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A Tale of Woese

A Tale of Woese

by Douglas Page©1998 Home Sci-Tech Medical Features Profiles Marriage Peril Bio Carl Woese leans back in his favorite public position, tilted in the swivel chair with his slender legs stretched out, his feet on the desk and computer keyboard on his lap. It is the posture in which he insists on being photographed. It is the image he prefers to project - relaxed and at ease.
This is also how Carl Woese protects his image. The legs could just as easily be a denim fence. The world he lets this close, but no closer. For Carl Woese is not at peace. Carl Woese (pronounced "woes") will talk all you want about his science. And his science is epic. This is the man who single-handedly revolutionized the science of biology. He'll hint at his disappointments and regrets. "I missed two opportunities to push two colleagues, and friends, to do the experiments that probably would have gotten them Nobel Prizes. Just paying a little more attention to what they were doing at the time might have made the difference." But he'd rather the world didn't know much more about him. He finds personal questions unnecessary, inconvenient and intrusive. "I do not favor cult of personality pieces. The one done on me in Science last May [Vol. 276, 2 May 1997] crossed the border into the uncomfortable. It's not that I have anything to hide; I just don't like my personal life written about, and believe one's science is fairly disconnected from one's personal life. All the junk written about Beethoven's irascible personality does not add at all to the appreciation of his music." Woese understands prepossession. His life's work lead to science of symphonic proportions. Twenty years ago he gave a recital and no one came.

Life in Three Forms
Before Carl Woese, life was believed to exist in only two forms: bacteria and everything else. Then, in 1977, after years of tedious, solitary work, Woese made an announcement that split the trunk of the tree of life as if struck by a lightning bolt. There were not two branches of life, he said. There were three. Woese declared the microorganisms whose RNA he had been studying for years alone in the red brick microbiology lab on the third floor of Morrill Hall on the campus of the University of Illinois deserved a branch of life all to themselves. These one-celled organisms, which had been classified with bacteria, Woese found were so different from bacteria - and from any other life form - he created a new domain for them, which he called archaebacteria. Later, the bacteria suffix was dropped and they are now called archaea. Until Woese's astonishing finding, biology had grown the tree of life with two main branches: bacteria (or prokaryotes) on one bough, and all other life forms - everything from paramecia to palm trees to Pavoratti, the eucarya (or eukaryotes) - on the other. The traditional distinction separating the two branches was the cell nucleus. Cells on the eucarya branch store their DNA in an intracellular sac called the nucleus. Bacteria have no nucleus and were thus placed in a tidy separate domain. The repair of a paradigm they didn't consider broken couldn't have provoked microbiology into a more belligerent stance. The entire science of biology reeled in disbelief at the announcement, as though it had been informed it had a third parent. Woese was telling biology it had overlooked or misclassified one third of all life, that their spectrum was missing a primary color. To make matters worse, Woese, who describes himself as "a molecular biologist turned evolutionist", wasn't even an 'authentic' microbiologist. His undergraduate work at Amherst College was in physics; his 1953 Yale University doctorate was in molecular biology, called biophysics at that time. Molecular biology concerns itself with the structure and function of macromolecules in living cells, notably with defining the structure of proteins and the role of DNA. Microbiology, on the other hand, is the study of microscopic and ultramicroscopic organisms, such as bacteria. A palace revolt inside microbiology would have been one thing, but when one of their most fundamental concepts was overturned by a maverick, the biology establishment crossed its arms and refused to recognize Woese's monumental phylogenetic contribution. It was as if he had somehow insulted them. Most scientists (1 of 4)6/10/2009 11:17:54 AM

A Tale of Woese

and graduate students shunned him. There was talk of Woese being crazy. Research funds continued to be scarce. "I suffered from a paucity of funds," Woese says, with some bitterness. "Throughout the 20 or more years in which I did my ribosomal RNA (rRNA) phylogeny work, the bulk of that funding came from the National Science Foundation's Systematics panel, but at a level that would embarrass any self-respecting assistant professor. Try as I might I could never get this panel to raise the level of funding; this despite the fact that my work was far and away the most important work this panel has ever funded." Not even when it came time to migrate from manual analysis to computer analysis could he motivate the panel to increase funding. "You would think that if any biologists cared about and understood the importance of evolutionary work, it would have been this particular panel," he says. "I ultimately gave up sequencing rRNAs." Among the research areas funded by NSF's Systematic Biology are "derived phylogenies, molecular evolution and studies that lead to improved classifications". His work was often dismissed as mere taxonomy. Other researchers were working with rRNA sequencing, but only Woese saw the sequencing's phylogenetic connection. "[That connection] wasn't something you thought about particularly in those days," says Norman Pace, an evolutionary microbial biologist at the University of California, Berkeley, a Woese friend and colleague for 30 years. "Taxonomy was considered to be a sort of dirty word in the mouth of molecular biologists. Many people told Carl that taxonomy was just a game, that he was wasting his time. Of course, it turned out to be more fundamental than that."

