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Business Of Biotech
The Discovery Of Microbes And Implications For Public Health Today, With Science Writer Thomas Levenson
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On this week's episode, Thomas Levenson, MIT professor and author of So Very Small: How Humans Discovered The Microcosmos, Defeated Germs — And May Still Lose The War Against Infectious Disease talks about what he learned in the writing of So Very Small, how cultural and political forces shape scientific progress, and what it means for drug developers, public health officials, and patients everywhere.
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Ben Comer:Welcome back to the Business of Biotech. I'm your host, Ben Comer, chief Chief editor Editor at Life Science Leader, and I'm thrilled to speak today with Tom Levinson, a professor at MIT's graduate program in science writing and the author of seven books on diverse topics, including the Science of Climate, A Musical History of Science, Isaac Newton's investigative work for the Royal Mint in London, Albert Einstein's Berlin Period, the Search for the Hypothetical , Vulcan and other topics.
Ben Comer:He's also the recipient of a Guggenheim Fellowship and has a Peabody Award to his credit for work he did on a series for PBS. Tom just recently published, at the end of April, a book on the history of germ theory called so Very Small how Humans Discovered the Microcosmos, Defeated Germs and May Still Lose the War Against Infectious Diseases. We're going to dive into some of the themes, people and issues Tom writes about in so Very Small, because the history of germ theory has important implications for public health today, as well as the development of new antibiotics and therapeutics. What's past is prologue, as Shakespeare wrote, and with the shakeup happening currently at NIH, HHS and FDA, I think it's a timely conversation. Thanks so much for being here, Tom.
Thomas Levenson:Thank you for having me. It's great to have a chance to talk with you.
Ben Comer:I thought we could start with the genesis of so Very Small. What made you want to write it?
Thomas Levenson:Well, I kind of have to blame my wonderful London-based editor, neil Belton, who is a formidable nonfiction editor and currently head of an imprint for Bloomsbury called Head of Zeus, over in London, for a variety of reasons. We met up for a coffee and he told me that he was working on this series of books that were supposed to be very short you know, 25,000 words or something on decisive moments. You know some like single incident that then could be, you know, used to look at something larger, and so, for example, he had the first production of Handel's Messiah, which opens up all kinds of interesting doors into, you know, music and you know the sort of social structure, all that kind of stuff. And another example he gave me was a look at the creation of Picasso's painting Guernica, about, you know, the Nazi bombing of this Spanish town during the Spanish Civil War. That was kind of a trial run for later blitzkrieg tactics, and these were great books. And he had, you know, a bunch of others that he had on his list and he's a very innovative editor.
Thomas Levenson:And he said I don't have any science, got to give me some science. And so at that time I just finished the Newton book you had mentioned and I was looking at some you, I was looking at some new stuff that also had some kinds of physics connections and I said, well, there's an obvious one. You know, when Albert Einstein goes up the mountain at Mount Wilson in 1930 and you come back where the universe has changed, he's seen the first images that say the universe is expanding and that's a complete you know, that's a real radical change in our understanding of you know, reality on the larger scale. I said the other thing that you know and I said I'm not the person to write this, I'm not a biology writer, you know I'm not saying this, but it's really been fascinating to me all these years that you have the germ theory revolution in the late 19th century. You know, depending on you, know, you can, you can sort of put the dates where you want, but you know by convention the date that Robert Koch one of the two sort of giant figures that are associated with the germ theory moment in particular, other being Louis Pasteur Koch figures out the life cycle of the anthrax bacillus and demonstrates decisively that that bacillus B, b anthracis is in fact the pathogen that brings about a case of anthrax. And that happens, you know, starting three days before Christmas in 1876. And he sort of finishes the experiments before the end of the next January, end of the next January.
Thomas Levenson:And so, like that, 1870s, 1880s, 1890s, decisive moment before disease and our understanding of our relationship to the worlds, of, you know, world's biology, the whole idea of the causation of disease, all these kinds of things is one way, and afterwards it's different, and it's different in ways that that give human beings huge advantages in the millennia long struggle with infectious disease. This is a great topic. Somebody should write this, go find somebody to write it. And he never did. Series came and went, all that was done, and he and I would meet over the years and I did two other books with him and with my American editors and we would occasionally talk about it, american editors, and we would occasionally talk about it. And I have to say I didn't know that there was really a full book there until I started thinking well, you know, how do you get to the moment where Koch, you know, figures out anthrax. It's just taking that as that sort of marker.
Ben Comer:And that was a story that you were already familiar with or already knew sort of marker, and that was a story that you were already familiar with or already knew the Koch and anthrax discovery.
Thomas Levenson:I knew the out, you know it's, it's. I'm a, I'm a magpie of a science writer and I read very widely, and so I know a little bit about a lot of the history of science and you know, but I wouldn't have called myself, you know, deeply knowledgeable, I feel like I. I know it pretty well now, but I was not more than 1870s newspaper reader. Level of knowledge up to that point was obviously the identification of microbes and specific as the agents of disease and specifically that each disease was associated with a single microbe. So there was a very carefully constructed chain of cause and effect and that's the great breakthrough that leads to all kinds of possibilities in responding to these infectious diseases. All kinds of great things that we'll talk about, I'm sure, in a few minutes.
Thomas Levenson:But the you know it turns, of course, on identifying the fact that microbes exist at all. Right, and I was thinking all right, well, when were bacteria discovered? And this I actually knew, and knew pretty well because I've spent a lot of time in the 17th century and spent a lot of time in the early days of the Royal Society. And basically, microbes were first seen in 1676 by this Dutch draper cloth merchant named Anthony van Leeuwenhoek. Again, apologies to anyone who speaks Dutch out there for my butchering of that name. I'm sure, sure, but you know, sort of like 200 years, almost to the day, runs between the first observation of microbes, bacteria, and the demonstration that they actually matter to us in a really consequential way.
