Thursday, January 31, 2013

If wartime penicillin was a wah pedal ....

Imagine the Nobel prize winner for medicine , Baron Howard Florey, being pulled off his efforts to discover new antibiotics in the late 1940s by an impatient Leo Fender.

Leo pleads, "Howard,make me a wah pedal, and make it quick ; I need something unique for my new guitar and amp line".

Howard takes his time, and delivers the pedal years late. But it is beautiful finished and has a high fidelity electronic circuit that is so pure that it delivers vanishingly small amounts of harmonic distortion (albeit at the cost of an anemic output).

I can already hear guitar players going "Oh, goody !"

Luckily for humanity, Leo has also telepathed the spirit of penicillin pioneer Henry Dawson back to earth and given him the same assignment.

Early next morning, Henry has the job all done : a crude but workable bread-board design, with screamingly high distortion impurities, but with a low battery drain design and the effect level preset on 11 on a scale of one to ten (aka ("stun").

It is very basic looking , with just one big button, set in the very middle of the sturdy front panel of the wah pedal.

Henry's genius is that this button simply says one word : MORE !

And that my friends, is the essential kernel of the conflict between these two giants of wartime penicillin....

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.

Wednesday, January 30, 2013

Wartime penicillin was "A Genie of Universal Healing", trapped by Florey in a military bottle...

... a Genie intended to remain secret, military and patented for the duration of the war, until others --- led by Henry Dawson --- fought to set it free to benefit all humanity.

Like the war itself, wartime penicillin was not a single event, as we tend to treat it today, but a six year long, world-wide process - a conflict in fact.

A conflict between the much more powerful and much more numerous Hares, led by Florey, who sought to seal off penicillin in many different senses of that phrase.

The small band of Tortoises , led by Dawson, sought to make penicillin free to mix , again in many different senses of that phrase.

The Hares had all the early running from 1939 till 1944, when the Tortoises suddenly appeared out of the dust , like the US Seventh Cavalry, to save the medical establishment's bacon just moments before the D-Day beaches became red with blood .....

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'.)

Monday, January 28, 2013

How wartime penicillin's American miracle cures were censored - and why

From early in 1942, American medical journal editors and authors joined scientific journal editors and authors already being "self censored".

Saturday, January 26, 2013

Florey delays penicillin for three more years : powdering the sick mice, May 1940

Just imagine for a moment if Howard Florey had actually done in May 1940 what he claimed he did for the rest of his life.

Alexander Fleming shares 1934 Nobel prize with Whipple, Minot and Murphy !

Waaaaaait a minute !!

Fleming didn't share the Nobel prize (for discovering penicillin) for  another dozen years.

True --- but he could have got the prize a lot earlier and saved a whole lot of millions of lives in the process , if he had only been a little bit bolder.

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 .

Thursday, January 24, 2013

January 1943 : that penicillin cured the incurable SBE is a military secret, but penicillin's chemical formula is not !

The American scientific journal "The Journal of Bacteriology" is a top journal in its field, read - at least in peacetime - by workers in that field the world over.

Yet in January 1943, it is revealing that one of the earliest and most persistent researchers as to the chemical structure of penicillin , Karl Meyer, is still free to publish his informed opinion on the formula for penicillin : C14H19NO6 or C14H17NO5 + H2O.

His co-author, clinician Henry Dawson, by way of contrast, is NOT free to reveal that he has achieved a truly spectacular medical event : curing the incurable, invariably fatal SBE with penicillin , still the acid test of all infectious diseases.

Nobel prize merely for concentrating penicillin into a SOLID for therapeutic use ?

Gloria T Sanders (in her 1986 book on amputations of the lower limbs) mentions in passing that Howard Florey was the first to concentrate penicillin into a solid, so it could finally be used in human therapy.

This has become a commonplace in recent years, as a Google search on "Florey" and "concentrated" will quickly reveal, replacing earlier claims that he was the first to "purify" penicillin.

