We do know that things go wrong in biological system[s], because this happens all the time; living things get sick and die. They also very often eat each other, or exist as diseases for each other. These realities mean that biological and ecological problems are much more intractable than physical problems, and are unsolvable in the enclosed context of a multi-generational starship.The challenges laid out in the essay are certainly worrisome. But this defeatist attitude is both strategically unwise and also betrays a lack of imagination--ironic coming from a titan of science fiction.
In fact, the very science that leads Robinson to give up on human long-term survival is what makes me generally optimistic. A short time ago these concepts--dynamic equilibrium, microbiome, hormesis/antifragility, bioaccumulation--didn't exist in any sophisticated way. The pace of our knowledge improvement in this area is only speeding up; I see no decisive reason why we can't figure out solutions. Indeed, experiments with long-term closed ecosystems are ongoing. Robinson is probably right that currently, humanity needs the earth's biosphere to survive. But there's no reason why we can't figure out a way to take it with us to the stars.
Quick overview of the great filter idea here.