In Our Time - Louis Pasteur

Episode Date: May 18, 2017

Melvyn Bragg and guests discuss the life and work of Louis Pasteur (1822-1895) and his extraordinary contribution to medicine and science. It is said few people have saved more lives than Pasteur. A c...hemist, he showed that otherwise identical molecules could exist as 'left' and 'right-handed' versions and that molecules produced by living things were always left-handed. He proposed a germ theory to replace the idea of spontaneous generation. He discovered that microorganisms cause fermentation and disease. He began the process named after him, pasteurisation, heating liquids to 50-60 C to kill microbes. He saved the beer and wine industries in France when they were struggling with microbial contamination. He saved the French silk industry when he found a way of protecting healthy silkworm eggs from disease. He developed vaccines against anthrax and rabies and helped establish immunology. Many of his ideas were developed further after his lifetime, but one of his legacies was a charitable body, the Pasteur Institute, to continue research into infectious disease.With Andrew Mendelsohn Reader in the School of History at Queen Mary, University of LondonAnne Hardy Honorary Professor at the Centre for History in Public Health at the London School of Hygiene and Tropical Medicineand Michael Worboys Emeritus Professor in the History of Science, Technology and Medicine at the University of Manchester Producer: Simon Tillotson.

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Starting point is 00:00:35 Thanks for downloading this episode of In Our Time. There's a reading list to go with it on our website, and you can get news about our programs if you follow us on Twitter at BBC In Our Time. I hope you enjoy the programs. Hello, Louis Pasteur, born in France in 1822, was one of the great scientists of the 19th century, and his work still has a profound impact on our lives today. He was the first to manufacture of vaccine,
Starting point is 00:01:00 tackling anthrax and then rabies, which led to the development of vaccines for other diseases. His research persuaded surgeons of the need for antiseptics to stop organisms in the air infecting open wounds. He discovered why wine, beer and milk can go off before they're ready to drink and found a way to preserve them, known as pasteurization. By the time of his death in 1895,
Starting point is 00:01:21 he was known as one of the founders of microbiology. He cut across disciplines, there were he said no such things as pure and applied signs. There were only signs and the application of science. We admitted to discuss the life and work of Louis Pasteur are Andrew Mendelsohn, reader in the School of History at Queen Mary University of London,
Starting point is 00:01:40 Anne Hardy, Honourie Professor at the London School of Hygiene and Tropical Medicine, and Michael Warboy's Emeritus Professor in the History of Science Technology and Medicine at the University of Manchester. Andrew Mendelso's background's important, as it is for most people, his interest. Can you tell us what part of France he grew up in,
Starting point is 00:01:57 what he was like, and what he got out of it? Right. Well, normally, I would actually say that in the history of science, the childhood background chapter, you can almost skip and you can move on to where they trained and so on. But I would say with Pasteur, we're looking at someone for whom the childhood background is actually, I would say, the key to the whole. And it is indeed in rural France. And it's a background in an agricultural environment. And he went on to be a chemist. And what makes that interesting is that here is a figure with whom we associate a revolution in medicine, who was not a medic,
Starting point is 00:02:30 and didn't come from a medical family the way Say Lister did, who set up a whole area, a new area of biology, but was not a biologist, but came from a French rural environment in which chemical processes were productive. So his father was a tanner, and he grew up literally in a tannery and around a tannery, in the winemaking area in the Jura Mountains,
Starting point is 00:02:55 in the town of Arbois. And so this meant that, to say that, somebody began their training in chemistry. In the second half of the 19th century, you might think, well, okay, what was important was synthetic chemistry and the area of chemistry that gave us the modern chemical industry and so on. But he was growing up in an area of France in which there were old practical arts like tanning, winemaking, that you could learn from.
Starting point is 00:03:24 And they were complicated. Tanning is a very, well, so I've read tanning is very complicated. That's right. a good tan or so. Did he learn about that? Did he help? He never contributed to tanning, but he was in an environment in which you had exactly as you say, so complex processes of production that were not new, so they'd been around for centuries, if not thousands of years, right, wine making and so on, but that you could engage with, you could find problems to tackle within those areas and you could tinker with them
Starting point is 00:03:52 and you above all could learn from them, and I think that's really crucial for Pesson. And he went from study to the workforce, the work face, time and time again. That is one of the things that distinguishes him. Another thing is that we're told that in his childhood he didn't like school much so he went drawing and painting and fishing. How did he leap from there to become a chemist? That's right. Well, he loved to sit
Starting point is 00:04:13 in the garden of the tannery by the river apparently and he did indeed do watercolours and later in life he actually gave lectures at the Ecole de Beausard in Paris because he knew a lot about the chemistry of paint and so on by that time so he wasn't giving lectures. There's a bit of a cum now and I want to be taught off on my paintings.
Starting point is 00:04:30 And I say, we want to know the chemistry of paint. Get on with it. Yeah. Well, he had a strong aesthetic sense, which may have fed into the fact that the first area of chemistry he worked in was crystallography, which we'll talk about probably later. But, and he, as you said, he never, in a way he never left.
