Showing posts with label systemic. Show all posts
Showing posts with label systemic. Show all posts

Monday, July 21, 2014

Topical and local antiseptics versus life-saving antibiotics

When did 'the miracle of penicillin' , as opposed to just penicillin itself - really begin ?


If your life is in imminent danger from a massive bacterial infection your medical team may well use antibiotics topically (around the skin next to an opening in the skin) or locally (inside that opening).

But unless your doctors are criminally insane, they will not limit their use of antibiotics to these two methods.

Instead, their main weapon will be massive repeated doses of antibiotics given by needle (perhaps also by mouth).

Only by this method will the drug be able to travel quickly and thoroughly, via your bloodstream, to every single living cell in your body to engage any and all the offending bacteria all at once : a full-out , full-frontal attack.

So, to the public - and to all but pedantics in the medical world - giving 'antibiotics' without a qualifying adjective , really means the systemic (through the bloodstream to all the body) use of those drugs on human patients.

Penicillin had been occasionally used on patients for twelve years before that fateful October day in Manhattan - topically and locally with mixed results .

As well it had found use in hospital labs as a simple means to clear most regular oral bacteria from suspected samples of "flu" bacteria (sic).

But penicillin had never been used as an antibiotic (and nor had any other microbe-produced metabolite) in the common meaning of that word.

Not until Dr Martin Henry Dawson gave those first shots of hospital-grown penicillin to two young men dying of subacute bacterial endocarditis (the dreaded SBE) : October 16th 1940 , in Manhattan's CUMC (Columbia University Medical Centre) .

Thats when the miracle of penicillin truly began ....

Saturday, June 7, 2014

Aaron Alston , penicillin's first SBE patient but second to get the historical injection

The known published facts are few


All the contemporary (1945 era) newspaper and book accounts - written by (or coming second hand from) participant eyewitnesses to the events themselves - make it clear that Martin Henry Dawson's first SBE/penicillin patient was a "negro" "man".

And that his name was"Aaron Alston" and that he subsequently "died".

The available record of the amounts and dates that Aaron received Dawson's penicillin - as published by key Dawson team member Dr Gladys L Hobby in her 1985 book on penicillin , Penicillin : Meeting the Challenge , ceases near the end of January 1941.

And that is all the published accounts show.

But now for new research and reasoned suppositions...

We can say that 1940s medical statistics indicate that Alston was a more likely than not a young adult when he entered the hospital with SBE .

It is clear from the census that the names Aaron and Alston is a combination found in a fair number of men in America in the first half century of the 29th century.

However , the censuses generally indicates they are usually negro and that their residences seem centred in the South - from rural Carolina into urban black centres like Washington and Baltimore.

But in the critical 1940 census , there is no Aaron Alston recorded in New York City or in nearby New Jersey and Connecticut.

Now the first SBE patients that Dawson dealt with in the public wards of his upper Manhattan Columbia University Presbyterian Hospital were simply there because they were poor and his hospital happened to be close to where their family lived or close to where they lived when they took ill.

They were not drawn there from great distances because Dawson was then a famous and successful expert in this nearly 100% invariably fatal disease.

Far from it , he hadn't in fact handled any SBE cases up to then as the lead doctor.

Alston almost certainly had to be residing within a three or four miles circle of the Presbyterian hospital, at most , at the time he took ill. But the census does not show this.

He may have moved to New York City after April 1940 and before September 1940 : because southern blacks were still coming north to the unofficial American black capital of Harlem , though there was rarely gold for them at the end of its tattered rainbow.

Harlem is well within the catchment area for the Presbyterian's public wards.

We seemed to have failed to find out anything more about Mr Alston.

But as it happens, the New York City individual death records up to 1948 have been hand indexed on computer by many volunteers and made available via Ancestry.com.

They show an Aaron Alston , born about 1911 , (that is about age 29 on date of his admission to the hospital in September-October 1940) has having died on Jan 25th 1941 in Manhattan.

I am not sure that the original  death record will reveal more more - but perhaps a last address in New York and the name of next of kin and their home town , but I feel 100% certain this is our Mr Alston.

