Penicillin in wartime: an alphabet soup of organizations passing the buck then hogging the credit

I am still not fully recovered from the disaster of my first public talk on wartime penicillin before Dalhousie University's  Medical History Society.

I was given a very generous amount of time by the Society's Jock Murray and Allan Marble to state my case but it didn't help : my choice for a title slide in my powerpoint presentation simply covered far too big a subject and left me no 'on the spot' wiggle room.

" Wartime Penicillin : from secret 'war weapon' to widely publicized 'beacon of hope' " is not a topic line easy to compress.

 (Though last night's blog entry on the Janus Month of March 1943 would have been a good attempt at compression.)

First person to ever read Fleming's 1929 penicillin article, REALLY READ IT, was Henry Dawson, in October 1940...

Very early in his investigation of  the antibacterial qualities of the liquid beneath a penicillium mold , probably by October 1928, Alexander Fleming came to a truly startling conclusion.

And it is not what you - or he - or any other doctor or scientist might have expected.

Fleming's seminal 1929 article on penicillin is missing two words : impurities and crude

Fleming, in this extremely famous article, defines his "penicillin" as consisting of  one or more soluble solid active ingredients in a liquid nutritional  broth, no more and no less.

He makes it clear that "penicillin" is merely a useful shorthand for that cumbersome longer phrase.

He never once uses the word impurities or impure or crude: to him his active ingredient is perhaps ALL  of the soluble solids left behind when the water is evaporated .

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 !

The re-invention of a military-only antiseptic into "bedside penicillin for all" creates a global beacon of hope for a world at war

the tiny stone the builders rejected

Despite the self-centred claims of physicists, the greatest benefits to humanity have generally been ardently pursued (invented), not accidentally stumbled upon (discovered).

DNA was discovered in 1860s by an Swiss doctor, but for most of us, it was really only discovered 125 years later in the late 1980s.

That was when it began to first be successfully used to solve unsolved criminal cases, when British researcher Alec Jeffries re-invented 'DNA' as a means to definitely identify biological evidence left at the scene of a crime.

ROP on this penicillin milch cow is beyond astounding : and it is all down to lactose intolerance !

Ironic isn't it ? Hundreds of millions of people have enjoyed longer lives thanks to the lactose intolerance of some slimy little mold.

Between Wartime Penicillin's initial failure ( Chemistry) and its final success (Biology) stood a third party : the humanitarians

When I call Henry Dawson "Penicillin's Third Man", I am being more than ordinarily facetious.

Penicilin's problem was chemistry-besotted biologists, the solution was  biologically-pragmatic chemists and the connecting threat were a tiny group of humanitarian-minded clinicians.

Penicillin : both its mold and its morals seem to hang out in basements and sewers

Rollo Martins the Canadian naif to Harry Lime's evil...

When I started looking into wartime penicillin, back in late 2004, I quickly felt like that other Canadian , Rollo Martins, learning far more about the immoral underbelly of  the official - and sunny - penicillin story than either of us wanted to know.

Was Alexander Fleming a coward ?

FLEMING avoided this ....

Hard to say --  but he definitely didn't have a chivalrous bone in his body.  And twice - while still a young man - when given a chance to be brave,  he fearlessly declined.

Florey vs Dawson : penicillin to be perfect & a war medicine OR an imperfect but universal medicine ?

Baby Patty Malone helped the whole world discover penicillin 

As should be well known, penicillin-the-molecule and penicillin-the-lifesaver were discovered September 1943 by the whole world, (not in September 1928 by Alexander Fleming) while natural-penicillin-the-universal-livesaver was invented on October 16th 1940 by Henry Dawson.

Sulfa's Alexander Fleming : Paul Gelmo, winner of 1939 medical Nobel for discovery of Sulfa

Sulfa the MIRACLE drug

Alas Paul Gelmo , discoverer of Sulfa, is not likely to ever be as famous as Alexander Fleming, the discoverer of Penicillin and it is a mystery worth investigating to ask why not.