Starting point is 00:04:50 I mean, he did. He went to Paris, but he made Paris work for agricultural France. And he was always going back to the field. so to speak, to the places where interesting things were happening. So field, he set up field laboratories to study silkworm disease in the south of France and so on. So he was in constant, he was no ivory tower scientist who went to Paris and that was it. You know, thank God to be out of the provinces or whatever. He was always going back there and bringing his laboratory with him.
Starting point is 00:05:18 Can you just summarize for us why chemistry became so important to the way his studies, his thought, his development? Well, this could take us quite far afield into the program. I suppose the most general way of putting it would be to say that chemistry, well, first of all, most industrial processes were chemistry. And chemistry itself grew out of pharmacy and metallurgy and all kinds of production processes in the 18th century. So there was always a relationship between, there could be a relationship between the theoretical and the practical, which became a hallmark of, you could take it in one way or the other. But Pastor always straddled the two. And I think that also was characteristic.
Starting point is 00:06:00 That chemistry as a field allowed him to do that very well. Thank you. Michael Warbois, he later had regrets over abandoning his early work as a chemist when he had visions, not I don't mean silly, where he had a vision of what life might be like. Can you tell us what that vision was and then why regretted demanding it? The vision came from the work that he did for his PhD on crystallography. and that set up really two branches of science, really. The first was the study of what's now called stereochemistry, which is the idea that you can have the same molecule,
Starting point is 00:06:37 but you can have it in mirror image forms. One, like if you look at your hand, you have a left hand and right hand. They're the same structure, but they're different. And that's a basic asymmetry left and right. And what he found in his work, that organic compounds, those produced by living organisms, tended to be mainly left-handed, but also right-handed as well. And so he had this idea that asymmetry was the key to understanding life.
Starting point is 00:07:08 Asymmetry. Asymmetry was the key to understanding life. And paradoxically, given his later work where he's now famed for defeating the idea of spontaneous generation, he was inspired early on in his course. career in his career that he might actually be able to create life. So he found some, he got some organic material and he subjected it to heat, to magnetism, to electric currents to actually see if he could create life. And this, the notion that asymmetry was the key to life was important. And there's a letter from his wife saying that
Starting point is 00:07:48 this could possibly make him the Galilei or Newton of biology. So you can see that there's a degree of ambition in the family very early on in his career. Can we push, can you push, can you develop that a bit further? Because it is fascinating. He did think that he, that life was the most curious thing of all, and that there was, he had found a key to it. How about, do you think he had? What do you think?
Starting point is 00:08:13 Well, we now know that life is much more complicated than that, the molecular violence. But as a start, somebody's got to start, and was it a good starting place? If we go back to where he started from, his PhD was, on crystallography and he was investigating that through the way in which light would be refracted through crystals. His teachers were working on quartz, but he worked on organic materials. And going back to Andrew's point, the key organic material that he worked on was tartaric acid, which is a product of the wine industry. And the sorts that he did his primary investigations. on were the sorts of tartaric acid, sodium aluminium tartrate.
Starting point is 00:09:00 And so he was investigating these crystals, and he found that it was long being known that in some instances fermenting fluids become clearer as they ferment. And this encouraged him to look to see if he could find a way in which microorganisms might be used distinguish between left and right-hand crystals. And if you could do that, then that may be the way to pursue left-handed crystals
Starting point is 00:09:34 and take left-handed organ and take things forward. Can you, he had a great, you've already said, his wife said, well, this is it, he's up there with Galileo and Newton. He was an extraordinary confident man. How important was that particular self-confidence, an enormous self-confidence to what he did? The idea of the key that, the idea that asymmetry is the key to life was one of, was he established as a principle.
Starting point is 00:10:01 And throughout his career, he was feigned really for two things. One was having quite strong principles that he wanted to follow in the spontaneous generation controversy, which we'll talk about later, the idea that only life can produce life. But on the other side, he was a great experimentalist. Experiment governed his whole approach. to the investigation of chemistry and biology as well. And this was, as Andrews said, both in the laboratory and in the field and in applied areas too. And a phenomenal keeper of multiple well-described, well-written notebooks.
Starting point is 00:10:39 Yes. Anne Hardy, what theories were there for the, what theories were there for the causes of disease before Pasteur came along? Well, there are three, essentially. We begin with contagion, which is the oldest of. them, which is the idea that somebody with an infectious disease can communicate that disease to somebody else, as in smallpox, as in bubonic plague. And the second idea that comes along in the 1830s, 1840 is a miasma theory, that is that the smells and things given off by rotting organic matter can generate disease of their own accord.
