COMMENTARY

Immunology in the spotlight at the Dover ‘Intelligent Design’ trial

Andrea Bottaro, Matt A Inlay & Nicholas J Matzke

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.

he latest skirmish in the ongoing contro- Although the magnitude of the win for sci- http://www.nature.com/natureimmunology Tversy about the teaching of evolution in ence education was a surprise to some, the US schools ended decisively on 20 December actual outcome of the trial was in very little 2005, when the introduction of ‘Intelligent doubt, for many reasons. Board members had Design’ (ID) in a public school biology class made clear, through public declarations at was struck down by US Federal Judge John board meetings and to the media, their inten- E. Jones as an unconstitutional establish- tion to have some form of religious creationism ment of religion. The case, ‘Kitzmiller et al. v. taught in biology classes alongside evolution, Dover Area School District’, was brought by which they considered akin to atheism. US 11 parents from Dover, Pennsylvania, repre- Supreme Court rulings have established and sented pro bono by the Philadelphia law firm repeatedly reaffirmed that governmental poli- Pepper-Hamilton, together with the American cies with the purpose or effect of establishing Civil Liberties Union and Americans United religion are inadmissible because they violate

Nature Publishing Group Group 200 6 Nature Publishing for the Separation of Church and State the First Amendment of the US Constitution.

© and assisted with scientific support by the It also did not help their cause that Judge Jones National Center for Science Education, the found that some of the board members “either Oakland, California–based nonprofit orga- testified inconsistently, or lied outright under nization devoted to combating creationism. oath” about some statements and about the The parents challenged the school district’s source of the donated Of Pandas and People Evolutionary immunology literature presented requirement that administrators read to ninth books, the money for which was raised by one at the Dover trial. “We can look high or we can graders a disclaimer raising doubts about evo- of the board members at his own church. look low, in books or in journals, but the result lution, suggesting ID as a better alternative The most important and far-reaching aspect is the same. The scientific literature has no explanation for life’s diversity and referring of the decision, however, was that the judge went answers to the question of the origin of the 2 students to the ID supplemental textbook Of beyond the narrow issue of the school board’s immune system.” Pandas and People, 60 copies of which had actions and ruled broadly on the nature of ID been donated to the school library. and its scientific claims. After a 6-week trial that More fundamentally, the decision represents included extensive expert testimony from both a considerable setback for ID advocates, who sides on science, philosophy and the history of claim that some examples of biological com- Andrea Bottaro is with the Department of creationism, Jones ruled that ID is not science plexity could only have originated by intelligent Medicine, Department of Microbiology and but “creationism re-labeled.” Coming from the mechanisms, and for their movement’s now Immunology and the James P. Wilmot Cancer George W. Bush–appointed, lifelong Republican almost-20-year-old effort to gain a foothold in Center, University of Rochester School of Medicine and church-going Judge Jones, the ruling was all school curricula and project an aura of scientific and Dentistry, Rochester, New York 14642, USA. the more stinging for ID advocates and made respectability. The ruling is also of great interest Matt A. Inlay is in the Department of Pathology, the predictable charge of ‘judicial activism’ to scientists, not only because of its importance Beckman Center, Stanford University, Stanford, harder to sustain. The ruling is likely to have a for science education but also because much of California 94305, USA. Nicholas J. Matzke is substantial effect on many other ongoing cases the trial’s extensive expert testimony, both for with the National Center for Science Education, (and possibly future court decisions) regard- and opposed to ID, focused directly on weighty Oakland, California 94609, USA. ing ID and evolution in science curricula from scientific topics. Judge Jones analyzed and dis- e-mail: [email protected] Georgia to Kansas to Ohio. missed the core ‘scientific’ assertions of the ID

