There seems to have been a recent revival of Behe’s “Big Scary Number” for how mutations can make changes in organisms. This is little more than an ID proponent’s attempt to find any way to discredit evolution in the hopes that people who don’t know any better will think that Intelligent Design has some kind of merit.
First of all, a point about Behe’s discussion in Edge of Evolution. In the book (pg 146), Behe says this.
So let’s accept my earlier conservative estimation, and spell out some implications. The immediate, most important implication is that complexes with more than two different binding sites—ones that require three or more different kinds of proteins—are beyond the edge of evolution, past what is biologically reasonable to expect Darwinian evolution to have accomplished in all of life in all of the billion-year history of the world. The reasoning is straightforward. The odds of getting two independent things right are the multiple of the odds of getting each right by itself. So, other things being equal, the likelihood of developing two binding sites in a protein complex would be the square of the probability for getting one: a double CCC, 10^20 times 10^20, which is 10^40. There have likely been fewer than 10^40 cells in the world in the past four billion years, so the odds are against a single event of this variety in the history of life. It is biologically unreasonable.
In this case, CCC means “Chloroquine Complexity Cluster” which is a made up term that means events that involve leaps of two simultaneous mutational changes. There are several problems with this.
The first is that 10^20 number. Where does that come from?
Miller makes the same mistake here that I addressed earlier when replying to Jerry Coyne’s response. The number of one in 10^20 is not a probability calculation. Rather, it is statistical data. It is perhaps not too surprising that both Miller and Coyne make that mistake, because in general Darwinists are not used to constraining their speculations with quantitative data. (SR emphasis)
However, Behe rather… exaggerates that particular claim. When we go to the peer reviewed paper[1] that Behe got this data from we find the following.
Chloroquine resistance in P. falciparum may be multigenic and is initially conferred by mutations in a gene encoding a transporter (PfCRT) (13). In the presence of PfCRT mutations, mutations in a second transporter (PfMDR1) modulate the level of resistance in vitro, but the role of PfMDR1 mutations in determining the therapeutic response following chloroquine treatment remains unclear (13). At least one other as-yet unidentified gene is thought to be involved. Resistance to chloroquine in P. falciparum has arisen spontaneously less than ten times in the past fifty years (14). This suggests that the per-parasite probability of developing resistance de novo is on the order of 1 in 10^20 parasite multiplications. (SR emphasis)
However, the problem is that is an off-the-cuff estimate with little to no evidential support. The author (White) admits as much in this paper (page 547).
The estimates for chloroquine and artemisinin are speculative. In the former case, this assumes two events in 10 years of use with exposure of 10% of the world’s falciparum malaria (Burgess &Young 1959; Martin&Arnold1968; Looareesuwan et al. 1996; Su et al. 1997 [2]
Further the author in [1] goes on to mention that the big scary number isn’t all that relevant to the discussion anyway.
The single point mutations in the gene encoding cytochrome b (cytB), which confer atovaquone resistance, or in the gene encoding dihydrofolate reductase (dhfr), which confer pyrimethamine resistance, have a per-parasite probability of arising de novo of approximately 1 in 1012 parasite multiplications (5). To put this in context, an adult with approximately 2% parasitemia has 1012 parasites in his or her body. But in the laboratory, much higher mutation rates thane 1 in every 1012 are recorded.
In other words, even if the odds of a particular form of resistance are 1 in 10^12 organisms, almost every person with the parasite has about 10^12 organisms in their body, which means it is likely that every person will have at least one parasite with resistant characters.
Here’s the thing though. We can actually study this stuff and look at what is happening in the genes of the malarial parasite. This was done in this paper Progressive increase in point mutations associated with chloroquine resistance in Plasmodium falciparum isolates from India by Mittra et. al.
In this paper, the authors sequenced the genes of several hundred malarial parasites in two groups, two years apart. The paper was written several years after Edge of Evolution and shows some very interesting things.
First is that for the Malaria parasite, resistance to the anti-malaria drug chloroquine appears to be located in two different genes. Now, since Behe says that having two genes with the correct mutation would have a probability (remember, this is based on an incorrect assumption by Behe) of 1 out of 10^40, then it’s most likely that chloroquine resistance can never evolve without an intelligent agent’s help.
This is actually perfect. Because we know that chloroquine resistance does exist, this is the ID proponents’ chance to show us how the designer made it. Sadly, that in the decade since this paper was written, no one has taken up that challenge… I wonder why?
Anyway, back to the genes. I’m going to give you a portion of the amino acid sequence. The letters aren’t important, but the changes in those letters are important. As I said, there are two genes and the wild type, that is non-mutated, have the amino acid sequence CMNKA in one gene and NY in the other gene. If you find a malaria parasite from a population that has never been exposed to anti-malaria drugs, that’s what you would see in those two genes (partially).