All we have really confirmed so far is that he was indeed a young man at time of his admission , as expected.

Why first patient but second to get the historic penicillin injection


Now while I am certain that Mr Alston was first SBE patient Dawson intended to treat with penicillin, I think he got it moments after Charles Aronson , the other SBE patient to get the historic penicillin injections on October 16th 1940.

Dawson's first major paper on penicillin and SBE was significantly the first penicillin paper not written by him with the help of the very reticent (as he himself was !) Dr Gladys Hobby, his lab chief.

Co-written instead with young Dr Thomas H Hunter, it positively gushes - for Dawson anyway - in giving forth the ages, initials of their name, gender, ethnicity,  dates of treatment, medical condition etc of all the SBE patients that Dawson had treated.

This was a style that Dawson had never shown before in 20 years of writing many, many medical articles.

Some doctors ("clinicians") simply tend to write articles that minutely detail the very 'grain' of  one (person's) case - while others ("researchers") prefer to report on the general conclusions drawn from treating one hundred similar cases.

(Both are valuable to doctors and scientists - but biographers won't be human if they didn't prefer the intimate details of the first type of articles !)

Dawson gets a chance in mid April 1944 to treat Charles Aronson a second time with penicillin for SBE .

This was because the little penicillin Charles had gotten in October 1940 had helped him survive his first bout of SBE.

He thus became that rare successful SBE case (about one in a hundred) that did so , back then.

Dawson indicates  in 1945 , that Charles had first entered the Presbyterian three and a half years earlier - ie mid October 1940 , confirming the common assumption that he was a very late addition to Dawson's Penicillin SBE program.

(Dawson knew he had too little penicillin to even treat Alston adequately, but he kind-heartedly treated both.

He was hoping perhaps that any small sign of a clinical response from either one of them might move Big Pharma to step up to the plate and mass produce the stuff --- for Aaron, Charlie and everyone else.)

Literally : the last shall be first 


But did Dawson really add Charlie at the last minute out of kind-heartedness alone ?

I believe the real reason was because Charlie was such a late addition to his ward's SBE patients.

When a new patient arrived with suspected SBE - a relatively slow killer, first a number of blood tests over a number of days must show the continued and not merely transitory presence of green strep in the blood stream to match all the other classic clinical signs of SBE,.

Then the ethical response is to immediately start treatment with the newest miracle drug , sulfa, and pray.

This is what happened to Aaron, who had been in the ward about a month when he first got his penicillin.

But because Charlie was such a late addition, there hadn't been time to start treatment with sulfa drugs .

So if Charles was treated with penicillin alone and did show a clinical improvement, Dawson's sulfa worshipping naysayers (and their lineup began around the block) could not say it was all due to their established sulfa , not his new penicillin.

(Remember that a lot of middle-aged doctors , the same age as Dawson , had first made their mark as early sulfa drug pioneers - any new miracle drug meant their acclaim was over. )

Behind the polite rancour of academic/scientific 'critiques' is often a lot of half-hidden ego and income concerns.

Dawson recalled, in his 1945 article , that the 1940 Charles was treated with penicillin on October 16 and 17th and then immediately (first) "started" on sulfa on October 22 and that he responded so well that he was released in December and was illness free for three plus years.

Ethically, Dawson would never have wasted half of his tiny amount of penicillin he intended for Aaron on Charles --- if he was already responding well to sulfa.

I think the reason it became so urgent to treat Aaron in mid-October (well in advance of the Dawson team's own original timetable for starting clinical trials) was because he had already been treated with sulfa and it had failed.

And maybe even made him extremely sick  because allergies to sulfa are common and serious.

But treating Aaron alone risked having any penicillin success disputed by the pro-sulfa lobby and this would only forestall drug company involvement - hurting Aaron as well as all others.

Hence Charlie not only getting treatment but getting treated ahead of Aaron , if only by moments.

Ask anyone : nothing starts off a (soon to be citation classic) medical article quite like an opening sentence like this one ---

"The first patient  ever treated with systemic penicillin had (then invariably fatal) SBE , but had not yet had time to start a sulfa treatment, however he responded so well to the penicillin that he has now been home fully recovered for over six months months."

