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29 April 2015

The Least Likely Man celebrates a genetic-code-breaking genius


The Least Likely Man celebrates a genetic-code-breaking genius

Marshall Nirenberg came from nowhere to win a key scientific race (Image: NATIONAL LIBRARY OF MEDICINE/SPL)

IN 1968, Marshall Nirenberg jointly won the Nobel prize in physiology or medicine for his decisive contribution to cracking the genetic code. Eight years earlier, Nirenberg and biochemist Heinrich Matthaei had used an artificial string of RNA featuring only the base uracil (U) to make the amino acid phenylalanine. The first word in the genetic code had been read: UUU codes for phenylalanine.

The Least Likely Man celebrates a genetic-code-breaking genius

The way the discovery emerged is the stuff of legend. In August 1961, at the International Congress of Biochemistry in Moscow, Russia, the little-known Nirenberg gave a talk to a couple of dozen delegates, who were amazed. Word spread. The next day, Francis Crick rejigged the schedule to allow Nirenberg to speak to hundreds of leading researchers. The audience, says Crick, was “electrified”.

In one bombshell experiment, Nirenberg and Matthaei had shown the world how to crack the code. Over the following six years, Nirenberg played a key role in identifying the function of all 64 three-letter words, or codons, in our DNA.

“In one bombshell experiment, Nirenberg and Matthaei had shown how to crack the code”

In this first biography of Nirenberg, Franklin Portugal, who worked in his lab, tries to unravel how the man went from being an average student studying caddis flies to a molecular biologist taking on such greats as Crick, Sydney Brenner and James Watson, and beating them at their own game.

Science historians are wary of “great men” explanations, whereas scientists writing history tend to revel in individuals. With Nirenberg, the two converge: he may have been in the right place at the right time, but he also had a unique insight into how to crack the genetic code.

This crucial discovery opened the floodgates: within a few months, Crick had demonstrated that each codon had three letters. But Nirenberg was nearly swept away by the flood, as biochemist Severo Ochoa in New York moved into the field and rapidly churned out papers, some of which did not even cite Nirenberg and Matthaei.

Nirenberg had the last laugh. He worked out complex biochemical procedures for identifying the exact nature of the RNA codons that the cell uses to introduce a particular amino acid into a protein, and Ochoa’s lab eventually bowed out of the race.

Portugal’s slim biography understandably concentrates on the years 1958 to 1967, using a unique legacy: dozens of lab diaries. In these, Nirenberg recorded ideas for experiments and jotted down exhortations to himself to work harder, and to his experiments simply to work.

Some of the diaries were cited by leading historian Lily Kay in her book Who Wrote the Book of Life? Portugal’s selection overlaps Kay’s, but neither satisfactorily explains why Nirenberg became fascinated by genetic code, nor what it was in his intellect and training that let him see a solution so many others missed.

In one of the book’s other threads, Portugal claims that Crick ignored Nirenberg’s alleged primacy in discovering messenger RNA, and effectively bullied him into sharing unpublished data.

In fact, Crick was extremely generous to the brilliant outsider. For example, he devoted the whole of a 1962 BBC lecture to Nirenberg. And he ended a Scientific American article in March of that year thus: “We are coming to the end of an era in molecular biology. If the DNA structure was the end of the beginning, the discovery of Nirenberg and Matthaei is the beginning of the end.”

Whatever the case, Nirenberg’s brilliant contribution deserves to be more widely known. Portugal’s fascinating book can only help.

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