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The Transforming Principle by Maclyn McCarty (review)

"Everyone knows" that DNA is the genetic material, that the sequence of the nucleotide components of DNA constitutes a code, that this code is transcribed into "messenger" RNA that moves through the cell to be translated into protein. The flow of "information" is from DNA to RNA to protein and the idea that this is so constitutes the central dogma of (molecular) biology. How everyone came to know that genes are DNA is the subject of this story told by the youngest member of the team that first came to that conclusion 40 years ago. In the course of telling us about his discovery of the nature of the gene, Maclyn McCarty tells something about the nature of experimental science, about American science and society 50 years ago, about himself, and about the relationship between experimental observation and our understanding of the facts. For those of us who have worked in laboratories there is the added joy of recognition as we read of cultures that do not grow for unknown reasons until for reasons equally unknown they once again respond, assays that work erratically, and trails followed enthusiastically only to lead nowhere. The difference for most of us is that McCarty's experiments truly affected the course of biology. Bacteriologists worked in a world apart from the biologists of the first half of this century. There is no nucleus in bacteria, and only a few supposed that there was anything analogous to the genes of "higher" organisms. The pneumococci (Streptococcus pneumoniae) display a special behavior. When they are isolated they show a complex carbohydrate coat. Different strains of pneumococci have very different coats, and the coat types are stable when the bacteria infect animals. In culture the coat can be lost. Once completely lost, the bacteria do not normally regain the ability to make the specific carbohydrate coat. In a mouse, or given the proper circumstances in the test tube, a heat-killed preparation of an encoated strain mixed with a live culture of a second, coat-free strain gives a viable culture producing carbohydrate characteristics of the heat-killed strain. In order to carry out this "transformation" in vitro, one needs to add a complex mixture of components including serum best obtained from chest fluids of patients. Extracts of the coated organisms seem to induce transformation (sometimes) when added to the coat-free cells. What is going on, and does it have anything to do with genetics? The initial discovery is made by Griffith in England and reported in 1927. The subject is taken up at the Rockefeller Institute by co-workers of an expert in