played as the greedy pro-patent guy.

Well, he is Jewish after all - he would be the greedy  money-grubbing one, won't he ?

Edward Abraham, who was there at the time, says that both were pro-patent to a degree - seeking Oxford University to control it ,(as the University of Toronto did insulin).

I agree.

The assumption was made that because Chain's father was in some sort of chemistry business in Germany Chain the PhD chemist would know all about the importance of patents.

(But we don't actually know if his father was involved in patents.)

But Florey ,the MD, would not anything about patents - against MD ethics in the UK at the time. Etc.

Bull dung !

Florey-the-son had wanted to be a chemist and was only nominally a MD in reality anyway.

His father had made his fortune by being the first into a new cutting edge technology, the first into high tech chemistry and trade marks, and by being the first in his state to obtain exclusive geographic rights to new processes.

Joseph Florey even tried to obtain at least one patent himself - for improvements in pneumatic tyres - applied for in Western Australia on May 16 1996, according to the local daily paper.

Leather making technology hadn't changed in around 10,000 years - so when it did, many in the industry refused to take the first leap.

Beyond how technically challenging the new ways of tanning leather were, was the fact that they were not public domain and free, as the tannin way of leather-making had been for centuries.

Florey took both risks and fell into a hot area of patents and licenses and paying high fees - or ignoring patents and fees and focussing on trade marks instead.

His many ads never claimed he had a patent for his chromella leather or even a patent license with a registered number - merely that he was the exclusive South Australia agent for it and held control of it as a trademark.

I haven't been able to find the original owner of chromella leather, but I believe very much they existed.

Here is why:

Florey's very first time he is mentioned in any newspaper seems to have been the month (October 1894) - even the day - he got that exclusive agency for chromella and he took out ads proclaiming that fact.

The word chromella almost never left the Australian papers, in some form or other, until well after his death.

His wealth seemed to have started around 1894 as well.

Having that chromella agency really seemed to have mattered.

But Joseph Florey having interests in tyres and patents of his own was news to me.

Patent talk would have been mother's milk to his son, Howard.

And I think we all owe Chain a heartfelt apology....

CHEMISTRY made Joseph Florey family rich and famous

Tanning leather is an ancient and highly skilled activity involving many chemical processes --- a process humans have been doing world wide for tens of thousands of years.

But tanning leather by use of formal chemistry (man-made rather than naturally found chemicals) is only about 150 years old and was brand new to the Southern Hemisphere when Joseph Florey set out to make his fame and fortune in the backward colony of South Australia.

This new method was called "chrome leather"  and consisted of tanning leather by means of various compounds of the metal chromium.

 The traditional, natural way, was via using tannin from the bark of various hardwoods, together with urine,dung and brains of animals and humans, as well as involving a lot of expensive, capricious hand labour.

 And a lot of time.

Joseph Florey was also a part owner of a new wattle plantation near Mount Cone in the interior of South Australia.

Wattles make an important variant of leather, suitable where chrome leather was too soft.

Till then,  virtually treeless South Australia had to import its tannin at great cost.

Chrome leather, by contrast, was modern, fast, machine-oriented, capital oriented.

It was made without the use of foul-smelling human urine and excrement collected by little poor children on the street corners of the poor neighbourhoods .

The chemically active ingredients of those natural products had been learned and synthetically made equivalents were used instead.

This was Victorian Progress and Joseph Florey never let anyone forget it - it was the focus of his firm's static displays at the Exhibitions of Industry and Progress so beloved by the Victorian and Edwardian middle class.

It was encompassed in his trade mark,Chromella, which he had secured throughout all of Australasia (sic). He repeatedly defended that trademark in expensive court cases.

Joseph Florey hadn't invented chrome leather but he acted as he had.

He successfully won via the courts , at least locally, the right to prevent any other competitor from using any trade name that hinted that their leather was produced by the 'chrome' method - though the patents on the original process had gone by then.

Chemistry - and a very competitive and ligatious nature - made the Florey fortune.

These were lessons learned well by Howard Florey and why he wanted to become a chemist - and why he was so highly competitive.

Ironically, chromium, a heavy metal, in those days and today gives many  customers contact dermitious or worse -- it is banned in very young children's shoes.

And its waste products are far worse for the environment than urine and dung ever were.

So today a new progressive modified organic, natural, method called 'wet white' is replacing the Old School chrome, wet blue, method......

Wednesday, September 22, 2010

Pity poor, poor pitiful Florey, surrounded by leftie subordinates

 Howard Florey got some very useful advice the day he arrived in America to protect Oxford University's Chromella Brand Penicillin from what he imagined were attacks on his left flank from Henry Dawson and his cohorts in deepest Brooklyn.

"Whatever you do, stay away from taking sides between the advocates of continuing social medicine (people like the US Surgeon General Thomas Parran) and those using the war as an excuse to roll back New Deal medical gains for the poor ( people like AMA godfather Morris Fishbein and the NAS's Lewis Weed.)"

(Dr Weed, upon whom the Hippocratic Oath lay lightly, saw medicines like penicillin and projects like germ warfare as highly useful weapons in a total war - and to test them the poor and the weak would be unwittingly conscripted into the war effort.)

This useful advice from Dr Gregg at the Rockefeller Foundation was wasted on Florey, the son of a hard-nosed industrialist and someone who loathed Blacks, Italians, Jews and trade unionists. (Just for a start.)

In fact, most of the problems that Florey had had with his subordinate Ernst Chain and his co-workers  Epstein and Duthie ,had come from of their left-wing social medicine-oriented politics.

Florey rather more preferred men like John Randal Baker, author of the controversial book RACE, if he had a choice as to who he wanted in his Institution.

Leslie Epstein (later Leslie Falk), from the Parran side of the debate, exacted his revenge on Florey by telling all on Florey's secret penicillin work to fellow Jew, Karl Meyer, working with Henry Dawson.

He thus setting into motion the wartime across ocean race to see whether Man or Nature would provide the lifesaving penicillin for the Allied wounded on the beaches of the upcoming Second Front.

And Thomas Parran got his revenge on A N Richards and C S Keffer from the Weed side of the debate, by releasing the penicillin to Baby Patricia which blow the lid off the whole secret effort to keep penicillin hidden until a chemical synthesis had been worked out.

After the war Parran and Falk joined up in Pittsburgh, still pushing a social medicine agency during a time in Cold War America the act of providing health care for all was regarded as the work of the Devil, in his human guise as Stalin.

America never did get decent medical care for its poorer citizens.

But hey, "We'll always have Penicillin. "

Won't we America ...?

Tuesday, September 21, 2010

WWII : German tanks mauling Polish horses to Polish horses hauling German tanks...

In September 1939, as reports emerged from neutral American and Italian journalists of 'fast-moving German panzer tanks destroying charges by the lumbering Polish horse calvary', the world's thumb-suckers all agreed: this war would see the Triumph of the Mobile Will over Stolid Matter.

A war of active chemical synthesis over passive biology and agriculture.

Of physics and active weather modification projects over the passive observations and avoidances of meteorology.

A war of fast tanks over slow horses; of high tech bombers and highly trained bomber crews over low tech shovels and the unskilled troops than employ them.

The weight of the Draft and Conscription would lay lightly on the population.

The mostly highly educated wouldn't even be drafted because scientists were too valuable to heft shovels overseas in some trench.

The highly skilled would either received deferments to remain in their home jobs or if drafted, would carry on their skills in the rear echelons of the war zone or would engage in combat from inside a high tech tank, plane or ship.

Only a relatively small number, the unskilled and the uneducated, the small and the thin, would end up assigned as riflemen.

They ,only, would be the ones to see an old fashioned war and to carry a backpack, a shovel and a rifle and to charge up and down hills at a trot and sleep in foxholes in the rain.

The highly scientifically educated A1s were each nation's most valuable asset - their least valuable asset was their chronically ill, medical-resource-consuming, too-sick-to-work, 4Fs.