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.

the epic triumph of DEMAND SIDE penicillin

All penicillin histories - to date - have been about what I call "SUPPLY SIDE" penicillin.

"Brilliant scientists, working day and night in the 15 years since September 1928, once again totally surprised humble but ever grateful lay people all over the world."

"They did so by dropping the new miracle cure penicillin  upon them, out of the blue, in September 1943."

This version of the saga says penicillin is best told in two competing stories or parts.

 But both parts are united in being all about active scientists --- with no role what so ever for us, the totally passive and inert citizenry, or in our roles as patients and patients' families.

Part One ,(1928-1937), features Dr Fleming - discoverer of penicillin - with far too many pages devoted to the mysteries of that discovery and with too few of the rest devoted to his efforts to bring his penicillin juice forward to the point of actually saving lives -----when used as an antiseptic.

Part Two, (1937-1940), features Dr Florey of Oxford University (all bow) and his years of wartime work on the chemistry of penicillin - all about his troubles extracting and purifying and synthesizing penicillin.

My book will be about Part Three, (1940-1943), the era of "DEMAND SIDE" penicillin. It will be all about the life-saving done by early penicillin doctors (not scientists), on the rare occasions when penicillin was diverted to the ward bedside and away from the synthetic chemists.

 It will focus on Dr Dawson - the patient. Yes, the patient.

Dawson was not unique in deciding to become a doctor after months spent in a hospital - Dr Colitti ( of Patty-Malone-and-penicillin fame) resolved to become a doctor after his own childhood bouts in hospital dealing with his spinal TB that left him a permanent hunchback.

For Dawson, his insights as a doctor dealing with chronically and terminally ill SBE patients could only have deepened when he himself became a chronically and terminally ill MG patient at about the same time.

Actually I will focus on Dawson, on his first penicillin cure Charlie Aronson, on Baby Patricia Malone's family and on the mother of a dead child he never got to save - Mae Smith, wife of Pfizer chief John L Smith.

In August 1943,Dr  Dante Colitti - inspired by Dawson's illegal SBE successes (an early example of ACTING UP) at another hospital a mile away, got Mr and Mrs Malone to also 'ACT UP' and publicly demand penicillin for their dying child.

Soon hundreds of families were doing the same all over North America and when enough Doctor Moms kicked up a fuss, even the stupidest men in Washington or Brooklyn listened - penicillin production really got moving, after 15 years of male excuses for 'not taking out the trash'.

CHRONICALLY ILL are always 4F

Med Schools in that era - and perhaps even today - hated the chronically ill because they refused to die or get better, within the only school term that could be devoted to that particular form of illness.

The chronically ills' failure to get better 'put paid' to the notion that Science was always successful.

And Society in general packed the chronically ill of low income families away in large impersonal institutions with too many patients and too little money.

It got worse in wartime - a lot worse. A lot of people feel free to unleash their inner evilness in wartime and the helpless are a safe target.

In Hitler's Germany, the chronically ill were actively gassed - particularly those 'useless mouths' type patients like the SBEs (Charlie) and MGs (Dawson) who needed lots of repeated interventions of  high tech medical care without any hope they would eventually recover and start back at productive war work.

In Vichy France or in the US, it was more subtle - the eugenics of benign neglect.

Budgets were cut for the chronically ills day to day living expenses so more money could go to the war, or simply back to the well to do taxpayer when no one was able to complain.

Many chronically ill in institutions died of hunger-induced  infections while the budget-cutters' consciences could remain unsullied.

 Chronic illness research efforts were re-directed away from these useless mouths 4Fs towards the 1As and war medicine.

 Many patients were conscripted,without their informed consent, in some very dangerous experiments for the war - humans being as badly and baldly treated and cast off as laboratory white mice usually are.

Dawson and his supporters rejected the artificial divide between Social Medicine and War medicine, between social penicillin and war penicillin.

They said , against Hitler and Tojo, social medicine was war medicine,in fact the best kind of war medicine.

They said are we fighting Hitler simply because he took raw materials and markets we once regarded as ours or rather because we detest his values with all our hearts?

