Darwin's Disciple

By Tom Nugent

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Microbiologist Carl R. Woese '50 in 1977 discovered an entirely new domain of one-celled organisms—the “archaea”—and thus rewrote the basic “phylogenetic tree of life” that had remained essentially unchanged since Darwin. His astonishing discovery shook the science of biology to its roots . . . and triggered some powerful resistance among mainstream biologists who continue to challenge his findings (see "When Theories Collide").

He's a legend in American biology, a research giant who has changed the way science thinks about evolution.

You'd never know it by looking at his lab. Tucked away on the third floor of an ordinary red-brick classroom building, Dr. Carl Woese's research facility at the University of Illinois hardly seems impressive at first glance: there are a couple of computers, a couple of battered filing cabinets, and a dog-eared paperback copy of Darwin's Origin of Species lying on a cluttered table.

Did this drab workspace really provide the setting for Woese's paradigm-busting discovery of a new form of life?

As the headquarters for one of the world's most complex and challenging scientific investigations, the lab strikes a visitor as surprisingly low-tech. Nor does the scientist himself seem especially imposing. Small-boned and slender at age 74, he wears a dull green work shirt, wrinkle-free polyester slacks that look as if they just came off the rack at Wal-Mart, and a pair of frayed Nike running shoes with their tongues hanging out.

At first glance it's hard to believe you're in the presence of a molecular biologist whose theories about the origins of life have stood contemporary evolution on its head.

Quiet and self-effacing—one colleague even describes him as “shy”—the soft-spoken Dr. Woese doesn't give many interviews. But if you can find a way to get him talking about how modern biology has “completely dropped the ball” by mostly ignoring the microorganisms that make up 95 percent of life on Earth, he'll startle you with the passionate intensity of his blunt declarations.

“I'm going to be scandalous about this,” he exclaims, when asked to describe his “most important contribution” to biology. “I've been put here to pick up where Darwin left off! All of his descendants dropped the ball—and you had to turn to some people who knew about molecular biology in order to get the ball rolling again. But now it's happening, and I'm feeling more hopeful than ever.”

He pauses, gazes around the dusty lab, then waves toward the flickering computer screens where vast arrays of RNA-sequencing data await his next operation. “I'll tell you this much: If Darwin were alive today, he'd be sitting in my lab—not in the lab of some 'classical evolutionist.' Because he would know where the forefront of evolution was. He knew it then, and he would know it now.

“The forefront is the molecular world. It's the microbial world as well—and that's 95 percent of the diversity of life on this planet!”

As many of his friends and colleagues have noted, the outspoken Woese (rhymes with “knows”) doesn't mince words while describing the “wrong turn” that mainstream evolutionary science took soon after Darwin. In the unvarnished opinion of this venerable microbiologist, who's been conducting research and teaching students at the University of Illinois since 1964, the “ball was dropped” when the evolutionists of the modern era began using their high-tech tools to analyze the dynamics of cellular physiology from moment to moment while losing sight, for the most part, of the key role played by evolution in the development of those very processes over eons.

According to Woese (whose early training at Amherst was in physics, not biology), the key flaw in contemporary evolutionary science has been its failure to confront the problem of how microorganisms evolved during the 3.5 billion or so years that preceded the emergence of larger life forms.

“Look, the study of life just doesn't make any sense unless you talk about evolution throughout its entire history,” he told Amherst. “Life is a historical unfolding, an ongoing process, and to understand that process you have to do more than just study it at any given point in time.

“The whole history of 20th-century biology—or at least mainstream biology, which is the molecular stream—has had very little respect for evolutionary matters. Until quite recently, in fact, it's been all about understanding biology in the here and now, in terms of structure and function. Well, I'm sorry, but that just doesn't do it. You've got to understand where the cell came from and what it is. And you've got to understand how communities of cells evolved together over millions of years, in order to see the picture of life in a coherent, comprehensive way.”

Sighing with frustration, he shakes his head. “Instead of taking microbial evolution into account, there was this sort of game the microbiologists were playing—a game called 'Let's take cells apart, and get a complete listing of their parts and how they work, and then we can put the cell back together again, okay?'

“Well, so what? So what? You won't understand cells simply by understanding their various parts! You have to have a concept of the whole—and a concept of the whole is one of the things you go to evolution for.

“As a researcher, I took the direction I did because I saw that the nature of cells can only be understood if you have some idea of how they came into being, of how they evolved over the entire history of life on earth.”

It took Carl Woese nearly 20 years of tedious daily labor to create his system for comparing the molecular structures of thousands of one-celled creatures, in order to assemble a road map (the “phylogenetic tree”) that would show how life evolved in the invisible world of the microorganisms. (“It's as if he'd lifted a whole submerged continent out of the ocean,” German biologist Gunter Wachtershauser told a reporter.)

While painstakingly studying microorganic gene sequences in 1977, Woese stunned the American biology establishment with his discovery of a group of one-celled organisms that were so different from known bacteria (the “prokaryotes,” in biological parlance) and plants and animals (the “eukaryotes”) that they amounted to nothing less than a “third domain” of life. He said that the archaea were anatomically different from both the prokaryotes and the eukaryotes.