Resources would be assigned to each, accordingly.

This would be the first fully Modern, first full Modernity, War : that would be the fundamental unity binding together the various combatant nations, despite the surface appearance of deep ideological differences.

Modernity united all combatant nations in this agreement: "There is nothing in Nature that Organized Man can not improve".

Natural Philosophy and active alternation would triumph completely , at long last, over passive Natural History and observation/ avoidance.

It was a time for Big Military Budgets , but relatively small military forces.

A time for Big Governments, Big Foundations, Big Businesses, Big Science.

The God of Modernity, all the thumb-suckers agreed, was on the side of the Big Battalions.

The stage was set so let the drama begin !

But entering Stage Left ,as unobserved as any airborne spore , came :

 'the Little Guy from Chrysogenum' ...

Monday, September 20, 2010

"Howard Florey stole the true story of wartime penicillin - we're here to steal it back !"

People ask what is the purpose of this blog/book "MO goes PO".

Here it is:

America - and Britain - and a whole lot of other countries made wartime penicillin.

No one stole penicillin (a natural product and hence already in the Public Domain) from anyone else - this was thanks to the pre-war legacy of Alexander Fleming freely spreading his unique strain of penicillium spores world wide.

It is true some  - in America - tried to control penicillin by sharing publicly-funded highly productive strains with only themselves and their pals - thankfully that scheme failed to do more than needlessly delay wartime penicillin's wide introduction.

On the other hand, Howard Florey and his post war supporters (many of whom are American) successfully and seemingly permanently 'stole' the true story of wartime penicillin away from America.

There was about nothing as petty as fighting over mere billions in dollars of profits.

This was the world's best known and best loved - and simply 'the best' - medical cure ever.

So it mattered muchly, which individuals, institutions and nations got the bulk of the glory for bringing it forth for All Humanity to enjoy.

This is was a battle over who controlled the Narrative and the Brand of the world's greatest Miracle.

Britain may have lost an Empire and its position as a World Power - but it clung onto penicillin-the-narrative.

All that America got was credit for the Manhattan Project and giving us the terror of Atomic Death to All Humanity.

Hardly a fair exchange.

I merely wish to suggest that the tiny "Manhattan Pilot" project had a very much bigger impact in the popular discovery of - and hence the immediate mass development of - wartime penicillin then it has been given credit for in the Florey-dominated story of wartime penicillin.

So  - and to recall Bono's memorable phrase in Rattle and Hum -
"we're here to steal it back !"

"Trust only CHROMELLA Brand Penicillin, manufactured in his Oxfordshire factory by Joseph Florey, Junior"

Howard Florey is famous for dismissing outright any idea that he might patent penicillin, or at least patent his extraction process.

Of course he dismissed the idea - he was Joseph Florey's son, and his family were no idiots in matters concerning Trade Patents, Trade Secrets and Trade Marks ---- far, far, far from it.

It had been the entire basis of the considerable Florey family fortune.

And when his father Joseph's industrial empire all came down around the Florey family, it was because the value of the father's most important asset, the reputation for quality engendered in customers' minds when they saw or heard the term Chromella Brand Leather, had been allowed to be be destroyed by Mr Florey, senior.

It was a lesson, Mr Florey, junior never forgot.

The well spring of the entire wartime penicillin saga lies in the murky business practises of the Anglo Saxon businessman in the Edwardian era , when firms were merged holus-bolus by wily operators and their stocks watered as frequently as one's own garden.

Jospeh Florey got very rich very quickly, probably by using the exact same unsavory practises that Max Aitken (Lord Beaverbrook) used to get very rich very quickly at exactly the same time in Halifax and Montreal Canada.

Henry Dawson also knew, at fairly first hand , about fluffed up industrial empires that grew quickly and collapsed like a house of cards.

His mother's cousin - and possibly her own banker-brother - had rapidly created a far flung lumber empire, based on borrowing a lot of a bank's money without normal collateral.

The failure never went public, though all the family knew, and the cousin lived a fraudulent life , very publicly pretending to still own and run the biggest lumber empire in Atlantic Canada, while actually the bank was quietly selling it all off in pieces, trying to recover its losses.

The discovery of anything pre-existing and natural like penicillin or of water or air or sunshine can't be patented - it is inherently PD - in the Public Domain for all to enjoy.

Patenting processes to extract or purify it are possible and were frequently employed.

But the true basis of the economic value (if any) of these patents would not lie in what was written on the patent documents.

No, if you paid the patent royalties faithfully and seemed (a) to be trustworthy and (b) a distantly located competitor, then their real value to someone with a license, was the Trade Secrets the patent-holder would tell you directly by sending over highly skilled employees to train your staff.

Pfizer was not alone in dismissing the worth of costly and hard-to-defend, short-lived Trade patents, preferring keep their complicated and subtle production methods top secret -Trade Secrets - for ever and ever.

There was a third route - the route the two Florey's ultimately took :
Trade Marks, "Branding".

Joseph Florey in his advertising said, in effect, "Everyone knows that the shoes I make are very well made and that they are called Chromella - to be sure the shoes you buy really are well made by seeking out that mark of my work."

He then threw the full weight of the law on anyone who dared to use his mark.

When Howard Florey was only one year old, for example, Joseph Florey brought a competitor ,The Hunter Boot Company, before the Supreme Court in Adelaide,seeking an injunction and 1000 pounds in damages, for inserting Chromella in one of their newspaper ads.

The judge dismissed the case - with all costs to be paid by Florey, finding the insertion an accidental error.

He still probably counted the case a victory though - it had put the Hunter Company to considerable bother defending themselves and no doubt many still felt that the insertion hadn't been a 'accident' in reality - so its reputation never did totally recover.

Any future competitor who was tempted to use the Chromella brand on their boots no doubt noted that Florey would be onto them like an attack dog.

The price wasn't worth the pain.

This is the style of doing business Howard Florey grew up with and this is how he made his fame and fortune when Ernst Chain dropped penicillin in his lap in March 1940.

Florey liked money very well, thank you very much - as did his wive, they obsessed about it in fact.

But it was not vast fortunes they sought,  for they could be here today and gone tomorrow, but the lifetime security of a upper middle class professional's salary and pension.

Scientific fame for Howard would bring those kind of professional positions - and it would restore the lost reputation of the Florey family - destroyed throughout Australia by media reports of angry shareholder meetings alleging something was fishy with Joseph Florey's shoe empire.

So first he went the Trade secret route, keeping all information about his extraction methods secret for a year and half, (March 1940-August 1941) despite Britain desperately needing all the
medical help it could get, in those terrible days of the Battle of Britain.

Entirely typical of Florey though - he had avoided WWI's trenches and he wasn't about to do anything extraordinary or risky in WWII either.

He was trying to get one of the drug companies in Britain to commit contractually to his extraction process, not for money directly of course (after all it was Heatley who had actually fine-tuned it, not Florey, by using well known standard chemical techniques suggested to Heatley by others.)

No, Florey would settle for a consultant's role - at a hefty consulting fee of course - that was the honorable way professionals got very rich without violating professional codes of ethics.

Chemically, there was no doubt that his extraction system worked.

But economically - always the weak spot in academic Oxford (see Ivory, Towers, and 'out of it') - it was a bomb, a disaster.

No firm could see it paying, but most - because it was wartime - still offered to voluntarily help improve the process enough to try and get enough penicillin for definitive human clinical trials.

Florey was resigned to this until March 1941 - after all his team had shifted to all out efforts to synthesize penicillin rather than do anymore than the two human cases he had attempted so far.

Then in that March of 1941, he got his own bombshell (Oxford itself was NEVER bombed , not even once) - word of the work of Dawson in New York.

Dawson too had his own penicillin factory - even bigger than Florey's and Dawson had won the race to be the first to put penicillin into a patient by needle - and he had gone public about it, in a public lecture, in February 1941.

