Life-saving penicillin can be a little bit fermented but not a little bit synthetic

If a medicine will save lives when nothing else will do so - in war as in peace - then Henry Dawson's example reminds us that our first moral requirement is to make it as much as we can, anyway we can, save lives anyway we can..... and only then try to perfect it.

Fermentation penicillin ( aka natural, biological penicillin) worked  (feebly) from day one (September 1928) but could be (and obviously was !) improved gradually.

By contrast, even after 15 years, synthetic penicillin in late 1943 still hadn't been gotten to work at all.  (IE, biologically : all resulting attempts showed no medical activity at all.)

In a way , synthetic molecules are completely like pregnancy.

As with pregnancy, there is no half-way house : you are or you aren't ; a synthetic molecule either works, or it doesn't.

In addition, even if synthetic penicillin could be gotten to work biologically, there were still two possible huge problems ahead of breaking out the champagne.

The yield could be much lower than the already low yield of Fleming's original strain of penicillium, not many magnitudes higher.

And the number of steps required in the synthesis and subsequent purification/ separation might require more, not less, money, equipment, manpower, care and close attention to detail than even the worst version of the fermentation method ever called for.

I have one word for you my boy. Rosebud ? No : quinine.

These are not just theoretical objections : as bad luck happens they all came to pass with synthetic penicillin.

The pursuit of  synthetic quinine , now a more than two hundred year long futile chasing of a tail by generation after generation of chemists , should have reminded the 1940s penicillin synthetic faithful of the possible pitfalls that could lie ahead......

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...

Part of "The Penicillin Holocaust" : Allied POWs dying needlessly of infection because the Allies decided they didn't deserve penicillin...

A whole lot of people died needlessly of infections that wartime penicillin could have/ should have cured --- all because the Allies decided to treat it as a military weapon of war --- only to be used to cure lightly wounded Allied combat troops, to get them back under enemy fire as soon as possible.

Clearly that meant they would rather not have to give penicillin to seriously wounded Allies men or to civilian patients at home or in neutral countries.

In addition, no penicillin for dying civilians in occupied nations or in enemy countries either.

None to enemy troops obviously or to enemy POWs ( though this latter decision was against past custom and current international law.)

But it also meant none for dying Allied POWS behind enemy lines either.

Millions of needless deaths : "The Penicillin Holocaust"

These are just some of the human and moral costs when medical doctors, in their role as government and military advisors, counselled keeping penicillin as a secret weapon of war rather than a public and universal lifesaver.

But one doctor sacrificed his own life to oppose this horrendous policy tooth and nail : Henry Dawson ....

Eliding chemical synthesis from the Pollyanna histories of Wartime penicillin

Every Pollyanna account of wartime penicillin has much blather on how (Florey) (Fleming) (you add a name) went to this or that firm asking it to grow some biological penicillin only to find much tea and sympathy but no eagerness to help.

"The yield is too small, the active ingredient too unstable and too hard to separate from the impurities" ,etc etc.

The accounts then goes on to say, that despite these doubts, the firms did rally around in an international joint effort (cue "The Special relationship" cliche) and today we have cheap, safe, abundant penicillin produced by biological methods.

*The End* (The peasant girl and her prince live happily ever after.)

But while every single firm did, in fact, say those very things about the difficulties of the biological process, they also said a great deal more besides.

Such as : "the chemists are sure to quickly synthesis such a small molecular weight molecule, just as they have with similarly weighted vitamins recently--- so we can't see investing  in a full scale biological process, only to see all that money wasted when that plant is immediately replaced by a fast cheap chemical synthetic process."

"So the best we can promise is a small pilot biological plant to produce a little penicillin for experimental treatment of a few patients, with the bulk going to our chemist to determine structure and then synthesis. "

This strong emphasis (right from the very beginning) on giving priority to the chemical synthesis of penicillin rather than an all-out effort to improve the biological yields of the penicillium has been elided out of the good-news story of penicillin.

 Partly this is because (a) it failed badly.

But mostly because (b) it delayed for several crucial years the needed research on upping biological yields and (c) prevented the saving of millions dying of wartime infections with the penicillin then-current technology could provide - if governments had wanted it to.

That last point in particular is elided out of existence by the penicillin pollyannas - and rightly so, because what it says about the Allies' behavior on penicillin and the saving of wartime lives is hardly flattering to our cherished collective myths of WWII.....

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....

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....

