Imagine the Nobel prize winner for medicine , Baron Howard Florey, being pulled off his efforts to discover new antibiotics in the late 1940s by an impatient Leo Fender.
Leo pleads, "Howard,make me a wah pedal, and make it quick ; I need something unique for my new guitar and amp line".
Howard takes his time, and delivers the pedal years late. But it is beautiful finished and has a high fidelity electronic circuit that is so pure that it delivers vanishingly small amounts of harmonic distortion (albeit at the cost of an anemic output).
I can already hear guitar players going "Oh, goody !"
Luckily for humanity, Leo has also telepathed the spirit of penicillin pioneer Henry Dawson back to earth and given him the same assignment.
Early next morning, Henry has the job all done : a crude but workable bread-board design, with screamingly high distortion impurities, but with a low battery drain design and the effect level preset on 11 on a scale of one to ten (aka ("stun").
It is very basic looking , with just one big button, set in the very middle of the sturdy front panel of the wah pedal.
Henry's genius is that this button simply says one word : MORE !
And that my friends, is the essential kernel of the conflict between these two giants of wartime penicillin....
Thursday, January 31, 2013
First person to ever read Fleming's 1929 penicillin article, REALLY READ IT, was Henry Dawson, in October 1940...
Very early in his investigation of the antibacterial qualities of the liquid beneath a penicillium mold , probably by October 1928, Alexander Fleming came to a truly startling conclusion.
And it is not what you - or he - or any other doctor or scientist might have expected.
Finding unknown substances that kill bacteria was and is a commonplace.
Finding a substance that kills bacteria without also killing the patient is a distinct rarity.
But the chances of finding a unknown substance that kills bacteria while (a) not killing the patient AND (b) while being a part of about two dozen other unknown compounds in a bath of 97% water ?
Well, sir, that simply is an event that has mathematic odds well beyond the calculating.
Let us label the Alec Fleming of this startling conclusion, "Fleming I" , because six months later he had - confusingly - become both Fleming I and "Fleming II", depending on his mood.
Fleming II consistently insisted, for the next fifteen years, that penicillin would not become a useful medication until chemists had purified it, discovered its chemical structure and recreated it as an artificial synthetic. Even then, it would only be good as an external antiseptic.
Talk about a parent praising their latest offspring with faint dams !
But while Fleming II's team had actually started down the chemists' path and had produced a much more concentrated (and semi-purified) material, he totally and abruptly abandoned this effort and never wrote it up in his seminal 1929 article.
He never even used this highly concentrated material (a thousand times more concentrated than original his liquid mixture) in any biological experiment.
It could just be that the businessman-bacteriologist Alexander Fleming, a frugal Scot, had more native arithmetic in him than almost all the doctors and scientists who followed him into penicillin - certainly more native arithmetic ability than almost all the writers I have read on the penicillin saga.
Because the two dozen unknown compounds swirling about together hadn't eliminated the anti-bacterial activity or caused a toxic reaction, removing them by purification was a 50/50 shot at improving- or reducing - those two valuable qualities.
Remember that : let me repeat it : purification might actually reduce the bacterial activity or increase toxicity. Synergy, working together, does many mysterious things.
In fact, Dawson's co-worker, Gladys Hobby ten long years later was only one of many who were convinced that crude impure penicillin worked better than the equivalent amount of units of pure penicillin did all by itself.
Balancing these unknowns, it wasn't mathematically likely that purifying penicillin 100% was actually going to make it a better medicine.
In fact, since with 1929 levels of original mold juice and the then current state of extraction technology, 100% pure penicillin was probably going to require losing 99% or more of the original anti-bacterial substance, 99 patients would now die so that 1 might receive 100% pure penicillin.
Let me go further, and recall some of the economics lesson professor John Graham taught me too many years ago.
Graham had a way of bringing economic jargon down to ground level, perhaps never more so than in explaining the term "opportunity cost".
I'd like to think that this is the way he'd explain Fleming I's decision to refute Fleming II's progress :
It is not just that purifying the penicillin juice to 100% results in so little penicillin output that 99 potential patients must die so one patient can be treated with 100% penicillin - that has no more medical efficacy than the original un-purified juice.