He also had treated more patients while focusing on a very well known and very well feared disease - Juvenis Interruptus (Rheumatic Heart Disease) - something that was very media-worthy.

Dawson too had a German Jewish biochemist with a lot bigger
reputation than Chain - in fact this man, Karl Meyer, had long standing contractual links with the American branch of a very famous international drug firm from Germany - Schering Corporation.

Dawson's team might well have beaten him on both patents and trade secrets already.

Florey panicked - ditched his erstwhile British drug company supporters - speeding off to battle Dawson on the grounds his family was most comfortable with - Trade Marks.

His ace in the hole was the unnatural respect every democratic American had for anything British and aristocratic - like the Oxford University Brand.

This brand was a winner world wide, in many areas of education - Oxford textbooks taught one the best way, the only way, to speak English or play music.

Only the Oxford  strain of penicillium, combined with the Oxford standard sample of purified penicillin and the Oxford method assay, was real penicillin , said Florey over and over, all through America.

This was total scientific hogwash but the Floreys hadn't climbed to the top of the Spencerian world of Survival of the Fittest by being concerned with niceties.

Off to battle !

Juvenis Interruptus more accurate for RHD ?

Someone ,who admits they are not a Latin scholar, wondered about my use of Juvenis Rumpo to describe RHD (Rheumatic Heart Disease.)

They thought Juvenis Interruptus seemed a more likely term, based on the much better known phrase coitus interruptus.

They may be right.

About four years ago,I had been reading an account of  some
notable early Rheumatic heart Disease (RHD) cases of a doctor who had specialized in that very serious and widespread disease.

He had mentioned RHD was also sometimes called "-------" (a New Latin medical term) which could be translated as Youth Interrupted in English.

I remembered his explanation why this little known term was so appropriate , but not his name or the actual Latin phrase.

I merely tried to translate the English term back into Latin, using a half dozen translation engines to get a consensus.

All used Rumpo ---- but I was concerned that when I back-translated the term back yet again into English - it came out  a youth torn into two (!)

Technically accurate, I suppose, to describe the break in youthful activities engendered when your loving parents learned you have had permanent damage to your heart caused by a bout of acute Rheumatic Fever, (RF) and that you must not tax your heart.

My brother, for example, had RF when he was four
and years later,when he was 20, a doctor examining him before he ran in a race, noticed he had a heart murmur.

 This was something his parents had not known, so he had not been overly-protected : his youth was not interrupted.

But in English, Rumpo is an unknown Latin term, while Interruptus is in fact a very frequently used term to create cod-latin phrases.

In any case, I will be glad to hear comments from people more familiar with Medical New Latin than me...

Saturday, September 18, 2010

"JUVENIS RUMPO" : curing RHD, Rheumatic Heart Disease

Another name for Rheumatic Heart Disease, which until the 1950s was our biggest single heart disease, is JUVENIS RUMPO , which can be loosely translated as "Youth ,Interrupted" .

Every mother ,between the 1910s to the 1960s, had to worry about about whether her children would have to endure the consequences of a severe case of acute rheumatic fever.

Some kids got lots of bouts of strep throat but never got rheumatic fever (RF) - others got it so gently that after the fever, sore joints or jumbled nervous system had gone, they had no reminders - and the disease never came back.

Other children got the disease - once - and  quickly died . End of story, almost.

Because if one child got it bad enough to die of it, it certainly meant your remaining children might also have the slight but definite genetic affinity for RF.

Similarly, even moms who had one child with a gentle case knew this didn't mean others in the family couldn't get the worse case possible.

And the fact that 4 kids of five didn't get RF ever, didn't mean number five child won't get it bad.

It was the uncertainty as to who and when , and how badly, and how frequently, someone in your family could get RF that made it a Sword of Damocles to all moms in that era.

Stage two worries were almost as bad.

Your child or children did get acute RF and didn't die.

Unfortunately, surviving one attack did not give immunity as it does in most diseases - in fact it means you are likely to get it again but even more intensely.

Get it again and again, each worse than before and you are certain to die.

That's death by acute RF.

More likely by the 1930s, was that you would survive even repeated bouts of acute RF.

But the permanent scars left on your heart muscle and heart valves meant that your mom would fret that if you played sports or did anything too vigorously - including romantic engagements.

It was felt that sexual intercourse might--- and pregnancy and child birth definitely would --- tax your heart murmur and bring on SBE (endocarditis) and death.

So ironically, Mom would take all the joys of youth out of your life in a loving attempt to bring you to adulthood alive.

But why bother if everything a young person liked to do, wanted to do, needed to do, was forbidden ?

This is why RHD was so frequently called Juvenis Rumpo .

 Not because RHD killed outright all the young people it effected - it never did kill more than a relatively small number - but because of the huge pall it hung over  the 'best years of their lives' for tens of millions of North American teenagers between 1910 and 1960 .

Fear of the Sword of Damocles was more damaging than the actual possibility it would really fall on a vital spot.

Dawson never did get to enjoy his youth times because he
volunteered to serve in the trenches of WWI.

His life mission was to see that as many other young people as possible did not see their youth be interrupted.....

Saturday, September 11, 2010

the moldS in Dr Fleming's letterS

A jab - I admit - at Eric Lax's famous book title, "The Mold in Dr Florey's Coat".

Florey and his team are usually applauded for their
"selflessness" in rubbing brown penicillin liquid/powder/spores (accounts vary in the endless re-tellings) into the seams of their clothing in May 1940.

 Their supposed intention was to ensure that precious penicillin could go out into the world to grow anew and save lives everywhere, even if the beastly Nazis did succeed in conquering Britain and the spires of Oxford.

"There will always be an England ...and England's precious gift, to Humanity, Penicillin". Etc.

But what if a single bomb had destroyed their Dunn Pathology Building, killing all the entire team and all their moldy coats?

Or if the Germans invaded Britain as fast as they had overrun the rest of Europe, so that no one from the Florey team got away to what remained of the Free World?

Was there an alternative to these theatrics?

Yes there was.

Three in fact.

(1) Do what Fleming had already done for 12 years and would continue to do - sprinkle a few of his spores into a folded paper as part of an ordinary unremarked-upon letter and mail it to anyone in the world, without charge, upon request.

But because there was an invasion coming, don't just wait for requests - mail out your version of Fleming's spores to all your friends and acquaintances ----- and ask them to store them and hide those precious spores.

 Or better yet, mail them Fleming's spores, together with what you have learned so far as how to extract , semi-purify and store dry penicillin and urge them to start their own research efforts based around that work.

(2) A bit late now, but if Florey did really think that Fleming missed the boat back in 1928 by not doing the "animal protection test" why didn't Florey do it in himself in 1929, when he received the manuscript of Fleming's first paper, as an editor of the journal that paper was submitted to?

Or in 1931, when one of his subordinates at Sheffield , Dr Cecil Paine, told him of his success in external applications of liquid penicillin in curing real diseases of human patients.

Why did Florey not immediately follow this up, by seeing if liquid penicillin would work as well in curing artificial internal  diseases in lab mice by way of a needle (ie internal application), aka "the animal protection test" ?

Or why did Florey not 'do the mouse' back in 1938, when he first began his research on penicillin  -- if it was that apparent that the vital "animal protection test" had been overlooked?

Any of these times would have revealed the power of penicillin as a internal, systemic, cure - ie as the first,best, modern antibiotic, rather than just another also-ran in the overcrowded and ineffective external antiseptic market.

But in 1929,1931 or in 1938, Britain and the world would have had the peacetime resources to quickly bring penicillin to market.

But waiting two years, till the Fall of France, to 'do the mouse' and only doing it because your subordinate, Chain, jumped the gun in a fit of pique hardly shows you were concerned about the fate of a unique life-saving drug.

(3) While retelling the tale of the spores rubbed into your clothing, admit it happened because only you were (inaccurately) convinced that your team were the only scientists in the world with (a) access to these unique penicillin-producing penicillium spores and (b) had found a method of extracting and preserving dry penicillin.

