In 1935, Stanley isolated needle-like crystals of the tobacco mosaic virus (TMV) that were 1,000 times more infectious than the juice from which they were made. He determined that the virus's protein had all the usual attributes of a pure chemical compound. In fact, it appeared to be a giant chemical molecule. Leading molecular biologists of the next generation characterized Stanley's finding as the effective beginning of molecular biology.

Subsequently, Frederick Bawden and Norman Pirie, then working at Cambridge, in England, found that TMV is about 94 percent protein and 6 percent nucleic acid (RNA). They determined that the active substance is not, as Stanley had supposed, a simple protein of high molecular weight, but a nucleoprotein — a protein chemically combined with a nucleic acid. Moreover, the nucleic acid portion of the virus enables it to reproduce when introduced into a living cell.

William H. Stein and Stanford Moore, who came to Rockefeller as postdoctoral fellows in the late 1930s, joined forces to fill the gaps in knowledge about protein structure. Scientists had determined that proteins function as enzymes, antibodies, hormones, oxygen carriers, and as the major building blocks of body tissue. But little was known of their structure — not even the composition of the amino acids that comprised a single protein.

In collaboration with Darrel Spackman, a young member of the laboratory, Stein and Moore invented an amino acid analyzer that automated and vastly accelerated the process of separating and quantifying the amino acids in a protein. Today, laboratories all over the world use the commercial descendants of this analyzer to determine the composition of purified proteins, physiological fluids, and foods.

Beginning in 1949, Stein, Moore, and a colleague, C. H. W. Hirs, began using these analytical methods to isolate and study the primary structure of bovine pancreatic ribonuclease, an enzyme that catalyzes the breakdown of RNA. (This enzyme had been isolated by Renè Dubos at Rockefeller.) In 1963, Stein, Moore and Hirs published the entire amino acid sequence for ribonuclease A — the first description of an enzyme's chemical structure and the largest protein decoded at that time.

Stein and Moore received the Nobel Prize in chemistry in 1972, along with Christian B. Anfinsin of the National Institutes of Health. The award recognized their contributions to understanding the interrelationships between the structure and activity of the ribonuclease molecule.