The unimaginable complexity of our evolved human systems.

In the face of all the current hubris about redesigning and engineering humans using modern genetic and biochemical tools, trying to reverse engineer brain systems that were never engineered in the first place, Randolph Nesse offers a very therapeutic essay. Here is a slightly edited version:

The products of natural selection are … not merely complicated in the way that machines are complicated, they are organically complex in ways that are fundamentally different from any product of design. This makes them difficult for human minds to fully describe or comprehend. So, we use that grand human gambit for understanding, a metaphor, in this case, the body as machine…it easy to portray the systems that mediate cell division, immune responses, glucose regulation, and all the rest, using boxes for the parts, and arrows to indicate causes what. Such diagrams summarize important information in ways we can grasp. .. But, they fundamentally misrepresent the nature of organic complexity.

Thinking about the body as a machine was a grand advance in the 16th century, when it offered an alternative to vitalism and vague notions of the life force. Now it is outmoded. It distorts our view of biological systems by fostering thinking about them as simpler and more sensibly "designed" than they are. Experts know better. They recognize that the mechanisms that regulate blood clotting are represented only crudely by the neat diagrams medical students memorize; most molecules in the clotting system interact with many others. Experts on the amygdala know that it does not have one or two functions, it has many, and they are mediated by scores of pathways to other brain loci. Serotonin exists not mainly to regulate mood and anxiety, it is essential to vascular tone, intestinal motility, and bone deposition. Leptin is not mainly a fat hormone, it has many functions, serving different ones at different time, even in the same cell. The reality of organic systems is vastly untidy. If only their parts were all distinct, with specific functions for each! Alas, they are not like machines. Our human minds have as little intuitive feeling for organic complexity as they do for quantum physics.

Recent progress in genetics confronts the problem. Naming genes according to postulated functions is as natural as defining chairs and boats by their functions. If each gene were a box on a blueprint labeled with its specific function, biology would be so much more tractable! However, it is increasingly clear that most traits are influenced by many genes, and most genes influence many traits. For instance, about 80% of the variation in human height is accounted for by genetic variation. It would seem straightforward to find the responsible genes. But looking for them has revealed that the 180 loci with the largest effects together account for only about 10% of the phenotypic variation. Recent findings in medical genetics are more discouraging. Just a decade ago, hope was high that we would soon find the variations that account for highly heritable diseases, such as schizophrenia and autism. But scanning the entire genome has revealed that there are no common alleles with large effects on these diseases. Some say we should have known. Natural selection would, after all, tend to eliminate alleles that cause disease. But, thinking about the body as a machine aroused unrealistic hopes.

The grand vision for some neuroscientists is to trace every molecule and pathway to characterize all circuits in order to understand how the brain works. Molecules, loci, and pathways do serve differentiated functions, this is real knowledge with great importance for human health. But, understanding how the brain works by drawing a diagram that describes all the components and their connections and functions is a dream that may be unfulfillable. The problem is not merely fitting a million items on a page, the problem is that no such diagram can adequately describe the structure of organic systems. They are products of miniscule changes, from diverse mutations, migration, drift, and selection, which develop into systems with incompletely differentiated parts and incomprehensible interconnections, that, nonetheless, work very well indeed. Trying to reverse engineer brain systems focuses important attention on functional significance, but it inherently limited, because brain systems were never engineered in the first place.

If bodies are not like machines, what are they like? They are more like Darwin's "tangled bank" with its "elaborately constructed forms, so different from each other, and dependent upon each other in so complex a manner." Lovely. But, can an ecological metaphor replace the metaphor of body as machine? Not likely. Perhaps someday understanding how natural selection shapes organic complexity will be so widely and deeply understood that scientists will be able to say "A body is like…a living body," and everyone will know exactly what that means.