WEBVTT 00:00:00.000 --> 00:00:02.859 If you think about the defining image of modern 00:00:02.859 --> 00:00:06.839 medical science, it's usually this picture of 00:00:06.839 --> 00:00:09.720 absolute pristine control, right? Oh, absolutely. 00:00:09.900 --> 00:00:12.480 Spotless steel counters. Yeah. Perfectly calibrated 00:00:12.480 --> 00:00:15.419 instruments. Researchers in these crisp white 00:00:15.419 --> 00:00:19.460 coats, executing like flawlessly planned experiments 00:00:19.460 --> 00:00:22.539 in sterile rooms. Right. Because we want to believe 00:00:22.539 --> 00:00:25.820 that the systems keeping us alive are born from 00:00:25.820 --> 00:00:29.939 pure, deliberate intent. Exactly. assumption 00:00:29.939 --> 00:00:32.619 that a world -changing breakthrough has to be 00:00:32.619 --> 00:00:34.479 the result of a perfectly straight line from 00:00:34.479 --> 00:00:37.500 hypothesis to discovery. When you dig into the 00:00:37.500 --> 00:00:40.299 historical source material, that pristine image 00:00:40.299 --> 00:00:43.100 shatters pretty quickly. It really does, which 00:00:43.100 --> 00:00:45.039 is why we're doing this deep dive today. If you 00:00:45.039 --> 00:00:47.380 are looking for thorough knowledge and multiple 00:00:47.380 --> 00:00:49.539 perspectives without being bogged down by dry 00:00:49.539 --> 00:00:52.140 textbook jargon, you are in the right place. 00:00:52.320 --> 00:00:54.539 The reality of medical advancement is just it's 00:00:54.539 --> 00:00:56.899 often Far more chaotic. Taotic is the perfect 00:00:56.899 --> 00:00:59.240 word. And looking at your backdrop right now, 00:00:59.340 --> 00:01:00.859 it seems you've already set the stage for us. 00:01:00.960 --> 00:01:03.619 I have, yeah. Because we're looking at a wildly 00:01:03.619 --> 00:01:08.260 clored 1920s bacteriologist's laboratory. I mean, 00:01:08.340 --> 00:01:10.579 there are stacks of Petri dishes, precariously 00:01:10.579 --> 00:01:14.000 balanced vintage microscopes shoved aside. Culture 00:01:14.000 --> 00:01:16.739 plates just left open. Yeah. Papers scattered 00:01:16.739 --> 00:01:19.719 absolutely everywhere. It is a spectacular mess. 00:01:19.799 --> 00:01:21.840 It's the exact working environment of the man 00:01:21.840 --> 00:01:24.840 we're focusing on today. a researcher whose own 00:01:24.840 --> 00:01:27.519 colleague famously noted that his monumental 00:01:27.519 --> 00:01:31.900 success was largely due to his excessive untidiness. 00:01:32.219 --> 00:01:34.680 Right. Today our mission is to explore how a 00:01:34.680 --> 00:01:38.159 string of wildly unpredictable accidents, a shockingly 00:01:38.159 --> 00:01:41.439 messy desk, and a lot of completely ignored research 00:01:41.439 --> 00:01:44.299 culminated in the discovery of penicillin. Arguably 00:01:44.299 --> 00:01:46.359 the greatest victory humanity has ever achieved 00:01:46.359 --> 00:01:48.659 over infectious disease. I mean, no question. 00:01:49.239 --> 00:01:51.159 But... To really understand this miracle cure, 00:01:51.260 --> 00:01:53.180 we can't just start with the famous moment in 00:01:53.180 --> 00:01:56.120 1928. No, not at all. You have to look at the 00:01:56.120 --> 00:01:58.939 bizarre series of accidents that even led Alexander 00:01:58.939 --> 00:02:00.920 Fleming into a laboratory to begin with. Because 00:02:00.920 --> 00:02:03.060 he didn't start out with this burning lifelong 00:02:03.060 --> 00:02:06.500 ambition to be a scientist. Far from it. He was 00:02:06.500 --> 00:02:08.680 a Scottish farmer's son. He actually moved to 00:02:08.680 --> 00:02:11.020 London and spent four years working in a shipping 00:02:11.020 --> 00:02:12.680 office. Right. He was just a shipping clerk. 00:02:12.919 --> 00:02:15.039 And he only goes to medical school at St. Mary's 00:02:15.039 --> 00:02:17.759 Hospital because he inherited a bit of money 00:02:17.759 --> 00:02:20.250 from an uncle. Yeah. And his older brother, who 00:02:20.250 --> 00:02:22.830 was already a physician, essentially nudged him 00:02:22.830 --> 00:02:24.610 and said, you know, hey, you should do medicine 00:02:24.610 --> 00:02:27.969 too. Which is wild. But even then, his pivot 00:02:27.969 --> 00:02:30.879 into bacteriology research. The field that defines 00:02:30.879 --> 00:02:34.080 his entire legacy came down to something as trivial 00:02:34.080 --> 00:02:36.919 as a hobby. A hobby, exactly. He was a private 00:02:36.919 --> 00:02:39.479 in the London Scottish Regiment, and he happened 00:02:39.479 --> 00:02:42.039 to be a remarkably good shot. A good marksman. 00:02:42.120 --> 00:02:45.319 Right. So naturally, he joined the medical school's 00:02:45.319 --> 00:02:47.680 rifle club. I found this detail in the sources 00:02:47.680 --> 00:02:50.539 so hard to believe. The captain of that rifle 00:02:50.539 --> 00:02:53.120 club realizes Fleming is about to graduate and 00:02:53.120 --> 00:02:55.580 leave. He doesn't want to lose him. Exactly. 00:02:56.159 --> 00:02:58.340 The captain desperately wants to keep his star 00:02:58.340 --> 00:03:00.620 shooter on the team to win an upcoming competition. 