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The Penicillin Myth
- tetris11 11mo ago(Off-topic:) Scrollbars, and their non-existence.
- jasonjmcghee 11mo agoIt's not the best implementation, but it's there (you just have to scroll a bit to get it to show).
- arjie 11mo agoOh I really enjoyed this one. 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.
- Joker_vD 11mo ago> 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".
- fainpul 11mo agoIsn'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.
- Joker_vD 11mo agoWell, yes. But the expected deviation from the mean is still ≈7.07. And the probability that the outcome will be either 93/107 or 107/93 is (slightly) higher than the outcome being exactly 100.
- fainpul 11mo agoBut those are 2 results. 100 / 100 is more likely than 93 / 107 (or any other specific result) is what I'm saying.
- Joker_vD 11mo agoDepends what you count as a result, I guess. "There is exactly N flips of a single kind" is also a viable definition, just as "The exact sequence of flips was x_0, x_1, ... x_199" is.
- paddleon 11mo agoYou can tell the difference between 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.
- stevenwoo 11mo agoIf 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.
- dexwiz 11mo agoWhat 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?
- stevenwoo 11mo agoRight, my bad for wrong terminology as biology nor botany is not my speciality either. I was thinking along the lines of XY for humans, then the ordinary two row, two column chart used to teach the basics of Mendel with pea plants and dominant/recessive non polygenic traits in introductory biology classes.
- dekhn 11mo agoThe traits he picked- hope I get this detail pedantically correct: had only two alleles, each allele had an obvious phenotype controlled mostly by that gene, the two phenotypes were binary (no intermediate "half-wrinkled-half-smooth"). and all segregated independently (different chromosomes, or far enough that the linkage was extremely weak). I remember my high school teacher speculating he inspected many different phenotypes and then reported his results on the final ones he picked where the results were nice. 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 https://review.ucsc.edu/spring04/bio-debate.html and https://review.ucsc.edu/spring04/twoversions.html 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...
- awkward 11mo agoSo 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.
- microtherion 11mo agocf The Harvard Law: "Under controlled conditions of light, temperature, humidity, and nutrition, the organism will do as it damn well pleases."
- kcexn 11mo agoIt'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.
- dj_gitmo 11mo agoThe Hare theory is a better story, regardless of whether it is true. I am surprised that it hasn't seeped into pop science lore.
- mordae 11mo agoHmm, 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.
- pickledoyster 11mo agoimo, this paragraph covers the essence of a good chunk of the article: https://en.wikipedia.org/wiki/Discovery_of_penicillin#Replication https://en.wikipedia.org/wiki/Discovery_of_penicillin#Replic...
- tolerance 11mo agoWriting like this does not belong on Substack.
- niemandhier 11mo agoThis stood out to me: “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.
- dooglius 11mo agoIs 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.
- jjk166 11mo agoIt'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.
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- dooglius 11mo agoCan someone with more experience in scientific writing comment on > 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.
- paddleon 11mo agoin scientific writing, you need to take 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.
- advisedwang 11mo agoThe goal of a paper is to write up the actual discovery, not to tell a story or explain irrelevant background. The steps he wrote there would confuse rather than elucidate the actual discovery.
- alexpotato 11mo agoOne 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. (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://en.wikipedia.org/wiki/Stainless_steel#History)
- commandlinefan 11mo agoI 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.
- jonny_eh 11mo agoThat one I could totally believe. Radar equipment + chocolate bar = very likely to occur.
- johnyzee 11mo agoThat was a lot of words to get to the point that Fleming probably misremembered the sequence of events when he retold the story 15 years later. He even mentioned this possibility at the time. Interesting article but not much of a mystery.
- keepamovin 11mo agoTangentially related: doxycycline helps improve muscle and tendon tear recovery by enhancing the performance of matrix proteins that form "scaffolding", by inhibiting factors that break them down. "By inhibiting MMPs, doxycycline helps preserve and remodel the ECM, accelerating repair and improving biomechanical strength (e.g., tensile strength and reduced creep/strain)". Crazy. I'm a big fan off high-ROI off-label uses of well-tolerated, cheap, out-of-patent "WHO essential medecines list" pharmas. There's much to be found there. Another tidbit: inderol (propranolol, beta-blocker) can aide PTSD recovery by reducing the emotional potency of traumatic memories when taken in a therapeutic replay.
- catlikesshrimp 11mo agoNot a mention of Clorito Picado? https://en.wikipedia.org/wiki/Clodomiro_Picado_Twight https://en.wikipedia.org/wiki/Clodomiro_Picado_Twight The contest is cold, but it deserves at least a fleeting hint
- glenstein 11mo agoIn 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.
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- kieranmaine 11mo ago> 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.
- mandevil 11mo agoThe cartoon 60% of the way down the article definitely feels like an "artists barely concealed fetish" thing.
- jjk166 11mo agoHare'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.
- jonny_eh 11mo ago> I would preserve the random dish for comparison to the more rigorous follow up experiment This would also explain why the dish was treated with formaldehyde for preservation, and why the dish still exists today.
- pcrh 11mo agoPreserving 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.
- NetMageSCW 11mo agoThe surprising part (or the smart part) is preserving a dish that was randomly contaminated with an unknown mold instead of throwing it out.
- mandevil 11mo agoBest take on serendipty versus effort in the history of science is, naturally enough, from Monty Python: https://www.youtube.com/shorts/1Hu0f_ti9EQ https://www.youtube.com/shorts/1Hu0f_ti9EQ Text from http://montypython.50webs.com/scripts/Series_3/99.htm 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. "
- fn-mote 11mo agoI wish this story were not framed as a “myth”. Far fewer people would read it if they knew the (presumed) truth - a small deviation from the story.
- Peteragain 11mo agoThe Flemming/Florey story is actually an interesting bit of science history, but it's about popular media and the romance of science v.s. how real science is done with patience, selfless dedication and a literature search. When Chain joined the Oxford lab, a literature search turned up 6 candidate "penicillins" which they went on to investigate. Fleming smoked a pipe, got to the office about 10, and was accessible (being in London). This version of the story admittedly comes from a Howard Florey biography I read 10 years ago..
- ggm 11mo agoIf it's the Leonard Bickel one, it's excellent. Fleming is a folk hero. Florey and Chain (and Du Pont, for industrialisation) did the real work.
- lynguist 11mo agoFor me the biggest plot hole of the popular penicillin discovery myth is clearly the open window story, including its multiple side plots with meteorological events. 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.