(Posted July 11, 1997 ? Issue 12; archived July 25, 1997)Review
A recent commentary in Science features MIT geneticist Eric
Lander's observation that the Human Genome Project, like many
large-scale endeavors, is often described by way of analogy to the Holy
Grail, the Manhattan Project, and the moon shot. Lander, a leading
participant in and enthusiast for genome sequencing, rejects these
labels, choosing instead the equally compelling if more modest
comparison with the periodic table of elements as the most accurate
description of the Genome Project and its place in the biomedical
sciences.
This view - that genes are the pieces but not the whole puzzle of
development and disease - is frequently lost amid the attention given
to gene cloning and sequencing. Into this debate comes Evelyn Fox
Keller's Refiguring Life: Metaphors of Twentieth-Century
Biology, a slim volume collecting three lectures originally
delivered as the Wellek Library Lecture Series at the University of
California, Irvine in 1993. Keller, a professor of the history and
philosophy of science at MIT, brings a much-needed historical
perspective to bear on the ways in which the perception and progress
of a field can be determined as much by language as by substance.
The first essay, "Language and Science: Genetics, Embryology, and
the Discourse of Gene Action," introduces her central theme,
which is that for much of this century a gene-centered approach to
biology has held sway not solely because transmission genetics is an
essential component of any comprehensive understanding of life, and
not solely because technical advances have made genes accessible to
laboratory scientists, but also because many of the leading
practitioners in the field defined genes as puppeteers, pulling the
strings of embryonic development.
The historical division between genetics and embryology has been well
documented, but Keller's essay has the great merit of identifying
telling phrases in the writings and speeches of the people who made
genetics a molecular science. She quotes H.J. Muller, in a speech
entitled "The Gene as the Basis of Life," to the effect
that, as opposed to the nucleus, the function of the cytoplasm
"lies only in its fostering the genes, and the primary secrets
common to all life lie further back, in the gene material
itself." And Alfred Sturtevant: "How does an egg develop
into a complex many-celled organism? That is, of course, the
traditional problem of embryology; but it also appears in genetics in
the form of the question, 'How do genes produce their effects?'"
Keller comments:
Once the problem of development
is translated into the question of how genes produce their effects, the
task is immediately - and almost miraculously - simplified. No longer
need a geneticist become bogged down in the complex dynamics of eggs
and multicellular organisms; studying single-celled organisms, which
provide a better opportunity to analyze "chains of reaction,"
ought to suffice.
In Keller's narrative, this view of development, cultivated in the
1920s and 1930s by American geneticists associated with Thomas Hunt
Morgan, culminates neatly in 1940 in the celebrated work of George
Beadle and Arthur Tatum on single-celled Neurospora, an
organism they exploited to show that one gene produces one enzyme;
that is, a gene produces its effects by catalyzing a specific
chemical reaction. Geneticists had discovered the power of organisms
like Neurospora and E. coli (and its attendant viruses)
to provide answers to fundamental questions about the biochemistry of
gene action. Classical embryologists, on the other hand, argued that
development was primarily a problem of differential gene
activation, not action, and that the components of the
cytoplasm - whether maternally inherited or elaborated during
development - must have a role in directing gene activity.
Of course, this latter view has been rescued by the thriving
discipline of developmental biology, which places genes in the
context of intercellular communication, cytoplasmic signaling
molecules, and gene regulatory elements, all serving to activate gene
expression at the proper times and places. This picture of life as
the result of both genetic and epigenetic processes appears
now to be so eminently reasonable as to lead the reader to suspect
that, however they described their field, geneticists must always
have had this in mind. Keller anticipates this objection in a key
passage:
But of course, the reader
might think, didn't we know this all along? Well, yes and no. Yes in
the sense that . . . it is the sort of observation embryologists used
to make all of the time. But no in the sense that, except for an
occasional aside . . . geneticists did not.
That the legacy of what Keller calls "the discourse of gene
action" is still influential can be seen in any number of recent
commentaries. University of California at Berkeley biologist Richard
Strohman, in the March 1997 issue of Nature Biotechnology,
feels it necessary to spend five pages explaining the inadequacy of
"the paradigm of the gene," which he believes "has
mistakenly evolved into a theory and a paradigm of life."
Gerald Edelman, addressing professional biologists as well as lay
readers in his 1988 book Topobiology: An Introduction to Molecular
Embryology, sets the stage with a reminder that even with the
knowledge of every last nucleotide in an organism's genome, one could
not predict the final product. Jurassic Park, in other words,
requires a dinosaur egg as well as dinosaur DNA.
Keller goes to great lengths to point out that the gene-centered
approach has been extremely powerful and has given us an unprecedented
understanding of living systems. Indeed, it is only relative to the
extraordinary claims made for the gene that this approach can be said
to be inadequate. In her second essay, "Molecules, Messages, and
Memory: Life and the Second Law," Keller outlines one such claim
in a discussion of Erwin Schrodinger's classic book What Is
Life?
Schrodinger's influential 1943 lectures attempt to explain the
phenomenon of life in a universe governed by the second law of
thermodynamics. How is the plan for development passed on unerringly
to succeeding generations, and how do organisms stave off the
inevitable decay that is mandated by the second law? Keller makes the
intriguing suggestion that Schrodinger invested the gene - an
aperiodic crystal, in his prophetic phrase - with the capacity to
carry out not only the former task, but the latter as well. That is,
in Keller's reading, Schrodinger saw the gene as what late nineteenth
and early twentieth century scientists referred to as Maxwell's Demon:
James Clerk Maxwell's vision of "a purely imaginary being who
could reverse the natural tendency toward dissipation." DNA, as
it would become known, carried not only stable information, but also
the intrinsic ability to produce an entire organism and prevent its
decay. For Schrodinger, as for Morgan and colleagues, attributing to
the gene such characteristics allowed them to sidestep questions too
difficult to answer, but too important to ignore.
