Showing posts with label glaxo. Show all posts
Showing posts with label glaxo. Show all posts

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.....

Wednesday, January 30, 2013

Fleming never saved Churchill, but Gladys Hobby saved Florey's sister when his own penicillin couldn't !

Howard Florey was never more sleazy than in his dealings with Henry Dawson's team, as he desperately fought to restore the family name that his father dis-honored, by trying to remain the sole "hero" of wartime penicillin.

Just try to imagine what an university ethics committee today might say about a professor using his main rival's unpublished paper, sent to him in secret by his close friend (the same government official who censored his rival's paper and forbade its release) to improve his own work that is about to be allowed to be freely published !

That is what full Professor Howard Florey and university vice president and full Professor A N Richards actually did to associate professor chemist Professor Karl Meyer of Dawson's team , in mid 1942.

(As they say, tenure is 'red in tooth and claw'.)

The multi-hatted Professor A Newton Richards was a Vice President of the University of Pennsylvania, head of the medical wing of the OSRD , chief consultant to Merck and one of Howard Florey's best friends.

Like Mayor Rob Ford, he also never met a conflict of interest he could resist.

(By contrast, when Norman Heatley met Meyer in January 1942, Heatley recorded that Meyer was willing to send his data to Florey, but Heatley boldly told his boss (Florey) he (Heatley) won't because it didn't seem right, not if Florey was about to publish and Meyer was forbidden to.)

However, Professor Richards was of a very different moral character and saw nothing wrong in sending Professor Meyer's embargoed chemical work on the structure of penicillin to his main academic rival, Professor Florey.

By contrast, Dawson bent over backwards to try and find a source of penicillin for Florey (even at places like Pfizer - a place Florey determinedly didn't want to visit), totally unaware of Florey's well known reputation in the UK for being an academic bush whacker and a magpie of other people's hard work.

Florey's real (if totally private) reason to come to America in 1941, was mainly to establish that he and Merck, not Dawson and Pfizer, was the real leader in the hunt for viable penicillin.

By late 1942, Florey felt sure that the dying Dawson and Pfizer (having joined Merck's cartel) was out of the race.

Sweet indeed then, when in August 1944, a sullen Howard Florey had to stand politely beside Dawson team member Gladys Hobby as she showed him the natural penicillin poring off the Pfizer lines, while Merck and Florey's team at Oxford had totally failed to produce any synthetic penicillin for the D Day beaches.

Florey had spurned both Pfizer and Glaxo, yet it was they who delivered most of the penicillin that landed on the Normandy beaches that day  --- "the stone the builders rejected" indeed.

Gladys Hobby saves Howard Florey's own sister  -- when he couldn't


Asa series of letters in the Royal Society Archive reveal, in  December 1952, Florey had to eat yet more humble pie, first begging and then thanking Hobby for sending her own latest antibiotic off to save the life of his sister (Hilda Gardner) in Australia when his own penicillin wouldn't work....

Wednesday, October 3, 2012

Duhig's Penicillin saved lives where Alexander Fleming failed - because of - not in spite of - "poorer" technology !

GLAXO's moral lowpoint: April '43
Briefly - very briefly - in April 1943, at the height of all the suffering and the dying of WWII, Glaxo the drug company had a tremendous technological success and an enormous moral failure.

Briefly , Glaxo was the world's largest producer of what little penicillin the world produced, 15 long years after its first discovery. But none of that penicillin - zero - went to directly helping World War Two's sick and the dying.

Instead it was all destroyed by Glaxo chemists, as part of in the war-long futile contest to see what drug company would be the first to see MAN make penicillin, instead of some slimey slime.

Much of the story of wartime penicillin was that sordid story.

The dark dirty story of an contest between alpha male chemists and CEOs and chemists manques (in particular), to see who could get the Nobel prize and the glory and the profit for the patentable total synthesis of penicillin --- rather than submerging all that testosterone in an all out attempt to aid the sick and dying now and fuss over the glory later.

