Who am I ? asks a very famous bright yellow powder from WWII

OK, Manhattan : Who am I ????

(a) In the popular imagination, I am often thought of as being a bright yellow powder (though if fact I might often be dark red or brown or even some other color).

(b) Oddly enough, it is exactly the same for me.

(a)  Some of my most important developments happened on Manhattan island, with strong Canadian involvement --- I think that was all about the word "Hope".

(b) Wow ! Me ditto,ditto,ditto !

(a) The international visual symbol for me is characters in dense black type on a bright yellow background.

(b) That's me too .

(a) A large sample of Americans (men mostly) voted me the top news story of the 20th century for the Newseum.

(b) A large sample of Americans (women mostly) also voted me the top news story of the century for the Newseum.

(a) A little boy is the dramatic climax of my story.

(b) Strange, a baby girl is the dramatic climax of my story as well.

(a) Much of my story happened on a campus at Columbia university and involved Columbia university professors.

(b) So did my story !

(a) I was top secret through most of WWII and I was regarded as one of the best Allied military weapons of the war.

(b) What can I say : ditto ditto .

(a) I am regarded as one of the top scientific discoveries to come out of WWII.

(a) Yeah ? Well so am I .

(a) I was a big project for the OSRD, who spent a fortune on me, until another government agency took me over : but the bosses at the OSRD still kept their hand in.

(b) The OSRD spent quite a bundle on me too - still kept doing so, even after I was taken over by another government agency.

(a) Oh yeah, well I was so important that I was flown all over the world in big bombers.

(b) Bet you weren't flown about as much as me in big bombers.

(a) I was a big deal in Britain : they even act like they invented me.

(b), Oh boy, don't I know that feeling.

(a) The British chemical giant, ICL looked for a while like it would be running me but Vannevar Bush of the OSRD soon stopped that.

(b) And that goes for me too.

(a) In my natural state, I hardly seem to exist, consisting of less than 1% of the natural mix.

(b) I know the feeling, too, actually being much less than 1% of the natural mix.

(a) Well I am so similar to others in the mix, at least in conventional chemical terms, that its a life's work to separate me from them.

(b) That's what all the chemists say about me - usually with a very deep sigh.

(a) I won't work at all, unless I am separated from my natural mix and am about 88% pure.

(b) Now there we finally do differ : because I still work perfectly well even if I am only one part in million of the original natural mix.

(a) There was (and is) a tremendous moral row over whether I should have been built at all but none whatsoever about all the money and effort spent on separating me from my natural mix.

(b) Odd, because while there is no debate at all about whether I should have been built, there is a serious moral debate underway about whether so much scarce wartime energy and resources should have been spent on separating me from my natural mix.

 (a) I am considered one of the biggest killing machines in history.

(b) Boy or girl, do we ever part company there : I am one of the smallest lifesavers ever, and one of the best too.

Can you answer this puzzler ?

(a) and (b)  So, dear reader : Who am I ? Who am I ?

Answer : (a) the U-235 in the Little Boy Bomb  (b) an early vial of Penicillin, who baby Patty Malone and  teenagerAnne Shirley Carter helped make an overnight world sensation in August-September 1943 .....

Thanks to SAMJ (the SOUTH AFRICAN MEDICAL JOURNAL), we can learn of first published guess as to penicillin's chemical structure

SAMJ : the South African Medical Journal

So much has been written about the earliest days of trying to determine the chemical structure of pure penicillin, in such truly massive tomes like "THE CHEMISTRY OF PENICILLIN" and "ANTIBIOTICS,VOLUME II", and much more delightfully in John Sheehan's lucid-but-learned "THE ENCHANTED RING" , that there seems little more to add.

But that is not so, thanks to the South African medical journal SAMJ and its enterprise at putting all of its over 100 years of back issues online and free to access.

It is little known that Karl Meyer, the chemist on the tiny pioneering Columbia university team ( the first ever to use penicillin as an antibiotic), contributed an unique intellectual portion to Henry Dawson's first presentation on penicillin.

This presentation was delivered in Atlantic City, at the 33rd annual meeting of the American Society for Clinical Investigation, ( the famous "Young Turks" ) May 5th 1941 --- attended by top medical researchers from all over the world and covered by the scientific and popular media.

To add to the journalistic fun, their more senior and sober counterparts, the American Association of Physicians, met the very next day in the same place - and the two generations of doctors didn't always agree on everything, naturally .

