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.....

Alexander Fleming's "HAY" identified?

I wish to offer up a possible identification of Alexander Fleming's long mysterious "HAY" bacteria and a possible explanation why it was among the very first bacteria he tested penicillin on.

It is well accepted that Fleming seeded that famous Petri dish at the end of July 1928, discovered that a mold had dissolved mature staph colonies on it in early September 1928 but that he only recorded his first experiment with the mold juice on October 30th 1928.

The results of this (quick) experiment implied to Fleming, I believe, that penicillium juice clearly inhibited the growth of staph-type (gram positive) bacteria .

However it had no effect on coli-type bacteria (gram negative) or acid-fast HAY-type bacteria (ie mycobacterium, the group of bacteria that causes Tuberculosis.)

The Timothy Hay Bacillus, Mycobacterium Phei , I suggest was that "HAY" bacteria and was used as a safe stand-in for the deadly tuberculosis bacteria that had killed so many lab workers in the past.

It is almost tuberculosis-on-steroid in some ways, but is almost completely harmless to humans.

Like all mycobacterium, it is one of the hardest types of bacteria to kill, because it is covered in mycolic acids that resist anything the chemical industry or the immune system can throw at them.

Perhaps Fleming thought an agent that could dissolve even mature staph colonies would be up for dissolving the tough coat of the mycobacterium group - if so he was disappointed.

Because it is not only harmless to humans, but is also the fastest growing of the very slow growing mycobacterium - always important for increasing lab productivity - Mycobacterium Phei seemed a useful addition to the well equipped Bacteriology Lab.

It also has a very unusual nucleic acid composition - 75% GC content - making it of interest to early workers in what we now call DNA research.

Parke Davis, the drug company that bought Fleming's institute's vaccines and serums , was very interested in this bug in the summer of 1928.

They had assisted a group at Yale in investigating some of its characteristics as they related to and contrasted with the deadly TB bug that was killing so many people world wide.

This was a potentially fresh approach to solving the age old TB problem - approaching the beast from an indirect angle.

This Yale team was led by Robert D Coghill - another famous leader in the penicillin saga.

Perhaps the Detroit drug firm had also communicated their interest in the Timothy Hay Bacillus to all researchers connected to Parke Davis International that summer --- including Fleming ?

I would be interested to hear what more experienced writers on Fleming and penicillin think of this suggestion...