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movement—immunology had an unexpectedly without secondary effector mechanisms (such on the internet, Behe simply ‘shrugged’ and large and relevant part in his reaching those as the complement system), which in turn said that evidence was not sufficient, asking conclusions. require antibodies for activation. These puta- instead for an infinitely detailed, step-by- Although the field of evolutionary and tive ‘chicken-and-egg’ conundrums are easily step mutation account (including population comparative immunology has a long and belied by existing evidence (http://www.talk- sizes, relevant selective pressures and so on) rich history, dating back at least to 1891 (ref. design.org/faqs/Evolving_Immunity.html). for the events leading to the appearance of the 1), and remains an exciting and rapidly pro- Behe also spends considerable time on what adaptive immune system (http://www.pand- gressing area of research, its direct involve- he alleges is a hopelessly intractable problem asthumb.org/archives/2005/06/behes_mean- ment in the controversies about evolution in in evolutionary immunology: the origin of ingle.html). schools can be attributed mainly to Michael the mechanism of somatic recombination That background set the stage for the cru- Behe, professor of biochemistry at Lehigh of antigen receptor genes. He argues that cial face-off at the trial. Kenneth Miller of University (Bethlehem, Pennsylvania), lead- because variable-diversity-joining recom- Brown University, a cell biologist and text- ing ID advocate and star expert witness for the bination is dependent on the coexistence of book author who has written extensively defense at this trial. In his 1996 book Darwin’s proteins encoded by recombination-activat- on evolution and creationism, was the lead Black Box2, a commonly cited example of ID- ing genes (RAG proteins), recombination witness for the plaintiffs. Over the course of based ‘science’, Behe devotes an entire chapter signal sequences and antigen receptor gene his testimony, Miller did his best to explain to the immune system, pointing to several of segments, it is ultimately too complex to have to the nonscientist audience the mechanisms its features as being particularly refractory to arisen by naturalistic, undirected evolutionary of antibody gene rearrangement and the evolutionary explanations. Behe’s antievolu- means because the three components could evidence corroborating the transposon tionary argument relies on a characteristic he not have come together in a ‘fell swoop’ and hypothesis. Then, 10 days later, Behe took calls “irreducible complexity”: the require- would have been useless individually. In fact, the stand. During cross-examination by the ment for the presence of multiple compo- Behe confidently declares that the complexity plaintiffs’ lead counsel Eric Rothschild, Behe nents of certain complex systems (such as a of the immune system “dooms all Darwinian reiterated his claim about the scientific litera- http://www.nature.com/natureimmunology multiprotein complex or biochemical cas- explanations to frustration”2. About the scien- ture on the evolution of the immune system, cade) for the system to accomplish its func- tific literature, Behe claims it has “no answers” testifying that “the scientific literature has no tion. As such irreducibly complex systems by as to how the adaptive immune system may detailed testable answers on how the immune definition work only when all components have originated2. system could have arisen by random mutation are present; Behe claims they cannot arise by In particular, Behe criticizes a 1994 and natural selection.” Rothschild then pre- the sequential addition and modification of Proceedings of the National Academy of Science sented Behe with a thick file of publications individual elements from simpler pre-existing paper advancing the hypothesis that the RAG on immune system evolution, dating from systems, thus defying ‘darwinian’ evolutionary system evolved by lateral transfer of a pro- 1971 to 2006, plus several books and text- explanations. karyotic transposon13, an idea initially sug- book chapters. Asked for his response, Behe By analogy with human ‘machines’, ID advo- gested in a 1979 paper14 and expanded in 1992 admitted he had not read many of the publi- cates argue that irreducibly complex systems (ref. 15). Behe ridicules the idea as a “jump cations presented (a small fraction of all the are most likely the product of an intelligent, in the box of Calvin and Hobbes,”2 with literature on evolutionary immunology of the

Nature Publishing Group Group 200 6 Nature Publishing teleological activity. Several scientists, includ- reference to the comic strip in which a child past 35 years), but summarily rejected them as

© ing ourselves, have criticized Behe’s argu- and his stuffed tiger imaginary friend use unsatisfactory and dismissed the idea of doing ment, pointing out how irreducibly complex a large cardboard box for fantasy trips and research on the topic as “unfruitful.” systems can arise through known amazing physical transformations. This exchange clearly made an impression evolutionary mechanisms, such as exaptation, The timing for the criticism could not on Judge Jones, who specifically described it ‘scaffolding’ and so on. Nevertheless, with have been worse, as soon after publication in his opinion: few exceptions3–6, the topic has been explic- of Darwin’s Black Box, solid evidence for the itly addressed mostly in book reviews7–10, transposon hypothesis began accumulat- In fact, on cross-examination, Professor Behe philosophy journals11,12 and on the internet, ing with the demonstration of similarities was questioned concerning his 1996 claim that rather than in peer-reviewed scientific publi- between the variable-diversity-joining recom- science would never find an evolutionary expla- cations, which may have allowed it to mostly bination and transposition mechanisms16 and nation for the immune system. He was presented escape the critical scrutiny of scientists while also between shark RAG1 and certain bacte- with fifty-eight peer-reviewed publications, nine gaining considerable popularity with the lay rial integrases17. Since then, a steady stream of books, and several immunology textbook chap- public and, in particular, with creationists. findings has continued to add more substance ters about the evolution of the immune system; In chapter 6 of Darwin’s Black Box, Behe to the model, as RAG proteins have been however, he simply insisted that this was still not claims that the vertebrate adaptive immune shown to be capable of catalyzing transposi- sufficient evidence of evolution, and that it was system fulfills the definition of irreducible tion reactions, first in vitro18,19 and then in not ‘good enough.’ complexity and hence cannot have evolved. vivo20–22, and to have even closer structural We find that such evidence demonstrates that Some of his arguments will seem rather and mechanistic similarities with specific the ID argument is dependent upon setting a sci- naive and misguided to immunologists. For transposases23. Finally, in 2005, the original entifically unreasonable burden of proof for the example, Behe argues that working antibod- key prediction of the transposon hypothesis theory of evolution. ies must exist in both soluble and membrane was fulfilled with the identification of a large form, which therefore must have appeared invertebrate transposon family bearing both Other important scientific points stood out simultaneously because one form would recombination signal sequence–like integra- during trial relating to other purported irre- be useless without the other. He also claims tion sequences and a RAG1 homolog24. When ducibly complex systems such as the flagellum that antibodies are completely functionless faced with that evidence during an exchange and the clotting cascade, the nature of science