Starting point is 00:11:23 And finally, there is spontaneous generation, which was developed by Felix Alexandre Proucher in the 1850s, and that was the idea that Pasteur came into such hot dispute with. And so when he came on the scene as a youngish man getting on with it, these three were around, which one did he obviously would know all about it? He know the field very well, to put it in mind. Which one did he seize on as the one he would follow most closely? I don't really, at this juncture,
Starting point is 00:12:00 I don't think he'd formulated that idea quite so clearly. I mean, he starts by engaging Proucher on the subject of spontaneous generation, which we're going to talk about later. Well, let's talk about now, because you recall keeps saying we'll talk about later. You know, I'll control that if you don't mind. So let's talk about spontaneous show duration. It's fascinating. Give us the battle lines there.
Starting point is 00:12:24 Well, Pousche argued that matter could just organise itself to produce new beings, as it were. And Pastor strongly disagreed with that. And he was just deep enough into his fermentation studies that he was beginning to, to move his way towards a germ theory of infection. We don't put it like that just yet, but that's where he was going.
Starting point is 00:12:57 And he knew that fermentation was caused by the intervention of microorganisms of some kind. And he famously engaged with Proucher in debate and effectively destroyed him. So nothing came of nothing as far as? Nothing, yes. His question is, his question is, you know. Where was there something?
Starting point is 00:13:17 And there's something he all thought was in the air? There were bodies in the air, just around the player. Yes, I mean, he had the... The air we breathed had things in it which made other things happen. Yes, there are yeast. And so microorganisms were effective in causing life. There are yeast spores, for example. And causing death as well because they broke things.
Starting point is 00:13:32 How did Edward Jenner's work on smallpox play into this? Okay. General is important because he is in fact the first person to produce a vaccine. This is about 50 years before. This is 1790s, yes. And smallpox, as we hope we all know, was a very unpleasant and deadly disease. It occurred in several different forms, so it could be very mild or it could be very severe. And Edward Jenner was a country practitioner, but he was well connected to the English scientific world.
Starting point is 00:14:07 He knew that the Hunter brothers, the great surgeons, and he was in communication with them. And he had a GP practice in rural Gloucestershire in a daring area. and one of the diseases that was present in the daring area among the cows was something called cowpox. And this is a point at which inoculation against smallpox had been introduced by Lady Mary, Wirtley Montague, from Turkey early in the 18th century. And by this time there were drives to inoculate people against smallpox. But to inoculate people against smallpox, you have to give them a dose of the disease itself. ideally you're giving them a mild case.
Starting point is 00:14:49 That doesn't always happen. So Jenna was busy inoculating his flock in his parish. And he came across cases where the inoculation would not take. He got a reaction, a sort of inflammation around the induction site, but he did not create a case of the disease. And over a number of years he collected a whole system. series of these cases, sometimes involving whole families. And in all these cases, he discovered that these individuals had had cowpox first.
Starting point is 00:15:24 So the milkmaids complexion? So the milkmaids... Yes. It was a reality. Well, it usually affected their hands. And that was where they got the infection from. So if you get cowpox, it was a mild view, and you got an injection, you didn't get some. So he was on to that, which was a major step forward.
Starting point is 00:15:42 Andrew Mendleton now, were you going to say something? That's fine. Andrew, can we talk about, Pastor, unless you put your hand at once as well, unless this is something massive with us, let's move on. What is his work on fermentation? Why was that so important to the development of his ideas? In a couple of ways.
Starting point is 00:16:03 I mean, first of all, it gave them a way to move beyond what had come before, so one-off, relatively one-off experiments to show that yeasts were living things and caused fermentation processes. Why is it choosing yeast? Well, fermentation processes were most familiar to people through the things that I mentioned before, wine making and the brewery. And there was a lot that was well understood about them.
Starting point is 00:16:37 And there was a scientist, let's say, in the 1830s, who showed that in order for fermentation to happen, or fermentation would not happen if you heated the air in which the fermentation to which the fermentation process was exposed and the reasoning was that this was killing whatever might be getting to your grape juice and turning it into wine that would have been alive and the heat was killing the life that was coming in
Starting point is 00:17:05 the living things that were coming with the air to your grape juice but that remained a kind of one-off experiment that showed that life was essential to fermentation process Whereas what Pasteur did is to generalize from that. So he showed that there was a microorganism associated with the souring of milk, with a lactic fermentation. And then he showed, he took this piecemeal world of fermentation processes, and he said, well, actually, there's probably a general principle here. And we can pursue it and find a whole series of microorganisms in relationship to processes that are both familiar. to us and that we can understand chemically.
Starting point is 00:17:47 And that generalization move, I would say, is, that's how to think about what it meant to create something like microbiology rather than just, well, we work on fermentation or we work on these practical problems or we do a bit of chemistry here or to create a, it's the generalizing from this or that phenomenon to a general principle. And in fact, he was ambitious. We talked before about how he, he, he. He had a theory of life that involved molecular asymmetry. Well, he had a theory of fermentation that he called,
Starting point is 00:18:22 it was, fermentation is la vie sans air, life without air, which is actually a highly, a principle at a much higher degree of generalization than, well, this bug causes souring of milk and that bug causes, gets us wine, right? So this was a higher order generalization he was always interested in. But where did he articulate that in, I think it's Chapter 5, a book called Study, on beer. So he always published books that were practical within which he developed guiding, ambitious
Starting point is 00:18:51 theoretical programs, which don't necessarily hold today, but allowed him to go from working on breweries to creating a whole area of science. It's that generalization move that's important. Michael, Michael Walboys, we've talked about micro
Starting point is 00:19:06 micro, how did, first of all, how did the technology of the time assist him? I mean, this is a technologically driven age and the masses of things that are happening when people didn't know how the plague came about, how they'd be bonneclay about, this came about. It's partly because scientists of the statue of Pasteur are seeing these things because they've got instruments.
