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1. The Killing Zone For Sperm | Pascal Gagneux

October 25, 2017 6 a.m.

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Related Story: Rad Scientist Ep. 1: The Killing Zone For Sperm | Pascal Gagneux


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Margot: San Diego is one of the largest scientific research hubs in the country. So who are the intrepid scientists in search of discovery- pushing the frontiers of human knowledge? This is Rad Scientist, where the scientist becomes the subject. I'm your host, Margot Wohl. Today's Rad Scientist studies infectious diseases and sperm. We’ll get into how those are connected later. But our story actually starts on a train in Thailand where our scientist met a stranger who was a very good conversationalist.
Pascal Gagneux: I'm Pascal Gagneux. I'm a Swiss American zoologist, who works at UC San Diego in the Department of Pathology. What really made me decide to go into biology, was a chance encounter with a recently graduated ecologist from Australia. Whom I met on a train ride in Thailand, where I was an exchange student.
I was 17 at the time. And we pretty much spent the whole night talking about: what it ecology? And after that train ride, I decided that this is what I wanted to do. I don't even remember his name. (Laughs) But this discussion had a big impact on me.
Margot: Not long after he graduated from college, Pascal picked up and moved over 3000 miles from Switzerland to Africa. He had landed a dream job, working for a primatologist.
Pascal Gagneux: His name is Christophe Boesch. It turns out, he was looking for someone to run his field site in West Africa, which was a chimpanzee field site.
I remember my advisor telling me, going to Africa, spending a year there will change your life. And he was right in many more ways than he probably even knew.
[transition: quiet music bed]
My first day in the forest, and Christophe just suggested that I, I go wander by myself and get an impression of the forest. And he said, "Well, you just follow that old lumberjack road, and you'll meet some, you'll see some interesting things."
There was no shortages of big and dangerous snakes there. It was completely packed with primates: colobus monkeys and black and white colobus monkeys and Diana monkeys. Jumping in the trees and making a lot of noise. Fruit dropping whenever they jump around. Lots of unknown mysterious noises from birds and other animals.
And then I suddenly hear this, "Bang, bang, bang, bang!" It sounded like a carpenter, somebody nailing something together. And my instinctive assumption was that there must be somebody building something. [Footsteps] I started walking towards the noise and there was a chimpanzee there. And he was cracking a very hard nut, with a huge stone hammer.
Margot: Pascal stood face to face with a chimp - the very species he came to Africa to study. And what he really needed from that chimp… was hair. You see, he was interested in measuring the genetic diversity of the chimp population. And he couldn’t ask the chimp - “hey can I just get a lock of your gorgeous hair?” So instead, when the chimps were out to play, he climbed into their nests in the canopy- sometimes 150 feet up to slyly get the goods. [sound effect Yoink]
He analyzed the DNA from the hair, and the results he found were startling.
Pascal Gagneux: Chimpanzees, as a species, seem to retain more genetic diversity than all living humans, which was kind of paradoxical to think that 100,000 chimpanzees have more genetic variation than all living humans, is ironic, to say the least.
Margot: So just 100,000 chimps have more genetic diversity than the entire human species -- all seven and a half billion of us. And Pascal wondered... why?
Pascal: It got me thinking about ways you could lose a lot of genetic diversity. And one obvious way would be diseases. Things that kill almost everybody off. Could it be that the reason humans are the way they are is not there they were some kind of goal, but that we might just be a side effect of the regime of diseases we’ve had in the past?
Margot: So, that’s a pretty big question. But to try to understand it, Pascal thinks small -- like, microscopic. Chimp and human cells are decorated with these tiny sugar molecules called sialic acids. But, the sialic acids themselves differ in small ways that may have a huge impact on disease risk.
Pascal Gagneux: Each one of your cells, carries hundreds of millions of these sialic acid molecules. In a sense, the cell surface, is like a nano-rainforest. If you made yourself small enough, that you sit on one of these outer leaflets of a membrane, you would be looking up at something like a 150 foot tree.
Margot: Kind of like the trees Pascal used to climb in the jungle. On these cell surface trees, the branches would be sialic acids. They're used for cell to cell communication, but they also act like a beacon for some not so welcome visitors.
Pascal Gagneux: So it's kind of a tell tale molecule, to any virus or parasite.
Margot: Malaria. There are some malaria strains that only infect chimps and some that only infect humans. Why’s that? Well, it seems like chimp malaria is looking for one kind of sialic acid beacon and human malaria is looking for another kind.
So, maybe one deadly Malaria strain looking for human sugars wiped out our population but left chimps unscathed. Remember, this is just one hypothesis for why chimp diversity is so much higher than human diversity.
So, malaria might use the sialic acid as a beacon to find host cells. But other diseases like gonorrhea and meningitis appear to use them as a way to evade the host immune system. Like an invisibility cloak! They’re basically saying, “Hey, I’m one of you. Let’s hang out. It’s all good.” And there is one other thing that wants to appear friendly to its host. It’s a tiny invader that acts a lot like a pathogen, but you might not think of it that way.
Pascal Gagneux: There's many parallels between a pathogen and a sperm.
Margot: I mean, I guess he is kind of right. Just like a pathogen, sperm enters a foreign host. And then it has make it past an immune system bent on its destruction. So, how does a sperm do it? Pascal asks you to take a moment to reflect.
Pascal Gagneux: Think back when you were a sperm.
Margot: You are one of 200 million sperm that invade the reproductive tract.
Pascal Gagneux: You get deposited in the vagina, completely its own ecosystem.
Margot: Compared to what the sperm are used to, it’s really acidic. And some of them won’t survive.
Pascal Gagneux: But then you have to make it through the cervix, which is a labyrinth. It has these really deep crypts. And a lot of sperm gets stuck right there.
Margot: You lucky few that find your way, must leave your fallen brothers behind. And make your way to the uterus, or as Pascal calls it ...
Pascal Gagneux: The killing zone for sperm. There are like 10 white blood cells from the female for each sperm.
Margot: White blood cells are the battalion of the immune system. And they’re ready to attack foreign invaders. Including you, little sperm. Out of the 100 million sperm that make it to the uterus, only 20,000 will survive. And those survivors have to make a choice. Which oviduct will you head for? Only one will harbor an egg.
Castle Guard: One of them leads to the castle at the center of the labyrinth. And the other one leads to ... Ba, ba, ba, boom! Certain death! (Ooo!)
Pascal Gagneux: But a few hundred make it to the right side. To the oviduct where there is ovulation, and those are the promising ones.
Margot: You’re almost at the egg, however, you're not home free yet. Because the egg has one last defense.
Pascal Gagneux: They have to etch their way through a huge layer of goop.
Margot: So, why does the female make it so difficult to fertilize her egg?
Pascal Gagneux: The vast majority of sperm possibly carry completely disastrous mutations. One way that females can improve the chance of the next generation, is to kind of deploy a series of very stringent check points. It would be a mixture between running the gauntlet and auditioning.

