Aarati Asundi (00:12) Hi everyone, and welcome back to the Smart Tea Podcast, where we talk about the lives of scientists and innovators who shape the world. I'm Aarati. Jyoti Asundi (00:20) I'm her mom Jyoti. Aarati Asundi (00:22) So, mom, you recovering a little bit? You were just telling me that you didn't drink your coffee this morning and you're a little bit out of it. Jyoti Asundi (00:30) Isn't that weird? I didn't even feel the need for coffee in the morning, but then my head started to buzz and I was thinking, wait, I did everything right. I did my yoga outdoors in a very cooling breeze which was really wonderful. And then I had a nice meal and then I'm thinking what did I miss that my head is buzzing. I slept well couldn't figure it out. I missed my one cup of coffee that I allow myself every day in the morning. I miss that by mistake. I didn't mean to Aarati Asundi (01:03) And now your whole system is thrown off. Jyoti Asundi (01:05) It's weird. So I am going to have my caffeine fix while I'm doing the podcast with you. Aarati Asundi (01:12) Perfect. Jyoti Asundi (01:12) And hopefully that buzzing will go away and I'll become productive. Aarati Asundi (01:15) Yes, hopefully you'll recover nicely. But the reason I brought it up is because it actually relates a bit to what we're talking about today. Jyoti Asundi (01:24) Okay, how does it relate? Tell me. Aarati Asundi (01:26) I'm curious if you'll recognize the name of the person we're doing today. his name is Theodore Escherich. Jyoti Asundi (01:34) No, and you know me and names. I'm useless. And without my caffeine fix, forget it. Aarati Asundi (01:40) Okay, but I know for a fact that you know his contribution to science. Theodore Escherich is the one who discovered Escherichia coli or E. coli, the bacteria. Jyoti Asundi (01:54) Oh! I thought- I spell it differently. I spell it Esher-ishia like that. Aarati Asundi (02:01) Ah yes. That is also a thing. Like the accent may be different or the way we pronounce it might be different because it's such a long, confusing word. Jyoti Asundi (02:10) Yes. Maybe if you had said Esher-ish because I know Esher-ishia coli. It's the fundamental organism, right? It's the one of the first gram negative bacteria ever discovered. Oh my god, I am excited to hear about the details of this story. You know, I started life with a bachelor's in microbiology. Aarati Asundi (02:33) Yes. So when I was researching this I was like, she's gonna enjoy this one. Jyoti Asundi (02:37) Yes, Aarati Asundi (02:38) We're gonna be talking all about bacteria, microbiology, and we're gonna be talking a little bit about your gut microbiome, which is how it relates back to your coffee situation. Jyoti Asundi (02:50) Very interesting. We are finally understanding the importance of gut microbiome. And not just that, it's good for your digestion and blah blah blah, and keeping a good physiology, but it's actually there are multiple studies now about the gut brain axis, about how your gut health directly impacts your brain health, your chances of getting dementia, your chances of getting Alzheimer's, all of that, and how that links to poor gut health. So this is going to be very good, episode I can tell. Aarati Asundi (03:27) Yeah, I would almost call him the father of the microbiome, although he didn't actually take it quite that far. But he was very interested in gut health and the bacteria that live in your gut. So we're gonna be talking all about that. Jyoti Asundi (03:40) Very interesting. Okay. Aarati Asundi (03:42) So let's get into his story. He was born on November 29, 1857, in Ansbach, Bavaria, which is Germany today. And Ansbach is very close to Nuremberg. His father, Ferdinand, was a physician and a district medical officer for the government. And Theodore was born to Ferdinand's second wife, Maria Sophie von Stromer, who was the daughter of an army colonel. We don't know much about Theodore's childhood. We do know that his mother Maria died when Theodore was five years old, likely during childbirth to Theodore's younger brother, who also died around the age of four or five. Jyoti Asundi (04:24) So at this point when the younger brother died, Theodore would have been closer to eight, nine years old. Aarati Asundi (04:29) Yeah, correct. Jyoti Asundi (04:30) Yes, got it. Okay. Aarati Asundi (04:31) Yeah, and this was a fairly common occurrence. People didn't know really about bacteria yet, we're not quite there in this time. But this is the same decade that Louis Pasteur is doing his famous experiments on fermentation and putrefaction. Jyoti Asundi (04:47) Yes. Aarati Asundi (04:49) And our friend Joseph Lister is also just starting to conduct experiments on sterilization during surgery. Jyoti Asundi (04:56) Yes. Okay. So this is past the point of Anton van Leeuwenhoek peering into his microscope. So we do know about bacteria, but we just don't know how totally pervasive they are. And how easily they can get into the body to infect. Aarati Asundi (05:14) Yeah, and I think there's still a lot of arguments happening right now about whether bacteria actually even exist or whether it's like the miasma, the bad air that causes infections... Jyoti Asundi (05:25) That's right that's right. Aarati Asundi (05:26) ...and you know, the four humors and all of that. Like there's still a lot of arguing going on. And Ferdinand, Theodore's father, as a physician, was very deeply concerned about high childhood mortality rates, especially among the poor. Jyoti Asundi (05:42) Yeah, and remember we are talking about how he has lost his second wife. We are not even talking about how his first wife died, but he's already lost wife number two. Aarati Asundi (05:53) I don't know about his first wife at all. I was looking. I couldn't find anything about did she die? Did they get divorced? What happened? Like I've no I have no idea. After Theodore's mother died, the family moved to Wurzburg, Germany, and Ferdinand remarried. Other than that, the only other clue we really have about Theodore's childhood is that he was a major prankster. At the age of twelve he got into trouble at school and was sent to a boarding school run by strict Jesuits, which is a Catholic male order promising poverty, chastity, and obedience. Jyoti Asundi (06:26) Okay, almost on the track of priesthood maybe? Aarati Asundi (06:29) Maybe? They- I think they just had