In fact Dawson saw no clinical response at all between cases of endocarditis and penicillin for one and a half long years and he didn't save anyone with the disease purely on penicillin alone until two years later.

But Charles's recovery might have been helped by the morale uplifting affect of simply knowing that he was Patient One of a touted new Miracle drug .

I can only hope that my research efforts eventually help Aaron Alston's relatives to gain some comfort from his short life.

They will learn that he helped bring penicillin into this world and that while it didn't help him personally, it has directly and indirectly helped ten billion of us in the seventy five years since he first received it.....

Tuesday, December 18, 2012

Fleming's non-toxic antiseptic was useless (and was called penicillin)

Toxic - but effective - antiseptic
An extremely non-toxic ,wide-spectrum (for its time)  germ-killer that can be used as a huge-dose, long term, systemic (ie something we safely introduce into the bloodstream), is a very rare indeed.

And highly valuable, even priceless, whenever our body faces massive body-wide infections that can kill us.

By contrast, what Alexander Fleming claimed to offer between the Fall of 1928 and the Fall of 1942, was a slow acting, non-toxic, wide-spectrum antiseptic (externally applied) germ-killer that was in very short supply and very unstable.


Forget, for the moment, most of Fleming's 'claims'.

The main point his listeners would take away was that this was a non-toxic antiseptic and as such, not particularly valuable.

Non-toxic and yet not particularly valuable ??!!

Yes, even fairly toxic systemics can sometimes be useful.

And as for antiseptic use, even very toxic substances can still be totally useful.

This confusion comes about because even doctors are frequently far too loose as to what they actually mean when they say a drug is toxic.

Toxic usually means - when you dig into the subject - it kills  tender cells, in our interiors , and when delivered via the blood supply.

But toxic chemicals poured into body cavities and wounds without access to the internal blood supply (aka antiseptics) can end up doing very little damage in the overall scheme of things.

Even if they kill our body's cells at lower levels of the drug than the level needed to kill bacteria cells, they still can be useful : the wound at first might be a mess of already dead human cells acting as a food source for deadly bacteria.

Later after the bacteria are dead and the dead human cells are flushed away, the toxic antiseptic can be withdrawn before it starts killing new living human cells.

So antiseptics don't really need to be non-toxic, to be effective.

But they do need to be cheap, abundant, have long term stability and non-complicated storage requirements : everything that Fleming's offering (Penicillin) lacked.

Limited visions indeed : comparing penicillin to gramicidin


Something that Gramicidin, its chief rival from 1939 to 1943, did offer in spades. (Gramicidin was highly dangerous if taken internally but quite useful if poured into open wounds.)

But even the act of medically comparing penicillin to gramicidin , as many  medical researchers did in those years, gives us a rare insight into their personal 'war aims'.

They saw the many different sulfa drugs as essential for all forms of infections, internal and external, military and civilian : and so scarce resources must be diverted to their mass production.

But the fact that they only saw penicillin as an antiseptic , meant they saw its use limited to wound-type infections - ie mostly for military personnel and even there, only for trauma infections.

This limited estimation of the worth of penicillin contrasts vividly with penicillin's biggest booster, Henry Dawson.

Quite simply, he said in 1941 that he saw penicillin has having "unlimited possibilities" and that "the government" should mass produce it for all , rather than wait for Big Pharma to get its act together.

If Dawson saw it first and foremost as a systemic (and most deadly infections are systemic), Fleming had spent the last dozen years flatly telling all his face-to-face listeners that penicillin would never ever work as a systemic.

He said this beginning  in 1928 and he clung to this fatally incorrect "belief" until at least 1942 or 1943.

Yes, Alexander Fleming should be honoured as the father of penicillin, but he should also be condemned as the father who also trying his hardest to kill his own child for 15 years....

Friday, November 30, 2012

Would penicillin have been available for patients in 1930, if Fleming had produced his '29 paper - and then died ?

