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Behe’s B Cell Bravado, Part 1

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June 11, 2010 Tags: Genetics
Behe’s B Cell Bravado, Part 1

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

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


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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Headless Unicorn Guy - #17206

June 11th 2010

Every time I hear the words “Intelligent Design”, I have to ask:

Intelligent Design as in “thinking God’s thoughts after Him”, a philosophical foundation of science descended from the “Natural Theology” of the 17th & 18th Centuries?

Or Intelligent Design (nudge nudge wink wink know what I mean know what I mean), the latest coat of camouflage paint for Young Earth Creationism Uber Alles?

Because the term has been hijacked by Ken Ham et al.

Dave - #17210

June 11th 2010

I think that one issue that exists is that we haven’t agreed on the basic ground rules of the discussion.  Some posts talk about the “theory” of evolution vs. intelligent design.  If we agree that evolution is species change through time (either marco or micro), then the discussion is about the theory of natural selection to explain that change or intelligent design.  Also, the discussion has to include all of the overwhelming evidence for deep time.  The earth is ancient, and that has to be part of the discussion.

Argon - #17211

June 11th 2010

Dave, Dr. Applegate writes at the end: “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…”

Enezio E. de Almeida Filho - #17223

June 11th 2010

Has Dr. Applegate read this letter Behe sent to Science but the editor refused to publish?


Bilbo - #17228

June 11th 2010

Hi Kathryn,

I’m glad to see you addressing Behe’s arguments directly.  Let’s hope your argument is better than previous attempts by others.

Rich - #17230

June 11th 2010

Dr. Applegate:

I, like Enezio (17223), would be interested in hearing your reaction to Dr. Behe’s above-cited letter.

unapologetic catholic - #17233

June 11th 2010

“Citing the courtroom theatrics of the lawyers who piled a stack of textbooks and articles in front of me” —Michael Behe.

In other words,  “I hadn’t done my homework.”  In a federal trial, each side is entiteld to demand informaiton from the other side in a process called discovery.When an expert is identified as a witness in a federal trial, that expert must prepare a wrtiten report and is entitled to demand information from the other side.  Behe could have asked prior to his deposition: “Produce all artilces describing the evolution of the immune system”  His expert opinion woudlbe strengthend inf none were produced.  He also knew he would be asked at his deposition before the trial if he had read those articles (He was, and he hadn’t).  If he had, he couldn’t plausibly assert evolution had no answer to immune system development.  He chose at his deposiotn to say he hadn’t read them to avoid uncomfortable questions he couldn’t answer.  To avoid perjury his answer at trial must be the same as his answer at this deposition.

In short he was unprepared, unfamilar with the research, and can’t complain about his lack of preparation as an expert or lack of familiarity with the literature.

Rich - #17236

June 11th 2010

Dear Un. Catholic:

The fact is that none of the articles produced in the courtroom explained how the immune system developed by neo-Darwinian means.  It was a massive bluff by the plaintiff’s lawyers.  Typically, you focus on the courtroom formalities instead of the scientific substance.  The substance is that the greatest neo-Darwinists in the world—Ayala, Coyne, Orr, Gross, etc.—can’t explain the evolution of the immune system in neo-Darwinian terms any more than they can explain whale evolution in neo-Darwinian terms.  I see that a young science Ph.D. (just received her doctorate in the past 8 months), Kathryn Applegate, is now writing a series of articles on Biologos which purport to address the evolution of the immune system.  I have no reason to believe that she will succeed when more experienced scientists like Ayala, Coyne, Orr, etc. have failed.  In any case, I’ve read every one of her articles so far, and so far she’s produced no evidence whatsoever.  However, the moment she departs from generalities and produces the step-by-step genetic recipe for creating an immune system from scratch, I’ll be the first to applaud.

Dave - #17240

June 11th 2010

Dear Rich

There are currently many transitional whale species.  Research by Thewissen and others.


Rich - #17242

June 11th 2010


You haven’t followed the detailed discussion re whale evolution on the other recent threads here.  None of the research alleged by anyone here has given the detailed explanations requested by evolutionary biologist Richard Sternberg,  The problem with most of the people here is that they think a set of putative transitional fossils constitutes a “mechanism”.  It doesn’t.  It just shows a mechanism-less sequence.  A mechanism involves the specification of hundreds of morphological changes, and the thousands of genetic changes needed to achieve those.  If you will promise me that Thewissen gives *the full set of morphological and genetic changes required to move from land lactation to marine lactation* , and *the full set of morphological and genetic changes required to move from nostrils to a blowhole*, etc., I will look up your reference.  But if you promise me this, and I look it up, and it’s not there, and I just see the same stupid set of fossil pictures that Ken Miller hawks on his travelling road show, I’ll never acknowledge any of your references as serious again.  The ball’s in your court.

