This is a transcript of the Gastropod episode Why Does Everyone Have Food Allergies These Days?, first released on June 25, 2024. It is provided as a courtesy and may contain errors.

BROADCASTER: A new report out shows that the rate of severe allergic reactions to foods, just like peanuts, has increased by nearly five times over just the past decade.

REPORTER: This government survey put out by the Centers for Disease Control and Prevention says that 1 in 20 U. S. kids have food allergies.

REPORTER 2: Nearly six million children in the U. S. now suffer from food allergies. That’s equal to two students in every classroom.

NICOLA TWILLEY: Some of the questions we get most often from you listeners are about food allergies—about the science, about the history, about treatments and tests? Lots of you have personal experience with this.

LOUISA GIFFARD: Hi Gastropod. My name’s Louisa and I’m allergic to tree nuts. That means every nut except peanuts, which are actually legumes, and coconut, which is not a nut at all. For some reason, pine nuts are okay as well.

NICOLE DEPOLO: Hi there, my name’s Nicole. I am a resident physician surgeon working in California and I am allergic to fish. Specifically, all fish that have bones. So, swordfish, salmon, tuna, mahi-mahi. Any of those, I am allergic to all of them.

SAHAR MODARES: Hi, my name is Sahar Modares. I reside in Gilbert, Arizona, in the U. S., and I’m a mom of three, an entrepreneur, and an absolutely big food geek. We have various allergies in our family, but the weirdest one I’d like to share is that of my five year old. She came out with allergies to nuts. She’s not allergic to all nuts, though. She can have hazelnuts, almonds, cooked walnuts, but not raw ones.

CYNTHIA GRABER: That is a little strange, but when you stop and think about it, the very idea of allergies at all is weird. Some normal thing that most people have no reaction to—suddenly that makes you sick? And it’s even weirder if you think about it in terms of food, like the things that are essential for us to live, some of them might actually kill some of us. And lots of you have questions about that.

TWILLEY: Many of those questions basically boil down to a couple of main ones.

MICHAEL DRUKER: Hi, I’m Michael from Ontario and I would love for Gastropod to look into why food allergies are a thing.

DEPOLO: The other question I have is, are allergies worse nowadays, or are we just better at diagnosing them?

TWILLEY: This episode, we’re diving deep: what are food allergies? What causes them, what if anything can prevent them? How are they different from sensitivities and intolerances? And if we have them, what can we do about them? This. of course. is Gastropod, the podcast that looks at food through the lens of science and history. I’m Nicola Twilley.

GRABER: And I’m Cynthia Graber, and this episode, we’ve got the answers to your questions. Or at least, the best answers science can provide.

TWILLEY: This episode is made possible in part by the Burroughs Wellcome Fund, in support of our coverage of biomedical research, and by the Alfred P. Sloan Foundation for the Public Understanding of Science, Technology and Economics. Gastropod is part of the Vox Media Podcast Network, in partnership with Eater.

[MUSIC]

THERESA MACPHAIL: Unfortunately, my father is my introduction to the world of allergies. So in 1996, he was driving in his car on a late summer day with the window open. And he stopped at a stop sign and a bee on its normal pollen gathering trajectory flew into his open window and stung him in the neck.

GRABER: Theresa MacPhail is a professor of medical anthropology and author of Allergic: Our Irritated Bodies in a Changing World. And as it turns out, her father was allergic to bee venom—he already knew that, but he didn’t know how serious his allergy was.

MACPHAIL: And he went into an anaphylactic response. Which is very rare with bee venom, but very frequent with things like food allergy. And so, he was dead on arrival by the time he got to the hospital 45 minutes later. So he passed away within 30 minutes of the initial sting. So I got a crash course in what can happen to our immune systems when it comes across something that it deems a threat.

TWILLEY: This happened when Theresa was just 24, and it was of course a tragedy. But it didn’t immediately set her off on a quest to understand allergies.

MACPHAIL: It was just an unfortunate series of events and I pretty much forgot it. Until I was diagnosed with hidden allergies myself.

GRABER: By that point, she was an academic and a writer and someone who asked all sorts of questions about medicine, so she was curious about her own diagnosis. And also, each time she mentioned to friends that she had just discovered she had allergies, they wanted to tell her about their own.

MACPHAIL: And it just opened up this whole world. And suddenly I wanted to know everything there was to know about this condition that so many of us have. And so many of us, kind of, don’t talk about or keep hidden.

TWILLEY: So Theresa began her quest to understand allergies at the beginning: with the immune system. Like she said, allergies are a response that can happen when your immune system is confronted with something that it perceives as a threat. So let’s take a look at this system and figure out how it determines whether any given food is friend or foe?

MACPHAIL: So typically speaking, your immune system, you might have heard the metaphor that it’s like a police officer. Like your, your white blood cells are police officers or immigration officers, I guess, is a better way of thinking about it. They’re patrolling your body, looking for things that aren’t supposed to be there and ejecting them or consuming them when they spot them.

GRABER: One type of white blood cell is a T cell, in particular a type of T cell called a T helper cell whose entire job is to circulate around your body, on the patrol to recognize bad stuff and call over other cells to get rid of it.

