Invention Playlist 4: Penicillin

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

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Episode Transcript

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production of I Heart Radio Hey, welcome to Invention. My

(01:27):
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,
in Dungeons and Dragons, Uh, you have all these various
demon lords h and they rule over various sort of

(01:49):
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 Ex. So
Zugmoy is the the demon lord of Fungui, the Queen
of fun Guy, the Master of Decay. And then opposing her,

(02:13):
Um Everett odds with her is jubile X, the Faceless Lord,
which is a god of ouzas and slimes and blobs,
you know, all the the ouzing, nasty creatures of Dungeons
and Dragons. And yeah, there they oppose each other. They're
constant war with each other and in some campaigns like
their forces and even there there, you know, embodied forms

(02:34):
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 I don't know, would
you call diseases slimes? Well, I feel like jubile Ix,
being the demon lord of uzes and slimes kind of
makes it the demon lord of of microbiology as well,

(02:57):
and you know, microves and and microbial illnesses. So okay, well,
so today we're going to be talking about penicillin. I
guess maybe one of 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

(03:18):
part series on psychedelics. Yeah yeah, looking at fungal psychedelics
and ongoing research into how these substances could enhance our
mental well being and 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 fun guy to do so, because we can certainly

(03:39):
look to various interactions between human hell the different fungi
species and their use and traditional medicine. We can point
to various products including 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
gonna briefly explod or the invention of penicillin, which is

(04:01):
often cited as the first true antibiotic technology. Of course,
antibiotics or medications that treat infections by killing, injuring, or
slowing the growth of bacteria in the body, and antibiotics
are a class of what you would generally call anti
microbial drugs, medicines that kill microbes that present a threat

(04:22):
to the body. Of course, an antibiotics generally fight bacterial infections,
whereas you could have others like antifungals that fight fungal
infections or anti virals that fight viral infections. Now, antimicrobials
and antibiotics are 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

(04:46):
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, 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 invasion and discovery is a little bit gray,

(05:09):
but we can, Yeah, we can pinpoint it and ultimately
like rolled out by or so, But so we can,
we can look to it. 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

(05:32):
invention came on the scene? Uh? And what came before
a widespread modern antibiotics was stupendous amounts 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

(05:55):
a certain extent, A lot of the suffering is just incalculable, um,
you know, especially if you go back and sort of
consider all of human history up to that point and
the various factors that that influenced infectius, disease and injury,
you know, the eventually the rise of germ theory, but
also the things like the rise of cities and so forth.

(06:16):
But but luckily, yeah, since it was such a recent invention,
we have some pretty incredible stats on the matter. Um,
you know, suddenly thinks to this new miracle drug diseases
that it 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

(06:37):
wound and with wounds were often talking about sepsis, which
is a term that was used by Hippocrates back in
the fourth century 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 cause

(06:58):
its injury. To its own tissue you in organs. But
just prior to the twentieth century, infectious diseases accounted for
high morbidity and mortality rates around the world, even in
the industrialized world. According to W. A. Adeg in the
Treasure called Antibiotics, from two thousand sixteen, the average life
expectancy at birth was forty seven years, forty six and

(07:21):
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,
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

(07:43):
cause of death in the United States changed from communicable
diseases to non communicable diseases like cardiov cardiovascular disease, cancer,
and stroke, and the average life ex expectancy at birth
rose to seventy eight point eight years. So the elder
you were no longer a mere four percent of the population,
but grow to become a whopping cent of the population.

(08:06):
So you know, we're talking about you know, profound changes,
just two 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
modern medicine, and a lot of people don't, I mean
that's mind. But if you have access to high quality,
modern science based medicine and you can get antibiotics and uh,

(08:28):
and 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
exacerbates it or something. Before antibiotics, this was just not
that people just died from diseases that you catch, like

(08:48):
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 cures that were
tempted we're pretty horrendous, you know, and and and had
and and generally did not work, you know, talking about
like using mercury and so forth. And you mentioned before

(09:09):
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. Yea. By the way, I think tuberculosis
has a you know, is a good example to look
at for some of these stats as well. According to

(09:31):
the CDC, 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 deep
t B. Uh most were residents of urban areas. In
nineteen hundred, the three leading causes of death in the

(09:52):
U S word pneumonia, tuberculosis and diarrhea and uh enteritis,
which together with diphtheria caused one heard 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

(10:13):
enjoy and say Europe in the United States. Um, Yeah.
TB 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

(10:33):
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 as 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

