(Synthetic) Penicillin - (NOT) meeting the Challenge : by Gladys Hobby (co-worker Karl Meyer)

It is a real pity that biochemist Karl Meyer left the writing of a real insider's account of wartime penicillin to his microbiologist co-worker Gladys Hobby.

Because Hobby's book "Penicillin : Meeting the Challenge", one or two gentle digs aside, is decidedly all moral uplift and hands across the water, marking her as "The Pollyanna of Penicillin".

Hobby's book sometimes is more fascinating for what she chooses to leave out than what she puts in it --- and yet she added a great deal of rare, even unique, information.

Meyer only really made one "for publication" comment about his part in wartime penicillin but it was frank and astringent.

It makes a reader wish he had said more : much, much more.

The major reason he didn't was because Meyer knew his role in saving the lives of thousands of SBEs and jumpstarting the fabulous success of native penicillin was all very well, but he was a biochemist damn it and his original goal was to synthesize native penicillin and replace it - not guide it up to the winner's podium.

Meyer had failed, partly because all chemists in the world also failed at this synthesis task --- and partly because he was treated very unfairly by his more powerful scientific competitors - and who wants to research and write a long book about your successful life's one big failure ?

By the time Meyer felt free to make even those few comments, for a book published in 1981, he was over eighty and the key penicillin players had almost all died.

In particular, Ernst Chain had just died a few months earlier.

Inspired by the death of Chain's boss, Howard Florey, in 1968, the first truly multi-continent account of wartime penicillin had come out in 1973, researched and written by Australian journalist and author Leonard Bickel.

Bickel did enough interviewing of minor front line participants still alive to uncover many fascinating, important but unreported/un-Pollyanna aspects of the saga.

His "Rise up to Life" included information from Gladys Hobby that first brought to those interested in the history of penicillin the forgotten efforts of Dr Martin Henry Dawson.

She said Dawson had pushed the North American development of early penicillin in an ultimately successful attempt to cure then invariably fatal SBE , the endocarditis that made Rheumatic Fever the leading killer of school age kids for half a century, a disease she said he had long made his personal crusade.

None of this was true - and she half knew that to be so.

I have found no evidence what so ever that Dawson ever mentioned SBE at any of the many scientific meetings he attended or that he wrote articles on it or did research into it.

And Hobby was his closest co-worker for ten years : she too had said, written and done nothing on SBE.

So Dawson had done nothing on SBE --- least not before October 1940, when the penicillin project at his hospital had already been underway for 5 weeks.

Hobby freely admits that she herself was away on vacation when the project began and she returned after several hectic weeks into the effort - so she could only know of the project's origins from what Meyer, Chaffee and Dawson told her.

The agreed plan, by the time she arrived, was that the native penicillin would be grown mostly by Hobby.

Then after being purified and its chemical structure figured out, it would be synthesized artificially, all this mostly done by Meyer and Chaffee, tasks expected to be completed sometime early in the New Year.

Then, and only then, would clinician Henry Dawson reach centre stage - injecting the synthetic penicillin into patients whose care he controlled as the sole attending physician among the small four person team.

A few days before Draft Registration Day, October 16th 1940, Dawson suddenly decided to put a very little of the very weak and very impure native penicillin into two patients with SBE, a disease whose cure, virtually all doctors agreed, would require lots of medication every day for weeks and weeks on end.

Dawson's tiny injections might raise the dying pair's morale but could have had no direct physical impact on their disease.

And it rather upended the team's agreed upon project protocol.

As that chemically-oriented protocol suggests, Meyer the biochemist had actually started the project.

But he waited a half century, till just after the death of Ernst Chain, to say exactly why he had.

In 1980, Meyer was interviewed by a young endocarditis researcher, Australian born Dr David T Durack, who was writing an article on the early history of the conquest of endocarditis by antibiotics for a book, edited by Allan Bisno, on infective endocarditis.

Meyer told Durack that in the late summer of 1940 he was incensed by the assignment of priority given to Meyer's own pioneering work on lysozyme in articles by Ernst Chain.

(Meyer probably didn't mention it but he was possibly even more incensed by Chain jumping his priority on Meyer's much more exclusive pioneering work on hyaluronan.)

Chain had been a fellow biochemistry student with Meyer in Berlin and even more importantly, both were not-yet-established-German-Jewish-emigre-scientists in the wartime Anglo-American medical research world.

For either, scoring a significant scientific discovery might keep them out of an internment camp, while a rival stealing their credit might mean a hard bed in that same internment camp.