If it truly was the latter - FDR's Four Freedoms -  we should contrast how we treat our old and weak against how Hitler treated his.

For we will all become old and weak someday.

By 1943-1944, a lot of people saw that Dawson was right - and penicillin's promise was held out to people in the occupied ,enemy, allied and neutral nations as a symbol of the rightness of the Allied Cause.

Until then it had been treated as one of the Allies' best war weapons - a strange term for a life-saver .

 Yes, Dr Dawson probably did 'go a little native' when he got MG and became a perpetually ill patient as well as life-saving doctor -----but Thank God for that !

In January 1945, when AMA boss Morris Fishbein, the American medical censor, finally let Dawson tell American GPs about his five years of successfully curing SBE with penicillin, Dawson could reflect he hadn't done too badly for a chronically ill 4F.

Most histories of penicillin - to date - act like Dawson withdrew to a shadow world of chronic illness and inactivity after he got his MG diagnosis around May 1941, so the authors can return to focus on his rival Florey.

But in the Spring of 1945, Dawson could say, like a lot of chronically ill people who kept on being highly productive despite the pain, "*I'm Still Here - and so is my penicillin !"

Partially because of Dawson and Colitti's ACTING UP, patients today are much more likely to demand quick relief rather than simply waiting for the desultory scientists to get it all perfect and pure before dropping it into our grateful little hands - and Thank God for that, too....

* "I'm Still Here !" is a copyrighted expression and used with the kind permission of the late copyright holder, Margo Takacs Marshall, 1928-2010

The Mystery of Penicillin's 18 missing years

I believe that all of the penicillin books up to now - and there have been hundreds of them - have basically been a series of 100,000 word excuses - "the dog ate my penicillin homework".

Excuses to us - the lay public - on behalf of Science in general or on behalf of one or other early penicillin researchers in particular.

But eighty years later, we lay people still want to know why it was that the best life saving medicine this world will ever see took an eighteen year vacation (from September 1928 till about September 1946) before local doctors around the world could routinely prescribe it to save a life.

Whether they are from the pen of a medical historian  seeking to defend all of Science/a particular team effort or the effort of a lay author defending an individual scientist they particularly admire, all those apologies basically come down to this:

The 18 year delay was due to technical difficulties, not moral failings - at least not the moral failings of my hero.

My book, by contrast, is not going to be a technical book - at least in its intentions.

(It will actually highly technical and highly accurate at times---- but only when needed to refute technical excuses and bromides.)

THE FIRST MORAL HISTORY OF PENICILLIN

Mine will be a Moral History of penicillin - it will lay out a thesis that it was moral failings, not technical difficulties, that delayed penicillin becoming popularly know and commonly prescribed during all those years of death and suffering that we now call The Great Depression and World War Two.

The two events caused an excess of 100 million premature deaths over what might have been expected in that 16 year period.

Even if we content to 'merely' reduce those excessive deaths and not seek to prevent many of the so-called normal infectious deaths, how millions might penicillin have saved if it was readily available by 1929-1930?

Or consider this: despite the new global threat from nuclear weapons, the Cold War period from 1945 till 1985 was actually an incredibly optimist period in world human history.

The promise of 1945's penicillin was sufficient, all by itself, to overcome the fear induced by 1945's A-Bomb.

For a generation, penicillin kept most of us buoyed up about ourselves and the world around us.

Could those good vibes - induced in 1928-1929 instead of twenty years later - have been enough, by themselves, to prevent the worst of the Great Depression and World War Two from even happening ?

We will never know.

 But I believe these questions are still big enough,eighty years on, for it to be worthwhile to re-examine the early penicillin saga to see if there is another explanation for the delay. One that will finally convince most lay people - and hopefully - even convince a few of the scientists.

DUHIG IS PROSECUTION'S KEY WITNESS 

In the Fall of 1943, in Brisbane Australia, 15 years after Fleming discovered penicillin, Dr J V Duhig saved the lives of a dozen seriously ill people using a form of penicillin juice no more sophisticated than what Fleming had on hand in November 1928.