Ben Comer:And I said that's a long time. Why did it take so long? And that was the question that got the book started. Why did it take so long? It made it a the 1660s. I'm going to butcher this as well, but Van Lowenhoek is sort of looking at these, you know, little squigglies, as a curioso, you know almost as a form of parlor entertainment, you know, and then 200 years go by before that connection is drawn between these microbes and infectious disease. How do you dive into that? How do you?
Thomas Levenson:get started. I sort of feel like as my professor hat goes on and it's like don't try this at home, kids, because I'm somebody who spends a lot of time. I like primary sources, I like reading the early philosophical transactions of the Royal Society and Leuvenhoek's letters and so forth. All of Leuvenhoek's not all of them, but an enormous corpus of Leuvenhoek's letters to the Royal Society and to others are online In English translation, parallel Dutch and English, and you can just go read them, play around with them, see what he was looking at, see what he was thinking about, see how he expressed himself.
Thomas Levenson:The you know there were. You know there's a body of history of science, work on germ theory, of course, and on the discovery of microbes, history of biology, and so I'll both look at some of the you know just to get started. I'll start, you know, getting some of people I know will be characters in the book and I'll try and get their words and their thoughts and their stories as just part of in my head, part of the sort of thinking through how the storytelling in the book. The book tries to make some arguments and, I hope, some fairly compelling and useful arguments, but it does so by telling stories that you can then draw meaning out of. It's not just sort of an academic essay. I don't work that way.
Thomas Levenson:So getting in touch with the people who are involved in the work is really an important first step, and the other first step is to really try and see what the arc of the book is where you know how this, how this, in particular this, this 200 years of halting discovery went from just seeing microbes to recognizing one of the important things that they they mean for us, mean for the earth, one of the important things that they mean for us, mean for the earth. So I spend some time with some of the scholarly literature on it. And then the thing I do and I do this quite early on, I do it as I'm writing the proposal for the book, which is about 10,000, between 6,000 and 10,000 words usually. So it's a fairly substantial document in itself I really try and think through what the arc of the book is as a matter of plot, what incidents are important to the development of this idea, and once I've got those, then it becomes quite simple. Simple as in, the task is simple, the work may not be easy. It becomes quite simple. You are simple as in, the task is simple, the work may not be easy, but you know, if you know, one thing I want to do is find out, you know, how the 17th century reacted to the discovery of microbes, and it is, as you say, primarily as kind of a a drawing room curiosity, much more than the sort of enormous scientific breakthrough which, I have to say, I was talking with somebody about this recently and it's still kind of bizarre, I mean think, what our reaction today would be to have real proof of life on other planets.
Thomas Levenson:It'd be a huge deal. In the 17th century no one had any idea that there was this whole realm of living creatures you know beyond our senses, inaccessible to us with the naked eye. And yet there they were, they were discovered, they could be seen by others once Levinhug showed them how an entire, previously unexpected domain of life. How is that not a big deal? I still don't, you know. I don't quite you know. The past is a different country, they do things differently there, but that still is kind of amazing to me.
Ben Comer:That's one of the things that I found really compelling about the book, where the way that is the way that you stitch these stories of individual people making discoveries and then trying to take them forward, sometimes against pretty remarkable reactions or pushback from society in general and even from other scientists. I mean, one of the themes that I wanted to ask you about in this book, I think, touches on the hubris of human beings. I mean, the cultural influence of Christianity runs very deep in Western culture, in the Bible God makes humans, you know, and his image grants them dominion over every living thing on earth, which gives rise to the great chain of being concept which you discuss, essentially a hierarchy developed in the Middle Ages, placing humans below God and angels, but above animals, plants and minerals, and it's the idea that we're not of nature but above and apart from it.
Thomas Levenson:And so I wanted to ask you know what you might say about that, how human hubris has played a role in the history of germ theory, acceptance and its practice that these lovely, cute little squiggling things that Latham Hook saw could matter to us if your whole cultural framework says, you know, agency flows down, god has ultimate agency and he grants it to it. Whatever you know, the gender of God passes it on to us and we, you know, as God's agents. And in the 17th century you had people, you know, who really understood themselves to be in some senses God's agents, or even, you know, mortal angels on earth. There's some beautiful writing about you know how this Isaac Newton himself had this sense of his role as as, as you know, directly deputized by God, in some ways very deeply held, I would say. You know, I think in, you know Western, in European and North American culture, american culture, you know the expansion of the European world, yes, the Christian sort of framework has enormous and lasting cultural significance, but the idea of human exceptionalism is one that's expressed in other cultures as well. But it's that sense that we are uniquely empowered in this world. We are big brains and opposing thumbs and we're a tool using, and God has given us this beautiful created world in which we can do things like you know, make our living through agriculture or honey or, you know, whatever it may be, and and I think that made it extremely difficult to recognize that something is diminutive and seemingly unimportant. I mean we hadn't that not knowing about them, you know, hadn't seemed to make a difference to us up to that point. You know, I think it's very hard to imagine those little critters, you know, swimming in a drop of water, as having agency on their own, you know, having some way to get at us.
