How we learned to mass-produce penicillin

Today, we are desperately trying to figure out how to combat and keep up with antibiotic resistance — the frustrating tendency for bacteria to evolve defenses against the drugs we depend on to kill them. Seventy years ago, researchers were faced with a very different problem — how to take penicillin, the antibiotic derived from mold, and turn it into something that could be produced in large quantities.

At The Body Horrors blog, Rebecca Kreston writes about this quest and how a single moldy cantaloupe helped launch the (unfortunately) brief era of antibiotic supremacy.

For something that grows so carelessly and freely on our fruits and breads, mass producing the white mold and its hidden wonder drug penicillin was devilishly difficult. After Alexander Fleming’s accidental discovery of a bacteria-killing mold contaminating his cultures of Staphylococcus aureus, it languished as a laboratory parlor trick until World War II and the desperate need for treatments to fight bacterial infections became quickly apparent

It would be another fluke – the discovery of a moldy cantaloupe - that would yield a particular strain of mold that could produce prodigious amounts of this “magic bullet” antibiotic. Factories with the expert know-how on man-handling yeast and fungi into yielding their strange fruits - alcohol distilleries and mushroom factories – were then tasked with the production of penicillin

I particularly dig this video she posted with the story, showing a behind-the-scenes look at how large quantities of penicillin were made during World War II.

Read Rebecca Kreston's full piece


  1. I’ve always found it fascinating that the famous psychedelic LSD was apparently first made via ERGOT a type of fungi/mold. I don’t know the mechanics of the process, but turning ugly green mold into fancy, bright shiny colors and hallucinations is certainly one of Mankind’s strangest achievements

    1. That’s basically the fungus’s defense mechanism. Eating ergot can already give you hallucinations, only it’s on top of nausea, paralysis, and that sort of thing. It used to happen to people because of infected grain, and was called St. Anthony’s Fire. Just like aspirin is based on the medicinal part of willow bark, LSD is basically a refinement of the symptom we wanted.

      1. I once took an extended college course concerning the history of psychedelics as they relate to modern society and social norms, but it turns out the course was all just an elaborate hallucination – go figure!

  2. My understanding was Fleming’s original discovery languished mainly because his group was interested in antiseptics, and it’s not really a cost-effective option for that. It was a little while until a different group started looking at internal uses, although finding a way to mass produce it was still important, of course.

    Also, antibiotics are a Pyrrhic victory? Microbes aren’t really getting worse today; instead they’re slowly going back to being hard to kill, the way they were in the first place. The very worst threat from nosicomial MRSA would be to compare to the tuberculosis and dysentery of the past. Parts of our victory may be fading, but a lot of people have been spared in the mean time, and how are we worse off?

    1.  If we used antibiotics sensibly — not shooting up farm animals so they could gorge themselves in feedlots without getting sick, or selling them over-the-counter to ignorant people who self-prescribe them for colds — we wouldn’t be dealing with nearly as many antibiotic-resistant strains.

      1. I agree entirely; and further, I’ll say it’s a shame drug companies and governments worry so little about developing replacement antibiotics. I just don’t think you can compare things to before the 1940s, and justifiably say “we’ve largely lost the war on microbes.” That really ignores what things were actually like – back then, you know, everything was a superbug without antibiotics to cure.

        1. Governments do not worry thanks to the doctrine of not interfering with the “free” market. While companies can’t be bothered because they have grown so large that the ROI on the research required will not satisfy their growth requirement (that eternal 3%). End result is that we are screwed unless some biotech startup has a “that’s strange” moment…

  3. I’d often wondered how we got from “Huh, I accidentally contaminated this petri dish with mold and it killed the bacterial culture” to widely-available antibiotics. I especially wondered this after BoingBoing posted the Time Traveler’s Cheat Sheet — if I were sent back in time, how on earth could I use the knowledge that bread mold produces penicillin to actually make antibiotics?

    I did some reading and found that you could grow the mold on a liquid medium like milk, and drink the milk, and thereby ingest some penicillin — but it was hard to get a high enough dose to reliably knock out an infection. I did hear about the discovery of the mutant strain of the mold that produced a lot more penicillin, but still didn’t know how you extracted and purified the pencillin itself from the growth medium.

    This video implies that, at least back then, you didn’t — you just dried the liquid medium into powder form and ingested that.

    I also wonder about quality control. How do you test the concentration of penicillin in the resulting powder?

    1. Me momma used to do that. Assay the batches, for the scientists who tweaked the production process.
      The film short-circuited the purification steps … they show this moldy gunk, and then a vial of powder magically appears.

      Assaying for potency involved diluting up samples of the extract, and then applying it to petri dishes of bacteria growing on a thin film of agar. Clear patches would appear on the agar where the bacteria had been killed off, and the diameter of the clear zone indicated the potency of the sample. Needless to say, they went through a lot of petri dishes.

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