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Marshall W. Nirenberg, 82; biologist, leader untangling life's genetic code

Marshall Nirenberg first amazed other biologists and then received the Nobel Prize in Physiology or Medicine in 1968. Marshall Nirenberg first amazed other biologists and then received the Nobel Prize in Physiology or Medicine in 1968. (Bob Schutz/Associated Press)
By Nicholas Wade
New York Times / January 22, 2010

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NEW YORK - Marshall W. Nirenberg, a biologist who deciphered the genetic code of life and received a Nobel Prize for his achievement, died last Friday at his home in Manhattan. He was 82.

The cause was cancer, said his stepdaughter, Susan Weissman.

In solving the genetic code, Dr. Nirenberg established the rules by which the genetic information in DNA is translated into proteins, the working parts of living cells. Understanding the code was a turning point in the history of biology.

Dr. Nirenberg identified the particular codons, each a sequence of three chemical units of DNA, that specify each of the 20 amino acid units of which protein molecules are constructed.

The achievement, in a critical experiment in 1961, was the more remarkable because Dr. Nirenberg was only 34 at the time and unknown to the celebrated circle of biologists, led by Francis Crick, who had built the framework of molecular biology.

Crick and his colleague Sydney Brenner had established, largely on theoretical grounds, that the code must be in triplets of the four kinds of chemical units of which DNA is composed. But they had not developed the experiments to work out which triplet corresponded to which amino acid.

Dr. Nirenberg amazed biologists when he and his colleague, the German scientist Johann Heinrich Matthaei, announced their identification of the first codon. He delivered another surprise when he beat out better-known scientists in the ensuing race to identify the other 63 codons in the genetic code. He received the Nobel Prize in Physiology or Medicine shortly afterward, in 1968. (Two other scientists shared the prize with him.)

Marshall Warren Nirenberg was born in Brooklyn and grew up in Florida. After earning a doctorate at the University of Michigan, he started work at the National Institutes of Health in Bethesda, Md., where he spent the rest of his career.

The project he chose was the synthesis of proteins, then being studied in mixtures of mashed-up cells known as cell-free systems. Dr. Nirenberg took the research a stage further by focusing on the genetic information that might be driving protein synthesis. He was joined by Matthaei, an excellent experimentalist, and the two decided to add lengths of RNA, a close chemical cousin of DNA, to the cell-free systems.

Success came when they added to their cell-free system an RNA molecule composed only of uracil, one of the four chemical units in RNA. The protein that emerged consisted only of phenylalanine, one of the 20 kinds of amino acids in proteins. Because the genetic code was known to consist of triplets, the experiment showed that UUU is the codon for phenylalanine, U being the symbol for uracil.

Dr. Nirenberg and Matthaei were such outsiders that they had not heard of messenger-RNA, made to transfer DNA’s instructions to the cell’s protein-making machinery. While biologists in the club were producing the first evidence for the existence of messenger RNA, Dr. Nirenberg and Matthaei had independently synthesized one.

By rights, their experiment should not have worked because natural messenger-RNAs carry at their front end a special codon that says to the ribosomes, “Start here,’’ a fact not known at the time. But the recipe for protein synthesis used by Dr. Nirenberg and Matthaei happened to contain twice the natural amount of magnesium, an anomaly that was later found to override the need for a start codon.

Dr. Nirenberg presented their findings at the next big conference of molecular biologists, held in 1961 in Moscow. His talk was given to an almost empty room, Horace Judson writes in “The Eighth Day of Creation,’’ his history of molecular biology. But one of the few participants recognized its significance and told Crick, who arranged for Dr. Nirenberg to give his talk again, this time in a large hall attended by an audience of hundreds.

Then followed the race to identify all the other codons, a prize that Dr. Nirenberg’s talk had placed in full view of a hall of better financed rivals like Severo Ochoa of New York University.

“It was a David-and-Goliath situation in which a young investigator without resources came into competition with a distinguished Nobel laureate like Ochoa,’’ said Philip Leder of Harvard, who joined Dr. Nirenberg’s laboratory after Matthaei had left.

Credit for the genetic code is often assigned to Crick and Brenner, who resolved its general nature through theorizing and with a clever experiment. But it was Dr. Nirenberg and Matthaei who cracked the code itself.

Judson, in his history, said efforts to test these ideas “achieved little until Matthaei arrived.’’

Leder recalled Nirenberg as “enthusiastic and magnetic.’’

“He had an idea every two or three minutes,’’ Leder said.