If only pneumonia had killed Alec, not John....
Imagine - if you will - that you're at a medical meeting - one of hundreds and hundreds that Alexander Fleming routinely attended between the Fall of 1928 and the Fall of 1942 and you happen to overhear Fleming regaling a small audience in the corridor about his 'wonderful' penicillin.


It is, he says (translated into today's medical terminology) a wide spectrum totally non-toxic anti-bacterial agent , the only one he as ever seen that doesn't harm the natural healing powers of the body's blood.

It is, Fleming says with great force , simply a great lab clearing agent for vaccine studies and potentially a useful antiseptic...

....And ? AND ?!  You wait for the other shoe to drop, somewhat impatiently : how is it as a systemic, for saving those dying from bacterial infections ?

Oh that, says Fleming indifferently , its useless for that.

And, he adds brutally honestly , as an antiseptic it is slow acting and is so unstable that it will only be useful if the chemists can synthesize it - but they haven't so far.

For fourteen years , I believe only one man stood between penicillin the potential life-saver for millions and penicillin the actual life saver for millions and that man was - unfortunately - Alexander Fleming.

The history of penicillin might have been quite different if only he and not his brother John had died of the pneumonia that Fleming's 1928 imperfect penicillin would have cured.

I can not believe that Fleming could offer such frequent public build-ups of his wonderful penicillin without someone in the audience venturing : well how do you rate its life-saving systemic qualities then ?

Fleming in his honest (but incorrect) way , would have had to say in public what he deliberately omitted from his published articles : 'as a systemic, I believe that penicillin is useless'.

This - more than anything someone else did or didn't do - dammed penicillin to wander useless in the desert for 15 years : its own discoverer damning it with the very faintest of praise ....

Thursday, November 29, 2012

Almost 15 years after Penicillin discovered, most of the world's serious penicillin cases had been treated by one doctor : Martin Henry Dawson

1943 Annual Report, Columbia University
In the Spring of 1943, Columbia University released its Annual Report and mentions , in passing, that Dr MH Dawson had supervised the treatment of 65 serious cases with penicillin for the National Research Council.

(Generally Columbia's lengthy wartime annual reports successfully managed to avoid talking about penicillin - a sure sign that it was ignored by academic science elsewhere as well throughout the war.)

If we can take "serious" to mean "treated systemically" , that probably means that the largest percentage of the world's systemic penicillin cases up to that point in time had been done by Dr Dawson alone !


(It is unclear whether or not the five endocarditis cases and the unknown number of other illnesses treated by Dawson with penicillin in 1940-1941 before the NRC got involved are among that total , but in any case it is an astounding figure.)

What we among the non-medical laity may still want to know is why was the world's best ever lifesaver ignored for so long by almost every other doctor in the world  ----  except by Dr Dawson ?

Why was his vision of the potential of hospital grown natural penicillin so different from their's ?

Has a cure for cancer already been found but no doctors recognize it ?


Was penicillin really a "Miracle" drug, a miracle instantly seen by all as is typical with Bible miracles - or was it more like the message to the three poor shepherd children at Fatima - a secret given only to those who retain a child's openness to new things ?

If almost all the world's doctors can ignore the open secret of penicillin right under their noses for 15 years way back then, would they recognize a cure for cancer if it appeared in the medical literature today ?


Thursday, September 13, 2012

If Alexander Fleming had to publish today : would systemic natural Penicillin have languished for 15 years ?

Worth more than GOLD
Most of today's biggest , most influential, most sought after scientific and medical journals demand that any article author(s) agree in advance to post all their notes and data (good and bad) online, before the journal will publish their concentrated (and usually upbeat) thesis in the article itself.

If this is done while the research project is ongoing, it is called "OPEN NOTEBOOK SCIENCE" , but some variant of it is increasing felt essential for fully credible research in highly contested areas of science. (And what area of science isn't ?)

So if Alexander Fleming's famous June 1929 article on penicillin was published today, he and his colleagues' note books would also have to have been online.

In Fleming's mind, he just had to leave in his private notebooks (aka : "massage the data") all the awkward evidence on penicillin's abject failure as a systemic.