95 % of the wartime penicillin story was shabby beyond belief, but 5% was truly heroic medicine at its best


It is a truly shabby tale ---- as shabby as the war itself.

Alexander Fleming was part of that shabby tale : he never deflected from his 14 year old belief that penicillin might be a good antiseptic ( ie not to be taken internally, as life-saving drugs must be), if and only the chemists learned to synthesize it.

Jim Duhig --- once he had learned how people like Henry Dawson had grown their own clinical penicillin and injected it in a semi-purified state into their patients without killing them - went a further step.

He "downmarketed" his technological requirements and didn't bother to even semi-purify his home-owned penicillin.

The penicillin he injected into dying patients in 1943-1944 was cruder than even the semi-purified penicillin that Fleming dabbed around the open wounds of patients in 1928-1929, 15 years earlier.

Fleming reported mostly failures with his semi-purified penicillin while Duhig's totally unpurified penicillin saved the lives of patients all doctors had placed 'beyond hope' !

How on Earth ?!

All attempts at purifying, concentrating or crystallizing penicillin came at great costs: the harsh chemical techniques destroyed most of the delicate penicillin, the efforts wore out the overworked wartime staff and introduced deadly chemicals into the penicillin (when removing deadly chemicals was the original point of the whole exercise ! )

Duhig focussed his tiny overworked crew into merely making more and more raw penicillin - ie in upping raw production - and then in carefully preserving that delicate lifesaver, until it could be quickly poured into the bodies of dying patients.

Per person-hour of effort, I suspect that Duhig got 10 to100 times as much clinical penicillin as Dawson, Fleming , Glaxo, Merck, Florey et all got for all their hard work.

(Dawson being at the 10x end and Florey at the 100x end.)

Only Robert Pulvertaft, despite working in the desert heat (!) of wartime Egypt, probably did as well in turning raw penicillin juice into saved lives , with the minimum of human effort.

The unconscious, untested, assumption had always been that the other materials in raw penicillin juice would cause a deadly allergic reaction in patients unless purified away.

Never considered - except by Henry Dawson's team - was the idea that raw penicillin's other unknown materials might actually help penicillin work - as they certainly rarely seemed to harm the patient.

The jury is still out on that idea --- but un-purified penicillin did in fact rarely, if ever, harm the patients.

But converting penicillin from a weak acid to a salt ( to stabilize it for longterm commercial storage and sales)  does bring the well known dangers of introducing too much salts into the delicate balance of salts in the heart-blood system.

(Since Duhig's totally un-purified penicillin remained a weak acid and not a salt, he could pump simply tremendous amounts of penicillin liquid into patients' blood without killing them.)

And it was only once penicillin was totally purified and given in high doses did some people - a very few people - start dying from an allergic reaction to ------- to PURE penicillin !

Call it groupthink or tunnel vision, but *eugenics' powers over mid century doctors and scientists was so strong, they never asked the most basic of all science questions.

They never asked themselves, " if a mixture of penicillin and impurities sometimes causes a sharp spike in temperature in some patients, is it caused by (a) those particular patients's body chemistry (b) the impurities (c) or the penicillin itself ?"

If only they had, millions of people might have lived out their full lives, starting in 1928.....

* Eugenics was merely the leading edge of a middle class culture obsessed with purity and a hatred of dirt that went beyond all bounds of rationality : only a Mary Douglas could begin to assess what was really going on in the middle class mind in the mid 20th century.


Friday, August 20, 2010

impure to PATIENTS, pure to CHEMISTS

Many scholars have doubted Big Pharma kept its word back in the Fall of 1941, when a dozen of its firms each promised to brew up hundreds (or even thousands) of liters of penicillin juice every week , so  penicillin could start flowing into dying patients' veins.

Because all throughout 1942,one of the worse years of the war for the Allied cause, very very few patients or soldiers seemed to get any of the life-saving  stuff.

