Penicillin

A fungal accident in the early 20th century opened the door for the medical wonders of the antibiotic age. In this episode of Invention, Robert and Joe explore what came before and how Alexander Fleming’s discovery changed the world. 

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Episode Transcript

Speaker 1 (00:03):
Welcome to Invention, a production of I Heart Radio. Hey,
welcome to Invention. My name is Robert Lamb and I'm
Joe McCormick and Robert. I know you want to talk
about D and D before we get to the real subject. Well,
I don't know, I was thinking about doing it last.
We can go ahead and talk about it up front. Um. Yeah, Well,

(00:24):
in Dungeons and Dragons, Uh, you have all these various
demon lords. Uh and uh, they they rule over various
sort of portions of the of of the fiend population
in the game. And there are two demon lords in
particular that I was thinking about in regards to today's episode. Uh,
and that that would be zug Boy and jubile X.

(00:45):
So zug Boy is the the demon Lord of fun Guy,
the Queen of fun Guy, the master of Decay, and
then opposing her, Um Everett odds with her is jubile X,
the Faceless Lord, which is a god of uzas and
slimes and blobs, you know, all the the using nasty

(01:05):
creatures of Dungeons and Dragons. And yeah, they're they oppose
each other. They're constant war with each other and in
some campaigns like their forces and even there they're you know,
embodied forms do battle with one another, and it actually
ties in a bit with the subject we're talking about
today of penicillin. Okay, so penicillin the fungus that fights

(01:28):
I don't know, would you call diseases slimes? Well, I
feel like jubile X being the demon lord of uzes
and slimes kind of makes it the demon lord of
of microbiology as well, and you know, microves and uh
and microbial illnesses. So okay, Well, so today we're going
to be talking about penicillin. I guess maybe one of

(01:49):
the great real weapons of zug Tamoi. But this this
came up, I think because we've been talking about fungus
on our other podcasts on Stuff to Blow Your Mind,
where we just finished recording a five part series on psychedelics.
Yeah yeah, looking at fungal psychedelics and ongoing research into
how these substances could enhance our mental well being and

(02:09):
helping the treatment of the psychological issues. And one of
our big take homes was that these fungi could help
save lives and improve the quality of human life. But
it would not be the first or only fung gui
to do so, because we can certainly look to various
interactions between human hell the different fungi species and their use,
and traditional medicine. We can point to various products including

(02:31):
you know, products of fermentation, for instance, including alcohol. But
there's an even better example of better living through fungi,
and that's penicillin. Right, So today we're going to briefly
explore the invention of penicillin, which is often cited as
the first true antibiotic technology. Of course, antibiotics or medications
that treat infections by killing, injuring, or slowing the growth

(02:54):
of bacteria in the body, and antibiotics are a class
of what you would generally call antimicrobial drugs, medicines that
kill microbes that present a threat to the body. Of course,
an antibiotics generally fight bacterial infections, whereas you could have
others like anti fungals that fight fungal infections or anti
virals that fight viral infections. Now, antimicrobials and antibiotics are

(03:18):
a gigantic subject area that we're of course not going
to be able to get into every nook and cranny
of the subject, but we hope we could have an
interesting introductory introductory discussion, maybe come back to antibiotics sometime
again in the future, because it's a it's a broad
invention that has lots of little invention tributaries throughout history. Yeah,

(03:38):
but it is such a fascinating case to look at,
and I think should make for a great episode of
invention here because for starters, it's it's a twentieth century
invention slash discovery. Often, of course, the line between invision
and discovery is a little bit gray, but we can, Yeah,
we can pinpoint it and ultimately like rolled out by
or so, but that we can, we can look to it.

(04:00):
We can look at the world before, and we can
look at the world after with it with the sort
of clarity that we don't always have with certainly older
or more ancient inventions. Exactly because we always like to
ask the question on this show, what came before the invention?
What what changed when this invention came on the scene. Uh,
And what came before widespread modern antibiotics was stupendous amounts

(04:21):
of death and misery from infectious disease in blood poisoning.
I was wondering, like, is it even possible to to
get stats on what the world of infectious disease looked
like before we had antibiotics around the mid twentieth century. Yeah,
I mean, to a certain extent, a lot of the
suffering is just incalculable, um, you know, especially if you

(04:43):
go back and sort of consider all of human history
up to that point and the various factors that that
influenced infectious disease and injury, you know, the eventually the
rise of germ theory, but also the things like they
the rise of cities and so forth. But but LUCKI yea,
since it was such a recent invention, we have some
pretty incredible stats on the matter. Um, you know, suddenly

(05:06):
thinks to this new miracle drug, diseases that had simply
ravaged the global population, like syphilis, could be cured. The
shadow of lethal infection no longer hung, at least as
heavily over every scrape, injury and war wound and with
wounds were often talking about sepsis, which is a term
that was used by Hippocrates back in the fourth century

(05:28):
b c. Meaning blood rod or blood poisoning, and he
was referring more generally, I think, to decay, but the
term came to be applied to blood poisoning, which arises
when the body's response to infection causes causes injury to
its own tissue and organs. But just prior to the
twentieth century, infectious diseases accounted for high morbidity and mortality