Because devoting all of your incredible amounts of labour, stress, time, expense, lab space to this purification effort, means your team can't find the time and space to simply produce more absolute units of the original penicillin, with the production technology they already have.
Nor can they find the time, energy and money to improve the biological yield of that original strain of penicillium mold.
In the real world of limited time and resources, when you open one door, you close many others.
Now Fleming II didn't actually go very far down the path of this (pointless) path of purification.
But his team did find success in the much easier and much more potentially useful concentration of penicillin juice ; aka simply removing most of the harmless water, as we do with concentrated orange juice.
If water is the one compound in the mixture known to be harmless, why bother ?
Fleming's strain of penicillium was actually a very potent producer of penicillin on (not in) water : eventually it produced 200 units of activity per ml of liquid in painstaking experiments in the lab, and routinely got at least 40 units in day to day industrial efforts.
But Fleming didn't know how to grow penicillium right to produce its potential in penicillin - and why should be ?
But he also didn't bother to try to find out, from other fungus farmers, how to grow it better.
He was a medical bacteriologist and he grew it as if it was a medically important bacteria.
The results were a disaster : he was lucky to get one unit of activity per ml of liquid.
But even the most careful technique of safely injecting large amounts of liquid by IV drip wasn't going to find a way to get anti-bacterial activity that diluted into the blood stream to cure really life threatening blood poisoning.
Success by this method, as several bold and brave doctors discovered in 1943-1944, wasn't actually that far off : in those early days, even massive infusions of 10 units per ml of liquid would save lives ,and at 40 units per ml of liquid all but the toughest infections could be beat back then.
So if Fleming II concentrated his original liquid down to a thick syrup, he'd have concentrated it enough to inject into patients --- without losing too much of the original scant penicillin in the process OR consuming all his team's limited energy, time and money in the process.
But at this point, another set of experiments convinced Fleming II completely (and totally wrongly) that penicillin would not work at all as a systemic - concentrated, purified or not.
If only he had injected his syrup, mixed with a little bit of saline solution, into a dying mouse, the mouse would lived.
And penicillin would have been in wide clinical use by December 1929, repeating the rapid pattern of Banting's insulin, but this time in spades.
However, Fleming I never put Fleming II's work or conclusions into his 1929 paper - only repeating his conclusions in private conversations , if pushed.
He found, (and so told hundreds of hospital bacteriologists all over the world) , that easy to make, 100% recovery , liquid penicillin worked well as a routine lab clearing agent and for use as an a non-toxic human antiseptic.
Now to October of 1940 , exactly 12 years after Fleming's original startling discovery about 'the non toxicity of impurity'.
Henry Dawson is waiting impatiently for his co-worker Karl Meyer to purify some of Fleming's penicillin up to what the team imagined was the level of purity acceptable to their famous teaching hospital's quality standards.
And to the level they imagined the deliberately vague but purity-obsessed Howard Florey had claimed he had achieved before safely injecting his penicillin into infected mice in the summer of 1940, saving their lives.
Suddenly, while impatiently waiting and pacing the floor, Dawson was presented with a truly Solomon's Dilemma.
He had expected to treat a single patient with SBE, provided the young man didn't die of the invariably fatal disease before Meyer had purified the penicillin to an acceptable level.
Now he suddenly had two young men dying of SBE.
Re-reading Fleming's original article gave him his solution : if purifying merely lent losing half or more (much more) of the limited material available, without making the resulting medicine any less toxic, why bother ?
Merely quickly concentrate the liquid penicillin, so most of the harmless impurities are left in, while the harmless but burdensome excess of water was left out - and you would be quickly left with enough penicillin to treat two patients - and all this could happen before the two men died.
So the spirit of Fleming I , not Fleming II, was guiding Dawson's hand when he injected the world's very first antibiotics , months ahead of schedule, into BOTH Aaron Alston AND Charles Aronson on October 16th 1940.
Fittingly, in this act of inspired charity, Matthew 20:16 was again fulfilled as the Last became the First to receive this healing balm.
(Alston was almost certainly black and Aronson almost certainly Jewish and in 1940s America both were hardly among the truly favoured peoples.)
After Dawson, a few others others would re-read Fleming's paper as if for the first time, and decided to prefer large amounts - today ! - of highly impure but non toxic penicillin, over small amounts of highly purified but no more non toxic penicillin, maybe, tomorrow.