Most penicillin historians seemed to have limited their knowledge of this seminal event to the New York Times report on it, easily available anywhere on microfilm.

But the official abstract of Dawson's presentation , formally published in the Journal of the Society in July 1941, mentions - in passing - two important subject areas that all the popular media left out in describing Dawson's paper.

His presentation talked of the methods of preparation ( and importantly made it clear this took place in Dawson and Meyer's hospital lab and not in some drug company lab), without saying anything more.

 Fortunately later articles do amplify on the earliest methods of growing and extraction in great detail.

But the precis also indicates that information as then known of penicillin's chemical nature , ie known as of late 1940-early 1941 , was discussed --- without saying what was speculated.

This speculation is NOT repeated in any later article, because this early speculation was not even close to penicillin's final chemical structure, as found with the help of hundreds of chemists, five long gruelling years later.

But, while I am not a chemist, I think I can say it wasn't a bad guess for what was known - almost by sight and smell - about the earliest dry penicillin powder.

Thanks to SAMJ, the South African Medical Journal

But back to SAMJ - because it was all down to one of their most enterprising correspondents , H O Hofmeyr, that we know anything at all about the earliest chemistry of penicillin.

Hofmeyr came from a very politically powerful Afrikaner family and so it is not surprising he was sent abroad, during WWII, to be South Africa's scientific eyes and ears in places like Washington DC.

He wrote a very complete diary of his visit to the Clinical Investigators annual meeting and it was published, in full ,in the September 1941 monthly issue of SAMJ.

I think I remain the only one to ever cite Hofmeyr's eyewitness report on the opening of the Age of Antibiotics.

I have always treasured his report on Dawson's paper , partly for his slightly snide tone relating that this particular paper caught the imagination of ("sniff") the ("popular") press who gave it ("lurid") headlines like 'Giant Germicide Yielded by Mold'.

But in addition, Dr HO ( as everyone called him) correctly noted in 1941 what current historians always, always miss : that Dawson's use of penicillin on subacute bacterial endocarditis, the dreaded SBE, was in some ways, highly conventional.

Hofmeyr said it still remained in 1941, the absolute "acid test" for the claims of every new potential chemotherapeutic agent.

But buried in middle of the paragraph, Hofmeyr indicates that the Columbia team is willing to speculate publicly that penicillin seems related to the hydroquinones.

The hydroquinones are a big family best known for their use in photo developing and skin whitening, but one in particular, paraquinone ,strikes me as looking, smelling and acting rather like early penicillin powder.

Yellow , arid penetrating smell, very sensitive to acids and bases, yes it sure does look, smell and act like early penicillin.

But paraquinone has only has about one third the molecular weight and number of atoms that penicillin has (and was thought to have in 1941) so it would have to be quite an elaborated version to fit the known facts.

WE have to wait to 1942 and the much better known journals such as NATURE and SCIENCE to find the next set of informed guesses as to penicillin's structural nature, but thanks to SAMJ, we have recovered an important fragment of medical history .....

Vitamin C pills vs oranges: a metaphor for the dueling penicillin of Aussie docs, Florey and Duhig

A nice big fresh juicy orange and a tiny white pill can both have the exact same amount of vitamin c in them : about 100 mg ,  just above the recommended daily intake of the vitamin for a adult.

The synthetic vitamin c pill (first invented in the 1930s) is of course  supposedly pure, but actually consists mostly of "harmless" filler . It is usually taken with a small glass of water.

The orange was - in the eyes of the Modernist 1930s - an impure source of vitamin c. The orange consisted mostly of harmless filler (pulp fibre and a great taste) and about the same amount of water as needed to fill a small glass.

Despite being "impure", a whole (100mg)  orange a day would actually be more healthy for you than taking half (50 mg) of a "pure" pill every day.

All the body craves is its fix of 100 mg of the "C" a day , not whether human minds consider that vitamin c to be pure or impure.

Unless the vitamin c is bound to something that renders it biologically inactive, the body considers it as fully pure and effective and dismisses what sort of filler and water it chanced to come bundled with.

It was exactly same with the human bodies our two wartime Aussie doctors Duhig and Florey had taken a sacred oath to protect.

Heroic penicillin at its best ...

From twelve one liter flasks growing penicillium fungus in his Brisbane hospital lab , in late 1943, Dr James Dunhig got 2500 cc of penicillin juice, averaging at best five biologically active units of penicillin per cc , or about 12,500 units in total.

