Monday, May 30, 2016

Lies, damned lies and peer-reviewed scientific articles

In a perfect world, elementary grade school kids could be set an series of simple arithmetic problems, based on the information contained within any number of peer-reviewed articles, published in highly reputable scientific journals, on the early wartime production of penicillin by penicillium fungus.

After all the basic arithmetic is dead simple, but unfortunately the  scientists were allowed to fudge the vital numbers , time and again, all to better flatter the humans nominally in charge of the penicilliums' production, the patients be damned.

Here is the start of one arithmetic question, again based solely on the information contained in most of those scientific publications, that one might set for a class of bright eyed grade six students :

The pioneering Meyer-Chaffe-Dawson-Hobby penicillin production effort have a nominal maximum capacity of 700 two litre flasks, each containing 13.5% penicillium medium by volume --- how much medium is that in cubic centimetres and in US gallons ?

(Fifty US gallons as it happens - by no coincidence, exactly the smallest possible amount to qualify the effort as pilot plant sized, rather than merely lab level sized.)

So it yields 50 US gallons or 190,000 cc of penicillin juice every two weeks..

The two weeks needed for each run is ten days devoted to production and four days devoted to initial seeding and post-op cleaning.

 Article readers would also know that at this time in the war, each cc of penicillin medium at the end of the run will contain, on average, about 2 units of penicillin biological activity.

So kiddies, if all the capacity is used and the penicillin survives without production mishaps, you will have 380,000 gross units of penicillin at hand after a typical two week batch run, yes ? Did every child get that answer?  Good !

Relative purity, not absolute efficiency, dominated early penicillin - but only absolute amounts of penicillin saves lives 

That means the whole effort will have yielded, in the gross, a single solitary tiny one quarter of a gram of pure penicillin in a huge 190 litres of water and other unwanted biological material.

Now the real hard work begins. A lot of expensive chemicals and a lot of expensive scientific labour will remove all of the water and some of the unwanted biological material, while also removing and or destroying some/most of the badly needed penicillin in the process.

Talk up the unimportant stuff

In the end, the chemists are sure to proudly announce in the article that they have a perfectly dry powdered solid penicillin with a relative purity level of 40 units per mg (or later on, 200 per mg or maybe even 1200 per mg).

Since a cc of mostly water is about 1000 mg or 1000 ml, getting even just 40 units of dry penicillin from one mg (one ml) instead of just 2 units from 1000 ml is a considerable achievement.

And the desperately waiting patients better hope the chemists weren't just jiving about their semi-purified being perfectly dry, because nothing destroys penicillin like being a little bit wet - it survives longest if either perfectly all dry or perfectly all wet.

Bury the Efficiency levels as too low to publish

But math teachers will quickly discover a problem when they seek to set a possible elementary level arithmetic question based around yield and efficiency.

Because nowhere ever will any of these articles ever tell readers just how many mgs of finished dry penicillin they got from say an initial start of 380,000 units of gross penicillin.

If the article had said it obtained, let us say 4750 mgs of dry penicillin at 40 units a mg, any bright school kid could work that out to be 190,000 units of dry penicillin --- and that from 380,000 units of wet penicillin that yields an efficiency level of 50%.

But the articles never do reveal the amount of finished penicillin in mgs and thus never have to reveal their efficiency.

I personally suspect the typical run final yields, in terms of clinical penicillin, were closer to 10% or even 0%.

Almost all of the precious life-saving stuff was destroyed by academic chemists doing their typical academic thing of trying to score really high purity figures (but no efficiency figures) to impress other academic chemists.

In the end, never giving their final yield in terms of numbers of mgs of solid penicillin was rather like asking their scientific readers (or my poor innocent elementary students) to complete this arithmetic question : 2651 divided by 17 over X equals what ?

Its fractions math, on LSD --played with a numerator but without a denominator. A joke - a disaster.

Leave it to an Irishman to do the job right, without working up a sweat

All this matters because an almost unknown scientist in Brisbane Australia regularly got yields of 100% ----- while doing almost nothing in the way of blood and sweat.

In fact he left all the production work to one elderly lab tech, E Pitcher.

This elderly man did all the work in this ultra efficient penicillin plant

This scientist, Dr Vincent Duhig, simply saw to it that the penicillin juice was 'harvested' at the point of maximum yield, instantly ran through a cheesecloth to remove any solids, quickly chilled it to preserve it and then slowly ran it into the veins of a dying patient through a slow IV drip a few scant hours later.

Duhig didn't even stop to determine the titration, in units, of his raw penicillin juice --- why bother, it was all that he had and he had a dying patient before him.

More and more and more was the only button he wanted pushed.

A consistent drip of sometimes as many as 3000 cc of penicillin juice per day (each cc having maybe 2, 4 0r maybe 8 units of penicillin within) into people with poor kidney function kept a constant if incredibly tiny amount of germ killing penicillin in their blood enough to let their body start the heavy lifting of fighting off their terminal infection.

Calling this 'heroic medicine' doesn't begin to describe it  --- today that same hospital in Brisbane would routinely use 10,000 times as much antibiotic power to achieve the same effect !

Ignoring Fleming & Florey and listening to Duhig would have saved thousands

Duhig made the point clear in his conclusions of his article : producing life-saving penicillin with minimal staff and money in a run of the mill general hospital was dead simple, if you just kept your eye on the patient first and kept the scientific wannabes at bay.

What he didn't say, but he could have, is after all that blood and sweat to produce dry penicillin, 100% free of water, the stuff is often totally useless.

Because penicillin so quickly leaves the body via the kidneys mostly unused, the dry stuff was often deliberately diluted all over again in a lot of water and run very very slowly into the veins of the patient to maximize the time the penicillin stayed in the blood, doing its job.

Duhig saw this necessity and simply cut out the middle man, cut out the hard work, expense and tremendous loss of the fragile penicillin -- and in doing so, saved many lives with a minimum amount of effort.

Duhig didn't work hard - he worked smart.

In 1943, Duhig the Irishman did what Fleming the Scot should have done 15 years earlier - started right into saving lives with the stuff.

Duhig used even less technology than even Fleming's team had (and they had very little) -- but he used his heart and his head instead.

The end result : a Nobel for the lazy Fleming and nothing for the doughy Duhig ---- ain't it always the way ......

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