Tuesday, February 24, 2015

First antibiotic penicillin patient : when did we learn his name?

How do we know what we know ?

I am very confident that the very first patient of the Antibiotic Era was a young black man named Aaron (Leroy) Alston and that he lived on St Nicholas Avenue in Harlem, New York City.

But when I was asked recently by one of Aaron's relatives (journalist Claude Jay) to demonstrate my proof, I was momentarily nonplussed.

That was when because I initially came across the statement that Aaron was the first systemic penicillin (penicillin-the-antibiotic) patient in history in early 2005, it was in about a dozen different books, all read at the exactly the same time.

(People who know what a bookworm I am, will not find that last statement at all incredible !)

I gradually assembled more information about that historic event and on Aaron himself , from scattered bits of evidence here and there - material I realized had never been assembled into a coherent and self-confirming whole.

My biggest breakthrough - discovering Aaron's death certificate - was quickly followed by my second biggest breakthrough , discovering Claude Jay himself.

That is because, outside of his medical records, Aaron was generally known to the world as Leroy, or more formally, as A. Leroy Alston.

Aaron Leroy Alston was a superb athlete  -- not just someone who died to furnish a footnote to someone else's story

I had held a strong clue that could have led me/ should have led me to Leroy years earlier.

But I discounted the evidence : that an A. Alston had won some very big amateur races in the NYC area.

I mistakingly assumed that anyone who had had acute rheumatic fever leading to severe heart valve damage, as Leroy/Aaron had to have had, couldn't possibly go on to be a top runner.

Now that I knew Aaron was also a Leroy Alston or an A. Leroy Alston and a great athlete to boot, I quickly found a good deal more about Leroy from newspapers of the day.

So I spent last week trolling through my files and the books on penicillin and rheumatic heart disease at Dalhousie University's medical library, trying to establish a timeline as to when the world first knew that Aaron was Patient One of the penicillin-the-antibiotic era.

I found nothing that named Aaron in the books and medical reports and newspapers of the war years.

NY World-Telegram first to get it (partially) right

But on the premature death of Aaron's penicillin doctor Martin Henry Dawson in April 1945, one New York newspaper, the World-Telegram, did correctly mention that his first penicillin patient was a Negro, as well as claiming that Dawson was the first to treat a patient with penicillin in the USA.

But the story not only does not name that patient, it confuses his story with that of the other first penicillin patient of Dawson's, Charles Aronson !

(Yes, Aaron was the first patient selected to receive systemic penicillin, but as the fates would have it, on the day he first received it, a new fellow sufferer (Charles) also got it at the very same time.)

The story describes Aaron as being 27 and being cured - that age and fate correctly belongs to Charles because sadly Aaron died despite the penicillin.

Now Dawson and his closest fellow worker, his lab chief Dr Gladys Hobby, were modest to the point of giving me a stroke.

The pair knew, when they initially read Howard Florey's August 1941 article on his team's first clinical use of systemic penicillin in February 1941, that Dawson's team had beat him by four months in first using penicillin systemically.

But maddeningly, they still modestly claimed only to be the first to do so in North America , in any newspaper interviews or medical articles published during the war years.

Hobby, I sense, had no great memory.

This is because already by 1949 (only 8 years later) and after consulting her own personal records (!), Hobby writing in a report for her then employer, Pfizer, says the first injection only happened on January 11th in 1941 !

Reading her later - more accurate - accounting, I can only suggest that in 1949 she meant to say that January 11th marked the first day of intravenous injections.

This after a series, in the months earlier, of first intracutaneous injections, then sub -cutaneous and then intramuscular injections.

(As doctors will know, there are actually dozens of different forms of medical injections - varying by both site and method.)

Hobby went to her grave also convinced that Dawson gave the first penicillin shots on October 15th 1940 - a statement she repeatedly gave to fellow penicillin historians who dutifully spread it far and wide.

I don't believe it --- and neither should you.

For nowhere in her ultimately relatively detailed chronological account of the first days of penicillin-the-antibiotic does she indicate when the totally new drug was first tested on a healthy volunteer before being injected into the two severely ill patients for real.

Even in the relatively relaxed medical research atmosphere of the 1940s, that would never have happened.