(10:53):
now you can get gonea recured in in uh like
four hours thanks to the you know, these new developments
in antibiotics. You know, it's just a it could be
difficult to put ourselves in that mindset, having grown up
in the wake of antihilotics, 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

(11:17):
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

(11:39):
course when he got an infection, so he died. I
think another U S pro 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 UH injuries and infections were just far more
likely to be lethal with you know, without modern antibiotics

(12:00):
to step in and UH and EID in the fight. Now,
there were some things that were kind of like versions
of antibiotics or anti microbials from before the discovery of
penicillin in ninety eight. Yeah, the best example from the
period just immediate immediately prior to penicillin would be the
sulfonamides or the sulfa drugs. And these were the first

(12:22):
antibacterials to be used systematically, and they were synthesized in
nineteen thirty 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

(12:44):
nineteen forty generally that's the day you see for when
penicillin actually became an 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

(13:07):
be sprinkled over a wound. So if you've ever watched
you know, some sort of period piece, so especially a
war piece from the twentieth century, and you see somebody
sprinkling powder 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

(13:30):
it also can't be used to treat syphilis, and it
also can't 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

(13:53):
useful medicine, 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.

(14:14):
I just remember people get cuts and then they get
infected and die giving the milk of the poppy. I
mean they have milk of the poppy. Okay, 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

(14:36):
could 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

(14:56):
look at the work of the Emory University bioarchy all
just George J. R. Meligos, who is now deceased, I
think he died in 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

(15:20):
and five fifty C. And so the bones came from Nubia,
which is a region of Africa along the Nile River,
but south of Egypt in 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

(15:40):
not the same as penicillin, but it is an antibiotic.
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

(16:01):
cellular factories. They build proteins that are needed in order
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 second half of the
twentieth century. Uh so what was it doing in the

(16:21):
bones of Nubian people who live like seventeen hundred years ago. Well,
our Melagos and colleagues followed archaeological clues to identify the
source of the tetracycline, which was beer. 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

(16:45):
is a byproduct of some bacteria. Okay, so it's a
bacterial byproduct, but essentially okay, So technically it's jubilex okay,
or point to jubile This is jubilex versus jubilex. Right, Well,
I mean that's going to happen with your demon laws
intra Jubilan warfare. Uh So, beer is made from fermented grain,
of course, and the fermented grain in this ancient Nubian

(17:08):
beer apparently contained the bacteria stripped to mices, which creates
tetracycling as a byproduct. But a question of course, so like,
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

(17:29):
beer with antibiotic producing bacteria and so to look at
a study from the American Journal of Physical Anthropology from
two of which arm Lagos was one of the authors.
The authors examine tetracyclin 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

(17:51):
suggests that these ancient people were intentionally producing this medicine.
And this links up with some evidence from other ancient
peoples 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 author has even found
evidence of a four year old child whose skull contained

(18:13):
lots of tetracycline 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,

(18:35):
and there are 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 and the diet, and this consumption of tetracycline is

(18:56):
consistent with other evidence 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
this oasis in Egypt. So it really does look like
people in ancient Africa discovered a somewhat effective form of

(19:16):
antibiotics centuries before the 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

(19:38):
or through injection would 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

(19:58):
fascinating discovery from the ancient world. Another 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 to detect.
So you have to wonder, like, are there were there

(20:21):
other cases of ancient peoples in various places 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 tetracycling does. Yeah, it
could have just been lost to history. I was reading

(20:43):
an interesting paper from Frontiers in Microbiology in two thousand
and 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
tetracycling and notes just what I was based least, just
saying like how easy it would be for evidence of
other uses of antibiotics in the ancient world to be

(21:04):
lost to us. Though he he also mentions that there
are other anecdotes from history about like cultural traditions that
show proto antibiotic technologies, and these other examples would include
red soils 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

(21:27):
some major risks in applying soil to wounds, and then
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

(21:50):
adapting them for human medicine. And you know, this is
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 for us, or the

(22:13):
deep ocean. 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,

(22:33):
right before the invention of modern antibiotics shows that humans
generally did not have effective 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

(22:54):
our key inventor here, Alexander Flintman. Today's episode is brought
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(24:44):
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 just our understanding of

(25:07):
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 plant kingdom. And uh,

(25:29):
there are a lot of talented folks working in this area,
but one of them might come as a surprise to
a lot of people. Um, and that's because her name
was Beatrix Potter. Uh wait, 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 and then just randomly on the Stuff to