I think most biochemistry experts agree that Karl Meyer was a far, far better biochemist all his life than Chain.

So for whatever reason(s) , Meyer's pioneering work was always closely followed up by Chain.

Only this time, Meyer would turn the tables --- follow up on Chain's pioneering work for once.

Try to beat Chain to the goal of purifying native penicillin to the point when its structure could be determined and then it could made by artificial synthesis.

A great story --- but how true ?

Because Chain didn't even submit his co-authored articles on hyaluronan and lysozyme until late September 1940 and late October 1940 and they weren't even published in the UK till December 1940 and no one in America could have read them before January 1941.

Was Meyer clairvoyant then ?

No - and Professor Ronald Bentley provides the solution.

He got to know Professor Leslie (Epstein) Falk late in both their careers and learned that Epstein had not just done his PhD thesis on lysozyme under Chain's close supervision but had also informally helped Chain in the early Oxford work on penicillin.

The Fall of France had prompted the US & UK governments to agree to return all the American Rhode scholars posthaste, because America was still neutral.

So Epstein couldn't even stay long enough to dot the last "i"s on his thesis, but he was in Oxford when Florey first injected penicillin into mice and cured their fatal disease without harming the mice with side effects.

Epstein felt the sudden uprise of excitement in Florey's entire institute and the move to keep it all hush hush until it had secured a commercial sponsor and had been published.

Epstein was Jewish and a leftist - Florey didn't much like either.

Epstein probably felt he owed Florey no particular loyalty as a result.

So he spilt the beans on the penicillin project, including Chain's expected role, to Meyer while using Meyer's expertise in lysozyme together with Meyer's reagents and lab space to finish his PhD - sometime between June 10th and September 7th 1940.

Like Epstein (and Chain for that matter), Meyer was also Jewish and left-leaning.

I personally feel that Epstein really liked Chain and only inadvertently let slip Chain's 'off the cuff' dismissive comments about Meyer's work.

Probably while recounting some of the endless 'colourful stories' that Chain's very mercurial personality tended to throw up.

Because I see nothing too offensive in either of Chain's relatively cautious articles (on Lysozyme and Hyaluronan) and in any case, they came out months after Meyer began his penicillin project.

No, Meyer, forewarned by Epstein in person what journal would get the Florey,Chain et al penicillin article and what month it might come out, lay in wait for whatever tidbits of new information on penicillin's curative effects the article might have.

He needed that information to be good because he needed microbiologists (Hobby) and clinicians (Dawson) on side, if he was to pull off the synthesis of penicillin.

Because there was no chemical test to tell you that you have actually synthesized penicillin - that could only be established biologically by skilled workers.

Now Durack also interviewed Hobby and Dawson's last co-worker Thomas T Hunter for his article and told them they'd be in it and when and where it would come out.

Hobby read Durack's article when it came out in 1981, that I am sure , including Meyer's bombshell revelation, and went on to publish her own account of wartime penicillin in 1986.

But she choose not to alter in any way her earlier claim to Bickel that their pioneering penicillin effort was led from the start by Dawson and was set up to defeat SBE with penicillin.

Meyer's account rang true, but Hobby wanted nothing in her book to upset its thesis that good will and a lot of hard work among united allies gave us the miracle of wartime penicillin.

If her work sold far less copies than Watson's 1968 "The Double Helix" one need not search hard to find why.

Her account of the 'drama' of wartime penicillin left out all the drama .....

Florey's "Unfinished": the unfaithful Vassal #2

In 2002, Milton Wainwright published "Fleming's Unfinished" .

Fleming was not some obscure Scottish composer and the "Unfinished" was not a musical work cobbled together from unpublished musical sketches after the composer's death and based on a close study of his mature style.

In fact a famous composer is rather undone if no one cares enough about them to find something that can be hacked into shape, published and performed to acclaim.

Now Fleming ,that is Sir Alexander Fleming, as one of the most famous names of all, is hardly thought of as someone badly done by in the "fame" department .

But among scientists, he is damned by faint praise - faulted for dropping penicillin almost as soon as he picked it up - leaving millions to die needlessly.

Milton Wainwright (and Ronald Hare, Gynn Macfarlane and Kevin Brown) have all pointed to Fleming's extensive notes on penicillin from the Fall of 1928 to the Fall of 1940 as proof he didn't quickly give up totally on penicillin as an antiseptic agent.

Wainwright goes much further and claims that Fleming had hopes for penicillin as an antibiotic in the common sense - something taken internally to cure life-threatening diseases.