This the single hard, hard, hard, hard ,hard, historical stone against which I am going to grind every author and every account that claims that there were 'technical complications' why the world had to wait 15 or more years to put the life-saving effects of penicillin to work.

Until and unless they can explain to everyone's satisfaction why Duhig could do this - but why Fleming/Florey and Dawson et all couldn't - I will not relent.....

"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....

VEGEMITE also had its hour ; one far fierce hour and sweet

Yellow Snow Bad; Yellow Uisce Beatha Good

It is no secret that Irishmen like their drink, even ( or perhaps, particularly) in wartime.

For a real Irishman likes nothing better than defying straitlaced authorites who think sugar and alcohol has higher uses in wartime than to just use in beverages - such as using them to make more and stronger explosive materials.

So in November 1943, it probably won't seem that unusual to see a feisty Irish-Australian named Jim Duhig sprinkle some yeast-like material over a vat of water and molasses and put it in a cool dark place for ten days.

We say yeast-like because yeast extract was unavailable in wartime Brisbane (Queensland) Australia.

Jim did what any quick thinking Aussie would do - he reached for that all purpose substitute, Vegemite in .3% solution, because after all, he did come from the land down under, where beer flows and strong men chunder.

Also not unusual was his decision to strain the resulting golden colored liquid at the bottom of the vat through a piece of cheesecloth and put it into bottles.

But what he did next might surprise you : he drew some of that golden liquor out in a big needle and stuck it - again and again - into a dying woman.

He saved her life with this golden uisce beatha and saved four other dying patients' lives with it as well, in addition to successfully treating another two dozen less severe infections with his brew.

Duhig's technique, as crude as it seems, is about as high tech as antibiotic science & industry ever has to get, if its only interest is in saving lives.

But it isn't and Jim Duhig's heroic actions came 15 years after Penicillin's initial discovery.

Millions would have lived ( longer - for we all must die at some time) if Alexander Fleming had felt in 1928 as Dr Duhig felt in 1943.

But he didn't and neither would have Dr Duhig in 1928.

It took someone else, someone far bolder than Fleming or Dunhig or Florey, to kickstart the radical-at-the-time idea that injecting natural penicillin into a patient's bloodstream was the best possible treatment of most life-threatening systemic bacterial infections.

That bold idea was first enacted upon on a tiny island, not far off the American coast, a few years earlier.....

Jim Duhig was indeed very Irish - his uncle was the archbishop of Queensland - but in real life he didn't brew liquor - or even drink - he was the head of a prohibitionist society.

But he did brew penicillin---- rather than see some patients die needlessly while waiting for Big Pharma to get its act together to do in decades what Jim had done in weeks !

Life is much stranger than fiction.

Dawson & Fleming : Penicillin Pioneers Poles Apart

Sir Alexander Fleming did not discover 'penicillin'.

Not in the common sense meaning of that word that we have all held since the early 1940s.

He certainly did discover that excretions from a certain penicillium mold killed a wide variety of dangerous bacteria without harming human cells - the first known substance to do so.

But he quickly declared that these natural excretions, which he labelled as penicillin, were useless at curing even the mildest of infections, if injected into the body.

FLEMING: PENICILLIN WILL ONLY BE USEFUL AS ANTISEPTIC AND ONLY IF PRODUCED SYNTHETICALLY

Fleming said that penicillin was only medically useful if dabbed on the surface of a wound (that is, when used as an antiseptic) and would only be viable as a conventional treatment if it was produced synthetically by chemists.

Martin Henry Dawson was another pioneer in penicillin research.

He did not discover penicillin and only became active with it eleven years after its discovery was announced in the scientific literature.

DAWSON: PENICILLIN WILL CURE IF INJECTED, EVEN AGAINST THE TOUGHEST INFECTIONS AND EVEN IF MADE NATURALLY

However, he not only believed that penicillin would cure if injected in the body, he believed it would cure the most incurable,intractable, infection that medicine ever faced : SBE, Subacute Bacterial Endocarditis.

