Leslie Orgel dies

Multifaceted biochemist was best known as proponent of 'RNA world' theory

Nov 1, 2007
Jonathan Scheff
Leslie Orgel, 80, the biochemist best known as one of the founding fathers of the 'RNA world' hypothesis for primitive life on Earth, died on October 27 from pancreatic cancer. In addition to his research into the origin of life, Orgel worked on a diverse range of subjects such as ligand field theory, cancer research and space exploration with NASA."He was always a scientist to the last minute," said M. Reza Ghadiri, a chemist at the Scripps Research Institute in La Jolla, California, who coauthored several papers with Orgel. "Until two weeks ago, he was working on a manuscript. And I have a couple papers still to be published with Leslie. For me, he was a great mentor as well as a collaborator."Born in London in 1927, Leslie Eleazer Orgel earned his doctorate in chemistry from the University of Oxford in 1951 and eventually landed in the theoretical chemistry department at Cambridge. There, he developed the ligand field theory for molecular bonding, which describes chemical bonding in metals. It was also at Cambridge that Orgel fell in with emerging biochemists of the time: Sydney Brenner, Francis Crick, James Watson and 16 others who formed the RNA Tie Club, where each member took a nickname from one of the 20 amino acids and wore a tie representing the chemical structure of RNA.Orgel was one of the first scientists to suggest that RNA, rather than DNA, was the replicating molecule that formed on primitive Earth as the basis of life. At Salk, Orgel become the professor and head of the Chemical Evolution Laboratory, where he continued to investigate possible origins of life.Formerly, theorists supposed that DNA formed in primitive Earth as the basis of life, but DNA is made of proteins and proteins can't exist without DNA. Orgel suggested -- as did Crick and Carol Woese, separately -- that both DNA and proteins could have descended from RNA and RNA could have evolved to its current, supporting role."What he did scientifically for the origin of life was pretty much everything," said Gerald Joyce, a biochemist at the Scripps Research Institute who was the first of only two Ph.D. students that Orgel ever accepted. In their book Origins of Life on Earth "he and Stanley Miller turned the origin of life into a science ... Leslie flushed out the entire agenda of origin of life science and then addressed them experimentally.""A classical biologist would look at life and describe it and write it in his notebook," Joyce added, but Orgel "looked at it like a chemist: how does it work and why does it work? How does a machinery like this self-synthesize?"With the discovery of ribozymes, Orgel began to refine his theory: attempts to form RNA under laboratory conditions that mimic the primordial Earth had limited success. Instead, Orgel suggested that RNA replaced a simpler precursor, peptide nucleic acid, which can be copied in the test tube.His quest to trace the development of life spanned decades. A paper he published with Crick in Nature in 1980, which has been cited more than 900 times, discussed nonspecific DNA in terms of the natural selection of preferred replicators within the genome. A later paper in 1992, cited more than 200 times, tackled the challenges facing non-enzymatic replication studies of prebiotic chemistry.As a scientist, Orgel dipped his fingers into multiple beakers. Besides his primitive life research, his early work focused on transition metals and his later RNA research helped lead to the synthesis of cytosine arabinoside, a chemotherapy agent; he also participated on NASA's Viking Mars Lander Program and SETI Institute's Center for the Study of Life in the Universe. Joyce added that "the toughest critic of Leslie Orgel's work was Leslie Orgel." As his Ph.D. student, Joyce said he found Orgel respectfully demanding, extending the same rigorous expectations of himself to those around him. And even though he was a theoretician by training, "he knew all the intricacies of experimental research. He was adamant that you can't do science in an armchair. He was just as happy to be right as wrong, because it was a real result."Orgel received many awards for his work, and was a member of the National Academy of Sciences, the Royal Society of London and the American Academy of Arts and Sciences. He is survived by his wife, Alice Orgel, his three children Richard, Robert and Vivian, and grandchildren."He was a gentleman," said Inder Verma, a Salk professor of biology and Orgel's longtime lunch companion. "He was very modest, willing to talk any subject ... He was what a classic scientist used to be: highly knowledgeable, interested in many subjects. He was a teacher, a mentor, and a friend."Jonathan Scheff mail@the-scientist.comImage courtesy of the Salk InstituteLinks within this article:R. Lewis, "Scientists debate RNA's role at beginning of life on earth," The Scientist, March 31, 1997. http://www.the-scientist.com/news/display/53817J.P. Ferris and L.E. Orgel, "Studies on prebiotic synthesism," Journal of the American Chemical Society, Aug. 20, 1966. http://www.the-scientist.com/pubmed/5916373M. Reza Ghadiri http://www.scripps.edu/chem/ghadiri/L.J. Lemen, L.E. Orgel and M.R. Ghadiri, "Amino acid dependent formation of phosphate anhydrides in water mediated by carbonyl sulfide," Journal of the American Chemical Society, Jan. 11, 2006. http://www.the-scientist.com/pubmed/16390101L.E. Orgel, Introduction to Transition-Metal Chemistry Ligand-Field Theory, John Wiley & Sons, 1961. http://www.amazon.com/H.F. Judson et al., "Going strong at 75," The Scientist, March 18, 2002. http://www.the-scientist.com/article/display/12927/P. Moore, "Francis Crick dies," The Scientist, July 29, 2004. http://www.the-scientist.com/article/display/22317/K. Heyman, "Watson, on and off camera," The Scientist, January 19, 2004. http://www.the-scientist.com/article/display/14345/RNA Tie Club http://nobelprize.org/educational_games/medicine/gene-code/history.htmlL.E. Orgel, "Prebiotic chemistry and the origin of the RNA world," Critical Reviews in Biochemistry and Molecular Biology, Mar.-Apr., 2004. http://www.the-scientist.com/pubmed/15217990Gerald Joyce http://www.scripps.edu/mb/joyce/L.E. Orgel and S. Miller, Origins of Life on Earth, Prentice Hall, 1974. http://www.amazon.com/L.E. Orgel and F.H. Crick, "Selfish DNA: the ultimate parasite," Nature, April 17, 1980. http://www.the-scientist.com/pubmed/7366731L.E. Orgel, "Molecular replication," Nature, July 16, 1992. http://www.the-scientist.com/pubmed/1630488L.E. Orgel, "Spectra of transition-metal complexes," Journal of Chemical Physics, 1955. http://scitation.aip.org/Cytosine arabinoside http://en.wikipedia.org/wiki/CytarabineNASA's Viking Mission to Mars http://nssdc.gsfc.nasa.gov/planetary/viking.htmlSETI Institute's Center for the Study of Life in the Universe http://www.seti.org/csc/index.phpThe National Academy of Sciences http://www.nasonline.orgBritish Royal Society http://www.royalsoc.ac.uk/The American Academy of Arts and Sciences http://www.amacad.org/Inder Verma http://www.salk.edu/faculty/faculty_details.php?id=54