The Penicillin Myth
asimov.press
asimov.press
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.
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?
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 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.
It is far from having a "lack of reproducibility" and in fact allowed others to quickly and accurately replicate his discovery.
And you can tell - ‘the history of penicillin’ implies a very different thing than ‘the myth of penicillin’ eh?
A mythology is just a system of stories and beliefs. Nationalism, religion, fandom, etc. All mythologies based on a shared set of stories. Some are more true (and/or complete) than others, but that's not the important part of being a mythology.
Note also that we do call mythology "history". It's just a matter of where you inhabit on the contextual spectrum. I'm sure you can think of several trivially-refuted examples, and I'm also sure that you realize that your preferred narrative is equally refuted by others.
You're correct of course, and they are not. But also the converse.
Mythology is also separated from history in the study of it, at least in the west, because history is required to be based on independently verified facts.
Mythology clearly is not.
That's convenient, if your preferred mythology matches up to your culture's mainstream accepted view of history. But it is not definitionally more correct.
This is the cognitive bias/belief side of Gell-Mann amnesia, as held by a culture.
I am not discounting the possibility that some mythologies are more true, or more supported, or more plausible, than others. Just that it's not a requirement or a disqualification.
Is there still a fundamental difference between what we ‘know’ about Zeus and Caesar?
You bet.
If for no other reason than one begs to be challenged with evidence (and has mechanisms to vet/change, etc!) and the other is the opposite.
Yes!
But both narratives are mythologies.
This is an interesting example. What we think we know about Caesar has lots of documentation (much of it written by himself), and the correspondence to truth for a great deal of it, is absolutely unknown.
I'd agree that the Caesar mythology is clearly more truthy than the Zeus mythology. But that doesn't make it any more of less of a mythology.
Caesar was born to a wealthy family, did lots of things, led armies, wrote lots of words, crossed a river, challenged some ideas, offended some people, got killed by a mob.
Add any more detail to that, and you're building a mythology. It doesn't matter if it's true. Every single one of those "facts" has a mythology attached to it, and the whole system of stories is the Caesar mythology.
You picked Caesar, which I think is an interesting but easily-debunked choice. Any historian of the era would agree that there's an enormous mythology built around Caesar's life.
Something simpler and more recent? Would you say there's no mythology around the Kennedys or the Clintons? (There is so much mythology around those people it's hard to imagine an argument otherwise).
Anywhere there's a collective interpretation of a narrative, there's a mythology.
(It might be important that "collective interpretation of narrative" is also a reasonable definition of "history", and that any interpretation is a likely introduction of error or at least lossy compression -- which is the same thing.)
Zeus didn’t, and in fact that is clearly acknowledged.
You’re building a giant vague narrative about something which is not vague at all.
We know that Caesar lived. We probably also know that Jesus lived. They are both real people (probably) and also icons.
Zeus did not live, as we understand him, but the notional Zeus is derived from earlier prototypes and it's even possible that there was a real human behind proto-Zeus as there is behind notional Jesus. There is more documentation behind Caesar, of course, but the full truth of "Caesar" the icon is equally unknowable.
All of these characters have extensive mythologies about the details, intentions, and meanings of their lives.
Many of those details are unverifiable-but-critical parts of their stories, and the purposes those stories serve. Even the verifiable points of truth have mythologies around their meaning.
This may devolve into a question of what is knowable and what is unknowable. Facts are very very important, but they are not the most powerful force in society.
If you want to argue that you are a scholar of the early Roman Empire, and you know everything there is to know about Caesar, that's fine -- but the scholarship changes, and all you are saying is that you can recite the most-accepted-today interpretation of sparse facts. Interesting, but not authoritative.
They say that history is written by the victors. Caesar was a victor until he was not. They do not say that history is truth.
I understand the confusion though.
Yes, there is always a degree of myth in common usage. Yes, there is always an element of distortion in history. And the further we go in time, the more history turns into myth as actual evidence gets lost, buried, destroyed, manipulated, etc. And history gets manipulated for political purposes.
But there is a giant valley between the common case of myth, and any formal study of history. For real reasons, because there are fundamental differences in approach and goals. Think 90/10 one way, 10/90 the other way (hopefully).
Because any study of history which isn’t solidly based on actual independently verifiable facts or evidence isn’t history, it’s just myth making. And those are different words for real reasons. Including trying to fight manipulation and BS. Something that is really important for us to remember, especially now.