Thomas Levenson:And I think there are two things. First of all, I think that human get at us, and I think there are two things. First of all, I think that human exceptionalism, even when the explicitly Christian framing of it drops away, that lasts into our own day, I mean that's still a very powerful, I think, cultural impulse and you can see it across. You know all kinds of things, including our politics right now. I mean you mentioned changes at NIH and so forth. I think some of the sort of deep you know where the license to do that comes from for the people who are trying to, you know, make these changes comes from. I think that sense of you know human beings as the actors and everything else is the acted upon. So that continues. And I also think that you know the great chain of being, in that sort of hierarchy of creation, is something that people you know applied as a notion to all kinds of other things, including human society. So, you know, in European or European world culture, you know upper class white men are at the top and everything else flows downhill.
Thomas Levenson:And that becomes a problem when you look at some very specific incidents in the history of germ theory, as for example, when not just the famous story in Vienna but the with Ignaz Semmelweis, but the earlier folks who figured out that horrible fever, childbed fever, this infection that kills women who have just given birth, you know there was a pretty clear series of demonstrations that this was a problem caused in some way by the doctors or midwives, the medical people attending those births, and people were able to document, you know, as early as the late 18th century, that this was most likely something that was transmitted.
Thomas Levenson:They didn't know what it was being transmitted, but the sort of epidemiological, the disease detective links between a doctor or midwife and a chain of patients who would suffer, all suffer these infections was really clear. You know it was established. Well, and in response to one of these, oliver Wendell Holmes Sr, not the Supreme Court Justice who was his son, but the dad, who was a poet and doctor and other things early in his career in the 1840s, you know, said this and the response you know he was a young doctor at the time and he was not a specialist in maternal care and the sort of leading textbook writing OBGYN doctor of the day in Philadelphia responded no, no, no, you know, that's the maunderings of a sophomore, couldn't be. And because this is a quote, a gentleman's hands are clean. So the idea of a hierarchy is there, yeah.
Ben Comer:Yeah, just by dent of being a gentleman, yeah, and I wanted to touch on some of the other historical misconceptions that have functioned as a, you know, a block or a resistance to acceptance of the scientific research. I wonder if you could explain, maybe briefly, miasmas and what role that concept played.
Thomas Levenson:Sure, I mean, think about, you know, an infectious disease outbreak before you know, like, for example, the incident that starts the book the Great Plague of London. So plague shows up in 1665. There's a first, you know there's an index case that probably isn't actually an index case, but there's an early case that people refer to in a poor parish. And then over the next couple of months a few more cases pop up, um. And then over the over the next couple of months a few more cases pop up and then um, then the disease becomes much more widespread and the death tolls start rising until you get um in what was still a quite small I mean a fairly small city by modern standards. You know enormous death tolls, 1 000, 2 000 people a week, whatever um. And you needed to explain two things how an individual case of the plague got started and then how did it spread. And there were a number of ideas about mechanisms of disease, some ideas that would you know from classical antiquity, about, you know, keeping the body in balance, the poor humors, some more more seemingly modern, though still with much of the same apparatus, so-called chemical, chemical medicine, where it was a more specific, you know some more specific substance that was in or out of balance. So that was how the disease, you know, that was sort of what the definition of disease was, something that caused your body to start running awry, which is and this is important to understanding why this idea was able to last so long. You know, at least as a metaphor, that's not a bad, you know, way to think about a disease, right, you know? Think about diabetes. Your insulin metabolism doesn't work anymore, your insulin levels go out of balance and you're in trouble and you treat it by, you know, you know, with, by one way or another, bringing those insulin levels back into, into a safe range. Everything we know about the mechanism of diabetes is different from what people know about the plague in 1665. But that sort of metaphorical level you can sort of see how it's an effective way to frame a disease, persuasive, an imbalance, right, yeah.
Thomas Levenson:And similarly for the contagion, for how to get it from place to place, how does it get to a person in the first place, and then how does it travel? A miasma literally means bad air, um, and so the idea was that there is some, you know, if you believe it, it's that every disease is simply god's judgment. God sort of opens the fissures of the earth and you know foul air bearing disease, you know balance, you know unbalancing stuff goes out and you know it allows for a disease to arrive someplace and you know if it's really in that sort of sense airborne, you can see how it would spread. They did in that period use the term and have the concept of contagion, which you know the root means literally to touch. So you would touch something that was, you know, affected by a disease and that touch would communicate something that could then be passed on. But by the 17th century, certainly, contagion had been sort of loosened as a concept had been loosened and sort of brought into the idea that proximity rather than actual, necessarily sort of mechanical touch was necessary. But once you have miasmas you have a way for the disease, that contagion, to occur and you know keep passing from person to person.
Thomas Levenson:And the important thing to understand is that you know you look at, you look at a disease spreading through a city, as the plague did through London in that period, and you combine the models of disease itself as an unbalancing and that the seeds of disease, whatever they may be they use terms like that, seeds of disease could be carried sort of invisibly on these, you know gusts of air, or you know air blowing it onto the person of the. You know somebody who's in a sick room and you know carries it with them in a breeze, blows it to the next person. However you want to, you know, start mapping out the individual scenarios in your head. It's not a bad description. And so the ideas persist, in part because you know, even if they don't tell you really what to do about an illness, other than sort of attempt to bring things into balance by, you know, cooling people or eating people or giving people beer, or you know bloodletting or whatever it may be. These, you know some way to bring one of the bodily systems into balance. There's no specific mechanism, so there's no specific treatment that's available. But if you're just trying to paint a picture of what seems to be happening, that does a pretty good job, and that's sort of.
