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The Search for the World’s Simplest Animal
On a sunny pre-pandemic afternoon at the beach near Santa Cruz, California, children shriek as the waves demolish their sand castles, and seagulls squawk over a discarded bag of salt-and-vinegar potato chips. Pelicans, sea lions, and fishermen flock to the end of an old wooden pier, attracted by schools of fish that shelter in the wreckage of a half-submerged tanker, the SS Palo Alto. The pier bristles with fishing poles, their long lines trailing into the water.
At the end of one of these lines, I hope, dangles an elusive, mysterious creature—not a fish, but the world’s simplest animal, Trichoplax adhaerens. Named after the Greek words for “hairy, sticky plate,” Trichoplax belongs to one of the most ancient animal lineages on Earth, a phylum known as Placozoa that is more than 650 million years old.
Trichoplax lacks nearly all the usual animal characteristics: It has no muscles, no stomach, and no neurons. Its minute, translucent body consists of just two layers of cells, surrounding a gooey, fibrous middle, and under a microscope it looks like a deflated beach ball covered in hair. Yet this shapeless, brainless animal can do remarkable things, including hunt for algae and defend itself with venom. Its human fans think the species is a budding scientific superstar, carrying clues to the origins of multicellular animals, brains, and cancer.
The way to trap a wild Trichoplax, according to experts, is to place glass microscope slides in a plastic rack that will hold them securely, but spaced far enough apart to allow seawater to flow through. Tether the case to a piece of fishing line, dangle it over the side of a pier or dock to a depth of at least a meter, and let it hang there for a week or two. If you are lucky, a Trichoplax will float into the case, stick to the glass, and start to clone itself.
Manu Prakash, the biophysicist I’m meeting on the pier, has not been very lucky lately. Although he captured one Trichoplax in Puerto Rico in 2018, it died before he could get it home to the lab, and he hasn’t caught one off the California coast in a year.
Prakash is 40, with dark brown curls and the concave, avid posture of someone who has been peering through microscopes since he was in elementary school—when he built his first scope, from a pair of his brother’s eyeglasses. “My brother was not happy,” he says. Prakash is a prolific inventor of scientific tools, and his creations often draw inspiration from toys and animals: His miniature chemistry lab has a hand-cranked wheel and tiny punch holes like a music box, and his paper centrifuge is based on a child’s whirligig. He is best known for an invention called the Foldscope, a $1 origami microscope that can be folded out of a sheet of paper embedded with micro-optics. He first became interested in Trichoplax when he decided to build a much bigger, more powerful microscope that could image every cell inside a freely moving animal.
Trichoplax’s simple body should have made an ideal study subject. But for a long time, none of the scopes he built could capture it: The animal kept wriggling out of view or off the slide. Prakash spent seven years building a microscope that could record Trichoplax in motion, at up to a million frames per second. Once the microscope was built, he and his team were able to watch as the organism moved in ways that had never been observed in other animals. Prakash was fascinated by Trichoplax’s seemingly infinite capacity to stretch and contract, like sticky dough between a toddler’s fingers. He wondered if its ability to tear itself apart and heal within seconds—“like Flubber,” he says—could inform the development of new materials that repair themselves and self-assemble.
Prakash studies a strain of Trichoplax clones descended from a population cultivated in Germany. But these domesticated animals don’t behave like the wild ones, and, most importantly, they won’t have sex in captivity. Until scientists can find sexually reproducing adults in the wild, or somehow coax them into having sex in the lab, there’s no way to observe their full life cycle, which could hold clues to how their simple bodies evolved, says Carolyn Smith, a neuroscientist at the National Institute of Neurological Disorders and Stroke: “We’re in a real pickle.” Tantalized by the prospect of finding previously unknown larval forms or metamorphic stages, embryos, and egg sacs, Prakash has traveled all over the world to collect Trichoplax from the shallow tropical seas where it typically dwells.
The chances of finding a Trichoplax in the frigid waters of Santa Cruz, already slim, seem even slimmer when my phone pings with a text. Prakash, who is battling a cold, is stuck in San Francisco traffic. An hour later, I receive another message: Prakash and the two lab members who will join our search have gotten lost, and gone to the wrong beach. When Prakash finally arrives, he’s wearing a pale-blue T-shirt that says experiment, learn, fail, repeat, and carrying a small Igloo cooler for transporting the animals. But when we get to the end of the pier, he can’t find the trap that one of his graduate students set out a couple of weeks ago.
