WWII : Constructionists vs Commensalists

Reductionism, still the philosophy of today's Popular Science, has admittedly had a lot of glass-half-filled success in the last few centuries.

It has totally succeeded in burrowing down below the surface of reality to the tiny objects at the base of all energy and matter ; reducing big macro objects that we can directly see and touch down to zillions of incredibly tiny objects we can only assume exists by way of indirect evidence.

But while Reductionism can explain how these tiny objects interact, more or less, it has totally failed to fulfill the real purpose behind all of its efforts : to construct new , better-built, versions of macro reality based on what we have learned about the tiny building blocks that make it up.

It turns out, to use today's Net jargon, that the so called laws of physics do not actually 'scale up' ( or 'scale down') all that well.

What we know about tiny quarks does not help us at all to account for the unexpected behavior of slightly bigger objects like the atoms in various phases of condensed matter, such as in solids and liquids for example.

To use a life-sized example of another scientific failure to scale up, this one from WWII logistics, we need only to look at the total failure of the German fuel truck on the Russian Front, after doing so well in Poland and France.

A sturdy army truck like the famous American deuce and a half can go pretty well everywhere a railway can't and so is the best means to get fuel to a fast moving invading armoured army.

But it burns a whole lot of fuel itself to get its few tons of fuel to the front.

But over distances of about one hundred miles from end of rail, it still is the best single way to get fuel to tracked armoured vehicles well out ahead of the slower ,wider, line of rail-supported advance.

But move the distance required to be travelled up to 800 miles out (and remember 800 more miles back in to get more tank and truck fuel) and the truck is a flop and a disaster.

Any truck trying to move up behind an aggressively invading armoured army that has been fighting an equally determined enemy , one who leaves nothing but scorched earth behind, is sure to be travelling over miles of badly damaged, badly overcrowded, muddy or dusty potholed roads and bridges.

The truck's gas and oil consumption soars as its miles per hour slows to a crawl. It can expect major damages from bad roads at least a few times on its 800 mile trek out and back - requiring the services of equally gas-guzzling repair vehicles.

Effectively, the truck is soon consuming more petro products on its two way trek than it can deliver to the tanks. (Remember, it must haul all of its own fuel and oil on itself, for the trip out and back, leaving ever less room for tank fuel.)

This wouldn't happen in peacetime, where the roads between Berlin and Moscow would be in excellent, fuel efficient, shape and where fuel and oil can be picked up at filling stations on route as required.

Once the cargo was delivered to Moscow, a return cargo is picked up to take back, to cover costs.

But war trucks 'dead-head' back, unless they can be used to safely carry lightly wounded men back to rear base hospitals.

Hitler's gambit to take over the world failed in 1941 when his physics of truck transport failed to 'scale up' to the world of real life.

Similarly the fact that chemistry had constructed totally new molecules of dyes and plastics out of little atoms didn't mean human chemists could construct molecules of penicillin just because the fungi could do so naturally.

Penicillin's formula was not the formula for nylon, 'scaled up'.

In biology, the ham-fisted efforts of human-sized geneticists to construct genes they wanted by massive doses of x-rays failed to work as well as the elegant way the tiny bacteria transformed each other with tiny but efficient HGT (horizontal gene transfers).

I am not dismissing the value of human railways and human chemical plants nor do I expect to see skyscrapers made by bacteria : I just insist along with (Martin) Henry Dawson, that there is a niche for everyone and we all are best at activities scaled to our own size and niche.

Reality can not be reduced to tenured human particle physicists at the top and quarks at the bottom (Reality reduced to Professors and Plasma),  with all of the rest of the stuff in between just useless feeders, not wanted on the voyage, yesterday's booster stages, enroute in Man's journey to the stars.....

Spores and Wartime Secrecy : can they actually co-exist ?

You might think I am going to talk about Anthrax spores and asymmetrical terrorist germ warfare.

But you are wrong, wrong, wrong.

I want to talk instead about wartime penicillin, and a part of it that is never ever discussed.