(05:50):
rates around the world, even in the industrialized world. According
to W. A. Adgy in the Treasure called Antibiotics, from
two thousand sixteen, the average life expectancy at birth was
forty seven years, forty six and forty eight years from
men and women, respectively, and this was due to the
dangers of smallpox, uh cholera, diphtheria, pneumonia, typhoid fever, plague, tuberculosis, typhus, syphilis,

(06:16):
and a host of other ailments that could afflict you.
And then during the antibiotic era that follow again you know,
arising in the middle of the twenty century, the leading
cause of death in the United States changed from communicable
diseases to non communicable diseases like cardio cardiovascular disease, cancer,
and stroke, and the average life ex expectancy at birth

(06:38):
rose to seventy eight point eight years, so the elderly
were no longer a mere four percent of the population,
but grow to become a whopping percent of the population.
So you know, we're talking about you know, profound changes
just to demographics based on this new uh, this new invention. Yeah,
the change is huge. I mean, we live in a
world now where if you have access to high quality

(07:01):
modern medicine, and a lot of people don't, I mean
that's something mind. But if you have access to high quality,
modern science based medicine and you can get antibiotics and uh,
and you can get to a hospital or see a doctor,
you very likely have a good chance to beat most
of the common infectious diseases that people get unless you
have some kind of you know, like another condition that

(07:22):
exacerbates it or something. Before antibiotics, this was just not
that people just died from diseases that you catch, like
diseases that are common for people to catch all the time. Yeah,
Or you had certain diseases like syphilis that were virtually uncurable,
you know, and and some of the the cures that
were attempted were pretty horrendous, you know, and and and

(07:45):
had and and generally did not work, you know, talking
about like using mercury and so forth. And you mentioned
before contamination of wounds. I mean, this is just a
huge thing, just like you know, you might, uh, you
might cut yourself while gardening and you die from it. Yeah,
and Heaven forbid you undergo say medieval gall stone surgery
or something like that. By the way, I think tuberculosis

(08:09):
has a you know, is a good example to look
at for some of these stats as well. According to
the c d C, t B was a leading cause
of death in the US in nineteen forty prior to
the rollout of antibiotic therapy in nineteen hundred, a hundred
and ninety four of every hundred thousand US residents died
from the t B. Uh. Most were residents of urban areas.

(08:30):
In nineteen hundred, the three leading causes of death in
the US word pneumonia, tuberculosis and diarrhea and uh enteritis,
which together with diphtheria, caused one third of all deaths,
and of these deaths, forty percent were among children aged
less than five years old. Now, to your point, and
not everybody has the access to antibiotics that say people

(08:56):
enjoy and say Europe in the United States, Um, Yeah.
T remains a leading cause of death from an infectious
disease in many parts of the world, particularly the developing world,
and some antibiotic treatments or antibiotic assisted treatments are more
complicated and more difficult than others. I mean, I know
the treatment for TB is not as say, easy as

(09:16):
the round of just orally administered antibiotics that you might
get for a standard bacterial infection. Right but it's suddenly
it was just a heralded rightfully so is as a
miracle invention. When it came about you, I saw an
image of of a sign I think a garbage can
ra a mailbox from the mid twentieth century, advertising that

(09:36):
now you can get gonna recured in in uh like
four hours thanks to the you know, these new developments
in antibiotics. You know, it's just a it can be
difficult to put ourselves in that mindset, having grown up
in the wake of antihiblotics, or at least most of us,
most people listening to this show. I was just thinking
about how many like US presidents died of infections of

(10:00):
various kinds. Uh that that that seems like that would
be a very unusual thing to happen now, But like
in the eighteen hundreds, James Garfield got shot, but it
wasn't the initial gun shot that killed him. He lived
for like, I think weeks afterwards, he got an infection
in the wound, I think because they were digging around
with dirty hands to try to get the bullet out
of him, and he and they didn't have antibiotics of

(10:22):
course when he got an infection, so he died. I
think another U s p. It was at William Henry Harrison,
who I think they think now died from probably like
drinking fecal contaminated water in the White House. Yeah, so
many different U UH injuries and infections were just far
more likely to be lethal with you know, without modern
antibiotics to step in and UH and EID in the fight. Now,

(10:46):
there were some things that were kind of like versions
of antibiotics or antimicrobials from before the discovery of penicillin
in nine Yeah, the best example from the period just
immediate immediately prior to pnicillin would be the sulfonamides or
the sulfa drugs. And these were the first antibacterials to
be used systematically, and they were synthesized in nineteen thirty

(11:10):
two in the German laboratories of bear A g. Now
you might be thinking about the timeline, Like, wait a minute,
didn't we just say that penicillin was discovered in twenty eight,
But it took a long time after the discovery of
penicillin's uh antibacterial properties for it to be made as
a useful medical tribe Like it was ninety generally that's
the day you see for when penicillin actually became an