This is why you kept your new penicillin success a secret, even from your prime funder, the MRC, and why you also didn't tell the scientific world of your extraction method in your August 1940 paper in Lancet.

And why as late as March-April 1941, you weren't telling any outsiders the details about your extraction methods --- not even to your many friends and colleagues overseas.

And why you only revealed your extraction methods in August 1941, after it appeared that a competitor in America had already released his own methods of extraction back in February 1941.

If Britain was About to Fall and All  Civilization About to Totter, these hardly sound like the actions of a selfless individual.

But they do sound  exactly like the lifelong characteristics of one Howard Florey - from ruthless 'take-no-prisoner' teenage tennis competitor to adult scientific 'bushwhacker'.

This is why the lazy, laidback Fleming almost got the only Nobel prize to be awarded for penicillin, instead of it going to the hardworking, ambitious, Florey and his hard-driving team.

You see ,the world had just been through the most brutal war it had ever seen, a war created by a hardworking, ambitious individual.

 So, yes, Fleming might well have been lazy on following up on penicillin - he freely admitted as much.

But lazy Fleming had also never denied anyone his unique spores - or sought any payment or even reminded them that he be mentioned in their scientific publications.

(It is worth recalling that until late 1945, those same 'Fleming Spore, albeit a little subcultured and subselected, were still supplying the world all of its therapeutic penicillin--- the many efforts to find better spores and make them workable had failed up until that date.)

And Fleming had never denied anyone his methods he himself had used to extract and preserve penicillin.

That is why he got - and deserved to get - the Nobel Prize for penicillin.

I,then, am also a partisan of Fleming's worth, like Milton Wainwright and Kevin Brown ---- up to a point.

I'd take his freewill "spores in a letter", in a New York instant, over Florey's secretive "spores in a coat", any day.....

Thursday, September 9, 2010

1941-1950: Friedberg revises SBE deathwatch

In 1950 Dr Charles Friedberg told the readers of JAMA, one of the world's leading medical journals for frontline doctors, not to forget that SBE was now the easiest of the common heart diseases to cure.

They listened.

 Friedberg had quite literally wrote the book on SBE, back in 1941.

The, ahem, old book on SBE.

In that 1941 book, Friedberg and chief co-author Emanuel Libman had carefully surveyed 1200 cases of SBE in detail and said 'no cures' - at least no cures by the efforts of doctors.

 However three percent might expect a spontaneous cure.

Until the next and the next attack -  for SBE was a repeater disease and so really inevitably fatal - over the short medium term period.

Another researcher at the time was even less hopeful - finding  out of 249 of his SBE patients, maybe one had a temporary cure.

But now in 1950,Friedberg's 'invariable fatal SBE' had become Friedberg's 'the most curable common heart disease' !

The reason for this amazing turn about, Dr Martin Henry Dawson, had died a little earlier, back in April 1945.

But these amazing 1950 conclusions were due to his pioneering 1940-1945 efforts to prove up penicillin as an anti-biofilmic agent , able to penetrate SBE vegetations and kill the bacteria without killing the patient.

It was a mission carried on and brought to a spectacular conclusion by his assistant Thomas H Hunter, after the war.

DOCTOR MOM  now had one Sword of Damocles removed from over her head --- thanks to a doctor from Columbia University.

Just in time too.

Because another doctor from Columbia university, Harold Urey, PhD, had just given her a new Sword of Damocles.

During World War II, in one part of Columbia,
the former Lt Dawson,(winner of the Military Cross with Citation),was busy(illegally) curing "4F" SBE patients.

 Meanwhile, in another part of Columbia, Urey-The-Pacifist, with his crew of war-exempt healthy, young "1A" scientists, was busy inventing the Cold War's most fearsome weapon: the gaseous diffusion process for the extraction of uranium for the mass production of nuclear weapons.

As a result, 1950s kids, of which I was one, were the healthiest and the most scared generation of kids ever raised.

Thank you, Columbia.....

Tuesday, September 7, 2010

Why I claim Warren Weaver was 'naive' over penicillin

Some have objected that Warren Weaver,long time chief of the Rockefeller Foundation Natural Sciences Division was one of the most astute men in American science.

I say he was a math teacher, placed in charge of allocating millions in grants devoted to discerning the 'deepest secrets of biology' and what he did not know about the basics of biology and medicine would fill a library.

In particular, can you see the people in the medical side of the Rockefeller Foundation buying the Florey and Chain claim of 1939 that penicillin was an enzyme (ie a foreign proteinand yet, once purified ,it could be safely injected into a vein as a systemic medicine?

Aren't we also always told that Fleming's penicillin was too
unsafe to inject as a systemic medicine?

This because the mold was grown in a foreign protein medium and so was too deadly to inject into humans.

Though Fleming ,in fact, showed that neither penicillin juice or the medium juice seemed to affect mice when injected into them.

Weaver knew next to nothing medical, but he loved a good line.

The line he always loved best was that chemists, physicists and mathematicians  and other hard science types would quickly clear out the soft descriptive clinical types holding up true medical progress.

So he gave Florey and Chain all they asked for.... and more.

A good thing really - because Florey would never have given penicillin a moment's notice, if he hadn't a nice grant to do so.....

Mae Smith ; the real life DOCTOR MOM that gave us penicillin

Readers sometimes asked me if DOCTOR MOM was a real person.

I usually say "No, Dawson was trying to reach all the Doctor Moms in America , via his success in preventing all the deaths and all the worries caused by childhood Rheumatic Fever."

But I have reflected and maybe my readers are right - yes, there was was one specific Doctor Mom that Dawson reached - perhaps, indeed, only one that he reached.

But one can be more than enough.

Her real name was Mae Smith, though she is sometimes known as Mrs John l Smith or ,more accurately, as Mary Louise Smith.

MAE SMITH in 1954
Her husband owned 25% of the Brooklyn Dodgers baseball team and after his death, she held those shares.

More books have been written on these , the original "Boys of Summer", than any other team.

Many people seem to rate the day the team left Brooklyn as more significant in the decline of America than Watergate or Viet Nam.

The other Mary Louise Smith is also very important in this story : she was the Smiths' daughter.

John L grew up in a small seaport in Connecticut and he loved to sail more than almost anything and he loved his cottage in his old home town.

One day when the family was out in the cottage, far from big cities and big city high tech hospitals, young Mary Louise said she had a stiff neck. And a headache. And a fever. And that in fact, she generally wasn't feeling very good indeed.

That put her family in a real panic.

Not as much as it did the local doctors - it was obviously Spinal Meningitis - still a deadly, every-minute-counts-disease even today with antibiotics.

By the time they got her to a big hospital, it was too late to even stabilize her - though surviving a late case of spinal meningitis can be a very mixed blessing - it often leaves you physically and mentally challenged.

An immediate (and I mean like yesterday) massive needle full of Penicillin was the best cure then , as it still is today.

Penicillin had been discovered at the time of Mary Louise II's death, but had not yet been produced, let alone mass produced.

In 1941 and 1942 and in 1943, as Dawson always naggingly reminded any and all visitors from John L.'s firm, it still was not being mass produced.

"But if it had been developed back then and if it was a staple in the black bag of even the smallest backwoods doctor, Mary Louise would be alive today."

"How many more Mary Louises would have to die needlessly before the world got enough penicillin to make a difference?"

And on and on.

John L had heard this all too many times before - he felt that Dawson simply didn't understand the technical and economic issues that prevented his firm from taking the plunge.

"What risk ", said Dawson , "are you not planning to take the company public, and to do a stock split?  This war has made you guys even richer - give something back to the fighting man - and the fighting woman."

I bet John L would go home at night, get a stiff drink and unwind at his wife, all about what a nag that Henry Dawson was -- "why he even said this and he dared say that."

I don't think John L bought Dawson's line.

