more HOBBY more PEARLS

GLADYS HOBBY in 1971, chairing the editorial board of the scientific journal she founded

Of course, people wanted more pictures of Gladys Hobby.

Well there is one color one, Hobby with Fleming, but it is all too common on the web already for me to add another copy.

But here are a few more, with pearls, natch.

I haven't put out any photos of  Meyer or Hunter or Odlum as they are well represented on the web.

But women always get short shrift, in photographs as well as in life in general.

I would really like to see a photograph of Eleanor Hahnel (of GAF industries in the 1960s) aka Eleanor Chaffee, (grad of the University of Connecticut 1937).

Or a photo of Miriam Olmstead (girlfriend of Robert Goddard of rocket fame), aka Miriam Lipman, spouse of artist Michael Lipman, aka a woman who did much to make Rheumatoid Arthritis and all auto immune diseases more understandable, if not yet much more treatable.

If you can help, leave me a comment below.

Until then, enjoy a few more pictures of Gladys Hobby:

Hobby in a formal pose , age about 75

From a picture taken of Hobby with Dr Ethel Florey, the clinician-wife who rode around on her bike in the rain collecting penicillin from patients' urine while her husband ,Howard Florey, played 'find the salami' with his mistress back in his apartment-like office at the DUNN ---- and then got most of the credit for Ethel's clinical penicillin work...ain't it always the way ?

Hobby finally gets her due

Today the best known member, at least among the general public, of the tiny Columbia University team that did the most to bring penicillin to the public as soon as possible (and did so over Columbia's dead body) is Gladys Hobby.

GLADYS LOUNSBURY HOBBY          Nov 19 1910 -July 4 1993

It is a fame she never enjoyed while still active in antibiotics.

The terminally ill Henry Dawson gets most of the credit for providing the moral energy and drive to the Columbia penicillin effort - something that Hobby and Meyer were always forthright in reminding people.

Karl Meyer lived the longest of the main foursome and lived long enough to see his lifelong scientific interest, hyaluronic acid, become a virtual growth industry.

The fourth member ,Eleanor Evelyn Chaffee (aka Mrs Eleanor Hahnel?), will emerge from the shadows, if it is the very last thing I do.

Thomas Hunter first saw fame for finishing Dawson's proof that penicillin could cure the incurable - SBE. Then he became a medical school dean best known for promoting medical education in the third world.

The fairy godfather of the team, Floyd Odlum, is probably best known today for displacing Howard Hughes at RKO.

Miriam Olmstead is today best known as a former girlfriend of the Rocket man, not Elton John, but rather Robert Goddard.

There were a few others, not as invisible as Chaffee ,but rarely connected today to this pioneering penicillin effort.

Hobby after penicillin went on to discover and prove up other big antibiotics and then take leadership roles in science organizations when few women were permitted to do so.

As a result we get many bare bones bios of her - celebrating what she did but not why.

The best - by far - of these is Elizabeth Moot O'Hern's "WOMEN SCIENTISTS" .

It is based on a 1977 interview with Hobby and includes some rare photos of Hobby - most other accounts re-cycle the photograph of Hobby shepherding Fleming about on his tour of South America.

{{What I really want is a photo of Hobby without her pearls - she always wore them - particularly at work in the lab - she was someone that people of my mother's generation would call a 'looker' because of her sharp dress and make-up.

Note the pearls ....

Perhaps this was a survival technique for daring to work above her station  in a very male-dominated world.

But those pearls ----I bet the woman wore them in the bath and to bed !

Perhaps not to church though - a true 'old skool' Presbyterian...}}

But O'Hern's admirable account fails to explain the 'why' in Hobby's four year struggle to bring penicillin to the public, over the opposition of many powerful forces.

I think Professor Jeremy Greene, from Harvard's History of Science Department, does a great job with the 'why' in his brief bio of Hobby in "NOTABLE AMERICAN WOMEN" edited by Susan Ware et al.

He focuses on her very first articles to explain how she came to hold a unique bridge role between the biological and chemical approaches to defeating bacterial infections.

Greene says she defends the validity of studying non-pathogenic bacteria .

(This was a real career-loser between 1870 and 1960 in medical science.)

Dawson's entire career - again opposed to his day job - was also devoted to exploring non- pathogens and pathogens as equally interesting and equally viable ways for commensal bacteria to survive in the human body.

This bonded Hobby to Dawson.

 A deep commitment to seeing new research put to work saving lives, even if it hadn't been all explained in scientific terms, was what bonded Meyer to Hobby.

Meyer was the rarest of 1930s biochemists - he was clinically oriented.... aka he was face to face people-oriented.

Dawson's team was very small and not well supported by his university --- but having two such unusual people to work with him (Hobby and Meyer) helped make up for this....

STALIN lives? at the DUNN ?

I sometimes think that atheists have taken over Oxford University and that they now worship scientists (provided their 'tough minded' enough) instead of God.

Sometimes this means that Oxford have to apply some of Stalin's favorite photographic techniques for making Commissars vanish.

Stalin excelled at first the bullet to the back of the head and then a generous application of photographic varnish to the front of the head ,applied to whatever official photographs that couldn't be tossed.

Wilson Baker was a harmless little man, a devout Quaker peace activist and a darn fine chemist - he's dead but not by any bullet to the head.

But the photo vanishing varnish does apply - he's been erased from the official portrait of the moment of Oxford's University greatest triumph - the (failed) effort to synthesize penicillin during World War Two.

Baker's fault was that his mere presence in an iconic photograph interfered with the Sir William Dunn School of Pathology's panty lines when it came to exalting their best known director, Baron Sir Howard Florey.

Florey is himself dead but he still a real little money maker for the Dunn, Oxford University, Oxford City and the whole bio-med-crazy rich and rapidly growing "Thames Valley".

The original iconic photo is in Britain's National Portrait Gallery, taken in 1944 by Wolfgang Suschitzky at the Dunn in Oxford as part of a a ICI-funded film on Britain's role in penicillin:

I have shamelessly taken this from Robert Bud's book on Penicillin, together with his caption and credit line.

Now here is another almost exactly similar photo, taken this time from Eric Lax's book on penicillin, with its caption and credit line to the Dunn Pathology School.

I don't know about Pathological, but I find this all definitely creepy:

I have made these photos very small ,to save bandwidth, but they sure look alike---- aside from the tighter crop of the Dunn version.

But now look closer at the figure of Florey from the Dunn version:

It sure looks like a bad "insert" job ala Joe Stalin's technique.

And doesn't our Florey's pose look very very familiar , in fact ,iconic to cliche-worthy familiar ?

Ah yes, Florey had no license to inject people.

 The stand-in shot of him using a needle of his famous live-saving penicillin, in lieu of something more heroic, has become a posed-up shot of him and his aide, Jim Kent, needling a mouse in May 1940.

 I think its a law that it must be used in every book and article on Florey,Oxford and penicillin.

Here it is,also from Lax's book, and again provided by the Dunn people:

What do you think ?

CDN CRUDE -PENICILLIN 1943

During World War II, from July 1944 till 1946, the Canadian Army in Europe produced an ordinary-soldier-oriented newspaper called The Maple Leaf.

Sort of a pale version of the American Stars and Stripes.

Its June 29th 1945 edition has an interesting story datelined Vancouver and entitled "PENICILLIN GROWN IN ITALY'S FIELDS".

Newly demobbed Private Donald MacRae, working in a BC logging camp as the first aid medic, is now free to tell an interesting operatic science tale that the highly dignified medical scientists had kept under cover till then.

It was March 1944 before penicillin was flowing freely through conventional channels to the Canadian military in Italy.

(Thank you Pfizer !)

Till then, the Canadian doctors in some hospitals grew unofficial penicillin from spores sent to them from Cairo - ie from Robert Pulvertaft - one of my heroes in the whole penicillin saga.

Nice to know a few lives were saved or helped by this effort.

The instructions certainly sound like Pulvertaft's style - cut a lot of unpeeled potatoes in two, throw in a bucket of warm water with the top exposed to airborne microbes, leave out and about.

Twenty four hours later, put the potatoes in a stew and enjoy.

But the water they soaked in, with the addition of a few mineral salts, was now just about perfect to grow a good brew of yellow penicillin juice in about 6 days, if kept in a cool dank basement.

Call it the poor man's corn steep liquor --- !!!!

(If keeping the potatoes from spoiling before reaching Italy was a priority, we can assume these potatoes might have come from Prince Edward Island via a Halifax convoy.)