TWILLEY: And when that T helper cell has decided that whatever it’s seeing is actually a deadly foe, no matter what it is, it kicks things off in your immune system.

MACPHAIL: And with allergies, what is happening is your T cells, a specific type of T cell called the T helper cell type 2 will see something like… an oak tree pollen. And it decides that it shouldn’t be here. It doesn’t like the looks of it. So it will take like a snapshot of it.

GRABER: Now first of all, the T helper cell overreacted, because oak pollen shouldn’t be something it needs to get rid of. But in any case, what happens next is that the snapshot of the protein triggers a whole sequence of events with a few different types of cells, and at the end of that, what happens is another kind of cell produces antibodies. Antibodies are disease-fighting proteins in your blood that bind to things like bacteria and viruses and neutralize them.

MACPHAIL: We have five different classes of antibodies in our bloodstream at any time, but IgE is the one that’s responsible for most allergies. So IgE, think of it as the bouncer at the door to different parts of your body.

TWILLEY: Or really, bouncers plural. These IgE antibodies are the twitchiest of all our antibodies, and they are now circulating all around your blood vessels, scanning the crowd for the oak pollen that the T cells warned them about.

MACPHAIL: The trouble is, is that the T cell has done its best, but IgE just has a general description. So, you’ve basically been given a snapshot that’s like, you’re looking for a guy who’s six foot two with blue eyes. Well, a lot of people look like that. So that’s why people can be allergic to multiple things in the same family. So, if you’re allergic to one tree nut, you might be allergic to more because they have genetic similarities in their protein structure.

TWILLEY: One six foot two guy with blue eyes is much the same as any other six foot two guy with blue eyes—just ask Hollywood. Easy mistake for IgE, or really anybody to make.

GRABER: So when an IgE antibody finds something that roughly matches that snapshot, it hooks up with another type of cell called a mast cell. Mast cells release all sorts of chemicals that can help with things like wound healing and defense against pathogens. And in this particular case, when the IgE antibody links up with a mast cell, the mast cell releases histamine.

MACPHAIL: And you have heard of histamine because you take antihistamines. [LAUGH] So histamine does several things in your body. It produces mucus, which is why you get stuffy. It causes itch, which is why you get itchy eyes and itchy skin. In asthmatic patients, it constricts the muscles around your lungs, so histamine is why you can’t breathe if you’re having an asthmatic attack. It’s a great mechanism. Unless it’s not.

TWILLEY: What Theresa means is these histamine-prompted responses, all the inflammation and mucus production and even diarrhea—they’re all actually super useful for tackling genuinely bad bacteria and viruses. Diarrhea and mucus, no need to picture this, but they are there to push things out of your body faster. The airways constricting—that stops bad things from getting deeper into your lungs.

GRABER: The swelling is because your blood vessels are expanding and also becoming more porous so that all the useful defensive and healing cells in your blood can get to the scene of the crime more quickly. The itching sensation seems to be a side effect of the histamines trying to get rid of something bothering your skin. Of course none of this is particularly comfortable when you have a rash or diarrhea because of something you ate.

TWILLEY: And if those mast cells release too much histamine, as is the case during anaphylaxis, that’s when things get really bad. Because it becomes kind of like a nuclear chain reaction. Your blood vessels expand so much to give those white blood cells access to their supposed enemies that your blood pressure drops, your heart speeds up to make up for that drop, and if you’re really unlucky, you can then have a heart attack.

GRABER: Another way an overactive histamine cascade can kill you is that it can just constrict all of your airways so intensely that not enough oxygen gets into your blood, and then your brain is starved of oxygen, and you die.

TWILLEY: But having a heart attack or suffocating seems like a bad idea in general. So why on earth would our immune systems be able to trigger a response that drastic?

MACPHAIL: Because it does seem rather strange that we would inherit this mechanism that could take us out of the gene pool.

GRABER: To understand this, we have to go back to these IgE antibodies. Remember, we have five kinds of antibodies, but most of the time, IgE is the antibody that triggers allergies. So why would we have an antibody that makes such quick snap judgments that it’s often wrong about what’s an ally and what’s an enemy?

MACPHAIL: They think that it has something to do with the environment that we evolved in, which would have been replete with a lot of venomous things. So insects and reptiles primarily.

TWILLEY: Based on some studies with snakes from Israel and sacrificial mice, what scientists believe is that the same twitchy IgE that can give us allergies, and can even lead to anaphylaxis—that was really useful to target and destroy fast-acting snake venom. The kind of venom that would have been more common in our early history as a species.

GRABER: Having a super-reactive immune system would have been useful for quickly identifying, targeting, and neutralizing that super fast-acting kind of venom. And if for some reason it occasionally overreacted and kicked off a histamine chain reaction that led to anaphylaxis? Well, it wouldn’t necessarily have been deadly if you were lying down.

TWILLEY: Theresa told us that the problem typically comes when you’re sitting or standing—that’s when that sudden drop in blood pressure and those constricted airways are more likely to be deadly. But our point is that these mouse and snake studies—they are the evidence researchers use to explain why an immune system that can malfunction and give us allergies and even anaphylaxis actually makes some evolutionary sense. Having a system that can misfire and kill you seems like it would be weeded out by evolution, but it hasn’t been, and we think that’s part of why.

