LOS ANGELES - Leslie Orgel, the Salk Institute theoretical chemist who was the father of the RNA world theory of the origin of life and who joined with Nobel laureate Francis Crick to postulate that life might have been seeded on Earth by a higher intelligence, died at the San Diego Hospice & Palliative Care on Saturday from pancreatic cancer. He was 80.
Reasoning that DNA was too complex to have been the first repository of genetic information, Mr. Orgel and others speculated that RNA could have preceded it, simplifying the evolutionary process. Even RNA is very complicated, however, so he also synthesized simpler molecules that could have arisen even before it.
"He would go for the fundamental questions of biology: why is biology the way it is and how did it get there?" said Gerald Joyce, a biochemist at the Scripps Research Institute in La Jolla, Calif., who earned a doctorate with Mr. Orgel in the mid-1980s. "He's tackled every problem on the origins of life."
Mr. Orgel believed that "evolution was always one of the interesting mysteries of science," recalled molecular biologist Inder M. Verma of the Salk Institute. "If we didn't know about evolution, how would we know anything about biology?"
While others in Salk's Chemical Evolution Laboratory were attempting to mimic the environmental conditions under which the first amino acids and other biological molecules could have formed roughly 4 billion years ago, Mr. Orgel turned his attention to the problem of the development of molecules that could carry genetic information.
At the beginning of the 1960s, most scientists still believed that DNA, which is the ultimate repository of genetic blueprints, was the first such storage molecule to have evolved. Mr. Orgel, however, thought it was far too complex.
He noted that information contained in DNA was necessary to make proteins, the large molecules that carry out most cellular activities. But proteins are also necessary to make DNA, producing what he termed a chicken-and-egg conundrum: Which came first?
Experiments in the early 1960s suggested that RNA, which today carries genetic information from DNA to the cells' protein-making machinery, could function as a genetic repository and as an enzyme. That versatility, combined with RNA's slightly simpler structure than DNA, hinted that it could have been the first large biological molecule to evolve. The primitive environment thus would have been an RNA world rather than today's DNA world.
Similar proposals were put forward by Crick and by microbiologist Carl Woese, and the idea eventually became widely accepted. DNA, the theory held, would have evolved later.
Mr. Orgel summarized the arguments for an RNA World in his 1973 book "The Origins of Life: Molecules and Natural Selection."
"Before life as we know it - which is DNA genes and protein enzymes - there was a different life-form on this planet: RNA-based life forms. We are descendants of a different life form," Joyce said. "This is almost universally accepted now."
Experiments by other researchers during the 1970s, however, showed that it was difficult to produce RNA under the primordial conditions of early Earth. The primary reason, Mr. Orgel speculated, was that ribose, the sugar component that forms the backbone of RNA, was not sufficiently stable to survive the low oxygen and high radiation conditions then prevailing.
He thus began to look for simpler "backbone" molecules that could have formed more easily and survived longer in the primordial environment. His team produced a compound known as peptide nucleic acid, or PNA, that is much simpler than RNA and that could copy itself in the test tube. Although this most probably was not the original genetic material, the work showed that the evolution of a more complex, self-replicating molecule from a simpler precursor is at least possible.
Ever one to consider a wide range of theoretical possibilities, Mr. Orgel mused about how a universal genetic code could have evolved. He and Crick proposed that it might have been brought to Earth by an extraterrestrial intelligence, a process called "directed panspermia." In an article in the journal Icarus, they said that while it is possible that life reached Earth in this way, the scientific evidence is so inadequate that no one can determine the probability.
Mr. Orgel is widely known for his so-called second rule, which states that "Evolution is cleverer than you are." The rule means that the trial-and-error methods of evolution can produce better results than centralized human planning and often are used to counter creationist arguments.
Leslie Eleazar Orgel was born in London. His interest in chemistry was cemented in his teens when he "spent a great deal of my time making and detonating explosives." He majored in inorganic chemistry at Oxford University.
He did his postgraduate work at the University of Chicago and the California Institute of Technology, where he was supposed to be studying with Linus Pauling but found himself spending large amounts of time with Max Delbruck, James Watson, and Alexander Rich. "By the time I left Caltech, I was hooked on molecular biology, but I didn't abandon inorganic chemistry until 1964," he said.
After Caltech, he returned to England, joining the chemistry department at Cambridge University. There he helped develop ligand field theory, which describes chemical bonding in metals. His 1961 text, "An Introduction to Transition-Metal Chemistry: The Ligand Field Theory," is considered a classic.
Mr. Orgel returned to the United States in 1964 when he became a founding fellow of the Salk Institute.