BIF402 Handouts Set 2

Encyclopedia of Bioprocess Technology: Fermentation, Biocatalysis, and Bioseparation

Edited by Michael C. Flickinger and Stephen W. Drew

Encyclopedia of Molecular Biology

Edited by Thomas E. Creighton

Encyclopedia of Cell Technology

Edited by Raymond E. Spier

Encyclopedia of Ethical, Legal, and Policy Issues in Biotechnology

Edited by Thomas H. Murray and Maxwell J. Mehlman · ENCYCLOPEDIA OF ETHICAL, LEGAL, AND · EDITORIAL BOARD · David Blumenthal

Massachusetts General Hospital, Boston, Massachusetts

Alexander Capron

University of Southern California Law Center, Los Angeles, California

Thomas Caskey

Merck & Co., Inc., West Point, Pennsylvania

Bartha Knoppers

University of Montreal, Montreal, Canada

Gil Omenn

University of Michigan, Ann Arbor, Michigan

George Rathmann

ICOS Corporation, Bothell, Washington

Charles Sanders

Commonwealth Fund, Chapel Hill, North Carolina

LeRoy Walters

Georgetown University, Washington, DC

James Wyngaarden

Washington, DC

Series Editor

Editorial Staff Executive Editor: Arthur Biderman

Editor: Glenn Collins

Managing Editor: John Sollami

Assistant Managing Editor: Kellsee Chu

Editorial Assistant: Hugh Kelly This book is printed on acid-free paper. Copyright  2000 by John Wiley & Sons, Inc. All rights reserved.

Published simultaneously in Canada.

No part of this publication may be reproduced, stored in a retrieval system or transmitted in any form or by any means, electronic, mechanical, photocopying, recording, scanning or otherwise, except as permitted under Sections 107 or 108 of the 1976 United States Copyright Act, without either the prior written permission of the Publisher, or authorization through payment of the appropriate per-copy fee to the Copyright Clearance Center, 222 Rosewood Drive, Danvers, MA 01923, (978) 750-8400, fax (978) 750-4744. Requests to the Publisher for permission should be addressed to the Permissions Department, John Wiley & Sons, Inc., 605 Third Avenue, New York, NY 10158-0012, (212) 850-6011, fax (212) 850-6008, E-Mail: PERMREQ .

For ordering and customer service, call 1-800-CALL-WILEY.

Library of Congress Cataloging in Publication Data:

Murray, Thomas H. (Thomas Harold), 1926– Encyclopedia of ethical, legal, and policy issues in biotechnology / Thomas Murray,

p. cm. Includes index. ISBN 0-471-17612-5 (cloth : alk. paper)

1. Biotechnology — Moral and ethical aspects — Encyclopedias. 2. Biotechnology

industries — Law and legislation — Encyclopedias. 3. Biotechnology — government policy — United States — Encyclopedias. I. Mehlman, Maxwell J. II. Title.

TP248.16.M87 2000 1740.96606 — dc21 00-021383

Printed in the United States of America.

PREFACE

The Wiley Biotechnology Encyclopedias, composed of the Encyclopedia of Molecular Biology; the Encyclopedia of Bioprocess Technology: Fermentation, Biocatalysis, and Bioseparation; the Encyclopedia of Cell Technology; and the Encyclopedia of Ethical, Legal, and Policy Issues in Biotechnology cover very broadly four major contemporary themes in biotechnology. The series comes at a fascinating time in that, as we move into the twenty-first century, the discipline of biotechnology is undergoing striking paradigm changes. Biotechnology is now beginning to be viewed as an informational science. In a simplistic sense there are three types of biological information. First, there is the digital or linear information of our chromosomes and genes with the four-letter alphabet composed of G, C, A, and T (the bases guanine, cytosine, adenine, and thymine). Variation in the order of these letters in the digital strings of our chromosomes or our expressed genes (or mRNAs) generates information of several distinct types: genes, regulatory machinery, and information that enables chromosomes to carry out their tasks as informational organelles (e.g., centromeric and telomeric sequences). Second, there is the three-dimensional information of proteins, the molecular machines of life. Proteins are strings of amino acids employing a 20-letter alphabet. Proteins pose four technical challenges: (1) Proteins are synthesized as linear strings and fold into precise threedimensional structures as dictated by the order of amino acid residues in the string. Can we formulate the rules for protein folding to predict three-dimensional structure from primary amino acid sequence? The identification and comparative analysis of all human and model organism (bacteria, yeast, nematode, fly, mouse, etc.) genes and proteins will eventually lead to a lexicon of motifs that are the building block components of genes and proteins. These motifs will greatly constrain the shape space that computational algorithms must search to successfully correlate primary amino acid sequence with the correct three-dimensional shapes. The protein-folding problem will probably be solved within the next 10–15 years. (2) Can we predict protein function from knowledge of the three-dimensional structure? Once again the lexicon of motifs with their functional as well as structural correlations will play a critical role in solving this problem. (3) How do the myriad of chemical modifications of proteins (e.g., phosphorylation, acetylation, etc.) alter their structures and modify their functions? The mass spectrometer will play a key role in identifying secondary modifications. (4) How do proteins interact with one another and/or with other macromolecules to form complex molecular machines (e.g., the ribosomal subunits)? If these functional complexes can be isolated, the mass spectrometer, coupled with a knowledge of all protein sequences that can be derived from the complete genomic sequence of the organism, will serve as a powerful tool for identifying all the components of complex molecular machines. The third type of biological information arises from complex biological systems and networks. Systems information is four dimensional because it varies with time. For example, the human brain has 1,012 neurons making approximately 1,015 connections. From this network arise systems properties such as memory, consciousness, and the ability to learn. The important point is that systems properties cannot be understood from studying the network elements (e.g., neurons) one at a time; rather the collective behavior of the elements needs to be studied. To study most biological systems, three issues need to be stressed. First, most biological systems are too complex to study directly, therefore they must be divided into tractable subsystems whose properties in part reflect those of the system. These subsystems must be sufficiently small to analyze all their elements and connections. Second, high-throughput analytic or global tools are required for studying many systems elements at one time (see later). Finally, the systems information needs to be modeled mathematically before systems properties can be predicted and ultimately understood. This will require recruiting computer scientists and applied mathematicians into biology — just as the attempts to decipher the information of complete genomes and the protein folding and structure/function problems have required the recruitment of computational scientists. I would be remiss not to point out that there are many other molecules that generate biological information: amino acids, carbohydrates, lipids, and so forth. These too must be studied in the context of their specific structures and specific functions. The deciphering and manipulation of these various types of biological information represent an enormous technical challenge for biotechnology. Yet major new and powerful tools for doing so are emerging. One class of tools for deciphering biological information is termed high-throughput analytic or global tools. These tools can be used to study many genes or chromosome features (genomics), many proteins (proteomics), or many cells rapidly: large-scale DNA sequencing, genomewide genetic mapping, cDNA or oligonucleotide arrays, twodimensional gel electrophoresis and other global protein separation technologies, mass spectrometric analysis of proteins and protein fragments, multiparameter, highthroughput cell and chromosome sorting, and highthroughput phenotypic assays. A second approach to the deciphering and manipulating of biological information centers around combinatorial strategies. The basic idea is to synthesize an informational string (DNA fragments, RNA fragments, protein fragments, antibody combining sites, etc.) using all combinations of the basic letters of the corresponding alphabet, thus creating many different shapes that can be used to activate, inhibit, or complement the biological functions of designated three-dimensional shapes (e.g., a molecule in a signal transduction pathway). The power of combinational chemistry is just beginning to be appreciated.