GRABER: One other thing scientists think IgE would have been good for in the past: it seems to bind particularly well to parasites like intestinal worms to try to kill them. So there’s logic to our immune system in general.

MACPHAIL: But an allergy is your white blood cells looking at something and responding to it in the exact same way they would a virus or a bacteria or a parasite.

TWILLEY: It’s doing the right thing at the wrong time, which sadly makes it totally the wrong thing. But also, understanding that allergy is this misguided immune response—it helps explain what is *not* allergy.

MACPHAIL: So if you’re having symptoms that are caused by something other than your immune cells, you have something else. So you have a sensitivity, or you have an intolerance, like say you have a lactose intolerance, you’re not producing the enzyme that breaks down lactose.

GRABER: If you have a sensitivity or an intolerance, you might have symptoms that are the same as symptoms from an allergy—nausea, or diarrhea—but if that response at its base is not triggered by your immune system, it’s not an allergy. I’m lactose intolerant, I am NOT allergic to milk.

TWILLEY: Similar response, quite different mechanisms behind it. In Cynthia’s case, the nausea she feels after eating dairy is nothing to do with her immune system, it’s that she’s lacking an enzyme that can break down a sugar in milk. There are a whole range of biological mechanisms that can cause uncomfortable reactions to food, but like we say, if they’re not caused by your immune system, they’re not an allergy.

GRABER: But when it comes to trying to figure out how long we’ve been experiencing allergies and how common they are, all of these overlapping symptoms makes it really hard to tell.

MACPHAIL: Anaphylaxis looks the same no matter what the trigger is. It looks like cardiac arrest. It looks like something else. So you’re, you’re having someone who can’t breathe, and whose heart rate is rapidly increasing. And with food allergy, here’s the problem: It happens 30 minutes later. So you have to be looking for that trigger. And if you’re confusing it with something else, it’s possible that people were having reactions and just dying. And the cause of death would have been listed as paroxysm or something.

GRABER: But there are some clues that people have been experiencing allergies to non-food things for thousands of years. There are ancient records of what today we know is anaphylaxis in the Middle East. Like, of an Egyptian pharaoh getting stung by a wasp, having what we would now call an allergic reaction, and dying.

MACPHAIL: So we have some cases, usually insect stings or venomous snake bites. So you will get descriptions of something that looks like anaphylaxis. So we know that the mechanism has been there since we’ve been there.

TWILLEY: But it wasn’t called allergy back then. That word and even the concept behind it didn’t really exist until much more recently.

MACPHAIL: So it starts with the Industrial Revolution in the 1800s and a lot more people showing up in the clinic with these colds that just won’t go away, asthma.

GRABER: This is what we’d now call hay fever, it’s an allergic reaction that affects the nose and lungs and throat. President Calvin Coolidge called it “rose fever” because it happened when the roses were in bloom. But nobody gave this type of response a scientific name or tried to explain what was actually happening in the body until a guy named Clemens von Perquet came onto the scene in the late 1800s.

MACPHAIL: So, Von Perquet is a German or Austrian clinician working at a kinder clinic, so a children’s hospital, in Vienna. And they are giving vaccines to these children. And he notices that some children, upon getting their second dosage of vaccine, are developing rashes, they’re getting fevers, they seem to be suffering from the second injection. And at first no one thinks he’s on to anything.

TWILLEY: At this point, vaccines were a pretty new thing—in fact the entire immune system was a relatively new discovery in science. The first partial descriptions of how that whole white blood cell-triggered response works were only being published in the 1880s. And the reason everyone ignored Von Perquet’s concerns was because back then, people thought the only thing the immune system could do was protect us.

MACPHAIL: They don’t even think it’s possible that the immune system can do any harm.

GRABER: But Von Perquet was seeing a reaction, and he started to think that the immune system was attacking at the site of the vaccines.

MACPHAIL: And he started to think, what if it can hurt us? So what if there’s a dark side of immunity?

GRABER: He called this response that he was seeing allergy, by combining two Greek words that meant “other” and “work,” because he was seeing the immune system do the good things it was supposed to do, the things that are its job—but then also, in some of the kids, go haywire and do its work but in a way that caused harm.

TWILLEY: Weirdly, the term anaphylaxis had already been coined at this point, in a long and winding story that involves the Prince of Monaco, massive jellyfish, and a dead dog, which you’ll just have to read Theresa’s book to get the full details. But anaphylaxis means “backwards defense.”

MACPHAIL: So it’s your immune system responding so strongly to something in an effort to protect you that it accidentally kills you. And they didn’t think it was possible for that to happen in humans.

TWILLEY: First because people weren’t even sure allergies in general were a thing—remember they thought the immune system could do no harm—but also because the original research involved a dog, not a human.

MACPHAIL: Until we finally have a case on record of someone being given egg, a child being given egg, and the same process happening to the child. And then, so it’s not until the 1920s that we realize this, this thing can happen in humans.

GRABER: Theresa says this egg story is one of the early clear examples of a food allergy. It’s likely that people had allergic reactions to food throughout history, but it would have been really hard to identify.

