Showing posts with label fleming. Show all posts
Showing posts with label fleming. Show all posts

Thursday, June 18, 2015

Penicillin, as from the Old Testament : capricious to the greedy and the hubristic ; malleable to the righteous

Psalm 51:7 -----  Purge me with Hyssop


To the large (government and industry supported) research teams privately committed to turning natural penicillin into a highly profitable patented MAN-MADE drug with a long shelf life, crude penicillin was a capricious, labile substance with a habit of disappearing as soon as it was produced.

As both their contemporary scientific articles and their later memoirs and biographies made abundantly clear.
Alexander Fleming and Howard Florey, for example, were for once fully in agreement on this accord.

But to the small unofficial clinically-oriented teams solely concerned with saving lives in the here and now, penicillin's reputation for instability was vastly overrated .

One even gets hints that they wondered if this well-publicized reputation of instability was a deliberate lie fostered by people like Florey, Fleming, Merck and the OSRD to keep later competing teams from seriously investigating the wonder drug.

The clinically-oriented teams' contemporary articles found first that the varying PH requirements of the rapidly growing and then hard starving penicillium fungus had to be well regulated, if the penicillin was not to be accidentally destroyed by the fungus itself, as fast as it was produced.

And then if the resulting crude penicillin liquid was kept very cold in a refrigerator, at the appropriate PH for penicillin, it would easily last the few days or weeks needed for it to be used externally or injected via IV/IM drip, on site at their hospital.

Any competent lab tech could handle the whole affair, is how one Australian team described what they felt was the largely routine growing, extraction and storing process.

Amazingly, both accounts of crude penicillin behavior are actually fully correct.

For example, by at least keeping their impure penicillin free of any external chemical reagents, the clinically oriented teams ensured their patients didn't suffer from the many man-made chemical impurities so commonly found in the supposedly purer commercial penicillin !

And they certainly didn't routinely lose most of the crude penicillin - and consume much scarce people-power - trying to extracting all of the harmless water in crude penicillin, merely to later add it all back in again as part of the injection process.

Because one can't inject dry penicillin ----- or dry anything.

Injections need plenty of fluids - basically water dressed up in a fancy name.

And in particular, penicillin works best if very very slowly dripped into a person's blood stream --- that means that crude penicillin is itself already at the right proportions of medicine and water to work well as a slow drip IV or IM.

Impure penicillin is a lot like the impure orange juice that traditionally supplied us with our Vitamin C needs - that tasty fruit juice works at least as well as today's little white synthetic Vitamin C pills do --- and has done so for millions of years.

So what was the reason for the endless mantra (cum lame excuse) of the Allied medical world needing pure penicillin and needing dry penicillin before it could begin to save the dying ?

G R E E D  &  H U B R I S   ---- impure and un-simple.

The only reason why 'pure' penicillin was needed was that pure penicillin is the only form of penicillin that can then be successfully broken down into its constituent parts - and only its constituent parts.

With all - and only all - of its parts known, chemists then thought they could quickly make a patented highly profitable analogue of natural penicillin, much much cheaper than the fungus could.

Americans and the English would hold those patents and then hold the rest of the world to ransom after the war.

But vast amounts of crude penicillin were accidentally destroyed in the processing along the way to yield up a gram or two of nearly 100% pure penicillin.

Then the chemists deliberately destroyed all that pure penicillin, to then look at the resulting constituent sub-parts.

Every one of their many experiments, from start in processing to finishing in destruction, wasted much clinically useful penicillin that could have saved many many precious lives.

Again, for example, briefly in the Spring of 1943 Glaxo was the world's leading penicillin producer - but almost all of that penicillin was then deliberately destroyed in the chemists' fruitless efforts to do something better than stupid little fungus.

Because, yes, old men in white lab coats and sporting PhDs from the best universities, in the middle of a deadly war, are just as capable of indulging in a useless pissing contest as a bunch of teenage louts.

All because they were determined not to let 'stupid' 'simple' fungus (their words) best 'the smartest chemists in the universe'.

Rather than simply buckling down to work with the fungus, as chemists, in an all out effort to make as much natural penicillin as possible - right now ! - to save all the war's dying.

For twenty long wasted years (1928-1948) the world of chemists tried to do something better that the tiny penicillium was already doing perfectly well, before finally publicly admitting defeat.

And the obsession with dry penicillin ?

Well, perfectly dry and hence perfectly stable penicillin was essential if a few huge drug factories were to supply all the vast world's continuing penicillin needs.

Most of the world's penicillin would have to remain viable for months or even years, as it waited to be transported around the world and then sit on warehouse shelfs until needed.

The same reason why most of our food is stuffed with preservative chemicals and shipped in, using much fossil
fuel, from warehouses a world away ----- the greed for seeing all the profits of the food business sit in fewer and fewer hands.

As a Christian, I like to think God took an early private revenge on all these greedy and hubris souls, before a second and more final round at Judgement Day.

Because Man has never been able to commercially best the humble fungus in making penicillin and crude penicillin is still the substrate for 90% of all of today's antibiotics .....

Sunday, January 4, 2015

The Manhattan (natural penicillin) Project : Googling up a Ghost

How an amateur historian in a small city used the new Google Search tools to recover the lost story of wartime penicillin

 

I first fell upon the lost story of wartime penicillin way back in the Dark Ages --- late in 2004.
My computer way back then was a Mac Plus with 1 meg of RAM and a 20 meg hard drive. My internet access was via dialup and I used text-base Lynx as my search engine.

With this primitive setup , I had still managed to play an important role in a highly successful national political campaign across the vastness of Canada.

I live in Halifax Canada, a small city by world standards, with at best a metro population of only about 300,000.

It holds Canada's biggest defence base, is one of Canada's five regional administrative capitals and is a major university town with half dozen universities.

But despite the fact that all the province's universities pool their libraries into one lending consortium, they collectively still don't rate as even a middle level research university library by Canada's modest standards, let alone by world class standards.

I had a BA from Halifax's Dalhousie University, nominally in political science, but really in Nova Scotian culture and history.

Locally I was considered to be a knowledgable amateur historian, particularly about the under-explored oddities of Nova Scotia history.

In fact, I only got interested in the history of early DNA and later wartime penicillin (of which I knew little and cared less about at the time) because three of the most notable figures were Nova Scotians - albeit all living and researching in New York City.

Now my on-the-ground knowledge of London UK is considerable - particularly compared to the sum total of seven busy hours I have spent to date on the ground in NYC !

But I must say that like any well educated English speaker worldwide, I feel I know the different neighbourhoods of both NY and London quite well thank you very much - from my lifetime of reading, watching movies and listening to music.

Like almost all historians, I was completely certain that any amount of physical walkabout over the geography of 21st century NYC would have still told me very little about how people in 1930s NY once felt and acted.

It proved the case - the streets of NYC looked exactly liked the (filmed on location) streets of LAW AND ORDER... that I already knew so well.

But even today in 2015, most archival material in archives or libraries is still not online.

So living in world class cities like NYC, London, Paris, Berlin, Moscow and Los Angeles still allows an amateur researcher take the local bus to do their primary research --- and still come up with a story of interest to an entire world.

The rest of us need to book expensive international flights and pay big city hotel bills for months at a time to do the same amount of research a local amateur (or local professional) historian can do over an extended period of weekends and evenings.

Fortunately I soon realized that while much of the lost history of wartime penicillin indeed lay in the archives of London and New York, where all previous books on wartime penicillin had been researched and written, much of that lost history was lost precisely because it hadn't occurred there.

Of the various earliest penicillin historians, perhaps only Australian science journalist Lennard Bickel (biographer of Nobel-winning penicillin pioneer Sir Howard Florey) back in the late 1960s and early 1970s had actually visited some of the off the beaten path penicillin sites early enough to catch some of their original flavour and speak to still living participants.

The later writers had fewer eye witnesses still alive and so had to hew closer to the physical paper archival sources located (in those pre-internet age) in just a few key cities - London, New York and Washington.

But with various Google search tools coming on stream in the early 21st century and with a better computer with true broadband, I quickly discovered I had better (and free) access to local newspapers' primary accounts of the more obscure aspects of wartime penicillin sitting in my own living room than did professional historians with sizeable research budgets sifting through OSRD penicillin-related vertical files in some Washington DC archives.

I still hadn't gained anything on the local advantage of living in a world class city and researching a world class local story via city bus.

But I had gained the local amateur historians' traditional advantage of having much more time to do research than do typical professionals.

Magazine editors, book publishers, tenure committees are always pushing professionals to conclude their research and publish the results.

All topics are badly under-researched thanks to this pressure. Professionals just hope to go back later for another bite or two at the subject area.

But I had lots of time, for several different reasons.

I faced no tenure committee or granting agency deadline.

All the key participants were dead by the time I had arrived - no longer any urgency to interview before they passed on.

And I was doing paradigm creating research not normal research - to use Thomas Kuhn's terms.

