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U of I's Loner Revolutionary

A quarter-century after being shunned as a radical, Carl Woese receives one of science's highest honors.

Carl Woese

Notoriously shy, yet uncompromising in his scientific convictions, the 75-year-old Woese started a revolution that shifted the emphasis of the study of evolution away from what can be seen with one's eyes to the biological lineage that is encrypted in an organism's cells.

In 1977 Woese discovered that a group of single-celled organisms that were classified as bacteria but were unlike any other form of life. The archaea, as he christened them, inhabited environments once considered too extreme to support life, such as sulfur springs, glacial ice, and volcanic vents. These environments likely mimic the conditions that existed on primordial Earth.

Woese's announcement that the archaea represented a new domain of life shocked scientists. Recalled a colleague, "It was as if Woese had announced that aliens had just landed in our backyard." The greater surprise, which scientists were yet to realize, was that the means by which Woese had reached his conclusion would redefine the way they studied evolution.

As is often the case with revolutionaries, Woese entered the field he was destined to change via an unconventional route. Woese earned his bachelor's degree in physics from Amherst College, then a doctorate in biophysics from Yale University. He joined the Department of Microbiology at Illinois in 1964, where he has been ever since.

It was at Yale that he became interested in the origins and evolution of DNA, the cellular structure containing the blueprints for constructing an organism. To trace DNA's evolution, Woese realized he needed a more complete "tree of life" for microbes. Trees of life are diagrams biologist construct to chart the evolutionary relationships among species. Woese reasoned that if he could find modern bacteria that were direct descendants of ancient microbes, he would likely gain insights into the structure of the first cell and the origins of the genetic code.

For centuries, scientists tried to understand nature and its evolution by concentrating on the big stuff—plants and animals. They grouped these species into elaborate "trees" based on differences and similarities they could see—leaves versus needles, six legs versus dozens, live birth versus egg laying. Fossils helped to fill in gaps in genealogical lineages.

Relying on physical differences for categorizing one-celled microbes proved trickier. Microbes came in only three discernable shapes—rods, spheres, and spirals. Attempts to group them based on other observable criteria also proved useless. For instance, grouping a microbe by whether it could convert sunlight into energy (algae) or was motile (amoeba) proved to be as arbitrary, and incorrect, as designating a whale as a fish because it could swim.

By the time Woese entered the evolution arena, scientists had begun looking at cell structure for clues toward organizing the unicellular world. They also had grouped life into two "super domains." The prokaryotes were simple structures with no nucleus—bacteria fit in this category. Eukaryotes had cell nuclei and included all the multicellular beings, from fungi to people.

In the early 1960s, scientists had developed techniques for separating DNA and RNA, the molecule that transcribes DNA, into their individual sequences of each nucleic acids. Nucleic acids are like the letters in the genetic alphabet, which when put together form words (amino acids), and the strings of genes become sentences (genes) that instruct cells on what proteins to form.

Scientists had determined that they could determine how closely one organism was related to another by comparing their gene sequences and counting the number of differences between them. The greater the differences, the less they were related.

"The concept of mapping evolution by comparing genetic similarities and differences had been on the table a few years before Woese," explains Norman Pace, a microbiologist at the University of Colorado who met Woese while a postdoctoral student at U of I. "But the other scientists didn't know which gene to use. Choosing the right gene is what Woese did brilliantly."

The genes scientists first used for comparison were for proteins, like insulin, that were not present in all organisms. Woese chose RNA, focusing on subunits called ribosomes. Because ribosomal RNA (rRNA) is essential to building the kinds of proteins that no life can do without, it is conserved as life evolves. rRNA is found in everything from bacteria to giraffes, making it ideal for tracing life's lineage.

The work was slow. For 10 years, working alone nearly every day, 8 to 12 hours at a stretch, Woese hunched over a light table scrutinizing the bar-code-like patterns on thin photographic film. The patterns represented the rRNA. The first gene took him a year to sequence—work that today can be done in days. By 1976 he had sequenced the ribosomal genes of 60 bacteria.

In April of that year, Ralph Wolfe, a long-time colleague and microbiologist in LAS, presented Woese with the organism that would alter the study of evolution. Wolfe had been studying a group of organisms called methanogens, which produce methane gas—the "marsh gas" that hangs over swamps. Although methanogens look the same as bacteria when viewed under a microscope, their biochemical behavior is much different. "We had no idea where they fit in among the bacteria," recalls Wolfe. "So I gave some to Woese to look at. A few days later he came walking down the hall, shaking his head, because they were like no other life form he'd seen. He reran the tests, eliminating any potential sources of error, and got the same results. They were neither prokaryotes nor eukaryotes, they were a whole new domain."

Norman Pace recalls Woese's reaction: "It was like he had seen the face of God in a microscope."

When Woese issued a news release in 1977 announcing his discovery of this third domain of life, other microbiologists didn't share his revelation. After a flurry of newspaper stories, interest in Woese's work evaporated. Replacing it was a bitter, decade-long battle between him and "the old guard" of microbiology. Wolfe was advised by a prominent Nobel laureate to distance himself from Woese's work for the sake of his career.

Some scientists ascribe the animosity between Woese and other biologists to the esoteric techniques Woese was using—he was one of maybe three scientists in the world who had mastered the laborious sequencing techniques then available. Others attribute it to Woese's loner personality, which was deeply wounded by rejection. Woese believes the cool response he received from the biological community was simply the price one pays for overturning established dogma.

At the time, scientists were saying that life evolved from some primordial first cell, but they had no notion of how life got from that cell to what exists today, content to attribute gaps in the lineage to "historical accidents." Woese presented them with a framework for tracing evolution back to that first cell. But this framework reconfigured the tree of life in startling ways. With the addition of a third branch for the archaea, the tree was now dominated by single-celled organisms. The eukaryotes were relegated to a small branch, with plants and animals occupying only twigs on that branch. Even more stunning was that based on the criteria Woese used in building this tree, the archaea were more closely related to people than they were to bacteria.

His discovery of the archaea also exposed how little scientists knew about a category of life that is now thought to constitute 95 percent of the biomass on Earth. "Imagine going out into the countryside and not being able to tell a snake from a cow from a mouse from a blade of grass," says Woese. "That was the level of our ignorance about microbes."

Throughout the "dark" years, as Woese crowned the years when he was shunned by the biology community, a small cadre of scientists remained loyal. And as more scientists began applying Woese's techniques, the data supporting his assertions grew.

By the mid-1980s, his tree of life was appearing in scientific papers and at meetings. Accolades began pouring in by the 1990s. First was a MacArthur Foundation Genius Award, then the Leeuwenhoek Medal, microbiology's top honor. In 2000, he was presented the National Medal of Science.

Today, entire chapters in college textbooks are devoted to molecular evolution. "It is only a matter of time until the ‘Woesian Revolution' will be taught in high schools and junior highs along with Darwin," asserts Wolfe. "His accomplishments are just that big."

Over the years, Woese has gained satisfaction in watching his revolutionary ideas become mainstream. And the accolades have softened the sting of the initial rejection.

coin

Although Woese skipped the White House ceremony in 2000 where he was awarded the National Medal of Science (he had work to do), he did go to Sweden to accept the Crafoord medal. He brought his family, too. After years of being an outsider, Woese is coming to terms with a new role—grandfather of a great new field.

Less than two weeks after Carl Woese accepted his Crafoord medallion, the University of Illinois learned that two more if its professors would soon be making a trip to Stockholm. Read more about the two Nobel Prize winners in Bringing Home the Gold.

By Holly Korab
October 2003