I suspect their grateful patients, plucked back from the grave, more than agreed with their re-reading of Fleming 1929.
A case of Jam Today , indeed .....
And it is not what you - or he - or any other doctor or scientist might have expected.
Finding unknown substances that kill bacteria was and is a commonplace.
Finding a substance that kills bacteria without also killing the patient is a distinct rarity.
But the chances of finding a unknown substance that kills bacteria while (a) not killing the patient AND (b) while being a part of about two dozen other unknown compounds in a bath of 97% water ?
Well, sir, that simply is an event that has mathematic odds well beyond the calculating.
Let us label the Alec Fleming of this startling conclusion, "Fleming I" , because six months later he had - confusingly - become both Fleming I and "Fleming II", depending on his mood.
Fleming II consistently insisted, for the next fifteen years, that penicillin would not become a useful medication until chemists had purified it, discovered its chemical structure and recreated it as an artificial synthetic. Even then, it would only be good as an external antiseptic.
Talk about a parent praising their latest offspring with faint dams !
But while Fleming II's team had actually started down the chemists' path and had produced a much more concentrated (and semi-purified) material, he totally and abruptly abandoned this effort and never wrote it up in his seminal 1929 article.
He never even used this highly concentrated material (a thousand times more concentrated than original his liquid mixture) in any biological experiment.
It could just be that the businessman-bacteriologist Alexander Fleming, a frugal Scot, had more native arithmetic in him than almost all the doctors and scientists who followed him into penicillin - certainly more native arithmetic ability than almost all the writers I have read on the penicillin saga.
Because the two dozen unknown compounds swirling about together hadn't eliminated the anti-bacterial activity or caused a toxic reaction, removing them by purification was a 50/50 shot at improving- or reducing - those two valuable qualities.
Remember that : let me repeat it : purification might actually reduce the bacterial activity or increase toxicity. Synergy, working together, does many mysterious things.
In fact, Dawson's co-worker, Gladys Hobby ten long years later was only one of many who were convinced that crude impure penicillin worked better than the equivalent amount of units of pure penicillin did all by itself.
Balancing these unknowns, it wasn't mathematically likely that purifying penicillin 100% was actually going to make it a better medicine.
In fact, since with 1929 levels of original mold juice and the then current state of extraction technology, 100% pure penicillin was probably going to require losing 99% or more of the original anti-bacterial substance, 99 patients would now die so that 1 might receive 100% pure penicillin.
Let me go further, and recall some of the economics lesson professor John Graham taught me too many years ago.
Graham had a way of bringing economic jargon down to ground level, perhaps never more so than in explaining the term "opportunity cost".
I'd like to think that this is the way he'd explain Fleming I's decision to refute Fleming II's progress :
It is not just that purifying the penicillin juice to 100% results in so little penicillin output that 99 potential patients must die so one patient can be treated with 100% penicillin - that has no more medical efficacy than the original un-purified juice.
Because devoting all of your incredible amounts of labour, stress, time, expense, lab space to this purification effort, means your team can't find the time and space to simply produce more absolute units of the original penicillin, with the production technology they already have.
Nor can they find the time, energy and money to improve the biological yield of that original strain of penicillium mold.
In the real world of limited time and resources, when you open one door, you close many others.
Now Fleming II didn't actually go very far down the path of this (pointless) path of purification.
But his team did find success in the much easier and much more potentially useful concentration of penicillin juice ; aka simply removing most of the harmless water, as we do with concentrated orange juice.
If water is the one compound in the mixture known to be harmless, why bother ?
Fleming's strain of penicillium was actually a very potent producer of penicillin on (not in) water : eventually it produced 200 units of activity per ml of liquid in painstaking experiments in the lab, and routinely got at least 40 units in day to day industrial efforts.
But Fleming didn't know how to grow penicillium right to produce its potential in penicillin - and why should be ?
But he also didn't bother to try to find out, from other fungus farmers, how to grow it better.
He was a medical bacteriologist and he grew it as if it was a medically important bacteria.
The results were a disaster : he was lucky to get one unit of activity per ml of liquid.
