The Elixir of Life

0:28Wait, you're listening. in New York City called Caveat. I always wanted to go there. It's really cute. It's got like a cabaret underground vibe. Are you finally singing? I feel like you've been just needing to get out there and sing. I did not sing in this show at all, but there were live musicians, including Dylan Keefe on his Upright Bass, our director of sound design. Okay, thank you all for coming out. Thank you. And a rock star of sorts. Adieu, Aver Mitra. Can we get some bring on music? Ooh, Aver. Thank you. Yeah. Thank you, thank you. So as you know, Avir Mitra is our ER doctor special correspondent who has done some of the most beloved medical mystery tales on the show.

1:09So many vultures, plane crashes. Thank you so much. Easter Island dirt. That's right, yeah. Yeah. And he had another one in store that he told on stage that night. Truly an odyssey. Takes us all over the globe. We blow by the Mennonite communities. We go to Gambia. We go back into deep evolutionary time to stage a reunion, a physical reunion with what Avir calls humanity's oldest friend.

1:46And he kicked off the whole thing with a bottle full of white liquid. We're talking about the magical substance that is breast milk. And because, as you know, I recently had a baby, the breast milk was provided by me. I have an eight-month-old. I am breastfeeding. I also use formula. This is not, we're not here to say one or the other is better. But instead... And so we just kind of held it up to the spotlight. Everyone was looking at it. And Avere kicked the whole thing off with just a simple question. I guess I'm going to throw it to the crowd. Like, if we just had to name the components of breast milk, and I'm going to take one off the table.

2:27We know that it's 87 % water. Okay, fine. That's easy. But the solid part, like name some things. What's in breast milk? Vodka. Depending on the mother's name. Yeah, right. Fat. Sugar. Sugar. Proteins. Hormones. Calcium. You guys are right. I mean, everything you're saying is right. But there is something that we've missed. It's called human milk oligosaccharides. And what's crazy is it's actually the third largest compound in breast milk, way above protein. So you have lactose, that's the sugar that someone mentioned. You have lipids, that's fat. And then you have these HMOs and they are strange.

3:12Wait, HMOs? Yeah, it's not your health care, health insurance organization. They are actually sugars. But as Avira told us, they are totally different than normal sugars. and they form into these kind of gorgeous but strange elaborate shapes. Branches and chains, ferns and weird shapes. And they are not found anywhere else in nature, just in human breast milk. Weird. In fact, Vir calls them alien sugars. And that's the number three ingredient in breast milk, alien sugar. The third biggest, yeah. You can't get them at the local grocery store. And what's crazy about it is humans can't digest this stuff at all.

3:57Like literally, no human being can do anything with these sugars. And no one ever really thought to ask, like, what's going on, really, until a scientist by the name of Bruce German came along and basically just asked a simple question. Why? Why would a mother who's got very precious limited calories, why would that mother literally dissolve her own body, taking all these precious nutrients and calories to make milk that needs to feed this baby? Why would the mom make these sugars that no baby can use? Why? so this is around 2005 Bruce is having these thoughts and this is the era sort of of the microbiome where we're all thinking about the microbiome and it's this idea that like we're basically human suits covered in bacteria filled with bacteria and so he has this hunch that's basically like okay well if we can't use it maybe there's a bacteria that can't that lives inside of a baby maybe there's a bacteria that lives in the baby's gut like food for a baby bacteria Right.

5:07So they design an experiment, basically taking an agar plate where bacteria like to grow. Okay. So they decide, okay, we'll take an agar plate, sprinkle the alien sugars on the plate, and throw a bacteria in there and see if it grows. If you eat it, you'll proliferate. If you don't, you're going to die. Exactly. Okay. Yeah, you got it. So they throw some bacteria, take a common bacteria that lives in the gut, throw it on there, throw some HMOs, it dies. It doesn't work. No luck. Try another one, no luck. Try a third one, no luck. Okay, how long is this taking? Well, so a year goes by. Yep. Bruce and his team are like begging, borrowing and stealing to get like any breast milk that they can, you know, begging on the street.

5:47Like, can I get some? You know, it's not working. A year goes by, two years go by. Okay. Finally, on the third year, boom, they find something. That was perfect. Ooh. Wow. Why do we prep for these podcasts? We could just do this. I know, let's just always do that. Okay. Okay, so they find something that's growing. You can see all this white stuff is bacteria that's growing. At this point, Avir shows us a picture of a plate with all this bacteria growing on it. Because they put it under a microscope, and it looks very strange. If you zoom in on the picture, this collection of squiggles... Zoom in a little more.