This crude, impure, liquid was strained but not processed - only kept chilled.

It was almost immediately put into a 42 year dying mother, a patient of Dr Geaney, in various sizes of IV doses (some as large at 600 cc) over a number of days -- and yet this impure medicine saved her life and home she went to her grateful and astonished family.

Dr Florey,originally from Adelaide, from the same 2500 cc of starting penicillin juice grown in his Oxford university lab in late 1943, also started off with 12,500 units of crude, unprocessed, penicillin.

But he chose to refine it over and over and over and over again, losing and destroying most of the penicillin in the long process.

Finally he ended up with a very little pile of relatively pure powder : one tiny mg of dried penicillin,  assaying about 1250 units of biological activity.

But you can't inject dry powder - no matter how pure - into a patient, so some of that oh so expensively extracted water had to be mixed again with the dry penicillin,  if it was to be usefully injected  in a dying patient.

Non-heroic penicillin, at its worst ...

But it wasn't - it was given instead to chemists, to be deliberately destroyed , all to make a more accurate assessment of penicillin's structure by examining its various sub components.

Then (in the middle of a deadly world war)  public domain penicillin could finally - profitably -  be synthetically analogued and  patented.

Just as well that Florey wasn't moved to waste any of his preciously pure penicillin on a dying woman, because 1250 units of penicillin , no matter how pure, couldn't save most dying adults but 12,500 units of impure penicillin sometimes did.

It is as I say, a classic example of the old saying that 'an whole impure orange a day will keep the doctor away, but half a pill of pure little white pill will not' ...

Dawson's DIY penicillin a postmodernist "shot across the bow" of Modernist Big Pharma

Two hundred years from now, only the first of the Dawson team's many articles on wartime penicillin will still be cited and still considered seminal.

This, despite the fact that Nova Scotia-born Henry Dawson's last penicillin article told a surprised world that invariable fatal subacute bacterial endocarditis (the much dreaded SBE) had finally been cured - by his penicillin method that he had pioneered 5 years earlier.

But instead it is Dawson's first penicillin first article, the "impure but non toxic" article of May 5th 1941, that had (and continues to have) ramifications beyond any one disease, ramifications indeed beyond even medicine and science itself.

In that article, delivered before a large group of international medical researchers in Atlantic City and widely reported by the popular and scientific media from The New York Times to the South Africa Medical Journal, Dawson deliberately paired and then contrasted two oxymoronic phrases.

But first, recall that Dawson chose to appear in front of all his peers to praise his new drug to the heavens AND announce that it had no therapeutic effect on a series of four SBE cases in a row.

Trust me on this one : normally scientists do not rush to the biggest conference in town to proudly announce repeated failure.

But it wasn't the lack of therapeutic success from his impure natural penicillin that Dawson was really so eager to announce.

Rather it was the lack of toxic effects from his crude homemade mixture of natural penicillin and its natural impurities that he was so proud (and perhaps amazed) to announce.

(In a sort of 'reverse Ivory Soap', his starting penicillin brew was far less than 99 and 44 100th percent impure :  pure penicillin made up only one part per million of his mixture !)

It could have had - perhaps even should have had - a highly deadly mycotoxin  poison buried somewhere in that fungus mix, but God took pity on Humanity and it did not.

We do not have a complete version of Dawson's report and ad lib comments , only various precis. But assembled together, I believe we can garner Dawson's actual words and phrases used to prescribe his main intent behind this article.

He described how his tiny team made their hospital-grown crude (impure) and natural penicillin, calling it both more potent and much less toxic than the factory-made chemically pure synthetic sulfa drugs, less potent and more toxic, made by Big Pharma .

His takeaway line, as the CBC's Don Connolly likes to say, is that "despite being impure, homemade natural penicillin was actually less toxic and much more potent than factory-made pure synthetic sulfa drugs."

"Living better chemically ?"

Today, in this postmodern age,  this statement might hardly seem controversial ; but in 1940, at the apogee of Modernity, to diss the Du Pont slogan of "living better chemically" was to indulge in sheer heresy.

At the same university as Dawson (Columbia) and at the exact same time, famed German-scholars-in-exile Adorno and Horkheimer were busy dismantling 500 years of Modernity, brick by brick, and patiently reassembling them as Postmodernity.

Perhaps posthumously, their fellow university colleague Henry Dawson can lay claim to being among Postmodernity's first scientific converts.....

