Patient ONE of the Antibiotics Era : how the saving of Charlie Aronson changed our world

During his lifetime, Dr Henry Dawson only gave penicillin to several dozen endocarditis patients, Charlie Aronson first among them ; only saved several dozen lives, Charlie among them.

Dawson's pioneering effort to inject Charlie with penicillin on October 16th and 17th 1940 (Dies Miribilis) certainly didn't directly save many lives.

But the moral fact that Dawson cared enough in the first place about Charlie-the-person, to pioneer in making and to giving him penicillin, has certainly saved tens and tens of millions of lives ever since Dawson's premature death in 1945.

If  only the greater cultural milieu surrounding Dawson and Charlie had been as willing - nay as eager - to save Charlie 'the 4F of the 4Fs' as Dawson was, it might also have been as willing - nay eager - to save the Jews of Europe as well.

Howard Florey saw potential enemies everywhere, but with "friends" like A N Richards and Robert Coghill, he hardly need bother looking any further

Howard Florey's correspondence twice notes that he has just received a higher yielding strain of penicillium from America.

Fleming never saved Churchill, but Gladys Hobby saved Florey's sister when his own penicillin couldn't !

Howard Florey was never more sleazy than in his dealings with Henry Dawson's team, as he desperately fought to restore the family name that his father dis-honored, by trying to remain the sole "hero" of wartime penicillin.

Just try to imagine what an university ethics committee today might say about a professor using his main rival's unpublished paper, sent to him in secret by his close friend (the same government official who censored his rival's paper and forbade its release) to improve his own work that is about to be allowed to be freely published !

That is what full Professor Howard Florey and university vice president and full Professor A N Richards actually did to associate professor chemist Professor Karl Meyer of Dawson's team , in mid 1942.

(As they say, tenure is 'red in tooth and claw'.)

Merck has credible excuses for being beaten on D-Day penicillin by Pfizer - but none whatsoever for being crushed by Commercial Solvent

Merck, the OSRD, Florey's Oxford team (all part of the synthetic penicillin obsession) continue to have many defenders among academia.

Howard Florey, Henry Dawson,Penicillin and the NEW YORK TIMES : how then-tiny Pfizer became the biggest drug company in the world

"Giant Germicide" article changed history ...

Myth much to the contrary, Howard Florey went to America in 1941 not looking for a way to save lives, but for a way to save Allied military lives without having to save Axis, Neutral or Allied civilian lives : he was looking for a top secret medical bomb, a weapon of war.

Roy S Koch "shows me the money" on wartime penicillin

In December 1944, a very youthful looking economist named Roy S Koch was heading up The Biologicals and Parenteral Solutions Unit, hitherto an unimportant sub-section of a sub-section of a sub-section, buried deep somewhere in the bowels of the powerful War Production Board in wartime Washington.

Then , overnight in August 1943, penicillin became one of those parenterally delivered biologicals and nothing was ever quite the same.

The elevator pitch for "By stubborn, Stars we steer"

Some people call it the takeaway sentence while others call it the elevator pitch : that line that tags a movie's every radio/TV spot and poster, the same line that got the movie green-lighted (financed) in the first place.

"A Rare Breed Indeed" : US wartime Int'l treaties on the A-Bomb, Lend-Lease, Bases for Destroyers ... and synthetic penicillin

Most of the antibiotics we use today (beta-lactams) are still the close relatives of the first and best-ever antibiotic, Penicillin G.

They are all still produced, by mold slime, ie naturally : and this will probably always be so.

They are produced almost as bulk chemicals, thousands of tons worth annually, a multi-billion dollar industry that lies at the very foundations of the multi-trillion dollar health industry.

But there is (and was) no international treaty, closely negotiated at the very top level (Lord Halifax and Dean Acheson) , at the height of total war and over an extended period of two years, on the patents and scientific information involved in this crucial production of natural penicillin.

Howard Florey sole hero of 1944 American national radio play on Penicillin

Here, Howard Florey rules !

Du Pont's Cavalcade of America  on NBC was a very well financed American national radio and later tv show, popular before and after WWII (1935-1957), that as Marcel Lafollette points out , often featured heroes from medicine and science.

Not surprising then that the series featured an half hour show on "The Story of Penicillin" as soon as the censors would let it : which interestingly enough was April 24th 1944  --- starring Howard Florey as the one-and-only who brought us the miracle of penicillin !

