In 1936, at the Rockefeller Institute on the Upper East Side of Manhattan, Oswald Avery, a microbiologist, wondered aloud if the carrier of the genetic information from old chromosomes to new might be DNA, but no one took much notice—at least not at that time.
In Britain, during the pre-war years, J.D. Bernal at Cambridge and William Astbury at Leeds, both crystallographers, began using X-rays to determine the structure of molecules in crystals. Astbury, interested in very large biological molecules, had taken hundreds of X-ray diffraction pictures of fibers prepared from DNA. From the diffraction patterns obtained, Astbury tried building a model of DNA. Published in 1938, the model was to remain constant throughout all the attempts to solve DNA's structure that were to come. However, Astbury made serious errors, his work was uncertain, and he had no clear idea of where to go from there.
In 1943, Avery, at 67, was still working at the Rockefeller Institute and experimenting with pneumococcus (bacteria that cause pneumonia). In 1928, he made a revolutionary discovery when he found that when DNA was transferred from a dead strain of pneumoccocus to a living strain, it brought with it the hereditary attributes of the donor.
Avery was hesitant about publishing his discovery as he was “not yet convinced that (he had) sufficient evidence.” A year later, however, Avery, with two colleagues, wrote out their research. They described an intricate series of experiments using the two forms of pneumococcus, virulent and nonvirulent. When they freed a purified form of DNA from heat-killed virulent pneumococcus bacteria and injected it into a live, nonvirulent strain, they found that it produced a permanent heritable change in the DNA of the recipient cells. The fact was that the nucleic acid DNA was the genetic message-carrier.
Still, the essential mystery remained; most were still perplexed at DNA’s ability to complete such complex tasks. Many believed that the answer must lie in the structure of the molecule. However, Avery and his co-authors, Colin MacLeod and Maclyn McCarty, could say no more than that "nucleic acids must be regarded as possessing biological specificity the chemical basis of which is as yet undetermined."
In 1943, Erwin Schrödinger, a Viennese physicist and 1933 Nobel Prize winner for laying the foundations of wave mechanics, gave a series of lectures in Dublin, called provocatively "What is Life?" He addressed the issue of the delicate separation of biology from physics and chemistry.
The lectures were published as a book the following year. To the molecular biologist and scientific historian Gunther Stent of the University of California at Berkeley, What Is Life? was the Uncle Tom's Cabin of biology—a small book that started a revolution.
In 1949, Erwin Chargaff was one of the very few who considered Avery's results and analyzed the proportions of the four bases of DNA. He found a curious correspondence: the numbers of molecules present of the two bases, adenine and guanine, were always equal to the total amount of thymine and cytosine, the other two bases. This ratio, found in all forms of DNA, cried out for explanation, but Chargaff could not think what it might be.
That is where Rosalind Franklin arrived at King's College London on January 5, 1951, leaving coal research to work on DNA. She teamed up with James Watson and Francis Crick and the “double helix” theory was born.
