The Genetic Code

After his and James Watson's breakthrough discovery, Francis Crick continued to do research on DNA at Cambridge. (He received his Ph.D. from that institution in 1953.) He wanted to learn how a DNA molecule carries information and how it uses that information to make proteins, which other scientists had shown to be genes' chief task in the cell. The actions of proteins, in turn, create the traits that show themselves in living things.

Crick and Sydney Brenner, a fellow Cambridge scientist, proposed in 1955 that the sequence of bases in a DNA molecule acts as a code to determine the sequence of amino acids in protein molecules. Each "letter" of the code, the two researchers suggested, is a set of three bases arranged in a particular order. With four bases to work with, there could be 64 (4 x 4 x 4) such combinations, more than enough to represent all 20 amino acids.

Marshall Nirenberg of the National Institutes of Health and other molecular biologists set out to "crack" the DNA code in the early 1960s, determining by experiment which amino acid each set of three bases stood for. They learned that several different

DNA's structure explains its power to duplicate itself. When a cell prepares to divide, the hydrogen bonds between the bases dissolve and the DNA molecule splits along its length like a zipper unzipping. Each half then attracts bases and backbone pieces from among the molecules in the cell, forming the same pairs of bases that had existed before. The result is two identical DNA molecules.

Other Scientists: Rosalind Franklin (1920-1958)

Rosalind Elsie Franklin was born on July 25, 1920, in London. Her well-to-do father at first discouraged her interest in science because he believed that higher education and careers made women unhappy. She persisted, however, and eventually studied chemistry at Newnham, a women's college in Cambridge University, graduating in 1941. Franklin did research on the structure of carbon molecules for the Coal Utilization Research Association during World War II and earned a Ph.D. from Cambridge on the basis of this work in 1945.

Franklin learned X-ray crystallography while doing research in France after the war. She became especially skilled at using the technique to study compounds that did not form crystals, which included most biological chemicals. This expertise brought her to Maurice Wilkins's laboratory at King's College, part of the University of London, in 1950. Wilkins hoped Franklin could take photographs that would help the group determine the structure of DNA molecules.

Some of Franklin's photographs were brilliant, and one of them helped James Watson and Francis Crick solve the puzzle of DNA's structure. (Wilkins has been criticized for showing this photograph to Watson without asking Franklin's permission first, but he felt that, as head of the laboratory, he had the right to do so.) Watson and others have said that Franklin herself might have worked out the DNA structure if she had had a scientific partner with whom she felt comfortable sharing her ideas.

Franklin left Wilkins's laboratory around the time Watson and Crick published their first DNA paper. She spent the rest of her all-too-short career studying the structure of viruses at Birkbeck, another college in the University of London.

Franklin died of ovarian cancer in 1958, when she was only 38 years old, leaving forever unsettled the question of whether she would have shared in the 1962 Nobel Prize given to Watson, Crick, and Wilkins. According to Franklin biographer Anne Sayre, J. D. Bernal, the X-ray crystallography expert under whom Franklin worked at Birkbeck, said of her, "As a scientist Miss Franklin was distinguished by extreme clarity and perfection in everything she undertook. Her photographs are among the most beautiful X-ray photographs . . . ever taken."

As a first step in making a protein, part of a DNA molecule (a gene) uses itself as a pattern to form a matching stretch of messenger RNA (mRNA). When the messenger RNA moves into the cytoplasm of the cell, it attracts matching short stretches of transfer RNA (tRNA), each of which tows a single amino acid molecule. With the help of an organelle called a ribosome, the transfer RNA molecules lock onto the matching parts of the messenger RNA, and the amino acids they carry are joined, forming a protein.

base triplets often stood for the same amino acid. Some additional groups marked the beginning or end of a gene. (Each DNA molecule contains hundreds or even thousands of genes.) By 1965, researchers had a "dictionary" that included all 64 three-base combinations.

While the details of the code were being worked out, Crick, Brenner, and others were learning the mechanism by which DNA uses its code to make proteins. Crick and Brenner suggested that DNA makes a copy of itself in the form of RNA (ribonucleic acid), which is like DNA except that it has a different kind of sugar in its backbones, and in place of thymine it has a different base, uracil. DNA normally cannot leave a cell's nucleus, but its RNA copy, which came to be called messenger RNA, can travel into the cytoplasm, the jellylike material that makes up the outer part of the cell.

In the cytoplasm, Crick and Brenner said, the messenger RNA encounters small bodies called ribosomes. A ribosome rolls along the messenger RNA molecule and attracts from the cytoplasm the amino acid represented by each three-base "letter" of the translated DNA code. Crick believed that what he called adapter molecules (later called transfer RNA) tow the amino acids to the correct spots on the messenger RNA. The amino acids then join together, forming the protein. The messenger RNA and the ribosome release the protein molecule into the cell. Brenner and other researchers in the early 1960s proved that this theory was essentially correct.

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