(11:32):
actionable thing in medicine. Uh So, yeah, before that, we
had the sulfa drugs and it had they had a
rocky start, but they did prove very effective in preventing
wound infections during the Second World War. They were used
on both sides in the in the form of sulfa
pills and also sulfa powders that would be sprinkled over
a wound. So if you've ever watched you know, uh,

(11:54):
some sort of period piece, so especially a war piece
from the twentieth century, and you see somebody sprinkling outer
over an injury, that is what that's supposed to be.
Sulfa drugs. They're not as effective as true antibiotics like
penicillin um and there are a number of possible side
effects that one that can take place, and it also
can't be used to treat syphilis, and it also can't

(12:16):
treat sulfa resistant infections. Now, of course, this is also
a twentieth century invention, So I was wondering, did anybody
come up with any version of antibiotics or proto antibiotics
before the twentieth century. We know that penicillin hadn't been
discovered and isolated and made stable as a useful medicine,

(12:37):
But were there any thing's like antibiotics or sort of
precursors of antibiotics. Well, because in Game of Thrones, right,
they have penicillin, don't they? Or they have some sort
of fantasy version of penicillin. I've never heard of that,
don't they? They have something that the the the the
old masters would mention having to do with with bread
and mold or something, didn't they. I don't remember that.
I just remember people get cuts and then they get

(12:58):
infected and die. Give milk of the poppy. I mean,
they have milk of the poppy that our Game of
Thrones are are George R. Martin readers will have to
write in on that, but I vaguely remember there being
like allusion to something like, uh, some sort of mold
based uh medicine that they were using. Uh, I could

(13:18):
be wrong in it. Well, I can't see that being
something that's thrown in there as a little aside, but
that like isn't widely recognized or used. Maybe uh. And
it's interesting how that kind of parallels some interesting pieces
of evidence for proto antibiotic technology in the real world,
even going back to ancient times. So I want to
look at the work of the Emory University bio archaeologist

(13:42):
George J. R. Meligos, who is now deceased. I think
he died inteen. But he's interesting, interesting scholar, and he
discovered something very curious back in nineteen eighty. So the
subject he was looking at was a set of human
bones from ancient Nubia, dating from between three fifty and

(14:03):
five fifty c E. And so the bones came from Nubia,
which is a region of Africa along the Nile River
but south of Egypt and what would be modern day Sudan.
And what these bones showed was evidence that the people
they belonged to had been taking tetracycline. Now, tetracycline is
not the same as penicillin, but it is an antibiotic.

(14:26):
It can be used to treat all kinds of infections,
from minor problems like acne, I think in concert with
some other drugs to major diseases like plague or tularemia
or even syphilis. And Tetracycline works primarily by binding to
the ribosomes of bacterial cells. Ribosomes are sort of the
cellular factories. They build proteins that are needed in order

(14:47):
for organisms to live and grow, and by binding to
the ribosome, tetracycline makes it difficult for the bacterium to
create new proteins. It was patented in the nineteen fifties
and became widely used in the in half of the
twentieth century. Uh so what was it doing in the
bones of Nubian people who live like seventeen hundred years ago. Well,

(15:08):
our Melagos and colleagues followed archaeological clues to identify the
source of the tetracycline, which was beer. Ah. Of course
beer is another one of Ultimately it falls under zugdmoise domain.
Oh yeah, though this is different because tetracycline is not
made from a fungus. It is actually an antibacterial that
is a byproduct of some bacteria. Okay, so it's a

(15:31):
bacterial byproduct, but essentially so technically it's jubilex okay, or
point to this is jubilex versus jubilex. Right, Well, I
mean that's going to happen with your demon inter Jubilan warfare.
Uh So, beer is made from fermented grain, of course,
and the fermented grain in this ancient Nubian beer apparently

(15:52):
contained the bacteria stripped to mices, which creates tetracycline as
a byproduct. But a question of course, so were these
traces of tetracycling in Nubian mummy bones a sign of
like a bad batch of beer they got contaminated by accident,
or were these people deliberately culturing their beer with antibiotic

(16:13):
producing bacteria and so to look at a study from
the American Journal of Physical Anthropology from twenty ten, of
which arm Lagos was one of the authors. The authors
examine tetracycling in skeletal remains from throughout this period and
the evidence indicates that the ancient Nubians were consuming these
antibiotics on a regular basis, and the authors suggests that

(16:34):
these ancient people were intentionally producing this medicine, and this
links up with some evidence from other ancient people's nearby,
such as the Egyptians that sometimes apparently used beer as
a treatment for conditions like gum disease and other types
of infections, and the authors even found evidence of a
four year old child whose skull contained lots of tetracycling

(16:57):
from this beer, suggesting that the child had been fed
high doses of this like antibiotic beer, perhaps in an
attempt to cure an illness, maybe the illness that killed him.
And so the levels of tetracycline residue found in the
bones of these mummies is only explicable if they were
repeatedly consuming this antibiotic in their diet, and there are

