Alexander Fleming's very first article on penicillin, supposedly a masterwork of basic science , had a fatal flaw - for itself and for untold millions of innocent patients between 1928 and 1943.
Fleming submitted it for publication, even though he hadn't done a fundamental test that every potential new anti-bacterial drug should have performed upon it, before any sort of valid scientific judgement can be passed.
Fleming , in a pique of hubris , rushed to judgement , prematurely and unfairly, on his new child - penicillin - and his erroneously wrong assessment almost strangled it before it was even born.
Fleming had totally failed to test how penicillin actually worked (or not) inside a real living body 'protecting' that body from a real disease.
Penicillin (and its many kin in the beta lactam family) will probably always remain, on balance, the world's best ever bacteria killer to be discovered.
However most of its advantages are also the source of its odd quirks cum grave disadvantages.
(For completeness, I will mention - in passing - that penicillin is a broad spectrum killer of many of humanity's most dangerous bacteria and that it originally didn't really work when taken orally.)
Now onto its really unusual features.
It is extremely extremely non-toxic for any drug , let alone a lifesaver, (only a tiny fragment of one percent of us are dangerously allergic to it - and this not an issue of toxicity , per say anyway.)
It is non-toxic partly because it diffuses extremely readily.
A failure to diffuse readily was a sometimes-fatal-to-the-patient flaw in its rivals the sulfa drugs.
A diffuse drug also kills better by reaching into the tiniest of places in a body to kill bugs hiding out there.
It diffuses well partly because it is reluctant to bind to most body bits - this reduces its potential for creating new toxic compounds and ensures all its killing power is saved for the bugs.
But a drug that diffuses well and doesn't bind to other chemicals also leaves a body very quickly - penicillin's biggest flaw.
And penicillin does not kill rapidly on contact like say sulfuric acid kills instantly on contact and it is (relatively speaking) a slow bacteria killer, or so it seemed at first.
But this is actually a bonus, not a bug , as computer programmers say.
It is rather stand-offish and only acts upon bugs that are actively growing ( ie actively killing us) and so does not waste its killing powers upon harmless bugs that co-exist with us and reproduce slowly.
Nor, as I have said, does it waste its strength by binding onto our own various body bits and creating dangerously toxic new compounds in the process.
So, if injected into the blood stream of a healthy young living being, penicillin will be seen leaving the body very soon afterwards via the urine, seemingly long before it has time to kill all of a bunch of normally reproducing bacteria.
As Fleming suspected from his basic science studies and so put into his dismissive 1929 report.
With the result that Fleming claimed penicillin as had absolutely no value as a life-saving antibiotic.
He thought penicillin could only work as an antiseptic - ie , useful when poured into body cavities or wounds that are 'unconnected' (relatively speaking) to the body's blood and kidney systems.
But we know in fact - from real life experience - that penicillin-the-antibiotic can knock the deadliest bugs off their feet in really sick people - clearly Fleming went badly, badly, badly wrong.
What's the explanation for penicillin's unexpected 'in-sick-bodies' success ?
Well, for a start, in seriously sick people the body systems slow down and penicillin rarely leaves as fast as in healthy young people - so penicillin can hang about longer to work its magic.
Sickness also causes inflammation that lets penicillin cross body barriers that normally bar it in healthy people.
And if penicillin is constantly dripped slowly slowly into a muscle instead of being rapidly shoved all at once into a vein (by IV injection) it will have a much longer time to work its magic before leaving via the urine.
And when Fleming said penicillin was a slow killer he really meant it took a while to kill all of his bacteria sample.
But penicillin actually begins killing some of the rapidly reproducing bacteria at once (and remember that rapidly reproducing bacteria is the best single definition of a really dangerous, as opposed to a relatively benign, infection).
Inside a real living body with its own anti-bacteria defences, even slowing that rapid bacteria growth a little helps breaks their stride and often the body can finally catch its breath and kill the bug mostly by itself.
(This is believed to be the reason that in the early days, incredibly tiny amounts of penicillin seemingly 'stopped' all-out bacterial infections that were judged certain to kill the patient in a few hours.)
Because penicillin was reluctant to bind to blood serum or pus, while it stayed only a relatively short time in the body even when slowly dripped into a muscle, it was also 'all work and no play' during its short shift on duty.
By contrast, the hard to diffuse sulfa drugs hung about for hours but wasted most of their strength binding uselessly to pus and such instead of hindering our bacterial foes.
All of this was determined years after the fact, in part via basic science research.
But for a real life clinician MD ( ie a front line ward doctor) this basic science work was a luxury - merely icing on a cake.
She or he simply had to learn how to improve lives - now - with a new medical tool without necessarily knowing fundamentally how it actually worked.
A medical tool can remain forever a big 'black box' to both doctors and basic scientists and yet improve the lives of millions.
For example, for years I helped give mental patients ECT "shock treatment" and saw it as the only thing that really improved their individual lives - even though we didn't know then - and don't know now - how it actually works.
Exalting "basic science" is a vastly overdone disease.