I, and almost every one else, disagrees that Fleming did see it that way... until August 1942 - making him penicillin's biggest Doubting Thomas.

Anyway, Wainwright implies that Fleming was just about to wrap up his 12 years of research on penicillin, when the Florey team's first article rendered it all moot. So Wainwright was going to try to finish it for him anyway.

 My belief is that Fleming had good cause to doubt penicillin's efficacy as a systemic, based on his lab work.

Fleming ,and the institute that he worked at, was never inclined 'to do the clinical' anymore than his nemesis, Howard Florey, was.

Both men avoided the wards, "preferring the deep,deep sleep of the laboratory bench to the hurly-burly of the hospital bed".

(And don't think that I haven't waited my whole life for a chance to misuse that quote in my writing...)

 Florey's father and his business was betrayed ,the Florey family claims, by an unfaithful servant - an accountant.

Certainly, Florey was notorious for acting like he trusted none of the scientists directly under his employ, while giving an unusually free hand to any researcher merely 'renting space' at his Institute.

Once bitten, twice shy, I guess.

Unfaithful Vassal #1, Ernst Chain, actually saved Florey's plodding bacon, when Chain broke ranks and broke protocol on the wide front/ slow moving penicillin project in March 1940.

This is because Unfaithful vassal #2, Leslie Epstein, didn't keep silent about the penicillin project when he returned to New York on June 10th 1940.

He talked it up to Dawson's teammate Karl Meyer that summer, along with the more unpleasant news that Chain meant to dish Meyer of some credit for the chemical meaning of Lysozyme.

 (This, the first big discovery of Fleming tied together Fleming and Florey and Chain and Epstein and Meyer and Dawson and Hobby.

 All, for different reasons, were keenly interested in its bacteria-dissolving nature and in anything (like penicillin) that looked to be similar.)

Now Chain and Meyer were both Jewish, German and unknown scientifically.

These two young bio-chemists knew they would soon end up in alien internment camps (as thousands like them eventually did) if they couldn't soon establish scientific reputations.

Every bit of citation credit helped - well worth fighting dirty over.

Meyer resolved to get revenge by beating Chain to the punch on the purification of penicillin - Chain's private baby.

He didn't start right away, but he planned to - even if Florey's team hadn't of published in August 1940.

Meyer had to wait till his team re-assembled in September 1940 after family vacations - he absolutely needed the services of a microbiologist and a clinician if he hoped to purify penicillin.

My version of Florey's "Unfinished" looks at what would have happened if Unfaithful Vassal #1, that is Chain, hadn't broke protocol on March 18th 1940 and had some of his penicillin powder stuck into two mice by the obliging Doctor John Barnes.

Florey hated doing anything twice - freely admitted hated doing routine clinical work.

(When you and I are dying of perfectly regular lobar pneumonia caused by perfectly regular Type II s. pneumococcus, that is "routine clinical work" to Florey - though possibly not to you and I !!!)

He always wanted to be the person to do something the first time - whether or not it had any meaning outside of that feat - the athlete of science.

I take some of that back - many things he disdained doing ever - first or otherwise.

He probably never ever gave a human a needle of penicillin - he had no privileges to do so but he didn't seek them either.

He was first and last a good animal experimenter.

Putting penicillin into mice was his job, not Chain's.

And Chain had agreed to it.

But to Chain , more than to Florey, penicillin was his project - a project to purify penicillin chemically.

The proof of any success he might think he had in purifying penicillin was dependent on demonstrating the material had biological activity.

For that, as Florey (and Fleming et al) could point out, testing it against bacteria in a petri dish was all that was needed - and Chain could do that, without having to gain a hard-to-get animal testing license.

The plan, the protocol, that Fleming and Chain had sold to the MRC and to the Rockefeller Foundation called for a methodical, through, step-by-step study of penicillin.

No rush - the Rockefeller grant was intended - unofficially - to run for years and the first payment wasn't even due till March 1st 1940.



So Florey might have felt that any animal testing was way too premature and could be held off till the Fall of 1940, when he might be less busy with his current, more important, research on shock and when Chain might be further along on the chemical side.

So animal protection tests on November 25th 1940, and publication in Lancet three months later, as planned - ie in late February 1941.

Too late to learn that Dawson has already announced his results at a public lecture at the NEW SCHOOL FOR SOCIAL RESEARCH on February 12th 1941 !

The wartime story of penicillin would then look very different.

If Florey's father was ruined by an unfaithful Vassal, Howard Florey can only be thankful that he was saved by an unfaithful Vassal....