But even the most careful technique of safely injecting large amounts of liquid by IV drip wasn't going to find a way to get anti-bacterial activity that diluted into the blood stream to cure really life threatening blood poisoning.
Success by this method, as several bold and brave doctors discovered in 1943-1944, wasn't actually that far off : in those early days, even massive infusions of 10 units per ml of liquid would save lives ,and at 40 units per ml of liquid all but the toughest infections could be beat back then.
So if Fleming II concentrated his original liquid down to a thick syrup, he'd have concentrated it enough to inject into patients --- without losing too much of the original scant penicillin in the process OR consuming all his team's limited energy, time and money in the process.
But at this point, another set of experiments convinced Fleming II completely (and totally wrongly) that penicillin would not work at all as a systemic - concentrated, purified or not.
If only he had injected his syrup, mixed with a little bit of saline solution, into a dying mouse, the mouse would lived.
And penicillin would have been in wide clinical use by December 1929, repeating the rapid pattern of Banting's insulin, but this time in spades.
However, Fleming I never put Fleming II's work or conclusions into his 1929 paper - only repeating his conclusions in private conversations , if pushed.
He found, (and so told hundreds of hospital bacteriologists all over the world) , that easy to make, 100% recovery , liquid penicillin worked well as a routine lab clearing agent and for use as an a non-toxic human antiseptic.
Now to October of 1940 , exactly 12 years after Fleming's original startling discovery about 'the non toxicity of impurity'.
Henry Dawson is waiting impatiently for his co-worker Karl Meyer to purify some of Fleming's penicillin up to what the team imagined was the level of purity acceptable to their famous teaching hospital's quality standards.
And to the level they imagined the deliberately vague but purity-obsessed Howard Florey had claimed he had achieved before safely injecting his penicillin into infected mice in the summer of 1940, saving their lives.
Suddenly, while impatiently waiting and pacing the floor, Dawson was presented with a truly Solomon's Dilemma.
He had expected to treat a single patient with SBE, provided the young man didn't die of the invariably fatal disease before Meyer had purified the penicillin to an acceptable level.
Now he suddenly had two young men dying of SBE.
Re-reading Fleming's original article gave him his solution : if purifying merely lent losing half or more (much more) of the limited material available, without making the resulting medicine any less toxic, why bother ?
Merely quickly concentrate the liquid penicillin, so most of the harmless impurities are left in, while the harmless but burdensome excess of water was left out - and you would be quickly left with enough penicillin to treat two patients - and all this could happen before the two men died.
So the spirit of Fleming I , not Fleming II, was guiding Dawson's hand when he injected the world's very first antibiotics , months ahead of schedule, into BOTH Aaron Alston AND Charles Aronson on October 16th 1940.
Fittingly, in this act of inspired charity, Matthew 20:16 was again fulfilled as the Last became the First to receive this healing balm.
(Alston was almost certainly black and Aronson almost certainly Jewish and in 1940s America both were hardly among the truly favoured peoples.)
After Dawson, a few others others would re-read Fleming's paper as if for the first time, and decided to prefer large amounts - today ! - of highly impure but non toxic penicillin, over small amounts of highly purified but no more non toxic penicillin, maybe, tomorrow.
I suspect their grateful patients, plucked back from the grave, more than agreed with their re-reading of Fleming 1929.
A case of Jam Today , indeed .....
Wednesday, January 30, 2013
Wartime penicillin was "A Genie of Universal Healing", trapped by Florey in a military bottle...
... a Genie intended to remain secret, military and patented for the duration of the war, until others --- led by Henry Dawson --- fought to set it free to benefit all humanity.
Like the war itself, wartime penicillin was not a single event, as we tend to treat it today, but a six year long, world-wide process - a conflict in fact.
A conflict between the much more powerful and much more numerous Hares, led by Florey, who sought to seal off penicillin in many different senses of that phrase.
The small band of Tortoises , led by Dawson, sought to make penicillin free to mix , again in many different senses of that phrase.
The Hares had all the early running from 1939 till 1944, when the Tortoises suddenly appeared out of the dust , like the US Seventh Cavalry, to save the medical establishment's bacon just moments before the D-Day beaches became red with blood .....
Like the war itself, wartime penicillin was not a single event, as we tend to treat it today, but a six year long, world-wide process - a conflict in fact.
