## Friday, August 15, 2014

### CCC's and the edge of evolution

Let me say, right from the beginning, that Michael Behe's book The Edge of Evolution is very interesting and provocative. Many of my colleagues think that Behe's main argument can be easily dismissed as the work of an uninformed IDiot who is blinded by his religion. There's some truth in that, but only a little.

The main thesis of the book is that there are some combinations of mutations that could theoretically be beyond the reach of evolution during the 3 billion years that life has evolved on Earth. Behe refers to this combination as a double CCC (1040). It's his estimate of the probability of a particular combination of four specific mutations arising by chance. Since we know that such combinations have arisen, Behe concludes that god(s) must have been involved.

There are many ways of exploring Behe's calculations in order to see if he has a point. The first problem is that the meaning of his conclusion is very unclear. Let's think about it this way ...

The probability of a particular bridge hand being dealt at a particular table is 5.36 × 1028 [52!/(13!)4] [see Bridge Probabilities (Wikipedia)]. The probability of two particular bridge hands being dealt in sequence at the same bridge table is about 1056 (actually closer to 3 × 1057). What this means is that every time you sit down and play a few hands of bridge you are experiencing probabilities that are lower than the double CCC that upsets Michale Behe. You don't act suprised when you see your bridge hand and you don't attribute it to any of the gods.1

Theme
Mutation
-definition
-mutation types
-mutation rates
-phylogeny
-controversies
This can't be what Michael Behe meant, can it? He describes a CCC as a "chloroquine-complexity cluster" and it's a cluster of two mutations—the ones that gave rise to chloroquine resistance in the malaria parasite. He says that the probability of this cluster arising is 10-20 (one in 1020). He thinks this is the probability of the double mutation but we've demonstrated already that his calculations and his logic are flawed [see Taking the Behe challenge! and Flunking the Behe challenge!].

Nevertheless, if the mutation rate is about 10-10 [see Why are the human and chimpanzee/bonobo genomes so similar?], then the probability of two particular mutations occurring is 10-10 × 10-10 = 10-20, which, by coincidence, happens to be the same number that Behe uses (even though his logic and calculations are wrong)2.

So let's go with CCC = 10-20 as the probability that a particular combination of two mutations will occur. For simplicity, we'll assume they occur in the same gene. Here's where this leads Michael Behe (pages 60-91) ....
What is the total number of creatures in the line leading to humans since it split from the line leading to modern chimps less that ten million years ago? If the average generation span of humanoids is rounded down, conservatively, to about ten years, then a generous estimate is that perhaps a trillion creatures have preceded us in the past ten million years. Although that's a lot, it's still much, much, less than the number of malarial parasites it takes to develop chloroquine resistance. The ratio of humanoid creatures in the past ten million years to the number or parasites needed for chloroquine resistance is one to a hundred million.

If all of these huge numbers make your head spin, think of it this way. The likelihood that Homo sapines achieved any single mutation of the kind required for malaria to become resistant to chloroquine—not the easiest mutation, to be sure, but still only a shift of two amino acids—the likelihood that such a mutation could arise just once in the entire course of the human lineage in the past ten million years, is minuscule—of the same order as, say, the likelihood of you personally winning the Powerball lottery by buying a single ticket.

On average, for humans to achieve a mutation like this by chance, we would need to wait a hundred million times ten million years. Since that is many times the age of the universe, it's reasonable to conclude the following: No mutation that is of the same complexity as chloroquine resistance in malaria arise by Darwinian evolution in the line leading to humans in the past ten million years.
Really? Does he really mean that there can't be any examples of two mutations occurring in the same gene since humans and chimps diverged?

Let's think about this in two ways. First, the theory. The current population of humans consists of seven billion people. Every single one of them is certain to carry mutations (base pair substitution) that have arisen in the past few million years in every single gene [see Why are the human and chimpanzee/bonobo genomes so similar?]. Their children will have about 100 new mutations. If we assume that only one of these occurs in a gene, then in the upcoming generation every single human on Earth will have a CCC (two new mutations in a single gene). Behe says that this is impossible.

Second, the practice. We know the sequences of the human and chimpanzee genomes so it's possible to compare the genes in the two species to see if there are any examples of two mutations arising in the same gene. I took the human fibinogen alpha chain and BLASTED it against the chimp genome. I used the amino acid sequences so we could see mutations that gave rise to new amino acids in the lineages leading to chimps and humans. The result is shown on the left.

There are 25 amino acid substitutions. I don't know which ones occurred in the chimp lineage and which ones occurred in the human lineage but let's just assume that there were 12 mutations in the human lineage that caused an amino acid substitution. The probability of each one is 10-10 (one in 1010) because that's the approximate mutation rate. The probability of any two of these occurring is 10-20. In addition, there's a further low probability that these mutations would be fixed in the human genome.3

We're way beyond a CCC.

Michael Behe says that no mutation of the same complexity as the CCC could arise in the human lineage by Darwinian evolution and yet there they are. And that's just one gene out of 25,000 genes. It looks like CCCs are abundant.

We have a problem.

There are four possibilities that I can see.
1. Behe was really talking about some other, unspecified, kind of mutation cluster.
2. He means something special when he says "Darwinian" evolution that doesn't rule out the more common kinds of evolution. (The fibrinogen example is nearly-neutral alleles that have been fixed by random genetic drift.)
3. The gods like to play around with fibrinogen genes.
4. Behe has made a mistake.

Discuss.

1. This is not quite true. In my circle of friends, I frequently hear the name of one of the gods (Jesus Christ!).

2. Behe says that the mutation rate is 10-8 but gives a reference that says it should be 2.5 × 10-9.

3. The real probability is much less because after the first mutation occurs the second one can be at any other site in the gene. In the case of the fibrinogen gene, there are 866 codons. That means at least 866 × 10-10 or a probability of about 10-7 that a second mutation will occur in the same gene.

#### 119 comments :

1. Let me start the discussion by giving you my take on the issue. I think that Behe is only thinking about one very particular combination of mutations. For example, he's thinking about the probability that evolution will produce a human fibrinogen with a proline at position 10 instead of a valine AND a leucine instead of a valine at position 130. The probability of that particular combination occurring is very low.

He seems to think that whenever we see such mutations they must have been the only possible way to evolve some new function or feature.

1. Yes, that is a recurrent problem with Behe's caculations. He often assumes that the observed pathway is the only way to get there. He also typically assumes that intermediate steps are detrimental or lethal, such that they cannot persist for any significant time in a population.

2. I've only read Behe in excerpts, but from those this is my impression too. He seems to be considering only very specific outcomes rather than categories of outcomes. Rather like the intuitive error most people make in considering the Birthday Problem. The odds that someone in a class of 20 has *your* birthday is clearly 20/365, but the odds that *some* two people in a class of 20 has the same birthday is 50/50. When you shift from a specific outcome to a class of outcomes combinatorics can work for you instead of, as it naively seems, always against you. This is the reason that so many things that seem like low probability events aren't really, because we are cheating by calculating the probability of a specific event and then imagining (or pretending) that that is the probability for some broad category of events.

But what is the class of outcomes we're looking for? Creatures evolving to have exactly the human genome? Creatures evolving to have exactly human gene regulatory networks? Creatures evolving to have functionally identical gene regulatory networks with humans (e.g. switching embryonic cell types in 20 generations, but doing the accounting in different ways, one with more of a marker, one with slower degrading marker, say)? Humans modulo body hair? Or some really broad category, like creatures evolving to have "origins asking intelligence”?

The set I think is apropos to Behe’s project is the latter. The question isn't "How can the human-chimp MRCA evolve into humans?" but, "How can the human-chimp MRCA evolve into some kind of origins questioning species?" And there's the rub. We have NO IDEA what the space of genomes that produce "origins questioning species" looks like, no idea of it's size or of the number of ways you can go from the human-chimp MRCA to some point in that space. The number of human-chimp MRCA genome transformations that could land you in that space could be vanishingly small or combinatorially large. We just don't know. And without a proper null model we can’t test the hypothesis. So far as I can see, that null model is close to unknowable.

Nevertheless, I do find myself trying to think if there is any way to come up with some kind of vague minimum bounds on that space. I think that is probably what Behe imagines he is doing but his target space is clearly vastly too small. The impulse to find some kind edge of evolution isn't ridiculous, I don’t think, it's just that even bounding the target space is an exceedingly difficult problem.

3. The odds that someone in a class of 20 has *your* birthday is clearly 20/365

Mmmm, no. It's about 1 - (364/365)^20 (ignoring the fact that there are leap years), that is 0,05339... . It only goes to show that people are almost always wrong when they use words like "clearly", talking of probabilities but not actually calculating them.

4. @Gluon Spring: "The odds that someone in a class of 20 has *your* birthday is clearly 20/365, but the odds that *some* two people in a class of 20 has the same birthday is 50/50."

My grandfather, non-twin sister, newly born cousin, and myself all have the same birthday.

5. Larry: "He [Behe] seems to think that whenever we see such mutations they must have been the only possible way to evolve some new function or feature."

I think what Behe means is that if the only possible way to evolve some new particular function or feature was by those two mutations (such as chloroquine resistance), then for species whose populations are too low, the probabilities that they will produce those two mutations are also too low. And from your comment that combinations of mutation similar to those that produced chloroquine resistance are beyond the reach of some species, it sounds as if you would agree with him about this.

6. No body in their right mind would disagree with that.

The issue is that Behe is insinuating that if those two mutations had not evolved, then it would not have been possible for life to find an alternative solution.

It's the "everything else lead to extinction" fallacy.

7. Hi Mikkel,

Behe observed that if the two (or four) mutations had not occurred in P. falciparum, it would not have developed chloroquine resistance, or at least not developed it in this short a time frame. And from that he deduced that species with much smaller population sizes facing the same type of hurdle would not have been able to evolve the solution by random mutation.

At this point in his book that seems to be the only point he is making. Not sure where you are getting the "everything else leads to extinction" bit.

8. I've been reading over some of Behe's replies to his critics regarding EoE, and I think he already addressed the issue that Larry brings up here in this post.

9. Behe observed that if the two (or four) mutations had not occurred in P. falciparum, it would not have developed chloroquine resistance, or at least not developed it in this short a time frame.

That is incorrect. What Behe is showing (even though he is not taking into account a lot of things that need to be considered, as we discussed in the previous thread) is the probability of P.f. gaining resistence with this particular set of mutations. But it should have been claer by now that neither Behe nor anyone else knows how many alternative ways to get resistence are there. At that point, he can't make any claim about resistence overall. Otherwise, he is just claming that only person A can win the lotery, instead of ANY person who bought the ticket.

10. Piotr: Ack! What a horrible gaff on my part. Serves me right for attempting an off-the-cuff comment so far after my bedtime.

Diogenes: Clearly, some power has been at work in your family.

Pedro: I think even if there was only one way to get resistance in P.f. and Behe could show it, Behe would still have major work ahead of him to demonstrate that evolving other traits of interest are similarly constrained.

11. Pedro: But it should have been clear by now that neither Behe nor anyone else knows how many alternative ways to get resistence are there.

But as Behe points out here, if there are other ways for P. falciparum to develop chloroquine resistance, they would be even less probable.

12. Gluon: Pedro: I think even if there was only one way to get resistance in P.f. and Behe could show it, Behe would still have major work ahead of him to demonstrate that evolving other traits of interest are similarly constrained.

Yes, and Behe does try to do that later in EoE. Eventually, I hope Moran and Behe will debate that as well. So far, I have enjoyed and appreciated Moran's taking the time to discuss these issues. I hope he finds the time to continue the discussion.

13. Ack! What a horrible gaff on my part. Serves me right for attempting an off-the-cuff comment so far after my bedtime.

In fact, you weren't far off, as 20/365 = 0.5479..., but with the intuitive logic you seemed to regard as "clear" the probability that someone in a group of 365 random people has the same birthday as you should equal 1, while it's really 0.6326...

It's fascinating how easy it is to be wrong about probabilities. Paul Erdős, one of the greatest mathematicians of the 20th century, was inexplicably confused by the Monty Hall problem and found it hard to accept the correct solution after it had been explained to him.

14. @Piotr Yes, humans have a particular blind spot for probability and even among the trained, intuition often leads one astray. Very few things in probability are actually obvious or "clear" in that sense, and so it's probably wrong, even when you have the right answer, to say that it is. I had read of experiments by Tversky and Kahneman illustrating how badly our probabilistic intuition fails, even among people trained in statistics, but the Erdős story is exceptionally striking.

In the case of the birthday problem, I did actually know how to compute it correctly (both versions). I've even taught this in a class. So I'm equal measures puzzled at why I came up with the bogus number and embarrassed that I did. I know I was quoting form memory the 50/50 result (inaccurately, it's closer to 23 people). In any case, your point is well taken: compute always.

15. Larry:

You write: What this means is that every time you sit down and play a few hands of bridge you are experiencing probabilities that are lower than the double CCC that upsets Michale Behe. You don't act suprised when you see your bridge hand and you don't attribute it to any of the gods.

How were these "cards" designed? How were they manufactured? How were they grouped together as a complete deck? How were they "dealt"?

Answer to each of these questions: human beings. I.e., intelligent agents. Your example proves that to overcome huge improbabilities in a "random" way won't happen. However, intelligent agents have no problem overcoming them.

You also write:

Really? Does he really mean that there can't be any examples of two mutations occurring in the same gene since humans and chimps diverged?

Let's think about this in two ways. First, the theory. . . . If we assume that only one of these occurs in a gene, then in the upcoming generation every single human on Earth will have a CCC (two new mutations in a single gene). Behe says that this is impossible.

But, of course, in any single infected human, 10^12 replications of the malarial parasite takes place, and so, within any infected human, given the malarial mutation rate and the sheer number of replications, you will have 'genes' within the parasite that differ by two a.a.s. So, I don't see how this can be what Behe intends.

It seems to me that Behe means that there is a "specific difference" at 'two' "specific locations" along the length of the gene. Given neutral drift, a two a.a. difference within a gene would be commonplace, but not a 'specific' difference at two 'specific locations.' The CCC has to do with both location and type of a.a. difference using the P. falciparum model.

I took the human fibinogen alpha chain and BLASTED it against the chimp genome. I used the amino acid sequences so we could see mutations that gave rise to new amino acids in the lineages leading to chimps and humans. The result is shown on the left.