Suddenly Woese and a longtime colleague at the University of Illinois, Dr. Ralph S. Wolfe, had blasted apart the century-old evolutionary paradigm that had grown out of Darwin's 1859 Origin of Species. That paradigm, taught to generations of American high school students, said that all life stems from two great organic kingdoms—the world of cells that lack a nucleus (the bacteria), and the world of “nucleated” cells (plants, animals, and eventually human beings).

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Woese's finding wound up as front-page news around the world. Almost overnight the discovery (primarily via comparisons of ribonucleic acid gene sequences in different microorganisms) of a one-celled, methane-based organism for which he created a new name, the “archaea,” began to challenge the fundamental truisms of evolutionary science—and to trigger heated controversy throughout the ranks of biological researchers. Suddenly, many biologists felt compelled to re-think their assumptions about the evolutionary relationships among different species, and they began to question the common scenario in which life began with a lightning strike into a primordial “chemical soup.” Faced with Woese's revelation—that there were three main branches on life's tree, not two—microbiologists now had to challenge their entire “phylogenetic classification” system, which had split all life forms into two basic groups (those with cell nuclei and those without).

According to the “classical evolutionists,” whose paradigm had reigned until Woese's revision, the great tree of life had divided at some point into those two great branches—the bacteria (no cell nucleus) and the kingdom of plants and animals.

Woese's discovery immensely complicated that simple explanation of life's evolution. At the same time, the fact that the archaea were methane-based microorganisms of the kind that can live only in hot sulphur springs, seabed volcanic vents, or similarly harsh environments raised the possibility that life may have begun not with a lightning strike into “primordial soup,” but deep within a cavern or undersea volcano as super-heated chemicals interacted over time.

Within a few years of his discovery, Woese's ideas were being debated by microbiologists everywhere, and he eventually won microbiology's most coveted prize, the Leeuwenhoek Medal, in 1992. He was elected to the National Academy of Sciences in 1998, received a National Medal of Science in 2000 and a $300,000 “genius” award from the MacArthur Foundation.

By discovering what most American biology textbooks now describe as “a simple cell-type that existed before the eukaryotes” (the one-celled ancestors of plants and animals and humans), Woese posed another troubling question for biologists: Was there, perhaps, a “universal ancestor” type of single-celled, non-bacterial life that over time evolved into birds, trees, dogs, apes and humans?

 

Recognizing the importance of Woese's discovery, many of today's introductory microbiology textbooks also feature his “phylogenetic tree” (an all-inclusive catalog of organic families and their lines of descent) as the opening illustration.

Most experts on evolution seem to agree that Woese's contribution to the understanding of biological evolution will remain a permanent landmark in American science. “His work has revised bacterial systematics, microbial ecology and the study of the origin of life,” says University of Georgia microbiologist Dr. William B. Whitman. “I don't understand why Carl Woese hasn't received the Nobel Prize.” Adds Dr. Charles Miller, the director of the University of Illinois' School of Molecular and Cellular Biology and a longtime Woese colleague: “Carl Woese is a legend in microbiology, and deservedly so. Yet he's also a dedicated teacher. He really enjoys working with our undergraduate students.

“I tell all the faculty we hire at Illinois, when I'm talking to them about the importance of our teaching mission, 'If a legend like Carl Woese can teach students day in and day out, so can you!' And Carl is not a pretentious guy. He's absolutely dedicated to his research, but on the personal level he doesn't take himself all that seriously. He doesn't demand homage every hour in the day. He's simply a researcher who has worked with astonishing tenacity, year in and year out, to come up with the discoveries that have made him famous.”

According to Miller and several other colleagues, Woese has survived the stresses of scientific controversy by keeping his sense of humor intact. Ask him what he does in his “spare time” for recreation, he growls: “I drink beer!” Then, hooting with laughter: “Really, I sit at home and drink beer! It's the cheapest way I can get drunk—and I get drunk so I can have ideas and write [scientific] papers better.

“Let's face it, I'm a pretty strange guy, and it's nice to loosen up. Beer helps me to unwind. I don't get drunk like you do at fraternity parties—I just sit there and get mellow and see the world in a few more dimensions!”

Born and raised in Syracuse, New York, Carl Woese arrived at Amherst in the late 1940s, after having experienced “one of the most unmemorable upbringings of anybody, okay?” The son of a consulting engineer and a graduate of the private Deerfield Academy, Woese landed on campus intending to study math and music, his two ruling passions. And when he shared a math prize with future Nobel Prize-winning physicist Henry Kendall '50 (a co-discoverer of the quark) in his freshman year, Woese assumed that he would go on to a career in mathematics.

