Discovery of DNA

Deoxyribonucleic acid (DNA) was first discovered in 1869 by Johann Friedrich Miescher (1844-1895), a young Swiss chemist studying in Tübingen, Germany. Miescher's interest in the biochemistry of the cell nucleus led him to collect used surgical bandages, from which he collected pus (white blood cells), which have very large nuclei. From these, he purified a new compound, which he termed "nuclein." Miescher showed that nuclein was a large molecule, acidic, and rich in phosphorus. Miescher continued to work with nuclein over the next two decades, turning for his source to salmon sperm, which have exceptionally large nuclei and were plentiful in the rivers near his laboratory. One of his students renamed the compound "nucleic acid."

In 1885 the German biologist Oskar Hertwig (1849-1922) suggested that nucleic acid might be the hereditary material, based on its presence in the nucleus and the growing certainty that the nucleus was the center of heredity. Despite this promising beginning, no further progress was made in understanding its true role until the 1940s.

The biochemistry of nucleic acid continued to be studied, however, and by 1900, scientists had learned that it was composed of three parts: a sugar, a phosphate, and a base (together termed a nucleotide). The five-carbon sugar is a ringed structure, and it forms an alternating chain with phosphate (a phosphorus atom surrounded by four oxygens). Also attached to the sugar is one of five different bases: adenine, cytosine, guanine, thymine, and uracil, usually abbreviated A, C, G, T, and U. The names of the bases are related to their historical origin: Guanine was isolated from bird guano, thymine from the thymus gland of calves, and adenine from calf pancreas ("adeno-" is a Greek root for gland); uracil is chemically related to urea; and "cyto-" means cell.

In the 1920s it was discovered that there were two types of sugars, ribose and deoxyribose, differing by the presence or absence of one oxygen atom. DNA was shown to incorporate the bases A, C, G, and T, while RNA (ribonucleic acid) incorporates A, C, G, and U. Much of this work was carried out by the German biochemist Albrecht Kossel (1853-1927) and the American Phoebus Aaron Levene (1869-1940).

Also by the 1920s, Thomas Hunt Morgan and his colleagues had shown that genes, whatever they were made of, were carried on chromosomes. Chromosomes were shown to contain both protein and DNA, so the question of which of these two substances composed the genes took center stage. The more complex chemical nature of proteins gave them the theoretical edge, an opinion given great and, in hindsight, unfortunate weight by Lev-ene, a widely respected biochemist.

Levene proposed the tetranucleotide hypothesis, which held that the structure of DNA was a monotonous repetition of the four nucleotides in succession. Levene's evidence was that DNA, which he had isolated from a variety of sources, had roughly equal amounts of A, C, G, and T. While the actual proportions he found were not exact, Levene attributed the differences to experimental error, rather than biochemical reality. Such a simple nucleotide a building block of RNA or DNA

and highly regular molecule as the one Levene proposed could not account for the diversity of life, however, and so DNA was assumed to play only a structural role in the chromosome.

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