Encyclopedia of Cell Technology.pdf
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ENCYCLOPEDIA OF
CELL TECHNOLOGY
VOLUME 1
Raymond E. Spier
University of Surrey
Guildford, Surrey
United Kingdom
A Wiley-lnterscience Publication
John Wiley & Sons, Inc.
New York / Chichester / Weinheim / Brisbane / Singapore / Toronto
ENCYCLOPEDIA OF
CELL TECHNOLOGY
VOLUME 2
Raymond E. Spier
University of Surrey
Guildford, Surrey
United Kingdom
A Wiley-lnterscience Publication
John Wiley & Sons, Inc.
New York / Chichester / Weinheim / Brisbane / Singapore / Toronto
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
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For ordering and customer service, call 1-800-CALL-WILEY.
Library of Congress Cataloging in Publication Data
Encyclopedia of cell technology / [edited by] Raymond E. Spier.
p. cm.
ISBN 0-471-16123-3 (cloth : set: alk. paper) —ISBN (invalid)
0-471-16643-X(v. 1 : alk. paper). —ISBN 0-471-16623-5 (v. 2 :
alk. paper).
1. Animal cell biotechnology Encyclopedias. 2. Plant cell
biotechnology Encyclopedias. 3. Cell culture Encyclopedias.
4. Cytology Encyclopedias. I. Spier, R. (Raymond)
TP248.27.A53E53 2000
660.6 —dc21
99-25295
Printed in the United States of America.
10 987654321
PREFACE
The Wiley Biotechnology Encyclopedias, composed of
the
Encyclopedia of Molecular Biology,
the
Encyclopedia
ofBioprocess 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 three-
dimensional 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 organ-
ism (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 pro-
teins. 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 cor-
relations 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 struc-
tures 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 com-
plexes 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 organ-
ism, 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 neu-
rons making approximately 1,015 connections. From this
network arise systems properties such as memory, con-
sciousness, and the ability to learn. The important point is
that systems properties cannot be understood from study-
ing 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, 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 con-
nections. 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 math-
ematicians into biology—just as the attempts to decipher
the information of complete genomes and the protein fold-
ing 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, two-
dimensional gel electrophoresis and other global protein
separation technologies, mass spectrometric analysis of
proteins and protein fragments, multiparameter, high-
throughput cell and chromosome sorting, and high-
throughput phenotypic assays.
A second approach to the deciphering and manipula-
tion of biological information centers around combinatorial
strategies. The basic idea is to synthesize an informa-
tional string (DNA fragments, RNA fragments, protein
fragments, antibody combining sites, etc.) using all combi-
nations 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.
A critical approach to deciphering biological infor-
mation will ultimately be the ability to visualize the
functioning of genes, proteins, cells, and other informa-
tional elements within living organisms (in vivo informa-
tional imaging).
Finally, there are the computational tools required to
collect, store, analyze, model, and ultimately distribute
the various types of biological information. The creation
presents a challenge comparable to that of developing
new instrumentation and new chemistries. Once again
this means recruiting computer scientists and applied
mathematicians to biology. The biggest challenge in this
regard is the language barriers that separate different
scientific disciplines. Teaching biology as an informational
science has been a very effective means for breeching these
barriers.
The challenge is, of course, to decipher various
types of biological information and then be able to
use this information to manipulate genes, proteins,
cells, and informational pathways in living organisms to
eliminate or prevent disease, produce higher-yield crops,
or increase the productivity of animals for meat and other
foods.
Biotechnology and its application raise a host of
social, ethical, and legal questions, for example, genetic
privacy, germline genetic engineering, cloning of animals,
genes that influence behavior, cost of therapeutic drugs
generated by biotechnology, animal rights, and the nature
and control of intellectual property.
Clearly, the challenge is to educate society so that
each citizen can thoughtfully and rationally deal with
these issues, for ultimately society dictates the resources
and regulations that circumscribe the development and
practice of biotechnology. Ultimately, I feel enormous
responsibility rests with scientists to inform and educate
society about the challenges as well as the opportunities
arising from biotechnology. These are critical issues
for biotechnology that are developed in detail in the
Encyclopedia of Ethical, Legal, and Policy Issues in
Biotechnology.
The view that biotechnology is an informational
science pervades virtually every aspect of this science,
including discovery, reduction of practice, and societal
concerns. These Encyclopedias of Biotechnology reinforce
the emerging informational paradigm change that is
powerfully positioning science as we move into the twenty-
first century to more effectively decipher and manipulate
for humankind's benefit the biological information of
relevant living organisms.
Leroy Hood
University of Washington
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