(17:18):
actually other archaeological remains that show evidence of antibiotic use
in the ancient world. For example, samples taken from the
fhemera of skeletons from the Dochlay Oasis in Egypt, from
people who live sometime in the late Roman period also
showed evidence of the same thing of tetracycline in the diet,
and this consumption of tetracycline is consistent with other evidence

(17:40):
showing a relatively low rate of infectious disease in Sudanese
Nubia during that time period, and a lack of bone
infections apparent in these remains from the this oasis in Egypt.
So it really does look like people in ancient Africa
discovered a somewhat effective form of antibiotic centuries before the

(18:01):
discovery of penicillin and the isolation and mass production of
focused anti microbial medicines. Now, to be clear, I think
like a beer that had tetracycling content from from being
cultured with bacteria like this probably would not be as
potent and focused and effective as like the isolated compounds
in the drugs you'd take orally or through injection would

(18:22):
be today, but it would have some effect, and it
appeared that it probably was somewhat effective in fighting infectious disease, right,
And of course they wouldn't know exactly what they had here,
but they knew they had some sort of beer that
seemed to some sort of of holy liquid that that
that had some sort of curative property to it exactly,
I mean, a fascinating discovery from the ancient world. Another

(18:44):
interesting fact, tetracycling is relatively unique in that it leaves
clear signatures in the bones that can be discovered long
after the person has died, so other antibiotics don't leave
these clear markers like this that make it easy for
archaeologists detect. So you have to wonder, like, are there
were there other cases of ancient peoples in various places

(19:08):
and times using some kind of antibiotics or bacterial or
fungal cultures uh to treat diseases like these ancient Nubian
people were, but that we don't have evidence of because
it doesn't show up in the bones like tetracyclin does. Yeah,
it could have just been lost to history. I was
reading an interesting paper from Frontiers in Microbiology in two

(19:29):
thousand ten by A. Roost dam Aminov called a Brief
History of the Antibiotic Era, Lessons Learned and Challenges for
the Future. And Amanov points out this unique quality of
tetracycline and notes just what I was basically just saying,
like how easy it would be for evidence of other
uses of antibiotics in the ancient world to be lost
to us. Though he he also mentions that there are

(19:50):
other anecdotes from history about like cultural traditions that show
proto antibiotic technologies and these other examples would include red
soil is found in Jordans that are used for treating
skin infections. It's been discovered that these soils contain some
antibiotic producing organisms, though I guess there are probably also
some major risks in applying soil to wounds, and then

(20:13):
also plants used in traditional Chinese medicine that actually do
have some antimicrobial properties. Yeah, because one thing we have
to remember is like the modern antibiotic effort is ultimately
based in going out into the natural world and finding
these weapons that already exist and then reusing them and
adapting them for human medicine. And you know, this is

(20:37):
essentially what is going on in traditional medicines as well.
And it also means that there are weapons out there
that either have not been discovered at all at all,
especially in particularly vibrant ecosystems, some of which of course
are threatened. All the more reason to uh for us
to not decimate say the rain forests or the deep ocean.

(20:57):
But then there are also things that may have been
discovered to some degree in the past but have been forgotten. Well. Yeah,
and that that does seem possible because despite all all
this evidence of ancient sort of proto antibiotic technologies. The
worldwide rates of death from infectious disease in the periods
for which we have data, right before the invention of
modern antibiotics shows that humans generally did not have effective

(21:22):
antimicrobials in that period. So maybe some of this knowledge
was lost over time. Alright, well, on that note, we're
going to take our first break. But when we come back,
we're going to return to the mold research of the
nineteenth century and ultimately to our key inventor here, Alexander Fleming. Alright,

(21:47):
we're back now. We'll get to Alexander Fleming in a
minute with the discovery of penicillin. But Alexander Fleming was
not the first person to notice that there might be
some anti microbial properties of certain fun guy. That's right,
there was, there was work going on in this area
prior to Flaming. Flaming was was, you know, picking up
on some of it, and uh, and really just overall

(22:10):
just our understanding of a fun guy in general was
was advancing. As we mentioned in our Psychedelics episodes, you know,
there was a time where we did not recognize fun
guy as being separate from the realm of plants before
we realized that it was a kingdom unto itself and
almost ultimately a kingdom that has a little more in
common with the animal Kingdom than it does with the

(22:31):
plant Kingdom. And uh, there are a lot of talented
folks working in this area, but one of them, mind
comes as a surprise to a lot of people. Um,
and that's because her name was Beatrix Potter. Uh the
way the bunny rabbit, the bunny rabbits, yes, off the
bunny rabbit fame. Uh, that was It was kind of
a curious coincidence because I was reading about all this

(22:53):
and then just randomly on the Stuff to Blow your
Mind discussion module, which is the Facebook group for people
who listen to the show to this ust episodes, someone
brought up Beatrix's Potter in regards to something to do
with squirrels, because there's a lot of squirrel uh a
squirrel content in the discussion module, And yeah, they brought
up Patrick's Potter. And Beatrix's Potter actually ties into this

