Leslie Orgel was born in London, England, on . He received his Bachelor of Arts degree in chemistry with first-class honours from the University of Oxford in 1948. In 1951 he was elected a Fellow of Magdalen College, Oxford and in 1953 was awarded his PhD in chemistry.
Orgel started his career as a theoretical inorganic chemist and continued his studies in this field at Oxford, the California Institute of Technology, and the University of Chicago.
Together with Sydney Brenner, Jack Dunitz, Dorothy Hodgkin, and Beryl M. Oughton he was one of the first people in April 1953 to see the model of the structure of DNA, constructed by Francis Crick and James Watson, at the time he and the other scientists were working at Oxford University's Chemistry Department. According to the late Dr. Beryl Oughton, later Rimmer, they all travelled together in two cars once Dorothy Hodgkin announced to them that they were off to Cambridge to see the model of the structure of DNA. All were impressed by the new DNA model, especially Brenner who subsequently worked with Crick; Orgel himself also worked with Crick at the Salk Institute for Biological Studies.
In 1955 he joined the chemistry department at Cambridge University. There he did work in transition metal chemistry and ligand field theory, published several peer-reviewed journal articles, and wrote a textbook entitled Transition Metal Chemistry: Ligand Field Theory (1960). He developed the Orgel diagram showing the energies of electronic terms in transition metal complexes.
Orgel formulated his protein-translation error-catastrophe theory of aging in 1963, (prior to the use of the term by Manfred Eigen for mutational error catastrophe) which has since been experimentally challenged.
In 1964, Orgel was appointed senior fellow and research professor at the Salk Institute for Biological Studies in La Jolla, California, where he directed the Chemical Evolution Laboratory. He was also an adjunct professor in the Department of Chemistry and Biochemistry at the University of California, San Diego, and he was one of five principal investigators in the NASA-sponsored NSCORT program in exobiology. Orgel also participated in NASA's Viking Mars Lander Program as a member of the Molecular Analysis Team that designed the gas chromatography mass spectrometer instrument that robots took to the planet Mars.
Orgels lab came across an economical way to make cytarabine, a compound that is one of todays most commonly used anti-cancer agents.
Together with Stanley Miller, Orgel also suggested that peptide nucleic acids – rather than ribonucleic acids – constituted the first pre-biotic systems capable of self-replication on early Earth.
His name is popularly known because of Orgels rules, credited to him, particularly Orgels Second Rule: "Evolution is cleverer than you are."
In his book The Origins of Life, Orgel coined the concept of specified complexity, to describe the criterion by which living organisms are distinguished from non-living matter. He published over three hundred articles in his research areas.
In 1993, Orgel presented at the "What is Life?" Conference at Trinity College in Dublin, Ireland along with many other prominent scientists exploring the origin of life research such as Manfred Eigen, John Maynard Smith and Stephen Jay Gould. Orgel's talk was on "Molecular Structure and Disordered Crystals."
Orgel died of pancreatic cancer on 27 October 2007 at the San Diego Hospice & Palliative Care in San Diego, California.