Its inherently asymmetrical medical nature.

Which appropriately enough, then  "drifts over" into its inherently asymmetrical military potential.

So lets start.

And lets start talking about just how the intellectually mis-guided (as well as seriously morally misguided) were the prolonged attempts by the medical establishment in both America and Britain to regard penicillium spores as something  that really could remain Top Secret medical military weapons.

And not just the wartime medical establishment, for recently author Eric Lax and his publishers felt they had a real winner in an exciting clock and dagger title for their book on wartime penicillin : "The Mould in Doctor Florey's Coat".

There was always something faintly Walter Mittyesque about Florey anyway - never more so than in the incident that gave this book its title.

Dunkirk was underway just as Florey at long last accepted that ole Flem's penicillin just might be priceless after all.

But how to save penicillin for the rest of the Allied cause, if Britain fell to the Germans ?

'Let's all rub penicillium spores in the inner seams of our clothing - so even if only one of us gets away, the precious fire of penicillin research can still be re-lit elsewhere'.

But none of these Oxford naifs seemed to have dared ask the boss (Florey) just how they came to possess these incredible spores in the first place.

Henry Dawson's first big scientific effort was in promoting the concept of HGT (Horizontal Gene Transfer) ,the instant transfer of genes between different species and even different families of Life, when its initial discoverer seemed reluctant to even publish his work.

Today it is believed that soil bacteria created the first beta lactam antibiotics about ten million years ago and  - via HGT - gave it to soil molds who modified it slightly and made it penicillin.

So, sometime in 1928, a particularly productive penicillin producer strain of penicillium mold blow into a fancy home in London.

Alexander Fleming's colleague John Freeman was an expert on allergies,  with many rich and powerful patients.

In 1928, Freeman heard a Dutch specialist claim that basement mold spores were the cause of many allergies.

 Freeman got his rich London patients (or more likely their scullery maids) to scrape molds off their basement walls to be tested by his most recent hire, Irish-born mycologist Charles La Touche, towards seeking  ways to gradually desensitize the patients against their particular household mold allergens.

La Touche had no high tech ways to keep spores inside his lab alone - not that I think in the long run a spore or two doesn't get out of the most secure modern facility.

There are many more fungus than us and they have and will be on the Earth a lot longer than us primarily because of their spores.

Their spores are incredibly tiny examples of temporarily suspended Life - Dried-up Life - inside a very hardy and bumpy package.

Tiny is the key here - so tiny they float anywhere and everywhere on the gentlest of breezes - down the hall and around the world.

Being bumpy but tiny and light doesn't hurt either - they can cling to almost any surface - like a human and its luggage bound for Australia, for example.

However if that surface is the tiniest bit damp and the tiniest bit tasty (they seem willing to eat almost anything faintly organic), they spring back into active slimey life.

One of La Touche's spores drifted out of his room and along the stairs to Fleming open Petri dish.

The rest actually wouldn't have been "legend", if Fleming hadn't promptly taken a sub culture of the resulting "spoiled" petri dish, and carefully and correctly preserved it.

Fleming did little to promote the medical use of penicillin in curing disease but he did vigerously promote it as a useful way for busy hospital labs to easily isolate the so called flu bacteria (sic) .

Dozens of labs world wide got a sample from him - they then gave samples of their samples to at least dozens of others.

That is how Florey got his penicillium spores he was so busy stuffing down his coat - from a sub culture Fleming had sent to the previous director of Florey's Dunn Institute.

The Free World beyond Britain had lots of  sub cultures of penicillium spores of the rare - right - type, even without Florey's belated act of charity.

In theory they didn't really need Fleming's spores, only his public article - but in practise, until 1943, they really did need his spores.

Examples of Fleming's spores were actually everywhere - some even better penicillium producers than his original un-mutated version as well.

But they could only be found by teams of researchers seeking hundreds of the right looking blue-green mold on walls and spoiled fruit, and then testing all for their possible anti-bacterial qualities.

