Wednesday, June 30, 2010

Pneumococcal capsule,Hyaluronan,Penicillin like electron, proton and neutron to Dawson

I have said that Martin Henry Dawson's roughly 20 year career as a medical scientist can be divided into three parts based on three types of streptococcus bacteria: s pneumococcus, s pyogenes and s viridans.

Another way to look at the three phases is to look at the key substance he was studying in each phase and contrast how our body felt about each of them.

The pneumococcus flourish in the blood stream and in our liquid-oriented parts of our body by wearing a sugar-coated capsule around themselves, to evade the non-adaptive part of our immune system.

But humans also have an adaptive immune system and it can learn to recognize the sugar capsule and kill the bacteria inside it.

To survive, the pneumococcus have learned, in their own counter defense, to make a 100 different capsules (or to wear no capsule at all !). When this in turn doesn't work, they trade the various capsules around by HGT - horizontal gene transfer - the only reason we humans could begin play around with DNA.

So Dawson's pioneering work on DNA is obviously still hot stuff.

In terms of the body's immune system, these sugar capsules are highly anti-genic : the body sees them as the enemy and goes into warp overdrive to deal with them.

Dawson then flipped 180 degrees and dealt with the capsule of the deadly GAS bacteria - a bug that can still kill humans in dozens of different ways.

Their trick is to have a capsule made out of something only animals make - this chemical hyaluronan is used all through the animal body in dozens of quite different applications.

We humans now use it ,in medicine, for dozens of additional uses.

Our body regards it as 100% gen, ie  "us" - the very us-ness of us.

Sometimes however the body in attacking the bacteria inside the hyaluronan capsule, thinks the capsule is also somehow non-human and then goes off attacking parts of the human body that look just like it.

This is called 'molecular mimicry' and it lies behind auto immune diseases like Rheumatic Fever that Dawson works so hard to cure.

Because so many of the diseases we are likely to get today are considered to be auto immune diseases, this also remains hot stuff in the area of medicine and science.

Finally Dawson flipped yet again ,180 degrees ,to take up the cause of penicillin in 1940 when it interested no one.

It is, at best, an okay killer of bacteria - when just viewed in its killing aspects. From the viewpoint of working doctors or pharma executives in 1940, its killing disadvantages far outweighed its moderate killing abilities.

Dawson saw beyond this, to grasp the one thing about penicillin which remains unique about it even today when there have been thousands and thousands of antibiotics tested
for their usefulness in fighting disease.

Some individuals are allergic to penicillin - very very few seriously.

But broadly speaking only some of us are allergic to something , while if it is toxic, it is toxic to all of us.

Penicillin isn't toxic to us - at all . The salt it is wrapped around, chemically speaking, can be toxic if we don't watch our fluid levels, but that is about it.

Our body regards this small molecule as basically invisible - it does not regard it as gen ( part of itself) or antigen (part of a pathogen) nor  even as a potential food - it passes quickly through our body, our liver above all, as invisible and as harmless as water.

Most doctors - Alexander Fleming above all - only saw the fact that penicillin passed quickly through the body as its prime disadvantage.

But Dawson had devoted just 15 years to substances that hung about the body only too well and his mind was 'prepared'  (in the Pasteurique sense of that word) to see the advantages of any substance that our body regarded as neither genic or antigenic or as food.

Penicillin was the neutron of the human immune system and Dawson put that neutron to work......


Dawson had been set to be the "invisible man", the Charles Fletcher of The Manhattan Pilot

I believe that for two critical weeks at the very beginning of the The Manhattan Project, Martin Henry Dawson was not set to be the team leader/senior investigator - in fact he was not expected to be involved at all.

The team was supposed to be led by the biochemist Karl Meyer, with someone (anyone) acting as the microbiologist to test the 'in vitro' activity of the penicillin produced , again with some doctor (anyone) from Columbia Presbyterian's eye clinic in the clinician's job  (the nominal job of Dawson on the final Pilot team) .

The penicillin pilot's aim, at that point, was simply (!) to purify and then synthesize penicillin - most of the small amounts of crude penicillin produced would have to be destroyed in crystallization (purification) experiments.

Only tiny, tiny amounts could be spared to show the resulting penicillin still retained the needed biological activity against bacteria on a glass slide or against bacteria on/in a human.

These were expected to be merely subordinate activities to the main show - "making penicillin".

Now any drug, not just penicillin, needs to be first proven safe for humans when taking internally and be available in huge amounts, before it can be injected into the body as a 'systemic' --- versus simply being dropping a bit of it into the restricted/external area around the eyeball as an 'antiseptic'.

Penicillin, in particular, quickly slips out of the body and so needs even larger amounts than most drugs to work successfully as a systemic.

This is why penicillin's first successes in Britain during the 1930 (but tragically for humanity never published), were in removing deadly bacteria from the area around the eyes.