But in India, where there is a significant problem with malaria and humans are routinely given the anti-malaria drug, the populations have the following mutations (I’ve underlined the changed amino acids).
In gene one
- CMNKA – 15.4%
- CMNKS – 0.4%
- CMNTA – 2.6%
- CMNTS – 4.9%
- SMNTA – 0.4%
- SMNTS – 61.8%
- CIDTS – 2.2%
- CIETS – 12%
And in the other gene
- NY – 0.4%
- YY – 0.4%
- NF – 69.5%
- YF – 29.7%
I included the relative abundance of each mutational group in the tested population (256 unique populations).
The wild type (CMNKA) has a minimum inhibitory concentration (MIC) of about 500 nanomoles per Liter (nmol/L) That means the CMNKA version starts being affect by the drug at that concentration (which is not much).
The SMNTS variant has a MIC of close to 2,000 nmol/L. The CIETS variant has a MIC of over 4,000 nmol/L.
What this means is that not only is a very specific mutation not required for chloroquine resistance, there are many mutations that can give that trait to the malaria parasite. Sure, some are more effective than others. If you look at the list of mutational effects for that gene you can see a pattern emerging.
The most resistant strain has 4 unique point mutations in the gene that results in 4 different amino acids. The resulting organism is 8 times more resistant than the wild type.
But then we add in the other gene. By itself the YF is only a few hundred nmol/L more resistant. But it also was shown to provide additional assistance to the first gene, increasing the resistance.
Now things start to get really interesting. This wasn’t really a study of just the mutations and drug resistance. It was also a study over time and space. About half of the total samples were taken from 2000 to 2001 and the other half were taken from 2003 to 2004.
The changes in the total populations over time were most interesting. There are a total of 15 possible combinations of the alleles of the two genes. In the first series, three of the combinations didn’t exist. They only appeared in the second time series. Meanwhile, two of the combinations were in the first series, but subsequently were not present in the second series. We can’t assume that they went extinct, but it’s possible.
Of the three new combinations, one had 2 mutations, one had 4 mutations and one had 5 mutations.
It gets even better.
Eight of our [samples] also contained intermediate mutated gene forms (7 [samples] with the CMNTA genotype and 1 [sample] with the SMNTA genotype), wherein a mutation was found at
codon 76, whereas codon 220 had the wt allele (figure 1A). A study has shown that [samples] with this intermediate form (the CMNTA genotype) show slightly higher IC50 values for CQ than do [samples] with the wt allele [16]. Therefore, it has been proposed that acquisition of CQR is a stepwise process, and that association with additional mutations would give rise to a higher level of CQR.
All that fancy stuff just means that as the genes become more mutated over time, they increase in resistance to chloroquine. This is dramatically unlike what Behe and other ID proponents have proposed… that is, one must have exactly the correct mutation, in combination, at the same time, or the whole thing won’t work.
That’s not the case at all. Mutations happen, a lot. And the vast majority of those changes have zero effect on the organism. Some have positive effects, some have negative effects. Plus, these are populations of organisms, with genetic diversity being shared through reproduction. Not a sudden “poof” of a new protein that must appear from nothing, exactly correct, or the organism dies.
Look at what we have here. We have 14 unique combinations of mutations across two different genes, that all result in at least some resistance to the drug. These combinations come from between 1 and 6 mutations unique point mutations from the original genes.
Michael Behe says a double event is biologically unreasonable. Yet, here we have two triple events, two quad events, 5 penta events, and 2 hexa events.
This shows why Behe is wrong. He is not thinking about populations of organisms evolving over time. He does not take into account the plasticity of the genome. He also does not consider intermediate steps which offer some resistance. Indeed, he thinks that the intermediate steps are effectively impossible. Yet, here they are.
Behe and other ID proponents, this is a perfect opportunity for you. Show us how your intelligent agent did this and only your intelligent agent can do this.
These are just point mutations. Super common. Happens all the time and easily within the range of biological systems. The results are clear. No designer is needed or required and Behe’s big scary numbers are based on flawed premises and are directly opposite what is observed in the real world.
At which point, I feel compelled to include this quote.
If your Personal Beliefs deny what’s objectively true about the world, then they’re more accurately called Personal Delusions
— Neil deGrasse Tyson (@neiltyson) September 13, 2015
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[1] White, N. J. 2004. Antimalarial drug resistance. J. Clin. Invest. 113:1084-92
[2] “The de novo selection of drug-resistant malaria parasites.” N J White and W Pongtavornpinyo Proc Biol Sci. 2003 March 7; 270(1514): 545–554.