Until miracle cures got rumoured about, no one in the world was willing to go to that much effort , just to test a troublesome possible antiseptic.

But by 1943, the miracle cure stories were out amongst the clinical doctors everywhere - and I do really mean everywhere.

Everywhere that Florey went, Egypt, Iran, Russia he had to endure local doctors thrusting excellent producing strains of penicillin molds in his face that they had found locally !

The Axis were just as quick off the mark - Japan got its strain by merely looking about locally.

And the clever Japanese correctly guessed - from one badly reproduced photo in an Egyptian picture magazine - just how best to produce the stuff !

The atomic bomb was effectively secret even if the US had proclaimed it was making one from the rooftops in 1942.

Uranium was everywhere - like penicillium spores - but a bomb from it takes the world's largest, most expensive, building ever built merely to get started on separating pure U-235 from the more abundant U-238.

And without 90% pure U-235,  no working bomb. No nothing.

Tons and tons of scarce money, time and effort kept the A-Bomb an American secret, even from the British and Canadians , let alone the Axis and Neutrals.

But by late 1943, popular magazine articles cheekily showed how one could make penicillin at home, on a kitchen top, for about $5 in equipment and growth mediums.

One didn't even need to go out searching for those semi-rare penicillin-producing strains by then.

In a surprising - even shocking - total volt face, the NRRL's Coghill and Raper had released the top two strains of penicillium.

 That's right, the top two strains that were then producing most of the Allies' military-bound penicillin - to the public American mold type collection in Washington where, as they told the readers of  JAMA worldwide, "anyone" can get some at a "nominal charge".

!!!!!!!!

Didn't they know there was a war on ?

No word if Argentina's Washington DC based scientific attache quickly took a cab over, got some samples and sent them off to his friends in Germany.

Clearly, penicillin was never a viable secret military medical weapon - Florey and Richards were both , to put it kindly, completely deluded to ever think so.

Deluded by utopian visions of near-total purity.

Because unlike the Atomic Bomb and U-235, penicillin's starting material (the spores) were both common worldwide AND its production fully successful even in a highly impure (aka low tech) state.

This was what Fleming had discovered in 1928 but never acted upon - this was the key insight that Henry Dawson brought to the penicillin story, starting on October 16th 1940....

HIGH MODERNITY's technology versus its science...

    By 1900, as Vaclav Smil reminds us ,most of the technology (machines, 'things' in David Edgerton's sense of that word) around us today had been invented and was in active use: as well as being further commercially developed and technically improved.
   They are still in use, still under constant commercial development and steady technological improvement.
   They are the fruits of the generation of The Children of High Modernity.

   While those children and their children were excited by the technology of High Modernity, my generation, the grandchildren of those Children of High Modernity, tend to ignore them and take them as commonplace.
    But what does excite us, at least the science-minded among my generation, is the science of High Modernity.
   A bit late - yes - about 100 years late, but better late than never.
   And remember, if we grandchildren ignore the technology of High Modernity, it can be equally charged that The Children of High Modernity and their kids, ignored the science of that era.
   Quantum physics and all its implications, bacterial Horizontal Gene Transfer and all its implications --- the most ground-breaking science of that era, was nominally published in the scientific literature and then studiously ignored in popular/applied science.
   Only now, in the post-High Modernity Era, The Era of Global Commensality, are we giving them their due.
   Well some Children of High Modernity did give them their due - their full due - in their scientific and in their social dimensions.
   I am writing an account of one such exception to the rule : Dr Martin Henry Dawson.
   Less curious about what he did - though he certainly changed our whole world for the better, forever - than seeking to find out why he did it.
   Why ever did this archetype of The Meek decide to take on the whole world - and then, unexpectedly, win?

ME? An AUTHOR ?! God, I hope not ....

Michael Marshall

As old Sam Johnson once opined long ago, has any author ever authored ---- except for money , for fame, for fortune ?

I suppose ---- a few.

No names spring to mind immediately, though.

