BOOK REVIEW
In the Twinkle of a Fly
Rudolf Raff
Coming to Life: How Genes Drive Development. Christiane
Nüsslein-Volhard. xiv + 166 pp. Kales Press, 2006. $29.95.
Christiane Nüsslein-Volhard is one of the pioneers in the
groundbreaking discoveries that revealed how genes regulate the
development of animal embryos. For this effort she shared the 1995
Nobel Prize for Physiology or Medicine with Eric F. Wieschaus and
Edward B. Lewis. In Coming to Life, she provides an
engaging and clear summary of what developmental biologists now
understand about how embryos work.
The existence of such an apparently simple guide shows how much we
have come to take for granted the explanation of development by gene
regulation. However, it should be understood that what
Nüsslein-Volhard describes actually represents the outcome of
one of the premier intellectual triumphs of human thought—one
that has been achieved within only the past two and a half decades.
Consider the profound difficulty embryonic development presents to
an observer. A complex organism, such as a chick, frog, insect or
human, arises in an orderly and magical way from an apparently
structureless egg. When embryology was in its infancy in the 17th
and 18th centuries, the thought was that no animal could arise from
such nothingness. Thus was born the theory of the homunculus: the
idea that an infinite set of tiny individuals were contained, one
within another, in each egg—or in each sperm (there was
vigorous disagreement as to which). Development was seen as the
visible unfolding of a preexisting individual. Unhappily for this
wonderful notion, in the late 18th century Caspar Friedrich Wolff
showed by microscopy that embryos contained cells but no
homunculus—there was no preformed entity.
So, whence comes the information needed to build an individual from
scratch? The rediscovery of Mendelian genetics early in the 20th
century suggested that genes provided the instructions, but the
theoretical foundations of how genes worked were still lacking, and
any demonstration that genes were crucial to development was slow to
come. With the work of François Jacob and Jacques Monod on
gene expression and regulation, the stage was set in the mid-1960s
to understand development in terms of the role of information copied
from DNA to messenger RNA and then used to construct proteins. By
the 1980s developmental genetics was beginning, and the first major
organism to draw its attention was the fruit fly, Drosophila
melanogaster, which had already been for some time the primary
species for the study of genetics.
The subtitle of Nüsslein-Volhard's book is How Genes Drive
Development. That's really the essence of her conception of
developmental biology, a view that guides the organization of the
book. She begins with chapters that introduce the genetic machinery,
heredity, chromosomes, genes and proteins. She moves on to a brief
discussion of the role of model organisms that have been crucial in
developmental genetics and proceeds to the first of these, D. melanogaster.
The development of Drosophila is indeed at the heart of her
story: She elegantly and plainly describes the search for genes that
regulate development and lays out the mechanisms by which their
expression generates patterns in the growing embryo, explaining
along the way how the proteins those genes encode interact with
other genes. Here's how it works: First, broad patterns are
produced, followed by ever more precise ones that block out the body
plan of a fly and the identities of its parts.
Nüsslein-Volhard's research has elucidated much of this. Hence
she can describe these goings-on authoritatively.
From there she explains general principles by which the overall form
of the organism arises. At work are various activities and
interactions among cells—interactions involving gradients of
certain molecules; the movement of signals generated by one cell to
influence its neighbors; growth; division; the maintenance of stem
cells; and specific patterns of programmed cell death.
Nüsslein-Volhard describes complex topics clearly, making an
invisible world visible to the reader.
The second developmental model system that Nüsslein-Volhard
presents is the zebrafish, which she uses to illustrate some of the
crucial developmental features of vertebrates. She was a leading
pioneer in building the developmental genetic study of these
organisms, just as she had been with the fruit fly—although
unfortunately in neither case does she discuss her own vital roles
with these developmental genetic systems.
Nüsslein-Volhard gives a nice but all-too-brief treatment of
the development of mammals and how it is studied. She uses this
outline to introduce major aspects of human development that we
indeed should all know about. She also discusses some aspects of
evolution in very broad strokes, usefully demystifying how animal
body plans arose. The most interesting chapter, apart from the
primary ones on developmental genetics, is the final one, on current
topics. There she gives a clear-eyed perspective on topics generally
clouded by contentious and not necessarily well-informed debate:
human cloning, in vitro fertilization, embryo research and stem
cells. Her discussion incorporates a sensitivity to the complexity
of ethical and legal issues.
As with any book that attempts a concise generalization of a complex
science, there are a few mistakes, mainly on historical points. Thus
when Nüsslein-Volhard suggests that before Darwin, embryonic
resemblances were thought to show "a lack of creativity on the
part of the Creator," she misses the point for 19th-century
scientists, who took them to show the use of a common ground plan.
Also, Ed Lewis did not discover Hox genes in the 1930s.
These genes were first detected by others, notably Richard
Goldschmidt; Lewis later ascertained their roles and inferred their
mode of evolution. The statement that humans did not descend from
apes is incorrect: We descended from primitive apes, ancestral both
to us and to living apes. These occasional errors do not affect the
core information and arguments of the book.
Nüsslein-Volhard has given us a compact, vibrant, lucid guide
to modern developmental biology. She makes the text informative and
precise, and renders difficult concepts readily understandable. The
book is illustrated with charming drawings by the author that
effectively illuminate her points. This is a marvelous introductory
resource to anyone wanting to understand what developmental biology
is all about.