Starting point is 00:19:29 Is that right? Can you develop that? Microscopy is certainly important, but it wasn't absolutely critical to Pasteur as it was later with Robert Koch and the development of bacteriology in Germany where Koch coming from a different tradition of botanical training was in charge. in the actual form of organisms.
Starting point is 00:19:46 Pasteur was a chemist moving towards physiology and was more interested in the processes that microorganisms initiated and sustained. So his main tools, he did use microscopes. I mean, crucially, in the work on silkworms, where this goes back to the question that you asked Anne about Pasteur's ideas on theories of disease, very early on, when he was asked to investigate silkworm disease, which was devastating
Starting point is 00:20:20 the industry in France, he worked on it for five years, and he explored a number of different ideas as to how it was actually caused. And he came up with some quite remarkable findings, and I think they typify a lot of his later work. He used the microscope to actually find that one of the diseases, there wasn't one disease, there were two diseases. is causing a problem. One of the diseases was actually you could see the corpussores, he didn't necessarily call the microorganisms at that point, you could see the corpuscles actually in the eggs and in the larvae
Starting point is 00:20:54 of the silkworm. So he was using microscopes and he tried to make microscopes available to the growers in the area to actually do this. The second disease was actually a form of silkworm diaries, I suppose is what you call it. It's now recognised as a viral disease.
Starting point is 00:21:18 But that was avoided by good horticulture, by making sure that the mulberry leaves weren't contaminated with disease, with the dust or whatever it was that was causing the disease. So he's using the microscope, he's using physiological methods. He's actually engaging with what we would now call stakeholders. He's giving lectures to the mayors, these towns, so he's making use of a whole range of technologies to investigate.
Starting point is 00:21:49 But as Andrew pointed out, graphically about in chapter 5 of a book on beer, he comes up with something which then becomes very important and resonating and continuing generalisation. And, and Hannity, he's a chemist, he becomes drawn into the study of animal diseases. Is he going, as it were, back to the childhood, back to what was around him and saying, these are real problems here and I've got to, you solved the problem with the silkworm industry. so that nobody's in suspense about that. And how did he get drawn into animal diseases?
Starting point is 00:22:20 You're right. The fermentation studies and silkworm diseases inspired him with the desire to do something about infectious disease, which, as we know, was a big problem in the 19th century, more than ever before because of the growth of towns and industrialisation and so on. And so he... he um he's sorry i've got i got myself stuck here um well we're talking about he got george animal diseases well he had to study the animal diseases because he was not a doctor
Starting point is 00:22:55 he's not qualified in medicine and if he had attempted to um study human diseases in humans the french medical profession would have had it in for him in a big way oh i see and And in fact, when he comes to administer vaccines, he never administers them himself. It's always a medically qualified colleague who does it. So he has to go to animal diseases. But there's also an ethical component there, which he made clear to Congress in a meeting in Copenhagen in 1884, when he said quite clearly that although it is allowable, experimentation is allowable on animals, it is criminal on man.
Starting point is 00:23:40 So there's a very clear understanding that, you know, it's a necessary evil. But you went, Andrew Mendelsohn, he went into the chicken problem of chicken. You would say so much. I mean, I think by the time he works on anthrax, I was going to talk about anthrax. Yeah, I mean, he, one does this,
Starting point is 00:23:58 given his success with beer and wine and silkworm, he's famous. He is the go-to guy. So, I mean, he is invited to work on some of the, on these problems because of his, because of his reputation. I was coming to anthrax. What does he do there that's important, Andrew? Well, yeah, I'll come to anthrax as well, but I think trying to put all that together in the sense that, I mean, it was a typical move, not just for Pasteur, but for many people at the time to study animal diseases. because you didn't have the problem of creating an animal model of a human disease. So never mind human experiment, but in order to work experimentally on human diseases,
Starting point is 00:24:42 you always had to figure out whether you could get something going in your laboratory that was a mouse or a guinea pig or a rabbit or whatever it was that you could use as a stand-in for a human being. But with an animal disease, you didn't have that problem because you were working anyways on an animal disease. and he actually started working on diseases of higher animals. Of course, he had worked on animal diseases when he worked on the silkworms, but with higher animals by working on chickens,
Starting point is 00:25:08 and that was a lot cheaper than working on anthrax because cows and sheep were more expensive experimental objects than chickens. So he was working on foul cholera. And it was also it had a practical importance. And as Michael was saying, whenever he does this work, you shouldn't imagine it that he's off on his own, saying, what am I going to do next? He's always communicating with the very vibrant world of French agriculture at the time,
Starting point is 00:25:34 which is organized in societies and local academies, and on which there is actually a buzzing world of publication, of investigation. So he's not the scientist arriving on the scene with a bunch of country bumpkins with their chickens. He is in a world that is already doing a lot of research on itself. But he comes with tools that they don't have, which is where the chemistry comes back in. and the microscope. So they don't have as much chemistry as he has. Can you tell us about the impact he had from his work on anthrax?