(23:14):
episode a little bit because, in addition to being the
author and illustrator of the you know, the Tale of
Peter Rabbit and associated British animal tales, she was also
a naturalist with a great deal of interest in astronomy
and most importantly of all, mycology. So she produced a
lot of just beautiful scientific watercolor illustrations of various fun

(23:34):
guy uh in her you know neck of the British woods, um,
and you know, as part of her studies, and she
studied a lot of local molds as well and did
illustrations of them. Uh. You know, she's she's ultimately a
very interesting character. That was you know, Unfortunately she lived
in a time in which, you know, the sexism of

(23:54):
the day prevented her from i think reaching the heights
of in the natural sciences that she would have been
afforded later on. But and then a lot of her
work is also just being i think rediscovered and appreciated
for the first time, you know, in recent decades. But
but yeah, the next time someone busts out some theatrics potter,

(24:14):
remember this is not just an individual who wrote some
fanciful tales and illustrated them like she was also just
she was out there studying the natural world and uh
and created in advancing our understanding of a mycology. She
was sort of looking into the hidden life of nature.
In multiple ways. Yeah, And you know, and I see
some sources out that they are like asking the question, Okay,

(24:37):
was Theatric's potter or she or a true naturalist, a
true natural scientists over she just a uh, you know,
an amateur that was just very interested in these things.
And I don't know, it's kind of a complicated question
to ask when you consider like the limitations uh in
the Victorian era for women. But I think undoubtedly she
she I would side with the fact that she was

(24:59):
a natural scientist. I mean, she authored or co authored
one paper if I remember correctly, So I'm gonna give her,
give her full credit. Was it about a fun guy?
It was? It was it was a mushroom in particular. Um,
I forget it was one of those related to the
rusula mushrooms, but I forget which species. But but yeah,

(25:19):
basically she was you know, she was kind of up
up against the patriarchy for the most part. Though. Yeah, Well,
is it time to turn to penicillin itself? Yes, let's
turn to this the key discovery here and our inventor,
our discoverer, Alexander Fleming. Okay, so who was Alexander Fleming? Okay?
So Fleming was born in eighteen eighty one died in

(25:40):
nineteen fifty five and he was a Scottish biologist, physician,
microbiologist and pharmacologist. He was the son of a farmer
and he observed and studied a great deal of death
from sepsis in World War One. He observed that while
um anti septics worked well at the surface, a deeper
wounds sheltered bacteria from the effects of things like sulfa drugs. Right, So,

(26:04):
if you have a kind of superficial wound, you could
clean it off pretty good and that might help protect
you from from bacterial infection. But if you have a
deep wound and say like dirty stuff, bits of soil
and other you know, just crud gets lodged deep in there,
you might not be able to clean the wound out
very well. Right, And that's exactly the kind of stuff
that's gonna get lodged in there, especially with your war

(26:26):
wounds where there is a you know, a stab or
you know, or or a deep cut, or a bullet
entering the body. What makes me think about the when
we were reading about the idea of Stegosaurus, perhaps weapon
iz I mean not consciously, but the stegosaurus perhaps uh
having an adaptation to weaponize infection against its enemies by

(26:48):
dragging its thagamizer spikes through the dong exactly. Yeah, having
dirty thagamizer spikes and then when it wacks the t
rex in the crotch with them, that that gets infected
later and eliminates a predator from the area. Yeah. And uh,
the the predators of the day would not have had
access to antibiotics certainly not or even that beer from
that we mentioned earlier. So uh, Fleming was you know,

(27:11):
devoted himself to research and he uh prior to penicillin,
he discovered lysozyme and naturally occurring enzyme and mucus and
other parts of the body then inhibits bacteria. So you know,
he was already you know, in this this area, you know,
looking for for new new breakthrough his new discoveries. But
then his biggest breakthrough of all is this discovery of penicillin.

(27:34):
And it's truly one of the more amazing invention slash
discovery moments from history because while he was exactly the
right person to make the discovery and then deserves all
the credit he was given, the key moment comes down
really to pure luck, and we simply don't know if
anyone else would have made the discovery if he had
not been there to observe it. Okay, so what happened

(27:56):
with this discovery? So around like ninety seven or so,
he had engaged himself in studying um staff Lecock either
or you know staff, and he had stacks of Petrie
dishes dish specimens in his lab, which I've seen described
as being kind of an untidy lab. So you know,
imagining all these like like Petrie dishes, full staff all
over the place, notes and so forth. And so the

(28:19):
key moment comes in September of nine, right, right, So
he has he has the staff Petrie dishes out and
then he leaves them for the weekend to go on
holiday with his family, and he when he comes back,
he expects to just see how they've progressed, see how
they've grown, but he finds that they haven't grown. In fact,
they have died. Something has ravaged his specimens. Yeah, now,

(28:39):
it's this is one of those stories where he gets
very narrativised. So you do have to wonder if some
details of it are embellished, how the story may have
changed over time. But This is the way the story
has been passed down, and and I think it seems
to be largely basically true. Uh. The way that I've
seen the story often told is that he comes in,

(29:00):
there's a blob of mold growing in one of the plates,
and all around the mold there's this halo of nothingness where,
you know, normally what you would see is that if
you've got a plate for culturing bacteria, there would be
these dots and blobs on the on the plate, but
instead there's this halo where there's no bacteria, bacterial dead zone. Now,
of course we know Staphylococcus is is a bacterium group

(29:23):
linked to all kinds of human disease and misery. I
think staff infections. Right, if this mold could kill staff,
that seems medically relevant. So what happened here? Well, Um
he realized that he was dealing with some sort of
a fun guy, you know, so he luckily there was
a mycologist with a lab just below Fleming on the
floor below his lab, a man by the name of C. J.