But to her credit, I think Mrs John L eventually did.

I bet, late at night, just when John L was trying to get some shuteye , she would softly bring up the question of 'why couldn't the firm take a little risk for once, do something extra for the war effort?'

I think it must have rubbed off eventually, because if his firm was cautious, John L was even more so.

But between late August 1943 till March 1944, that 'stiff little man' was like a man possessed, so determined was he to get a big new, NATURAL, penicillin plant on line as soon as possible.

(This was just at the very time that the Florey team at Oxford University were semi-secretly announcing that they had totally synthesised penicillin chemically and that to continue to rely on natural production by the mold was a 'retrograde' step - so John L was betting against the received opinion.)

But they went ahead anyway: shifts of crews building around the clock, lit by Klieg Lights and posters everywhere reminding employees that this was a "Race Against Death."

 "The quicker this building is done, the quicker penicillin can go out to the wounded boys at the front."

It paid off  because by D-Day Pfizer, his firm, was producing most of the world's penicillin---and the company has never looked back.

We never did get any of that wonderful 'Refined Penicillin' out of the chappies at Oxford - but 'Brooklyn Crude' pulled us through the war anyway.

And I like to think a lot of the credit for starting Pfizer on the road to becoming the world's biggest company should go to a quiet but persistent push from  "Doc" Mae Smith.....

DEMAND SIDE penicillin versus SUPPLY SIDE penicillin

Long ago, it was realized that a University Registrar could often be a high school teacher's best friend.

If, for example in Canada, the Registrar at a big provincial university like the University of Toronto held firm that no one would be admitted to any science undergraduate course without a suitable pass in German, then school board administrators all across the biggest Canadian province of Ontario would dig deeper to pay for properly qualified German language instructors.

Most other provinces, in turn, bowed down to Ontario's greater wisdom and followed suit.

 And even the kids,learning from negative feedback from older siblings and friends who failed to get into university because of poor German, knuckled down and learned the language.

But if the university regulations required German but the Registrar frequently ignored it, then a different sort of feedback got back to school boards, teachers , pupils and parents.

Dawson recognized this as a sort of Demand Side Economics: making penicillin ,like learning university science level German, was bloody difficult, and given any choice, drug companies , like high school kids everywhere, would much rather do something, anything, easier.

But if the paying customers was screaming, money in fist, demanding penicillin and willing to turn to anyone who had it --- even the most stubborn of old school drug firm chemist would reluctantly knuckle down and learn the new skills required - or face the alternative of the unemployment lines.

Dawson focussed on the ultimate customer - the Doctor Mom and offered her a solution to her number one fear in 1940 - Rheumatic Fever.

If he could only publicize his hopes and successes with natural (ie unpatentable) penicillin to her, the public, her demand would push the drug firms to learn that difficult art of growing natural penicillin  in massive quantities.

Members of the public yelling to doctors and druggists and government bureaucrats and the professionals and scientists yelling back is sooooo undignified, so Italian family at suppertime, so Operatic.

But it works and it works quickly - if not quietly.

Florey and his supporters took the exact opposite tack: Supply Side Economics.

"Don't, For God's Sake,tell the public we have had success with patients treated with penicillin - they'll only ask for it for their dying brood- and we haven't yet fully tested it in every imaginable disease and clinical situation."

" We haven't learned its full structure and particular molecular shape and so we haven't yet synthesized it."

"Keep everything secret until we can surprised a delighted and grateful public with fully determined, fully formed, fully patented-up-the-jing-yang artificial penicillin at their local drug store."

This would be the much slower, but much dignified, route - the professionals would appear fully professional - an act they can pull off fairly well, given enough time and money.

The public and the media would appear so supplicant and so grateful to the wonders of science - an act they too had learned very well.

So in 1943-1944, which side won; which form of economics worked the best ???

My ebook, MO goes PO, out October 16th, will tell which side actually got us the D-Day penicillin and which side was nothing but talk....

Monday, September 6, 2010


You remember all those wartime movies that tried to build a sense of unity within diversity , both among Americans and among Americans and their erstwhile Allies?

The platoon had to have a WASP for the Captain, but the rest of the enlisted men and Non-Coms were a bundle of ethnic and regional stereotypes.

The tough Sergeant  from Tennessee or Texas, the scared kid from somewhere in the milk-fed Mid West,the weedy smart Jewish kid, the Italian aleck from Brooklyn with an accent you could cut with a knife , sorry NOI-IF.

If our multi-ethnic infantry platoon meet anyone from the British army, all the British enlisted men men were short and stubby and talked in a broad sort of Cockney that you only really meet at the discharge door at Wormwood Scrubs - or on a theatre stage.

The officers were all tall and thin and talked in a plummy voice  redolent of Oxbridge or Whitehall.

It must have been something like that the day that John L first met Sir Howard Florey,FRS and offered to take him to see the Dodgers play.

This after Florey had spent an uncomfortable hour with Gladys Hobby watching the natural penicillin vials tumble off the Pfizer production line faster than an Oxford chemist could change their final, final formulation for their synthetic penicillin molecule.

Alec Fleming would have been delighted - Florey would just have turned stiffer than normal and said he had another urgent war-related engagement elsewhere and then would have gone off to the nearest washroom to change the pickle up his ass.

The duel between Brooklyn and Oxford was not just a difference of penicillin science between artificial chemistry and natural biology.

It has also a battle between two types of social classes and cultures - Brooklyn crude and Oxford refined.....

Milton Wainwright's thesis on whining Oxford postdocs

Mea Culpa.

I admit it, I originally dissed Dr Wainwright's theory that much of the anti-Fleming abuse really came from a small group of Florey's Oxford post-docs, unable to accept that the world did not rise and set in Oxford.

But I have changed.

As I followed the letters of  Florey and Heatley vetching for four years that all penicillin - to be worthy of the name penicillin - must measure up to the OXFORD STANDARD, my Canadian hackles rose.

My grandmother came from the suburbs of Manchester Lancashire and my granddad from Petley Bridge in Yorkshire -- they never spoke OXFORD ENGLISH and they promptly moved to a country where that sort of nonsense never mattered.

To read Florey telling A.N. Richards to keep secret any differences between Oxford and American penicillin - as if strep bacteria cared a toss - is to see a citizen of a nation who has lost the financial war  still acting like they ruled the world, that George Washington had never won, and that they could still lay down the rules on how everyone was to speak and assay penicillin.

Read Milton Wainwright , particularly on Fleming - he says a lot of interesting things and raises a lot of interesting points...

Why HEATLEY rather than Fletcher,Chain or Jennings ?

The attempt to make Oxford penicillin the "Received Pronunciation" of world penicillin....

OXFORD :"First we take Manhattan, then we take Berlin, Paris and Cape Town..."

Fletcher could have accompanied Florey to America to remind Americans that Britons had also ,me-too, used penicillin to treat patients... after Dawson did it first in America.

Chain could be there, to say penicillin was his idea and that Florey only got interested after it got promising - and to admit, yes, his own chemical work was not yet as advanced as Meyer and the Schering Corp was in America.

Jennings could have gone along to say that Britain did the first animal protection test (which Fleming didn't do) but that, yes, Dawson did the first human protection test, in America.

But Heatley-the-invisible, he'd never steal any glory from Florey.

And he was the assay man - the man who would act like the schoolmaster he looked like - checking every American firms' penicillin sample to measure it against the Oxford Standard, and docking marks for any firm that failed to measure up.

For just as nobody anywhere else spoke as good an English as OXFORD ENGLISH , so too nobody's penicillin would ever quite measure up to to the Oxford Standard, the Received Pronunciation  of penicillin, the only penicillin you could prescribe on the BBC or give to the King.

Two points: (1) the supposed standard, OXFORD PENICILLIN, was actually composed of 98% rubbish - and don't get me started about Oxford in general.

