This lecture is a progress report on my effort to analyze the possible reasons for the persistence of genes that increase disease vulnerability.  The obvious important ones are the inevitability of mutations and environmental variation. If those could be eliminated, would most disease vulnerability be eliminated?  I argue that much would remain for two reasons. First,  maximizing gene transmission can increase disease vulnerability via several routes. Second, traits with asymmetric fitness functions are  stabilized at mean values that maximize fitness despite variation that leaves some individuals off the edge of a fitness cliff.  These perspectives offer a potential explanation for highly heritable diseases caused by thousands of alleles with tiny effects.