Immunology in the Spotlight at the Dover 'Intelligent Design' Trial

The May 2006 issue of Nature Immunology contains a "Commentary" essay on the role that evolutionary immunology played in the now-famous cross-examination of Michael Behe on Day 12 of the Kitzmiller v. Dover trial in the fall of 2005. The essay is coauthored by Nick Matzke, NCSE Public Information Project Director and a key behind-the-scenes player in the Kitzmiller case. Matzke teamed up with two immunologists to write the article: Andrea Bottaro (Department of Medicine, Department of Microbiology and Immunology and the James P. Wilmot Cancer Center, University of Rochester School of Medicine and Dentistry) and Matt Inlay (Department of Pathology, Beckman Center, Stanford University). Both are contributors to the Panda's Thumb weblog, and have written detailed critiques of Behe's claims about immunology (Bottaro, Inlay). These critiques served as an inspiration and guide for Matzke during preparation of the immune system section of the Behe cross-examination.

The Nature Immunology commentary reviews the background of the case, the science supporting the transposon model for the evolutionary origin of the adaptive immune system's rearranging antibodies, the problems with Behe's claims about the system, and recounts this dramatic episode of the Behe cross-examination.

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

Andrea Bottaro1, Matt A Inlay2 & Nicholas J Matzke3

1 Andrea Bottaro is with the Department of Medicine, Department of Microbiology and Immunology and the James P. Wilmot Cancer Center, University of Rochester School of Medicine and Dentistry, Rochester, New York 14642, USA.

2 Matt A. Inlay is in the Department of Pathology, Beckman Center, Stanford University, Stanford, California 94305, USA.

3 Nicholas J. Matzke is with the National Center for Science Education, Oakland, California 94609, USA.

Correspondence should be addressed to Andrea Bottaro

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.

Evolutionary immunology literature presented at the Dover trial. "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."2

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 Box2, 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 exceptions3, 4, 5, 6, the topic has been explicitly addressed mostly in book reviews7, 8, 9, 10, philosophy journals11, 12 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 (

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"2. 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 transposon13, an idea initially suggested in a 1979 paper14 and expanded in 1992 (ref. 15). Behe ridicules the idea as a "jump in the box of Calvin and Hobbes,"2 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 mechanisms16 and also between shark RAG1 and certain bacterial integrases17. 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 vitro18, 19 and then in vivo20, 21, 22, and to have even closer structural and mechanistic similarities with specific transposases23. 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 homolog24. 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 (

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:

In fact, on cross-examination, Professor Behe was questioned concerning his 1996 claim that science would never find an evolutionary explanation for the immune system. He was presented with fifty-eight peer-reviewed publications, nine books, and several immunology textbook chapters about the evolution of the immune system; however, he simply insisted that this was still not sufficient evidence of evolution, and that it was not 'good enough.'

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.

