Basic Bioethics Glenn McGee and Arthur Caplan, series editors Pricing Life: Why It’s Time for Health Care Rationing Peter A. Ubel Bioethics: Ancient Themes in Contemporary Issues edited by Mark G. Kuczewski and Ronald Polansky The Human Embryonic Stem Cell Debate: Science, Ethics, and Public Policy edited by Suzanne Holland, Laurie Zoloth, and Karen Lebacqz Engendering International Health: The Challenge of Equity edited by Gita Sen, Asha George, and Piroska Östlin Self-Trust and Reproductive Autonomy Carolyn McLeod What Genes Can’t Do Lenny Moss What Genes Can’t Do Lenny Moss A Bradford Book The MIT Press Cambridge, Massachusetts London, England © 2003 Massachusetts Institute of Technology All rights reserved. No part of this book may be reproduced in any form by any electronic or mechanical means (including photocopying, recording, or informa- tion storage and retrieval) without permission in writing from the publisher. This book was set in Sabon by SNP Best-set Typesetter Ltd., Hong Kong and was printed and bound in the United States of America. Library of Congress Cataloging-in-Publication Data Moss, Lenny. What genes can’t do / Lenny Moss. p. cm.—(Basic bioethics) “A Bradford Book” Includes bibliographical references and index. ISBN 0-262-13411-X 1. Genetics—Philosophy. I. Title. II. Series. QH430 .M674 2002 660.6¢5—dc21 2001056298 Contents Series Foreword ix Acknowledgments xi Introduction xiii 1 Genesis of the Gene 1 2 The Rhetoric of Life and the Life of Rhetoric 51 3 A Critique of Pure (Genetic) Information 75 4 Dialectics of Disorder: Normalization and Pathology as Process 117 5 After the Gene 183 Notes 199 References 205 Index 217 Series Foreword We are pleased to present the sixth volume in the series Basic Bioethics. The series presents innovative book-length manuscripts in bioethics to a broad audience and introduces seminal scholarly manuscripts, state-of- the-art reference works, and textbooks. Such broad areas as the philos- ophy of medicine, advancing genetics and biotechnology, end-of-life care, health and social policy, and the empirical study of biomedical life will be engaged. Glenn McGee Arthur Caplan Basic Bioethics Series Editorial Board Tod S. Chambers Carl Elliot Susan Dorr Goold Mark Kuczewski Herman Saatkamp Acknowledgments The following individuals contributed to the realization of this work and have my everlasting gratitute: Mina Bissell, Paddy Blanchette, Jeff Botkin, Nancy Burke, Candace Brower, Andrew Cooper, Caroline Damsky, Mary Davis, Alexis Kurland Deeds, Eric Kurland Deeds, Bert Dreyfus, Brian Eden, Arthur Fine, Paul Griffiths, Joseph Heath, David Hull, Kuni Kaneko, Karin Klein, Elizabeth Lloyd, Ed Manier, Thomas McCarthy, Paul Millea, Leslie Mulligan, John Opitz, Susan Oyama, Beverly Packard, Gordon Parry, Bill Ramsey, Bob Richards, Kate Ryan, Phil Sloan, John Stubbs, Suzanne Tronier, Steve Watson, Steve Weinstein, and Bill Wimsatt. Extra-special thanks go to Angela Alston, Carolyn Gray Anderson, David Depew, Steve Downes, Sabrina Haake, Glenn McGee, Bob Perlman, and Harry Rubin. A portion of this research was supported by funding from the ELSI program through the Center for Genetic Science in Society at the University of Utah. Introduction There can be little doubt that the idea of “the gene” has been the central organizing theme of twentieth century biology. And biology, especially since the inception of its molecular revolution of the 1940s and 1950s, has become increasingly influential in academic venues, including phi- losophy, public life and policy, medicine and the health sciences gener- ally, and in everyday self-understanding. More recently the promises and prospects of new biotechnology to cure diseases and offer novel repro- ductive options, and correlatively to win or lose fortunes on the stock market, both further magnified by media attention associated with the Human Genome Project, have brought the gene into even greater public prominence. The selection of my topic was motivated by the high stakes that our understanding of biology has come to have on a variety of levels. Intellectually, in its impact on the humanities, arts, and human sciences; ethically, in its formative effect on human identities and our underlying interpretation of what it means to be human; and socially, with respect to the defining, normalizing, and pathologizing of human difference. The title What Genes Can’t Do is meant to recall What Computers Can’t Do by Hubert Dreyfus and to suggest, by analogy, my aspiration to influence a powerful social-technical trend by way of a philosophically guided, empirically argued critique. Philosophically speaking, what I hope to provide is a platform upon which new naturalistic lines of thought can interweave biological and sociocultural threads at a very fundamental level. Above all, the present work hopes to contribute to freeing the “naturalizing” enterprise from the unnecessary burdens of preformationistic