# An Open Letter to Dr. Michael Behe (Part 6)

Dear Dr. Behe

Reflecting on your previous post, and the current one, I would like to note that both your mutation rates (10-4) and effective population size (109-1010) are too high. By a factor of around a hundred thousand.

The commonest estimates for HIV mutation rates are between 1x10-5 and 4x10-5, with 2.5x10-5 the most common. Well, what’s a half log unit between friends? More serious is your population size estimate. Here I’d like to introduce you to the concept of effective population size.

Your number is the total population of viruses. Now, not all members of a population reproduce. In population genetics, the effective population size is defined as the number of adults in a population contributing offspring to the next generation (yes, I know that viruses don’t have “adult” reproducing stages, bear with me for a moment). In a population of adults, some adults may not reproduce because there is a difference in the number of males to females. Some may not reproduce because disease or heredity renders them sterile, so the number off reproducing members will always be lower than the total population.

In considering mutational effects, and generating new mutations, you need to consider the effective population size, not the total population size. In HIV, this is important as viruses may replicate in immune cells that die or are cleared before the virus particles can become infective, or the HIV virus goes dormant. As well, there is a very high replicative failure rate in HIV, many copies of the virus are defective and cannot make copies of them selves, or infect other cells.

So what is the effective population size of HIV? It’s been estimated to be between 103 and 105 (depending on the kinds of assumption you make[1]). Even using the highest estimate, this is 10,000 to 100,000 times smaller than the figure you use. You can immediately see that your estimates of the number of mutations available to HIV are concomitantly smaller.

It’s not as if you could be unware of this, your own references show the the effective population sizes are smaller. For example the Rodrigo paper (PNAS, 1999, 96:10559-61 cited in 15, see page 290 of “Edge of Evolution”) where they say:

It has been estimated that the total number of HIV-infected cells in a human host is between 107 and 108 (6). However, only a portion of infected cells produce viable viral particles that go on to infect other cells. … [estimates of infected populations] place the value at around 103 infected cells

and then go on to give other estimates of up to 105 for HIV populations. Same goes for Althaus CL and Bonhoeffer (J Virol, (2005), 79:1313572-78, also listed under 15 in “Edge of Evolution”).

The viral population in an infected patient may indeed represent such a population limited in size, since current estimates of the effective population size range from 500 to 105.

They point to some evidence from the rise of resistance in HIV that is consistent with a low effective population compared to the total population.

Coffin MJ (Science, 1995, 267:483-89), is your source for the “each and every possible single-point mutation occurs” quote. This old paper uses the total population only, they do not account for the effective population. Well, it was an early report, and this incorrect use of the total population was pointed out in a subsequent comment (Levy JA, et al., Science. 1996 Feb 2;271(5249):670-1) noting that “most of these viruses are not infectious”. All evidence points to the fact that double point mutations are not occurring once per day as you claim (see also Seo T-K et al., 2002, cited in the references. Your viral replication rates over a humans lifetime seem to be a bit off as well)

So, your comments about the ability of HIV to explore all of its mutation space in the course of a single infection is basically incorrect. Also note that these estimates of effective population size are in contemporary populations, with highly evolved, very transmissible virus. When the YRKL Glogi binding sequence and the Vpu viroporin evolved, this was in a much more weakly infective and replicative virus (the high infectivity of modern HIV can be traced directly to these two mutations), in a much smaller population of humans. So the proto-HIV, which evolved these allegedly “unimpressive” binding sites, was even more restricted in its exploration of mutations than the modern one.

You also continue to use your “impressedness” as an indicator of the reality of binding sites. The haemoglobin S binding site isn’t particularly impressive, yet you use it as your own example. Mutations in the LTR which confer survival by generating new binding sites are no less impressive than your own example.

But again, this is irrelevant. Your claim is that it takes several simultaneous mutations to produce a protein-protein binding site. The probability that two (or three) given mutations will occur simultaneously is completely independent of the function of the two proteins binding together, or how impressed we are by the function. Whether the bound proteins make a molecular machine, or just glug together, the probabilities of a given two or three site simultaneous mutations is the same.