Meyer ,working in an eye clinic ,knew these truths better than most. In fact, he did involve two doctors from his clinic to use some of his penicillin with their patients but both doctors (Von Sallmann and Thygeson) seemed dubious about its usefulness around and in the eyes (as well they should have been).

 The results were not spectacular and were published a few years later.

Eyes were saved in the early 1930s from a lifetime of blindness with treatments of diluted crude penicillin that in total must have consisted of only 1.6 Oxford units of biological activity (that is equal to one millionth of a gram of pure penicillin).
By contrast, Dawson's disease of choice to test penicillin upon, SBE, subacute bacterial endocarditis, may today require 1.6 billion units of penicillin to cure.

That is one kilogram of pure penicillin - one billion times as much penicillin.

It was known in 1940 that SBE would need an extraordinary large amount of whatever drug that could kill the bacteria in its vegetations because of the unique location of the lesions and the poor blood supply of the heart valves they rested upon- that is the problem in fact that still makes SBE the 'gold standard' of intractable infections.

All drugs to date, as of 1940, had to be used in such large amounts to kill the bacteria that they killed the patient first - because even a relatively "non-toxic" drug is deadly if used by the shovelful !

It was Dawson's genius to see that penicillin's strength was not what the popular books on it still proclaim - its ability to kill bacteria - but rather its ability not to kill the patients, even when used in extraordinarily high amounts for months at a time.

And SBE proved to be just the disease to demonstrate that fact....


Tuesday, June 29, 2010

Agape Science: thinking commensally : going Po

I have often said my Martin Henry Dawson project is "all about love" - all three variants of it.

Eros, romantic love, might seem a stretch.

However Dawson had seen too many fellow teenagers die in the trenches of WWI, without ever even having had a kiss or a girlfriend ,to fail to understand what a diagonsis of Rheumatic Fever meant to kids, back in those days.

Doctors and friends told parents in total earnestness, that any extra stress on their child's heart after they had had Rheumatic Heart Disease could kill them.

That meant no dancing,  or sexual intercourse or pregnancies and childbirths - all the things that make a young person's life worth living !

Patria love or philia/filial love, love of one's own family and their country, was the reason why the 'greatest generation ever'  finally went off to fight.

But patriotism isn't that high on the scale of wrong or right, in the way Jesus reckons things.

He placed agape love, the willingness to die, if necessary, for someone else's country well above the willingness to die to save one's own country.

Here America fell down .

Twenty seven times, by my count, small groups of American citizens came before their congressmen to plea for Congress to intervene militarily when their ( or the family's) homeland was invaded.

Peter only refused 3 times - American did it it 27 times between 1931 and 1941.

(Not that my country - Canada - was all that much better.)

One wonders if Japan had gone into Russia instead of Pearl Harbour would America had gone to war at all in World War Two ?

Even on December 8th 1941, FDR and Congress only went to war against Japan - it took Hitler declaring war on America to bring it out fighting against the greatest evil our world has ever known.

Dawson had already taken up arms years earlier to defend a little country from a bully and been wounded twice for his efforts and gotten the Military Cross with citation for his bravery.

But in this war, he was dying and unfit for military service overseas.

Still he exhibited agape love and agape science when he sought to save the lives of people America's leaders in science and medicine said were unworthy of much medical attention in times of war....


"Going Po" /"Going Native"/"Letting Down the Side"

I have often wondered about why Martin Henry Dawson's legacy was so quickly - and quietly - 'disappeared' after his early death.

I mean Penicillin was very big news, Rheumatic Heart Disease remained the leading killer and crippler of school age kids (well above the numbers affected by polio), DNA was becoming big news.

I think one explanation was that many of his contemporary fellow doctors and scientists felt that he had 'let down the side' or 'gone native' when he 'went Po' and tried so hard to save the lives of people that many of them considered unworthy of much medical attention at the height of Total War.

I think Dawson would argue - but only if he was forced to argue, with a gun at his head ! - that the whole point of that Total War, the whole point of the quarrel with our Japanese and German cousins, really revolved around the question 'were all lives worth saving, or only some ?'

He was sure which side the Axis was on, he thought that the Allies were on the other.

Publicly, they were - they just didn't mean to see it carried out in practise.

When Dawson did so, he exposed their inconsistencies : talk versus walk.

No one ever honors someone who reveals them to be hypocrites.....


What a difference one little substitute word can make...

My partner Rebecca said some very nice things about this, my new blog.

But I am afraid I misled her a little in describing my take on Postmodernity.

I meant to say that Modernity was a particular and peculiar form of  'Aesthetics masquerading as Science' ---- and functioning as an entire worldview and ideology.

And that Postmodernity was more than 'just' the aesthetics of contemporary painting, pop music and architecture - it was another particular form of Aesthetics and also functioning as an entire worldview and ideology.