The official version of wartime penicillin had successfully withstood superficial challenges to its myth because it had all its archival evidence favouring its claims in a few large well organized collections --- and historians are only human.

They much rather devote all their energy to extensive close reading of a few big well organized definitives archives on a subject and then call it a day.

Why spend years and much money trying to track down vagaries that might or might not exist in the end?

So most historians - even historians sceptical of the offical version history of penicillin still end up in the same few spots, visiting the usual suspects.

In particular, Washington holding the NRRL, OSRD and NAS COC collections and London (and nearby Oxford) for the Fleming and Florey collections.

In the New York area, Merck (a major keeper of the official version flame) was far more active with its wartime archives than as Pfizer - not really a part of the official version.

By contrast - and almost by definition - those wartime penicillin activities arising up against the OSRD-Oxford cartel had no official Allied governments' support or funding.

And without either, the institutions employing these renegades had no incentive to collect and keep archival records of their wartime penicillin activities.

Anyone doing this type of research was going to have to devote lots of time ferreting out what evidence that could be found here and there and everywhere.

I saw no current researchers who still cared that deeply and exclusively about wartime penicillin - official or un-official version.

I had no competition - I could take my time.

And I needed it : initially I merely suspected mysteries more by the presence of submerged hints and black holes in the evidence than with some sense that I knew exactly what I was looking for and exactly where to find it !

I just sat at my home computer patiently typing in endless variants on the few key words I had, hoping Google would eventually throw up some unexpected new document to point me ever onward.

And a dozen years later, I think I am finally seeing a clearer view of the alternative penicillin history ....

Tuesday, September 16, 2014

1928-1948 : 'normal' scientists and doctors loved penicillin but detested penicillium

What if Fleming's team , in early 1929, HAD easily purified penicillin and then synthesized and patented analogues of it ?


Contrary to myth , there never was any 1928-1948 resistance, at all, by normal doctors and scientists to the injecting of penicillin to save lives - just provided it was the penicillins that we have today.


These penicillins are all made by someone else while someone else will gladly come and deliver them to any doctor's door.

Just as chemists have worked hard to ensure these modern penicillins have a long and profitable shelf life in doctors' offices.

Someone else, actually lots of 'somebody elses', have also worked very hard to ensure that all the safe dosages and bad side effects have been found and are made are clear to everyone - laity and GPs alike.

These modern penicillins cum beta lactams emerge as crystal pure white and are usually at least partially semi-synthesized.

They are made in gleaming porcelain-white factories in high tech stainless steel tanks - operated by men mostly.

Men who almost never even seen the yucky green slime hidden inside those opaque stainless tanks.

Nature and the natural has been removed as far as possible from the scene - Man instead, is everywhere.

It would still be best if Man had synthesized penicillin totally out of basic chemicals off the shelf but that can't be.

So while the slime still does all the actual hard work (actually makes the tasty steak), Man (medical and scientific PR) does its best to sell the sizzle instead.

The green slime is rendered as Man-made as possible before anyone has to see or touch the stuff.

Yes, normal doctors and scientists have always loved modern penicillin - it was just ancient natural penicillium molds that they (largely unconsciously) feared and detested.

Fleming in 1929 , Florey in 1940 and 1941, Dawson in 1941 and 1942 : no one responds to their Good News gospels


All three detailed to the entire world of doctors of the wide anti-bacterial potency, the extremely low toxicity and the ease of production of natural penicillin in any hospital lab .

Yet in the many published books on early penicillin there are almost no clear accounts of any  - let alone many - doctors responding to all those articles with a request for some of the starter penicillium spores.

There were no shortage of patients dying of penicillin-treatable diseases in those days.

Just seemingly a shortage of doctors willing to use elbow grease to make the penicillin to save lives - a job a later doctor admitted could be easily done by 'any' hospital lab technician.

And I just don't buy that.

I remain convinced that in the medical world from 1928 to 1948,  there were many, many hard working doctors willing to practise very heroic medicine and willing devote long hours to saving the dying.

So why the moral holdback in the sole case of penicillin - particularly when it will probably turn out to be the easiest to make, safest lifesaver to deliver that will ever be found ?

Its about the mold - not the medicine


The answer, I suggest, lies back beyond the medicine to the mold itself - our ancient (and ongoing) muddled relationship with yeasts, mushrooms and molds.

Generally we like yeasts and mushrooms but detest molds - though all are but different visible forms of the same basic being - the fungus.

To over-simplify terribly, we should think of mushrooms as the above-ground flowering heads of underground molds with the yeasts very much like the tiny spores those mushroom heads' periodically release.

Some yeast/spores are good - bread, beer - others spoil food and ruin whole crops.

Some mushrooms are among the tastiest of foods - while other ours are among our fastest fatal poisons.

Moreover by 1900 ,most of us olny saw yeast and mushrooms as divorced from nature - bought packaged in stores.

By contrast, we didn't really consciously buy mold - all by itself - in stores : though we did buy mold-infected cheeses instead.

Instead, in those largely pre-plastic polymer days - we did see mold in nature and in our homes almost daily ---- and hated doing so.

Mold spreading and spoiling our foods , ruining any clothing made of natural products stored in dark damp warm places, rotting wet wood fixtures, growing vigorously up dank dark basement walls.

Mold seemed associated with death and decay - who hadn't come across an animal body dug up by a dog and seen the mold threads running all through the shrunken corpse ?

It even smelt bad ( actually we simply associated its smell with negative situations !)

The fact that it was slimy, slippery, and jelly like was the worst.

Though we often like like materials and even food that is slippery and jelly-like.

But mold only grew by decaying something else : a black spot quickly became a furry and slimy jelly only by visibly dissolving what was once seemingly dry and solid with fixed boundaries  into a watery gell with fluid boundaries.

Now humanity isn't that upset by violent death - not by the way we love war, murders and the slaughter of animals.

And the molds rarely kill what they consume - they usually feed on the those who have died naturally or at others' hands.

So it it isn't the deadness of death they evoke - only the decay of death - the breaching of definite boundaries between the fixedness of solid substances and the fluid state of liquids.

A  mold (gell) is neither solid or liquid - or rather, worse, it is both.

The ever changing slimy mold is the very symbol of modernization or globalization - the mixing and intermingling of everything and anything in ever new unexpected ways.

By contrast, the 100% pure rationally-made chemical synthetic, built from the bottom up by chemists out of known consistent pure atoms, with consistent known repeatable results, is the very symbol of Modernity.

I buy Roger Griffin's thesis - even if he doesn't - that all Modernity (not just Fascist Modernity) was a reaction against Late Victorian modernization and globalization that progressive moderns both sought and feared.

So I see this twenty year battle (between using slime mold to save lives or waiting until it has a chemical synthetic before doing so) as a key battle between Modernity and modernization.

Perhaps even the key battle : the result being the end of Modernity and the birth of a post-Modernity far more willing to seek power-with-nature rather than only wanting power-over-nature....

Friday, September 5, 2014

Penicillin fame , September 1941 : when cat Florey is out of town, mouse Fleming begins to play ...

Alexander Fleming never asserted his quite spurious claim that he had long advocated a lifesaving role for penicillin until the beginning of September 1941.

That was exactly the time when the person most likely to be able and willing to accurately dispute that claim, his friend and fellow penicillin pioneer Howard Florey, was (in) conveniently out of the country and unable to respond because of war restrictions on communications.

When one of the UK's biggest newspapers - the Daily Herald - took up Fleming's claim from his letter to the editor in the British Medical Journal (BMJ) , the infamous "Fleming Myth" was fully made.

Because , quite quickly, both popular and learned journalists took up and repeated the myth on and on throughout the next month.

Nobody from Florey's team at Oxford University refuted the the myth before it grew.

None there dared speak up for the boss , for like present day Canadian Prime Minister Stephen Harper, Florey was a controlling individual who particularly hated the popular media.

Florey had done nothing to diminish Fleming and had been the picture of kindness to him - which itself  was rather unusual for Florey.

He would continue to bend over backwards towards Fleming for at least another year .

For example, by personally delivering some of his own precious penicillin to Fleming to help him save a life - the only injection of penicillin Fleming ever gave in the 14 years since he first discovered the substance.

I feel that Alexander Fleming was sneaky in the way he operated this end run around his friend when that friend's back was turned.

 I have a feeling that Leonard Colebrook could provide other examples of when  his friend Alexander Fleming also was sneaky in how he had gradually replaced Colebrook in the affections of their joint boss, Sir Almroth Wright.

In person, Florey was instantly hard to like and Fleming was instantly easy to like - but superficial surface impressions did not convey the true nature of either man ..








Wednesday, July 23, 2014

Memo to RAMZI YOUSEF : Wartime Manhattan gave the world's first penicillin shots --- as well as the world's first A-bomb

Manhattan's first ever penicillin shots (75 years ago next  October 16th 2015) were a deliberate act of provocation by Dr Martin Henry Dawson.

