Immunology in the spotlight at the Dover 'Intelligent Design' trial

Immunology had an unexpected and decisive part in challenging the claims of 'Intelligent Design' proponents at the US trial on the teaching of evolution in public schools in Dover, Pennsylvania.

The latest skirmish in the ongoing controversy about the teaching of evolution in US schools ended decisively on 20 December 2005, when the introduction of 'Intelligent Design' (ID) in a public school biology class was struck down by US Federal Judge John E. Jones as an unconstitutional establishment of religion. The case, 'Kitzmiller et al. v. Dover Area School District', was brought by 11 parents from Dover, Pennsylvania, represented pro bono by the Philadelphia law firm Pepper-Hamilton, together with the American Civil Liberties Union and Americans United for the Separation of Church and State and assisted with scientific support by the National Center for Science Education, the Oakland, California–based nonprofit organization devoted to combating creationism. The parents challenged the school district's requirement that administrators read to ninth graders a disclaimer raising doubts about evolution, suggesting ID as a better alternative explanation for life's diversity and referring students to the ID supplemental textbook Of Pandas and People, 60 copies of which had been donated to the school library.

Although the magnitude of the win for science education was a surprise to some, the actual outcome of the trial was in very little doubt, for many reasons. Board members had made clear, through public declarations at board meetings and to the media, their intention to have some form of religious creationism taught in biology classes alongside evolution, which they considered akin to atheism. US Supreme Court rulings have established and repeatedly reaffirmed that governmental policies with the purpose or effect of establishing religion are inadmissible because they violate the First Amendment of the US Constitution. It also did not help their cause that Judge Jones found that some of the board members "either testified inconsistently, or lied outright under oath" about some statements and about the source of the donated Of Pandas and People books, the money for which was raised by one of the board members at his own church.

The most important and far-reaching aspect of the decision, however, was that the judge went beyond the narrow issue of the school board's actions and ruled broadly on the nature of ID and its scientific claims. After a 6-week trial that included extensive expert testimony from both sides on science, philosophy and the history of creationism, Jones ruled that ID is not science but "creationism re-labeled." Coming from the George W. Bush–appointed, lifelong Republican and church-going Judge Jones, the ruling was all the more stinging for ID advocates and made the predictable charge of 'judicial activism' harder to sustain. The ruling is likely to have a substantial effect on many other ongoing cases (and possibly future court decisions) regarding ID and evolution in science curricula from Georgia to Kansas to Ohio.

More fundamentally, the decision represents a considerable setback for ID advocates, who claim that some examples of biological complexity could only have originated by intelligent mechanisms, and for their movement's now almost-20-year-old effort to gain a foothold in school curricula and project an aura of scientific respectability. The ruling is also of great interest to scientists, not only because of its importance for science education but also because much of the trial's extensive expert testimony, both for and opposed to ID, focused directly on weighty scientific topics. Judge Jones analyzed and dismissed the core 'scientific' assertions of the ID movement—immunology had an unexpectedly large and relevant part in his reaching those conclusions.

Although the field of evolutionary and comparative immunology has a long and rich history, dating back at least to 1891 (ref. 1), and remains an exciting and rapidly progressing area of research, its direct involvement in the controversies about evolution in schools can be attributed mainly to Michael Behe, professor of biochemistry at Lehigh University (Bethlehem, Pennsylvania), leading ID advocate and star expert witness for the defense at this trial. In his 1996 book Darwin's Black Box, a commonly cited example of ID-based 'science', Behe devotes an entire chapter to the immune system, pointing to several of its features as being particularly refractory to evolutionary explanations. Behe's antievolutionary argument relies on a characteristic he calls "irreducible complexity": the requirement for the presence of multiple components of certain complex systems (such as a multiprotein complex or biochemical cascade) for the system to accomplish its function. As such irreducibly complex systems by definition work only when all components are present; Behe claims they cannot arise by the sequential addition and modification of individual elements from simpler pre-existing systems, thus defying 'darwinian' evolutionary explanations.

