REVIEW REVIEW RNA Biology 11:3, 1–6; March 2014; © 2014 Landes Bioscience Looking in the right direction Carl Woese and evolutionary biology Nigel Goldenfeld I nstitute for Universal Biology; Institute for Genomic Biology, and Department of Physics; University of Illinois at Urbana-Champaign; Urbana, IL USA Carl Woese is known to the scientific community primarily So began a scientific partnership and friendship that lasted through his landmark contributions to microbiology, in par- more than a decade until his death. During that time, we met ticular, his discovery of the third Domain of Life, which came to nearly every day and talked on the phone or via email other- be known as the Archaea. While it is well known how he made wise. Looking back at these fragments of correspondence, it is this discovery, through the techniques he developed based on remarkable to note how much of our future trajectory was set in his studies of rRNA, the reasons why he was driven in this scien- those initial exchanges. Carl had indeed set his sights on a goal tific direction, and what he saw as the principle outcome of his of making biology a quantitative science with roots in complex discovery—it was not the Archaea!—are not so widely appre- dynamical systems, but his enlisting a theoretical physicist to his ciated. In this essay, I discuss his vision of evolution, one which distribute. transcends population genetics, and which has ramifications cause was more than a way to help create a new breed of biolo- not only for our understanding of the origin of life on Earth and gist—one with better math skills. Carl himself had trained as a elsewhere, but also for our understanding of biology as a novel physicist, with a BA in Mathematics and Physics from Amherst not class of complex dynamical systems. College in 1950 and a PhD in Biophysics from Yale three years later. Thus, he was no stranger to the great value that quantifica- tion could provide to biology. In fact, what Carl wanted was to Do complete his understanding of the evolutionary history of all life At exactly 2 pm on Friday September 20, 2002, I received the on Earth, a program of research that he had begun to think about most important email of my life. Originating from a computer seriously during the 1960s. That program of research had been mysteriously called “ninja,” the sender wasted no time on getting articulated with clarity in a letter to Francis Crick dated June 24, to the point: 1969, a lengthy extract of which was reproduced in our article on “This is Carl Woese, over in Life Sciences. I’d like to talk to the historical and conceptual relationship between microbiology, you at some point about moving the teaching of biology into the molecular biology, and evolution theory.1 21st century. Molecular biology clearly has lost (run out of) its “If we are ever to unravel the course of events leading to the vision, and a new and very different biology needs to emerge. I evolution of the prokaryotic (i.e., simplest) cells, I feel it will be Bioscience. have been told of your interests, and know, thereofore [sic], that necessary to extend our knowledge of evolution backward in time you are atune [sic] to what I’m talking about. I would like to see by a billion years or so. i.e., backward into the period of actual at least some cognizance on the part of card carrying biologists Cellular Evolution.”1 of complex dynamic systems, an appreciation for the fact that the Carl had famously spent much of the following decade set- cell is indeed a complex dynamic system and evolved in such a ting this investigation into motion, through his work on rRNA, manner. My telephone is 3–9369, if you care to discuss the mat- culminating in the celebrated discovery of both the relatedness Landes ter with me.” and tripartite structure of life by Woese and Fox in 1977,2 and Naturally, I responded with alacrity, writing that ultimately leading to a new proposal for the classification of life3,4 “I am a theoretical physicist, but tend to work on topics that that is today the mainstream view. Not so frequently empha- are regarded as out of the mainstream by most of my colleagues sized, the finding that all life is related implies the existence of … I don’t know very much about biology, and worse, I don’t a last universal common ancestor (LUCA), now known to be think I have the sort of mind that can be engaged by or penetrate positioned between the Bacterial and the Archaeal/Eukaryotic ©2012 much of the subject. Despite these handicaps, …” branches and representing in one extreme view a single organ- Carl’s response was frank and, to be honest, tremendously ism, or in another view, a community of associated organisms. exciting to me: Although the significance of these two discoveries is hard to “You may not feel too much at home with biology as it now exaggerate, and despite Carl’s manifest pride in this remarkable stands, but if I am any judge the field is decidedly moving to accomplishment, he was deeply dissatisfied with it, disappointed meet you.“ by a necessary limitation of his chosen instrument of biological revelation: the ribosome. The highly conserved nature of the ribosome, in particular 16SrRNA, made its molecular sequence Correspondence to: Nigel Goldenfeld; Email: [email protected] a brilliant choice to mark the dynamics of evolution writ large; http://dx.doi.org/10.4161/rna.28640 however, 16SrRNA sequence comparison only tracked (or more Submitted: 03/21/2014; Accepted: 03/21/2014 accurately, defined) the lineages of organisms whose cellular www.landesbioscience.com RNA Biology 1 structure included ribosomes. In the modern era that leaves out occurred, but the speed of evolution. In fact, the work that had viruses of course, but in the era before LUCA, it necessarily leaves made the most impression on him was G.G. Simpson’s Tempo out all of life. LUCA was not just the last universal common and Mode of Evolution,10 because its analysis of the fossil record ancestor but a representative of the first organisms which exhib- echoed something that had puzzled Carl right from the early ited translational machinery in sufficiently advanced form to be results with Fox: How could evolution have achieved so much, traced by 16SrRNA phylogeny. Earlier classes of life would not starting from an abiotic earth and attaining an essentially modern have translational machinery recognizable as related to today’s translational machinery in a time frame of what could be at most ribosomes, and thus would be invisible to 16SrRNA phylogeny. one billion years? My early discussions with Carl centered on this Woese’s program to uncover the evolutionary history of life on issue, because Carl had the intuition that some understanding Earth had apparently run into a roadblock. of complex dynamical systems would be pertinent to the issue. The spectacular success of molecular phylogeny in uncov- That is to say, he felt that the picture of evolution, which had ering the three Domains of Life overshadowed Carl’s original emerged from the modern synthesis during the first half of the endeavor. Carl was convinced that to get his original program on 20th century, was somehow missing an important aspect of the track, he would need to make a conceptual advance. One of my evolutionary process. One way to phrase this seeming inadequacy first questions to him was why are there only three Domains of is to ask how population genetics can possibly be considered as a Life? I was not attaching any special significance to the number full explanation of the evolutionary process, when, by construc- three, but the fact that number is of order unity, and not one tion, the biological world before there were genes as such was hundred, for example, is surely significant. What does this tell us manifestly beyond the regime of validity of the theory. Carl had about the singularity that is LUCA? What does it tell us about already given a lot of thought to life before genes, and in the same distribute. life before LUCA? Carl was extremely animated by these and year as the discovery of the Archaea had, in another magnificent related questions, but I soon found that there were more urgent paper also with Fox, initiated conceptual discussion on such a preoccupations on his mind, because there were challenges to phase of life, which he called the “progenote.”11 not the very notion of Tree of Life itself, arising from the increasing The progenote was a phase of life in which the distinction recognition of the evolutionary impact of horizontal gene trans- between genotype and phenotype had not yet emerged. Carl con- Do fer (HGT). Remarkably, in understanding these issues, the life sidered the emergence of the genotype–phenotype relationship to before LUCA problem also began to be resolved. be the primary force shaping the evolution of the cell, an argu- Horizontal gene transfer—the transmission of genes from one ment he based on the simple incisive observation that the trans- organism to another unrelated organism—was being invoked as lational apparatus is large and complex, perhaps more than any an invalidation of the concept of lineage, thus casting doubt on other cellular machinery. Carl attributed the size and complex- the idea that post-LUCA, a Tree of Life was a meaningful concept ity to the requirements for accuracy of the translational process, (for a review, see ref. 5).