very strict rules about being obedient and since he was such a prankster and quote unquote rough boy, they were- Jyoti Asundi (06:38) They wanted to beat the prank out of him by sending him to such a strict school. Aarati Asundi (06:43) Yes, he was sent to this school in Austria for three years. However, according to one source, it didn't really seem to have that much of an effect on him. Yeah. Jyoti Asundi (06:52) Yes, that- that makes complete sense because if you have a independent spirit, if you have strong will, you will learn to navigate that kind of cruel system until you can get out again. Aarati Asundi (07:05) Yes. Theodore went back to Wurzburg to complete his education, and then he went to the University of Wurzburg for medical school in 1876. He got his medical degree in 1881, and then he spent a few months at a military hospital in Munich before returning back to Wurzburg. Here he became an assistant to Dr. Carl Gerhardt, who was a doctor of internal medicine at the Julius Hospital. But Dr. Gerhardt was also interested in pediatric medicine and was in charge of the small infant clinic at the hospital and had written a textbook about childhood diseases. So, thanks to his influence, Theodore also becomes interested in pediatrics and actually even wrote his doctoral thesis on "Marantic thrombosinusitis and cholera infantum" which, as far as I can understand, is studying brain blood clots in infants who had cholera. Jyoti Asundi (08:02) Oh okay. Uh-huh, uh-huh. Aarati Asundi (08:03) Theodore highly respected Dr. Gerhardt, but Wurzburg was not the best place to specialize in pediatrics. So under Dr. Gerhardt's advice, Theodore left to go to Vienna to study pediatrics in depth at Saint Anna's Hospital, which was the first German speaking children's hospital. Here he studied under some of the most prominent pediatricians of the time, including the chair of pediatrics at the University of Vienna, Hermann von Widerhofer. But he also started to develop here an interest in bacteriology. So now we've gotten to the point that Louis Pasteur has shown that microorganisms were responsible for spoiling wine, beer, and milk, but that heating the liquid up to between 60 to 100 degrees Celsius, killed most bacteria and molds. Jyoti Asundi (08:55) Yes. Aarati Asundi (08:56) Joseph Lister had taken on this idea and started successfully operating on patients in sterile conditions to reduce the frequency of infections. Jyoti Asundi (09:06) Yes, yes. You talked about that in your episode number three, I think. Aarati Asundi (09:10) Yes, episode three! Jyoti Asundi (09:11) Yes, yes! Which is a fascinating story of these times. They should go and listen to the story of Lister. Aarati Asundi (09:18) It's a little bit bloody and gory, but it's- it's really interesting. Yeah. Jyoti Asundi (09:21) But it condenses five lifetimes into a little over an hour episode and it's really worth it, I think. It's one of the best episodes. Aarati Asundi (09:29) Yes, it was a really fun one. And Robert Koch had discovered that a bacterium causes anthrax, which is a disease that is deadly to livestocks and sometimes humans. Jyoti Asundi (09:40) Yes. Aarati Asundi (09:41) So scientists were now finally more or less on board with the idea of microorganisms, but it's still a very new field. Jyoti Asundi (09:48) Yeah, it's just starting out. The immense scope of what a bacteria can do, whether good or bad, is still just now- they are touching- it's like the tip of the iceberg at that particular time in history. Aarati Asundi (10:02) So Theodore, now with his interest in pediatrics and preventing infant mortality, and now also his new interest in how bacteria might cause diseases, he conducted the first ever bacterial analysis of a mother's breast milk. And he found that although breast milk is naturally sterile or has very low amounts of bacteria, if the mother was sick and had a fever, that bacteria would show up in the breast milk. Jyoti Asundi (10:32) That's right. That is very good point. Yeah, yeah. Aarati Asundi (10:35) I do have to caveat this though, because more recently, scientists have found that breast milk is not actually sterile. It does contain very low levels of beneficial microorganisms that help populate the baby's microbiome. But Theodore probably would not have seen any of this just because of the, you know, technology at the time. Jyoti Asundi (10:54) Yes. The low the low population density of those microorganisms. Aarati Asundi (11:00) Yeah. He's looking at samples under a microscope and he's not seeing anything because the concentration or the amount of bacteria is so low. The other method he tried was culturing the bacteria or trying to give the bacteria the right conditions to grow and multiply so that you could detect them. Jyoti Asundi (11:20) Yes. And each one has its own. And I think we talked about this in the episode where we did the Mycobacterium and how hard it is to grow them. Aarati Asundi (11:32) Yes, it would have been very difficult. Jyoti Asundi (11:34) Yes. It would it would- yeah, some of them are really difficult to grow, so you think it's nothing is there, but actually there is something lurking. Aarati Asundi (11:42) And actually I didn't know this, but breast milk also contains compounds that suppress bacterial growth. Jyoti Asundi (11:48) Nice. Aarati Asundi (11:48) So that would have made it even more difficult if you were trying to culture it. Jyoti Asundi (11:52) Yes. Hmm. Aarati Asundi (11:54) And then even if he did get lucky once or twice, he might have reasonably assumed that the sample had gotten contaminated somehow. So even today, actually, I was looking it up. It's a very difficult question to figure out what bacteria are in breast milk naturally. And we've only really started to understand it after 2003, thanks to genetic sequencing. Jyoti Asundi (12:18) Ah nice Okay. Okay. Aarati Asundi (12:20) So interesting. But the main point is here he found that if the mother is sick, the bacteria does come through into the breast milk. Jyoti Asundi (12:27) Yes. Aarati Asundi (12:27) And then can get passed on to the baby. Jyoti Asundi (12:30) Yes. Aarati Asundi (12:31) After his time in Vienna was up, he briefly went to Paris, where he sat in on lectures by the famous French neurologist Jean-Martin Charcot, who I don't know if you remember, but we mentioned him in a