BOOKS ET AL.

EVOLUTION proteins evolve and how proteins interact, and he completely ignores a huge amount of God as Genetic Engineer experimental data that directly contradicts his faulty premises. Unfortunately, these errors Sean B. Carroll are of a technical and will be difficult for lay readers, and even some scientists “The Lord hath delivered him into mine such as vertebrate classes). He also accepts (as (those unfamiliar with molecular and hands.” he has before) the 4.5-billion-year age of evolutionary genetics), to detect. Some people Earth and that we share a common ancestor will be hoodwinked. My goal here is to point hose are the words that Thomas Hux- with chimpanzees. That certainly won’t go out the critical flaws in Behe’s key arguments ley, Darwin’s confidant and staunchest over well in some camps. and to guide readers toward ally, purportedly murmured to a col- Behe also explores some ex- some references that illus- T The Edge of league as he rose to turn Bishop Samuel amples of Darwinian evolution trate why what he alleges to Wilberforce’s own words to his advantage and at the molecular level, including The Search for the be beyond the limits of rebut the bishop’s critique of Darwin’s theory an extensive treatment of the Limits of Darwinism Darwinian evolution falls at their legendary 1860 Oxford debate. They evolutionary “trench warfare” by Michael J. Behe well within its demonstrated are also the first words that popped into my fought between humans and Free Press, New York, 2007. powers. head as I read Michael J. Behe’s The Edge malarial parasites over the mil- 331 pp. $28, C$33.99. Behe’s chief error is min- of Evolution: The Search for the Limits of lennia—all in the context of ISBN 9780743296205. imizing the power of natural Darwinism. In it, Behe makes a new set of what Darwinian evolution “can selection to act cumulatively explicit claims about the limits of Darwinian do.” So what’s the problem? as traits or molecules evolve evolution, claims that are so poorly conceived The problem is what Behe asserts Dar- stepwise from one state to another via inter- and readily dispatched that he has unwittingly winian evolution can’t do: produce more mediates. Behe states correctly that in most done his critics a great favor in stating them. “complex” changes than those that have two adaptive occurring

In Darwin’s Black Box: The Biochemical enabled humans to battle or allowed instantaneously at two specific sites in one on October 11, 2007 Challenge to Evolution (1), Behe had for- malarial parasites to evade the drugs we throw gene are very unlikely and that functional warded the notion that certain biochemical at them. Behe’s main argument rests on the changes in proteins often involve two or more systems were “irreducibly com- sites. But it is a non sequitur to leap plex,” could not have evolved to the conclusion, as Behe does, stepwise by Darwinian mecha- that such multiple–amino acid nisms, and thus were intelligently replacements therefore can’t hap- designed. Since that earlier book, pen. Multiple replacements can Behe has played a key role in the accumulate when each single (ID) movement, amino acid replacement affects www.sciencemag.org including a star turn as a defense performance, however slightly, be- witness in the 2005 Dover school cause selection can act on each board case. Despite his testimony— replacement individually and the or, I should say, partly because of changes can be made sequentially. what he said (2)—ID was ruled to Behe begrudgingly allows that be a religious concept and its only “rarely, several mutations can

teaching in public schools uncon- sequentially add to each other to Downloaded from stitutional. improve an organism’s chances of Behe, a professor of biochem- survival.” Rarely? This, of course, istry at Lehigh University, has is the everyday stuff of evolution. found an audience among various Examples of cumulative selection flavors of creationists who find changing multiple sites in evolv- Darwinian evolution incompati- ing proteins include tetrodotoxin GRAIL

Y ble with their religious views and resistance in snakes (3), the tuning

HOL see scientific validation in Behe’s of color vision in animals (4),

THE claims. Clearly, this book’s main audience assertion that two or more simultaneous muta- cefotaxime antibiotic resistance in bacteria

AND would be that constituency, although they tions are required for increases in biochemical (5), and pyrimethamine resistance in malarial will find some parts very discomfiting. For complexity and that such changes are, except parasites (6)—a notable omission given

PYTHON instance, Behe explicitly accepts the ability of in rare circumstances, beyond the limit of evo- Behe’s extensive discussion of malarial drug- random and selection to account for lution. He concludes that “most mutations resistance.