6:22It's beautiful. ...become... Zoom in a little more. These individual little... Little more. Y shapes. And so this is the bacteria that likes to eat the weird alien sugar in the breast milk. Exactly. And so it turns out this bacteria is called Bifidobacterium infantis. Bifidobacterium infantis, never heard of it. Yeah, we can just call it Bifid for short. It is shaped like a Y and with one of the little spires kind of bent over like a little puppy dog ear. It's kind of cute. Anyway, this was the only bacteria they could find that actually ate those alien sugars in breast milk. Huh, yeah. So, yeah.

7:01Okay, so does that mean this is in my baby's belly? Well, that's the next question. Exactly right. So you found out of the thousands of bacteria, you found one that can eat these sugars. That's crazy enough. Because we can't eat them, but it has all the genes and all the enzymes to eat these sugars that we make that we can't eat. It's just weird, right? So you would think, okay, this should be in some baby's guts. Yeah. And so the way to look for that is, you know, when you have bacteria in your gut, you're going to poop out some of that bacteria. So you really got to get into poop. You know, that's where this story is going.

7:39And so basically from there, Bruce and his team need to start collecting dirty diapers, you know, which I don't know if that's an upgrade from begging for milk. But that's where they're at. So Bruce is working at UC Davis. He's around getting his friends and neighbors and strangers on the street to give him their dirty diapers. Let's culture it. Let's see if we can find some Bifid in there. Yeah. But no, you can't find any Bifid in any of these diapers. They're just not. So that theory gone? Well, it might just be where they're located, you know. So they realize they need to sort of expand the search.

8:15And that's where this idea starts what I call the amazing global baby diaper hunt. Okay. So it turns out that the Gates Foundation, for some reason, has collected stool samples from all over the planet. I'm not sure why. Okay. Don't tell Elon Musk about this, please. Basic science! You never know! So they have just baby poop, like, just lining their walls, I guess. I don't know. Just libraries of poop? Just libraries of poop from all over the world. So Bruce calls them, you know, sets up a meeting and says, can I get some of this? Let me get some of this poop. So yeah, they set up a deal where they're going to send him poop from all over the world.

8:59And they're going to look all over the place. So they look. They start looking at poop in Denmark. Okay. And no bifid. Okay. Scandinavia, Switzerland, no bifid. Okay. But then they get to Gambia. Huh. Bifid. It's there in the poop. Cambodia. Bifid? It's there. Rural China. Bangladesh. They have bifid. Huh. Weirdly, the only people in the U.S. Yeah. Mennonites. men and knights have the bifid the babies have it very strange why some places and not others well that's the question at this time they don't really know why here why not there yeah it's a mystery i mean it certainly could be you know maybe this bacteria survives in a certain climate maybe it's genetic differences maybe it's lifestyle differences it's an open question okay does he have any guesses of like there's obviously some bacteria we like that are great for god health some we don't want is it does he have any sense of what it's actually doing right that's the next question is bruce and the team guy by the name of david mills all these amazing scientists want to figure out what is this bacteria doing yeah so what they do is they do another experiment they basically take some cells from the gut which you can take you can culture them and you can put them on a plate and when you put gut cells on a plate they actually automatically form themselves into a wall and so it's kind of cool because you know gut cells what they're supposed to do is basically form a wall and anything you eat or drink has to basically go through those cells to get to your body.

10:21So it wants to make sure all the food is the right food. It's all broken down properly. All the good stuff comes in. All the bad stuff stays out. That's what the gut cells do. So they form into this wall. The gut's being formed into Petri dish. They throw some bifidobacterium on the Petri dish and see what happens. And right away they notice that the bacteria are able to sort of latch onto the walls of the gut. Just like hang there, like mountain climbers. And they start proliferating really fast and basically coating the whole wall. Whoa. So this Y-shaped bacteria that likes alien sugars, with enough time, it's almost like wallpaper on the inside of the baby's gut?

10:57Yeah, exactly. It's like wallpaper on the walls. Okay. So I guess I ask again, is this a good thing? Right. We don't know if it's good or not. So to answer that, I got to tell you a story. Okay. I love a story. Dylan, guys, I'm going to need a little bit of like rogue, don't try this at home. just don't try this type of stuff at home okay so our story centers around dr shara sheldon who at the time is a phd student okay now she's studying this stuff she goes to a lecture where bruce is talking about these results and she sticks in the back of her mind meanwhile her father is a professor at the vet school and he works at a lab like at the not at a lab at a barn that's raising these thoroughbred horses.