(2) There were in fact many many strains of penicillium producing many many different types of penicillin, depending on what they had to eat and how acidic their surroundings were etc. This is Reality at ground zero. But Florey spent the next 4 years denying and downplaying any existence of differences in types of penicillin.

His only chance at grasping the golden ring was to constantly maintain his claim that he was the first to purify penicillin - he couldn't have this claim disputed by people asking which of the twenty variants of penicillin did he ,ahem, first 'purify' exactly ?!

I don't know if Florey played chess - but he had the chess player's skill of always thinking six moves ahead of anyone he thought might possibly be his opponent as he clawed his way to the top of English Society.

And when he was a Baron and president of the Royal Society, you'd never guess he had been born in the Outback - his English was now far more RP than his penicillin ever became....

Thanks to DOCTOR MOM, "he (and she) will be coming home!"

Most wartime GIs who drank too much Schenley whiskey and ran their jeeps off the road and woke up in the hospital with a penicillin drip in their arm, never realized that not only did Schenley sell them the bite of a snake but they also sold them the cure.

That wartime penicillin might have come from Schenley Labs.

Their whiskey is still here  - but their penicillin is long gone.

But Schenley did have the satisfaction for having produced the most iconic image of the entire saga of early penicillin.

Printed in rich vivid glossy magazine color, this ad featured the realistic style painting of a medic putting penicillin in the arm of a wounded Marine in a place that looks to be Tawara, as photographed by Marine photographer Norman Hatch.

 Seventy years later, Hatch's photos remain the gold standard of 'you are there' combat photography.

This famous island battle first brought home to America just how bloody this war was going to be - particularly because of the casualty count.

 But mostly because Hatch's grim photographs were deliberately released, rather than censored, to toughen up Americans at home to the mounting death toll that lay ahead.

So the ad's painting immediately conjured up a grim backdrop to any magazine readers in 1943-1945.

But the cutline below was pure uplift : "Thanks to PENICILLIN...
he will come home !"

Often rendered in the retelling as "Thanks to Penicillin, he will be coming home !"

The combination of image and cutline basically assures home viewers worried about their relative overseas that "Despite the vicious fighting and the terrible jungle conditions, thanks to penicillin, he WILL be coming home !"

This ad went totally unremarked upon during the war.

 But in the 65 years since, it has grown by leaps and bounds in importance as almost every scholar today finds it to be the best single wartime expression of the sheer hope that grew in a world (bone tired of 15 years of Depression and War) that something good must lie ahead.

Usually, their subtext when recalling this ad is "Thanks to Big Science bringing us Penicillin, he will be coming home !"

I don't think this is true at all.

I believe that if left to their own devices (along with scads of our tax dollars) it would have been 1946 or later before enough penicillin would had been produced to help the soldier at the front , let alone the patient back home.

I think there were two competing strategies to speed up the production of wartime penicillin.

One was develop scientific evidence on a very wide and deep front ("Big Science") to convince scientists in universities, hospitals, corporate research labs and in bureaucratic offices that a small shift in international wartime priorities was justified to produce large amounts of penicillin as a supplement to the sulfa drugs for illnesses resistant to sulfa like those caused by staph bacteria.

But that only enough penicillin needed to be produced to aid the fighting men, at least until the war was finally won.

I hope you sense the contrast between a massive effort of "means" to secure a limited "end".

This was Howard Florey and his supporters' thesis.

The other strategy was proposed by just one man - a soon-to-be dying man - in  September 1940 and maintained by him until his death in April 1945.

Martin Henry Dawson.

He said penicillin had already been privately discovered, in 1928 by Fleming, but no one had been roused and no lives had been saved.

Penicillin had also been publicly discovered,( ie published in the scientific media) in 1929 by Fleming and again in 1940 by Florey but no one had really been roused and no lives had been saved.

Dawson proposed instead to have penicillin popularly discovered - by Doctor Mom.

It was a Man's World back in 1940 .

(It mostly still is, but not as bad as back then !)

But even in 1940 women voted, bought much of the family's purchases and they were the daughters, mothers, sisters and spouses of the prominent men who ultimately ran things.

If they got on the case of the men to bring them penicillin and they stayed on the case (as women are very good at doing - some dare call it 'persistent nagging') , even reluctant men will eventually give in and get moving.

So Dawson persuaded Meyer and Hobby and Chaffee, his entire team of 'little science', to refocus their primary aim of their newborn penicillin pilot project.

He said they should immediately and narrowly focus on curing  a single disease, Rheumatic Fever-induced Subacute Bacterial Endocarditis.

This disease was the one that all parents in the western world regarded as a constant Sword of Damocles over their heads ,at least until all their children had gotten safely into their early twenties.

Tuberculous might be the disease feared more by the poorest families and Diphtheria and Scarlet Fever  might have been feared more in grandma's day, but from about 1910 to 1960, Rheumatic Fever (RF) was the number one killer of school age kids .

In addition, the invariably fatal subacute bacterial endocarditis (SBE) it brought to many Rheumatic Fever 'survivors' was a big killer of youth and adults all along life's journey.

But the main point of the myth of The Sword of Damocles was not the pain of the instant the sword actually did fall and kill you but rather that the situation made you afraid all of your life, just waiting for the day the sword might fall.

Most parents never experienced their children getting RF or SBE but all dreaded it might happen someday.

RF starts with a child getting a sore throat or tonsillitis from strep bacteria.

Think about it - what child doesn't get tons of those, even today with antibiotics?

Before antibiotics, the kids might cure themselves.

But one attack did not bring immunity.Your children got them again and again  - like the common cold they were common, endemic ,ubiquitous.

Always the fear was that this strep throat attack will lead to something worse. Many kinds of worse, but the deadliest and the most common was Rheumatic Fever (RF).

Most times, nothing happened. But like Russian Roulette, for no good reason one strep throat attack or tonsillitis attack could lead to RF.

Now RF could kill your child outright, during the very first attack.

But in most cases, the child lived, even emerged unharmed.

But again it did not bring immunity.

Far from it, one incident of RF made a child more vulnerable to another and more severe attack of RF and so on and so on, ever downhill.

Now suppose the child survived all those severe repeater attacks but with a damaged heart - particularly damaged heart valves.

Now in their teens, the child was less likely to see RF ever again, but instead they faced the fact that ordinarily harmless tooth bacteria, swept into their blood stream by a single vigorous tooth brushing, could settle in on their damaged heart valves and lead to an 'invariably fatal' case of SBE.

They might , nevertheless, fight off a single bout of SBE - as perhaps as many as 10 to 20% did.

(The near 100% death rate for SBE as normally reported, was biased by only counting cases sick enough to end up in hospitals. But autopsy work often revealed hints of healed SBE scars on the valves of young traffic accident victims.)

But again, and I know I am a broken record, one cure of SBE did not prevent those tooth bacteria from settling in again on your valves - and the second bout was fatal.

RF induced SBE was a chronic ,invariably fatal, disease.

Dawson treated patients as young as 10 and as old as 60. After penicillin, patients were found to dying of RF mediated SBE into their seventies - deaths often disguised as a 'stroke' .

More bad news : the kind of strep throat bacteria that gives you RF grow more virulent by being passed back and forth repeatedly between humans in close contact.

If you had lots of children,  that meant that your chances that several would get RF and SBE was higher than the statistical average, even when corrected for the number of children you had.

That is if you had six kids and a small house, their chances that one
of them would get RF should be six times 3.3 per 100,000 ( ie 1 in 5,000) but in fact it was much higher than this - more like 1 in a 1,000.

Small houses and big families being more common among poorer families, they got hit the hardest, resulting in it being called The Polio of the Poor.

But no family was really immune.

Dawson knew that a report of a cure for either RF or SBE would grab the attention of every single DOCTOR MOM in the world.

And Doctor Mom, not Dad (in charge of the bread winning), was the person in charge of the entire family's health -- if she wanted penicillin , now, she would get it - or governments (even wartime governments) would tremble.