Larry - #17250

June 12th 2010

I’d advise commentors here not to waste their time with Rich. He portrays himself he as a “skeptic of Neo-darwinism”, but he is in fact just another creationist unwilling to actually look at any evidence you provide him with. Whatever you show him will not be acceptable so don’t waste your time. He is willing to dismiss the overwhelming evidence for common descent that comes from entire genome comparisons with no more than a series of incoherent ramblings about “naturalistic presuppositions” and bogus, meaningless “common design” arguments. Even Behe, whose ideas are the topic of this post, recognises that common descent is beyond scientific dispute. People who can’t acknowledge this are simply not worth talking with.

Larry - #17251

June 12th 2010

Furthermore, his icon Richard Sternberg is no more an “evolutionary biologist” than any of the PhD level biologists who are associated with Biologos. As real scientists who are employed at serious academic institutions have pointed out, his understanding of some pretty elementary biology is, at best, unconvincing.

Creationists, Introns, and Fairly Tales

In rage deaf as the sea, hasty as fire

beaglelady - #17253

June 12th 2010


You are right.  Besides, whale evolution has been discussed on this thread, where RIch trotted out his favorite RIchard Sternberg whale video. And Rich walked away from the thread. 

btw, I would welcome a BioLogos post on whale evolution, perhaps by an expert such as Thewissen .

Gregory - #17258

June 12th 2010


In defence of Rich, two points. 1) He is not a creationist, just like you are (probably) not a universalistic evolutionist. 2) He accepts common descent, in so far as accepting the mutability of species.

To say “common descent is beyond scientific dispute” is itself unscientific.

Would you not admit that “common design” can be in some cases an interesting hypothesis, for example, in that many Ford, Honda, Phillips, Nokia products share aspects of a ‘common design’?

In other words, I would caution you against over-reaching (there are many possible injuries people face when they don’t stretch or warm-up properly & then over-reach themselves) on topics that are still open for discussion by working scientists and scholars.

I’m not sure your level of education. Rich has a PhD in intellectual history. This qualifies him at least to address the evidence presented by scholars in multiple fields. I’m not sure; what makes you so qualified? In the internet age respect has to be earned. Throwing mud at brothers & sisters is probably not the best idea unless a friendly mud-fight is what is sought.

Just 2 cents on ‘wording’ communication.

p.s. do you call yourself ‘neo-Darwinist,’ Larry? If so, why?

Bilbo - #17264

June 12th 2010

Hi Kathryn,

I hope I’m not being too picky, but I think you made it sound as if Behe wasn’t aware of the “hundreds” of papers on the evolution of the immune system.  What Behe actually wrote was,

“There are other papers and books that discuss the evolution of the immune system. [7]  Most of them, however, are at the level of cell biology and thus unconcerned with detailed molecular mechanisms, or else they are concerned simply with comparison of DNA or protein sequences.  Comparing sequences might be a good way to study relatedness, but the results can’t tell us anything about the mechanism that first produced the systems.
“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.” (DBB, p.138)

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.  Hopefully, you’ll show us how that has all changed in the last year.

Bilbo - #17265

June 12th 2010

I guess I should add that his endnote begins, “Examples include….”

Larry - #17267

June 12th 2010


Rich does not accept common descent between humans and other organisms, most specfically other apes. I discussed this with him the other day and pressed him on it; he simply refused to engage with the data that we now have.

Common descent between humans and chimps is beyond scientific dispute in the same way that an ancient earth and heliocentrism are. What people who offer these common design arguments do is just try to take all the evidence for common descent and say “God just made it that way.” It’s as much an argument as saying God made the earth look old or the the earth to just appear to orbit the sun. If creationist biologists have analysed common design as an alternative within their own literature and dismissed it (Todd Wood) then you have to be incredibly intellectually dishonest to continue to use it.

Rich - #17275

June 12th 2010


Thanks for your corrections to Larry and your accurate restatement of my position.  I never knew you cared. 

Rich - #17277

June 12th 2010


You should check your facts before making claims.  Sternberg has a Ph.D. *specifically in evolutionary biology* (unlike any of those who write columns for Biologos, whose Ph.D.s are usually in population genetics or cell biology or the like, if they are in biology at all, as opposed to physics or Biblical studies).  Sternberg also has another Ph.D. in theoretical biology.  Anyhow, his qualifications are irrelevant to his argument, which no one here has dealt with.

Regarding common descent, I don’t recall any exchange with you on that topic.  I never denied common descent to you or anyone here.  At the most I said to certain people that common descent was not demonstrated by the kinds of arguments they were giving.  The point I was making there was about epistemology, not about common descent.  I was trying to expose the fact that most TEs are unaware of the metaphysical presupposition they are making—naturalism—when they say that similarities in morphology or the genome “prove” common descent.  Take away the assumption of naturalism, and the proofs go up in smoke.  But it’s nearly a hopeless task to argue epistemology here, as most of the commenters appear to be completely untrained in philosophy.

Nick Matzke - #17284

June 12th 2010

“I was trying to expose the fact that most TEs are unaware of the metaphysical presupposition they are making—naturalism—when they say that similarities in morphology or the genome “prove” common descent.  Take away the assumption of naturalism, and the proofs go up in smoke.”

You can make exactly the same argument against DNA forensics and paternity testing.  Why don’t you try arguing in court that these things are invalid because they rely on “naturalism”?

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