Grace Zhong, a graduate student in Prakash’s lab who is studying how Trichoplax senses its surroundings, texts her lab mate to ask for directions. Eventually, they locate the spot, but the trap is gone. As a set of waves rolls in, making the old pier creak, Prakash speculates that the line holding the trap must have been snapped in the surf, or broken off by sea lions. He predicts that we’ll have better luck with the traps in the Monterey Bay marina, which is more sheltered. I’m skeptical—by the time we arrive in Monterey, an hour’s drive south, it will be close to sunset. As I’ll soon learn, however, Prakash is not easily deterred on the trail of wild Trichoplax. To him, the search for the world’s simplest animal is no casual field trip, no mere holiday outing, but a quest.
Although he’s one of the youngest scientists to fall for Trichoplax, Prakash is far from the first. The weakness for the amoeba-like creature often begins unexpectedly, when it squirms into a researcher’s field of view. The German zoologist Franz Eilhard Schulze, who discovered the animal, spotted it as it crept along the interior of a saltwater aquarium meant for other species. Smith saw her first Trichoplax when it glided across her microscope slide while she was examining some sea sponges.
In the late 1800s, when Schulze discovered Trichoplax, biologists were arguing about the origins of the animal kingdom. Inspired by Schulze’s find, the German zoologist Otto Bütschli speculated that the common ancestor of all animals was, like Trichoplax, a pancake-shaped creature with no digestive system that crawled along the seafloor grazing on algae. But another 19th-century biologist, Ernst Haeckel, had a different idea. Based on an organism he’d found while studying sponges off the coast of Norway—a tiny sphere of cells covered in whiplike tails that he called Magosphaera planula, or “magician’s ball”—Haeckel thought that the first multicellular animal did not crawl but swam, filtering food from seawater.
Haeckel’s hypothesis overshadowed Bütschli’s, likely because Haeckel was the more famous and flamboyant of the two scientists, says Vicki Pearse, a retired marine biologist and one of the world’s foremost Trichoplax experts. It also didn’t help that scientists couldn’t agree on what kind of animal Trichoplax was, she notes. When the embryologist Charles Sedgwick Minot wrote about Schulze’s find in Science, in 1883, he described Trichoplax as “an animal quite different from any thing hitherto known,” which “bears a strong resemblance to a sponge larva.” Dismissed as an immature sponge or jellyfish, Trichoplax fell into scientific obscurity until the zoologist Karl Grell found the animals in some seaweed he’d collected at the northernmost tip of the Red Sea. Grell cultivated the clonal strain of T. adhaerens that most researchers now grow in their labs, and studied it carefully under an electron microscope. He concluded that it belonged in its own distinct phylum within the animal kingdom, which he named Placozoa, meaning “flat animals.” At the time, scientists believed that T. adhaerens was the only living placozoan, but they have since uncovered a good deal more genetic diversity within the phylum. (A new genus includes the species Hoilungia hongkongenis, named after a shape-shifting dragon king in Chinese mythology.)
Although there’s still a fair amount of uncertainty about how the earliest animals are related to each other, recent genomic-sequencing studies suggest that placozoans were not the common ancestor to all living animals, and that either sponges or comb jellies came first, David Gold, a paleobiologist at UC Davis, says. Although Trichoplax comes from an older lineage than most animal groups alive today, “there are a few groups that appear to be older,” he notes.
Even if placozoans are not the oldest animals, they’re still some of the weirdest. Trichoplax’s genome, published in 2008, contained a surprising twist, Athula Wikramayake, a developmental biologist at the University of Miami, says. Despite having the simplest bodies of all animals, placozoans carry many of the same genes as humans do, including numerous genes involved in building brains and other complex organs, like those in the digestive system. Placozoans contain far more genetic complexity than scientists ever guessed, Wikramayake says. “The question is, what are they doing with it?”