Because at some point, something either did actually happen or not, and for folks who care, that matters. If people don’t, that’s fine - but let’s not confuse anyone by confusing the resulting cool stories with actual history eh?
It's a mistake to pretend that any "historical record" is not littered with these things. More so as the years tick by, more so if there's any contention around influence or meaning of the person/story. (Aside: This is why I will not watch Oliver Stone movies.)
There is (usually) a bright line between truth and falsehood. We almost never know where that line is.
Sure, some details are documented and plausible. These are probably true, unless there are details that are very important or useful to some group.
And some details are incredible and fanciful. Probably "false" although possibly derived from some kernel of truth or substantively true but simplified/embellished for audiences over time.
The deeper you dig, the more you realize that all stories are incomplete at best, and likely several layers deep in manipulation or at least imperfect interpretation. We are all imperfect interpreters.
Do I believe that Caesar crossed the Rubicon in 49 BC? Yes -- with very high certainty.
Do I believe that he uttered Iacta Alea Est just before doing so? Maybe -- it's romantic and flatteringly displays his executive strength, and IIRC he wrote that he did.
If you want to delineate "history" from "myth" on the "truthy-falsy" spectrum, you may choose to do so with that example. But this history and mythology are inseparable, so the distinction is untrustworthy and often not useful anyway.
You can redefine words if you want, but don't pretend your definitions are useful for clear communication with others.
A mythology is not necessarily untrue, although they do have a tendency toward expansiveness, which has a coincident trend toward favored interpretations.
But the ultimate truthiness (if it can be measured at all) is neither requirement nor disqualification, vis a vis being a mythology.
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.
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.
"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.
93 heads, 107 tails and
93 tails, 107 heads
but not between
100 heads, 100 tails and
100 tails, 100 heads.
So while those are two results (93/107 and 107/93), they really only count as two separate outcomes if you pre-specify that the first number is heads.
If instead you consider symmetries, where there are 2 ways to get 93/107 and only one wall to get 100/100, then you have more likelihood for the 93/107 outcome because you have two ways to get it.
It will be a bell curve with 100/100 as the peak
Intuitively, this seems right to me, but sometime statistics do not follow intuition.
But the summed probability of the “not too far away results” is much higher, i.e. P([93, 107]\{100}) > P([100]).
So if you only shoot 100/100 with your coin, that's definitely weird.
Not if you only try once.
For "coin flips", read: human lives, financial investments, scientific observations, historical observations (how many distinct historical analogues are available to you), dating (see, e.g., "the secretary problem" or similar optimal stopping / search bounding problems).
With sufficiently low-numbered trial phenomena, statistics gets weird. A classic example would be the anthropic principle: how is it that the Universe is so perfectly suited for human beings, a life-form which can contemplate why the Universe it so perfectly suited for it? Well, if the Universe were not so suited ... we wouldn't be here to ponder that question. The US judge Richard Posner made a similar observation in his book "Catastrophe: Risk and Response" tackles the common objection to doomsday predictions that all have so far proved false. But then, of all the worlds in which a mass extinction event has wiped out all life prior to the emergence of a technologically-advanced species, there would be no (indegenous) witnesses to the fact. We are only here to ponder that question because utter annihilation did not occur. As Posner writes:
By definition, all but the last doomsday prediction is false. Yet it does not follow, as many seem to think, that all doomsday predictions must be false; what follow is only that all such predictions but one are false.
-Richard A. Posner, Catastrophe: Risk and Response, p. 13.
<https://archive.org/details/catastropheriskr00posn/page/13/m...>
For a fair coin, hitting 100/100 is ~5%, vs. ~30% falling in [97; 103] \ {100}. You can simulate here: https://www.omnicalculator.com/statistics/coin-flip-probabil...
That's because "something slightly off the middle" is a large group of possible results. Of course you can assemble a group of possible results that has a higher likelihood than a single result (even the most likely single result!). But you could make the same argument for any single result, including one of the results in your "slightly off the middle" group. Did you get 97 heads? Well you'd have a higher likelihood of getting between 98 and 103 heads. In fact, for any result you get, it would have been more likely to get some other result! :D
Isn't that the point? The odds of getting the "most likely result" are lower than the odds of getting not the most likely result. Therefore, getting exactly 100/100 heads and tails would be unlikely!