I may stand alone - even stand naive - in believing the drug companies' pledge.

But I admit that I also read the fine print in that promise - the drug companies would indeed seed all that raw penicillin juice flasks that they had promised, but not "all" of the resulting penicillin would go to the patients - only "some" of it would.

In April 1943, GLAXO patted itself on the back and said it was the largest penicillin producer in the world.

It probably was.

But NONE, zilch, zero, zip of that world-beating supply was going to the soldiers, sailors, airmen or civilians that month.

Let see, that meant no penicillin for all the burn victims of the HMS Dasher disaster or for the people crushed in the Bethnal Green Tube disaster and no penicillin for the American wounded in the Battle for Bougainville.

So where was all the penicillin going that was produced in Glaxo's Aylesbury and Greenford plants?

It was all off to the chemists at Glaxo and Wellcome, to be degraded and destroyed in their ongoing attempts to achieve total synthesis of penicillin.

I hear a lot of chat that "we couldn't get any penicillin for my mother during WWII because the military had it all" but this was never so.

The military at the frontline hospitals frequently made its own unofficial and unrefined penicillin when it got tired of the scientists back home trying to perfect artificial penicillin.

Pulvertaft did it for the British Army in Cairo - he taught the nearby Royal Air Force to do likewise and the Canadian Army in Italy took up his idea.

Back in Britain, the Royal Navy under Green set up its own unofficial penicillin plant using Gordon Gin bottles instead of Glaxo's Bonny Baby milk bottles - gin bottles of which they had a great deal of, for some reason ( joke !)

Out west in Utah, US Army major Frank Queen started trying to make his own penicillin.

 He was tired of seeing boys from Guadalcanal still lying about with rotting bone
infections, ten months after they were first wounded and evacuated, with sulfa drugs only making them vomit rather than killing off their infections.

The military always said and acted upon, "a bird in the hand today is worth a million birds in the hand tomorrow" - they were only interested in technology that could be mass produced for this war, preferable this year.

General Grove always insisted he had to be a brute, because if you give scientists a pile of money and equipment and no one to ride herd on them, they will always go for the most interesting scientific problems but not deliver anything 'good enough' in time to be useful.

In other words, the better the scientist, the worse the engineer - they are not deadline or budget oriented by nature - they need a firm hand.

The military finally did plump for natural penicillin - produced in mushroom farms if that got the job done - rather than wait for the chemists.

The military's decision to demand natural penicillin now,ironically, got badly needed penicillin into the veins of dying civilians as well.

I think all the firms were guilty of this.

 Florey was not alone in getting raw penicillin juice instead of semi-purified dry penicillin from one company he was cooperating with (Kemball-Bishop). That meant he had to purify the penicillin he needed for patient trials.

Dawson got penicillin juice from Pfizer, starting back in October 1941.

But not till five months later did he get semi purified penicillin from them.

When he asked, back in November 1941, he was told all the pure stuff Pfizer could produce and more was going to Pfizer's Doctor Walton J Smith - if Dawson wanted some pure penicillin ,he could purify it himself from the raw juice.

Doctor Smith was not an MD - he was a PhD in Chemistry - an organic chemist - he set about degrading and destroying the purest stuff that Pfizer could produce, while Dawson's patients got the impure stuff.

Kemball-Bishop, a partner of Pfizer, did the same to Florey in the fall of 1942.

Now Pfizer and Kemball-Bishop were fermentation experts, not really drug companies.

If they, the most biologically-oriented of any of the firms involved in penicillin, were hell-bent on creating synthetic penicillin from the very beginning, how much more so the chemically-oriented firms like Merck and Squibb and ICI ?

It is a Big Lie, in the most accurate sense of that word, to say the search for pure penicillin was done for the patients' benefit.

Many dying patients, in a frontline dugout or in a SBE ward, would have settled for any kind of penicillin now, over a promise of perfectly pure artificial penicillin for the lucky patients who came along long after they themselves died for lack of help.