00:03:00.900 --> 00:03:03.180 It's just, it's so absurd to give Fleming an 00:03:03.180 --> 00:03:05.740 excuse to stay at St. Mary's. The captain suggests 00:03:05.740 --> 00:03:08.199 he join the hospital's research department. Specifically 00:03:08.199 --> 00:03:11.039 to work under Sir Omroth Wright. Yes. A pioneer 00:03:11.039 --> 00:03:13.990 in vaccine therapy and immunology. purely to 00:03:13.990 --> 00:03:15.849 keep him on the rifle team. It is staggering 00:03:15.849 --> 00:03:18.490 to realize that the trajectory of modern medicine, 00:03:18.889 --> 00:03:22.030 the very existence of antibiotics hinged on a 00:03:22.030 --> 00:03:24.210 local rifle club trying to stack their roster. 00:03:24.229 --> 00:03:27.449 It really is. But OK, let's untack this. This 00:03:27.449 --> 00:03:30.009 accidental career placement puts Fleming exactly 00:03:30.009 --> 00:03:32.430 where he needed to be when World War One erupts 00:03:32.430 --> 00:03:34.930 in 1914. Right. He and his colleagues are sent 00:03:34.930 --> 00:03:37.969 to a military hospital in Boulogne, France. And 00:03:37.969 --> 00:03:40.849 what he sees there completely changes his understanding 00:03:40.849 --> 00:03:42.949 of medicine. Because the conditions in the Those 00:03:42.949 --> 00:03:45.889 field hospitals were horrific. I mean, soldiers 00:03:45.889 --> 00:03:49.189 with deep jagged shrapnel wounds were dying at 00:03:49.189 --> 00:03:51.490 alarming rates. But not from the initial trauma. 00:03:51.569 --> 00:03:54.449 No, from sepsis, severe bacterial infections. 00:03:54.849 --> 00:03:57.030 And the standard medical protocol at the time 00:03:57.030 --> 00:03:59.789 was to continuously treat these wounds with chemical 00:03:59.789 --> 00:04:03.090 antiseptics. Like carbolic acid, hydrogen peroxide, 00:04:03.189 --> 00:04:05.069 things like that. Exactly. And this is where 00:04:05.069 --> 00:04:07.830 the source material gets incredibly counterintuitive 00:04:07.830 --> 00:04:10.590 because Fleming observes these treatments and 00:04:10.590 --> 00:04:14.250 begins to suspect that the very antiseptics are 00:04:14.250 --> 00:04:16.790 pouring into the wounds are actually making the 00:04:16.790 --> 00:04:19.250 infections worse. They were killing more soldiers 00:04:19.250 --> 00:04:21.529 than the infections themselves in some cases. 00:04:21.689 --> 00:04:23.990 Right. I really want to break this down because 00:04:23.990 --> 00:04:27.069 how can an antibacterial chemical cause a patient 00:04:27.069 --> 00:04:30.050 to die from bacteria? What's fascinating here 00:04:30.050 --> 00:04:32.490 is that it comes down to a fundamental misunderstanding 00:04:32.490 --> 00:04:36.250 of battlefield wounds. These chemical antiseptics 00:04:36.250 --> 00:04:38.970 worked perfectly well in a glass tube or on a 00:04:38.970 --> 00:04:41.290 surface scratch. Sure, out in the open. Right. 00:04:41.500 --> 00:04:45.319 But shrapnel creates deep cavernous wounds. The 00:04:45.319 --> 00:04:48.139 deadly anaerobic bacteria, the kind that thrive 00:04:48.139 --> 00:04:50.860 without oxygen, were buried deep inside the tissue. 00:04:51.180 --> 00:04:53.199 So the chemical antiseptics couldn't penetrate 00:04:53.199 --> 00:04:55.720 deeply enough to reach them. Exactly. But they 00:04:55.720 --> 00:04:57.939 could reach the patient's own white blood cells. 00:04:58.060 --> 00:05:00.879 Oh, wow. Yeah. Fleming actually conducted some 00:05:00.879 --> 00:05:03.360 brilliant experiments, even blowing his own custom 00:05:03.360 --> 00:05:07.199 glassware to simulate deep wounds to prove this 00:05:07.199 --> 00:05:09.379 mechanism. He showed that the chemicals were 00:05:09.379 --> 00:05:12.279 toxic to human leukocytes. Right, the white blood 00:05:12.279 --> 00:05:14.560 cells that make up our immune system's primary 00:05:14.560 --> 00:05:18.699 defense. These cells normally perform phagocytosis, 00:05:19.060 --> 00:05:21.620 where they engulf and destroy invading bacteria. 00:05:21.819 --> 00:05:24.519 OK, so to use an analogy, the standard medical 00:05:24.519 --> 00:05:26.220 treatment of the time was basically like carpet 00:05:26.220 --> 00:05:28.660 bombing a city to get rid of a few criminals. 00:05:28.899 --> 00:05:30.519 That's a great way to look at it. You end up 00:05:30.519 --> 00:05:33.279 destroying the local police force, the body's 00:05:33.279 --> 00:05:35.439 natural white blood cells, while the criminals, 00:05:35.620 --> 00:05:38.779 the deep bacteria, are just hiding safely in 00:05:38.779 --> 00:05:41.199 underground bunkers where the surface bombs can't 00:05:41.199 --> 00:05:43.459 even reach them. And with the police force dead. 00:05:43.759 --> 00:05:46.160 The criminals completely take over. It makes 00:05:46.160 --> 00:05:48.000 total sense when you frame it like that. And 00:05:48.000 --> 00:05:50.779 this battlefield observation is the crucial turning 00:05:50.779 --> 00:05:53.800 point. It permanently shifted Fleming's mindset. 00:05:54.160 --> 00:05:56.980 He realized the prevailing philosophy that medicine 00:05:56.980 --> 00:05:59.879 should just find stronger poisons to kill bacteria 00:05:59.879 --> 00:06:02.680 was deeply flawed. You can't just poison the 00:06:02.680 --> 00:06:05.240 body and hope the bacteria die first. Exactly. 