Dawson was eventually proven right, reducing one of the most feared fatal diseases of young adults to a serious disease that was treatable and containable.

And Dawson's position on synthetic penicillin also was poles apart from that of Fleming (and of Fleming's rival Florey !) : it was 'synthetic if necessary but not necessary synthetic' .

In fact, he early on teamed up with the one penicillin manufacturer who put the production of natural penicillin in time to help the D Day invasion troops over mirages of synthetic penicillin some time after the war ended.

That company, Brooklyn's Pfizer, produced 80% of the penicillin that landed on the beaches of Normandy : natural not synthetic penicillin and intended for use by injection, not as an antiseptic .

Fleming certainly deserves some of the credit for penicillin.

But the fact that it took twelve years after his initial discovery of its healing powers before Dawson became the first person ever to give a dying patient a needle of antibiotics is a tragedy that must also be laid directly at Fleming's feet....

Sharp Elbows plentiful in Penicillin Fame Saga

Imagine our surprise when we consulted The Times over the
(in) famous exchange in the Times' Letters section over who
deserved the credit for penicillin, to discover that the whole
affair had actually been started by a letter from TRC (probably
Glaxo ) seeking to grab more than its fair share of the growing acclaim !

And while Fleming, finally, got to work doing something useful
with penicillin in the latter part of the war, Florey devoted
much energy in that same period to giving a similar-sounding
historically oriented lecture, over and over, to various professional meetings.

Its sole intent seemed to have been to undercut Fleming's claim
to be the first to discover and use penicillin, but to do so by
means of an oblique attack so Florey couldn't be publicly seen as 'reaching' for fame - something too undignified for a FRS...

That whole period from August '42 till the naming of the Nobel
winners turned out to have witnessed quite an organized effort
by the Oxford group to grab the bulk of the credit - albeit doing so by avoiding public and the general media.

Its almost worth a book on its own - a prime example of how scientific and public acclaim is organized and manipulated.

Fleming & Florey exchange roles; now its Florey who is the modest one

"Breaking the Mould", BBC4's docudrama on the role Howard Florey's Oxford University team played in the

Public discovery of Penicillin , does the impossible.

Publicly at least, Alexander Fleming was a the very model of a modern modest man.

Howard Florey, was always described, by his oldest and closest friends, as witheringly blunt and relentlessly ambitious.

Yet this take on Florey successfully convinced the vast majority of the many British journalists viewing the film that their parents' hero Fleming had feet of giant clay and that somehow generations of earlier Britons had overlooked the sterling modesty of Dr Florey.

If any of these journalists had consulted any one of the many biographies of either Fleming or Florey they would have seen a more complex and much more interesting story.

Simply put, there is much to strongly dislike and much to greatly admire in the character and actions of both men.

In terms that fiction writers and readers will understand, they would both be very much three dimensional characters, well rounded; always capable of surprising the reader.

Cardboard - even when well acted - is no substitute for the

multi layered complexity of real life...

Breaking The Mould over Fleming

The reviews of BBC4's docudrama, "Breaking the Mould" are in.

The verdict from the UK's scribbling classes is this : Alexander Fleming was lucky, lazy and undeserving of his past fame.

But these paid scribblers are usually sixty years old and younger - too young to remember 'The War' or even the Festival of Britain, and inclined to think that the Beatle-led Pop Explosion was their country's greatest ever export.

Why not - the events of 1962 to 1966 was probably the seminal event of their youth.

But Brits old enough to remember the collective British response to their displacement at the end of World War II by the USA and Russia and the loss of their Empire are all retired now and their response will come later, in letters to the editor.

Worshipful, unquestioning admiration for Alexander Fleming's role in Penicillin and similar admiration of his counterparts in

the fields of Radar and Jets was the key part of that collective response.

As these people retire from the work world and the oldest among them die off, is Fleming about to undergo a honest re-assessment by Britons of his role in the greatest medical discovery ever ?

AR hopes so - but we will wait till the letters from those readers come in.....