(25:50):
Blow your Mind Discussion module, which is the Facebook group
for people who listen to the show to discuss episodes,
someone brought up Beatrix 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 beatrics. Potter actually ties into
this episode a little bit because in addition to being

(26:12):
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 guy uh in her you know, neck of the
British woods um and you know, as part of her

(26:35):
studies and just 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 the day prevented her from i think
reaching the heights of in the natural sciences that she

(26:55):
would have been afforded later on. But and then a
lot of her work is also just being i think
rediscovered and appreciated it for the first time, you know,
in recent decades. But but yeah, the next time someone
busts out some Theatric's Potter, Remember this is not just
an individual who wrote some fanciful tales and illustrated them

(27:16):
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 there that
are like asking the question, Okay, was Beatric's Potter or
she or a true naturalist, a true natural scientists over

(27:37):
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 a natural scientist. I mean,
she authored or co authored one paper if I remember correctly,

(28:00):
So I'm I'm gonna give her give her full credit.
Was it about a guy? It was? It was it
was a mushroom in particular. Um, I forget it was
one of those related to the Russula mushrooms, but I
forget which species. But but Yeah, 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

(28:22):
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 nineteen fifty five, and he
was a Scottish biologist, physician, microbiologist and pharmacologist. He was
the son of a farmer and he he observed and

(28:45):
studied a great deal of death from sepsis in World
War One. He observed that while um antiseptics worked well
at the surface, a deeper wounds sheltered bacteria from the
effects of things like sulfa drugs. So, if you have
a kind of superficial wound, you could clean it off
pretty good and that might help protect you from from

(29:07):
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 wounds where there
is a you know, a stab or you know, or
or a deep cut or a bullet entering the body.

(29:29):
What makes me think about the when we were reading
about the idea of stegosaurus perhaps weapon ize I mean
not consciously, but the stegosaurus perhaps uh having an adaptation
to weaponize infection against its enemies by dragging its thagamizer
spikes through the dung exactly. Yeah, having dirty thagamizer spikes
and then when it wacks the t rex in the

(29:51):
crotch with them, that that gets infected later and eliminates
a predator from the area. Yeah, and that 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, devoted himself to research
and he uh, prior to penicillin, he discovered lysozyme and

(30:12):
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. And
it's truly one of the more amazing invention slash discovery

(30:34):
moments from history because while he was exactly the right
person to make the discovery and just 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
with this discovery? So around like nine or so, he

(30:56):
had engaged himself in studying um staphlocock either it 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 key
moment comes in September of nine, right, right, So he

(31:19):
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 it's
this is one of those stories where he gets very narrativised.
So you do have to wonder if some details of

(31:41):
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, there's a blob
of mold growing in one of the plates, and all
around the mole there's this halo of nothingness where you know,

(32:02):
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 a bacterium group linked
to all kinds of human disease and misery. I think
staff infections. Right, if this mold could kill staff, that

(32:25):
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.
Law Touche. And in fact, it's also been suspected that

(32:45):
the mold and question that killed um Fleming's staff might
have drifted up from a Latch's lab, adding an extra
element of weird chance to this whole situation. Okay, so
perhaps his sam bowls were contaminated by stuff from the
lab next door or down the floor. That's that's what
That's not. That's not a theory that's presented in every source,

(33:08):
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 up in studying the secretion this this mold juice

(33:29):
as I've seen it called uh 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 the back also against the bacterium that causes diphtheria. Interestingly,
while Fleming did see applications for penicillin and curing disease,
and he mentioned them briefly in the paper he published

(33:50):
in ninety nine about this discovery about UH the the
antibacterial 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

(34:10):
sensitive species, 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

(34:35):
turn this accidental 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 compound that was causing the

(34:56):
effect and stabilize it and make it make it generally
use full. 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,

(35:18):
and supplied the penicillium strain to anyone requesting it. But
he really he could never crack the knot ultimately, and
he didn't finally make this discovery of the process for
for stabilizing and isolating the compound, and by ninety Amanov
writes that Fleming finally abandoned dis quest. But fortunately it

(35:39):
was right about 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

(35:59):
going on, so research 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

(36:21):
to like they 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 Floory carried out vital experiments

(36:44):
showing that penicillin could protect mice against infection from deadly
stripped 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 scrap the side
of his mouth while pruning roses and had developed a
life threatening infection with huge abscesses affecting his eyes, face,

