Moises Velasquez-Manoff, author of An Epidemic of Absence, talks with EconTalk host Russ Roberts about his book--a discussion of why allergies and autoimmune diseases have been on the rise in the developed world for the last half-century. Velasquez-Manoff explores a recent hypothesis in the epidemiological literature theorizing the increase is a response to the overly hygienic environment in rich countries and the absence of various microbes and parasites. Velasquez-Manoff also considers whether reintroducing parasites into our bodies can have therapeutic effects, a possibility currently under examination through FDA trials. The conversation continues a theme of EconTalk--the challenge of understanding causation in a complex world.
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About this week's guest:
Moises Velasquez-Manoff's Home page
About ideas and people mentioned in this podcast episode:
Books:
An Epidemic of Absence: A New Way of Understanding Allergies and Autoimmune Diseases, by Moises Velasquez-Manoff at Amazon.com.
Articles:
"The Worm Turns", by Moises Velasquez-Manoff. June 29, 2008, New York Times, Idea Lab.
Podcast Episodes, Videos, and Blog Entries:
Taleb on Antifragility. EconTalk.
EconTalk Episodes with Gary Taubes. EconTalk.
Oster on Pregnancy, Causation, and Expecting Better. EconTalk.
Taleb on Skin in the Game. EconTalk.
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0:33
Intro. [Recording date: February 10, 2014.] Russ: Before we get started today I want to list the Top 10 episodes of EconTalk for 2013....
1:18
[Recording date: February 10, 2014.] Russ: My guest is Moises Velasquez-Manoff, author of the remarkable book, An Epidemic of Absence: A New Way of Understanding Allergies and Autoimmune Diseases, which is the subject of today's podcast. This book was recommended to me by a listener, [?]. I'm sorry I missed it the first two times around in hardcover and paperback, but I'm glad I found it. For better or for worse, it vindicates a lot of my Dad's views of the world, as we'll see as we go on--sometimes hard for a son to accept. My dad was not obsessed with cleanliness and germs. As it turns out, as your book points out, that this may be sometimes a surprisingly good thing. It is an incredible book; it's from the cutting edge of medicine and science. Equally valuable, it is written without hysteria or overconfidence, which is rare. And although it's a book about disease, it deals with many issues that arise here on EconTalk, as listeners will notice. Let's begin. Moises, what are autoimmune diseases and what has happened to their prevalence along with allergies over the last century or so? Guest: Well, they've increased very precipitously. So, an autoimmune disease is when your immune system, which you normally think of as protecting you against things like the common cold or just regular infections, that your immune system actually turns on some aspect of your own body. So, I actually have an autoimmune disease called alopecia areata where my immune system has essentially turned against my hair follicles and rendered me hairless, for the most part. An allergy is a slightly different thing. An allergy is when your immune system turns against some protein in the environment. That probably does not pose a real threat. In this case peanuts are maybe the best example because they've become so prevalent. So then the reaction to the protein becomes injurious to you. And again, peanuts are a good example where people can go into anaphylactic shock and their airways close up and they can die from encountering this sort of innocuous substance in the environment which really poses no threat. It's a mistake of the immune system. All these diseases have increased in the developed world, especially late 20th century, probably earlier, but people were busy with wars in the early 20th century. Definitely late 20th century. And allergies between 2- and 3-fold in the developed world, maybe more. And autoimmune disease, depending on which one, up to celiac is between 4- and 5-fold, about--celiac is a sort of autoimmune disease that's triggered by a protein in wheat and other grain--it's called gluten. Multiple sclerosis (MS), inflammatory bowel disease--these are all sort of broadly included under the category of autoimmune and inflammatory diseases. Russ: And one of the reasons that I found the book so fascinating is I think anybody roughly my age--I'm 59--has noticed this increase in things like peanut allergies. And we think, well, my first thought, I have to confess as an economist is: Well, this is just a measurement issue. This is something that wasn't diagnosed before; we thought it was something else. And this explains, I thought, lots of phenomena that seemed to have increased in the last 10, 20, 30, 50 years. Another example might be autism. We get to doctors more; the doctors know more; we have more classifications. So things that got ignored before, misclassified, got classified correctly. That's always been my suspicion, and after reading your book--that suspicion is wrong. Explain why. Guest: Well, there are several ways to deal with that problem. Which I think is a real problem. And some of the measured increase I think is almost invariably due to just improved diagnosis. On the other hand, if you can go to populations right now that are side by side and see very different prevalences of allergic disease by objective measures--and usually allergic disease, there are two ways of measuring, really. One is by doing a skin prick test, which is basically take a little bit of allergen, like pollen, that people are often allergic to, and prick the skin and sort of rub it in there. And then you see the resulting wheal, which is like a little swelling. And that's a measurement of the allergic tendencies of that person. The other way is even more direct and that's simply to measure the allergic antibody that that person has. So, to have an allergic disease you have to have this antibody to that substance--that is, that binds that substance, sort of directs your immune system to that substance; in this case, let's say against peanuts, because it's an easy example. So you have IgE [Immunoglobulin E] that's specific to peanuts. That is, Immunoglobulin E--it's a kind of antibody. You can measure that directly. If you have it, you have a propensity to be allergic to peanuts. If you don't, you don't have that. And so you can go to populations living side by side, usually exposed to different environments, and see that the prevalence of these antibodies and the prevalence of positive skin prick tests, the wheals or the swellings, are very different. And there are different populations--I go through a number of them--where this observation has been made in the late 20th and early 21st century. And is still being made. And it's sort of like the big detective question--the big mystery is what is different about the two environments when you have people who are often genetically the same in the sense that they come from the same ancestral population and yet have these very different propensities to develop allergic disease. Russ: And I mention my age because when I was in first grade, in 1960, which was a long time ago, nobody had peanut allergies. It was unheard of. So the question is: Were people dropping dead then but they didn't know it was a peanut allergy, because somebody brought out a sandwich or somebody placed something in a sandwich that somebody didn't know about. And the answer apparently is: No; people actually are more allergic to peanuts than they were in 1960. Which is hard to understand because evolution goes very slowly, we tend to think. What could be really so different about how my body reacts to peanuts? But of course as you point out, it's more than just peanut allergies. It's cat allergies, hay fever, it's asthma, it's inflammatory bowel disease, it's multiple sclerosis. There are a number of factors that have increased. And I think if you ask most people, and I think a lot of doctors until recently what the cause of those increases were, they'd say: Well, it's pollution--they look for things obviously that have changed over the last 50 years. You look for something that's correlated with it. It's pollution, it's chemicals in the environment. And they may have some role, as you point out toward the end of the book.