  1. Metchnikoff, E. Lectures on the Comparative Pathology of Inflammation; Delivered at the Pasteur Institute in 1891 (Dover, New York, 1968).
  2. Behe, M.J. Darwin's Black Box: the Biochemical Challenge to Evolution (Free Press, New York, 1996).
  3. Thornhill, R.H. & Ussery, D.W. J. Theor. Biol. 203, 111–116 (2000). | Article | PubMed | ISI | ChemPort |
  4. Aird, W.C. J. Thromb. Haemost. 1, 227–230 (2003). | Article | PubMed | ISI | ChemPort |
  5. Pennock, R.T. Annu. Rev. Genomics Hum. Genet. 4, 143–163 (2003). | Article | PubMed | ISI | ChemPort |
  6. Keller, E.F. Ann. NY Acad. Sci. 981, 189–201 (2002). | PubMed |
  7. Orr, H.A. Boston Review XXI, 28–31 (1996).
  8. Coyne, J.A. Nature 383, 227–228 (1996). | Article | ISI | ChemPort |
  9. Cavalier-Smith, T. Trends Ecol. Evol. 12, 162–163 (1997). | Article |
  10. Pomiankowski, A. New Scientist 151, 44–45 (1996).
  11. Shanks, N. & Joplin, K.H. Philos. Sci. 66, 268–282 (1999). | Article | ISI |
  12. Weber, B. Biol. Philos. 14, 593–605 (1999). | Article | ISI |
  13. Bartl, S. , Baltimore, D. & Weissman, I. Proc. Natl. Acad. Sci. USA 91, 10769–10770 (1994). | PubMed | ChemPort |
  14. Sakano, H. , Huppi, K. , Heinrich, G. & Tonegawa, S. Nature 280, 288–294 (1979). | Article | PubMed | ISI | ChemPort |
  15. Dreyfus, D.H. Mol. Immunol. 29, 807–810 (1992). | Article | PubMed | ISI | ChemPort |
  16. Van Gent, D.C. , Mizuuchi, K. & Gellert, M. Science 271, 1592–1594 (1996). | PubMed | ChemPort |
  17. Bernstein, R.M. , Schulter, S.F. , Bernstein, H. & Marchalonis, J.J. Proc. Natl. Acad. Sci. USA 93, 9454–9459 (1996). | Article | PubMed | ChemPort |
  18. Agrawal, A. , Eastman, Q.M. & Schatz, D.G. Nature 394, 744–751 (1998). | Article | PubMed | ISI | ChemPort |
  19. Hiom, K. , Melek, M. & Gellert, M. Cell 94, 463–470 (1998). | Article | PubMed | ISI | ChemPort |
  20. Vaandrager, J.W. , Schuuring, E. , Philippo, K. & Kluin, P.M. Blood 96, 1947–1952 (2000). | PubMed | ISI | ChemPort |
  21. Clatworthy, A.E. , Valencia, M.A. , Haber, J.E. & Oettinger, M.A. Mol. Cell 12, 489–499 (2003). | Article | PubMed | ISI | ChemPort |
  22. Messier, T.L. , O'Neill, J.P. , Hou, S.M. , Nicklas, J.A. & Finette, B.A. EMBO J. 22, 1381–1388 (2003). | Article | PubMed | ISI | ChemPort |
  23. Zhou, L. et al. Nature 432, 995–1001 (2004). | Article | PubMed | ISI | ChemPort |
  24. Kapitonov, V.V. & Jurka, J. PLoS Biol. 3, e181 (2005). | Article | PubMed | ChemPort |
We thank the authors of the articles and books on the evolution of the immune system presented during the trial ( and contributors to Panda's Thumb ( and Talkorigins Archive ( for suggestions during the trial and for comments on this manuscript. The decision, trial transcripts and all court documents are available through the National Center for Science Education (

Scientific literature on the evolutionary origin of the immune system

Supplementary Material

Supplementary Material for: Bottaro, Andrea, Inlay, Matt A., and Matzke, Nicholas J. (2006). "Immunology in the spotlight at the Dover 'Intelligent Design' trial." Nature Immunology. 7(5), 433-435. May 2005. (Subscription no longer required: DOI | Journal | Google Scholar | PubMed | Supplementary Material)

Scientific literature on the evolutionary origin of the immune system

This is the list of books, textbook chapters, and articles that were presented to Defense expert Michael Behe during cross-examination in the Kitzmiller v. Dover Area School District trial about the constitutionality of teaching "intelligent design." The cross-examination was conducted by Pepper-Hamilton attorney Eric Rothschild. Behe summarily dismissed the mass of scientific literature on the evolution of the immune system, despite the fact that it contradicted his previous assertion that the scientific community had "no answers" on the question. This episode was cited in Judge Jones's ruling against intelligent design, and various press accounts.

Sections: BooksTextbook chaptersArticlesNote
See also: Annotated Bibliography | Long Unannotated Bibliography


Beck, G., Cooper, E. L., Habicht, G. S. and Marchalonis, J. J., eds. (1994). Primordial Immunity: Foundations for the Vertebrate Immune System. New York, The New York Academy of Sciences. (Library | PubMed | Amazon | Google Print)

Du Pasquier, L. and Litman, G. W., eds. (2000). Origin and Evolution of the Vertebrate Immune System. Current Topics in Microbiology and Immunology. Berlin, Springer. (Library | Amazon | Google Print)

Hoffman, J. A., Janeway, C. A. and Natori, S., eds. (1994). Phylogenetic Perspectives in Immunity: The Insect Host Defense. Austin, R. G. Landes Company. (Library | Amazon | Google Print)

Kelsoe, G. and Schulze, D. H., eds. (1987). Evolution and Vertebrate Immunity: The Antigen-Receptor and MHC Gene Families. Austin, University of Texas Press. (Library | Amazon | Google Print)