Drug companies would rush in to take her money.

This was Dawson's thesis.

He had a small crew - four people, no government or foundation funding, with curing a single disease as its sole thrust. But against those small 'means', look at its broad 'ends'.

Doctor Mom, said Dawson, would see to it that her entire family all got lots of penicillin, now, not after the war - penicillin enough for  both Frank on the battlefield on Tarawa and for little Susie in the Rhemuatic Fever ward in America.

Was he right - or did Florey's view prevail?

I will 'tell all' - on October 16th this year - in my e-book "MO goes PO".....

Sunday, September 5, 2010

1941 penicillin:Porton Down GERM WARFARE yes, patients no

The Florey Archives at London's Royal Society has a Florey letter (HF/1/3/2/1/19 )(previously 98HF.35.1.19)  that didn't get shredded but probably was intended to be.

Dated December 4th 1941, it is addressed to Doctor "Cameron" at "Porton" and mentions scientists "Courtice" and "Gaddum".

Florey says ICI penicillin is at Porton and he is glad that Gaddum wants lots and lots of penicillin.

In December 1941, no one had much penicillin - certainly no patients in UK got any - and only Dawson's patients in the USA.

This must be some of the very first ICI penicillin ever produced - not for patients - but for 'Porton' .

One of Florey's very closest of his (very few) friends was Paul Fildes, very near the top of Britain's WWII Germ Warfare effort, which was centred at Porton Down.

That place has been for a century Britain's leading gas and germ warfare centre - in fact one of the top centres in the world for this highly secret activity.

Florey's first biographer, Bickel, indicated that in 1939, Florey had been asked by the War Office if he would be a consultant in 'poison gas research' (probably because of his proven skill in doing lethal experiments on small animals and his middle-aged chickenhawk attitude to the upcoming war.)

Florey had agreed.

I have always wonder if Florey's mystery month , mid July-mid August 1941, was somehow connected with him having informal talks on germ and gas warfare with various American researchers.

Certainly, Florey go top clearance for his trip to America from US and British officials - penicillin ,alone, seemed too unproven to warrant this kind of assistance.

Now Penicillin and Porton is like Jeckyll and Hyde to British audiences - no wonder this letter has never been mentioned in all the hagiography on penicillin and Florey.....

 GR - Gordon Roy- Cameron *
FC -Frederick Colin- Courtice *
JH -John Henry- Gaddum

* Part of Florey's power was his cultivation of a network among the sizable Aussie contingent working in the UK - these two are but a tiny part of this group. Florey also cultivated ex pat britons who had taught in Australia.

Fleming versus Dawson on Endocarditis

Hardly dueling Scots, though.

Fleming's  Cheadle Prize winning medical essay "DIAGNOSIS OF ACUTE BACTERIAL INFECTIONS" (the only time I know of that he seriously engaged the subject of endocarditis) was written in 1909 and published in the ST MARYS HOSPITAL GAZETTE (volume15 , pages 67-69,72-77).

Most biographers of Fleming felt this early essay nevertheless set out the course of his life's work - which extended for another 45 years - so it is well worth a close reading.

Dawson confounded the essay's conclusions on intravenous injections to treat endocarditis in March 1942, with his first success in reducing bacterial colonies in endocarditis patient's blood.

Critics of vaccines said endocarditis's constant shedding of small amounts of bacteria directly into the bloodstream should lead to a natural immunity against them but instead actually only led to death.

Fleming dosed himself with a staphylococcic vaccine via an intravenous injection directly into the bloodstream.

 (Staph was then a far less virulent bacteria than it is today.)

He lived, having only a slight headache and fever, but gained no increased resistance to staph.

Intravenous injections of vaccines gave maximum infectious effects and minimal increases in natural antibodies said Fleming.

Despite the fact that all of Fleming's considerable wealth came from his great skill in injecting the very dangerous drug Salvarsan directly into veins, he seemed dubious on 'systemic' or intravenous medications in general.

I think this is partially why he never tested penicillin as a systemic medicine in humans - or animals.

Not till 1940 did Dawson do so for humans and Florey for animals...

Thursday, September 2, 2010

Dawson, Florey and the multiple suppliers

Dawson first turned down Pfizer and then a month later accepted their offer of penicillin extracts, at the same time his co-worker Meyer was working with a potential competitor of Pfizer called Schering and Co, while at same time  Dawson, Meyer, Hobby and Chaffee were producing their very own penicillin !

This was not unique.

Florey produced his own penicillin and was willing to ask for penicillin from any commercial firm and got commercial supllies from at least Merck, ICI and Kimball and Bishops, the latter two on a regular basis.

Why ?

And how were conflict of interests avoided?

I believe none of the commercial firms had a problem if a doctor wished to stick their penicillin (and that of all their competitors,) into patients.

 Even if the doctor(s) first concentrated the commercial liquid
extracts up to a minimal level necessary for therapy - say to a dried state of 30-50 units per mg.

None of this would affect the commercial interests of the firms.

But it would be unfair if a doctor used commercial extracts to improve extraction processes or to do chemical synthesis work on the firms' offerings.

The firms were spending lots of money on these sorts of activities and hoped to eventually profit from it.

They won't want the doctor get to the patent office first or pass on the information on to their favorite commercial firm.

So Dawson, who cared not for the chemical synthesis of penicillin, could treat patients with Pfizer penicillin, while Meyer the chemist used his own penicillin or that of Schering to do chemical studies.

Everybody happy.

Florey did likewise - using mostly ICI penicillin on his famous second series of treatments of patients but not using any of it for chemical studies, while his own team's penicillin mostly went to the team chemists to be destroyed in chemical studies.

It hardly jibs with the heroic image of either group now does it?

I can only say that very quickly, Meyer dropped synthesis studies and shifted to chemically altering penicillin into an ester so it worked better (ie worked slooooower) inside patients.

Morally, it is hard to fault this sort of chemical work.

Oxford claimed (ala LADs' PEN) that it produced 500 litres of penicillin a week between the Fall of 1940 till May 1944.

That is 400 million units of useful, injectable penicillin, in Duhig Units.
J V (James Vincent)  DUHIG
I feel sure than Duhig's first reaction would be the same as mine: "Bull feathers".

I bet a check of the published records will show that only 4 million units of Oxford-created penicillin ended up being used for patients in that period.

(To keep things in perspective, in 2010, 4 million units - 4 MegaUnits - is what you might receive as a daily dose, for an average serious infection. But in 1942, it should be enough to treat 40 patients with life-threatening illnesses.)

Gladys Hobby, quoting a ICI report on Oxford's efforts, says in 1941 they were producing 2 grams a week at 16-32 units a mg, ie 15,000 to 30,000 units a week or a maximum of 1 to 2 million units a penicillin a year at the outside best.

I have seen an estimated figure of 13 million units produced in total between 1938 till 1944, coming - it seems - from Norman Heatley, and that seems to match this report fairly well.

Trevor I Williams, in probably the best single book on the Oxford team ,"HOWARD FLOREY", says that even in 1942, half of the final Oxford penicillin went to the chemists.

I believe all, or almost all, went to the chemists from 1943 onwards.

Doctor Mom has a right to be skeptical about the Lads....

still in widow's weeds in 1946, at a film industry meeting

Mom's penicillin versus Lads' penicillin

That's 'DOCTOR MOM' by the way, and 'LADS' as in British Lad's magazines (a weak rendering in North American terms might be "its a guy thing" - a stronger rendering would be that Connie Kaldor song about "Jerks" .)

I have tried out various names for what I am now calling Doctor Mom's penicillin: pragmatic penicillin, patients' penicillin --- all share a common drive - to save lives , now.

Lads' penicillin can also be usefully be called prestige penicillin, purified penicillin, priority penicillin, scientific paper penicillin, scientific penicillin ,scientists' penicillin.

The goal here is "who can get 100% pure, stable, colorless penicillin crystals first - dam the poor yield and dam the poor patients, forget that there is a War on."

