In his book, The Edge of Evolution, Michael Behe calculated the odds of a malaria parasite developing resistance to chlorquine by assuming that two separate mutations were necessary. Here's what he said on page 57 ...
How much more difficult is it for malaria to develop resistance to chloroquine than to some other drugs? We can get a good handle on the answer by reversing the logic and counting up the number of malarial cells needed to find one that is immune to the drug. For instance, in the case of atovaquone, a clinical study showed that about one in a trillion cells had spontaneous resistance. In another experiment, it was shown that a single amino acid change at position number 268 in a single protein, was enough to make P. falciparum resistant to the drug. Se we can deduce that the odds of getting that single mutation are roughly one in a trillion.There's more, but let's pause here to describe the Behe challenge. Here it is in his own words.
Talk is cheap. Let's see your numbers.I decided to take the Behe Challenge: Taking the Behe challenge!. The idea was to try and calculate the probability of chloroquine resistance arising in a population of malarial parasites. I don't doubt that this is a rare event but I have serious doubts about Behe's calculations.
In your recent post on an earlier reviews of my book The Edge of Evolution you toss out a lot of words, but no calculations. You downplay FRS Nicholas White's straightforward estimate that—considering the number of cells per malaria patient (a trillion), times the number of ill people over the years (billions), divided by the number of independent events (fewer than ten)—the development of chloroquine-resistance in malaria is an event of probability about 1 in 1020 malaria-cell replications. Okay, if you don't like that, what's your estimate? Let's see your numbers.
I also pointed out that there's a big difference between the mutation rate and whether a resistant strain becomes established enough to be detected. It's the different between mutation and fixation. Behe seems to be confused about this difference. He seems to think that all you need to do is calculate the probability of the mutations occurring.
Let me emphasize, again, that I'm not questioning the fact that mutations are rare events. What I'm doing is answering Behe's challenge to relate that fact to what we know about mutation and evolution. It turns out that Behe's calculations are suspect. It also turns out that the actual estimates are very much more difficult than Behe imagines.
Let's look at the rest of Behe's paragraph from page 57 in his book.
On the other hand, resistance to chloroquine has appeared fewer than ten times in the whole world in the past half century. Nicholas White of Mahidol University in Thailand points out that if you multiply the number of parasites in a person who is very ill with malaria times the number of people who get malaria per year times the number of years since the introduction of chloroquine, then you can estimate the odds of a parasite developing resistance to chloroquine is roughly one in a hundred billion billion. In shorthand scientific notation, that's one in 1020.No, that's NOT the odds of a parasite developing chloroquine resistance. It's the odds of the mutations occurring times the odds that it will become well enough established to be detectable.
I tried to meet the Behe challenge by showing how I would calculate the odds of the mutation(s) occurring and why my calculations differ from Behe's. It's still a long shot but that doesn't mean that Behe's calculations and assumptions are correct.
Behe didn't like my answer. He says,
Moran doesn't seem to actually have much confidence in his own numbers. He asks the readers of his blog to help him correct his calculations—which is a commendable attitude but makes one wonder, if he's so unsure of the likelihood of helpful combinations of mutations, whence his trust in mutation/selection? In response to the commenter who alerted him to the huge number of parasites in a million people he writes, "This is why meeting the Behe challenge is so difficult. There are too many variables and too many unknowns. You can't calculate the probability because real evolution is much more complicated than Behe imagines." But, again, if he thinks everything is so darn complicated and incalculable, on what basis does he suppose he's right?I don't suppose that I'm right for many reasons. For one, I don't know the probability of a chloroquine-resistant parasite surviving transmission through the mosquito host. I don't know whether the various intermediates are more fit than their ancestors of less fit, and by how much. I don't know the frequency of the various alleles in the parasite population. I don't know whether all the humans in an infected region need to be treated constantly with chloroquine in order to detect a chloroquine-resistant strain.
What I do know is that Behe's calculations are wrong. On what basis does he think he's right?