Penicillin shots across the bow against the Allied medical establishment for using the excuse of war medicine preparation to dismiss efforts of social medicine directed at the poor and minorities.

He felt that penicillin should be deliberately given a high enough wartime production priority to be able to give penicillin to all those in wartime dying from lack of it .

This would serve as a very public rebuttal to the Axis who felt only the 'fit' from the 'fittest' nations deserved medicine, food and indeed life itself.

Wartime penicillin for all the Allied armed forces and civilians , as well as for Allied and enemy POWs, and the people in Neutral lands ,  even via the Red Cross into the occupied lands and eventually used to save the lives of former enemies.

The aftershock from Manhattan's first penicillin shots radiated out in ever-widening circles.

The then modest biological firm of Pfizer , from Brooklyn , was quickly recruited by news of those historical first shots and began helping out Dawson.

But first Dawson had to demonstrate success against a hitherto invariable fatal disease (SBE) to really suggest what penicillin might do if it was mass produced.

 He did so, starting in November 1942, by 'going off the reservation' and used some OSRD controlled penicillin to save a group of women dying of SBE - something the OSRD strictly forbade - which meant abandoning them to a certain death.

But the astounding success he had with SBE was enough evidence for Dawson's former patient , industrialist Floyd Odlum , to suggest to his boss at the powerful (the New Deal-oriented) War Production Board (WPB) that it greatly up the original production proposed by its rival Vannevar Bush's OSRD .

But Big Pharma sat on its hands, convinced it could make much more money for a much smaller investment (and without a need to learn new skills) when it had synthetic (aka patentable) penicillin instead of this dangerous natural penicillin - which could be made by any competitor.

Such as Dawson - whose modest hospital pilot plant was for several months , the world's "biggest" penicillin producer !

Dawson had certainly convinced a fellow colleague and fellow WWI vet, Dr Rudolph (Rudy) N Schullinger in the Surgical Service of his hospital.

Rudy went overseas in mid 1942 with the CUMC's wartime Second General Hospital unit to Oxford England. Dawson had full-blown Myasthenia Gravis (MG) by that date or he would have been the Lab Chief for that military hospital.

Rudy Schullinger tried very hard to get some of the OSRD's penicillin sent into the European Theatre of War so he could both treat wounded American troops in wartime and contribute the results to the ongoing research pool.

Despite repeated entreaties the OSRD would have done of it !

Thankfully Schullinger's protests finally did pull some some penicillin out of the hands of stay-at-home civilian researchers and into the frontlines (before the war ended).

Though it was only to be used to treat american troops , he broke Regulations and used a good deal of it to save the life of a British soldier dying of the same disease Dawson was trying to cure - endocarditis !

(Dawson's "Acting Up" was infectious .)

Then another former patient , med resident Dr Dante Colitti , threw an emotional spanner in the works - suggesting to the parents of a dying two year old girl from Queens called Patty Malone that they call up Citizen Hearst's biggest paper and beg them to get penicillin the OSRD was denying her.

The Hearst media empire's emotional accounts of rushing the penicillin to the little girl with "just seven hours to spare" gripped first a nation and then a world.

It gripped - in particular - the hearts of Mr and Mrs John L Smith . They had lost a young girl to meningitis that mass produced penicillin - as Dr Dawson always insisted - could easily have cured.

The normally hyper-cautious Smith - the boss of Pfizer - now threw all caution to the wind - ordering his firm to build the world's first really big penicillin plant in as few months as a 24/7 schedule could produce.

Bolder yet - he decided to use the penicillin allocated to his firm to do synthetic studies (to secure a share of the future patents) to save the lives of people in New York  with SBE that his government was refusing to save.

A mysterious woman (probably the otherwise very upright Gladys Hobby) would arriving offering bottles of penicillin without labels to doctors like Ward J MacNeal and Leo Loewe with the oblique suggestion it might just help their SBE patients - and then disappear.

At the time it seemed clear to people inside Big Pharma that Smith had recklessly threw away a certainty of big future profits for Pfizer, just to help save the lives of a few worthless nobodies.

But his - and our - salvation lay in the most unlikeliest of all places : the former eugenic laboratories at Cold Spring Harbour in Long Island , once one of the intellectual godfathers to the Nazi holocausts agains Jews, Slavs and the 'unfit'.

For several years, its new (non-eugenically oriented) director Milislav Demerec had pleaded in vain with Vannevar Bush's OSRD to let him help develop more productive natural strains of penicillin-producing penicillium.

But the OSRD - like Florey and Fleming in England - had its heart set on a man-made synthetic triumph with penicillin - they had no intention to share the glory with anyone small and weak  - let alone microbes.

Once again , the WPB saved the day. Its Office for Production Research and Development (OPRD) had about one hundredth the budget and influence of Vannevar Bush's better known Office for Scientific Research and Development (OSRD).

But the OPRD had street smarts in spades and it wisely gave a tiny amount of money and a lot of morale-boosting support to Demerec's and the spectacular results has repaid that debt a million fold and more ever since.

Demerec gave the penicillium spores a nasty sunburn under an ordinary tanning lamp - most died from the radiation.

But a few survived and were soon producing ten - then one hundred and today 50,000 times as much penicillin from the same amount of feedstock as Fleming's original strain (and Fleming's was an extraordinarily good natural producer !)

Yet Demerec remains the most unsung among all the unsung true heroes of the wartime penicillin story : a case once again where the moral scum - not the moral cream - rises to the top of the fame charts.

Now Dawson's team wasn't the only team in New York thumbing their nose at Big Pharma and Big Medicine by starting a penicillin grow-op.

A doubting doctor John Mahoney out on Staten Island Marine Hospital questioned the OSRD's claim that penicillin couldn't cure syphilis .

With unofficial help from Dawson's team they started growing their own and tested their theory on "Easter" Bunnies (as they told their innocent children) that they kept in their home garages over the Easter holidays !

The public clamour from Doctor Mom for "more penicillin now !" that had started with the story of Patty Malone really took off with the thought that with penicillin families need no longer be threatened with VD from errant husbands.

We can't negate the atomic Manhattan Project and Hiroshima.

But Manhattan Penicillin ,the other Manhattan Project , can point with pride to the fact that 80% of the penicillin landed on D-Day (in its first ever mass clinical trial) came from Pfizer's Marcy Avenue Brooklyn plant and that plant went on to supply the biggest chunk of the world's penicillin for the rest of the war.

So much penicillin that America - not the Britain of Nobel prize winners Florey and Fleming ( who were still chasing the decade old chimera of synthetic penicillin and only then mass production) - supplying most of the penicillin for the Allied, Neutral, occupied and Enemy lands.

And that in turn ushered in a Pax Americana based on diplomatic gifting of abundant New York penicillin.

Dawson's dream of abundant - non-patented - penicillin cheap enough to help all has come true - it is life-saving too cheap to meter, lifesaving far cheaper than bottled water.

It has beaten back age old diseases kept endemic by residing among remote and poor people not reached by clean water, adequate food and proper health care.

As a result a sort of herd immunity has occurred as ten billion of us since 1940 have indirectly had better health from seeing diseases like Rheumatic Fever fade from sight.

No, the 250,000 lives lost at Hiroshima and Nagasaki can never be re-gained by actions in other areas - but I think I have offered up evidence to terrorists like Ramzi Yousef and others that wartime Manhattan was at least as much from Venus as it was from Mars.

And if Manhattan citizens are too modest to blow their own horn about its decisive role in making cheap abundant penicillin available to ALL in a world tired, huddled and wretched - then the rest of us should do it for them.

We can't continue to let a terrorist like Ramzi Yousef be the last word on Manhattan's wartime role ....
















Sunday, July 20, 2014

Ramzi Yousef - and the British - mustn't be allowed to forge the last word on Manhattan's wartime role

Yes, a thousand times yes, many of the events that birthed the Atomic Bomb that killed 250,000 did in fact occur on Manhattan and in the surrounding Greater New York City area.

But there was another wartime Manhattan project which has saved far far far more lives than the A-Bomb ever took : a wartime project a lot more from Venus than from Mars, a project more Emma Lazarus than Gordon Gekko.

Manhattan began by birthing the first ever use of antibiotics on October 16th 1940.

Columbia University Medical Centre associate professor and medical doctor Martin Henry Dawson aimed to see the wartime development of "Penicillin-for-All" : for friend, enemy and neutral alike.

Yes, even in -- especially in -- a Total War against an opponent who thought only the 'fit' of the 'fittest races' deserved medicine , food and life.

The Anglo American scientific-medical establishment hotly opposed Dawson but his tiny team of misfits and unfits persisted.

Dawson told the world of his first ever use of penicillin as an antibiotic in February 1941 and again in May of that year.

The second one caught the attention of the American media and through a big story in the New York Times , the eye of a then small citric acid producer in Brooklyn called Pfizer who soon began a prolonged engagement with Dawson's project.