8:13
Russ: The shocking claim is something else, and that is the essence of your book. And what is that? Guest: Right. So, starting let's say about two decades ago people started asking not what was added to the environment, which as you say is a sort of logical way to pursue this question, going by history, but what had been removed from the environment that might have prevented the emergence of these diseases. This is an old hypothesis actually that goes back farther than people realize, back to the 1960s even people were making observations that for example if you grew up without a toilet but used an outhouse that your risk of multiple sclerosis was lower. What a mystery--that's very bizarre. Russ: Seems like a spurious correlation is what you'd assume. It's correlated with something like income; not correlated with something like a toilet. Guest: Exactly. And what's funny about that is it may literally be the toilet, the sanitary amenities that are important. But to get back to the history of this idea, the hygiene hypothesis, which I think is a horrible phrase, and I'll get into that later--and a lot of other people do, too, but we'll use it anyway because everyone else does--is sort of born in 1989 with a paper by epidemiologist David Strachan. He's British, actually he may be Scottish; he's working in Britain; he looks at tens of thousands of birth records of people born in the 1950s, as I recall--it's been a while since I've read that paper--and then looks at what correlation could you make with a child that predicted their adult risk of hay fever. And what he finds is that, I think it was over 10 if I'm recalling correctly, 17 variables that he looks at, is that the single variable that correlates with protection is how many other kids are in the house when these kids are infants or very young. So, the more other kids there are, the lower their risk of hay fever when they are in their early 20s. So that's very odd. He said it's probably infections: when there are a lot of other kids around, you are more likely to get infections. It's sort of like an amplifier of contagion. And that's invariably true. But then in the subsequent decade people are looking for the infection and they can't identify it. And what has happened with this explosion of research on the microbiome, which is really in the last decade, the last 5 years especially-- Russ: Define that. What is the microbiome? Guest: The microbiome is the collection of microbes that actually lives inside of us. So, microbes in our body right now actually outnumber our cells by a factor of 10 to 1. Ten times as many microbes as you carry cells, your cells. That's because they are a lot smaller than your cells; that's why they all fit. Most of them fit in your gut, but they are really all over the surface of your body. And what's there has a very important implication for how your immune system works. It sort of calibrates your immune system. And there is lots of suspicion that it has sort of changed over the course of the 20th century in particular for many reasons. One is you just simply don't inherit the same microbes because you are not exposed to them, and that's due to improved sanitation and to, interestingly, smaller families--just less crowded. So that was sort of what David Strachan was seeing all those years ago, that there was this correlation with large family size protecting against the younger kids. So that's one direction that all this research is now pointing in. So the hygiene hypothesis essentially starts as this thinking about infections. At this point no one really--well, very few people I should say--really think that infections of the type David Strachan was talking about, which were called [?] measles and that kind of thing, really protect. And that's simply because they can't get a signal of protection when they do these epidemiological studies. What has been consistent is that kids who grow up with other kids, very young, are protected; they think it's more of a microbiome effect. Kids [?] who grow up with animals--dogs in particular seem to be protective. Kids who grow up on farms seem to be protected. Kids who grew up in situations where they have, as I mentioned, not very good sanitary amenities seem to be protected. And so these things are probably all markers for a transmission of microbes. You have to think of it as an ecosystem. And an ecosystem in science, a more diverse ecosystem is stronger, more robust than a less diverse ecosystem. And for probably some of the same reasons it seems that the diversity of our internal microbiome, our internal system of microbes, is better for our health. The more diverse it is, the better. Now there are of course people coming up with data--you come up with a rule and then immediately someone comes up with data that suggests it's not true. So that's already emerging. But I think for now that's holding as a rule. And really what scientists want to discover is which sort of keystone species--so like if you look at the African savanna, it's sort of shaped by certain species, like the elephant--they keep it more savanna-like by trampling trees and they have an outside impact. So there are probably keystone microbes in our, on and in our body, that are especially important for our immune calibration. And the trick is to figure out which ones they are so we can create some sort of probiotic. And then also to figure out when we need to have contact with them. Because timing is clearly extremely important. If you are an adult and you go to a place where there is not very good sanitary amenities, it's not going to help your allergies. Russ: Not good for you. Guest: Yeah.