previous episode on Alfred Binet. Jyoti Asundi (12:48) Oh! I think- yes, yes, yes, yes. We are really cross-linking so many people at this point. This is so fun. Aarati Asundi (12:55) Yeah, I think this is just gonna happen more and more as we continue to do more and more scientists. Jyoti Asundi (13:00) Yes. Aarati Asundi (13:01) We're just gonna be like, all these people are running around in the same circles. Jyoti Asundi (13:05) Yes. Yes. And they are talking to each other, learning from each other. Aarati Asundi (13:09) Yeah, so like quick reminder, before Alfred Binet developed the IQ test, he spent time working at the Salpetrier hospital with Charcot on hysteria. And they were conducting experiments on patients trying to show that they could control a patient's behavior under hypnosis using a magnet. Jyoti Asundi (13:29) Yes. Aarati Asundi (13:30) And of course that turned out to be completely false, but it did get Theodore interested in the potential therapeutic power of hypnosis, although he never actually tried it on patients himself. Jyoti Asundi (13:41) All right. Aarati Asundi (13:42) But I just thought that was a fun little connection and tidbit. Jyoti Asundi (13:44) Side connection, yes. Aarati Asundi (13:46) Yes. So now he's finished with his travels, Theodore goes back to Germany and finally settled down in Munich. Here he got his certification to become a lecturer in pediatrics and had access to multiple labs, including Max von Pettenkoffer's Hygienic Institute, Otto von Bollinger's Bacteriology Lab, and Carl von Voitt's Physiological Institute. And these are all really big names among German scientists. I was kind of looking briefly into all of them and I'm like, each of them deserves their own episode. So yeah. Jyoti Asundi (14:22) I see. We'll get there. Aarati Asundi (14:25) We'll get there. Yeah. But mainly he has access to all of these, really great laboratories. And he's a very multidisciplinary guy, so he's interested in all of this. Jyoti Asundi (14:35) It's not just the laboratories, right? It is the brains that come are that live in those laboratories. Aarati Asundi (14:39) Yes, the people as well. Yes. Yeah. Jyoti Asundi (14:42) The people, yeah, the bright minds and the inquisitive souls that are really asking those pertinent questions in those days. Aarati Asundi (14:51) Yes. Usually when we talk about a lab, we're not talking about the equipment. We're talking about the people. Yes. Yeah. Jyoti Asundi (14:55) Correct. We are talking about the people, yes. Aarati Asundi (14:59) He learned the very latest bacterial culturing techniques from a man named Wilhelm Frobenius, who himself had learned under Robert Koch. Jyoti Asundi (15:10) So the baton is being passed in a very distinguished lineage of bacteriologists. Aarati Asundi (15:17) Yeah. In October 1884 there was an outbreak of cholera in Naples. Robert Koch had just discovered that same year that cholera is caused by a bacteria, vibrio cholerae. Jyoti Asundi (15:29) Okay. Vibrio. Yes, Vibrio cholerae, yes. Aarati Asundi (15:33) So, Dr. Gerhart, whom Theodore still kept in touch with, advised him to go to Naples for a few weeks to study the disease. He did, and he was very easily able to identify the Vibrio cholerae bacteria using Robert Koch's methods. In many cholera patients, though, especially those suffering from diarrhea, he found another new bacterium, Campylobacter jejuni. He studied this bacteria carefully but never actually committed to saying that it was the cause of diarrhea. Possibly because he didn't always find it in every patient with diarrhea, but this piqued Theodore's interest. Robert Koch had been very successful in finding one bacteria that caused one disease. So Bacillus anthracis causes anthrax, Vibrio cholerae causes cholera, very clear cut, one-to-one disease causing bacteria. Jyoti Asundi (16:32) Yes. Aarati Asundi (16:33) But Theodore was thinking about diarrhea and dysentery, which were often the cause of death in children suffering from a variety of illnesses, including cholera, but also smallpox, typhoid fever, and the plague. And it was so prevalent that Theodore reasoned that this type of dysentery probably wasn't caused by one bacteria like the other diseases, but rather that something else in the body was changing, probably with the intestinal bacterial population when the child got sick. Jyoti Asundi (17:09) Ah yes, the idea that there is somebody- an opportunistic bacteria maybe taking over now that the immune system of the body has been brought down by the main pathogen, be it cholera or typhoid or whatever, smallpox or whatever, now a secondary tier of bacteria, who are laying low and not really able to do much, they are not that strongly pathogenic. Aarati Asundi (17:35) And who are already existing in the body. Jyoti Asundi (17:38) Yeah, and they are not doing much because they can't do much, because the immune system is so strong against them. But now, with a suddenly susceptible immune system, they are able to raise their little heads and cause additional damage. Aarati Asundi (17:52) Yes, yes. So he was like, I think that's what's happening. Something else in the body is changing and the bacterial population in the body changes because of that. And that's how diarrhea and dysentery are caused. And that's what actually leads to the child's death, because they're dying of the symptoms of dehydration. Jyoti Asundi (18:14) Yes. Aarati Asundi (18:16) So back in Munich now, Theodore starts to study the infant's microbiome... Jyoti Asundi (18:21) Okay. Aarati Asundi (18:21) ...although he didn't call it the microbiome at the time. I'm just using that term for ease. Jyoti Asundi (18:27) Yes, and since it's already well known that whatever is in the gut is currently called the gut microbiome, for our listeners we can just use that term so that it's easier to understand. Aarati Asundi (18:38) Yeah, but that's truly what he was interested. He was interested in the bacterial population in the gut of infants... Jyoti Asundi (18:44) Okay. Aarati Asundi (18:45) ...and how it changed after birth and how it allowed for food digestion and whether it changed during sickness. He said, "At a time when Koch's experimental methods reap such rich laurels in the newly revealed field of etiology and pathology infectious diseases, it might appear to be a useless, almost thankless task to