The new biology of Carl Woese

Carl Woese. Photo courtesy of Don Hamerman.

Carl Woese, one of the giants of contemporary biology, passed away a day before New Year’s Eve (see the NY Times obituary). Woese, an American microbiologist from the University of Illinois, revolutionized our understanding of life with the discovery of a new domain of living organisms, the Archaea, and the creation of a universal tree of life made of three main branches (Bacteria, Archaea and Eukarya) (Woese, 1990). This discovery is already more than thirty years old, but is not very well known to the general public, to say the least… And now with Woese’s death the possibility of a Nobel nomination vanishes.

Everything we do nowadays in microbiology labs is to some extent influenced by the work done by Woese in the seventies and eighties. This is one reason why I entitled this post “The new biology of Carl Woese”. The other reason is a 2004 article by Woese, “A new biology for anew century”, which offers a great perspective on our job and which contains some juicy controversial elements. But let’s begin with the landmark contribution of Woese to the field of biology.

Before the sixties and the advent of molecular phylogeny, the classification of bacteria seemed an insoluble problem, since morphology and metabolism were not good enough to allow us to order the bacterial life forms. Woese, a physicist by training, decided in 1966 that he could give it a try using the powerful tools of molecular biology. At that time many researchers had turned towards proteins in order to build phylogenetic trees, following the pioneer work of Linus Pauling on hemoglobin. Woese didn’t follow the consensus and decided to use ribosomal RNA as source material. Thanks to a tedious technique called oligonucleotide cataloging, he was able to reconstruct the rRNA sequence and did that for about sixty bacteria. It took ten years.

In 1976, Woese used his technique on methanogens, a diverse group of microbes that nobody knew how to classify, and bingo! He had stumbled on something that no one suspected: a new kind of living organisms, neither bacteria nor eukaryotes, the Archaea. He published his findings in PNAS (Woese & Fox, 1977), but the reception by the scientific community was far from enthusiastic. The Nobel laureate Salvador Luria told Woese’s colleague, Ralph Wolfe, that he should dissociate himself from this “nonsense” in order to maintain his reputation. Ernst Mayr, the famous evolutionist, also dismissed the idea of a third domain of life as nonsense, and he kept this view until his death in 2005… (In a 2002 interview to Bioessays, Mayr said that “Only a non-biologist could have come up with this”.) So did Lynn Margulis, as you can read in this previous post. As to those who were not openly opposed to Woese’s conclusions, they were mostly silent. This initial backlash left profound wounds in Woese, even years after the resistance had faded away. Today, the three domains of life phylogeny has become textbook knowledge; in labs all around the world, microbiologists use ribosomal RNA to characterize environmental isolates, without bothering to culture the microbes in the first place! And a great resource such as the Ribosomal Database Project would not exist but for Carl Woese’s work. (I found most of the information above in a very interesting article by Virginia Morell, published in Science in 1997.) 

Interestingly, Woese’s work correlates with the development of biotechnology, particularly high-throughput DNA sequencing, which led to the human genome project and continues to unleash giant projects such as the human microbiome. This is the science of entrepreneurs such as Craig Venter, and certainly a far cry from the past. This powerful but technique-oriented biology, however, left Woese unimpressed. In his article “A new biology for a new century” (Woese, 2004), he wrote, p. 173:

“By the end of the 20th century, however, the molecular vision of biology had in essence been realized; what it could see of the master plan of the living world had been seen, leaving only the details to be filled in. How else could one rationalize the strange claim by some of the world’s leading molecular biologists (among others) that the human genome (a medically inspired problem) is the “Holy Grail” of biology? What a stunning example of a biology that operates from an engineering perspective, a biology that has no genuine guiding vision!”

And he added, p.185: “Biology today is little more than an engineering discipline.” The culprit, according to Woese, is the reductionism that permeated biology throughout the 20^th century. But what does one mean precisely by reductionism? Woese distinguishes what he calls “empirical reductionism” from “fundamentalist reductionism”. The former is nothing more than the methodology that scientists follow (we are reductionist – one may say analytical – because, you know, that works…). In contrast, “fundamentalist reductionism” is a world view that asserts that knowing the constituents is enough to know the whole, and this one Woese finds problematic. He wrote, p.174: “It is impossible to discuss modern biology without the cacophony of materialistic reductionism throughout.” This is an exciting claim, although I don’t think it’s easy to separate the “empirical” from the “fundamentalist” reductionism, and to say which one influenced most the development of biology.

Woese acknowledged that reductionism had helped to solve important problems in biology, but he thought that it was time to move on:

“The molecular cup is now empty. The time has come to replace the purely reductionist “eyes-down” molecular perspective with a new and genuinely holistic, “eyes-up,” view of the living world, one whose primary focus is on evolution, emergence, and biology’s innate complexity.” (p.175)

Let’s be ambitious and tackle the big questions again! Evolution, development, the origin of life, the complexity of interactions between organisms, these are all topics that need to be explored further. This is a heartening message, because it tells us that we are far from being done with biology. (Woese compared the contemporary situation in biology with the one of physics at the end of the 19^th century: people claimed that everything was known… Until it was turned upside down in the 20^th century. Woese believed the same thing may happen to biology in the 21th century.) For Woese, one of these big questions is the evolution of the cell (Woese, 2002). And indeed, this is one of the rare topics that hosts a true controversy in the scientific community these days! 

I tend to be skeptical when I read the word “holistic”, because too often it means hollow concepts in disguise. But from someone like Carl Woese, it is a different story. He did his share of “reductionist” biology, so he knew what he was talking about. I also feel that nowadays biology is not as exciting as it could be. We are making catalogs of everything: catalogs of genes, of proteins, of genomes, of organisms… We need to remember that cataloging is not per se a final goal of biology… We will see whether Woese’s vision of biology unfolds in the 21th century!

Let’s give the final word to Woese, one of the greatest biologists of our era:

“Our task now is to resynthesize biology; put the organism back into its environment; connect it again to its evolutionary past; and let us feel that complex flow that is organism, evolution, and environment united. The time has come for biology to enter the nonlinear world.” (p.179)

Photo credit: Don Hamerman.

References

• Woese C. R. and Fox G. E. (1977). Phylogenetic structure of the prokaryotic domain: the primary kingdoms. PNAS Vol.74, pp.5088-5090.
• Woese C. R., Kandler O. and Wheelis M. L. (1990). Towards anatural system of organisms: Proposal for the domains Archaea, Bacteria andEucarya. PNAS Vol. 87, pp.4576-4579.
• Morrel V. (1997). Microbiology’s scarred revolutionary. Science Vol. 276, pp.699-702.
• Woese C. R. (2002). On the evolution of cells. PNAS Vol. 99, pp.8742-8747.
• Woese C. R. (2004). A new biology for a new century. Microbiol Mol Biol Rev Vol. 68, pp.173-186.