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.

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.

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.

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....