But since the solid penicillin was in fact not a whit more stable than Fleming's original liquid penicillin, if  both were properly stored, it offered no advantages to Fleming's wet stuff and a whole lot of disadvantages.

Wednesday, January 23, 2013

James Baxter's Pulitzer Prize winning nonsense about wartime penicillin

As part of OSRD's campaign to spin its considerable successes and many failures, William College president and historian  James Phinney Baxter III was hired in mid war (1943) to assemble a bewitching mixture of hitherto-secret facts and sheer blarney, called "Scientists Against Time".

It sure fooled the 1947 Pulitzer Committee, but it shouldn't continue to fool us.

Monday, January 21, 2013

Science's faith-based belief in the non-toxicity of pure natural Penicillin

For an entire generation of scientists, doctors and science reporters (those working between 1929 and 1949), it was an article of absolute faith that pure penicillin was non-toxic.

But how did they know? How in the hell did they know ?

For during most of those years they had never seen anything like pure penicillin , let alone given it an extensive work-out down in the hospital wards.

Who am I ? asks a very famous bright yellow powder from WWII

OK, Manhattan : Who am I ????
(a) In the popular imagination, I am often thought of as being a bright yellow powder (though if fact I might often be dark red or brown or even some other color).

(b) Oddly enough, it is exactly the same for me.

(a)  Some of my most important developments happened on Manhattan island, with strong Canadian involvement --- I think that was all about the word "Hope".

(b) Wow ! Me ditto,ditto,ditto !

Thanks to SAMJ (the SOUTH AFRICAN MEDICAL JOURNAL), we can learn of first published guess as to penicillin's chemical structure

SAMJ : the South African Medical Journal
So much has been written about the earliest days of trying to determine the chemical structure of pure penicillin, in such truly massive tomes like "THE CHEMISTRY OF PENICILLIN" and "ANTIBIOTICS,VOLUME II", and much more delightfully in John Sheehan's lucid-but-learned "THE ENCHANTED RING" , that there seems little more to add.

But that is not so, thanks to the South African medical journal SAMJ and its enterprise at putting all of its over 100 years of back issues online and free to access.

Vitamin C pills vs oranges: a metaphor for the dueling penicillin of Aussie docs, Florey and Duhig

A nice big fresh juicy orange and a tiny white pill can both have the exact same amount of vitamin c in them : about 100 mg ,  just above the recommended daily intake of the vitamin for a adult.

The synthetic vitamin c pill (first invented in the 1930s) is of course  supposedly pure, but actually consists mostly of "harmless" filler . It is usually taken with a small glass of water.

The orange was - in the eyes of the Modernist 1930s - an impure source of vitamin c. The orange consisted mostly of harmless filler (pulp fibre and a great taste) and about the same amount of water as needed to fill a small glass.

Dawson's DIY penicillin a postmodernist "shot across the bow" of Modernist Big Pharma

Two hundred years from now, only the first of the Dawson team's many articles on wartime penicillin will still be cited and still considered seminal.

This, despite the fact that Nova Scotia-born Henry Dawson's last penicillin article told a surprised world that invariable fatal subacute bacterial endocarditis (the much dreaded SBE) had finally been cured - by his penicillin method that he had pioneered 5 years earlier.

Sunday, January 20, 2013

Henry Dawson "jump-started" The Age of Antibiotics because, almost alone in the medical world, he wasn't obsessed with 'purity' but rather with 'charity'

We have the records of only a few contemporary reactions to Henry Dawson's surprise decision to dramatically kick-start The Age of Antibiotics, 12 years after it should have begun but three months before it was scheduled to begin , but they are suggestive.

Pure Sulfa or Salvarsan drugs were far more toxic than impure crude penicillin : so what was the fuss REALLY about then ?

Before 1945, an entire generation of doctors world wide (except for perhaps a half dozen of them) were more willing to put pure but toxic sulfa or salvarsan drugs into their patients than put impure but non toxic penicillin into them.