Henry Dawson "jump-started" The Age of Antibiotics because, almost alone in the medical world, he wasn't obsessed with 'purity' but rather with 'charity'

We have the records of only a few contemporary reactions to Henry Dawson's surprise decision to dramatically kick-start The Age of Antibiotics, 12 years after it should have begun but three months before it was scheduled to begin , but they are suggestive.

Gladys Hobby, his assistant, entered the Meyer-Hobby penicillin project a few weeks into it, after taking a late summer vacation.

She returned, she told penicillin author Leonard Bickel just 20 years later, to "an air of excitement filling the Dawson-Meyer lab" , Dawson had "immediately begun to work on this new project" and she "was at once caught up in his eager search".

Dawson was willing to wait "only eight days" after Meyer began purifying his first ever brew of penicillin before, "full of excitement" he injected this just-begun-being-purified material into two dying patients .

One patient died, one went home cured - Dawson refused to credit his small amount of "extremely low potency" penicillin with this cure, but he was "heartened" by the "low toxicity" of this "extremely crude" preparation. "No serious toxic effects observed."

Hobby later wrote in her own book on penicillin, that Dawson had "recognized immediately that penicillin .... might be effective in the treatment of ...subacute bacterial endocarditis in particular". The product used on October 16th 1940, she admits, was "crude" , "slightly purified (concentrated)" , even "extremely crude" .

At first, only the "low toxicity" of the "crude and impure" penicillin was noteworthy , not its curing ability.

On May 5th 1941, Dawson addressed hundreds of the world's top research doctors in Atlantic City, an event traditionally well covered by the popular media.

So we learn - via the New York Time's famous Atomic Bill Lawrence that Dawson admitted to the audience that despite his "crude" penicillin not being "pure", "no serious toxic effects were observed."

Via science journalist Steven Spencer, writing in America's largest evening paper, the Philadelphia Evening Bulletin, we learn that Dawson said that his penicillin was not toxic even when given in doses far beyond those dosages needed to clear up infections -- a distinct advantage over the sulfas, which are toxic to some people."

He said, reports Spencer, that penicillin had "unlimited possibilities."

Finally, an opponent of Dawson, Stanhope Bayne-Jones tells Howard Florey in strict confidence in July 1941, that Dawson is "quite honest" but "uncritically enthusiastic" .

I think I have demonstrated what was Dawson's key insight into penicillin, the insight that drove his excitement and his passion.

It was that he realized that  even a crude mix of hospital-made natural penicillin with all its natural impurities still in it was both potent AND non toxic  (in fact more potent and much less toxic than drug-company-made PURE sulfa drugs).

So morally, a doctor could not wait for 100% pure natural penicillin or for 100% pure synthetic penicillin, before starting to use penicillin to save the dying by systemic injections.

He had discovered unrefined natural penicillin's big secret....

Pure Sulfa or Salvarsan drugs were far more toxic than impure crude penicillin : so what was the fuss REALLY about then ?

Before 1945, an entire generation of doctors world wide (except for perhaps a half dozen of them) were more willing to put pure but toxic sulfa or salvarsan drugs into their patients than put impure but non toxic penicillin into them.

I will go further:  an entire generation of doctors were willing to seen letting their patients DIE, rather than be seen by other doctors as putting an impure substance into those dying patients.

an obsession with Purity - before even the patients' life 

In The Age of Modernity, before 1945,  an obsession with purity had its hands tight around the throat of medical morality ....

Wartime penicillin's biggest secret was "hidden in plain sight", on the pages of the very first article on penicillin

The real reason why the tortoise Henry Dawson, despite starting almost three years late, beat the hare Howard Florey to become the first ever to put an injection of an antibiotic into a human patient, is to be found inside wartime penicillin's biggest secret.

Unexpectedly, wartime penicillin's biggest secret was not stamped "TOP SECRET" and was not buried under lock and key in some government cabinet in Washington or London.

Instead, Henry Dawson discovered it in October 1940, incredibly enough "hidden in plain sight" , on the pages of Alexander Fleming's very first article on penicillin from back in 1929.

Hidden from even its own author for all those years ; remaining hidden to almost everyone ever since - except for a very few caring and observant wartime doctors.

The great secret is all about non-toxicity and natural penicillin.

No, no , no, ---- don't jump the gun.

Its not that penicillin is non-toxic (because in some crucial ways it is not).

Rather more surprising, the great secret turns on the lucky fact that natural penicillin's natural impurities are so relatively non-toxic.