(29:46):
La Touche. And in fact, it's also been suspected that
the mold and question that killed Um Fleming's staff might
have drifted up from Latch's lab, adding an extra element
of we your chance to this whole situation. Okay, so
perhaps his samples were contaminated by stuff from the lab

(30:07):
next door down the floor. That's that's what that's not.
That's not a theory that's presented in every source, but
it does pop up fairly frequently. So specifically, this mold
was what would later be identified as a strain of
Penicillium notatum, and it was obvious that it secreted something
that prevented staff bacteria from growing, and so Fleming followed

(30:30):
up in studying this secretion, this this mold juice as
I've seen it called uh he. He He found that it
didn't only prevent the growth of Staphylococcus, it worked against
common bacteria like Streptococcus or ninja caucus and uh and
thea also against the bacterium that causes diphtheria. Interestingly, while
Fleming did see applications for penicillin and curing disease, and

(30:52):
he mentioned them briefly in the paper he published in
ninety nine about this discovery about the anti bacterial properties
of Penicillium uh he primarily thought of this secretion of
penicillium as a tool for bacteriologists to sort strains of
bacteria basically into penicillin sensitive versus non penicillin sensitive species,

(31:16):
and that that that could be useful in the lab. Yeah,
so he sometimes criticized is really not understanding completely what
he had here, not having the vision to see where
it could go. Well, I don't think he completely understood,
but he did indicate that this could possibly have uses
in medicine. Um So Fleming and his assistance Stuart Kratak
and Frederick Ridley tried for years to turn this accidental

(31:40):
discovery into a stable, isolated compound that would be useful.
And this is this was a problem because like so
you've got this secretion from the mold, it molds, making
some juice. It's kind of getting stuff wet with this
this stuff that that that fights bacterial growth. But they
couldn't isolate the comp hound that was causing the effect

(32:01):
and stabilize it and make it make it generally useful.
So to quote from Amanov's paper Amanov that I mentioned earlier, quote,
for twelve years after his initial observation, Alexander Fleming was
trying to get chemists interested in resolving persisting problems with
the purification and stability of the active substance, and supplied

(32:23):
the penicillium strain to anyone requesting it. But he really
he could never crack the nut ultimately, and he didn't
finally make this discovery of the process for for stabilizing
and isolating the compound. And by Amanov writes that Fleming
finally abandoned dis quest. But fortunately it was right about

(32:44):
that time that a capable team at Oxford University, including
the researchers Howard Floory and Earnst Chain or China, they
picked up on this research and they they kicked off
the research project that would eventually break through on this. Uh.
And they're all these interesting stories. So of course this
is wild. World War two is going on, so research

(33:05):
conditions are not ideal. And uh, they're all these stories
about how they turned their lab at Oxford into this
giant incubation center or sort of factory for mold. Like
they employed all these lab assistants who are these women
who had been referred to in some sources as the
penicillin girls, and they would work to like to they

(33:26):
would work to grow the penicillin and buckets and tubs
and basically every container that they could um and uh,
eventually they did. They were able to isolate and stabilize
this compound. So to quote from an article from the
American Chemical Society, quote in nineteen forty Floory and that
would be Howard Flory carried out vital experiments showing that

(33:49):
penicillin could protect mice against infection from deadly strepped to
cock eye. Then, on February twelve, nineteen forty one, a
forty three year old policeman, Albert Alexander, became the first
recipient of the Oxford penicillin. He'd scratched the side of
his mouth while pruning roses and had developed a life
threatening infection with huge abscesses affecting his eyes, face, and lungs.

(34:13):
Penicillin was injected and within days he made a remarkable recovery.
But unfortunately, despite this recovery, which lasted for a few days,
they ran out of the drug and Alexander eventually got
worse again and he died. And I was reading that
they were so desperate to cure him that after Alexander
urinated while on his antibiotic course, they would collect the

(34:36):
urine and try to extract the penicillin he excreted again
so that it could be re administered to him. Uh.
And I should mention also that the process that the
Oxford team relied on to extract and purify the penicillin
in the mold juice was led by another important biochemist,
a guy named Norman Heatley. But this case of Albert
Alexander shows an obvious early problem they had, which was

(34:58):
the problem of ska old. They simply lacked the ability
to make penicillin at the scale that would be needed
to treat even one person, let alone the whole world. Uh.
The strain of mold that they were using didn't make
enough of it, and this led to the search for
other species of the same fungal genus Penicillium, which would,