Manning, M. J., ed. (1980). Phylogeny of Immunological Memory. Developments in Immunology. Amsterdam, Elsevier/North-Holland Biomedical Press. (Library | Amazon | Google Print)

Marchalonis, J. J. (1976). Immunity in Evolution. Cambridge, Mass., Harvard University Press. (Library | Amazon | Google Print)

Síma, P. and Vetvicka, V. (1990). Evolution of Immune Reactions. Boca Raton, CRC Press. (Library | Amazon | Google Print)

Stewart, J. (1994). The Primordial VRM System and the Evolution of Vertebrate Immunity. Austin, R. G. Landes. (Library | Amazon | Google Print)

Vetvicka, V. and Síma, P. (1998). Evolutionary Mechanisms of Defense Reactions. Basel, Birkhäuser Verlag. (Library | Amazon | Google Print)

Vetvicka, V., Síma, P., Cooper, E. L., Bilej, M. and Roch, P. (1994). Immunology of Annelids. Boca Raton, CRC Press. (Library | Amazon | Google Print)

Warr, G. W. and Cohen, N., eds. (1991). Phylogenesis of Immune Functions. Boca Raton, CRC Press. (Library | Amazon | Google Print)

Textbook chapters

Flajnik, M. F., Miller, K. and Du Pasquier, L. (2003). "Evolution of the Immune System." Fundamental Immunology. Edited by W. E. Paul. Philadelphia, Lippincott Williams & Wilkins: 519-570. (Library | Amazon | Google Print)

Klein, J. (1986). "Evolution of Mhc." Natural History of the Major Histocompatibility Complex. New York, John Wiley & Sons: 715-762. (Library | Google Print)

Síma, P. and Vetvicka, V. (1992). "Evolution of Immune Accessory Functions." Immune System Accessory Cells. Edited by L. Fornusek and P. Síma. Boca Raton, CRC Press: 1-55. (Library | Amazon | Google Print)


Agrawal, A., Eastman, Q. M. and Schatz, D. G. (1998). "Transposition mediated by RAG1 and RAG2 and its implications for the evolution of the immune system." Nature 394(6695): 744-751. (PubMed | DOI | Journal | Google Scholar)

Bartl, S., Baltimore, D. and Weissman, I. L. (1994). "Molecular evolution of the vertebrate immune system." Proceedings of the National Academy of Sciences 91(23): 10769-10770. (PubMed | Journal | JSTOR | Google Scholar)

Bernstein, R. M., Schluter, S. F., Bernstein, H. and Marchalonis, J. J. (1996). "Primordial emergence of the recombination activating gene 1 (RAG1): Sequence of the complete shark gene indicates homology to microbial integrases." Proceedings of the National Academy of Sciences 93(18): 9454-9459. (PubMed | Journal | JSTOR | Google Scholar)

Burnet, F. M. (1971). "Self-recognition in colonial marine forms and flowering plants in relation to the evolution of immunity." Nature 232(5308): 230. (PubMed | DOI | Journal | Google Scholar)

Cannon, J. P., Haire, R. N. and Litman, G. W. (2002). "Identification of diversified genes that contain immunoglobulin-like variable regions in a protochordate." Nature Immunology 3(12): 1200-1207. (PubMed | DOI | Journal | Google Scholar)

Cannon, J. P., Haire, R. N., Pancer, Z., Mueller, M. G., Skapura, D., Cooper, M. D. and Litman, G. W. (2005). "Variable Domains and a VpreB-like molecule are present in a jawless vertebrate." Immunogenetics 56(12): 924-929. (PubMed | DOI | Journal | Google Scholar)

Cannon, J. P., Haire, R. N., Rast, J. P. and Litman, G. W. (2004). "The phylogenetic origins of the antigen-binding receptors and somatic diversification mechanisms." Immunological Reviews 200(1): 12-22. (PubMed | DOI | Journal | Google Scholar)

Clatworthy, A. E., Valencia, M. A., Haber, J. E. and Oettinger, M. A. (2003). "V(D)J recombination and RAG-mediated transposition in yeast." Molecular Cell 12(2): 489-499. (PubMed | DOI | Journal | Google Scholar)

Cohn, M. (2006). "What are the commonalities governing the behavior of humoral immune recognitive repertoires?" Developmental and Comparative Immunology 30(1-2): 19-42. (PubMed | DOI | Journal | Google Scholar)

