Showing posts with label george w merck. Show all posts
Showing posts with label george w merck. Show all posts

Saturday, January 19, 2013

Did Merck consultant A N Richards diss penicillin during the first two years of the war?

Read any "Pollyanna" history of wartime penicillin and you quickly garner the impression that wartime Washington's top medical research bureaucrat, AN Richards of the famous OSRD organization, first learned of penicillin when his former student Howard Florey dropped by in the Fall of 1941.

In my opinion : "Bullfeathers" !

Richards was the key outside consultant for Merck and had been so since 1931 , so key that he acted more like a trusted insider, rather than playing the traditional role of an external naysayer brought in to correct too much internal group-think.

Since November 1939, a full two years before Richards is traditionally described as first getting involved in "this 'ere pen-E- cil-in stuff", Merck had been working fitfully on trying to learn the structure of  public domain natural penicillin with the hope its chemists could produce patentable, profitable "look alike" analogues.

Memo had flown back and forth and committee and board meetings had been called and minutes written.

Hard to believe that Richards the pharmaceutical expert consultant was not consulted formally and informally - ever - during those two years of internal Merck debate on the merits of seriously spending money on synthesizing penicillin.

But the silence from Merck and Richards on just what Richards said to Merck about the potential of penicillin between November 1939 and August 1941 is deafening.

It isn't at all like Richards or Merck to modestly not to claim credit for their early prescience on penicillin.

 In fact Merck brass went to enormous length to do just so in the major article "Wartime Industrial Development of Penicillin in the United States", written and researched in the late 1970s (with exclusive access to secret Merck archives) by company senior executiveW H Helfand.

Mysteriously, Richards name is totally absent during this article's discussion of the two years of Merck debate about penicillin, before Florey arrives at Richards' doorstep in Philadelphia.

However Helfand's article quotes Merck executive Osgood Perkins recalling that despite a memo "from so-called experts urging Merck not to waste time on it", in 1940 the company top brass decided to grow penicillin with the aim of isolating its active ingredient.

Now Osgood Perkins was a famous actor of that era but he never worked for Merck.

 However the equally famous Wall Street lawyer George W Perkins did - in fact he was the brother-in-law of the company president George W Merck and served as chief operating officer for several decades, including the war years.

(And like his brother in law, Perkins worked at the top of America's highly secret germ warfare program when America formally went to war but still kept a close eye on his company.)

But the quote is from Lennard Bickel's book on Howard Florey, Rise up to Life, and in it, Bickel says he quotes Merck executive Osgood Nichols (also referenced as Osgood Nicholls by Bickel) in conversation with AN Richards in the early 1960s.

(Osgood Nichols probably saw the memos while researching "By Their Fruits" , a book about Merck and Waksman.)

Now I have determined that Bickel did screw up names (but only slightly) in his book, so I feel certain we are looking at Nichols, not Perkins, for the source of this quote.

Richards is silent to Osgood as to who the so called experts might be (and surely he would know) but rushes to defend Florey.

Just exactly how Helfard screws all this so badly is hard to ken.

I suspect that those "so-called experts" included both the much honored Richards and the equally much-honored Columbia university medical researcher, Nobel prize winner and long time Merck consultant Dickinson Richards.

Dickinson worked literally next door to Henry Dawson, who did the most work on penicillin in North America between 1940 and 1941.

So this Dr Richards (no relation to AN Richards) saw the world's then most extensive penicillin efforts (microbiological production, chemical research and clinical efforts with the seriously ill) close up and personal every day.

Thus his opinion on penicillin , as a Merck medical consultant since 1935, between 1940 to 1941 had to be valuable to Merck - but what was it ?

I suspect one of the "the so-called experts" who dissed penicillin was Dickinson Richards.

Why ?  Because Helfand does not mention Merck offering to help Dickinson Richards' floor mate Dawson in his penicillin efforts in this very long article tasked with detailing everything and anything positive that Merck had done on penicillin before Florey arrived.

 (But we do know what a third outside consultant to Merck said about penicillin because Helfand does quote him extensively.)

 Soon to be Nobel Prize winner Selman Waksman is recorded as being strongly in favour of working up penicillin.

I believe that Helfand's job in this article was to recall all the good news and elide any bad news on Merck and penicillin 1939-1941 and he did his job rather well.

I think it would have rather spoiled the seamless panty lines of the traditional "Pollyanna" version of wartime penicillin served up by academic historians, to have revealed that AN Richards knew all about Merck's dilatory efforts with penicillin for two years but did little to speed it along. (And may have even of dissed it.)

Much better is to say that as soon as Florey first told Richards about the wondrous penicillin, Richards leaps into patriotic action to help Britain (cue The Special Relationship)  and soon the world has penicillin oozing out of its pores....

Wednesday, January 16, 2013

Roy S Koch "shows me the money" on wartime penicillin


In December 1944, a very youthful looking economist named Roy S Koch was heading up The Biologicals and Parenteral Solutions Unit, hitherto an unimportant sub-section of a sub-section of a sub-section, buried deep somewhere in the bowels of the powerful War Production Board in wartime Washington.

