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.....

A full two years after Florey arrives at Peoria, the NRRL starts looking for new sources of penicillin strains..."Soon" ?

Penicillin: II. Natural Variation

and Penicillin Production in

Penicillium notatum and

Allied Species

If pollyanna historians says two years - in the middle of a war - is "soon" , then I guess it must be so.

"Howard Florey arrives in Peoria in early July 1941 and "soon" planes of the American Air Transport Command are delivering moldy earth samples from the four corners of the world.... and that is why we have abundant penicillin today."

I always knew this story had to be bunk : the Air Transport Command won't even be in the four corners of the world for another year or two or three.

Ken Raper, the man at NRRL who directed that search and should know best says (in the1945 peer reviewed article at the top of this post) that the search started in June 1943.

Ie, after the OSRD stepped back from two years of navel fluff removal and the OPRD got involved in its typically no nonsense way.

If the OSRD's infamous AN Richards wasn't so hell-bound on a chemical synthetic solution, the NRRL would have gotten money and encouragement a lot earlier to search for higher producing strains than those held already by the NRRL  --- and these strains were key to the final successful chapter in the long penicillin saga...

Florey quickly flees the biology of NRRL Peoria for the chemical comforts of Merck

Howard Florey probably spent no more than a few hours of his whole life in the labs of the NRRL at Peoria, Illinois where most of the fruitful work that gave us the antibiotics revolution was actually done.

Within hours, he had dumped his sidekick Norman Heatley there to toil on the rural farmer-like task of growing penicillin, because Florey preferred much more the urban chemistry-oriented approach of firms like Merck and Squibb and ICL.

Florey was no country hick and disdained 'farming' penicillin

Florey after all had wanted to be part of the then most glamorous part of science( chemistry) and only took up medicine as the easiest way for an Australian to get employment in scientific research (as a medical "doctor" , he hated dealing with patients and in fact, hated dealing with people in general.)

He remained a chemist-manque all his life.

Hence why he avoided doing any hands-on research at NRRL Peoria on increasing the biological yield of penicillin .

He much preferred the chemical synthesis approach of Merck and of its chief scientific consultant, A N Richards, new head of the war  medicine section of the war weapon research organization, the OSRD....

ROP on this penicillin milch cow is beyond astounding : and it is all down to lactose intolerance !

Ironic isn't it ? Hundreds of millions of people have enjoyed longer lives thanks to the lactose intolerance of some slimy little mold.


That mold makes penicillin : in the beginning, very little,  only converting about one millionth of the war-rationed sugar that was so lovingly fed into penicillin.

Turns out that was the biggest part of our problem : we were feeding it far too well, on easy-to-digest sugars and so it failed to produce any penicillin.

But as soon as we learned to starve it slowly, by giving it milk sugar, (lactose) a sugar it didn't exactly live to eat , it started into giving us tons of penicillin.

Lactose stresses the diets of molds something wicked and when they get food-stressed, but not to the point of actual starvation, they play defence .

The penicillin they start making kills and keeps at bay possible bacteria competitors for what little suitable food the mold can lay its threads upon.

But actually starve a mold (and early researchers often accidentally did that), and they started to rapidly self-suicide themselves in despair.

But feed it lousy lactose, just at the right time, just after its had a day or two of easy living on some nice sugar and protein, and it will produce tons of penicillin.

Literally : annual penicillin product induced by human industry is now at least 20,000 metric tonnes a year.

In 1928, it was about one micro-gram. That's about what Fleming saw in the bottom of his petri dish and it was about as much penicillin as was used in its first cure : curing a newborn baby of a lifetime of blindness , in 1930.

A micro gram is 1 millionth of a gram , so there are a billion of these tiny micro grams in a kilogram of penicillin ( ie about 2 pounds of penicillin). And a trillion of them in a metric tonne of penicillin ( ie about 2000 pounds of penicillin if you are old school.)

So we now produce 20,000 thousand trillion times as much penicillin today as we did 85 years ago.

Fleming's particular penicillium mold was actually very good producer - seemingly the best in the world for 15 years, but only produced one micro gram of penicillin in every gram of liquid medium.

That is a million parts junk to one part money ratio, unbelievably dismal in comparison to every other fermentation process in commercial use at the time.

Today, we get 50 milligrams of penicillin per gram of medium : that is 50,000 times better.

That is a 5,000,000 percent improvement in about 50 years.

Think your grandfather's prize milk cow had an outstanding ROP improvement ?

Try this rapid a percentage improvement on for size !

The main reason why we didn't see this sort of improvement for almost 20 years after Fleming found his mold is because we let chemistry guide our thinking ; trying hard to extract ever more of the penicillin we did manage to produce.

But as I used to say to the CUPE picketeers whenever the Gerry Regan government boasted of the size of its final, final, contract offer : " ten percent of nothing is .... still nothing" .

Only by learning to starve penicillium molds, which we had done by late 1944, did we begin to see enough penicillin to make the stuff a paying proposition , not a charity case, for Big Pharma.

But you can read all the best known books on war time penicillin - and I believe I have - and yet never read one word said about starvation of the molds.

The same goes for present day articles from historians and social scientist about wartime penicillin.

Only articles and books from physical scientists actually working in the fermentation industries routinely mention starvation stress in regards to being essential to penicillin production but even they seem to quote articles from the early 1950s as being the first to signal this fact.

But what then to make of little gem from July 26th 1941 from a letter from Norman Heatley to Howard Florey, just three weeks into Florey's effort to get American Big Pharma to make penicillin on at least a pilot plant scale?

Heatley is at a spanking brand new research facility in Peoria, set up by the US Department of Agriculture to find new uses for farm surpluses - particularly surpluses of low value farm wastes.

He is working with Andrew Moyer : one part mold genius to two parts paranoid nutter.

Already, just ten days after looking at penicillin for the first time, Moyer hazards a guess that penicillin production might be dependent on a starvation metabolism.

If Moyer had only been listened to - and there is no sign that any scientist or bureaucrat then - or historian since - ever did, we might have had commercial penicillin flowing by the Fall of 1941 not the Fall of 1944.....