It's been twenty years since Michael Behe published Darwin's Black Box and Intelligent Design Creationists are flagellating themselves over the fact that it had so little impact on creationism. The USA is becoming more secular with each passing year. Religion is on the decline.In their attempt to deal with their defeat, the main ID blog has been publishing "Behe's Greatest Hits," which is a euphemistic way of saying "Behe's Greatest Failures." The latest one caught my eye. It's Best of Behe: An Open Letter to Professors Kenneth Miller and PZ Myers.
It takes you back more than two years to July 21, 2014. That's when Michael Behe issued his challenge to PZ Myers and Ken Miller. The challenge was based on his book The Edge of Evolution and specifically on the development of chloroquine resistance in Plasmodium falciparum. Behe starts with the assumption that cloroquine resistance is extremely rare—it occurs with a probability of roughly 10-20. He concludes that resistance requires at least two different mutations that must occur simultaneously in an individual suffering from malaria while being treated with chloroquine.
The first assumption is approximately correct. Chloroquine resistance is rare. He was criticized for the second assumption; namely, that the overall probability of chloroquine resistance is just the probability of two mutations occurring simultaneously (e.g. 10-10 × 10-10 = 10-20).
Here's the challenge,
What's puzzling to me is your thinking the exact route to resistance matters much when the bottom line is that it's an event of probability 1 in 1020. From the sequence and laboratory evidence it's utterly parsimonious and consistent with all the data -- especially including the extreme rarity of the origin of chloroquine resistance -- to think that a first, required mutation to PfCRT is strongly deleterious while the second may partially rescue the normal, required function of the protein, plus confer low chloroquine transport activity. Those two required mutations -- including an individually deleterious one which would not be expected to segregate in the population at a significant frequency -- by themselves go a long way (on a log scale, of course) to accounting for the figure of 1 in 1020, perhaps 1 in 1015 to 1016 of it (roughly from the square of the point mutation rate up to an order of magnitude more than it). So how do your calculations account for it?I decided to answer Behe's challenge. This led to a series of back-and-forth blog posts where I tried, unsuccessfully, to convince Behe that he was wrong. The first point is that the overall probability of developing resistance to chloroquine is not just the probability of the mutations occurring in one individual. It's that PLUS the probability that the mutations will become fixed in the populations and subsequently detected by health care workers. Since the detected rate is 10-20, the probability of the mutations must be much higher.
The challenge was answered but you won't see any mention of that in the latest post on Evolution News & Views (sic).
A Key Inference of The Edge of Evolution Has Now Been Experimentally Confirmed July 14, 2014 (Michael Behe)
So, Michael Behe Was Right After All; What Will the Critics Say Now? July 16, 2014 (Casey Luskin)
Quote-mined by Casey Luskin! July 17, 2014 (PZ Myers)
An Open Letter to Kenneth Miller and PZ Myers July 21, 2014 (Michael Behe)
A Pretty Sharp Edge: Reflecting on Michael Behe's Vindication July 28, 2014 (Ann Gauger)
Michael Behe and the edge of evolution July 31, 2014 (Larry Moran)
Taking the Behe challenge! Aug. 1, 2014 (Larry Moran)
Laurence Moran's Sandwalk Evolves Chloroquine Resistance Aug. 13, 2014 (Michael Behe)
Flunking the Behe Challenge! Aug. 13, 2014 (Larry Moran)
CCC's and the edge of evolution Aug. 15, 2014 (Larry Moran)
How Many Ways Are There to Win at Sandwalk? Aug. 15, 2014 (Michael Behe)
Guide of the Perplexed: A Quick Reprise of The Edge of Evolution Aug. 20, 2014 (Michael Behe)
Understanding Michael Behe Aug. 22, 2014 (Larry Moran)
Drawing My Discussion with Laurence Moran to a Close Aug. 26, 2014 (Michael Behe)
Michael Behe's final thoughts on the edge of evolution Aug. 27, 2014 (Larry Moran)
After all that, I failed to explain to Michael Behe what the data actually showed. It showed that chloroquine resistance develops in a two- or three-step scenario where the first steps involve an effectively neutral allele that accumulates in a population by random genetic drift. This is a fairly rare event but it happens in populations that have not been exposed to choroquine. The final step is the one that confers chloroquine resistance when the parasites are exposed to chloroquine.
After all that, Michael Behe still thinks I am defending a scenario where the first steps have to be deleterious in the absence of chloroquine so that all two (or three) mutations have to confer some level of chloroquine resistance in a stepwise manner. He thinks this is the standard Darwinian explanation. This is how he closes the debate, revealing a mind so closed that issuing a challenge was pointless.
I wrote in my last post that I had cited chloroquine resistance in Edge as a likely example of the two-mutation phenomenon, and that Summers et al. recently "confirmed" that it did need two mutations to pump chloroquine. Moran responds, "This is a little bit misleading and possibly a little bit disingenuous. Everyone understood that chloroquine resistance was rare and that it almost certainly required multiple mutations."
I'm afraid it is he who is playing the ingénue. There's a big difference between simply requiring serial additive mutations for some maximal effect and requiring multiple mutations before you get an effect at all. The first is a run-of-the-mill, gradualist Darwinian scenario: one mutation comes along, helps a bit, spreads in the population by selection, which increases the base from which the second mutation may arise; the second appears, helps a bit more, spreads, and so forth. Lather, rinse, repeat.
But if the first required mutation (or second, or third) doesn't help, or positively hurts, then the gradualist scenario is interrupted. The first mutation does not spread in the population (in fact it's actively kept in check by negative selection), so the number of organisms with the mutation does not increase and can't provide a larger base within which the second mutation can arise. The Darwinian magic is turned off.
How Much Does that Hurt?
Enormously. For most species, missing even one such baby step increases the required population size/waiting time by a factor of millions to billions. If even one step in a long and relentlessly detailed evolutionary pathway is deleterious, then a Darwinian process is woefully impaired. If several steps in a row are deleterious, you can kiss the Darwinian explanation goodbye.