COMMENT Carl Woese (1928—2012) Discoverer of life’s third domain, the Archaea. arl Woese brought a fiercely creative undertaking, which involved analysing more of the relationships between living things, mind, seasoned with rigour, to the than 100 organisms and spanned many Woese’s analysis had an impact on ribosome biggest questions in biology. By years, paid off richly. biology. Woese realized that one could use Cshowing almost single-handedly that living RNA sequences to determine the double- organisms fall into three domains — Bac- helical folding, or secondary structure, teria, Eukarya and a previously unknown of RNA molecules. Woese and I used this group called the Archaea — he transformed approach to work out the secondary struc- our understanding of how living organisms tures of 16S and 23S ribosomal RNA. These NOLLER HARRY are related and how they evolved. comparisons identified the nucleotides Woese, who died on 30 December, was in ribosomal RNA that are universally born in Syracuse in New York in 1928. His conserved — and therefore crucial to its undergraduate education was in physics function — at a time when many believed and mathematics at Amherst College in that the RNA served merely as a structural Massachusetts. In 1953, he earned a PhD in scaffold for ribosomal proteins. biophysics from Yale University in New Woese’s work also spawned a new branch Haven, Connecticut. of microbiology: the use of sequence analy- After taking up a research position at the sis to study natural microbial populations. General Electric Research Laboratory in Combining phylogenetic sequence analysis Schenectady, New York, Woese began think- and the polymerase chain reaction — which ing about the evolution of the genetic code. In amplifies DNA fragments into thousands or 1964, the molecular biologist Sol Spiegelman millions of copies — makes it possible to iden- recruited him to the microbiology depart- tify the microbes in samples from any source, ment at the University of Illinois in Urbana, including the ocean and the human body. where he spent his entire academic career. At first, Woese’s discovery of the Archaea At Illinois, Woese examined the nucleo- was met with scepticism and even hostility. tide sequences of 5S ribosomal RNA (a This, combined with Woese’s view of him- component of ribosomes, which build pro- self as a rebellious outsider, resulted in an teins) from different organisms. He quickly often polemical writing style. He took on realized that ribosomal RNA is an ideal adversaries as formidable as microbiologist chronometer for measuring evolutionary Roger Stanier, taxonomist Ernst Mayr and distances between living things. It has a even Charles Darwin. Yet Woese eventually slow mutation rate, performs an identi- received the recognition he deserved, includ- cal function in all organisms and, because ing the Crafoord Prize in Biosciences from the ribosomal RNA interacts specifically with a Royal Swedish Academy of Sciences in 2003. multitude of proteins, the genes encoding it One day, the analysis of 16S RNA from Carl once confided to me that a key to are unlikely to jump between individuals of a methane-producing organism gave an his success was “the principle of dynamic different species. astonishing result. The familiar pattern of incompetence”. Visitors to Carl’s lab were Woese had discovered a window into the 100 or so spots, each containing small certainly impressed by his indifference to microbial phylogeny. Until this point, the stretches of RNA, was altered in an unusual the mountain of unopened post. His wife field had been hopelessly muddy, with way. Several spots present in all bacterial Gabriella became so concerned that she identifications of microorganisms based on 16S ribosomal RNAs were missing. New persuaded him to let her open the enve- qualitative characteristics such as differences spots had appeared, corresponding to ribo- lopes; among them, she found one with a in shape. In the early 1970s, Woese realized somal RNA sequences never seen before. months-old Dutch postmark. The letter that the sequence of 5S ribosomal RNA con- Woese had captured the signature of a informed Carl that he had been awarded the tained too few nucleotides (120) to provide a different domain of life. Leeuwenhoek Medal by the Royal Nether- way to classify thousands of organisms. This The ribosomal RNAs of some other lands Academy of Arts and Sciences — an led him to take on the daunting task of ana- micro­organisms also produced this strange honour that is given only once a decade and lysing 16S ribosomal RNA, which contains pattern, including those of ‘extremophiles’, that he shares with Louis Pasteur. more than 1,500 nucleotides. some of which live at temperatures up to Carl will be deeply missed by colleagues, Woese began sequencing fragments of 100 °C and secrete sulphuric acid. In 1977, friends and family. His impact on our under- 16S ribosomal RNA from every micro­ Woese and his postdoc George Fox pub- standing of biology is irreversible. ■ organism that he could get his hands on, lished their discovery of ‘archaebacteria’ using RNA ‘fingerprinting’ — a method (now called Archaea) in the Proceedings of Harry Noller is professor of molecular, cell developed by British biochemist Fred Sanger. the National Academy of Sciences, proposing and developmental biology and director of the The technique involves separating fragments that these organisms were as distantly related Center for Molecular Biology of RNA at the of RNA in an electric field according to their to bacteria as bacteria are to eukaryotes. University of California, Santa Cruz, USA. nucleotide compositions. Woese’s enormous As well as transforming our understanding e-mail: [email protected] 610 | NATURE | VOL 493 | 31 JANUARY 2013 © 2013 Macmillan Publishers Limited. All rights reserved.