I think I have now found a succinct way to describe the difference between Modernity and Postmodernity and it is in the new subtitle of this blog .

Taking the widest view of the term Postmodernity : converting it - but only very slightly -  from my emphasis on ethics and morality to one of aesthetics - it can be phrased as a difference in  the sort of people we find aesthetically attractive.

Today we are far more willing to see attractiveness in many more body shapes,  skin colors and lifestyles - or at least to let other people see beauty in people we don't find  that particularly attractive.

It is typical of this Postmodernity era to learn of a recent poll saying that most of us find a person of mixed color ( the tawny or coffee colored flesh tone so common in places like Brazil) as the most attractive physical type.

(Just as it is a hangover from our grandparents' Modernity era to learn that most high fashion models continue to be the icy blue-eyed blonds of  1930s Aryan wet dreams.)

My take is that between 1939 and 1945 (and in the immediate postwar period), many - but by no means all - of the middle class educated people in the most modern countries in the world changed their minds.

They decided, albeit in a subdued and inchoate fashion, that  all  life was in some sense
worthy of life and dignity and worth.

When they repudiated Eugenics (and again not everybody did) they repudiated the core tenets of Modernity --- just as Professors Adorno and Horkheimer had insisted they had to do in 1944, in their famous little mimeo-book ( Dialetic of the Enlightenment), circulating throughout the campus of Columbia University in New York City.

Currently, there is no record of what Professor Martin Henry Dawson, also at the same university at the same time, thought about Adorno and Horkheimer's claim - or in fact about virtually anything - we have no personal papers.

But in his public 'biography of deeds', he certainly acted in a postmodern fashion - giving up his life to save the life of someone (Charlie Aronson) who many American doctors considered a prime example of the fact that only 'some life is worthy of life'.

In one of those improbable coincidences that make up reality,Dr Foster Kennedy advocated that only some lives are worthy of life and that all others should be killed (at the annual meeting of the American Psychiatric Association) on the same day as Dawson first announced (at the annual meeting of the American Clinical Society) that he was trying to save the lives of the unfit, with some penicillin he had brewed up himself.

In a sense, to Kennedy's statement, Dawson merely substituted the little word "all" for "some" and then forcibly acted upon that statement, against the greatest of obstacles.

Mo only truly goes Po when somebody actually does something concrete.

 And it was Martin Henry Dawson putting PoMo thought into PoMo action that made all the difference - for Charlie and then ultimately, for all of us .....


Sunday, June 27, 2010

Martin Henry Dawson, the born subordinate.

He had a number of life-changing ideas but he was too cautious and too polite to go all out in proclaiming them and his colleagues and opponents knew it.

In a metaphorical sense, he was the proverbial 'coward of the county' .

I don't think he disobeyed but one order in his entire life.

But when he did.... our whole world changed for the better, forever.


Friday, June 25, 2010

We agree WHEN Mo started going PO, but not necessarily why

                  Martin Henry Dawson , on enlistment, 1915

My partner, Rebecca, has tried to explain the meaning behind the title of my latest blog "MO goes PO" .

All I can add is that there is overwhelming agreement that the Mo-to-Po revolution began fairly abruptly, in 1945.

You remember 1945, the end of 'double-u, double-u, two' , the so called last good war and the last good generation.

Few people have given a good account why PoMo began then, AND in the nations of the moral victors.

If the good guys are just won the war against the bad guys, why were the good guys leading the way in uneasily evaluating their own values ?

I hope "MO goes PO" succeeds in telling us why....


Thursday, June 24, 2010

This is my new blog for my MARTIN HENRY DAWSON project

I will post the finished segments ( albeit not likely in their proper chronological sequence) here, one week after the 'final' version of each segment has had a chance to pass my 'wiggle test'.

That is to say, I will print out a reduced size, B&W 'final version' copy on my computer printer and see how it reads on paper, after it has been lying around my house a day or two.

For sometimes you catch things you didn't when the segment was on the computer screen, no matter how often you re-read and re-edited it.

In time, I will also put each of these segments in my 'MO goes PO'  public archives - my 16 GOOGLE SITES websites.

But this time, they will be in their intended chronological order, leaving blanks for the segments not yet published.

One GOOGLE SITES website for each of 15 Scenes (in three Acts)  --- plus one for the author's Afterword.

No more than 26 segments maximum per Scene - hopefully not that many ! - so I can label them from A to Z.

So their numbering will be labelled 3c and 16j etc , indicating that the first is the third segment of Act I, Scene 3, while the other is the tenth segment in the author's Afterword.

Think of it as a sort of Play or Musical covering six years (exactly - September 2nd 1939 to September 2 1945) in three hours...

I will reserve my right totally, to revise/ revise/ revise each 'final' segment - but you will at least be able to follow the revisions publicly.