00:06:05.579 --> 00:06:07.740 He realized you had to work with the body. You 00:06:07.740 --> 00:06:09.879 had to find something that was lethal to microbes, 00:06:10.360 --> 00:06:12.879 but completely harmless to human tissue. He knew 00:06:12.879 --> 00:06:15.540 the body had its own internal police force. He 00:06:15.540 --> 00:06:17.360 just didn't know how to harness it. Right, and 00:06:17.360 --> 00:06:19.980 you can't exactly engineer a revolutionary biological 00:06:19.980 --> 00:06:22.500 defense mechanism from scratch in the 1920s. 00:06:22.660 --> 00:06:24.480 No, you basically have to wait to stumble upon 00:06:24.480 --> 00:06:28.819 it. Which brings us to 1921 and the legend of 00:06:28.819 --> 00:06:31.379 that incredibly chaotic laboratory you have behind 00:06:31.379 --> 00:06:34.959 you. Yes, the famous mess. Fleming's colleague, 00:06:35.120 --> 00:06:37.930 VD Allison, openly admitted that if Fleming had 00:06:37.930 --> 00:06:40.189 been a tidy scientist, he never would have made 00:06:40.189 --> 00:06:42.550 his two great discoveries. Because a tidy scientist 00:06:42.550 --> 00:06:44.470 throws out experiments the moment they become 00:06:44.470 --> 00:06:47.490 contaminated. Precisely. Fleming, however, tended 00:06:47.490 --> 00:06:49.750 to leave his cultured plates sitting around for 00:06:49.750 --> 00:06:52.970 weeks. And in late 1921, Fleming is suffering 00:06:52.970 --> 00:06:55.730 from what the medical texts politely call acute 00:06:55.730 --> 00:06:58.350 carissa. He had a heavy cold. Right, he had the 00:06:58.350 --> 00:07:00.709 sniffles. And he's working at his desk, leaning 00:07:00.709 --> 00:07:03.230 over an agar plate, thickly covered in a yellow 00:07:03.230 --> 00:07:06.389 bacteria. And a drop of his own nasal mucus, 00:07:06.569 --> 00:07:09.110 his snot falls directly onto the bacterial culture. 00:07:09.250 --> 00:07:11.089 And like we said, most people would toss the 00:07:11.089 --> 00:07:13.269 ruined plate in the bin. But Fleming leaves it. 00:07:13.509 --> 00:07:16.069 He leaves it. And when he examines it later, 00:07:16.490 --> 00:07:19.620 he notices something fascinating. The area immediately 00:07:19.620 --> 00:07:22.339 surrounding the drop of mucus isn't just slightly 00:07:22.339 --> 00:07:24.379 affected. It's completely clear, right? Yes, 00:07:24.540 --> 00:07:27.500 a totally transparent ring. The opaque bacterial 00:07:27.500 --> 00:07:30.000 colonies have been utterly obliterated. He's 00:07:30.000 --> 00:07:32.699 literally melting the bacteria with his own bodily 00:07:32.699 --> 00:07:35.319 fluids. And he immediately tests it. He creates 00:07:35.319 --> 00:07:37.879 a cloudy yellow suspension of the bacteria in 00:07:37.879 --> 00:07:40.959 saline, drops in a tiny amount of fresh mucus, 00:07:41.160 --> 00:07:43.699 and within two minutes, the entire test tube 00:07:43.699 --> 00:07:46.439 turns completely clear. The bacteria just gone. 00:07:46.620 --> 00:07:49.370 Gone. He discovered an enzyme, which he named 00:07:49.370 --> 00:07:52.329 lysozyme. It essentially breaks down the chemical 00:07:52.329 --> 00:07:55.089 bonds in the bacterial cell wall, causing the 00:07:55.089 --> 00:07:57.750 bacteria to burst open and die. And what follows 00:07:57.750 --> 00:08:00.509 this initial discovery is, honestly, it's one 00:08:00.509 --> 00:08:03.189 of the more surreal experimental phases in the 00:08:03.189 --> 00:08:05.089 history of medicine. Oh, you mean the tear milking 00:08:05.089 --> 00:08:07.850 operation. The tear milking operation. Fleming 00:08:07.850 --> 00:08:10.850 realizes that if this enzyme is in his nasal 00:08:10.850 --> 00:08:13.949 mucus, it must be in other bodily fluids. So 00:08:13.949 --> 00:08:16.350 for weeks, he and his research team forced themselves 00:08:16.350 --> 00:08:19.050 to cry. They try rubbing onions in their eyes, 00:08:19.089 --> 00:08:21.730 which doesn't work well enough. So they switch 00:08:21.730 --> 00:08:24.949 to squeezing raw lemons into their eyes just 00:08:24.949 --> 00:08:27.449 to produce tears to test. I mean, the dedication 00:08:27.449 --> 00:08:30.209 is wild. It is. And the demand for tears in the 00:08:30.209 --> 00:08:32.669 lab actually outpaced what the researchers could 00:08:32.669 --> 00:08:34.769 produce themselves. Didn't they start paying 00:08:34.769 --> 00:08:37.809 the staff? They did. They paid laboratory attendance 00:08:37.809 --> 00:08:40.350 a bounty of three pence for every contribution 00:08:40.350 --> 00:08:42.029 of tears they could provide. That's amazing. 00:08:42.269 --> 00:08:45.230 Fleming went on to test egg white, blood, pus, 00:08:45.590 --> 00:08:48.730 semen, and found this lysozyme enzyme almost 00:08:48.730 --> 00:08:52.429 everywhere. He had discovered the first antimicrobial 00:08:52.429 --> 00:08:55.269 protein that constitutes part of our innate human 00:08:55.269 --> 00:08:58.539 immunity. It's an incredible breakthrough in 00:08:58.539 --> 00:09:00.720 immunology. But, okay, reading through the sources, 00:09:00.759 --> 00:09:02.659 I had a hard time understanding the reaction. 00:09:02.679 --> 00:09:04.980 A public reaction. A scientific reaction. He 00:09:04.980 --> 00:09:07.799 discovers this incredible natural bodily defense. 00:09:08.179 --> 00:09:10.759 He presents these findings in December 1921 to 00:09:10.759 --> 00:09:12.960 the Medical Research Club, then the next year 00:09:12.960 --> 00:09:15.779 to the Royal Society, where he literally dissolves 00:09:15.779 --> 00:09:18.799 the bacteria Mycococcus lysodacticus right in 00:09:18.799 --> 00:09:20.720 front of their eyes. Yes, live demonstration. 