A chemist could grow old and die before they figured out why the mold preferred this rather foul smelling mess rather than their pure and expensive 'defined mediums' with added amino acids.

But an ecologist- or a housewife - could explain it in an instant.

Basically the potatoes were being deliberately put on the road to spoiling and rotting for 24 hours before being cooked and eaten.

For millions of years the fungi had adopted themselves to eating half rotted food - not simple amino acids nor complex proteins either - but rather half digested proteins etc.

Sloppy Seconds, as it were.

Andy Moyer knew what he was about when he told all visiting British researchers that they needn't think the NRRL's farm surplus corn steep liquor was the only thing that would make penicillium grow penicillin - almost any complex dirty -and dirt cheap- farm cast off might work.

"Go look about at what the British breweries throw out, " he said.

POWs and civilian prisoners have always known that potatoes make great contraband brew - now we see it saves lives too !

#3 in an occasional series of articles about morally resolute individuals and food and unofficial penicillin uniting to save lives when the medical establishment, governments and drug companies fell flat.

(#1 Duhig,unofficial penicillin and Vegamite saves lives in Brisbane.)

(#2 Dawson, unofficial penicillin and Jack Frost brown sugar save lives in New York.)

a patient died with every Alumina run

During the thick of the fiercest combat in WWII, the entire US Navy got the same amount
of scarce purified patient-ready penicillin as did just nine American Drug Companies , "for their own use".

I've read this statement in dozens of penicillin accounts without asking - "why so much patient-ready penicillin for just nine companies and what on earth did they need it for?"

After all, other patient-ready penicillin was being allocated for clinical trials run by a separate organization, the NAS-COC - the drug firms had no hand in it.

Their routine testing for anti-bacteria activity took incredibly tiny amounts of penicillin - about one millionth the amount allocated to them.

What these accounts have elided out of their story is that all of this patient-ready penicillin was being destroyed in experiments to totally purify and totally synthesis penicillin, at a time when patients were dying because of lack of penicillin.

"The Chemistry of Penicillin", a massive monograph released by Hans Clarke of Columbia University in 1949, was the official history of the six year long unsuccessful effort to synthesis penicillin in commercially-salable quantities, an effort that involved thousands of chemists and technical workers, millions of dollars and the best university and industry teams in the Allied countries.

In every way, it was a parallel effort to the Columbia University-based portion of the Manhattan Project.

 Not just in its scale but also in the fact that it too started with a yellow powder consisting of a mixture of substances that were 99.99% alike and could only count itself successful when it ended up with one shiny clear crystal that was 100% pure.

The Bomb would have dropped on Hiroshima with or without success from Columbia's chemists --- but the Cold War wouldn't have happened if they had failed.

All the Cold War Bombs, on all sides, were built with molecule-separation technology perfected at Columbia during WWII.

By contrast, the molecule-separation technology that gave us pure crystals of penicillin came from the Wool Institute of Northern England in 1938 and proved useful enough to win a Nobel prize for its two developers.

And if you hear me once, you'll hear me a million times - their work was not peer-reviewed-grant-based research  - (ie,it wasn't DIGNIFIED SCIENCE  but OPERATIC SCIENCE  to use my own terms).

The origins of this technique (chromatography) are even more interesting - they came from a Russian botanist and were long ignored by chemists because, (a) well he was a botanist after all and (b) it was all way too easy.

Chemists adhere to the notion that if you aren't in pain after you exercise, you haven't done it enough - every chemist's scientific papers are a testosterone-rich tale of endless amounts of back-breaking effort and mounds of chemical reagents used up to achieve the end result.

But chromatography worked so well it is now one of the most widely used chemical techniques - it relies on the fact that even molecules that almost totally alike are still absorbed onto other molecules at ever so slightly different rates.

(Note that in separating the two types of almost similar uranium for the Bomb, it was known they had slightly different weighs and sizes and so it was hoped they would tend to go through tiny holes at slightly different rates .)

They did, but sooooooooo slowly that some molecules put into the production line in the mid-1940s were still inside the same production line 40 years later when the Cold War ended !

Now it is true that this is a physical process ,not a chemical process, in the final analysis but the effort to make it all happen was really a physical chemist's type of work, rather than something a regular physicist would excel at.

In Dutch, the word for Chemistry is Scheikunde - "the art of separation" - a very good way to describe much of chemistry - and frequently the part of it judged most useful/most profitable to industry and society.

Back to the process by the Wool Institute's Synge and Martin, as applied to penicillin.

In this process, during each run of the process, 5 to 7 grams of patient-grade penicillin  (that is between 2.5 and 25 million units of penicillin depending on the year the work was done) was poured down a column of alumina or silicon gel, and the penicillin separated itself out into various colored bands.

These different colored bands of sticky wet alumina were carefully cut apart with a knife
and then the biologically most active colors were used in further tests to get almost pure samples of various types of penicillin.

Think about how those chemists must have felt as they performed each run- they weren't heartless men and women.

They knew that each run used up and destroyed enough patient-grade penicillin to save the life of  six children with blood poisoning or one young adult with SBE (sub acute bacterial endocarditis). Sulfa drugs weren't working - so no penicillin meant death.

The Chemistry of Penicillin describes many of these runs and the specific amounts of penicillin used in each run.

I love facts and figures and dates and prices (up to a point) and hate the fact that most accounts of penicillin either avoid them - or worse - screw them up by factors of one thousand or more ( mistaking grams for milligrams is routine, for example).

The facts and figures in this massive tome of a book look reliable to me and I feel that it -and they - are underused resources.

Even more useful are the facts and figures that are not there.

The firm (Pfizer) that produced most of World War II's penicillin, the firm that was the first to make patient-ready penicillin, a firm early into the blessed circle of synthesis research, is almost totally absent from this book in any meaningful way.

It had a vast amount of experience, having worked with penicillin almost longer than anyone else and it was making lots of money and taking on lots of talented staff during the war.

It even got the second or third largest allocation of penicillin to play with.

Yet with all these advantages, it produced almost nothing remotely useful towards the synthesis of penicillin.

This isn't just me (a totally non-chemist) saying this.

Accounts years later that tend to give an summary overview of the road to synthetic penicillin, written by penicillin chemists with no axe to grind, see nothing in Pfizer's work to highlight. Even very minor penicillin players get more attention than Pfizer.

So where did all that Pfizer experimental penicillin go then, if not into useful synthesis work?

John L -(John L Smith ,head of Pfizer's penicillin efforts) -care to explain ?

"I secretly broke my solemn signed agreement with my government and diverted the penicillin away from synthesis to give to patients dying of SBE, patients that that very same government had refused to treat."

Why ?

"Because I had just bet the farm and Pfizer's entire fate on the guess that my biologists on this side of the Hudson could make deep tank penicillin successfully - and make it better and quicker than Merck's chemists could make artificial penicillin on their side of the Hudson. I was betting that soon there would be more penicillin than we would know what to do with - plenty for Second Front soldiers AND SBEs here at home."

"Was I right; was I right ?!"

Yes, you were. And some SBE patients and their families are very grateful you bucked your wartime government and diverted penicillin towards dying SBE patients.

"Well, I must say I learned how to divert penicillin and 'buck' from the best - Henry."

Dawson ?

"Yes,the old stubborn mule, Henry Dawson ..."

"4Fs and WOMEN and the GRACE of GOD"

The Official History of Vannevar Bush's famous wartime science agency the OSRD, home to World War Two's 'elitist science' , is called "ORGANIZING SCIENTIFIC RESEARCH FOR WAR" and was written by Dr Irvin Stewart.

In discussing penicillin and the medical section of the OSRD, Stewart claims that "Laboratories cannot be run by 4-Fs or Women or by the Grace of God alone." (Page 107).

Well, I know a great book or movie title when I see one and so I took up Irvin Stewart's intended insult to 4Fs and Women (and God) with relish.

Two 4F doctors called Dawson and Hunter together with three women scientists called Hobby,Chaffee and Olmstead could run a lab very well indeed ------and did more than anyone else to bring us NATURAL penicillin in time for the D-Day beaches and all those wounded young soldiers.

And the Grace of God no doubt came in handy a lot....

the Coghill versus John L race

In October 1943, a committee of three chemists, including the head of the US Agriculture Department division of NATURAL Fermentation, said that SYNTHETIC penicillin would a reality in six months - in April 1944.

" Bet the farm on it ! "

That was a mighty good deadline for synthetic penicillin true believers to aim for .