He felt that revealing it would have diminished any serious attention being paid to penicillin's considerable - if more modest - possibilities as an antiseptic (if synthesized) and as an useful clearing agent when working with specimens of the 'flu' bacteria (sic).

Medicine's biggest ever boo-boo ?


This dismal "evidence" remained in his private notebooks and he never referred to them in his lifetime because (a) until 1943 he believed his original assumptions were still correct (b) after 1943 and until his death in 1955,  he lacked the guts to admitting he had made one of medicine's biggest ever boo-boos.

But if his notebooks had been nakedly exposed, some readers might have felt Fleming was right - his "in vitro" assumption against natural penicillin as a systemic lifesaver was fully correct.

 But some other readers might have asked, "why don't we get a definitive answer ; let's test the theory "in vivo" , in an actual patient (human or animal) ?"

Because if in 1929 some researchers had seen from Fleming's notebooks that he hadn't undertaken these vital "protection tests" and decided to make good this obvious shortfall, by 1930 penicillin might have been saving lives, not gathering dust in some British curio museum.....

Monday, September 10, 2012

Nova Scotian-born Dr Henry Dawson and the "Invention" of systemic - natural - penicillin


The "Invention" of systemic - natural - penicillin


Discovery vs Invention
Many substances were "discovered" many years (sometimes centuries) before they were (re) "invented" as having a highly useful medical effect.

It is only since Aug 1945 (and the ascendancy of Physics over Chemistry as the Queen of Science) that we have devoted all our adulation to "discovery" , rather than "invention" in medicine.

Carbolic acid and sulfa's both had early dates of discovery (versus their much later first medical use) .

Alexander Fleming is - wrongly - credited with discovering the penicillin we have used since 1940 - but what did he actually do ?

 Fleming in fact thought his penicillin would be useful as a sort of "Plan B" antiseptic -- and only if pure and synthetic.

Howard Florey - ten years later - thought his penicillin would be a useful "Plan B" back-up systemic to Sulfa -- but again, only if pure and synthetic.

By contrast, right from the start and until his death, Martin Henry Dawson thought that natural (even if impure) systemic penicillin would be the "Plan A" choice to cure the incurable, to save the unsavable --- starting with those dying of invariable fatal SBE.

Only two people in New York worked with penicillin in 1940, despite a war (with millions soon to be dying of infections) raging the world over.

 One doctor published a conventional article in JBC, reminding bacteriologists how useful crude penicillin could be as an agent to clear common throat bacteria from suspected specimens of influenza bacteria.

That was about all that penicillin was in (semi-) common use for, in 1940. Just as carbolic acid had its various non-clinical uses in the days before Lister "re-invented" it as a life-saver.

The other doctor, Dawson,  saw crude penicillin as the most likely cure for SBE.

NOT because it was a super-killer of bacteria, but for some less sexy but rather more "useful" characteristics: it combined nearly-limitless non-toxicity with an extraordinary diffusion ability.

He could thickly saturate the blood stream with penicillin without killing the patient, and hope some would still diffuse in past the thick vegetations (bio-films) of SBE, as that saturated blood rushed past the diseased heart valves at breakneck speed.

Some modern SBE patients have needed as much as a kilo of pure penicillin over many months - that's 1.67 BILLION units of penicillin - but have beaten the disease.

Still while penicillin - and only penicillin - could save an SBE in the 1940s, SBE was a prodigious user of then very scarce penicillin, so Dawson also had to morally kick start ("invent") an entire "natural penicillin" industry into existence, to deliver the amount of penicillin needed for his SBE patients.

(As a by-product, the rest of the world soon got as much penicillin as anyone could need - so much so it was soon feed to cattle as a growth stimulator, partly to absorb some of the production.)

I say his "invention" was by moral argument, because the scientific and commercial consensus then was that only synthetic (patentable) penicillin could do the trick.

But only when Dawson morally convinced the head of Pfizer, John l Smith, to take a very great financial risk and go against the consensus of his industry, did the miracle of penicillin really begin to happen....