Leslie Orgel

Biography

Born in London, England, Orgel 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, published several peer-reviewed journal articles and wrote a textbook entitled Transition Metal Chemistry: Ligand Field Theory (1960).

Orgel formulated his error catastrophe theory of ageing in 1963, which has since been since experimentally refuted.

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.

Orgel's lab came across an economical way to make cytarabine, a compound that is one of today's 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 Orgel's rules, credited to him, particularly Orgel's 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 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.

Nucleobase Synthesis

Orgel proposed a novel solution to a problem with Juan Oro's proposed mechanism of nucleobase synthesis on the early Earth, which relied on the reaction of five molecules of hydrogen cyanide (HCN) to form adenine. The problem with this was that it would require much more concentrated hydrogen cyanide than evidence suggested was present.

Orgel suggested that the hydrogen cyanide was frozen in solution. This would concentrate HCN molecules in the spaces in between the crystal lattice of ice, and also solved the problem of HCN being too volatile in a liquid water solution.

Nucleoside Formation

For nucleoside (nucleobase + ribose sugar) synthesis, Orgel suggested an almost opposite approach, heating a mixture of ribose and the purine nucleobases hypoxanthine, adenine, and guanine to dryness in the presence of magnesium ions. This reaction puts the glycosidic bond in the correct position in two ways: the nucleobase attaches to the correct carbon on ribose, and in the correct orientation (the beta anomer).

However, the synthesis was later criticised because it only worked most with hypoxanthine, a nucleobase that is not relevant to current life on Earth, and because it was not specific for the ribose sugar and could instead be applied to other sugars.

RNA Polymerization

Continuing his work exploring the prebiotic synthesis of RNA, Orgel suggested a solution to the problem of condensing nucleotides to form nucleic acid polymers, an energy-demanding process. To counteract this energy barrier, he proposed a nucleotide with an imidazole ring attached to the phosphate group. The imidazole would be a good leaving group for the condensation of nucleotides.

Orgel also theorised that one single strand of RNA could have been the template for the first life on Earth and that these imidazole-activated nucleotides could have used this DNA template strand to polymerise and replicate. However, in lab experiments, this only worked when the DNA template strands were rich in the nucleotide cytosine, and furthermore, there so far is no proposed prebiotic synthesis for how an imidazole-activated nucleotide could be formed on the early Earth.

Directed Panspermia

Though he later downplayed the hypothesis, Orgel, along with Francis Crick, proposed a detailed panspermia scenario for the origin of life on Earth, going so far as to suggest that life on Earth was designed by an alien species and sent to Earth. They proposed a design for the spaceship that aliens could have used to seed life on Earth.

RNA World

In the late 1960s, Orgel proposed that life was based on RNA before it was based on DNA or proteins. His theory included genes based on RNA and RNA enzymes. This view would be developed and shaped into the now widely-accepted RNA world hypothesis.

Almost thirty years later, Orgel wrote a lengthy review of the RNA World hypothesis. This review highlighted many proposed syntheses for RNA and its parts in abiotic conditions, noted the significance of the discovery of ribozymes (RNA molecules that function as enzymes just as Orgel had once predicted) and at the same time, demonstrated nucleic acid polymers with alternatives to ribose such as threose nucleic acid (TNA) and peptide nucleic acid (PNA).

In conclusion, Orgel wrote, "One must recognize that, despite considerable progress, the problem of the origin of the RNA World is far from being solved."

Awards

Books