11:44Oh, okay. So thoroughbred horses, if you don't know, you know, those are those really expensive horses that, you know, they eat way better food than you and I. Yeah. Their lives are definitely more valuable than ours. Like, these are expensive horses. Yeah. Okay. But there's a problem at the barn. Every new foal that's being born to these horses after a few days is getting diarrhea, fevers, and then dying. Oh. Yeah. And that's sad Sad because we like horses, but also sad because they're losing like hundreds of thousands of dollars every time. On every foal. Okay. Okay. And the problem is next week there's going to be like 20 more foals being born.

12:22Oh, no. And yeah. So basically what they do is they find out what's going on. And it turns out these horses are infested with like one of the worst diarrheal bacteria that we have. And if anyone works, does anyone work in health care or anything like that? I mean, what's that one bacteria, diarrheal illness that we don't want to deal with? C. diff. C. diff, exactly. A lot of C. diff. You know it. Once you've smelled C. diff once, you'll never forget. A viewer showed a picture of C. diff that was right behind us on stage. Okay. It looks kind of like a dynamite stick, like exploding corndog situation.

12:57Yes, the corndog dynamite stick. This bacteria is terrible. Okay. Like you can't, if you spray this with antiseptic, if you spray it with Purell, like it won't die. Like this thing doesn't die. It's really hard. It needs very strong antibiotics. It kills people all the time. We see this every time in the hospital. And it was killing these horses. So these foals infested with C. diff. The dad, who's the professor who works there, is talking to his daughter about it and commiserating. And the daughter goes, wait, I just heard a lecture by this guy, Bruce German. And he was talking about this bacteria that coats the walls.

13:29Like, let's give this to the horses. So the dad goes, yeah, I mean, let's try it. So they take the bacteria from Bruce, they culture it, they mix it up with some milk, and then when the foal is just born, they squirt it into the foal's mouth. Like with a little baby bottle? Yeah, a little baby. Squirt it in and see what happens. Hope for the best. It's only$100 ,000 on the line. Right. Okay. And lo and behold, what happens is, sure enough, 20 foals are born, none of them get C. diff, all of them do fine. Whoa. Incredible. Wait, can we get a round of applause for Shara? Rebel science. Again, don't try it at home.

14:04Like clinical trials are good, but ingenuity. Okay. So I want to play my interview with her because I wish I could tell you the story stopped there, but it continues on. Oh, okay. Let's see. I was like, good job, Brain, for remembering the random lecture with Frius German. So in the room, we're actually now watching a video of the interview where you can see Shara on the left put together, short, dark hair. And then Avira on the right is like kind of sweaty. and was just saving lives, maybe. There are so many random lectures I had in med school that I will never remember. Like, I don't know how you did that.

14:40I loved it, though. I thought it was the neatest thing. I don't know. Okay, so that's an amazing story, but I know that the story doesn't end there. What happens next? So time goes on. I'm still doing my PhD and got married, got pregnant, And then I had my baby, wealthy baby. Everything's going great. And then the change comes. And we started dealing with a lot of gas, a lot of crying, just like he looked like he was in pain. We were trying everything for the gas, the little gas drops out of natural, the bicycle kicks, all kinds of things. So I just was getting quite desperate to find something that would work.

15:28and we kind of hit the breaking point when my husband was out of town. And so I'm alone with the baby and it was so bad. He was up like all night, just in pain, gassy. And I was like, this is not going to work. And I said, we need something. And so I remembered the bifidobacterium and I said, I'm going to email Bruce. And so I sent a desperate email saying, please, please, I know you have some of the Bipidobacterium still. Like, I'd really like to try it. Okay, and so does he email back? Like, does he take a week to email back? He got back to me right away, and he said, you can drive up and get it.

16:15And I loaded up in the car, drove to Davis, and went in, and we got, like, a little bag, just a brown paper bag with samples in there. and the syringe. No way. What, they're in like little vials or something? No, they're in little sachets, like a little rectangular packet that you can rip across and pour out. Okay, yeah, you got it. Like a bag of drugs, basically. Yeah. You know, you're using stuff that's being tested for research, so it's not very pretty. Right. I get home. I'm very excited to try this. I grab one of the little sachet packets out and I open it and I see there's like a powder in there.

16:57It had kind of an interesting odor, I noticed. And then I mix it in with the breath milk and then suck it up in the syringe. And then my mom helps me hold Connor and we hold his head and we put the syringe into his mouth, squirt it in. So we did that and they said, just do one dose a day. So, you know, I'm sitting there with aided breath waiting to see if anything happens, watching him like a hawk. and we didn't really see any changes right away. So I was a little disappointed because you're desperate at this point, right? I want results. I'm so tired. Right. And it took two days. So, and then it worked.