00:09:21.120 --> 00:09:23.259 And the response from the scientific community 00:09:23.259 --> 00:09:28.299 is absolute crickets. Total silence. Why? Was 00:09:28.299 --> 00:09:30.580 he just a terrible public speaker? Was he a bad 00:09:30.580 --> 00:09:33.559 salesman for his own science? Well, his presentation 00:09:33.559 --> 00:09:36.039 style was famously understated, but that wasn't 00:09:36.039 --> 00:09:38.580 the real issue. What's fascinating here is the 00:09:38.580 --> 00:09:40.600 clinical limitations of what he had found. OK, 00:09:40.720 --> 00:09:42.779 what do you mean? The specific bacteria he was 00:09:42.779 --> 00:09:45.700 melting in front of them, microcaucas, lysodehicticus, 00:09:46.240 --> 00:09:50.080 is generally harmless to humans. Lysasi was brilliant 00:09:50.080 --> 00:09:52.340 at destroying harmless environmental microbes, 00:09:52.700 --> 00:09:54.840 but it was largely ineffective against the lethal 00:09:54.840 --> 00:09:57.179 disease -causing pathogens that were ravaging 00:09:57.179 --> 00:09:59.299 hospitals. Oh, so it didn't solve the immediate 00:09:59.299 --> 00:10:02.259 crisis. Exactly. The medical community was desperately 00:10:02.259 --> 00:10:05.279 searching for a cure for lethal diseases. So 00:10:05.279 --> 00:10:07.779 they viewed his discovery as a fascinating, but 00:10:07.779 --> 00:10:10.870 ultimately useless biological curiosity. I see. 00:10:10.889 --> 00:10:13.250 So it's a proof of concept. He proves that a 00:10:13.250 --> 00:10:16.129 natural human -safe antibacterial agent can exist. 00:10:16.490 --> 00:10:18.629 But he needs a much bigger weapon to take out 00:10:18.629 --> 00:10:20.669 the real killers. Right. And he wouldn't find 00:10:20.669 --> 00:10:23.850 it until 1928, when his legendary untidiness 00:10:23.850 --> 00:10:26.549 strikes again. Here's where it gets really interesting. 00:10:27.070 --> 00:10:31.389 It's September 3rd, 1928. Fleming returns to 00:10:31.389 --> 00:10:33.789 his St. Mary's laboratory after a family holiday 00:10:33.789 --> 00:10:36.690 in Suffolk. And before he left, he had inoculated 00:10:36.690 --> 00:10:40.009 several culture plates with saff Which is a highly 00:10:40.009 --> 00:10:42.570 dangerous bacteria that causes severe infection. 00:10:42.649 --> 00:10:44.870 Yeah, very dangerous. But instead of storing 00:10:44.870 --> 00:10:47.190 them in an incubator, he just left them stacked 00:10:47.190 --> 00:10:49.250 on a bench in the corner of his room. And while 00:10:49.250 --> 00:10:52.570 he was away, a stray fungal spore drifts up from 00:10:52.570 --> 00:10:55.169 the laboratory directly below his. The room of 00:10:55.169 --> 00:10:57.570 an allergy researcher named Charles J. Latouche. 00:10:57.730 --> 00:11:00.190 Right, it drifts up and lands on one of Fleming's 00:11:00.190 --> 00:11:02.509 open plates. So when Fleming returns and begins 00:11:02.509 --> 00:11:04.850 sorting through these haphazard stacks of plates, 00:11:05.470 --> 00:11:08.450 he notices the fungal contaminant. It was later 00:11:08.450 --> 00:11:11.090 identified as a rare strain called penicillium 00:11:11.090 --> 00:11:13.230 rubens. And it's growing right in the middle 00:11:13.230 --> 00:11:16.070 of the plate. Yes. But what catches his eye is 00:11:16.070 --> 00:11:19.649 the perimeter around the mold. The deadly Staphylococci 00:11:19.649 --> 00:11:22.289 colonies closest to the fungus haven't just stopped 00:11:22.289 --> 00:11:24.629 growing. They are undergoing lysis. They are 00:11:24.629 --> 00:11:26.990 dissolving. Dissolving. Just like the bacteria 00:11:26.990 --> 00:11:29.990 exposed to his tears years earlier. And looking 00:11:29.990 --> 00:11:33.210 at this profound medical breakthrough, literally 00:11:33.210 --> 00:11:35.830 the ultimate weapon against infectious disease, 00:11:36.350 --> 00:11:38.950 Fleming famously just mutters, that's funny. 00:11:39.690 --> 00:11:41.669 Exactly. It's the understatement of the century. 00:11:42.629 --> 00:11:45.409 But his mind was prepared by the lysozyme discovery. 00:11:45.669 --> 00:11:48.090 He knew exactly what he was looking at. A biological 00:11:48.090 --> 00:11:50.710 agent producing a substance that destroyed bacteria 00:11:50.710 --> 00:11:53.710 without harsh chemicals. But how exactly does 00:11:53.710 --> 00:11:56.679 the mold do it? The sources mention it attacks 00:11:56.679 --> 00:11:58.639 the bacteria, but what's the actual mechanism 00:11:58.639 --> 00:12:01.740 that makes it so deadly to pathogens, but perfectly 00:12:01.740 --> 00:12:05.580 safe for humans? It's brilliantly specific. Penicillin 00:12:05.580 --> 00:12:07.759 targets a key structural component that bacteria 00:12:07.759 --> 00:12:10.740 rely on, but human cells simply don't have. Okay, 00:12:10.820 --> 00:12:13.620 what is it? Bacteria are encased in a rigid cell 00:12:13.620 --> 00:12:16.759 wall made of a mesh -like polymer called peptidoglycan. 00:12:17.039 --> 00:12:19.159 Penicillin molecules bind to and disable the 00:12:19.159 --> 00:12:21.940 enzymes that the bacteria use to weave this mesh 00:12:21.940 --> 00:12:24.139 together. So they can't build their walls properly? 00:12:24.539 --> 00:12:26.500 Right. So when the bacteria try to grow and divide, 00:12:26.899 --> 00:12:29.440 their cell walls become inherently weak and flawed. 