MACPHAIL: It wouldn’t have been clocked that, oh, perhaps the milk that this person drank a half an hour ago is what led to this reaction.

GRABER: But gradually, by the 1920s, all of these discoveries and new understandings came together and scientists finally realized that yes: our immune systems could actually turn against us.

TWILLEY: So, long story short, allergies, including super severe ones, have always been around, and for at least a century we’ve known something about the biology of what’s happening when we have an allergic reaction. But here’s my question: why? What is it that triggers the white blood cells to get tough on an otherwise perfectly harmless substance? And is that immune reaction happening to more people more often these days?

GRABER: We’ve got those answers after this word from our sponsors.

[BREAK]

GRABER: When people first started to name what they called hay fever in the early 1800s, they were trying to figure out what was going on, why people were suffering, but they had no idea.

MACPHAIL: They really don’t understand the mechanisms at all. The theories are, it could be related to heat. Because they thought no one got allergies in India. [LAUGH] They were wrong, but that was a possibility, that perhaps it had something to do with heat or not heat. Perhaps it had something to do with the ozone in the air, so they tested ozone. Perhaps it was dust or pollution or soot in the air.

TWILLEY: But honestly the main response to this mysterious new ailment, this hay fever, was to shoot the messenger. When in doubt, blame the patient.

MACPHAIL: In the beginning, who’s showing up in 1820 to the doctor complaining of a cold that won’t go away? Well, it’s people who don’t have anything else wrong with them. So it’s primarily people who are white, worried, and well. Otherwise, well. And so, you get this idea that someone with a nervous temperament or someone who was quote unquote “on the weak side.” I would be remiss if I didn’t point out that the majority of people showing up were either, you know, these, elite, wealthy, highly educated men, but primarily we’re talking about women. And so you’re getting these women showing up in the clinic with these symptoms that are otherwise unexplained, and you’re getting the male physician saying, well, she’s just neurotic. This is a nervous system disorder. Get yourself under control.

GRABER: As time went on, the immune system became better understood, but then another new aspect of our biology was discovered, and that was our genes. And so doctors took detailed family histories to try to understand how allergies might be passed down through the generations.

TWILLEY: But genes were not the simple answer patients and their doctors were looking for at all. Scientists did find some genetic markers that seem to predispose people who have them to developing allergie.

MACPHAIL: So we know there are about 141 gene segments related to allergic disease.

TWILLEY: Obviously 141 gene segments is a lot, with a lot of different effects, and scientists haven’t yet managed to tease out what all of them do, and how that might be related to allergy.

MACPHAIL: Some of the issues are that we know that people who have allergy, some of them have more mast cells. So, they simply have more white blood cells lining their skin and digestive tract and nose than the rest of us. So their B cells are pumping out more IgE than other people. So if you have more IgE, you’re going to have a stronger reaction to something.

TWILLEY: Which is actually an asset in some situations—people who have these super robust immune systems, yes they are more likely to have allergies, but also, they’re less likely to get certain cancers.

GRABER: But the exact genetic link to allergies is still an open question. In a twin study that scientists conducted a couple of decades ago, identical twins with the same DNA shared a peanut allergy about two-thirds of the time, but fraternal twins who have different DNA were slightly *more* likely to share an allergy. Which is not what you’d expect if it’s entirely due to a genetic link.

MACPHAIL: So, we know some biological mechanisms that people are prone to that lead to allergies. But, I’m sure there are more out there. We don’t know how those 141 genes interact with other genes, for instance. We don’t know the magic combinations.

TWILLEY: What we do know is that allergies really are on the rise.

MACPHAIL: Absolutely. We know that allergies have been increasing for around the last 50 to 70 years.

TWILLEY: Yay, finally some certainty! Even if it’s not exactly great news.

GRABER: Not to make this more complicated, but in theory what looks like an increase could actually be because we’re testing for allergies more frequently today. Theresa says that there’s been a real increase in testing since she was a kid in the 70s, and so scientists do attribute some of the increase in allergies to increased public awareness.

MACPHAIL: But the way that we know that, over time, historically, this has changed is you can look at data like ER data. So who is coming into the hospital for anaphylactic events? And so you can see a clear increase in the 1980s and 1990s for things like that.

GRABER: Theresa told us it’s not easy to come up with absolute numbers of how many people experience allergies, but some organizations estimate that about 30 percent of American adults have some kind of allergy.

TWILLEY: And this modern increase is not just limited to Americans, or even to the younger generation. The World Health Organization estimates that about 10 percent of people all over the world have a food allergy, and they’re increasingly likely to be adults.

NESTLE HEALTH SCIENCE CHIEF: Two hundred and forty million people suffer from food allergies, and these numbers keep increasing.

REPORTER: A new study finding severe allergic reactions to food have skyrocketed more than 300 percent over the last 10 years. Half of adults with food allergies develop them after age 18.

TWILLEY: This rapid spread of allergies qualifies as an epidemic. So what’s causing it?

GRABER: One of the theories scientists have to explain our increase in allergies is something you might have heard of, it’s called the hygiene hypothesis. The theory is that, in our modern lives, everything is cleaner. Our water is cleaner, for one. And also, we’ve become obsessed with cleaning absolutely everything around us, and so we’re not exposed to as many different types of bacteria and parasites that are important to train our immune systems.