Thomas Levenson:One of the big problems for getting to germ theory is you have to come up with something that's not just more correct but is in some ways, you know, more persuasive, more directly supported, has some, you know, leads to some direct possibility of action, and that takes a long time, especially, as you know, in some senses miasma theory is quote true, I mean, yeah, if you live on top of a sewer, if you don't have, you know, especially as you know, in some senses miasma theory is quote true, I mean, yeah, if you live on top of a sewer, if you don't have, you know proper hygiene and all these kinds of things. You know the bad smells and the you know decaying flesh and all this sort of stuff are signals that something's going on. Miasma theory doesn't tell you what is going on, but you know, it's a, it's close enough to be difficult to dislodge.
Ben Comer:Right, right, and it creates essentially a barrier for someone who is making a discovery and attempting to go against that now commonly accepted wisdom. I wonder and there were a number of names that I had not heard in this book, which is another reason I really liked it that I had not heard in this book, which is another reason I really liked it. I wonder if you could give an example or two of some of the maybe lesser sung historical figures who helped develop the science behind germ theory, and you talk about a number of different diseases in the book, so I'll let you choose. Well.
Thomas Levenson:I think consistently the figure that people are most surprised about hearing is Cotton Mather. We know Cotton Mather as this. You know. I certainly you know I live here in the Boston area and Cotton Mather is our. You know hellfire and brimstone witch burning. You know Puritan Bible thumper. You know Puritan Bible thumper and you know he was all those things.
Thomas Levenson:But he was also somebody who apparently as a young man actually thought about becoming a doctor, was profoundly interested in the. You know he didn't have a disciplined mind, he was a complete magpie, but he was profoundly interested in the natural world. He became a fellow of the Royal Society. He sent them you know lots of letters about sort of American curiosities, some of which were, you know, clearly sort of you know he was credulous about, about wild reports, but some of it was very you know a lot of natural history. He was fascinated with medicine. He composed an entire book called the Angel of Bethesda. That was manuscript. He left it as a manuscript when he died and it wasn't actually discovered and published until you know the 20th century. But it's a sort of an encyclopedia of everything that he could gather about health care and medicine, how you would prepare recipes for you know this or that and it contains some really interesting things about germ theory, in fact, actually to me very important. He comes into the book because he is one of the two great sort of English speaking pioneers of immunization it's not true vaccination but it's the predecessor, it's the precursor to modern vaccination, inoculation with smallpox. He learned about that process from his enslaved servant, a man he named Onesimus, who had been born in Africa and taken from Africa to Boston and then gifted to Mather by some of his parishioners. And Onesimus had had smallpox inoculation. He received that in Africa and so when Mather asked him if he had had smallpox, mather records his answer as yes and no, didn't have it in the wild, had a reaction to the smallpox inoculation and is now immune to the smallpox inoculation and is now immune.
Thomas Levenson:Shortly after, you know, a few years after that conversation, an Italian doctor working in Constantinople in the Ottoman Empire reports that the you know Turkish medicine does the same thing and that was published in the Royal Society's transactions and Mather saw it and wrote to the secretary of the Royal Society's transactions. And Mather saw it and wrote to the secretary of the Royal Society saying I can affirm this. I've heard this story from my slave and from other people who've had contact with Africa. And the next time a smallpox comes to Boston I want to try it here, which he did to significant success and significant opposition. I mean anti-vax sentiment starts right at the beginning. It's still with us but has its roots in the reactions to these experiments in the early 18th century, and so that's one of the ways Mather gets into the story.
Thomas Levenson:The other way is this remarkable? In this Angel from Bethesda manuscript he writes down explicitly the speculation that these microbes that Levenhut and he names Levenhut, you know by name cites him. These microbes the term was animicules, these little animals, as they were known that Levenhut has identified. They're everywhere, they're on leaves and they could be the sources of specific diseases, and we should really look at that. And to me that's both fascinating. This is in like 1720, 1721, something like this.
Thomas Levenson:So, 150 years before germ theory proper actually makes its way into science, as it were. And it's important to me because it shows that the difficulty in working out germ theory wasn't simply, and perhaps for much of this period, not mostly scientific. It was one of finding the ways to ask the right questions and then pursue it. You know, mather was not an experimentalist. He was not a disciplined man, disciplined scientific mind, so he wasn't the person to follow that up, but he could think it right, and there was at least one or two other people who were thinking the same thoughts then, but they were still born thoughts. Nothing happened, and that, to me, is one of the things I really want to understand in the course of. You know the story I tell in the book.
Ben Comer:I think it's easy in 2025 to looking back at history and seeing. You know, the gentleman's hand is always clean. You know, miasma, we just talked about looking backward and saying, wow, it's incredible that you know these brilliant discoverers and people who made these forward leaps in germ theory faced resistance. You know, we couldn't be in a situation like that today. We couldn't have those same kinds of dogmas and biases In 2025, you write in the book. It's hard to recognize what one's assumptions omit, all the more so when those assumptions are born of individuals and a society's shared beliefs about the interplay of the natural and human worlds. My question is you know they're difficult to identify. I think that should go without saying. But are there some existing biases or dogmas today in medical or scientific research, and how might we go about better detecting them?
Thomas Levenson:That's a huge question and it's tricky because some of the issues are with scientific research and some of them are with sort of the questions for the larger. You only do the science that a society is willing to entertain right. We're seeing that explicitly. There was an election in November. The results of that election were what they were and there are decisions being made about what the NIH should be doing, what the NSF should be doing and so on, basically every federal government science research agency and you know you can only do what, and that's in some sense that's the expression of what you know a substantial chunk, you know enough of a chunk of our society now to achieve political power. That's what they think is important or unimportant and that's not necessarily what a scientist, an individual scientist or you know a discipline as a you know consensus or near consensus might find important as a consensus or near consensus might find important. So right now, for example, you have explicitly a shifting of NIH attention, health and Human Services attention from infectious diseases to so-called chronic diseases.