14:11
Russ: The harder part about this book and these hypotheses is that the 20th century is a great triumph of knowledge and medicine both in terms of cleanliness and hygiene, sewage, all kinds of things like that; but also antibiotics, the elimination of all kinds of horrific diseases that kill people, through vaccination and also treatment. We really understand a lot of things we didn't understand 100 years ago. But what your book argues, and what this science is suggesting, is that--not that we necessarily did too much, but that this improvement came at a very large price for some people. So talk about--let's talk about worms. And by the way, if you are eating during this podcast, which I know some listeners do, the book is not, and this conversation may not always be conducive to digestion. I just want to mention that up front. For somebody who is a little squeamish, as I am, talking about worms and giving yourself worms on purpose, which is part of our conversation, is a little bit difficult to take. But be prepared. And a spoiler alert. So, Moises, talk about why the removal of worms from our systems--we are talking here about hookworms, tapeworms, and other--pinworms--why is that possibly a bad thing? Guest: Yeah. Let me just address one thing you said, though; I don't want this to be unclear; and that is that vaccines are good for us for many reasons--clearly because they've helped with infant mortality being the greatest reason, but also because the organisms that protect us are not the same ones that we vaccinate against, necessarily. So, we vaccinate against polio and measles--none of those infections have shown up to be protective. In other words it's possible to keep the bad at bay of the world of yore, which is the world, of the late 19th century say, where there is a high infections load in poor families at least--1 in 5 children died before age 1. To keep the improvements that we've had which are tremendous and monumental and have changed human existence, and still address this problem. And still keep our vaccines. So I just want to be clear on that point. Now, for worms, the deal with worms, parasites, is that if you look around the animal kingdom every animal has an array of parasites that they've co-evolved with. It seems that it's impossible to exist on this earth without being parasitized, simply because parasites can out-evolve you. Their lifespan, their procreative life cycle is less than yours, typically. So, for hookworms, say, depending on the species, it lives just a few years. And so it can keep evolving. Whatever you live--if you are lucky you live 60 years--you can't evolve as quickly as a worm can evolve. So basically you are stuck with a few. They are there. And what they do to survive inside of your body is they tweak your immune system. That's one of their tricks. They convince your immune system that they belong. And the way they do that is by inducing some of the cells, some of the sort of, the mechanisms that help you tolerate things. So that, for example, if you don't have a peanut allergy and you eat peanuts, it's not the immune system is ignorant of the peanut. It's that the immune system sees the peanut and tolerates it. It's not a big deal. That's how we want it to be, right? When you have a peanut allergy, the immune system sees the peanut and rejects it, and sees it as an enemy. Now, what the parasites do is they convince you to tolerate them and treat it like some food that's supposed to be there. That's how they live for years inside of their hosts. And by strengthening that part of your immune system, the thinking goes, they then prevent allergic disease and possibly the autoimmune disease from ever emerging. So now you back up for a second. You realize that that kind of tweaking of your immune system was constant throughout not just our evolution but through probably most animals' evolution. You rarely find an animal that is not parasitized by a few parasites at some point in its life. Usually early in life you are parasitized the most. And that's when of course these diseases tend to emerge these days in humans, early in life. So you have this strengthened, let's just call a part of the immune system that's like a muscle, that helps you tolerate things. That helps you not respond; that helps you, say if you are a very well-balanced person and people provoke you in a way that could lead to some sort of conflagration, you are just very well balanced; you have an equilibrium, you don't respond. That's what those parasites help you do--they help strengthen that part of your immune system, that aspect of yourself. So then you remove parasites, something that started happening late 19th century but really gathered steam at least in the developed world in the early 20th century, and you've removed the influence on that aspect of the immune system that has been there since time immemorial. And when they do these studies in Africa where populations still are parasitized, where they will take a bunch of kids; they will de-worm them and basically measure how their immune function changes before and after. And you see an immediate rebound in allergic reactivity. And immediate decline. So everything that I talk about in terms of the ability to hold back and the ability to attack, your immune system that is, that corresponds to certain types of immune system molecules. And they can see--the molecules that correspond with holding back, they decline, they go down. The whole balance of your immune system changes. The fact that they can see that immediately after de-worming suggests that it sort of happened to us historically as a population. In the United States, you don't remember, but half, large swaths of the South were parasitized up until the 1920s, 1930s. I mean they were already supposedly being cleared at that point. The kids still had a lot of hookworm in the South. And it was a sort of public health triumph that they got rid of all this hookworm. Russ: And it has--you should mention--worms are not pleasant sometimes. Guest: Oh, absolutely. I can tell you from personal experience--there is no doubt that these parasites are not entirely benign. They are taking something from you. A parasitic lifestyle means they are essentially stealing from you. They steal nutrients. Hookworms actually suck your blood, but there are other parasites that just steal your food. Russ: Doesn't it come--you said it comes from the Greek word, 'to sit at the table'? Correct? Guest: Yeah. Russ: Great phrase. They are eating with you. You don't realize it because you don't see them, but they are chowing down. Guest: That's right. The way I think about it, actually I've come to think about it--so there's this whole rethinking of the immune system that's going on. We've focused on, since the advent of germ theory in the 19th century, the firepower the immune system has and how to train your immune system to recognize enemies in advance. That's what a vaccine does--you get some protein that represents measles, say; you train your immune system to recognize it so when it sees the real thing, it fights it off. But there is this other aspect to the immune system that's immensely important and that's shutting down aggression before it starts harming you. Because your own aggression can also cause collateral damage. The prime example is what happens in septic infections, where every organ begins to shut down because you have this infection. It's not the bacteria necessarily that's shutting down the organ. It's that your immune response has become so overwhelming that your whole body just collapses. The way an organism works--it just collapses. So there is this whole rethinking now going on about tolerance as a survival strategy, recognizing that you can destroy yourself with your own firepower. That when you start throwing grenades and they are landing too near you, which they invariably do inside your body, you also harm yourself. And so controlling that aspect of your immune system is also necessary to survival. Now what's interesting about parasites is that if you--part of what they are doing is tweaking your immune system so they can live, so they can survive. But also part of it may be that you've learned through experience--by experience I mean millions of years of evolution--that if you over-respond to a parasite, which is a very large animal living inside of you, you will destroy yourself. So you hold back. And so one way to think about this is like you've fought to a kind of standstill. And I always think back to the cold war, as an example, where you have two entities that are at loggerheads to each other. But since war is essentially the enemy, there is this frozen state of affairs, that ensues, that sort of congeals. And I think that the human immune system with parasites is very similar--you sort of end up holding back. Because it's like mutually assured destruction if you over-respond. Now of course there are nuances here. You are actually responding. But it's a very tightly controlled response, and part of the response is making sure that no other inflammation--inflammation being the thing that destroys you here--is able to spread from this site of where you are actually fighting--like if it's a hookworm, it's sort of, its body, its mouth is wrapped around some part of your intestine. They are very small; they are about a centimeter. But they are basically eating the lining of your intestine. And so you are responding at the site, but you are also tightly controlling that. And it's the control, the nonresponse, the anti-inflammatory, the ability to hold back, that then is important for not over-responding to other proteins in the environment.