attempt to distangle the apparently completely unregulated mass of intestinal bacteria dependent on a thousand contingencies in normal stools. When, however, I have by now devoted a year almost exclusively to this special study, I did this in the conviction that the exact knowledge of these conditions is essential not only for the physiology of digestion, where intestinal putrefaction remains an unknown and an incalculable X, but also for the pathology and therapy of the bacterial intestinal diseases." Jyoti Asundi (19:42) It is true. It is detangling a complex mix of bacteria- the complex mix of bacteria that live in the gut is not going to be an easy task. He's just bitten off a big chunk. It's hard enough to think of isolating out of all these organisms who is the causative and who are the passengers on the train who are taking advantage. But then just going in and looking at how is the microbiome in the gut adjusting? And today we know that the microbiome is a very complex system where a human being does need to have a good microbiome in it. It has healthy organisms in it. Aarati Asundi (20:19) Hold that thought. Jyoti Asundi (20:23) Okay, okay, okay. I'm stepping too far ahead. Aarati Asundi (20:24) So he studied fecal samples of newborn babies during their first days of life and found that the bacteria in the gut went through three distinct phases. As soon as the baby was born, he could barely find any bacteria in the gut at all, and he was calling it sterile actually. But within the first four to seven hours of birth. The intestine became populated with about 20 different types of bacteria, all of which he described in detail and which he suggested came in through the air that the baby breathed... Jyoti Asundi (20:57) Okay. Aarati Asundi (20:58) ...and could vary depending on the baby's environment. However, once the baby began to breastfeed, two bacteria in particular seemed to kind of just take over the intestine completely. The first he named bacterium lactus aerogenis, which took over the upper part of the small intestines. Jyoti Asundi (21:18) Okay. Aarati Asundi (21:19) The second was a slender rod-shaped bacterium, which he called Bacterium coli commune. Years after Theodore's death, this second bacteria, Bacterium coli commune, was eventually renamed Escherichia coli, or E. coli. Jyoti Asundi (21:38) I see! Aarati Asundi (21:40) Yes, in 1918. Jyoti Asundi (21:42) Okay so he was not the one who named it after himself. Got it. Aarati Asundi (21:46) Correct, yes. Other scientists suggested that it should be named for him. And it was because it had become by this time such a key model for biologists for many, many reasons. Jyoti Asundi (22:02) Oh many reasons. I don't know where would biology be today without E. coli. Aarati Asundi (22:07) Yeah, it's very, very useful. First and foremost, as Theodore himself found, it was very easy to grow. Jyoti Asundi (22:14) Yes. Aarati Asundi (22:15) It has a doubling time of only 20 minutes and it tolerates a wide range of conditions, which is very useful. It's not very finicky about like you have to be at this exact temperature and use these exact nutrients or this exact media on which to grow it. It's like, I can I can do whatever you kinda give me. So that's really useful for scientists who are studying all different types of things. Jyoti Asundi (22:38) Yes. Aarati Asundi (22:39) It was also very easy to find in the gut. Theodore noted that the types and relative amounts of the bacteria in the baby's gut is vastly different than adults. E. coli makes up less than 1% of bacteria in the adult gut, and we have hundreds of types of bacteria living in our guts, not just 20 like a newborn does. But still, despite that, E. coli is very easy to find and culture. And scientists found that even though most strains of E. coli are harmless or even beneficial, some strains do cause digestive disorders like diarrhea, urinary tract infections, and neonatal meningitis. Jyoti Asundi (23:18) Yes, I think they are called the enteropathogenic E. coli. Aarati Asundi (23:22) Yes, and later on, E. coli proved to be very easy to manipulate. We could study bacterial genetics, DNA replication, recombination, gene regulation, mutation, like a ton of Nobel Prizes ave been awarded to scientists doing work in E. coli. Jyoti Asundi (23:40) Yes. Aarati Asundi (23:41) So although Theodore did not determine the cause for dysentery in children at this time, his findings about the newborn's gut microbiome, shall we say, laid the foundation for understanding children's nutritional health and digestive disorders. In 1886, Theodore published a book called The Intestinal Bacteria of the Infant and The Relation to the Physiology of Digestion, which propelled him to becoming the foremost expert in bacteriology in pediatrics. Jyoti Asundi (24:13) This- this is so important actually to first define, to really do that deep dive study of what quote unquote constitutes normal. Aarati Asundi (24:22) Yes, yes. Jyoti Asundi (24:22) So he's looking at how does a normal baby behave in terms of its gut microbiome? How does it change? When does it populate and all of that? He's looking at the whole history of the gut microbiome from birth to those early years and then on into adulthood. So if you know what is normal, only then can you say that this is abnormal. Aarati Asundi (24:45) Yes. Jyoti Asundi (24:46) Only then you can superimpose that and say something is wrong, we need to fix this. Aarati Asundi (24:50) Exactly. So that's what he was doing in this book. He laid out the different stages of gut colonization by bacteria and how these bacteria aid in digestion. He showed that the bacterial populations could change depending on whether an infant was breastfed versus given cow's milk. And he became a really big proponent actually of breastfeeding the infant. Because very importantly, he laid out the concept of the infant gathering good naturally occurring bacteria that help us and are needed for normal digestion. Jyoti Asundi (25:27) Yes. Even today we collapse this whole concept into saying the mother's milk provides natural immunity to the baby. And yeah, we think of it in terms of antibodies from the mother or in terms of immune cells or whatever, but actually it is this also, the bacteria that come with it. Aarati Asundi (25:46) Yeah. and this was a novel concept at the time