I think the “second” question about second order effects was really the main question here. If the intentional beneficial effects don’t quite add, that’s no great tragedy, but if combining multiple edits produces unexpected changes, some of which are bad, that’s kind of a deal killer. I don’t find the chart you reference to be very convincing, since it only lists a handful of characteristics that are sufficiently common to have names and have been studied in such an analysis. For every one of those there are likely countless less frequent and/or more subtle “bad” variations whose correlation with the things we’re trying to fix we have no idea of. Informally, don’t you have to wonder why, if a small number of edits would seem to lead to a clearly superior genome, natural selection hasn’t happened upon some of those combinations already? How can we know what combinations were “tried” earlier in our evolution with long-term negative consequences?
I think the “second” question about second order effects was really the main question here. If the intentional beneficial effects don’t quite add, that’s no great tragedy, but if combining multiple edits produces unexpected changes, some of which are bad, that’s kind of a deal killer. I don’t find the chart you reference to be very convincing, since it only lists a handful of characteristics that are sufficiently common to have names and have been studied in such an analysis. For every one of those there are likely countless less frequent and/or more subtle “bad” variations whose correlation with the things we’re trying to fix we have no idea of. Informally, don’t you have to wonder why, if a small number of edits would seem to lead to a clearly superior genome, natural selection hasn’t happened upon some of those combinations already? How can we know what combinations were “tried” earlier in our evolution with long-term negative consequences?