24:52
Russ: So, we're going to get to this eventually. I just want to alert listeners to the fact that there are actually people--Moises is one of them--who deliberately introduce worms into their body to reduce their autoimmune disorders. With some success, we'll see whether it's real or not. We'll talk about that. But the metaphor that I like when thinking about this is the leaning against the wall. So, you are leaning against a wall and all of a sudden the wall disappears and you fall over. The problem with that is that it's a metaphor. So, the proof is in the science, not the story telling, which is what makes medicine and science potentially better than economics sometimes. So, let's take a couple of examples where people have gone in depth to look at some of these phenomena. Talk about Sardinia, the island of Sardinia off the coast of Italy. And what happened with malaria there. Guest: Sardinia had an epidemic of malaria for possibly millennia, for at least since the Carthaginians, perhaps before. They usually blame it on the arrival of the Carthaginians; it came from North Africa. So, that's over 2000 years of malaria. I think it's [?] 3000, actually. But, any case, it's a very isolated population. They haven't interbred with other people, and so their genome has been shaped by the constant just picking of malaria, the constant basically killing of the people who could not survive malaria. So malaria basically was eradicated in the 1940s, after WWII that is, in the space of just a few years. They went in with DDT (dichlorodiphenyltrichloroethane) and sprayed the whole island. They sprayed a lot of DDT, which is another story. But then people who had evolved, in theory, with malaria, suddenly no longer had it. Russ: Which sounds like a good thing. It's great. Guest: It is a good thing. Russ: You say they 'evolved to survive it.' But of course it still killed people, especially children, I assume, and older people. So the amazing thing about this, the thing that makes it so challenging to me, is it's extremely uncertain. It's not black and white. It's not a switch that goes on and off. So, they had evolved these genetic responses to malaria that were fabulous for most people. And now--well, we don't need them any more. Because now people are not going to die from malaria, not going to get sick, not going to be harmed by it. So that seems like a good thing. But what happened? Guest: Two autoimmune diseases started increasing dramatically: multiple sclerosis and Type 1 diabetes. It's now number 2 in the world for Type 1 diabetes, for the prevalence. Type 1 diabetes is when your immune system turns against your pancreas, which produces insulin for your body. And then multiple sclerosis is very high; it's abnormally high at that latitude. Multiple sclerosis tends to increase the higher the latitude, so like Canada, Stockholm have very high rates. Supposedly places like Italy are supposed to have intermediate rates. But the closer you look that sort of rules doesn't seem to apply. In any case, Sardinia is this hotbed of autoimmune disease. And so there is some thinking now, because it literally--there is like this Year 0 when they eradicate malaria. There is some thinking that the malaria does something similar to what the worms do--that is, a chronic malaria infection, not the acute phase; when you first get it, you can get very sick, but a chronic malaria infection suppresses your immune system. So if you evolved with this constant immune suppression, and then you suddenly remove it, it's going to reveal things to natural selection. Meaning that it's going to possibly create new diseases. But in this case the twist is that the very tendencies in the immune system that produce autoimmune disease in the absence of malaria may have actually helped manage the infection, may have actually helped fight off malaria when it's present. So this is a very important broader lesson. First of all, it tells us what immune disease is--what some of the genetic components of autoimmune disease, what they are good for. Autoimmune disease--the genes associated with it are very widespread in the population, in the human population that is. And when geneticists sort of look at how prevalent they are, it seems like they have actually become more prevalent in the past 15,000 years or so. Which suggests that they have some use. So, autoimmune disease is very costly. It's a huge cost to fitness, if we are looking at this from a point of view of natural selection. They should be ¬deselected for, those genes should be constantly removed from the population, not enriched. But what they see is that they are enriched. Suggesting two things: 1. They are good for something; and 2. Possibly, at least in my interpretation, they probably did not cause the same disease as they do now in the modern environment. And then we have the example of Sardinia, where basically in 60 years we have seen that--we don't know exactly what genes are in that case, but autoimmune disease that was before almost nonexistent, has gone up to some of the highest rates in the world, in the space of like 2 or 3 generations. And then there is this coincidence of timing with the eradication of malaria. Of course I should point out that with the eradication of malaria, it's sort of the arrival of modernity. And it's everything else that I talk about also happens when they eradicate malaria. So they lose their worms; they get better sanitation; their food becomes more sterile. Everything happens at once; it just happened very quickly there. Russ: So, and just to get a feel for the magnitudes: again, it's all complicated. It's not like every single person on the island all of a sudden has diabetes or multiple sclerosis. The rates for multiple sclerosis if I remember have about tripled what they are on the Italian mainland. Which is an enormous increase. But it's not everybody who gets it. Guest: No. That's right, yeah. It was, as I recall, about one in--I'd need to fact-check this but I think it was around 1 in 700 or something like that. Russ: I can't remember. But it's not just the timing, right? They understand something about what fights malaria and its prevalence in people. So, for example, on the island, people at higher altitudes on the island are less prone to malaria because the mosquitoes don't go up there as much. And they--people who have lived on those altitudes for presumably centuries or for at least a long time, they have less malaria-fighting, and they are less likely to get these diabetes and MS. Is that correct? Guest: Yeah. There is that association. So in some of the areas--so Sardinia is unusual compared to like Sicily or Corsica, which are these gigantic mountains that kind of come out of the ocean very dramatically. Sardinia is kind of flat and marshy. There are mountains; there are these areas where the mountains come up. But otherwise the hydrology is very unique, and it's very conducive to mosquitoes. So they were unusually prone to having malaria, once it arrived. In those areas where the malaria intensity seemed to be the greatest in past [impasse?], they see this sort of enrichment of some of the [?]--these are genes that also predispose to autoimmune disease, to put it simply. But it's very minor. What's interesting though, that example you made, is that up the mountain there is another trait that is also important in fighting malaria. It's called thalassemia. That's the disease it causes. It's a kind of congenital anemia; where it's this thing where you get two copies from each parent; then you get the anemia. But if you get just one copy then you are protected from cerebral malaria, which is the kind of malaria that kills you. So those genes do become less prevalent as you go up the mountain, and that was sort of the seminal bit of work that was done, actually, in Sardinia in the mid-20th century showing that disease had had this impact on the human genome in a way that was measurable. But there are likely many adaptations to malaria, because it is such a complicated pathogen and so wily in so many ways and so costly. It'll kill you. So it's a very strong selective force.