(37:08):
and lungs. 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,

(37:30):
they would collect the urine and try to extract the
penicillin he excreted again so that it could be readministered
to him. Uh. And I should mention also that the
process that the Oxford team relied on to extract and
purify the penicillin and 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,

(37:53):
which was the problem of scale. 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,

(38:14):
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 day

(38:35):
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 mouldy one. But the mold
on this cantalope turned out to be a strain of
penicillium called Penicillium chryso geum, which Marco says naturally produced

(38:57):
at least about two hundred times as my 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 its

(39:21):
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. I'm

(39:42):
Colleen with joined me the host of Eating While Broke podcast,
While I eat a meal created by self made entrepreneurs,
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(40:03):
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(40:26):
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(40:48):
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every single Monday on the Black Effect Podcast Network. Hello,
I'm Minni drive her and on my podcast Many Questions,
I asked trailblazes across different disciplines the same seven questions,
questions about the inflection points in their life, what they

(41:09):
like least about themselves, and what relationship has to fined
love for them. This season, I'm coming back with new
trailblazes like Blondie vocalist Debbie Harry, journalist and television host
Jeremy Clarkson, editor in chief of Instar Magazine Laura Brown,
and creative Juggernaut Goldie. Join me as we continue this
exploration on season two of Many Questions on the I

(41:30):
Heart Radio app, Apple Podcasts or wherever you get your
favorite podcasts. All right, we're back. So we often don't
don't do a lot of what ELFs on invention. I
thought we we kind of dode to a certain extent.
But I mean a lot of times it's a harder
case to be made, like what if this had not

(41:51):
been invention in dated right or discovered? Because in most
cases you can you can you can look at the data,
you can look at other individuals were like if the
Right brothers had not invented the airplane, uh not, you know,
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

(42:13):
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
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

(42:35):
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.
Probably you know, in the early nineteen forties, they estimate,
so we could still well have it have arrived in
the antibacterial age. However, they also explored the possibility that

(42:58):
we might have simply not made the discovery at all,
and it's an interesting argument. So I want, 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, 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

(43:20):
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 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

(43:42):
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 think
about that. There was there was so far as these
researchers could determine you know, no 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. Slmon Waksman,

(44:04):
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, 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

(44:25):
this halo appears in the Petrie 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 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

(44:47):
that takes place over the next few decades. Yeah, and
there are various 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 happen? And in the wider world, because again penicillin
comes online during the Second World War, and so that

(45:07):
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 scaled up just to make
sure that Allied soldiers had access to it at D Day. UM.

(45:31):
So there's a legitimate question if you 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, we would have had to depend on the
solfa drugs, uh you know, an imperfect alternative to true antibiotics,

(45:56):
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 of true um antibiotics well beyond the nineteen sixties.
And this is also true if the Access Powers had

(46:17):
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
relatively good job at reducing battle casualties. So not to
just completely um, you know, cast aside the effectiveness of

(46:37):
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
lived potentially if there had been penicillin around. And so

(46:59):
they point out that, uh, 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

(47:21):
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

(47:45):
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

(48:08):
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

(48:28):
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,

(48:49):
what if the antibiotics 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
back materia and other disease causing microbes are over time evolving.
Antibiotic resistance are evolving too to be powerful enough to

(49:09):
survive our anti microbial 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

(49:33):
the threats on each side. And so you know, 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 not not

(49:56):
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 forties through the nineteen
seventies are are considered like the golden age of antibiotic research,

(50:16):
and we haven't seen, at least 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

(50:37):
reached out into the natural war between between fungi and
the microbial legions, and we we stole some of the tools.
We stole some of that Promethean fire when we had
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.

(51:00):
I'd be interested. Do you out there, you the listener,
do you work 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

(51:23):
surface here though, thanks to antibiotics, hopefully that scratch will
not uh get interesting 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

(51:44):
of the greatest inventions or discoveries. Again, however you want
to classify it from the twentieth century, yeah, totally. In
the meantime, if you want to check out other episodes
of Invention, you can check out our homepage. It's invention
pod dot com and that'll have all the episodes right there.
If you want to support the show, and we would
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(52:05):
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and reviews Wherever you got this podcast, huge thanks as
always to our excellent audio producer, Maya Cole. If you'd
like to get in touch with us to let us
know feedback on this episode or any other, to suggest

(52:25):
a topic for the future, just to say hello, you
can email us at contact at invention pod dot com.
Invention is production of I Heart Radio. For more podcasts
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(52:49):
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