Molecular biology
Sterling Professor of Molecular, Cellular and Developmental Biology and Chemistry
Yale University, Connecticut
Nobel Prize in Chemistry in 1989 (jointly with Thomas R. Cech) “for their discovery of catalytic properties of RNA”
Sidney Altman was born in Montreal in 1939, the second son of poor immigrants. His mother worked in a textile mill and his father in a grocery store. It was from them that he learned that hard work in stable surroundings could yield rewards, "even if only in infinitesimally small increments". Two events sparked his early interest in science. The first of these was the development of the atomic bomb. The second occurred seven years later when he received a book on the periodic table of the elements and he saw the elegance of scientific theory and its predictive power.
When he was in high school he wanted to enrol at McGill University, but an unexpected series of events led him to study physics at the Massachusetts Institute of Technology. During his final semester at MIT, he took a short introductory course in molecular biology to find out what all the excitement was about. That course familiarised him with nucleic acids and molecular genetics and prepared him for future encounters with these topics.
After earning a bachelor’s degree from MIT in 1960, he spent eighteen months as a graduate student in physics at Columbia University. From Columbia he went on to study physics on a summer programme while working in Colorado, and it was there he decided to enrol as a graduate student in biophysics. He started working on the effects of acridines on the replication of bacteriophage T4 DNA at the University of Colorado Medical Center and then he joined Mathew Meselson’s laboratory at Harvard University to study a DNA endonuclease involved in the replication and recombination of T4 DNA. Two years later he joined a research group at the Medical Research Council Laboratory of Molecular Biology in Cambridge, England.
At the MRC laboratory he started the work that led to the discovery of RNase P and the enzymatic properties of the RNA subunit of that enzyme. The discovery of the first radiochemically pure precursor to a tRNA molecule enabled him to start working as an assistant professor at Yale University in 1971, becoming a full professor in 1980, and in 1985 the dean of Yale College for four years. In 1989 he returned to the post of professor on a full-time basis.
In 1989 he was awarded the Nobel Prize, together with Thomas Cech, for their discovery of catalytic properties of RNA. Altman’s discovery concerns fundamental aspects of the molecular basis of life: a catalyst is a molecule which can facilitate a chemical reaction without being consumed or changed. Virtually all chemical reactions taking place in a living cell require catalysts, which are also called enzymes.
Until Altman and Cech’s results were published, all enzymes were considered to be proteins, whose specific properties and functions are determined by hereditary characters, or genes, composed of deoxyribonucleic acid, better known as DNA.
During the 1970s, Altman studied how the genetic code of DNA was transcribed into RNA. This process requires, apart from the actual transcription, a shearing and splicing of the RNA molecules, because the DNA strands contain regions which are not essential for making proteins, and the excess codes are also transcribed into the RNA molecules. Before the RNA can be further used by the cell, these extra pieces of nucleic acid have to be removed and the useful pieces rejoined. Like all chemical reactions in a cell, this RNA shearing and splicing requires enzymes. It was during the search for the enzymatic proteins of these reactions that Altman made his surprising discovery – the enzymes were not proteins but nucleic acids.
The discovery of catalytic RNA has altered the central dogma of the biosciences. Moreover, it has already had a profound influence on our understanding of how life on earth began and developed. It is very likely that the RNA molecules were the first biomolecules to contain both the genetic information and play a role as biocatalysts.
Catalytic RNA also provides gene technology with a new tool, with the potential to create a new defence against infections. In 1997 Altman experimented with a method to fight antibiotic resistance, by inserting artificial genes into bacteria in order to make them highly sensitive to two widely used antibiotics, ampicillin and chloramphenicol.
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