33:38
Russ: So, let's talk about the hookworm underground and how it got started. Tell us what it is, this phenomenon of people injecting themselves deliberately with various types of parasites and why did anyone start to think that was a good idea? Guest: Yes. Well, back up. So, in the 1990s, people started thinking about some of the parasite questions I've been talking about. Mostly because they understood the immunology. And they understood that parasites suppress the immune system. And they began--and they noticed also some populations that were parasitized, these diseases were far less prevalent. So they began to think: Well, how about we deliberately introduce parasites as a way to cure some of these diseases? It's an outrageous idea. But then a gastroenterologist named Joel Weinstock, who is now at Tufts U., developed a parasite, and medicalized it so it was in theory safe. The parasite is native to pigs. And the reason he chose this parasite is it cannot reproduce sexually in humans. So that you give it to the person and no one else gets it. That's the idea. The context, the historical context, is: we spent lots of money in this country getting rid of parasites. The last thing you want to do is reintroduce them to the population, right? Russ: And you talk about how, when people would suggest these transmission mechanisms for allergies and autoimmune problems, the outrage that many in the medical profession, in the fields of science had to the idea that there was something beneficial about this scourge that we had eliminated. Guest: Yeah! Russ: It's hard to--it's difficult to accept. It's emotionally unpleasant. But intellectually, it's deeply disturbing. It's like being told: Oh, we always were told to wash our hands, that that's good for you. And doctors really should wash their hands. But it turns out maybe, sometimes, dirty hands are good for you. That's horrifying. Guest: Right. Russ: As you say, it's outrageous. So, what happened with this pig worm? Guest: So, he developed it--this is actually in testing right now for FDA (Federal Drug Administration) approval; and I should point out that some of the results--the early results were amazing. They were so impressive. It was like 3 dozen people and a 75% remission rate for Crohn's Disease. It was unbelievable. And now it's in testing. And some of the results have been very lackluster, so far. So we don't really know if it works yet. But in any case, a bunch of underground people are reading this science. I mean, this is published in reputable journals. It makes sense to a certain kind of mindset that's kind of ecologically and holistically oriented. Russ: And if you have a chronic disease, you'd love to try something different, if whatever you've been trying isn't working reasonably. Right? Guest: Absolutely. I mean, I think actually at some point it's a rational--it's a very rational choice. Where everything else failed; or where maybe you see--you see problems in some of the available therapies, like the TNF (tumor necrosis factor) inhibitors, which can increase the risk of infection for some cancers and stuff. Usually those are much bigger in people's minds than they are in reality. But still, you perceive it as a gigantic threat. That is, you can take Remicade [?] or something, and then your risk of some of these other life-ending events goes up. Right? So you say, okay, well here's a parasite; and you read all the literature; and you say: Oh, the parasites have been with us forever; they are actually benign. And then you find out that there are some people who now sell them for deliberate infection in an underground way. Or you have to go to Mexico. And there's always amazing sort of remarkable stories of remission that you can find all over the Internet. And then you say, Okay, well, I'm going to try it, because what do I have to lose? And I think that's actually in some cases a rational decision. But I do also think that there is this tendency to ignore. First of all, the bad news isn't up there, because it's not being promoted by the people who are selling this stuff. That is, the cases that did not turn out so well. And also, all the caveats and [?] bad possibilities are totally ignored. Because there is this desperation that is driving people to do this. Russ: The other part that is I think--that comes out--you don't talk about it explicitly. But dosage is always going to be challenging. There is always an issue of how many, how much, which worm to take. So there is a lot of inevitable trial and error that is--some of that is going to fail and is going to have some really unpleasant side effects. Why don't you talk about your own experience and why you did what you did and how you went about it? Guest: Right. So, to connect the dots here, the pig whipworm stuff is sort of the inspiration. Then another fellow at the U. of Nottingham in the United Kingdom starts experimenting with hookworm because that's what he studied his whole life. And same observation--in Papua, New Guinea everyone has hookworm naturally; there's very little, a low rate, of all these diseases. You are studying them. And I should point out that also the animal studies universally suggest that--almost universally, I should say--that if you have a parasite infection not only does it prevent these diseases, it possibly can treat it. Right? So, you have a lot of evidence that says it's possible. Anyways, based on experimentally infecting people at the U. of Nottingham, in fact they start with themselves--there's a whole, about 7 scientists, who start infecting themselves just to see what happens. Which is interesting in its own right. And it's sort of based on that that this underground movement starts forming. You say, look, these scientists are willing to do it; it can't be that bad. And that was sort of [?]-- Russ: And they don't know anything about scientists, obviously. But yeah, I take the point. Scientists do a lot of things to get a breakthrough, right? To be associated with some incredible increase in knowledge. And they are willing to accept the downside. Which can be death. But, so go ahead, carry on. Guest: And so I sort of decided--well, so there are these underground operations that are selling this thing. And I've interviewed at this point probably over a dozen people who have had amazing success. Also some people who haven't had that great success. And I decide to go join them, both as a sort of Gonzo reporting expedition, number one. Number two to sort of test the idea of what having a parasite is really like. From one camp--the sort of, the traditional public health people are saying they are horrible, it's a scourge on humanity [?]; they make people starve; they make kids not go to school; they retard brain development. All those things I think are true. And then there's the other side.