Davis, M. M. (2004). "The evolutionary and structural 'logic' of antigen receptor diversity." Seminars in Immunology 16: 239-243. (PubMed | DOI | Journal | Google Scholar)

Dreyfus, D. H. (1992). "Evidence suggesting an evolutionary relationship between transposable elements and immune system recombination sequences." Molecular Immunology 29(6): 807-810. (PubMed | DOI | Journal | Google Scholar)

Du Pasquier, L. (2000). "The Phylogenetic Origin of Antigen-Specific Receptors." Origin and Evolution of the Vertebrate Immune System. Edited by L. Du Pasquier and G. W. Litman. Berlin, Springer. 248: 159-185. (Library | PubMed | Amazon | Google Print)

Du Pasquier, L. (2001). "The immune system of invertebrates and vertebrates." Comparative Biochemistry and Physiology Part B Biochemistry & Molecular Biology 129(1): 1-15. (PubMed | DOI | Journal | Google Scholar)

Du Pasquier, L. (2005). "Meeting the demand for innate and adaptive immunities during evolution." Scandinavian Journal of Immunology 62(s1): 39-48. (PubMed | DOI | Journal | Google Scholar)

Eason, D. D., Cannon, J. P., Haire, R. N., Rast, J. P., Ostrov, D. A. and Litman, G. W. (2004). "Mechanisms of antigen receptor evolution." Seminars in Immunology 16: 215-226. (PubMed | DOI | Journal | Google Scholar)

Flajnik, M. F. and Du Pasquier, L. (2004). "Evolution of innate and adaptive immunity: can we draw a line?" Trends in Immunology 25(12): 640-644. (PubMed | DOI | Journal | Google Scholar)

Galaktionov, V. G. (2004). "Evolutionary Development of the Immunoglobulin Family." Biology Bulletin 31(2): 101-111. (PubMed | DOI | Journal | Google Scholar)

Gould, S. J., Hildreth, J. E. and Booth, A. M. (2004). "The evolution of alloimmunity and the genesis of adaptive immunity." Quarterly Review of Biology 79(4): 359-382. (PubMed | DOI | Journal | Google Scholar)

Hansen, J. D. and McBlane, J. F. (2000). "Recombination-Activating Genes, Transposition, and the Lymphoid-Specific Combinatorial Immune System: A Common Evolutionary Connection." Origin and Evolution of the Vertebrate Immune System. Edited by L. Du Pasquier and G. W. Litman. Berlin, Springer. 248: 111-135. (Library | PubMed | Amazon | Google Print)

Holmes, E. C. (2004). "Adaptation and Immunity." PLoS Biology 2(9): 1269-1269. (PubMed | DOI | Journal | Google Scholar)

Hughes, A. L. and Yeager, M. (1997). "Molecular evolution of the vertebrate immune system." BioEssays 19(9): 777-786. (PubMed | Google Scholar)

Janssen, B. J. C., Huizinga, E. G., Raaijmakers, H. C. A., Roos, A., Daha, M. R., Nilsson-Ekdahl, K., Nilsson, B. and Gros, P. (2005). "Structures of complement component C3 provide insights into the function and evolution of immunity." Nature 437(7058): 505-511. (PubMed | DOI | Journal | Google Scholar)

Ji, X., Azumi, K., Sasaki, M. and Nonaka, M. (1997). "Ancient origin of the complement lectin pathway revealed by molecular cloning of mannan binding protein-associated serine protease from a urochordate, the Japanese ascidian, Halocynthia roretzi." Proceedings of the National Academy of Sciences 94(12): 6340-6345. (PubMed | Journal | Google Scholar)

Jones, J. M. (2004). "The taming of a transposon: V(D)J recombination and the immune system." Immunological Reviews 200(1): 233-248. (PubMed | DOI | Journal | Google Scholar)

Kapitonov, V. V. and Jurka, J. (2005). "RAG1 Core and V(D)J Recombination Signal Sequences Were Derived from Transib Transposons." Public Library of Science Biology 3(6): e181:0001-0014. (PubMed | DOI | Journal | Google Scholar)

Kaufman, J. (2002). "The origins of the adaptive immune system: whatever next?" Nature Immunology 3(12): 1124-1125. (PubMed | DOI | Journal | Google Scholar)

Klein, J. and Nikolaidis, N. (2005). "The descent of the antibody-based immune system by gradual evolution." Proceedings of the National Academy of Sciences 102(1): 169-174. (PubMed | DOI | Journal | Google Scholar)

