Very cool story. However, the unlikeliness of Hare's story seem to be highly overstated. A cold spell may have been unlikely, but we can't count that against Hare's account given that we know it actually happened. Another of the coincidences is also common to the other account: he still had to luck across the correct mold by chance. So the only distinguishing unlikelihood is Fleming forgetting to incubate (or the incubator failing, etc.) the plate, which is hardly winning the Powerball unlikely.
In contrast, the other hypothesis (at least as presented here) seems like it would have been easy to back up if it were true. Did Fleming test any other molds for lysozymes in his lab notebook or is penicillium the first and only mold recorded? Did he record any other lysozyme searching experiments happening at this time (or near this time)? And what exactly where the staph experiments he was working on at the time (was it being used a lysozyme control already as hypothesized)? All of this seems like it should be at least partially present in the lab notebooks and so would be easy to support the Root-Bernstein theory if true. If not present at all, it makes Root-Bernstein harder to believe. Perhaps these were omitted for brevity but they should be verifiable.
Unfortunately, I wasn’t able to access Fleming’s notebooks and independently confirm their contents. My descriptions were taken from Hare and Root-Bernstein’s books. Yet, even if I could, I’m not sure how helpful they would have been.
In 1982, Hare lamented the fact that, although the notebooks had been deposited in the British Library, “There are long breaks in the dating for which there is no obvious reason, and the complete absence of some researches known to have been carried out. To make matters worse, although the books are available for inspection, they cannot be used or cited without the permission of the owner of the copyright, who refused it for this article... Historians of modern medical science, when dealing with the Fleming Papers, should be warned in advance of this hazard.”
Whether that situation has improved, I don’t know.
That's very unfortunate, though the situation with the copyright likely has changed. That Hare paper says Lady Fleming controlled copyright on Fleming's notebooks (which at the time were at the British Library) and prevented him from reproducing aspects of it. Assuming that Lady Fleming is Alexander's second wife Amalia Fleming, she passed away in 1986. The lab notebooks are now apparently housed at the Fleming Museum: https://www.fleming.gr/impact/fleming-museum in Greece (where Amalia is from).
"For example, Craddock provided his own account of the famous discovery in a letter to Hare. He began by explaining that he started working in Fleming's laboratory, which was shared with Maclean, in August 1928 whilst Fleming was on holiday at Mildenhall. Craddock confirmed that the agar plates were stacked in a pile at the right hand side of the bench and had been used by Fleming before he went on holiday. When Fleming returned, Craddock moved up 1/2 a floor to the big laboratory in which Day also worked. Within a few days of the discovery, Craddock was put to work on growing the mould for the production of mould juice. "
This quite backs up Hare's account but with the caveats that I cannot verify the primary source (attributed to the "Hare archive") and that it was from a 1956 letter and therefore as susceptible to the faults of memory as any other account (could he really have remembered which side of the bench the plates were placed on the first day he worked in a lab?).
Another tidbit from the same secondary source is that after discovering Penicillium, Fleming's notes do show him going on to culture many other molds to search for the same effect. Root-Bernstein's account depends either upon him getting lucky the first time or on him doing this repeatedly but not recording it (despite recording later attempts).
Moreover, there appear to be several accounts of the accidental discovery of the mold growth on the plate, from Fleming, Craddock, Pryce, and Macfarlane. There are contradictions (Pryce claims to have spotted it first) and none are contemporary but no one seems to contradict the basic idea of seeing a plate upon return from vacation that suggested antimicrobial effects.
Lastly, it does seem that the cultures being left on the bench (and not incubated) is part of the "official" story (Fleming says so in his 1929 publication) and therefore hardly an obstacle for Hare's accounting.
All told, the more I read, the more fits with Hare's account. One point to the contrary is that if the windows weren't open (as Hare claims and seems likely) then would the indoor temperature of the lab (which was in use by others at the time of Fleming's vacation) actually have reached the outdoors temperatures that Hare claims are necessary? I guess the heat wouldn't have been on at that time of year so it's plausible.
I did find, not the contents of Fleming's notebooks, but a sort of index of them: https://www.yumpu.com/en/document/view/3275148/the-alexander-fleming-papers-british-library (it requires a free account to download a pdf version). Apparently the Craddock notebooks of the relevant time (1928) were at the British Museum at the time. The many mentions of testing mold are either undated or are after the penicillin discovery.
Currently a few chapters into The Demon Under the Microscope by Thomas Hager (2006) which seems to be about the history of antibiotics. We haven't gotten to Fleming yet but I imagine it will be touched on at least, I'm curious now what version of the story it will tell.
That is an excellent book. I can't recall 100%, but I think it doesn't cover penicillin and instead focuses on the sulfas and Bayer's chemists throughout. But I could be wrong!
You're right. I'm nearer the end now and this is just about Sulfa. But thanks to this article I've added Miracle Cure: The Creation of Antibiotics and the Birth of Modern Medicine to me to-read list.
