Deb Aronson

Carl Woese and the Three Flavors of Life

First appeared in Muse: the magazine of life, the universe, and pie throwing in June 2010 under Profiles

You may not have heard of Carl Woese, but his discovery shook the very roots of biology. At a time when scientists believed all life on Earth could be divided into two categories, Woese (rhymes with “rose”) discovered a third. He persevered in the face of strong opposition, and ultimately triumphed. In the process, he opened our eyes to the vastness and diversity of the world of microbes.

Back in the 1950s, when the race was on to figure out how cells stored genes and passed them to the next generation—a race that James Watson and Francis Crick “won” by determining the structure of DNA—Woese, an elfin man with a powerful brain, was asking different questions.

What did the earliest cells look like? How did they evolve into what they are today? Ultimately, Woese wanted to know how cells, the “most essential units of all life,” got here in the first place. While the rest of the scientific world excitedly studied the roles of specific genes in a given organism—biology in the here and now, in other words—Woese believed molecular biology and genetics could help trace life back to its very beginnings.

Vanilla and Chocolate

Until Woese came along, scientists divided all life on Earth into two “domains”: eukaryotes and prokaryotes. Eukaryotes (you-CARRY-otes) are organisms whose cells have a nucleus—a sac inside each cell that holds its DNA. They include many-celled animals, plants, and fungi, and some single-celled organisms such as amoebas. Prokaryotes, also called bacteria, have just one cell with no nucleus (their DNA floats freely inside). That was it: organisms came in just two flavors; vanilla and chocolate, day and night. Woese thought this too; he had no reason—yet—to question it. On this classical tree of life, there were many twigs devoted to the eukaryotes, which had been intensely studied. Prokaryotes, about which much less was known, occupied a separate branch.

To get to the root, so to speak, of the tree of life, Woese sought the missing link—the most primitive cell in existence. “The microbial world was, basically, terra incognita for a long time,” says Woese. “I thought that’s what I would do first thing, bring in the prokaryotes.”

No Stripes, Beaks, or Spots

This might sound simple, but it definitely was not. Bacteria are notoriously difficult to study and to classify. Some need to be kept in a very special environment (one without oxygen, for example). And, because they can transfer their genes easily from one to another, that bacterium you think you are studying might have already changed.

From the outside, all bacteria are either rod-shaped or spherical, with the occasional spiral thrown in. Without stripes, beaks, or spots, they can’t be classified as easily as zebras, toucans, and ocelots can. To complicate things more, no one could see inside bacteria, so they couldn’t be classified based on how they looked internally either. Microbiologists, scientists who study microscopic organisms, eventually threw up their hands in despair and lumped all bacteria into a single group—the prokaryotes.

But Woese thought differently. Maybe it helped that he was not trained as a microbiologist, so he didn’t get the memo that classifying bacteria was a pointless and impossible exercise. In any case, he believed that to really understand the evolution of cells he had to determine how these single-celled creatures were related to one another, and for that he needed to create a family tree.

“Evolution” might make you think of primates coming down from the trees and walking on two legs, or the ways in which finch species on the Galapagos Islands differ from their mainland cousins. But evolution encompasses all life forms, not just many-celled eukaryotes. “It was an intuitive leap to begin with,” says Woese, “when I realized what I’ve got to do is go study evolution.”

But How?

Fortunately, a new method of comparing the RNA or DNA of different organisms had just been developed. It used enzymes to snip strands of the genetic material at precise points into short sequences. Strands from one organism could then be compared to another to find similarities and differences. Results showed up as fuzzy spots in distinctive patterns on X-ray film. But, while the technique worked, no one had yet used it on bacteria. Woese believed he could, but he was heading into risky territory with no guarantee that his effort would pay off. [Instead of studying the bacteria’s DNA, which contained their entire genomes, Woese decided to use only the ribosomal RNA—genetic material inside the ribosomes, or protein-making machines.]

“The question was how similar or different one taxon (or organism) was from another, and the degree to which two [RNA] sequences were similar or different,” says Woese. “If they were too similar you wouldn’t get anything meaningful, and if they were too different you wouldn’t see anything you could interpret.”

Luckily for Woese, the sequences, like Goldilocks, fell right in the middle.
It was mind-numbing, repetitive, solitary, and tedious work. It took him three years to sequence the RNA from about 100 bacteria and a few eukaryotes: duckweed, mouse, and yeast, representing plants, animals, and fungi.

“I couldn’t get very distracted because I had to use my mind very intensely at a low level,” he says. “I was very involved with the analysis of these spots. They were not simple to analyze. It took a lot of experience, not a lot of intelligence, but a lot of experience.” Woese was one of the only people in the world who could read and interpret the X-ray films. Today, with computers and automated sequencers, the work that took him thousands of hours would take less than a week; sorting through the strands of RNA would take a computer less than one day.

