Wednesday, June 17, 2015

Social Penicillin : the story of 'Penicillin-For-All'

Was October 16th 1940 the date of the world's first ever injections of social penicillin ?

Well, first, let us consider this question :

Can a hospital system actually make citizens feel sick or feel well, even if they never ever visit in their entire lives ?

On the surface, that seems a very ridiculous question - what earthly good are hospitals if they don't actively try to make sick people better?

But I argue to the contrary.

That, perhaps, over all people and over all their lifetimes, a hospital's greatest value or damage is the sort of moral values it radiates forth, on behalf of the society around it.

If it has a great reputation for serving all equally, regardless of their income, ethnicity, gender or age, if it says 'everyone is valued' - it raises everyone's self esteem.

And it is medical fact that high self esteem, all by itself, is a powerful, cheap and non-toxic preventive and curative medicine.

Or perhaps the hospital is best known for first testing your financial worth before it even tests your blood pressure and is also well known for ill-treating patients, even if they have sufficient income, if they are of the wrong ethnicity, gender or age group.

That sentiment is damaging to the self esteem of the people in those unfortunate groups.

Again, it is a medical fact that the stress of lifelong low self esteem acts to lower our immune response --- indirectly making us, if not actually 'sick', a whole lot 'sicker' whenever we do fall ill.

I believe that History's first ever injections of penicillin, ushering in the Age of Antibiotics, offered no drug-induced clinical value whatsoever to the patients receiving them and that the doctor giving those injections (Henry Dawson) well knew that.

These injections then were not of penicillin-the-chemical-drug but rather shots of 'social penicillin', a phrase I have coined in homage to 'social medicine' .

The very real clinical value these injections represented was in the uplift in spirits it gave to these two young patients and to all others suffering from their disease.

For SBE (heart valve endocarditis caused by Rheumatic Fever) - was a disease their families were always being told was invariably fatal.

And totally resistant to all known treatments, in fact the very Mount Everest or Gold Standard of resistant infectious disease.

Abandon hope, all ye that enter here.

But Dr Dawson believed that three combined characteristics of penicillin ( with only the last being totally unique) would beat the unique set of difficulties presented by this dreaded disease and finally conquer infection's Mount Everest.

That is he knew that (a) penicillin killed strep bacteria readily(b) was small & highly diffusible and (c) was totally non-toxic, even if given in enormous amounts.

Only a recently acquired medical community revulsion against injected crude fungus slime into the human bloodstream had denied this lifesaver to tens of millions of dying patients over the previous twelve years.

Dawson resolved to break that medical taboo, a taboo perhaps even held by the other members in the tiny four person team working with penicillin at his hospital.

Dawson, as a busy ward clinician, was actually the junior member of the team, at least in the beginning.

Karl Meyer, gifted biochemist, together with his chemist assistant Evelyn Chaffee, would destructively analyze the fungus penicillin grown mostly by microbiologist Gladys Hobby and then chemically synthesize artificial penicillin.

Hobby would confirm that both the natural and artificial penicillin indeed had biological activity - testing it on killing microbes.

In the beginning, Dawson would mostly run interference with the hospital authorities, above all in securing rare permission to deliberately grow gallons of fungus, with all their highly mobile spores, in a normally highly antiseptic hospital setting.

Only a planned four months after the beginnings of the project would Dawson take centre stage, when he injected synthetic penicillin into actual patients assigned to 'his' ward.

Now Dawson knew that chemically either natural or synthetic penicillin were equally good at defeating SBE.

But defeating SBE required more than just an effective bug-killing medication ---- SBE uniquely needed simply enormous amounts of medicine, particularly to kill such relatively small amounts of a very fragile bacteria.

SBE bacteria live on the heart's Rheumatic Fever damaged valves, sheltered behind a tough but semi-porous barrier of biofilm (then known as vegetation).

Normally medications diffuse gently and slowly into and around the individual cells of an organ via the incredibly tiny blood capillaries.

And like a lobster trap, once in around the cells it is not that easy for the medication to leave, and the molecules of the drug have a long time to work their magic.

But like ear lobes, the valves of the heart have virtually no capillaries. Yes, they are literally bathed in blood all the time, but the blood surges by them at an incredibly fast pace, as measured in terms of the motion of molecules.

The chances of a molecule successfully diffusing (aka moving via random thermal motion) its way over to the biofilm and finding its way in by the rare small opening in the biofilm, in the millisecond it pulses over the valve surfaces, is near zero.

About as likely as U235 separating from U238 simply by their varying rate of diffusion through tiny holes.

And we all know the trillions it has cost the world to make that diffusion technology work !

But in both cases, brute force technology will indeed slowly win through.

For penicillin, that meant about a thousand steady hours of the constant pulsings of trillions of tiny penicillin molecules a second bouncing their way past the biofilm surface.

The laws of probability would eventually ensure enough made their way into the biofilm's rare tiny holes to kill the bacteria within and end the infection.

In plain english, while a single unit of penicillin might cure an infant from lifelong blindness caused by a meningitis eye infection, easily over a billion units of penicillin today might be needed to cure a particularly stubborn case of SBE.

That a seriously ill patient can receive that much of any medication without any ill effects is why doctors still call penicillin magic.

In October 1940, Dawson could only guess at the ultimate amount of the SBE medication needed for a permanent cure.

But he did know the small amount of penicillin the team had grown in the five weeks since they started the project and its relative strength, by weight, against number of bacteria per a unit of mouse body weight.

He could even compare his figures against similar calculations performed by Howard Florey's team in Oxford a few months earlier.

And as a very experienced bacteriologist and clinician, Dawson was particularly good at converting lab mouse cures rates per weight of medicine into their effective impact on adult sick humans weighing two thousand times as much.

But that was actually for infections by highly virulent bacteria, but in readily accessible organs.

SBE involved very weak bacteria but in very inaccessible locations - perhaps the two conditions could thus be crudely equated.

Still no matter how he sliced it, the penicillin at hand was far far too small an amount and far too weak in strength to really combat SBE.

But on this day, it wasn't really the SBE bugs that Dawson was seeking to combat - but rather it was the moral values of the society around him.

He didn't like the values his hospital and his society was radiating to a world at war - and he sought to change it.....

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