Fascinating article
Very cool story. However, the unlikeliness of Hare's story seem to be highly overstated. A cold spell may have been unlikely, but we can't count that against Hare's account given that we know it actually happened. Another of the coincidences is also common to the other account: he still had to luck across the correct mold by chance. So the only distinguishing unlikelihood is Fleming forgetting to incubate (or the incubator failing, etc.) the plate, which is hardly winning the Powerball unlikely.
In contrast, the other hypothesis (at least as presented here) seems like it would have been easy to back up if it were true. Did Fleming test any other molds for lysozymes in his lab notebook or is penicillium the first and only mold recorded? Did he record any other lysozyme searching experiments happening at this time (or near this time)? And what exactly where the staph experiments he was working on at the time (was it being used a lysozyme control already as hypothesized)? All of this seems like it should be at least partially present in the lab notebooks and so would be easy to support the Root-Bernstein theory if true. If not present at all, it makes Root-Bernstein harder to believe. Perhaps these were omitted for brevity but they should be verifiable.
Unfortunately, I wasn’t able to access Fleming’s notebooks and independently confirm their contents. My descriptions were taken from Hare and Root-Bernstein’s books. Yet, even if I could, I’m not sure how helpful they would have been.
In 1982, Hare lamented the fact that, although the notebooks had been deposited in the British Library, “There are long breaks in the dating for which there is no obvious reason, and the complete absence of some researches known to have been carried out. To make matters worse, although the books are available for inspection, they cannot be used or cited without the permission of the owner of the copyright, who refused it for this article... Historians of modern medical science, when dealing with the Fleming Papers, should be warned in advance of this hazard.”
Whether that situation has improved, I don’t know.
https://pubmed.ncbi.nlm.nih.gov/7047933/
That's very unfortunate, though the situation with the copyright likely has changed. That Hare paper says Lady Fleming controlled copyright on Fleming's notebooks (which at the time were at the British Library) and prevented him from reproducing aspects of it. Assuming that Lady Fleming is Alexander's second wife Amalia Fleming, she passed away in 1986. The lab notebooks are now apparently housed at the Fleming Museum: https://www.fleming.gr/impact/fleming-museum in Greece (where Amalia is from).
"For example, Craddock provided his own account of the famous discovery in a letter to Hare. He began by explaining that he started working in Fleming's laboratory, which was shared with Maclean, in August 1928 whilst Fleming was on holiday at Mildenhall. Craddock confirmed that the agar plates were stacked in a pile at the right hand side of the bench and had been used by Fleming before he went on holiday. When Fleming returned, Craddock moved up 1/2 a floor to the big laboratory in which Day also worked. Within a few days of the discovery, Craddock was put to work on growing the mould for the production of mould juice. "
This quite backs up Hare's account but with the caveats that I cannot verify the primary source (attributed to the "Hare archive") and that it was from a 1956 letter and therefore as susceptible to the faults of memory as any other account (could he really have remembered which side of the bench the plates were placed on the first day he worked in a lab?).
Another tidbit from the same secondary source is that after discovering Penicillium, Fleming's notes do show him going on to culture many other molds to search for the same effect. Root-Bernstein's account depends either upon him getting lucky the first time or on him doing this repeatedly but not recording it (despite recording later attempts).
Moreover, there appear to be several accounts of the accidental discovery of the mold growth on the plate, from Fleming, Craddock, Pryce, and Macfarlane. There are contradictions (Pryce claims to have spotted it first) and none are contemporary but no one seems to contradict the basic idea of seeing a plate upon return from vacation that suggested antimicrobial effects.
Lastly, it does seem that the cultures being left on the bench (and not incubated) is part of the "official" story (Fleming says so in his 1929 publication) and therefore hardly an obstacle for Hare's accounting.
All told, the more I read, the more fits with Hare's account. One point to the contrary is that if the windows weren't open (as Hare claims and seems likely) then would the indoor temperature of the lab (which was in use by others at the time of Fleming's vacation) actually have reached the outdoors temperatures that Hare claims are necessary? I guess the heat wouldn't have been on at that time of year so it's plausible.
I did find, not the contents of Fleming's notebooks, but a sort of index of them: https://www.yumpu.com/en/document/view/3275148/the-alexander-fleming-papers-british-library (it requires a free account to download a pdf version). Apparently the Craddock notebooks of the relevant time (1928) were at the British Museum at the time. The many mentions of testing mold are either undated or are after the penicillin discovery.
Reads like a thriller!
And whatever happened I'm grateful it did.
Currently a few chapters into The Demon Under the Microscope by Thomas Hager (2006) which seems to be about the history of antibiotics. We haven't gotten to Fleming yet but I imagine it will be touched on at least, I'm curious now what version of the story it will tell.
That is an excellent book. I can't recall 100%, but I think it doesn't cover penicillin and instead focuses on the sulfas and Bayer's chemists throughout. But I could be wrong!
You're right. I'm nearer the end now and this is just about Sulfa. But thanks to this article I've added Miracle Cure: The Creation of Antibiotics and the Birth of Modern Medicine to me to-read list.
Brilliant, thoughtful writing on a topic that couldn't be more relevant right now.