In my opinion, we're possessed by a cultural epidemic of think pieces doing rich and nuanced science history, but wrongly framed in the form of correcting "myths" that, in their substance amount to quibblings over narrative emphasis. It's easy to get taken in by the framing because it truly is enlightening, and the argument goes down so smooth because its embedded in a rich, curious, and fascinating scientific history that otherwise embodies best practices I would happily celebrate.
But the key details about the story of penicillin are that a moldy plate showed bacteria-free clearing, Fleming saw it, isolated the mold, proved its germ-killing filtrate and published the finding, which is the heart of the story and which is not a myth.
I'm sure it's true enough that St Mary's windows were usually kept shut to keep pathogens in and contaminants out, that London's August 1928 cold snap would have slowed staph growth, that Fleming's first notes Or 8 weeks later than the actual event, and that a modern plate seeded with bacteria first will not produce the celebrated halo unless the mold is given a head start. The article makes much of the fact that today’s researchers cannot reproduce the famous halo if they add staph first, yet that difficulty rebuts a sequence Fleming never claimed to have used.
These points are significant, even fascinating, yet the article inflates them into a strobe-lit "MYTH" banner, turning normal human imprecision about times and temperatures into evidence of wholesale fiction, which abuses the ordinary friction of any retrospective account and punishes the story for the very human messiness that makes it instructive.
The window quibble, the incubator gap, and the replication protocol do not touch the central, uncontested fact that chance contamination plus observational curiosity gave medicine its first antibiotic.
It's a myth in the most literal way. Fleming published and promoted his results despite a lack of reproducibility. By the time he won the Nobel Prize, he had backformed or misremembered a folksy story about an open window. That's textbook mythmaking.
It can both be fine to have a glib story to tell schoolkids and important to recognize that the actual intellectual process is messier and more complex.
I have now actually read Flemming's 1929 manuscript that first described penicillin [0]. It is a careful and well documented scientific report describing the action of penicillin on various species of bacteria, how to produce it, and some of its chemical properties. It describes how penicillin can kill bacteria isolated from the throats of nurses, and shows that it has low toxicity in mice, and is possibly safe for use in humans: "Constant irrigation of large infected surfaces in man was not accompanied by any toxic symptoms, while irrigation of the human conjunctiva every hour for a day had no irritant effect."
It is far from having a "lack of reproducibility" and in fact allowed others to quickly and accurately replicate his discovery.
The path to his discovery may have been difficult to replicate, but the fact that the mold could kill other bacteria was not, and was immediately replicated.
It just wasn't seen as relevant because, at the time, few people imagined its internal use in humans and it was instead seen more as a tool for other microbiologists and the like. The jump to "And then I see the disinfectant, where it knocks it out in a minute. One minute. And is there a way we can do something like that, by injection inside or almost a cleaning?" took quite some time.
> The window quibble, the incubator gap, and the replication protocol do not touch the central, uncontested fact that chance contamination plus observational curiosity gave medicine its first antibiotic.
This is the same conclusion as the article. IMO, the importance of challenging the myth is that it has hisotrically taken precendence over your (and the article's) conclusion.
FTA
> Fleming’s 1929 penicillin paper may have been written as a linear process, but that’s almost certainly not how the discovery occurred. And by eliminating these complicated twists and turns, Fleming inadvertently obscured what may be one of the most important lessons in scientific history: how combining a meticulous research program with the openness to branch out into new directions led him to Nobel Prize-winning success. Neither rigid plans nor the winds of chance are enough on their own; discovery requires both.
I think that the author had the conclusion wanted before picking the story that supported the desired conclusion as best. To me that story overlooks too many documented facts as well as human behavior. They complain that it requires lottery odds for the first story to happen while ignoring that one win is documented - there was a cold snap exactly when Fleming we t on vacation. Both stories require the winning odds of the mold contaminating a culture - the mold wouldn’t have needed to be identified if Fleming was deliberately experimenting with a known mold from his colleague. So the only undocumented luck left would be the use of that contaminated culture just before vacation.
And which is more likely - Fleming imagining the initial discovery happening right as he returned from vacation or that he remembered those important details but forgot more minor ones?
> The window quibble, the incubator gap, and the replication protocol do not touch the central, uncontested fact that chance contamination plus observational curiosity gave medicine its first antibiotic.
