Behe’s B Cell Bravado, Part 1

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June 11, 2010 Tags: Genetics

Today's entry was written by Kathryn Applegate. You can read more about what we believe here.

Behe’s B Cell Bravado, Part 1

In my last couple of posts, we examined a classic example of evolution in action—the production and selection of antibodies. Evolution in the body is a documented reality, but how did the process for generating antibodies come about in the first place?

Intelligent Design proponent Michael Behe says scientists don’t have the faintest idea. In his 1996 book Darwin’s Black Box, he laments, “Although great strides have been made in understanding how the immune system works, we remain ignorant of how it came to be” (136). As evidence, he cites two brief articles (in his view, the field’s “best efforts”) before dismissing their conclusions out of hand. He continues, “We can look high or we can look low, in books or in journals, but the result is the same. The scientific literature has no answers to the question of the origin of the immune system” (138).

But is science really silent on this topic? So much blood, sweat, tears, and NIH money have been spent on the study of the immune system that a complete lack of answers about its beginnings would, as Behe suggests, mean doom for evolutionary theory. The truth is, according to Web of Science, even by 1996 hundreds of peer-reviewed papers had been published on the subject, each contributing a tiny piece to the overall puzzle.

Quick review: components of the antibody diversity system

Behe argues that three aspects of the immune system—clonal selection, antibody diversity, and the complement system—are irreducibly complex and pose “massive challenges to a putative step-by-step evolution” (138).

Because we have already examined how antibody diversity is generated, we will limit our discussion to the evidence for how this ingenious system might have arisen. Much more could be said about other aspects of the innate and adaptive immune responses.

Recall that the genome contains several clusters of gene segments (red and green in the figure below), each of which has tens to hundreds of members. In B cells, proteins encoded by two Recombination Activating Genes (RAGs; blue) join together one member from each of the clusters by excising the DNA between them. The genome of each B cell is thus irreversibly altered in a unique way, depending on which segments are joined, such that the recombined gene segments code for the antigen-binding site of that B cell’s antibody.

RAG1 and RAG2 can’t bind just anywhere on the DNA; they recognize special sequences called Recombination Signal Sequences (RSSs; orange and yellow). RSSs are found flanking each gene segment, similar to special cues we use in grammar like capitalized words at the start of sentences and punctuation marks at the end. The RAG proteins home in on two randomly-chosen RSSs, bring them physically close to one another, and cleave the double-stranded DNA at both gene-RSS junctions. DNA repair machinery then repairs the break, joining the two gene segments together and the two RSSs together. The closed loop of DNA containing the RSSs gets removed, while the recombined gene is now ready to code for an antibody..

Behe’s mistaken assumptions

Behe argues that a minimally functional antibody diversity system needs three components: the antibody genes themselves, start and stop signals (like RSSs), and machinery to cleave and rejoin the DNA at the signals (like RAG and the DNA repair proteins). He can’t imagine how a multi-component system could have arisen by a gradual process, because each component is dependent on the other two for the whole shebang to work.

From the start, Behe makes the faulty assumption that antibody receptors incapable of recombination would be useless. He writes:

A primitive system with only one or a few antibody molecules would be like the propeller turning at one revolution per day: not sufficient to make a difference... Because the likelihood is so small for the shape of one antibody being complementary to the shape of a threatening bacterium—perhaps one in a hundred thousand or so—an animal that spent energy making five or ten antibody genes would be wasting resources..." (130-1).

What Behe fails to recognize is that many, many receptors in the immune system do their jobs without gene arrangements. These receptors bind to molecules commonly found on the surface of harmful microbes. In fact, some 90% of animal species on the planet don’t even have adaptive immunity, so antibody production by a gene rearrangement mechanism cannot be imperative for life (though humans and other vertebrates are quite dependent on it now). Contrary to Behe’s assumption, the first antibody genes could easily have had useful functions without RSSs and RAGs.

A family of molecules called the Toll-like receptors (TLRs) demonstrates the utility of having an all-purpose microbe detector that does not require millions of randomly-generated variants. TLRs, located on the surface of special immune cells in the blood, recognize bacterial cell walls and virus-specific DNA sequences, causing an all-out attack by the body on the foreign invader. In the process, some of the host tissue gets destroyed, but this collateral damage is a necessary cost to slow down the infection.