(And by the way I almost never call it "penicillin" when I am thinking about it or even when I talk about it - I call it simply
"PEN" rather as the British chemists called their reports, the PEN reports, and just as the paper tags on patients undergoing penicillin treatment during the war were also labelled PEN.)

(Yellowcake uranium (easily mistaken for early dried penicillin powder or dried mustard) together with the wartime 'products' derived from it, were also given prominent labels with black letters and symbols on a bright mustard yellow background.)

Mom's pen is expressed in a ratio of units of penicillin actually ready for use in human patients over a period of time.

As in :"Pfizer released 500 mg of dry penicillin, (the famous Lot #696) assaying at 50 units a mg, for Dawson to use on his patients in March 2nd 1942 - a total of 25,000 units of therapeutic penicillin."

Or : "Starting in October 1941,Pfizer released to Dawson a 5 gallon carboy of non-concentrated penicillin juice every week, the juice assayed at an average of 2 units a ml, so if injected immediately into a patient in the form of a drip IV, that was 160,000 units of therapeutic penicillin a month ." 

Lads' penicillin can be found described - ad nausem - throughout almost any account about penicillin.

Its boastful vagueness stands in for the most basic of basic arithmetic.

Here is one example, picked at random from the recent book on early penicillin:

We are told that the Royal Navy set up a 'small' production unit in 1942. Even if you follow the penicillin saga closely, this might be the first time you have read of this effort - it must have been small potatoes.

Apparently not so, for in the very next sentence we are told their weekly production was 200 million units.

To put this in context, Pfizer - the world's largest drug firm and a company you have heard of , said it produced 400,000 units of penicillin in March 1942.

(If you have a good memory, you will recall that not all of this ended up in patients' veins - Dawson seems to have only got 25,000 units and he was Pfizer's only clinician at this point.

 Most of this semi-purified dry penicillin was probably destroyed by Pfizer chemists trying to degrade it enough to guess at the building blocks of its assembly by the penicillium.)

In early 1943, it took two months for the entire American pharameutical industry to produce as much penicillin as the Royal Navy's little operation at Clevedon produced in a week.

Count me more skeptical of this story than Robert Bud is.

Another example, from Macfarlane's biography of Howard Florey.

It is the claim that production at Oxford had been 500 litres a week for a few months by January 1941.

Wednesday, September 1, 2010

Meyer to Durack: I started penicillin to get back at Chain

In 1981 Harcourt Brace Jovanovich published "Treatment of Infective Endocarditis" ,edited by Alan L Bisno.

You can read it on the stacks at your closest medical school library.

I suppose the most cited article is the first, a "Review of  Early Experiences in Treatment of Bacterial Endocarditis, 1940-1955", by David T Durack, M.B., D Phil.

 I first read it very early in 2005.

Durack is from Australia, came to Oxford as a Rhodes Scholar, and was soon regarded as one of the best young doctors around anywhere.

He did a very through review of his chosen subject, reading through the early articles closely.

 Quickly he saw something in Dawson's and Hunter's first article on SBE patients treated by penicillin that others writing about penicillin or endocarditis hadn't fully sensed .

The disease of endocarditis was in fact the very first disease to ever be treated by an antibiotic, in the modern sense of that word.

(And even perhaps cured by an antibiotic, if you want to go out on a limb - others have - but I hesitate.)

(In any case, an event that happened on October 16th 1940 - an anniversary seventy years old this year - hence my urgency in trying to finish this book as soon as I can.)

An antibiotic in the modern or common sense meaning of that word is a medication produced by microbes that is taken internally and that can save lives.

(By contrast, antiseptics are often man-made chemicals and are applied externally and are intended as a band-aid solutions for minor cuts and bruises.)

To doctors, this means an antibiotic is a systemic medication and in the case of the original penicillin (aka Penicillin G), one administrated by needle - ie parenterally.

All this fully met by Dawson's first needle of penicillin stuck into a dying patient seventy years ago next month.

Durack managed to personally contact the three key surviving members of Dawson's team and I feel he must have asked some very probing questions.

Hunter and Hobby added interesting tidbits to the historical record, but Karl Meyer dropped the biggest bombshell.

Well it was a bombshell to me anyway, because I have this thing  (call me a stickler) for exact dates and figures.

Hobby and Hunter weren't at Columbia in early September 1940 when the decision to begin the penicillin project was taken and Dawson never publicly spoke how it came about.

Karl Meyer had never publicly spoke out about his motives either---- until 1981, when he was 83.

 I rather doubt he ever told Dawson,Chaffee or Hobby about his motives back in 1940-1945.

His personal motives hardly seemed to mount a high moral plane that might bring others in help out.

Meyer had recently been incensed, says Durack, by an article from Ernst Chain on lysozyme that slighted Meyer's earlier work (in 1933-1936) on lysozyme.

Durack quotes Meyers as saying that when he read, in August 1940, the first Oxford article in LANCET on penicillin, he determined to quickly purify penicillin, before Chain could, to pay him back.

Durack then moves on to the matters more pertinent to the actual subject of his review.

I, on the other hand, had a much greater interest in this particular matter and as a result I had available a greater variety of other information to try and make sense of this 'claim' of Meyer.

First, I doubted that Meyer in New York could have read a copy of Lancet with a cover date of August 24th, much earlier than about September 7th in peacetime, let alone when Britain was at war.

Secondly, in an 1990s oral interview with Meyer's boss in 1940, (Phillips Thygeson), Dr. Thygeson describes Meyer as a rather typical type of chemist who is (rightfully) worried that others will steal their data.

In old fashioned mystery books circa 1880 to 1940s, the 'formula' stolen from the safe was always chemical--- not math or physics or biology.

Only in chemistry is something extremely valuable to the world outside Science reducible to a page or two of formulas and symbols.

The most famous modern chemist of them all, Robert Burns Woodward, liked to make public his total synthesis of yet another impossible-to-synthesis natural material in a brief announcement of not more than a page or two.

It was as a sort of 'guy thing' type bravado, common in male chemists involved in scientific pissing contests --- but it does mean than valuable chemical results are easily stealable.

I knew Meyer and Chain had known each other since their student days in Berlin and that both were young German Jewish emigres
 very insecure about their ability to avoid a wartime internment camp --- very eager to garner citation credits, if only for the sakes of their families.

And by mischance, both were interested in the same very ,very, very narrow area of science and so bound to trip over each others' feet.

A rivalry seemed a distinct possibility.

Only one problem ---a very very big one --- Chain only published one article on lysozyme, and it didn't even get submitted to the British editors till October 28th 1940, let alone get published and find it way to America.

The Columbia penicillin effort was begun about September 9th 1940, months before this ----so could Meyer read into the future?!

I had to put Meyer's 'claim' on the mental back burner.

Then in early 2010, I read Ronald Bentley's "Leslie A (Epstein) Falk, 1915-2004, and Penicillin production at Oxford", published in the JOURNAL OF MEDICAL BIOGRAPHY, Volume 15, May 2007.

Bentley mentions that in Chain's sole article on lysozyme (of which Epstein, not Chain, is the lead author), Epstein (LE) thanks "Dr K Meyer" for lab space and assistance.

So sometime between June 10th 1940 (Epstein's return to New York) and early October 1940, Epstein was in Meyer's lab and presumably mentioned (a) how Epstein planned to dis-credit Meyer's early work and (b) that Chain was now working on penicillin and that work was very,very fruitful and would soon be published.

Alerted and incensed about (a), Meyer was also alerted about (b) so as to watch all ports for an article---- and to start attracting Dawson and Hobby to see the virtues of penicillin as a research subject.

Meyer, Chaffee and Hobby would probably have remained content to just grow enough penicillin to try and purify it.

But Dawson saw its capabilities as a possible ABF agent (anti bio-filmic agent) and the rest...... is history.

Seven flasks became seven hundred flasks, etc....