Thomas Levenson:That's a choice. I think it's a wrong choice. I think it's a terribly dangerous and scary choice. But you know that tells you that. You know there's an assumption there. There are that and again, like most assumptions throughout the history of all this, it's not altogether wrong that you know there are the, the 21st century, intensely urbanized, you know very um sort of quote, mediated in all kinds of ways, not just media. But you know, our food is mediated through a whole bunch of systems and all this kind of thing right, a more sedentary workforce, yeah all that sort of stuff.
Thomas Levenson:so it's. It's not wrong to say that this has some consequences, and it should be. You know it's important to study, but you know B anthracis is still out there. Yersinia pestis, the plague microbe, is still out there. The cholera microbe is still out there. You know the smallpox virus is not that's extinct in the wild, but polio is still just out there and could, under certain circumstances, roar back. Tuberculosis is very much there, killing a million people a year. Worth focusing on. That's an unexceptional comment.
Thomas Levenson:If you say chronic diseases are the essential problem, you know microbes get a vote right. Yeah, you know we may wish that infectious disease was not a potential threat, but that, in a token, gets you on the subway, as it were. I think one important thing to remember is we may know more facts. We may have more coherent and in some ways rigorous theories that we use to organize those facts than people did in the past. It's not we made we do. We understand infectious disease down to the level of molecules and individual changes in genomes that produce different pathogenic effects, all these kinds of things, and our predecessors did not. But that knowledge isn't the same as saying that we are smarter than our predecessors, or that our habits of mind are somehow cleansed and more you know, more rigorous they're not. You know we're not smarter than you know Isaac Newton and Robert Boyle and you know all those folks, huygens, or whoever you want to you want to throw in.
Ben Comer:We have the same hardware.
Thomas Levenson:Yeah, and so you know, it would be presumptuous of me, as you know, a popular science historian, to say you know, these are the assumptions that people are making in science and medicine that are clearly going to. You know, these are the assumptions that people are making in science and medicine that are clearly going to, you know, bite us in the butt. But I feel pretty confident saying that those tricky assumptions exist.
Ben Comer:Are there parallels that you see between mapping the human genome and mapping the microcosmos?
Thomas Levenson:Yes, and I see them both. As you know, it's an. You know doing so produces this extraordinary trove of of facts and I think one of the things that's most fascinating to me about the Human Genome Project. You know, I'm I'm I'm not in my first youth, as you can tell from my hair color and all that. I'm old enough to remember. And, and you know, I'm not in my first youth, as you can tell from my hair color and all that I'm old enough to remember. And you know, I started work as a science writer in the 1980s and it was a big deal to sequence a single gene and to identify its protein.
Thomas Levenson:You know you'd look for the gene for you know sickle cell trait or the gene for Huntington's or whatever. And you know very intense search for these particular sequences of DNA. And you know a whole PhD thesis would be a graduate student working through one gene, or even you know part of one gene, because it was so laborious and so slow. And in that context people said oh great, we sequence. You know, we build the technology, we do all this sort of stuff and we sequence the whole human genome and then we'll know how to build a human being and we'll understand all these diseases and we'll be able to do all this stuff. And so they sequence the whole human genome and, with each successive level of detail and precision in our understanding of the basic information environment of molecular biology, how DNA works in us or in a planarium, the C elegans flatworm or whoever the chimpanzee what's been striking is how much more complex it turns out to be Our assumptions about what kinds of knowledge and power we will get out of doing, say, sequencing the human genome. You know, as we now know I mean I was just seeing a marvelous paper that suggested that there is an important, you know, rna mechanism for deciding which of a couple of different proteins sequences of DNA may produce.
Thomas Levenson:That it sort of dictates which bits of DNA get expressed and you make different proteins. And this is one of the ways you get to build something as complex as you or me. The ways you get to build something as complex as you or me despite the fact that we only have 20 or 30,000 genes, which was one of the first shocking and very difficult to understand results of doing the Human Genome Project. How could you make us out of so few genes, especially when seemingly simpler creatures in some cases had many more genes. What's that all about?
Thomas Levenson:And I think the same is true of the microbial world, cataloging the entire microbial world, especially if you include, as modern usage does, viruses as a subset of the microbial world. You do all that. I mean there's a question of what it means to catalog them, identifying strains, doing genomes for each of them, the whole. You know there are lots of things you can do, enormous amounts of useful stuff to come from that. At the same time, I think it will expose us to enormously fascinating problems that simply doing that cataloging will not be sufficient to help us figure out.
Ben Comer:And I think a similar thing is happening with. To get back to microbes, the microbiome, there were a number of drug companies who you know. In the last 10 years, or maybe 10 years ago, there was a real effort to design drugs that targeted the microbiome for various conditions and I think people found out you know, because of the clinical failures that that system is much more complicated than we initially understood and it's still, I think, largely a mystery. But is that germ theory's next frontier, the microbiome?
Thomas Levenson:I think, I mean, I think it's certainly it's of interest. I mean, one of the things that's fascinating is all right, you know you have something like. You know, you know name your poison the rabies virus, or you know the cholera, you know cholera, whatever. And there's a sort of relatively simple sequence of cause and effect. They, you know you, get infected with this particular microbe, certain. You know, as we didn't then, but we now know, for example, what specific molecular events the cholera microbe sets in motion to start sloughing the lining of your intestines and your guts and all that, dehydrating you and all these terrible things. We understand that at a mechanistic level pretty well, very well. So that's one thing.