This so-called innate immune response—the first line of defense—occurs immediately upon infection, while antibodies take several days to produce. Without innate immunity, the animal might die before antibodies even have a chance to work. The fact that virtually all multi-cellular organisms have TLRs indicates how critical they are to survival.

If innate immunity is so effective that 90% of animals live just fine without adaptive immunity, it’s natural to wonder why some animals do have it. A major advantage it provides is an immunological “memory” of past infections, making it easier to fight off similar pathogens in the future. (Vaccines work on this principle—by exposing the body to inactivated or dead viruses, we give B cells a “heads up” so they can make and store antibodies before the real thing hits.) Antibodies also enable targeted killing of the pathogen, preventing further damage to the host by the non-specific innate immune response.

There’s another way to ask why some animals have an adaptive immune response: rather than seek to explain what added function or advantage it serves, we can ask about the mechanism by which it came to be in the first place. That will be our topic in my next post

References:

Bottaro, Andrea, Inlay, Matt A., and Matzke, Nicholas J. “Immunology in the spotlight at the Dover 'Intelligent Design' trial.” Nature Immunology. 7(5), 433-435. May 2005.

Inlay, Matt. "Evolving Immunity: A Response to Chapter 6 of ". http://www.talkdesign.org/faqs/Evolving_Immunity.html

Travis, John. “On the Origin of the Immune System.” Science. 324(5927), 580-582. May 2009.


Kathryn Applegate is Program Director at The BioLogos Foundation. She received her PhD in computational cell biology at The Scripps Research Institute in La Jolla, Calif. At Scripps, she developed computer vision software tools for analyzing the cell's infrastructure, the cytoskeleton.

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Nick Matzke - #17285

June 12th 2010

“His endnote lists two more papers and a book.  If you read his letter to Science, from last year, it looks like Behe’s assessment from 13 years earlier still held up. “

His letter wasn’t published, because his dismissal of the immune system evolution literature is silly.  The RAG transposon hypothesis was dismissed by Behe in 1996 and has accumulated many passed tests and experimental successes between 1996 and 2005 (and after).  Why oh why, dear Bilbo, did scientists discover a “wild”, free-living transposon that shared sequence similarity with the immune system RAG genes, when the ONLY reason they had to look for such a transposon was the evolutionary hypothesis that RAG was descended from a transposon?
http://ncse.com/creationism/legal/annotated-bibliography-evolutionary-origin-vertebrate-immune

Cheers, Nick


Rich - #17286

June 12th 2010

To Nick M:

I’m not *in principle* against inferring past events based on present evidence.  Thus, if ballistics allows us to trace the pathway of a bullet back into the past, to determine the position of the shooter at the time of firing, I see no problem with that.  If the physics of radioactive dating is sound, I see no problem with extrapolating backward to a 4.5 billion year old earth, or whatever the current date is.  I don’t object in principle to such back-reasoning even in genetics.  So if someone wishes to speculate about past genetics events based on certain genomic similarities and differences, I have no problem with that, as long as such speculations are labelled as speculations and not irrefutable facts of nature.  Behe has no problem in seeing in the genomes of various creatures evidence of historical connections.  My point was that such inferences aren’t rigorous proofs, and can’t rule out direct creationist interpretations of the same data.  I’m not defending direct creationism, merely pointing out that, philosophically speaking, it hasn’t been refuted.  In any case, I’ve repeatedly said that my target was not common descent but the ND explanation for the macroevolutionary process.  It’s simply inadequate.


Argon - #17288

June 12th 2010

I think Behe’s letter demonstrates the problem of ignoring practical, physical limits in reconstructing past evolutionary events. That is, time erases details. The fine-grain detail goes first followed by larger scale details. Originally in his first book, Behe asked for ‘feasible’ explanations to counter his claims. It’s since become clear that what he requires is a description of how each base pair or mutational variation was acquired and how each change affected the evolutionary trajectory. This is simply not possible for any system in the deep past. It’s not a limitation of evolutionary theory, it’s more of a practical limit.

