American Scientist

Lamarck's Signature: How Retrogenes Are Changing Darwin's Natural Selection Paradigm. Edward J. Steele, Robyn A. Lindley and Robert V. Blanden. 286 pp. Perseus Books, 1998. $25.

Sperm and egg cells are evolution's darlings. A basic principle of contemporary Darwinism, seemingly confirmed by generations of geneticists following the suggestion of the great German biologist August Weismann, is that the germ cells and somatic cells are in distinct and separate compartments. A mutation in a somatic cell may affect the fitness of an organism, but unless the identical mutation also occurs independently in the germ line—an exceedingly unlikely event—it is invisible to posterity. The opposite view—that somatically acquired characteristics can be inherited—was put forward by the French evolutionist Jean Baptiste de Lamarck, whose name, like Ptolemy's, is inextricably linked with a failed theory.

Several immunologists now disagree, at least in part. In Lamarck's Signature, Edward Steele, Robyn Lindley and Robert Blanden suggest that genes encoding immunoglobulins have arisen via recombination in immune cells followed by retrotransposition into the germ cells of the same organism. They say that in every B lymphocyte there are clusters of so-called V, D and J genes. On stimulation by a foreign antigen, rearrangements occur in each mature B cell so that one each of the V, D and J genes is spliced together to yield a gene encoding the heavy and light chains of the antibody molecule. The theory then goes that this spliced-together V(D)J gene undergoes "somatic hypermutation" whereby the V(D)J transcripts are reverse-transcribed and incorporated back into the genome. Because the reverse transcriptase enzyme has a rather low fidelity when copying the RNA back into DNA, many of the B cells will carry mutated V(D)J genes, a few of which will turn out to encode an antibody molecule that binds the antigen with even higher affinity. These B cells will proliferate rapidly. Now the key point: At some frequency, these "successful" V(D)J transcripts will be captured by endogenous retroviruses and will be inserted, by an as yet unknown mechanism, into the germ cells where they can be transmitted to the next generation.

The evidence that supports this argument is incomplete but compelling. Simply put, the structure and sequence of V genes in the germ line has been found to exhibit characteristics that are normally associated with rearranged and reinserted somatic-cell V genes in B cells. As summarized above, the authors' argument is a bold but reasonable conclusion as to the origin of these "somatic type" V genes in germ cells. If true, it suggests that the driving force behind the rapid evolution of the vertebrate immune system is, remarkably enough, Lamarckian.

Professional biologists will probably spend most of their time on chapters 5 and 6, where the crux of the argument is presented. In the first four chapters, Steele and colleagues acquaint lay readers with some of the main features of the immune response in a clear and thorough outline. The book is marred a bit by the somewhat aggrieved tone that enters into the discussion, implicitly in most cases but explicitly in an introductory chapter on the history of their hypothesis and also in an epilogue aimed at critics. Only those closest to the debate will know if it has been conducted fairly, although there is a blurb on the dust jacket from The Australian quoting an anonymous writer as saying that the discussion has been "punctuated by bruising encounters with the British scientific establishment." Maybe so, but how could it be otherwise given that the target is arguably the most successful theory in the history of biology and the evidence limiting its explanatory power is so obviously incomplete, even as it demands attention and further experimentation?—Alan I. Packer, Genetics and Development, Columbia University College of Physicians and Surgeons