Wednesday, February 20, 2013

On a day when most other youth got America's first peacetime draft card, Aaron & Charlie got History's first needle of antibiotics : Dies Mirabilis ,October 16 1940

When the possibility of  your nation joining a world wide war looms, getting your first ever draft registration card must feel just like getting the kiss of death, to a young man on the campus of Columbia University.

But when you are a young man on another part of Columbia's campus who has been written off  'as soon to die from an invariably fatal disease', getting instead History's first ever needle of antibiotics, must feel just like getting the kiss of life.

Hence the spooky Janus-like nature of Dies Mirabilis , October 16th 1940.....

Majority of Americans remain silent as Woodrow Wilson's legacy is brutally destroyed : 1938-1941

Thank God Almighty that Adolf Hitler declared war on America, because without it, would America have ever gone to war against the greatest evil the world has ever known ?

The fact remains that between September 1938 and December 1941, the majority of Americans had stood silent as the legacy of their own president Woodrow Wilson was brutally dismembered by the twin 'evil empires' of Hitler and Stalin.

Czechoslovakia, Poland, Estonia, Latvia, Lithuania, Finland, Yugoslavia were all creations of Wilson's direct efforts at Versailles.

The larger spirit of Wilson's efforts : that small nations should be allowed to live without being swallowing up by their larger neighbour's brutal might  had , until 1938-1941, kept countries like Belgium, Luxembourg, Denmark, Albania, Norway, Holland and Greece independent.

Now that too was all gone.

Still the majority of Americans kept silent and indifferent ; they wanted to keep out of the "conflict between the nations" of Europe.

Conflict between nations ???!!!

When I learn that a high school senior and football star has walloped the hell out of a primary toddler his girlfriend was supposed to be minding, I do not call it a "conflict between school students" though that is technically and legalistically correct.

I call it child abuse and deadly assault : the 5 year old didn't start this "conflict" , the 17 year old went to war on it.

So it was when Russia invaded Estonia or Germany invaded Denmark , without any cause besides sheer evil greed.

Morally the excuses most Americans gave then for not going to the defence of the weak against the strong would not stand up in a court today, if they were accused of just standing by while a 17 year old football star beat the crap out of a 5 year old child.

And in a higher - moral - court , they did not stand up then.

This was the sort of moral cesspool that Henry Dawson was swimming against when he defiantly decided to introduce the Age of Antibiotics by treating the "weakest of the weak", the "4Fs of the 4Fs" with his crude penicillin, on the very day America choose to celebrate its "1As of the 1As" : Draft Registration day, October 16th 1940...

Tuesday, February 19, 2013

Resetting the Allied moral compass so that it diverged from the Nazis, not merely followed a muted parallel course

It remains unknown whether Henry Dawson expected his quixotic wartime efforts (to "waste" weaponized penicillin on 'useless' SBEs ) to go as far as they ultimately did.

He certainly was extremely unhappy that America was treating its wartime 'SBE lives unworthy of life' in almost as bad a fashion as Nazi Germany was known to be doing to its SBEs and others seen as "useless mouths".

But did he suspect his assault on weaponizing penicillin would extend beyond the Allies' horrific wartime neglect of the poorer chronically ill ?

He probably couldn't have foreseen just how quickly the pipeline of ever-newer ever-better sulfa drugs would dry up or just how quickly so many strains of deadly bacteria would become resistant to any sulfa drug , leaving penicillin as the  only  wartime lifesaver between disease and death.

This meant de-weaponizing penicillin had consequences far beyond those people suffering from SBE and denied their only chance at life.

If weaponized penicillin had remained throughout the war successfully censored and had remained denied to the civilian world (as weaponized DDT successfully was, never let us forget) , it would have ranked as one of WWII's major war crimes, like Katyn Forest or Auschwitz.

Millions of people around the world during WWII would have died needlessly from massive infections that only penicillin alone could have stopped.

Penicillin in 1943 was not as it is today,  just one among dozens of antibiotics - it was the only one - and in addition, no new anti-bacterial sulfa drugs were coming along to replace the ones that bacteria had so rapidly grown resistant to.

Refusing to divert a tiny amount of war resources to make penicillin available to civilians - anywhere and everywhere - was to refuse them Life itself.

Worse, there was no trade-off  to debate ; penicillin, like sulfa before it, was no war-winning secret medical weapon, at least in its intended war-winning use at the front .

Brand new (front line) wounds either contain abundant alternative bacteria foods to the deadly sulfa 'food' (the Fildes theory, known since 1940) or contain abundant proteins to bind to penicillin and render it useless.

However penicillin, and sulfa, were very useful a little further back in the military hospital system, as a life-saving systemic in cases of possible blood poisoning.

The case against secret weaponized penicillin gets even worse.

As an impure natural drug, penicillin would have taken the Germans at least a year or two or three to successfully mass produce it , even if its virtues had been sung from the heavens by the American media in 1942.

But as a pure synthetic penicillin in supposedly cheap abundant mass production (an event that in fact as not yet ever occurred) the chemistry-minded Germans would have rapidly back-engineered the drug and synthesized it rapidly themselves.

Because remember it took 15 years of hard effort to purify natural penicillin enough to determine its structure - but only months thereafter to 'synthesize' it artificially.

Back-engineering that synthesis would also only have taken months.

Penicillin's real secret was just how difficult the mass production of natural penicillin could be if you set your mind on doing everything the hard way ---- not the OSRD-Merck-Oxford fantasy of secret synthesis.

Dawson certainly set up the stage for the Allies re-setting of their moral compass , from his endocarditis efforts from September 1940 to September 1943 : but it was the immediate outcry resulting from the Patty Malone and Marie Barker cases that forced them to actually do something concrete.

His gut instinct in 1940 ,that not treating the otherwise fatal subacute bacterial endocarditis would prove the acid test for the Allies' pernicious morality, certainly was correct.

But while he couldn't have foreseen how far his actions would impact, he wouldn't have been unhappy that they did so......

The Cure for Auschwitz Disease : "Dawson's Crude" : .56% penicillin ...and 99 and 44/100ths pure love

Pray there comes a day when most premature deaths really are 'Acts of God', when even the best of money and the best of medical care could not result in a happy ending.

But until that happier day, most premature deaths in the world - in peace as in war - are 'Acts of Humanity' , or rather 'Acts of Lack of Humanity'.

Sins of Omission : premature death caused because the people dying are not judged (by others more fortunate) as worthy of devoting much money or effort towards saving.

In war, comparatively few people die as soldiers dying of mortal wounds gained in combat.

The Nazis' behavior provides a particularly clear example of this.

They fed and cared for  the captured POWs and enemy civilians of some nations (the Dutch for example) but for other (Russians and Poles for example) many or most of these people were shot after battle or left to starve and die of disease from lack of food, medical care and shelter.

The food and fuel saved as a result meant that no German citizen went hungry or cold.

The right kind of German civilian anyway.

Using the war as excuse, the Nazis killed many German civilians, those judged 'life unworthy of life' , to free up food and hospitals for other Germans.

In another well known example of  WWII's Sins of Omission, Winston Churchill ignored the pleas of his top British officials in India and let four million poor Bengali civilians needlessly starve to death in 1943-1944 ,rather than divert some food and some shipping from  Allied peoples he judged more worthy of receiving them.

Even the different death rates from wounds gained in combat  , among the so called "modern" nations engaged in World War Two is revealing.

The Americans and British generally devoted more resources to saving their wounded compared to the Germans, Japanese, Russians and Italians.

 As a result,more western Allied troops survived the same severity of wound as experienced by troops of these other nations.

'Of course', I hear you say, 'they were richer nations, it was easy for them !'

But no : they had a choice, because the extra money devoted to this extraordinary care of the wounded could have been allocated elsewhere: to more and better anti-tank artillery, for example.

An extraordinary effort to produce the best anti-tank artillery ever made was , in fact, probably the cheapest way for the Western Allies to have ended the war against Germany at least a year earlier than it did, saving millions of lives all around.

I raise the genuine issue of better earlier anti-tank artillery versus the best possible military health care to remind us that even total war still leaves us with genuine moral choices.

More Lancaster bombers versus more 17 pounder anti-tank guns versus raising everyone's morale by generously providing penicillin enough for all people were some of the choices - part political, part moral, part economical - that leaders had to make in WWII.

Making the wrong ones meant the war dragged on longer than it had to, costing more lives lost.