(35:19):
maybe they thought, produce higher concentrations of the penicillin filter rate.
And I was reading an interesting article by the University
of Michigan physician and medical historian Howard Markle that tells
a really interesting story. I've never heard about this. Uh.
So the story goes like this. Apparently, one of the
assistants at the Oxford lab showed up for work one

(35:39):
day in ninety one with a cantalope that she'd bought
at the market because it was covered in a weird
looking golden mold, which is great because this would be
the one case where somebody is picking over the fresh
produce produced to like find the MOULDI one, But the
mold on this cantalope turned out to be a strain
of penicillium called Penicillium chryso geum, which Marco says naturally

(36:01):
produced at least about two hundred times as much penicillin
as the original strain that they've been studying. And then
later Marco writes that the same strain was subjected to
mutagenic processes in the labs, like bombarding it with X
rays and stuff, to produce a mutated strain that would
make up to a thousand times as much penicillin as
the old school fleming mold. So by penicillin is on

(36:26):
its way to becoming a viable medicine. All right. On
that note, we're going to take a quick break and
when we come back, we're gonna look at the impact
of penicillin, and we're gonna look at it, and I
think a fun way by considering a really interesting what
if alright, we're back. So we often don't don't do

(36:52):
a lot of what IF's on invention. I thought we
we kind of do. It's a certain extent, but I
mean a lot of times it's a harder case be
made for, like what if this had not been invention
invented right bit or discovered because in most cases you
can you can you can look at the data, you
can look at other individuals work, Like if the Right
brothers had not invented the airplane, uh, had not you know,

(37:14):
created that that first prototype that really showed what was possible. Like,
clearly there were there were other individuals in the world
working on this. Someone would have cracked it. If if
Runkin had not discovered X rays in eighteen ninety whatever
year it was, somebody else would have discovered them pretty soon. Right,
But when it comes to penicillin, uh, it potentially gets

(37:35):
a little more complicated than that. I ran across a
cool article on the topic titled what if Fleming had
not discovered penicillin? And this was published in the Saudi
Journal Um of Biological Sciences by al Harvey at All.
The authors admit that that certainly, if Fleming hadn't made
the discovery someone else might have in the years to follow,

(37:57):
probably you know, in the early nineteen forties. They they estimate,
so we could still well have it have arrived in
the antibacterial age. However, they also explore the possibility that
we might have simply not made the discovery at all,
and it's an interesting argument. So I want to read
a quote from the paper here. Quote. Of course, penicillin
could have been discovered the day after Fleming missed the opportunity,

(38:21):
but in reality, there was no parallel discovery that took place.
As a result, anyone taking an interest in penicillin during
the nineteen thirties did so in the knowledge of Fleming's work.
In particular, there seems no reason to believe that Flory
and Chain would have discovered penicillin, since their work depended
on Fleming's famous paper and their access to one of

(38:42):
his penicillin producing cultures. Okay, so that's referring to the
thing I mentioned about how how Fleming and his assistance
were just like sharing the penicillium straining out with everybody, like, hey,
can you figure out what's going on with this? Can
you isolate the secretion or the compound in the secretion. Yeah,
so so to think about that there was there was
so far as these researchers could determine, you know, no

(39:04):
other effort out there that would have struck paydir. In
the absence of Fleming's research, the Oxford group wouldn't have
been looking for it. Selman Waksman, the father of modern
antibiotics is he sometimes called, who made several key discoveries later,
was also inspired by Fleming. So it's it's one of
these cases where like he seems to be the epicenter uh,

(39:26):
well not not only him, but just then the the
the the seemingly chance encounter h in his lab that
day that that where suddenly this halo appears in the
petri dish, and that gives birth to a to a
whole class of other discoveries. Right, because not all UH
antibiotics are derived from penicillin, the penicillin class of antibiotics

(39:49):
becomes sort of like one sort of grandfather class. But
then there are all these other classes that are discovered
during this golden age of antibiotics that takes place over
the next few decades. Yeah, and they're very just additional
medical breakthroughs that would not have occurred without penicillin, such
as organ transplant. But then there's also the question like
what would have what would have happened in the wider world,

(40:11):
because again, penicillin comes online during the Second World War,
and so that you can easily ask, well, what would
have happened if Allied troops had not benefited from access
to antibiotics that D Day? I've never thought about that.
In fact, before looking at this episode, I probably would
not have known the answer to whether or not they
had access to antibiotics. Well, penicillin production was actually swiftly

(40:34):
scaled up just to make sure that Allied soldiers had
access to it at D Day. UM, So there's a
legitimate question to be asked, might the Allies not have
won the Second World War without penicillin? Um? I think
there are a lot of factors to consider there. I
don't think that it's quite a gotcha question, but it's
it's worth thinking about. The authors argue that without Fleming's discovery,

(40:59):
we would have had to do and on the sulfa drugs, uh,
you know, an imperfect alternative to true antibiotics, and these
uh you know, these were described in the nineteen thirties
and Fleming worked with him prior to his discovery, but
without penicillin in play, the authors argue that sulfa drugs
might have become the standard and even pushed the discovery

