Taking development seriously: Toward a genuinely synthetic biology

Abstract

<p>The Human Genome Project (HGP) is nearing completion, and shortly we will have access to the complete genetic sequence of an average human being. Hopes are high that the sequence will contribute profoundly to medicine in particular, but also to our understanding of our evolutionary past. Of course, detractors have long insisted that because the HGP represents a victory for formalism in biology, determining the function of DNA sequences will remain an outstanding problem for at least the next several decades. Moreover, it is not clear that having the complete sequence will be significantly useful to biologists seeking to understand gene function in the first place. What can we expect in the postgenomic era? I reject the very idea that a complete, encapsulated sequence of a human genome is foundational to biological understanding. I set my investigation within the framework of the ancient debate between preformationists and epigenecists. I survey and conceptually analyze arguments on both sides, especially as they relate to the separation of genetics and embryology in the early part of the twentieth century. I identify modern variants of both preformationism and epigenesis, and note their reconciliation in the form of a Modern Consensus on development established after the neo-Darwinian Synthesis in biology in the 1940s. Drawing on recent work in molecular and developmental biology, I challenge the seeming intuitiveness of the Modern Consensus and its subsumption of developmental concerns under the aegis of molecular genetics. I then propose and defend an alternative synthesis of preformationism and epigenesis, and of genetics and developmental biology, according to which development (epigenesis) does not reduce to mere gene activation. I underscore the practical benefit of my perspective through a lengthy discussion of the psychiatric genetics approach to schizophrenia.</p>