Personally for me, while less important, I really appreciate the investigation into the narrative.
I agree that the science is more important and the results don't care about the story.
The balance is that we don't need to go around correcting everyone, but knowing more about the details of the story is worth my time in reading this piece. I think the article strikes the right tone.
To be anal about being anal, the article doesn't preclude Fleming's account. It argues that it's unlikely, but countless highly improbable things are happening every second. On this topic somehow Ancient Egyptian poultices (and in cultures onward - though they are the oldest recorded account) even used moldy bread to treat bacterial infections, somehow stumbling onto genuine antibacterial aspects for an absurdly counter-intuitive treatment that has a real effect. However it was initially discovered back then, let alone replicated and confirmed, must have been through an unimaginably improbable series of events. Yet it happened. That's rather the story of humanity.
myth /miTH/ noun
1. a traditional story, especially one concerning the early history of a people or explaining some natural or social phenomenon, and typically involving supernatural beings or events.
2. a widely held but false belief or idea.
You can redefine words if you want, but don't pretend your definitions are useful for clear communication with others.
Got a quick insight about how penicillin works: interferes with cell-wall building which is a destroy and recreate process by preventing the recreate part.
Got a quick view into the scientific process and communication: Fleming focused on the insight - penicillium kills staphylococcus - and left out the circuitous detail. This is important so that the big win here is very clear.
And got an insight into human nature and memory: Fleming didn’t tell the accidental contamination story until much later. It could possibly be even an idea someone else might have come up with which then took root in his mind (ironic haha!)
The communication aspect reminds me of Mendel’s far too perfect ratios for his pea plants. That kind of “repeat till difference clear” statistics would be decried today but perhaps that was to communicate rather than to determine.
And finally, I really enjoy reading about human process innovation because I think it’s a big factor in how Humanity grows. The lab notebook has to be some kind of star performer here - Fleming’s notes allow us to look back like this.
When I experiment with things, I naturally lean to keeping notes on my test protocol, observations, and results. But not because of some personal genius. It’s just the standard way I was taught as a child in our science labs.
I won’t claim to the rigor of a microbiology lab but even just the process notes help a lot, which is useful since I’m just testing molecules on myself.
If you are not familiar with more of Mendel or plant biology, he got extremely lucky in picking a two chromosome species. The next plant he picked had more than two chromosome types so he spent the rest of his life hitting his head against the wall - obvious to us but him not having a theory and expertise with microscopes to explain his pea results hampered him greatly beyond his initial pea plant studies.
What do you mean by a two chromosome species? A quick google says pea plants have 14 chromosomes. I only looked because I had never heard of a species only having two chromosomes. Do you mean the traits he was selecting for only had two alleles?
It's a shame that Fleming misremembered his process of discovery and created a myth of accidental discovery.
I like the Root-Bernstein narrative more. That in the monotonous execution of routine experiments for something unrelated an unusual observation 'forced' them to discover penicillins antibacterial properties.
Not an accidental discovery by good fortune in a serendipitous sense. An accidental discovery of a brute force exhaustive search. The narrative of we spent months meticulously examining hundreds of samples is less romantic, but is one that supports the importance of funding scientific inquiry.
We won't make progress by hoping people leave culture plates out on window sills. We make progress when we fund meticulous exhaustive efforts of discovery.
> Mendel’s far too perfect ratios for his pea plants.
"Remember, if you flip a coin 200 times and it comes heads up exactly 100 times, the chances are the coin is actually unfair. You should expect to see something like 93 or 107 instead".
Isn't 100 / 100 the most likely outcome for a fair coin? Sure it's unlikely that you hit exactly that result, but every single other result is even less likely.
What I'm trying to say: if you get 100 / 100, that's not a sign of an unfair coin, it's the strongest sign for a fair coin you can get.
The chance of exactly 100 heads from 200 fair coin flips is approximately 5-6%. Qualitatively, that's not particularly strong evidence for an unfair coin if you did only one trial.
You could also argue that 100 out of 200 on a fair coin is more likely than any other specific outcome, such as 93/200, so if the argument is that the coin is "too perfect", you then also have to consider the possibility that the coin is somehow biased to produce 93/200 much more often than anything else, vs. 100/200.
In a real-world scenario, if you saw a result significantly far from 100 (like 150 heads), you might suspect the coin is unfair. However, seeing exactly 100 heads gives no reason to suspect the coin is unfair; it's the result most consistent with a fair coin.
