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Thursday, July 29, 2010

Foster, Woodruff & McDaniel: is it true?

More precisely, was it all of the truth - or was it published by the bosses of Merck as a deliberate half-truth?

I have a real "moral" problem with an scientific article from 1943.

1943?

Like 68 years ago?

Exactly - and one of the junior authors (Dr Boyd Woodruff) is still alive and active, albeit as active as any 94 year old scientist can be!

And he seems a very nice man from an interview or two I have read of his.

The article comes from "the research lab" of Merck, so I suppose Merck's production staff on the factory floor can always offer up a 'plausible deniability' of the article's claims.

It was submitted for publication on May 28 1943, and published in November 1943.

Most journals ,even then, let you add short addendums till very near the actual date of printing.

It is entitled :

"MICROBIOLOGICAL ASPECTS OF PENICILLIN, III - PRODUCTION OF PENICILLIN IN SURFACE CULTURES OF PENICILLIUM NOTATUM

Now it was no secret, then or now, that the Florey team in Oxford, along with his funders at the MRC and the Rockefeller Foundation,along with his friend John Fulton at Yale, together with the OSRD, the CMR, the chemical chief at NRRL (formerly from Yale), and the COC were all extremely close to George W Merck and Merck inc.

The head of the OSRD and its chief legal counsel, along with the head of the CMR and the head of the COC all ended up on the board or acting as consultants to Merck.

Their real bond was that almost all were chemist-manques --- or as we'd say today, chemist wannabes.

The prestige of chemists never shined brighter than the years of their growing up and adulthood and so they worshipped at its fountain only a little more fervently than the average educated person did.

Florey wanted to be a research chemist - his parents said being a medical doctor was more practical.

Richards ,the head of the CMR, was an indifferent student until he fell under the spell of a chemist - he ended up teaching the new subject of pharmacology - a very chemically-oriented area of expertise.

Merck had wanted to be a research chemist - his father's early death made him the head of his (very,very) chemically-oriented drug company.

Remind me to tell you a very funny story sometime on just how chemically-oriented Merck Inc was back in the 1930s.

Robert Coghill headed up the very biologically-oriented Fermentation Division at the NRRL, but he had been a chemist and longed to do real chemistry work - ie synthesize things.

Richards at the CMR really controlled penicillin in North America, to the extent anyone did.

This article won't have come out, unless Richards was 100% happy with it.

I re-stumbled on this article (I had read it many times before) when I had problems documenting a frequently made claim of other authors on early penicillin : that the chemistry of penicillin was the only area that was censored during the war years.

I found that articles on the general and specific chemistry of penicillin were extremely abundant from 1928-1943.

I found that for the period August 1941 to about January 1943, it was actually articles on the clinical use of penicillin that were totally non-existent, and on both sides of the Atlantic.

No where would 'Doctor Mom' finds reports in her local newspaper of people snatched from the jaws of death by penicillin during that crucial 18 month period - I think these good news stories were deliberately discouraged and held back until the drug companies and the government could produce a rabbit out of their hats.

And I found no mention anywhere, until Raper and Coghill's articles in May 1944 (when the penicillin crisis had ended in a sudden and unexpected total triumph) about the new productive sub-strains of  Fleming's original feeble penicillium mold developed at the NRRL from January 1942 onward.

(NRRL 1249 ,1249.B , 1249.B21)

Or of the way that production soared with the subsitution of corn steep liquor and lactose for sucrose and yeast extract,something the NRRL (and the OSRD/Richards) knew back in December 1941.

I got the distinct impression that nobody (except maybe Florey himself) knew about the real significance of lactose/corn liquor combo and not even Florey got access to these distinctly better sub-strains of penicillium.

Since Florey and Dawson (and lots of others) were struggling to produce their own penicillin until 1943-1944, ie from 2 years after these discoveries, news of all of this would have meant they would have got 10 to 20 times the yield from their existing equipment and staff effort.

They would no longer be beholden to the drug companies or the OSRD and Richards - which just might have been the point.

This article would have been read by the entire microbiology world - it was published in the Journal of Bacteriology (ASM), the leading microbiology journal in the Americas - a vast agriculturally advanced part of the world and so a hotbed of microbiological research of the practical sort.

The impression for a professional microbiologist reading this article , back in 1943,  is that Merck Inc ,itself, in mid-1943, had tested a few substrains of penicillium, finding some better and some worse than Fleming's original....all pretty ho hum.

And that it found the best medium to grow penicillin on was Dawson's dirty (cheap-impure-complex) brown sugar. Again the formula was publicly available and not really a great help for a hospital lab trying to produce enough penicillin to cure one extremely ill patient a month.

(I think the average teaching hospital laboratory department needed to produce about one million units of clinical penicillin a month without extraordinary requirements of staff, space or effort  if it was to feel it was worthwhile continuing working on clinical penicillin trials ,independent of what the drug companies and government would provide , ON THEIR TERMS.)

The Merck researchers said that they had tried lactose and found it no better than dirty brown sugar. No mention of corn steep liquor at all.

So was Merck using Fleming's old strain, and a dirty brown sugar medium to make all of its commercial penicillin in the Fall of 1943?

I do not believe so - and I will not believe so till I see dated photographs and hear eye witnesses under oath.

I accept that ,during war, firms and institutions will not tell their own citizens all what they are doing.

If you can't tell the truth about something, better to remain silent.

But I do not accept that you spread deliberate disinformation - which is what I think this article did - and still does.

I think it deliberately low-balled the state of the art, circa Fall 1943, of Merck's effort to increase the yield of penicillin juice produced by the mold, before the chemists stepped in to increase the yield of clinical penicillin concentrated from that juice.

This article feels like it was written in about March 1942, not in May or November 1943.

If that is so,who was it designed to mislead by being released ?

 Clearly not Squibb,Pfizer,Withrop,Abbott etc - those firms that had been working with penicillin for a few years and had a pretty good idea of the state of the art of natural penicillin production in mid to late 1943.

But hundreds of other firms might want to 'try their hand' at penicillin (175 firms did apply to do just that, just after this article was submitted).

Giving them just enough information to try their hand and then to retire discouraged might just be what the Merck leadership had in mind....

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