The reason why mutations have to happen simultaneously in the same organism, according to Michael Behe, is because any one of them, by itself, is detrimental. This defines the edge of evolution because it's a result that cannot be achieved by mutation and selection (or by drift).
Behe is correct. If a given phenotype absolutely requires that two mutations happen simultaneously then this is going to be almost impossible in most species.
Behe uses the example of drug resistance in Plasmodium falciparum (malaria parasite). Resistance to atovaquone occurs quite often so that's probably due to a single mutation. Resistance to chloroquine, on the other hand, is rare so it's probably due to multiple mutations in the relevant gene (PfCRT, a gene that encodes a transporter protein) [Quinine and Malaria, The Edge of Evolution, Understanding Mutation Rates and Evolution].
The first "prediction" has been shown to be false. A recent paper by Summers et al. (2014) looks at the common chloroquine resistant strains of the malaria parasite and concludes that, indeed, multiple mutations are required but they accumulated in a stepwise manner. Some of the required mutations were beneficial, some were neutral, and some were detrimental.
Here's the relevant figure (see below) from their paper. Each of the haplotypes (labelled D27, GB4, Ecu1110 etc.) represent a different strain of Plasmodium. The ones that are underlined are the commmon chloroquine resistant strains. There are two families, shown in figure A and figure B.
The authors were able to test the effects of various mutations in order to measure the strength of the transporter protein (chloroquine uptake). They discovered that all chloroquine haplotypes had a K76T mutation (red circle). (This is a lysine to threonine substitution at amino acid 76.) By itself, this was neutral with respect to chloroquine resistance (blue arrows) but in combination with N75E OR N326D (pink circles), the strain acquired a low level of chloroquine resistance (green arrows). Several additional mutations were required in order to confer a significant level of resistance and some of these reduced the level of chloroquine uptake (red arrows).
All of the strains (except D17) are found in naturally occurring Plasmodium populations and the probable pathways to each of the major chloroquine resistant strains are shown. It takes at least four sequential steps with one mutation becoming established in the population before another one occurs.
None of the mutations occurred simultaneously as Behe claimed in his book.
So, how do the IDiots deal with this result, which shows that chlorquine resistant strains can easily evolve without ever coming close to the edge of evolution?
A Pretty Sharp Edge: Reflecting on Michael Behe's Vindication]. The author is Ann Gauger.
I am writing a post that shouldn't have to be written. It's about Dr. Michael Behe's book The Edge of Evolution, what it predicted, how that prediction was confirmed, and how his detractors continue to quibble and obfuscate, claiming that even if he was right he was still somehow wrong. That's not the way scientists are supposed to operate.I sure hope you turned off your irony meter.
In science, theory that explains data and makes a prediction that is experimentally verified is considered to be confirmed. That's the way it is supposed to work. Einstein's general theory of relativity, Mendeleev's periodic table, and many other theories have been verified this way.
Now let's look at Behe's theory. Malaria is a devastating disease caused by the parasite P. falciparum. These parasites are quick to develop resistance to most drugs, but they have had a hard time overcoming chloroquine, requiring more than ten years to develop resistance. In fact, sixty years since the drug's introduction, and after more than 1020 malarial parasites total, resistance to chloroquine has developed fewer than ten times. Why?
In The Edge of Evolution, Behe proposed an answer. His explanation -- his hypothesis, if you will -- is simple. The mutation rate of P. falciparum is roughly 1 in 108 mutations per base pair per parasite. There are on average 1012 parasites in the human body -- that's enough for more than a thousand copies of every possible single mutation to exist somewhere in each infected person. So if resistance required only one mutation, it should have appeared in a few days. However, it took more than a decade for resistance to emerge. Behe argued that therefore at least two mutations must be required for the parasite to develop resistance to chloroquine. Furthermore, those two mutations must each be of no use as single mutations, and those two mutations must be present together in the same organism in order to confer resistance to the drug.
Why did Behe make these predictions? It's a simple calculation, really. If two simultaneous mutations are required for resistance, the rate of that double mutation occurring can be calculated by multiplying the single rates together. That makes the rate for two mutations roughly 1 in 1016 mutations per base pair per parasite. To find those two mutations would require many more trials than are available among the 1012 parasites in each person infected. However, 1020 parasites (the total present in a single year) represent more than enough opportunity for that double mutation to occur.
Ann Gauger's post is a followup to an exchange that occurred last week when Casey Luskin suggested that Behe's critics should apologize [So, Michael Behe Was Right After All; What Will the Critics Say Now?]. PZ Myers made approximately the same points that I made and he was supported by Ken Miller [Quote-mined by Casey Luskin!] [Falling over the edge].
What we're seeing here (and elsewhere) is a massive failure of the IDiots' ability to deal with inconvenient facts.
UPDATE: Michael Behe, himself, has posted three (count 'em) recent articles on Evolution News & Views (sic). He claims that his ideas on the limits of evolution have been vindicated by confirmation that chloroquine resistance requires more than one mutation. It's important to keep in mind that every single scientist who ever looked at this problem back in 2007, when The Edge of Evolution was published, knew that more than one mutation (and fixation) was required for chloroquine resistance. None of those scientists thought that this was even close to the edge of evolution. They still don't.
A Key Inference of The Edge of Evolution Has Now Been Experimentally Confirmed
It's Tough to Make Predictions, Especially About the Future
The Edge of Evolution: Why Darwin's Mechanism Is Self-Limiting
Summers, R. L., Dave, A., Dolstra, T. J., Bellanca, S., Marchetti, R. V., Nash, M. N., Richards, S. N., Goh, V., Schenk, R. L., Stein, W. D., Kirk, K., Sanchez, C. P., Lanzer, M. and Martin, R. (2014) Diverse mutational pathways converge on saturable chloroquine transport via the malaria parasite’s chloroquine resistance transporter. Proceedings of the National Academy of Sciences. published online April 11, 2014. [doi: 10.1073/pnas.1322965111]