00:12:29.820 --> 00:12:31.659 The internal pressure of the bacteria causes 00:12:31.659 --> 00:12:34.360 them to literally burst open. Wow. And human 00:12:34.360 --> 00:12:37.440 cells? Because human cells have flexible membranes 00:12:37.440 --> 00:12:41.379 instead of rigid peptidoglycan walls. The penicillin 00:12:41.379 --> 00:12:44.059 simply ignores them. It's the perfect targeted 00:12:44.059 --> 00:12:46.919 strike. He grows this mold in a pure culture. 00:12:47.460 --> 00:12:50.340 He originally calls it mold juice, which is gross. 00:12:50.419 --> 00:12:53.440 Very appetizing. Right. He finds it kills the 00:12:53.440 --> 00:12:56.600 pathogens that cause pneumonia, meningitis, diphtheria, 00:12:56.879 --> 00:12:59.759 scarlet fever. He officially names it penicillin 00:12:59.759 --> 00:13:02.960 in 1929. He writes a paper. He takes it back 00:13:02.960 --> 00:13:05.179 to the medical research club. And what happens? 00:13:05.480 --> 00:13:07.379 The exact same thing that happened with lysozyme. 00:13:08.000 --> 00:13:10.759 Utter indifference. It's maddening. Henry Dale, 00:13:10.899 --> 00:13:12.840 who is chairing the meeting, later admitted he 00:13:12.840 --> 00:13:14.860 didn't sense any striking point of importance 00:13:14.860 --> 00:13:17.360 in Fleming's speech. But the source material 00:13:17.360 --> 00:13:20.360 reveals there's a very real physical reason it 00:13:20.360 --> 00:13:22.940 didn't catch on immediately. Fleming essentially 00:13:22.940 --> 00:13:25.100 stumbled upon the blueprints for a warp drive, 00:13:25.440 --> 00:13:28.480 but in 1920 science just didn't possess the metallurgical 00:13:28.480 --> 00:13:30.940 tools to build the engine. That's a great analogy 00:13:30.940 --> 00:13:33.620 because identifying the mold's antibacterial 00:13:33.620 --> 00:13:36.279 properties was biology. but turning that mold 00:13:36.279 --> 00:13:38.840 juice into an injectable drug. That requires 00:13:38.840 --> 00:13:42.820 chemistry. Exactly. Penicillin is a highly unstable 00:13:42.820 --> 00:13:46.059 molecule. If you try to extract it using the 00:13:46.059 --> 00:13:48.440 chemical methods of the day, the molecule simply 00:13:48.440 --> 00:13:51.139 degraded and vanished. It was too fragile. Think 00:13:51.139 --> 00:13:53.840 of it like trying to extract a remarkably intricate, 00:13:54.220 --> 00:13:57.399 incredibly fragile origami structure out of a 00:13:57.399 --> 00:14:00.480 swamp. using a bulldozer, just end up destroying 00:14:00.480 --> 00:14:03.000 the very thing you were trying to save. Fleming 00:14:03.000 --> 00:14:05.980 enlisted biochemists, but they all failed to 00:14:05.980 --> 00:14:08.659 chemically purify it. They couldn't isolate the 00:14:08.659 --> 00:14:11.200 penicillin to produce it in large usable amounts. 00:14:11.200 --> 00:14:13.379 Oh, they couldn't. And so it just languishes, 00:14:13.799 --> 00:14:15.820 completely forgotten by the wider medical world 00:14:15.820 --> 00:14:18.100 throughout the entire 1930s. But if we connect 00:14:18.100 --> 00:14:20.600 this to the bigger picture, here is where Fleming 00:14:20.600 --> 00:14:23.720 deserves immense credit. Despite being ignored, 00:14:24.039 --> 00:14:26.519 despite the repeated chemical failures, he kept 00:14:26.519 --> 00:14:28.700 the original mold alive. He just kept feeding 00:14:28.700 --> 00:14:31.340 it. He meticulously cultured it, week after week, 00:14:31.379 --> 00:14:34.139 year after year. He distributed samples to anyone 00:14:34.139 --> 00:14:37.019 who asked. He essentially acted as a caretaker 00:14:37.019 --> 00:14:40.279 for this fragile discovery for 12 long years, 00:14:40.600 --> 00:14:42.539 just hoping that chemistry would eventually catch 00:14:42.539 --> 00:14:45.159 up to his biology. Which sets up an incredible 00:14:45.159 --> 00:14:48.320 relay race of scientific discovery, because the 00:14:48.320 --> 00:14:51.200 final sprint to the finish line, the actual creation 00:14:51.200 --> 00:14:53.820 of the drug, Doesn't happen in Fleming's lab 00:14:53.820 --> 00:14:56.320 at St. Mary's. No, it happens at Oxford University 00:14:56.320 --> 00:14:58.980 starting in 1940. A brilliant team at Oxford, 00:14:59.419 --> 00:15:02.259 led by the pathologist Howard Flory and the biochemist 00:15:02.259 --> 00:15:05.120 Ernst Chain, decides to systematically study 00:15:05.120 --> 00:15:07.960 natural antibacterial substances. And they dug 00:15:07.960 --> 00:15:11.519 up Fleming's 1929 paper on penicillin and requested 00:15:11.519 --> 00:15:14.340 a sample of the live mold. And it's a third member 00:15:14.340 --> 00:15:16.960 of their team, a biochemist named Norman Heatley, 00:15:17.299 --> 00:15:20.019 who finally solves the origami problem. Heatley 00:15:20.019 --> 00:15:22.159 was brilliant. The sources say he figured out 00:15:22.159 --> 00:15:25.179 how to purify it by changing its acidity. How 00:15:25.179 --> 00:15:27.820 does shifting the pH magically stabilize this 00:15:27.820 --> 00:15:30.600 incredibly fragile molecule? Keatley's mechanism 00:15:30.600 --> 00:15:32.740 was a stroke of genius called back extraction. 