I will go further:  an entire generation of doctors were willing to seen letting their patients DIE, rather than be seen by other doctors as putting an impure substance into those dying patients.

Wartime penicillin's biggest secret was "hidden in plain sight", on the pages of the very first article on penicillin

The real reason why the tortoise Henry Dawson, despite starting almost three years late, beat the hare Howard Florey to become the first ever to put an injection of an antibiotic into a human patient, is to be found inside wartime penicillin's biggest secret.

Unexpectedly, wartime penicillin's biggest secret was not stamped "TOP SECRET" and was not buried under lock and key in some government cabinet in Washington or London.

Saturday, January 19, 2013

Life-saving penicillin can be a little bit fermented but not a little bit synthetic

If a medicine will save lives when nothing else will do so - in war as in peace - then Henry Dawson's example reminds us that our first moral requirement is to make it as much as we can, anyway we can, save lives anyway we can..... and only then try to perfect it.

A full two years after Florey arrives at Peoria, the NRRL starts looking for new sources of penicillin strains..."Soon" ?

Penicillin: II. Natural Variation
and Penicillin Production in
Penicillium notatum and
Allied Species

If pollyanna historians says two years - in the middle of a war - is "soon" , then I guess it must be so.

Part of "The Penicillin Holocaust" : Allied POWs dying needlessly of infection because the Allies decided they didn't deserve penicillin...

A whole lot of people died needlessly of infections that wartime penicillin could have/ should have cured --- all because the Allies decided to treat it as a military weapon of war --- only to be used to cure lightly wounded Allied combat troops, to get them back under enemy fire as soon as possible.

Eliding chemical synthesis from the Pollyanna histories of Wartime penicillin

Every Pollyanna account of wartime penicillin has much blather on how (Florey) (Fleming) (you add a name) went to this or that firm asking it to grow some biological penicillin only to find much tea and sympathy but no eagerness to help.

Florey quickly flees the biology of NRRL Peoria for the chemical comforts of Merck

Howard Florey probably spent no more than a few hours of his whole life in the labs of the NRRL at Peoria, Illinois where most of the fruitful work that gave us the antibiotics revolution was actually done.

Did Merck consultant A N Richards diss penicillin during the first two years of the war?

Read any "Pollyanna" history of wartime penicillin and you quickly garner the impression that wartime Washington's top medical research bureaucrat, AN Richards of the famous OSRD organization, first learned of penicillin when his former student Howard Florey dropped by in the Fall of 1941.

In my opinion : "Bullfeathers" !

Friday, January 18, 2013

The morality of good - temporary - military secrets and bad - semipermanent - military secrets

There is little morally to fear for all of us agreeing to keep  traditional (and temporary) military secrets such as all troop movement before the planned big invasion.

Wartime penicillin's six year odyssey : from secret war weapon to widely publicized beacon of hope

Without really meaning to, we tend to reify World War Two from a six year long process into a single event ("the war"), when we say things like "millions of women went to work in factories for the first time in their lives in WWII".

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.

Like Admiral Byng, but in reverse, AlexanderFleming was given a Nobel prize "pour encourager les autres"

Alexander Fleming pursued, preserved and publicized a foolish observation that turned out to be.... not so foolish after all.

That 'ever-climbing' Aussie Howard Florey: year by year his listed degrees got longer and longer

While we all know the differences between a BA, MA and PhD , few of us can fathom the distinctions between a BM/MB, and DM/M.D. in the field of medicine --- even when our life literally depends on it.

Thursday, January 17, 2013

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.

Wednesday, January 16, 2013

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.

Wartime Penicillin was a race between a Tortoise and a Hare,unexpectedly the Tortoise won but the Hare got to phone-in the results...

People invariably find the story of wartime penicillin fascinating because 75 years after the earliest events, it still remains a real puzzler with lots of inexplicables and unanswered questions.

The story of wartime penicillin is actually quite clear.... but it is its history that seems so full of holes and silences.