So many other good details that get to how impossibly multivariate biology research is, like the need to have several days at the exact temperature.
It's not uncommon for results in biology to have this kind of snag in reproducibility even now. Sometimes it's due to attributing variations to something like "steady hands at the bench", but other times it can even be a deliberate attempt to prevent rivals from duplicating a process before it can be patented and privatized.
Hare's theory predicts that there would need to be a cold snap at just the right time, and lo and behold there was. Probability isn't an issue if the only reason you are considering the probability is because the event already happened. Indeed the low probability of such an event transpiring goes a long way towards explaining why the discovery was not made earlier.
Root-Bernstein's theory makes no such testable predictions, and it solves the issue of an incomplete record on September 3rd with incomplete or inaccurate records elsewhere. It seems to me extremely plausible that fleming did not record the results of a botched, uncontrolled experiment but still recognized it as an indicator of something interesting that warranted follow-up. If I were in his position I would preserve the random dish for comparison to the more rigorous follow up experiment. I certainly don't put any stock into the argument that if the story had gone as Root-Bernstein describes it would have been too circuitous for scientific publishing, if anything it would be much more harmonious with standard scientific writing than the chance observation story.
- Fleming lived next door to an unsecure mycology lab.
- The temperature during the time period was low enough that if Fleming had left a contaminated culture unattended and non-incubated, he would have had a very high chance of getting the results he became famous for...
Well, given that the probability of discovering penicillin in those conditions is pretty high (say, if he forgot/neglected to incubate one out twenty batches, a 5% chance), and the prior probability of discovering penicillin any other way is extremely low (otherwise other scientists would have found it), bayesian calculus says the stroke of luck hypothesis is probably correct.
Preserving biological/medical specimens with formaldehyde so that they may be re-examined later is a common practice that still occurs today. So it isn't surprising here.
The alternative would be to freeze the specimens, but that is more cumbersome than stacking formaldehyde-fixed plates on a shelf, and specimens may alter upon repeated freezing and thawing.
One of my favorite "myths" about the discovery of stainless steel:
Metallurgist is trying out all kinds of steels looking for a particular attribute. He would dutifully record each recipe + test in a notebook but if a particular batch didn't have the attribute, he would throw it out a window into an outdoor scrap pile.
Several months go by and he's cleaning up the pile and notices that one of the blocks has no rust or corrosion. He knows that the pile is six months old but doesn't know which of the recipes this block was connected to.
So he repeats ALL of the block recipes from the last 6 months but labels each block so he can figure out which recipe led to the "stainless" steel.
I recall reading that the microwave oven was invented by a physicist after he walked by a radiation chamber and the chocolate bar in his pocket melted... makes me wonder if there was any historic license taken in that case as well.
Hmm, sounds like the spores must have come from the outside. Otherwise he'd be saying his colleague has contaminated the building with improperly stored fungal colonies and he himself let those spores contaminate his lab. So yeah, definitely from the outside.
"Presenter[John Cleese]: Penguins, yes, penguins. What relevance do penguins have to the furtherance of medical science? Well, strangely enough quite a lot, a major breakthrough, maybe. It was from such an unlikely beginning as an unwanted fungus accidentally growing on a sterile plate that Sir Alexander Fleming gave the world penicillin. James Watt watched an ordinary household kettle boiling and conceived the potentiality of steam power. Would Albert Einstein ever have hit upon the theory of relativity if he hadn't been clever? All these tremendous leaps forward have been taken in the dark. Would Rutherford ever have split the atom if he hadn't tried? Could Marconi have invented the radio if he hadn't by pure chance spent years working at the problem? Are these amazing breakthroughs ever achieved except by years and years of unremitting study? Of course not. What I said earlier about accidental discoveries must have been wrong. "
“Despite this close professional association, however, Hare claims to have played no part in the discovery or original research on penicillin nor to have discussed them with Fleming”
It’s nice to see that the bickering about who stole whose research does not affect all old discoveries.
Is it common in cases for someone with no involvement at all to claim involvement? Usually disputes I've heard of are when multiple people are involved, and they're arguing about who played a crucial vs minor role.