A conflict between the much more powerful and much more numerous Hares, led by Florey, who sought to seal off penicillin in many different senses of that phrase.
The small band of Tortoises , led by Dawson, sought to make penicillin free to mix , again in many different senses of that phrase.
The Hares had all the early running from 1939 till 1944, when the Tortoises suddenly appeared out of the dust , like the US Seventh Cavalry, to save the medical establishment's bacon just moments before the D-Day beaches became red with blood .....
Fleming never saved Churchill, but Gladys Hobby saved Florey's sister when his own penicillin couldn't !
Howard Florey was never more sleazy than in his dealings with Henry Dawson's team, as he desperately fought to restore the family name that his father dis-honored, by trying to remain the sole "hero" of wartime penicillin.
Just try to imagine what an university ethics committee today might say about a professor using his main rival's unpublished paper, sent to him in secret by his close friend (the same government official who censored his rival's paper and forbade its release) to improve his own work that is about to be allowed to be freely published !
That is what full Professor Howard Florey and university vice president and full Professor A N Richards actually did to associate professor chemist Professor Karl Meyer of Dawson's team , in mid 1942.
(As they say, tenure is 'red in tooth and claw'.)
The multi-hatted Professor A Newton Richards was a Vice President of the University of Pennsylvania, head of the medical wing of the OSRD , chief consultant to Merck and one of Howard Florey's best friends.
Like Mayor Rob Ford, he also never met a conflict of interest he could resist.
(By contrast, when Norman Heatley met Meyer in January 1942, Heatley recorded that Meyer was willing to send his data to Florey, but Heatley boldly told his boss (Florey) he (Heatley) won't because it didn't seem right, not if Florey was about to publish and Meyer was forbidden to.)
However, Professor Richards was of a very different moral character and saw nothing wrong in sending Professor Meyer's embargoed chemical work on the structure of penicillin to his main academic rival, Professor Florey.
By contrast, Dawson bent over backwards to try and find a source of penicillin for Florey (even at places like Pfizer - a place Florey determinedly didn't want to visit), totally unaware of Florey's well known reputation in the UK for being an academic bush whacker and a magpie of other people's hard work.
Florey's real (if totally private) reason to come to America in 1941, was mainly to establish that he and Merck, not Dawson and Pfizer, was the real leader in the hunt for viable penicillin.
By late 1942, Florey felt sure that the dying Dawson and Pfizer (having joined Merck's cartel) was out of the race.
Sweet indeed then, when in August 1944, a sullen Howard Florey had to stand politely beside Dawson team member Gladys Hobby as she showed him the natural penicillin poring off the Pfizer lines, while Merck and Florey's team at Oxford had totally failed to produce any synthetic penicillin for the D Day beaches.
Florey had spurned both Pfizer and Glaxo, yet it was they who delivered most of the penicillin that landed on the Normandy beaches that day --- "the stone the builders rejected" indeed.
Asa series of letters in the Royal Society Archive reveal, in December 1952, Florey had to eat yet more humble pie, first begging and then thanking Hobby for sending her own latest antibiotic off to save the life of his sister (Hilda Gardner) in Australia when his own penicillin wouldn't work....
Just try to imagine what an university ethics committee today might say about a professor using his main rival's unpublished paper, sent to him in secret by his close friend (the same government official who censored his rival's paper and forbade its release) to improve his own work that is about to be allowed to be freely published !
That is what full Professor Howard Florey and university vice president and full Professor A N Richards actually did to associate professor chemist Professor Karl Meyer of Dawson's team , in mid 1942.
(As they say, tenure is 'red in tooth and claw'.)
The multi-hatted Professor A Newton Richards was a Vice President of the University of Pennsylvania, head of the medical wing of the OSRD , chief consultant to Merck and one of Howard Florey's best friends.
Like Mayor Rob Ford, he also never met a conflict of interest he could resist.
(By contrast, when Norman Heatley met Meyer in January 1942, Heatley recorded that Meyer was willing to send his data to Florey, but Heatley boldly told his boss (Florey) he (Heatley) won't because it didn't seem right, not if Florey was about to publish and Meyer was forbidden to.)