There are 25 amino acid substitutions.

Well, this is a little baffling. Behe's argument is that this could not have happened by 'chance,' not that it couldn't have happened.

If you assume that God doesn't exist, nor any other god with supernatural powers and intelligence, then that leaves material forces. But you can't "prove" evolution gives the proper answer by "assuming that God doesn't exist." It seems like you would have to prove that God doesn't exist---or any other god-like being. Can you do this?

16. "Your example proves that to overcome huge improbabilities in a "random" way won't happen. However, intelligent agents have no problem overcoming them."
The fact that the cards are manufactured by people is irrelevant. That has no bearing on the random dealing of a subset of those cards. You could have 52 different rocks and randomly pick a subset of them. That the cards were made in a factory in China and the rocls picked up out of a field have no bearing whatsoever on the probabilities of picking any defined subset of them.

"Well, this is a little baffling. Behe's argument is that this could not have happened by 'chance,' not that it couldn't have happened."

So the next logical conclusion is that some invisible omnipotent force supernaturally intevened to make those 25 aa substitutions? I propose a simpler hypothesis: Behe's calculations are wrong.

Evolution says nothing about the existence of god; it is irrelevant to the evolutionary theory. Nobody has to prove god doesn't exist to study evolution.

17. "The CCC has to do with both location and type of a.a. difference using the P. falciparum model."

That's not how Behe got to his conclusion about cloroquine resisitance in P. falciparum. We have been over this in another thread, so I repeat:

Behe's major mistake is that he assumes the ten or so instances of CR that have been documented represents all instances of the evolution of CR in P. falciparum. The chance of developing CR in Behe's calculations, 1 in 10^20, is 10 (or so) divided by the total number of malaria parasites that have grown in all human victims over the study period. This makes an assumption: That those 10 instances of documented CR are the only instances ever to have evolved in the history of the species. This is a completely unsubstantiated assumption. It also necessitates at least 3 corollary assumptions:

1. That all of those cases of CR arose in a population exposed a level of treatment with cloroquine such that CR rose to sufficient levels in the parasite population to be detected by health workers and documented to the point it could be published in peer-reviewed literature. Otherwise those instances of CR could not have become part of Behe's numerator in the 10^-20 calculation.
2. No instances of CR arose in a mosquito, or else
3. Every instance of CR that developed in a mosquito went on to infect a human who then went on to fulfill the requirements of 1.

2. I hate to admit it but I'm a bit confused now. I know that in 1/3 of proteins there are no differences between human and chimp. The other 2/3 average between 1-2 amino acids per protein. I know that some proteins, like those in the immune system and ECM proteins are evolving quickly but 25 seems much higher than the neutral rate. Is this true?

1. No, it's the neutral rate but I had to pick a protein that was less well conserved than most.

3. Iantog, keep in mind, larger protein = more sequence = more mutations. If humans and chimps are on average 1% different in coding DNA, then 200 base pairs of coding DNA will have about 2 fixed differences. If fibrinogen is 866 codons, that's 866x3 base pairs, that's about 26 DNA differences expected. Which, wow, is about what we see. You'd have to convert to amino acids for the amino acid difference count.

4. I think Behe's argument and it's flaws are a lot simpler than Larry is suggesting, but I don't have time to re-type my TREE review or comments in previous threads. He's trying to show that protein-protein binding sites are extremely unlikely, and that multiprotein systems are effectively impossible to evolve naturally, thus trying to justify his original "irreducible complexity" claims from his 1996 "Darwin's Black Box". Perhaps the "Edge of Evolution" strategy was easier than actually grappling with cooption processes, phylogenetic reconstruction of the evolution of complex systems, and the overwhelming strongly evolutionary evidence from molecular homology, which are the things we were hoping he would address, and still has not.

1. Nick,
I think you're right about what Behes ultimate argument is and the links you gave me from Musgrave etc in 2007 on an earlier post were exactly on point.

The numbers I gave above were from a paper on the chimp genome. They say 2/3rd have 1 or 2 differences. I'm assuming the average protein is 300aa. That would make the overall difference about 0.4%

2. Matzke, no need to retype your TREE. Your blustering, arrogant posturing is more helpful. And your infamous 'tantalizing hints' subliminal blunder in your supposed refutation of the IC of the bacterial flagellum tells us about the quality of your conclusions.

furthermore, that the T3 has been shown to more likely be the devolution of the BF tells us we ought to take your comments with a pinch at most.

See, to make a persuasive argument, it is not enough to throw throw calculations around.....but theres a nice side effect - fighting in the trenches unwittingly helps blunt the rhetorical power of the IDiot epithet..... you must persuade that your arguments are logically sound.

You have not done so.

Neither has Larry or Diogenes.

Tantalizing hints is about all you've (pl) got so far.

Carry on.

3. Nick M, your TREE review was spot on, and issues like cooption, contingency in evolution of metabolic pathways, the ease with which protein subunits can mutate and produce new metabolic properties, etc., have never been addressed by Behe. They get in the way of his simplistic multiplication of probabilities (i.e. "throwing calculations around"....Steve owes me another irony meter).

4. Steve: "you must persuade that your arguments are logically sound.

You have not done so.

Neither has Larry or Diogenes."

Um, whom exactly must we "persuade"? Westboro Baptist Church? The Discovery Institute? Religious fanatics? Who exactly must we "persuade"?

You demand we "persuade" you? Hell no. Your argument is just the usual scam, "I will give a million dollars to anyone who trims my lawn to my satisfaction." You demand we do your work for you, but if you don't define "to my satisfaction" in objective terms, before we do all your work, then you're pulling a scam. You expect us to do all the work so you can shift goalposts on us AGAIN. No, we're not going to bite.

All we have to do is refute Behe's claims with facts, not "persuade". Which we did in spades and over and over and over again, and Behe will not acknowledge and does not accurately describe the refuting evidence. Every single one of Behe's arguments involved factually false assertions, or redefinitions of the scientific method, or both.

Behe has repeatedly claimed that is impossible for protein-binding sites or functional sites to evolve because they are IC. Back in 2007, as soon as he claimed that, a grad. student, ERV, smacked him down by pointing out that HIV evolved a Vpu that became a gated ion channel and gained protein-binding sites. This post from 2007 listed newly evolved protein binding sites refuting Behe, including Vpu viroporin and its multiple, interacting, new interaction sites, Vpu's Golgi targeing sequence YRKI, the D/GXLRLL sequence in HIV-M subtype C, the new gene in HIV-2 from duplication and mutation of gene Vpr, and HIV protein gp120 evolving a switch from binding the CCR5 coreceptor to the CXCR4 coreceptor.

Another post from 2007 details how binding sites can be produced by single mutations, particularly those in bovine seminal ribonuclease, and single-residue changes that create binding sites found by Grueninger et al.

To pile on, in the 1990's James Wells published high-profile papers on alanine-scanning mutagenesis where every amino acid on a protein's surface was mutated to alanine. He found most of the binding energy in binding sites came from one, two, or three amino acids, the so-called "hot spot" which made up a small part of the binding surface. Everything outside the "hot spot" is dispensible or "reducible" thus refuting irreducible complexity.

All this and more was well-known to molecular biologists long before 2007 when Behe wrote his shit book. So there was no excuse for him writing such shit. Which is why no molecular biologist paid it any attention, except perhaps to get douche chills watching Behe face-plant. After the book came out, even grad. students like ERV and Nick Matzke (now Dr. Matzke) could easily piled up evidence proving him wrong. Behe eventually conceded that *one* protein binding site had evolved (Vpu) but that count is still wrong for Vpu and for protein binding sites in general. Behe systematically ignores easily, easily obtained refuting evidence. Therefore our refutations need not "persuade" him.

5. Nick,

I think it's actually quite difficult to explain what's wrong with the argument that I describe in my post, I know it's taken me several years to recognize all the flaws in his book. You must be a lot smarter than me!

6. Hi Larry,

I appreciate your taking the time to grapple with Behe's arguments, which is helping to elucidate the issues. He seems to be in "interactive mode" regarding internet debates about these topics, so I expect that he will probably have a reply sometime soon.

Meanwhile, given that you have admitted that the type of combinations of mutation involved in developing chloroquine is beyond the reach of some species, perhaps you can explain why that would be so, in spite of the argument that you have presented here.

7. oops...that was supposed to be "developing chloroquine resistance...."

8. Dear Dr. Moran,

I am really enjoying the back and forth in this dialogue. A few points:

1) Michael Behe has repeatedly and explicitly made clear that he does not mean the word 'simultaneous' in the way you have accused him of meaning. He does not intend to say a double mutation, occurring in the same replication cycle of a single replicating cell. He is talking in terms of functionality, not history. And in that respect, he is correct: in order to function, and for resistance to work, a cell needs at least two key amino acids in place at the same time. I think it is bordering on dishonesty to keep accusing him of something he is emphatically denying. That is all he is saying. How is he wrong?

2). The mutations in fibrinogen and (the 100 mutations from parent to offspring) is a case of drift. But Behe is not imagining neutral floating and exchange: he is asking about solutions to specific adaptational problems, created by non-generic environmental pressures, that impose demands that can only be met by highly specific adaptational trajectories (key residue switches and specific enabling mutations in specific sequence).

1. John Block:
"1) Michael Behe has repeatedly and explicitly made clear that he does not mean the word 'simultaneous' in the way you have accused him of meaning. He does not intend to say a double mutation, occurring in the same replication cycle of a single replicating cell. He is talking in terms of functionality, not history. And in that respect, he is correct: in order to function, and for resistance to work, a cell needs at least two key amino acids in place at the same time. I think it is bordering on dishonesty to keep accusing him of something he is emphatically denying. That is all he is saying. How is he wrong"

Here is why Behe is wrong, and why the only one being dishonest is Behe:

I don't remember the exact probabilities involved, so consider this situation:

The probabiltiy that a single mutation needed for resistance is 1 in 10^8. We need two such mutations for resistance to occur. To arrive at (10^-8)(10^-8) = 10^-16, you have to make these assumptions: that these mutations are independent, simultaneous to the extent that they are in the same individual and on the same DNA molecule. That is the reason for the insistence on a simutaneous double mutation. Under any other scenario, the probability is different.

A corollary assumption to the simple multiplication of probablities calculation is that either single mutation is highly deleterious or lethal, such that it cannot presisit in a population for any length of time.

If single mutations were slightly beneficial, neutral, or slightly deleterious, they could persist for long periods of time in a population, increasing or decreasing in a population by chance.

Bringing two needed mutations together that have evolved in two individuals of a sexually reproducing species, or sequentially accumulating the two needed mutations in the same lineage is a much different probability that just squaring the mutation rate of DNA.

So if Behe insists on multiplying probabilies of single mutations to get to a double mutation, he has in fact limited himself to the scenario of simultaneous mutations. Any variation "in terms of functionality" change the probabilitiy. And not talking in terms of history is just silly, for the reasons I explained above. And "at the same time" means simultaneous.

2. John Block:
"But Behe is not imagining neutral floating and exchange: he is asking about solutions to specific adaptational problems, created by non-generic environmental pressures, that impose demands that can only be met by highly specific adaptational trajectories (key residue switches and specific enabling mutations in specific sequence)."

Where I think Behe goes wrong is that he assumes that demands can only be met by "highly specific adaptional trajectories". It turns out there is generally more than one solution to a problem, and intermediate steps along trajectories do not have to each be individually advantageous. In terms of protein interactions, the assumption that several simultaneous amino acid changes are necessary to make a functional interaction site are demonstrably false.

3. Chris,

As you probably know, and as Behe has emphasized repeatedly, he did not just square a mutation rate to get a probability. Nicholas White estimated that the prevalence for resistance (or one could correctly say, the occurrence plus a selective sweep detectable at reasonable thresholds) is 1 in 10^20. Period. Dr. Moran's numbers were very close to this estimate. You can also make a scenario that depends on selective coefficients, which can be alterable. How is the rate appreciably different if the first mutation occurs in dad, and the second mutation occurs in son? Instead of 10^-8 x 10^-8 (plus maybe some compensatory mutations), what should it be? I think you are describing a situation known as stochastic tunneling. What do you think of Douglas Axe's article about this very thing? The point is that Behe's main point is 10^-20 is rare. How you arrive at that number: whether 10^-8^2, or whatever, doesn't really matter. All that matters is that some adaptive trajectories are rare. And when one sees that when such a small biochemical alteration severely limits evolution, and makes it huff and puff in its most powerful engine (the parasites and viruses), what would happen at the level of lumbering mammals?

Sexual recombination can bring things together, but, as you know, it is also important that recombination can tear things apart. Things like population size need to be accounted for.

Finally, what evidence is there that there are so many viable adaptive trajectories for specific adaptational demands? Particularly, with respect to choloroquine and malaria resistance? There are a handful of possibilities; none are very probable. The reasonable assumption is that evolution for mammals couldn't have used very many of these types of complex adaptations. But it is intuitive that constructing elaborate cell parts and physiologies would require complex adaptations. How does one solve this riddle without circularly assuming what one needs to prove? Is everyone just assuming all of major evolution goes by atavoaquone like steps, instead of chloroquine? Why?

4. Why not?

What would persuade us that evolution cannot do anything without perpetual tinkering from outside - that in this enormously multidimensional space there are NO evolutionary paths between the majority of historic forms?

5. "Michael Behe has repeatedly and explicitly made clear that he does not mean the word 'simultaneous' in the way you have accused him of meaning."

Behe was proven wrong on malaria resistance, so now he and Gauged are trying to redefine the meaning of "simultaneous." The double mutant is not simultaneous, it's sequential.

Sequential is not simultaneous. This is the kind of word game Behe always played with Irreducible Complexity, redefining every word in it-- he redefines "several", he redefines "part", he redefines "remove." No more. The dishonesty is Behe's and Gauger's.

The CR double mutant is Irreducibly Complex and it evolved, so evolution can create IC structures. There are numerous other examples, particularly newly evolved binding sites in HIV, all of which Behe claimed were impossible. Then there:s affinity maturation.

As for switching to the hominid line, neither Behe nor you has ever pointed to even a single, NOT ONE, irreducibly complex protein binding site in humans but not apes. You imagine there are many. Your imagination is not enough. If there were many, you would cite one. You did not because there are none so far as you know. Tell your church audiences that.

