- May 15, 2005
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The situation is more complicated than that, I'm afraid. The key mutation I'm talking about requires at least three other mutations (and possibly as many as eight) to function. (Whether the other mutations are needed to produce the resistance, or instead to compensate for the change in protein function caused by the key mutation, is not known.) So it wasn't a single mutation that only occurred once -- it was a sequence of at least four mutations, three of which provided only very weak selective advantage by themselves.
This multi-step mutation process is much more unlikely to occur than a single mutation, and probably explains why chloroquine survived as an effective drug for 20 years, while sulfadoxine-pyrimethamine (which requires a simpler set of multiple mutations for resistance to occur) lasted less than five years, and at least one other drug has been lost to drug resistance while still in clinical trials.
Incidentally, looking at the literature, I see that the same key mutation has occurred in the wild at least four times, once in southeast Asia, once in Papua-New Guinea and twice in South America. It has also been seen repeatedly in lab experiments. In reality, any population of malaria that is exposed to CQ will develop resistance to it eventually.
In any case, your original claim was that the chance of any beneficial mutation occurring was essentially zero. Now we're arguing about a just one beneficial mutation that has occurred at least a half dozen times independently. Do you recognize now that your original claim was incorrect?
(Incidentally, malaria is not caused by bacteria, but by single-celled parasites.)
For the sake of the argument, I will assume your data to be correct. But you are talking about a species that passes through a number of generations equal to our entire recorded historynin a single month, and for which you can lift a number of individuals similar to our entire population in a single teaspoon. So considering how fast they reproduce, and how many there are in the entire world, I would consider a hundred such cases in the multiple decades since the cure for malaria was discovered, to be a fraction so small that it is essentially zero. It would, even in that case, be one in far less than a quintillion, and I am persuaded that even that number that is multiple orders of magnitude too large.
I cannot even begin to comprehend how many quintillions of reproductions must have taken place in this species during the period we are discussing, but I would estimate it in the millions or billipons.
If you remember, my original observation was thatno beneficial mutation has ever been demonstrated in anything above a single celled lifeform. I am not aware of a simgle exception to this rule, and I doubt that there is one.
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