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S A R A H S.

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EDITO
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POSTGENOMICS
Perspectives on Biology
after the Genome

POSTGENOMICS

POSTGENOMICS
Perspectives on Biology
after the Genome

Sarah S. Richardson and Hallam Stevens, editors


duke university press Durham and London 2015

2015 Sarah S. Richardson and Hallam Stevens


All rights reserved
Printed in the United States of America on
acid-free paper
Typeset in Whitman
by Westchester Publishing Services
Library of Congress Cataloging-in-Publication Data
Postgenomics : perspectives on biology after the
genome / Sarah S. Richardson and Hallam Stevens,
editors.
pages cm
Includes bibliographical references and index.
isbn 978-0-8223-5922-7 (hardcover : alk. paper)
isbn 978-0-8223-5894-7 (pbk. : alk. paper)
isbn 978-0-8223-7544-9 (e-book)
1. Human Genome Project. 2. Human gene mapping.
3. Genetic engineeringMoral and ethical aspects.
4. GenomicsMoral and ethical aspects. I. Richardson,
Sarah S., 1980 II. Stevens, Hallam.
qh445.2.p678 2015
611'.0181663dc23
2014044249

Permissions:
Chapter 4, The Polygenomic Organism, by John
Dupr, rst appeared in The Sociological Review 58
(2010) and is printed by permission of the publisher, John Wiley and Sons. 2010 The Author.
Editorial organization 2010 The Editorial Board
of The Sociological Review.
Parts of Chapter 8, From Behavior Genetics to
Postgenomics by Aaron Panofsky, rst appeared
as part of his book, Misbehaving Science: Controversies and the Development of Behavior Genetics.
These parts are reproduced by permission of the
publisher, University of Chicago Press 2014.
All rights reserved.
Cover art: Connectogram image courtesy of Dr.
John Darrell Van Horn, University of Southern
California.

contents

foreword

Biologys Love Affair with the Genome


Russ Altman vii

Beyond the Genome


Hallam Stevens and Sarah S. Richardson 1

The Postgenomic Genome


Evelyn Fox Keller 9

What Toll Pursuit: Affective Assemblages in


Genomics and Postgenomics
Mike Fortun 32

The Polygenomic Organism


John Dupr 56

Machine Learning and Genomic Dimensionality:


From Features to Landscapes
Adrian Mackenzie 73

Networks: Representations and Tools


in Postgenomics
Hallam Stevens 103

Valuing Data in Postgenomic Biology: How Data


Donation and Curation Practices Challenge the
Scientic Publication System
Rachel A. Ankeny and Sabina Leonelli 126

From Behavior Genetics to Postgenomics


Aaron Panofsky 150

Dening Health Justice in the Postgenomic Era


Catherine Bliss 174

10

The Missing Piece of the Puzzle? Measuring the


Environment in the Postgenomic Moment
Sara Shostak and Margot Moinester 192

11

Maternal Bodies in the Postgenomic Order: Gender


and the Explanatory Landscape of Epigenetics
Sarah S. Richardson 210

12

Approaching Postgenomics
Sarah S. Richardson and Hallam Stevens 232
bibliography 243
contributors 281
index 287

foreword Biologys Love Affair with the Genome

Postgenomics is the unavoidable consequence of an intense love affair


between biomedical scientists and the human genome. The discovery of
the double-helical structure of dna in 1953 lit the ame. The breathtaking
rapidity with which this discovery lead to the entrenchment of the central dogma (dna rna protein), the cracking of the genetic code, the
emergence of genetic engineering technology, and the early understanding
of Mendelian diseases created an expectation of exponential increases in
our ability to measure and interpret dna information. dna satises the
compulsions of many scientists: measurable, discrete, molecular (yet apparently integrative), deterministic, and evolvable. If a little dna sequence
was good, then a lotthe genomewould be great. With the prospect of
greatness, reasonable people are prone to hyperbole: save money, develop
cures, predict disease, learn about our ancestors, and bring justice to all. It
can be hard to judge harshly someone in love.
But even the most intense love affairs simmer and require nurturing.
The breakneck speed of the courtship slows to a more reasoned set of discussions, negotiations, and settings of expectation. Some love affairs do
not survive these adjustments, but others transition to a lifelong shared
adventure. Postgenomics commences with an inventory of the successes
and disappointments of the genome; we lift our heads, look around, and
gure out what the future holds.

