Alexander Rich (1924–2015) Biologist Who Discovered Ribosome Clusters and ‘Left-Handed’ DNA

OBITUARY COMMENT Alexander Rich (1924–2015) Biologist who discovered ribosome clusters and ‘left-handed’ DNA.

first came across Alexander Rich worked out the structure of Rich in 1963. He was on the a Z-DNA fragment bound to an cover of that year’s 13 May issue RNA-editing enzyme. He and his

Iof Newsweek with his PhD student colleagues also showed how the JOSIAH D. RICH Jonathan Warner. The two of them pathogenicity of the vaccinia virus, had just discovered clusters of ribo- and probably of the smallpox virus, somes called polysomes — crucial correlated with a virus-specific pro- components involved in the build- tein binding to the host’s Z-DNA. ing of proteins. Rich’s interest in the latest Rich, who died on 27 April, was discoveries across diverse disciplines born in 1924 in Hartford, Connecticut was irrepressible. During the 1970s, to immigrant parents from Russia and he worked as an adviser for NASA, Eastern Europe. He grew up during weighing in on projects exploring the Great Depression in Springfield, the possible existence of life on Mars. Massachusetts, attending a technical He also ventured into biotechnology secondary school by day, and work- and co-founded three companies: ing nights at a local rifle factory. At Repligen, Alkermes, and in his 80s, one point, his family went to live at a 3-D Matrix. local YMCA club after being evicted Rich received numerous honorary from their home. Against the odds, degrees and awards, including the US Rich made it to Harvard University National Medal of Science, presented in Cambridge, Massachusetts, grad- to him in 1995 by then US President uating with a bachelor’s degree in Bill Clinton. biochemical sciences in 1947. Two In spite of such a broad sweep of years later, he received a medical degree from to the identification of DNA sequences, for achievements, Alex was best known among Harvard Medical School in Boston. instance using the northern blot technique. close colleagues for his self-possession, large In 1949, Rich joined chemist Linus Pauling Today, it forms the basis of DNA chips, which personality, critical intellect and humanity. at the California Institute of Technology are used to measure the expression levels of He and his wife Jane held legendary parties (Caltech), in Pasadena, where he stayed for tens of thousands of genes at once. at their classic brick house near Harvard five years, and learnt about X-ray crystallog- Rich’s work on polysomes, carried out in Square, bringing together all sorts of people, raphy. To his regret, he never published with 1963, revealed how active ribosomes — the including his four children and now seven Pauling; when asked what Rich had achieved protein builders of cells — line up along a grandchildren. during his tenure, Pauling apparently replied: messenger RNA molecule, like beads on a A few years after I saw him on the cover “not much, but he must have learned a lot”. string. As the ribosomes move along the of Newsweek, Alex and I became faculty col- Indeed he had. From Caltech, Rich went mRNA, the corresponding amino acids are leagues at MIT. We had endless conversations, on to lead the physical-chemistry sec- stitched together to produce proteins. The ate as often as five times a week at a fish res- tion at the US National Institute of Mental work established a defining mechanism in taurant in Cambridge, and drove around in Health (NIMH) in Bethesda, Maryland. In protein building. his dreadful old and enormous cars. On one 1955, during a leave period at the Caven- In 1973, he made the first determination occasion, the police stopped us, suspecting dish Laboratory in Cambridge, UK, he and of an RNA double-helix structure at atomic that his wild gesturing — to explain a theory Francis Crick determined the structures of resolution. This was followed, in 1974, by of evolution to me — indicated drunk driving. two important proteins: polyglycine II and the solution of the L-shaped structure of a Alex was unstoppable. Once, because collagen. Back at the NIMH in 1956, three transfer RNA molecule, which was made of a weeknight family obligation, I had to years after the discovery of DNA’s iconic simultaneously by Rich’s MIT group and decline yet another of his dinner invitations. double helix, Rich and his colleagues discov- Aaron Klug’s group at the Medical Research He responded immediately: “No problem, I ered that RNA can also form a double helix, Council Laboratory of Molecular Biology in will come instead to your home later in the and even a three-stranded helical structure. Cambridge, UK. evening to talk”. And he did. ■ The findings paved the way for studies that Rich is perhaps best known for his discov- showed RNA’s capacity to fold into complex ery of a DNA structure in which the double Paul Schimmel is professor of cell and architectures. helix winds to the left instead of the right. molecular biology at the Scripps Research In 1958, Rich became an associate profes- In 1979, he, along with crystallographer Institute in Jupiter, Florida, and La Jolla, sor at the Massachusetts Institute of Technol- Andrew Wang, revealed this stable, ‘left- California. He was a colleague of Alexander ogy (MIT) in Cambridge. There he showed handed’ DNA structure, dubbed Z-DNA, Rich at the Massachusetts Institute of that RNA could hybridize with, or bind to, using X-ray crystallography. After showing Technology in Cambridge from 1967 DNA to form a double helix. From the early that Z-DNA can influence the production onwards. 1970s, this phenomenon was widely applied and alteration of certain mRNA molecules, e-mail: [email protected]