DDT and the myth of "a product of WWII science"

There is no more tired (or dishonest) a journalistic bromide than the claim that this or that boon to humanity was discovered, invented, developed and produced by WWII scientists.

What actually happened, ninety nine times out of a hundred, is that belatedly some senior military or scientific bureaucrat reluctantly agreed to let some underlings spend money on a 'half-baked' idea that had been discovered or invented years earlier but had seen little commercial success up to now.

Meet the DOCTOR MOM who brought us wartime penicillin when it could do us some good, not 5 years after the war ended

MAE SMITH

Her name is Mary Louise (Pelliter Becker) Smith,  but she was much better know as Mrs Mae Smith or Mrs John L Smith.

Needed : a MORAL history of Wartime Penicillin

SBE fatal to heart valves

It is impossible to write a truthful scientific or economic history of how wartime natural penicillin production became the template for today's enormous biotechnology industry.

Nova Scotian-born Dr Henry Dawson and the "Invention" of systemic - natural - penicillin

The "Invention" of systemic - natural - penicillin

Discovery vs Invention

Many substances were "discovered" many years (sometimes centuries) before they were (re) "invented" as having a highly useful medical effect.

Former OXFORD UNIVERSITY chemist found - in National Portrait Gallery !

its all about this gold

Congratulations to Wolfgang Suschitzky , honored with a retrospective of his best known photographs at Britain's National Portait Gallery - including the un-butchered , original, version of his most enduring image.

The Boys of Summer '44 : DODGERS tank but Brooklyn shines in extended road trip: Omaha,Utah,Juno,Gold,Sword ...

   In that crucial summer of 1944, the Dodgers were on their way to the cellar in baseball, but despite that, something far greener and far more golden than "A Tree" was growing in Brooklyn and for a time, best-selling author Betty Smith had to move aside for an unknown chemist called "John L" (Smith).
   During WWII some say that there was a sign at the entrance to Brooklyn, off the Brooklyn Bridge, that said "Welcome to Brooklyn, the Borough that Builds."

   The borough that builds indeed !
   During WWII, Brooklyn was most famous for the Brooklyn Naval Yard ,where the US Navy was building the Iowa class battleships , the world's biggest killing machines.
   Less well remembered is Brooklyn's lead role in building the world's smallest lifesaving machine : tiny ampules of penicillin from Pfizer's Marcy Avenue Plant.
   Along with lots of weapons and K-rations, the D-Day beaches had plenty of those ampules delivered to the beaches, against all odds, in just the nick of time for the first mass clinical trial of the world's first - and best - antibiotic.
   Penicillin must be the only antibiotic that was literally baptised by fire.
   Most of the penicillin on those blood-stained beaches came from just one plant: and that plant was Pfizer's, hitherto if know at all, known for making citric acid for soda pop.
  A definite thirst quencher, but hardly a lifesaver - except in Coke ads.
   If Pfizer boss, "John L", (or more likely his wife, Mae) hadn't become a last minute convert to the life-saving powers of fungi-grown penicillin over the mirage of man-made penicillin, there won't have been any amount of penicillin on those beaches.
   Brooklyn isn't the industrial power it once was - the jobs have all gone to China and Mexico - but when it had to, it did it up right.
   The Boys of Summer that summer weren't just from Brooklyn, they were from all over - and they really needed Brooklyn and Pfizer to bat 1.0 if they were to pull through.
  They did --- and they did.
   In that light, who really cares if the Dodgers tanked that year .....

Two races against a dead - line, when "dead" not just a figure of speech

It was probably in late October 1940 , induced by the strain of setting up the world's first ever use of  penicillin-the-antibiotic, that Dr Martin Henry Dawson began his long slow slide into a terminal case of MG (Myasthenia Gravis).

A Canadian study had only recently determined
that a sufferer from  MG at that time lived an average of four and a half years.

Some lived much longer --- some much less.

However a rational individual , such as Dr Dawson was, would say he had till late April 1945 to live out his life.

He was proved exactly right - dying April 27th 1945.

I can't say he died happy, but I can speculate he didn't die unhappy .

Dawson lived just long enough to have the highly skeptical medical community around the world accept his claim that (systemic) (naturally-grown penicillin) (can cure SBE) --- yes, even the toughest cases of this hitherto invariable fatal disease more formally known as Subacute Bacterial Endocarditis.