6. John,
"As you probably know, and as Behe has emphasized repeatedly, he did not just square a mutation rate to get a probability. Nicholas White estimated that the prevalence for resistance (or one could correctly say, the occurrence plus a selective sweep detectable at reasonable thresholds) is 1 in 10^20. "

Sorry, I thought you were talking about Behe's calculations of evolving new protein interactions, where he assumes changes must be several and simultaneous and multiplies mutation rates. The probablitity of chloroquine resisitance evolving Behe cites is wrong for different reasons, which have already been commented on in the discussion to the "flunking Behe's challenge" post. I direct you there for why 1 in 10^20 is most probably way off.

7. John Block: "As you probably know, and as Behe has emphasized repeatedly, he did not just square a mutation rate to get a probability."

No, that's exactly what he did, according to his DI co-worker Ann Gauger. Here she is in her own words, just a few days ago:

Gauger: "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 [italics in original]...

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 10^16 mutations per base pair per parasite."" [Ann Gauger at ENV, July 28, 2014]

Ann Gauger is saying the same thing we said. When we say it, you accuse us of dishonesty. When she says it, do you consider her a scientist and intellectual?

John Block writes: "in that respect, he is correct: in order to function, and for resistance to work, a cell needs at least two key amino acids in place at the same time. I think it is bordering on dishonesty to keep accusing him of something he is emphatically denying."

Why are you accusing us of dishonesty but not accusing Ann Gauger of the same? She just said the same thing we are saying.

Clearly, you are wrong. We accurately described Behe's assertions and you didn't. Why are you not accusing Behe and Ann Gauger of dishonesty?

8. Here is more of Gauger's waffling: "To find those two mutations would require many more trials than are available among the 10^12 parasites in each person infected. However, 10^20 parasites (the total present in a single year) represent more than enough opportunity for that double mutation to occur.

His critics focus on Behe's use of the word "simultaneous." Getting two simultaneous mutations is ridiculous, they say, and so multiplying two rates together is ridiculous.

Maybe the two mutations happened simultaneously, meaning together in the same molecule in one generation. It is possible. Maybe the mutations happened one at a time. We don't know..." [Ann Gauger at ENV, July 28, 2014]

Actually Ann, we do know. They happened one at a time. One mutation is neutral and the other is deleterious but not fatal, so either way, they happened one at a time. The odds of it happening that way are much higher than simultaneous mutations, so Behe and Gauger are wrong.

I ran a simulation of the replication of malaria, including simulation of parasites being passed from one patient to the next.

I simulated the cases where:
1. One single mutant is neutral and one single mutant is lethal. This is not a realistic model for malaria because for real malaria, one single mutant is deleterious but I'm modelling it as lethal.

2. Both single mutants are lethal, so double mutation must be simultaneous or nothing. The "double lethal" is a toy model, not real malaria, it's an "apple" I use to compare to Behe's "orange".

I have to emphasize this because Behe, last time he quoted my numbers, compared my "double lethal" numbers against his malaria predictions, comparing my apples to his oranges! That infuriated me, but no apologies from Behe.

Consider the numbers after 700 malaria replications (about 48 serial infections, since I'm only including ~14 replication of parasite in each patient's liver and ignoring ethryocyte infections.)

After 700 replications (48 serial infections), if the double mutant has a selection coefficient of s=0.01:

If one single mutant is lethal and one single mutant is neutral, the fraction of double mutants (among all parasites) = 1.45 * 10^-11

If both single mutants are lethal (simultaneous double mutation required), the fraction of double mutants (among all parasites) = 1.44 * 10^-13

The sequential "single lethal" process is 100 times higher than the simultaneous double mutant.

After 700 replications (48 serial infections), if the double mutant has no advantage (no chloroquine), selection coefficient of s=0.0:

If one single mutant is lethal and one single mutant is neutral, the fraction of double mutants (among all parasites) = 3.4 * 10^-13

If both single mutant are lethal (simultaneous mutation required), the fraction of double mutants (among all parasites) = 9.7 * 10^-16

The sequential "single lethal" process is 350 times higher than the simultaneous double mutant.

9. There is a general mathematical rule, regarding the "sequential" vs. "simultaneous" mutation pathways (which Behe and Gauger treat as being equivalent), that they are in fact different by a multiplicative factor that increase the more replications that have passed. It gets rapidly bigger over time, but IDiots behave like's it's a small number or "within a stone's throw" as Behe said. This mathematical rule applies if you assume the double mutants have no advantage (no chloroquine), s = 0.0.

1. (SEQUENTIAL path, fraction of double mutants when one single mutant is lethal and one single mutant is neutral) / (SIMULTANEOUS double mutants, where both single mutants are lethal) =
(# of replications that have passed + 1)/2.

Above I gave you the example of 700 replications passing, the ratio was 350.

Another rule:

2. CBF = (SEQUENTIAL path, fraction of double mutants when both single mutants are neutral) / (SIMULTANEOUS double mutants, where both single mutants are lethal) = # of replications.

If natural selection applies to double mutants (chloroquine is present) the CBF is not as big, but still grows over time.

I figure that malaria parasites replicate about every other day, so this factor, which I call the "Creationist Blunder Factor" (CBF), grows by > 160 every year.

How wrong is Michael Behe? How much time you got?

10. Here is a fundamental misunderstanding of evolutionary theory:

"Furthermore, those two mutations must each be of no use as single mutations,"

Whether or not mutations are of use, or not, by themselves is not a requirement in evolutionary theory. They could be useful by themselves, or not. They could be neutral, or advantageous, or detrimental to any degree. this does not disqualify them from taking part in evolution. It changes the probability that a partucular outcome will happen. That is all.

11. It is very telling that John Block has not been back to respond to Diogenes wrt Behe and Gauger's dishonesty.

I guess the god-goggles knob was cranked to 11.

12. Finally, what evidence is there that there are so many viable adaptive trajectories for specific adaptational demands?

Well, there IS evidence of different paths being evolved to achieve the same adaptation. The Flavobacterium, Sp. KI72, that evolved nylon-digesting enzimes, evolved a different set of enzimes than Pseudomonas aeruginosa, which also evolved nylon-eating enzimes, but different ones. How many more variants can there be? 1? 10? 100?

It would alos be good not to forget about frameshift mutations, which have the potential to produce significant, and fast, changes with functional viability. Point mutations isn't all there is for evo to work with:

http://www.sciencedirect.com/science/article/pii/S0888754306001807

9. 3). It seems intuitively rational to think that if chloroquine can impose such severe demands by virtue of a harsh adaptive pressure, then certainly something like a land mammal morphing into a whale to live in the open ocean, or a will face similar imminent demands. Consider a parallel. H5N1 is a virus that is having a hard time evolving to be transmissible between humans. It needs five mutations (or some combination) to exploit a new niche. Yet it can't seem to get it yet. Now, if H5N1 can't get the mutations to exploit a new niche, how can a whale?
Reference: http://www.npr.org/blogs/health/2014/04/10/301432633/scientists-publish-recipe-for-making-bird-flu-more-contagious
"Two mutations enable improved binding of the H5N1 bird flu virus to cells in the upper respiratory tract of mammals," Fouchier told Shots in an email. "Another mutation increases the stability of the virus. The two remaining mutations enable the virus to replicate more efficiently."

4). For Nick: You are extremely competent, so much respect. But in gentleness I say this: what can't be imagined if you are vague enough? Co-option is full of breezy just-so stories, with no rigorous numbers, no solid biochemical data about potential detrimental side effects, nothing. You could imagine co-option covering the transitions on the covers of the Animorphs books series. Behe is trying to get through the bluster by being more rigorous. So he has test cases. When you can pin down adaptations that depend on the accumulation of neutral mutations, with no known alternative co-optive value, you have gained rigor, not lost it. Why is this a bad thing? Also, Behe accepts homology but says the key functional switches are not due to trial and error. Same pattern, some other mechanism. This is a fair hypothesis. Last of all, he is right: the hypothesis that 'something interesting happens somewhere' is unfalsifiable. How can I non-circularly verify this without assuming what I have to prove?

1. if H5N1 can't get the mutations to exploit a new niche, how can a whale?

You can't compare a virus to whales. Plenty of viruses have overcome transmissibility problems. What does that teach us about the evolution of the avian lung? Nada.

2. Allan,

The point is not that transmissibility never evolves; but that some instances are painfully slow. If all of major phenotypic and biochemical evolution was like atovaquone resistance, then it would be no problem. But that is just the question we are asking. Is it reasonable to *assume* it is so? There is an obvious increasing scale of difficulty in evolutionary problems: atovaquone resistance is easy, then chloroquine resistance harder, H5N1, etc. Where to place the evolution of the whale? You're telling me that evolving the entire physiology of a whale should be thought of as way easier than a bug getting cholorquine resistance or H5N1 getting transmissibility. What? When you translate population numbers, they don't make sense. There is a niche. Particular adaptations have to be in place to take advantage of it. I seriously doubt that the niche for transmissibility of H5N1 among humans is more severe than a land animal living in the open ocean. Call it incredulity. But it is better to be incredulous than be a sucker for any old explanation. Especially one that refuses to come to grips with numbers and details

Why shouldn't we be cautious before accepting claims that seem to violate basic intuition?

3. John Block, by "basic intuition", don't you mean your programming? In your case that would be religious (christian) programming, right?

Tell me, is your "basic intuition" okay with a man living inside a fish, and a woman being turned into a pillar of salt, and dead people getting out of their graves and walking around, and demons, and angels, and a guy walking on water, and a guy feeding thousands of people with just a bit of food, and a talking serpent, and eight people along with two (or seven) of every organism on Earth fitting into a wooden boat that doesn't get destroyed during a year of the most violent destruction the world has allegedly ever suffered, and goats and sheep having striped or spotted offspring because they were looking at striped sticks while mating, and a guy who's now called 'Jesus' was/is the illegitimate son of a so-called god named yhwh (and other names) and that he also got out of his grave and walked around with a big, bloody hole in his side and bloody holes in his hands and feet and then flew up into the sky to a place called 'Heaven', and that the 'Jesus' guy actually was/is 'God' in a different form, and that the so-called 'Holy Ghost' actually exists and is yet another form or part of the yhwh-jesus guy?

My "basic intuition" and my education, observations, knowledge, and experiences tells me that those things are totally fictitious and ridiculous.

4. I think you're neglecting to consider how many organisms fail to evolve and subsequently go extinct because they end up in some kind of trap they can't evolve out of. Basically you're missing the big picture.

By zooming in on the evolution of whales without considering that life covers basically the entire planet and how random sampling is going on constantly in every environment, and how many countless species went extinct during the whale transition (and how long it took), you can make any specific transition seem unreasonably lucky.

There are probably more viruses failing to evolve transmissibility and going extinct, than there are successful ones. There were probably plenty of terrestrial mammal species that went extinct because they didn't alight on the right solution. The whale solution was one of those that worked. And then here's the fact that the fossil record implies it took tens of millions of years.

It seems to me eminently more reasonably that, in a vast sea of random sampling, occasional solutions will be found over many generations at the cost of countless failures - than it does to say an invisible guiding force is slowly (really, really, really slowly, so slow it's almost like it just evolves on it's own) picking out mutations with some secret goal.

That's before we start considering mammalian physiology and developmental biology (gene regulation networks). Slightly relocating nostrils and the shape of limbs, spread out over many generations, seems to me wholly unremarkable (and we have a lot of evidence that these kinds of modifications are possible, from countless experiments going from fruit flies to the domestication of dogs and many livestock), in comparison to evolution at the molecular level where we consider individual mutations and how they affect protein-protein interactions, which is a lot more "ratchet" like.

When you say we need to evolve "the entire physiology of a whale", we need to remember we already have the entire physiology of a mammal, and that most of the evolution required between the two is to change developmental timings and adjust (up or down) the strength of various developmental signals.

On closer inspection, the two situations simply don't lend themselves to the comparison you're erecting.

5. John,

You simply cannot compare the difficulties faced by a virus, in tussling with a very harsh, specialist and defensive environment, with the issues involved in changing the developmental program of a multicellular soma in a sexual eukaryotic species. Those things - multicellularity, sex, eukaryotic cells, and an environment which is not itself generally reacting to repel you, change the game completely. "Some instances are painfully slow". This is like "some mutations are deleterious". Evolution proceeds by the paths that are explorable; that some are not is not denied.

6. GishGallop. Ditch and switch. Our creationist friends, having lost the argument over how protein binding sites can't evolve (they can, they did, and it happened recently while we were watching), now "ditch" their false assertions about protein binding sites (buh-bye!) and "switch" to false claims about anatomy. And which anatomy? Whales, of all things!

It takes guts for creationist to cite whales against evolution! For many decades creationists argued that no intermediate between land animals and marine mammals could exist even in principle-- they insisted that intermediates were not merely not yet found, but impossible even in principle, and creationists "proved" they were impossible, by imagining an intermediate and then imagining it dying. Their argument, to prove impossibility of intermediates, was the "irreducible complexity" argument-- change any part and it's dead; I imagine it changed and I imagine it dead-- long before Behe copied the creationist idea and changed the name.

Luckily, scientists ignored the creationist imagination and looked for evidence, finding a suite of fossil species intermediate between land animal and whales. You'd think creationists would find it interesting when confronted with exactly the things that for decades they had called "impossible"?

No. With creationists, intermediates go from "Impossible, that's all!" to "Bo-ring! Nothing to see here" without ever passing through a stage of "Hm, interesting." Confronted with intermediate fossils, creationists just cried, "Fraud! Scientists faked the fossils! And, the creator can make intermediates if he wants to. Can you prove an all-powerful God is unable to create intermediates?"

Well, yeah, I can-- the last several decades of creationist literature, which said intermediates were impossible in principle.

Are you claiming that aspects of whale physiology are irreducible complex? Which ones? Given that fossil intermediate species exist, how can you claim that any aspect of whale physiology is irreducible complex?

Why should we trust arguments about "impossible intermediates" and "irreducible complexity" when the so-called experts who claim to be able to see "irreducible complexity" have been proven wrong by the irreducible being found reducible, and reduced over and over and over again?

7. John Block -

What are the chances your parents found each other, out of all the people on Earth? And their parents, and their parents, and their parents...? Therefore, odds are strongly against your existence. Please prove to me you are real. (It must be a miracle!)

Actually, it's all down to something Behe himself said in his book:

the likelihood that such a mutation could arise just once in the entire course of the human lineage in the past ten million years, is minuscule—of the same order as, say, the likelihood of you personally winning the Powerball lottery by buying a single ticket.