Fungus are very much a mixed bag on the toxicity front. Lots of them are so non-toxic that we love to eat them as our daily food : bread, beer, cheese, mushrooms, tofu and treated milk products.

Others release tiny amounts of toxins (mycotoxins) so toxic they rate up there with the most deadly poisons we know, by weight.

Back to 1928.

After about ten days of activity, and after a good straining through a lab filter to remove all solids, a gram of Fleming's 1928 penicillium liquid medium contained one part per million of penicillin -- one microgram of penicillin , ie about 1.6 units of bacteria killing activity .

97% of that gram was pure water and the remaining 3% were natural impurities - mostly organic acids.

We humans eat organic acids all the time - particularly in preference to their alkaline opposites, the bases.

Unfortunately, in a the world obsessed with eugenic purity, the good news ended with this particular penicillium strain's thankful lack of general toxicity.

The Age of Modernity liked things to be distinct and separate, not buried together in mixtures : it demanded purity in everything, from the German race to the Allied brand of penicillin.

Unfortunately for this obsession with purity, those various natural acids produced by the penicillium were so much like penicillin chemically (though not at all in anti-bacterial activity) that they were almost impossible to separate from penicillin without either destroying it and or losing it along the way.

In September 1940, at the start of their teaching hospital's first term, Henry Dawson had agreed to restrain his instinct to try and save lives.

Restrain himself, until his fellow team member, chemist Karl Meyer, had purified their penicillin (that the tiny team was home- growing) to a point where it was judged 'pure' enough to inject safely in a human body.

The projected launch date was the start of next school term, in early January 1941: ironically the exact same time Howard Florey's team was scheduled to start injecting their 'purified' penicillin into humans ! Dawson's team didn't know this, how close they came to be 'also-rans' .

Florey thought his team so far ahead he felt no particular urgency to rush into saving lives ; purity and not humanity, was always more his 'thing' anyway.

But ultimately Dawson couldn't stand to stand idly by as two young boys died needlessly from the dreaded and invariably fatal SBE (subacute bacterial endocarditis).

Not when he was convinced that penicillin's unique combination of non-toxicity, potency and diffusibility  could save them.

He had not much literature on penicillin to read and re-read while waiting for the difficult process of purification to succeed , not in October 1940: only five articles .

Suddenly he realized that there was a possible solution to his moral dilemma , in that literature and right there under his nose all the time.

 All five authors, beginning with Fleming, had mentioned that natural penicillin's natural impurities were not really toxic - at worse, a minor irritant.

So why continue to purify and purify penicillin - at an enormous cost in labour and in penicillin losses?

Why labour to purify it past the point where it could be concentrated (like orange juice),  just enough to have a useful therapeutic effect without literally drowning the body in excess water ?

At that time, Dawson team was often making penicillin brew so weak that pouring it directly into a human body (by IV drip) would require putting a kilo of water into the blood stream for every 1000 units of penicillin activity !

But one go around of initial concentration cum purification might result in a little dirty brown powder that assayed 8 units per mg (one thousands of a gram) - 50 mgs of this powder dissolved in a gram of a suitable liquid, 3 times a day, would give the patient 1200 units of penicillin --- without the risk of drowning them internally.

And so on October 16th 1940, Henry Dawson jumped the gun and launched the Age of Antibiotics three months ahead of schedule.

Later on, by mid 1942, the raw penicillin juice made in hospitals assayed at around 40 units per ml of medium (about 25 times as pure) and it no longer needed to be even concentrated like orange juice (because even that resulted in heavy losses and needless additions of chemical contaminants).

It could simply be strained of solids, bottled and stored in a cold dark refrigerator until injected into a patient (and not merely dabbed into the patient's open wound, which was as far as most other penicillin pioneers were willing to go with non drug-company made penicillin.)

This is what a few brave penicillin pioneers (salute their heroic efforts please !) did : Robert Pulvertaft, James Duhig, and Zinaida Yermolieva.

Admittedly ,the first two did save lives by injecting raw penicillin into patients' blood supply, while still expressing some reluctance to do so  - by contrast, the soviet team led by Ms Yermolieva  did so routinely - all the more praise to them !

An unnecessary penicillin holocaust ...

If  only crude raw penicillin had been used to save lives, starting in 1928, millions of people would not have needlessly died world wide , in  a totally unnecessary holocaust bigger than anything Hitler had planned for the Jews .....