Thursday, August 27, 2015

Way out of his comfort zone

I was not truly 'surprised' that the normally highly diffident Dr Martin Henry Dawson broke his own team protocol and became the first person in history to inject an antibiotic (dirty natural penicillin) into a patient, 75 years ago this October 16th.

For the diffident Dawson had done something similar at least once before, pushing on with his equally pioneering research into the horizontal transfer of DNA between microbes, against the express orders of his boss at NYC's Rockefeller Institute.

That totally ruined his career prospects at the world's most attractive centre for doing medical research --- so this new decision to merely jump his own tiny team's protocol would have far less dire career consequences.

But what did surprise me - and did so for a very long time (years and years and years in fact) - was his twin decisions made the month earlier.

Fungus growing - and starving - on a massive scale

First was his decision to grow massive amounts of the fungus mold, penicillium n.

Massive as in obtaining 50 US gallons of penicillium liquid per run - the very size of a typical drug industry pilot plant project.

Like most ambitious bacteriologists, Dawson was extremely narrowly focused on learning all he could about just one tiny segment of the bacteria world and so he gave only a glance at all the other bacteria - and tried to ignore viruses and fungus, etc,etc completely.

In his case, he had focused on the then deadliest of all microbe families - the streps (which included the s. pneumococcus).

He had grown massive amounts of the various streps successfully and routinely but massive fungus growing for clinical not lab work would be much different.

Firstly, it would all have to be done with an eye to making penicillin economically on a long term basis, particularly when set against penicillin's cheap and abundant competitors, the sulfa drug family.

Occasionally growing small amounts of pathogens like pneumococcus for some personal science experiments is one thing - 'costs versus sale returns' don't really come into it.

It is far different when one grows de-natured pathogens to supply a huge public market demanding equal and cheap access to vaccines, as Alexander Fleming well knew, because he ran such a business in his London hospital.

His hard earned knowledge of costs versus profits may have lessened the willingness of Fleming and his huge drug company partner (Parke Davis) to grow large amounts of 'his' penicillium, considering how small the amounts of penicillin produced as a result.

Unlike his naturally made - and very profitable - vaccines, Fleming always insisted his penicillin would only come into clinical use when it was made artificially by chemists.

Secondly, Dawson would be growing massive amounts of penicillium fungus to an effort to scale up tiny amounts of an infrequently produced and highly fragile distinctly second rate secondary metabolite.

Why is that so noteworthy ?

Because all bacteriologists, like all farmers, work to make as much biomass as possible, as cheaply, quickly and easily as possible.

As many big viable bacteria/apples/pigs as quickly, cheaply and routinely as possible.

It was a piece of cake to get the penicillium n. to bulk up quickly and cheaply but when they did so, they produced no penicillin at all !

It seemed to everyone that penicillin was sort of like green poop in humans - a rare waste product produced when a body ate a food it didn't like and got very sick as a result .

Learning to grow penicillium n. so as to make lots of penicillin routinely and economically went on after the war as well as during it and it involved at least as much scientific manpower hours as did the entire nuclear Manhattan Project.

And - a distinct rarity - most scientists thought this might be the case, right from the start, and this is why Fleming and Howard Florey and almost all the others differed from Dawson and focused totally on man-made synthetic penicillin making efforts.

I can't really explain Dawson's decision to get involved in mass fungus making except to say that his career had been devoted to demonstrating how smart the supposedly stupid microbe really was.

He certainly thought the penicillium might be damed good at making penicillin, merely by dint of hundreds of millions of years of trying.

Perhaps then it was the overweening hubris of the 'synthetic penicillin' crowd that might have perversely pushed him much further into mass making of fungus than his own personal inclinations would have done.

SBE rather than septic arthritis

Dawson ran a day clinic for chronic arthritic patients, people who normally who returned to their home and daily work afterwards.

About as low on the totem pole in status at a world famous research-oriented teaching hospital as one can go.

SBE, sub-acute bacterial endocarditis, is today seen as a dire medical emergency disease, likely to be fatal even with the best and extremely extensive treatment, and something managed by the top heart specialists and heart surgeons.

A disease near the top of the status world of big hospitals.

Not to be handled by the guy in the basement running a day clinic for little old ladies with badly bent fingers.

If it was an impossibly long stretch for Dawson to focus on SBE we must ask why he did not focus on septic arthritis instead.

This (surgically oriented) disease of dangerously infected joints was still a bit of a stretch for a day clinic director but it was a form of arthritis, his speciality after all, and like SBE it also a disease likely to prove fatal and one that would only be cured by penicillin.

Now, Dawson certainly did deal with septic arthritis cases in his wartime penicillin work but he didn't really focus on them.

As a result of his wondering off his own arthritis estate onto the faraway property of the SBE experts, Dawson greatly aroused a lot of anger from his colleagues.

He may have intended just that.

I have found no indication that the efforts by medical conservatives to use "war preparation" as an excuse to roll back Social Medicine ever evoked septic arthritis as a disease and patient type to be abandoned and left to die.

But that definitely turned out to be the case with SBE - I suspect Dawson saw this plan coming early on and for this reason, and this reason alone, he focused on the SBE patient rather than the septic arthritic patients....

No comments:

Post a Comment