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....

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.....

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".....

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...

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....

MARJORIE DAWSON , 

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.

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....

Fleming proved penicillin "non toxic to animals, even in large doses", says Florey and Chain

Soldiers with guns. In our cities. We're not making this up.

Florey and Chain really did say that about Fleming, in their famous  penicillin grant application to the British Medical Research Council in September 1939.

It hardly squares with their claim for a place in the eternal scientific sun for finally doing the animal tests that Fleming didn't do.

 But it does explain why they didn't do any animal testing with  penicillin between Spring 1938 to Spring 1940 - and only then over Florey's loudly protesting dead body.

Why bother?

"Fleming's already done that."

But if the tests had been done in Spring '38, we might have had plenty of commercial penicillin by September 1939.... saving many,many lives...

Chain irks boss - puts snakes before lysozyme

When Ernst Chain was hired as the Dunn Pathology School's biochemist in the Spring of 1935, his new boss, Howard Florey only asked one specific thing of Chain.

Florey wanted him to determine the chemical action of Lysozyme, an enzyme that Florey thought might be the cause of ulcers (particularly his own ulcer!)

But Chain first turned to his own work on the chemical action of the enzyme that made some snake venoms so extraordinarily  and so quickly lethal in truly tiny amounts.

But now, in early 1936, he was made aware that someone he knew of very well indeed, a fellow German Jewish biochemist emigre he had met earlier in Berlin, Karl Meyer, had been and done up  Lysozyme already.

The papers had been submitted in late 1935 and a little research revealed that Meyer had already published on Lysozyme in the prestigious journal SCIENCE , based on work from 1933.


So Chain had to scramble - and from this date, he regarded Meyer as his biggest rival in studying lytic (dissolving) enzymes.


 What had happened was that both men, unaware of each other's interest, had settled on this same narrow area of science to base their life's work upon !


And since both men, plus plenty of others, mistakenly regarded penicillin as a lytic enzyme, a showdown was sure to come one day.


For both men, this 'guy thing' dueling over citation credit in a obscure backwater of science got badly away from them when it turned out penicillin had more than academic importance.


In the case of Meyer, he gave up the control of his penicillin project to his colleague Martin Henry Dawson.


He did so, when it became clear that powerful elements of the American and British governments were determined to see that Meyer was to play no role in the chemistry of penicillin.


 They indicated this by engaging in repeated acts of censorship of his publications and by firing his colleagues from the Schering Corporation of America.


Chain also lost his penicillin project to his boss Florey, when the animal studies of the substance suddenly got interesting.


(Florey was well known for letting you do all the heavy lifting on a project that you and him were supposedly jointly involved in, only to have him steal it from under you if something promising turned up.


 He got away with it, technically, because he was the senior investigator - but it hardly made him popular. 


And it explains why the lazy but likable Fleming got most of the credit for the Oxford team's work.)


But Florey had no interest in the clinical side of penicillin and quickly became just the administrator of the overall Oxford penicillin project, away from England almost more than he was home.


Now Chain could regain some control, by throwing himself into the 
work to purify and then totally synthesize penicillin - something Chain and the Oxford team did in February 1944.


But it turned out the yield was terrible and the process long , difficult and very expensive.


Meanwhile, Dawson had gotten his chosen corporate partner, Pfizer, morally committed to producing as much penicillin as possible as soon as possible.


That meant NATURAL (microbe-made) penicillin - the way we still produce all the various penicillins and beta lactam antibiotics.


In the end, Nature batted last and it batted long.


The supposedly simple, unchanging, (etc) creatures in the Domain of microbes vanquished the efforts of all the best PhDs in the human Domain of Chemistry.


Chain never returned to Lysozyme  - penicillin , even his failed 
synthetic efforts, still gave him a knighthood and a Nobel prize.


Why bother?


Meyer got no personal gain out of his four years of penicillin efforts - just personal heartaches.


But he had the quiet satisfaction that his personal efforts to save a few lives had moved Pfizer, the company that finally gave us the mass penicillin that saved millions of lives.


In 1946, the war over, Meyer turned back to Lysozyme, with his wartime research assistant on penicillin, Eleanor Chaffee ( now Hahnel) helping him.


Meyer kept up his work on Lysozyme and other lytic enzymes long past his formal retirement.


By then Chain, noticeably mellowing in his later years, had died.


Meyer , too, finally revealed his secret, the one he never told Chaffee, Dawson or Gladys Hobby.


He had originally embarked on penicillin merely to get back at Chain for failing to adequately credit him on his own Lysozyme work from way back in 1936.


This is truly Operatic Science - the way that Science all too often really works, if scientists would only admit it .....

how I got into this 'penicillin thing'

People are frequently curious how I got involved in this penicillin book.

 They ask "do you have a medical or science degree or something?"

I don't - particularly the 'something' .

All I can say is that all my life I have been badly bitten by the curiosity bug.

I have always been intensely curious - about anything and everything.

Like a dog with a bone.

Here , for example, is a picture taken on Vancouver's English Bay Beach in the Fall of 1960.

My parents treasure it :

I have just turned nine and while all other kids are running around playing in the sand, there I am sitting and reading a newspaper that some adult had thoughtfully/thoughtlessly left behind.

I don't know whether this curiosity is a gift from God or a curse from God, but there it is....

Michael Marshall, penicillin researcher, age nine, relaxing on  beach...