Eventual Recognition
What it turned out to be was splendid, ultimate science. Recognition eventually reached him in the form of a 1984 MacArthur Fellowship, a 1988 election to the National Academy of Sciences, and a 1992 Leeuwenhoek Medal - microbiology's medal of honor. "His contributions to biology have far exceeded that of many others. His work has revolutionized bacterial systematics, microbial ecology and the study of the origin of life," said microbiologist William B. Whitman, University of Georgia, Athens. "I don't understand why Carl Woese hasn't received the Nobel Prize." In fact, Pace says, "Woese was nominated for a Nobel Prize this year [1997] by another Nobelist. I helped put the Nobel portfolio together. But there's no category. There's medicine, chemistry and physics. So he won't get it." Confirmation that archaea are more closely related to humans than to bacteria came last summer when the first complete genome structure of an archaeon - Methanococcus jannaschii - was announced in a paper coauthored by Woese and Gary Olsen, from The Institute for Genomic Research. Unlike most eukaryotes, the genes of M. jannaschii are densely packed with little noncoding DNA between them, Olsen said. Its proteins, however, show structural similarities to eukaryotic proteins. The apparatus that synthesizes RNA in the cell is different from that of bacteria and seem to be a simpler version of that found in eukaryotes. The proteins that relicate DNA also have no counterparts in bacteria, more closely resembling those found in eukaryotes. "The data confirm what we've long suspected," said Woese, "that the archaea are related to us, to the eukaryotes. They are descendants of the microorganisms that gave rise to the eukaryotic cell billions of years ago." Woese began in the late 60s with the intent of discovering the evolutionary history of microbes, whose evolution covers most of Earth's 4.5 billion year history. "Biology's mandate is to reconstruct the history of life on this planet as far as is possible," Woese, 67, says. To start, he required a phylogeny, or family tree of all organisms. However, none existed for bacteria. Microbiology had tried for decades to classify bacteria according to such things as shape and metabolism, without success. "The ultimate scientific goal of biological classification cannot be achieved in the case of bacteria," Roger Stanier states in his significant textbook, The Microbial World. However, Woese's lack of training as a microbiologist liberated him from the confines of disciplinary bias, permitting him to pursue problems thought impenetrable by microbiology. His physics background encouraged him to believe if one looks close enough simple principles underlie everything. In order to construct his own phylogeny, Woese focused on ribosomal RNA, genetic material abundant in all cells of all organisms, calculating their characteristics might yield clues to their evolutionary history. Thus, Woese began his slow, 10 year walk on the beach, overturning rRNA fragments from thousands of samples from a variety of bacteria, arranging them by genetic similarity, using a rare technique called oligonucleotide cataloging. In this prosaic process, rRNA molecules (strings of four nucleotides - adenine, cytosine, uracil and guanine, or A,C,U,G) are cut into fragments at every G residue. The fragments are then further subdivided with enzymes, allowing the researcher to compare oligonucleotides from other microbes to determine whether a relationship existed. This technique, once known only to Woese and one or two other people in the world, is now the standard approach used to identify and classify all micro-, and many macro-, organisms. After following this intricate trail for a decade, a University of Illinois colleague, Ralph Wolfe, suggested Woese try the technique on some methane-producing bacteria that no one quite knew where to classify. They had been lumped in with the prokaryotes because they 'looked' like bacteria. When Woese finished examining their rRNA sequences, he found these methanogens were no more related to prokaryotes than (2 of 4)6/10/2009 11:17:54 AM