Instead he fell in love with physics while studying under William M. Fairbank, who would go on from Amherst to become “one of the great low-temperature physicists in the world.” Fairbank inspired Woese to go on for his physics Ph.D. at Yale, and it was there that Woese became fascinated with biophysics: the study of biological processes at the molecular level. After earning his doctorate in 1953, Woese took a brief fling at medical school (“I couldn't bear to treat sick children, so I quit”), then studied at the famed Louis Pasteur Institute in Paris and worked for a while in an experimental biophysics lab operated by General Electric. By 1964 he had signed on at the University of Illinois where, ever since, he has taught microbiology and studied the molecular processes that go on inside single-celled creatures.

Soon after arriving in Urbana-Champaign, Woese dared to tackle a fundamental problem in microbiology—a key problem that had stumped both Stanford's C.B. van Niel and Roger Stanier of Cal-Berkeley, the leading microbiologists of the generation preceding Woese's. The problem, in a phrase: How could you classify—or “phylogenetically order”—the vast ranks of bacterial and other one-celled organisms, given the fact that their small size and vast complexity made it extremely difficult to study and identify their anatomical and physiological features?

Years later, after gaining a worldwide reputation for solving the problem by making the key identifications at the molecular level by sequencing genetic macromolecules and then comparing one organism's genetic inheritance to another's, Woese realized that his training in physics at Amherst had played a major role in his discoveries. As he later told reporters: “I hadn't been trained as a microbiologist, so I didn't have their bias [against classifying micro-organic species]. And my physics background had taught me the vital importance of using 'Occam's Razor' whenever I could, because it had taught me that most questions—no matter how seemingly complex—usually turn out to have rather simple, straightforward answers.”

And so began what for Woese would be several decades of analyzing cellular RNA in order to compare one type of microorganism against another, en route to his over-arching accomplishment: the establishment of a phylogenetic map, or “tree of life,” which allows biologists everywhere to understand the ancestral links among everything that lives on earth.

An epochal accomplishment? Most biologists today will readily agree, even though a few dispute Woese's identification of the archaea as a “separate domain of life.” [See “When Theories Collide.”]

Ask Woese himself, though, what he makes of his 1977 discovery, and he'll surprise you by pooh-poohing the idea of his own genius.

“Look, I'm just an average guy, okay?” he says with a light-hearted chuckle. “I just happen to have a pretty good intuition regarding biology. I may have brought the complete phylogenetic tree into being, but all I am is a midwife. I'm just glad I was there to help bring it in.

“Do I feel proud about it? Yeah, sometimes. But it's not a 'Yertle the Turtle' kind of feeling, and I don't sit around thinking how great I am. I don't do this kind of work for monetary gain, and I don't do it for the kind of societal gain that you might receive for winning the Nobel Prize.

“I come in here every day because I love this stuff, that's all.”

He looks around the dusty, crowded lab and breaks into a contented smile.

“To be able to study the past, and to look back down the road into what was happening three or four billion years ago—what a privilege!”


When Theories Collide...

Ernst Mayr & Carl Woese Lock Horns In “Archaea” Dispute

By Tom Nugent

Carl Woese believes the “tree of life” contains three branches: the bacteria (prokaryotes), the plants and animals (eukaryotes), and a third group of one-celled creatures (the archaea) which also represents a “unique domain of life” on Earth.

Ernst Mayr, emeritus professor of comparative zoology at Harvard University, insists that Woese has it wrong—that there are only two branches on the “tree”: the bacteria and the plants/ animals. (This is the traditional way in which life forms have been classified since Charles Darwin.)

“Dr. Woese's work in microbiology is very important, and he is certainly a pioneer,” Mayr told Amherst in a recent interview.

“But unfortunately, he has greatly over-emphasized the importance of the archaea. There is no justification for giving them the same rank as the eukaryotes, or for classifying them as a new domain.

“The archaea are actually prokaryotes, and elevating them to the rank of a domain is simply absurd. I think the problem may be that Dr. Woese was trained in physics—and he applied his lack of knowledge about biology to his methods of classification.”

Although the debate may sound at first like a battle over mere semantics, it's actually quite important in the ongoing struggle among scientists to determine the future course of biological research. That's because the two points of view actually describe two radically different approaches to identifying and classifying life forms: “molecular” versus “morphological.”

If Woese's view prevails, most biologists will probably end up accepting his molecular-analysis-and-RNA-sequencing yardstick as the best tool for classifying one-celled creatures. But if Mayr proves to be more convincing, biological science will probably stick with the more traditional morphological approach, which calls for identifying one-celled life on the basis of cellular anatomy and physiological characteristics.
Both camps have their strong supporters, but many biologists today seem convinced that Woese's high-tech molecular approach will ultimately prevail. The University of Illinois microbiologist suggested as much, himself, in a recent paper on the debate with Mayr, published in the Proceedings of the National Academy of Sciences in July 1998, where he declared:

“The disagreement between Dr. Mayr and myself . . . concerns the nature of Biology, itself. . . . His is the biology of visual experience, of direct observation. Mine cannot be directly seen or touched; it is the biology of molecules, of genes and their inferred histories.”

Tom Nugent is a freelance writer who lives in Hastings, Mich.

Illustration: Karen Greenburg

Photos by: Bill Wiegand