One possibility is that Trichoplax used to have complex features like neurons, but lost them. Although it’s intuitive to think that simple animals always evolve into more complicated ones, “lots of [animal] groups have become simpler over time,” Gold says. Some parasitic worms, for example, have given up complex stomachs and eyes because they no longer need them: They get all their nutrition from their hosts. Mark Martindale, a marine biologist at the University of Florida, suspects that Trichoplax may have followed a similar evolutionary route. The lab-grown animals may simply be larval placozoans, while sexually reproducing adults exist as parasites in the bodies of marine organisms—perhaps in a fish’s kidney, he says. A simpler explanation, according to Vicki Pearse and other scientists, is that genes that encode neurotransmitter-like molecules in Trichoplax evolved to produce nervous systems in later animals.
In Prakash’s lab, located in the leafy bioengineering quad at Stanford University, he and his graduate students, postdocs, and lab technicians are less concerned with figuring out where Trichoplax fits into the story of animal evolution than how it manages to live such a full life—creeping along the ocean floor, sensing its surroundings, eating algae—with such minimal equipment. “Where does behavior come from in a system that doesn’t have neurons?” he asks. He’s also interested in the shape-shifting animal’s basic physical properties: “Is it a liquid? Is it a solid? Is it something in the middle?”
One thing Trichoplax cannot do, Prakash recently discovered, is swim. Some scientists say it can swim—including Pearse, who says she’s seen it. Others say it can’t. In a nod to the swimmer-versus-crawler debate of the 19th century, Prakash decided to give Trichoplax a swim test.
The test took place in one of Prakash’s recent inventions, a Ferris wheel–inspired contraption he calls the Gravity Machine. Composed of a thin plastic wheel full of water, the Gravity Machine rotates vertically in front of a powerful microscope, acting as an aquatic treadmill for microorganisms. Even in the narrow disk, which is less than half an inch wide, Trichoplax is so small that finding it with the naked eye is like searching for a dust mote in a gymnasium.
“That’s it!” Prakash said, as a translucent speck flew across the microscope’s computer screen. “That’s just dust,” objected the doctoral student Deepak Krishnamurthy, who helped invent the contraption. “That’s it! Zoom in!” Prakash said again. It was another piece of dirt. Minutes passed, then, “Lock, lock, lock!” This time, the speck was Trichoplax. As it drifted, the animal seemed to be flailing. It folded and shape-shifted, resembling a taco, then a dumbbell, then a bicycle seat.
“It’s falling,” Krishnamurthy said.
“Poor Trichoplax. It doesn’t know how to swim,” Prakash said. “This is going to be the shortest paper ever.”
Like Trichoplax, Prakash and his 15 to 20 graduate students, postdocs, and lab technicians seem to move in a thousand directions at once. One day I watched as Prakash taught a new doctoral student, Hannah Rosen, how to suction Trichoplax out of a petri dish full of seawater and settle them on a slide. Move too slowly, and the animal will attach itself stubbornly to the syringe, Prakash explained, his hand darting toward the slide with the speed and precision of a heron’s beak. To prevent Trichoplax from creeping off the slides, Prakash has built a small well out of double-sided tape, which he calls a jail. “For the first 30 designs we made, it figured out how to break out of the jail,” he said, with obvious fondness. “It can slip under even the tiniest of gaps. It’s quite remarkable.”
Under low magnification, the Trichoplax looked like a miniature work by Jackson Pollock— splatters of paint, frozen mid-sling. As Rosen zoomed in, however, an animal flowed across my field of vision, rapidly propelled by its scintillating ciliary fringe. It morphed before my eyes, transforming from something that resembled Australia into a ghostly, yawning head. As Rosen zoomed in further, the cells seemed to be simultaneously flowing as one, like a spilled milkshake running downhill, then jostling up against one another, like thousands of people rushing out of a stadium. Rosen and I stared at the animal, transfixed. “This is as chaotic as life can get,” Rosen said. For a moment I envied Trichoplax and its brainless, shapeless flow.
From the perspective of an evolutionary biologist, Trichoplax lies on the cusp between unicellular and multicellular animals—a turning point when single-celled, sperm-like organisms banded together as unified animals. To physicists like Vivek Prakash (no relation to Manu), who worked on Trichoplax in Manu’s lab at Stanford and recently started his own lab at the University of Miami, the animal is an example of “active matter”—a system that has no central authority but still maintains its coherence. Examples of active matter can be found everywhere in nature, including the acrobatic maneuvers of flocks of starlings, and the shimmering bait balls formed by schools of fish. Life itself depends on leaderless coordination, starting with the exquisitely choreographed balance of physical forces required to sculpt tissues in a developing embryo.
