E.S. Russell
When E. S. Russell published The Interpretation of Development and Heredity in 1930, the gene was still an unknown “factor” — a small segment of a chromosome of uncertain physical nature. What was known was that in sexual reproduction some of the parental chromosome segments were distributed among the offspring in general accordance with the results Mendel had obtained for certain traits of peas. There was, in these cases, a satisfying mathematical regularity seeming to govern both the occurrence of traits and the corresponding behavior of chromosomes. This made it appear obvious to many biologists that the chromosomes — that is, the unknown “factors,” or genes, they contained — would fully explain the traits.
This was not at all obvious to Russell, however — nor was it obvious to the many embryologists and developmental biologists who complained that the geneticists in fact had almost nothing to say about the actual occurrence of traits in living organisms. After all, those traits arose from the embryo through elaborate processes of development, and there was already strong evidence that the complement of chromosomes remained the same in cells throughout the organism during this development. How could something that remained the same in all the different tissues and organs, from liver and skin to heart and nerves, explain the development of these organs from an original, undifferentiated zygote?
Many of these critics, including Russell, pointed out that the genetic experiments of the day showed only how differences arose when genes were mutated. Derange a particular gene, and the fruit fly's eye color changed. But to take this as evidence that the gene explains the eye color was rather like saying the ignition key not only is required for the automobile's movement, but also explains the drive train.
Russell's critique was surprisingly prescient, retaining a great deal of validity even in the post-double helix era of the molecular gene. He by no means downplayed the significance of chromosomes, saying (quite rightly) that they appeared to be crucial for maintaining the metabolism of the organism. But instead of looking to them for a causal explanation of the rest of the organism, he foresaw a time when they would, in our understanding, be fully integrated with the entire physiology of cell and organism. This would require us to “throw off all traces of the particulate conception of heredity” — a conception that sees little bits of chromosomal substance as explanations for traits.
Moreover, rebelling against the atomistic habits of thought that made genetic elements into fixed, determinate, and particulate things, transferable from one position on the chromosome to another without change in their character, he wrote that the difference between two chromosomes “may quite well be a slight though discontinuous chemical or stereochemical change affecting the chromosome as a whole.” That is, we should look not merely for atomic genes, but for overall changes of significant form.
These points capture the main substance of the revolution now developing under the name of “epigenetics.” The entire cell continually sculpts and re-sculpts its chromosomes without at all changing the actual DNA sequences that were so long equated with genes. This shaping activity, which we have every right to think of in artistic terms, determines what gets expressed from the DNA.