It is not enough to say Churchill won the war in 1945 ; better to ask, could he have won the war in 1943 ?

In 1940, Henry Dawson was battling a near universal mindset among the world's research-oriented doctors of that time : that a medical researcher's only task was to determine that disease A was caused by bug B and that bug B was killed by compound C.

Then, like sleeping under a bridge, the researchers considered that the cure for disease A was open to rich and poor alike : pay for three weeks of needles at $10 a shot: together with doctors fees, say $250 in total.

When the annual wages of the working poor, if they found work, was very lucky to be $750 in 1940, that was a cure well beyond their reach.

Besides the fact that their disease might be far harder to cure than that of someone well off, due to the cumulative affect of their lack of good nutritious food for years and years.

Or that fact that living, as they did, in poor and crowded housing, disease A was more likely to come back again, even after an impossibly expensive cure.

Now what if disease A is something one gets from having open wounds - such as the open wounds all civilian mothers have after childbirth, or the open wounds that soldiers get after exposure to shell fire in battle.

How do we judge western Allied governments unwilling to provide the only life saver for disease A , either to any civilian moms (except those personally known to lead disease A researchers) or to any soldiers with wounds so severe they will be discharged and pensioned off, if they live ?

And how do we judge these governments when at the same time, they are gladly willing to provide live-saving compound C  (totally free !) to men who had either very high and very low peacetime incomes, just as long as their war wounds (by sheer luck) are only moderately severe and they can be expected to return soon to combat duty ?

Is this attitude not different in kind from that of the Nazis, but merely different in degree ?

Dawson had no realistic expectations that a few small injections of a very crude penicillin powder, hastily made in a few weeks, would cure such an incurable invariably fatal disease as subacute bacterial endocarditis, (SBE), then as now the acid test of all infectious diseases.

His powder had only about 8 to 9 units of penicillin per mg in it ; ie it was only about .56% pure.

The rest (the remaining 99 and 44/100ths worth),was in many researchers' minds, "junk".

Rather as they later described most of our DNA : "junk".

I believe Dawson considered his little bit of brown powder to be .56% penicillin and 99.44% pure love.

99.44% pure care, concern, caring.

For Dawson was judging his attempt to save Aaron Alston and Charlie Aronson by a much different - and much more moral - acid test.

To Dawson, SBE in the Fall of 1940 was not the acid test of infectious disease, but rather the acid test of pernicious morality.

These SBE patients were be judged to be 1940 America's "4Fs of the 4Fs", suffering from the militarily most useless disease on earth and not worthy of wasting any precious medical resources upon.

Now a doctor named Francis Peabody that Dawson had hoped to train with (but who died of cancer before that could occur) had earlier and famously said that the care of the patient begins (only begins in fact ) if the doctor first cares about the patient.

A single doctor can't hope to directly save everyone dying in a big war.

But by setting a very public example about caring for the least of these, those judged "unworthy of life", even in the midst of a war , they can hope to begin to still the trigger fingers of those all too willing to kill prisoners  just because 'it is too much bother to bring them back to our own lines'.

Only when the world is willing to care about "useless" others, even in the midst of wars, can we expect to begin to see war deaths reduced to combat mortal wounds, and then to ultimately see lesser and shorter and less brutal wars.

Only in a world where ordinary people care about others judged "useless", can we expect to still the hand that dropped the pellets at Auschwitz .

Which is why I earnestly claim that Dawson's Crude was the best and only cure for the Auschwitz Disease ....

"Pax Penicillia" : how Churchill's Britain won the war and lost the peace

The decision by Winston Churchill's (Tory) Minister of Supply (MoS) not to divert the money for one additional Lancaster squadron, used to bomb civilians in Europe, towards providing enough penicillin for British (and European) civilians resulted in Churchill's Tories winning the war for Britain --- but at the cost of losing the peace.

By contrast, when the (left-leaning) War Production Board (WPB) decided to greatly up the production level of American penicillin from the miserably niggardly amounts proposed by the (right-leaning) OSRD , the resulting surplus provided State Department diplomats with the amazing opportunity to wrestle Victory's moral  authority from Britain (which claimed - somewhat incorrectly - to have stood alone against Hitler) to the tardy latecomers Americans.

Forget Chewing Gum and Coca Cola, or even the A-Bomb , the single best means for American diplomats to win friends for America was by providing the gift of life to people dying of sulfa-resistant infections all over the world.

And thus, American "Pax Penicillia" replaced the "Pax Britannica"...

Saturday, February 16, 2013

Penicillin's "Bengali Famine Years" : 1943-1944

It was not America and Britain, it was not even the British and American governments ,that made the momentous decision, between late 1942 and early 1943, not to divert tax money just a little away from bombs and towards penicillin production instead.

This decision led, over the period of 1943-1944,  to a Bengali Famine-like situation among the Allies over shortages of live-saving drugs for civilians.

It was only one government agency in each country that made that decision ; albeit all-powerful agencies in the middle of a war.

But I do not believe they acted contrary to the informally expressed sentiments of their country's war cabinets.

Let the record note their names : Vannevar Bush's weapon-developing agency known as the OSRD in America and the Ministry of (Army) Supply (MoS) in Britain, with the common link urging them into this course being Sir Howard Florey.

By contrast, diverting even a tiny tiny amount of the government's war resources to the issuing of firm standing orders for penicillin purchases could have provided adequate semi-purified natural penicillin to treat all cases (civilian and military) of patients dying from blood poisoning that were resistant to the only life-saving alternative, the sulpha drugs.

Let me make it perfectly, morally, clear : the fundamental issue was not that penicillin was in short supply : it was that any method of saving those dying of sulpha-resistant blood poisoning was in desperately short supply.

These diverted resources , expressed as firm government orders for penicillin at currently profitably prices ,would have stimulated private capital to make good use of current technology and of idle rural factories that had closed because of the war , as well as unskilled rural labour also left idle because of the war.

As models that this could have and in fact did work in practise, one only needs, in the case of Britain, to point to Glaxo's first low tech but efficient penicillin factories cobbled out of bits of unused space in other people's factories.

And in the American case, to point to an enterprising rural mushroom farmer called Raymond Rettew who briefly became the world's biggest penicillin producer, in the late spring of 1943.

FDR's party did not lose the 1944 election over this issue , because another part of his American government (the WPB, War Production Board) chose to totally reversed this decision, and in spades.

But Churchill's party did ultimately pay the full price for this decision made by the MoS (led by his fellow Tory, Sir Andrew Duncan) not to push for enough penicillin production resources to help civilian as well as soldier, later in the war.

That was when his party overwhelmingly lost the general election it was supposed to romp home in, July 2nd 1945 .

Churchill's equally callous decision not to stop the wartime Bengali Famine in which four million people died ( "If there really is a famine, why hasn't Gandhi died?" he sneered) probably also sealed the chances of Churchill's Britain holding onto the Indian Empire.

If Florey had been even moderately left wing rather than very right wing, he might have gone to other more left wing oriented agencies of the British and American governments and the wartime penicillin story could have been very different .

If the wartime history of Civil War Era America was written as historians write the Pollyanna story of wartime penicillin, there would be only one America and one government ,with no sense at all of conflict between different parts of America.

My work on wartime penicillin will make it very clear that two agencies of the American government, the OSRD and the WPB were not in agreement on penicillin production levels and methods but in conflict.

 Just as in the UK,  Howard Florey/MoS and Harry Jephcott/Glaxo were not in agreement on these same issues but in conflict.

And I will make it clear that there were no technical reasons why civilians could not have penicillin in 1943-1944 , rather it was the result of a political and moral decision not to produce one less bomber squadron if that was the cost of bring penicillin to dying civilians.

For these were penicillin famines by government fiat : Bengal-on-the-Potomac and Bengal-on-the-Thames.....

Friday, February 15, 2013

"Weaponized" penicillin to be a frontline Army wound powder and hence the needs of the Navy, Air Force and Civilians are not relevant...

One of the most historic of meetings and dates in the whole extended penicillin saga occurred on September 25 1942 at Portland House in London England .

 In fact one key participant at the meeting sensed this so greatly that he even whispered that history was going to view it that way, into the ear of the chairman as the meeting broke up.

In many ways, this meeting was very odd as well as being very historic.

Mostly because who called it and who it asked to attend.

It was called by one of the powerful of the many British wartime Ministries, the Ministry of Supply (MoS), which  actually only supplied the Army (and perhaps in few things , the other two armed services as well) - but never ever supplied civilian needs.