Because April 1944 was about the last possible date for any sort of penicillin to enter the US Army supply pipeline, be transported to the  Kansas City Kansas central army medical supply depot and then be shipped all the way back again to the East Coast and shipped
across the Atlantic to the Southern England ports, to be loaded on hospital ships bound for D-Day's beaches.

If this chemist (Robert D Coghill) had been proven right, he would have put his own Division out of business - so he had a conflict of interest about a mile wide and mile deep.

A conflict of interest between his natural chemist's fetish to achieve the complete synthesis of anything and everything and the duty he owned to his employers at the Agriculture Department.

But across town, another chemically-oriented key mover and shaker, was having a change of heart.

John L (John Lawrence Smith, the head of Pfizer) was leading one of the firms heavily involved in synthesising penicillin.

But moved by the plight of a child so like his own daughter that he had earlier lost to meningitis, he was secretly breaking the spirit of the wartime laws governing penicillin.

 Scarce amounts of penicillin that he should have been devoting to chemical synthesis John L was instead giving to doctors (under the table) to save the lives of people dying of SBE, a traditionally always-fatal form of endocarditis.

John L was also busy backstopping his own private bet that he could produce billions of units of NATURALLY-brewed by the April 1944 deadline.

He did this by having his crew work night and day under powerful Klieg Lights with posters reminding his employees that every delay would cost lives.

And he did this be accepting the second-best as more than good enough : he didn't build a brand new shiny factory like all his competitors were doing.

He took over a ice making plant (a sort of milk plant, in many senses) and adapted it quickly to produce deep tank penicillin.

Coghill and the other synthesis believers were working just as quickly, in labs all over America and Britain, fueled by lots of taxpayers' money.

But the work was not going anywhere useful.

Meanwhile Pfizer was now producing more penicillin than even their wildest estimates had allowed for and Coghill threw in the towel and, being a good bureaucrat, moved smartly to Plan B.

In April 1944, with the biological production of penicillin an outstanding success, it was suddenly deemed to no longer be a deep military secret and Coghill spilled all the details in public - claiming his division was responsible for its success.

In a sense that was true - his low level employees had made natural penicillin possible - but Coghill himself,had been busy trying to screw them in the ear by creating synthetic penicillin to make all their work irrelevant.

More importantly, if biological penicillin was now a big success, shouldn't that mean that it was MORE of a military secret than ever - not less?

Was it really only kept secret so that synthetic penicillin could gain time to trump it ?

In May 1944, Coghill ( in his other role as the erstwhile head of the Fermentation Division ) had to go inspect the fermentation tanks at Pfizer and see vials of 100,000 units of penicillin come off the Pfizer line faster than he could count.

And Coghill the Chemist had to stand there while Pfizer's Biologists went about with shit-eating grins.

A GREEN Day indeed.

Chemists and Chemistry, the Queen of the Sciences from 1840s to the 1940s, received a blow that day that they never really recovered from.

I'd give anything to be there, the day that Modernity died and Post Modernity was born....

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...

The things they buried...

I know, I know, a shameless knock-off from Tim O'Brien's classic.

What I am about to compare is the contrasting ways Fleming and Florey chose to deal with the more amateurish and stochastic areas of their involvement in the Penicillin Saga.

Fleming's discovery of penicillin was not - Horrors ! The Shame of it ! - peer-reviewed funded.

It was an accident and he wasn't being paid to discover or develop it.

 But he made the most of that fact and in fact delighted in it.

He preserved the famous accidental Petri Dish so that all can still see it in the British Museum, 82 years later. He saved a bit of the accidental mold, sent its children out to any that asked.

 Hundreds of collections worldwide still keep its great-grandchildren going and growing.

He kept his sparse notebooks for the entire period 1928-1945 dealing with his steady work on penicillin - not bold or visionary work sadly - but he still kept proof of just how little he did do -and revealed it for all to see, without shame.

He and his institution (St Mary's Hospital) positively delight in exposing and preserving just how amateurish his penicillin work was -- there is a museum dedicated to that amateurishness and the sheer unlikely stochastic-ness of his discovery.

Unauthorized but sympathetic biographers of Florey's work with penicillin also delight in revealing the utterly amateurishness of Florey's extraction equipment, assembled as it was from old bathtubs, coal hoppers, pie tins etc etc - Rube Goldberg on Acid.

Not Florey though: no, no, never.

He always (mis) presented his team as having a much more sophisticated operation than what even a well-equipped teaching hospital's Lab Service could ever put together.

 He even told anyone foolish enough to ask that only his Oxford-produced penicillin or that produced by Big Pharma was safe to put into patients .

And that any teaching hospital lab's penicillin was bound to be unsafe .

All this despite the fact that Florey was not , in the conventional sense, a clinically-oriented medical doctor with patients and hence in a position to properly judge patient safety.

Instead he was a medical researcher working in a lab on basic science.

Part of this animus against teaching hospitals was because Florey hated patient-oriented doctors with a passion, but mostly it was because he wanted to keep his part in the penicillin Saga on the Dignified/peer-reviewed funded/team side rather than the heroic individual/amateur/unfunded side of the story.

But in fact his penicillin plant or that of any drug company, from 1940 till about mid 1944, was as purely amateurish as those run by individuals out of a corner of a hospital lab - perhaps differing only in being a tiny bit bigger.

But the minute he heard that Pfizer was producing more NATURAL penicillin in 5 minutes than his lab had produced in 5 years,Florey shut down his penicillin plant and had all his Rube Goldberg extraction equipment torn up and then buried in a backyard rubbish heap.

After his death,Norman Heatley built some replicas for museum use.

 But generally Florey supporters have explained this by saying that  Florey was forced to use amateur methods at first, until he assembled a vast Anglo-American joint effort involving governments, universities, corporations and the military, all working together, to bring us high tech penicillin - Big Science at its best.

Academics just love this myth, the myth that says if the taxpayer just gives science lots of money and then stays out of the way, they will pull rabbits out of hats every time.

The public loves the other myth - that kindly old Fleming discovered penicillin just messing about and gave it to the world without charge ------and that it was a piece of cake to get it into mass production.

Neither myth is totally untrue but both only give a part of the story.

Hopefully my effort will give a fair hearing to both Fleming and Florey but include the rest of the penicillin Story as yet unheard.....

Biggest disease that penicillin conquered

....was not SBE, Subacute Bacterial Endocarditis, as important as it was and as important as it was to Martin Henry Dawson.

I am not writing my account of the Penicillin Saga because it conquered SBE.

I am going after much bigger game.

The dreadful disease I think NATURAL penicillin conquered in 1944 was Modernity.

I think today's GREEN movement can trace some of its beginnings to that blue green penicillium mold's triumph against the best efforts of man to recreate everything natural in an artificial form, merely because they could.

Defeating Modernity was the best thing natural penicillin ever did.

That's why I am writing this work - that's why I do what I do....

World's most important medical journal?

That's easy - there are only four types to consider when announcing a really important medical discovery.

Number four - but way at the bottom - is announcing a new medical discovery in the pages of something like LANCET or JAMA, the journals that medical doctors read .

Number three would be if that new medical discovery got reported in NATURE or SCIENCE, the journals that scientists read.

Number two would be if that new medical discovery ended up on the business pages of THE NEW YORK TIMES, the pages that the men with money read.

But all of these still remain near the bottom in importance in their ability to move a discovery out of the lab and into the GP's handbag - quickly.

Doctors,scientists and businessmen do many worthy things, but moving quickly is rarely one of them.

No,alone and way at the top as my choice to move people to action would be if that new medical discovery became attached to a human face and ended up on the pages of a women-oriented magazine in your neighbourhood supermarket's magazine stands.

 Doing so, directs it to the immediate attention of........ "DOCTOR MOM".

Don't believe me ?

That's what happened back in August 1943, when Dante Colitti and CITIZEN HEARST put their heads together to make the wartime government of FDR stop focusing on killing long enough to think about the living.

At the beginning of August 1943, I bet one educated person in a million worldwide could tell you what penicillin was. By the end of September 1943, I bet 90% not only could tell you but also wanted to know why their government wasn't making it available to their citizens like yesterday .

Fifteen years earlier, penicillin had first become privately known, to Alexander Fleming.

Fourteen years earlier, penicillin had first become publicly known - as scientists are wont to say in their self-absorbed way- when it was published in a peer-reviewed journal with a few hundred readers.

And there it sat, in the British Museum of medical curios, basically unused.

It was only when penicillin became popularly known, virtually overnight 15 years later in August 1943, that it began to be used en masse to save lives.

Now getting the attention of DOCTOR MOM , a very,very busy person, is never easy but once you do that, Ms or Mr Discoverer ---- stand back a safe distance and watch the wheels spin !