Monday, June 7, 2010

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 ....


Martin Henry Dawson's lifework- Lobar Pneumonia,Rheumatic Fever,SBE : when hosts overreact


When harmless tiny bacteria called S. pneumococcus living peacefully in your throat get blown the equivalent of 1000 miles deep into our lungs - they panic.

Who won't?

More fatally, so does our body's immune system.

Like a latter day 'Bomber Harris', the immune system 'area bombs' our lungs - too often the collateral damage is us.

S. pyrogenes bacteria is so used to surviving in us, its only home on Earth, that it begins to look like us - and when our immune system overreacts to a case of strep throat, it might start attacking our heart tissue instead of the long since defeated strep throat : the result is often- fatal acute Rheumatic fever.

Lucky you, you've survived a couple of attacks of Rheumatic fever - except for a scared
heart valve ---- a valve messed up by your own immune system.

Now you've neglected your teeth and gums a little and the gums tend to bleed when you do brush them.

This allows some harmless S. viridans (green strep - the bacteria that makes unbrushed teeth look ,well, sort of green - not actually the reason they are called green strep but a colorful coincidence !) to get into the blood stream and start whirling around your body much faster than the Space Shuttle does with us.

Naturally the green strep panic and start looking for a new safe home before giant white blood cells swallow them for dinner.

All these bacteria can't move - they are basically tiny blogs of jelly who can stick to particular types of human cells, if they have the right kind of adhesive on their surface for that kind of cell and they happen to bump into it and not the wrong sort of cell.

Its all a lot of hapstance.

Hardly your usual predators, right??

Usually, the green strep gets eaten before it makes that safe haven. But for people with scared heart valves, the scar tissue (produced by our immune system - remember ?) is
just the sort of thing that could be that safe haven.

If they make it into these scar areas' depths, while whirling past at space-travel-like speeds, they attach themselves to the scars.

The immune system reacts by creating more scar tissue, which inadvertently prevents white blood cells from getting in and at the green strep.

The green strep start re-creating dental plaque (and tartar) right on the heart valve - taking a biofilm meant for our mouth and teeth and replicating in not too dissimilar circumstances at the heart valve.

A normal biofilm colony eventually lets loose bits of itself in the liquid swirling over it to form mini colonies elsewhere - the green strep on the heart valve do the same.

We call those particular mini colonies 'embolus showers' and if and when they reach a heart/ lung or brain blood vessel with a restricted passage, they will block it and kill us.

Explaining and preventing or curing these three serious/common/fatal diseases was to be Martin Henry Dawson's lifework.

In a sense, he succeeded well beyond his expectations and changed our world , for the better, for ever.

All three dieases are the unexpected side effects of us and our fellow commensals scrambling to adjust to a micro change in our body's environment.

Just as global warming today is making all of the world's commensals scramble to adjust to a macro change in our environment.....


Sunday, June 6, 2010

Martin Henry Dawson - the Commensal Doctor

Martin Henry Dawson 1896-1945

S. Pyrogenes/GAS Strep/Hemolytic Strep - whatever you call it, this bacteria is usually regarded as the single deadliest pathogen we humans face over our lifetime.

This is because the list of fatal diseases it is implicated in runs into pages and can involve almost every part of the body,in any age group , in any part of the world.

Paradoxically, S. pyrogenes is only found in humans - it exists no where else - and usually lives peacefully - more or less - in our throats, as it has for millions of years.

It hoes a narrow row - but it hoes it deep and long - it can outwit anything our body or our mind's invention can put up to remove it, as it struggles to get by.

Martin Henry Dawson spent 20 years (all of his tragically short life as a scientific researcher) also hoeing a narrow row, deep and long.

He tried always to remain focussed on one area: the consequences for both of us, human and oral strep, of co-sharing one body so intimately all of our collective life.

A rarity in his day, he tried ,as a medical scientist, to see our body from its bacterial flora's point of view: to study how they wiggled and twirled -genetically- as they struggled to survive in our body's hostile environment.

Some bacteria is only 175 billionths of a metre "tall" - that means the body of an adult male is exactly as big to them as our Earth is to us - they aren't in any way aware they are 'invading' a body - they see us only as a vast hostile & lush world.

Early humans also didn't know they lived in a tiny part of a big sphere of rock that in turn only made up a tiny part of the entire universe - they saw no further than area immediately around them.

It is always worth recalling that we are actually 90% them and 10% us, if you count the number of bacterial cells on us, versus all the cells of our internal organs.

Without any of us, they would quickly die in hours - without them, we would die in a few months.

We must co-exist together, diners at a common table - commensals as a biologist or theologian would say.

Dawson never used that term as far as I know ( he died, after all, in 1945, before the word came into common use in medical or religious circles), but he lived his life as if it was the central core of his being as a scientist.....