Ronald Clark in his biography of Ernst Chain says this meeting was proceeded by the Ministers of (army) Supply and  (civilian) Health, Sir Andrew Duncan and Ernest Brown, jointly "taking the idea of the immediate mass production of penicillin to the War Cabinet".

If so, it was possibly informally done via a Ministry "Minute" to the War Cabinet as neither gentlemen were ever members of the small War Cabinet : even in peacetime many many British politicians become ministers, without ever being becoming cabinet ministers.

And significantly, no one from Brown's civilian-oriented department was at this historical meeting.

This is a very important matter to resolve definitely, in part because the peculiar nature of this crucial meeting spelt the doom of  Winston Churchill and his party in the election of June-July 1945.

How on earth did penicillin the universal lifesaver ever come be re-jigged as something only useful to the combat needs of the British Army ?

None of the drug firms summoned to this meeting (which did NOT include the very politically powerful firm of ICI ) had any real political or military influence - they didn't push for the meeting to take place but merely came when they were called.

 But two of the four scientists had the meeting certainly did have good credentials with the Army ( but not Navy or Air Force) medical authorities and were of the correct Tory stamp: Howard Florey and Alec Fleming.

They had pushed for this meeting with the Army's supply department.

So, the army-oriented MoS was there in full force with six top officials along with two top officials from the Army Medical Branch charged with drug procurement for frontline casualties.

Missing in action at this meeting - by design - was the Navy, Air Force and any officials representing the Civilian interest in penicillin production.

Florey and Fleming both strongly saw penicillin as basically a useful supplement to the cheap abundant and systemically-oriented oral sulfas,  with penicillin to be used primarily as in "local applications" for frontline combat wounds.

True, the Navy and Air force casualties were more often treated at large hospitals (and more often simply died in action)  than in the case of the Army.

The Army had to deal with the fact that more of its casualties emerged as alive but wounded ,compared to the other services, which was the good news ---- but the bad news was that their wounds were usually about to get badly infected as a result of the primitive conditions at the front line.

A highly concentrated anti-bacterial drug with a long storage life and stable under almost any conditions as a dry powder (ie highly pure as well as highly concentrated) seemed essential.

Then and only then could it be suitable to sprinkle on open wounds immediately as they occurred on the front lines by barely trained medics or ordinary soldiers themselves.

 Or for a busy front line doctor  in am ambulance tent to inject, with a little sterile water, in or around those open wounds, within hours of the wounding.

Chemically, sulfa was born fulfilling these requirements - but penicillin didn't really meet them until after the six years of war was long over.

But unfortunately, no thorough controlled clinical trials of this claim that a frontline local application anti-bacterial medication would be essential for wounded survival was ever done.

At war's end, the general assessment was that, in fact, the frontline powders and needlefuls of these "local" penicillin and sulfa (ie applied directly into the wound) were not essential.

 Instead, the wonderfully low rate of death from wounds (versus either the much worse record of WWI or of WWII Germany)  was felt to be more due to the Allies' quick thorough debridement (removal) of dead wounded flesh , front line blood transfusions and policy of rapid evacuations of wounded soldiers to clean, quiet ,well equipped base hospitals .

That ---- and the general good health of  wounded Allied troops, because they had been kept well fed and lived in warm sanitary conditions in the months before being wounded.

In the military base hospitals and civilian general hospitals,  wartime sulfas and penicillin did prove to be reliable life savers when given as a systemic, if and when blood poisoning was suspected.

In fact, "crude" liquid penicillin (totally un-concentrated and totally un-purified) injected by needle and prepared in the hospital daily by Dr Duhig, saved lives as a systemic at a Brisbane general hospital --- and could have done so in the military equivalent.

Ooops ! It did do so, at Cairo's largest military hospital, where Dr Pulvertaft treated patients with liquid systemic crude penicillin he made daily in the hospital.

How did the Navy, RAF and the public, along with those politicians sworn to protect these groups of humans beings, react to the idea that penicillin was to be made under the control of the Army and for war casualties only ?

Seemingly with initial indifference - though by the Spring of 1943, a freelancing Navy Surgeon Commander had converted the Admiralty's under-producing vaccine operation to a huge penicillin factory supplying all of the Royal Navy's penicillin needs.

The Admiralty had always 'looked after its own', had always produced its own vaccines and serums so it didn't take long before the Navy medical brass had a look around at the penicillin factory and beam approval.

(Unlike the Army and Air Force, they had won the battle to retain the supplying of their needs by a naval units controlled directly by the Admiralty itself.)

For some rather sad reasons, the Air Force had relatively few wounded, for its size, and for other reasons, the treating of the wounded and returning them to battle was not an operational priority.

Over the course of the whole war, each of the British armed service got about one third of the money spent on the war. But in terms of manpower, of five people in uniform there were three in the army versus one in the RAF and one in the Navy/Merchant Marine.

This is because the RAF and RN/Merchant Marine had lots of big expensive machines that if  "taken out of action" usually resulted in a 100% loss (aka "sunk" or "crashed"), while except in disastrous retreats, this rarely happened to the Army and its smaller cheaper machines.

The Allied Armies proved very much better, for example, at recovering even badly damaged tanks , as compared to the Germans.

In terms of personnel killed, the story is more complex.

Most of the RAF were never in real danger of dying but among those that flew, rather than maintained aircraft on the ground, the death rate was very high -often as much from operational accidents as enemy fire.

In Bomber Command, 55 of 100 fliers died before finishing their tour of duty.

Again there were relatively few wounded fliers versus a high rate of deaths - with the relatively few that survived their plane being hit only doing so by remaining out of the war, as German POWS.

People losses anyway and quite frankly , were not a big concern to the RAF : it never had a shortage of qualified recruits.

The RAF was seen as very glamorous to those determined to be very brave and seen a very secure place to spend the war to those with peacetime technical and engineering skills and no urge to be brave.

 Manpower sustaining by speeding the recovery of the wounded was never a critical issue for any of WWII's air forces.

Replacing lost machines ( and frequently the training of new flier recruits) was always their obsession instead.

The world's navies were almost as attractive as the air forces, and rarely suffered from manpower worries and wounded recovery worries.

Instead, the sudden loss of entire town-sized machines (battleships or aircraft carriers) with all two thousand on board dead at one stroke, from a single torpedo or bomb, was their admirals more realistic nightmare.

In addition, while the Merchant Marine had particularly high losses of lives, against the relatively small number of its personnel, the merchant marine crews' relatively high pay and lack of onerous military discipline kept manpower replacement issues at bay.

When all factors are combined, at a gross figure level, the three armed services all lost about the same percentage of dead against the total number enlisted in each service, though as I have shown, the chance of death in service fell very unevenly.

In the case of the Army, it fell hardest on the infantry, followed by the tank crews and often the combat engineers.

Because almost no one wanted to join the infantry, it had few volunteers and generally the infantry got those conscripted recruits so totally lacking in useful education and technical skills that no other section of the Army wanted them.

To combine metaphors : incredibly enough, in all the Allied military , the very pointy end of the offensive stick came from the very bottom of the barrel.

In a nutshell, this is why the Germans and Japanese proved so very hard to defeat.

Over the whole war, the death rate varied greatly among the three services - the Navy death rate actually went down as the war progressed, the RAF's deaths peaked in 1943-1944, while in the case of the Army it was expected to rise suddenly and sharply to WWI Western Front levels, following the invasion of Europe.

The Army faced a short sharp period of potentially huge casualties - most wounded and infected but in Allied hands, not POWS.

If they weren't too badly wounded and the right anti-bacterial medication was at hand, the Army might be able to get most of the wounded back into battle formations before the war ended.

Just as well ,as there were no new men hustling to enter the infantry replacement pipeline at the other end.

At the very least, the thought that if and when they got wounded, the Army could heal most of them, would make the infantry less reluctant to rise up and advance against deadly Mortar and Machine Gun fire.

Or so the Army brass fondly believed.

I have tried to make the Fall of 1942 case for the British Army making penicillin just for itself seem as sensible as possible.

But in fact, it was a case going around with its nose full of Coke and Ecstasy.

In the fall of 1942, the really big medical story wasn't the rise of penicillin ; it was the decline of the previous wonder slash miracle drug : the Sulfas.

After five years of ever newer, better sulfas coming on market, that pipeline had died.

It was a double whammy of disaster, because now the current sulfas were proving less useful as more and more bacteria were becoming resistant to them.