Durack and Bentley provide more clues

Let us turn first to a little known medical paper by Dr David T Durack, who based his article in part on a personal conversation with the biochemist of Dawson's tiny four person team, a person moreover who started Columbia's pioneering penicillin effort even before Dawson joined it.

Around 1980, Durack contacted that biochemist Karl Meyer, a distinguished scientist then in his early fifties and in full control of his faculties and memory.

(Durack's article was published before Hobby published her definitive 1986 book on penicillin but was never mentioned by Hobby - signalling to me that Hobby and Meyer were hardly close after Dawson's death.)

Durack's article, "Review of Early Experience in treatment of bacterial Endocarditis, 1940-1955", I found in the book "Treatment of Infectious Endocarditis", edited by Alan L Bisno.

Meyer's story at first seemed incredible to me, but as I gathered up more information here and there, it was confirmed by an article by Ronald Bentley at various key points.

Meyer had gone to a Berlin medical school with his fellow (German) (Jewish) student Ernst Chain and I believe had taken a mild dislike to him, something very easy to do with the mercurial Chain.

Now in September 1940 he had learned (directly via Chain's former graduate student, Jewish American Leslie Epstein*) that Chain was taking credit for important work first done by Meyer on Lysozyme and that he was now trying to synthesize penicillin.

*Read Bentley's fascinating account of Leslie Epstein Falk struggling with Chain to grow a little penicillin in the Fall and Spring of 1939-1940 and when Epstein is ordered out of Oxford only months before finishing his PhD, how he completes it partly thanks to a stay with Meyer at Columbia.

For both Chain and Meyer, I believe an elbows- out attitude, even against fellow German Jewish emigre scientists, was morally right in 1940.

Both knew that if they didn't prove themselves quickly to be top scientists in some way, they would end up interned by the German-and-Jew-distrusting Anglo-Saxon government elites, stuck in miserable prison camps along side Nazi Germans.

Meyer and Chain both thought synthesizing a small (350 Dalton weight) molecule like penicillin would be a breeze.

Meyer simply involved Dawson to do the early biological activity tests and then to do the much later clinical trials, after the drug had been synthesized.

Dawson jumped Meyer's gun, insisting on testing the drug's efficacy inside the human body long before it was synthesized.


Partly to save the lives of two young men before him who he thought were being discarded by a medical establishment using the excuse that they were gearing up for total war.

Partly to secure Meyer's flank, because the biochemist was working after all in a hospital, a workplace oriented strongly to instantly applied science, not in a more leisurely basic research lab.

So Meyer tells Durack, on October 15th 1940, penicillin was indeed injected for the very first time, as Hobby (and all those after her) claimed.

But not injected into a patient.

Injected instead by Dawson into Dawson acting as the human guinea pig to test it for human toxicity - Dawson believing it was better that he the doctor died than the patient doing so.

(Entirely typical of the decorated war hero Dawson, as was entirely typical the decision of war shirker Sir Howard Florey not to risk his 'valuable' life testing his penicillin on himself !)

But Durack reports (indirectly - no names are used) that Dawson only injected Charles Alston, not on Charles and Aaron.

This could be because he also interviewed Dr Thomas T Hunter.

Hunter was a later member of Dawson's team, who never met Aaron but who did meet Charles many, many times.

He first met him in the Spring of 1944 when he came back with a second attack of endocarditis and was cured by Dawson yet again, this time by penicillin alone instead of with a little penicillin and a lot of sulfa drugs.

Hunter did further checkups on the health of Charles until early 1946 at least - so his story naturally stuck in Hunter's mind years later.

Hobby was not on the team - but still in close touch - when Charles returned in the Spring of 1944 - maybe why she remembered him much less.

This raises a significant point - why do almost all writers choose to mention just Aaron or just Charles instead mentioning both ?

Penicillin writers and their hidden agendas

Because most writers have a not so hidden agenda.

(Mine is that I think Dawson got a raw deal from history for his pioneering HGT and Penicillin work.)

To date, most others writing about wartime penicillin have sought, above all else, to exalt Howard Florey over the man who they feel wrongly gets the credit for penicillin-the-antibiotic, Sir Alexander Fleming.

They are equally worried that the real credit should not slip off of Fleming's mantle only to fall onto that of the colonial Henry Dawson.

