American Scientist

Perspectives on Genetics: Anecdotal, Historical, and Critical Commentaries, 1987-1998. James F. Crow and William F. Dove (eds). xi + 723 pp. University of Wisconsin Press, 2000. $19.95.

Since 1987 Genetics has prefaced each monthly issue with a (usually) short historical reminiscence or review under the heading "Perspectives: Anecdotal, Historical, and Critical Commentaries on Genetics." Now the first 140 articles in this series have been brought together in this large book, which provides a sort of patchwork history of genetics, from the earliest post-Mendelian times to the present. James F. Crow and William F. Dove, as editors of the series, commissioned most of the pieces and quite often ended up writing them themselves. Crow was evidently a particularly willing writer, with 26 articles under his name, all a pleasure to read.

The articles are of several distinct types. Many mark anniversaries—the 30th birthday of Holliday's recombination model (Frank Stahl), the 40th anniversary of the discovery of bacterial transduction (Norton Zinder), 75 years of chromosome mapping (James Crow), and so on. Many of these are authored by people who were themselves closely involved in the events commemorated.

Other essays offer brief accounts of the lives and scientific achievements of pioneering geneticists, including Francis Galton, T. H. Morgan, J. B. S. Haldane, Sewall Wright, R. A. Fisher, A. H. Sturtevant, A. F. Blakeslee, R. A. Emerson, H. J. Müller, Lancelot Hogben, Lionel Penrose, and, coming closer to our own day, Alfred Hershey and Howard Temin. Some of these personalities reappear throughout the book: Sturtevant, Haldane and Müller in particular are pervasive presences. Most of the articles have serious points to make, and only J. T. Bonner's amusing essay largely devoted to his social encounters with Haldane is purely anecdotal.

Several contributions review the current state of particular fields?for example, DNA repair, genetics of the nematode worm, homeotic mutants of Drosophila. On the whole, these subject reviews are perhaps the least successful pieces in the book; the writing is dense because the authors were under space constraints, and the articles may be heavy going for those not already acquainted with the topics under review.

Most articles occupy three to six double-column pages, including references. But some are longer, and one, a review of the too-often overlooked work of the French theoretical population geneticist Gustave Malécot (by Thomas Nagylaki), fills 16 pages and is in the style of a regular scientific paper.

The editors have aimed to cover genetics in all its aspects, from the populational and evolutionary to the microbial and molecular. Joshua Lederberg looks back at the beginnings of bacterial genetics, and Frank Stahl and Norton Zinder elucidate key advances in our understanding of the genetics of bacteriophages.

On the population genetics side, the most striking development over the past 35 years—the discovery of the near-universal occurrence of perhaps inconsequential sequence variation in proteins—is dealt with from two different points of view. Richard Lewontin, who was mainly responsible for bringing the prevalence of enzyme polymorphism to our attention, thinks that its evolutionary significance is still questionable, whereas Ward Watt thinks that he and his colleagues already have evidence of differences in fitness associated with variation with respect to glycolytic enzymes in butterflies. Arguably, the most realistic, if uninspiring, conclusion is that most natural enzyme polymorphisms are nearly neutral with respect to fitness most of the time.

Probably the most important event in mid-20th-century genetics was the discovery of the divisibility of the gene. This is dealt with mainly from the perspective of work with Drosophila in an article by Mel Green, who was the first, with Ed Lewis, to deal with the paradox of pseudoalleles. In this context, one might have expected something more in the book about the decisive impact of the work of Seymour Benzer on intragene mapping in bacteriophages.

A much earlier difficulty in thinking about genes, which I mention because it was completely new to me, is revealed by Raphael Falk and Sara Schwartz. They recall that at the beginning of T. H. Morgan's studies of Drosophila he thought it logical to name mutants after the genes positively responsible for their phenotypes, which, on the basis of the theory that mutations were losses of gene function, would have to be the unmutated gene(s) whose function(s) remained. This convention of genetic symbolism became unusable as soon as it became evident that there was more than one remaining gene helping to determine each mutant phenotype. Morgan sorted out this unnecessary confusion by 1913, but our present authors still seem to have problems, drawing the conclusion that Morgan's mistake was in trying "to have his cake and eat it," as if the studies of development and heredity ought to be mutually exclusive!

In the foregoing paragraphs I have touched on just a few of the highly miscellaneous articles in this book. It perhaps makes more sense to ask whether there are any important areas of genetics that have not been covered. In the context of evolution, I was surprised to see no mention of the concept of punctuated equilibrium, which, according to Stephen Jay Gould and Niles Eldredge, throws the whole neo-Darwinian consensus into doubt. Perhaps the editors thought—as indeed, I think—that this controversy has been greatly overblown, but, even so, some attempt to put it into perspective would have been in order. On the more molecular side, the field of mitochondrial heredity (particularly of yeast), which has arisen in large part as a result of the work of Piotr Slonimski in Paris, surely merited some attention. This would have made a good story, rising as it did from nothing to virtual completion within the past 40 years. Just as important, though much further from completion, is the new wave of epigenetics—that is, cell-heritable changes that do not depend on differences in DNA sequence. Two articles, one by Steven Henikoff and the other by Allan Spradling and Gary H. Karpen, do indeed deal with position effect variegation, but without relating it, as much as would now be possible, to the general importance of self-maintaining states of chromatin during development. An even more revolutionary topic omitted from consideration here is that of prions, but it is probably too soon to expect anyone to have a Perspective on that!

Although this large and somewhat unwieldy volume does not include everything in genetics that one might consider important, it does cover a great deal of the subject, to the extent that many will probably find themselves using it as a sort of informal encyclopedia, or at least a rewarding museum. It would have been even more useful as a reference book if more trouble had been taken over the preparation of the index.