Tuesday, January 15, 2013

Penicillin's four most famous patients shouldn't have been PATIENTS... according to the research protocol

When anal-retentive children grow up, if indeed they ever grow up, they either became clients of Madame X the Dominatrix... or they become medical research scientists devoted to extremely strict and rigid clinical trials with firm protocols and hard-fast deadlines.

Monday, January 14, 2013

A forgotten meme from "The Golden Age of Mysteries" held sway over wartime penicillin : to the detriment of the dying

The grey-haired teenagers of the 1870s to 1890s, the guys who actually ran World War Two, grew up on the stories of the Golden Age of Mysteries and Detectives, starting with Sherlock Holmes' Study in Scarlet in 1887.

And one thing you quickly learned in all those thousands of books in dozens of languages was that the formula that the spy had stolen from the safe - the formula upon which the fate of the Empire ( or perhaps even the world) hung - was never a formula in physics or biology or geology or astronomy.

It was always a formula in Chemistry : always a formula for the synthesis of some extremely powerful explosive or fuel or drug.

Sunday, January 13, 2013

"I sail by stubborn stars, let rocks take heed.."

"... and should I sink... then sinking be my creed".

And that poetry stanza  was  in fact very much the bold personal credo of Kenneth Leslie , poet and anti-fascist activist (1892-1974).

Most of the penicillin grown in its first 15 years, was wasted on useless attempts at synthesis, not used to save the dying

If my claim be wrong : show me the money !

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.

Saturday, January 12, 2013

For female pioneers of wartime penicillin, 1910 was a very good year ...

Dorothy Crowfoot , Gladys Hobby and Nancy Atkinson were about the only women who played an independent role in the development of wartime penicillin.

The A-Bomb and synthetic penicillin were attractive war weapons, not because they were easy - but because they were hard

Shades of President Kennedy explaining his decision to push for an all-out effort to land men on the Moon before the end of the decade, "not because it was easy but because it was hard" !

The 20 year effort to synthesize Penicillin : "technically sweet" but morally purposeless

The Chemistry of Penicillin (1949)  has more words in it than the Bible and is so heavy that if dropped from a plane, it would kill more people than penicillin has saved.

My review of it could consist of just three words : "why?" and "technically sweet" .

Friday, January 11, 2013

Medical ethics - not medical techniques - are probably the leading way to decrease or increase deaths due to war

How doctors and nurses morally regard all of their fellow human beings, rather than how they medically treat their actual, relatively few, patients, is probably the number one determinate in whether wars are relatively bloodless or particularly bloody.

The entire culture takes many of its moral cues from the medical professionals and when they (as in WWII Germany and America )  sanction or even advocate neglecting or killing those judged lesser than others, this attitude bleeds across the whole country and into the actions of its troops --with horrendous consequences.

Thursday, January 10, 2013

By stubborn, Stars we steer : sometimes charisma can be over-rated ...

"Be careful how you walk, so you won't step into the charisma" warns one cartoon character to the other : ie, don't mistake apparent charisma for actual bullshit.

Henry Dawson oozed non-charisma in spades but what he did have by the buckets full was mere ordinary stubbornness.

By stubborn , Stars we steer...

Considering all that this dying man did achieve with just his extra-ordinary stubbornness and his penicillin-of-hope, it is safe to say that charisma can sometimes be over-rated....

Like synthetic penicillin, the harder the A-Bomb was to make, the more attractive it was to the OSRD

Late in 1942, Britain's highest political, military and Intelligence leadership decided that the Atomic Bomb was almost certainly too difficult and too expensive for Hitler's Germany to produce during World War II ---- if only because it would take too many resources from more pressing necessities for the Nazi war machine.

Sunday, January 6, 2013

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 !