that he's saying that these bacteria are good and they're naturally occurring and they help us. They're beneficial. Jyoti Asundi (25:56) Yes, correct. Aarati Asundi (25:57) Because up till now, you know, Lister is trying to avoid bacteria. Koch is saying all these bacteria are causing diseases. Louis Pasteur is like, we need to heat up our food to get rid of bacteria so it doesn't spoil our food. Jyoti Asundi (26:09) That's right. Aarati Asundi (26:09) And here Escherich is coming in and saying, "There are good beneficial bacteria. We shouldn't just try to kill all bacteria." Jyoti Asundi (26:16) Yes. We shouldn't just try to destroy them. In fact I think if there were no bacteria, very soon there would be no humankind at all. Aarati Asundi (26:25) They're just live on us, they live in us, they help us so much. Jyoti Asundi (26:29) And also how much they help the farmer in the soil. The soil bacteria are so key. Aarati Asundi (26:35) Oh those nitrogen fixing bacteria, yeah. Jyoti Asundi (26:37) That's right. All those things, yeah. So it's- it's incredible how much work they do. Aarati Asundi (26:42) Yes. Jyoti Asundi (26:42) And no pay and no unions or anything. Aarati Asundi (26:45) I know. Nothing. Jyoti Asundi (26:46) They just do it. Aarati Asundi (26:47) We give them a good environment to live in and they work for us. Jyoti Asundi (26:51) They help us, yes. Aarati Asundi (26:53) He also recognized that there were different types or strains of E. coli, and he suggested that those different strains could be responsible for causing localized infections like diarrhea and gastroenteritis. But his claim was really only proven several decades later. So he's the one who gave that first suggestion that, you know, different strains could be doing this, but he fell short of actually proving it. Jyoti Asundi (27:21) It reminds me of the gremlins. The gremlins can be really cute and wonderful and beautiful but then If you do something wrong, there they go, they become really bad. Aarati Asundi (27:30) Yep. Yep. Jyoti Asundi (27:31) They- they're a double edged sword. Keep them under your control. They're good but... Aarati Asundi (27:33) Yep. Yes. We they're good but only if you take care of them, yes. Jyoti Asundi (27:39) Yes. Sorry, my poor brain is all over the place. Aarati Asundi (27:43) Yes, drink more coffee. Jyoti Asundi (27:46) My coffee is over. Aarati Asundi (27:47) Aw! _______________________________________________________________________________________ Aarati Asundi (27:56) Hi everyone, Aarati here. I hope you're enjoying the podcast. If so, and you wish someone would tell your science story, I founded a science communications company called Sykom, that's S-Y-K-O-M, that can help. Sykom blends creativity with scientific accuracy to create all types of science, communications, content, including explainer videos, slide presentations, science, writing, and more. We work with academic researchers, tech companies, nonprofits, or really any scientists. To help simplify your science, check us out at sykommer.com. That's S-Y-K-O-M-M-E-R.com. Back to the story. _______________________________________________________________________________________ Aarati Asundi (28:43) So Theodore stayed at Munich studying infant nutrition and digestion until 1890, when at the age of 33 he was called to work at Graz as a professor of pediatrics and the director of the Saint Anna's Children's Hospital. Jyoti Asundi (28:59) That's very early. He's getting a lot of responsibility and risen to a very high position fairly early there. Aarati Asundi (29:06) Yes. These years at Graz were some of his happiest. He did a lot to renovate and expand the children's hospital. Under his direction, the clinic's neonatal mortality rates dropped to 39%, which seems high today, but considering that it was as high as 72% in other big city hospitals, 39% is pretty good. Jyoti Asundi (29:30) Yes, almost half, right? Yes. Aarati Asundi (29:32) Mm-hmm. Yeah. Jyoti Asundi (29:34) He dropped the infant mortality rate by almost 50% of what it was. Aarati Asundi (29:38) Yes. He also built a new section of the hospital for children who needed special care after birth. Like a little ICU. Jyoti Asundi (29:45) Like a NICU? Aarati Asundi (29:47) Yeah. Jyoti Asundi (29:47) Like a NICU. Aarati Asundi (29:48) Exactly. He was the first person to use a weak electric current as a diagnostic device to see if a patient's muscles and nerves were damaged, so that's interesting. Jyoti Asundi (29:59) Yeah. Aarati Asundi (30:00) And then after 1895, when Wilhelm Rontgen, who we also covered on the podcast... Jyoti Asundi (30:07) Yes. Aarati Asundi (30:08) ...discovered x-rays, Theodore started using them to study bone development in children. Jyoti Asundi (30:15) Oh nice. Okay, okay. Aarati Asundi (30:17) And I think he started doing experiments to see like did the bones develop better if you gave the baby certain supplements like cod liver oil or something like that, like, you know, seeing if there was any difference. Jyoti Asundi (30:30) Although today that method would not stand scrutiny because... Aarati Asundi (30:34) Oh yeah. Jyoti Asundi (30:35) X-rays for checking whether cod liver oil is working on the bones is going to cause more harm than good. But that's what they knew in those days. Aarati Asundi (30:43) Yeah they didn't know that and I think it really speaks to how interested he is in children's development and making sure like, you know, he's a very strong proponent of breastfeeding because now he knows that it helps populate healthy gut for bacteria for the infants and now he's like, How do we make sure their bones develop properly? How do we make sure that they avoid sickness? Like he's very, very into this. Jyoti Asundi (31:05) And he's really using cutting edge technology to develop his methods and to develop his theories. And he's very willing to overturn existing paradigms because I can see at least in those days, people who were rich usually hired nurses to nurse the babies or something or even felt that it was very demeaning to have the baby nurse off of the mother and for him to push and say no the mother's milk is actually very valuable. Please make sure that your infant gets it so that it gets a good start in life. That is very good of him to do that. Aarati Asundi (31:43) Yes. Even if you hire a wet nurse, that's