Then thanks to Dawson's former patient (and Manhattan resident) Floyd Odlum , one agency (the War Production Board (WPB) -- out of many for the Allies -- caught his vision too.

They ordered that enough American wartime penicillin to be be produced to save all those dying in the Allied civilian and military worlds , with enough left over to save many of those dying in the rest of the world as well.

But Big Pharma sat on its hands, hoping public domain natural penicillin might soon be replaced by high profit patented synthetic penicillin.

But when another former patient of Dr Dawson,  Dr Dante Colitti from the Bronx , broke the embargo on going to the popular press to plead for government penicillin for dying baby Patty Malone of Queens.

Soon a local Manhattan news story broke big - first going stateside (thanks to the newspaper chain of Citizen Hearst) and then going international , despite the war censorship.

(Good News travels fast --- never faster than in the middle of a Bad News War.)

Pfizer boss John L Smith was moved because the plight of the little Patty because it reminded him so much of the unhappy circumstances surrounding the un-necessary meningitis death of his daughter Mary Louise. (Penicillin usually quickly cures cases of frequently fatal meningitis.)

She had died basically because the (healthy) Alexander Fleming couldn't get off his fanny in the early 1930s to make penicillin in the same way that the (terminally ill) Dawson had done in the 1940s.

John L and his wife must have had a serious heart to heart pillow talk about this one night because soon the normally extremely cautious Smith had thrown off all traces.

'Damn the rest of Big Pharma, and damn petty government regulations forbidding Pfizer and Smith from giving away secret penicillin to keep people alive.'

He ordered in Klieg Lights and put the firm on a 24/7 mad rush to complete the world's first really big penicillin plant.

He was moved as well by all the successes Dawson was having in curing endless kinds of diseases with penicillin - and by the unexpected discovery made in a Staten Island hospital that penicillin quickly and safely cured the age old scourge of syphilis.

John L was big Dodgers fan - he owned part of the club - and in the early summer of 1944 the baseball team stiffed.

Despite this , Brooklyn still scored big on an extended road trip : Omaha, Utah, Juno , Gold and Silver.

For 80% of the penicillin that landed on D-Day came from Pfizer's converted ice-cube plant on Marcy Avenue in "The-Borough-That-Builds" -- and for the rest of the war Pfizer supplied by far the biggest portion of the world's penicillin.

Obviously more than just a tree grew green in Brooklyn that summer.

Britain had discovered penicillin and done almost all the work on it until Dawson's first ever injections of penicillin-the-antibiotic on October 16th 1940.

But the attitude of the leading British researcher, Oxford's Dr Howard Florey , was directly opposed to Dawson's humanitarian values.

He wanted penicillin kept secret and used only as a weaponized medicine , something that would give Allied troops a surprise advantage over the Germans.

Allied civilians and POWs , along with the dying in the occupied countries, the neutrals and the enemy would just have to wait at the back of the bus.

In addition, Florey (and Fleming) banked all his hopes on the chimera of cheap synthetic penicillin - something still not achieved - or ever likely to be!

So as American natural penicillin (and not British synthetic penicillin) flew by plane all over the the world, very highly publicized in the global media, to save dying children in Allied and Neutral countries (some like Australia a former close ally of Britain and ironically , the home of Florey !) , something very important for our post-war world happened.

Pax Britannica , sustained up to now by collective memories the British bravery under the Blitz, faded and was replaced by the new Pax Americana.

Or perhaps Pax Penicillia ? Pax Manhattana ? Pax New York ?

When Dawson died of his terminal disease in the spring of 1945 , just after the death of FDR and just before those of Mussolini and Hitler, his passing got a moment of respectful recognition for all he wrought.

But Dawson safely dead, Fleming and Florey got all the credit ever since though they had signally failed to produce any synthetic penicillin for either the war effort or for the world's dying.

The were aided by Britons , all of them - from top to bottom , unconsciously determined to recover something from a costly war they supposedly won.

Ever since then, the British have rivalled the Russians in the number of important wartime inventions and discoveries that only they supposed did the fundamental work in --- even though the hard evidence says many people in many nations made important contributions over many decades.

Penicillin , along with radar and the jet , occupies the very Parthenon of this false-memory syndrome.

If left to British science - and left to Churchill's Conservative British government - the war or the postwar would never have seen cheap abundant penicillin produced all over the planet.

Endless endemic diseases would not have been knocked back - millions would have died - with billions suffering ill health.

Come on up Manhattan and New York - on October 16th 2015 take a deep bow for your role in wartime's humanitarian "Penicillin-for-All" - you fully deserve it !

And Ramzi Yousef and all your terrorist ilk - Manhattan penicillin has saved far more of your kinfolk than your bombs will ever kill - at least try and show a hint of respect.

Don't be like the ungrateful British....

Tuesday, May 27, 2014

Finally ---- a penicillin movie with a genuine hero - a North American hero to boot !

My book series will be the first books - ever - about the dramatic events of wartime penicillin that will feature a North American, Canadian-American Martin Henry Dawson, as its chief protagonist.

And it will thus be the first ever to feature a genuine hero as its chief protagonist.

Give credit to your typical cigar-chomping Hollywood producer - they have consistently seen what 75 years of academics have failed to see : that the proposed 'heroes' of an wartime penicillin film, Alec Fleming and Howard Florey, are in fact pure box office poison to the women who form the bulk of the audience for any medical drama.

By contrast, Henry Dawson looks like the self-less medical hero from classic Hollywood central casting -  but on steroids : this truth being stranger and stronger than any possible fiction....

Thursday, October 24, 2013

Penicillin is not Avastin, but it could have been...

My book - The smallest Manhattan Project  - is about us , all 10 billion of us , here today or years dead, whose lives have been improved by the advent of inexpensive penicillin.

In a sense, this book is a rarity : one written from the patient's eye view of how that drug came to be ; a welcome change after decades of endless books exclusively devoted to how penicillin looked to the people who discovered and developed it.

Penicillin is frequently called the Miracle Drug but few consider that its biggest medical miracle was really in fact its cost, or rather 'lack of cost'.

Because the diseases that penicillin treats are contagious,  patients too poor to afford a cure remains a reservoir of the most virulent strains, waiting to infect the rest of us.

There actually were methods of preventing much of these diseases before the development of penicillin : they included the ready availability of good jobs, good food, cleaner and bigger homes, greater social respect.

Baring that, only the worldwide availability of a drug that would cure those diseases once they started up, at a price that almost all could readily afford , could reduce these diseases from being endemic or epidemic to just names in a dusty medical textbook.

That is why I can say, with absolute assurance, that even those of us who have never had a single treatment of beta-lactam (penicillin family) antibiotics are in better health today because the grandparent of them all, Penicillin G , is water cheap - literally a lifesaver "too cheap to meter" .

But it almost didn't happen , we almost lost "inexpensive penicillin".

We almost got an expensively patented synthetic drug more akin to Avastin and all those other $100,000 a year plus medications.

"The smallest Manhattan Project" is the story of a doctor ( himself slowly dying of another unrelated disease) who sacrificed his own health to see penicillin from the patient's point of view.

His name should be honoured for all time.

This, despite the fact that he did not discover penicillin and then neglect it (Fleming) nor did he start its re-discovery and eventual development, albeit while pursuing a pathway that nearly killed off that development (Florey).

Dr Martin Henry Dawson, for that was his name, merely said penicillin should be made available - now! - for every single patient whose life could be saved by it , even during the height of a Total War .

Nay, he went much, much further.

Dawson in fact said all should have access to life-saving penicillin, particularly in the middle of a Total War.

That was because that war was supposedly being fought against one opponent in particular, solely because that opponent's core philosophy said that 'some lives are more worthy than others'.

How could we continue to conduct that war with any moral vigour when our own medical establishment was 'me-tooing' Hitler's doctors ?

Now the mantra 'Penicillin for all who needed it regardless of their income level or skin colour' in the mid-1940s meant its mass production, given the vast amount of infectious disease endemic in those years.

And mass production has its myriad ways of driving production costs down, down , down --- as happily happened in the case of Penicillin G in almost textbook manner.

'Penicillin for all' quickly became 'inexpensive penicillin for all' and once that happened, penicillin began to work almost like the way a good public health vaccine program should work : the treatment of the many ultimately offering 'herd protection' to all the rest of us, free of charge.

Insulin is another drug frequently called a miracle drug.

But the sad fact is that it is far more common today than it was beforeinsulin was discovered, for a variety of reasons.

By contrast, the names of all those bacterial household scourges that so terrified our mothers and grandmothers are not even known to most of us under the age of 50, and most doctors practising today have never seen a case of them.

And that is just the sort of modern day miracle that Dawson's mantra of 'penicillin for all' can produce.

For the complex truth is that our choice of medical ethics has economic consequences and these in turn feedback and have medical consequences.

The case of what the mantra of 'penicillin for all' ultimately led to should be taught in every health economics and health ethics oriented university department for just those very reasons....