I have written before of the jaw-dropping fact that by 1950, just five short years later, it was widely agreed that SBE had become, to quote Dr Charles Friedberg in the world famous medical journal JAMA, "the most common form of heart disease that can be cured."

In early 1945, as Dawson lay dying, with his labours just completed, he won his race by the narrowest of margins.

 JAMA , house organ of the American Medical Association (AMA) finally agreed to feature his long article on his four and half year battle - against his colleagues, his own government and his own body - to offer up "PROOF OF CONCEPT" on his bold claims.

Because he actually made three different, equally bold, claims.

He said the incurable SBE could be cured.

He said penicillin was  much better as a systemic antibiotic, if people would only try it, than it ever was as Alexander Fleming's topical antiseptic.

Finally, and most boldly by far, he said naturally grown penicillin , grown by trillions of incredibly tiny little biotech factories called unicell fungi , would be cheaper, better, more available than anything chemists might be able to synthesize.

He said that the big wartime projects of MOdernity's 'Chemical Man' are not inevitably smarter than the efforts put for by the smallest and weakest members of Life.

In 1945 that offered up a stinging rebuke to the entire civilized world.

It was a sting felt never more strongly that in Germany, home of Modernist Chemistry, which had recently put its chemistry to its most spectacular use ever --- in the steam baths of Auschwitz.

He was proven right, then, on all three points and is still right today.

Dawson's decision to work with Nature, not against her, and work with Nature's 's weakest beings to save humanity's weakest beings, was COmmensality at its finest.

His battle to save a handful of SBE patients (judged to be the lowest of the low , the 4Fs of the 4Fs, during a war effort focussed on 1A soldiers) moved an older couple in Brooklyn New York .

They had lost a daughter in the age before Dawson introduced antibiotics into a doubting world.

The husband, egged on by his wife, resolved to do something about it.

At that time he was the boss of a medium sized company that was best known for making citric acid for the soda pop industry.

He would stick that company's neck way out on the line and gamble big on Dawson's claim that the tiny little penicillin factories could do the job better, faster, cheaper, safer, than anything American's chemists could come up with.

Once he made that decision he went all out - like Sir Arthur Conan Doyle's stockbroker Dodds in the short story, "A Shadow Before" , he became a bear in a bull stock market .

If his gamble failed - and all the betting money said it would - his firm would be ruined.

But Oh ! If it succeeded !

If it succeeded, penicillin would arrive just in time, after all, for the expected heavy casualties of D-Day and just in time for the millions of people around the world dying of infectious diseases as a result of years of wartime malnutrition.

His firm would smothered in thanks and drowned in profits.

That man, John L Smith, was proven right by Dawson and his firm, Pfizer, never did look back from that decision.

For Dawson, his race against a dead-line was a personal race --- to prove up his concept, against fierce resistance from his body and his government, before he himself was - dead.

On the same tiny island (Manhattan), in the same time period
(WWII) , at the same university (Columbia), there was another much better known race against a deadline.

This dead-line was peace - the end of the war.

If the war ended before the Manhattan Project offered up its "PROOF OF CONCEPT" by successfully wiping out a city filled with people and factories, the atomic bomb would die still born - billions spent but the bomb never used.

After all, billions were spent on poison gas and germ warfare yet none of it was ever used.

Because along with Peace came massive spending cuts on war projects.

All that research money would vanish forever, at war's end - unless there was PROOF OF CONCEPT of this untried super weapon.

It was this, not the fear of a Nazi Atomic Bomb, which had vanished in Britain or Russia by the Fall of 1942 and not incidentally both were the enemies of Germany most likely to be on the dying end of a German A Bomb, which actually drove the American Manhattan Project.

The dead in this dead-line was 100,000 dead civilians : PROOF OF CONCEPT personified in ash and traces on the concrete.

This cold callous mental calculation, by scientists as well as military men, was MOdernity at its very worst.

So, two parallel but totally different races against dead - lines , operating a few hundred metres apart from each other in Harlem : MOdernity versus COmmensality.

Now there's a story !

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.....

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.....