Starting point is 00:26:07 So, well, the first thing to say about anthrax would be that he sort of missed the boat in the sense that the year before he started to publish on anthrax, Robert Koch had published a paper. This is the German bacteriologists. They're more or less contemporaries and more or less rivals. Yes, so they're rivals, but they come from two completely different backgrounds. which gets us back to two pastures childhood. We can come back to that maybe, but just quickly about anthrax.
Starting point is 00:26:32 So a lot of people studied anthrax because under the microscope it was big and unmissable, whereas the proliferation of all kinds of other microbes under the microscope was difficult to distinguish. But the anthrax rods were actually big and visible. So there was a lot of work on this. But Kho demonstrated that these inert, apparently inert rods actually had a life cycle. so they with a spore stage and so he did he showed that they were alive and and they underwent division and so on and so when pastor got on the scene most people would have said that the question of whether these anthrax rods found in the blood of anthrax animals dead of anthrax are alive and therefore we have a germ theory of anthrax it was pretty much tied up but there were sort of a host of doubters and and so the beginnings of pastur's entree into anthrax were not all that important. What became important is when he began to manipulate the virulence of anthrax,
Starting point is 00:27:36 which happened after he'd begun to do this with the cultures. So we're talking about cultures in the lab in glass dishes and in flasks of the chicken cholera, a foul cholera microbe. So it's really at the stage of how can we, manipulate the pathogenic power of these microscopical creatures. Michael you both mentioned Koch. Can you just bring him more into play, K-O-C-H? The German bacteriologists who had it went on a different line. The two of them
Starting point is 00:28:11 actually make one, don't they? Make a hell. Well, they wouldn't agree with that. I'd just be too neat for my own good, yeah. Yeah, Koch was a German public health doctor who trained in botany and as well as his medical career. And in the 1870s, Khock developed, you don't know it, bacteriology as we know it, which is using microscopy to identify specific organisms, using stains to make them easier to see in the microscope,
Starting point is 00:28:44 to critically culturing organisms on agar plates, on flat plates. Pasteur was doing most of his culturing in tube. and one of the criticisms that the Cox school made of Pasteur was that his experimental technique just wasn't as effective and as clean as theirs were. So Cox's emphasis is much more on the causes of disease. He's trying to find specific organisms that he can associate with diseases. He does it first with anthrax. He then does it with wound infection diseases. and then in 1882, 1883, which is when Cock and Pasteur really begin to engage in controversy,
Starting point is 00:29:27 he finds the tuberical bacillus and then the cholera, the cholera bacillus in 1883. And interestingly, with cholera, by that point, he actually goes to France to investigate a cholera outbreak in France, that he's kind of, when this starts, as Andrews said in 1876, Cock is the unknown and Pasockes is already the European star of this emerging field of microbiology. By 1882, 1883, when they first start to lock horns, Cock is the coming man. And it's Cox bacteriology, which effectively is the one which goes on to dominate. And if you look at the lists of who discovered which microbes,
Starting point is 00:30:11 most of them are in the Cox score. The Pasteur score scientists make very few classical. discoveries. Their work is mainly on vaccines and variable virulence. But the vaccines is, to put it mildly, very important, massively and can we come to that? How did
Starting point is 00:30:30 Pastor, the problem of rabies was a strong, and partly because that did affect humans, and he tackled that. Can you tell us a little about that? Yes. I think it's important to remember the story Andy didn't tell earlier, which is that
Starting point is 00:30:45 Pastor in his childhood in the juror had witnessed a rabid wolf attack in his home village. And the only preventive for that kind of, I mean, it was known that rabies was transmitted that way through the bites. And the only preventive that was then possible was quarterization with red hot irons and smithy. And the young pastor heard the cries of those people being quarterized and it deeply traumatized him. So there's that memory there in his background. What kick-starts him off is that there's a young veterinarian called Galtier, who was working on rabies at that time.
Starting point is 00:31:31 And in 1879 he publishes a report in which he says, states that rabbits are the ideal laboratory animal for experiment with rabies. and also makes a suggestion that because rabies has a very long incubation period and humans between the bite and manifestation of symptoms it can be a minimum of one to two months to a maximum a year or more and that given that there is that symptomless period it would be possible to develop a remedy which could be administered before the symptoms and so what did pastor do? So pastor gets to work on rations.