Krem, M. M. and Di Cera, E. (2002). "Evolution of enzyme cascades from embryonic development to blood coagulation." Trends in Biochemical Sciences 27(2): 67-74. (PubMed | DOI | Journal | Google Scholar)

Laird, D. J. (2002). "Immune System." Encyclopedia of Evolution. Edited by M. Pagel. Oxford, Oxford University Press. 2: 558-564. (Library | Publisher | Amazon | Google Print)

Lewis, S. M. (1999). "Evolution of Immunoglobulin and T-Cell Receptor Gene Assembly." Annals of the New York Academy of Sciences 870: 58-67. (PubMed | Google Scholar)

Lewis, S. M. and Wu, G. E. (1997). "The origins of V(D)J recombination." Cell 88(2): 159-162. (PubMed | DOI | Journal | Google Scholar)

Lewis, S. M. and Wu, G. E. (2000). "The old and the restless." Journal of Experimental Medicine 191(10): 1631-1636. (PubMed | Journal | Google Scholar)

Litman, G. W., Anderson, M. K. and Rast, J. P. (1999). "Evolution of antigen binding receptors." Annual Review of Immunology 17: 109-147. (PubMed | DOI | Journal | Google Scholar)

Marchalonis, J. J., Adelman, M. K., Schluter, S. F. and Ramsland, P. A. (2006). "The antibody repertoire in evolution: Chance, selection, and continuity." Developmental and Comparative Immunology 30(1-2): 223-247. (PubMed | DOI | Journal | Google Scholar)

Marchalonis, J. J., Hohman, V. S., Kaymaz, H., Schluter, S. F. and Edmundson, A. B. (1994). "Cell Surface Recognition and the Immunoglobulin Superfamily." Primordial Immunity: Foundations for the Vertebrate Immune System. Edited by G. Beck, E. L. Cooper, G. S. Habicht and J. J. Marchalonis. New York, New York Academy of Sciences. 712: 20-33. (Library | PubMed | Google Print)

Marchalonis, J. J., Jensen, I. and Schluter, S. F. (2002). "Structural, antigenic and evolutionary analyses of immunoglobulins and T cell receptors." Journal of Molecular Recognition 15(5): 260-271. (PubMed | DOI | Journal | Google Scholar)

Marchalonis, J. J., Kaveri, S., Lacroix-Desmazes, S. and Kazatchkine, M. D. (2002). "Natural recognition repertoire and the evolutionary emergence of the combinatorial immune system." FASEB Journal 16(8): 842-848. (PubMed | Journal | Google Scholar)

Marchalonis, J. J. and Schluter, S. F. (1994). "Development of an Immune System." Primordial Immunity: Foundations for the Vertebrate Immune System. Edited by G. Beck, E. L. Cooper, G. S. Habicht and J. J. Marchalonis. New York, New York Academy of Sciences. 712: 1-11. (Library | PubMed | Google Print)

Market, E. and Papavasiliou, F. N. (2003). "V(D)J Recombination and the Evolution of the Adaptive Immune System." PLoS Biology 1(1): 24-27. (PubMed | DOI | Journal | Google Scholar)

Messier, T. L., O'Neill, J. P., Hou, S.-M., Nicklas, J. A. and Finette, B. A. (2003). "In vivo transposition mediated by V(D)J recombinase in human T lymphocytes." The EMBO Journal 22(6): 1381-1388. (PubMed | DOI | Journal | Google Scholar)

Nonaka, M. (2000). "Origin and evolution of the Complement System." Origin and Evolution of the Vertebrate Immune System. Edited by L. Du Pasquier and G. W. Litman. Berlin, Springer. 248: 37-50. (Library | PubMed | Amazon | Google Print)

Nonaka, M. and Miyazawa, S. (2001). "Evolution of the Initiating Enzymes of the Complement System." Genome Biology 3(1): 1001.1001-1001.1005. (PubMed | DOI | Journal | Google Scholar)

Nonaka, M. and Yoshizaki, F. (2004). "Evolution of the Complement System." Molecular Immunology 40(12): 897-902. (PubMed | DOI | Journal | Google Scholar)

Ohno, S. (1994). "MHC Evolution and Development of a Recognition System." Primordial Immunity: Foundations for the Vertebrate Immune System. Edited by G. Beck, E. L. Cooper, G. S. Habicht and J. J. Marchalonis. New York, New York Academy of Sciences. 712: 13-19. (Library | PubMed | Google Print)

