NATURE|Vol 450|29 November 2007 NEWS & VIEWS OBITUARY Leslie Orgel (1927–2007) SALK INST. Chemist, molecular biologist and pioneer in the study of the origins of life. Leslie Orgel was a brilliant man who excelled the field of prebiotic chemistry. Miller in two very different scientific areas. So demonstrated the abiotic synthesis of amino disparate were these fields that most would acids in a mixture of gases that was thought think his accomplishments were those of to simulate the atmosphere of the prebiotic two different individuals. Chemists know Earth. This experiment was highly significant of his classic work on devising ‘ligand-field to Orgel, and when he went to La Jolla he theory’, which provides an understanding sought to address the problems of life’s of the structural and physical properties of origins by integrating prebiotic chemistry transition-metal complexes. ‘Orgel diagrams’ and molecular biology. Accordingly, his focus have become a standard way to depict the was not on the machinery of contemporary various energy states of these complexes, metabolism (amino acids that form proteins), and Orgel was recognized for his but on the machinery of a primitive genetic achievements in this area by his election as a system (nucleotides that form RNA). rigorous experimental validation. This, he fellow of the Royal Society at the unusually Orgel addressed many aspects of the felt, was especially true in the field of the young age of 35. But a broader group of origins of life on Earth, including the origins of life, where “theories are a dime a people know that Orgel set the agenda for prebiotic synthesis of the building-blocks dozen and facts are in short supply”. He took the experimental study of the origins of life. of nucleic acids, the joining together of great pleasure in a positive result, to the point He pursued that agenda with vigour and nucleotides to form polynucleotides, and the of rooting for the pen on a graph-plotter intellectual clarity right up until his death non-enzymatic copying of RNA. He was the during chromatography experiments. But on 27 October. first to demonstrate that information can be he also delighted in negative results, because Born in London, Orgel began his career as transferred from a preformed RNA template they pushed him to devise new hypotheses. a chemist at the University of Oxford. But it to a newly synthesized RNA molecule in This, of course, is the way scientists are wasn’t long before his second love for biology a purely chemical system. The concept of supposed to behave, but Orgel was one of the became apparent. Orgel was one of the small information transfer was critical for Orgel few who actually did so. circle of scientists who were present at the because his ultimate goal was to demonstrate Following the discovery of catalytic RNA, birth of molecular biology. Between 1954 and a chemical system that is capable of Orgel continued to pursue the RNA-world 1955 he worked at the California Institute of undergoing darwinian evolution. “After that,” hypothesis as both a strong proponent and a Technology with Linus Pauling, purportedly he would say, “the rest is just history.” The tough critic. He pointed out that the notion engaged in theoretical chemistry. But Orgel origin of life, in his view, is defined as the of an RNA world hardly solves the problem spent most of his time that year talking with origin of evolutionary history. of the origins of life, and suggested that RNA the founding fathers of molecular biology — In the late 1960s, Orgel — along with was preceded by some other genetic material, such as Alex Rich and James Watson — and Crick and the microbiologist Carl Woese just as DNA and protein were preceded learning from the likes of George Beadle and — proposed that early life on Earth was by RNA. Many of his later publications Max Delbrück, who later won Nobel prizes based on RNA genes and RNA enzymes, concerned experimental studies of possible for their work on genetics. rather than DNA genes and protein enzymes pre-RNA-world molecules. His theories From 1955 to 1963, Orgel was a faculty as it is today. Fifteen years later, following the brought him into conflict with creationists, member in theoretical chemistry at the Nobel-prizewinning discovery by Thomas who sometimes quoted Orgel out of context, University of Cambridge, where he wrote his Cech and Sidney Altman of RNA enzymes pointing to his admitted uncertainty about seminal book on ligand-field theory. It was in contemporary biology, Orgel’s proposal life’s origins as if this were a failing of the here that his enthusiasm for biology grew came to be known as the ‘RNA world’ scientific approach. It was, of course, typical through extensive conversations with Sydney hypothesis. of Orgel and of the best practice of science. Brenner and Francis Crick. I was a graduate student in the Orgel He had no time for proponents of ‘intelligent Orgel was a member of the RNA Tie Club, laboratory when word came that Cech had design’, and avoided those prone to magical an informal association of academics who discovered self-splicing RNA enzymes. thinking. aimed to solve the DNA coding problem No work was done at the bench that day; When engaged in scientific discourse, — the relationship between the sequence of everyone was at the blackboard, as Orgel led a Orgel was intellectually demanding, but a gene and that of its corresponding protein. rapid-fire discussion of how an RNA enzyme never unkind. As his student — and over the Each member was assigned a different amino might bring about the replication of RNA, decades since then — if I were to advance a acid (Orgel was threonine) or nucleotide and of how such an enzyme might arise. dunderheaded hypothesis, he would frown base, and given a woollen tie decorated At afternoon tea — a tradition in the Orgel slightly and begin his corrective response with a stylized double helix. Club members laboratory — Crick joined the conversation with the words: “With respect…”. Like all exchanged ideas freely, and played a large and the pace quickened. There was no those who knew him, I had the deepest part in getting Orgel hooked on molecular crowing from Orgel that he had predicted respect for Leslie as a scientist, colleague and biology. By 1964, when he moved to the Salk catalytic RNA, and no complaining that he dear friend. Institute in La Jolla, California, his second had overlooked the possibility that RNA Gerald F. Joyce scientific career had begun. enzymes might still exist today — only the Gerald F. Joyce is in the Departments of The seeds of Orgel’s arguably greatest joy of fresh scientific ideas triggered by new Chemistry and Molecular Biology, The Scripps contributions to science were planted in experimental facts. Research Institute, 10550 North Torrey Pines 1953, when Stanley Miller performed an Although Orgel was a theoretician, he Road, La Jolla, California 92037, USA. influential experiment in what would become always demanded that theory be subject to e-mail: [email protected] 627.