Wednesday, August 4, 2010

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...

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