Wednesday, February 6, 2013

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.)

Within a minute or two into the talk, I felt like crawling into a hole  and disappearing forever --- I could see by the faces of the audience that I was giving far too much unknown information far too quickly.

Any two or three of my powerpoint slides, from the forty two I had actually come with, could have formed the basis of an interesting talk and a lively amount of discussion afterwards.

Eight and a half years of research has finally made me more or less comfortable with the vast array of sound-alike organizations involved in wartime penicillin,  and their activities are just as important as the individual stories of individuals like  Fleming, Florey and Dawson.

But trying to establish what the OSRD and OPRD were in the first place, even before trying to show how much at odds these two similar sounding government agencies really were on penicillin is a month's work - not a small part of a 40 minute talk.

It is entirely my fault - because the night before the lecture I had noticed that even a well known expert on the history of wartime penicillin (name omitted !) still managed to badly confuse the two in an major article in a digitalized book I found on the internet.

And when a printed work is digitalized and put on the internet, an error is forever and eternity --- and visible to all, worldwide.

That is why my penicillin work  will remain electronically fluid on this blog and in website e-books.

 My errors of fact and interpretation (and I expect and even hope to make many) will be instantly correctable as new information comes to light or savvy readers spot errors and typos.)

And another thing about individuals and institutions when Cinderella unexpectedly turns into the Queen of the Ball.

 After passing the buck for years, they now suddenly tack hard right and start clawing each other to take all the credit .

Sorting who actually did what when, not what they claimed ,after the war ,in expensive official histories, that they did, is  itself a work of many lifetimes...

Thursday, January 31, 2013

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.

Finding unknown substances that kill bacteria was and is a commonplace.

Finding a substance that kills bacteria without also killing the patient is a distinct rarity.

But the chances of finding a unknown substance that kills bacteria  while (a) not killing the patient AND (b) while being a part of about two dozen other unknown compounds in a bath of 97% water ?

Well, sir, that simply is an event that has mathematic odds well beyond the calculating.

Let us label the Alec Fleming of this startling conclusion, "Fleming I" , because six months later he had - confusingly - become both Fleming I and "Fleming II", depending on his mood.

Fleming II consistently insisted, for the next fifteen years, that penicillin would not become a useful medication until chemists had purified it, discovered its chemical structure and recreated it as an artificial synthetic. Even then, it would only be good as an external antiseptic.

Talk about a parent praising their latest offspring with faint dams !

But while Fleming II's team had actually started down the chemists' path  and had produced a much more concentrated (and semi-purified) material, he totally and abruptly abandoned this effort and never wrote it up in his seminal 1929 article.

He never even used this highly concentrated material  (a thousand times more concentrated than original his liquid mixture) in any biological experiment.

It could just be that the businessman-bacteriologist Alexander Fleming, a frugal Scot, had more native arithmetic in him than almost all the doctors and scientists who followed him into penicillin - certainly more native arithmetic ability than almost all the writers I have read on the penicillin saga.

Because the two dozen unknown compounds swirling about together hadn't eliminated the anti-bacterial activity or caused a toxic reaction, removing them by purification was a 50/50 shot at  improving- or reducing - those two valuable qualities.

Remember that : let me repeat it : purification might actually reduce the bacterial activity or increase toxicity. Synergy, working together, does many mysterious things.

In fact, Dawson's co-worker, Gladys Hobby ten long years later was only one of many who were convinced that crude impure penicillin worked better than the equivalent amount of units of pure penicillin did all by itself.

Balancing these unknowns, it wasn't mathematically likely that purifying penicillin 100% was actually going to make it a better medicine.

In fact, since with 1929 levels of original mold juice and the then current state of extraction technology, 100% pure penicillin was probably going to require losing 99% or more of the original anti-bacterial substance, 99 patients would now die so that 1 might receive 100% pure penicillin.


Let me go further, and recall some of the economics lesson professor John Graham taught me too many years ago.

Graham had a way of bringing economic jargon down to ground level, perhaps never more so than in explaining the term  "opportunity cost".

I'd like to think that this is the way he'd explain Fleming I's decision to refute Fleming II's progress :

It is not just that purifying the penicillin juice to 100% results in so little penicillin output that 99 potential patients must die so one patient can be treated with 100% penicillin - that has no more medical efficacy than the original un-purified juice.

Because devoting all of your incredible amounts of labour, stress, time, expense, lab space to this purification effort, means your team can't find the time and space to simply produce more absolute units of the original penicillin, with the production technology they already have.

Nor can they find the time, energy and money to improve the biological yield of that original strain of penicillium mold.

In the real world of limited time and resources, when you open one door, you close many others.

Now Fleming II didn't actually go very far down the path of this (pointless) path of purification.

But his team did find success in the much easier and much more potentially useful concentration of penicillin juice ; aka simply removing most of the harmless water, as we do with concentrated orange juice.

If water is the one compound in the mixture known to be harmless, why bother ?

Fleming's strain of penicillium was actually a very potent producer of penicillin on (not in) water : eventually it produced 200 units of activity per ml of liquid in painstaking experiments in the lab, and routinely got at least 40 units in day to day industrial efforts.

But Fleming didn't know how to grow penicillium right to produce its potential in penicillin - and why should be ?

But he also didn't bother to try to find out, from other fungus farmers, how to grow it better.

He was a medical bacteriologist and he grew it as if it was a medically important bacteria.

The results were a disaster : he was lucky to get one unit of activity per ml of liquid.

But even the most careful technique of safely injecting large amounts of liquid by IV drip wasn't going to find a way to get anti-bacterial activity that diluted into the blood stream to cure really life threatening blood poisoning.

Success by this method, as several bold and brave doctors discovered in 1943-1944, wasn't actually that far off : in those early days, even massive infusions of 10 units per ml of liquid would save lives ,and at 40 units per ml of liquid all but the toughest infections could be beat back then.

So if Fleming II concentrated his original liquid down to a thick syrup, he'd have concentrated it enough to inject into patients --- without losing too much of the original scant penicillin in the process  OR consuming all his team's limited energy, time and money in the process.

But at this point, another set of experiments convinced Fleming II completely (and totally wrongly) that penicillin would not work at all as a systemic - concentrated, purified or not.

If only he had injected his syrup, mixed with a little bit of saline solution, into a dying mouse, the mouse would lived.

 And penicillin would have been in wide clinical use by December 1929, repeating the rapid pattern of Banting's insulin, but this time in spades.

However, Fleming I never put Fleming II's work or conclusions into his 1929 paper - only repeating his conclusions in private conversations , if pushed.

He found, (and so told hundreds of hospital bacteriologists all over the world) , that easy to make, 100% recovery , liquid penicillin worked well as a routine lab clearing agent and for use as an a non-toxic human antiseptic.

Now to October of 1940 , exactly 12 years after Fleming's original startling discovery about 'the non toxicity of impurity'.

 Henry Dawson is waiting impatiently for his co-worker Karl Meyer to purify some of Fleming's penicillin up to what the team imagined was the level of purity acceptable to their famous teaching hospital's quality standards.

And to the level they imagined the deliberately vague but purity-obsessed Howard Florey had claimed he had achieved before safely injecting his penicillin into infected mice in the summer of 1940, saving their lives.

Suddenly, while impatiently waiting and pacing the floor, Dawson was presented with a truly Solomon's Dilemma.

He had expected to treat a single patient with SBE, provided the young man didn't die of the invariably fatal disease before Meyer had purified the penicillin to an acceptable level.

Now he suddenly had two young men dying of SBE.

Re-reading Fleming's original article gave him his solution : if purifying merely lent losing half or more (much more) of the limited material available, without making the resulting medicine any less toxic, why bother ?

Merely quickly concentrate the liquid penicillin, so most of the harmless impurities are left in, while the harmless but burdensome excess of water was left out - and you would be quickly left with enough penicillin to treat two patients - and all this could happen before the two men died.

So the spirit of Fleming I , not Fleming II, was guiding Dawson's hand when he injected the world's very first antibiotics , months ahead of schedule, into BOTH Aaron Alston AND Charles Aronson on October 16th 1940.

Fittingly, in this act of inspired charity, Matthew 20:16 was again fulfilled as the Last became the First to receive this healing balm.

(Alston was almost certainly black and Aronson almost certainly Jewish and in 1940s America both were hardly among the truly favoured peoples.)

After Dawson, a few others others would re-read Fleming's paper as if for the first time, and decided to prefer large amounts - today ! - of highly impure but non toxic penicillin, over small amounts of highly purified but no more non toxic penicillin, maybe, tomorrow.

I suspect their grateful patients, plucked back from the grave, more than agreed with their re-reading of Fleming 1929.

A case of Jam Today , indeed .....

Saturday, January 26, 2013

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 .

Fleming says that this (mixture) of soluble solids and nutritional broth is non-toxic to the extent that it can be injected in a mass of one fortieth of body weight without harm.

