Books and Arts

Nature 453, 1181-1182 (26 June 2008) | doi:10.1038/4531181a; Published online 25 June 2008

Making genetic history

Jerry A. Coyne1

BOOK REVIEWEDIn Pursuit of the Gene: From Darwin to DNA

by James Schwartz

Harvard University Press: 2008. 384 pp. $29.95, £19.95, euro dollar22.50

Making genetic history

BETTMANN/CORBIS

Fruitful collaborations were formed in Thomas Hunt Morgan's fly genetics lab.

When I was a student, 'doing genetics' meant crossing two different strains or species. Now it means sequencing DNA, preferably human. Between these two poles lies the history of genetics, a pathway fraught with sharp turns, steep gradients and dead ends — and engagingly recounted in James Schwartz's new book.

Despite its subtitle, In Pursuit of the Gene is not a comprehensive history of genetics, but focuses solely on classical genetics. Schwartz, a science writer, begins with Charles Darwin's ill-fated 'pangenesis' theory of the inheritance of acquired characteristics, and runs through the rediscovery of Gregor Mendel's work on inherited traits. The story continues with the consolidation of Mendelism and chromosomal inheritance by Thomas Hunt Morgan and his students in the 'Fly Room' lab at New York's Columbia University, where modern genetics began, and concludes in 1946 with Hermann Joseph Muller's Nobel Prize in Medicine for inducing mutations with X-rays. Later history, from the discovery by Oswald Avery and colleagues that DNA was the 'transforming principle', to the Human Genome Project, is squeezed into a 12-page epilogue. Those seeking a history of molecular genetics should read Horace Freeland Judson's magisterial The Eighth Day of Creation (Simon & Schuster, 1979).

Many histories of genetics cover the same ground. What distinguishes Schwartz's account is his impeccable scholarship, based on many primary sources, and his ability to keep the narrative moving, interweaving discoveries with the strong and eccentric personalities who made them. He does not slight the science, describing experiments in detail so dense that the reader is advised to keep a pencil and paper handy. The effort required to understand the book may, sadly, remove it from the ambit of popular science.

The book's apogee is its tale of the "Mendel Wars" around the beginning of the twentieth century, the struggle to bring together Mendel's ideas on heredity and Darwin's theory of evolution. On one side were the Mendelians, including Francis Galton, William Bateson and Charles Hurst, who accepted Mendelism but considered natural selection as ineffective, seeing evolution as occurring by 'macromutations', or single genetic changes of very large effect. On the other side stood the biometricians, most notably Karl Pearson and Raphael Weldon, who accepted the ubiquity of Darwinian selection but rejected Mendelian genetics. Given the strong egos involved and the fundamental nature of the science at stake, the battles Schwartz recounts were fierce. Friendships were destroyed, careers threatened. After a particularly contentious meeting about the genetics of horse coat colour at the Royal Society in London, Pearson hissed at Hurst, "You shall never be Fellow here as long as I live".

Other high spots in the book include the early and now largely forgotten work on cytological genetics by Walter Sutton and Edmund B. Wilson, involving years of eye-strain from squinting at confusing chromosomal preparations of sea urchins, aphids and grasshoppers. These studies established that different chromosomes carry different hereditary factors, yet occur in pairs that become separated during the formation of gametes in meiosis, giving essential physical support for Mendel's laws.

The book's longest section details the immense contributions of research on the fruitfly Drosophila melanogaster to our understanding of heredity. Schwartz explains how, from 1912 to around 1930, Morgan and his 'boys', Alfred Sturtevant and Calvin Bridges, along with Muller, were "responsible for the integration of Mendelism and the chromosome theory that is the basis of genetics". Within a few years, this conjunction of remarkable intellects in a tiny laboratory led to methods for mapping chromosomes both genetically and cytologically, and to the discovery of sex linkage, chromosome inversions, nondisjunction and many other phenomena that now form the dogma of transmission genetics.

Alas, here we find a major flaw. Schwartz notes that he was inspired to write his history by reading Elof Carlson's worshipful biography of Muller, Genes, Radiation, and Society (Cornell University Press, 1981). But this only generates further hagiography: the discussion of Muller's work occupies a quarter of In Pursuit of the Gene, a disproportionate chunk. Schwartz gives the impression that Muller, or ideas purloined from him by others, was behind nearly every advance in fly genetics. Sturtevant's contributions are given short shrift, Morgan is portrayed as a conniver who acquired his Nobel status on the backs of his students, and Bridges — perhaps the finest pair of eyes ever to peer at a magnified fly — is dismissed as being "famous for stealing other men's wives as well as their ideas". Schwartz does not mention the work of Lewis Stadler, who independently discovered X-ray induction of mutations in barley at the same time as Muller's work on Drosophila. Like many plant geneticists, Stadler was marginalized as a glorified crop breeder.

It is easy to sympathize with Muller, who had a tumultuous life and was the perennial underdog: Jewish, short, bald and with a high voice. Fractious, and possessed of unpopular socialist views, he floated from university to university, winding up in the Soviet Union until he fled to escape Trofim Lysenko's destruction of Russian genetics. Yet during all these peregrinations he maintained an uninterrupted programme of research. It is a scandal that Muller did not secure a tenured academic job until he was 55 — he won the Nobel prize a year later.

Muller was one of the best geneticists of the twentieth century, a visionary who predicted the rise of molecular genetics and the use of association mapping to identify genes for human behaviours. He was also difficult to work with, obsessed with credit and depressive to the point of once attempting suicide. Schwartz repeatedly states that Sturtevant, Bridges and Morgan tried to ruin Muller's reputation by stealing his ideas and slandering him, but the evidence is unconvincing. Working together in the Fly Room, talking science as they worked on flies in what was a continuous lab meeting, it is not surprising that they shared ideas and information. After all, it was Sturtevant who gave Muller the idea of using lethal alleles to measure mutation rates.

The other 'boys' were not slouches. Bridges discovered nondisjunction, thereby proving the chromosomal theory of heredity, and published it as the first paper in the first issue of the journal Genetics. He constructed the first map of genes on autosomes, did fundamental work on sex determination and produced maps of Drosophila salivary-gland chromosomes that have never been bettered. Sturtevant was the first to establish, while still an undergraduate, that genes are arrayed linearly on chromosomes. He devised the chromosomal fate mapping later used so effectively by the geneticist Seymour Benzer, founded Drosophila taxonomy and, by studying the action of eye-colour mutations in the fly, became the father of biochemical genetics. But neither Sturtevant nor Bridges was obsessed with priority: Sturtevant was the most modest of men, whereas Bridges, a great womanizer, had more pressing interests.

In Pursuit of the Gene should be required reading for all biologists unfamiliar with the history of genetics. Schwartz shows how quickly science can advance when a group of first-class minds encounters a fertile but unploughed field. Progress in genetics, as in all modern science, was truly a collaborative affair. There was no Darwin of genetics — not even Muller. There was, and is, plenty of credit to go around.

  1. Jerry A. Coyne is a professor in the Department of Ecology and Evolution at the University of Chicago, Illinois 60637, USA.

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