So, the top medical journal in the world ????

I'd rate THE LADIES HOME JOURNAL pretty high....

Pearl Harbour Saves Florey?

As long as America was at peace ,America's businesses could compete against each other relatively freely without the ability of the "dollar a year men" in Washington to make use of  " the emergency " to misuse government's wartime muscle to restrain competition, so as to favor the firms they represented in peacetime.

If Japan's attack on Pearl Harbour hadn't happened, America would have probably remained a neutral at least throughout the first half of 1942 - long enough for Pfizer and Dawson to be free to fully publicize the life-saving powers of naturally-brewed penicillin in the national media.

This would have been enough, in peacetime, to create an overwhelming public demand for its immediate mass production.

Penicillin would then become just another in a series of remarkable drug discoveries that first emerged as a small but notable success and just kept on growing in importance.

Sulfa drugs started that way - they really had no immediate or dramatic success to introduce themselves to the world.

Rather it was a series of notable successes, among a number of different years and a number of different continents that gradually made them famous.

Newer and newer sulfa variants kept on being discovered and were then put to work curing additional diseases.

Likewise,Penicillin's initial success would have focused attention on the possibility of ever more drugs from molds and bacteria - as of course happened from about 1947 onwards to today, but in a non-dramatic ,and above all, industry-directed fashion .

85 years after sulfa and penicillin first emerged in the lab (around 1928), only one drug has got any kind of universal dramatic legend attached to it and this is penicillin.

The deleterious effect of the American declaration of war on what should have been its normal emergence from lab to drug company to its acceptance by GP and patient is the reason why.

Without Pearl Harbour happening in December 1941, Florey and Merck would have been free to pursue their synthetic penicillin mirage while Dawson and Pfizer would have been equaly free to introduce natural penicillin - first grown in large trays and then from deep tanks.

The winner would have been the same (Pfizer) but they just might have emerged in May 1942 rather than be delayed until May 1944.

Ie, it would be as if the dramatic events of May 1941 to May 1944 never ever happened.

Let us go to a concrete example:

J. Chem. Educ., 1941, 18 (12), p 552

DOI: 10.1021/ed018p552.2

Publication Date: December 1941

This is a monthly publication of the American Chemical Society.

 In 1941, when the public heard the word scientist, they thought only of chemists - chemistry was the Queen of the Sciences back then to an extent we can't begin to imagine ,unless we were living back then.... before 1945 (Physics) and 1953 (Biology).

This journal was directed towards chemistry teachers and undergraduates in North America's high schools and universities--- a huge audience well beyond more prominent chemistry journals with a select but tiny audience.

This particular column was a monthly roundup of news from the popular press that had a chemical industry aspect to them.

Just reading the column in its entirety makes it clear that "WHAT"S BEEN GOING ON" for December 1941 was written and released before Pearl Harbour.

Using language from The New York Times's description of Dawson's work on penicillin back in May of 1941, the paragraph seems a little out of date to fit this speedy "up to the minute" news digest column's style.

It credits Fleming with discovering penicillin in 1929, but says nothing happened to it until Dawson at Columbia proved it up.

I admit it - I love it !!!

No mention of Oxford nor Florey no Merck no OSRD nor of the NRRL and COC.

I think it reflects a little quiet PR spin that Pfizer put behind on its corporate decision to seriously help Dawson use Pfizer-brewed NATURAL penicillin on clinical cases.

That brewing, and that corporate decision, happened in mid October 1941, a date much closer to the date the column would normally have been researched and written --- rather than about events from way back on May 5th 1941.

A Merck-oriented paragraph on penicillin in this same time period would have credited Florey and ignored Dawson totally.

Merck never had to do that media-spinning, not after Pearl Harbour.

One wartime government agency,the OSRD-CMR, run by Merck men, now controlled almost all of the news on penicillin and they spun it to focus exclusively on Florey and hence indirectly on Merck.

But they forgot to put a muzzle on Dante Colitti  (and Doctor Mom) and penicillin became a legend despite the best efforts of  OSRD,Merck and Florey....

PoMo Green versus Institutional Green

We all know institutional or hospital green, though we probably don't know much about it.

Technically it is called Chromium Oxide Green and though it is no longer made (much) it was a technical wonder in its day.

Most chromium paint wasn't green - the green color was selected for the paint used in public institutions like prisons (remember the Green Mile ?), hospitals and institutions for the chronically ill and mentally insane.

Today it gives a bad vibe for being associated with these places of discomfort and shame, but this pastel like shade of green was originally selected because color scientists judged it the most calming shade for institution inmates.

The reason why it was made from chromium oxide was because this paint was tough tough tough and chemically toxic - it resisted stomach contents and common hospital cleaners AND because it was so tough and smooth,that made it harder for germ-sustaining dirt to hang about.

It was the most typical color of the Streamlined Moderne Decade from about 1934-1944 - by no coincidence the Apogee of the Modernist Age.

But that is soooooo yesterday.

Today's green is PoMo Green and it is not a paint at all - it is the natural verdant color of Nature itself - green grass, green trees, green ocean deeps.

The very first PoMo green?

Glad you asked !

It was all those Kodachrome-vivid color photographs of green-blue penicillium molds in the color supplements so popular during the World War Two years (when neither TV or film gave you much color) that appeared post the Spring of 1944.

That was about the time when it became embarassingly apparent that man-made medicine was being eclipsed by life-saving medicine from a humble and slimy low life normally found in our basements --- a shock Modernist Science never really recovered from.

Now it would just take Adorno and Horkheimer to make it official, which they did - in The Dialectic of the Enlightenment.

Move over Mo, Po has arrived.....

"Jabbing" BIG PHARMA awake

Good things happen when you quit the shilly-shalling and "do the clinical" - ie 'stick the needle in and see what happens'.

I have said before that it was in October 1940 - the same month that Martin Henry Dawson jabbed the very first needle of antibiotics in a patient - that the American Drug Companies and the American medico-scientific establishment (NAS-NRC) finally woke up and started smelling the coffee on penicillin.

Example ?

That very month, Squibb asked for a sample of Fleming's penicillin mold from the culture collection in Peoria.

They did the smartest thing that Squibb ever did in the entire Penicillin Saga - they threw the chemists out of the building and let the mycologists get down and into it.

Don't you wish all the other labs had done ditto?

 Alexander Fleming, unfortunately, seemed to really hate mycologists - and he rarely - in public anyway - disliked anyone

Thankfully, the result was a much improved strain from Fleming's original and it was eventually called NRRL 1249. (January 1942)

All praise to Dr Geoffrey Rake and his co-workers at Squibb who never get any thanks for giving us life-saving penicillin in time for D-Day.

Instead the big losers in the penicillin affair, the chemists, have written all the official histories, blowing smoke rings so we won't see how they failed to deliver on their promises.

Other claims to the contrary,history is usually written by the losers - at least "the losers with l'argent..." *

Mycologists take a bow : thanks to you , it was natural NRRL 1249 and its offspring , 1249.B21, (December 1942) that delivered most of the penicillin produced in World War II.

The chemists just delivered papers and articles instead....

* Canadian-anglophone-only joke --- Yanks and Brits/Anzacs etc can safely ignore it

NRRL1249.B21 was WWII's top secret

It is not hard to replicate an Atom Reactor - just ask Joe,Mao, Winnie or Chuck.

(Stalin, Mao Tse Tung, Churchill and de Gaulle.)

Even George gave it a good shot.

(George Laurence was a junior Nova Scotia-born scientist who decided to build one on his  own time,by himself and with his own money --- he did a good enough job of it to be invited , along with Canada, into the very small wartime circle  of the atomic bomb elite.)

The American Army built one - along with a few Bombs.

But they found The Bomb a piece of cake compared to building a Frank Sinatra.

Since the original guy was draft-exempt because of a torn eardrum (no wonder he sang so good !), I am sure the Army tried - it was bad for the fighting man's morale to have the gal-pal back home swooning over a 4Fer.

NRRL 1249 B.21 sounds like a top secret bomber, or a new super explosive, but it actually was just a bit of mold like you might scrape off an orange or a dank basement wall.

But it was a lot more like a Hollywood star or a Billboard chart-topping singer - an exact replicate couldn't be build and even a close substitute won't do at all.

All or nothing.

When the Russians and the Japanese heard rumours that the Germans, British and Americans were building an uranium bomb, based on the principle of fission they could at least hope to duplicate it.