Then , overnight in August 1943, penicillin became one of those parenterally delivered biologicals and nothing was ever quite the same.

One of Koch's jobs was tallying the actual amounts, month by month, firm by firm, of medical grade penicillin that passed from the FDA's approval into the military or civilian supply chain.

In those excited anxious days with American families's sons, brothers and fathers dying left (Pacific) and right (Atlantic) in record numbers, all eyes and ears were on the progress reports on penicillin production.

Everyone, in their own way, was pitching in to help American industry finally deliver the goods, 15 years later but better late than never.

Above all the American taxpayer was working overtime to pay for that promise of expanded production.

 Paying for the government building of private-firm-run buildings, paying through extra personal taxes for the shortfall caused by the writing off of excess corporate taxes, paying for military and civilian expeditors, paying to aid to university researchers who were in turn aiding corporate coffers - on  and on and on.

 So a corporate failure to make good on a public promise to deliver a lot of penicillin, with the help of lots of taxpayers' money, was going to seem tantamount to committing an act of treason.

Hence Koch's carefully collected figures had to remain a closely guarded secret : American corporations may fail to deliver all the time, but the American public is never ever to know.

But in 1958, about 55 years ago and almost 15 years after the figures were first collected, a muckraking US government inquiry into price-fixing in the antibiotic business did reveal the figures --- even put it in a public domain documents so all the world could quote them freely.

But I have never seen anyone do so and I have read an awful lot on wartime penicillin : so if I am wrong, please email me at my email on this blog.

Anyway, the figures are posted above and you can access the report  ("Economic Report on Antibiotics Manufacture" )  online --- this chart is from the appendix, page 331.

In January 1944, the Hare side of the race to make - and define - wartime penicillin was feeling pretty good : Merck had produced some actual therapeutically-effective penicillin by human synthesis (take that you nasty mold !), a result soon confirmed by the Oxford Hares and by other American Hares.

Yields were much lower than the mold-made penicillin and the impurities both more abundant and much more lethal than in the naturally-made penicillin , but the chemists (hundreds of the best chemists in the world) were working on it.

Soon the pesky Tortoises of  wartime penicillin, mostly obscure johnnies come lately, could be kissed off - their brand new plants just so yesterday, so very obsolete : growing mold like some rural farmer and then making things by fermentation.

 In this Modern Age !

Really, the nerve !

Still, in January 1944, some of the leaders in the secret effort to make penicillin by synthesis are still putting up a good front in aiding the build-up of penicillin supplies for the widely expected opening of the Second Front (D-day) in the late spring or early summer.

Their production of natural penicillin was quite good - compared to even a few months earlier.

The all-mighty Merck (leader, along with Howard Florey in Oxford England, of the penicillin Hares) delivered 3.1 billion units that month, about as much as some obscure mushroom farmer (Reichel) did , buried somewhere out in the backwoods of rural Pennsylvania.

Merck wasn't going to really go all out to produce a lot of natural penicillin for the boys overseas, not when they were about to blow the world away with their very own "technically sweet" synthetic penicillin.

But the boss, George W Merck, was still determined to be patriotic none the less, "do his bit".

Pfizer, another part of the New York area Hare triad, led the production, just barely, with 3.98 billion units.

Squibb ,the third of that triad, was not pulling its weight - even the War Production Board could barely contain their anger , as the folks at Squibb laying back on the oars --- producing just .61 billion units.

The Mid-West group of Hares hadn't done as well, but they hadn't been at it as long : Abbott did .71 billion, Lilly .43 , Upjohn .07 , Parke Davis .03.

Let us jump to April 1944.

Synthetic penicillin yields are still so low that they were a joke - making even Fleming's small amounts that he produced in 1928 look enormous in comparison.

But almost everyone's natural penicillin output has improved --- it was getting close, after all, to make the deadline to get into the pipeline to Kansas City's big depot and then out again to Southern England for the D-Day medical supply loadings.

Every drug CEO wanted to boast later in ads that it was his firm's penicillin that had won the day in the invasion of Nazi Europe.

Reichel had fallen way back below its January output and Merck hadn't even doubled its output.

But Squibb had increased its supply by 10 times , albeit from a low base and Abbott had done almost as well.

(Commercial Solvents had increased its output by 300 times, from a very low base - but it was a real newcomer.)

Pfizer switches sides and kills Modernity ...


But Pfizer wasn't playing fair, for it had turned from being a Hare into a Tortoise : it had increased its natural penicillin output by 10 times, from a very high base and doubled it again in May : producing more than the entire world's penicillin plants combined.

By July, Merck was almost producing less than it had in January, while Pfizer was producing 25 times as much as it had in January.

Still no early sign of synthetic penicillin production and Pfizer was on its way to producing enough penicillin for the entire world,naturally, with or without Merck's 'technically sweet" synthetic stuff .

Modernity had just taken a fatal shot to the base of the neck and deep down, everyone knew it....