By analogy with human 'machines', ID advocates argue that irreducibly complex systems are most likely the product of an intelligent, teleological activity. Several scientists, including ourselves, have criticized Behe's argument, pointing out how irreducibly complex systems can arise through known evolutionary mechanisms, such as exaptation, 'scaffolding' and so on. Nevertheless, with few exceptions, the topic has been explicitly addressed mostly in book reviews, philosophy journals and on the internet, rather than in peer-reviewed scientific publications, which may have allowed it to mostly escape the critical scrutiny of scientists while gaining considerable popularity with the lay public and, in particular, with creationists.

In chapter 6 of Darwin's Black Box, Behe claims that the vertebrate adaptive immune system fulfills the definition of irreducible complexity and hence cannot have evolved. Some of his arguments will seem rather naive and misguided to immunologists. For example, Behe argues that working antibodies must exist in both soluble and membrane form, which therefore must have appeared simultaneously because one form would be useless without the other. He also claims that antibodies are completely functionless without secondary effector mechanisms (such as the complement system), which in turn require antibodies for activation. These putative 'chicken-and-egg' conundrums are easily belied by existing evidence (http://www.talkdesign.org/faqs/Evolving_Immunity.html).

Behe also spends considerable time on what he alleges is a hopelessly intractable problem in evolutionary immunology: the origin of the mechanism of somatic recombination of antigen receptor genes. He argues that because variable-diversity-joining recombination is dependent on the coexistence of proteins encoded by recombination-activating genes (RAG proteins), recombination signal sequences and antigen receptor gene segments, it is ultimately too complex to have arisen by naturalistic, undirected evolutionary means because the three components could not have come together in a 'fell swoop' and would have been useless individually. In fact, Behe confidently declares that the complexity of the immune system "dooms all Darwinian explanations to frustration". About the scientific literature, Behe claims it has "no answers" as to how the adaptive immune system may have originated2.

In particular, Behe criticizes a 1994 Proceedings of the National Academy of Science paper advancing the hypothesis that the RAG system evolved by lateral transfer of a prokaryotic transposon, an idea initially suggested in a 1979 paper and expanded in 1992. Behe ridicules the idea as a "jump in the box of Calvin and Hobbes," with reference to the comic strip in which a child and his stuffed tiger imaginary friend use a large cardboard box for fantasy trips and amazing physical transformations.

The timing for the criticism could not have been worse, as soon after publication of Darwin's Black Box, solid evidence for the transposon hypothesis began accumulating with the demonstration of similarities between the variable-diversity-joining recombination and transposition mechanisms and also between shark RAG1 and certain bacterial integrases. Since then, a steady stream of findings has continued to add more substance to the model, as RAG proteins have been shown to be capable of catalyzing transposition reactions, first in vitro and then in vivo, and to have even closer structural and mechanistic similarities with specific transposases. Finally, in 2005, the original key prediction of the transposon hypothesis was fulfilled with the identification of a large invertebrate transposon family bearing both recombination signal sequence–like integration sequences and a RAG1 homolog. When faced with that evidence during an exchange on the internet, Behe simply 'shrugged' and said that evidence was not sufficient, asking instead for an infinitely detailed, step-by-step mutation account (including population sizes, relevant selective pressures and so on) for the events leading to the appearance of the adaptive immune system (http://www.pandasthumb.org/archives/2005/06/behes_meaningle.html).