Uranium isn't particularly scarce and the basic principles of fission were made known to all atomic physicists worldwide between 1938 to 1940.

The costs and difficulties of the chemistry and engineering were far more daunting, in practise - but it could be done, given a little time - ah, Joe ?

But without a spore or two of NRRL 1249.B21 or NRRL 832 or NRRL 1951 (still in use world wide 65 years later) , you were reduced to using Fleming's original "PD" spores - freely available - but only producing 2 units of penicillin per milliliter not 200 units a milliliter.

That meant if you weren't part of the NRRL-OSRD charmed circle, you'd have to do 100 times as much labour as those specially favoured by Coghill and Richards.

A sweet deal for a few lucky corporations - particularly since it was all paid for by the long suffering taxpayer.

Let's recap: the private stuff was PD but the publicly funded stuff was proprietary.

Only in America, you say ?

Let's just call it a New Deal for the Rich and Influential.....

NDM-1 SUPERBUG - the TRURO connection

A mobile gene that creates an enzyme that destroys almost all known antibiotics have been reported in NATURE this week, leading the news around the world.

Bacteria (and microbes generally), kick dust in the face of Charles Darwin and his theories of genetic inheritance.

They can send their 'seed' sideways - not just vertically down to their offspring like humans with PhDs -  but also to other species or even towards other forms of life.

It is called HGT ( for Horizontal Gene Transfer) (aka Transformation) and Martin Henry Dawson from Truro,Nova Scotia (the doctor whose biography I am writing) was the first person to try to make HGT a big issue in the science world.

That happened between 1928 to 1943 but unfortunately few scientists back then cared to face his unpleasant message ---- "simple creatures are anything but."

(And its corollary, that scientists are less brillant than they think they are.)

If we start dying en masse from these new superbugs, maybe more of us will start listening to Dawson's still-pertinent message

Why stop at THREE mold samples...

...when  four would feel oh so good?

In 1970,Lennard Bickel, using information from Gladys Hobby, says that Martin Henry Dawson and Karl Meyer used a sample of Alexander Fleming's penicillin-producing strain received from Roger Reid in Baltimore to deliver History's first jab of antibiotics October 16 1940, before a sample of  Ernest Chain's strain of penicillin-producing mold arrived from England via the wartime postal service.

Chain's sample - if it even was penicillium notatum - turned red and gave off no penicillin.

This story was repeated by Hobby in her 1985 definitive book on the wartime development of penicillin ---- and by most penicillin authors ever since.

Reid had originally got his penicillin strain in November 1930 from Charles Thom, the world expert on penicillium strains.

Who had gotten his sample from Harold Raistrick who got his from Fleming who got it as a contaminant in the air drifting upwards from the lab of LaTouche who scrapped it off a basement wall of somebody very rich in Belgravia.

(Finally !

The idle rich do something useful.....)

On July 9th 1941, Howard Florey visited Charles Thom who says that HM Dawson ( ie MH Dawson) contacted him directly to get a sample of Fleming's strain, after Chain's strains arrived in late October 1941.

So Dawson contacted at least three people that Fall of 1940 for a good penicillin-producung strain of the mold : Chain, Reid, Thom.

Why not then Alexander Fleming ???

Why not go to the Source, the Mother Load ?

This might account for Fleming's boss (Dr Wright) knowing all about penicillin-making at New York's Columbia University in March 1941, as referenced in Dr John Hedley-Whyte's account.

Dawson had meet Fleming at least twice, for sure --  in 1936 and 1939 when both were high poo-pahs in International Microbiology Congresses.

Anyone got any opinions on this ??

The Crude and the Dignified, ...

....are two wildly different versions of the Saga of Penicillin Development during World War Two.

You know only too well the Dignified version, as propagated by the OSRD of Vannevar Bush and by just about every academic writer on penicillin (I think it is a requirement for them to retain tenure or something) - I call it the dignified rendition of "The Revenge of the Nerds".

Martin Henry Dawson's efforts to grow, purify and apply his own homegrown penicillin to
save patients dying from invariable fatal SBE - all the while fighting off his own hospital, his own government and his own (dying) body - is the most tasteless,  the most over the top and the most crude Hollywood medical bio-pic imaginable ,since the days of the dying Marie Curie laboring long into the night over her radium ores ,in a tin shed with a leaky roof.

A Forties three hankie melodrama full bore, for sure.

Enough to make any modernist scientist recoil in distaste.

Fair enough - stone-heartedness is a disease  -and they are more to be pitied than blamed, etc etc.

But the patients, the punters, the bums on the seat love it.

They like - nay - love and worship - the idea of doctors who care about them enough to be willing to die for them.

I'm telling the tale for them ---- and in hopes that a few modernist scientists and academics might re-think how they deal with the real people affected by their lab efforts....

Australians give away British Store

Mark Oliphant flew to America in a bomber to beg them to make the Atomic Bomb after British scientists had pushed its development while the American government held back.

Howard Florey flew to America in a Clipper plane to do ditto with Penicillin, a British development that the American government had also put on the back burner.

For both Australians, they did this out of strong personal conviction that it was the right thing to do.

It is true that both also did it with approval from some mid to upper level bureaucrats within the British government.

But there hadn't been anything like a full debate at the top of the British government  about the matter, before the Australians were allowed to give away the store.

If there had been, it might have led to very different decisions on what was to become so portentous to Britain's dismal post-war fate.

Try to imagine our world post-1945 if the British , not the Americans , held the whip hand in atomic bombs and penicillin.....

The NEEDLE that wasn't there....

.... changed History.

In the early 1940s ,a parent was bemoaning to a doctor that by the time he got his sick child to the New London hospital from his summer home in Stonington Connecticut a few miles away, the doctors told him it was too late and his sixteen year old daughter Mary Louise was dead from spinal meningitis.

The doctor lectured him, as was his want, that if every GP carried a needle and some penicillin G in their black bag and gave it to every suspected case of meningitis, without waiting to get the patient to hospital to have their spinal fluid tapped and typed, no child ever need die from meningitis.

But unfortunately, the doctor went on to say, drug company executives are still too slow off the mark and GPs have no penicillin to put into their bags, 15 years after its discovery....shooting a meaningful glance at the parent.

The parent went home and thought about it a while  ---- God he hated that guy - always wanting more and always giving you a lecture instead of thanks for whatever you could give him ------- but he did think about it and probably even talked it over with his wife.

Who knows what happened that night. Did he tell his wife," I'd like to help Henry but you know me, I don't like to move quickly."

And perhaps his wife said softly, "I know" and then immediately wished she had never said it.

Perhaps they always agreed to never again talk about that awful night so long ago.

Who knows ?

What we do know, is that something totally unexpected happened, thanks to that parent.

True he was notoriously known as a very frugal and cautious man, but now that he actually decided to ' do something about it'  , he worked like a whirling dervish.

His name was John Lawrence Smith and if you know his name at all, you know him as one of the owners of the famed Brooklyn Dodgers.

During June 1944, the Brooklyn Dodgers had one terrible road trip after another.

But John L's other Brooklyn team scored one knockout after another that June in 1944, in places like Omaha ............ Utah ...... Juno ...... Silver........ and  Gold.

This is the true story of  " How Omaha Got Its 'P' " - and the doctor's advice is still good today - doctors are still advised to carry and use a needleful of Pen G on every suspected case of meningitis, ASAP, if they want to save a life.

If your child's life has been saved by a prompt needleful of Penicillin G, aka benzylpenicillin , offer up thanks to that parent.

(John L Smith ,the head of Pfizer, when it produced most of the penicillin that landed on the D-Day beaches - British and Canadian beaches as well as the American ones.)


And of course to that ever nagging doctor ,Martin Henry Dawson...

If you don't like NEEDLES....

.... here is the guy you don't like:

MARTIN HENRY DAWSON
1896-1945

On October 16th 1940, on the 8th floor male ward of New York's famous Columbia Presbyterian Hospital, Dr Dawson stuck the first ever needle of antibiotics (penicillin) into patient
Charles Aronson, launching a billion needle jabs of antibiotics in the seventy years since.

OUCH !

This Fall marks the 70th anniversary of the much feared/ much revered antibiotic needle - at New York City's CUMC.

And if  CUMC are true to form, they will totally ignore it:

Plus ça change (plus c'est la même chose)

Penicillin a sidebar to WWII

One of the major differences in my account of the development of penicillin from all the others, is that I don't plan to tell the 'exciting' story of penicillin, with World War Two merely as part of the backdrop.

The fact is that during the war penicillin was never more than a sidebar to the main story, even on both sides of September 1943 when it was a major news item for about eight weeks .

