Thursday, November 12, 2015

Dawson's Burrs - Part Two

During the inter-war period and for long time afterwards, medical researchers who wanted to fit inside (and more importantly, rise inside) their profession's norms focussed exclusively on studying virulent microbes and treating acute illnesses.

But right from the start, at two of the world's top medical research centres (Rockefeller Hospital and Columbia Presbyterian Hospital), Henry Dawson defied those norms, taking a wide 'inclusive' view of research possibilities that took him well outside the medical Pale.

And ten billion and counting of us, since 1940, have had better lives, because he chose to do so.

For Dawson (and his later associate Dr Gladys Hobby), right from the start, choose to focus on avirulent microbes and the treatment of those with chronic illnesses.

Virulence, virility - and chickenhawks...

For his alpha male/male colleagues, the proper bacteria variant to study was one that was highly mobile and well protected behind thick walls and capsules -- for this made them more virulent and virile.

They generally called this variant, type S.

Dawson choose instead, or so it seemed to them, to perversely focus on immobile, avirulent, a-virile variants that went under the names of R,L and V (vegetation) types.

In vain would Dawson protest that he had no vertical hierarchy in his study projects - no rejecting the 'higher' S types for the 'lower' R types.

He saw all of them : S,R,L,V,M as merely equally valid solutions, along a horizontal continuum, to unique environmental situations.

And he in fact had positioned and named his new variant, the M type, as a super-virulent (in the right environment) version of the already highly virulent S type !

the Gender War - always bigger than mere military wars

It is impossible not to see the Gender War lurking behind in this academic battle over which bacteria type to focus study upon.

Alpha male male lead researchers focusing on highly mobile beings with coats of thick armour while a female researcher (and her emasculated boss) focuses on beings that don't move about much and had no tough armour to protect them.

It all sounds like male knights in armour fighting it out to see who wins the damask damsel in distress.

But it gets morally worse, because in an age of popular eugenics, this scientific disdain for studying the immobile, armour-less bacterial variants seemed to call up echoes of an equal disdain for studying the immobile and defenceless institutionalized chronically ill.

Look after such people was supposedly 'gobbling up' the tax dollars of members of the upper middle class, such as leading research doctors.

Whereas in Nature, they would quickly die off as losers in the struggle for survival.


Dawson heard all this, over and over, in the table talk of his colleagues, but he ignored it - in fact railed against it in private.

Henry Dawson had no vertical hierarchy of worthiness to judge which type of patient illness was worth or not worth focusing upon, anymore than than he did for deciding which bacterial variant to study.

As I said, he held a wide inclusive vision of what medical research could be and should be, for the entire fifteen years of his career before he started his natural-penicillin-for-all project in late 1940.

But it hadn't put any hard burrs under any hard saddles among his colleagues.

His (personal) study of avirulent bacteria via its contrasts actually better defined the attributes of their virulent bacteria.

And like it or not, society was not about to haul the institutionalized ( read: working class & poor) chronically ill into the wilds and abandon them to their fates, so some doctors needed to be assigned to treating them - and that was Dawson's day job.

And regardless of what anyone thought about Dawson's 'wild' ideas on bacterial variants, his work with the chronically ill was judged to be very sound as he frequently reined in the wilder speculations of others also researching chronically illnesses.

selecting the hardest saddles, the toughest burrs

But in the Fall of 1940, Dawson deliberately set out to put the hardest possible burrs under the hardest possible saddles and await the resulting pushback - because he intended to give as good as he got, confident that in the end, external  public opinion would outweigh internal scientific opinion.

Dawson knew that the scientific establishment felt it had the best possible reasons to abandon SBE patients to their dire fate during wartime.

But Dawson also felt that he would win if his unwillingness to go along with their abandonment forced the scientific elite to go public to defend those reasons.

