Natural selection based on the differential multiplication of variant types cannot exist before there is material capable of replicating itself and its own variations, that is, before the origination of specifically genetic material or gene-material.

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.

We do not know of any enzymes or other chemical defined organic substances having specifically acting auto-catalytic properties such as to enable them to construct replicas of themselves. Neither was there a general principle known that would result in pattern-copying; if there were, the basis of life would be easier to come by. Moreover, there was no evidence to show that the enzymes were not products of hereditary determiners or genes, rather than these genes themselves, and they might even be products removed by several or many steps from the genes, just as many other known substances in the cell must be. However, the determiners or genes themselves must conduct, or at least guide, their own replication, so as to lead to the formation of genes just like themselves, in such wise that even their own mutations become .incorporated in the replicas. And this would probably take place by some kind of copying of pattern similar to that postulated by Troland for the enzymes, but requiring some distinctive chemical structure to make it possible. By virtue of this ability of theirs to replicate, these genes–or, if you prefer, genetic material–contained in the nuclear chromosomes and in whatever other portion of the cell manifests this property, such as the chloroplastids of plants, must form the basis of all the complexities of living matter that have arisen subsequent to their own appearance on the scene, in the whole course of biological evolution. That is, this genetic material must underlie all evolution based on mutation and selective multiplication.