That background set the stage for the crucial face-off at the trial. Kenneth Miller of Brown University, a cell biologist and textbook author who has written extensively on evolution and creationism, was the lead witness for the plaintiffs. Over the course of his testimony, Miller did his best to explain to the nonscientist audience the mechanisms of antibody gene rearrangement and the evidence corroborating the transposon hypothesis. Then, 10 days later, Behe took the stand. During cross-examination by the plaintiffs' lead counsel Eric Rothschild, Behe reiterated his claim about the scientific literature on the evolution of the immune system, testifying that "the scientific literature has no detailed testable answers on how the immune system could have arisen by random mutation and natural selection." Rothschild then presented Behe with a thick file of publications on immune system evolution, dating from 1971 to 2006, plus several books and textbook chapters. Asked for his response, Behe admitted he had not read many of the publications presented (a small fraction of all the literature on evolutionary immunology of the past 35 years), but summarily rejected them as unsatisfactory and dismissed the idea of doing research on the topic as "unfruitful."

This exchange clearly made an impression on Judge Jones, who specifically described it in his opinion:

We find that such evidence demonstrates that the ID argument is dependent upon setting a scientifically unreasonable burden of proof for the theory of evolution.

Other important scientific points stood out during trial relating to other purported irreducibly complex systems such as the flagellum and the clotting cascade, the nature of science itself and the lack of experimental tests and supporting peer-reviewed publications for ID. But the stark contrast between the lively and productive field of evolutionary immunology and the stubborn refusal by ID advocates such as Behe to even consider the evidence was undoubtedly crucial in convincing the judge that the ID movement has little to do with science. As Rothschild remarked in his closing argument,

Thankfully, there are scientists who do search for answers to the question of the origin of the immune system. It's the immune system. It's our defense against debilitating and fatal diseases. The scientists who wrote those books and articles toil in obscurity, without book royalties or speaking engagements. Their efforts help us combat and cure serious medical conditions. By contrast, Professor Behe and the entire intelligent design movement are doing nothing to advance scientific or medical knowledge and are telling future generations of scientists, don't bother.

Evolutionary immunologists should be pleasantly surprised by and proud of the effect their scientific accomplishments have had in this landmark judicial case. This commentary is meant to acknowledge their contribution on behalf of the Dover families, their lawyers and all the activists for rigorous science education who have participated in these proceedings. Most importantly, however, the Dover case shows that no scientific field is too remote from the hotly debated topics of the day and that no community is too small and removed from the great urban and scientific centers to be relevant. Immunologists must engage their communities and society at large in events related to public perceptions about science. Now more than ever, the participation of scientists is essential for the crafting of rational policies on scientific research and science education.

Am I to assume you are not a native speaker?

You can assume what you like.

Knock off the side issue of typos and your irrational dislike of non-native speakers or people you wrongly assume to be something they are not

Why do you think I dislike you? I was just trying to help you.

Everyone makes typos apparently including even you (gasp), I make more than most.

You make more than just typos.

Isn't this fun?

You made the claim that genetics had driven evolution, and not vice versa. Stultis pointed out in 44 that this was indubitably not true about population genetics, which was developed by evolutionary biologists fro evolutionary biology. In 46 you simply reiterated your claim without addressing the point about population genetics, except to make an idiotic and profoundly ignorant cheap shot about population genetics 'to the extent there is any merit to it'.
Stultis replied that the founders of pop. gen. (Fisher, Haldane and Wright) were evolutionary biologists. You never replied to that -- I don't blame you, the only rational reply would be to admit you were wrong, and you seem incapable of that -- instead going off on a tangent about McClintock and transposons.

You made the claim that genetics had driven evolution

Driven evolutionary understanding, yes.

My point is made by the contributions of those three (eugenicist propaganda being the main contribution of one of them) compared to those of Hunt and McClintock.

Transposable elements and their relation to evolution is a major example. Genomic comparison that is possible today focus largely on repeat element distribution because it turns out that this type of DNA discovered by McClintock doing structural chromosomal work in tandem with genetics is a major portion of the genome. These elements are now known to have been a major driving force in evolution -- and in my opinion the major driving force.

King Prout actually made the same point as I as well.

...instead going off on a tangent about McClintock and transposons.

It was not a tangent but came directly in response to Stultis citing "fragile breakage" and referencing a paper looking at genomic rearrangements.