Trichoplax is a single animal whose cells behave like a flock—but only up to a point, Manu Prakash and his colleagues have found. Working together, Trichoplax’s beating cilia can drive the animal toward food and away from danger. But the cilia are only loosely coordinated. When they beat in opposite directions, the animal stretches, sometimes splitting into two or three separate clones. Sometimes the cilia will create a small fracture that widens into a hole, forming a donut shape that then breaks open into a long, skinny string.
By analyzing hundreds of hours of video of Trichoplax in motion, Prakash and his team are now working to quantify just how big the animal can get before the cilia tear it apart like rebellious armies. They’re also trying to figure out how Trichoplax’s thin tissues remain intact, even as the cilia pull its body in opposite directions. One clue comes from the waves of cellular shrinkage and expansion—faster than any observed in other animals—that allow the animal’s tissue to switch rapidly from soft to stiff in order to absorb physical stress.
In the computer simulations that the Stanford lab has built based on Trichoplax’s body and motion, Prakash and his team have begun to tweak aspects of the animal’s biology to create new properties that don’t exist in nature. When the team virtually strengthens the protein bonds between Trichoplax’s cells in a computer model, for example, the resulting animal is stiffer and displays new patterns of motion. For Prakash, Trichoplax is a kind of primordial Play-Doh—a way not only to understand animals that exist today but also to discover synthetic animals and materials that could exist, he says.
Among the many unsolved Trichoplax puzzles, one of the most mysterious is how the animal’s individual cells talk to one another. Smith, the neuroscientist at the National Institutes of Health, wants to know how Trichoplax senses its food, moves toward it, and releases the chemical signals necessary to make its cilia stop beating while it dumps out digestive enzymes and absorbs nutrients through its bottom layer. In other words, if the thousands of cilia that propel Trichoplax behave like a flock, where are their shepherds?
Smith and her colleagues have found a series of evenly spaced cells along Trichoplax’s periphery that she thinks may help herd the cilia by secreting a chemical signal that makes them pause. The chemicals are similar to the neurotransmitters that regulate appetite and contractions of the digestive tract in humans, according to the neurobiologist Diego Bohórquez, of Duke University. When many animals are grouped together, a single Trichoplax releasing the chemical can trigger its neighbors to secrete as well, causing the whole group to slow down and graze on algae “much like bison on a grassy plain in Yellowstone,” Borhórquez wrote in a 2018 article in the scientific journal Brain Research.
There’s much more to learn about Trichoplax’s movements, however, Smith notes. The molecules that cause the animal’s cilia to pause work far too slowly to control Trichoplax’s fastest movements, she says. “If you watch movies of the animal gliding on its cilia, you see that the animal can change directions really rapidly, within seconds or less than seconds.”
Ultimately, Prakash hopes to understand how Trichoplax can survive the violent forces of its own mutinous body—as well as harsh environments like the rugged California coast, where a six-foot wave can pummel tiny ocean creatures with the force that a 1,000-mph wind would have on a human being.
When Prakash and his team reach Monterey, a red tide caused by billions of plankton has turned the water so dark that it looks like obsidian. Crouching in the sheltered harbor of the Monterey marina beside a sailboat christened Diablito, Prakash slides his arm elbow deep into the water and draws up a length of fishing line. This time, the trap is intact.
Prakash hands it to staff scientist Hazel Soto Montoya, who puts it in the Igloo cooler with reddish seawater she has filled at the marina. Soto Montoya is currently studying the symbiotic bacteria that live in Trichoplax’s body, so she wants to re-create the ecological milieu in which they found it, red tide and all.
Next, we drive to the Hopkins Marine Station, a venerable Stanford lab set on a cypress-ringed outcrop of rocks jutting into the Pacific Ocean. It’s nearly dark, but Prakash decides that the team should search the tide pools surrounding the station for smooth, flat rocks or shells where Trichoplax may lurk unseen. Rolling up the cuffs on our pants and donning waterproof shoes, we tiptoe over pale-green sea anemones and crowded colonies of indigo mussel shells. As the sun sets, turning the tide pools violet, Prakash holds up a rock and turns it over in his hand. “It is impossible to find them, because there are literally infinite places they could be,” he muses.