Privately, amongst themselves, doctors often abandoned hopeless cases to their fates.

no patient 'left behind'

But they never admitted this in public because this would clash with medicine's often publicly stated claim that no disease was ever incurable (given enough research gold showered upon it) and no patient was ever "left behind".

In a war where everyone was supposed to suffer together, America being seen publicly as "leaving its young SBEs behind" would be untenable - and this soon proven the case once penicillin triaging became known in the late summer of 1943.

That was number one of Dawson's burrs.

Public Domain (primitive and female) vs Synthetic (profitable and male) penicillin 

Burr number two was Dawson advocating the cultivating of and injecting of natural Public Domain penicillin (basically the metabolic poop and pee of penicillium slime) into the human bloodstream to saving incurable SBEs.

This raised any number of flags in the minds of scientists, drug company presidents and general decision makers.

This was the age of High Modernity, 1875-1965, after all.

A quick thumbnail sketch of High Modernity would be that educated people in that era were totally obsessed with separating the normal from the abnormal and then firmly policing both their boundaries to keep them firmly apart.

The slimy fungus, being neither solid soil or wet water, straddled that mental/moral boundary and  lived by dissolving solid (dead) things and turning them into slime.

No wonder that High Modernists like HP Lovecraft and Adolf Hitler were famous for regarding fungoid growths as the ultimate form of evil and horror.

Almost people did back then, to some extent.

One only has to remind oneself that we still hold that the ultimate symbol of atomic horror and evil to be another fungus --- the mushroom cloud.

Molds like penicillium lived in dank dark basements when they weren't dissolving our food and clothing.

The news that natural penicillin was a tiny component of mold's metabolic wastes ( poop and pee in human terms) only heightened the emotional horror at the thought of injecting that stuff into the temple of the human bloodstream.

(Because yes, High Modernists also had very funny ideas about blood as well).

Another problem was that natural penicillin was made by naturally found penicillium.

Thus this penicillin was inherently Public Domain and even worse, made by a low tech process : everyone was legally and even technically able to make the stuff, driving down the price in a global sea of competition.

The cost advantages clearly went to rural firms with access to low cost farm wastes, employing low wage rural workers and located on cheap abundant land with great access to massive amounts of running water.

The existing drug firms were located in high cost urban areas and made their massive profits by holding patents on life-saving drugs.

War or no war, the mass production of life-saving penicillin would have to wait, in their eyes, until it was patented and that meant it had to be synthesized into improved analogues on the natural version.

As it happens, an impossibly tall order (we still haven't been able to make penicillin commercially profitable by total synthesis.)

The drug bosses and most chemists didn't see it that way at the time.

'Letting Down the Side'

After all, hadn't they recently made all the new life-saving sulfa drugs by total synthesis --- and synthesized the external natural antiseptic gramicidin. Even synthesized the fairly big molecule (176 Daltons) that was Vitamin C.

Dawson knew that the gramicidin molecule was very small and hence simple to make, while 'synthetic' vitamin C  actually had to be made partially by microbes, if it was to have any vitamin effect inside the body.

(Biological molecules made to the right formula and basic shape don't work if they bend in the wrong 'stereo' direction --- microbes always get this right, human chemists can't.)

Penicillin had been worked upon by many top chemists by the Fall of 1940 and had yielded no success.

Dawson noted that its molecular weight (350 Daltons) was eerily like that of the very much studied morphine and quinine.

These two had proven, in over a century of concentrated effort, to be unable to be humanly synthesized at a commercial price.

It goes without saying, I hope, that these two molecules are highly unusual molecules with highly unusual properties.

Yet they are made up of the ordinary atoms that are the building blocks of all organic chemistry.

Their uniqueness must lie then in their shape - the way these ordinary atoms are twisted in ways that chemical processes alone won't do on a regular basis.

Microbes and enzymes

Microbes twist chains of bog ordinary atoms into interesting twists by the use of enzymes.