However, Professor Richards was of a very different moral character and saw nothing wrong in sending Professor Meyer's embargoed chemical work on the structure of penicillin to his main academic rival, Professor Florey.
By contrast, Dawson bent over backwards to try and find a source of penicillin for Florey (even at places like Pfizer - a place Florey determinedly didn't want to visit), totally unaware of Florey's well known reputation in the UK for being an academic bush whacker and a magpie of other people's hard work.
Florey's real (if totally private) reason to come to America in 1941, was mainly to establish that he and Merck, not Dawson and Pfizer, was the real leader in the hunt for viable penicillin.
By late 1942, Florey felt sure that the dying Dawson and Pfizer (having joined Merck's cartel) was out of the race.
Sweet indeed then, when in August 1944, a sullen Howard Florey had to stand politely beside Dawson team member Gladys Hobby as she showed him the natural penicillin poring off the Pfizer lines, while Merck and Florey's team at Oxford had totally failed to produce any synthetic penicillin for the D Day beaches.
Florey had spurned both Pfizer and Glaxo, yet it was they who delivered most of the penicillin that landed on the Normandy beaches that day --- "the stone the builders rejected" indeed.
Gladys Hobby saves Howard Florey's own sister -- when he couldn't
Asa series of letters in the Royal Society Archive reveal, in December 1952, Florey had to eat yet more humble pie, first begging and then thanking Hobby for sending her own latest antibiotic off to save the life of his sister (Hilda Gardner) in Australia when his own penicillin wouldn't work....
Monday, January 28, 2013
How wartime penicillin's American miracle cures were censored - and why
From early in 1942, American medical journal editors and authors joined scientific journal editors and authors already being "self censored".
Like them, they were asked (virtually required) to submit all articles they were uncertain about, to a NAS/NRC advisory for vetting before printing or submitting.
Supposedly the NAS medical sub-committee was only censored the chemistry of penicillin , but in fact this wasn't consistently imposed until March 1943,when it fell in line with the UK's more legally formal move in this direction.
Between January 1942 till late in 1943, this system's real ambition was to successfully keep every "miracle cure" by penicillin out of medical and scientific media - and thus, by reverse osmosis, out of the daily press.
If the American public didn't hear about this miracle drug, then the chemistry-savvy Germans won't either ---- at least not before D-Day, or so the thought went.
I think the key for this method's success was that the OSRD/CMR/COC controlled (a) all the significant new strains and all the new information on how to make penicillin in mass qualities, (b) controlled all supplies of the resulting therapeutic penicillin (c) and as well was busy dangling $500 million in high-overhead contracts to cash and equipment starved university administrators.
So it could successfully tell the university researchers, commercial penicillin firms and the medical accredited investigators, peep one word and no more penicillin/ penicillin information/ cash.
Informally, the OSRD/CMR/COC tried to fend off all requests for stories on this rumoured new wonder drug from non-science journalists, who they had no hold over.
Science journalists - hello William l Laurence ! - were already totally self-embedded in this self censorship. (Color me surprised ...)
General reporters also read popular science stories for possible leads, so with none coming forth on penicillin, they actually made very few such requests.
Of course when a *Hearst* *city desk editor* got a *Pulitzer* for *spot news reporting* for saving the life of a baby with the miracle cure penicillin (and modestly reporting the story as well) , all that changed.
(I always thought the real miracle was the Pulitzer Committee giving a prize to a Hearst paper, the arch enemy of George Pulitzer. That and a city desk editor breaking a Pulitzer-worthy foot leather news story without ever leaving his desk (or phone.)
But what I am not sure of , was Byron Price ever asked by the OSRD/CMR's Dr A.N. Richards to amend his codebooks to ask editors to avoid any any mention of penicillin.
I have a request on this out to a real expert on the American experience with self censorship in WWII....
Saturday, January 26, 2013
Florey delays penicillin for three more years : powdering the sick mice, May 1940
Just imagine for a moment if Howard Florey had actually done in May 1940 what he claimed he did for the rest of his life.
The one small/simple experiment that Alexander Fleming never did in 1928 and the one small/simple experiment he absolutely needed to do , to become for all time, the fully respected "discoverer" of penicillin.
At least in the eyes of scientists, doctors, historians and knowledgable lay people.