Thomas Levenson:We have these like sort of point source, individual microbes doing individual things in your body. But it was, you know, as you're saying, with this rise of sort of microbiomic medicine, the realization that we have more bacterial cells, microbial cells in our body than we have human cells that we live. You know, in some ways we're just the tube that carry. You know, we're the chauffeur for all these microbes. We just carry them around the world, you know, and they're doing their thing and using us for their ends. But they're also symbiotes, you know, obviously you know the gut microbiome is crucial to your. You know your digestion and your digestive health.
Thomas Levenson:If that goes awry, you get all kinds of bad things. And when that's healthy, you don't have ulcers, you have all these, you know desired outcomes occur, and this recognition that there is this intensely complex ecosystem, you know this whole again sort of microbial microcosmos within our own bodies, within each of our own bodies, that, when it's healthy, is serving essential functions for us. And you obviously see examples throughout the kingdom of life. You know microbes that do great things to allow plants to fix nitrogen microbes. You know they're all kinds of all kinds of different ways in which, in which sort of macro scale organisms interact with these micro scale ones in ways that are productive for both.
Thomas Levenson:So, and you know, in some senses, the diseases that result from some disruption of one's microbiome are conditions that may, you know, sort of require a kind of germ theory-like breakthrough to understand. Is it the extension of germ theory specifically Will? Well, you know germ theory was really built around isolating individual microbes and going through a series of steps to rigorously show what their properties were and what their effects were on whatever they have to infect. And I don't think that simple sort of fairly straightforward experimental protocol is going to really be the driver of what is, I think, a much more complex, much more multidimensional systems biology problem.
Ben Comer:Right, they're not working in isolation and you know there's been some really fascinating research done on the gut brain access with implications for diseases like Parkinson's and Alzheimer's disease. So yeah, I mean it seems like a really difficult one to even study. I wanted to ask you about antibiotics. You raised the issue of responsible use of antibiotics in so Very Small, as well as the implications of antibiotic resistance. What kind of policies or funding mechanisms do you think are needed to adequately address this issue?
Thomas Levenson:First of all, I'd like to shout out to some of the people I've talked to over the years or stuff I've read, who've helped me understand microbial resistance. You know, microbial resistance, uh, maren McKenna's writing has been really great and, and she's, you know, she's an incredibly powerful thinker and reporter on this stuff. And, uh, you know, there are lots of others. Laurie Garrett has written very well about this stuff. Um, you know, and, and so you know, nothing I say is unique or original. You know, original to me, these are thoughts that people have been working out for a long time.
Thomas Levenson:That said, the antibiotics as a drug that a for-profit drug discovery system is going to produce, that's a real problem, and it's a problem for a couple of reasons. One is antibiotic resistance means that any new antibiotic has, you know, either a finite lifespan or real constraints on how you use it in order to preserve its effectiveness, when you know, when resistance is so readily developed and then, you know, spread. And the other thing is that antibiotics, even antibiotics that are effective, you know the great thing about them is they work right. You know, you get an ear infection, your kid gets an ear infection, you give them a week or two of some drops or a pill and and they're better, and that's all, it's there chronically, exactly right you know they're not statins, right, right and uh.
Thomas Levenson:and so the the, just the know, this is not a criticism of a for-profit drug company, it's just a fact. These are not the kinds of compounds that those kinds of institutions are set up to develop. So, yes, that means you know. Yet, that said, the economic return on an end of, you know, on a successful antibiotic is enormous. Right, all those lives saved, all those sick days you know, eliminated, all that sort of stuff, the benefit to society is huge and can be counted in money terms and it's huge in money terms is huge and can be counted in money terms and it's huge in money terms. Um, so these are drugs that that have a social, a clear dollars and cents as well. As you know, it's good not for human beings not to die, it's good for human beings not to suffer. There's a, there's a moral and, and you know, just kind of like, um, just sort of a civic value to it.
Thomas Levenson:But there's also, you know if we are going to, you know, be, as the old phrase has it, homo economicus. If we're going to think that way, it makes sense on, you know, that sort of accounting level as well. And if individual, you know, if Merck or GlaxoSmithKline, beecham or whoever it may be, isn't set up to do that, then somebody else has to, and that somebody else has to be essentially, uh, so a social commitment. You know, we have to decide. We're going to spend our money, our tax dollars, on it. We're going to develop the research. We're going to support nonprofit.
Thomas Levenson:Um, you know, it could be governmental, could be non-governmental, doesn't matter, but we need to have an antibiotic and, more broadly, antimicrobial drug research program. That is something we, as an individual nation, united States, as a, you know, developed world with the resources to do this, that's something we need to pay for. And we need to pay for it not just because it's the right thing to do, not just because it will save lots of lives, but because it's, you know, it's part of creating a sustainable, you know, flourishing, thriving and economically as well as you know, by any other measure successful society.
Ben Comer:And ideally a majority and I'm just speaking about the US here, but ideally a majority of people would come together and demand that tax dollars be spent to research and develop these new antibiotics that so far has been difficult to generate. I mean, maybe another option is angel investors the exceedingly rich are being talked into. Maybe, instead of investing in space travel and investing in the development of new antibiotics which one is more likely to happen is what I guess I'm getting at Is it convincing enough people or is it, you know, convincing the rich?