Behe keeps calculating odds with the perspective that there is only one "correct" mutation of set of mutations by which evolution can take place, and therefore we're restricted to the odds of *you* winning the Powerball. But there are many, many mutational/evolutionary paths organisms can take and have taken, so the perspective we should have is, what are the chances that *someone* will win the Powerball? And that happens all the time, doesn't it?

Every time you read about another Powerball winner, remind yourself that this is an example of Dr. Behe being wrong about the math he uses regarding evolution.

10. Behe's reasoning succinct:
Look at something that has happened, for example the evolution of the eye. Then you pick out some event in the eye's evolution, like a specific mutation that happened. You say "that mutation is special, if it didn't happen the eye would not have evolved" or something to that effect. Then you show that that mutation is just one possibility out of some extremely vast space of outcomes that could have happened instead and say that, hey look, that one special mutation must have happened but, because it was so unlikely it can't have happened naturally.

But what Behe fails to consider is that ANY specific mutation that would have happened would have been just as unlikely. Even if eyes never evolved, we could sit back now after the fact, pick a specific mutation that happened in the chain of events up until now and show that, what happened here in THAT case was ALSO unbelievably unlikely, so THAT had to have been designed too. It just didn't lead to eyes, it lead to something else. Maybe nothing at all. But it would still be just as unlikely as the eye scenario.

Then we do the same for the third mutation out of all the possible ones, and show that if THAT would have happened instead, IT would have been unfathomably unlikely too, so it must have been designed instead.

Soon we have done it for the total space of outcomes, picked out every single one and used the same line of reasoning to show that whatever happened was so unlikely, it can't have been chance. After all, it was THAT single specific thing that happened, and why THAT one out of the total space of possibilities?

To Behe and the ID people: You must be able to see how this kind of reasoning can always be erected after the fact, for any imaginable situation, to show that it was unlikely to some extreme degree. What is the use of it then? It doesn't tell us anything about what caused the events to happen. Something will happen, and that something will always be just as unlikely when looked at after the fact in this way.

Behe's sitting here now, as the red dot in this image:
http://i.imgur.com/ocrmtsS.gif
... thinking "oh man look how many ways it could have been different", neglecting to consider the same reasoning could be used for any one of all the other outcomes.

11. Behe is asking why Plasmodium hasn't evolved new complex systems in the last 10,000 years:

http://www.evolutionnews.org/2014/08/how_many_ways_a088981.html

Look at life's history, Behe. It took more than a billion years for life to go from bacteria to eukaryotes (that too, thanks to endosymbiosis). And another 2 billion years to go from simple eukaryotes to multicellular animals. Once the basic animal body plan was established, variations on a common theme produced diverse animals in, a relatively quick, 0.5 billion years. The vast majority of time elapsed on getting the eukaryotic cell right. And it has changed little ever since.

Complex novel systems are difficult to evolve and has happened only rarely over vast time periods. For the most part, evolution works by tweaking existing structures. If the hand of God was involved, we'd expect all these events to have unraveled significantly faster. Humans should have appeared shortly after the earth formed and not 4.5 billion years later!

1. Vimale: "Behe is asking why Plasmodium hasn't evolved new complex systems in the last 10,000 years"

By Behe's definition of irreducible complexity, Plasmodium did evolve new irreducible complexity in ~10 years; and there are more examples in HIV, in bacteria that evolve to degrade or digest man-made chemicals like PCP and nylon, genetic algorithms, etc. So irreducibly complex systems can evolve.

12. According to Behe's logic, no one can win the Powerball lottery after buying one ticket. Yet it happens. And happens. And happens.

1. Hi Anthro,

Actually, I think Behe's argument would be that if not enough tickets are sold, then probably no one should win the Powerball lottery. If enough tickets are sold, then somebody should win the lottery.

If we compare this to getting a CCC, then I think Behe's argument is that only a very small number of mutations result in a "winner" (a selectable biological state?) If not enough mutational combinations can happen in a certain time frame, then we should be surprised that there is a winner.

So the question is, how many possible winners are there? If there are plenty, then even a small number of possible mutational combinations would do. If there is a very small number, then it wouldn't do.

13. Several responses

To Diogenes: I believe I understand your assessment, but I disagree. To you agree that at least two mutations have to be in place --to key residue changes from wild type--have to be in place before a cell has functioning CR? That is all Behe is saying. Behe never said that the nature of chloroquine resistance or the parts for the bacterial flagellum means they had to pop into existence 'simultaneously', all at once, in the same cell or replication cycle. He is saying that until you have function, evolution (or random chance, for that matter) can produce some improbable combination (sequentially, or whatever), but the rate will be drastically slowed: probably beyond the waiting times available. A process of coherent, sequential accumulation without much functional value gives you values like 10^20 genomes to yield an adaptation, and those kinds of figures just wouldn't make sense when translated to mammalian evolution.

To quote Behe himself:

"There is a lot of chatter at Sandwalk deriding the idea of "simultaneous" mutations (which was not intended in my book The Edge of Evolutionin the sense it is being taken there, and which at this point I would gladly replace with other words simply to avoid the distraction). Yet it matters not a whit for the prospects of Darwinian theory whether the pathway consists of two required mutations that are individually lethal to a cell and must occur strictly simultaneously (that is, in the exact same replication cycle), or whether it consists of several mutations each with moderately negative selection coefficients, or consists of, say, five required mutations that are individually neutral and segregating at some appreciable frequency in the population, or some other scenario or combination thereof. The bottom line for all of them is that the acquisition of chloroquine resistance is an event of statistical probability 1 in 10^20."

I do not see how this is dishonest, and it seems to misrepresent Behe's position to assert that he is stating otherwise.

1. Yes, when we look back in time, picking out some particular series of events will look incredibly improbable among them total space of possible outcomes.

The issue with this kind of reasoning is that because we are the result of what happened, Behe thinks this means that outcome is special. After all, if it didn't happen we wouldn't be here.

I've already explained what is wrong with this kind of reasoning above. So have others. First off, he neglects to consider that in the place of the particular sample of bodiversity we have, it is entirely possible that *something else* with the same prior probability would have developed instead. Had that happened, those organisms could have been sitting there making the samme fallacy Behe is.
Another issue is the lack of perspective. There are a lot of failures, a lot of extinctions of everything from countless individuals to entire lineages happening through this process of mutation and searching for "solutions". These mutational paths aren't some curious, magical thread that is consistently, miracously defying the odds when something functional appears. The failures are real and manifest and substantially outnumber the successes. That's what one would expect from an evolutionary process of random sampling, not the kind of miraculous handpicking of mutations Behe's designer is supposedly engaging in.

2. Behe's basically making it seem like every other possible outcome is guaranteed extinction. Had any other combination of mutations happened, the planet would be a barren wasteland. That seems to be his insinuation. It had to be us or none at all, so it must be a miracle.

3. "I do not see how this is dishonest, and it seems to misrepresent Behe's position to assert that he is stating otherwise"

It's dishonest because the 1 in 10^20 is based on very bad assumptions. See the "flunking Behe's challenge" discussion at Sandwalk.

4. John Block: "Behe never said that the nature of chloroquine resistance or the parts for the bacterial flagellum means they had to pop into existence 'simultaneously', all at once, in the same cell or replication cycle."

Again, false. Here is his co-worker Ann Gauger, just a few days ago, defending him.

Gauger: "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...

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 10^16 mutations per base pair per parasite."
[Ann Gauger says Behe meant "simultaneous" when he said "simultaneous", ENV, July 28, 2014]

You call us dishonest when we accurately describe Behe's assertions. Why do you not call Ann Gauger dishonest for saying the same thing?

Why do you think Behe writes post after post after post attacking us for accurately describing what he wrote, but has not written one post criticizing Gauger for describing what he wrote?

It's Dover all over again-- just like on the witness stand at Dover, when Behe lied about what he wrote about the entire blood clotting cascade being IC in "Darwin's Black Box", then had to redefine what he meant by "system." It's exhausting to argue with Humpty Dumpty.

14. To Allen and others:

I believe it is fair to compare adaptational challenges between species. H5N1 isn't facing some harsh environmental stress: all that is happening is that it does well in its local environment, and could do even better if it collected the mutations to exploit a new niche (aka, the upper respiratory tract of humans to become transmissible). But it can't exploit the new niche, because it can't get the mutations: at least, not yet. Similarly, the open ocean is a new niche for an ancient land animal. But, in order to live there, some non-arbitrary changes have to be in place. Since, according to Behe's first rule of evolution (this actually was peer-reviewed), most of life will fiddle and tinker and break what they have to get by, instead of drastically building new structures to change everything. This is what we observe when we try to simulate evolution in a lab. I think that it is much more likely that local adaptive peaks, combined with severe constraints a new niche would impose on mutational routes to elaborate and embellished adaptive structures, would have kept those ancient mammals landlocked instead of sojourning on some long and (presumably) torturous evolutionary pathway. To me, and I think to anyone looking at this problem, you can't presuppose say that changing the body of a land animal into the body of an ocean animal would be as easy as atovaquone, and not so near as difficult as H5N1. The changes need to be coordinated. I think Ric Sternberg has made an argument about the whale's reproductive physiology being something so drastically different than a land animal that one would naturally, intuitively and reasonably expect coordinated changes of the nature of CR entanglement or difficulty. But when this is imposed, the numbers and generation times and mutations don't add up. Now, you mention that multicellular sexual organisms are different than parasites and such. This is true: but there is every reason to think that small organisms with fast mutation rates and large population sizes will be able to explore more evolutionary options, not less. Sexual recombination brings things together but also tears things apart.

As far as saying, why not? This is, I say, unreasonable. If you were to invent a spliceosome, or a ribosome, or DNA repair, or the mechanism by which red blood cells eject their nuclei, can anyone really soberly think that no entanglement on the level of CR or H5N1 will be looming? That two nucleotides are hard for these latter cases, but the former cases, which involves such drastic interrelatedness and complexity and molecular movements and entangled parts, would not be as hard? This is unreasonable. I think Harvard biologist George Church agrees. He says, look at the ribosome. It can't do it its trick with less than 53 proteins, and no one has been able to create artificial ribosomes that can do substantial, controlled, coded peptide synthesis without it. No one has recreated a (detailed) model of the adaptive trajectory in terms of mutational candidates, actual molecular characterizations of what is going on, etc. When and how did those protein pieces come together? This is more like atovaquone than CR: that is the claim. I think this statement does not enjoy a level of warrant to presuppose its own truth, but must be verified by evidence.

1. John Block: "If you were to invent a spliceosome, or a ribosome, or DNA repair, or the mechanism by which red blood cells eject their nuclei, can anyone really soberly think that no entanglement on the level of CR or H5N1 will be looming? "

Again, the creationist imagination is not enough. You imagine an intermediate and you imagine it dying. That's not good enough; you need some evidence.

Behe always says, "Well, protein binding sites of the complexity of CR can't evolve in the hominid line," but he cannot point to a single example of a newly evolved protein binding site that would need to evolve in the hominid line. Not one. He just imagines they're there. Imagination is not good enough.

Anyway almost all our protein-binding sites are homologs to things we inherited from ancient animal ancestors, or back to the earliest eukaryotes, even bacteria.

The specific mechanisms you mention, "the spliceosome, or a ribosome, or DNA repair" evolved in our eukaryotic or bacterial ancestors that had vast populations sizes, rapid replication rates, and hundreds of millions of years to evolve these things. You imagine an intermediate and you imagine it dying. Your imagination does not impress us.

We want evidence. There's a huge amount of evidence that protein-binding sites evolve easily, including HIV Vpu, Vpr gene duplication in HIV 2, bovine seminal ribonuclease, and obviously, affinity maturation in the immune system. So Behe's argument is dead wrong, wrong wrong wrong, and it has not taken off amongst molecular biologists because any of them can cite refuting counter-examples off the tops of their heads.

Behe should have surveyed the literature on molecular biology before he wrote both his books. He clearly did not, he just shouted "No scientist in the world knows the answer, that proves God did it." His failure to survey the literature on molecular biology and to pretend like he has is abysmal. He's wrong wrong wrong, he will never win molecular biologists to his side.

2. It's funny particularly funny, because there's plenty of phylogenomic analyses done on ribosome evolution that unambigiously show the ribosome has a long evolutionary history, with some protein subunits substantially predating others. These have also been correlated with tRNA and aminoacyl-tRNA-synthetase evolution to show that these structures have been coevolving for at least 3 billion years.

See for example:
Structural Phylogenomics Retrodicts the Origin of the Genetic Code and Uncovers the Evolutionary Impact of Protein Flexibility

Data like this is being outright dismissed by the IDiots as "imagination" and "assumption". They don't bother actually trying to explain why they think the findings of these kinds of analysis are invalid. No, a simple dismissal is enough, and then a bit about being flabbergasted by words like "gears", "information" and "factory". Seriously, the word "information" is bolded constantly, as if mere information was some magical entity impossible to understand or produce through natural means.

So much for serious scholarship.

Data is being dismissed, as if it means nothing or doesn't exist. That's willful ignorance.

3. Seriously, some one read that ENV article, it's beyond pathetic. Whoever wrote that crap is so impressed with terminology, even words like "assemble" are bolded.

Does this IDiot think there's an invisble angel sitting inside the ribosome, "assembling" the proteins?

4. John, You have decided (without subjecting it to experimental test) that H5N1 would 'do better' if it did something else. Maybe so, maybe not. An ancient land animal, meantime, with a vastly different genome size, recombination and a multicellular developmental program, that doesn't have to hijack another cell's replicative machinery and bypass its defences in order to proliferate, starts to wander offshore, and experiences selective adaptation for an incresingly aquatic mode. This is implausible because a virus is struggling to find the serial mutations to enable it to cross species? Whales don't explore genetic and phenotypic space in the same way as viruses. This is a very important point.

Spliceosomes, ribosomes, DNA repair? Accelerating from a Trot to a Gallop. Organisms at some point in the past discovered them, but couldn't have because H5N1 is struggling to get where it 'should' be.

I have run out of ways to say, politely, that it is a dumb argument, so I'll just have to come out and say it: it's a dumb argument!