17:40Oh, wow. Okay, what do you mean it worked? The change was just so drastic. It was like a switch had clicked And he just was so much happier. He was sleeping. He didn't have the gas constantly and just seemed so much more relaxed. And I just, I was like, this is working. And this is exactly what was missing from his microbiota. Well, you know, the scientist in me has to ask, like, you know, could this have just been a coincidence, you know, like, or placebo effect? Obviously, you really wanted to see some results. How do you know for sure that this did that? I would be doing the same thing, right?

18:27Oh, this is just the placebo. But the amount of dirty diapers had been very consistent. I had been keeping track because I love data and I'm a nerd. So I was keeping track of all of these things. And to go from that 8 to 11 down to 2, I knew it was doing something. Wow. I got to say, I mean, was there ever a part of you that felt afraid to essentially be experimenting on your firstborn child? Or did you just feel that confident? I mean, I felt really confident with it. I mean, there's a small part of you that's like, oh, yeah, I'm giving this novel thing to my baby. But when I saw all the benefit, it was like, this is right and it's working and everything's good.

19:14But it is scary. Oh, wow. I just have to say, is there any other better image of sleep deprivation than like, this thing smelled a little weird, but let's put it down. Such a good thing. Wow. Okay, go, Shara. I mean, okay, but to follow up on your question there, do we know what, is there still a chance that could have been placebo? Do we have any clue about what's actually happening at the cellular level? like what is going on? Yeah so Bruce sort of made a deal with Shara like I'll give you the bacteria you give me his diapers. Common theme we're seeing emerge here. So that's what he does he sort of collects Connor's diapers and a bunch of other kids too and he's sort of seeing what's going on let's check the microbiome let's check the stool see what's happening.

20:05Yeah. Let's look for a subtle change like a change of five ten percent in your microbiome I mean that's huge. Yeah. But what he finds is actually Connor's diapers went from having zero bifidobacterium to being 80 % bifidobacterium. Whoa. And this is like insane because, you know, it's not, we're not even, this isn't normal microbiome stuff. This isn't like diverse ecosystem. This is just like domination. It's like a monoculture in there. Yeah, exactly. It's all bifid. Wow. Yeah. Okay. So they noticed that and that's interesting. Another thing they noticed is, well, just like babies eat and they poop while these bacterias are eating these alien sugars and they have to poop too.

20:45But what they're seeing is the poop that these bacteria are creating are acid. So they're creating acidic poop. And the thing is bacteria can't really grow that well in acid. So it's acid prevents bacteria, most bacteria from growing. But it turns out the bifidobacterium is totally chilling in the acid. But the idea is it may be keeping other bacteria away. Okay. Can I, can I just make sure I understand what's going Absolutely. Okay, so bifid is the thing that eats the weird sugar in breast milk. And if you put it in a baby's gut, it'll receive that sugar, it'll eat the sugar, it'll bloom, and it'll wallpaper the gut.

21:23But also it'll like edge out all the other bacteria. With its acid poop, yes. With its acid, right. It is like bully wallpaper kind of. Okay, and the idea is that the bully wallpaper is what helped Shara's baby have less gas and less pooping pain or whatever? Yeah, I mean, we don't know what was happening inside Shara's baby for sure, but that is exactly Bruce German's theory. And, you know, Avir pointed out there's a lot of such situations, especially in a newly developing baby gut, that if the wrong kinds of bacteria get in there, it can release toxins and poke holes in the gut wall. And allow things to pass through.

22:01Instead of going through the cells, they sort of go in between the cells and around the cells. So bacteria can get in, toxins can get in, undigested food particles could get in. And that's called leaky gut. Leaky gut. Yeah. And according to Avere, that can cause a lot more problems than just gas pain or diarrhea. And for this baby that just got an immune system like two months ago, he's trying to figure out what the hell is going on and it gets very overwhelmed and confused. It gets inflamed. The immune system is hyperactivated. And it causes a lot, you know, it could cause a lot of problems. So Bruce's theory is that, you know, going back to bifid coating the walls of the gut.

22:37When bifidobacterium is here, the bifidobacterium sticks to the walls, prevents any other bacteria from coming there. So that basically nothing bad gets into the body. And the immune system can actually like learn and do its thing. And to be clear, so this is a bacteria that most babies, especially here in the US, right now do not have. Exactly. And what's wild is you can actually see the disappearance over time. Because if you look back over time at poop samples from across the world, which there are, one of Bruce's grad students at the time actually did this, Bethany Henrich, she looked at the historical data and found that baby poop back in the early 1900s used to be way more acidic, like everywhere.

