Biologists have long attempted by chemical means to induce in higher organisms predictable and specific changes which thereafter could be transmitted in series as hereditary characters. Among microorganisms the most striking example of inheritable and specific alterations in cell structure and function that can be experimentally induced and are reproducible under well defined and adequately controlled conditions is the transformation of specific types of Pneumococcus.

If the results of the present study on the chemical nature of the transforming principle are confirmed, then nucleic acids must be regarded as possessing biological specificity the chemical basis of which is as yet undetermined.

The inducing substance, on the basis of its chemical and physical properties, appears to be a highly polymerized and viscous form of sodium desoxyribonucleate. On the other hand, the Type m capsular substance, the synthesis of which is evoked by this transforming agent, consists chiefly of a non-nitrogenous polysaccharide constituted of glucose-glucuronic acid units linked in glycosidic union. The presence of the newly formed capsule containing this type-specific polysaccharide confers on the transformed cells all the distinguishing characteristics of Pneumococcus Type III. Thus, it is evident that the inducing substance and the substance produced in turn are chemically distinct and biologically specific in their action and that both are requisite in determining the type of specificity of the cell of which they form a part. The experimental data presented in this paper strongly suggest that nucleic acids, at least those of the desoxyribose type, possess different specificities as evidenced by the selective action of the transforming principle.

The fundamental biological variant is DNA. That is why Mendel's definition of the gene as the unvarying bearer of hereditary traits, its chemical identification by Avery (confirmed by Hershey), and the elucidation by Watson and Crick of the structural basis of its replicative invariance, are without any doubt the most important discoveries ever made in biology. To this must be added the theory of natural selection, whose certainty and full significance were established only by those later theories.

The discovery that DNA is the stuff of genes can be traced to Oswald Avery, a practitioner who wanted to learn how bacteria cause pneumonia.

What do all of these pioneers [Archibald Garrod, Oswald Avery, Peyton Rous] have in common? First, they were physicians who were trained in basic science. To them, it was not a question of physiology or medicine. To them, medicine was physiology. Second, they showed technical courage in using the most advanced scientific methods to solve medical problems.