Woese didn’t mind the work. He persevered; he was patient, curious, and stubborn. His outsider’s personality also helped—he’s not unfriendly or a loner, exactly, he’s simply unconcerned about what others think. He asks the big questions, rather than shying away from them.

“About certain scientific things I have what’s called the courage of my convictions, though I don’t view myself as a courageous man,” Woese says. “The data are either right or wrong, and if they’re right you’ve got to make sure they are right. I trusted my intuition and then the data.”

Vanilla, Chocolate, and Strawberry

In the course of his research, Woese found, as he had suspected, that the RNA of the eukaryotes and the prokaryotes could be divided into two very clear “classes,” which were different from one another. Then, one day in 1976, 10 years after he began this bacterial family tree, Woese’s buddy Ralph Wolfe introduced him to a new creature that changed everything.

Wolfe liked to study outlandish prokaryotes that live in very hot, oxygen-free environments and produce methane gas (the stuff of farts). Wolfe finally succeeded in both growing these so-called methanogens in the lab and labeling them with radioactivity so that their RNA could be sequenced.

When Woese began studying Wolfe’s methanogen, he expected it to fit nicely into the prokaryote side of the two-domain system. “The big surprise was when we finally did do one of these methanogens … uh-oh, it didn’t fit into the prokaryote signature,” he recalls.

The methanogen didn’t fit with the eukaryotic signature, either. But it had certain spots in its RNA common to the prokaryotes, and certain ones common to eukaryotes. “We were clearly dealing with recognizably the same sequence, and it came in three different flavors instead of two,” says Woese. “It was this amazing walk through a garden of new plants. There’s something new here,” he remembers thinking. “We’ve got a fish on the hook.”

A fish on the hook indeed: it was a new life form. Woese named it archaea (ar-KAY-uh). This finding was huge, thrilling, and completely unexpected: it was as groundbreaking as Copernicus’s discovery that the earth orbited the sun. And Woese didn’t stop there. He looked at more methanogens to see if they fit this new pattern.

The more methanogens Woese studied, the more convinced he became that they represented a different form of life; the sequences that made up their ribosomal RNA were of a third form. And, because they share some characteristics with both eukaryotes and prokaryotes, Woese determined that the archaea are the most primitive cells, and the closest we have come so far to finding the common ancestor of all life on Earth.

Once he was completely confident of his results, he and Wolfe published their findings. There are three forms of life—archaea, bacteria, and eukaryotes—rather than two. Woese felt as if he had broken through an intellectual roadblock that had held people back in their thinking about evolution without their even realizing it.

Annoyed but Undaunted

But the belief that life forms belonged in two camps was very strong among scientists, even though no one had ever tested that assumption before. Some very important scientists pooh-poohed the announcement, even suggesting Woese was a crackpot, and that his findings were absurd.

“The belief that [all bacteria should be lumped together] was very strong,” says Woese, despite the fact that bacteria had originally been classified together only because they were all microscopic.

Wolfe, the methanogen expert, was friendly with Nobel Prize winner Salvador Luria. When the newspapers ran the story about the three domains of life, Woese says that Luria called Wolfe and told him, “You are in trouble; you’ve got to disassociate yourself from this chump. Your reputation is at risk.” Wolfe paid no attention to that advice, but it shows how some people felt about Woese’s findings.

Woese was annoyed but undaunted. He was used to working on his own and, as he says, he had the courage of his convictions. So for another 20 years he continued his research even though some scientists, including some very important ones, shunned him.

Meanwhile, Woese learned more and more about archaea. He looked at many archaea that lived in extreme conditions, either in hot springs such as those at Yellowstone National Park, where the water is so hot and acidic it can peel the flesh off your bones in a matter of minutes, or in deep sea vents that spew boiling gases into the oceans. Woese and others suggest that it may be in environments like these that life on Earth (perhaps in the form of archaea) first began. Astrobiologists are investigating whether archaea might also provide useful clues or ideas about what life might be like on other planets.

But in the course of his research, Woese and others also realized that archaea are everywhere; they live in extreme conditions and in the soils of suburbia. Gradually, scientists began to appreciate that the bulk of living organisms are not the zebras and toucans and duckweed that we know so much about, but the meek and mild, or at least microscopic, microbes.

Woese’s story of persistence has a happy ending. As more and more scientists recognized his accomplishments, he has been showered with awards and prizes, including the MacArthur “genius” grant, the Crafoord Prize (the equivalent of a Nobel Prize in molecular biology), and the Leeuwenhoek Medal, microbiology’s highest honor. (Antonie Leeuwenhoek is known as the father of microbiology because he worked to improve early microscopes and observe single-celled animals.) The Leeuwenhoek Medal is particularly apt, considering that, thanks to Woese, microbes—both archaea and bacteria—are finally getting the attention they deserve, as is Woese himself.