(That is, this liquid mixture appears to be safely injectable in a mouse and a rabbit to the equivalent of  a single bolus of 1500 to 2000 cc into an average adult human.)

And Fleming isn't the only one never to use impurities or crude in describing penicillin in a scientific report, in the twelve years between 1928 and 1940.

Clutterbuck & Raistrick in 1932 do not use the words impurities or crude, nor does Roger Reid in 1934, or Elizabeth Pickering at Squibb in 1937 or Siegbert Bornstein in 1939.

But Howard Florey, the chemist manque , the anti-clinician, he sure does in 1940.

He might even ask his potential readers, "Purity : how many ways do you want it ?"

Despite being a very short article - almost more of a scientific note  in the style of letters to the journal Nature - Florey manages to inject the words "purify" , "not a pure substance", "impure" and "impurities" and talks constantly of his "penicillin preparations" as if they are something quite different and advanced from Fleming's liquid penicillin.

But, in fact, Florey has merely concentrated all the soluble solids by evaporating away the water, so that 4 tiny units of anti-bacterial activity are no longer in a gram of water and solubles, but in a milligram of solubles.

But two thirds of the scarce anti-bacterial activity has been lost in this totally unnecessary and expensive and complex effort : and in any case, this dry powder has to have water added back into it, to inject it for use !

Dawson, Pulvertaft, Duhig, Yermolieva , Berger (among a mere handful of all the world's doctors ---- maybe just .01% of them  thought this way) seemed to have picked up on Fleming's crucial point.

A point he quickly missed, because he publicly always said that the substance would have to be synthesized pure by chemists before it might be a useful antiseptic .

But his original point was true, nevertheless.

It was this : that regardless of whatever was the compound(s) with that mixture of soluble solids that had the anti-bacterial powers, the water and other solids had no harmful effect and needn't be laboriously purified out - or even concentrated by evaporation - at a tremendous loss of the anti-bacterial matter.

Dawson is at pains to introduce the word "crude" repeatedly in his 1941 article, but with a much different point that Florey's article a few months earlier.

Dawson wants to hammer home that despite the crudity of this mixture of the anti-bacterial activity and the other soluble solids, it was still non-toxic even when injected ( finally) into the human blood stream : life-saving does not have to wait until the chemist's apple has been polished to a 't' .

Dawson is , in a sense , "The James Lind of Penicillin".


Put in another way, James Lind said we don't know which compound (later determined to be vitamin c) it is in limes that prevents scurvy but that shouldn't stop us from using it - NOW ! - to save lives.

Almost two hundred years later, another Scottish (Canadian) doctor (Henry Dawson) said pretty much the same thing.

The lesson might be this : chemists, let the sleeping dogs of chemical perfection lie -----  while we clinicians get on with saving lives.....

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 !

(CALV 440424 380 The Story of Penicillin : episode 380, April 24 1944 is very easy to stream or download from the internet.)

Which is to say this half hour national show aired at a time when the OSRD-AMA-NAS triad was still successfully holding back all press interest in penicillin the miracle (by claiming the triad had legal censorship powers that it actually didn't possess.)

Could it be that even the powerful OSRD had to bow before the enough more powerful chemical giant, in part because it was a prime contractor of the A-Bomb ?

But what I  find so interesting about this show - beyond the fact that I do not recall reading about it from any penicillin historian's writing - is that it clearly announces at its onset that its one and only star is "Howard Florey".

Was the show an attempt to discredit Pfizer's sudden success  with non-chemically produced penicillin ?


(Because of all the months of the six years of war, April 1944 was the one I'd been most inclined to credit Pfizer's John L Smith as the man who finally brought us penicillin.)

Because that months of all months was the very first month that billions of units of the hitherto invisible miracle suddenly started pouring out of his rapidly-improvised Marcy Avenue ice plant cum biological penicillin brewery.)

Perhaps the triad felt a need to suddenly burnish the reputation of the big loser in the race to provide penicillin for D-Day :  that loser being synthetic penicillin and Florey's synthetic efforts at Oxford University.

 And believe me, having listened to as much of this half hour show as I could stand, Florey is indeed portrayed as the one and only star of this miracle of medicine.

Florey has an entire army of fans among present-day historians claiming he was elbowed out the fame-feeding-trove by that big mean bully Alec Fleming.

I have always found this hard to stomach.

Florey, in fact, was seemingly born with at least four sharp elbows of his own.

He also had a strong reputation, as a scientist, of being as ready to use his fists to win scientific arguments as  Fred Banting or Vannevar Bush ever did.

I wonder if his academic defenders will still howl " he wuz robbed" after listening to this old radio show ?

Monday, December 31, 2012

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.


The great medical pioneer Joseph Lister clearly re-invented carbolic acid, when he took it from just one of many industrial solvents and turning it into a global life-saver.

Paul Gelmo "invented" sulfa as man-made chemical in Vienna in 1908 and it was routinely patented in 1909 by Bayer the chemical giant hoping it might yet be a useful chemical intermediate reagent.

But not until Gerhard Domagk , also of Bayer, who systemically tested every one of his firm's new chemical creations for its medical potential, was its life-saving abilities "discovered".

But I still hold this to be a case of re-invention.

 It took an awful lot of grit and determination during the Great Depression to waste scarce company money by systemically and thoroughly testing every one of the thousands of chemicals Bayer made, on then very remote possibility one might have medical applications.

The Nobel committee obviously agreed with me - giving Domagk the inventor and not Gelmo the discoverer the Nobel Prize for sulfa.

Alexander Fleming accidentally discovered penicillin in1928 and "discovered" it was only useful as a military-style antiseptic.

In 1940, Florey and Chain accidentally discovered that penicillin also might work as a systemic.

But like Fleming (by 1940) ,they still choose to emphasize its rather limited application against combat wounds infected by staph bacteria : a tiny, tiny, TINY proportion of all the deaths caused by WWII.

They were hardly alone : I was amazed to discover in my research that I could find no penicillin-making researcher between 1928 and 1945 who first put their penicillin to work as a human systemic life-saver, before they also tried it on localized wounds.

With one crucial exception: Henry Dawson.

In October 1940, months ahead of the schedule that he and his three fellow researchers had already worked out, he choose to inject systemic penicillin into two young men suffering from invariably fatal endocarditis.

At least one of the men - unexpectedly - lived.

It wasn't because of Dawson's penicillin : at an estimated 8 units per mg, it was about .56% pure.

Useless Junk ? Or Love, Hope and Charity ?


The rest (99.44%) was junk - or as I like to emphasis : "99 and 44 100ths percent pure love....hope... and charity" -- bedside penicillin.

A good bedside manner has probably saved more lives throughout history than all but a tiny handful of medications.

I contend that Dawson deliberately used his tiny amounts of home-made penicillin as part of his traditional clinician's bedside manner, to rally his patients' own body defences against their disease.

As prove, I offer up Gladys Hobby, a fellow member of his tiny team, who said she daily walked through Henry Dawson's wards, showing the patients the growing penicillium in flasks, hoping their rising interests in their treatment might rally their psychic resources.

Dawson was not content to reserve his invention of "bedside penicillin" to the handful of endocarditis patients that his small home-made supply could hope to treat.

So Dawson quickly told a convention of his colleagues (the world's top clinical researchers) that natural penicillin had "unlimited possibilities", thousands times stronger than the then acclaimed synthetic sulfas, but without their toxic side effects and inability to work well in blood and pus.

These researchers took his claims home to their labs all over the world.

Meanwhile popular media, like the New York Times , Newsweek and the wire services, spread his gospel throughout North America.

He tried to get the American government - in 1941 -(and by extension all Allied governments) to take over the production of penicillin form Big Pharma and mass produce it themselves in quantity.

Instead, wartime government bureaucrats, who were themselves paid consultants to Big Pharma , censored Dawson's conventional scientific methods to spread his good news - by restricting his access to scientific journals and restricting what he could say at scientific conferences.

But in wartime, person-to-person gossip becomes the new telegraph.

So Dawson was able to keep on spreading the word until most all of the doctors in metropolitan New York and beyond had heard of his unexpected successes with systemic natural penicillin, curing incurable endocarditis , the "Gold Standard" of infectious diseases.

Penicillin , he said, didn't have only a limited wartime role, limited to just being applied to local staph infections in combat wounds or to cure self-inflicted military VD cases.

He said it  had unlimited possibilities and could cure many of the diseases that plague a peacetime nation or a multi-million man wartime military --- if only government bureaucrats opened their eyes, their hearts and their pockets and gave it a "fair go" .

When the world's general populace, after the story of Baby Patricia broke worldwide, catch Dawson's "vision thing" , governments were forced to play catch up in the production of actual penicillin.

Meanwhile, they too caught Dawson's "vision thing" and governments all over the world turned their propaganda machine full blast to tout penicillin as a beacon of future health and hope for all , if only the Allies win this war.