It's common for people who have close associations to have events that could be construed as involvement, and when someone does believe they are involved in something important, they tend to claim their involvement was important. It would be so easy to inflate a random conversation or a little common courtesy assistance as something more. It takes some genuine humility to take stock of all your interactions and conclude that you had nothing to do with one of the most important discoveries in history, and more still to admit that you thought nothing of it at the time.
Readit News
But the key details about the story of penicillin are that a moldy plate showed bacteria-free clearing, Fleming saw it, isolated the mold, proved its germ-killing filtrate and published the finding, which is the heart of the story and which is not a myth.
I'm sure it's true enough that St Mary's windows were usually kept shut to keep pathogens in and contaminants out, that London's August 1928 cold snap would have slowed staph growth, that Fleming's first notes Or 8 weeks later than the actual event, and that a modern plate seeded with bacteria first will not produce the celebrated halo unless the mold is given a head start. The article makes much of the fact that today’s researchers cannot reproduce the famous halo if they add staph first, yet that difficulty rebuts a sequence Fleming never claimed to have used.
These points are significant, even fascinating, yet the article inflates them into a strobe-lit "MYTH" banner, turning normal human imprecision about times and temperatures into evidence of wholesale fiction, which abuses the ordinary friction of any retrospective account and punishes the story for the very human messiness that makes it instructive.
The window quibble, the incubator gap, and the replication protocol do not touch the central, uncontested fact that chance contamination plus observational curiosity gave medicine its first antibiotic.
It can both be fine to have a glib story to tell schoolkids and important to recognize that the actual intellectual process is messier and more complex.
It is far from having a "lack of reproducibility" and in fact allowed others to quickly and accurately replicate his discovery.
https://pmc.ncbi.nlm.nih.gov/articles/PMC2048009/
It just wasn't seen as relevant because, at the time, few people imagined its internal use in humans and it was instead seen more as a tool for other microbiologists and the like. The jump to "And then I see the disinfectant, where it knocks it out in a minute. One minute. And is there a way we can do something like that, by injection inside or almost a cleaning?" took quite some time.
This is the same conclusion as the article. IMO, the importance of challenging the myth is that it has hisotrically taken precendence over your (and the article's) conclusion.
FTA
> Fleming’s 1929 penicillin paper may have been written as a linear process, but that’s almost certainly not how the discovery occurred. And by eliminating these complicated twists and turns, Fleming inadvertently obscured what may be one of the most important lessons in scientific history: how combining a meticulous research program with the openness to branch out into new directions led him to Nobel Prize-winning success. Neither rigid plans nor the winds of chance are enough on their own; discovery requires both.
And which is more likely - Fleming imagining the initial discovery happening right as he returned from vacation or that he remembered those important details but forgot more minor ones?
Personally for me, while less important, I really appreciate the investigation into the narrative.
I agree that the science is more important and the results don't care about the story.
The balance is that we don't need to go around correcting everyone, but knowing more about the details of the story is worth my time in reading this piece. I think the article strikes the right tone.
And you can tell - ‘the history of penicillin’ implies a very different thing than ‘the myth of penicillin’ eh?
You can redefine words if you want, but don't pretend your definitions are useful for clear communication with others.
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Got a quick insight about how penicillin works: interferes with cell-wall building which is a destroy and recreate process by preventing the recreate part.
Got a quick view into the scientific process and communication: Fleming focused on the insight - penicillium kills staphylococcus - and left out the circuitous detail. This is important so that the big win here is very clear.
And got an insight into human nature and memory: Fleming didn’t tell the accidental contamination story until much later. It could possibly be even an idea someone else might have come up with which then took root in his mind (ironic haha!)
The communication aspect reminds me of Mendel’s far too perfect ratios for his pea plants. That kind of “repeat till difference clear” statistics would be decried today but perhaps that was to communicate rather than to determine.
And finally, I really enjoy reading about human process innovation because I think it’s a big factor in how Humanity grows. The lab notebook has to be some kind of star performer here - Fleming’s notes allow us to look back like this.
When I experiment with things, I naturally lean to keeping notes on my test protocol, observations, and results. But not because of some personal genius. It’s just the standard way I was taught as a child in our science labs.
I won’t claim to the rigor of a microbiology lab but even just the process notes help a lot, which is useful since I’m just testing molecules on myself.
I like the Root-Bernstein narrative more. That in the monotonous execution of routine experiments for something unrelated an unusual observation 'forced' them to discover penicillins antibacterial properties.
