Review
Geneticists love to make mutations in their favorite experimental organisms. When they say an organism "has good genetics," they usually mean that it is relatively easy to induce interesting mutations in them and to use a variety of molecular biological tricks to identify the genes in which the mutation has occurred. The fruit fly Drosophila melanogaster has been a favorite organism for this purpose since the pioneering work of Thomas Hunt Morgan. Probably the best known Drosophila mutant is Antennapedia, a particularly dramatic example of mutation in which legs have taken the place of antennae. Antennapedia and its mutant cousins in other species have been the object of intensive study by developmental geneticists around the world, but except for the occasional newspaper headline, no one takes much notice of this mutant menagerie outside of university lecture halls.
The exceptions, of course, like the mutants themselves, are of great interest. A short time after Ian Wilmut's cloning experiment hit the front pages, an experiment by the British developmental biologist Jonathan Slack and his colleagues got opinion columnists writing yet again about science run amok. Slack had identified a genetic pathway that was required for posterior development in another favorite experimental organism, the toad Xenopus laevis. When he and his colleagues overexpressed individual components of this pathway in a developing Xenopus embryo, the tadpoles that were produced were headless. After an interview or two, and some offhand speculation on the possibility of cloned headless humans being produced as sources of immunologically compatible transplantable organs, "the case of the headless frog" became an irresistible news story all over the globe.
Slack had previously written an excellent book on embyrology, From Egg to Embryo, and either he or his publisher must have realized that there was a germ of a book in this headless frog business. In his new book, Egg and Ego, Slack has used his fifteen minutes of fame as a springboard to take on the media-driven misapprehensions that allowed a somewhat obscure bit of developmental biology to turn a scientist into a celebrity. The "egg" in the title represents the subject of developmental biology, which is Slack's area of interest, and the "ego" is the human side of science - the personalities, motivations, and desires that drive any human enterprise. It's an "almost true story" in that he has changed the names of some of the people described in the more autobiographical sections of the book.
Slack writes very well. His facility with language and his sense of humor sustain the reader's interest, even as he moves from topic to topic in a somewhat random manner. Although there are dozens of anecdotes sprinkled throughout, three major themes can be identified. The first is the day-to-day business of being a bench scientist. Egg and Ego opens with a brief description of an important experiment: Slack's demonstration in 1986 that fibroblast growth factor (FGF) could promote the formation of mesoderm (the middle of the three primary germ layers of an embryo and the origin of all body musculature, connective tissues, blood, cardiovascular, and lymphatic systems) when applied to Xenopus embryos.
This is followed by an entertaining account of the isolation of pure FGF from 10 kilograms of cow brains. He also includes a potentially frightening aside. When he and his colleagues were breathing in the aerosolized products of "100 liters of slimy, smelly homogenate" of bovine brain, they had not the least concern for bovine spongiform encephalopathy (BSE), aka. "mad cow disease." His characteristic dry wit perhaps concealing a sigh of relief, he adds: "Whether one can catch BSE by breathing in brain aerosol, we do not know. But we are still here, and the degeneration of our brains is no worse than might be expected 13 years on."
The second theme introduced by the FGF experiment is a scientific genealogy of sorts. Every experiment has a history: a line of thought or a string of results or an unforeseen technical advance that makes it possible. In Slack's telling, the Xenopus embryos prodded by FGF into making muscle represent the convergence of two venerable areas of research, each extending back to the 1930s. One is the rich tradition of classical embryology, in which investigators like the celebrated Hans Spemann and Hilde Mangold identified regions of developing embryos that are capable of altering the fates of neighboring cells. The other is the equally storied field of growth factors and their use in the development of protocols for maintaining cells and tissue in culture. Slack realized, as he peered at his sausage-like Xenopus embryos, that growth factors and inducing factors are one and the same.
Biologists studying the timing and control of cell division have had a similar meeting of the minds. Yeast geneticists studying certain mutants that were defective in cell division identified the very same molecule that scientists studying the maturation of Xenopus eggs were homing in on - a protein kinase that is now known to be a universal regulator of mitosis. In a way, though, the convergence of these fields covers even more ground, since it is now known that growth factors and cell cycle components are implicated in cancer. Slack is very good on this subject, and he argues convincingly that his own field of developmental biology is positioned at the nexus of many seemingly disparate areas of research.
The other major areas of life in the biology lab that the author covers in some detail might be lumped under the heading "science as a career." Slack describes, in consistently blunt terms, the need for budding scientists to work at "a good place" with "good people" and to publish in "the fashion journals," i.e. Science, Nature, and Cell. He implicitly (and occasionally explicitly) argues against this narrow view of success in science, but the skeptical, non-tenured reader might argue that it's all too easy to take potshots at the system from a secure, well-funded perch at "a good place."
In Slack's defense, he fires at least one shot in his own direction by relating the story of how he and his colleagues, Peter Holland and Chris Graham, got a small commentary entitled "The Zootype and the Phylotypic Stage" published in Nature. Referring to this work as "a piece of dilettante-ish nonsense written in the most ridiculous florid language," he suggests that he effectively duped Nature into publishing a less-than-worthy paper because it was pithy enough to attract media attention. As recounted by Slack, the whole episode is essential reading for anyone who wants a glimpse of the editorial process.
There are other amusing tales attached to each serious subject in the book, including an account of a lavishly catered scientific meeting in Japan at which the international character of science ran up against persistent cultural differences. Novelist David Lodge, who spoofs this sort of thing better than anyone in novels such as Changing Places and Small World: An Academic Romance, might want to pick Slack's brain for some new material. At the very least, readers of Egg and Ego will get a fresh, entertaining perspective on many aspects of contemporary science from someone who is still in the thick of it.
Alan I. Packer is currently a postdoctoral fellow in the Center for Reproductive Sciences and Department of Genetics and Development at the Columbia University College of Physicians and Surgeons.
Excerptblockquote>The general public does not know anything about classical experimental embryology. To them, if a headless tadpole is in the news, then it is a novelty, and some people may feel that such experiments are cruel to tadpoles and should be stopped. It is a sobering thought that when Spemann received his Nobel Prize, the publicity would have been restricted to a few serious articles in a few serious newspapers, but when a science story hits the wires today, it can be flashed to billions of people in a few minutes.