fine, they're still getting breast milk, but don't give them cow's milk or animal milk if you can help it. Like that's not going to be as beneficial. Jyoti Asundi (31:54) Yeah, there was I think stigma against nursing in certain societal echlions. The higher- the more rich you were, the more you felt like, this is so pedestrian and this is so peasant-like. Aarati Asundi (32:07) Like, almost vulgar. Yeah, it's like almost vulgar. Jyoti Asundi (32:09) Exactly. Aarati Asundi (32:11) Like we ladies do not do such things. Jyoti Asundi (32:12) Exactly. And so it's like, no, I'm sorry, but man is the one who sexualized the breast and it was the if the primary purpose in fact was to feed the infant what it really needed to get a good start in life and he pushed that agenda. So that's really good. Aarati Asundi (32:28) Yeah, he's like, "Don't fight nature. Nature has this system set up for a reason. Do it." Yeah. Jyoti Asundi (32:35) That's right. That's right. Aarati Asundi (32:37) He was also very up to date on different diseases. So he wrote a book on diphtheria, which is a bacterial infection that affects the nose and throat, making it hard to breathe and swallow. Jyoti Asundi (32:49) I think we have a diphtheria vaccine now that is administered very early on today. And again, we are going backwards in science. where people are fighting it and saying no, no vaccinations, but these are the little things that really help. Aarati Asundi (33:06) I know about diphtheria really only because of that animated movie Balto, which is one of my favorites. You know, the whole dog sled race thing to bring the antiserum. Jyoti Asundi (33:16) That's right. To get the anti-serum to the village Aarati Asundi (33:20) Yeah. Coming with this like big case of anti-serum to help the children who are suffering from diphtheria. And I'm like, man, people... people have forgotten what hard times we went through at the turn of the century. Like all over the world children were suffering and dying from these childhood diseases because we didn't know what caused them and then we didn't know, you know, how to cure them. And actually, Theodore's work in diphtheria or his the book that he wrote about diphtheria was inspired by Emil von Behring, who later went on to win the first ever Nobel Prize in physiology or medicine in 1901 for developing an antiserum containing diphtheria antitoxin... Jyoti Asundi (34:07) Oh wow. Aarati Asundi (34:07) ...which saved thousands of children's lives. So, you know, this guy won a Nobel Prize for this. And for us to be going back and saying like, no, I don't believe in vaccines... It's like he created the first ever cure for it and was hailed as a hero at the time, you know? So it's just kind of crazy. Jyoti Asundi (34:27) We insist on making mistakes that don't need to be made. Aarati Asundi (34:31) Yes. We're getting too comfortable. But back to Theodore. Theodore was also an amazing teacher. He attracted some of the very best and brightest minds in pediatrics. He always made sure that when he supervised the student, their name was listed first or alone on publications so that they could kind of make their mark, even if he mentored them. Jyoti Asundi (34:53) That is generous. That does not exist at all. I mean it's i that's a that really exists in a vaccuum, I think. In fact, if there is something good happening, everybody comes along wanting their name on it. I have seen situations where somebody develops something and the higher ups come in and say we'll present it to senior people, we'll present it to the executive board, or whatever and then the person who actually did it is sidelined into obscurity so often. Aarati Asundi (35:26) Well, it actually reminded me of again, yet another person that we covered on the podcast, Bridget Askonas, who was an immunologist, and she did the same thing. Yeah. Jyoti Asundi (35:35) I remember her. Yes, I remember her. Aarati Asundi (35:38) She just like gave all of her students the credit and just said, No, it was all you, you did everything. So he was kind of very much the same way, like, "Yeah, I was a mentor, but you're the one who did all the hard work. you get your name on the publication. You don't even need to list me." But if any student came to him asking for what project they should work on because they weren't sure they didn't have an idea, he would always suggest something related to his favorite subject, bacteriology. Jyoti Asundi (36:06) Yes. Aarati Asundi (36:07) So even though he's a pediatrician, bacteriology is kind of like his real love. On a personal level, here in Graz, he also met and married his wife, Margarethe von Pfaundler, who was the daughter of a physics professor at the University of Graz. Margarethe was a very talented oil painter, and many years later she would become a member of the Academy of Fine Arts in Vienna. She and Theodore had two children together: a son named Leo and a daughter named Sonya. And it seemed like they were all a very happy family. They would spend some summers with Margarethe's family in a large farmhouse near a lake where they would all enjoy boating. And Theodore's father-in-law, Leopold Pfaundler, which is the physics professor, he worked with Theodore to build a new type of walk in incubator for babies at the clinic who might need that extra care. Jyoti Asundi (37:02) So don't bring the baby out at all. Just go in and sweat it out yourself with the baby because the babies haven't yet developed the homeothermal ability, the ability maintain homeostasis, where you are able to regulate your body temperature to 37. And you don't have that early in life, and then you don't have it actually late in life as well. That's why older people they do get cold very easily because of that. They start to lose that ability. And so it's like, okay, you keep the baby at 37 so that it doesn't suffer deep fluctuations and can steadily become healthy, and you go in there. Very cool. It's like the warm room today. Aarati Asundi (37:47) Yes. And so in this case, like instead of having a little box that held one baby, it's like, let's try a bigger walk in type of situation. So he's just experimenting with all of these things, seeing what'll work. Jyoti Asundi (37:56) Fantastic. Yes. Aarati Asundi (37:58) And his father in law's like, Yeah, let I'll use my physics knowledge and help you build this. Jyoti Asundi (38:03) Yes. Aarati Asundi (38:04) So thanks to his brilliant career at Graz, his fame spread, and in 1902 he was unanimously nominated to take over the role of Chair of Pediatrics at the University of Vienna and become again the director of the Saint Anna's Children's Hospital there. Jyoti Asundi (38:21) Okay. Aarati Asundi (38:22) And it was kind of a full circle moment because he was taking over the position of Hermann von Widerhofer whom he had studied under when he first went to Vienna way back when his career was just starting. Jyoti Asundi (38:34) Nice. Aarati Asundi (38:36) Vienna's pediatric hospital was very outdated, and so Theodore spent a lot of time essentially rebuilding the type of modern clinic that he had built in Graz. Jyoti Asundi (38:45) Okay. Aarati Asundi (38:46) He installed a laboratory, an X-ray clinic, and the first of its kind, an open-air terrace on the roof. Jyoti Asundi (38:55) Nice! Sounds so good. Aarati Asundi (38:56) Yes, so that children could probably go breathe the fresh air and he recognized the therapeutic benefit of that. Jyoti Asundi (39:04) Yeah, he understands the therapeutic benefits of being with nature. A child probably just can step out into the terrace Aarati Asundi (39:08) Mm-hmm, yes, and just smelling the fresh air. Jyoti Asundi (39:12) and that itself is so rejuvenating, yes. Aarati Asundi (39:14) Yes. Meanwhile he continued his interest in bacteriology, writing a long chapter about E. coli in the Handbook of Pathogenic Microorganisms. And in 1904 he was the only European pediatrician to be invited to the St. Louis World Fair where he gave a lecture to the International Congress of Arts and Sciences on the foundation and objectives of modern pediatrics at the turn of the century. Jyoti Asundi (39:42) So this- he's now come to the USA, to Saint Louis in America in Missouri. Aarati Asundi (39:47) Just for the- just for giving a lecture. Jyoti Asundi (39:49) Just for the conference, yeah. Aarati Asundi (39:50) Yeah, that's correct. Jyoti Asundi (39:50) But because he's primarily based in Europe, so I was just confirming that this is an international conference. Yeah, got it. Aarati Asundi (39:57) Yes, and he's the only European pediatrician who was invited to give a talk there. And then in 1906 he was named court counsellor by Emperor Ferdinand Joseph of Austria and was often invited to court dinners, so his fame is just spreading like crazy. So things were going really well for the family until in 1904 Theodore's son, Leo, who was nine years old and studying at a private institution in Graz suddenly fell sick. He was diagnosed with appendicitis, but in spite of the best possible care, without any antibiotics, he died. Jyoti Asundi (40:37) Oh no, heartbreaking. Aarati Asundi (40:39) His death profoundly impacted the whole family. Jyoti Asundi (40:42) Yeah. Aarati Asundi (40:43) Margarethe especially felt an enormous amount of guilt for having let Leo go to boarding school so far away from home. And it took a toll on their marriage, so much so that for her 36th birthday, Theodore gave Margarethe a picture of himself with the inscription, "What God has joined, man should not separate." Kind of reminding her that she still has people who love her and not to, know, break their marriage up in her grief. Jyoti Asundi (41:12) Yeah, don't abandon the marriage. We already lost enough. Aarati Asundi (41:16) Yes. Jyoti Asundi (41:17) Oh man, so heartbreaking. I've heard of this though where each parent is ridden by guilt when a child dies and then the marriage does suffer because of that. Aarati Asundi (41:28) Yes. And I'm like, I totally understand that. And he's trying desperately to make sure that does not happen to them. Jyoti Asundi (41:35) Okay. Aarati Asundi (41:36) Yeah. The family moved to a different house, probably because you know their current house was too painful Jyoti Asundi (41:39) Yeah, the memories are too much. Aarati Asundi (41:44) And Theodore was also grieving, but he couldn't just stop working at this point. He's risen to such a high position and he has so much going on. Jyoti Asundi (41:54) And also that is the right thing to do, correct? I mean, yes, you have suffered a loss, but then you have to pick yourself up and move on. You cannot wallow in grief. It doesn't bring back the person. Aarati Asundi (42:04) Yeah, they still have their daughter yeah. Jyoti Asundi (42:07) You have a purpose in life also. You suffered a lot, but that does not give you the right to throw away the rest of your life and let it be consumed by grief alone. Aarati Asundi (42:18) I'm sure that's also like what he decided to do. He's like, I'm just gonna throw myself into my work and try to separate my grief a little bit and so he had several publications that he was working on. He had formal dinners to attend, and by this time he was even being called on as a medical consultant for Tsar Nicholas II of Russia's son, Alexei Nikolovich, who famously was a hemophiliac, and we all know how that story went, so... Yeah, so he's being called to all these, very you know he's dealing with emperors families and, you know, the Tsar's family. Jyoti Asundi (42:59) Yes. He's the renowned expert Aarati Asundi (43:03) He is the pediatrician that you want taking care of your child. Jyoti Asundi (43:06) Mm-hmm. Aarati Asundi (43:08) In 1908, Theodore was finally able to gather the finances to build a brand new children's hospital in Vienna called the Imperial Institute for Maternal and Infant Care, and it was something that he had been trying to gather support for ever since he moved there. The institute's aim was not only to have a state of the art hospital for newborns, but also to educate new mothers on the best way to care for their children in order to lower infant mortality rates. Jyoti Asundi (43:36) You know, this is almost ironic that a person whose passion is pediatrics, taking care of children, has to lose their own child. That is that is a real irony there. But then in addition, I'm looking at it and saying a loss of a child is an immeasurable pain. No parent should have to face that. But that pain can be manifested in the life of the parent in many ways. The lowest level, like I said, is to wallow in it and to succumb to alcoholism or something like that. The second level is to kind of find another person to blame and just say you you did not do this and you