15. Finally, what can't be refuted if we resort to, 'many things fail, and something interesting happens somewhere'. That explains little because it can explain everything. If flies don't change for millions of years, you just assume further change was just one of those failures; if a mammal goes to a whale, it is just one of those successes. Quantitative analysis seems to be just given the boot. This will not do. Some adaptations are hard, others easy. Some will never occur in the history of the universe. We must not just assume that everything in existence is a result of the easy ones. Looking at the intuitive complexity of CR, and then organisms, it is a legitimate question whether there is more complexity of a certain type than can be evolved in the universe's resources.

1. There are a lot of problems with what you are saying, John. First, you've utterly failed to deal with all of the basic problems with Behe's argument that I detailed in the TREE review. Rebut that in detail -- no one has, including Behe -- if you want to have a start at getting serious. For bonus points, suck it up and admit the points where he is wrong. There are several, e.g. his claims about "irreducible complexity squared" in cilia, where that is just flat-out the case. Even Behe himself hasn't bothered to do this yet, which is why we don't take him serious, except Larry when he is in a curmudgeonly mood.

Regarding "many things fail, and something interesting happens somewhere". That doesn't explain EVERYTHING. It wouldn't explain the situation where humans had a completely different genetic code from everything else, for instance. But it DOES help explain how certain pathways that seem to involve somewhat more amounts of luck than usual (such as double mutations) are actually not so improbable, considering all of the things that were not so lucky and their genetic lineages died out.

It's an undeniable fact that most individuals in populations do not leave descendants long term, and it's an undeniable fact that most species have gone extinct. Pretending these background facts aren't there is what will not do.

Re: whales -- please get serious. What, exactly, was so hard to evolve? Do you deny that evolution can change body size? Do you deny that evolution can gradually move a nose up the skull into a blowhole position? What?

And, beyond being specific about what you think evolution can't do, any real scientific researcher would do due diligence on these sorts of questions before cavalierly claiming that all the experts don't know what they are talking about. This involves: (1) comparative biology -- is the feature in question actually specific to whales? Is it found in any form in relatives? In fossils? Have you actually done the scientific thing and bothered to look up any data relevant to your question, or are you just trolling on the internet hoping you can troll other people into doing all the hard comparative research work for you? And (2) have you actually bothered to do a literature search on the topic of the evolution of X? Why should anyone in science take you seriously if you haven't? Google scholar is your friend.

2. "Finally, what can't be refuted if we resort to, 'many things fail, and something interesting happens somewhere'."

That is what we observe. It doesn't need to be refuted, it is an empirically discoverable fact. We would not be reasoning honestly if we started ignoring things that don't fit into this picture you construct, where things that evolve are so obsenely improbable they are miraculous.

A perfect example is the Leski long term evolution experiments with E coli, and the evolution of aerobic citrate transporter. Suppose we go back to the beginning of that experiment, compare the very first clone that was used in the experiment, with one of the lastest clones. Then we compare the genomes of the two and count all the mutations (IIRC over 600 mutations have been fixed, and we only know what very few of them do) and then we try to compute the probability that that specific set of >600 mutations would have happened?

It's going to be a lot smaller than the probability or the CCC that Behe is trying to argue sits on "the edge" of evolution.

"That explains little because it can explain everything."

Uhm, no. For example, if we constantly saw things easily evolve, but actual laboratory investigations showed that there were no possible alternative functional trajectories, we would have very strong reasons to doubt that what evolves was just the result of random sampling.

The issue is exactly what I alluded to above, that Behe is trying to insinuate that everything but what ended up happening was a path to extinction.

"If flies don't change for millions of years, you just assume further change was just one of those failures; if a mammal goes to a whale, it is just one of those successes. Quantitative analysis seems to be just given the boot."

What do you mean given the boot? Are you saying patterns of extinction and diversification has not been subjected to quantitative analysis? If so, you'd be wrong.

"This will not do. Some adaptations are hard, others easy. Some will never occur in the history of the universe."

Yes and the trick is figuring out which are which. You can't just assume you can transfer the results from single-celled parasites responding to certain antibiotics to changings in timing and magnitude of developmental signals in huge multicellular animals. They are simply not the same.

"We must not just assume that everything in existence is a result of the easy ones."

Who does that?

"Looking at the intuitive complexity of CR, and then organisms, it is a legitimate question whether there is more complexity of a certain type than can be evolved in the universe's resources."

It is an entirely reasonable question, but honestly answering it requires that we refrain from engaging in patently unjustifiable equivocations, or that we ignore certain observations like extinctions.

3. One aspect of the intellectual dishonesty of ID proponents is somewhat tangential to this discussion but relevant: when Newton came up with his gravitation theory, the orbits of the planets were shown to be unstable. Some people were quick to point out that god was stabilizing the orbits for our benefit. Laplace, ~150 years later, showed that a mechanistic explanation was perfectly suitable. Then Mercury was the problem. ~100 years later, Relativity took care of that. The History of Science (and religion) is full of god-of-the-gaps claims that just kept (and keep) being pulverized to oblivion.

Let's imagine, for the sake of the argument, that Behe is right and that the present molecular evolutionary models we have are insuficient and that the probabilistic arguments are actually clear and irrefutable; why exactly would it follow that god/design is the answer? Isn't it far more sane and sensible that the models we have now would just be wrong and that better mechanistic ones would be needed? That perhaps there are mechanisms that we are not aware of? Given the entire history of science why exactely would this *not* be a much more reasonable position than another god-of-the-gaps argument? When two hypothesis are available, showing that one is wrong doesn't make the other right, specialy when there is zero evidence for the alternative (gods, miracles, resurrections, magic). Compared to ID, even Natural Genetic Engineering or the strong versions of Panspermia sound plausible. Why not one of those instead? Isn't it obvious that there is an agenda here that has little to do with science and more with conforting our faith? Behe, Dembsky, and Denton, know this fully well.

4. Pedro, the judge's opinion in the Dover case goes on at length about this false argument that there are only two choices, and thus for anything evolutionary theory can't explain in full right now, ID is the only alternative. That of course is why virtually all ID argumentation and research consists of trying to raise questions about evolution. The only pro-ID argument I can recall that is not of this form is the paper I believe Jonathan Wells co-authored saying "It looks designed to me, therefore it *was* designed."

16. To the whole truth: Part 1

I did not bring religion or Christianity up: you are the one who asked. So no one jump on me for preaching here: the whole truth brought the issue up, I am merely responding.

Your claim is that miracles are preposterous because they are unfamiliar to your experience. This is not, I believe, a sound line of reasoning. If God exists, and if he can create a universe of matter and energy, is it strange to think that he could create a loaf bread to prove a point? So the question cannot begin with, 'can bread materialize out of air?' It has to begin with, 'Is God real and omnipotent?' If atheism and materialism is true, then yeah: the stories about miracles are all wrong. But that is assuming the truth of atheism and materialism. We must put all worldviews not the table for evaluation and not rule out any a priori.

What evidence would be convincing enough to bear the weight of proof for the miraculous stories of the Bible? I'll make two points, the second probably more interesting than the first to you. First: I happen to believe that God, if he exists, can give a man knowledge and warrant for his existence directly interacting with him personally: not merely by propositional deduction from logic, but by experience (i.e., the difference between someone feeling and knowing pain firsthand, vs a scientist deducing a patient is in pain from neural structures)

1. In order to determine whether god is omnipotent, we first have to actually discover god and then test it. This can't just be assumed, and personal revelation is pretty far from anything I would consider evidence.

It doesn't matter what you personally believe god can or cannot do, to give you certain experiences. That isn't useful evidence to people who don't recieve these kinds of supposed revelations.
Even worse, I have yet to hear from some one who recieves these experiences how they would go about distinguishing their experiences from very realistic halluscinations or other kind of psychoemotional phenomena that we already know and can show people engage in.
Some people really, really, really believe they're Napoleon. They probably feel it just as strongly as you feel you're communicating with god. Your conviction and the emotive value you assign to your experience isn't evidence that a god is talking to you, particularly when we know people are prone to powerful halluscinations and self-deception of these kinds.

In point of fact, given this knowledge, we should be extra skeptical about claims of personal revelation through *experiences*.

Extraordinary claims require extraordinary evidence. A feeling you get inside you is not even mundane evidence, it is terrible evidence. But an omnipotent god is an extraordinary claim.

2. John Block said: "We must put all worldviews not the table for evaluation and not rule out any a priori."

Well then, let's put Satanism on the table, and Voodoo, and Pastafarianism, and Wicca, and every personal worldview that any human has now and has ever had. That, of course, would include every individual's version of christianity and all other religions throughout the entire history of humans.

How would you suggest that all the caveman worldviews be presented and evaluated? You don't want to leave out all the caveman worldviews, do you?

17. To the whole truth (part 2)

But second, if one needs evidence, specifically evidence from within the Bible (as opposed to extra biblical proof for a deity, like the nature and existence of physical laws and fine tuning), look at Isaiah 53 (and in the larger context, 49-53): written hundreds of years beforehand, does this not remind you of Jesus in very good detail?

Or look at the book of Daniel. Look at chapters 2, 7, 9 and 11. Every single scholar who has ever looked at this says that the uncanny knowledge, accuracy, and prediction of the future (from the Medo-Persian empire to Alexander to Antichous IV to (more conservative scholars would say) the Roman-Jewish war and destruction of the 2nd temple at 3 and 1/2 years into the war) proves one of two things: either Daniel was written after the fact, or it is divine in origin. Period. Too much super-accuracy and precision for anything else. There are good reasons for thinking Daniel was written beforehand. There is a paucity of Greek words in Daniel, the Greek words that are used are few (3) and for musical instruments of international currency, the Persian words are old (circa 350 BC) and not well translated by the time of a late date, the style and syntax of the Aramaic seems old and Imperial (similar to 5th century Elephantine papyrus, and not later Aramaic), the Hebrew resembles Ezekiel's Hebrew (which is old) and the subject-object-verb order is different than a second century date, Daniel seems to be aware of hard-to-know historical events (such as Belshazzar's co-regent reign) lost to later historical writers like Herodotus and Xenophon, etc. Also, the papyrological evidence (papyri dating to 125 B.C.) and widespread use in the Qumran community as canonical sectarian literature support, and the date of the establishment of the Essene community vs. the completion of Antiochus' reign, could point to an early date for Daniel as well, since it is hard to see how something composed just 40 years sooner would gain such prominence in a sectarian community. There is an open question whether Daniel was included in the Greek Septuagint originally, which was translated 250 B.C. (too early for a late date authorship), but there may be good reasons for thinking it was. It would mean that only 30 years after it was written, it would have to have been received as canon and spread to Alexandria, approximately 300 miles away. Finally, this is more tenuous, Ezekiel (a book that is early and no one really questions this) may make mention of Daniel in Ez. 14: 14, 20; 28:3. I have my doubts here, but it should be on the table.

I would point you to commentaries such as: the Expositor's Bible Commentary on Daniel, the Tyndale Commentary on Daniel, Survey of the Old Testament by Gleason Archer, etc.

There are still problems and issues with Daniel. I do not deny this. But it is not so straight-forward as you are saying. Whether supernatural events happen is a claim, and before ruling it out, evidence must be referred to.
And finally I would say, read the Bible with an open heart. I used to read the Bible just to pick out the bad bits and disprove it. But really read it. If Jesus was a maniac or fanatic, why would he be so selfless and thinking and teaching so much about the poor? Most fanatics claiming divinity are enormously self-indulgent. There may be an authenticity to his character that substantiates his claims.

1. if Jesus was a maniac or fanatic, why would he be so selfless and thinking and teaching so much about the poor?

How refreshing, the regurgitated vomitus of C.S. Lewis.

If you are going to use his pathetic "trilemma" as an argument you should be honest enough to quote your source.

2. I like how we're being treated to a case of bible study, but ID is of course just about good science.

*yawn*

3. John Block, I brought up religion because it's obvious that you and other science and evolution deniers are deniers because of your religious programming and agenda.

I read Isaiah 49 through 53 and Daniel 2 through 11. To me it's all gibberish. It's actually painful to read because it's so incoherent. It goes around and around and every which way and nothing that matters can be derived from it. It sounds like the ramblings of a person who's insane and/or high on LSD or a similar drug. Any parts that are comprehensible (rarely more than a few words in a row) are depressing, fear mongering, threatening, and monstrous.

You said: "But second, if one needs evidence, specifically evidence from within the Bible (as opposed to extra biblical proof for a deity..."

I can think of various ways that someone could provide evidence or even proof of the existence of the so-called 'Christian God', but here are just a couple of those ways. Any person claiming that they're a christian could allow me to tie them up and throw them into a raging fire, or drop them into a den of hungry lions and leave them overnight. If the christian can survive the flames without their skin or clothes even being singed or not be injured or eaten by the lions I'll admit that the so-called 'Christian God' exists.

I don't think it's unreasonable to expect a currently living christian to get their so-called 'God' to do the things in the bible that 'God' allegedly did in the past, such as something as easy (to an allegedly 'omnipotent God') as protecting a christian from fire or lions as described in the bible.

Tell you what, I'll make it even easier. If 'God' has a pizza with my favorite toppings delivered to my door within the next hour I'll believe in 'him' and worship 'him'. 'He' should be able to do that with very little effort. A large bottle of root beer or cola would be appreciated too.

4. Jesus prophesied he would return before all his apostles had died. They all died and Jesus did not come back. He was a false prophet and in the Bible the penalty for false prophecy is death.

Jesus gave his followers "superpowers" like immunity to drinking poison and venomous snakes. The "Snake Salvation" guy handled venomous snakes, got bitten and died. His father got bitten and died. His son got bitten and almost died. Jesus made false prophecies.

As for CS Lewis' "Mad, Bad, or God" trilemma, I would vote for options that Lewis didn't consider: 1. Jesus never existed and his sayings come from halluciniacs who channeled Jim as their spirit guide in dreams, 2. He was misquoted by antisemitic fanatics, or alternatively 3. Bad. The guy described in the gospels is a violent, prejudiced, incomprehensibly vengeful, deceitful, terrible person. He lies to his family, is bigoted against Canaanites, curses a fig tree for not bearing fruit out of season, and tells his followers to sell their possessions and buy swords. If he existed, which I doubt, he was either misquoted or a terrible person.