BROOKLYN CRUDE versus OXFORD REFINED

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.....

impure to PATIENTS, pure to CHEMISTS

Many scholars have doubted Big Pharma kept its word back in the Fall of 1941, when a dozen of its firms each promised to brew up hundreds (or even thousands) of liters of penicillin juice every week , so  penicillin could start flowing into dying patients' veins.

Because all throughout 1942,one of the worse years of the war for the Allied cause, very very few patients or soldiers seemed to get any of the life-saving  stuff.

I may stand alone - even stand naive - in believing the drug companies' pledge.

But I admit that I also read the fine print in that promise - the drug companies would indeed seed all that raw penicillin juice flasks that they had promised, but not "all" of the resulting penicillin would go to the patients - only "some" of it would.

In April 1943, GLAXO patted itself on the back and said it was the largest penicillin producer in the world.

It probably was.

But NONE, zilch, zero, zip of that world-beating supply was going to the soldiers, sailors, airmen or civilians that month.

Let see, that meant no penicillin for all the burn victims of the HMS Dasher disaster or for the people crushed in the Bethnal Green Tube disaster and no penicillin for the American wounded in the Battle for Bougainville.

So where was all the penicillin going that was produced in Glaxo's Aylesbury and Greenford plants?

It was all off to the chemists at Glaxo and Wellcome, to be degraded and destroyed in their ongoing attempts to achieve total synthesis of penicillin.

I hear a lot of chat that "we couldn't get any penicillin for my mother during WWII because the military had it all" but this was never so.

The military at the frontline hospitals frequently made its own unofficial and unrefined penicillin when it got tired of the scientists back home trying to perfect artificial penicillin.

Pulvertaft did it for the British Army in Cairo - he taught the nearby Royal Air Force to do likewise and the Canadian Army in Italy took up his idea.

Back in Britain, the Royal Navy under Green set up its own unofficial penicillin plant using Gordon Gin bottles instead of Glaxo's Bonny Baby milk bottles - gin bottles of which they had a great deal of, for some reason ( joke !)

Out west in Utah, US Army major Frank Queen started trying to make his own penicillin.

 He was tired of seeing boys from Guadalcanal still lying about with rotting bone
infections, ten months after they were first wounded and evacuated, with sulfa drugs only making them vomit rather than killing off their infections.

The military always said and acted upon, "a bird in the hand today is worth a million birds in the hand tomorrow" - they were only interested in technology that could be mass produced for this war, preferable this year.

General Grove always insisted he had to be a brute, because if you give scientists a pile of money and equipment and no one to ride herd on them, they will always go for the most interesting scientific problems but not deliver anything 'good enough' in time to be useful.

In other words, the better the scientist, the worse the engineer - they are not deadline or budget oriented by nature - they need a firm hand.

The military finally did plump for natural penicillin - produced in mushroom farms if that got the job done - rather than wait for the chemists.

The military's decision to demand natural penicillin now,ironically, got badly needed penicillin into the veins of dying civilians as well.

I think all the firms were guilty of this.

 Florey was not alone in getting raw penicillin juice instead of semi-purified dry penicillin from one company he was cooperating with (Kemball-Bishop). That meant he had to purify the penicillin he needed for patient trials.

Dawson got penicillin juice from Pfizer, starting back in October 1941.

But not till five months later did he get semi purified penicillin from them.

When he asked, back in November 1941, he was told all the pure stuff Pfizer could produce and more was going to Pfizer's Doctor Walton J Smith - if Dawson wanted some pure penicillin ,he could purify it himself from the raw juice.

Doctor Smith was not an MD - he was a PhD in Chemistry - an organic chemist - he set about degrading and destroying the purest stuff that Pfizer could produce, while Dawson's patients got the impure stuff.

Kemball-Bishop, a partner of Pfizer, did the same to Florey in the fall of 1942.

Now Pfizer and Kemball-Bishop were fermentation experts, not really drug companies.

If they, the most biologically-oriented of any of the firms involved in penicillin, were hell-bent on creating synthetic penicillin from the very beginning, how much more so the chemically-oriented firms like Merck and Squibb and ICI ?

It is a Big Lie, in the most accurate sense of that word, to say the search for pure penicillin was done for the patients' benefit.

Many dying patients, in a frontline dugout or in a SBE ward, would have settled for any kind of penicillin now, over a promise of perfectly pure artificial penicillin for the lucky patients who came along long after they themselves died for lack of help.