40:12
Russ: So we are not saying, just for the record, for those listeners out there: This is not the advice section of the episode. We are telling an historical episode in Moises's life. Go ahead, Moises. Guest: And I do not recommend that people follow my lead at all. I recommend that people be very cautious about how they proceed with the amazing stories that they can find all over the Internet. Okay. But at any case, I decide to test this. And I'm also curious because I have food allergies and hay fever and this autoimmune disease. And I'm curious seeing what effect it's going to have. And of course I'm aware that other humans have done this voluntarily. Russ: You also have alopecia. Guest: Yeah. Russ: Explain what that is and why that's relevant. Guest: I believe I mentioned this earlier. It's an autoimmune disease where your immune system turns against your hair follicles. And I've had it since age 11. It starts as a few bald patches on the head, at least did for me. And then those bald patches multiply and expand. And for me they left me mostly hairless for most of my life. I didn't expect that to go away. What I really thought, though, judging for some of these studies on animals and humans, is that maybe I'd lose my food allergies. That was really exciting to me. Actually the thing that bothers me the most out of everything that I have is my peanut allergy and my sesame allergy, in the sense that, you don't know always what's in your food, and sometimes you get some of this stuff. And then you have to go--for me, I go eject, forcefully. In any case, so I go down to Tijuana. And you actually don't inject yourself with these parasites. What happens is the larva, which are microscopic--you cannot see them--they go through your skin. And they have this kind of amazing journey through your body. They end up in your small intestine a few weeks later. Russ: I think it's worse that you don't inject them, actually. You put them basically over your skin and you feel them going in, right? Guest: Yeah, well, they eject some sort of various enzymes that essentially digest your skin so they can wiggle through it. Russ: Lovely. Guest: You know, if you look at these things dispassionately, they are really marvels of evolution. I mean, how did they come up with this life cycle? How did they end up in the right place? Russ: They don't have GPS (global positioning system). It's a great point. We just take it for granted that they wander in and they end up in your intestine. But that's extraordinary. Guest: Yeah, it is. And one of the dangers of parasites generally, and one of the critiques of Joel Weinstock's pig whipworms, is that parasites are native [?] are usually very specific to their hosts. So that the hookworm is native to humans, that hookworm is native to humans--it can do this amazing voyage through the body without ending up in the wrong place. But oftentimes when animals end up with parasites that are not native to them, it can kill them. Because then they can end up migrating to the wrong place. To the brain, to the central nervous system, to the liver--and they cause horrific disease. Whereas if they were in their native host, they would cause very minor, or actually, I'd say, relatively minor symptoms. Right? Russ: And turning out badly is both for the host and the parasite. The parasite does not want to kill you. That's bad for the parasite, if it has no host. Guest: Exactly. This is not like, let's say, the plague, or let's say like smallpox, where it multiplies exponentially in a very short period of time with the idea of jumping to another host, leaving you as a sort of used-up husk. What the strategy of these parasites is, is to live for a year. [?]-- Russ: They just want a taste. They don't want the whole meal. They are at your table. They are like, Can I have another bite? Can I try that? Guest: Right. With hookworms they are actually eating you. Which I can tell you, you can actually feel, in the sense that you feel this kind of ache. But okay, so there were these very interesting, well, not-so-interesting side-effects, that are sort of what you expect. There are these things that are kind of latching themselves on to your small intestine, which is a little ache and some, you know, effluence. That stuff sort of faded with time. It never entirely--the ache anyways. But what was remarkable was that my hay fever went away entirely for about half of hay fever season. My eczema went away. My hair did not grow back. My food allergies did not go away. And so I saw some sort of tweaking of the immune system. But for me it did not--the costs did not outweigh the benefits. For me, actually, the whole experiment worked more as a way of sort of showing that everyone who is talking about parasites, from both the pro and the con side, they are both right. Yes, it's true that parasites manipulate the immune system. I can feel it, or that is, I can observe it. In a sample size of 1. But it's supported by all these animal studies. And yes, it's also true that they have a cost. And you can feel that as well. Now, any people that didn't have any symptoms--and there's some evidence from experimental, from Australian scientists who were experimenting with hookworm trying to treat celiac disease, interestingly. But they in fact themselves--and it seems like the harder your immune system pushes back, the fewer worms you end up with but also the more it kind of hurts you. So really what's hurting you is your own immune response. Which ties back in to what I was talking about earlier, about your immune response and what hurts. So, maybe I was someone who had a very overwhelming immune response. I don't recommend it. It was interesting. I've interviewed plenty of people for whom it sort of made the difference between progressing, let's say multiple sclerosis or other terrible autoimmune diseases and sort of just bringing those things, grounding them to a halt. So it's possibly beneficial. That's in the works, being tested, in a scientifically rigorous way. Which is what we need. I think ideally what is going to happen is that scientists will either, 1. they will isolate the molecules these parasites use to subvert your immune system and just create drugs out of those, or 2. They will breed a kind of benign parasite that has no cost and all benefit. And the best example is kind of like: the Chihuahua is descended from the gray wolf. They are very closely related genetically, but they look very different; they act very differently around you. And the idea would be to breed a parasite that is to its ancestors that is what the Chihuahua is to the gray wolf. Which is all cuddly cuteness and goodness and none of the savagery and ferocity of an actual wild thing. Russ: I was told that if you need a heart valve replaced, you can either get one from a pig, which is evidently somewhat like ours, or you can get a plastic one. What we need is--the pig ones tend to work better. They don't last as long, but they work better, evidently. So what we need is the plastic worm that works better, that's more like the real worm but it's emotionally easier to deal with as well.