Either a disease's bacteria totally failed to respond to sulfa and the patient died, or so large a dose need to be given that some patients again died from sulfa's toxicity at high dose levels.

This was not some sort of a Army front line versus RAF or Navy base hospital versus civilian home GP issue --- the stuff just didn't work as well as it used to ---- anywhere : in the UK , in battlefields world wide, in Germany and in Russia.

Full stop.

Sulfa's improved replacement - and it might be penicillin, who can tell  ? - would face immense pressure to made in sufficient quantities to fulfill all needs all over the world, in civilian systemic use as well as front line local antiseptic use.

This was Florey and Fleming's greatest intellectual failure : the inability to see this.

Now neither of them were conceptual thinkers, as even their most ardent supporters admit in print - they were uniquely tied to the concrete and conventional here and now rather than to abstract speculation.

 By contrast, Rene Dubos didn't have their success in finding a useful anti-bacterial medicine from microbes, (his luck was bad) but he could  clearly see the Big Picture issues in ways those two could never hope to.

I do not know where Dawson stood for sure on this conceptual versus concrete issue since we have no personal papers of his - but the fact that Dubos always felt highly of him suggests a hint.

Certainly if deeds are better than mere words, Dawson never acted at all as if penicillin had to be first weaponized before it could become useful to humanity.

He was the first to give the world a patient successfully treated by a life-saving antibiotic because he saw semi-crude penicillin as more than good enough to inject safely into a human being : Dies Mirabilis, October 16th 1940.....

Wednesday, February 13, 2013

The first - and internally fatal - Tory response to the Beveridge Report : the Ministry of Supply takes over Penicillin ...

To make sense of this claim, we need to clear as to what the role of Britain's powerful wartime Ministry of Supply actually was.

The Ministry of Supply (the MoS) was never the British equivalent of the American War Production Board (WPB), no matter how many times this claim is offered up.

In fact, it was very much closer in spirit to Vannevar Bush's powerful Office of Scientific Research and Development (the OSRD) per the role set out for both under statute , than it was to the statutory role set out for the WPB.

Britain's Ministry of Supply strived to supply the military's needs - period. Unlike the WPB, it did not try to arbitrate between the conflicting demands of civilian and military claims upon scarce material and manpower.

Equally, the OSRD did  NOT deal with all of America's wartime science and research efforts , a point that no doubt Jesus Christ himself will have to repeat again and again to academics on Judgement Day and on into all Eternity.

It only dealt with that amount of science and research that involved the designing of  (but not the production of)  new weapons that could come into use, during the current war.

Bush was very very careful to sharply limit the parameters of his organization, all to make it more dominant within its narrow but vital sphere.

So when Howard Florey went to both the OSRD and to the Ministry of Supply to help in the production of penicillin - rather than going instead to ask help from the American Public Health Service and the British Ministry of Health, he had already made it very clear where his penicillin priority lay.

He wanted additional penicillin production yes --- but only sufficient to supply the armed forces, period.

Florey was strongly conservative, as were all the key individuals within the Minister of Supply and the OSRD : Big Government to them was abhorrent.

Thus the sudden willingness, eagerness even, of the Ministry of Supply in the Fall of 1942 to go all out and seize control of all of the British commercial penicillin production has to be seen as ideologically surprising.

Unless it can (and should) be seen as the opening conservative counter-attack against the rumoured radical notions of the Beveridge Report.

A preemptive move to ensure that the Ministry of Health (also run by a Tory minister but with wider than just military responsibilities) didn't dominate penicillin production.

If is often claimed that the Ministry of Supply took over all of penicillin production because the Scottish-born minister was an old pal of fellow Scot, Alec Fleming, who asked him to do so.

Politicians -  grant us at least this - do not spontaneously fall upon old friends and their requests with open arms --- not  unless it suits us.

In September and October 1942, Fleming's request much suited Duncan and the British Tories.

In late September and October 1942, the tenor of the Beveridge report, though as yet unreleased, was well known within the top officials of Whitehall.

It called for a placing the values of equality and egalitarianism at the core of the British government - a notion intensely hostile to Tory values.

For penicillin, all this Beveridge "equality" talk could only mean one of two things.

It might mean divvying inadequate amounts of penicillin equally between dying civilians and dying soldiers - when Tories felt the most vital hope of penicillin was that it would help maintain current front line troop levels without the need to "call up" middle class men (their voters) now at home engaged in war work.

Or it might mean diverting the cost of one additional Lancaster squadron (three million pounds) away from the all-out bombing of civilian Germany , towards creating more penicillin factories on the successful Glaxo model.

Glaxo had taken up space in bits of idle factories and by using local cheap and plentiful unskilled labour,( aka women) , had cheaply but efficiently produced a lot of penicillin with current low technology methods and equipment.

(Basically making penicillin as if it was a milk product , using the very abundant modern dairy equipment existing everywhere thanks to the 1920s civilized world's mania over pure milk.)

A lot of similar factories could be quickly brought up to speed, supplying a good deal of penicillin, without requiring too much vital material like stainless steel, already in desperately short supply.

If all this sounds very familiar, that is because this solution is what Britain in the end was forced to do -  but very late and only under intense public pressure.

If it had been done wholeheartedly in the Fall of 1942, there would have been no highly public late 1944 civilian penicillin famine crisis.

But the Conservative bits and bob of the Coalition Government wanted no part of equality and penicillin was just the first of many counterattacks against the threat of Beveridge.

They were unsuccessful in the extreme, blowing what had to seem to them (and to Labour !), a sure electoral victory at war's end.

"Unfair distribution of a vital commodity in short supply" , to quote The Times (of all people !) referencing an earlier debate over Hugh Dalton's fuel rationing proposals , was totally anathema to the British public.

In June 1945, what little polling type information we have suggests it was the unfair rationing of medical services that moved people to Labour .

The most current example of that unfair medical rationing had to be rationing difficulties with life saving penicillin.

Let me repeat that : "life saving". This was not just temporary unfairness in allocating housing or clothing : this was the unfair allocation of life itself.

You can't get a more "vital commodity" than life itself : to switch from the specialized language of the economist to that of the political scientist trying to account for a surprise pattern of vote changing, "life" is a very salient issue.

If so, the unexpected and total defeat of Churchill's Tories in June 1945 can be seen as having its origins in the Fall of 1942, when the Ministry of Supply (and Howard Florey) successfully re-defined the shortage of penicillin (contra Beveridge),  as a shortage of military penicillin, civilians be damned.....

Tuesday, February 12, 2013

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

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

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

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

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

Immaterial that Charlie was almost certainly Jewish as well : the point to Dawson was that Charlie was a fellow human being, end of story.

Social medicine, Dawson's domain, says that medicine is not just the narrow manipulating of bio-chemical activities to save lives.

It holds instead the view that most people die prematurely, not because their bodies failed or because medicines failed, but because the world around them see them as not worth much, so not worthy of much effort, time and expense to try to save them.

Doctors who challenge these utilitarian views by their voices and their actions indirectly save far more lives than do their equally competent colleagues who may directly save more lives, but who are content to only save the lives their culture deems worthy of saving.

The Allies (rather like the Axis, differing only in degree not in kind) divided the world of World War Two into three parts, like Gaul.

There were the enemy-oriented people and the allies-oriented people : themselves further divided into 1A allies and 4F allies.

Until June 1943, only enough American resources were going to be devoted to penicillin to ensure that the needs of the 1A allies would be met.

Then the American WPB (Wartime Production Board) made its most surprising decision ever : that a considerable portion of America's bomb and bullet making potential would be diverted instead to making lifesavers - penicillin lifesavers enough to save soldier and civilian alike.

This was not a decision followed by Britain , Canada and Australia.

They decided to divert only enough of their country's resources to penicillin-making to fill the needs of their armed forces at a minimal level.

Winston Churchill and his Tory-dominant government took the lead on this decision, by their broad hints and inaction (if nothing else), and the other Commonwealth nations chose to follow his lead rather than that of the WPB.

A single additional Lancaster bomber squadron is about three million pounds in 1943 money,(about a million pounds in planes , plus two million pound  more for the 500 members of the squadron , hangers, armaments, fuel etc).

This amount would have paid for enough new penicillin production facilities such that by early 1944 , Britain's could have supplied its civilians as well as its soldiers.

Ie, match the Americans' penicillin output, despite using a lower level of technology.