The morality of good - temporary - military secrets and bad - semipermanent - military secrets

There is little morally to fear for all of us agreeing to keep  traditional (and temporary) military secrets such as all troop movement before the planned big invasion.

By their very nature, such secrets are no longer a secret two or three days into battle.

But Enigma code-breaking, The (atomic) Bomb, the Proximity Fuse and Wartime Penicillin were all military secrets with huge moral costs attached.

Enigma was only kept secret for so long by sometimes deliberately not revealing to the effected military units the grim fate before them that the code-breaking revealed --- all in an attempt to keep the code-breaking secret from the enemy long enough for code-breaking to reveal (and foil) huge plans by the enemy.

This moral dilemma has kept the Enigma industry churning out lots of books and movies, 75 years after the events.

Proximity fuses were so wonderful that we couldn't use them against the Germans, convince they would find one unexploded and  quickly duplicate it and then use it to horrible effect against our bomber streams because it was actually more useful to them than to us.

This is the same dilemma that the Germans faced about the nerve gas they invented, because they rightly feared we could make better use of it than they could --- so they never used it and kept it secret.

(At least the Germans didn't put much effort into producing nerve gas  because it more or less fell into their laps- while proximity fuses were one of the single biggest scientific and engineering effort of the entire war - in my view, a mammoth mis-allocation of scarce war resources.)

The Atomic Bomb could not remain a 'secret' for very long once it was used, because it was seemingly so war-endingly successfully.

Hence nations big enough to afford it simply felt they had to pour immense amounts of money, expertise and national willpower into duplicating what the Americans had hoped to keep secret for at least a generation.

The entire American civic culture changed, for the worse, when the American atomic establishment decided atomic information could actually be "born secret and kept secret government property", even at the moment a new concept first formed in a scientist's mind !

What really kept the Bomb a 'secret' , quote unquote , is the expense and complexity of making it consistently successfully.

Everyone on Earth had heard of The Bomb, knew what it did , what it was made up and even basically how it worked : the American government had showed them all this in the public Smythe Report.

But a successful Bomb, like the Devil , was in the details ; these were complicated, expensive and remained secret to all but the best foreign spies.

And this - presumably - was how the Allies expected to keep the "Penicillin Secret" once they unleashed it as a secret medicine weapon only for Allied frontline casualties on D-Day (if Patty Malone and that damned beta-lactam ring hadn't spoiled the plan).

Who could really expect to keep the good news about penicillin's life-saving powers away from the general public (aka the relatives of frontline troops), as soon as  millions of Allied casualties were coming back home alive, while enemy POWs from the same battle  were dying like flies ?

No, like The Bomb, penicillin would quickly become uniquely famous  all around the world and only remain a 'secret', quote unquote, because the Allied scientific elite figured that the information as how to make it could remain secret from the enemy for at least a year, because it was complex and expensive.

Remember, even the atomic bomb secret was broken in the end, but only about six years after it became first known to Britain, France and Russia that an A-Bomb would likely work.

That's the length of the entire (long drawn-out) WWII.

So a permanent military secret kept for as short a time as a year long, might still be viewed as long enough to be militarily effective.

But penicillin was no where as complex or as expensive as proximity fuses or nuclear weapons : in fact, it is a piece of cake for every and any hospital bacteriology lab to make safely and cheaply, in amounts sufficient to save the lives of all the people in that hospital dying of infections no other medication could help.

In normal situations, those really are not large numbers, spread over an entire year and over an entire country: in peacetime, there needn't ever be a penicillin crisis, for least for the dying of infections would get it when they really needed it.

But a huge invasion like D-Day requires an extraordinary amount of penicillin over a few days or weeks, in a small area , under fluid combat conditions that obviously doesn't allow much in the way of crude penicillin-making labs in sedate base hospitals.

So war weapon (frontline battle) penicillin really did require a lots of stable penicillin in a dry power, to be useful.

But in fact, even without Patty Malone to tip them off,  as soon as word of penicillin great success got about, the enemy would start making it by the crude means known in the vast amount of public literature on penicillin.

But the cost of keeping penicillin a non-public success before unleashing it on D-Day, was in denying it for civilians in Allied,Neutral, Occupied and Enemy countries for years and in fact, in denying it to ordinary soldiers dying of infections penicillin could cure, again between 1940 and 1944.

That is literally millions of needless deaths --- at least as much as the Jewish Holocaust.

It was and is , a horrific moral crime, a deliberate crime promoted by doctors.

And it is why I write about wartime penicillin , 75 years after its events...