Margot: Pascal’s studies on sperm and infectious disease, conducted in a laboratory at
UCSD, were inspired by his time in the jungle. Like his advisor told him, Africa would change his life. And it certainly inspired his choice of dwelling in a time of transition.
Pascal Gagneux: You know, I have been camping for the last four months. Because we're remodeling our house.
Margot: His wife and two kids are campin' out. In a Volkswagen van, under a banana tree, in their backyard.
Pascal Gagneux: And around it, I built a platform of wood. On which I put a kitchen: with a sink and hot water, and a stove, and an oven. I have an eight and a ten year old girl. So, I built them, them a little house 8x10 foot with a frame. So that they have a secure and dry place for their paperwork and their homework and their games and stuff. And then all their friends want to come and have play dates with them. [Laughing] The rest of the camp is just tarps and tents. And the fire burning all the time. And this is much plusher than Africa.
Margot: That’s it for this episode of rad scientist. At the end of each episode there will be a short bit of radio play that will be different every time. I call it the Moment of Xenopus - named after the frog genus. So here it is, the first ever Moment of Xenopus: Technobabble.
[Techno music plays with long scientific terms spoken over the music.]
This podcast is supported by the KPBS Explore Project, bringing local content to the radio. This episode was produced by me, Margot Wohl. Grant Fisher is our audio mix master and theme song composer. Shahla Farzan is script editor. Logo by Kyle Fisher. At KPBS, Emily Jankowski is technical director, Melanie Drogseth is program coordinator, Jill Linder is programming manager, Nate John is innovation specialist, and John Decker is director of programming. Additional music was by Podington Bear, Scott Gratton, 24th Element, D Smilez, Metro Stock 99. Also, a shoutout to Jackie Sojico and Daniel Potter for feedback for this episode.
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