5. @The whole truth Indeed. The Bible is full of examples of ways to show that god exists. In the story in 1 Kings, Elijah shows the proper way to impress upon someone the existence of god: by getting fire to fall from the sky and land on an altar. While not unassailable , it's at least evidence of some sort. Notably, he mocked the prophets of Baal for their god's failure to show up: “Shout louder!” he said. “Surely he is a god! Perhaps he is deep in thought, or busy, or traveling. Maybe he is sleeping and must be awakened.” Elijah strikes the right note here. Why shouldn't we use the exact same taunts when your god fails to show up now?

Now, in Sunday School I was taught that that story was the proof. That's clearly ridiculous. If stories were evidence, then this story doesn't make sense, since in the story Elijah already had the stories of the parting of the Red Sea and the Plagues and other sundry stuff he could have quoted to the prophets of Baal as 'evidence'. But he didn't do that because everyone knows stories aren't convincing evidence. So he does something reasonable, and arranges a demonstration. Whoever wrote 1 Kings knew that nothing less would seem convincing.

6. "Every single scholar who has ever looked at this says that the uncanny knowledge, accuracy, and prediction "

Yeah. You know what would be uncanny? An appendix in the Bible listing the first thousand digits of the decimal expansion of Pi, and then blocks of 100 digits from the expansion starting at digit i = 2^n for a couple hundred integer values of n. There is no way to forge that, no way to write the 'prediction' after the fact. We'd spend the rest of eternity computing the next block listed in that appendix and each time we found the next block that this ancient book already knew it we'd get a little confirmation of how remarkable this book is. That would be uncanny.

But we don't get anything like that do we? We don't get even simple observations, like that matter is made up of atoms, or that radio waves exist, or penguins, or how useful it is to boil one's drinking water. It is a myopic book of mostly soap opera concerns of god(s) and humans, who likes/hates/has sex with/kills who, whose silence on virtually the entire realm of hard won human knowledge is not only unconvincing, but actually very damning.

7. And it has been a couple of days and no pizza and pop has been delivered to me. Bummer.

8. The whole truth wrote:

"And it has been a couple of days and no pizza and pop has been delivered to me. Bummer."

I'm just curious... Did you pray for it...???

18. John Block,

Re: Isaiah 49-53, summary: The people of Israel are suffering. God has abandoned them, or so it seems. The people of Israel are to blame for the suffering, because they have disobeyed God. God still loves them, though, and will be reconciled to them once the necessary price is paid. The suffering servant's suffering and death will be an appropriate sacrifice and will reconcile Israel to God. This is a generic prophecy that might fit anyone who suffers and dies for an ideal. It has often been interpreted that Israel's suffering will reconcile humans (or at least Israel) to God.

Jesus, assuming with little evidence that the reports in the gospels are accurate, ministered to the Jewish people when they were suffering under Roman rule. Got their hopes up (intentionally or not). Was killed. Jesus' life was reported by people consciously fitting his life to prophecy (e.g. read Matthew). Not surprisingly, it fits as written, but that doesn't mean that the prophecy referred to Jesus. (It could refer to many, many others, including the Maccabees, or to no individual at all.) The important part of the claim that Isaiah 53 refers to Jesus is that Jesus' death should reconcile humans (or at least Israel) to God and end human (or Israel's) suffering. Historical evidence that humans (or Israel) no longer suffered after his death is not obvious. The Bible says we're reconciled, but that evidence is pretty circular.

Book of Daniel: For the moment I'll assume that the prophecies do match history without a lot of interpretation, but that could be wrong. (it's been a long time since I read Daniel, which as I recall is a very odd book.) You yourself say that it could have been written quite late, after the events it supposedly prophesizes. Not mentioned: it could be a rewriting of an early work with new information and perspectives. Such literary forms were common, and not only in what became biblical books.

Your interpretations of the Biblical works you cite might be right, but they are certainly not compelling. They are especially not compelling for people who do not believe in God, or at least do not believe in the Biblical God(s). Convincing evidence for the truth of some Biblical claims could theoretically be found, but so far results fall into two categories; no evidence, or evidence that the claims can be explained by natural processes.

Given the level of (non)belief here, you'd be more effective to stick with non-Biblical evidence, if there were non-Biblical evidence for God. But of course the temptation to discuss religion becomes irresistible when someone else brings up the religious arguments! As I well know. :-)

19. Could someone help me out of a spot of confusion here? I'm not getting to grips with this particular topic at all for some reason. I've no doubt overlooked something rather obvious.

Why are hominid generation times, population sizes and mutation rates being used to determine the likelihood of mutations occurring in a apicomplexan parasite? And why is the remote past being used to determine the likelihood of resistance to a drug that was invented in the 1930s? Are these mutations supposed to be "set up" in advance, or something?

Shouldn't it be the genomes of the parasites and their population sizes that matter?

20. Hey Everyone,

After this series of posts (and it will have to be a series, since it is too much text for one), I am going to bow out of the discussion. When I reply to one or two people, it isn't that bad; when everyone starts to comment, it is really too much to reply to all of it. I am one person and I have time limits.

But, on the flip side, this is a very interesting discussion.

I am going to reply to Nick Matzke first. So Nick, this is addressed to you.

I'll take your points out of order.

1. Do I think evolution can change body size or nose position? Sure. Within limits. Artificial breeding on this point is suggestive: if you try to embellish and elaborate extremes (short noses, huge and small sizes, etc.) usually the lifespans decrease and the health problems and breathing problems increase. The fittest are those mid-size mongrels that stay stable. With regard the to whale, this question is extremely pertinent. In this transition sequence, the size increase was tremendous, no fitness was lost, and longevity may have been gained. How was this achieved at a molecular level? Why is it different than artificial breeding, which strains the health of the organism the more extreme the variation becomes? And, again, there seem to be absolute size limits to dog breeds, just as there are absolute size limits to human beings.

You suggested I had not done any work on Google scholar to support exaggerated claims to entangled molecular or physiological parts that more resemble CR than atovaquone like evolutionary steps. But I cited George Church about the ribosome (it can't do its trick without 50+ proteins, and there is no substantial information from lab studies or artificial ribosomes that those proteins could operate in the context of a co-opting cell--or even if there could be such a thing as a cell--without the ribosomal proteins working in tandem to begin with.) More to the point about whales: Rick Sternberg has a Vimeo or Youtube lecture about whale evolution in which he does look at unique and entangled aspects of the whale's reproductive physiology, and suggests that from population genetic information, this is beyond the edge of evolution.

But even at the level of brute common sense, I reserve the right to be skeptical of the claim that everything in the major sequences like ribosome evolution or whale evolution is just like the easiest cases of resistance or alteration. It seems obvious that big changes are required. And what we see is that when evolution barely slides up the scale of difficulty, from atovaquone to chloroquine, then evolution is huffing and puffing in its most powerful regime (bacteria and viruses) to do things like coherently accumulate a few neutral mutations. Translated to mammalian population numbers, it doesn't make sense. It is by no means obvious that this stuff can evolve.

1. evolution is huffing and puffing in its most powerful regime (bacteria and viruses

Bacteria have had 4 billion years, and they are still doing much the same as they always did. They aren't 'evolution's most powerful regime'. They throw numbers at the issue, is all.

Simple replication with mutation does not have the power that a population with crossover does to explore phenotypic space. It is a vital distinction. You cannot simply extrapolate across kingdoms.

2. "With regard the to whale, this question is extremely pertinent. In this transition sequence, the size increase was tremendous, no fitness was lost, and longevity may have been gained."
It also took tens of millions of years and you're wrong, compared to the ancestral population, the fitness value ON LAND went to zero. Whales simply cannot live on land.

Fitness is context specific. When you say selective breeding produces less fit specimens, you mean in some specific context. The very fact that some people elect to breed these odd mutations means they have high fitness in that context. Dogs may be bred for a few hundred years to get very big, and suffer some consequences because of that. But here the selection constraint is size, they don't become any less fit. Fitness is defined as reproductive success, if you only breed for large dogs, then the large dog is by definition the most fit.

Whales make terrible savanna predators, they're not any more fit than the terrestrial mammalian species they evolved from, only in the context of an aquatic lifestyle. Longetivy is not a useful measure of evolutionary success, it says nothing about how good you are at finding a mate and producing copies of yourself, or whether you can find food or shelter.

You try to extract absolute size limits from selective breeding programs which have been running for, at most, centuries. During the course of such experiments, what is usually explored is the combinatioral variation available in the standing genetic diversity of the population. Add 10 million years of actual mutations on top, in addition to sexual recombination, and you might start to see some results.

This is not an ad-hoc excuse, the actual transitions in the fossil record are spread over tens of million year periods. We get the same time-scales when we try to estimate the transitions when using the molecular clock. It would be senseless for us to then start demanding evolution produce whales or elephants in decades or centuries. Only to people who have an emotional and political agenda clouding their judgement does such demands sound reasonable.

3. It's very stupid to compare the limits on the sizes of DOGS to the limits on the sizes of whales. Marine creatures can evolve to be far larger because buoyancy supports their weight. In the case of whales, we have the intermediate fossils and we can see that their pelvis, hind limbs etc. grew progressively smaller until they were vestigial. This was clearly possible because water buoyancy supports the weight of the whale.

(And, on a related points, dogs can get extremely large, much larger than their wolf ancestors; the Tibetan mastiff is the size of a small pony, and terrifying.)

Again I point out that for decades, creationists claimed that no intermediate could possibly exist between land animal and whale; they were not merely "not yet found", but impossible in principle according to creationists. These claims of "impossible, that's all!" were based on "irreducible complexity" arguments: 'I imagine a whale with one part changed or missing; I imagine the whale dying; therefore, my imagination has proven that the ten trillion evolutionary pathways to making a whale are all impossible.' This is the "irreducible complexity" argument, it was always based on creationist imagination, not evidence, and it was permanently buried when scientists found a suite of fossils for the intermediates between land animal and whale. There is another amazing sequence of intermediates for the evolution of afrotheria (from the common ancestor of elephants and sirenians) into sirenians like the Stellar sea cow. There are intermediates in the evolution of pinnipeds (seals). As for marine reptiles, there are intermediates in the evolution of of ichthyosaurs, mosasaurs and plesiosaurs. But creationists used "irreducible complexity" arguments to claim impossibility of any land to marine transition.

If the evolution from land to a fully aquatic lifestyle required new "irreducibly complex" structures, intermediates should be impossible. In fact, many were found; so that argument is falsified.

21. 2. I did not come here to defend every last claim of Behe's. To tell me to suck it up and admit Behe is wrong in certain respects seems to assume that I can't bear the thought he is wrong to begin with. Not so. Yes, in EoE, in one single sentence in the chapter (I could be wrong, because I just skimmed it!), Behe refers to a paper that suggests that IFT is universally conserved to all ciliate formation. In your TREE Review, you point out that this is not entirely correct. I am happy to admit this. I will even give it a bit more detail.

Rare cases exist in which cilia are assembled without IFT. In these cases it is not clear (to my knowledge) what workaround the cell uses, but it is not to suggest that there isn't some complex construction sequence very much like IFT going on. Behe has an appendix about the bacterial flagella's encoding and construction being a problem, so by no means is the IFT independent construction of the cilia resolved by saying it doesn't use IFT. It could use some other monstrously complex and integrated system. Things must be explained in terms of an adaptive trajectory that avoids many sequential but non-adaptive mutational steps.

But notice one more thing: the danger of extrapolating from the exceptions. It is only under unusual, but relevant, circumstances that cilia form without IFT: the cilia in such instances are made in the cytoplasm instead of in contact with, or enclosed by, the plasma membrane. This is a big adaptive difference. The environment and location of construction imposes major non-arbitrary constraints. An important question, then: For all cilia constructed outside of membranes, and perpetually built and rebuilt, are there any examples that do not have IFT homologs or IFT machinery? This is relevant. How was that transition made to fit that particular adaptive problem? Adaptive problems require very specific and constrained solutions, as we discern from Thornton's studies of adaptive histories.

It seems fair to say that the IFT is the primary (or only?) known adaptive solution for constructing building cilia outside the membrane. There is yet so much to learn about IFT, that it seems that our lack of knowledge of rare, IFT-independent construction should not let us boast that adaptive trajectories would be simple hill climbing exercises. They could be just as complex in construction. Consider what is yet unknown about IFT itself:

"A framework for the entire IFT process has been established, but important questions remain. For example, how do the components assemble to form a functional complex? What is the three-dimensional structure of the IFT machinery? What is the role of each component in the complex? And how do the IFT particles interact with the IFT motors? All the motors that are directly involved in IFT-particle transport appear to have been identified and characterized, but how they are activated and deactivated in the right place and right time is not known. Other questions, such as how the IFT machinery turns around at the tip of cilia, how the components are reorganized at the base and tip of cilia, and how the cargo is uploaded and downloaded, need to be elucidated. To answer these questions, a combination of approaches, including biochemistry, genetics, cell biology, electron microscopy and X-ray diffraction, is necessary."

http://jcs.biologists.org/content/122/7/889.full

22. To conclude on the origin of the IFT: the primary point of Behe's chapter remains:

"Yet if modern malaria can't deal with the single amino acid change of sickle hemoglobin, why should we think that the IFT system would be supplied by random mutation in some ancient cell?"

What is the most direct answer to this question?

3. You state, "It's an undeniable fact that most individuals in populations do not leave descendants long term, and it's an undeniable fact that most species have gone extinct. Pretending these background facts aren't there is what will not do."

I never pretended these facts do not exist. What I am asserting that their relevance is negligible to the problem as Behe has phrased it. I also think it has minimal relevance to the problem as any lay person intuitively grasps what is going on.

Consider: If in a game of poker, you deal two or three straight flushes to yourself, or even one, then I (or any man) will assume you are a cheat. You can vaguely say that there are so many other failures out there in poker, and so many other similar card games being played where hands are dealt, that it isn't unlikely that this would happen somewhere and that you would get this now. But, until you show me statistics, I won't believe you. Even after you show me statistics, if it happens somewhere in the universe, I probably won't believe I am so lucky to have it happen in front of me.

Similarly, we *rarely* and only very *slowly* see multiply-required mutation trajectories build to anything. Note: not just to some specific adaptation in specific gene in a specific lineage, but to ANY generic multiply-essential mutation-constellation in any gene for any adaptive problem. What evidence is there to the contrary? Where is the known double or triple mutant that wasn't suppose to occur so quickly, but did anyway, because of all the other failures and options? The waiting times are all the same, and all slow, because each adaptation is contextualized by the gene and resides in a restricted portion of sequence space, because, as you say, most adaptions are very very far away (you can't hop from flagella to hemoglobin, etc). It's not like you mutate one amino acid, and say, because sequence space allows for infinite adaptive combinations, this mutation will be good in one of them. No, epistatic factors in genes and sensitivity of chemistry in proteins and isolation in sequence space does not permit this.