If this is a problem for evolutionary theorists, it’s also a problem for IDists who would like to demonstrate that there was not natural route to feature ‘X’ in the past. Such claims, if we’re going to assume some symmetry to the debate require the IDists to determine exactly what precursors systems the immediate ancestors would have had and show that the next step was not viable. Such reconstruction is likewise hard to do.

The best bet, for a practical scientist is to examine the most recently emerged systems because the necessary, definitive information more likely to be found in them.


Argon - #17290

June 12th 2010

An alternate approach for IDists, and in my opinion a better way overall, would be to develop a positive theory of design. YECism at least made some positive assertions about how the world should appear that could be differentiated from ‘natural’ explanations.


Rich - #17293

June 12th 2010

Argon:

I don’t know where Behe or any other ID proponent has asked for the detailed *actual* evolutionary pathways.  I concede that this would be an unreasonable thing to ask.  However, it is not unreasonable to ask for some detailed *hypothetical* evolutionary pathways, i.e., a series of genetic changes which, in principle, could turn a land-lactation system into a marine-lactation system, or move a double nostril way back on the skull to become a single blowhole, or whatever.  My argument is that almost no one has provided even hypothetical evolutionary pathways for any of the detailed morphological transitions that would be required in whale evolution.  This is not just a practical limit, but a limit of neo-Darwinian theory itself.  If neo-Darwinian theory is sound, it should be able to say:  “If a genetic accident knocked out *this* gene and rotated *this* one, and then fused *this* one with *that* one, the morphological effect would be X, and X would give the creature a stepwise survival advantage en route to marine lactation.”  But where are the accounts of this sort?  When I ask for them, I get repeatedly referred to pictures of fossil whale ancestors.  Why can’t ND evolutionists grasp what’s being asked of them?


Larry - #17296

June 12th 2010

Rich,

Sternberg’s site lists his qualifications as

Ph.D., Systems Science (Theoretical Biology), May 1998

Ph.D., Biology (Molecular Evolution), December 1995



I fail to see how this makes him any more of an “evolutionary biologist” than Darrel Falk, Dennis Venema, or any other people here who hold PhDs in biology. If he were such an expert in this field he would be employed at a more prestigious research institution than the Biologic Institute, an organisation which has a scientific output indistinguishable from zero.
You refused to accept any evidence at all for common descent so there is no reason to expect a response to your endless appeals for “detailed morphological transitions that would be required in whale evolution.” You are demanding infinite, minute technical details from what you refer to as “neo-Darwinism” while apparrently advocating a model with no support from the scientific literature, zero explanatory power, and no mechanism.


Larry - #17297

June 12th 2010

correction:
*apparently* advocating a model…

(not sure where that second ‘r’ came from)


P.S. Does Biologos plan on ever allowing posters to preview comments?


Rich - #17298

June 12th 2010

Larry:

I never refused to accept any evidence for common descent.  I merely distinguished between “evidence” and “proof”.  People here were overstating what had actually been proved, and I was merely being a good philosopher and counselling epistemological caution.  But as neo-Darwinism is ideology (which tolerates no moderation of expression) more than science (which always carefully qualifies what is known), it is not surprising that my caution angered the ideologues here.

Sternberg’s special study within biology is evolutionary theory.  If you’d taken the time to read some of the material on his website other than a list of his degrees, you’d know that.  His discussion of evolutionary theory there is certainly more sophisticated than anything I’ve seen in the celebrated books of Collins and Miller.

You speak of Sternberg’s current employer as not being prestigious enough.  Would you take the time to make a list of the scientists who currently write columns on Biologos, and examine the institutions they work in, and give me your estimation of the degree of scientific prestige of those institutions?


Nick Matzke - #17301

June 12th 2010

It is ridiculous and laughable to indignantly demand the exact (or even possible) molecular steps for the evolution of some morphological trait, ***when we don’t even have the sequenced genome of the organism in question*** (i.e. we don’t have a whale yet), ***let alone*** the sequenced genome of many relevant living relatives (i.e., at least several whales from the major groups, plus relatives like hippos, pigs, and other artiodactyls), ***let alone*** a reconstruction of how genetics (plus other factors) result in whale anatomy *right now*.

