“‘I said, ‘Yes.’
“He said, ‘Well, that’s the end of my universe.’”
Sukhdeo found that while he couldn’t get liver flukes to swim upstream to any particular cue, certain chemicals like bile made them react violently. He had seen the same strange reaction in Trichinella when he exposed it to the chemical pepsin. And then, as he was chewing over his data he realized that he had been looking at the problem from the wrong angle all along. He had been looking at the fluke or worm as a free-living creature, not as a parasite. A body is not a peaceful ocean. It’s a sealed space in which fluids churn and slosh. A scent released from one organ can’t spread smoothly and tranquilly through other organs. An airborne odor spreads out evenly, essentially to infinity, but a chemical marker inside a body must come up against any of a number of barriers, bouncing back and saturating the territory, destroying any clues it might have offered.
Sukhdeo explained his realization to me in his office, waving his arms at the wall. “For a gradient to form, you need an open-ended system, and you can’t have turbulence. If I put a piece of toast here, you would smell it and know where it is. If I closed the room, quickly it would saturate. Because it’s in a closed sysem, you can’t have a gradient. If you put guts in this room, they would do the same thing.”
The world of a parasite isn’t like our own—it has its own constraints and opportunities. Because of the strange conditions found inside a body, Sukhdeo wondered whether parasites might be able to navigate not with gradients but by simply reacting to a few different sorts of stimuli. Konrad Lorenz had shown that free-living animals in the outside world rely on reflexive behaviors when they find themselves in predictable situations. If you’re a goose and one of your eggs starts to roll out of your nest, you can perform a set of automatic actions to get it back: stick out neck, pull back neck, bend head down. That should get the egg under your beak and back into the nest without requiring you to pay much attention to the egg itself. If a biologist should sneak a goose’s egg out from under its beak in the middle of this sequence, the goose will keep pulling its neck back anyway.
Sukhdeo wondered whether parasites relied on these kinds of programmed behavior more than free-living creatures. A body is in some ways more predictable than the outside world. A mountain lion born in the Rockies has to learn the shape of its territory and relearn it whenever a fire or a landslide or a parking lot suddenly changes the topography. A parasite can travel through a rat, safe in the knowledge that it crawls through a little biosphere that’s almost identical with any other rat interior. The heart is always between the lungs, the eyes in front of the brain. By reacting in a certain way to certain landmarks on their journey, parasites can be transported where they need to go. “Everything else is irrelevant,” says Sukhdeo. “They don’t have to waste time generating neurons to recognize everything else that’s going on.”
Now all the weird behavior of Trichinella and liver flukes settled down into straightforward recipes for success. Trichinella sits tight in its muscle capsule as it falls into the stomach. There it picks up one of the chemicals, known as pepsin, that breaks food down in the stomach; in response, Trichinella starts to flail. “The first movement causes them to break out of that cyst. You can see them whipping until the tail lashes out and they’re out in the stomach.” The piece of meat they’re lodged inside passes out of the stomach and into the intestines, where there’s a duct from the liver down which bile flows to help with digestion. And bile is the second trigger, making them change from their whipping movement to a snakelike slither. That lets them move out of the food and into the intestines.
Sukhdeo figured out a way to test this idea. “What if I changed where the bile came in?” he said. “I had learned a lot about surgery, and I could stick a cannula with bile anywhere I wanted.” Wherever along the intestines he moved the source of the bile was where Trichinella would settle. “The only reason they went where they went was because of bile.”
Sukhdeo turned to his liver flukes, and he found that they also followed rules instead of gradients. Because they have a longer journey than Trichinella, they need three rules instead of two. When a liver cyst tumbles into the intestines, it’s sensitive to bile as well. When it senses it, it starts twitching—“it goes spastic,” says Sukhdeo. As it writhes, it breaks open its cyst, and the same movements drive it through the mushy wall of the intestines and into the abdominal cavity. A liver fluke has two suckers, one by its mouth and one by its belly. It can crawl by extending its front sucker, clamping it down, and then pulling up the rest of its body and anchoring it with the belly sucker. Flukes can also crimp—their whole body suddenly contracts in a violent spasm, and they let go of both suckers.
These kinds of movements are all that a fluke needs to get to the liver. It doesn’t need a copy of Gray’s Anatomy showing it the way. When it emerges out of the small intestines, it crimps itself out into the abdominal cavity, eventually reaching the smooth wall of abdominal muscles. The following day, the fluke switches to creeping. Now safe from the torrents of the intestines, it creeps along the abdominal wall without having to worry about getting washed away.
At this point, a creeping liver fluke will almost always reach the liver, no matter which way it travels. You might expect that the fluke at least has to know a few things: which way is up and which is down, for example, or the fact that the liver is next to the pancreas but not the gallbladder. Not so. The fluke takes advantage of the fact that the abdominal cavity is like the inside of a beach ball. Even if it crawls straight down to the bottom, it will reach the liver if it simply continues to crawl in a straight line, coming back around to the top, where the liver sits. That’s why Sukhdeo found that 95 percent of flukes enter the liver from its upper side where it meets the diaphragm—the summit of the abdominal cavity. Despite the fact that a liver’s underside is big and closer to the intestines, only 5 percent penetrate it from that side.
It took a decade for Sukhdeo to figure out how these two parasites navigate. These days he is almost respectable. To his surprise, he was offered a job as a parasitologist at Rutgers despite his years in limbo. He has a lab full of students eager to decipher the navigation of other parasites. He’s thinking of ways to turn his discoveries into a way to kill parasites by giving them navigation signals at the wrong time. And he has many more puzzles to work on. When I last spoke to Sukhdeo, he was working on another fluke. It also starts out in a snail, but when it emerges from this host, it seeks out a fish instead of a sheep. As the fish swims past, the fluke snags onto the fish’s tail and burrows into the meat. It then makes a beeline through the muscle for the fish’s head and comes to rest within the lens of the fish’s eye. “It seems that all the ideas people had before were wrong, so we’re starting from scratch,” he said.
Sukhdeo has earned the respect of other parasitologists for having shown that there is a behavior to parasites, that they make their way through the unique inner ecology of their hosts’ bodies, and that you can figure out the rules they obey. He even got an award not long ago for his work, a plaque that he hands to visitors with a puzzled look. “When they gave it to me, I said, ‘Why am I getting this?’ I had been blackballed for so many years.” There’s a note of nostalgia when he talks about being ignored and ridiculed. He once submitted a paper to a journal about animal behavior and was rejected. When he asked the editor why, the editor reread the paper and accepted it, saying, “I had no idea parasites behaved. Please excuse my vertebrate chauvinism.” And his old advisor wasn’t the only parasitologist to tell him he was making a mistake. “At a meeting I went to, I was saying that we had to use ecological concepts when we were looking at parasites, and I got this old parasitologist standing up and shouting ‘Heresy!’ with the spittle coming up. A heretic!”