Biotechnology and the Human Genome: Innovations and Impact

178 Pages·1988·11.124 MB·English

by  Jack B. McConnell (auth.), Avril D. Woodhead, Benjamin J. Barnhart, Katherine Vivirito (eds.)

BIOTECHNOLOGY AND
THE HUMAN GENOME
Innovations and Impact
BASIC LIFE SCIENCES
Alexander Hollaender, Founding Editor
Recent volumes in the series:
Volume 34 BASIC AND APPLIED MUTAGENESIS: With Special Reference
to Agricultural Chemicals in Developing Countries
Edited by Amir Muhammed and R. C. von Borstel
Volume 35 MOLECULAR BIOLOGY OF AGING
Edited by Avril D. Woodhead, Anthony D. Blackett, and
Alexander Hollaender
Volume 36 ANEUPLOIDY: Etiology and Mechanisms
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Volume 38 MECHANISMS OF DNA DAMAGE AND REPAIR: Implications
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Volume 39 ANTIMUTAGENESIS AND ANTICARCINOGENESIS MECHANISMS
Edited by Delbert M. Shankel, Philip E. Hartman, Tsuneo Kada,
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Volume 40 EXTRACHROMOSOMAL ELEMENTS IN LOWER EUKARYOTES
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Edited by Avril D. Woodhead and Keith H. Thompson
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Edited by Avril D. Woodhead, Michael A Bender, and Robin C. Leonard
Volume 44 GENETIC MANIPULATION OF WOODY PLANTS
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Volume 45 ENVIRONMENTAL BIOTECHNOLOGY: Reducing Risks from Environmental
Chemicals through Biotechnology
Edited by Gilbert S. Omenn
Volume 46 BIOTECHNOLOGY AND THE HUMAN GENOME: Innovations and Impact
Edited by Avril D. Woodhead and Benjamin J. Barnhart
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Edited by Oliver Nelson
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BIOTECHNOLOGY AND
THE HUMAN GENOME
Innovations and Impact
Edited by
Avril D. Woodhead
Brookhaven National Laboratory
Upton, New York
and
Benjamin J. Barnhart
u. S. Department of Energy
Washington, D.C.
Technical Editor
Katherine Vivirito
Brookhaven National Laboratory
Upton, New York
SPRINGER SCIENCE+BUSINESS MEDIA, LLC
Library of Congress Cataloging in Publication Data
Science Writers Workshop on Biotechnology and the Human Genome (1987:
Brookhaven National Laboratory)
Biotechnology and the human genome: innovations and impact 1 edited by Avril O.
Woodhead and Benjamin J. Barnhart; technical editor, Katherine Vivirito.
p. cm.-(Basic life sciences; v. 46)
"Based on the Science Writers Workshop on Biotechnology and the Human
Genome, held September 14-16,1987, at Brookhaven National Laboratory, Upton,
New York"-T.p. verso.
Includes bibliographies and index.
ISBN 978-1-4684-5549-6 ISBN 978-1-4684-5547-2 (eBook)
DOI 10.1007/978-1-4684-5547-2
1. Human chromosomes-Analysis-Congresses. 2. Chromosome mapping
Congresses. 3. Biotechnology-Congresses. I. Woodhead, Avril O. II. Barnhart, Ben
jamin J. III. Title. IV. Title: Human genome. V. Series.
[ONLM: 1. Base Sequence-congresses. 2. Biotechnology-congresses. 3.
Chromosome Mapping-congresses. 4. Genetic Intervention-congresses. W3
BA255 v. 46 1 TP 248.6 S416b 1987J
QH431.S37781987
573.2'12-dc19
DNLM/OLC 88-22398
for Library of Congress CIP
Based on the Science Writers Workshop on Biotechnology and the
Human Genome, held September 14-16,1987, at
Brookhaven National Laboratory, Upton, New York
© 1988 Springer Science+Business Media New York
Ori9inally published by Plenum Press, New York and London in 1988
Softcover reprint of the hardcover 1s t edition 1988
All rights reserved
No part of this book may be reproduced, stored in a retrieval system, or transmitted
in any form or by any means, electronic, mechanical, photocopying, microfilming,
recording, or otherwise, without written permission from the Publisher
PREFACE
This book is based on the proceedings of the Science Writers Workshop
on "Biotechnology and the Human Genome: Innovations and Impacts" held at
the Brookhaven National Laboratory on September 14-16, 1987. The aim of
this workshop which was sponsored by the Office of Health and Environmental
Research of the Department of Energy (DOE) was to provide a forum in which
science writers, reporters and other interested individuals could gain a
firsthand knowledge about the scope and direction of the human genome initi
ative and its supportive technologies. The speakers were leaders working in
scientific disciplines that are either integral parts of the Department's
genome project or that represent important ancillary science.
The Department of Energy's human genome initiative is a logical ex
tension of its long term commitment to investigating genetic damage from
exposures to radiations and energy-related chemicals. It will exploit comp
utational, engineering and biological capabilities within and as well as
outside the DOE national laboratories to develop the technologies and re
sources which will lead to a complete description of the human genome at the
molecular level. Knowledge of the entire human genetic map and the genomic
sequence will allow investigators to more rapidly and effectively identify
genes involved in genetic diseases, individual variabilities including radi
ation sensitivities, and physiological processes, as well as to make unpre
cedented inroads into evolutionary relationships.
Investigators in national laboratories, universities, and industry are
developing new technologies and using them to construct physical maps of
human chromosomes made up of linearly ordered fragments of DNA, developing
new techniques for use in determining the chemical sequence of the genetic
code, and improving data acquisition, storage and analysis capabilities
using the computer resources such as those at the Los Alamos National Labor
atory. These and related technological developments in the fields of biol
ogy, chemistry, physics, instrumentation, automation and computing will play
a key role in scientific research aimed at gaining a better understanding of
