Lethal Mutations
EVOLUTION NEEDS mutations in genes expressed in the early phases of embryonic development, since it’s in the early phases that basic body plans and organs are laid down. For evolution to do anything more than tinker with existing species within narrow limits, it has to be able to mutate the fundamentals—body plans, core architecture, that sort of thing. Such early phase mutations do occur, but here’s the catch: Those mutations are always harmful or lethal. The physiologist and Nobel Laureate Thomas Hunt Morgan performed systematic experiments with fruit flies (Drosophila) in the early twentieth century. He saw that those mutations that influence the basic structures of the animal, which occur early, are without exception harmful, leading to crippling malformations or death. (See Figure 6.1.)
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Experiments carried out later with various test organisms have come to the same conclusion: Mutations that influence the basic body plan of organisms are harmful, often lethal. The geneticist John F. McDonald calls this problem “the great Darwinian paradox.” He expresses the problem as follows: “Those (genetic) loci that are obviously variable within natural populations do not seem to lie at the basis of many major adaptive changes, while those loci that seemingly do constitute the foundation of many if not most major adaptive changes are not variable within natural populations.”12
So the mutations that evolution needs in order to build new body plans do not occur, and those that do occur, evolution doesn’t need.

John F. McDonald, “The Molecular Basis of Adaptation: A Critical Review of Relevant Ideas and Observations,” Annual Review of Ecological Systems 14 (1983): 77–102.
Quoted from HERETIC, ONE SCIENTIST’S JOURNEY FROM DARWIN TO DESIGN, by Matti Leisola and Jonathan Witt.
FIGURE 6.1—Non-viable mutants of fruit fly Drosophila: From left to right: A) Mutant with twisted wings, B) Mutant with short wings that cannot fly, C) “Antennapedia” mutant with legs where antennae should be and that cannot multiply, D) “Eyeless” mutant that is blind.