Starting point is 00:32:14 and this involves kennels full of dogs which make a lot of noise and a lot of other animals and it's a very hitomous procedure and the idea of the can you just mention sorry I mean what he does is he he he used in the laboratory he tries to alter the virulence of the various virus this is where the word attenuation has a place can you explain to this as what is attenuation is in some way weakening the power of the organism
Starting point is 00:32:44 and Pasteur finds that there are various ways of doing this. The classic way is to do it by exposure to air, which he thinks that the virus. I mean, people don't know at this stage that the virus is an intracellular parasite. Virus is a term which had been used for a chemical poison, but now it's thought to be a kind of living organism, but no one's actually seen this, and indeed nobody does see it until the 1930s, I think. So he begins to play around with altering the virulence of this, by exposure to oxygen, by using antiseptics, by passing the virus through different laboratory animals.
Starting point is 00:33:22 So if you pass it through rabbits, the virulence increases. If you pass it through monkeys, I think it diminishes. So he plays around with this. And he then starts to develop protocols with dogs, where you try to build up immunity by giving different gradation, by starting off with a very weak, a very weak, virus and then building up to try to encourage immunity, but he also tries other ways of doing it. And he has some success with dogs, but it's quite unpredictable. Rabies is actually quite a difficult disease to work on in the laboratory because the infection
Starting point is 00:34:02 is complicated, that it requires, the virus needs to get into the nerve fibres in order to be effective. And so one of the techniques that he uses is to actually inoculate the virus into the brains of rabbits directly, rather than give them injections into the blood. Andrew. Andrew Mendelso. I just wanted to say that perhaps the way to think about the bigger picture of this strange thing we're calling attenuation, which just means a weakening of the virulence of microorganisms, we'd be to say that far from the idea that the contributions of Pasteur and
Starting point is 00:34:42 Kohlhen, the others, was to say that far from the idea that the contributions of Pasteur and Kach and the others was to say that was to show that germs cause disease. In Pasteur's case, it was to say, well, actually germs cause disease under certain conditions and under the other conditions, they don't. People, everybody doesn't get TV. Well, exactly. And whereas Koch was very, Koch came from a completely different tradition, not just that he was a medic, but he came from a tradition of several centuries that focused on what you said before,
Starting point is 00:35:08 on contagion. And he was interested in establishing clear causal relationships and blocking them, blocking the germs, whereas attenuation was how can we use our artificial means in the lab to cultivate them and weaken them. But he began to manufacture vaccines in his laboratory. This was one of the great things that happened. How quickly did that take on these manufactured vaccines and how effective were they? Well, certainly the rabies vaccine, we have to, the rabies vaccine was, was took on was replicated all over the place. So it was, it was very quickly established in many places around the world. And you have to remember that
Starting point is 00:35:50 the rabies vaccine had this dramatic quality that it wasn't a prevention. It was something given to somebody who had already been bitten. So it's not like vaccine that we get today when we get as a child and we'll keep us from getting something later. The anthrax vaccine was quickly taken up around throughout France. A lot of statistics were kept. And so on the other hand, there then was a pretty long pause period before it was possible in medicine to establish a whole array of vaccines. I would say there was an initial model that was very successful. Michael. One of the points that I think is worth saying, which is going back to the smallpox thing, is that Pasteur appropriated the term vaccine from Jenna in order to
Starting point is 00:36:39 legitimate that his practice was of the same type as generous use. So we use the term vaccination today for all of these things, but it actually comes from vaccinia, which is cowpox. So Pastor did that. I think the second thing to say is that by this time, I mean, the rabies thing was kind of, I mean, some people have argued, it was the first medical breakthrough. It's the first laboratory-based cure,
Starting point is 00:37:04 which actually kind of reaches the front pages of newspapers. This was really big news in Paris. People flocked from all over the world. People bitten in India got on a boat and traveled to Paris to take the cure. You know, that's whatever it's six weeks because of the long incubation period. This was the beginning of the thing that we see regularly in the papers today of medical breakthroughs, reaching the public. And, Anhelly, how did his work influence ideas of cleanliness in hospitals? That again goes back to the fermentation story to begin with.
Starting point is 00:37:41 I mean, the great English surgeon Joseph Lister, he was actually a Scot, was very interested and stimulated by Pasteur's ideas about fermentation. And one of the big problems in hospital practice at that time was wound infections, whether it's wounds caused by accidents or wounds caused by surgery. So it's whether they came out of the wound or got into. the wound. Yeah, I mean, but what Pasteur had identified was that microorganisms are involved in processes of decay and that's what Lister clocks onto that, you know, there's all this
Starting point is 00:38:20 dying flesh around these wounds and he begins to use antiseptic means. He uses carbolic acid to cleanse his operating sites. The youngologist is a death to Pastor very generously throughout his life. Yes. He does. And from there he goes on and develops and it ends up spraying his entire operating theatre with boracic acid to... And then you get... To kill any lingering germs so that you don't get asepsis, sepsis and asepis.