47:27
Russ: Before we leave this topic, though, tell the story of what happened in Buenos Aires when their economy collapsed. Because, again, if you are a highly skeptical person--which I often am on this program, although occasionally I get sucked in by books like this and I want to believe every page. I just want to confess to that to the listeners. Because when you get a paradigm shift like this, it's like: Okay, now I know the truth. And you have to always fight your impulse--and as a journalist I know you do, too--to say, Now I've found the truth; it's all here. And again I want to emphasize that in the book, Moises is very careful about the claims he makes and what we know and how limited it is and the complexity of this problem. Which again reminds me a great deal about economics. But I love the Buenos Aires story as a great confirmation bias case for me. Susceptible to it. Talk about what happened. Guest: So, the economy was in turmoil. Basically this was in the early 2000s. There was some sanitary backsliding--people stopped picking up trash, the sewer maybe stopped working. And what happened is, there was a neurology clinic there that served some of the poor neighborhoods, the people from poor neighborhoods. Lots of multiple sclerosis patients. And multiple sclerosis, for the listeners, is basically when your immune system attacks the fatty coating of your neurons and it sort of causes this creeping paralysis. And the coating is called myelin. So it's an autoimmune disease where you are attacking some aspect of your central nervous system. Some of those patients started showing up with parasite infections because of this sanitary backsliding that was occurring in this broader context of economic turmoil. And so these neurologist, Jorge Correale, he knew about Joel Weinstock's book; he knew also about this sort of revisionist thinking on parasites, that there was this evolutionary component, that maybe they'd always been there applying pressure to our immune system, and that they could strengthen your immune system's ability to not overreact. And so he gave his patients a choice. He said: look, we can keep the worms--that is, I can deworm you or you can keep the worms and we'll see what happens. So, some of his patients decided to keep the worms. I think it was about 14. Russ: Yeah, I think you said a dozen. Guest: Yeah. Something around there. It's been a while. Russ: Still a small sample, but bigger than 1. Guest: Yes, very small sample. Again, the reason that some of this stuff is even considered in humans of course is that it's first shown in animals. Animals are obviously far more conclusive. Again, though, rodents are not people, as we well know. And often what happens is that what seems to work in animals does not work in people. But at that point I think there were a number of rodent studies [?] that showed that parasites could have this magical effect to stop a number of autoimmune diseases. And in that case they just used an extract of one of the parasite eggs for the multiple sclerosis animal [?] animals. In any case, what happens essentially is that the multiple sclerosis, which is this kind of advancing disease, comes to an almost complete halt. It doesn't completely stop, but it almost completely stops. And this is viewable by objective measures, by magnetic resonance imaging (MRI). He also does blood work. And then he monitors them for about 5 years. And then some of the patients are sick of having parasites; they are sick of the side effects. And so he deworms some of the patients. Russ: At their request. Guest: At their request. The whole time he's been taking blood samples, measuring the [?], which are immune system transmitters, immune system molecules that give you a gauge if you are in an inflamed state, if you are not in an inflamed state. In any case, what he sees is that the whole balance of the immune system shifts from pre-deworming to post-deworming, where those molecules that indicate strong anti-inflammatory capacity decline dramatically, immediately after you deworm. And then the disease started right back up again for those patients he dewormed. Now, again, this is not an experiment. This is something that occurred naturally. It's observational. What's nice about it is that it's prospective [?] the least, supported by animal studies. And what's happening now is that they are actually testing 'worm therapy', as it's come to be known, on people with multiple sclerosis, both using the pig whipworm in the United States and using hookworm at the U. of Nottingham. So we'll know if it really works soon enough. Actually, the preliminary stuff shows that it works on like four cases, by a neurologist named John Fleming at the U. of Wisconsin, Medicine. That was sort of a--you just test it to see if there are any side effects or negative serious consequences. Russ: What do you mean, 'four cases'? Guest: MS patients. Russ: Four people who have been so far under this FDA (Food and Drug Administration) protocol. Guest: Yeah. Russ: It's important to mention, by the way, that while the worms have side effects, for most people anyway, the current state of treatment for most of these autoimmune disorders also have side effects; or there is no treatment. Guest: That's absolutely right. These are very, very difficult diseases to treat. Number 1, the people who created the drugs that are available, would probably argue that they are your best bet. But a lot of people just don't respond to the available drugs. A lot of them work on the--not the ones for MS but the other inflammatory diseases--they basically block some aspect of your ability to be inflamed. So, TNF alpha, tumor necrosis factor alpha, is this thing that helps you mount a very strong attack against pathogens. It also is activated inappropriately in autoimmune disease. So they essentially block that. But then that increases the risk of some infections, because you have basically hobbled an aspect of your immune system. Now, I should also point out that parasite infection also increases the risk of other infections, because it does the same thing by different mechanisms. It's suppressing some aspect of your immune system. But as far as anyone knows, it doesn't increase the risk of some of the cancers that the tumor necrosis factor alpha, some of those. So your immune system is also important for catching cancers before they grow and spread. So, if you hobble some aspect of your immune system you may increase the risk of some cancers. And it's a very, very tiny increased risk, but it is there. It exists for these current drugs. I think what's most important is that people who have these diseases perceive the risk to be very terrifying and very great. Whether it is or whether it isn't. They say, I have this disease and here I'm going to take this drug that increases the risk of two other problems, that are life-ending problems. That are not small problems. The absolute risk of that happening to them is very small but it looms very large in their imagination. Russ: Rightfully so. Go ahead. Sorry. Guest: Well, it just--excuse the calculus where--parasites you can get rid of, if [?] for you. In theory you can just take a deworming drug. You take a one-day, two-day course and you get rid of them in a second. And you get rid of them, again. But in terms of the cost-benefit analysis, I feel like people who are facing these diseases--in a way they are making the most rational decision. You are an economist--rationality depends on what the other factors are, right? Russ: It's all about tradeoffs. And one of the lessons of this book, which is really extraordinary, is there's no free lunch. I don't think--I'm pretty sure that phrase doesn't appear in the book, but that's really one of the lessons of the book. Everything comes with a side effect; everything comes with a cost. And this incredible health success to taking the macro--we're talking about the micro, to make a decision about how to treat a disorder, but at the macro level when we think about public health, a lot of the triumphs of the 20th century, which we correctly celebrate, came with unintended consequences, it appears. And that just fascinates me.