That experiment was to inject some of his mouse juice again into a mouse - but this time a mouse deliberately infected with massive amounts of bacteria, not a healthy mouse.
All to see if his penicillin juice could pricelessly save lives by working internally to root out massive infections, not to merely become another in a long line of antiseptics, to be dabbed on cuts merely as an aid to hurry up their natural scaring and healing.
Fleming never did this experiment.
Fleming would have to have slowly injected half a gram (cc/ml) of penicillin juice into an acutely ill 20 gram mouse, and since each gram had about 4 units of antibacterial activity in it, that would have been only 2 units of antibacterial activity per dose.
He'd have to repeat this about every 16 hours for perhaps three days to cure the mouse.
By contrast, because Florey first concentrated that penicillin juice down to about one thousandth of its original volume by boiling the water away in a vacuum, he ended up with mere milligrams of a dry brown powder - each mg containing the same antibacterial units as a gram of the original penicillin juice.
But after all this hard work, he also LOST two thirds of the original penicillin activity.
(He'd be fired if he did that for long in a commercial industrial fermentation operation !)
He dissolved 10 of those mgs of dry penicillin powder into .3 cc of distilled water ( back to the future again !) and injected perhaps 20 to 40 units of antibacterial activity into another acutely sick 20 gm mouse, saving its life in one large intense dose.
Luckily his mice did not die of needle fever during that single big dose - Fleming's need to give weaker injections, repeated over a longer period of time, did at least reduce the chance of severe side affects.
Properly handled, Fleming's strain routinely actually will give at least 40 units per gram of juice.
Then one half gram of his juice would give the exact same effect as 10 mg of Florey's dried powder (10 units in both cases.)
So an alternative path to Florey's tiresome and loss-inducing concentrating and purifying of tiny amounts of antibacterial activity in the original juice was to fire the team chemist and hire instead an industrial mycologist (fungus fermentation specialist) who knew how to starve a mold into giving more , not less, penicillin !
Up till Florey, all those who had written scientific articles on penicillin had acted as if it would be used as a non-toxic and wholly natural liquid , much as natural liver extracts were used to save those with pernicious anemia.
Florey introduced a totally new - and totally bogus - wrinkle into the effort to put penicillin to work saving lives.
He suddenly claimed that penicillin juice was NOT non-toxic - unknown parts of it was toxic "impurities" and that only the fully pure penicillin was non-toxic.
Though how he knew this, well in advance of getting anywhere near full purification, I best leave to your wild imagination !
Particularly if you knew some healthy person who died suddenly of anaphylactic shock after a routine dose of 100% pure penicillin.
I am afraid I can never forgive Florey for the wasted years and wasted diversion of effort into purifying penicillin juice instead of simply pouring it - NOW ! - into dying patients.....
The one small/simple experiment that Alexander Fleming never did in 1928 and the one small/simple experiment he absolutely needed to do , to become for all time, the fully respected "discoverer" of penicillin.
At least in the eyes of scientists, doctors, historians and knowledgable lay people.
That experiment was to inject some of his mouse juice again into a mouse - but this time a mouse deliberately infected with massive amounts of bacteria, not a healthy mouse.
All to see if his penicillin juice could pricelessly save lives by working internally to root out massive infections, not to merely become another in a long line of antiseptics, to be dabbed on cuts merely as an aid to hurry up their natural scaring and healing.
Fleming never did this experiment.
Crucially, neither did Florey.
Fleming would have to have slowly injected half a gram (cc/ml) of penicillin juice into an acutely ill 20 gram mouse, and since each gram had about 4 units of antibacterial activity in it, that would have been only 2 units of antibacterial activity per dose.
He'd have to repeat this about every 16 hours for perhaps three days to cure the mouse.
By contrast, because Florey first concentrated that penicillin juice down to about one thousandth of its original volume by boiling the water away in a vacuum, he ended up with mere milligrams of a dry brown powder - each mg containing the same antibacterial units as a gram of the original penicillin juice.
But after all this hard work, he also LOST two thirds of the original penicillin activity.
(He'd be fired if he did that for long in a commercial industrial fermentation operation !)
He dissolved 10 of those mgs of dry penicillin powder into .3 cc of distilled water ( back to the future again !) and injected perhaps 20 to 40 units of antibacterial activity into another acutely sick 20 gm mouse, saving its life in one large intense dose.