The key change in the Allied governments' approach was that "for all" as it became clear that the voters did not agree with an Allied war effort that deliberately limited the supply of life-saving medicine and then triaged the world into the people worth saving and those not worth saving.

That - they said - sounded awfully familiar : wasn't that also Hitler's line ?

Well it was certainly Modernity's line : the  methods of instrumental rationality ruled all the modern nations from America to Germany.

By contrast, Dawson's general systemic was 'general' in the widest sense of that word.

 He thought it was particularly important in a Total War against Absolute Evil to give - and be seen giving - life-saving health care and food & shelter to all : it  was the best single reason why people should be willing to fight and die for the Allies' cause.

And seventy five odd years later, was he not right ?

Penicillin has a powerful mystique that tens of thousands of other useful medications ,combined, can't hope to match.

Dawson's crusade to make his inexpensive, abundant, safe "bedside penicillin" a commonplace at hospital beds the world over , in war and in peace , is the major reason we grant penicillin that mystique....

Tuesday, December 11, 2012

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.


That mold makes penicillin : in the beginning, very little,  only converting about one millionth of the war-rationed sugar that was so lovingly fed into penicillin.

Turns out that was the biggest part of our problem : we were feeding it far too well, on easy-to-digest sugars and so it failed to produce any penicillin.

But as soon as we learned to starve it slowly, by giving it milk sugar, (lactose) a sugar it didn't exactly live to eat , it started into giving us tons of penicillin.

Lactose stresses the diets of molds something wicked and when they get food-stressed, but not to the point of actual starvation, they play defence .

The penicillin they start making kills and keeps at bay possible bacteria competitors for what little suitable food the mold can lay its threads upon.

But actually starve a mold (and early researchers often accidentally did that), and they started to rapidly self-suicide themselves in despair.

But feed it lousy lactose, just at the right time, just after its had a day or two of easy living on some nice sugar and protein, and it will produce tons of penicillin.

Literally : annual penicillin product induced by human industry is now at least 20,000 metric tonnes a year.

In 1928, it was about one micro-gram. That's about what Fleming saw in the bottom of his petri dish and it was about as much penicillin as was used in its first cure : curing a newborn baby of a lifetime of blindness , in 1930.

A micro gram is 1 millionth of a gram , so there are a billion of these tiny micro grams in a kilogram of penicillin ( ie about 2 pounds of penicillin). And a trillion of them in a metric tonne of penicillin ( ie about 2000 pounds of penicillin if you are old school.)

So we now produce 20,000 thousand trillion times as much penicillin today as we did 85 years ago.

Fleming's particular penicillium mold was actually very good producer - seemingly the best in the world for 15 years, but only produced one micro gram of penicillin in every gram of liquid medium.

That is a million parts junk to one part money ratio, unbelievably dismal in comparison to every other fermentation process in commercial use at the time.

Today, we get 50 milligrams of penicillin per gram of medium : that is 50,000 times better.

That is a 5,000,000 percent improvement in about 50 years.

Think your grandfather's prize milk cow had an outstanding ROP improvement ?

Try this rapid a percentage improvement on for size !

The main reason why we didn't see this sort of improvement for almost 20 years after Fleming found his mold is because we let chemistry guide our thinking ; trying hard to extract ever more of the penicillin we did manage to produce.

But as I used to say to the CUPE picketeers whenever the Gerry Regan government boasted of the size of its final, final, contract offer : " ten percent of nothing is .... still nothing" .

Only by learning to starve penicillium molds, which we had done by late 1944, did we begin to see enough penicillin to make the stuff a paying proposition , not a charity case, for Big Pharma.

But you can read all the best known books on war time penicillin - and I believe I have - and yet never read one word said about starvation of the molds.

The same goes for present day articles from historians and social scientist about wartime penicillin.

Only articles and books from physical scientists actually working in the fermentation industries routinely mention starvation stress in regards to being essential to penicillin production but even they seem to quote articles from the early 1950s as being the first to signal this fact.

But what then to make of little gem from July 26th 1941 from a letter from Norman Heatley to Howard Florey, just three weeks into Florey's effort to get American Big Pharma to make penicillin on at least a pilot plant scale?

Heatley is at a spanking brand new research facility in Peoria, set up by the US Department of Agriculture to find new uses for farm surpluses - particularly surpluses of low value farm wastes.

He is working with Andrew Moyer : one part mold genius to two parts paranoid nutter.

Already, just ten days after looking at penicillin for the first time, Moyer hazards a guess that penicillin production might be dependent on a starvation metabolism.

If Moyer had only been listened to - and there is no sign that any scientist or bureaucrat then - or historian since - ever did, we might have had commercial penicillin flowing by the Fall of 1941 not the Fall of 1944.....

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.


I mean that penicillin's main problem was - dating from September 1928 - was that its initial (biological) investigators  -names like Fleming,Florey and Richards spring to mind - tacitly accepted penicillium production levels of one microgram of penicillin per gram of medium as a given.

 As a result, they sought - blinker-eyed - only one possible solution : the total chemical synthesis of penicillin.

By contrast, it was chemist Larry Elder who finally pushed mycologists into doing their jobs like people on a mission, not people politely going through the motions.

And it was Larry who sought out "farmer-minded" scientists from any and all fields to up penicillium yields the old-fashioned way, the way farmers had successfully done so with other species for thousands of years : trial and error selective breeding.

But before people like Larry could be called in on the file, the public in September 1943 had to be outraged, ("its been 15 years since penicillin was discovered and  its still in desperately short supply !") and demanding that the authorities put new people on the job to finally start making this stuff - now - and in bulk.

Elder, Colitti, Queen, Hearst never get the credit they deserve


The humanitarians like Henry Dawson, Robert Pulvertaft, Rudy Schulinger , Frank Queen and Dante Colitti all pushed the civil and military powers to be to make penicillin available for all who are dying - now !

And when the purple-toned slash yellow press of Citizen Hearst picked up on their efforts, all the pieces fell into place.

In less than six months, the government of America was pulling a little bit of its money out from making nuclear bombs and germ warfare and towards saving lives and the job was done.

 America - and soon the world - would be awash with cheap naturally-breed penicillium-made penicillin....

Tuesday, December 4, 2012

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.


About all I originally knew about wartime penicillin was from recalling a CBC TV production (originally from Britain ?) that involved a policeman dying of a cut from a rose bush and a doctor named Fleming .

(I had seen it in the late 1950s, back when I was about eight years old.)

That and the fact that the peacetime penicillin clan was a firm family friend - having saved my family many times from serious illness.

I had no idea of penicillin's Canadian connection - like virtually everyone I wasn't aware there even was one.

I gradually and dimly recalled penicillin coming up in a great British film called The Third Man.

I looked at a video of it again and then, on a visit to my brother in Britain, read a great book on how the film and novella came to be.

From both video and the book about the film and novella, I got a strong sense of the extraordinary moral over (and under) tones that penicillin has and that the other three hundred or so existing commercial antibiotics completely lack.

I am only guessing why The Third Man is rated , not near the top of the all time best British films (a dead cert that), but at the very toppermost of the very top : but for me it is the penicillin sub-text.

Britain, unlike Japan and Germany, had really and truly lost the war and so its wartime scientific discoveries like penicillin, jets and radar were seen as absolutely essential to retaining the British sense of collective self esteem.

And so for Harry Lime to muddy penicillin's (and Britain's) good name by , in effect, using it to murder helpless kids , was for them a worse crime against humanity than anything short of Auschwitz.

Sewers as a metaphor for both good - and evil 


Dark ,cool ,dank, concrete sewers and basements is where penicillin the green and gold agent of life actually originally came from - but it was also the true home of that agent of death, Harry Lime .

This was a masterstroke from Greene and Reed ,the one Ying and Yang symbol that puts this film over the top.....

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.


Fleming joined an infantry unit when he was 19 and the Boer War was a year old and despite being a crack shot , he never volunteered to go and fight.

He remained with that infantry regiment, the Scottish London Rifles, enjoying laying at war until 1914 when a real war broke out.

He quit the regiment in 1914 (April, apparently) and thus avoided going into battle with them on October 1914 at Messines Ridge.

His regiment is forever remembered for being the first  ever Territorial Army unit to go into general war action : but Fleming wasn't among them.

Aged 33 when war broke out, Fleming was young enough to be conscripted but unexpectedly got married - shocking his friends.

(Marriage among lifelong bachelors is always very popular in wartime.)

As a married man ,he needn't fear conscription -- at least until after December 1916, when the marriage exemption was ended. Later the upper limit for conscription was raised from 41 to 51 , but in any case he was well under those limits and healthy as an ox.)

In any case, Fleming was already in military uniform, working at a desk job in a medical lab, well behind the front line.

Fleming and Florey : what a pair !


Howard Florey was equally (not) brave : a first rate, highly competitive athelete, he claimed health reasons for why he didn't join his fellow students in the Australian Army in WWI.