We know well enough the costs of a Lancaster squadron and  the costs of Glaxo's low tech but highly efficiently run bottle-penicillin factories , to be able to make this claim with a great deal of certainty.

Churchill, however, chose 'LANCs over PEN' and paid for it in the surprising election results of June 1945 ; the inequalities of  wartime health care provision being the number one reason most people chose the egalitarian Labour Party over the war-winning Tories.

America's super abundance of wartime penicillin allowed it to use penicillin as a tool of diplomacy , replacing British influence with that of the Americans at every turn : replacing Pax Britannica with Pax Americana,  again causing Churchill to "win the war but lose the world".

Dawson did not force the WPB to make the decision it did, though certainly his uniquely civilian oriented approach to penicillin treatment, starting way back in September 1940, must have played a part.

But the WPB pledge was just that : a pledge - it was up to industry to carry it out.

Industry was willing - even eager - to build high tech buildings out of extremely scarce materials now suddenly obtainable thanks to top-of-the-drawer allocation quotas for would-be penicillin producers.

Postwar, those buildings would give them an early lead on their competitors.

But they weren't so willing to make biological penicillin in those shiny new buildings, not with rumours than synthetic penicillin was just months away.

Dante Colitti forced their hand.

In August 1943, the junior staffer, a surgical resident at a small hospital a mile from Henry Dawson's hospital,  was about to get married and go on a honeymoon. He didn't have to go poke his nose into the affairs of a patient in the non-surgical part of the hospital.

But he did.

He was moved by what he had heard about the dying Henry Dawson a mile away being willing to steal government penicillin to save the weak and the small.

 And perhaps because Colitti himself was a lifelong "cripple", suffering from TB of the spine.

Dante decided to risk his own career by intervening over the other more senior doctors' heads on a patient that wasn't even his --- urging the patient's parents to call the Hearst newspaper chain directly, to ask them to help obtain the tightly rationed penicillin needed to save the baby's life.

The resulting day by day heart-rendering accounts and photos of the life-saving efforts for little Patty Malone finally - albeit 15 years late - put a human face on penicillin.

Suddenly the population woke up to the fact that they wanted/  needed  penicillin -right now ! - and what was their Congressman doing to see that it happened ?

Doctor Mom, in high dudgeon , can provoke fear even in generals, industrialists and Presidents and soon John L Smith, boss of the biggest potential penicillin producer (Pfizer) got the moral message as well.

The chain reaction : Dawson + Charlie : Dante Colitti and Patty Malone:  John L and Mae Smith and memories of their own dead daughter  + Pfizer : tons of and tons of penicillin by April 1944,  is clear enough .

Also clear enough is an ageless message : one person, even if they are dying, can indeed make a world-quaking difference .....

Sunday, February 10, 2013

Penicillin : biologic 1929-1939 , chemotherapeutic 1939-1949

In 1944, Frank M Berger ( later creator of the post-war drug Miltown but then just a worker in a local municipal public health lab in the remotes of northern England)  came up with an unique way of making and using penicillin.

On second thoughts, his method might well have been done first by Alexander Fleming's Wright-Fleming vaccine institute and their pharmaceutical distributor Parke-Davis about 15 years earlier : Penicillin the Biologic.

On further further reflection : should have been done first by Alec Fleming.

Berger's penicillin was only concentrated and purified to the point that not too much penicillin was lost or too much scarce labour and expensive equipment used to create and extract it.

This biological penicillin, Berger claimed,  was safe, potent and cheap  ---and liquid.

Liquid --- and stored cold in the hospital that made it, ( not usually stored more than a week at most), until the next life-threatening case of blood poisoning in that same hospital was cured by its systemic (ie by needle) application.

The immediate use of whole liquid blood (another biologic dismissed earlier in the war) right at the front lines of combat was/is vital for survival of the badly wounded soldier.

But immediately pouring penicillin or sulfa into the man's dirty wound (ie via "local" application) - counter-intutively - is not.

Quickly getting him back to a hospital-like setting where penicillin or sulfa can be given him systemically, and under more carefully monitored conditions, was still useful.

But, it proved not essential to do so immediately even there ; often the staff could afford to wait to first see if signs of systemic infection were present (usually via a temperature rise.)

Ie, Howard Florey's 1939 claim that penicillin was only useful if made into a dry powder that remained stable at room temperature for months at a time was totally in error --- if life-saving was to be its main (wartime) role.

Berger's efforts were merely the best thought out among the number of doctors advocating biologic penicillin, not by any means the first (Dawson) or the most stunning (Duhig) .

By contrast, Florey was the chief high priest of Penicillin the  Chemotherapeutic, (pure,dry,powdery), from first to last its leading advocate....

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

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

The first, in November 1941 ,was obtained from Dr Rake at Squibb - a higher producing mutant from Fleming's original strain.

The second time in November 1943, some un-named strains were obtained from Robert Coghill of the NRRL , while he was visiting Oxford .

But in the two crucial years in between ?

I see bugger all evidence that Florey got the latest improvements in penicillium strains as they emerged at Peoria. (Prove me wrong, please) .

The mycologists at the NRRL research centre in Peoria had steadily improved and improved and improved again Rake's variant and their final version, NRRL 1249.B21 produced - via surface cultivation - most of the world's wartime penicillin until quite late in the war.

At that point, submerged strain NRRL 832, from a non-Fleming strain first found in Belgium, took over.

I believe that Merck's chief consultant and OSRD medical chief ( giant conflict of interest alert !) A N Richards, supposedly Florey's second closest American friend, using as an excuse that America was now at war, deliberately held back the giving these improved strains to Florey.

All to further America's ( sorry ! Merck's) post-war commercial opportunities.

Nicolas Rasmussen, in his article "Of  'Small Men', Big Science and Bigger Business", looks much closer than most historians at the day to day workings of the medical wing of the famous OSRD.

 He points to several examples where Richards authorizes the further spending of taxpayers' money, supposedly only for war weapons, on drug research that no longer had an obvious military use, because he claimed that keeping  American's edge in their development would definitely benefit the nation.

If not in this war, or any war, how would the drug's successful development benefit a nation at war - supposedly the sole purpose of the OSRD, whose mandate was set up to expire the moment peace was declared ?

Richards doesn't say.

So let me suggest a more sinister purpose , because Rasmussen does not.

I note that the two examples that Rasmussen gives where the OSRD spends taxpayers money on projects that no longer seemed to have a military need were pet projects of Merck, the firm that Richards advised.

The first was the chemical synthesis work on penicillin , carried on well past the point (say June 1944)  when biological penicillin was being produced en masse and cheaply.

The other was after mid 1943, when it was clear that cortisone would not help pilots fly higher longer - an important advantage for any nation's air force if proven so.

Merck got nothing for all the money it spent on synthetic penicillin but its finally successful efforts on cortisone was and is one of its biggest successes for both its scientific reputation and its pocketbook (the two of course being closely related).

First success with Cortisone would be an advantage to America as well as Merck, over European (Swiss) competitors --- but synthetic penicillin's success could only have come by crushing fellow American firm Pfizer and given the field to Merck.

How then would that serve America's interests, rather than merely Merck's?

Because Europe wasn't even in the running on biological penicillin in 1944.

Perhaps Richards, already a pensioner when he took on the job of heading the OSRD medical wing and with the rigidity of old age, still believed synthetic penicillin would better Pfizer's penicillin in price and yield.

Then Merck would beat their only European synthetic penicillin rival : Florey !

Normally, Vannevar Bush's OSRD - as in denying the British to atomic energy research - did a better job of using taxpayers' military-assigned money to screw America's European Allies' commercial chances after the war , without favouring any one American firm.

Richard's willingness to screw Pfizer and even his friend Florey, shows just how much further he was prepared to go to aid Merck.

But he needed pliant helpers  to succeed.

Luckily for him, the  NRRL's Robert Coghill seemed to have had a hard time accepting that research paid for by his employer , the US Department of Agriculture and ultimately the American public, belonged to the USDA.

And that this research shouldn't only go where a different agency's chief bureaucrat, A N Richards, wanted it to go - though he hadn't paid for it and had no statutory (legal) control over it.

However , I see Coghill, a misplaced chemist running a biological program, wanted in so badly on a "technically sweet" chemical problem (the synthesis of penicillin) that he sold out the farmers he had sworn to help.

Synthetic penicillin would only negate the ready market for  hundreds of thousands of tons of farm waste corn steep liquor, farm waste whey and farm waste crude brown sugar, all used in the natural fermentation of penicillin and other antibiotics coming along in the pipeline.