Not all new binding sites will make a flagellum, they are more likely to make something like the L-type calcium channel, where you have a core unit that functions okay in the absence of partner proteins, but works better when partner proteins bind to it (RAMPS and adrenomedullins are similar, and my beloved imidazoline binding site may turn out to be a RAMP-like protein interacting with the LPA receptor).

The main point is that binding sites are binding sites, no matter how impressed you are with them, and you claim is that binding sites pre se are very improbable to evolve. But it is clear from the Vpu example that they do evolve, and that they contribute significantly to the survival of the virus.

And that is just Vpu, there is also the LTR’s, evolution of CXCR4 binding and binding that leads to upregulation of TRAIL. And I haven’t exhaustively looked fro all possible examples of binding site evolution.

I do hope you will publish an erratum for your book.

Yours sincerely
A male featherless biped named Ian Musgrave
[1] See this book for a discussion of effective population size in HIV, and commonest HIV mutation rates. See also Seo T-K et al., (2002) Estimation of Effective Population Size of HIV-1 Within a Host: A Pseudomaximum-Likelihood Approach Genetics 160: 1283–1293
Update 20-11-2007 I’ve tided up some typos and taken the liberty of adding in a section dealing with the references from Dr. Behe’s book.

“Impressive Complexity” - successor to Irreducible Complexity and Specified Complexity?

Anyway, once this particular discussion is over and Behe claims victory on his comment-disabled blog, you might want to ask him some questions about a much larger organism. Now that the DI has hired long-time Bigfoot advocate Michael Medved, I’m sure that Behe, who’s never at a loss for words (whether they’re relevant is another story), has a lot to say about it.

Thanks for this series Ian.

Bigfoot? I seem to remember hearing recently that someone had confessed to creating the hoax?

Same thing for Loch Ness’ Nessie too.

When will the DI scammers confess?

This is a troll site, and a troll series. I love the fact that Dr. Behe doesn’t do this site the honor of actually visiting it. Good job Dr. Behe.

The Troll Said:

This is a troll site, and a troll series. I love the fact that Dr. Behe doesn’t do this site the honor of actually visiting it. Good job Dr. Behe.

So, then, how does this explain the fact that Mr Behe has not bothered to do any scientific experiments with Intelligent Design, has bothered to find any scientific applications for Intelligent Design, or even bothered to do any scientific research at all for the past decade or so since he wrote “Darwin’s Black Box”?

Is there a link to see all 6 open letters to Behe on one page?

If not that would be a cool thing to do for those of us who have been following the series.

Nothing is more ironic than HeartofGold’s toll comment. Ian provides facts and figures and stays on topic blog after blog. Does HeartofGold provide evidence, stay of topic? No. And Behe keeps saying “looks like”, “seems like”, “not impressive”. I like his claim that since it doesn’t use ATP, it is not a complex machine. ID’s best is constantly making up definitions and moving the goal posts. Way to go, featherless Ian.

Grammar/spelling police:

The main point is that binding sites are binding sites, no matter how impressed you are with them, and you claim is that binding sites pre se are very improbable to evolve.

Rolf Aalberg Wrote:

Bigfoot? I seem to remember hearing recently that someone had confessed to creating the hoax?

Even if so, Medved seems to be a “true believer” and would likely remain committed even if someone confessed the hoax. Besides, some pseudoscience apologist is bound to say that the confession was coerced. Medved’s defense of Bigfoot’s existence is - no kidding - that new species keep getting discovered all the time. OTOH, if the DI is not keen on his belief in Bigfoot, he may become strangely silent about it from now on.

I have links to all the “Open Letter” posts in the HIV section of my big list. Clicking the tag links just after the post might also be useful.

Here is part of Dr Behe’s response:

Yes, one overlooked protein-protein interaction developed, leading to a leaky cell membrane. However, in the past fifty years many, many more potential viral protein-viral protein interactions must have also developed but not been selected because they did the virus little good. That, dear readers, is “restricted choice,” a very large contributor to the edge of evolution.

It sounds to me like he’s talking about natural selection.

It sounds to me like he’s talking about natural selection.

He is discounting its role. What he means here is that given population size x mutation rates versus the search space, HIV could have found all beneficial viral protein-protein interactions by now through random search.