Starting point is 00:38:54 And then the whole surgery becomes aseptic. And then it goes on to develop when other surgeons take this up and take it to further extremes. So you get the lab coats and the rubber gloves and the masks and hats, caps by the end of the century. I mean, Lister himself was practicing in the old-fashioned way in his ordinary street clothes,
Starting point is 00:39:12 but his own operating coat, which was covered in bloodstains and microbes, yes. Andrew. I was just going to say the other way of tying hospital cleanliness back to Pasteur would be to say that, of course, the problem we have today
Starting point is 00:39:26 is resistant strains, resistant microorganisms that don't aren't responding to our antibiotics. And you could say that the perspective that Pasteur developed or his team or at the time already included attention to what he already saw as the evolution of microorganisms at the time.
Starting point is 00:39:46 So the point being that there are a lot of 19th century science and roots of both the problems and the possible solutions to those problems go way back. So yes, medical breakthroughs, but on the other hand, actually long continuities established at the time that should make up. sometimes a bit wary about whether the solution that might serve us best is the one that's on the headlines, and maybe it's actually an old idea that we need to think about again. Michael Warboy's past as being described by you as a very great experimentalist. Can you briefly tell us how he arrived at that?
Starting point is 00:40:24 It was really the tradition of chemistry. Again, chemists at that time were laboratory scientists. They were developing a whole range of technologies to investigate the... the inorganic and organic compounds. In the early work on crystallography, it was the polarimeter to do that. So he was a great kind of, he had all these tools,
Starting point is 00:40:51 and he took them from chemistry to the study of life. But he was a tremendously hard worker, and as you mentioned earlier, he was an assiduous note-taker. And he was a very, although he had grand grand, grand principles in terms of ideas. In the laboratory, he was quite pragmatic.
Starting point is 00:41:11 He would change his mind quite quickly. And if something didn't work, he would try something else. And he also had a team of, mostly had a team of people working with him, which was partly goes back to his ambition. And he was quite good at gaining money for his research. He got support from the French state for the silkworm work. He was sponsored by the industry. So he was very good at, at the...
Starting point is 00:41:35 kind of organising research. He was very business-like in the way he operated. Very briefly, because we're near the end. What would you say his legacy was, Andrew? Oh, Pasteur's legacy. In a way, I'd say Pasteur's legacy was Pasteur, Louis Pasteur, in the sense that he showed us a model for what one form of scientific life can be. So it's not academic, although he was academic,
Starting point is 00:41:57 nor is it what we know today with the entrepreneur. It was public, it was engaged with the practical problems of the day, but it was deeply theoretical and even cosmic in his engagement. I mean, he really wanted to show how microscopical beings actually made the whole cycle of life operate. So we have to come to an end. Thank you very much. Andrew Mendelsohn, Michael Warboys, and Anne Hardy next week we'll be discussing the history of the idea of purgatory, where he said all souls of sinners are cleansed by fire.
Starting point is 00:42:30 Thank you for listening. And the In Our Time podcast gets some extra time now with a few minutes of bonus material from Melvin and his guests. I want to say, I want to put up Emil Rue as the unsung hero here because Pasta actually pinched several of his ideas, his research. I mean, they had a, he was one of a medical co-worker, and it was he who did the chicken collar experiments. and demonstrated the attenuation feature.
Starting point is 00:43:04 That was Ruse's work, which was hijacked by Pasteur's fan club, as Pasteur's own work. And also did the crucial, made the crucial connection in rabies between the injection of rabid material and its lodging in the spinal cord. and it was he who first thought of the procedure which eventually became established, which was the drying, taking the spinal cord to the rabbits, drying them out in different degrees.
Starting point is 00:43:40 And this story comes from Pasteur's nephew, wasn't it, who was a laboratory assistant, and he was one day putting a load of flasks into the hot cabinet, and Pastor was passing by, and there was one that interested him, and he said, who's is that? and Loire said it's Monsieur Rousse and Pastor took a look at it and he took it away with him
Starting point is 00:44:01 and that jar contained a piece of rabbit spinal cord which was desicating and Pastor adapted that to his own use and we go on for that interesting the portrait and I currently the portrait
Starting point is 00:44:20 which is always shown is of Pastor looking at this rabbit brain as if, you know, kind of musing on it, as if this is, this is, this is my great, this is my great, great, breakthrough. Yeah. Does that story bother the two of you? I mean, mine story.
Starting point is 00:44:36 Yes. Sure, I think Rue should have gotten more credit. On the other hand, what would he have done with it? And, I mean, he was a reclusive guy who, yes, it probably wasn't fair. What the other thing to say is, of course, they did actually publish together.
Starting point is 00:44:52 So, yeah. There were many co-authored papers. And there was, in a sense, I mean, Pastor was not just sort of using people around him. He created a form of collective work, of teamwork. I wonder if you could say the same about a lot of the great Renaissance paintings coming from the studio. If you look closely at the best bits, it's not by Michelangelo, it's by that little guy in the corner. He did all the borders. We observe the board as the best painted bits and the painting.