Coghill did publicly announce that he was giving the top two commercial strains of penicillium (presumably NRRL 1249.B21 and 832) to the entire world in November 1943, about the same time as Florey first mentions having them.

Why ?

I can only suspect because they were about to become obsolete, as synthetic penicillin seemed only months away.

By April 1944, that no longer seemed so and Coghill was back on the side of the biological angels, publicly praising Pfizer's biological penicillin and modestly claiming a role in their success.

Coghill's talents seemed rather wasted in democratic America - I can see him as the ultimate bureaucratic survivor in Stalin's Russia, adroitly changing sides as the situation shifted, moment by moment.....

Friday, February 8, 2013

Re-setting the Allies' moral compass : the acid test of penicillin for wartime endocarditis

Please correct me : but in all my research I could find no indication that in his 15 years of medical research before October 16th 1940, (and he was a world-class expert in the area of strep bacteria) Henry Dawson had never written or spoken one peep - not one peep - on the subject of endocarditis, a very common and deadly disease, usually caused then by a variant of strep bacteria.

Dawson was a scientist who spoke and wrote a lot , so his silence , until October 16th 1940, was surely hardly from lack of opportunity.

Nor was it bureaucratically and professionally easy, in October 1940 anymore than it would be today, to go from being the director of an outpatients' clinic on chronic arthritis to suddenly becoming the lead doctor on a totally new treatment of such an acute cardiac illness as subacute bacterial endocarditis (SBE).

At least not in a big teaching hospital, with all boundary-conscious specialists rigidly defined in each area.

So we are still left with the puzzle explaining why Dawson literally gave his life to suddenly treat and cure this hitherto incurable disease, endocarditis.

It helps to recall that as a paid up member on the side of Social medicine at a time when War medicine was in the ascendancy in the corridors of Columbia Presbyterian Medical Centre that Fall, Dawson's ears must have zeroed in on the disease quickly voted "the absolutely lowest priority disease in all War medicine" : and that SBE.

The overall consensus that that the SBEs consumed endless amounts of medical care, generally only to quickly die anyway.

Or if they did by some weird chance recover - this time - they couldn't much useful war work with their weakened heart and anyway would surely succumb to a second bout of SBE.

Dawson might even have agreed with this assessment , albeit reluctantly, before October 1940 : nothing, not even the much vaunted brand new sulfa drugs, did anything to extend the SBEs' chances.

But to Dawson, if not to any one else in the world,  the written claims about this new , as yet untested, drug penicillin seemed to offer a way out.

It promised activity against SBE's green strep bacteria, good diffusibility and above all , near absolute non-toxicity.

The latter was critical because ("Blood, blood everywhere and not a drop to drink") ironically the heart's values have almost no internal blood supply and must be 'dabbed' by a drug filling the entire blood supply, as it whistles past the heart valves at break neck speed.

An internal "antiseptic" as it were.

Any drug strong enough to instantly push its way through the thick vegetation on the heart valves and quickly kill the strep within , as it rushed on by at 'breaking the speed limit speeds' was also strong enough to be toxic to the entire human body.

SBE was a "disease designed by a committee" : a committee of Devils creating a disease so devilish as to even frustrate God Himself.

SBE seemed an impossible cure -- surely a quick death following upon benign neglect was the most merciful choice ?

But none of the SBE experts seemed to feel as he felt ; none was willing to do the sort of heroic medicine required to at least give crude penicillin and SBE  the old school try.

Did Dawson begin to feel that this indifference to the possibility of curing SBE, "the polio of the poor", was just an excuse?

Did he not buy the claim that the difficulties of preparing penicillin together with all the preparations for war medicine and  for prioritizing medicine for the 1A fit  was the real reason for inactivity on SBE ?

Or was it really just an excuse to roll back New Deal efforts to do something medically for the poorest and weakest (the 4Fs) among us ?

Were there not strong rumours about that the Nazis were also abandoning the poorest and the weakest among the German patients, also using the necessities of war to justify their actions ?

Whatever ethical speculation led him to his decision, it is a fact that on October 16th 1940, Henry Dawson made the wartime treatment of the weakest of the weak, the 4Fs of the 4Fs, the ultimate acid test for the moral compass of the Allied cause.

It took him years - and cost him his life - but he got that moral compass set right, right in the middle of a bloody war.

Finally, treating the SBEs, the least of these, as we would want ourselves to be treated, became the practise of the Allies, not just another plank in their hollow public rhetoric....

two is a coincidence, three is a pattern : the OSRD on the weak and the strong

It is a commonplace to note that Vannevar Bush's wartime agency the OSRD, the biggest of Washington's many wartime scientific bureaucracies, favoured the strongest companies and the strongest universities.

Coincidence, say many.

But the fact that the OSRD, the strongest companies and the strongest universities all ganged up together to deny penicillin to America's weakest of the weakest seems more than a long stream of coincidences : it betrays a pattern......

Henry Dawson puts the Allied treatment of the weak and the strong to the "Acid Test"

This was Henry Dawson's Acid Test : during World War Two, did the treatment of the weak and the strong by the nations that ultimately made up the Allies differ in kind or only in degree from that of the Axis nations?

Any single individual - let alone a single dying individual - could not pose that question across a broad spectrum of issues and expect to force a response.

But in focussing tightly upon the Allies' differential medical treatment of the lightly wounded combat soldier and of his high school pal back home dying of endocarditis, Dawson did manage to hit a sore spot among the Allies --- across America and Britain in particular.

In late 1943 , Henry Dawson was able to make the Allied public realize that , on this issue,  their elite leaders differed far less in kind from the "the weak must die so the strong can flourish" philosophy of the Axis that anyone could have comfortably imagined back in 1939.

When the Allied public forced their leaders to alter course and provide penicillin, during wartime, for endocarditis patients, the whole of civilized thought shifted course --- permanently.

No mean response for a persistent little team locked away in a ward, a lab and a doctor's office ......

Thursday, February 7, 2013

Dies Mirabilis : October 16th 1940 : the first ever peacetime 1A Draft and the first ever 4F penicillin needle

Oh, to be there , just to see the Janus-like faces of Columbia University's campus on dies mirabilis, October 16th 1940.

Over in one corner, led by blustery University President Butler himself, most of the campus was busily and very publicly (cue the news reel cameras) engaged in the nation's first ever peacetime draft registration process : busy triaging the best 1A youth away from the 4F rejects.

Over in another corner of the campus, a tiny band of four individuals was just as busily triaging away in the opposition direction.

Led by two world war one frontline military veterans, they had deliberately - almost provocatively - picked this, of all sacred days in WASPish America's calendar - to usher in the Age of Antibiotics.

Their choice of the first ever patients was equally provocative, not merely that one was Black and the other one was Jewish, but because both were SBEs : the 4Fs of the 4Fs, in Draft Registration terms.

 Both were dying from the disease rated as about "one hundred and ten" on a priority list running from one to one hundred on diseases of military priority.

Later on (by 1943), Columbia's campus again resumed a Janus-like cast, as one part beavered away at The Bomb, determined to se it at working ,killing, before peace broke out , while in another part of the campus, our tiny team was at work trying to see penicillin in high production, before death and pestilence broke out in the occupied lands.

But I like to think we will never again see such a contrasting day in such a small place, as we did on October 16th 1940 at Columbia University ....

Wednesday, February 6, 2013

OSRD /1942: did Manhattan Project type thinking bleed over and obstruct the Penicillin Project as well ?

It is crystal clear that Merck's top scientific advisor A N Richards was never a strong advocate for fast-paced penicillin development within Merck, as that drug company casually messed about with penicillin, from November 1939 till August 1941.

That is, Merck had 18 months of some sort of commercial and scientific activity around penicillin , before Howard Florey actually arrived on the scene.

But Florey eventually made Richards a strong convert to the idea of having Richards' military medical weapon oriented agency , the famous OSRD , use penicillin for secret military advantage over the Axis.

It is not clear that this would have extended - in practise - to denying penicillin to dying Axis POWs.

 But keeping penicillin a secret from the Axis definitely would have denied penicillin to dying Allied POWs behind Axis lines : something that all of Florey's, Richards' and Fleming's present day defenders universally ignore.

Very much to his credit then that WWI vet and WWII military officer and doctor Robert Pulvertaft did dis-obey orders and shared the secrets of penicillin production with Axis-friendly Turkish doctors.