I do genomics, and I plan to do postgenomics. But this volume compels


me to examine what I do and why I do it. The chapter authors combine
a deep understanding of the history and technical content of modern
genomic science with largely contrarian (to many genomicists, at least)
interpretations of the signicance and impact of the work. They expose
signicant biases in the way we formulate, justify, communicate, and defend work in genomics. Surprisingly, however, their analyses do not lead to
despair, but to opportunity.
The chapters in this book highlight unrecognized and unexamined assumptions and suggest novel analyses and experiments. Evelyn Fox Keller
refers to the linguistic habits of geneticistshabits that I have tried to
master and also tried to avoid being fooled by. Keller reminds us that the
genomes program is dynamic and reactive. John Dupr emphasizes that
individuals are in fact combinations of multiple genomes. It is sometimes
easy to overlook inconvenient facts that violate our abstractions, but as
Mike Fortun celebrates in his marvelous meditation on Toll!, an openness to the genomes surprises can gratify and motivate.
Adrian Mackenzie shows how as the genomes shape moves from linear to high dimensional, it provides more features than anyone can possibly
interpret. In light of this, we may need to move to alternative representations of physiology that are more integrative. But, as Hallam Stevens makes
clear in his analysis of network metaphors in postgenomics, the distinction
between reductionist and holist is more complex than we thought. Epigenetics, for example, is thought to provide a nonreductionist mechanism
for studying the interaction between gene regulation and the environment.
As Sarah Richardson argues in her examination of maternal-fetal epigenetics, however, epigenetics claims often mirror classic genetic reductionist explanations in their focus on the mechanism of regulation of gene
expression. Similarly, Sara Shostak and Margot Moinester point out that
looking at environmental measures at multiple levels (molecular, cellular,
tissue, organism) involves forms of reductionism that inevitably obscure
some dimensions of the environment, including high-level environmental
abstractions such as a neighborhood.
Intriguing questions about the reward and funding structure of the sciences accompany the postgenomic moment. One example is the increasingly dispersed nature of scientic knowledge production. As we integrate
multiple databases, the legitimate coauthorship claims of data curators suffer from their distance (in both place and time) from the other authors.
Rachel A. Ankeny and Sabina Leonelli explore how we can give credit to
those who have shared and annotated data. Funders such as the National
viii foreword

Institutes of Health greatly benet genome research, but funding focused


principally on genomics can lead to distortions. Aaron Panofsky examines
how certain areas of behavioral genetics have been lavishly rewarded despite consistent failure to deliver, while Catherine Bliss looks at how genomics research in the eld of race- and ethnicity-based health disparities
may be crowding out public health and social science approaches.
Postgenomics: Perspectives on Biology after the Genome delivers important
scientic and social messages. One scientic message is that the genome
sequencing projects were neither unmitigated successes nor failures, but
rather the start of a newly enabled era in which determining the sequence
of four dna bases is easy, but understanding its role in biological systems
is incredibly challenging. One social message is that postgenomics should
not be simply the playground of former genomicists now turned postgenomicists. Instead, there is a credible argument for a reset and evaluation
of what the most promising and fruitful areas of investigation are likely to
be. We should resist the temptation to merely declare the obvious next
steps: epigenetics, environmental characterization, and large-scale population sequencing. Rather, we should pause and consider the range of societal and scientic responses to the past fteen years of work and choose
questions and strategies that allow us to marry discovery and its benecial
applications.

russ altman
Palo Alto, California
January 2014

foreword

ix

contributors

russ altman
http://helix-web.stanford.edu/people/altman/
Russ Altman, md, PhD, is a scientist at Stanford University Medical School,
where he is a professor of bioengineering, genetics, and medicine, and of computer science by courtesy. He is chair of the Department of Bioengineering
and director of the program in Biomedical Informatics. Altmans research
focuses on the application of bioinformatics to basic molecular biological
problems. Since the inception of the Human Genome Project, Altman has
played a leading role in the development of genomics database and bioinformatics technologies and of the eld of pharmacogenomics. He is a past
president and one of the founding members of the International Society
for Computational Biology. He is the principal investigator for the Pharmacogenomics Knowledgebase, a database that curates knowledge about the
impact of genetic variation on drug response for clinicians and researchers.
He is also the principal investigator for the Iranian Genome Project. Altman
received his ba in Biochemistry and Molecular Biology from Harvard College and his md and PhD in Medical Information Sciences from Stanford.