I am certainly no 'author' .

How dare you ?

Some have tried to smeared my name .

Called me a pamphleteer.

 I picked up their smears and spread them more generously over my whole body : I am a pamphleteer and I am quite proud of it.

Has any pamphleteer ever pamphleteered, except for passion ?

Maybe, some, can't say I can think of any.

Profit and pamphleteering just don't seem to go together , not in the way that pamphleteering and passion do.

My blog posts are in the PUBLIC DOMAIN , and are designed to be globally commensal.

Like HGT (Horizontal Gene Transfers) I hope they cross fertilize intellectual discussions around dinner tables, the world over.

So if I blog with what seems excess passion, do not expect me to apologize (at least not very often !).

In this century's war of words and deeds between the old and the new science, real worlds are at risk : I believe there can be no neutrals in this war over Life.

Which side are you on ?

I know I have picked mine.....

Recombinant DNA and HGT's contribution to the penicillin saga

Where does one begin?

The beta-lactam molecular 'core' was originally created by bacteria and was only later was moved by HGT/ recombinant DNA into some fungi .

Those fungi then created the penicillin-variants of that very special fused beta-lactam ring .

But while this HGT operation was obviously fundamental to there being a penicillin saga to begin with, it had little direct impact on how the 1929-1944 penicillin saga actually unfolded.

But the four years of hard work and disappointments that Martin Henry Dawson endured between the Fall of 1926 and the Fall of 1930  working on HGT and recombinant DNA exchanges did make him the best qualified researcher in the world to put up with the temperamental penicillium between the Fall of 1940 and the Fall of 1944.

 His pioneering work with R to S type  (and S to S type) HGT exchanges between Strep pneumococcus bacteria made him eminently qualified to stand up to all the difficulties in growing penicillium to produce penicillin.

Dawson was the first in the world, together with Richard Sia, to successfully induce R to S pneumococcus HGT DNA exchanges in a test tube after most other researchers threw up their hands in despair and moved onto other research.

But he was no quitter and he pulled it off after years of failure.

Dawson then went on, with Agnes Warbasse, to do the same with S to S HGT DNA exchanges and this remains extremely difficult to do naturally, as Dawson did it.

He then went on to successfully grow colonies of M and L types of bacteria, all part of his effort over the roughly 15 years between 1926 and 1941 to establish that R,M,L were fully co-equal equivalents or alternatives to S types of bacteria - not defective or deficient versions of it.

This postmodernist notion naturally was seen as bizarre or worse in the strongly modernist atmosphere of medical research between the wars.

I see it as the bacterial equivalent of Dawson treating 4F civilians as the exact moral equivalent of 1A soldiers, not as defective 'useless mouth' variants,  despite the reign of Total War Utilitarianism ruling western medicine between 1940 and 1945.

Dawson's pioneering HGT DNA/ Q-sensing work taught him ethics and it taught him technical skills - both which he called upon to get penicillin successfully launched......

Three classic examples of HGT are a key motif in lifework of Martin Henry Dawson

Martin Henry Dawson 1942 - suffering from terminal Myastenia Gravis

From the 1920s till the 1950s, Martin Henry Dawson published more articles and made more public presentations on Horizontal Gene Transfer (HGT) than any other scientist - in fact more than all of them combined -- quite simply 'No Dawson, No DNA'.

But he died, tragically young, in 1945, though not before seeing through three different projects that involved HGT - though he was probably only convinced that HGT was involved in the first.

Not to say he didn't have strong personal suspicions in the other two cases - but it seemed too wild to be prudent to talk about publicly.

S. pneumoniae are detected and eaten by our adaptive immune system based on the the more than 90 different goo capsules that surround each of the 90 different strains of s. pneumoniae bacteria.

One way to survive being eaten is to quickly and randomly change your 'cap' - or not wear one at all.