TWILLEY: Theresa says there is evidence that kids who grow up in environments that are maybe a little more like the ones our ancestors lived in, albeit usually with modern plumbing—those kids can develop fewer allergies.

MACPHAIL: There’s really good data that if a child under the age of three grows up at a farm—and the key here is a farm with livestock—and goes in and out of that livestock barn, the chances that they will develop any allergic disease go so low. That’s so protective for them. And we’re not sure why. Something about farmhouse dust. What’s in that dust? Well, probably bacteria from the animals, pet dander, like dander from the animal skin. So something about that is also helpful to our immune cells in those early stages of learning to tolerate more and more things. So we know that the hygiene hypothesis is partially correct, but can’t be fully correct. Because farmers still get asthma, farmers still get food allergies. So it can’t possibly be just as simple as you know, if you’re having a kid you move to— [LAUGH] you move to a farm for three years and bing, bam, boom, you don’t have any allergies.

GRABER: Another theory isn’t about food but it is about how our environment can have an impact on the increase in allergies: it involves air pollution. Diesel exhaust particles are tiny and they can burrow deep into our lungs, and pollen actually attaches itself to those diesel particles. Pollen getting deeper into our lungs could be leading to higher levels of asthma.

TWILLEY: And frankly there’s more and different varieties of pollen around thanks to changes in farming and urban tree cover. But also, pretty much everything in our environment has changed. And what’s interesting is that other creatures who share these new environments that we’ve created in our cities and homes and industrial farms—creatures like our pets and our livestock— they’re increasingly suffering from allergies too.

GRABER: All our immune systems are just meeting up with things they’re not used to in our new modern world.

MACPHAIL: So think about everything we come into contact with. The man-made chemicals, different types of food. Different types of bacteria. And they’re not getting exposed to things that they would have gotten exposed to in the past, like parasites. Older forms of bacteria and viruses. And we have made so many changes in such a short amount of time, evolutionarily speaking, like we’re talking about 200 years, which is a blip compared to 500 million years.

GRABER: Five hundred million years ago is when some parts of our immune system first evolved. This ancient system is dealing with all sorts of assaults it never had to manage before.

TWILLEY: When it comes to food allergies specifically, one Gastropod’s favorite things could be among the culprits: microbes!

GRABER: Drink!

MACPHAIL: If you look at two infants, one of which has a milk allergy and one of which does not have a milk allergy, you find a different genetic makeup of their gut microbiome. So they have different types of bacteria and in different quantities. And what we are busy doing now is trying to figure out which bacteria are protective of food allergy, and which might be causing the trouble.

GRABER: One angle of this theory is that all of the microbes living on the lining of our gut, they form an important barrier because our gut lining itself is pretty thin. And maybe there are fewer microbes, or they’re not the strong kind that are good for defending the borders. So that might mean our gut is letting through larger particles of food proteins that never got through before, and the proteins get into the blood, and our immune system thinks, “invader!”

TWILLEY: So many theories!

MACPHAIL: There are several and none of them are the smoking gun. When I would try to get experts in the field, so these immunologists who are working on this very issue, to come down on a single cause, they refused and said it’s everything. [LAUGH]

TWILLEY: Excuse me while I just go bang my head against a wall.

GRABER: So food allergies are increasing, but on the practical side, if you eat a lot of foods all together, which is what a meal is, how can you figure out what you’re actually allergic to—and then what can you do about it? That’s coming up, after the break.

[BREAK]

TWILLEY: So we don’t know what exactly is causing this rise in food allergies, but we do know some things about them. Like what foods you can be allergic to. Spoiler alert: it’s also everything.

MACPHAIL: The common culprits are nuts. So tree nuts, ground nuts. Corn, soy, milk, shellfish. Those are the big ones. The newcomer, the new kid on the block, is sesame. So we’ve seen a growing number of kids that have an allergy to sesame. So there are some foods that are common culprits, but really—and this might sound a little bit scary—technically speaking, you could develop an allergy to anything you ingest.

TWILLEY: And just to make sure I can keep banging my head against a wall: if you want to know why *these* particular foods, why do these seem to be the ones that are most likely to trigger immune systems? Well, that’s not super clear either.

GRABER: With tree nuts it seems to be something about the size and stability of their proteins. With shellfish it seems to be because the proteins are similar to those in other irritants like dust mites and even cockroaches.

TWILLEY: But also this is something scientists are still actively trying to tease out: why these particular proteins trigger reactions more commonly, and others don’t.

GRABER: And another thing that perplexes scientists is why some people can safely eat a small amount of a given food before having a reaction and others cannot, at all.

MACPHAIL: Some folks literally will get a massive reaction simply from cross contamination. Which can be something as simple as, you go to get an ice cream, someone just got peanut butter ice cream, you ordered vanilla, but they didn’t wash the scoop in between. And just that trace amount of leftover peanut butter ice cream on your vanilla can be enough to send someone to the ER. For other people, they can eat maybe up to two or three nuts before they have a response. And that can—ugh, even worse, it can change over time. So, you might have a mild reaction one day and then three years later, here you are thinking, oh, I just have a mild allergy and then surprise, surprise, you find yourself in the ER.