Friday, January 4, 2013

Penicillin : a bunch of biologists who put all their faith in chemistry vs two chemists who put all their faith in biology

In the Alice Through the Looking Glass world of wartime penicillin it should hardly be surprising that about the only strong supporters of natural ,biological, penicillin in the upper echelons of the overall enterprise were two professional chemists : Larry Elder of the American Office for Production Research and Development (the OPRD) and Harry Jephcott of the British drug company, Glaxo.

Or that the group most strongly bewitched by the thought of synthetic penicillin were a bunch of medical doctors with Howard Florey and Alexander Fleming leading the charge (with the OSRD and MRC close behind): the sort of scientists who might have been thought would normally occupy a place at the biological end of  hard science.....

OPRD and Dawson vs OSRD and Florey : social or war penicillin ?

If America was to win the war for the Allies by being becoming a ponderous and relentlessly-slow grinding mill of the gods ( a veritable "Arsenal of Democracy" as President Roosevelt proclaimed) than sometimes Vannevar Bush's OSRD (Office of Scientific Research and Development) worked hard against that objective, never more so than with Penicillin (and DDT).

Thursday, January 3, 2013

Was it me who said Peer Review is too often "Lions reviewed by Donkeys" ?

I guess it was.

I mean that all too often 'cutting edge' research  - paradigm-shifting research - will be rejected by normal science reviewers.

Instead, a scholar's work should be posted online and judged, over time, by a jury of all of their peers the whole world around, not just by six anonymous ( and usually over-worked) colleagues.

If it stands up, then, and only then, should it be considered for formal review by a senior journal in their field....

Gradually mass produce natural penicillin, starting in 1940, but ban all mention of the word in newspapers : half way moral approach ?

Producing enough penicillin for all Allied civilians and all Allied soldiers but keeping all word of it out of the newspapers and scientific journals might have been the best possible moral approach on its wartime use.

Chloroquine : hiding one of WWII's most valuable secrets in 'plain sight' : in the scientific literature

To understand how OSRD fumbled the ball on synthetic penicillin but neatly hid the fact with lot of the taxpayers' money, consider the similar case of chloroquine, the best anti-malarial drug of WWII (aside from natural quinine) and a truly horrific example of the stupidity that can result from the excessive secrecy of war science.

Keep something out of the newspapers and it can remain a secret forever - even when it is not : the case of wartime DDT

Hard to explain why both the Germans and the Japanese of WWII failed to make use of DDT to reduce their truly immense manpower losses due to endemic insect borne diseases : its use alone, could have prolonged the war a year or two more.

After all, knowledge of how to make the stuff was in the public domain, and in the open scientific literature, having been synthesized more than seventy(70) years earlier.

Penicillin an excellent war weapon because it was so hard to synth, not in spite of that

An excellent antiseptic like synthetic gramicidin was cheap to make, fast acting, stable and a very effective bacterial killer.

But as a weapon of war, it lacked the ability to remain secret for very long .

Henry Dawson's war aims : "You catch more flies with honey than with vinegar..."

The Allies, convinced their troops lacked the Nazi and Japanese killer instinct, spent most of the war trying to prove Dawson wrong by demonstrating that they could be tougher than tough.

But given their overwhelming advantage in men and material over the Axis, it didn't seemed to be working very fast.

Tuesday, January 1, 2013

The 180 degree flip of wartime penicillin : from secret weapon of war to public weapon of propaganda

War is not at all like the playing fields of Eton , many reports to the contrary.

Both sides get advance notice of the time, place and nature of the activity in sports - and there is a strictly enforced set of rules.

By contrast, a successful military offensive operation is far more than half won if it is kept secret to the last moment and beyond.

Like Penicillin, DDT was a slow killer, so naturally biologists used to the hitherto rapid biological killers, promptly ignored both

Put a bunch of scientists in a room and get them to bet on a race between a tortoise and a hare and they'll plunk their money on the rabbit every time.

That is one big reason why 'we almost lost DDT and penicillin' , to paraphrase a famous wartime ad from the Ayer agency : a bactericide or insecticide that was slow but steady has no great appeal to your average alpha male scientist......

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.