1. "Similarly, we *rarely* and only very *slowly* see multiply-required mutation trajectories build to anything."

What is "anything" in this context? Does the Long term evolution experiment with E coli count? Lemme guess: No, you don't think so.

What would you expect the E coli experiment should have produced, if evolution was really true? I mean, you seem to imply it isn't. So given that, you would have expected more from the experiment. Give us an example and tell us why that is what you would expect, what lead you to think that should be the expected result.

How rarely is *rarely* and is this more rare than we would expect, given the rate of evolution implied over the entire history of life?

How slowly is *slowly* and is this slower than we would expect, given the rate of evolution implied over the entire history of life?

Does the result make sense when extended over the entire history of life?

You really need to acquaint yourself with the concept of geological time.

"Where is the known double or triple mutant that wasn't suppose to occur so quickly, but did anyway, because of all the other failures and options?"

What does that even mean, "wasn't supposed to occur so quickly"?
Yes, larger populations can sample greater portions of phenotypical space in shorter time. The two, population size vs rate of discovery of solutions due to mutation, should be directly linked. I'm not aware of any experiment that says otherwise.

"The waiting times are all the same, and all slow, because each adaptation is contextualized by the gene and resides in a restricted portion of sequence space, because, as you say, most adaptions are very very far away (you can't hop from flagella to hemoglobin, etc)."

The waiting times for what? How slow are they? Should they be faster, and if so how fast? Why do you think that?

"It's not like you mutate one amino acid, and say, because sequence space allows for infinite adaptive combinations, this mutation will be good in one of them. No, epistatic factors in genes and sensitivity of chemistry in proteins and isolation in sequence space does not permit this"

Now you're just talking gibberish.

2. John Block, I think your evasion regarding Behe's claim of SIMULTANEOUS mutations is quite pathetic. Here you say: "I did not come here to defend every last claim of Behe's. To tell me to suck it up and admit Behe is wrong in certain respects seems to assume that I can't bear the thought he is wrong to begin with"

Then admit that he was wrong about chloroquine resistance in malaria. Behe said the mutations were simultaneous, he was wrong, and now he's trying to redefine the word "simultaneous" because he's losing. Now you have written:

"Michael Behe has repeatedly and explicitly made clear that he does not mean the word 'simultaneous' in the way you have accused him of meaning. He does not intend to say a double mutation, occurring in the same replication cycle of a single replicating cell.... he is correct: in order to function, and for resistance to work, a cell needs at least two key amino acids in place at the same time. I think it is bordering on dishonesty to keep accusing him of something he is emphatically denying. That is all he is saying."

But that is exactly what Behe meant, and how he calculated it, according to Behe's DI co-worker Ann Gauger just a few days ago:

Gauger: "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...

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 10^16 mutations per base pair per parasite."
[Ann Gauger at ENV, July 28, 2014]

Why do you not accuse Gauger of dishonesty as you have accused us?

Here is Gauger again, spelling out exactly what "simultaneous" means:

"His critics focus on Behe's use of the word "simultaneous." Getting two simultaneous mutations is ridiculous, they say, and so multiplying two rates together is ridiculous.

Maybe the two mutations happened simultaneously, meaning together in the same molecule in one generation. It is possible. Maybe the mutations happened one at a time. We don't know..."

So Ann Gauger and Michael Behe keep claiming, to this day, that "sequential" and "simultaneous" are the same thing. Therefore they were right. Experimentally that's falsified, we know the mutations were sequential, not simultaneous. Mathematically, there is a mathematical law that the difference between "sequential" vs. "simultaneous" double mutations grows larger by a factor of at least 1/2 for every round of replication. Thus, the size of their error grows enormous over time; it is an error of unlimited size.

You accuse us of dishonesty, but you evade refuting evidence.

23. So there are two problems as I see it. First, the idea that, 'all the successes are explained by the great number of actual failures in the fossil record, and the infinite number of potential other adaptive solutions that could have occurred but never made it to the light of day' is an idea that has not been, and probably cannot be, quantified or in fact, falsified. How can I know you are correct without making the assumption you are? Is there an independent model that one can show? Are there absolute cutoffs (such as, we expect X% failure for triple-mutation adaptations, and such mutations did or did not occur in this historical trajectory, etc)? No. Everything seems completely non-quantitative and ill-defined. No one knows or has given detailed models concerning what it takes to construct developmental circuitry, kernels, pathways, whatever else in evolutionary sequence. 'Large numbers in ancient populations' are just asserted to take care of the problem. How can someone actually know and test this, without asserting the hypothetical possibility that it is true? This is like having a theory of gravity with no real constant values or precise variable relationships. 'Things attract other things' is true, but it is not a theory of gravity.

Secondly, it seems to ignore what is in front of our eyes. Some adaptations are easy, some hard, and they occur exactly in proportion to their probabilities. The fact that several ancient species of fish died long ago doesn't really help H5N1, because they are testing different adaptive problems at different ends of sequence space, and the probabilistic resources of one does not really count toward the end of solving the problems in the other. If whale evolution can be broken down into atovaquone steps, that's perfectly fine, it can evolve. But intuitively, and even from more detailed research and considerations from Sternberg, it seems more entangled than CR, and if so, it is hard to see how it will evolve.

1. John Block: "No one knows or has given detailed models concerning what it takes to construct developmental circuitry, kernels, pathways, whatever else in evolutionary sequence. "

How the \$%&* would you know? In fact, scientists have made great advances in reconstructing how developmental circuitry evolved. You're wrong because you learned your science from creationists like Michael Behe who don't do Google searches but just say "No scientist in the world knows the answer", and they say that to church audiences, not at scientific conferences because church audiences can be lied to, but real scientists won't swallow that. "No scientist in the world knows the answer" is not found in the scientific literature, it's only found in the creationist literature, and not cited properly. Therefore it's permanently on ignore.

2. And another thing Block, do not cite that lying creationist Sternberg ever again unless you are going to copy and paste his equations, or a citation to the peer-reviewed literature. If you copy and paste his equations, I can demolish them. I take an interest in equations; I will not watch videos of creationists lying about stuff that's not in the peer-reviewed scientific literature. But Sternberg doesn't give equations in his YouTube videos, so \$%&! him. He's another lying creationist and I wouldn't trust him to balance my check book. You think citing an authority "Sternberg" is making an argument. Not where population genetics is concerned! Copy and paste equations or GTFO.

3. P.S. I did listen to the debate of Sternberg and (I think) Meyer vs. Prothero and (I think) Pennock (?). Sternberg pulls ridiculous numbers out of his ass, and doesn't tell us how he computed them, or what his assumptions were, and he calls it "population genetics." Bullshit. He's not a population geneticist. If he had such numbers he should publish them in journals of population genetics not journals of unrelated topics, like Electrical Engineering, the way Dembski does with his "information theory"! He doesn't even tell us what the hell he was computing. Copy and paste the equations by which he derived the numbers, which I may then demolish, or GTFO.

4. Everything seems completely non-quantitative and ill-defined. No one knows or has given detailed models concerning what it takes to construct developmental circuitry, kernels, pathways, whatever else in evolutionary sequence.

As Diogenes has said rather forthrightly, if you think this, (1) you are quite wrong, and (2) it shows you haven't bothered to do much if any reading in the scholarly literature, where hundreds of papers on just this type of topic are published in peer reviewed scientific journals every single year.

Far from demonstrating problems with evolution, what you have thus demonstrated is that your faiths (in God and against evolution) have made you lazy and overconfident. Do the necessary background research, *then* consider yourself qualified to comment.

24. 4. You say that this explanation is not so vague as to cover any possibility: such as drastically different genetic codes.

First, what makes drastically different codes prohibitive? Because they are the ultimate example of entanglement and irreducible complexity, of changing too many features at once to ever be well-coordinated in evolution, right? I am asking if coordination of this magnitude or of a smaller but prohibitive magnitude might be seen in some of the alleged historical transitions.

Now, though it is true that your proposition is falsifiable, the falsifiability criterion is weak. Imagine if the great falsification test of Mendelian genetics was that cows can't directly breed horses? There has to be much more rigorous analysis than that, and there must be much finer and more subtle and more rigorous test for your proposition that 'many trials are adequate to produce the adaptive complexity of the biosphere'. Numbers and quantification must make an entry into the argument.

Interestingly, it is not a prediction of evolutionary theory that there cannot be alternative biochemistries in a biosphere. Alternative biochemistry and coding (even wildly different coding) is not precluded. In fact, (very good) speculators like Paul Davies say that there might be remnants of exotic life in extreme parts of the biosphere today. If we were to find a species with an alternative biochemistry, one could say it is just a descendant of one of those opposing lineages that came up with a different adaptive solution. Or you could say that it is the standard code, just evolved beyond all traces and recognition, sort of like how in the 1980s there was an idea that life was built up from clay replication and that all traces had been lost to history.

1. Nobody was saying there can't be be alternative biochemistries or different genetic codes. What they're saying is it would be absurdly unlikely for one organism closely related to another to rewrite it's entire genetic code through a simple mutational process (and regardless of population size), for well known biochemical reasons. The extant organisms physiology is intrinsically tied to the established code's structure, so if you changed too many codons too drastically so they end up coding for different amino acids, you most probably end up breaking most of the extant proteins the organism is made of. Such changes would be lethal in most cases.

The population size of organisms required to put such mutational change within the realm of plausibility would probably produce a bacterial colony bigger than the entire Milky way galaxy(you sould have to simultaneously mutate every protein and RNA structure related to the genetic code and translation, into an alternative translation system that still works but with a different code), so such an ad-hoc postulation would instantly lose credibility for other reasons. So no, we couldn't just sweep everything away with ad-hoc references to past huge population sizes.

And no, we couldn't just magically erect speculations that two organisms with wildly different codes nevertheless share recent ancestry. If they did happen to share ancestry, it would have to lie so far in the past it would probably have to lie before the origin of the extant code. Nevertheless, we would not be justified in inferring common descent between two such organisms.

2. Now the interesting question becomes, do you have an example of an organism with a wildly different genetic code, or is this just a mindless hypothetical?

3. Shifting goalposts. He's trying to invoke the argument of Walter ReMine in "The Biotic Code". ReMine says evolution is non-falsifiable because there could in principle be organisms with totally different genetic code, biochemistry, etc.

Stupid argument. First, if creationism is true, anything is possible, including violations of physical law. Second, evolution is still falsifiable because if we found organisms with totally different genetic code, biochemistry etc., we would have a whole new set of testable predictions: we would start by repeating our analyses on the other tree of life, e.g. start with phylogenetic analyses on tree 2, then see when its complex structure appear in the fossil records-- does it form a reliable and robust tree; do the complex structures more in more general taxa appear in the fossil record before the complex structures in more specific taxa; etc.

25. Two last things for Nick + others:

1. With regard to IFT and cilia. I think the last point I would like to make is to consider a perhaps slightly exaggerated analogy. Certain mousetraps have been shown to require a sophisticated type of robot for assembly. Other mousetraps--rare exceptions, built under different constraints--do not. No one really is totally clear how those other mousetraps are built, and what robots they do or do not require. But surely just pointing out that some mousetraps are built without a robot doesn't explain the presence or origin of the robot's involvement? How did this robot (IFT) come to control mousetrap building (cilia construction) under specific circumstances (i.e. non-cytoplasmic construction)? How did it do it avoiding strenuous adaptive pathways?

2. Pattern vs. mechanism. Suppose I have a theory that the planets go round the sun by an inverse cube law. The pattern is right; the mechanism wrong. Similarly, from a logical standpoint, it is entirely possible that whales descended from a common ancestor, but it does not follow that the mechanism has to be what everyone says it is. In fact, there may be good reason to believe the numbers aren't adding up, just as an inverse cube's numbers wouldn't add up.

There is also a question of how many intermediate fossils we should expect to find given the nature of the transition, but that depends on contingent factors of fossilization, but also on the non-quantitative parts of the theory: we don't know how many speciation events would be required, population sizes, developmental alterations and rearrangements, etc. It would be impossible to say. But, while understandable, this is not an attractive feature of the theory.

1. John Block shifts the goalposts: "There is also a question of how many intermediate fossils we should expect to find given the nature of the transition"

We know under creationism how many there should be: zero! Creationists invoked "irreducible complexity" arguments to say that intermediates were impossible in principle, not just not found yet. If the evolution of whales involved gaining "irreducibly complex" structures, then there should be no intermediates. One is enough to falsify creationism, but we have many for cetaceans, sirenians, pinnipeds, etc.

26. This reply is addressed to Barbara and the whole truth:

First, Barbara, I actually really appreciate your friendly tone and the comments you made. I regard them as very serious and well-informed. Here is how I would reply:

First, predictive prophecy can absolutely be a vindicator of faith. If in science I predict a result on the basis of theory, and it happens to some extraordinary degree of precision, it is entirely probable that the prediction-verification scheme vindicates the theory.

So consider Isaiah's Suffering Servant once again. Once again, keep in mind this book was incontestably finished hundreds of years before Jesus. Here are the facts about this servant;

1. He will personify Israel, and in this capacity be called to bring Israel to God, but will be rejected by his own people, to the point that he experiences great grief because he seems to fail. [Is. 49:3, 5; Is 53: 2-4]

2.God will not let the Servant ultimately fail in his mission, but will make eventually reconcile Jacob (aka Israel) to himself and make the Servant a great light to all nations (both Gentile and Jew) and bring salvation to the ends of the earth. [Is. 49:6]

3. He will perform miraculous deeds of deliverance and healing [Is. 35:5-7; 49:6-7; 61:1-3]

3. He shall be exalted, but only after first undergoing tremendous suffering [Is. 52:13, 53]

4. He will offer his back to those who attack him. They will spit on him and tear out his beard [Is. 50:6] (This has always been my understanding, but I recognize there are other opinions about this particular verse)

5. He will bear the griefs, afflictions, iniquity and punishment of those who have gone astray [Is. 53:4, 6]

6. He will be pierced for the transgressions of others and not himself (because he himself is righteous), and be cut off from the land of the living as a guilt offering and atonement before God [Is. 53:5, 8, 10]

7. He will be buried, but will live again, be vindicated, make intercession for sinners, and be satisfied. [Is. 53: 10-11]

8. He will be highly exalted [Is. 52: 13]

My question is, can you name any other person, any of the Maccabes or whatever, who come close to fulfilling these verses? Who died and lived again? Who were pierced for the transgressions of others, and there life was an expiating atonement as a guilt offering before God?