GRABER: All this uncertainty creates enormous anxiety. For allergy sufferers, it can upend their lives because food is everywhere and we all have to eat every day.

MACPHAIL: Suddenly imagine living in a world where everything you eat is suspect. That’s what it’s like. So imagine the next time you go to eat breakfast, lunch, dinner, whatever, your snack, that you have to stop first because the thing that you could put into your mouth can kill you. Most of us don’t have to worry about that. But once you get that diagnosis… the world becomes a different place. Suddenly you’re hyper-aware of the way your body reacts to the world around it. And that can be really, really scary and really, really stress inducing.

TWILLEY: For parents and caregivers of young kids who are allergic, there’s another challenge.

MACPHAIL: You have to try to get a child to understand that it’s serious, but you don’t want to scare them. So you have to thread this needle that’s very, very fine, about having them be aware enough that they don’t accidentally ingest something that could cause a problem, without making them terrified of eating.

GRABER: And on top of it all, popular culture doesn’t take allergies super seriously.

MACPHAIL: So if you are watching a TV show and they want you to know that someone is a nerd or is nervous or is a loser, they have a food allergy. And it just drives me bananas. They either have a food allergy or they whip out their puffer because they have asthma.

ADULT: Okay, give me all your peanuts, goobers, and fluffernutters!

BART SIMPSON: Ohhh… why should we have to give up our salty snacks just to keep one allergic kid from exploding? Who is this selfish jerk, anyway!

MILLHOUSE: It’s not me, I swear! I’m only allergic to honey, wheat, dairy, non-dairy, and my own tears! [SOBBING] Oh, no! Call my allergist!

LEONARD: Here you go. Pad Thai, no peanuts.

HOWARD: But does it have peanut oil?

LEONARD: I’m… not sure. Everyone keep an eye on Howard in case he starts to swell up.

SHELDON: Since it’s not bee season, you can have my epinephrine.

TWILLEY: Just a small selection of allergy jokes courtesy of The Simpsons and The Big Bang Theory.

MACPHAIL: I think a lot of us tend to pooh-pooh food allergy. You see so many jokes in the media about it. And I think people just don’t really understand the level of stress. Just for comparison’s sake, here in Mount Sinai at the Jaffe Center for Food Allergy Research, they did a study that found that the parents of children with severe food allergies have stress equal to or greater than someone who just had a massive heart attack.

TWILLEY: All of this stress is once you even know what you or your kid are actually allergic to. But unfortunately the process of figuring out what your immune system is so upset about is not super simple and relaxing either.

MACPHAIL: And the reason for that is—and I’m sure everyone listening to this is going to have a reaction to this. The skin tests and the blood tests are inaccurate. So, it’s, if you get a skin test and especially for food allergy, it’s notoriously inaccurate. 50 percent false positivity rate. Blood is around the same.

GRABER: The skin prick test people take today has been around in a similar form for about a century. What happens is that doctors inject just a tiny amount of what might be causing an allergy under your skin, like a miniscule sample from a nut or from clams, and then you wait and see if you have a reaction to either of those.

TWILLEY: There are a lot of problems with this test, a couple of which are that, one, there’s no requirement that the samples in the test are standardized, so one test can use one substance at one strength, and another can be completely different. For another thing, only four fish species out of the hundreds that humans eat are even available in test form. And of course any reaction on your skin might just be a local reaction to something in the injection, not an actual allergy.

GRABER: And as Theresa pointed out, you can get a positive test and still have a 50-50 chance of not actually being allergic to that thing. Theresa also mentioned blood tests—if you have negative skin pricks, you might then have some blood drawn and that blood is mixed up with what you might be allergic to to see if there’s a response.

TWILLEY: These tests are also notoriously inaccurate. Like Theresa said, about half the time when someone has a positive result to a food on the blood test, they WON’T have a reaction to that food when they’re given an oral test. There’s a bunch of reasons for that. For one, you’re testing undigested food, and the proteins that can trigger an allergic response are often changed during digestion. And then sometimes, a local overreaction can skew the result positive when overall you’re not allergic.

GRABER: On top of all that, people can have all sorts of symptoms of what they might think is a food allergy, but they never test positive to anything on any test. Actually this is one place where the tests are most useful: they can be used to rule out an allergy, because if you’re negative on an allergy test, you’re most likely not allergic to that thing.

TWILLEY: So then it could be that you’re allergic to a food that doctors haven’t tested you on yet, or you might have an intolerance or a sensitivity, not an allergy.

GRABER: But people get frustrated by not having an answer and they really do believe they have a food allergy, and so some people turn to testing themselves using at home IgG sensitivity tests. IgG *is* one of those antibodies that’s released as part of the immune response, like we described earlier, but Theresa says these tests are garbage.

MACPHAIL: IgG, everyone produces it to every food we ingest. In fact, they think it might be protective. So a top food allergist here in New York said to me that if you don’t produce IgG when you drink milk, he’s worried. [LAUGH] If you’re regularly eating something, you’re going to have IgG antibodies that respond to that thing.