56:08
Russ: I want to get back to my dad. And we'll get to my mom, too. So, my dad--he makes fun of me and my siblings because we care about hygiene and keeping our hands clean when we cook. And he'll--just to get us going. He'll walk into a restaurant and he'll eat food off of somebody's plate that's left; he'll walk by a piece of something--and he knows it drives us nuts. He wants to just get at us. But he was on to something, it turns out, perhaps. But my mom--here's what's interesting. I was born in Memphis, Tennessee, in 1954. My mom was born in Memphis, TN in 1932. So, 1932, it's possible that the worm environment of Memphis was not entirely cleaned up, being in the South, and it is a city. It would have been better if I'd been born in Tupelo, Mississippi. But I wasn't. So I was born in Memphis. I'm not allergic to many things. And it raises the possibility, among thousands of other factors, but what your book reminds us of is that you mom and your grandmother and your father, but particularly your mom--they don't just pass on their genes. We all understand that there are certain genetic advantages and disadvantages people have for health, that a lot of these things that we're obsessed with we're stuck with. We want to fix them with exercise or diet, but genetics goes a long way toward explaining a lot of things like our likelihood of a heart attack or cancer, etc. But what your book points out is that it's so much more complicated than that, because your whole microbial environment that you are born in and born with, emerge from the womb with, depends a lot on your mom. And your grandmother. And that adds the complication level--it's a whole new level of complication. It's fascinating. Guest: The thing about the worms, I should point out, is that there are many organisms that apparently beneficially tweak our immune system. Parasites are just one. Parasites clearly have a cost; maybe they have a benefit. But the promise of the research on the microbiota is that there are organisms that are all beneficial. And that have no costs. And that those can be leveraged to fix some of these problems. So growing up in Memphis; there may have been worms; there may not have been worms; there may just have been access to a healthier microbiota. And then there are also certain microbes in particular, like helicobacter pylori, which again have this sort of good side and bad side. But most people who have helicobacter pylori, which is associated with stomach cancer, actually harbor it just fine. And it also seems to prevent some of these diseases from emerging, at least from epidemiological and[?] animal studies. So, to go back to this question of what happens to mom: here, my book, what I'm talking about, converges with this really rapidly developing and supremely important field of epigenetics, where basically the signals that come from your mother for the 9 months that you spend in the womb are signals that shape how you develop. So that many of the predispositions to diseases decades later seem to be set by the environment of your mom while she is pregnant and what's happening to your mom. There are some sort of great historical examples where, for example, in WWII in the Netherlands there was a famine that struck; there was a Nazi blockade. And the mothers who were pregnant then, they were able to track the children who were born to those mothers, and decades later they had increased risk to basically the suite of Western diseases--which are heart disease, some cancers, diabetes. Decades later. They were able to correlate this with this event. And other events of famine, in China and elsewhere. And of course they can do it with animals as well. So they are able to show causation. And what happens--there are two things that happen. One thing is that the signals that are coming actually guide things like brain development, the signals that are coming from your mom. Since we are talking about the immune system--they in a sense are training the immune system, giving a sense of what to expect. They are saying: you need to turn this up a little bit, turn this down a little bit, because x, y, and z has apparently got Mom on guard so you need to be ready as well. So you can look at it as something that is supposed to be adaptive. The problem is it can be pushed out of an adaptive realm. With infections, for example. Infections, prenatal infections are a risk factor for many, many different problems, from schizophrenia decades later in the offspring, in the child, for autism increasingly seems. And also for asthma, very interestingly. These apparently different diseases that manifest in different periods of life all share this common risk factor of Mom's immune system being activated to fight off a disease, to fight an infection. Russ: That Dutch hunger winter that you talk about--the idea there would be that because these moms were pregnant during a time when food was very scarce, the kids over-processed their food as they became adults and were more prone to obesity and metabolic syndrome. That's the claim, right? Guest: That's right. So, epigenetics--genes are fixed, but how you translate the genes into proteins and hormones is obviously not fixed. You can turn it up or turn it down. That's what gets tweaked by Mom's experience. So they are essentially prepared in utero, in the womb, for a starvation situation. And what they come into, at least in Western Europe after the War is over is not a starvation situation. So the thinking is it's a kind of mismatch of what they are prepared for, epigenetically, and what they encounter in a basically affluent country in the West. Even though that wasn't immediately true after WWII; but eventually it was. And our very different things. So they are epigenetically maladapted to the environment that they encounter.
1:02:45
Russ: Let's step back a bit from this particular example. One of the things the book does, unintentionally I think, is the world is in some ways a more alarming place than you thought. It's one thing when you see these pictures of what, say, your cell phone looks like or your bathroom, when you look at it under a microscope. We are aware that there are these things under the surface that we can't see that make life sometimes not so good. And here we are saying, some things we were afraid of we couldn't see, some of them made life pretty good. What are the lessons f