Ah, finally, an answer that addresses anything.

So Behe grudgingly admits what seems to be the core argument of his book (‘protein-protein interaction sites improbable to evolve’) is wrong.

Even more impressive is that he has to admit that an ‘irreducible complex’ viroporin structure is evolved, and easily to boot:

First, although there apparently are five or so copies of Vpu in the viroporin complex, that does not mean that five binding sites developed. Only one new binding site need develop for one area of a protein which binds to a different area of the same protein, to form a homogeneous complex with, say, C5 symmetry. That is all that is required for a circularly symmetric structure to form. [Emphasis added.]

Remember that for Behe it is enough that if the ‘original’ (really, the current) function disappear if the structure loses one part to proclaim ‘irreducible complexity’. “An irreducibly complex system cannot be produced directly (that is, by continuously improving the initial function, which continues to work by the same mechanism) by slight, successive modifications of a precursor system, because any precursor to an irreducibly complex system that is missing a part is by definition nonfunctional.”.

Here it is several molecules (without any functional precursor system) that have combined to have the exactly right rotational symmetry , which is a lot different from having any functional “new binding site”.

Seems to me that Behe in one small letter revokes both his ‘irreducible complexity’ and his ‘improbable complexity’. That’s one small step for a man, one leap for a giant scam. But unfortunately neither will accept the result.

Torbjorn (#135387), one must be careful about the definition of irreducible complexity, since it evolves in response to evasive selection.

Dembski’s definition is not too different: “A system performing a given basic function is irreducibly complex if it includes a set of well-matched, mutually interacting, nonarbitrarily individuated parts such that each part in the set is indispensable to maintaining the system’s basic, and therefore original, function. The set of these indispensable parts is known as the irreducible core of the system.” (No Free Lunch, 285)

However, Behe’s revised definition differs and is more process-oriented: “An irreducibly complex evolutionary pathway is one that contains one or more unselected steps (that is, one or more necessary-but-unselected mutations). The degree of irreducible complexity is the number of unselected steps in the pathway.” (A Response to Critics of Darwin’s Black Box, by Michael Behe, PCID, Volume 1.1, January February March, 2002)

BTW, I thought you’d like to know that you share (part of) your name with Michael Medved. (“Medved” means “bear” in Russian.)

Ummm, the term troll must be that same as the term science. I suppose if you are a creationist, anything that elucidates the natural processes that result in the diversity of all life on earth is blasphemous or troll by mere definition.

Behe has repeatedly simply defined the facts out of existence as not applicable (a pile of journal papers and books on the evolution of the immune system were simply not applicable.) It is a tidy way to clean up his position when confronted with evidence to the contrary and is well accepted by his creationist groupies.

As dull as Behe is on these matters, this is important work. Behe’s lies must not be allowed to stand without criticism regardless of how dull and tedious the man has become.

So let’s see. The first error is 9.24 mDmb (the edge of acceptable), while the second error is at least 61.4 mDmb, for a total error of at least 70 mDmb! That’s not very good science, Mikey.

Has anyone thought to tell Mr. Behe about the evolution of cell adhesion molecules, particularly in the IG Superfamily? Why, that’d be a double-whammy: evolution of protein binding sites AND evolution of the immune system!

In fact, it’d be a quadruple whammy:

Evolution of protein binding sites - Evolution of vertebrate cell adhesion molecules for transient but nonetheless finely tuned strength of adhesion - Evolution of viral adhesion molecules to latch on to a host molecule and out-compete the intended partners

Evolution of the immune system - Vertebrate - Invertebrate

Ho hum…

Dave Cerutti:

Has anyone thought to tell Mr. Behe about the evolution of cell adhesion molecules, particularly in the IG Superfamily? Why, that’d be a double-whammy: evolution of protein binding sites AND evolution of the immune system!…

Umm, how about Stuck on you, biological Velcro and the evolution of adaptive immunity, which is on just that topic.

FWIW, catching up on old threads:

@ Olorin:

Thanks for the information, both on “IC” and on my name!

FWIW, catching up on old threads:

Olorin, thanks for the reply and the info on names.