23:23It's just been subtly changing all this time. And you can, yeah, over the last hundred years in places like the U.S., it started trending over to neutral. There's this very clear line. And it's showing that basically our baby's poop used to be acidic to a pH of five, which is acidic. Okay. And it's slowly been working its way up to neutral. And it's like this very clear thing if you map it out. Huh. And again, you said the bifid makes the acidic poop. So watching it get less acidic, is that like watching a disappearance? Exactly. At this point, Bruce and the team is sort of being like, wait, this is a sign.

24:03This is the marker of Bifid and it's going away. That's what they see. Wow. You're making me miss this thing. I feel like we should get it back. Yeah. Well, that is where we are going next in the show. First, we're going to take a brief intermission. But when we come back, we will not only address that, We're going to have special guests live on stage. We're going to hear about cease and desist orders from the FDA coming down to doctors. And we're going to be doing some real life, I guess you could call it, experimentation on the audience. On babies? Not babies. On adults in the bar. Stick with us.

24:49Okay. Okay, Latif. Lulu. Radiolab. We are back playing the live show I did with Avir Mitra, telling the story of this baby gut bacterium that seems to be protecting the baby's gut. And we didn't delve into this much, but also feeding the baby's gut cells, keeping them going strong, but also appears to be disappearing from our species all over. And according to Bruce German, our main scientist, it is time to bring Bifid back. At this point, Bruce goes from being just a normal scientist, show up to work, do your research, to becoming a borderline evangelist. His daughters won't take him to the family dinners because this is all he talks about.

25:34He told me that. He sees a baby in a stroller across the street. He's going to sprint over to the baby, throw some bifido back to your madam. And he actually mortgages his house and gets his coworkers to do the same. They sell the boat, do all these things to start their own startup to sell bifidobacterium. Whoa. Right. Which you can buy and which we may or may not have. Ooh. And this is just like he's selling bacteria in a jar? Bacteria in a jar. Okay. Okay, now at this point in the show, I just need to pop out and say, Avere told a story that honestly I have not been able to shake since that night.

26:11And it's kind of like the story of Shara and her baby, but on steroids. and it starts when Bruce and his team connect with a guy named Brian Scatolini. Brian Scatolini is an MD, PhD and he's a neonatologist who works at OHSU in Portland. So he's working there and as a neonatologist, it's a beautiful thing because you get to see these little tiny preemies grow into like full-fledged adults. But there is one thing that's like the worst thing that happens in NICUs and basically that's this. so Avira is showing us this picture it's like a CT scan kind of thing and you can sort of tell that it's like the scan of a gut but it seems to be almost like ballooned out so what we're looking at is a preemie's belly and it's filled with gas, it's very distended and this baby's not doing well this is called necrotizing enterocolitis also known as NEC and basically what's going on is like a bacteria an adult bacteria has somehow made its way into the baby's gut, has sort of bloomed and taken over, and is like completely destroying the gut wall, producing all this gas and all these bad things.

27:20Huh. That looks painful, scary. Very scary. Yeah. Yeah, I mean, when I was a resident, I rotated in NICUs, and it's terrifying because these preemies can go from being normal and then overnight they can totally crash, get this, and the mortality is very high once they get this. Yikes. So Brian gets sort of wind of this bacteria and they both have this thought, well, maybe we could try bifidobacterium. In the preemies? In the preemies. Okay. He gets some of the bifidobacterium from Bruce and the team and the company and he just starts giving this to the babies. Without checking with parents or?

27:56Right. Pretty much like this is on formulary now. We're going to give it to them. I'm having mixed emotions about this idea. Sure. Okay. Yeah, I agree. Okay. And you've got to think, he's not just waiting until they get NEC to give it to them. He's giving it to all the preemies, even the ones that would be fine without it. Like a preventative measure. Exactly, a preventative. And lo and behold, he finds that the incidence of NEC goes from 11 % down to 2%. It was actually 2.7%. Insane. That's huge. Yeah. Okay. And this goes on for years. There's in fact years that go by that they don't see a single incidence of this.

28:30Of NEC? Right. In the NICU? In the NICU. he publishes about it and he's sprinkling live it this whole time yeah it's just sprinkling this was in we'll get to that so he does this and he finds that it's working other NICUs are starting to take this up so anyway I've been talking about Brian enough I want to bring Brian up himself so Brian if you're here let's bring it up come on down you can come over here