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How Biochemist Keith Fox Thinks About Enzyme Origins…And Why He Should Think Again

Keith Fox

Keith Fox’s scientific credentials are rock solid — Professor of Biochemistry at the University of Southampton and Senior Executive Editor of Nucleic Acids Research, a premier science journal for work on DNA and RNA. He’s a leading figure in his field.

Protein evolution, however, isn’t his field. If there were any doubts about that, his recent wild speculations on the origin of enzymes should put them to rest.

Enzymes are the special class of proteins responsible for carrying out the sophisticated chemistry of life. Research my colleagues and I have done on these remarkable molecular reactors has challenged the claim that they originated by natural selection acting on accidental mutations. My recent book — Undeniable: How Biology Confirms Our Intuition That Life Is Designed — describes some of this work by placing it in the context of the familiar principle that accidental causes are incapable of inventing clever things.

Provoked by a favorable review of the book, Fox wrote a critical response that employs the usual Darwinian tactic of pretending that sophisticated functions are easy to stumble upon in rudimentary form, and then easy to perfect. The enzymes we see in life are large molecules made by joining the twenty amino acids in precise sequence to form long chains that fold up into complex shapes to do their jobs with extreme speed and precision. But according to Fox, “their primitive predecessors would have been much less efficient, maybe speeding up reactions [relative to background rates in water] by (say) two-fold.”

Fox knows that a mere doubling of background rates would be “pathetic” in comparison to the enzymes we see in cells, but he doesn’t seem to realize just how pathetic it would be. He says enzymes speed their reactions up “by as much as a billion-fold,” whereas in reality even simple reactions involving just one reactant can be sped up nearly a billion billion-fold by the wizardry of enzymes. For more complex reactions the acceleration can be effectively infinite, because in many cases these reactions don’t occur at all in the absence of enzymes.

A mere doubling of the background rate would therefore be pathetic indeed! Fox nevertheless sees no reason to doubt that primitive enzymes performing so poorly could have been “the first step on the long evolutionary road of trial and error, improving the activity in a stepwise series of events, climbing the mountain one step at a time, rather than one-giant leap.”

That’s the usual story line, but when you press people who work on protein evolution for details, they always take refuge in the excuse that these things happened so long ago we really shouldn’t expect to be able to reconstruct the specifics. Best to settle for vague once-upon-a-time stories.

Well, Fox has now broken with that tradition by supplying details. According to his critique of my book, the primitive enzymes he refers to could have consisted of a mere two amino acids linked together. Not the hundreds needed in today’s cells for doing simple chemical conversions or the thousands needed for reading genes or generating ATP. Just link the twenty amino acids in pairs — 400 combinations in total — and those myriad sophisticated tasks can all be performed, he thinks. Don’t expect high performance right away from such crude beginnings, but that’s bound to come with time, says Fox.

Hmm. And maybe SpaceX happened by accident when Elon Musk stumbled upon a bolt and a nut working like a rocket and a communications satellite (crudely, of course).

In truth, the reason enzyme scientists would never make the claim that Fox made is that they know it can’t be backed up. No one with any experience in the field thinks they can go into the lab and find pairs of amino acids that do the work of enzymes.

As I indicated in my full response to Fox’s critique of my book, although he hasn’t given us anything of scientific significance, he has revealed something important about his own perspective. Considering his prominence in the dialog on science and faith (Associate Director of the Faraday Institute for Science and Religion) this is worth noting in itself. Since Fox would never offer wildly unfounded guesses on his own research (of the kind he has on evolution) it’s hard to escape the conclusion that he takes evolutionary science much less seriously than he takes his own science.

Maybe he thinks his goal of persuading non-scientists doesn’t call for the facts to be handled with the care his scientific colleagues expect. People naturally assume that professional biochemists speaking on matters of biochemistry must know what they’re talking about, and maybe Fox is too willing to take advantage of that.

And maybe you, as one of those people, will see things differently now that you know this.

Fox is, of course, as welcome as anyone to speak to the Darwin-versus-design debate, but if he wants people to take him seriously, perhaps he should view that as a privilege to be earned by public trust rather than a right bestowed by the academy.

Photo: University of Southampton, by Chris T Cooper (Own work) [Public domain], via Wikimedia Commons.

Douglas Axe

Maxwell Professor of Molecular Biology at Biola University, Senior Fellow, Center for Science and Culture
Douglas Axe is the Maxwell Professor of Molecular Biology at Biola University, the founding Director of Biologic Institute, the founding Editor of BIO-Complexity, and the author of Undeniable: How Biology Confirms Our Intuition That Life Is Designed. After completing his PhD at Caltech, he held postdoctoral and research scientist positions at the University of Cambridge and the Cambridge Medical Research Council Centre. His research, which examines the functional and structural constraints on the evolution of proteins and protein systems, has been featured in many scientific journals, including the Journal of Molecular Biology, the Proceedings of the National Academy of Sciences, BIO-Complexity, and Nature, and in such books as Signature in the Cell and Darwin’s Doubt by Stephen Meyer and Life’s Solution by Simon Conway Morris.



amino acidsbiochemistryDNAenzymesevolutionFaraday Institute for Science and ReligionKeith Foxprotein evolutionUndeniableUniversity of Southampton