00:15:33.440 --> 00:15:36.320 Penicillin is a weak acid. Keatley realized that 00:15:36.320 --> 00:15:39.740 if he made the mole juice highly acidic, the 00:15:39.740 --> 00:15:42.059 penicillin molecules would happily dissolve into 00:15:42.059 --> 00:15:44.379 an organic solvent like ether. OK, so that leaves 00:15:44.379 --> 00:15:46.759 a lot of the water -based impurities behind in 00:15:46.759 --> 00:15:49.909 the swamp. Exactly. But ether evaporates quickly 00:15:49.909 --> 00:15:51.870 and isn't exactly something you want to inject 00:15:51.870 --> 00:15:54.649 into a patient's veins. No, definitely not. So 00:15:54.649 --> 00:15:57.490 he then reversed the process. He introduced the 00:15:57.490 --> 00:16:00.649 ether mixture to water that was slightly alkaline. 00:16:01.129 --> 00:16:03.830 The pH shift caused the penicillin to abandon 00:16:03.830 --> 00:16:06.509 the ether and dissolve back into the water. Leaving 00:16:06.509 --> 00:16:10.110 it highly concentrated and vastly purified. Exactly. 00:16:10.149 --> 00:16:12.210 It's like coaxing the delicate origami across 00:16:12.210 --> 00:16:14.389 a chemical bridge, leaving all the mud behind. 00:16:14.679 --> 00:16:18.059 They finally have a stable, purified form. They 00:16:18.059 --> 00:16:21.039 start running trials, and the success is staggering. 00:16:21.539 --> 00:16:24.080 Which leads to a moment in 1942 that honestly 00:16:24.080 --> 00:16:26.440 feels like it was scripted for a movie. The case 00:16:26.440 --> 00:16:29.259 of Harry Lambert. Ah, yes. Harry Lambert was 00:16:29.259 --> 00:16:31.480 an associate of Fleming's brother. He was admitted 00:16:31.480 --> 00:16:34.440 to St. Mary's Hospital with streptococcal meningitis. 00:16:34.580 --> 00:16:37.399 Which is a severe, usually fatal infection of 00:16:37.399 --> 00:16:39.720 the tissues surrounding the brain and spinal 00:16:39.720 --> 00:16:42.629 cord. Very fatal. Fleming initially tried treating 00:16:42.629 --> 00:16:45.250 him with sulfa drugs, which were the new standard 00:16:45.250 --> 00:16:48.409 chemical treatments of the late 1930s, but Lambert's 00:16:48.409 --> 00:16:50.769 condition was deteriorating rapidly. He was slipping 00:16:50.769 --> 00:16:53.970 into a coma. Desperate, Fleming tests his original 00:16:53.970 --> 00:16:56.909 penicillin mold against Lambert -specific bacteria 00:16:56.909 --> 00:17:00.580 in the lab and finds it susceptible. So he immediately 00:17:00.580 --> 00:17:03.480 calls Howard Flory at Oxford and practically 00:17:03.480 --> 00:17:06.319 begs for their entire supply of the newly isolated 00:17:06.319 --> 00:17:09.119 purified drug. Flory sends it over and Fleming 00:17:09.119 --> 00:17:12.259 makes an incredibly bold, unprecedented move. 00:17:12.400 --> 00:17:14.759 He doesn't just inject it into Lambert's muscle. 00:17:14.980 --> 00:17:18.059 No, he injects the purified penicillin directly 00:17:18.059 --> 00:17:20.900 into Harry Lambert's spinal canal. The medical 00:17:20.900 --> 00:17:23.460 risk there was immense. It was huge. But the 00:17:23.460 --> 00:17:25.859 results were miraculous. Lambert showed signs 00:17:25.859 --> 00:17:28.380 of improvement the very next day and completely 00:17:28.380 --> 00:17:30.900 recovered within a week. Fleming published this 00:17:30.900 --> 00:17:34.140 clinical case in The Lancet in 1943, and the 00:17:34.140 --> 00:17:36.480 world finally woke up. And suddenly we are in 00:17:36.480 --> 00:17:38.900 the middle of World War II, and the British War 00:17:38.900 --> 00:17:41.720 Cabinet realizes they need mass production immediately. 00:17:41.980 --> 00:17:44.079 But the British infrastructure is being bombed, 00:17:44.279 --> 00:17:46.440 right? Right. So American pharmaceutical companies 00:17:46.440 --> 00:17:48.779 are brought in to scale up Heatley's extraction 00:17:48.779 --> 00:17:51.759 process. And by D -Day in 1944, they had produced 00:17:51.759 --> 00:17:54.339 enough penicillin to treat all the wounded allied 00:17:54.339 --> 00:17:58.140 troops. It's an unprecedented industrial mobilization. 00:17:58.420 --> 00:18:01.579 It truly was. But as the drug saves thousands 00:18:01.579 --> 00:18:04.700 of lives, the media gets involved and the story 00:18:04.700 --> 00:18:07.440 takes a weird turn. Right. Because when the news 00:18:07.440 --> 00:18:10.259 of Harry Lambert's miraculous recovery broke, 00:18:10.740 --> 00:18:14.930 the press was hungry for a hero. The Times eagerly 00:18:14.930 --> 00:18:17.769 interviewed Fleming. But over at Oxford, Howard 00:18:17.769 --> 00:18:20.269 Flory had implemented a strict self -imposed 00:18:20.269 --> 00:18:22.650 gag order. He believed scientists shouldn't seek 00:18:22.650 --> 00:18:25.529 media coverage, so he flatly prohibited his team 00:18:25.529 --> 00:18:28.180 from talking to the press. So the media only 00:18:28.180 --> 00:18:31.220 has one guy willing to talk, Alexander Fleming. 00:18:31.900 --> 00:18:34.299 And they run with it. They solely glorify him. 00:18:34.640 --> 00:18:36.819 They construct this romantic narrative of the 00:18:36.819 --> 00:18:39.519 lone genius whose messy desk single -handedly 00:18:39.519 --> 00:18:41.980 saved the world. And Fleming himself was deeply 00:18:41.980 --> 00:18:44.259 uncomfortable with it. He humbly referred to 00:18:44.259 --> 00:18:46.910 it as the Fleming myth. It's a fascinating study 00:18:46.910 --> 00:18:49.390 in how history is shaped by narrative convenience. 