MONTY the variation within and differences between that built the great structures of life must have Behe seems to lack any appreciation of the closely related species (but not higher taxa been nonrandom.” In short, God is a genetic quantitative dimensions of molecular and trait AFTER , engineer, somehow designing changes in evolution. He appears to think of the func- DNA to make biochemical machines and tional features of proteins in qualitative terms, SUTLIFF The reviewer, the author of The Making of the Fittest, is at higher taxa. as if binding or catalysis were all or nothing JOE

: the Laboratory of Molecular Biology, Howard Hughes Medical Institute, University of Wisconsin, Madison, WI But to arrive at this conclusion, Behe relies rather than a broad spectrum of affinities or

CREDIT 53706, USA. E-mail: [email protected] on invalid assertions about how genes and rates. Therefore, he does not grasp the funda-

www.sciencemag.org VOL 316 8 JUNE 2007 1427 Published by AAAS BOOKS ETAL.

mental reality of a mutational path that pro- lessons from some earlier gaffes. He has again 10. Y. V. Budovskaya, J. S. Stephan, S. J. Deminoff, P. K. teins follow in evolving new properties. gone “public” with assertions without the Herman, Proc. Natl. Acad. Sci. U.S.A. 102, 13933 (2005). This lack of quantitative thinking underlies benefit (or wisdom) of first testing their 11. P. Beltrao, L. Serrano, PLoS Comput. Biol. 3, e25 (2007). a second, fatal blunder resulting from the mis- strength before qualified experts. 12. M. J. Behe, in Darwinism, Science or Philosophy?, J. taken assumptions Behe makes about protein For instance, Behe once wrote, “if random Buell, V. Hearn, Eds. (Foundation for Thought and Ethics, Richardson, TX, 1994), pp. 60–71. interactions. The author has long been con- evolution is true, there must have been a large 13. A. Bottaro, M. A. Inlay, N. J. Matzke, Nat. Immunol. 7, cerned about protein complexes and how they number of transitional forms between the 433 (2006). could or, rather, could not evolve. He argues Mesonychid [a whale ancestor] and the 14. M. J. Pallen, N. J. Matzke, Nat. Rev. Microbiol. 4, 784 (2006). that the generation of a single new protein- ancient whale. Where are they?” (12). He 15. R. Liu, H. Ochman, Proc. Natl. Acad. Sci. U.S.A. 104, protein binding site is extremely improbable assumed such forms would not or could not be 7126 (2007). and that complexes of just three different pro- found, but three transitional species were teins “are beyond the edge of evolution.” But identified by paleontologists within a year of 10.1126/science.1145104 Behe bases his arguments on unfounded that statement. In Darwin’s Black Box, he requirements for protein interactions. He posited that genes for modern complex bio- EVOLUTION insists, based on consideration of just one type chemical systems, such as blood clotting, of protein structure (the combining sites of might have been “designed billions of years antibodies), that five or six positions must ago and have been passed down to the present A Multilevel change at once in order to make a good fit ... but not ‘turned on’.” This is known to be between proteins—and, therefore, good fits genetically impossible because genes that Exploration are impossible to evolve. An immense body of aren’t used will degenerate, but there it was in David Jablonski experimental data directly refutes this claim. print. And Behe’s argument against the evolu- There are dozens of well-studied families tion of flagella and the immune system have n the natural world, as in human societies, of cellular proteins (kinases, phosphatases, been dismantled in detail (13, 14) and new complexity is almost always organized proteases, adaptor proteins, sumoylation evidence continues to emerge (15), yet the hierarchically. From the nested structures