Thomas Levenson:I mean, I'm certainly not against trying to persuade. You know Bill Gates, who already is very active philanthropically in the health care space, but you know Jeff Bezos and you know whoever to to put as much money as they care, to as much money as they as they can, uh, into antibiotic research and basic science. You know, say, basic biological, or you know, uh, sciences, whatever, uh, because you know many of these things derive. You know the, the, the, the, the translational gap between curiosity driven basic discovery and developments that directly benefit human beings. That gap has been shrinking and you know many of the great ideas that then you know serve human beings well, come from, you know, rapidly emerge from stuff that you can't predict but are, you know, can't predict individually, but that we know from decades now of experience. This, you know, sort of curiosity-driven basic science is the seed corn for all kinds of technology development. That sort of flows downhill from it. So, yeah, absolutely, you know, get those, get those billionaires to give back in that way. But I don't think that's a reliable, sustainable source of you know where we, what we really need, what we really need.
Thomas Levenson:The science is not, you know, part of the problem with billionaires or anyone is. You know, you saw it, for example, in Silicon Valley people investing in sort of media ventures. They'd be really interested in it, right. And then after a while you say, okay, well, I did that, it's not. You know it's not sustaining on its own or whatever. I'm going away and the enterprise goes away. And you know, all of a sudden you have a gap where that used to be. If you do that in science, the problem is not just that you know an experiment that's happening at the moment. The funding goes away, stops, I'm sure. You know. You know and your audience knows you know much better than I.
Thomas Levenson:But you know really good labs have developed over time institutional culture. You know set of sort of informal knowledge. You know something as you know, maybe as seemingly silly as you know, that cell sorter over there needs to be, you know, encouraged in this way to do its job right. And you know just how the machines work or whatever. But there's also, you know, sort of a collective act of thinking that goes on in productive, interesting labs and you pull the funding and those people scatter and the machines go away and the space gets reused.
Thomas Levenson:It takes just to set up a good lab to do really cutting edge work in a lot of these now increasingly precise and sort of nanoscale or microscale disciplines. Just the physical act of setting up the lab is, you know, could be a year, or you know, even more in some cases, and you know the informal knowledge is more than that. You know it takes a while to build back a team that really knows, you know, can sort of communicate in efficient and productive ways, so relying on billionaires who may come and go, whose interest may wane when a result doesn't happen, and so forth, unless those billionaires are willing to endow institutions Sort of what happened with the Broad Institute and some other, the Weiss Institute at Harvard and some other, the Weiss Institute at Harvard, places like that they actually have endowments and they can sustain themselves. People are willing to do that. That's great.
Thomas Levenson:But truly the scale of science these days and the scale of our societies, where US is what? 330, some million people, many trillion dollar a year economy, you know, if you want to make a difference on that scale you need sort of social level funding and I think you need to do so in a way that is not subject to the, you know, each change of administration's whims. I mean the idea not just that you're changing the focus of NIH or NSF, but that you're canceling 400 grants that have already been awarded, on which work is being done. Those labs will shut down, they'll lose all that institutional infrastructure, that capacity and the hit to US science and the hit to our ability to develop new antibiotics, develop new vaccines, to look for new ways of, you know, addressing microbial issues altogether that will be set back for years to decades and that will have not just American impact. It will hurt us, hurt our economy and so forth, but obviously it has worldwide impact and it has life and death impact on a lot of people.
Ben Comer:Right and a number of the endowments coming in from family offices and people are often targeted to a specific disease. You know they're focused on cancer or cardiology or a rare disease, not so much. You know large endowments for basic science. I mean the NIH, I think, does the vast majority of that kind of work or has done that kind of work in the past. Are there any other, I guess, potential consequences that you could name around? Funding cuts to the NIH? What's happening there right now?
Thomas Levenson:Well, I think you know again I don't know more than what any of your audience knows from careful reading of you know the newspapers and then perhaps you know the next two or three levels down of more specialized publications. Clearly you know shutting off funding for you know, some scientific research or a lot of scientific research, directly affects those particular research programs. Cutting off the science educational pipeline, which is one of the things that happens when you cut funding for scientific research, you don't get graduate students in, you don't have as many graduates in places. Undergraduates, universities lose the ability to educate undergraduates, certainly undergraduates who need scholarships and all that kind of stuff. So you're going to have a sort of broader based skill loss. That'll happen, that is likely to happen. Another thing that's going on is a lot of the just reading this morning, before we got on this conversation, about a bunch of the sort of data collection that the federal government is doing across a wide range of domains, from food poisoning to weather disasters and everything in between.
Ben Comer:Right, yeah, disease monitoring.
Thomas Levenson:A lot of that is going away, at least temporarily, and that means two things. One is bad things can happen out there and we won't know about it and therefore can't address it or learn from it. You know, I mean, there's one of these bad disasters is they teach you something you know, at great cost. But we won't even be able to do that because we won't know we, you know, the scientific community, the research community won't know that. You know an event has happened because this monitoring that we've come to rely on has gone away, that you know an event has happened because this monitoring that we've come to rely on has gone away. And I don't I mean I don't see how you easily replace that. I mean we just have to, you know, I think, fight those decisions. They're ill judged. I think you know it's one thing to say I don't want to do. You know I don't want to research cancer, I want to research obesity.
Thomas Levenson:You know, look, you know, then, vice President Biden's one of the moonshot on cancer. That was a, that was a decision about what direction to go, and there were, I think, a lot of scientists who said, as as with the war on cancer, the original Nixon war on cancer that it's a mistake to just put all your focus on that singular complex of diseases. There's lots of other things that we need to know, including the basic science that will help illuminate cancer and lots of other stuff. So you know there are choices that different administration makes and you know, okay, they get elected, they should make those decisions. But that sort of unilaterally disarming our ability just to find out stuff either about nature or about what's happening in our society, as nature has its way with us, that leaves us in an extremely vulnerable position, and I'm really I'm not sure I've answered your question, but I will say that that makes me quite scared For our audience, listeners in leadership positions at biotech companies, at pharma companies.