Events elsewhere in the war moved penicillin forwards or backwards in importance in the eyes of war planners and nothing anyone in the entire circumscribed world of penicillin development had anything like the impact upon penicillin development that changes on the war front did.

The Eisenhower-Marshall proposed dates for a major cross-channel invasion - in summer 1942 or March 1943 (Operation Sledgehammer and Operation Roundup) - meant the US Army accepted and indeed demanded mass quantities of so-so but available medical supplies now over the possibility of better medical supplies later.

Penicillin was put on the back burner - deliberately - even though its superior qualities to sulfa was sensed early on.

The decisions to take the British tack of delaying the cross-channel invasion till May 1944 (or later), allowed US Army planners, early in 1943, to admit that the sulfa drugs had always had a lot of problems and that they were increasing in intensity.

Sulfa faced growing and widespread bacterial resistance.

In addition, powdered sulfa had proven frequently deadly when used in 'real life' sun-baked combat areas where water is usually in short supply.

This, in my view, was the result of too many combat-shy senior doctors making assumptions about battlefield conditions, when they had actually avoided the battlefield as young men during World War One .

The existing Army Surgeon was sent into retirement in the Spring of 1943 and a less cautious general (Norman Kirk) replaced him --- this has not been recognized as one of the new key factor in penicillin's improved prospects in getting up to mass production in America in late 1943.

But above all, penicillin now gained the time it needed if it was to be to eased into the military medicine cabinet.

All because of the extra year of breathing room gained for war planners because of the revised dates for the cross channel invasion from 1943 to 1944.

Martin Henry Dawson's 'SBE and penicillin' work went on regardless of the war's ebb and flow and his first success with SBE patients in the Spring of 1943 had roused John L Smith of Pfizer and others and so we might have had abundant penicillin by early 1944 ,irregardless of the new military demand for it ---we will never know.

The two penicillin stories ran in parallel ,not in series, and their climax coming together during the Spring of 1943 was, in fact, a coincidence ....

How to tell a lie - and prosper

On February 1st 1964, the journal NATURE ran a long feature article by Dr A N Richards, a foreign member of the Royal Society, a professor emeritus in pharmacology at the University of Pennsylvania and the head of the medical section of America's all powerful science agency, the OSRD......


(Blogger ate about 1000 words right about here - I'll re-type it when my temper cools down - I have learned to print my blog posts out as PDFs right away since this 'incident' - ARRRGH !!!!!!)

 ......Fulton had been out in Central California investigating aviation medicine for the military and had wandered into a lab where a fungi researcher was working with this fungi ,without proper modern precautions, and Fulton was soon stricken onto death.

(Or he simply got it during the days he spent on a military base deep in this valley - the more likely explanation but a lot less colorful story...)

The disease was worked up by the American Military during the Cold War to use as a possible Germ Warfare weapon but in fact it was usually not fatal even if not treated.

But if it spreads from your lungs to everywhere else in your body, it was and is usually fatal.

Fulton eventually knew he was very sick from this fungus but he also knew he was also getting the best possible care one of the best medical schools in the world would naturally give to one of its most senior doctors - he wasn't excessively worried.

Nor where his doctors, until they took a routine swab from a unrelated boil he had on his abdomen to type it for sulfa treatment. Unfortunately, to their shock, it was filled with the fungus --- it seemed he was a goner and all kinds of "heroic' ( ie risky, foolhardy) medical interventions were suggested, as he seemed likely to die anyway.

Fulton had been telling his main doctors that his very best friend Howard Florey was  working with a totally new substance,  penicillin ---- produced by another fungus --- and finding it could kill an ever-widening array of microbes.

These doctors decided not to tell Fulton that his boil meant he likely faced a painful death and instead enlisted him to pull strings to get some penicillin for  a fellow patient, Anne Miller.

They secretly would divert a bit of it, to see if killed off rival fungus and so save Fulton.

This was good peacetime science - but in wartime, the medical establishment tended to say, if it isn't a common military disease, let the man die - we need the penicillin more elsewhere.

Luckily for Fulton, the military had lots of bases in this valley and military men were getting sick and dying from this fungus - so a military need could be evoked - in a stretch.

Merck, the OSRD,and the COC had all gotten pitiful pleas for penicillin before the phone calls from John Fulton---- and turned them all down.

The calls usually involved SBE, an almost always fatal form of endocarditis that - in those days - usually stricken young teens and young adults.

These kids were considered by the medical establishment as the $Fs of the $Fs, as people not worth wasting penicillin on during an all out total war.

Martin Henry Dawson had said since 1940 that he felt that penicillin could cure SBE - war or no war - and they should be saved.

No other doctor in the world believed strongly that they should - at the time.

Most still didn't feel SBEs could be cured or were a priority, even at the time of his death in 1945 - by which time he had about three dozen cures - some cured for as long as three years with a repeat bout.

Norman Heatley of Florey's Oxford University penicillin team was working for Merck and reporting everything back to Florey in England.

He had already recorded in his diary, in November 5 1941 and December 3 1941, receiving pleas to provide penicillin to individuals dying of SBE, while visiting labs in Canada, Dawson's home country.

Merck, the ORSD, the COC hadn't helped young Joan Murray with her SBE then, so why help Anne Miller now ?

(Heatley, not a medical doctor, seems to have felt in his 1942 diary that Miller might have SBE.)

Let us, for a moment, return to Richards.

The thesis of  Richards and  all the other medical bureaucrats in charge of wartime penicillin was simple - "give us lots of taxpayers' money, leave us alone away from taxpayer scruntiny, and we will produce penicillin quickly and cheaply and distribute it objectively and absolutely without favouritism."

In fact, the very first case the OSRD/COC and Merck was involved in was a blatant case of favoring the mighty and the wise over the weak and foolish.

Once it was secretly told to a very few people - perhaps only Richards - that the penicillin for Miller was also going to go to help save Fulton, it made it likely that penicillin would be forthcoming.

In his own right, Fulton was considered a valuable part of the medical brains that America felt it needed to husband if it was to win the war --- he and his own doctor, Francis Blake, were high up in the war medicine committees deciding American health priorities.

The scientists found that even the politicians, the military and the business elite (and perhaps the general public as well) agreed that healthy, fit 1A  scientists shouldn't be drafted - too valuable to the war effort.

The same thinking said penicillin was wisely used if it saved Fulton --- unwisely used if it merely went to save 4F useless SBE kids..

More importantly, Fulton was the very best friend of Florey, a man with few really close friends.

The other closest friend that Florey had in America was Richards himself.

Richards and Merck needed Florey on their side if they were to convert a largely British effort into a profitable venture for Merck in America.

While Blake secretly pulled strings for Fulton and Fulton openly pulled strings for Miller, the key person, I believe, was Richards.

The OSRD and CMR, the COC ,the NRRL,the British MRC and TRC, Merck and other drug firms , the NRC-NAS, the military Surgeons General, basically every official and semi official body connected to wartime penicillin all reveal a long paper trail of documents showing they usually bowed to Richards' dictates.

Luckily for Fulton, while the penicillin didn't do anything for his strain of fungus, careful nursing care kept him alive till his own body pulled him through.

He apparently never knew how he had been 'used' to help save his own life.

Anne Miller's case was not the first one involving penicillin in North America.

Dawson and Meyer's homebrew penicillin and Pfizer penicillin had treated at least 15 cases by March 14th 1942, the day Anne Miller got her famous first needle.

One had gotten penicillin - in fact history's very first needle of penicillin - and been cured - but not by penicillin.

Some had been cured by Dawson's penicillin - but the penicillin hadn't been injected internally as an antibiotic only dropped into an eye as an antiseptic.

A few cases of Dawson's had already been treated by the first commercial penicillin used clinically in North America - Pfizer lot number 696, first injected March 5th 1942, according to his co-worker, Gladys Hobby,in her lab records and correspondence file, as recounted in her 1985 book, PENICILLIN - MEETING THE CHALLENGE.

Because Pfizer wasn't in the OSRD-COC-Merck-Squibb agreement, its commercial penicillin wasn't counted by Richards and the OSRD when it came to proclaiming Anne Miller the first patient cured by penicillin in America.

Nor was Abbott or Eli Lilly, both huge drug companies back then, soon to do their own independent-of-the-OSRD/COC clinical trials.

But interestingly, the OSRD/COC were glad to add Dawson's cases, produced from this invisible Pfizer penicillin, to their total of the first 100 cases treated by penicillin in America.