You’ve got to walk before you can run, and you’ve got to assess evolution of feature X based on the evidence we have so far.  The fact that no one has done whale genomes and evo-devo yet is not evidence against evolution!.  The evidence we *do* have at the moment—e.g. fossil whales with intermediate blowholes (!!!)—is strong confirmation of evolution.

There are a few cases where we are getting to the really detailed stage—e.g. nematode vulvas, various Drosophila features—but the details are usually too complicated for popular discussion and thus totally ignored by creationists.


Argon - #17306

June 12th 2010

Rich: “I don’t know where Behe or any other ID proponent has asked for the detailed *actual* evolutionary pathways.”

Behe routinely derides the pathways proposed for systems like blood clotting and the evolution of the immune system as not providing the explicit details and physicochemical interactions at each step in a chain of selective steps.

See:
Behe—In Defense of the Irreducibility of the Blood Clotting Cascade: Response to Russell Doolittle, Ken Miller and Keith Robison
http://www.arn.org/docs/behe/mb_indefenseofbloodclottingcascade.htm

Under section c: “What Would an Explanation Look Like?”


Rich - #17307

June 12th 2010

Nick M:

You’ve just made my case.

On another thread I asked a question something like this:

“At our present level of knowledge, we have to confess that the ability of neo-Darwinian processes to turn a land mammal into a whale has not been demonstrated.  True or false?” 

Notice that the question did *not* draw any inference about the truth of intelligent design, and notice that it said *nothing* about the truth or falsity of macroevolution as a process.  It addressed merely the capacity of neo-Darwinian mechanisms to achieve their purported results.

What you are telling me now is what I already surmised, i.e., that we simply do not know enough about how whales and artiodactyls “work” to give anything like a detailed neo-Darwinian account of the transition from one group to the other.  And the only thing I have argued here is the logical consequence of this, i.e., that we should therefore not assert a neo-Darwinian whale origin as a *fact*, rather than a *possible explanation*.  For that I have been lambasted as anti-common-descent, a creationist, anti-scientific, miracle-mongering, etc.  Go figure.


Argon - #17308

June 12th 2010

Of course, this lack of detail creates a problem for Behe’s IC arguments as well because he cannot adequately define what the ancestral conditions were for the system he describes and thus cannot certify his claims.

Now Rich, I will agree with you that detailed steps have not been worked out in the vast majority of biochemical systems. The trajectories of any system involving more than a few interactions are largely indeterminable with our current level of technology. Still, the overall evidence is sufficiently strong to support common descent and the idea that natural mechanisms both do currently and have in the past influenced the development of species and some traits. If ‘natural’ evolutionary mechanisms truly are causally insufficient, we cannot determine this at our current level of knowledge. Some might hope that this leaves some room for alternate mechanisms. Personally, I would find that hedge to be pretty thin gruel or a flimsy foundation upon which to base a metaphysics involving an “interactive” designer, but YMMV.


Mike Gene - #17311

June 13th 2010

Argon:

An alternate approach for IDists, and in my opinion a better way overall, would be to develop a positive theory of design.

Been doing dat for years now. 


Nick (Matzke) - #17312

June 13th 2010

Well, this is dull.  Let’s liven it up.  Rich, do you think the whale fossil record supports the idea that whales evolved gradually, or not?


Rich - #17315

June 13th 2010

Nick M:

“Supports”, yes; “proves”, no.

What the fossil record by itself (sans detailed mechanisms) cannot establish is (a) whether neo-Darwinian mechanisms alone were sufficient, or even nearly sufficient; (b) whether the sum total of all naturalistic explanations offered so far (neo-Darwinian, Margulis, self-organization, etc.) were sufficient, or required tweaking, steering, etc. from some non-natural source.

Regarding (b) I carry no brief for supernatural causes as such.  I support “intelligent design”, but my understanding of “design” includes the possibility of wholly natural, self-organizing evolution.  However, nothing I’ve seen in any of the arguments for naturalistic evolution convinces me that evolutionary biology is anywhere near being able to rule out supernatural intervention, either for the origin of life or for subsequent developments.