Starting point is 00:45:19 I think that goes on in any collective, doesn't it? Yeah. I think there's a lot to that. Right. And he did cultivate this team over decades, and Rue eventually became the director of the Pester Institute for many, many years. But I think that the capacity of each of those people to contribute, actually, to something major, did come back to what Pester set up for them. And in that sense, would Rue have existed if Pestor hadn't rescued him from dropping out of medical school
Starting point is 00:45:52 said, hey, come and work with me. And yes, there is an important point to make about credit. I agree with that. But I think you have to see it in the bigger picture. Yeah, and Rue swallowed his anger and his fury and continued working with Pasteur. Absolutely, yeah. And, you know, I mean, stayed devoted to the maison, you know,
Starting point is 00:46:14 throughout his life, so to speak. One thing we didn't talk about was kind of Pasteur's personality. And there was this kind of, not paradox. but there was great loyalty from his team. But also, he wasn't easy to get on with. I don't think the evidence is that he wasn't a people person. But nonetheless, he built good teams, he had good relations with them. And this was absolutely crucial going forward.
Starting point is 00:46:40 If you're not a good people person, you've built good team and you've had good relations. I mean, any normal sense of the word being a people person, the absurdity of saying I'm not a people person, it's all the stupidest phrases that's now circulated. I'm sorry I used it. Pretty odd, Michael. I saw the quotations, as you said it. But he seems pretty good people, person.
Starting point is 00:46:59 He'd put a team together, keep them going, and they all worked on something very important. And it was a huge devotion. Yeah, I mean, they could see how important the project was. Also, you know, he had a big stroke in his late 40s, major stroke down the left side, then he'd another stroke a bit later. He'd lost three of his five children.
Starting point is 00:47:16 There was things going on to stop him being a people person. No, I mean, the point was, that he was ambitious, he was confident, he would regularly take on his critics. I mean, he was, he wanted to defend his priority in lots of cases. He was driven, perhaps if that's another term I shouldn't be using. But what you're saying, really, which is very interesting, is the continuities of science.
Starting point is 00:47:46 When you earlier, Jenna does this and therefore he takes up the baton. All the scientists I talk, you say, well, that's the way it is. Well, exactly. I mean, I think one could add to that and say that if you think about what the kind of medical breakthroughs of the 20th century that really affect everybody's lives from childhood on, although there are problems now, vaccines and antibiotics, right? Penicillin, so to speak, and vaccines. And those are, even though we live in this world in which we expect things to come from, you know, yesterday, from today's news, actually those are 19th century science, really. And they go back, they don't all go back. The point is not to say, oh, it all goes back to the genius of Pasteur. That's not really the point at all. But the point to say there was a very productive relationship between the practical arts, fermentation, chemistry, and Pasteur, I think of as a kind of lens,
Starting point is 00:48:38 a powerful magnifying lens, that focused all these resources and forces that he had around him on these problems. And he did, I mean, he certainly was, he certainly, I mean, driven is a word that one can use. I mean, he was, he lived this science all the time, but he did it very, in a very collective way, at the same time that Glory did tend to focus on him.
Starting point is 00:49:00 I mean, he and his wife were a team, the pictures that show the research at the silkworm sites down in the south of France. He's sitting there with him, and so he worked together with people in those ways. That's coming back. We keep coming back to Pasteur. We want to keep talking about medicine.
Starting point is 00:49:17 But actually, Trace's descriptions, I said that we were supposed to talk about, a pasta yesterday. We have our excuse in print in the radio time so you can't argue with that. No, no. I think the other great legacy
Starting point is 00:49:31 thing, which is not necessarily Pasteur himself, is the Pasteur Institutes and the actual establishment of medical research, as we know it, kind of, you know, the expectation that new vaccines, cures for
Starting point is 00:49:46 disease, greater understanding of disease will come from dedicated research institutes. And that was a result of the success of rabies. When I said medical breakthrough, I wanted to put it in inverted commas, because these medical breakthroughs are kind of, as we've said, they're continuous.
Starting point is 00:50:07 They come from a continuity of work, but they are used by scientists and pastures. As they become breakthroughs in order to attract public attention to attract funding. And the Pastor Institute was the major outcome, of in institutional terms, the pastours work. And then very quickly, we have similar institutes in Germany, in Britain, in the States,
Starting point is 00:50:31 and this is the way we now think about medical research. Well, you could say there are a number of models. One is the research university, which was essentially a German invention, with institutes of research devoted to particular subjects, which was very much imported into the United States and less so here until at a later stage. And then there is, of course, what we have today,
Starting point is 00:50:50 there's the entrepreneurial science where a pastor was somebody who actually took out quite a few patents but he did that he never capitalized on them so he never went into business so his is a third model between the more familiar ones of the research university academic research and the the industrial or corporate or entrepreneurial way of pursuing research and this was a the pastoral this is very much a different a third way of doing that public but also partly private subscription funds way of doing research. The producer is hovering at the door with an offer that you're not allowed to refuse. You can refuse it if you want.
Starting point is 00:51:27 Do you like tea or coffee or something from flask? Coffee please. There are many more science and discussion programs from Radio 4 to download for free. Find these on the website at BBC.co.com.uk slash Radio 4.

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