These very large molecules with their own interesting shapes easily capture, bend and bind small molecules into powerfully biological active molecules in just a few steps, at ordinary temperature and pressure, using little energy and few or no exotic materials.

Human chemists can sometimes use millions or billions of dollars of equipment, chemicals, heat and highly paid scientific labour to replicate what the tiny weak primitive microbes easily toss off --- but usually not.

Not, at least, in a cost effective profitable manner.

Today, this is well understood and well accepted by young would be scientists and Wall Street investors who bypass chemistry and physics for microbiology.

But it was hard to accept seventy five years ago, when the High Modernity version of Progress was strictly linear - the ancient and stupid microbes at the very bottom and the contemporary and brilliant European scientists at the very top.

It was impossible to accept - or permit - slimy nobodies like the fungus to make something as potentially life-saving as penicillin far better than the smartest chemists in the universe could --- it would be like allowing  the darkies in India and China to make all our life-saving drugs.

(Er, they do today, don't they ?!)

Using natural penicillin was like 'letting down the side', 'going native', 'losing face'.

bravely staying home to synthesizing penicillin, to avoid being a man out on a battlefield

And the ever popular Gender and Class War emerged again in the wartime arguments over penicillin production.

Tender little penicillium molds were raised by hand by working class women, almost exclusively - while synthetic penicillin would be manufactured by middle class male chemists.

During WWII, male workers frequently rioted if woman were allowed to do manufacturing jobs, because their unstated fear was that would free up the males to be drafted to fight overseas.

Just as in the Vietnam era, men who openly admitted they were scared of dying overseas and so fled to Canada were disdained, while those who found a minor medical defect or suddenly married and impregnated a wife and evaded going 'legally' were quietly admired.

Males openly admitting fear were 'letting down the side'.

But men who successfully concealed their fear behind bold war talk while finding excuses to avoid the draft, the yellow chicken hawks, ended up in Congress.

So chemists in WWII didn't riot to keep women out of penicillin production so men could avoid the draft, they simply talked about how male chemists had to be able to make penicillin cheaper, faster, easier and better than stupid microbes and silly women.

As the official historian of America's wartime scientific research organization, Vannevar Bush's famous OSRD, put it so eloquently, "Science couldn't advance simply by using 4Fs, women and the Grace of God", it needed legislative protection to keep its virile young male scientists away from the bullets and bombs of war.

Dawson knew the internal scientific arguments supporting synthetic penicillin won't stand up to external public examination - and the really important but unstated fears about women, darkies and the draft would never even be raised.

The Allies, led by engineers like Vannevar Bush and General Leslie Groves, were already in full accord with the general public that basic scientists, given enough money and time, would spend the entire war happily polishing and re-polishing their scientific efforts - rather than quickly getting them into production and onto the battlefield.

'Fifteen years to try and synth penicillin was far long enough - abandon it or at least scale it back, and go with the bird in the hand - we need penicillin to replace the failing Sulfa drugs - STAT !'

Equally public opinion would rightly suspect the big drug companies of delaying mass production of life-saving penicillin until it could be profitably patented.

Again, after the experiences of WWI, it was near universal, on the right as well as the left, to suspect war profiteering everywhere.

Natural-Penicillin-for-all : Dawson's triumph

Dawson succeeded. In spades.

The Allies originally had planned to only make enough natural penicillin as to aid the chemists' efforts to break some of it down to synthesize back up again and thus learn how to totally synthesize it from scratch.

And natural or artificial, they only planned to make as little penicillin as possible for clinical use - only for the lightly wounded among Allied frontline combat troops.

In the end they mass produced wartime natural slime-made penicillin in sufficient amounts to help all those in need of it :  all the Allied wounded, even enemy wounded, and all the civilians needing it - in the Allied countries and Neutral Countries, then in liberated Occupied Lands, and finally for enemy civilians and Allied POWs in enemy lands.

An inclusive coalition indeed.

Gadfly or burr under the saddle, there is no end of good that a little prick can do....

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