Dawson with Sia and Warbasse, between 1928 - 1933, showed this to be done by biofilm colonies (it can only happen in close-quartered biofilm colonies, not in widespread thin populations of planktonic bacteria) by the bacteria taking a vote by exchanging chemical emails (Quorum-sensing/ aka Q-sensing) and then agreeing to exchange the DNA genes needed to change capsules.

By 1934, Dawson had become interested in the capsules of s. pyrogenes, mostly because they were NOT of interest to our adaptive immune system !

He discovered this is because they were made up of something the human body needs to use like wampum - Hyaluronan - the same stuff injected into wrinkles to restore their cosmetic youthfulness !

Our immune cells see this stuff in use everywhere in the body in dozens of different situations - it screams "self" like nothing else - so they leave it alone.

But only 6 species of bacteria make this goo - it is an energy intensive process and if it didn't get used to protect our commensal bacteria from attack of the white blood cells whenever they venture into the blood stream, it would only become a fatal burden to make.

Evidence is strong that these few bacteria borrowed the basic technique & the genes to make it from some animal host a long time ago (HGT between animals and bacteria does occur) and adapted it to suit themselves.

Since the s. pyrogenes are our single deadliest killer bacteria and this capsule a crucial means for them being able to do their work inside us and survive, this shows again what HGT means to us, in highly practical terms - it can kill us.

Finally, Dawson successfully cured the deadliest common heart disease of his day - SBE, endocarditis caused by green strep , s. viridans - normally harmless long term residents of our mouth.

He did so, starting 70 years ago this October 16th, with penicillin.

Penicillin is merely the best known of a very large family of antibiotics that still are our major life-savers - the beta lactams.

Most are made by bacteria and effectively force other bacteria to give the producers a wide berth.

Because only a few fungi make beta lactams compared to many bacteria, because the fungi's penicillin gene cluster looks to be so close to all the bacteria beta lactam creating structures, and because bacteria were here well before fungi, most experts feel that HGT was the means for the penicillin-making genes going from bacteria to fungi and then into us as an life-saving medicine.

But bacteria are mostly resistant to penicillin you say.

HGT again - the cluster of genes of resistance to penicillin existed long before Dawson put penicillin to work as an antibiotic in 1940.

When it became needed for bacteria to survive, they rapidly spreading it about around the world - by HGT ....

@arcadianrecord

Top-Down Genetics versus Mashup Genetics

'Must confess.

We never did like the term 'Horizontal Gene Transfer' , aka HGT ( sometimes otherwise known as LGT ,for Lateral Gene

Transfer).

In particular we always hated that 'transfer' bit.

The denotation is accurate enough, but its connotations conjure up entirely the wrong impression.

We'd bow in the direction of Dawson and call it HGT , Horizontal Gene Transformation.

For in fact the incoming bits of DNA disrupt - creatively - the existing fat and comfortable set of genes in the organism being invaded and the end result isn't some tidy orderly transfer of assets from one bank account to another, but more in the order of a micro-scale catastrophe.

There said it.

Catastrophe, cat-as-tro-phe - not neo-catastrophism, because we don't think it ever really went away - not out there in the real world and not out there in the real minds of many.

Only scientists and their fellow travelers consigned the word to a sudden death.

They said catastrophes rarely happen and when they do they are only local and short term - and soon we will be able to predict and prevent even these rare local events.

Catastrophes at the level of cells and microbes simply never happened.

But they do - we multi-celled creatures are the result of one such genetic mashup - when one sort of bacteria survived inside another type of bacteria to the point where it became part of the bacteria, inside its own cell walls and created the first multi-celled being .

Nine months later,more or less, you and us emerged.

There is no intellectual crime lower than seeking support for some or other human theory by claiming it merely reflects the laws of nature.

But...

But it is interesting to tease out the parallels for human creativity in the current moves to mashup old boring top down controlled copyrights to see what crawls out of the shell and the tremendous effects HGT has had in the past in mashing up stale boring old top down Vertical genetics to see what happens.

Penicillin , after all, was the result when a bacteria and a yeast decided to mashup their quite different DNAs....