And the metaphors continue to appear, as Keller describes in her final
essay, "The Body of a New Machine: Situating the Organism Between
Telegraphs and Computers." The emerging view is that at the heart
of living systems is information; therefore the encoding, storage, and
processing of information is a proper subject of study for biologists
in the era of the personal computer. Terms like "code,"
"message," "informatics," "network," and
"algorithm" flow back and forth between computer science and
developmental genetics, each field informing the other. One clear
example can be found in a recent issue of Development, where
Maria Arnone and Eric Davidson write of gene regulatory elements:
"These systems are remarkably complex. Their hardwired internal
organization enables them to behave as genomic information processing
units."
Overall, Keller writes in highly readable, jargon-free prose. She mines
the literature of genetics, physics, embryology, and computer science to
produce mini-histories, showing us how metaphorical language can have
lasting effects on the course of science. Indeed, one of the most
enjoyable aspects of this book stems from Keller's command of the
literature. The extensive list of references she provides should encourage
many interested readers to visit the mustier regions of the science library
in search of one article or another.
For those scientists unpersuaded of the interest and relevance of work on
the history of science, Refiguring Life might change a few minds. Keller,
with a background in bench science, is fully conversant with the substance
of the science and is sympathetic with the scientists whose language she
dissects. It is difficult to break new ground in science without a theoretical
framework in mind, and inevitably some of these theories will
turn out to be inadequate or incomplete, however useful they were at the
time. "Productive blindness," she calls it, and concludes, "How else,
after all, could science possibly proceed?"
This is a fine book, of interest to any biologist curious about the hold
that genomics has on the scientific - and popular - imagination. It reminds
us, through insightful and detailed arguments, that debates over terms and
analogies in biology are neither new nor insignificant. Whether our words
do justice to the complexity of our science is something that will be
decided only by future generations, who, as Keller points out, will labor under
metaphors of their own choosing, for better or worse.
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.
But a funny thing happened on the way to the holy grail. That
extraordinary progress has become less and less describable within the
discourse that fostered it. The dogmatic focus on gene action called forth
a dazzling armamentarium of new techniques for analyzing the behavior of
distinct gene segments, and the information yielded by those techniques is
now radically subverting the doctrine of the gene as sole (or even primary)
agent. It has also become conspicuously evident that there were all along
serious problems with the discourse of gene action - in addition to its
productive blindness to questions of development and cell differentiation.
Evelyn Fox
Keller: A Bibliography - the Critical Theory Institute of UC Irvine
maintains this page, which has links to her bibliography and selected reviews
of her work.
This view - that genes are the pieces but not the whole puzzle of
development and disease - is frequently lost amid the attention given
to gene cloning and sequencing. Into this debate comes Evelyn Fox
Keller's Refiguring Life: Metaphors of Twentieth-Century
Biology, a slim volume collecting three lectures originally
delivered as the Wellek Library Lecture Series at the University of
California, Irvine in 1993. Keller, a professor of the history and
philosophy of science at MIT, brings a much-needed historical
perspective to bear on the ways in which the perception and progress
of a field can be determined as much by language as by substance.
The historical division between genetics and embryology has been well
documented, but Keller's essay has the great merit of identifying
telling phrases in the writings and speeches of the people who made
genetics a molecular science. She quotes H.J. Muller, in a speech
entitled "The Gene as the Basis of Life," to the effect
that, as opposed to the nucleus, the function of the cytoplasm
"lies only in its fostering the genes, and the primary secrets
common to all life lie further back, in the gene material
itself." And Alfred Sturtevant: "How does an egg develop
into a complex many-celled organism? That is, of course, the
traditional problem of embryology; but it also appears in genetics in
the form of the question, 'How do genes produce their effects?'"
Keller comments:
That the legacy of what Keller calls "the discourse of gene
action" is still influential can be seen in any number of recent
commentaries. University of California at Berkeley biologist Richard
Strohman, in the March 1997 issue of Nature Biotechnology,
feels it necessary to spend five pages explaining the inadequacy of
"the paradigm of the gene," which he believes "has
mistakenly evolved into a theory and a paradigm of life."
Gerald Edelman, addressing professional biologists as well as lay
readers in his 1988 book Topobiology: An Introduction to Molecular
Embryology, sets the stage with a reminder that even with the
knowledge of every last nucleotide in an organism's genome, one could
not predict the final product. Jurassic Park, in other words,
requires a dinosaur egg as well as dinosaur DNA.
And the metaphors continue to appear, as Keller describes in her final
essay, "The Body of a New Machine: Situating the Organism Between
Telegraphs and Computers." The emerging view is that at the heart
of living systems is information; therefore the encoding, storage, and
processing of information is a proper subject of study for biologists
in the era of the personal computer. Terms like "code,"
"message," "informatics," "network," and
"algorithm" flow back and forth between computer science and
developmental genetics, each field informing the other. One clear
example can be found in a recent issue of Development, where
Maria Arnone and Eric Davidson write of gene regulatory elements:
"These systems are remarkably complex. Their hardwired internal
organization enables them to behave as genomic information processing
units."
