2012 : WHAT IS YOUR FAVORITE DEEP, ELEGANT, OR BEAUTIFUL EXPLANATION?

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Professor of Psychiatry, UM Medical School; Professor of Psychology, University of Michigan; Co-author, Why We Get Sick

Natural Selection Is Simple, But The Systems It Shapes Are Unimaginably Complex

The principle of natural selection is exceedingly simple. If some individuals in a population have a heritable trait associated with having more offspring, that trait will (with a few caveats) become more common in the population over the generations.

The products of natural selection are vastly complex. They 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.

This metaphor makes 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. Teachers teach them. Students dutifully memorize them. But, they fundamentally misrepresent the nature of organic complexity. As Haldane noted in a prescient 1917 book, "a living organism has, in truth, but little resemblance to an ordinary machine." Machines are designed. They have discrete parts with specific functions, and most remain intact when turned off. Individual machines are manufactured following identical copies of a single blueprint. In contrast, organisms are evolved. They have components with indistinct boundaries and multiple functions that interact with myriad other parts and the environment to create self-sustaining reproducing systems that whose survival requires the constant activity and cooperation of thousands of interdependent subsystems. Individual organisms develop from unique combinations of genes interacting with each other and environments to create phenotypes, no two of which are identical.

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.

Natural selection shapes systems whose complexity is indescribable in terms satisfying to human minds.  Some may feel this is nihilistic. It does discourage hopes for finding simple specific descriptions for all biological systems. However, recognizing a quest as hopeless is often the key to progress. As Haldane put it, "We are thus brought face-to-face with the conclusion which to the biologist is just as significant and fundamental, just as true to the facts observed, as the conclusion of mass persists is to the physicists… the structure of a living organism has no real resemblance in its behavior to that of a machine… In the living organisms…the "structure" is only the appearance given by what seems at first to be a constant flow of specific material, beginning and ending in the environment."

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.