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itself and the lack of experimental tests and their lawyers and all the activists for rigorous 3. Thornhill, R.H. & Ussery, D.W. J. Theor. Biol. 203, supporting peer-reviewed publications for science education who have participated in 111–116 (2000). 4. Aird, W.C. J. Thromb. Haemost. 1, 227–230 ID. But the stark contrast between the lively these proceedings. Most importantly, how- (2003). and productive field of evolutionary ever, the Dover case shows that no scientific 5. Pennock, R.T. Annu. Rev. Genomics Hum. Genet. 4, 143–163 (2003). immunology and the stubborn refusal by ID field is too remote from the hotly debated 6. Keller, E.F. Ann. NY Acad. Sci. 981, 189–201 advocates such as Behe to even consider the topics of the day and that no community (2002). evidence was undoubtedly crucial in convinc- is too small and removed from the great 7. Orr, H.A. Boston Review XXI, 28–31 (1996). 8. Coyne, J.A. Nature 383, 227–228 (1996). ing the judge that the ID movement has little urban and scientific centers to be relevant. 9. Cavalier-Smith, T. Trends Ecol. Evol. 12, 162–163 to do with science. As Rothschild remarked in Immunologists must engage their commu- (1997). his closing argument, nities and society at large in events related 10. Pomiankowski, A. New Scientist 151, 44–45 (1996). to public perceptions about science. Now 11. Shanks, N. & Joplin, K.H. Philos. Sci. 66, 268–282 Thankfully, there are scientists who do search more than ever, the participation of scien- (1999). 12. Weber, B. Biol. Philos. 14, 593–605 (1999). for answers to the question of the origin of the tists is essential for the crafting of rational 13. Bartl, S., Baltimore, D. & Weissman, I. Proc. Natl. immune system. It’s the immune system. It’s policies on scientific research and science Acad. Sci. USA 91, 10769–10770 (1994). our defense against debilitating and fatal dis- education. 14. Sakano, H., Huppi, K., Heinrich, G. & Tonegawa, S. Nature 280, 288–294 (1979). eases. The scientists who wrote those books and 15. Dreyfus, D.H. Mol. Immunol. 29, 807–810 ACKNOWLEDGMENTS articles toil in obscurity, without book royalties (1992). We thank the authors of the articles and books on the or speaking engagements. Their efforts help us 16. Van Gent, D.C., Mizuuchi, K. & Gellert, M. Science evolution of the immune system presented during the 271, 1592–1594 (1996). combat and cure serious medical conditions. By trial (http://www2.ncseweb.org/kvd/exhibits/immune/ 17. Bernstein, R.M., Schulter, S.F., Bernstein, H. & contrast, Professor Behe and the entire intelligent index.html) and contributors to Panda’s Thumb Marchalonis, J.J. Proc. Natl. Acad. Sci. USA 93, 9454–9459 (1996). design movement are doing nothing to advance (http://www.pandasthumb.org) and Talkorigins Archive (http://www.talkorigins.org) for suggestions 18. Agrawal, A., Eastman, Q.M. & Schatz, D.G. Nature scientific or medical knowledge and are telling during the trial and for comments on this manuscript. 394, 744–751 (1998). future generations of scientists, don’t bother. 19. Hiom, K., Melek, M. & Gellert, M. Cell 94, 463–470 The decision, trial transcripts and all court documents (1998). http://www.nature.com/natureimmunology are available through the National Center for Science 20. Vaandrager, J.W., Schuuring, E., Philippo, K. & Evolutionary immunologists should be Education (http://www2.ncseweb.org/wp/). Kluin, P.M. Blood 96, 1947–1952 (2000). pleasantly surprised by and proud of the 21. Clatworthy, A.E., Valencia, M.A., Haber, J.E. & 1. Metchnikoff, E. Lectures on the Comparative Pathology Oettinger, M.A. Mol. Cell 12, 489–499 (2003). effect their scientific accomplishments have of Inflammation; Delivered at the Pasteur Institute in 22. Messier, T.L., O’Neill, J.P., Hou, S.M., Nicklas, J.A. had in this landmark judicial case. This com- 1891 (Dover, New York, 1968). & Finette, B.A. EMBO J. 22, 1381–1388 (2003). 2. Behe, M.J. Darwin’s Black Box: the Biochemical 23. Zhou, L. et al. Nature 432, 995–1001 (2004). mentary is meant to acknowledge their con- Challenge to Evolution (Free Press, New York, 24. Kapitonov, V.V. & Jurka, J. PLoS Biol. 3, e181 tribution on behalf of the Dover families, 1996). (2005). Nature Publishing Group Group 200 6 Nature Publishing ©

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