It's beginning to look like professor Michael Behe won't be responding to Dr. Kathryn Applegate's critique of his claim that the [adaptive] immune system did not evolve by strictly Darwinian means. So although I am not a biologist, I thought I would offer my reactions. First, let me make it clear that I like and respect the people at Biologos, including Dr. Applegate. They have a good spirit about them and I enjoy commenting there. So my rebuttal is offered in a respectful, friendly manner, and I hope it is taken that way.
In chapter 6 ("A Dangerous World") of his book Darwin's Black Box, Behe writes,
…I have looked at three features of the immune system — clonal selection, antibody diversity, and the complement system — and demonstrated that each individually poses massive challenges to a putative step-by-step evolution. But showing that the parts can't be built step by step only tells part of the story, because the parts interact with each other….an animal that has a clonal selection system won't get much benefit out of it if there is no way to generate antibody diversity. A large repertoire of antibodies won't do much good if there is no system to kill invaders. A system to kill invaders won't do much good if there's no way to identify them. At each step we are stopped not only by local system problems, but also by requirements of the integrated system. p.138
Dr. Applegate's offers a critique of Behe in three parts. In
Part 1, she writes,
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 , 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.
I think Applegate has scored a point, but it's not clear how big a point. Given that jawed vertebrates already had an innate immune system that produced a few antibodies, would producing a few more antibodies make enough of a difference to be selectively advantageous? I'll return to this when I discuss her part 3. Meanwhile, the rest of Behe's second thesis, that the clonal selection and complement systems seem to be interdependent remains intact. More importantly, Behe's first thesis, that the clonal selection, antibody diversity, and complement systems are irreducibly complex still hasn't been addressed.
It's in Part 2 that Dr. Applegate offers her hypothesis on how "the antibody diversity generating system—one of Behe’s best examples of irreducible complexity—could have developed gradually."
Applegate agrees with Behe that
…that the antibody production system has three interdependent components, as shown in Figure 1: 1) clusters of gene segments that can be combined in different ways to code for antigen receptors (red and green), 2) start and stop signal sequences between these gene segments, called RSSs (orange and yellow), and 3) machinery to cut and rejoin the DNA at the RSSs (blue).
Applegate then presents the transposon hypothesis, that a section of a bacterial genome including RAGs and RSSs jumped to the genome of a jawed vertebrate. There appears to be strong evidence for the similarity between the RAGs of bacteria and vertebrates, so such a hypothesis sounds initially plausible. Once it jumped,
Suppose the transposon became inserted within a pre-existing, non-rearranging antibody gene (see Figure 3, step 1). (At this point in history, both vertebrates and invertebrates already had perfectly useful antibody-like receptor proteins—they just didn’t rearrange; see Part I.) The inserted transposon sequence would have the effect of splitting the gene into two segments.
When the cell began to read the host gene, the bacterial RAG genes were interpreted instead. The resulting RAG proteins snipped out the transposon and pasted it into a new location in the genome (step 2). Over time the RAG genes became immobilized in the genome, never to jump again. The RAG proteins still recognized the RSSs, though, and continued to excise the DNA between them. Now, instead of cutting out the transposon, they cut out the short stretch of DNA separating the two halves of the original antibody gene (step 3). Thus, the gene segments were reunited and voila! The antibody gene could make protein again.
Suppose that in a future generation, the gene segments duplicated. This would create more gene segments, allowing some limited recombination to take place. Suppose that later still, the whole set of gene segments underwent duplication. Successive rounds of duplication and divergence would lead to the diversity of gene segments we see today (step 4).
First, it's important to realize that Applegate only discusses one of the three systems that Behe has presented: the antibody diversity system. So even if her argument is sound, Behe's arguments that the clonal selection and complement systems are irreducibly complex remain completely intact.
Second, I think one could argue that what we have is one irreducibly complex system — RAGs + RSSs — becoming another — RAGs + RSSs + antibody genes. This is not a direct Darwinian pathway. No two parts of the system create antibody diversity. It takes all three. So we would have an indirect Darwinian pathway. Behe has admitted that such systems can arise. He just thinks the probability for such systems diminishes the more parts that are needed in order to achieve selective advantage. Are there reasons to think that Applegate's hypothesis is improbable? Perhaps. Here are my thoughts:
If the RAG was inserted randomly into a genome of a jawed vertebrate, would it likely have some selective advantage or become fixed in the population by genetic drift? The fact that RAGs do not show up anywhere in the genomes of jawed vertebrates, except in genes for the immune system suggests that neither was the case.
In that case, the hypothesis seems to depend upon the very lucky occurence of the transposon first landing in the genes for the immune system. What are the odds of that happening?
But now given that amazing scenario, what would be the selective advantage? How many different antibodies would need to be produced to confer selective advantage?
In Wikipedia's article on the adaptive immune system, we are told,
A very small proportion (less than 0.01%) of the total lymphocytes are able to bind to a particular antigen, which suggests that only a few cells will respond to each antigen
So for an immune system (such as ours) that produced a trillion different antibodies, it would take one hundred million different antibodies in order to make sure that some antibody binds to a particular antigen.
So there seem to be some reasons to be doubtful that the transposon hypothesis will result in an immediate selective advantage. If there was no immediate selective advantage, what are the odds that the mutation would have survived long enough to achieve such an advantage?
And there may be other problems that I have not even thought of.
In Part 3, Applegate takes Behe to task for supposedly ignoring the vast body of scientific literature that deals with the transposon hypothesis. But it's not at all clear that Behe has ignored it. What seems more likely, as Behe remarked in his letter to Science, is that he recognizes (as apparently Applegate does not) that "speculation is not data, let alone an experimental result. Students are poorly served when they are not taught to distinguish among them."