The idea that the Servant is a righteous remnant within Israel breaks down as well. I would defer you to 'The Gospel According to Isaiah 53' by Darrell Bock.

1. I'm going to repeat a recommendation of a book by a noted Bible scholar that helps explain and put into historical context the "fulfillment of [Old Testament] prophecy" we see in the New Testament regarding Jesus: http://www.amazon.com/How-Jesus-Became-God-Exaltation/dp/0061778184

27. Everybody has been missing a very important point which invalidates Behe's figure of 10^20 parasites being necessary: Behe's population size of parasites per malaria patient, 10^12, is almost certainly wrong, or at least irrelevant to its evolution. The parasites only number a trillion in the late stages of infection, but those cells mostly either get killed by drugs or die with the patient, and their genes, however mutated, are almost never passed into the next generation. The gametocytes that get into the mosquito and therefore passed to the next patient mostly come from the generation of Plasmodium parasites that emerge from the liver, with a population size in the low hundreds of thousands, not from the parasites that eat erythrocytes, with a population in the trillions. This vastly reduces the number of parasites, far below Behe's number of 10^20.

What should the number be then? Well, about 220 million people a year get malaria [says Wikipedia] and suppose there are twelve rounds of infection (one a month), then 18 million people have malaria in each round of infection. Suppose 1/3 get chloroquine; the parasites in the chloroquine environment would be in 6 million patients per round of infection, or 73 million a year. Chloroquine was introduced clinically in 1947 and CR appeared in the 1950's. Say 10 years to evolve chloquine, so 10* 73 million = 730 million patients on chloroquine. The parasite population that comes out of the liver, "early infectors" as I call them, might number 250,000. The total number of parasites in earlier generations to get the population up to that size would be twice that, about a half million.

So (73 million patients on chloroquine per year) * (10 years) * (a half million parasites per patient) = 365 Trillion parasites = 3.65 * 10^14 parasites. This makes Behe's numbers wrong by a factor of 300,000.

But I think even this number is too generous. Parasites and diseases have population sizes that go through huge variations, boom and bust cycles, unlike the (approximately) constant population sizes of mammals and complex animals. With complex animals, each mutant has a reasonably good chance of being transmitted at least to the next generation. But with malaria and other disease germs, the population crashes when the patient dies (or the germs get killed by drugs) and only a small subset of all the genes had transferred to the next patient.

In the case of Plasmodium, the next patient may get only 10 to 30 sporozoites from the mosquito, so the vast majority of the mutations from the previous patients' infection just die and leave no offspring-- unlike mammals or complex species, where the population bottlenecks are less severe and less regular. Since (at most) only 10 or 30 (dliploid) alleles can survive from one infected patient and enter the next infected, patient, I would argue that the effective population size for malaria should be 10 or 30 parasites per patient times the number of patients in each round of infection, say (220 million / 12) *(1/3 on chloroquine).

Let's be generous and say 30 per patient. Then:

(73 million patients on chloroquine per year) * (10 years) * (30 parasites per patient) = 22 Billion parasites = 2.2 * 10^10 parasites. This makes Behe's numbers wrong by a factor of 4.5 billion.

Note that the "effective" population size for Plasmodium parasites must be far smaller than a trillion. What matters is, what is the *minimum* population size capable of transmitting mutant alleles? When an infection starts, it's 10 to 30. If in each round of infection, 6 million people are on chloroquine, then the "effective" population of Plasmodium capable of transmitting mutant alleles is 60 to 180 million parasites ON EARTH, NOT a trillion per patient and NOT even a trillion on all of Earth.

1. I got these figures from a comment left at Sandwalk by Steven LaValle, ignored by mostly everyone here: "I would like to mention something about that 10^20 number that shows up in Edge of Evolution. I was puzzled how Dr. Nicholas White could know that number, so I went back and read his articles. He was actually trying to figure out where resistance arises in the population and whether or not it might be worthwhile to concentrate efforts at some aspect of that population. In the model for the infection, about 10 to 30 sporozoites enter the blood stream and enter the liver, where they go through about 15 rounds of replication and emerge as a population 100,000 to 300,000 and begin that 48-hour cycle.

The population becomes detectable when they reach about 10^8 and the patient is considered well enough when it falls below 10^8 again. It is not possible to support 10^14 parasites but 10^13 can be supported.

What Dr. White did is estimate the number of clinical cases in a given time frame [Diogenes notes: apparently 50 years, 1947-1997] and multiply by the higher number, 10^13 - this is the 10^20 figure. Since fewer than 10 cases of resistance had showed up in that period, he reckoned the population size required to allow one resistant strain to emerge at 10^19 parasites.

So, where where these 10^19 parasites? It turns out that they would probably be in a child under the age of five who was being treated by chloroquine (there is some in nearly every person in some countries). Given the reasoning above, it would also be in a child who had been infected and suffered recrudescence of the infection...

The gametocytes, for the most part, come from that first population to emerge from the liver and not the later population. Those later parasites, the bulk of them, are either killed by the treatment or die with the patient."
[Steven LaValle comments, Aug. 11 2014]

2. These numbers mean that CQR-type evolution is in fact accessible to mammals and other complex animals, contrary to what has been repeatedly claimed by Michael Behe and John Block. If there are 6 million patients on chloroquine in each round of infection, and each patient when he gets infected gets 10 to 30 sporozoites from the mosquito, then the minimum global population of Plasmodium in a chloroquine environment would be 60 to 180 million parasites. Now compare that to hominids, which for most of their evolution had a population of about 100,000 (though there was a bottleneck where the population went down to about 13,000.) So the parasite population is 1,800 times larger than that of hominids.

What about replication time? I figure that Plasmodium replicates about every other day (because they spend two weeks in the liver and undergo 15 rounds of replication; then the gametocytes from that generation go into the mosquito, which transmits the sporozoites to the next patient, which I figure will add two weeks, so one month per round of infection.)

Hominids have a generation time of about 25 years. However, that's not replication time. Human cells go through many replications from the fertilized zygote stage to get the individual large enough to produce gametes; for male humans it's about 30 replications IIRC. That increases the human mutation rate. So let's say hominids have one replication per year, while Plasmodium has one replication every other day. Thus, Plasmodium's replication rate is ~160 times faster than humans.

So if population sizes for hominids were 1,800 times smaller and 160 times slower, and if CQR evolved in Plasmodium evolved in 10 years, then hominids can evolve the same amount as Plasmodium CQR did in about 10*1,800*160 = 2.9 million years. Of course humans split off from apes 6 million years ago, so CQR-type numbers could happen in a hominid-specific line.

Moreover, if we're talking about double mutants, sexual recombination is more important for complex animals than for Plasmodium, so it would play a larger role.

3. "Mechanism promoting multiple DNA mutations described by scientists":

http://www.sciencedaily.com/releases/2014/08/140813131152.htm

And if anyone is interested, there are also several recent articles about malaria at Science Daily.

4. On the subjects of protein folding, search space and landscapes, and all that jazz, there's this interesting article:

"From eons to seconds, proteins exploit the same forces":

http://www.sciencedaily.com/releases/2014/08/140813131152.htm

28. Barbara,

In reply to the fact that Matthew 'fit' Old Testament texts to Jesus, I would encourage you to read 'Right Doctrines from the Wrong Text' by G.K. Beale, and 'The New Testament Commentary on the Old Testament' by Beale and Carson. The treatment is extensive and they also include essays from those who disagree with Matthew's and Christianity's interpretation. My take? It seems obvious that Matthew, writing to a Jewish audience well acquainted with Scripture, was not using a direct line of mechanical fulfillment. It is called midrash and homiletics, and it is/was an acceptable literary practice of rabbis for millennia. We must give Matthew a bit of credit.

To the whole truth:

It seems like you are so angry. Why? I am not tying your arm behind your back or demanding anything from you. You are the one who brought up the Bible. You seem like a highly intelligent and likable person, but it seems to me also plain that you have never consulted any academic resources or Biblical scholarship about the Bible. I don't know if this is you, but there are so many people--like Pinker and Hitchens--who read from the KJV as if it is the best translation, and read Deuteronomy or Exodus, and almost act as if they are finding shocking new things that the Church suppressed or overlooked. Read any commentary series. The commentaries cover almost every problem--science, ethics, contradictions, history, whatever--that one can find. They have already addressed much harder problems than Dawkins knows about, because Dawkins and company have a shallow reading of the text. I know you are intelligent; I am asking you just to apply this intelligence in looking at the best defenses and resources. This seems plain in your treatment of Jacob's goat genetics, Sodom and Gomorrah, etc. Also in your admission that nothing in Daniel seems to make sense to you. I can tell from this comment you have never read a commentary on it. The prophecies are very plain, and the symbolism is unmistakable. This is not my conclusion, or the Christian conclusion, it is the universal conclusion of any scholar--atheist or Christian--who is well trained and reads thoroughly. Suggestions? The Expositor's Commentary Series, Tyndale, NIV Application, etc.

Finally, can miracles happen today? There is a book by Craig Keener, called Miracles, that purports to characterize some cases. But even without considering that, let me ask you: before you do anything else in testing Christianity, is the character of Jesus in the Gospels (read them all carefully) somehow morally lacking to you? When he tells to mourn with those who mourn, to forgive, to feed the poor? Your anger seems to suggest to me that you don't just merely think it is a false idea, but a hateful and contemptible one. But where does Jesus look like a self-indulgent, hateful criminal or crook to deserve this scorn?

1. John Block said: "...but it seems to me also plain that you have never consulted any academic resources or Biblical scholarship about the Bible."

There's no such thing as academic resources or scholarship about the bible, in the way that you're asserting. The bible is a variously translated, variously edited, variously interpreted, horribly written, incredibly boring, antiquated, mostly incomprehensible, contradictory collection of monstrous, impossible, sado-masochistic fairy tales. It doesn't take "academic resources" or "scholarship" to figure that out.

You asked: "...is the character of Jesus in the Gospels (read them all carefully) somehow morally lacking to you?"

And: "But where does Jesus look like a self-indulgent, hateful criminal or crook to deserve this scorn?"

Well, since you asked, here are just a couple of things in the bible that you seem to have missed:

Think not that I am come to send peace on earth: I came not to send peace, but a sword. - Jesus in Matthew 10:34

But those mine enemies, which would not that I should reign over them, bring hither, and slay them before me. -Jesus in Luke 19:27

Sounds self-indulgent and hatefully criminal to me.

29. Barbara,

Finally, in reply to Daniel: I said a late date for composition was possible, but I gave a list of reasons why I thought it could be early (e.g. the use of Imperial Aramaic and old persian words, hard-to-know historical details of the Babylonian empire, etc.) I was just trying to say, if you can date Daniel before the prophecies, then the prophecies are genuine and unambiguous. If this is the case, then there is no reasonable possibility of denying it is divine in origin. As for stages of composition: I do not doubt the possibility that documents can be revised. There are several Qumran literary works that may well have been. But my point was that both the Hebrew and the Aramaic of Daniel fit an old date, so that, whether it went through different phases of editing or addition, genuine prophecy would still exist.

To quote Gleason Archer:

"In light of all the data adduced under the four categories just reviewed, it seems abundantly clear that a second century date for the Hebrew chapters of Daniel is no longer tenable on linguistic grounds. In view of the markedly later development in the areas of syntax, word order, morphology, vocabulary, spelling and word-usage, there is absolutely no possibility of regarding Daniel as contemporary [with the sectarian documents of the second century]. On the contrary the indications are that centuries must have intervened between them...The complete absence of Greek loan-wors, apart from musical instruments of inter nation currency, points unmistakably to a time of composition prior to the Alexandrian conquest. It is utterly inconceivable that after 160 years of Greek overlordship (as the Maccabean theory insists) there would be a complete absence of Greek terms pertaining to government and administration..."

I realize that Archer may be wrong. Other experts disagree with him. But you have to evaluate the reasons on their own merit. His argument looks to me to be very plausible. So my point is that one cannot just assume, as the whole truth did in his original reply, that because miracles are recorded in the Bible, that it is absurd. There may be evidence that miracles occur.

1. There may be evidence that miracles occur, sure, but we can't be justified believing in that because it says so in an old book. People fool themselves and can be fooled by others. Given that this is the case, to substantiate claims of miracles they have to be submitted to direct empirical test under controlled conditions by professionals.

Millenia old books cannot justify extraordinary claims. Extraordinary claims require extraordinary evidence. Really old books is terrible evidence.

2. John, Mikkel has alluded to what I'd describe as the "meta-evidentiary" problem. A couple of thousand years ago, as evidence of miracles we have pillars of fire and seas being split. Now we have *better* opportunities for observation (everywhere - if there were a pillar of fire or a sea splitting anywhere on Earth today, it wouldn't be missed), but for "miracles" we're down to faces on tortillas or a pattern of fertilizer spray on a window that looks to some people like European Renaissance paintings of Mary. It's a property of reality that more opportunities for observation result in more observations. With miracles, we see many more opportunities and few or no observations. What conclusion does this lead to regarding whether miracles are real?

30. Behe's posted his reply to Larry:

http://www.evolutionnews.org/2014/08/guide_of_the_pe089161.html

1. Hey Bilbo, why don't you contact your hero Behe and ask him why he doesn't reply to Larry and others HERE? If Behe has the one and only, omnipotent, omniscient designer-creator-god on his side I would think that Behe should at least have enough balls to discuss/debate his claims directly with people who challenge and refute his claims. Posting his claims on ENV, where no "reply", discussion or debate is possible, is the act of a coward.

2. I agree. Behe is a coward who won't comment here, who did not address our points nor did he accurately describe our objections. "Edge of Evolution"'s claims were experimentally falsified and Behe's figure of 10^20 is known to be wrong by a factor of 10^5. Since Behe squared 10^20 to get 10^40, his error is at least 10^10.

3. Such an infantile and pathetic response...would be interested in seeing a list of your peer reviewed and published works