Frequently it really means "exalt those academic scientists who don't work helping people" over "honouring their lesser brethren who actually do dirty their hands helping humanity directly with applied science".
Because real families tend to feel a lot more grateful to the frontline doctors saving their mother at midnight than they do to back room lab scientists working a nine to five regular shift.
This tends bugs the basic scientist no end and they over-compensate by claiming an exalted role for basic science in laying a foundation for all applied science.
History fails to support this claim , by the way.
Doctors Fleming and Florey , the two best known penicillin pioneers, shared a fatal common revulsion for the clinical side of being an MD - they much preferred being in the lab and away from people suffering.
(Today, they would be just plain PhDs without the humbuggery of pretend MD licenses --- but back then non-MDs got no respect in medical science or biochemistry.)
Their revulsion was fatal for penicillin patients because much of the drug's behavior in sick patients (its only really useful quality) simply could not be predicted from its activity in Fleming's test tubes or in Florey's healthy young lab animals.
Dawson , by contrast, liked being with patients and simply did his 'basic' penicillin research while stuffing what little penicillin he had into very sick people and closely watching the results.
He learned its basic nature while also saving lives and he did so steadily from 1940 to his death in 1945.
But far as we know, Florey never did ever stick a single needle of penicillin into a patient and Fleming is really on record of doing so only in August 1942.
So what does this all have to do with 'peer review' ?
I do not believe that the editors of the journal that accepted Fleming's first penicillin article actually put it out to a realistic peer review.
If it had been , at least one of the reviewers would have called for a basic 'protection test' ( seeing if penicillin could protect from a disease in an animal and then perhaps in a human patient) before urging the accepting of the article for publication.
Peer review is much criticized today - but who doesn't wish that it had been applied, in full strength , in 1929 to Fleming's article ?
If a basic protection test had been tried - and seen to work - penicillin would probably been rapidly put into clinical practise by 1930 ( remember that before 1936 and the sulfas , there were no anti-bacterial drugs).
And yes - it need to be much better known that one of the editors who so shoddily accepted Fleming's article was Dr Florey !
Because Florey and his many powerful partisans have made so much of Fleming's failure to try a basic protection test upon penicillin.
But editor Florey failed to request one in 1928 and failed to do such a test himself for 12 (twelve) more years - doing so only after his underling Ernst Chain dared to try something similar in March 1940.
Wartime penicillin is often described (by the British mostly) as a twin triumph : British science and American industry.
I think in the case of this refusal of both Florey and Fleming to do a simple protection test with penicillin for 12 wasted years , British science was hardly shown at its best...
Fleming submitted it for publication, even though he hadn't done a fundamental test that every potential new anti-bacterial drug should have performed upon it, before any sort of valid scientific judgement can be passed.
Fleming , in a pique of hubris , rushed to judgement , prematurely and unfairly, on his new child - penicillin - and his erroneously wrong assessment almost strangled it before it was even born.
Fleming had totally failed to test how penicillin actually worked (or not) inside a real living body 'protecting' that body from a real disease.
Penicillin (and its many kin in the beta lactam family) will probably always remain, on balance, the world's best ever bacteria killer to be discovered.
However most of its advantages are also the source of its odd quirks cum grave disadvantages.
(For completeness, I will mention - in passing - that penicillin is a broad spectrum killer of many of humanity's most dangerous bacteria and that it originally didn't really work when taken orally.)
Now onto its really unusual features.
It is extremely extremely non-toxic for any drug , let alone a lifesaver, (only a tiny fragment of one percent of us are dangerously allergic to it - and this not an issue of toxicity , per say anyway.)
It is non-toxic partly because it diffuses extremely readily.
A failure to diffuse readily was a sometimes-fatal-to-the-patient flaw in its rivals the sulfa drugs.
A diffuse drug also kills better by reaching into the tiniest of places in a body to kill bugs hiding out there.
It diffuses well partly because it is reluctant to bind to most body bits - this reduces its potential for creating new toxic compounds and ensures all its killing power is saved for the bugs.
But a drug that diffuses well and doesn't bind to other chemicals also leaves a body very quickly - penicillin's biggest flaw.
And penicillin does not kill rapidly on contact like say sulfuric acid kills instantly on contact and it is (relatively speaking) a slow bacteria killer, or so it seemed at first.
But this is actually a bonus, not a bug , as computer programmers say.
It is rather stand-offish and only acts upon bugs that are actively growing ( ie actively killing us) and so does not waste its killing powers upon harmless bugs that co-exist with us and reproduce slowly.
Nor, as I have said, does it waste its strength by binding onto our own various body bits and creating dangerously toxic new compounds in the process.
So, if injected into the blood stream of a healthy young living being, penicillin will be seen leaving the body very soon afterwards via the urine, seemingly long before it has time to kill all of a bunch of normally reproducing bacteria.
As Fleming suspected from his basic science studies and so put into his dismissive 1929 report.
With the result that Fleming claimed penicillin as had absolutely no value as a life-saving antibiotic.