00:18:49.990 --> 00:18:52.670 Sir Henry Harris, a later Oxford professor, summed 00:18:52.670 --> 00:18:54.789 up the true collaborative nature of the discovery 00:18:54.789 --> 00:18:57.269 perfectly. He said, without Fleming no chain, 00:18:57.450 --> 00:18:59.349 without chain no flori, without flori no heat 00:18:59.349 --> 00:19:01.549 leave, without heat leave no penicillin. It required 00:19:01.549 --> 00:19:03.589 the biologist to find it and the chemist to build 00:19:03.589 --> 00:19:06.230 it. I have to ask you though, knowing he didn't 00:19:06.230 --> 00:19:08.630 purify it, knowing he couldn't turn it into a 00:19:08.630 --> 00:19:11.589 usable drug himself, is it fair that Fleming 00:19:11.589 --> 00:19:14.250 gets statues in Madrid? His face is on the five 00:19:14.250 --> 00:19:16.529 -pound Scottish banknote. He has an asteroid 00:19:16.529 --> 00:19:18.769 named after him. While the Oxford team is often 00:19:18.769 --> 00:19:21.549 forgotten. Right. Is that fair? Well, fairness 00:19:21.549 --> 00:19:24.769 is rarely how history operates. The public, especially 00:19:24.769 --> 00:19:27.609 during a brutal global war, desperately needed 00:19:27.609 --> 00:19:31.329 a single, relatable hero. A team of biochemists 00:19:31.329 --> 00:19:34.049 meticulously tweaking the pH levels of ether 00:19:34.049 --> 00:19:38.279 in a laboratory. just isn't as romantic or accessible 00:19:38.279 --> 00:19:41.119 as the story of an everyday doctor noticing a 00:19:41.119 --> 00:19:43.500 stray mold on a dirty plate. That's true. It's 00:19:43.500 --> 00:19:45.920 a better story. And to Fleming's credit, he never 00:19:45.920 --> 00:19:48.480 tried to steal their glory. He constantly praised 00:19:48.480 --> 00:19:51.539 Florian Chain in his speeches, and in 1945, the 00:19:51.539 --> 00:19:54.240 Nobel Prize in Physiology or Medicine was rightly 00:19:54.240 --> 00:19:56.319 shared jointly between all three of them. Speaking 00:19:56.319 --> 00:19:58.460 of the media and myths, we should probably clear 00:19:58.460 --> 00:20:01.019 up a massive historical fable that still circulates 00:20:01.019 --> 00:20:02.839 today. It's an incredible story, but totally 00:20:02.839 --> 00:20:05.849 false. The Winston Churchill Connection. Yes, 00:20:06.230 --> 00:20:08.890 the wondrous fable, as Fleming himself called 00:20:08.890 --> 00:20:11.950 it. There is a persistent myth that Fleming's 00:20:11.950 --> 00:20:15.089 father saved a young Winston Churchill from drowning 00:20:15.089 --> 00:20:18.259 in a bog in Scotland. And in gratitude, Churchill's 00:20:18.259 --> 00:20:21.220 aristocratic father supposedly paid for Alexander 00:20:21.220 --> 00:20:23.920 Fleming's medical education. Right. And the story 00:20:23.920 --> 00:20:26.740 then perfectly loops back around, claiming that 00:20:26.740 --> 00:20:28.799 when Winston Churchill fell deathly ill with 00:20:28.799 --> 00:20:31.700 pneumonia during World War II, it was Fleming's 00:20:31.700 --> 00:20:34.140 penicillin that saved his life. It sounds like 00:20:34.140 --> 00:20:36.940 an email forward you'd get from a relative. And 00:20:36.940 --> 00:20:39.400 none of it is true. None of it. Churchill's life 00:20:39.400 --> 00:20:41.779 was saved during World War II when he fell ill 00:20:41.779 --> 00:20:44.339 in Tunisia. But the medical records show he was 00:20:44.339 --> 00:20:46.099 treated with a completely different medication. 00:20:45.930 --> 00:20:51.690 a synthetic sulfa drug called M &B 693. The reality 00:20:51.690 --> 00:20:54.210 of Fleming's later years was much more grounded 00:20:54.210 --> 00:20:56.930 in the practical and ethical challenges of introducing 00:20:56.930 --> 00:20:59.329 a miracle drug to the world. For instance, the 00:20:59.329 --> 00:21:01.549 money. Right, the patents. When two American 00:21:01.549 --> 00:21:04.049 scientists patented a method for increased penicillin 00:21:04.049 --> 00:21:06.930 production in the United States in 1944, Fleming 00:21:06.930 --> 00:21:09.930 was furious. He believed medicine shouldn't be 00:21:09.930 --> 00:21:13.539 a commodity. He famously stated, I found penicillin 00:21:13.539 --> 00:21:15.980 and have given it free for the benefit of humanity. 00:21:16.480 --> 00:21:18.539 Why should it become a profit -making monopoly 00:21:18.539 --> 00:21:21.180 of manufacturers in another country? He was a 00:21:21.180 --> 00:21:23.660 purist in that regard. But while the world was 00:21:23.660 --> 00:21:25.819 busy fighting over patents and celebrating the 00:21:25.819 --> 00:21:28.559 dawn of the antibiotic age, Fleming was already 00:21:28.559 --> 00:21:31.380 looking ahead. Seeing the dark side. Yes. And 00:21:31.380 --> 00:21:34.000 his foresight regarding how humanity would misuse 00:21:34.000 --> 00:21:37.259 his gift was chillingly accurate. This might 00:21:37.259 --> 00:21:39.599 be the most mind -blowing part of the entire 00:21:39.599 --> 00:21:43.380 deep dive. In 1945, during his Nobel Prize lecture, 00:21:43.920 --> 00:21:46.299 Fleming delivers an explicit prophetic warning. 