But imagining a Canadian dying of sulfa-resistant blood poisoning in a German POW camp and the Canadian POWs being told by the German doctor, 'we could save him , if only we had a bit of this Allied-invented penicillin that we've been hearing rumours of'.

When the Canadians ask why doesn't the doctor get some, the doctor says that if the Allies won't even share penicillin with their own dying civilians, how can they be expected to share it with the enemy ?

But could penicillin have really ever have been a potentially secret and successful medical weapon ?

Here I , following closely on Henry Dawson's thinking,  definitely part company with Florey and his friend Richards.

Henry Dawson demonstrated - in just five weeks - and under conditions as fully primitive as Fleming's, that one could quickly make a lot of crude penicillin that was non-toxic when injected into humans.

If Fleming and Dawson could do so, (quickly, easily and cheaply, ) so too could the fired up Nazi war machine.

Not so, said Florey -and his side kick Richards.

The scientific characteristics of penicillin haven't changed at all since September 1928, but now , thanks to Florey, the scientific rhetoric totally had.

Florey tells his readers and listeners, to ignore completely what Fleming-the-author says is "penicillin".

To wit, 'a mixture of about two dozen unknown compounds in a slurry of water that is non-toxic even if injected in very large volumes internally, and yet has marked anti-bacterial affects'.

In my revision of the facts, says Florey in his first August 1940 article, "penicillin" is now actually just one of those compounds.

All the rest and all that water are just dirty, dank and dangerous.

Only if penicillin is first pure, dry and stable is it any good.

Because where it is really good , is in the front lines as a local antiseptic for open war wounds (here I do still agree with Fleming) ---- and that idea won't work if crude liquid penicillin must kept viable in portable electric refrigerators.

Who ever has heard of such things ?

But as Florey tells Richards how complex and difficult the purification process is, Richards grows despondent again, but never the less this information does go into the back of Richards brain.

Only to re-emerge in early 1942, when the forces of war censorship and secrecy can be employed in full bloom.

Because complex and expensive separation and purification processes had become very much a two-edged sword for American military science and industry.

Artificial rubber was vital to the war effort - it was easy to make but a real bugger to separate the good rubber from the bad.

Dried blood products held real promise at the front lines - but only if their separation wasn't so complex.

And the Atomic Bomb - a piece of cake to make it work - if only we could get enough pure U-235 separated.

At some point early in 1942, these problems suddenly became military and commercial opportunities in the minds of the OSRD's highest officers.

If only rich, un-bombed America could solve these complex purification problems - and then keep the details secret - this would give them a big military advantage over their poorer enemy opponents.

And give America a post-war commercial advantage as well over its smaller poorer Allied friends like Britain.

So just as we see an abrupt turn around , in mid 1942 , from the OSRD re sharing much atomic information with the British, we start to see the British also get less information from the OSRD about penicillin research as well.

Like synthetic rubber, synthetic quinine, dried blood products and U-235, the very expensive complexity of pure penicillin suddenly made it more, not less ,of an attraction to the military weapon-oriented OSRD.

The key was to keep secret from the American voters and taxpayers just how many miracle cures were happening with the current - relatively impure -penicillin.

Because if they knew that, the newspapers would be filled with it and the Germans and Japanese would hear about it via Neutral nation reporting.

They they too would also start curing their base hospital wounded with crude semi-purified penicillin ,largely negating the military advantage of fully dry stable pure penicillin.

But was there really ever an absolute need for dry stable penicillin to use it in the front lines ?

Poppycock !

Because it turned out that good old crude liquid blood was actually much better than the complex dried stuff at saving soldiers' lives and could just as easily be used even in combat : good old fashioned low tech American ingenuity (not from the OSRD high tech boys of course) came to the rescue.

Cheap, rugged, disposable,  parachute-portable plywood ice boxes kept blood and penicillin cold, with refills of ice every couple of days........

Spores and Wartime Secrecy : can they actually co-exist ?

You might think I am going to talk about Anthrax spores and asymmetrical terrorist germ warfare.

But you are wrong, wrong, wrong.

I want to talk instead about wartime penicillin, and a part of it that is never ever discussed.

Its inherently asymmetrical medical nature.

Which appropriately enough, then  "drifts over" into its inherently asymmetrical military potential.

So lets start.

And lets start talking about just how the intellectually mis-guided (as well as seriously morally misguided) were the prolonged attempts by the medical establishment in both America and Britain to regard penicillium spores as something  that really could remain Top Secret medical military weapons.

And not just the wartime medical establishment, for recently author Eric Lax and his publishers felt they had a real winner in an exciting clock and dagger title for their book on wartime penicillin : "The Mould in Doctor Florey's Coat".

There was always something faintly Walter Mittyesque about Florey anyway - never more so than in the incident that gave this book its title.

Dunkirk was underway just as Florey at long last accepted that ole Flem's penicillin just might be priceless after all.

But how to save penicillin for the rest of the Allied cause, if Britain fell to the Germans ?

'Let's all rub penicillium spores in the inner seams of our clothing - so even if only one of us gets away, the precious fire of penicillin research can still be re-lit elsewhere'.

But none of these Oxford naifs seemed to have dared ask the boss (Florey) just how they came to possess these incredible spores in the first place.

Henry Dawson's first big scientific effort was in promoting the concept of HGT (Horizontal Gene Transfer) ,the instant transfer of genes between different species and even different families of Life, when its initial discoverer seemed reluctant to even publish his work.

Today it is believed that soil bacteria created the first beta lactam antibiotics about ten million years ago and  - via HGT - gave it to soil molds who modified it slightly and made it penicillin.

So, sometime in 1928, a particularly productive penicillin producer strain of penicillium mold blow into a fancy home in London.

Alexander Fleming's colleague John Freeman was an expert on allergies,  with many rich and powerful patients.

In 1928, Freeman heard a Dutch specialist claim that basement mold spores were the cause of many allergies.

 Freeman got his rich London patients (or more likely their scullery maids) to scrape molds off their basement walls to be tested by his most recent hire, Irish-born mycologist Charles La Touche, towards seeking  ways to gradually desensitize the patients against their particular household mold allergens.

La Touche had no high tech ways to keep spores inside his lab alone - not that I think in the long run a spore or two doesn't get out of the most secure modern facility.

There are many more fungus than us and they have and will be on the Earth a lot longer than us primarily because of their spores.

Their spores are incredibly tiny examples of temporarily suspended Life - Dried-up Life - inside a very hardy and bumpy package.

Tiny is the key here - so tiny they float anywhere and everywhere on the gentlest of breezes - down the hall and around the world.

Being bumpy but tiny and light doesn't hurt either - they can cling to almost any surface - like a human and its luggage bound for Australia, for example.

However if that surface is the tiniest bit damp and the tiniest bit tasty (they seem willing to eat almost anything faintly organic), they spring back into active slimey life.

One of La Touche's spores drifted out of his room and along the stairs to Fleming open Petri dish.

The rest actually wouldn't have been "legend", if Fleming hadn't promptly taken a sub culture of the resulting "spoiled" petri dish, and carefully and correctly preserved it.

Fleming did little to promote the medical use of penicillin in curing disease but he did vigerously promote it as a useful way for busy hospital labs to easily isolate the so called flu bacteria (sic) .

Dozens of labs world wide got a sample from him - they then gave samples of their samples to at least dozens of others.

That is how Florey got his penicillium spores he was so busy stuffing down his coat - from a sub culture Fleming had sent to the previous director of Florey's Dunn Institute.

The Free World beyond Britain had lots of  sub cultures of penicillium spores of the rare - right - type, even without Florey's belated act of charity.

In theory they didn't really need Fleming's spores, only his public article - but in practise, until 1943, they really did need his spores.

Examples of Fleming's spores were actually everywhere - some even better penicillium producers than his original un-mutated version as well.

But they could only be found by teams of researchers seeking hundreds of the right looking blue-green mold on walls and spoiled fruit, and then testing all for their possible anti-bacterial qualities.

Until miracle cures got rumoured about, no one in the world was willing to go to that much effort , just to test a troublesome possible antiseptic.

But by 1943, the miracle cure stories were out amongst the clinical doctors everywhere - and I do really mean everywhere.

Everywhere that Florey went, Egypt, Iran, Russia he had to endure local doctors thrusting excellent producing strains of penicillin molds in his face that they had found locally !

The Axis were just as quick off the mark - Japan got its strain by merely looking about locally.

