RICHARD STROHMAN – “The 20th century is well named as the Century of the Gene. Biologists focused on establishing linkages of genotype (the genetic composition of the organism) to phenotype (what the organism looks and behaves like) and, in relationship to public health, to the mechanisms by which the phenotypes of premature senescence, disease, and death are encoded in the genome. All of the essential data have been amassed in the databases known as the genome (all the genes), and the proteome (all the proteins), and the relationship of these informational sources to the disease-health phenotypes of individuals has been laid out in terms emphasizing an agent-based causality: defective genes encode defective proteins which cause defective phenotypes.
Causality, however, is a complex subject that has plagued the scientific discourse ever since Aristotle laid down guidelines for distinguishing the various forms of causality and the trajectories leading from cause to effect. Efficient cause emphasizes workers as the agency or processes actually used for bringing agents together to build a usable structure. But processes are dynamic and mostly complicated. In biology they are considered to be complex beyond anything found in the physical sciences of inanimate materials.
In 20th-century biology, the pursuit of dynamic processes of efficient cause was assumed to be too difficult: its mechanisms were buried in evolutionary time and were inaccessible. What remained constant (conserved) were the agents, genes and proteins, and they became the focus for understanding living systems. In the Aristotelian causal topology these agents constitute the material cause. This mistaken assumption on the part of biologists, that the agents of material cause could also be the agency through which a phenotype is constructed (efficient cause), is now being acknowledged as an epistemological error of great importance.
Certainly genes are essential for defining any phenotype, but by themselves they remain just inert materials. In order for genetic information to be replicated or “decoded” and used to assemble phenotypes, the DNA must first be manipulated by systems of enzymes and small molecules that constitute the efficient cause for constructing phenotypes. Nearly all biologists now acknowledge this reality. Figure 1 provides a summary of this second informational system: an epigenetic system, so named because of its ability to activate and silence elements in DNA and thereby to produce specific patterns of gene expression and proteins in a context-dependent (time and place) manner.
Figure 1 is holistic in that it views the organisms of the modern world as entities inseparable from their genes or from the external world in which they exist: together they form a coevolutionary whole. Twentieth-century biology could not advance beyond its molecular view because the work of molecular biologists, for many reasons, could not and did not include fundamental research into the molecular biology of the genome-environment interaction in ways that would inform their mutual shaping of one another within a single lifetime.
Health promotion and disease prevention in society are products of that mutual shaping, so that molecular biology, complemented by epigenetic self-organizing systems, may for the first time be said to address the question, “How does living in the world become translated into the language of our genes and into gene-based processes of survival?” Thus does modern molecular biology complete its search for genetic answers and, more specifically, to the challenge put by Barbara McClintock in her Nobel Prize acceptance speech of 1984: “We know about the components of genomes. . . We know nothing, however, about how the cell senses danger and initiates responses to it that are often truly remarkable.”