00:21:46.460 --> 00:21:49.000 He had noticed during his early laboratory experiments 00:21:49.000 --> 00:21:52.039 that if you expose bacteria to non -lethal quantities 00:21:52.039 --> 00:21:55.019 of penicillin, the bacteria don't just survive, 00:21:55.220 --> 00:21:57.980 they adapt. They develop resistance. He understood 00:21:57.980 --> 00:22:00.319 the evolutionary biology at play. If you don't 00:22:00.319 --> 00:22:02.700 destroy the entire bacterial population, the 00:22:02.700 --> 00:22:05.240 survivors learn to synthesize enzymes that neutralize 00:22:05.240 --> 00:22:07.809 the drug. So he stood on the world stage and 00:22:07.809 --> 00:22:10.869 warned that, and I quote, the ignorant man may 00:22:10.869 --> 00:22:13.509 easily underdose himself and by exposing his 00:22:13.509 --> 00:22:15.910 microbes to non -lethal quantities of the drug 00:22:15.910 --> 00:22:18.579 make them resistant. He went as far as saying 00:22:18.579 --> 00:22:20.619 that thoughtless people playing with penicillin 00:22:20.619 --> 00:22:23.180 would be morally responsible for the deaths of 00:22:23.180 --> 00:22:26.019 others who later succumbed to those new invincible 00:22:26.019 --> 00:22:28.980 organisms. The absolute irony of it. The man 00:22:28.980 --> 00:22:31.380 who discovered the ultimate cure spent the rest 00:22:31.380 --> 00:22:33.880 of his life warning us that our own behavioral 00:22:33.880 --> 00:22:36.819 flaws, our tendency to stop taking pills when 00:22:36.819 --> 00:22:39.500 we feel a little better, could render the greatest 00:22:39.500 --> 00:22:42.500 medical victory completely useless. It highlights 00:22:42.500 --> 00:22:44.920 an important question. Discovering a medical 00:22:44.920 --> 00:22:46.500 intervention is only half the battle, right? 00:22:46.500 --> 00:22:48.779 Right. The mechanism of the drug is perfect, 00:22:48.920 --> 00:22:52.299 but human behavior is not. Ye saw the impending 00:22:52.299 --> 00:22:54.980 crisis of antibiotic resistance decades before 00:22:54.980 --> 00:22:57.390 it became the global emergency it is today. So 00:22:57.390 --> 00:22:59.470 as we look at the breadth of this incredible 00:22:59.470 --> 00:23:02.029 story, Fleming's physical legacy is still very 00:23:02.029 --> 00:23:04.789 much with us today. The laboratory where he discovered 00:23:04.789 --> 00:23:07.569 penicillin at St. Mary's is a museum in London. 00:23:07.890 --> 00:23:11.529 Just a few weeks ago, in March 2025, a massive 00:23:11.529 --> 00:23:14.170 mural featuring his portrait was unveiled in 00:23:14.170 --> 00:23:16.470 his hometown of Darvel in Scotland. There's even 00:23:16.470 --> 00:23:18.490 a new Wetherspoons pub opening this September 00:23:18.490 --> 00:23:20.829 in Paddington named the Sir Alexander Fleming. 00:23:21.049 --> 00:23:23.630 His name is immortalized because his observation 00:23:23.630 --> 00:23:26.509 fundamentally divided human history. There was 00:23:26.509 --> 00:23:29.470 the era before antibiotics, where a scratched 00:23:29.470 --> 00:23:32.309 knee could kill you. And the era after antibiotics, 00:23:32.490 --> 00:23:34.809 which allowed for modern surgery, organ transplants, 00:23:34.950 --> 00:23:37.490 and global population growth. So what does this 00:23:37.490 --> 00:23:40.150 all mean? It's an unbelievable journey. From 00:23:40.150 --> 00:23:42.750 a Scottish farm to a shipping office to a rifle 00:23:42.750 --> 00:23:45.910 club. From his own snot -melting harmless bacteria 00:23:45.910 --> 00:23:48.990 to a stray mold spore drifting through an open 00:23:48.990 --> 00:23:52.029 window onto a famously untidy desk. It serves 00:23:52.029 --> 00:23:54.289 as a potent reminder that while scientific progress 00:23:54.289 --> 00:23:56.869 requires rigorous methodology, chemistry, and 00:23:56.869 --> 00:24:00.130 peer review, it also requires an open mind. A 00:24:00.130 --> 00:24:02.369 mind willing to look at a completely ruined experiment 00:24:02.369 --> 00:24:04.910 and say, that's funny, instead of throwing it 00:24:04.910 --> 00:24:07.509 in the trash. Which leaves us with a completely 00:24:07.509 --> 00:24:10.509 new angle to ponder. built right out of today's 00:24:10.509 --> 00:24:13.309 sources. We started this deep dive by talking 00:24:13.309 --> 00:24:16.789 about pristine environments. In our modern world, 00:24:17.029 --> 00:24:20.269 we are entirely obsessed with clean desk policies. 00:24:21.190 --> 00:24:24.549 We demand perfectly optimized workflows. Aggressively 00:24:24.549 --> 00:24:27.210 sanitized digital environments, inbox zero, we 00:24:27.210 --> 00:24:30.430 try to scrub out all the chaos. But if Fleming's 00:24:30.430 --> 00:24:33.369 own colleague was right, and his two world -changing 00:24:33.369 --> 00:24:36.450 discoveries were entirely dependent on his untidiness, 00:24:37.079 --> 00:24:39.400 By relentlessly trying to eliminate the mess 00:24:39.400 --> 00:24:42.440 from our lives and workspaces today, are we accidentally 00:24:42.440 --> 00:24:45.000 sterilizing our own potential for happy accidents? 00:24:45.140 --> 00:24:47.039 It certainly makes you wonder what invisible 00:24:47.039 --> 00:24:49.059 breakthroughs we might be wiping away with our 00:24:49.059 --> 00:24:51.579 antiseptic wipes. If Alexander Fleming had been 00:24:51.579 --> 00:24:53.980 forced to use modern productivity software and 00:24:53.980 --> 00:24:57.359 keep a spotless desk, would we even have antibiotics 00:24:57.359 --> 00:24:59.480 today? Something to think about. Sometimes the 00:24:59.480 --> 00:25:01.200 most important thing you can do is just let things 00:25:01.200 --> 00:25:03.420 get a little messy. Keep your eyes open for the 00:25:03.420 --> 00:25:05.500 unexpected. You never know what might be growing 00:25:05.500 --> 00:25:06.140 in the margins.