Ben Comer:are there any lessons, any cautionary tales, any messages that you would hope they might glean from so Very Small?
Thomas Levenson:Well, I think you know one is that you should probably you know it's really hard for a startup, I know, which is always just, you know, trying to get everything done before the money runs out. But there's this, you know, you got to have a little room in your hip pocket for something unexpected. You know, I think, the some of the critical, there were these interesting ways by people which may, by which people made the inferences that finally led to germ theory. Some was, you know, just repeatedly identifying the presence of a microbe in a disease without knowing what the mechanism was. And another was, you know, just repeatedly identifying the presence of a microbe in a disease without knowing what the mechanism was.
Thomas Levenson:And another was, you know, really doing a complete reconstruction of, you know, for example, how cholera propagates through a population that was essentially all of germ theory except for the germ itself. These were people, were able to work with these ideas and think them through and they provided a foundation for real breakthroughs to come. So I think you know that, that you know saving a little bit of budget, a little bit of time, allowing a certain number of projects that that may be not quite directly on the main line of of of your applied research programs is probably a useful thing. More broadly, I would say that I think the phenomenon of infectious disease is something we have largely allowed ourselves to forget about because of the extraordinary success of vaccines against all the common diseases of childhood and many other diseases, and the power of antibiotics since the end of World War II.
Ben Comer:It's a really good point and I think I'll just quickly interject here the primary source. Accounts of people dying from cholera in the book were so shocking to me because, you know, it's something that we haven't seen here in my lifetime in the US and just the speed at which they died you know people from from all walks of life it was it was really shocking in a way to read about that, how people experienced it in real time.
Thomas Levenson:Absolutely. And I think you know the COVID pandemic was kind of a warning because, terrible as it was, as disruptive as it was, as many people around the world who died of it it was, you know, as a novel disease goes. It had what roughly, you know, before the advent of the vaccine and so forth, it had a roughly 1%, I think, mortality rate, something like that. I mean forgive me if my memory is playing tricks, but I think it was in that range which is terrible, but not society, devastating Right Right. Society, devastating right Right. Imagine. And oh, by the way, to me COVID is one of these great, both tragic stories of failure because of the, you know, ultimately political resistance to basic public health that led to many more unnecessary cases and deaths, and this extraordinary triumph of science. I mean to go from the public announcement of a disease in December to its entire genome being sequenced within January, so within weeks, not months to a basic vaccine design that's there and manufacturable by, I think, april and is in people's arms a couple months after that as a test to widespread manufacture and distribution by the end of the year, to less than a year after the first emergency disease. I mean that is a testimony to the extraordinary capacity of modern molecular biology, virology, and to the, you know, the industrial and intellectual capacity of both the government and, you know, the various startup and established pharma firms that were involved in getting that vaccine out. I mean, that was a triumph. That was a triumph.
Thomas Levenson:What I worry about is the next emergent disease may have similar transmissibility to COVID, may have the same global reach, because air travel is, you know, part of our fabric now but has a mortality rate or, you know, has you know, more severe consequences, though you know, long COVID and so forth is pretty darn severe but and a higher mortality rate. Imagine if COVID had had, say, a 3% mortality rate instead of one. So you catch the disease and you have a 1 in 33 chance of dying. That would be. I think just that change doesn't sound huge, would be enough to be. That would be. I think just that change doesn't sound huge would be enough to be, I think, a much more socially disruptive. I mean, obviously, tragically, individuals and families involved.
Thomas Levenson:But you know, imagine if you know and COVID was, as I said, this sort of relatively mild warning, you know, reminder that the microbial world, the viral world, is still out there and still interacts with us in ways that we don't always love. The viral world is still out there and still interacts with us in ways that we don't always love, and I think one of the things that would be really worth your listenership's attention is to think hard about the kinds of infectious disease threats that people who look at things like zoonotic diseases, diseases that leap from animals to people, and perhaps some of the more conventional or more familiar older diseases like measles, which is making a comeback because our vaccination levels are dropping All that you know those are areas of both fascinating scientific inquiry and possibly important commercial. You know work as well.
Ben Comer:Absolutely Well. We are running short on time here, tom. It's been a real pleasure speaking with you. I really appreciate you being here.
Ben Comer:Tom Levinson is a professor at MIT's graduate program in science writing and his newest book is called so Very Small how Humans Discovered the Microcosmos, defeated Germs and May Still Lose the War Against Infectious Diseases. Humans discovered the microcosmos, defeated germs and may still lose the war against infectious diseases. I'm Ben Comer and you've just listened to the Business of Biotech. Find us and subscribe anywhere you listen to podcasts and be sure to check out new weekly videocasts of these conversations every Monday under the Business of Biotech tab at LifeScienceLeadercom. We'll see you next week and thank you for listening. At lifescienceleadercom. We'll see you next week and thank you for listening.
Ben Comer:Avantor is a leading life science tools company and global provider of mission-critical products and services to the life sciences and advanced technology industries. Avantor works side-by-side with customers at every step of the scientific journey to enable breakthroughs in medicine, healthcare and technology. Avantour's portfolio is used in virtually every stage of the most important research, development and production activities at more than 300,000 customer locations in 180 countries. For more information, visit avantoursciencescom or find them on LinkedIn, x formerly Twitter and Facebook.