baggage and thereby better xiv Introduction to allow for the re-embedding of the self-understanding of human lan- guage and knowledge in contingent social and developmental processes. In the course of attempting to get the story right about genes a wide variety of issues are addressed, often in the context of minidialogues with a variety of key contributors, some from the remote past and others from the hot-off-the-press present. In order to help the reader ward off the danger of losing the forest for the trees, I will first offer a brief overview of the text. The work begins with a wide-ranging historical reconstruction and conceptual analysis of the meaning of “the gene” that results in defining and distinguishing two different genes. Each of these can be seen as an heir to one of the two major historical trends in explaining the source of biological order: preformationism and epigenesis. The preformation- ist gene (Gene-P) predicts phenotypes but only on an instrumental basis where immediate medical and/or economic benefits can be had. The gene of epigenesis (Gene-D), by contrast, is a developmental resource that pro- vides possible templates for RNA and protein synthesis but has in itself no determinate relationship to organismal phenotypes. The seemingly prevalent idea that genes constitute information for traits (and blueprints for organisms) is based, I argue, on an unwarranted conflation of these two meanings which is, in effect, held together by rhetorical glue. Beyond this historical, conceptual, and rhetorical inquiry the bulk of this work then concerns itself with an empirically up-to-date analysis of the cell and molecular basis of biological order and of the pathological loss of the same. In each of these chapters I structure my analysis with the idea in mind that the conflated view can be held empirically accountable. I do not conjure up straw men to represent that position but rather use what I take as the most historically influential formulations of the gene-as- information-for-phenotypes position as my points of reference. In the first instance I use Schrödinger’s early and highly influential thermody- namic argument for why a solid-state “aperiodic crystal” must be the core of biological order. The task here is really twofold: first to recall that Schrödinger had a real argument for the promotion of his famous hereditary code-script metaphor and second to indicate how and why we can now see that his Introduction xv argument was mistaken. In the second instance, that concerning disor- der, my principal point of reference is the somatic mutation hypothesis. Albeit in evolving forms, some version of the somatic mutation hypoth- esis has dominated cancer biology throughout the twentieth century. I mean to show how a bifurcation in the understanding of cancer com- menced with the “phylogenetic turn” that took place at the beginning of the twentieth century and resulted in an ongoing dialectic between genetic determinists at the center and developmentalists at the margins. I have reconstructed the history and fortunes of the somatic mutation hypothesis program in part to give shape and philosophical meaning to the recurrent challenges that have been brought forth from the margins. Philosophers of biology have hitherto steadfastly avoided the topic of cancer (almost as if talking about it could make it catching). But in con- sidering the loss of organismic order (and the corresponding emergence of malignant order) philosophically charged questions about the dis- tinction between normal and pathological come quickly to the fore. Carefully considered, the research trajectory of the somatic-mutation hypotheses when confronted by its own empirical shortcomings provides some of the most cogent evidence against the conflated preformationist view from which it arose. With this somewhat bare-boned structure in mind, I will now try better to prepare the reader for some of the winding curves and vistas that come up along the way. A main objective of chapter 1 is to account for how a putatively misguided notion of the gene could have possibly arisen and in so doing to clarify just what is conceptually at issue. My principal strategy is that of reconstructing the conceptual pathway to our contemporary genes as a highly contingent transformation of those basic life concepts which held sway during the nineteenth century. Telling this story is complicated by the need to debunk two pervasive myths about the life sciences—namely, that realbiology only begins with Darwin and that the conceptual ground of genetics owes its existence to some chancy rediscovery of the work of Mendel. The particular bone I have to pick with these myths has nothing to do with the giving or taking of scientific credits but rather with their role as impediments to a coherent conceptual history of our most basic bio- logical concepts. With respect to the nineteenth century, I have benefited