I on October 11, 2007 enzymes, etc.) that recognize short linear pep- same old assertions for design reappear here of armies and corporations to the classical tide motifs in which only two or three amino as if they were uncontested. biological progression from molecule to cell acid residues are critical for functional activity The continuing futile attacks by evolu- to tissue to body to species, the “particles” at [reviewed in (7–9)]. Thousands of such re- tion’s opponents reminds me of another each level tend to be grouped into ever more versible interactions establish the protein legendary confrontation, that between Arthur inclusive units. However, despite the ubiquity networks that govern cellular physiology. and the Black Knight in the of natural hierarchies, their Very simple calculations indicate how eas- movie Monty Python and the evolutionary implications have ily such motifs evolve at random. If one Holy Grail. The Black Knight, Evolution and the Levels been anything but clear. assumes an average length of 400 amino acids like evolution’s challengers, of Selection Evolution and the Levels of www.sciencemag.org for proteins and equal abundance of all amino continues to fight even as each by Samir Okasha Selection is a major contribu- acids, any given two–amino acid motif is of his limbs is hacked off, one tion toward putting this contro- likely to occur at random in every protein in by one. The “no transitional Clarendon Press, Oxford, 2006. 275 pp. $55, £30. versial area on a coherent con- a cell. (There are 399 dipeptide motifs in a fossils” argument and the ceptual and philosophical foot- × ISBN 9780199267972. 400–amino acid protein and 20 20 = 400 “designed genes” model have ing. Samir Okasha’s argument possible dipeptide motifs.) Any specific been cut clean off, the courts hinges on two components, three–amino acid motif will occur once at ran- have debunked the “ID is science” claim, and neither of them new but here powerfully and dom in every 20 proteins and any four–amino the nonsense here about the edge of evolution creatively integrated and extended. First is the Downloaded from acid motif will occur once in every 400 pro- is quickly sliced to pieces by well-established fundamental distinction between two dis- teins. That means that, without any new muta- biochemistry. The knights of ID may profess parate kinds of multilevel selection (MLS), tions or , many sequences that these blows are “but a scratch” or “just a flesh often conflated despite their formal introduc- are identical or close matches to many interac- wound,” but the argument for design has no tion 20 years ago (1), with even earlier prece- tion motifs already exist. New motifs can arise scientific leg to stand on. dents. The failure to appreciate this distinction readily at random, and any weak interaction has generated an enormous amount of confu- can easily evolve, via random mutation and References 1. M. J. Behe, Darwin’s Black Box: The Biochemical sion, at times bordering on fury, and Okasha’s natural selection, to become a strong interac- Challenge to Evolution (Free Press, New York, 1996). use of this conceptual framework brings tion (9). Furthermore, any pair of interacting 2. Kitzmiller et al. v. Dover Area School District et al., exceptional clarity and precision to a wide proteins can readily recruit a third protein, and Memorandum Opinion, 20 December 2005; range of issues. In essence, for MLS1 the sole so forth, to form larger complexes. Indeed, it www.pamd.uscourts.gov/kitzmiller/decision.htm. 3. S. L. Geffeney et al., Nature 434, 759 (2005). focal level is the individual (at any level), but has been demonstrated that new protein inter- 4. S. B. Carroll, The Making of the Fittest: DNA and the its fitness depends partly on the group to actions (10) and protein networks (11) can Ultimate Forensic Record of Evolution (Norton, New York, which it belongs. The classic example is the evolve fairly rapidly and are thus well within 2006). 5. D. M. Weinreich, N. F. Delaney, M. A. DePristo, D. L. seeming paradox of altruism: how can selec- the limits of evolution. Hartl, Science 312, 111 (2006). tion drive behavior that aids others at the Is it possible that Behe does not know this 6. W. Sirawaraporn et al., Proc. Natl. Acad. Sci. U.S.A. 94, body of data? Or does he just choose to ignore 1124 (1997). it? Behe has quite a record of declaring what is 7. V. Neduva et al., PLoS Biol. 3, e405 (2005). The reviewer is in the Department of Geophysical Sciences 8. R. P. Bhattacharyya, A. Reményi, B. J. Yeh, W. A. Lim, and Committee on , University of impossible and of disregarding the scientific Annu. Rev. Biochem. 75, 655 (2006). Chicago, 5734 South Ellis Avenue, Chicago, IL 60637, literature, and he has clearly not learned any 9. V. Neduva, R. B. Russell, FEBS Lett. 579, 3342 (2005). USA. E-mail: [email protected]

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