Like Florey, and unlike Dawson and Hobby , they realize Dawson was the first to ever give a needle of penicillin-the-antibiotic and hence it was he who ushered in our Age of Antibiotics.

Further they know that Dawson championed natural penicillin (and it is worth noting that most of our current antibiotics are still based on the original natural penicillin), to be made by Pfizer and others.

Florey and Fleming, by pointed contrast, strongly championed synthetic penicillin, to be made by ICI (Imperial Chemical Industries) and others.

ICI never made a single commercial drop of the synthetic stuff - no one ever has - and 80% of all the penicillin landed on D-Day and there after came from Pfizer alone.

Seemingly hard then not give Dawson the lion's share of the wartime penicillin glory - but it can be done, if you work at it.

So these agenda-driven writers dutifully note, in almost footnote fashion, that Dawson indeed gave history' first (very small) penicillin injection.

They then decide to focus on just one of the two initial patients (Aaron), the one that died.

Next they note that Dawson quickly got Myasthenia Gravis and that he also died.

All half truths, but enough truth in them so they feel they needn't cover his four further years* of clinical penicillin activities between April 1941 and April 1945.

*Dawson had much, much longer period of clinical involvement with wartime penicillin than did either Florey or Fleming.

Hunter and Durack, by contrast, want to see Dawson's first medical glass as half full.

So they focus on Charles (the other one of the original pair, the one who lived) as the first patient to ever receive penicillin.

Someone, they imply, as a result went on to survive a hitherto invariably fatal disease.

The truth is that two low status young men - one a black and another a Jew - got history's first penicillin shots basically out of the agape concern of a doctor who wasn't even their lead doctor or a specialist in their disease.

One patient, Aaron, was extensively treated with penicillin but still died, while the other patient Charles was responsive to sulfa (unlike Aaron) and lived.

The little penicillin Charles got had almost no effect clinically but it sure boosted his morale and that might have helped save him as much as the massive sulfa doses.

Bickel to the rescue

Now we move ahead in time to about 1970, when Australian write Lennard Bickel decides to write a biography* of Australian born penicillin pioneer Sir Howard Florey, who had just died in 1968.

"Rise up to Life", first published in 1972.

He interviews anyone who he can find who was there at the time to talk about wartime penicillin, tracking down people in America, Britain and Australia.

Many buried names and stories only survive today because of his fine journalistic efforts.

Bickel wanted to exalt his fellow countryman of that there is no doubt, but he did not wish to bury Dawson - in fact he exhumed him from the grave of human forgetfulness.

I do not believe that Hobby would have even written her seminal account of wartime penicillin without Bickel .

His book and the reaction to it, finally convinced her, almost 25 years after the fact, that Dawson had indeed been the first in the world to inject systemic penicillin and hence held a story worth recalling.

Because we know she told Bickel in circa 1970 interviews for his book that she was still convinced that Dawson was merely the first to treat patients in the USA alone with penicillin.

And she - citing her notes - claimed he had treated only one patient on that historic day, which she said was October 15th 1940 - and that the patient died.

But at least and finally, she brought forth his name : Aaron Alston.

And she talks forthrightly about Dawson's fatal Myasthenia Gravis.

But she - and Bickel - make it clear that if he worked less as a result of this crippling disease, he still worked full out on penicillin till his death in the spring of 1945.

Since Bickel became the key - almost primary source level - "go to source" for most of the academic accounts of wartime penicillin, it is remarkable how this clear statement of his four more years of penicillin activities could be so twisted and ignored.

Flash forward to 1985, Hobby has retired after a modestly successful paid career working at at Pfizer on new antibiotics and a Veterans' hospital working on TB and a more successful volunteer career as a editor of various scientific society journals.

She has gotten to know everybody who was anybody in early penicillin in both North America and in Britain.

Yale University* Press, her publisher was admirably demanding and so Hobby trolled deep to firm up her claims - even consulting a Miss Louise Good for her lab records of the early use of Dawson's penicillin.

If only Yale was as demanding upon its own staff, who persist in claiming that their University was the first place to use penicillin in America.

Dawson was their first and was also the first to see cures with local (topical) use of penicillin to treat staph eye infections.

But Yale can rightfully claim a first, for inn March-April 1942, they successfully treated a case and saved a life with the systemic use of penicillin alone.

