John Tooby makes an argument I had not seen elsewhere:
“Every human child contains roughly 100 new mutations—genetic changes that were not present in their parents. To be sure, many of these occur in inert regions, or are otherwise “silent” and so do no harm. But a few are very harmful individually; and although the remainder are individually small in effect, collectively they plague each individual with debilitating infirmities.
These recent estimates are striking when one considers how, in an entropy-filled world, we maintained our high levels of biological organization. Natural selection is the only physical process that pushes species’ designs uphill against entropy toward greater order (positive selection), or maintains our favorable genes against the downward pull exerted by mutation pressure (purifying selection). If a species is not to melt down under the hard rain of accumulating mutations, the rate at which harmful mutations are introduced must equal the rate at which selection removes them (mutation-selection balance). This removal is self-executing: Harmful genes cause impairments to the healthy design of the individuals they are situated in. These impairments (by definition) are characteristics that reduce the probability that the carrier will reproduce, and thereby reduce the number of harmful genes passed on. For a balance to exist between mutation and selection, a critical number of offspring must die before reproduction—die because they carry an excess load of mutations. …
Now, along comes the demographic transition—the recent shift to lower death rates and then lower birth rates. Malthusian catastrophe was averted, but the price of relaxing selection has been moving the mutation-selection balance toward an unsustainable increase in genetic diseases. Various naturalistic experiments suggest this meltdown can proceed rapidly. (Salmon raised in captivity for only a few generations were strongly outcompeted by wild salmon subject to selection.) …
No one could regret the victory over infectious disease and starvation now spreading across the planet. But we as a species need an intensified research program into germline engineering, so that the Enlightenment science that allowed us to conquer infectious disease will allow us to conquer genetic disease"
(h/t Scott Alexander)