And the clever Japanese correctly guessed - from one badly reproduced photo in an Egyptian picture magazine - just how best to produce the stuff !

The atomic bomb was effectively secret even if the US had proclaimed it was making one from the rooftops in 1942.

Uranium was everywhere - like penicillium spores - but a bomb from it takes the world's largest, most expensive, building ever built merely to get started on separating pure U-235 from the more abundant U-238.

And without 90% pure U-235,  no working bomb. No nothing.

Tons and tons of scarce money, time and effort kept the A-Bomb an American secret, even from the British and Canadians , let alone the Axis and Neutrals.

But by late 1943, popular magazine articles cheekily showed how one could make penicillin at home, on a kitchen top, for about $5 in equipment and growth mediums.

One didn't even need to go out searching for those semi-rare penicillin-producing strains by then.

In a surprising - even shocking - total volt face, the NRRL's Coghill and Raper had released the top two strains of penicillium.

 That's right, the top two strains that were then producing most of the Allies' military-bound penicillin - to the public American mold type collection in Washington where, as they told the readers of  JAMA worldwide, "anyone" can get some at a "nominal charge".


Didn't they know there was a war on ?

No word if Argentina's Washington DC based scientific attache quickly took a cab over, got some samples and sent them off to his friends in Germany.

Clearly, penicillin was never a viable secret military medical weapon - Florey and Richards were both , to put it kindly, completely deluded to ever think so.

Deluded by utopian visions of near-total purity.

Because unlike the Atomic Bomb and U-235, penicillin's starting material (the spores) were both common worldwide AND its production fully successful even in a highly impure (aka low tech) state.

This was what Fleming had discovered in 1928 but never acted upon - this was the key insight that Henry Dawson brought to the penicillin story, starting on October 16th 1940....

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...

Tuesday, February 5, 2013

Wartime Penicillin's coke-addled Janus Month : March 1943

In March 1943 (midway through the war) , for the very first time in WWII, a part of wartime penicillin research that had been hitherto public was finally and effectively put under official government censorship : anything involving the chemistry of penicillin.

At the very same time, other (hitherto effectively secret) parts of the penicillin story were about to become globally publicized in official government propaganda !

"I am not making this up", as Canada's Liberal Party is wont to say.

The chemical nature of penicillin was about to become Top Secret and there was to be no more public articles by Howard Florey's or Henry Dawson's team, in journals like NATURE and SCIENCE, all about the chemical structure of penicillin to aid German or Japanese chemists on how to synthesize penicillin themselves.

But given the wide availability of all the previous chemistry structure-oriented articles in these two, the biggest of all general science journals in the world, the Axis might not need much further help.

Because back issues of these two journals were still easily available to the scientific diplomatic attaches of the many still-neutral nations  in  capital cities like London, Ottawa and Washington, the Axis chemists may not have needed to employ spies, to seek out the newest secret research .

But the Top Secret classification reflected a new found confidence at Merck, Oxford and the ORSD that the penicillin molecule had finally been cracked and the chemistry of the molecule was a commercial and possibly military secret well worth keeping.

Even Robert Coghill, the penicillin czar at the fermenatation-oriented NRRL labs,  was about to turn his coat to the side of synthesis.

What better time then to hand the hated finicky biological approach to penicillin production to the War Production Board, (the WPB) ?

Who cared if the WPB and the normally-secretive US Army seemed determined to widely publicize , to Allied, Axis and neutral nation alike, just how good this new fangled penicillin really was for military medicine ?


Because for the first time in the war, parts of penicillin other that its chemistry (such as its clinical miracle cures which had been hitherto in America effectively if unofficially censored) were going to become the focus of official government propaganda  and broadcast to the heavens.

Janus month indeed.

In an variant on "the first shall be last and the last first", what had been public was about to become secret and what had been secret was about to become public.

In January 1943, Karl Meyer, the chemist of Dawson's team, could still publish the team's latest best guess on the chemical formula for penicillin, but the team still couldn't discuss their results on treating patients since October 1940.

By January 1944, Dawson could publish his success with patients and penicillin to the world via  JAMA, but later that same year, Meyer's harmless paper on biological products of penicillin written to be delivered at a conference,  was forced to be withdrawn at the last minute, for fear he'd say something chemical and hence secret.

Bizarre but true ...... !

America LOSES WWII : because of quarrels between government agencies, such as over Penicillin

The above headline sounds bizarre to our ears, because we are  used to only hearing it being used as the standard explanation given as to why Japan and Germany lost the (largely technical and scientific) world war against the Allies.

After all, both of these nations had talented and committed cadres of scientists and engineers but endless feuding between various sub sections of the government seriously diluted the impact they might have had on the war, if only they had worked together.

In Japan the Army and Navy Departments frequently seemed more at war with each other, than with America.

In the case of Germany, each of the senior figures in the Nazi hierarchy commanded a lot of semi-independent resources and each Nazi war lord seemed to spend as much time trying to grow at the expense of their political bureaucratic rivals, as in uniting against the common enemy.

But Vannevar Bush chooses, in the foreword to his famous "ENDLESS FRONTIER",  not to see any serious conflicts in the American and Allied scientific and technical effort.

And we believe him - the historians (grateful for the steady diet of research grants to peacetime academics that he is credited with having created) above all .

And after all his side won ----- shouldn't that alone silence all potential criticism ?

Still, in this particular foreword, he chooses to blow his particular agency's horn very very carefully indeed,  when it comes to penicillin.

So for once, it is not his own OSRD that he credits with seeing that "our grievously wounded men" got penicillin in time : he says  it was "the government"  that did the bang up job of co-ordinating the research and development that speeded penicillin up to the front.

For a very conservative Republican ,like Bush, to be praising "the government" is truly a startling sight. He more usually carefully distinguishes agencies like his own highly conservative OSRD from the left wing agencies filled with New Dealers, such as the WPB's own OPRD.

But what could he do ?

For his own right wing OSRD agency chose to take the totally wrong turn on the way to moving penicillin to the D-Day beaches and delivered not one tiny sliver of its vaunted synthetic penicillin to our troops or anyone else : not on June 6th 1944 and in fact, not ever.

It was left to the left wingers in the OPRD to get literally tons of penicillin to the Allied side, between the time they first took up the cause in September 1943 and the end of the war.

They did this not merely by the unimportant but useful work they did on the production side - for by statute this was their job, just as the OSRD's job was not production but research - but by also doing the OSRD's job , in an area of research that the OSRD choose to seriously neglect.

 That was the OSRD-neglected research in studying ways to up the very front end of the penicillin process  : upping the initial biological yield of penicillin.

Biology : horrors !  Just saying that word in front of Bush and the OSRD was like waving a garlic-infused cross at a vampire.

So we must credit the left wing OPRD with starting the research that resulted in that biological yield ( ie , yield before extraction) now being 2500 times as productive as it was in 1943 when the OSRD threw up its hands at the problem.

Just as the quarrelling Japanese Army and Navy did on radar, the two warring branches of Bush's "the government" , the OSRD and OPRD , came to a fork in the road on penicillin and instead of uniting to find a way to use the least resources to solve the problem, they disagreed and pursued independent courses.

Bush's Orwellian use of words like "the government" or "the nation" or "the Allies" ,to explain who won the war , allows him to dissolve any internal conflicts those huge collectivities might have encountered in very slowly moving their overwhelming larger populations into defeating much smaller and very resource-strapped enemies.

So historians mustn't simply accept Bush's Orwellian arguments on blind faith but instead carefully ask , if the nation or government "did" this or that , did that mean that all the nation/government do this or that or did just parts of it do while other parts disagreed, stood around doing nothing or even held things up ?

After all, on the evidence of their own internal memos, the OSRD not merely failed to produce the penicillin that saved our "grievously wounded", they also had no intention of wasting penicillin on anyone who couldn't aid the war effort on recovery, if they didn't have to.

That meant no wasting penicillin, if they had to choose, on those so severely wounded that if they did make a recovery, it would be to discharge and a permanent disability pension.

 And it meant, that if they had to chose between saving a boy dying of endocarditis and instantly curing a boy GI of VD so he could quickly return (to perhaps die) on the Italian frontlines, they'd won't help the endocarditis case, because his disease-weakened heart would not let him do much for the war effort, even if he did recover.

So, if the only thing I ever do in my life is to destroy the OSRD's reputation for furthering penicillin when what they actually did was hold it up and then conspire to use it for truly wicked eugenic ends, I will consider my life well lived....