He thought penicillin could only work as an antiseptic - ie , useful when poured into body cavities or wounds that are 'unconnected' (relatively speaking) to the body's blood and kidney systems.
But we know in fact - from real life experience - that penicillin-the-antibiotic can knock the deadliest bugs off their feet in really sick people - clearly Fleming went badly, badly, badly wrong.
What's the explanation for penicillin's unexpected 'in-sick-bodies' success ?
Well, for a start, in seriously sick people the body systems slow down and penicillin rarely leaves as fast as in healthy young people - so penicillin can hang about longer to work its magic.
Sickness also causes inflammation that lets penicillin cross body barriers that normally bar it in healthy people.
And if penicillin is constantly dripped slowly slowly into a muscle instead of being rapidly shoved all at once into a vein (by IV injection) it will have a much longer time to work its magic before leaving via the urine.
And when Fleming said penicillin was a slow killer he really meant it took a while to kill all of his bacteria sample.
But penicillin actually begins killing some of the rapidly reproducing bacteria at once (and remember that rapidly reproducing bacteria is the best single definition of a really dangerous, as opposed to a relatively benign, infection).
Inside a real living body with its own anti-bacteria defences, even slowing that rapid bacteria growth a little helps breaks their stride and often the body can finally catch its breath and kill the bug mostly by itself.
(This is believed to be the reason that in the early days, incredibly tiny amounts of penicillin seemingly 'stopped' all-out bacterial infections that were judged certain to kill the patient in a few hours.)
Because penicillin was reluctant to bind to blood serum or pus, while it stayed only a relatively short time in the body even when slowly dripped into a muscle, it was also 'all work and no play' during its short shift on duty.
By contrast, the hard to diffuse sulfa drugs hung about for hours but wasted most of their strength binding uselessly to pus and such instead of hindering our bacterial foes.
All of this was determined years after the fact, in part via basic science research.
But for a real life clinician MD ( ie a front line ward doctor) this basic science work was a luxury - merely icing on a cake.
She or he simply had to learn how to improve lives - now - with a new medical tool without necessarily knowing fundamentally how it actually worked.
A medical tool can remain forever a big 'black box' to both doctors and basic scientists and yet improve the lives of millions.
For example, for years I helped give mental patients ECT "shock treatment" and saw it as the only thing that really improved their individual lives - even though we didn't know then - and don't know now - how it actually works.
Exalting "basic science" is a vastly overdone disease.
Frequently it really means "exalt those academic scientists who don't work helping people" over "honouring their lesser brethren who actually do dirty their hands helping humanity directly with applied science".
Because real families tend to feel a lot more grateful to the frontline doctors saving their mother at midnight than they do to back room lab scientists working a nine to five regular shift.
This tends bugs the basic scientist no end and they over-compensate by claiming an exalted role for basic science in laying a foundation for all applied science.
History fails to support this claim , by the way.
Doctors Fleming and Florey , the two best known penicillin pioneers, shared a fatal common revulsion for the clinical side of being an MD - they much preferred being in the lab and away from people suffering.
(Today, they would be just plain PhDs without the humbuggery of pretend MD licenses --- but back then non-MDs got no respect in medical science or biochemistry.)
Their revulsion was fatal for penicillin patients because much of the drug's behavior in sick patients (its only really useful quality) simply could not be predicted from its activity in Fleming's test tubes or in Florey's healthy young lab animals.
Dawson , by contrast, liked being with patients and simply did his 'basic' penicillin research while stuffing what little penicillin he had into very sick people and closely watching the results.
He learned its basic nature while also saving lives and he did so steadily from 1940 to his death in 1945.
But far as we know, Florey never did ever stick a single needle of penicillin into a patient and Fleming is really on record of doing so only in August 1942.
Peer Review and Alexander Fleming
So what does this all have to do with 'peer review' ?
I do not believe that the editors of the journal that accepted Fleming's first penicillin article actually put it out to a realistic peer review.
If it had been , at least one of the reviewers would have called for a basic 'protection test' ( seeing if penicillin could protect from a disease in an animal and then perhaps in a human patient) before urging the accepting of the article for publication.
Peer review is much criticized today - but who doesn't wish that it had been applied, in full strength , in 1929 to Fleming's article ?
If a basic protection test had been tried - and seen to work - penicillin would probably been rapidly put into clinical practise by 1930 ( remember that before 1936 and the sulfas , there were no anti-bacterial drugs).
And yes - it need to be much better known that one of the editors who so shoddily accepted Fleming's article was Dr Florey !
Because Florey and his many powerful partisans have made so much of Fleming's failure to try a basic protection test upon penicillin.
But editor Florey failed to request one in 1928 and failed to do such a test himself for 12 (twelve) more years - doing so only after his underling Ernst Chain dared to try something similar in March 1940.
Wartime penicillin is often described (by the British mostly) as a twin triumph : British science and American industry.
I think in the case of this refusal of both Florey and Fleming to do a simple protection test with penicillin for 12 wasted years , British science was hardly shown at its best...
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