Opal, S. M. (2000). "Phylogenetic and functional relationships between coagulation and the innate immune response." Critical Care Medicine 28(9): S77-S80. (PubMed | Journal | Google Scholar)

Pancer, Z., Amemiya, C. T., Ehrhardt, G. R. A., Ceitlin, J., Gartland, G. L. and Cooper, M. D. (2004). "Somatic diversification of variable lymphocyte receptors in the agnathan sea lamprey." Nature 430(6996): 174-180. (PubMed | DOI | Journal | Google Scholar)

Plasterk, R. (1998). "Ragtime jumping." Nature 394(6695): 718-719. (PubMed | DOI | Journal | Google Scholar)

Richards, M. H. and Nelson, J. L. (2000). "The Evolution of Vertebrate Antigen Receptors: A Phylogenetic Approach." Molecular Biology and Evolution 17(1): 146-155. (PubMed | Journal | Google Scholar)

Roth, D. B. (2000). "From lymphocytes to sharks: V(D)J recombinase moves to the germline." Genome Biology 1(2): 1014.1011-1014.1014. (PubMed | DOI | Journal | Google Scholar)

Rothenberg, E. V. and Pant, R. (2004). "Origins of lymphocyte developmental programs: transcription factor evidence." Seminars in Immunology 16(4): 227-238. (PubMed | DOI | Journal | Google Scholar)

Sakano, H., Hüppi, K., Heinrich, G. and Tonegawa, S. (1979). "Sequences at the somatic recombination sites of immunoglobulin light-chain genes." Nature 280(6): 288-294. (PubMed | DOI | Journal | Google Scholar)

Schatz, D. G. (1999). "Transposition mediated by RAG1 and RAG2 and the evolution of the adaptive immune system." Immunologic Research 19(2-3): 169-182. (PubMed | Google Scholar)

Schatz, D. G. (2004). "Antigen receptor genes and the evolution of a recombinase." Seminars in Immunology 16(4): 245-256. (PubMed | DOI | Journal | Google Scholar)

Schluter, S. F., Bernstein, R. M., Bernstein, H. and Marchalonis, J. J. (1999). "'Big Bang' emergence of the combinatorial immune system." Developmental and Comparative Immunology 23(2): 107-111. (PubMed | DOI | Journal | Google Scholar)

Schluter, S. F., Bernstein, R. M. and Marchalonis, J. J. (1997). "Molecular origins and evolution of immunoglobulin heavy-chain genes of jawed vertebrates." Immunology Today 18(11): 543-549. (PubMed | DOI | Journal | Google Scholar)

Stavnezer, J. and Amemiya, C. T. (2004). "Evolution of isotype switching." Seminars in Immunology 16(4): 257-275. (PubMed | DOI | Journal | Google Scholar)

Thompson, C. B. (1995). "New insights into V(D)J recombination and its role in the evolution of the immune system." Immunity 3(5): 531-539. (PubMed | DOI | Journal | Google Scholar)

Vaandrager, J.-W., Schuuring, E., Philippo, K. and Kluin, P. M. (2000). "V(D)J recombinase-mediated transposition of the BCL2 gene to the IGH locus in follicular lymphoma." Blood 96(5): 1947-1952. (PubMed | Journal | Google Scholar)

van Gent, D. C., Mizuuchi, K. and Gellert, M. (1996). "Similarities between initiation of V(D)J recombination and retroviral integration." Science 271(5255): 1592-1594. (PubMed | Journal | JSTOR | Google Scholar)

Zhou, L., Mitra, R., Atkinson, P. W., Hickman, A. B., Dyda, F. and Craig, N. L. (2004). "Transposition of hAT elements links transposable elements and V(D)J recombination." Nature 432: 995-1001. (PubMed | DOI | Journal | Google Scholar)


During his direct testimony, Plaintiffs' expert Kenneth Miller highlighted eight articles on the development and confirmation of the transposon hypothesis for the evolutionary origin of the adaptive immune system. During the cross-examination of Michael Behe, Miller's list was given to Michael Behe first, followed by the rest of the literature. Miller's eight articles partially overlapped with the list of 58 articles in the Behe cross-examination exhibit; they have been combined to produce the articles list above. Also, a few of the available books were not read into the record, being available only as photocopies, or difficult to explain quickly (i.e. Immunology of Annelids).