Monday, February 8, 2016

Big Penicillin : Big Lie ?

If you've read one account as to how the Allied world moved to the mass production of natural penicillin in the early Spring of '43, you've read 'em all.

It goes roughly like this :
Alfred Richards of the OSRD-CMR , together with Chester Keefer of the NAS-COC, having together briskly proven the clinical efficacy of the new medication, now 'asked' the WPB to just as briskly move the drug into high production. They wanted the War Production Board to increase monthly output by an incredible 100,000% in a year's time, so that the Armed Forces' desperate needs could be met. Working hard together, (here cue 'hands across the water') the sweat, labour and ingenuity of American companies, scientists and workers soon achieved the impossible. (Here insert wild applause.)

In fact, left to their own devices and un-prodded by outside forces, these two scientists, together with their rubber stamp committees, would have polished the penicillin apple forever in civilian research settings far from the battlefront wounded  --- until Merck redeemed the honour of Man The Chemist and unleashed a patented, synthetic, version upon the world.

Casablanca - the conference not the movie - was fundamental

What changed most fundamentally in January 1943 was the US Army's reluctant acceptance, after the Casablanca Conference with the British, that their eagerly sought invasion of Hitler's Europe would be postponed to early summer 1944.

There were two military medicine consequences flowing from that realization.

One was military medicine finally admitting the repressed evidence of the many failings of the sulfa drugs, the world's miracle drugs between 1936 and 1942.

In September 1942, some chemists had proven that all the antibacterial possibilities (positions) of the basic sulfa molecule had already been obtained. And germs were rapidly becoming very resistant to the existing sulfas.

One solution was to up the dosage but this merely increased the long known toxic dangers of these drugs. In any case, the sulfas had never worked against many important military germs and were often worse than useless in open combat wounds - harmful even.

Yet the Army's pre-Casablanca invasion protocol was in training all its medical staff - from top surgeons in the big rear echelon hospitals down to green front line medics - to liberally pour sulfa powder into open wounds as soon as they occurred.

The mass production of cheap abundant, stable powdered sulfa made that possible.

Allowing a few enterprising medical officers to bring the superior, but injection only, penicillin to the battle-lines on an experimental basis would only cloud this protocol.

But now a delay of a year and a half would allow the Army to experiment safely with all the possibilities of this new penicillin before the Big Push.

Secondly, with no D-Day on the near horizon, General Marshall could finally safely fire his current Army Surgeon General James Magee, for reasons unconnected with the penicillin versus sulfa debate.

But Magee was the sturdiest bulwark of the Richards-Keefer rubber stamp team on the notion of going glacially slow on wartime penicillin and not letting it anywhere near the frontline wounded.

A new Army Surgeon General might not prove as putty-like on the issue.

Army officers going off the Magee reservation on penicillin

Worse, it was no longer just a few pioneering American medical officers  demanding a bit of free frontline penicillin from the CMR and COC.

For now the British Army (in the person of liason officer Colonel Frank S Gillespie) was investigating paying  handsomely for massive amounts of American made penicillin from Richards' 'worthy few' penicillin firms (Merck & Squibb).

This pair, together with Pfizer to a lesser extent, had given all the tiny amounts of clinical penicillin they had produced in 1941 and 1942 free to the CMR-COC.

They now wanted to be able to sell lots of the stuff to the British and start making some returns for their investors.

Some in the US Army had so given up on both Magee and Richards/Keefer that they were actually home-brewing their own crude penicillin to help save those Army wounded dying from chronic severe deep bone infections.

Painfully, one of them was a young protege of Richards from way back in the day when Richards did research rather than just push paper.

Army by-passing Dr No

The published accounts always claim that it was the OSRD itself suddenly taking the lead on the move to mass produce natural penicillin, done by tearing open the OSRD's own 'worthy few' cartel and letting every manufacturer and every scientist in to try and make the stuff.

They date this request from the OSRD to the WPB to open up the process to late May or early June 1943.

Given that Dr Richards had rejected almost every such offer of manufacturing and scientific help, from all over North America, between 1941 and 1942 and his continuing preference to restrict the number of firms and scientists working on the secret synthetic manufacture of penicillin, it simply doesn't ring true.

Nothing in the published accounts actually contradicted this version but even in this 'official' OSRD version both the Army and the WPB sure seemed well up to speed on penicillin very quickly on what was then a very publicly unknown substance.

In fact, very early in 1943, the Army, at a level below General Magee, decided it needed penicillin, to supplement the failing fading sulfa before the big fight on D-Day.

And because they normally thought in terms of billion dollar programs and even a world awash in penicillin would cost less than another navy cruiser, they wanted it fast.

After all, they reasoned, greatly expanding its production would still hardly put a new strain on 1943's currently scarce resources.

These middle level military bureaucrats quickly figured out that the main roadblock to obtaining that result lay with Richards in Washington (and to a much less extent, Keefer in Boston).

They worked around him and presented him with a bureaucratically fait  accompli.

Cutter letter tells all

Recently, while researching in the records of the WPB and OSRD in US National Archives II in College Park Maryland, I cam across a PS at the bottom of a letter, indicating that a few weeks before May 12th 1943, a Cutter Laboratories rep and WPB penicillin chief John McManus had already visited Dr Richards at OSRD headquarters in Washington DC.

The Cutter rep was almost certainly Ted Cutter himself, judging by his oral history recollections.

This is truly amazing ---- Cutter had never produced a human drug before, let alone mass produce a very labile drug by a difficult fermentation process.

And it was relatively small in size and located in very remote (in the current world of penicillin research and production at least) Berkeley California.

But it had successfully made some very clever indeed veterinarian vaccines for half a century and was heavily involved in supplying the Army with vital lifesaving blood 'fractions'.

Both of these processes required the utmost attention to detail and the Army medical purchasing staff were powerfully impressed.

The Army had had a look at Richards' 'worthy few' and very unimpressed.

They figured that Cutter, even totally new to the game, could do as good - or better - a job as the veterans of three or four years effort.

The Army dragged Cutter into it and even offered to supply, basically free, a new factory for Cutter to run and even to re-tool it for free if synthetic penicillin ever arrived.

Above all, they promised they would deliver the same priority-busting efforts to get scarce new equipment as they had already done for Cutter to fractionate blood.

Cutter knew the Army had indeed gone the extra mile or five for them over blood equipment and trusted them to do the same with penicillin.

Cutter, together with the near by Shell Oil research facility (!) ended up doing globally important research in penicillin and, as well, provided its share to the mass production of natural penicillin.

I seriously doubt, from Ted Cutter's oral recollections, that Cutter was one of the many penicillin stones that supposed penicillin builder Richards had earlier rejected.

But if Cutter had sought to get in on penicillin by approaching Richards, it would have been turned down flat.

Green newcomer Cutter provided more than its share towards the precious natural penicillin ready, literally,'just in the nick of time' for the Allied troops on D-Day.

Richards' fair-haired boys at Merck, penicillin veterans for almost five years by then, shamefully did not.

That alone speaks volume on where the true credit for just-in-time D-Day penicillin lies...

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