Some scientists believe that Trichoplax, with its stripped-down body plan and easy-to-manipulate genome, could be a useful model organism for medical researchers. It’s especially intriguing because it breaks the rules that most lab animals follow: Unlike mice or fruit flies, Trichoplax has an indefinite life span, rapidly heals, and never—so far as scientists can tell—develops cancer. “We’re always trying to figure out what the rules are,” says Billie Swalla, a biologist at the University of Washington who studies regeneration in weird animals like acorn worms, which can regrow their heads. Studying rule breakers like Trichoplax, which can tear themselves apart and heal in minutes, could yield insights into the treatment of human injuries like damaged spinal cords, she says.
While Prakash agrees that the animal holds great promise for biomedical research, his pursuit of Trichoplax is about more than its practical applications. “I also study it for its beauty and elegance,” he says.
We explore the tide pools until the sun goes down, then go out to dinner. Only as the meal ends, around 9 p.m., does it dawn on me that Prakash intends to go back to the lab that night to keep searching for Trichoplax. The team has microscopes set up in one of the Hopkins Marine Station classrooms—a quiet, monastic room well suited to the search for tiny, near-invisible organisms in slide after slide after slide. After sitting in the harbor for a couple of weeks, each slide is a tangled jungle of biofilms and other organisms, any one of which could be concealing a tiny, flat, transparent Trichoplax. A single slide can take an hour to search, and each of the three cases contains 20 slides. It seems like the kind of activity that could drive a person crazy, I comment to Zhong and Soto Montoya. Yes, they nod, with beatific smiles.
When the team leaves for the lab, I retreat to my dorm room at the Monterey hostel, defeated. I am not hardcore enough to hunt wild Trichoplax, I think. I take a nap. At 11:32 p.m., my phone lights up. It’s a video text showing Zhong and Soto Montoya huddled around the microscope, looking buoyant. Zhong has found a Trichoplax. “That’s it, 110 percent,” Prakash says. “It’s beautiful, beautiful!” On a computer screen that shows the display from the microscope, Trichoplax looks like a glowing, pulsing orb surrounded by cosmic protoplasm. Soto Montoya finds a second, bigger animal. They sign off and keep scanning each slide, one by one, until 4 a.m.
Later that morning, I reconvene with the team. Prakash’s cold has gotten worse, and Soto Montoya and Zhong are swaying with exhaustion. Still, they sit down, pull the remaining slides out of the seawater bath, and start looking for more animals.
They keep a close eye on the two wild Trichoplax they’ve found. “Is it alive? Is it happy?” Zhong asks. Both are alive, though their happiness is harder to assess. The team will have to flush the seawater regularly and keep it at the right temperature, or bacteria and algae will start to overgrow the Trichoplax and kill them, Prakash says. He instructs Soto Montoya and Zhong to draw whatever organisms they find around the two animals on the classroom blackboard, in order to document the ecosystem. Bit by bit, a chalk menagerie of minute ocean creatures fills the blackboard. To identify the microorganisms, Prakash refers to a famous textbook on marine invertebrates, Animals Without Backbones, which was co-written by Vicki Pearse and her husband, John, another famous marine biologist. (The couple live down the street from the Hopkins lab.) The animal names sound like pasta: vorticellids, spirobids. One of the drawings looks, to my exhausted brain, like a martini olive with cat whiskers.
Sleep deprived and sniffling, but still determined to make the most of the team’s final hours in Monterey, Prakash decides to immerse more traps at an abalone farm in the harbor. To access the farm, we climb down a cold, wet ladder into the dark shadow of the dock, and stand amid slippery piles of drying salt-encrusted kelp.
Sea lions lounge on the pylons around us, barking and farting. Prakash places the traps inside the abalone cages, where they will be protected from waves and curious sea lions, and uses thick ropes to lower the cages into the water. The quiet, deep water seems like the perfect place to catch more Trichoplax. Soon, Prakash and his students will be back to find out if it is.
Cover illustration by Melanie Lambrick.
Posting of this article is courtesy of The Atlantic. The article originally appeared in Life Up Close, a project of The Atlantic supported by the HHMI Department of Science Education.
(c) 2017 The Atlantic Monthly Group LLC (This article was originally published on the website www.TheAtlantic.com and is republished here with The Atlantic's permission.)
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