A Tale of Woese

they were to eukaryotes. They were different. The implication was clear and stunning: a third form of life had been found. The announcement made more of an impact on the front-pages than it did in biological circles, a reaction that wounded Woese. Though his work is now well-established among scientists, there is residual acrimony that acceptance of his work was so slow. "He's unhappy with the scientific reception," Pace says. "In my opinion, unjustly at this time." Magnanimously, Woese offers an explanation for the hesitation in acceptance. "Initially, there was considerable antagonism," the Syracuse, NY, native recalls. "At the time of the discovery of archaea, biologists firmly believed that the living world divides in the first instance into two primary groupings - the prokaryotes and the eucaryotes, and that all prokaryotes (like their eukaryotic counterparts) were of a kind. There was no room for the archaea in this world view; the idea of a third primary group was absurd." Buttressed by the conviction of the righteous, Woese survived the scorn. "For the most part I ignored my critics and bulled ahead. The experimental power of what we were doing was immense and I knew it would sweep everything before it. This does not mean I was untroubled by the criticisms, but understanding a paradigm shift was happening and this kind of response was typical, was reassuring." Pockets of resistance remain. "I oppose Woese's recognition of three equivalent domains because his socalled archaebacteria are much closer to the [bacteria] than to the eukaryotes," says Ernst Mayr, emeritus professor of zoology at Harvard University. "Both subdivisions of the prokaryotes [bacteria and archaebacteria] share the absence of a nucleus and of mitosis and a large portion of the genotype. I do not doubt that the eukaryotes are derived from the archaebacteria. . . However, to give the archaebacteria the same high rank as the eukaryotes would produce a totally distorted classification." Woese, who likes plaid shirts, old sneakers and detests meetings, permits his reticence to dissipate somewhat when responding to critics. "Mayr is a special case," he says. "He cut his evolutionary teeth at a time when morphology ruled, when if two things were not morphologically distinguishable one tended to lump them together. He appears to realize that the archaea and bacteria are phylogenetically distinct, yet to call this spade a spade (as I maintain Darwin would have done) is beyond him."

Good-Old Boy Criticism
Woese considers most criticism of the archaeal concept factious. "It has little substance, otherwise it would have been published outright, and science would have benefitted," he says. "Usually the criticism occurred in a 'good-old-boy' context, where it amounted to no more than carping and mutual-reassurance. The years of ostracization may have left Woese cynical about biologists, but not about biology. He is passionate about the future of his science. "Microbiology is undergoing a quiet revolution," he says. "The way we look at microorganisms is changing. The way we look at microbiology, its place in the pecking order of biological sciences, is changing. Microbial ecology has finally become true ecology; a microbial niche can now in principle, for the first time, be defined in organismal terms. Microbial diversity has once again become a respectable thing to study." Maybe one day it will even become a respectable thing to teach. The status of biological instruction, especially in the high schools, disturbs Woese. "Biology is poorly taught in general at the high school level," he says, referring to the polarization of evolution by the scientifically heterodox. "Scientifically, the matter is simple. The essence of biology is evolution, and biology should be taught from an evolutionary perspective. Yet, although evolution is covered to some extent in high school biology courses, it bears the scarlet letter and is taught in a guarded fashion, embalmed in caveats. The reason for this is obvious, as are the pressures on textbook publishers." Woese removes himself from the "politically cathected" evolution vs. creationism issue. "I like my science pure. I don't see any fundamental contradiction between science in the big view and religion in the big view." Woese believes biology itself has ironically locked arms with the creationists in putting negative pressure on biologic instruction. "It comes from within the core of biology itself," he says. "Biology today is structured about the molecular paradigm. Molecular biology, which derives from classical physics doesn't see evolution as basic, that it's an almost trivial collection of 'historical accidents'. "I am not at peace with the state of biology today," he says. "It is in a revolutionary mode, and the revolution needs some guidance of the kind it is not receiving. The way we teach biology is not right. Evolution should be the centerpiece." What remains for Woese? What does a man do who has already reconfigured an entire scientific discipline? (3 of 4)6/10/2009 11:17:54 AM

A Tale of Woese

Woese is focused on attaining proper appreciation for the microbial world. "Microorganisms account for most of the biomass on the planet and are an essential foundation on which the global ecosystem rests," Woese believes. "Microorganisms play an absolutely essential role in the survival of the human race. My goal is to work for a recognition of what I feel is the real biology, a science that is not a half-science as it is now, but a science that stands along side of physics as one of mankind's basic windows on the world, a science that can help man cope with his future, and not just solve immediate problems. "I want biology to be our pathfinder, not just our handmaiden." ............................................................ Suggested Reading Bult, C., et al, "Complete genome sequence of the methanogenic archaoen, Methanoccus jannaschii", Science 273, Aug. 23, 1996. Olsen, G.J., Woese, C.R., "Ribosomal RNA: a key to phylogeny," J of the Federation of American Scientists for Experimental Biology 7:113-123, 1993. Woese, C.R., Kandler, O., Wheelis, M.L., "Towards am natural system of organisms: Proposal for the domains Archaea, Bacteria, and Eucarya," Proceedings of the National Academy of Sciences, 87(12):45764579, Jun 1990. -endThis profile appeared in Science Spectra (No. 12, 1998).

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