ONE DANG FINCH AFTER THE OTHER:

There are many other problems besides proteins.  One of the most basic, and the last I'll mention here, calls into question the whole idea of gene mutations driving macro-evolution -- the emergence of new forms of organism, versus mere variation on existing forms.

To help create a brand new form of organism, a mutation must affect a gene that does its job early and controls the expression of other genes that come into play later on as the organism grows.  But mutations to these early-acting "strategic" genes, which create the big body-plan changes required by macro-evolution, seem to be invariably fatal.  They kill off the organism long before it can reproduce.  This is common sense.  Severely deformed creatures don't ever seem fated to lead the way to glorious new forms of life.  Instead, they die young.

Evidently there are a total of no examples in the literature of mutations that affect early development and the body plan as a whole and are not fatal.  The German geneticists Christiane Nüsslein-Volhard and Eric Wieschaus won the Nobel Prize in 1995 for the "Heidelberg screen," an exhaustive investigation of every observable or inducible mutation of Drosophila melanogaster (the same patient, long-suffering fruit fly I meddled with relentlessly in an undergraduate genetics lab in the 1970s).  "[W]e think we've hit all the genes required to specify the body plan of Drosophila," said Wieschaus in answering a question after a talk.  Not one, he continued, is "promising as raw materials for macroevolution" -- because mutations in them all killed off the fly long before it could mate.  If an exhaustive search rules out every last plausible gene as a candidate for large-scale Drosophila evolution, where does that leave Darwin?  Wieschaus continues: "What are -- or what would be -- the right mutations for major evolutionary change?  And we don't know the answer to that."

There is a general principle here, similar to the earlier principle that the number of useless polypeptides crushes the number of useful ones.  The Georgia Tech geneticist John F.  McDonald calls this one a "great Darwinian paradox."  Meyer explains: "genes that are obviously variable within natural populations seem to affect only minor aspects of form and function -- while those genes that govern major changes, the very stuff of macroevolution, apparently do not vary or vary only to the detriment of the organism."  The philosopher of biology Paul Nelson summarizes the body-plan problem:

Research on animal development and macroevolution over the last thirty years -- research done from within the neo-Darwinian framework -- has shown that the neo-Darwinian explanation for the origin of new body plans is overwhelmingly likely to be false -- and for reasons that Darwin himself would have understood.

Darwin would easily have understood that minor mutations are common but can't create significant evolutionary change; major mutations are rare and fatal.

It can hardly be surprising that the revolution in biological knowledge over the last half-century should call for a new understanding of the origin of species.

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