Charles Aronson's life was saved too, and much earlier - in December 1940 - but by lots of sulfa and perhaps a little contribution from pioneering penicillin.

Good's work

Good seems to be the sole source in Hobby's 1985 book "Penicillin : Meeting the Challenge" of Hobby's new information on Aaron and on who she calls Charles Aronson, his fellow needle pioneer on October 16th and 17th 1940.

Now I could reliably confirm the relatively detailed information on patient C.A. found in Dawson and Hunter's 1945 JAMA article on their clinically successful use of systemic penicillin in curing subacute bacterial endocarditis.

Dawson and Hunter's C.A. had to be Good and Hobby's Charles Aronson, born in 1913 and thus highly likely to be a young Jewish-American man with that name from the Bronx found in the 1940 US Census.

Similarly, it seemed clear from Good's information that Aaron had died in the Columbia-Presbyterian Hospital, in the Borough of Manhattan, in the days around January 18th 1941.

So I could then overcome a problem unique to the New York City death certificate of that era.

They are easy to obtain and quite detailed - but do not give the cause of death, unlike those of most other jurisdictions - that information is given to the city government alone in another document.

So in a city that big, and when one seeks someone with an ethnically common name, one needs the borough the death was registered in and the exact day of death to safely match death certificate of a particular Aaron Alston with the unique penicillin/endocarditis Aaron Alston.

Thanks to Claude, I could now find newspaper accounts of Aaron Leroy Alston getting sick and then dying in the time periods that Hobby and Good address - both sets of data confirming each other.

So there you have it - Aaron Alston , the very first to receive penicillin-the-antibiotic is never directly named in any of a dozen or so clinical medical articles published during or just after the war years at the time that do reference him but indirectly.

His name and his connection to the first ever use of penicillin-the-antibiotic is mentioned in dozens of more recent medical history oriented academic articles, all dating after Bickel's pioneering book of 1972.

In addition, Aaron's story is mentioned in least one wire service story from Warren Leary, the AP science reporter.

 In early October 1978, Leary reported that the longstanding belief that the British had been the first to inject penicillin into a patient was wrong.

Leary based his claim on a recent report in the Journal Chemistry from Dr George Kauffman that talked of Dawson's pioneering work.

One suspects Kauffman in turn had recently read Bickel's new book !

Aaron's story is still distorted

Gladys Hobby's penicillin book is probably found in every first class medical research library in the world and she gives the most detail about Aaron Alston - my blog aside.

Problems persist : author and wartime penicillin pioneer John C Sheehan, in a MIT Press* published book, "The Enchanted Ring" , confusingly thinks Aaron Alston is the doctor giving that very first needle to some unnamed patient.

He even regards Dawson's team, operating in the same hospital, as totally separate from 'Dr Alston' and his team !

*New Yorker magazine stories are throughly fact-checked, scientific journal articles a little, university press books by distinguished scholars from the same university as is publishing their book ? Not so much.

Okay, now for the biggest and serious problem : the near universal inclination for all sorts of researchers, even historians who really should know better, to read into Dawson's 1941 claim that he treated four SBE patients with penicillin all unsuccessfully, as meaning they all died.

Yes, SBE was then 99% fatal on its first presentation, but Charles Aronson was in that 1%, cured by sulfa, a little penicillin, God's grace and his own documented ability to survive more lives than a cat.

I know for certain the names of three of Dawson's first five SBE patients, that they were all five clinical failures re treatment with penicillin, that two Aaron Leroy Alston and George M Conant) died for sure, one lived for sure (Charles Aronson).

The other two I know nothing about, except that they were likely young men from the greater NYC area and that their likely months of admission were April 1941 and October 1941.

All the team members that treated them are dead and the hospital records from that time destroyed - we will likely never know more unless some family member remembers a relative dying of SBE around those dates at Columbia Presbyterian.

We have good information on the two dozen later SBEs that Dawson subsequently treated - but only have three full names provided by Hobby's book all which have so far produced dead ends.

What we need most for Aaaron is a picture of him.

I recall much of the fifty year mystery of blue singer Robert Johnson wasn't lack of reliable data about his life, but rather a lack of an ability to put a human face on a terribly interesting individual.

I feel the same about the fascinating Aaron Leroy Alston 1910-1941...

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