Not an accidental discovery by good fortune in a serendipitous sense. An accidental discovery of a brute force exhaustive search. The narrative of we spent months meticulously examining hundreds of samples is less romantic, but is one that supports the importance of funding scientific inquiry.
We won't make progress by hoping people leave culture plates out on window sills. We make progress when we fund meticulous exhaustive efforts of discovery.
"Remember, if you flip a coin 200 times and it comes heads up exactly 100 times, the chances are the coin is actually unfair. You should expect to see something like 93 or 107 instead".
What I'm trying to say: if you get 100 / 100, that's not a sign of an unfair coin, it's the strongest sign for a fair coin you can get.
You could also argue that 100 out of 200 on a fair coin is more likely than any other specific outcome, such as 93/200, so if the argument is that the coin is "too perfect", you then also have to consider the possibility that the coin is somehow biased to produce 93/200 much more often than anything else, vs. 100/200.
It's not uncommon for results in biology to have this kind of snag in reproducibility even now. Sometimes it's due to attributing variations to something like "steady hands at the bench", but other times it can even be a deliberate attempt to prevent rivals from duplicating a process before it can be patented and privatized.
Root-Bernstein's theory makes no such testable predictions, and it solves the issue of an incomplete record on September 3rd with incomplete or inaccurate records elsewhere. It seems to me extremely plausible that fleming did not record the results of a botched, uncontrolled experiment but still recognized it as an indicator of something interesting that warranted follow-up. If I were in his position I would preserve the random dish for comparison to the more rigorous follow up experiment. I certainly don't put any stock into the argument that if the story had gone as Root-Bernstein describes it would have been too circuitous for scientific publishing, if anything it would be much more harmonious with standard scientific writing than the chance observation story.
Given that we know that:
- Fleming lived next door to an unsecure mycology lab.
- The temperature during the time period was low enough that if Fleming had left a contaminated culture unattended and non-incubated, he would have had a very high chance of getting the results he became famous for...
Well, given that the probability of discovering penicillin in those conditions is pretty high (say, if he forgot/neglected to incubate one out twenty batches, a 5% chance), and the prior probability of discovering penicillin any other way is extremely low (otherwise other scientists would have found it), bayesian calculus says the stroke of luck hypothesis is probably correct.
This would also explain why the dish was treated with formaldehyde for preservation, and why the dish still exists today.
The alternative would be to freeze the specimens, but that is more cumbersome than stacking formaldehyde-fixed plates on a shelf, and specimens may alter upon repeated freezing and thawing.
Metallurgist is trying out all kinds of steels looking for a particular attribute. He would dutifully record each recipe + test in a notebook but if a particular batch didn't have the attribute, he would throw it out a window into an outdoor scrap pile.
Several months go by and he's cleaning up the pile and notices that one of the blocks has no rust or corrosion. He knows that the pile is six months old but doesn't know which of the recipes this block was connected to.
So he repeats ALL of the block recipes from the last 6 months but labels each block so he can figure out which recipe led to the "stainless" steel.
(Probably not the real story but always loved this telling of it. Actual Wikipedia history is here: https://en.wikipedia.org/wiki/Stainless_steel#History)
https://www.youtube.com/shorts/1Hu0f_ti9EQ
Text from http://montypython.50webs.com/scripts/Series_3/99.htm
"Presenter[John Cleese]: Penguins, yes, penguins. What relevance do penguins have to the furtherance of medical science? Well, strangely enough quite a lot, a major breakthrough, maybe. It was from such an unlikely beginning as an unwanted fungus accidentally growing on a sterile plate that Sir Alexander Fleming gave the world penicillin. James Watt watched an ordinary household kettle boiling and conceived the potentiality of steam power. Would Albert Einstein ever have hit upon the theory of relativity if he hadn't been clever? All these tremendous leaps forward have been taken in the dark. Would Rutherford ever have split the atom if he hadn't tried? Could Marconi have invented the radio if he hadn't by pure chance spent years working at the problem? Are these amazing breakthroughs ever achieved except by years and years of unremitting study? Of course not. What I said earlier about accidental discoveries must have been wrong. "
“Despite this close professional association, however, Hare claims to have played no part in the discovery or original research on penicillin nor to have discussed them with Fleming”
It’s nice to see that the bickering about who stole whose research does not affect all old discoveries.