(41:19):
of true um antibiotics well beyond the nineteen sixties. And
this is also true of the Access Powers had risen
in victorious in World War Two, because the Access Powers
depended on sulfa drugs as their their key treatment. Um.
You know, they do point point out that, you know, quote,
despite the fact that the Germans and their allies were
at a considerable disadvantage, Uh, the sulfa drugs did a

(41:41):
relatively good job at reducing battle casualties. So not to
just completely um, you know, cast aside the effectiveness of
sulfa drugs, but still they were not as effective as
true antibiotics. It's weird to think about the political implications
of specific medical technologies. Yeah, and then when you get
down to the curious cases of individuals, it also gets interesting.
We already touched on presidents who died that would have

(42:05):
lived potentially if there had been penicillin around. Uh. And
so they point out that that SOFA drugs saved Churchill's
life in ninety three when he was suffering from pneumonia
as well as FDR's life. But there's also evidence by
the way that actual penicillin may have saved Hitler's life.
Following the Staffenberg assassination attempt of July nine, this was

(42:30):
the plot that tried to kill Hitler with a briefcase bomb,
like where some of the officers conspired against him and
they put a briefcase bomb in the room with him,
and it did explode, but he was protected by like
a heavy table that prevented it from killing him. He
was obviously injured, and I think he had like nerve
damage after that. So the idea here is that perhaps
his injuries were treated by by penicillan. Yeah, that's at

(42:54):
least an argument has been made that they had access
to penicillin. I'm unclear on how they would have obtained it,
you know, I'm sure maybe there's a spy story there.
I don't know, but the idea being, well, if he
had if he had didn't have access to penicillin, then
perhaps he would have died, and that would have arguably
ended the war, you know, in a different manner, forcing
us to reimagine an entirely different post war world. So

(43:18):
again we're playing with with what EFF's here and and
also we in my understanding is we don't know for
sure that Hitler had access to penicillin following that assassination attempt,
but there is the overall scenario of the Allies having
penicillin and having this ramped up penicillin production leading into
D Day. Yeah, that is really interesting. I had never

(43:38):
contemplated that before. Um Now, something that I we do
often have to think about and we should probably acknowledge
at the end here before we move on. Maybe this
will be something to come back and UH do in
the future with a recent invention episode is the idea
of a possible end of the antibiotics age. I mean,
this is a kind of scary thing to imagine, Like

(43:58):
what if the antibiot next age is essentially a period
in history that has a beginning and an end. Because
as we you've you've probably heard about this, many disease
causing bacteria and other disease causing microbes are over time
evolving antibiotic resistance are evolving to to be powerful enough

(44:19):
to survive our antimicrobial drugs. And I think specifically one
thing that's exacerbating this is overuse of antibiotics and people
not taking the entire course of antibiotics when they're given them. Yeah,
because again, to come back to the Zagdamoy jubile X
war scenario, you know, it is an ongoing battle and
the forces evolve, uh to uh to better deal with

(44:43):
the threats on each side. And so you know, we're
we're we're we're seeing this occur. We're seeing the overuse
of antibiotics producing uh, you know, strains that are that
are resistant, and it's reversing some of the therapeutic miracles
of the last fifty years, and and underscores the importance
of disease prevention in addition to treatment, and that means

(45:05):
not not abandoning some of our other vital tools for
human health like vaccination. Oh yeah, we should come back
and revisit vaccinations or maybe even various different vaccinations in
the future. Yeah. Another thing to keep in mind that
I don't think we mentioned earlier was that the nineteen
forties through the nineteen seventies are are considered like the
golden age of antibiotic research, and we haven't seen at

(45:28):
least if we haven't seen any new classes of antibiotics
emerged since that time period right now, there have been
new developments in antibiotics, but I think the way I've
read it is that they're generally modifications on existing classes
of antibiotics, sort of like we we haven't. We haven't
found anything radically new since then. Basically, we reached out
into the natural war between between fungi and the microbial legions,

(45:53):
and we we stole some of the tools, We stole
some of that Promethean fire when we we keep adapting
that fire to our own purposes, but we haven't. We
haven't found any new weapon from that world. And uh,
and then their ongoing war continues to change. I'd be interested.
Do you out there, you the listener, do you work

(46:14):
in medical research? Are you working on areas involved in
antibiotic resistance? The future of anti microbials? I please get
in touch with us. I would like to hear about that.
What what are you doing in your work and what
does the future look like to you on the inside. Absolutely,
we would we would love to hear from you. Again,
we've only really scratched the surface here though thanks to antibiotics,

(46:35):
hopefully that scratch will not uh get interested life threatening infection.
But yeah, there's a lot more history here, but but
hopefully what we've done here today is of course highlight
just a very very cool story from the history of
inventions and discoveries and human history and outlined the impact
of of one of the greatest inventions or discoveries. Again,

(46:57):
however you want to classify it from the toy a century, yeah, totally.
In the meantime, if you want to check out other
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(47:19):
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(47:44):
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