Also, if you were aware of the latest understanding of genomic evolution made possible by the various genome projects and bioinformatic analyses of the data you'd know the centrality of transposable elements to evolution.

It was not a tangent but came directly in response to Stultis citing "fragile breakage" and referencing a paper looking at genomic rearrangements.

Which, however, I retracted as coming solely/directly out of evolutionary research when you demonstrated that it had been recognized previously wrt cancer research, etc. (Although it does still appear to me that the recent recognition of fragile breakage as a much more general phenomena and a "normal" process, i.e. not just associated with disease processes, stemmed from the evolutionary research.)

I note that you have not retracted your claim about evolutionary biology never internally generating important insights in spite of the example of population genetics, which still stands, and was a central element in a broad and revolutionary advancement of theory and research (i.e. "neodarwinism").

Genomic comparison that is possible today focus largely on repeat element distribution because it turns out that this type of DNA discovered by McClintock doing structural chromosomal work in tandem with genetics is a major portion of the genome.

More advice: 'genomic comparison' is singular and the subject of the sentence; 'focus' must agree in number with it. Hence, this should read 'Genomic comparison that is possible today focuses largely on repeat element distribution.'

It's difficult for those whose native language contains no such subject verb agreement, but perseverance is important. You also need some commas in there.

Your main point is nonsense in any case. Most molecular evolution analysis is done using genes, ribosomal RNA, and mitochondrial DNA. Transposable elements are of limited use for large scale phylogeny, precisely because they're so mobile. As an example, here's the table of contents for the current issue of MBE. Of fourteen papers, I count two that discuss transposable elements in any respect; almost all of them, however, discuss gene phylogeny.

Your main point is nonsense in any case. Most molecular evolution analysis is done using genes, ribosomal RNA, and mitochondrial DNA.

Was done. Genes, rRNA and mitochondrial DNA have been used prior to full genome sequences because they were available.

Transposable elements are of limited use for large scale phylogeny, precisely because they're so mobile.

Their mobility is why they were the driving force for the chromosomal rearrangements associated with evolution.

You simply do not follow, nor understand, genomic evolution -- which is one and the same with evolution at its most basic level. This has ben my observation on these threads that the people most vociferous for evolution don't even know the research. At least you've moved in to the 1980's. Most here are still in the 19th century.

And, focusing on typos or grammar issues is a sign of not having anything else to harp on.

The way you do it it is also a personal attack, but hey that's you.

Now try and actually focus on something concrete. What of the following is nonsense:

Was done. Genes, rRNA and mitochondrial DNA have been used prior to full genome sequences because they were available.

I posted the table of contents for the last issue of MBE. Oh, I'm sorry, I should have spelled it out; Molecular Biology and Evolution. It's a journal. A journal is a place scientists publish their work. This month's TOC is a fair reflection where the field was 6 months ago. Only a tiny minority of papers was concerned with transposons.

h. At least you've moved in to the 1980's. Most here are still in the 19th century.

I posted an analysis of a 2006 table of contents. Ignoring unfortunate facts doesn't make them go away; it makes you mendacious by omission. When someone posts a rebuttal of some point you make, as Stultis did, as I have, you just ignore it. But hey, that's you.

And, focusing on typos or grammar issues is a sign of not having anything else to harp on.

I'm disappointed you don't appreciate my well-intentioned attempts to help you.

The way you do it it is also a personal attack, but hey that's you.

You have no basis for complaint. I asked you to stop posting personal insults. You refused. Now you're trying to represent my constructive suggestions on how you might improve your own posts as attacks.

Now try and actually focus on something concrete. What of the following is nonsense: Genomic comparison that is possible today focus largely on repeat element distribution because it turns out that this type of DNA discovered by McClintock doing structural chromosomal work in tandem with genetics is a major portion of the genome.

It's false. Apparently your reading is as weak as your writing. Published genomic comparison still focuses mainly on genes and other coding elements.

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