The Evolutionary

A year after winning a MacArthur “genius” grant, UT biologist David Hillis is still tracing branching patterns on the tree of life—and chasing frogs.

June 2000By Comments

David Hillis has spent many wet nights chasing frogs. Once, when he was camping in Queensland, Australia, it started to rain, and to hunt frogs without getting his clothes wet, he set out naked into the rainforest. Another time, he was in Mexico with a group of undergraduate biology students when a downpour at three in the morning forced them from the beach where they had camped; the eighteen-mile drive to the nearest town lasted until dawn because he kept stopping the van to jump out and examine the giant frogs making their way across the road. The first time he asked his wife for a date, when they were freshmen at Baylor University, he invited her to go out and listen to frogs. (Before that, he had invited her to come up to his room to listen to “Voices of the Night,” a record of frog calls. She refused.)

But frogs aren’t the half of it. Hillis, 41, an evolutionary biologist and the director of the School of Biological Sciences at the University of Texas at Austin, won a $295,000 MacArthur Fellowship grant last year; one thing he hopes to do with the money is travel to Madagascar to study crayfish. (The MacArthur “genius” grants recognize individuals of exceptional creativity and promise; past Texas winners include political activist Ernesto Cortes, writers Cormac McCarthy and Sandra Cisneros, poet Edward Hirsch, mathematician Karen Uhlenbeck, and the late disaster-relief expert Fred Cuny.) Every year, the MacArthur Foundation’s selection committee evaluates the recommendations of more than one hundred nominators from a range of disciplines and awards twenty to forty grants of $200,000 to $375,000, with no strings attached. For Hillis, the grant means freedom to pursue projects that might not receive backing from traditional sources, like the National Science Foundation. “Most grant agencies like to fund projects that are pretty much a sure thing,” he says. “But in the history of science, the things that have turned out to be the most fascinating are also the most risky.”

In fact, says Hillis, his entire career has been an example of how pursuing an obscure interest can yield unexpected rewards. He has been a key contributor to the field of phylogenetic analysis, which is concerned with figuring out how life-forms are connected on the evolutionary tree. “When I first started working on phylogeny, as a graduate student, most people considered it to be a very limited field that was only applied to a small area of biology, taxonomy, but I was interested in it, so I pursued it,” he says. “But it turns out that my work has lots and lots of different applications to many different areas.” Those applications range widely—from tracing the origins of human diseases to figuring out that whales are more like cows than was previously thought. Two years ago, phylogenetic analysis of HIV samples helped convict a Louisiana doctor of injecting his ex-girlfriend with the virus that causes AIDS.

With the help of the techniques that Hillis and others have developed, biologists of all stripes are mapping the course of evolution, using computers to draw the branching patterns that connect species or individual organisms to their common ancestors.

Though Hillis spends much of his time in the lab or on the computer—developing the theory and methods of phylogenetic analysis—he remains an eager field biologist. One Friday evening in March, I accompanied Hillis and a group of graduate students on a trip to Bastrop County to look for frogs. The early spring in Central Texas had been dry, not so good for frogging (which is best done on warm, wet nights), but they had decided to try anyway. As we left Austin it was warm, at least, and the bruise-colored sky, sliced periodically by lightning, seemed to promise rain. Sure enough, a couple of hours later we found ourselves sitting in his truck on a stretch of pastureland dotted with small ponds, listening to hail beat down on the windshield as we waited out the storm.

Hillis is like the kid who not only collects snakes but whose enthusiasm makes all the other kids want to collect snakes too. He is friendly, pensive, and attends closely to his surroundings, about which he is hugely knowledgeable. While waiting in the truck, he cheerfully ran down a list of half a dozen local frog calls. “So the Houston toad sounds like this, high-pitched”—Hillis, trilling his tongue, produced a Houston toad sound. “The chorus frog, Strecker’s chorus frog, is a single note”—he made a noise like wind whistling through a crack—“and the Hurter’s spadefoot sounds like someone throwing up. When a bunch of them are calling, it sounds like a whole fraternity throwing up”—Hillis made several retching sounds.