did not do this and everybody points fingers at each other and nothing ever gets done. But then the third level of expressing that pain is to sublimate it, where you say, "Yes, I suffered immense pain, but I don't want other parents to suffer the same as I did. And so I'm going to do everything in my power to make life better for other people's children." Aarati Asundi (44:44) Yes. Jyoti Asundi (44:45) And what's in my power to make other children's life better? Build that pediatric hospital, make mothers happier, make pregnant women healthier and make newborn children happier and just create the resource chain that is required for good birth, good infancy, good pregnancy and all that. So that is the way that Theodore has chosen, which is really remarkable. And we have a lot to learn from that. Aarati Asundi (45:14) Very admirable. Jyoti Asundi (45:16) Yeah, the first time I encountered this thought process was when I was first introduced to the concept of Mothers Against Drunk Driving, the MADD. And that's what that's what was going on there also, that same thought process. It's like I have lost a child to drunk driving. And that pain is immeasurable. nothing I do is going to bring her back or bring him back, my child back. So what can I do? All I can do is try to see that this is not repeated for another mother. So I take all that energy, all that grief, all that anger... Aarati Asundi (45:53) Anger. Jyoti Asundi (45:54) ...everything that I have, I take it and make sure it does not happen again. Aarati Asundi (46:00) Yeah. Jyoti Asundi (46:00) Try to change the law. Try to change the situation so that it does not happen again to somebody else. Aarati Asundi (46:07) Bring awareness. Yeah. Jyoti Asundi (46:08) Bring awareness, yes. So that is remarkable. Aarati Asundi (46:10) Yeah. It takes such a strong person to be able to do that though. Like I do not blame anyone who like sits and wallows in their grief because I can't- I can't imagine, losing someone like that. And so it just takes such an incredibly strong person to be able to take that grief and turn it into something positive and it may take many years, you know, it may for you to be able to do that, but if you are able to do that, like that it's just incredible, so inspirational. Jyoti Asundi (46:43) Yes, beautiful. Aarati Asundi (46:44) So yeah, he became extensively involved in creating the building plans and he actually saw the foundations and the wall structures being built. However, in February 1911, when he was visiting his clinic wards, he started to complain of a headache and strangely started to speak to people in French and other languages. The following day on February 15, 1911, Theodore suddenly died from an apparent cerebral hemorrhage at the age of 54. Jyoti Asundi (47:20) Oh very young. He suffered a stroke. Aarati Asundi (47:21) Very young. Mm-hmm. And he was clearly in the middle of things. He never got to see the completed institute that he had campaigned for years for. He also left behind several unfinished papers, including a publication on scarlet fever. And when you think about it, in Theodore's lifetime, like if you look back on it, his main claim to fame was as a renowned pediatrician. His work in bacteriology was really only like 1/4 of the papers that he ever wrote. Jyoti Asundi (47:56) Incredible that- yeah, one fourth of his work is also so amazing that it could be two lifetimes for other people. Aarati Asundi (48:06) Yes, and although his discovery of E. coli, or he called it Bacterium coli commune, was very impressive and even noteworthy at the time, I don't think that he or anyone at the time really could have predicted how fundamental E. coli became to molecular biology. It just.... Jyoti Asundi (48:28) Correct. Aarati Asundi (48:29) ...you know, I think for him it was kind of like, yeah, I did discover that. That was cool. You know, and he recognized that it was important. He recognized that, it is in everybody and it's this, ubiquitous, like it's just everywhere. This kind of- this bacteria is just everywhere and therefore it needs to be studied and understood because it's just so prevalent everywhere. But I don't think he really understood the magnitude of the tool that he had discovered. Jyoti Asundi (49:00) Yes, he- they did not realize what an easy tool it would be f in molecular biology. Like it lends itself to genetic editing, genome editing. It lends itself to manipulation. So it's so easy to make so many different constructs out of it and apply it as a tool in different situations. Aarati Asundi (49:20) But I just thought it was so interesting that, you know, the thing that we know him for, Escherichia coli, actually in his lifetime not his main claim to fame. He was a pediatrician. That's you know, he was the best pediatrician. Yeah. Jyoti Asundi (49:35) That is so amazing. That is so amazing. And so important that right then he- I mean, this this is important that he brought out that bacteria are double edged tools. Yes, they cause a lot of harm, but they are vital for our benefit as well. You cannot dismiss them and then just create some sort of a toxin that'll destroy all bacteria ever born. Any bacteria that ever dare to live on this earth is now destroyed by this by this medicine that I've created. No, we do need them to maintain the correct health of the gut, which then applies to the brain We have figured that part out. They are important for human life in every way you can think of. Aarati Asundi (50:23) Yeah, So that is the very interesting, surprising story of Theodore Escherich. Jyoti Asundi (50:28) Beautiful. This was fantastic, truly fantastic story. I loved it. Really enjoyed it. And and also Aarati Asundi (50:33) Spoke to your microbiology heart. Jyoti Asundi (50:37) And also to that idea of doing greater good even when tragedy strikes your life. This was a beautiful story. Thank you so much. Aarati Asundi (50:47) I'm glad you liked it! Thanks for listening. If you have a suggestion for a story we should cover or thoughts you want to share about an episode, reach out to us at smarteapodcast.com. You can follow us on Instagram, TikTok, and Blue Sky @smartteapodcast and listen to us on Spotify, Apple Podcasts, YouTube, or wherever you get your podcasts. And leave us a rating or comment. It helps us grow. New episodes are released every other Wednesday. See you next time!