GRABER: You might think, okay, whatever, people are just misdiagnosing themselves, but the problem is that they then cut out that food, or those foods, from their diet, and that could be really harmful nutritionally, they might not be getting enough of the nutrients they need.

MACPHAIL: But the other danger is that say you have the genetic predisposition, say you have an underlying sensitivity, you might have been tolerating that food. So you’re—you have an underlying sensitivity, we’ll just use corn. Your body’s handling it just fine. It’s tolerating it. And then you get this IgG test back and you say, Oh my God, I reacted to corn. I have to stop eating corn. What happens is then you are depriving your immune cells from tolerating that thing. It stops seeing that thing in the neighborhood. It stops seeing corn. And then accidentally, the next time you see corn, you might have given yourself the very thing you were trying to protect yourself from.

GRABER: I know this seems confusing. Usually if your immune system has a predisposition to recognizing something as an enemy, you’d think, that’s it, it’s an enemy, and I *should* avoid it. But that’s not always the case, because if your body has a chance to learn that it’s just a normal visitor to the neighborhood and not an invader, that can keep the alarm bells from going off, and stop you from developing an allergy, even with your existing predisposition.

MACPHAIL: So it’s a really dangerous game that we play, when we try to play “do I have a food allergy?” by ourselves.

TWILLEY: There is a gold standard test to find out if you do actually have food allergies: a double-blind, placebo-controlled oral food challenge. Basically you have to go to a clinic or hospital, in case you have a reaction, and you can only test one food at a time, in increasing doses over a period of weeks.

GRABER: Just from this description you can tell that it’s expensive, and it takes a long time. And if that weren’t enough of a reason for people to not want to bother, it’s also scary, because you could be deliberately eating something that will give you a serious reaction. And even if you’re in a hospital, that’s still not fun.

TWILLEY: So in the absence of any testing breakthrough for now, allergists are left just kind of figuring it out.

MACPHAIL: What they tend to do is… sort of like patching together a mystery. So a good allergist is like a good detective. They take different things. So they’ll take a look at your skin and blood tests. Because sometimes the negatives are, are a good way. So if you get a negative response on your skin or your blood, that’s fairly accurate actually. So they look at that. And then they look at your symptoms. So they’ll have people do elimination diets. So you’ll eliminate certain foods, track your symptoms. So all of that taken together, sometimes you can get at it even if you haven’t had the double-blind food challenge.

TWILLEY: So that is how you more or less figure out that you have an allergy. But then what can you do about it?

GRABER: When allergies were first discovered, more than a century ago, the only tool doctors had for sufferers was to tell them to stay away from the thing that gave them hives or nausea or whatever. Theresa says unfortunately, that’s pretty much still the case.

MACPHAIL: For food allergy, the standard is still avoidance. So for most folks, they’re just going to get the treatment plan that says try not to eat this thing, try not to come into contact with this thing. And that can be really, really challenging.

TWILLEY: Historically, once food allergies were finally recognized as a thing in the first few decades of the 1900s, people also tried a kind of gradual desensitization approach. They would eliminate the food they were allergic to from their diet, and then very slowly introduce it back in teeny tiny amounts. But, it mostly didn’t work. People stayed allergic.

GRABER: The next big piece of medical advice was to not give your kid certain foods that were known to be more common sources of allergies, like peanuts, until they were three years old.

MACPHAIL: Turns out that was the worst advice anyone ever gave anyone.

TWILLEY: Because all those kids didn’t have a chance to train their immune systems early on in life that peanuts were friends, not foes. So the whole strategy backfired and actually led to an increase in peanut allergies.

MACPHAIL: But it was the best we could do at the time. Again, we didn’t know as much as we know now.

TWILLEY: More recent research shows that actually if you feed children peanuts regularly from infancy they’re much much *less* likely to develop peanut allergies.

GRABER: But that’s not failsafe, kids do still develop allergies even if they eat a wide variety of foods from an early age. So now one of the treatments is a more scientific approach to peanut protein desensitization.

BROADCASTER: It’s been a holy grail of sorts in the medical world. How to prevent peanut allergies, the most dangerous food allergy in children. In tonight’s special report, Sylvia Perez has more on this first-of-its-kind, FDA-approved treatment that could be a real game changer.

REPORTER: It’s called Palforzia, and it’s the first ever drug to make peanuts bite safe, meaning preventing a severe allergic reaction.

TWILLEY: Palforzia, this breakthrough miracle holy grail? It’s peanut powder. It’s just very standardized, purified peanut powder. And the treatment is basically just that desensitization idea, made much more scientific and controlled. It’s called immunotherapy.

GRABER: The idea is that if a kid’s immune system is constantly activated by a tiny tiny amount of peanut protein, then it gets a little tired of reacting and so it doesn’t react anymore. The problem is that it only stops reacting to that tiny bit of peanut protein, like maybe at the end of the treatment it’s the equivalent of being able to tolerate one or two peanuts.

MACPHAIL: A lot of people think that immunotherapy means like at some point, you can just eat a jar of peanut butter [LAUGH] at the end, and that’s not true. Most people are still having symptoms from the thing that they’re allergic to, but their bodies are not going into full fledged anaphylactic response anymore. And they have to maintain that. So you can never stop maintaining the exposure.