The rain ended abruptly, too soon to have soaked the ground; worse, it had brought with it a sharp, frog-discouraging drop in temperature. Circling one pond after another with flashlights and headlamps, Hillis and the students didn’t hear any calls and found only a few bullfrogs and leopard frogs. Still, they went after what animals they could: “Snake!” someone yelled at the sight of a small, dark head peeking out of the water, and Hillis, in long pants and high-top canvas sneakers, a headlamp strapped to his forehead, scrambled into the water to grab it. “Over here!” someone else called, and everyone ran through the thick mud to gather around the prize find of the evening: a large diamondback water snake coiled in the brown muck of the water’s edge, the pearly rear half of a catfish protruding from its wide-open mouth.

Trying to understand what Hillis does is a bit like following him through the mud as he seizes one animal after another: He tackles a wide range of problems. What ties them together is his passion for evolution itself. “To me,” he says, “it’s fascinating to think about the cotton fibers in my shirt, and myself, and if you went back a billion years ago, we have the same ancestors, the cotton plant that produced the cotton fibers in my shirt, and myself. If you went back a billion years ago and saw that one lineage of organisms splitting into two, it would have seemed completely insignificant at the time—two very closely related species—but follow those lineages forward in time, and it makes a big difference if you’re me or the cotton fibers in my shirt. At least it makes a big difference to me!”

His boyhood was spent moving from place to place—one long lesson in the diversity of living things. In 1964, when he was five, the family headed off to the Congo; his father, William, an epidemiologist with the Air Force, had been sent there to study hepatitis in chimpanzees. “All the kids’ toys were stolen on the trip over, but they had a whole zoo outside: monkeys, giraffes, elephants, zebras,” says William Hillis (who is now a professor of biology at Baylor). “It was a biological heaven to grow up in.”

The family’s stay in the Congo was cut short by the revolution that broke out the following year, but Africa had left its mark on Hillis. “It’s part of the reason I became interested in biology,” he says. “The way I entertained myself mostly was running around and catching butterflies and lizards. We didn’t have television or many other kids to play with, so I ran around the jungles of Africa, catching things.”

The entire Hillis family seems to have been standing near the front of the line when scientific talents were handed out: David’s mother, Argye, holds a Ph.D. in biostatistics; his younger sister, Beth, is a neurologist at Johns Hopkins, while his older brother, Danny, is a prominent computer scientist—known, among other things, for having built a computer out of Tinkertoys when he was an undergraduate at MIT and for starting the company Thinking Machines. (After the MacArthur grants were announced, the Dallas Morning News managed to contact William Hillis before he’d heard the news; when the reporter said, “I’d like to congratulate you on your son’s having won the MacArthur,” he replied, “Which one?”)

While Danny was the more serious one, David was “Huck Finn,” recalls Argye Hillis. “He was always out in the woods, turning over rocks, going fishing, having fun.” After Africa, the Hillises went on to live in Louisiana, Maryland, India, and then Maryland again, where David went to junior high and high school. William joined the faculty at Johns Hopkins, and David joined the Maryland Herpetological Society.

He would eventually publish eight scientific papers based on research he did while in high school. In one of his projects, designed to determine how environmental conditions affected the breeding patterns of salamanders, he enlisted the help of friends to construct a fence, several hundred feet long and ten inches high, by the edge of a pond where he had seen salamanders breeding the year before. The fence served to block the salamanders from entering the pond, guiding them instead into pitfall traps—cans or buckets that Hillis and his friends had buried at ten-foot intervals along the fence. From February until April of 1976, the seventeen-year-old Hillis checked the traps before school and again at dusk, counting and measuring the salamanders, noting the weather conditions, and recording these and other observations in one of the field journals he’d been keeping since junior high. (The fact that he liked to spend rainy nights watching salamanders breed, says Hillis, “probably explains why I didn’t have much of a social life in high school.”)

He chose to go to Baylor because it had a good natural history museum, and met his future wife, Ann Mackie, his first semester (“I spent the first six months trying to set him up with my roommate, since she was into frogs and so was he,” says Ann Hillis, now the director of U.T.’s Speech and Hearing Center). He also met Henry Fitch, the father-in-law of one of his professors and a University of Kansas herpetologist. In 1979, when he was twenty, Hillis took a semester off to accompany the 69-year-old Fitch on a four-month expedition to Mexico and Central America, during which they examined hundreds of species of plants and animals, including frogs of the genus Rana, which would later be the subject of Hillis’ Ph.D. dissertation.

