Universal Code

The discovery of E. coli's sex life gave scientists a way to dissect a chromosome. It turned out that E. coli has a peculiar sort of sex, with one microbe casting out a kind of molecular grappling hook to reel in a partner. Its DNA moves into the other microbe over the course of an hour and a half. Élie Wollman and François Jacob, both at the Pasteur Institute in Paris, realized that they could break off this liaison. They mixed mutants together and let them mate for a short time before throwing them into a blender. Depending on how long the bacteria were allowed to mate, the recipient might or might not get a gene it needed to survive. By timing how long it took various genes to enter E. coli, Wollman and Jacob could create a genetic map. It turned out that E. coli's genes are arrayed on a chromosome shaped in a circle.

Scientists also discovered that along with its main chromosome

E. coli carries extra ringlets of DNA, called plasmids. Plasmids carry genes of their own, some of which they use to replicate themselves. Some plasmids also carry genes that allow them to move from one microbe to another. E. coli K-12's grappling hooks, for example, are encoded by genes on plasmids. Once the microbes are joined, a copy of the plasmid's DNA is exchanged, along with some of the chromosome itself.

As some scientists mapped E. coli's genes, others tried to figure out how their codes are turned into proteins. At the Carnegie Institution in Washington, D.C., researchers fed E. coli radioactive amino acids, the building blocks of proteins. The amino acids ended up clustered around pellet-shaped structures scattered around the microbe, known as ribosomes. Loose amino acids went into the ribosomes, and full-fledged proteins came out. Somehow the instructions from E. coli's DNA had to get to the ribosomes to tell them what proteins to make.

It turned out that E. coli makes special messenger molecules for the job. The first step in making a protein requires an enzyme to clamp on to a gene and crawl along its length. It builds a single-stranded version of the gene from RNA. This RNA can then move to a ribosome, delivering its genetic message.

How a ribosome reads that message was far from clear, though. RNA, like DNA, is made of four different bases. Proteins are combinations of twenty amino acids. E. coli needs some kind of dictionary to translate instructions written in the language of genes into the language of proteins.

In 1957, Francis Crick drafted what he imagined the dictionary might look like. Each amino acid was encoded by a string of three bases, known as a codon. Marshall Nirenberg and Heinrich Matthaei, two scientists at the National Institutes of Health, soon began an experiment to see if Crick's dictionary was accurate. They ground up E. coli with a mortar and pestle and poured its innards into a series of test tubes. To each test tube they added a different type of amino acid. Then Nirenberg and Matthaei added the same codon to each tube: three copies of uracil (a base found in RNA but not in DNA). They waited to see if the codon would recognize one of the amino acids.

In nineteen tubes nothing happened. The twentieth tube was filled with the amino acid phenylalanine, and only in that tube did new proteins form. Nirenberg and Matthaei had discovered the first entry in life's dictionary: UUU equals phenylalanine. Over the next few years they and other scientists would decipher E. coli's entire genetic code.

Having deciphered the genetic code of a species for the first time, Nirenberg and his colleagues then compared E. coli to animals. They filled test tubes with the crushed cells of frogs and guinea pigs, and added codons of RNA to them. Both frogs and guinea pigs followed the same recipe for building proteins as E. coli had. In 1967, Nirenberg and his colleagues announced they had found "an essentially universal code."

Nirenberg would share a Nobel Prize for Medicine the following year. Delbrück got his the year after. Lederberg, Tatum, and many others who worked on E. coli were also summoned to Stockholm. A humble resident of the gut had led them to glory and to a new kind of science, known as molecular biology, that unified all of life. Jacques Monod, another of E. coli's Nobelists, gave Albert Kluyver's old claim a new twist, one that many scientists still repeat today.

"What is true for E. coli is true for the elephant."

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