Like Fleming, in WWII now that he was safely too old for combat, Florey was a real chicken hawk on conducting an aggressive war policy when it came to rationing penicillin away from dying civilians and towards unfaithful soldier husbands with a dose of the clap...

Saturday, December 1, 2012

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

patricia (Patty) Malone penicillin breakthrough september 1943
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.


Penicillin-the-molecule was ignored in June 1929, firstly by Alexander Fleming himself and secondly by the world.

This was because Fleming on that date indirectly denied any possibility of penicillin ever becoming a lifesaver, ie a systemic ( spread through the blood system) medication.

As a result, Fleming - and the world - yawned.

Contrast this with Banting team's excited, animated, passionate announcement --- at a Boxing Day medical conference just a few years earlier  -- that it was  just two weeks away from injecting insulin-the-lifesaver into a dying patient.

(What a Boxing Day present for millions of diabetics and their familes !)

You can just bet that insulin-the-lifesaver and insulin-the-molecule were discovered together, by the entire world, at that moment.

What about Howard Florey then ? Didn't he play some role in penicillin ?

Yes, some role.

But Florey ,along with Fleming, and along with the British and American governments together with the leading firms in the pharmaceutical world, was convinced that penicillin first must be perfected (100% pure, industry-made, probably synthetic, tested-onto-death) before being used on humans .

 And even then 'humans'  really meant 1A military personnel only, at least during the war.

In addition, they all only saw penicillin as an useful supplement to the existing sulfa drugs - mostly for use in sulfa-resistant staph infections.

Truly a perfectionist and limited vision of wartime penicillin.

One can only begin to imagine the high prices that would be charged governments and patients for such perfect material.

Chain deserved less credit for his chemistry and more for his pushiness , in forwarding the penicillin story to a happy conclusion...


By way of total contrast, only five weeks after learning of penicillin's lifesaving potential (and here Florey and above all Chain deserve the credit) , Dawson was injecting life-saving penicillin into 4F civilians ( Negroes ! Jews !) dying from a strep infection (SBE) , using imperfect , impure, hospital-made, natural, penicillin made by slimey molds.

Yes, like Banting's first insulin injections, Dawson's first penicillin injections 'stung like a bee', from natural impurities still in it. The stings, in both cases, did no permanent (or even temporary) harm.

To Dawson (and to Banting, his model) saving dying patients today with imperfect, impure medication was preferable to letting them die so we can maybe save dying patients, years from now, with a perfected pure medication.

These clashing visions of penicillin ran throughout the war with Florey's vision overwhelming dominant until Dawson's success with -stolen - government issue penicillin on SBE patients inspired another local doctor (Dante Colitti) to jump over the traces for his dying patient as well.

The resulting  heart-stirring story of baby Patty Malone ( late August - early September 1943) broke the media floodgates and the entire civilian world began to "ACT UP" and demand Dawson-style penicillin - now !

By 1944, the Allied governments, dragging the still reluctant Big Pharma firms along with them, had caved.

Semi-purifed, semi-perfect - CHEAP- natural penicillin was being mass produced and being made available for all, as fast as that was humanly possible.

And not just Allied civilians as well as Allied military personnel , but for Axis POWs , Neutral nation civilians and ultimately even Axis civilians.

Canadians Banting and Dawson and Canadian Medicare : there is a pattern here :  a strong belief in medical care that is universal in theory as to who is permitted to receive it (everyone, anywhere) and universal in practise (as a result of being very inexpensive).

But it wasn't something simply discovered and instantly received with acclaim by everyone - as science historians want you to believe how science works : as a totally bloodless affair.

 Instead, it was invented by some humans and contested fiercely by some other humans until finally most humans accepted it.

Invented by people like Banting, Dawson and Douglas ...

Wednesday, September 12, 2012

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.

(And in truth Paul Gelmo did not win the 1939 Nobel in Medicine for his discovery. Gerhard Domagk, the actual winner, deserved his Nobel for sulfa about as much as Ernst Chain did his Nobel for penicillin --- which is to say "still in doubt".)

Gelmo invented cum discovered  sulfanilamide in 1908 as part of his PhD in organic chemistry, doing what Germans of his generation did best : churn out endless synthetic variants of dyes.

It had no known uses, although 11 years later it was found to have some anti-bacterial quantities by American biochemist Michael Heidelberger.

Voices off, unheard  : the cries of the dying


But Heidelberger didn't feel any moral urgency to push to have it tested clinically, to see it it might actually save lives.

(Heidelberger, a later colleague of Martin Henry Dawson , similarly declined to assist Dawson in the development of penicillin - thus missing on the ground floor action of the century's two biggest lifesavers.

Cry not for Michael - he outlived Gelmo and Dawson and died showered in laurels, apparently for never uttering an unconventional thought over his long, long life : an all around, don't-rock-the-boat, team player.)

Domagk did two things with Gelmo's sulfa , one good one bad.

The good thing is that he did what Ernst Chain did ,but which Fleming refused to do : he tested the substance at hand "in living creatures ("in vivo") despite it have failed earlier test tube tests ( "in vitro tests").

Once inside animals, surprise, surprise, it did work and it did fight off the deadliest of infections.

The bad thing he did is that he went along with his employer, I G Farben, when it delayed telling the world about this life-saving drug (the only one available at the time, mark you) for years, while it sought to invent a patentable analog of it.

Neither I G Faben or Domagk felt any moral urgency to put the drug they did have at hand on the market at once, profitably-patentable or not.

The actual dye that Domagk was originally charged with testing consisted of two separate molecules ( one of them sulfa) loosely bonded together to form a beautiful ruby-red dye---- a totally new dye and hence very patentable.

Ie potentially very profitable as a dye - but not as a drug.

This was because "in vitro", bonded together inside a test tube, the two molecule "patentable" ensemble did nothing medically.

 But once in a living body,"in vivo", the body's enzymes quickly cleaved the bonds between the two molecules and the sulfa portion - once on its own, quickly brought bacteria growth to a stop.

Sulfa could and did save tens of millions of lives.

 But as sulfa was now Public Domain (PD) 25 years after its original discovery, it would make no real money (only worldwide gratitude and acclaim) for I G Faben, and so they stalled releasing this life-saving miracle.

But as they never could find an analogue for sulfa , I G Faben finally and reluctantly released the original 2 molecule dye without telling anyone that it cleaved apart in living bodies and the active ingredient was a dirt cheap, abundant (and PD) byproduct of many dyeing operations.

Domagk-the-hero has to be forever tainted for his part in this delay.

Fleming also never tested his penicillin in a living being with a disease - he just did "in vitro" testing that told him that penicillin killed bacteria slower than it was secreted out of the body - thus to the never-one-to-waste-a-motion Fleming it seemed so useless as a systemic that it was not even worth testing "in vivo".

He felt no moral urgency in "just double checking" his hunch.

When Howard Florey - pushed hard by Chain - did finally test penicillin almost 12 years after it had been first discovered , he found it did kill artificial infections inside animals - it did work , "in vivo" !

But while he was an editor of the journal that Fleming's original 1929 article appeared in and so could have demanded Fleming do the "in vivo" tests to double check Fleming's hunch, he never did so.

That he did so only 12 years later - and this when pushed hard by Chain - hardly displays any moral urgency on his part to test this potential life-saver.

Sulfa and penicillin - successes "in vivo", failures "in vitro".

Like I G Faben , though not because it could be profitably patentable as a result, Fleming and Florey put all their priorities to see penicillin made synthetically before it was given mass distribution.

Martin Henry Dawson was all alone in believing that natural penicillin was perfectly acceptable to be mass produced and put to work right away, because people all around were dying daily without it.

Dawson thus invented a moral reason why natural penicillin should be mass produced "today - if not sooner".

It was this 'moral urgency' that Dawson alone brought to its invention, that finally led to the development of mass produced life-saving systemic penicillin.

 A moral urgency that Fleming, Florey,Heidelberger and I G Faben all so obviously lacked.....

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Why My Urgency ?

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Histories of WWII all start with the presumption that it was a war raged between humans and human ideologies, with Nature’s climate and geography as side issues easily surmounted.My blog, on the contrary will only accept that it was conflict between humans and their ideology that STARTED the war but that it was the barriers thrown up by Mother Nature (geography & climate) that turned it into a war that lasted between 6 to 15 years and expanded to thoroughly involve all the world’s oceans and continents. High Modernity may have started the war convinced that Nature had been conquered and was about to be soon replaced by human Synthetic Autarky and that only human Tiger tanks and human Typhoon planes were to be feared. But by the end, more and more people had lost their naive faith in Scientism and were beginning to accept that humanity was thoroughly entangled with both the Nature of plants, animals & microbes as well as the Nature of so called “lesser” humanity. By 1965, the world was definitely entering the Age of Entanglement. Billions still believed - at least in part -with the promises of High Modernity but intellectually & emotionally, it was no longer dominant...

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