My approach is not to dogmatize.  It’s as wrong to say, “We *know* that Darwinian means *couldn’t have* made whales (as some ID people do) as to say, “We know that Darwinian means *could have* made whales (as the atheists & TEs do).  The proper attitude for a scientist to take is Sternberg’s:  “What is the evidence that Darwinian means could have made whales?”


Rich - #17316

June 13th 2010

Nick M (continued):

Sternberg concludes, at least tentatively, that Darwinian means appear incapable of explaining the evolution of whales.  He bases his conclusion on certain calculations which are of course open to dispute.  But generally speaking, he’s going about things the right way.  He doesn’t start out by excluding wholly naturalistic explanation, or even neo-Darwinian explanation.  Rather, he asks:  “What would neo-Darwinian processes have to be able to do, and how fast would they have to be able to do it, in order to produce the result they are alleged to have produced?”  He bases his reasoning, his calculations, etc., on that question, not on the Bible, on the assumption of supernatural causes, on the desire to combat atheism, or anything of the sort.  Thus, he keeps the debate on the scientific plane.  One can disagree with him, but one can’t accuse him of smuggling creationism into his assumptions or calculations.  If all debates over evolution were carried on in this manner, things would be much more civilized.  But people from Biologos put on the war paint the moment anyone questions the sufficiency of NDE, even for genuine empirical or theoretical reasons.  That’s not science, that’s ideology.


Larry - #17320

June 13th 2010

Rich,

Demanding ‘proof’ is a big waste of everyone’s time. Science doesn’t really prove anything. It certainly hasn’t ‘proven’ that the earth is old or that the earth orbits the sun. You are asking for impossibly high levels of certainty and detail. What exactly could ever be ‘proof’ that “whales evolved gradually?” I can think of nothing other than possibly discovering an ancient video camera that extra-terrestrials brought here and left that actually recorded the entire event.

Regarding Sternberg, his CV contains little (or nothing) of note in the last 6-7 years. Most (if not all) the biologists I have seen on here are employed at Christian or secular universities and other institutions. I have tried to contact Mr Sternberg via the e-mail address on his website in order to try to understand what exactly his position is, but I have yet to receive a response.


Larry - #17321

June 13th 2010

Rich,

You claim not to deny common descent. Do you accept for example that different fruit fly species, such as Drosophila melanogaster and Drosophila pseudoobscura, are related by common descent? If you do, how would you deny that humans and chimpanzees are also related when their genomes are much more similar than what everyone appears to accept as just divergent fruit fly species?


Nick (Matzke) - #17325

June 13th 2010

What Larry said—plus, how in the world could science *ever* get enough evidence to exclude the supernatural as a cause?  Even in a controlled lab experiment, where you are watching the proteins react in solution (or whatever), you cannot formally exclude the abstract possibility that some supernatural entity interfered.

You should tell us what the criteria are for scientifically determining when, and when not, some supernatural intervention has occurred, if you want science to take the supernatural seriously.  Thus far no one I’ve seen has been able to do this…and this is a big part of the reason scientists don’t write “or maybe there was supernatural intervention” at the end of each of their papers hypothesizing and testing natural cause explanations for things.


Rich - #17337

June 13th 2010

Nick M:

I find it odd that atheists and TEs can never accept a limited claim for what it is, but always insist on reading more into it than is there.

I didn’t propose that supernatural intervention had occurred, or suggest criteria by which we might determine that.  I made the very limited claim, backed by your own analysis of our current lack of knowledge, that, since we have only the vaguest idea how the morphological changes involved may have occurred, we cannot logically rule out a role for the supernatural.  And as I said, I wasn’t carrying any brief for the supernatural, just making a logical point, as a sort of brake on Darwinian overconfidence. 

As a matter of practice, it is actually not that hard for a science to achieve a state where we think that it is unlikely that supernatural intervention would ever be needed to explain an event.  Many fields of chemistry and physics are already there.  Cosmology and evolutionary biology, however, are not.  This does not bother me, as I see no a priori reason why origins should always be explicable scientifically.  They might be in some cases and not in others.  I can live comfortably with either result, but atheists and TEs can’t.  Why is that?


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