In his study of Rana he combined more-traditional research with molecular phylogenetic methods, examining enzymes and DNA in the various frogs. It was an uncommon approach at the time, but the use of phylogenetics has since become widespread. Phylogenetic analysis is based on comparisons: Often, the reason related species share similar “characters,” such as wings or lungs, is that the present-day species are descended from a common ancestor who possessed some primitive version of that character; by looking at the species’ similarities and differences in the present, inferences about their evolutionary history can be drawn. What has changed recently is that scientists are now able to use genetic information in trying to puzzle out evolutionary relationships, comparing gene sequences and inferring how those sequences mutated over time. “So for instance, if you find out that all mammals have a particular nucleotide at a particular position [in a gene], then you can infer that the most recent common ancestor of mammals also probably had that same nucleotide at that position,” says Hillis. “If you see variation in that information, then you have to construct where the changes occurred in time.”

In other words, little differences in genes can indicate branching patterns on the tree of life. To trace those patterns requires not only recently developed methods for extracting, cloning, and sequencing genes but also considerable computing power. “We’re dealing with, oftentimes, tens of thousands of nucleotides in a given gene, and with changes across many hundreds or thousands of individuals or species, so it can be computationally really complex,” says Hillis. Much of his work is figuring out how to approach the computational problems: what the best methods are for tracing evolution by computer, and how to apply those methods to large sets of data.

The range of applications of these techniques gives the lie to the notion of evolutionary biology as a musty, museum-bound enterprise. “An unusual example of an application that people hadn’t really thought about until recently is viruses,” says Hillis. “Viruses change very quickly, and so one of the big applications of phylogenetic analysis is tracing the origin of new human diseases—looking at how they’re spreading through populations. HIV is a good example of that; it changes extremely quickly. So you can trace back in time and figure out when it came into human populations, how many times it has come into human populations, and what’s happening now. That information is really important for developing new AIDS vaccines and also can be used for actually tracing individual infections.” Hillis testified in the 1998 Louisiana criminal case against Dr. Richard Schmidt, who was accused of injecting Janice Trahan, his former lover, with HIV from one of his patients, after she ended their affair. Scientists at the University of Michigan and Houston’s Baylor College of Medicine determined the genetic sequences of virus samples from Trahan, Schmidt’s patient, and other HIV-infected individuals in the local population. Hillis then analyzed those sequences to infer the evolutionary history of Trahan’s virus strains, finding that they were indeed closely related to the patient’s strains.

On a day in February when I visited Hillis’ office, three jars were arrayed on his desk, each containing a pale, spindly-legged, flat-snouted salamander preserved in ethanol. Hillis was one of the scientists who identified the famous Barton Springs salamander, an endangered species that has played a central role in Austin’s development wars; more recently he has co-authored papers, to be published later this year, identifying several new salamander species and tracing the phylogenetic relationships among the different species of Central Texas.

The same techniques that helped incriminate Schmidt can be used to infer the history of the Edwards Aquifer, which feeds the region’s springs. Present-day salamanders are descendants of the few ancient ones who survived, millions of years ago, when the Southwest was transformed from a cool, wet region to a hot and arid one. “Most places like this, the salamanders have gone extinct,” Hillis says. “In Texas, what happened is they managed to find these little isolated cool, wet environments, mainly these springs and cave systems.” Those springs and caves might as well be desert islands as far as the salamanders are concerned, since they can’t get from one to another. So, to take one example, populations north of the Colorado River have been separated from those to the south for some twenty million years, ever since the river cut down through the limestone strata of the surrounding plateau. Determining how the different salamanders are related and how they evolved yields insights into the shaping of the land itself. “The history and relationships of these salamander populations record the whole geological history of the Edwards Plateau over the past several tens of millions of years,” says Hillis.

Biologists are finding history revealed at the molecular level, a record of life on earth inscribed in genetic material, and Hillis is at the forefront of this endeavor. “He’s an absolutely brilliant person,” says his friend Robert Baker, a mammologist at Texas Tech. “People often have said that scientists are characteristically childlike in their behavior, but of all the people that I hang around with, he is the one most like a kid. He’s like a four-year-old. He goes to work and has a great time. It’s just a joy to see how his mind works.”

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