AND Hobby says that Richards knew and personally approved Pfizer sending this commercially-produced penicillin to Dawson to use clinicallly , though Pfizer was not bound to listen to Richards at all.

A few of the most careful historians today say that Anne Miller was the first person cured by penicillin provided by the OSRD and I think this is exactly right.

But there was a vast world of penicillin activity around the globe between 1938-1945 and much of it was not directed by the OSRD or any OSRD-bodies in other countries - it was the work of individuals who like Dawson merely thought they could do something right now, not perfect or big, that might help save a few lives around them.

Ironically once those agape scientists and amateurs got to Doctor Mom, she lit the fire under Richards' ass that finally got us penicillin en masse,overnight, 15 years after it was first discovered...

addendum : I just discovered that TV  megastar Dr Gregory House did reference Fulton's rare fungus disease in one of his episodes....

Roth Spots, eye doctors lead way with penicillin

All the many good claims to be "the first ever penicillin case" involved eye problems ---- even Martin Henry Dawson's SBE cases!

In this order:

Paine/Fleming ---- pen as an antiseptic.

Dawson/Fletcher ----------pen as an antibiotic.

Let us not forget that the first to "concentrate" penicillin was another eye doctor, young Doctor Ridley, under Fleming's watch back in 1929.

Karl Meyer was a biochemist in an Eye department and needed some thin excuse to go along with Dawson's plan to use penicillin to cure SBE --- a heart disease.

Dawson's excuse - even thinner - was that SBE was a sequel of Rheumatic Fever which had arthritis as one of its features and might be connected, somehow, to Rheumatoid Arthritis.

Most doctors till recently, felt the surest sign of SBE was Roth Spots, white spots, on the retina.

Curing SBE would also cure the Roth Spot eye problem....

Working with the like-minded

Why didn't Martin Henry Dawson work with the biochemist (Michael Heidelberger) that his own Department already had among its staff?

Why did biochemist Karl Meyer work on penicillin with Dawson rather than with clinicians in his own department?

Dawson did work with Heidelberger - but only once  - once in their entire 15 year career together in the Department of Medicine.

Meyer did get two clinicians in his own department of Ophthalmology to try penicillin - but they won't publish until penicillin had become respectable.

His own boss (Phillips Thygeson) pretty well admitted he couldn't get along with Meyer.

Dawson's boss (WW Palmer) didn't believe anything could permanently cure SBE --- he also was on the same chemically-oriented wavelength as Heidelberger - who he had personally hired.

Dawson was much more biologically - almost ecologically - oriented.

Beyond that, Dawson got on with Karl Meyer because Meyer was a very rare biochemist, at least in those days.

He actually wanted his biochemical work to have an immediate and direct
impact on the patients' well being.

Dawson, too, always put the individual patient before the dictates of
abstract Science.

Pulvertaft, Queen, Duhig were all in bacteriology departments - I think this is why their penicillin pilot plants, while less important than Dawson's pioneering effort, probably came off better - and with a lot less heartaches - because growing penicillin was a natural fit in such departments.

Life isn't always fair - you must deal with it as it comes - but I wonder would Dawson have gotten Myasthenia Gravis if his boss had been more in tune with Dawson's vision of the potential of penicillin?

Ignoring 'day jobs' at our peril

Historians may think they are telling a faster paced tale when they leave out the minutiae
of ordinary daily life to focus on the high points of their subject's life - reasoning that these dramatic episodes are why you are buying their book.

But real people - even larger-than-life heroic real people - are worn down each day by picking up baby nappies at the store, taking out the trash, dealing with colleagues and relatives, answering routine letters or phone calls.

Remembering Mother's Day cards -- trying to fix a bank overdraft.

Perhaps the events they are famous for only took up a small fraction of each day during the period in question - squeezed in between the rest of their life.

All the more credit then for changing diapers and changing the world - when most of us can barely get through our routine day.

Alexander Fleming was ,mostly, the manager of a very large Vaccine Factory -- he discovered penicillin in his spare time.

I will not be the first or the last to say that how he dealt with penicillin after he discovered it was highly colored by the need to keep his vaccine factory profitable - because it paid for the entire institute he worked for.

Florey's day job was even more demanding - he did his famous mouse experiment in Room 46 of the Dunn Institute of Pathology that he ran.

That room number alone should tell how truly huge the Dunn Pathology Building really was.

He could have a hundred people in and about that building - and because he didn't have a hugely profitable vaccine line to sustain it, he spent most of his time trying to secure long term grants to pay them and buy them supplies and equipment.

He always freely admitted that is why he got interested in life-saving penicillin--- as an easy way for an increasingly desperate Institute Director to secure a nice large long term grant.

An honest account of Florey and penicillin would also mention his personal research interests outside of penicillin - which ranged very widely.

 His mistress/closest co-worker intimated in a famous postscript in a letter to Norman Heatley that not till early 1942, four years after the penicillin project got started at Florey's institute, did it become the top research interest of Florey himself !

So for the years 1938-1941, how much time did Florey really give each day to the only research work he is remembered for today?

And Alfred Newton Richards over at the OSRD CMR - how much time did he really give to penicillin on a day by day basis ?

Supposedly plenty to judge by the hagiographies he had commissioned.

But when I follow the actual money trail from the OSRD to penicillin researchers --- or rather the non-money trail ---- I am left feeling he did nothing for penicillin much of the time.

Most of the millions he dished out each year - when millions meant plenty - went elsewhere - and I trust the money trail far more than I trust the post-success spin doctors.

Martin Henry Dawson had a day job too.

He ran an Arthritis Clinic - and in those days, arthritis was a symptom, not a cluster of diseases - much as fever isn't a disease but a symptom of many diseases.

Arthritis occurs ,transiently, in many diseases, so trying to determine what unusual disease a person might mean dragging them over to Dawson to get his opinion.

This kept the job interesting but it meant that it couldn't be regarded as a routine affair that could be handed of to a junior member while Dawson engaged in his personal research interests.

He fitted in his penicillin work between the Clinic hours, teaching classes, marking papers, doing grand rounds, helping grad students, attending committee meetings - going to his Dad's funeral back in Nova Scotia - picking up a great Persian carpet cheap the day the World's Fair closed.

Maybe while picking up baby food for the new baby because Marjorie was running late at her school.

Or maybe he did some penicillin work in between sitting down on a couch to recover his strength as his Myasthenia Gravis kicked in.

That is Real Life stuff.

And I intend to put Real Life back into my account of the Penicillin Saga.

Jack Frost Dark saved more lives ....

... than Al-Qaida will ever spend.

If you live in the Greater New York area, you don't need to be told that the Jack Frost brand of dark brown sugar, made in Yonkers, is good stuff.

Damn good stuff.

Your doctor might not agree though - so here is an argument that should appeal to their
medical 'sense of being': did they know that Jack Frost Dark led to the development of the greatest life-saver the world has ever known??!

I know, I know, I also said this about Vegamite, but both stories happen to be true.

Alexander Fleming got a lot of criticism over his use of ox heart medium to grow the first penicillin.

This abuse came from the first generation of penicillin authors -all sycophants of Howard Florey and all modernist to the core.

Ox heart medium is rich and complex and undefined - ie we don't know what all is in it or in what percentages.

As a result, chemists ( the modernist archetype ) hate it with a passion.

They prefer something like the all synthetic Czapek-Dox 'defined' medium - a bland mixture of water and salts you could just see Jeremy Bentham urging the British government to use to feed prisoners ,because it meant that they would remain alive while ensuring that they got no illict enjoyment from their food.

Unfortunately, the penicillium mold hates the stuff as much as prisoners do - it prefers the rich murk of the ox heart stew.

Fleming grew his mold juice in 4 to 5 days in ox heart stew while the chemists led by Raistrick took 15-20 days to get their mold juice on the sparse Quaker-approved diet.

(Interestingly, Fleming started his penicillium on a synthetic medium (Sabouraud's). He did know about them and used them ,despite what his hostile biographer, Ronald Hare, says.

But he found pre-digested extracts of spoiled meat made the penicillium produce faster AND was much much cheaper to buy. Engineers would approve on both counts - though chemists won't.)

Florey, being a chemist-manque, dismissed the ox heart brew and went for some Czapek-Dox synthetic purity instead. But it was so slooooow, and so he "modified" it.

In fact he modified it right back to Fleming's brew, more or less: he added brewer's yeast  (the cast-offs from brewing beer - rich, dirty, complex, undefined, cheap.)

Vegamite is basically brewer's yeast.