There's probably a dorm-quality insight there about the supreme unlikeliness of being, though: out of all the possible universes, this one, etc...
> "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".
Inverting the statement makes it read something like this:
You are more likely to not get 100/100 than you are to get exactly 100/100
...which is exactly what I was saying. Nobody is arguing that there is a single value that might be more likely than 100/100. Rather, the argument is that a 100/100 result is suspiciously fair.
A slightly imperfect split is more likely to convince your teacher that you did the assignment. Intuitively this should be obvious.
You could just as easily say "you should be suspicious if you flip a coin 200 times and get exactly 93 heads, because it's far more likely to get between 99 and 187 heads."
For example, you take the top five cards, and you get a royal flush of diamonds in ascending order. In theory, this sequence is no more or less probable than any other sequence being taken from a randomly shuffled deck. But given that this sequence has special significance to people, there's a very good reason to think that this indicates that the deck is not randomly shuffled.
In theory terms, you can't just look at the probability of getting this result from a fair coin (or deck or whatever). You have to look at that probability, and the probability that the coin (deck etc.) is biased, and that a biased coin would produce the outcome you got.
If you flip a coin that feels and appears perfectly ordinary and you get exactly 100 heads and 100 tails, you should still be pretty confident that it's unbiased. If you ask somebody else to flip a coin 200 times, and you can't actually see them, and you know they're lazy, and they come back and report exactly 100/100, that's a good indicator they didn't do the flips.
Eh, this only makes sense if you're incorporating information about who set up the experiment in your statistical model. If you somehow knew that there's a 50% probability that you were given a fair coin and a 50% probability that you were given an unfair coin that lands on the opposite side of its previous flip 90% of the time, then yes, you could incorporate this sort of knowledge into your analysis of your single trial of 200 flips.
That's true of every result. If you're using this to conclude you have a weird coin then every coin is weird.
"More likely"? How can you even estimate the likelihood of the coin being "an imperfect PRNG" based on a single trial of 200 flips?
If a student was tasked with determining some physical constant with an experiment and they got it exactly right to 20th decimal place - I'll check their data twice or thrice. Just saying. You continue believing it was the most likely value ;)
Graphing here https://www.wolframalpha.com/input?i=graph+%28%28N%2F2+choos... and it does look like it's only a slight improvement in likelihood, so I did overstate the claim. A more interesting case would be to look at some self-correcting physical process.
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.
Unfortunately, most modern genotypes and phenotypes in humans don't follow these patterns, and over the years, genetics devloped an entire vocabulary and physical model to explain them, although at a fairly abstract level. None of it made any sense to me so I follow the biophysics/molecular biology approach which tends to consider many more underlying physical details
There's a related story, https://review.ucsc.edu/spring04/bio-debate.html and https://review.ucsc.edu/spring04/twoversions.html which shows how different fields think about the genotype/phenotype relationship. Grinding up steering wheels to figure out how they work...
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.
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.
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.
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.
Why was he placing plates streaked with staphylococcus near a window and then peering at them every few days?
Perhaps he was testing some other hypothesis that didn't turn out? The effect of sunlight on staphylococcal growth, maybe? Or perhaps the window is simply incidental?
He only noticed after he got back from vacation, or so the story goes. And it may not have been an open window, could have been a desk near the doorway.
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.
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.
Another tidbit: inderol (propranolol, beta-blocker) can aide PTSD recovery by reducing the emotional potency of traumatic memories when taken in a therapeutic replay.
https://en.wikipedia.org/wiki/Clodomiro_Picado_Twight
The contest is cold, but it deserves at least a fleeting hint
Fleming is a folk hero. Florey and Chain (and Du Pont, for industrialisation) did the real work.
And that that story exists and has PREVAILED despite the fact that everyone knows that the same building was housing a mycology laboratory only a flight of stairs away, and that it was the mycology colleague La Touche who identified the penicillin.
> It’s too circuitous and indirect for a scientific report
The preceding paragraph does not seem unreasonable to me--maybe a bit too glib, but nothing that couldn't be touched up.
100 articles at 6 pages each
and condense them to 1 article of 6 pages
And add how your method/insight moves the conversation forward, along with describing your method/insight.
The reason why scientific writing can be hard to read from the outside is the 100:1 compression. Decompression of that can require some knowledge of the field.
Also, some people are just bad at writing.