Sidney Altman, Who Stumbled on a Breakthrough in Genetics, Dies at 82

Sidney Altman, a molecular biologist who was awarded the Nobel Prize for Chemistry for sharing in the discovery that ribonucleic acid, or RNA, was not just a carrier of genetic information but could also be a catalyst for chemical reactions in cells — a breakthrough that paved the way for new gene therapies and treatments for viral infections — died on April 5 in Rockleigh, N.J. He was 82.

Yale University, where Dr. Altman spent most of his career, announced the death but did not specify the cause.

The discovery that RNA could function as an enzyme upended one of the central tenets of biology: that proteins are necessary to perform chemical reactions in cells.

“The discovery of catalytic RNA has altered the central dogma of the biosciences,” the Nobel Institute said in announcing that Dr. Altman would share the 1989 chemistry prize.

The discovery also suggested an answer to an age-old chicken-and-egg question about how DNA, the double-helix building blocks of life, and proteins could have arisen without carriers like RNA to transmit their codes. Dr. Altman’s work posited that simple RNA molecules had come first.

As seems to happen so often in science, Dr. Altman stumbled upon his discovery. “I wasn’t looking for what I found,” he said in a 2010 interview with Harry Kreisler at the Institute for International Studies at the University of California, Berkeley.

He had studied how a small RNA molecule, called transfer RNA, carries genetic code to make new proteins. Some of the code is not necessary, so an enzyme cuts it out before it is used.

Then, in 1978, Dr. Altman began studying an RNA-cutting enzyme from E. coli bacteria that was composed of an RNA molecule and a protein. He managed to separate the two pieces and test them to see how they reacted in the enzyme process. Much to his surprise, he discovered that the protein did not perform as an enzyme without the RNA molecule. He later discovered that the RNA molecule could be the catalyst, even without the protein.

The finding ran completely contrary to what at the time was established theory, which held that it was the proteins that were the catalysts in enzymes.

The discovery of what are now known as ribozymes was so radical that Dr. Altman had trouble getting it accepted.

Joel Rosenbaum, a professor of cell biology at Yale and a colleague of Dr. Altman’s, told Chemistry World magazine that when Dr. Altman first tried to get other scientists to accept his research, “the community of molecular biologists, including several at Yale working on RNA, did not want to believe the work.”

Dr. Altman, left, in a Yale laboratory with Thomas A. Steitz in 2009, the year Dr. Steitz received a Nobel Prize in Chemistry. Dr. Altman spent most of his career at Yale.Credit…Douglas Healey/Associated Press

“He had a hard time obtaining invitations to speak at scientific meetings and, indeed, getting his work published,” Dr. Rosenbaum said.

Dr. Altman’s work was eventually validated, aided by the research o Thomas R. Cech, a professor at the University of Colorado Boulder who independently discovered the same phenomenon as Dr. Altman, and who shared the 1989 Nobel with him.

The Nobel Institute in 1989 called their work “the two most important and outstanding discoveries in the biological sciences in the past 40 years,” declaring that it had “a profound influence on our understanding of how life on earth began.”

And the institute expressed hope for what these discoveries might lead to: protections in organisms against viral infections, the creation of virus-resistant plants, cures for viral infections like colds in humans and — “a more futurist possibility” — the outright correction of genetic disorders.

Sidney Altman was born on May 7, 1939, in Montreal, the second son of Victor and Ray (Arlin) Altman. His mother was a textile worker; his father ran a grocery store.

The family had little money, but Dr. Altman, in an autobiographical sketch for the Nobel Institute, credited his parents with setting a good example that stayed with him for the rest of his life. “It was from them,” he wrote, “that I learned that hard work in stable surroundings could yield rewards, even if only in infinitesimally small increments.”

Dr. Altman became fascinated by science as a boy — first by news of the detonation of the first atomic bomb, when he was 6 years old, and then by seeing the periodic table of the elements, which, he wrote, gave him a sense of “the elegance of scientific theory and its predictive power.”

He had intended to enroll at McGill University in his hometown, but he changed course when he was accepted by the Massachusetts Institute of Technology. He studied physics at M.I.T., but in his final semester, out of curiosity, he took an introductory course in molecular biology and found it compelling.

After M.I.T., he spent 18 months in a graduate physics program at Columbia University, but he said he was not really happy there. He wanted to be an experimental scientist and there was no opportunity at Columbia, so he quit and went back to Canada.

The next summer, he was offered a job writing about science for an institute in Boulder, where he could also take summer courses.

One night he wound up at a party talking to George Gamow, a well-known physicist, cosmologist and writer. Dr. Altman explained that he was dissatisfied with physics but fascinated with biophysics. Dr. Gamow suggested that he go to the University of Colorado in Denver, which had a good biophysics department.

Dr. Altman went down the next day and met Leonard Lerman, a scientist who was known for his work on DNA and who was then doing research at the university’s medical center. The two agreed that Dr. Altman would enter the Colorado graduate program as one of Dr. Lerman’s students.

Under Dr. Lerman, Dr. Altman found his direction. He obtained a doctorate in biophysics in 1967 and then a fellowship to Harvard, where he worked in the laboratory of the distinguished molecular biologist Mathew Stanley Meselson.

Dr. Altman at a biotechnology event in Bangalore, India, in 2008.Credit…Dibyangshu Sarkar/AFP via Getty Image

Two years later, Dr. Altman had the chance to join the Medical Research Council Laboratory of Molecular Biology in Cambridge, England. The lab was led by two of the most renowned scientists in the field: Sydney Brenner, who would be a Nobel laureate, in 2002, and Francis Crick, who had helped decode the structure of DNA, a landmark work for which he shared the 1962 Nobel Prize in Physiology or Medicine.

“I felt as if I was joining the equivalent of Bohr’s group in Copenhagen in the 1920s,” Dr. Altman wrote, referring to Niels Bohr, the Danish physicist who laid the foundation for understanding the structure of the atom. “It turned out to be scientific heaven.”

Dr. Altman worked in Cambridge until 1971, when his work on transfer RNA led him to Yale as an assistant professor. He worked there for the rest of his career, serving as chairman of the biology department from 1983 to 1985 and dean of Yale College from 1985 to 1988.

Dr. Altman, who was Jewish, was involved in the Judaic studies program at Yale and was an honorary trustee of the university’s Joseph Slifka Center for Jewish Life.

He became a United States citizen in 1984 but retained his Canadian citizenship.

Shortly after he arrived at Yale, Dr. Altman married Anne Korner, a molecular biologist. The marriage ended in divorce in 2018. He is survived by their two children, Daniel and Leah, and four grandchildren.

Dr. Altman once told Yale News that in the biological sciences, “so much of what we observe is still far beyond our grasp.”

“Thus,” he added, “an ‘elegant’ experiment in the biological sciences (as in most of science) is one that tests one specific prediction in a way that allows the result of that prediction to stand above the noisy background of secondary phenomena.”

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