Florey retained the concept of his all important 'purity' (in his own mind ,at least) while he got the speed of faster production from this dirty stew.

Coghill, out in Peoria at the NRRL, was a chemist, but a chemist-out-of-water, in charge of a biologically-oriented Fermentation Station.

He devoted much time and effort to try to first purify and then synthesise penicillin - when that failed, he fell back to raving about the use of corn steep liquors to speed production times and increase penicillin output.

Corn steep is another industry cast-off, the stuff left over after all the pure starch has been removed from corn.

It is complex, undefined, dirty and cheap.

Coghill and Merck and many others spent the entire war, trying to figure out what was the one ingredient in corn steep liquor that gave the much better results they got with it.

They planned to synthesis that one ingredient and then dump the corn steep like a used condom.

Others, like the Dawson team, just took the dirty complex stuff as a 'black box' and a gift - they wanted penicillin for patients ,not penicillin for academic papers and academic acclaim.

In the end, it was dozens of things in the corn steep or the dirty sugar that the mold loved - we still use this stuff today - as 'undefined' as ever.

Chalk one up for the post modernist way of thought.

Adorno, the German philosopher working on the Columbia campus in 1941 could explain (and did explain) this Modernist preference for inefficient and expensive defined growth mediums over cheap and efficient but undefined growth mediums.

(Or for that matter, the equally odd Modernist obsession of favoring toxic but defined drugs over drugs that are undefined but perfectly non-toxic. As a patient, I know which one I would prefer to have coursing through my veins !)

In his 1944 "DIALECTIC OF ENLIGHTENMENT", published at Columbia, (the seminal work that ushered in the post modernist era), he said that the Enlightenment's promise to lead us out of the darkness of ignorance was really an exaggerated fear of the unknown.

Not a sensible fear of the dangerous but an a priori fear of anything unknown, even ahead of things that are dangerous but known.

For penicillin read Dangerous= toxic.

Let us turn, finally, from Adorno to Meyer and Hobby and Chaffee and Dawson.

In 1942, they told the world of their secret food for their pilot penicillin plant: Jack Frost Dark.

Many others, Merck Inc among them, took up their idea, seeking the dirtiest, darkest, cheapest substitute they could find in their own local area --- if Jack Frost wasn't around.

The best brown sugar was natural or industrial brown sugar - sugar with lots of crude molasses's minerals and bio-organism waste products still in it.

It could be gotten directly from some sympathetic sugar factory chemist. Since so many industry chemists in the New York area were German or Jewish ( or both) in those days, Meyer wouldn't have found it hard to get a few hundred pound bags right off the boats from the West Indies.

It was dirt-cheap and because it was also dirty, it gave the best yield of penicillin .

You see 'defined' medium means we know exactly what the microbes like to eat, to make them produce what ever it is we want.

But using complex, un-defined ,industrial cast-off brews means we throw our hands up in the air and admit we really don't know Nature.

Instead we gave them everything and the kitchen sink and said "pick whatever you think suits you best".

I see the entire Penicillin development story 1940-1945 as a prime example and the most suitable metaphor of the shift from Modernity to Post Modernity.

So while I am making a little sport with Vegamite and Jack Frost Dark - I am also deadly serious .

 Both of these common domestic foodstuffs did not just give us greater penicillin supplies when they were so badly needed.

They also represented some of the first examples of the green post-modernist way of viewing Man's relationship to Nature's creatures as being co-equals rather than Master and Slave --- when we feed penicillium Jack Frost or Vegamite, we say " maybe you are smarter than us" .

Pass the brown sugar won't you ?

Iron Ring to Martin Henry Dawson's kids

People sometimes ask if I think if Martin Henry Dawson deserves a Nobel Prize for all his efforts in medicine and science.

Nobel Prizes only go to living scientists -a maximum of three per prize - and more often than not the Nobel Committee gives it to the wrong living scientists !

No, I think we Canadians should honor our fellow Canadian Henry Dawson in our own Canadian way.

He was not - formally - an engineer, unlike his two brothers.

But I think he fully deserves the symbol of a true engineer - the famous iron ring.

Engineers don't usually invent something truly new and significant - that is the scientist's job.

But they are the people called in to scale it up from the lab bench to pilot plant, then to full scale production, so it can start doing some good for humanity.

The people who should have been ordering the engineers in to do this work in the case of penicillin - the owners and executives of the big and little pharma firms in the UK,USA and Canada - declined to do so.

So a dying doctor - Henry Dawson - did it all up instead.

The first patient cured back in 1931 (by Cecil Paine) with penicillin-the-antiseptic, a newborn baby facing a lifetime of blindness, needed only the equivalent of one microgram (mcg) of pure penicillin.

That is the amount found in a milliliter (ml) --- or an eyedropper's worth--- of the unprocessed penicillium juice.

(A microgram is a thousandth of a milligram or a millionth of
a gram or a billionth of a kilogram.)

A milliliter (ml) aka a cubic centimeter (cc) aka a gram (gm) of liquid penicillium juice was needed (during 1928-1941) to produce that microgram.

That is a extraction ratio of one to a million, solid from liquid.

In terms of solid out from solids in, it took about 100 grams of relatively expensive solid "food"/ medium to produce 1 mg of solid bioactivity -BEFORE the huge producing and purifying losses found in large scale operations run at routine competency.

I would say that only 10% of nominal penicillin producing capacity was actually converted to finished clinical penicillin, between 1940-1942 ,in the larger pilot plant operations, based on the numbers and type of patients treated.

That is, in plain english, a conversion ratio of 1 kg of solid food producing 1 mg of solid bioactivity - a million to one ratio.

With these sort of ratios, engineers can already see the difficulties that lie ahead - before I tell them about penicillin's extreme lability and fragility...

The smallest test tube we have available is all the factory needed to produce a mcg or two of penicillin.

 Which is enough to save Paine's baby, or one of Howard Florey's famous baby mice, or provide the material needed for Fleming to do all his 1928-1929 initial research using his patented micro-slide cell approach.

Scale it up 1000 times, you would now need a half dozen 2 liter Ernlenmeyer flasks to grow 1000 mcg's ( ie one milligram) worth of penicillin  - about as much as Duhig and Gray used to save lives with in Brisbane in 1943.

But Dawson wanted to scale the Mount Everest of infectious disease - green SBE - the  most dreaded form of the dreadful endocarditis.

He had a few lucky patients who held a strain of green strep in their heart valves that was as sensitive to penicillin as ordinary pyogenes strep was - so he could cure them with just a million times as much penicillin as Pain's baby or Florey's mouse - ie a gram of the stuff.

But other patients of his had SBE from strains about one thousand times less sensitive than ordinary pyogenes strep.

For them, he needed a kilo of pure penicillin- one billion times as much as Paine's baby needed.

That means he and his tiny pilot plant on the eighth floor of Columbia P and S would need
to process a million liters of penicillium juice over a two or three month period - ie 10 production runs of 100,000 liters each.

(That is about 200,000 milk bottles a run. In a big city dairy setup, that means processing 1000 milk bottles an hour, every hour, 24/7 for eight days straight, for each run.)

He couldn't have done that in P and S , even if his bosses had been helpful - which they weren't--- to put it mildly.

But Columbia University is set in th verye heart of New York's dairy factory district - the university fathers could have leased a vacant dairy and produced this quantity of penicillin, (much as the University of Toronto did with insulin in 1922 when they had an opportunity to help humanity.)

Dawson wanted so badly to save any and all SBE patients, not just those who were relatively healthy and had sensitive strains of bacteria, but died in early 1945 before he could get his hands on the huge amounts of penicillin needed.

But his assistant Thomas H Hunter soon had enough penicillin to save anyone who had SBE, no matter how old and sick - Dawson's ultimate goal.

Dawson knew penicillin could do the job from the moment he first read about it back in September 1940 - he knew it didn't need more purifying and perfecting for years and years - just a swift application of the production engineer's "MORE button" .

His "Manhattan Pilot" had to be content with only producing between 50 Imperial gallons and 100 US gallons of penicillium juice per eight day run - with a 50% production loss, just enough to save one SBE patient (with a very sensitive green strep strain)  every two months.

However, he never  actually got that level out of his 700 two liter Erlenmeyer flasks pilot plant, because he never got the cool dark room (or two or three) he needed on a permanent basis, if his penicillium were to settle down and produce.

Columbia chose instead - because it did have a choice, as Brian Mulroney said - to perfect the process (gaseous diffusion) that produced most of the world's nuclear bombs  ---- ironically in that same dairy district that was more suited to making life-saving penicillin...