TWILLEY: Which means you have to keep eating a tiny bit of peanut all the time to be able to not die when you’re exposed to peanuts.

MACPHAIL: Now, the problem with this is it doesn’t work for everyone. And we’re not so sure why. It could be because the biological mechanisms behind their allergies are different somehow than the people that it works for.

GRABER: So it’s not for everyone, and also, like the gold standard oral food challenge, immunotherapy can be stressful because it could cause a severe allergic reaction. As a result, not everybody who has a peanut allergy wants to try it.

TWILLEY: So what is a person with a food allergy to do, surely there must be other drugs?

GRABER: There actually aren’t great options out there right now. There’s a drug that’s been newly approved for food allergies, but what it does is basically prevent anaphylaxis for people who are accidentally exposed to small amounts of some of the most common allergens, it doesn’t make people not allergic to that thing anymore.

TWILLEY: If you’re taking this drug and you’re exposed to a trigger food, it sort of works like a sponge to mop up some but not all of those IgE antibodies that your white blood cells produce.

MACPHAIL: Those drugs are tamping down on people’s anxiety. So if you go on a drug like that for prevention, what you’re really doing is lowering your anxiety about your son going or daughter going to a birthday party and accidentally having a cupcake with something that triggers them in it, then they won’t die from that thing. But other than that, we’ve got nothing.

GRABER: There are a number of treatments that scientists are working on. One researcher Theresa met is focusing on the gut, she’s trying to find a way to make our guts less leaky so that fewer of the larger food proteins get through. She’s looking at microbial interventions or other ways to strengthen that gut lining.

TWILLEY: Other scientists are trying to use genetic engineering. Some are working on the foods themselves, trying to breed crops that don’t make the particular proteins that people tend to react to. Some are working on the people, trying to engineer a less reactive immune system.

MACPHAIL: So if we can somehow, the theory is if you could just wipe the T cell memory. So those T cells, if you could just get them to forget that they don’t like milk, then you would solve the whole problem. And then you could reintroduce it, perhaps tagging it with something our bodies do like. So training it to accept that thing, that could be a really nice solution. Unfortunately, all of this stuff is going to take, you know, if I had to guess another 10 years, 20 years for some of this to go through the whole rigorous clinical trial phases that they have to go through, but it’s promising.

GRABER: Meanwhile people are trying to solve this problem for themselves, they’re dosing regularly with local honey and taking probiotics. And they’re avoiding vaccines or genetically modified foods in the fear that those are causing more allergies. But Theresa says none of these approaches work. Honey’s lovely, but it won’t cure or prevent an allergy.

TWILLEY: But it’s easy to understand why people turn to these bogus remedies, because figuring out how to deal with an allergy is hard within our current medical understanding and medical system. Theresa says doctors spend very little time on allergies in school.

MACPHAIL: And there’s not a ton of allergists. And if you’re looking at a food specialty allergist, then there’s even fewer of them.

GRABER: Theresa deals with her own seasonal allergies, but in terms of trying to prevent any more allergies in the future, she only had one real personal suggestion, and that was, yes, microbes.

MACPHAIL: So I just think of myself as an organism… that’s a complex organism. With all of these other cells in and on me. And I try to think about what I’m giving to them or what I’m exposing them to. And that’s something we can all do.

TWILLEY: Yes, Gastropod is in the pocket of Big Microbe. You know what I’m going to say: Eat your beans and kimchi!

GRABER: But of course as we always say on the show, personal changes can only go so far. Theresa pointed out that societal changes are critical for keeping today’s allergy epidemic under control and making life easier for those who do have allergies.

MACPHAIL: I advocate strongly for things like clean air. Because of course the environmental part of this is real. So clean air, clean water, clean food. So I just try to advocate where I can for good environmental policies. And then I try to remember that I am making decisions for those cells as well as me. And if they’re happy, I’m happy.

TWILLEY: But at the end of the day, really, when it comes to food allergies, it’s a case of stay tuned. The unknown unknowns are still pretty substantial. We just don’t fully understand how our immune system decides whether things are friend or foe.

MACPHAIL: And that’s one of the most fascinating things, to be honest. If you ask me what is the most fascinating thing that I learned in researching and writing this book, it’s that we don’t really understand tolerance. Theoretically speaking, everything we put into us that is not us should create an immune response. The fact that it doesn’t is kind of miraculous.

[MUSIC]

GRABER: One story we loved but couldn’t include in the episode is the discovery of alpha-gal—it’s the story of how a tick bite can give you an actual meat allergy, an unprotected hike in the woods could leave you allergic to hamburgers. We have that story in our special supporters newsletter, find out more at gastropod.com/support.

TWILLEY: And while you’re at our website, we have links to Theresa McPhail’s book, Allergic: Our Irritated Bodies in a Changing World. Thanks this episode to Theresa and to our fabulous producer Claudia Geib, as well as to all of you who shared your own allergy experiences, we really appreciate it.

GRABER: We’ll be back in a couple of weeks with a brand new episode, ‘til then!