Luckily his mice did not die of needle fever during that single big dose - Fleming's need to give weaker injections, repeated over a longer period of time, did at least reduce the chance of severe side affects.
Properly handled, Fleming's strain routinely actually will give at least 40 units per gram of juice.
Then one half gram of his juice would give the exact same effect as 10 mg of Florey's dried powder (10 units in both cases.)
So an alternative path to Florey's tiresome and loss-inducing concentrating and purifying of tiny amounts of antibacterial activity in the original juice was to fire the team chemist and hire instead an industrial mycologist (fungus fermentation specialist) who knew how to starve a mold into giving more , not less, penicillin !
Up till Florey, all those who had written scientific articles on penicillin had acted as if it would be used as a non-toxic and wholly natural liquid , much as natural liver extracts were used to save those with pernicious anemia.
Florey introduced a totally new - and totally bogus - wrinkle into the effort to put penicillin to work saving lives.
He suddenly claimed that penicillin juice was NOT non-toxic - unknown parts of it was toxic "impurities" and that only the fully pure penicillin was non-toxic.
Though how he knew this, well in advance of getting anywhere near full purification, I best leave to your wild imagination !
Particularly if you knew some healthy person who died suddenly of anaphylactic shock after a routine dose of 100% pure penicillin.
I am afraid I can never forgive Florey for the wasted years and wasted diversion of effort into purifying penicillin juice instead of simply pouring it - NOW ! - into dying patients.....
Alexander Fleming shares 1934 Nobel prize with Whipple, Minot and Murphy !
Waaaaaait a minute !!
Fleming didn't share the Nobel prize (for discovering penicillin) for another dozen years.
True --- but he could have got the prize a lot earlier and saved a whole lot of millions of lives in the process , if he had only been a little bit bolder.
For almost 40 years, sufferers from invariably fatal (but fortunately relative rare) disease pernicious anemia had been kept alive by a natural substance: liver.
Over time, the amount of natural- raw - liver they had to eat every day fortunately got smaller and smaller and the scientists edged ever closer to defining exactly which little compound it was in liver that kept them alive.
(Vitamin B12).
That happened 28 years after Whipple's initial discovery and about 10 years later after that, it became available as a partially synthesized product.
These three didn't 'wait for the chemists to purify and then synthesize my discovery' before using it to save lives, to use Fleming's words about his discovery.
They richly deserve their Nobel prize.
But if Fleming had only done what Duhig did in 1943 in Brisbane ; ie inject Fleming's 1928 penicillin juice into dying patients, he too might have gotten a Nobel Prize soon after his discovery.
After all, he had stated publicly that his juice, un-touched by chemists' hands - killed deadly bacteria and was harmless to animal or human bodies.
If Fleming had but tested his penicillin juice's possible systemic effects therapeutic effects on even a single mouse, the life saving might have begun in 1928 not in 1943.....
Fleming didn't share the Nobel prize (for discovering penicillin) for another dozen years.
True --- but he could have got the prize a lot earlier and saved a whole lot of millions of lives in the process , if he had only been a little bit bolder.
For almost 40 years, sufferers from invariably fatal (but fortunately relative rare) disease pernicious anemia had been kept alive by a natural substance: liver.
Over time, the amount of natural- raw - liver they had to eat every day fortunately got smaller and smaller and the scientists edged ever closer to defining exactly which little compound it was in liver that kept them alive.
(Vitamin B12).
That happened 28 years after Whipple's initial discovery and about 10 years later after that, it became available as a partially synthesized product.
These three didn't 'wait for the chemists to purify and then synthesize my discovery' before using it to save lives, to use Fleming's words about his discovery.
They richly deserve their Nobel prize.
But if Fleming had only done what Duhig did in 1943 in Brisbane ; ie inject Fleming's 1928 penicillin juice into dying patients, he too might have gotten a Nobel Prize soon after his discovery.
After all, he had stated publicly that his juice, un-touched by chemists' hands - killed deadly bacteria and was harmless to animal or human bodies.
If Fleming had but tested his penicillin juice's possible systemic effects therapeutic effects on even a single mouse, the life saving might have begun in 1928 not in 1943.....
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