human biology. It is anticipated that this and several other Departmental
initiatives will strengthen the Nation's economic and technological competi
tiveness and set the stage for the biology of the 21st century.
Many of our colleagues put a great deal of effort into ensuring the
success of our meeting and we are most grateful to them. In particular, we
thank our coordinator, Helen Kondratuk, for creating an optimal environment
for the meeting. Neal Tempel's sensible suggestions saved the day for us
more than once. Nancy Siemon carefully and patiently transcribed and pre
pared the manuscripts.
v
COMMITTEE
Avril D. Woodhead, Chairperson
Benjamin Barnhart
Charles P. DeLisi
Richard B. Setlow
Benno P. Schoenborn
Helen Z. Kondratuk, Workshop Coordinator
vi
CONTENTS
Whence We've Come, Where We're Going, How are We
Going to Get There? ............................................. 1
J. B. McConnell
Overview of Human Genome Research .................................... 5
C. P. DeLisi
Mapping the Genome ................................................... 11
C. R. Cantor and C. L. Smith
Human Genome Sequencing .............................................. 29
W. Gil bert
Establishing the Order of Human ...................................... 37
Chromosome-Specific DNA Fragments
A. V. Carrano
The Genbank Database and the Flow of Sequence
Data for the Human Genome ....................................... 51
C. Burks
Proteins: Dynamics and Function ...................................... 57
M. Karplus
The Use of Neutrons to Show How Proteins Work ........................ 63
A. A. Kossiakoff
Synchrotron Radiation: A Probe for Biomedical
Research ........................................................ 79
R. M. Sweet
Round Table Forum. The Human Genome Initiative:
Issues and Impacts .............................................. 93
Moderator: B. J. Barnhart
Discussants: F. J. Ayala
T. H. Murray
W. Gilbert
J. C. Cassatt
M. W. Bitensky
DNA Sequencing Technology ............................................ III
M. A. Kashdan and G. L. Trainor
The Practicability of and Necessity for Developing a Large-Scale
DNA-Base Sequencing System: Toward the Establishment
of International Super DNA-Sequencing Centers ................... 119
A. Wada
vii
High Resolution Electron Microscopy for Structure
and Mapping .................................................... 131
J. F. Hainfeld and J. S. Wall
Applications and Implications of Genome Related
Biotechnology .................................................. 149
T. Friedmann
The Human Genome Project: A Doe Perspective .•.•.......•.....•........ 161
Benjamin J. Barnhart
Participants ........................................................ 167
Index ............................................................... 171
viii
WHENCE WE'VE COME, WHERE WE'RE GOING,
HOW WE'RE GOING TO GET THERE
Jack B. McConnell
Johnson and Johnson
1, Johnson and Johnson Plaza
New Brunswick, NJ 08933
I will discuss three points on mapping and sequencing the human
genome. My first concern is the increasing rate and pace of change in
health care, which occurs throughout the whole of society, as it also
occurs in data management and information, but is especially marked in the
health care field. The second concern is the sense of urgency with which I
feel we should approach this task. The implications for clinical medicine
of knowing the sequence of the human genome are absolutely staggering. The
ability to diagnose, treat, and possibly eliminate hereditary diseases is
an opportunity that we should move on to with dispatch. There also are
economic concerns, which I will discuss later. The third point is the or
ganization necessary to achieve the task of mapping and sequencing. It
will be a difficult task. So far, the field of science and technology has
operated as a cottage industry and that may not serve the nation well in
this situation. We may need to create a different organization to achieve
the task.
There are changes moving through the health care field that hardly
would have been imagined a few years ago, certainly not a few decades ago.
The life expectancy of a man born in 1900 was 48 years, for a woman it was
52 years. It is now 72 and 78 yrs respectively, which has given our popu
lation a 50 percent increase in life expectancy in one generation. Never
before in the history of humankind have we been able to achieve anything
such as this. A few years added here and there in the 19th century in
creased the life expectancy by 6-8 percent for the whole century. This
increased life expectancy of 50 percent is outstanding. We may even begin
now to think about reaching our maximum lifespan, and the time may soon
come when most of us live out our lives in health and die within a very
narrow age range.
What are the reasons for this? There are several. The one I like
best comes from one of my favorite philosophers, Woody Allen, who said,
"Some people try to achieve immortality through their offspring or their
works, but I prefer to achieve it by just not dying!" There are other
reasons for increased longevity, such as improved sanitation and better
nutrition. Of the whole list, those may be the two most important ones.
Other reasons are better diagnosis and treatment of disease and improved
education on health care, but undergirding and supporting the whole of this
is our research and development system. In no other country in the world
is there a research and development system anywhere near as vigorous as
that in the United States.
What have been the results of that system? The research and develop
ment system has been the driving force that has moved the health care field
through two technical revolutions in my working lifetime, and we are now
well into the third. The results of the system are that three of the ten
leading causes of death known in 1940 will be abolished in 1980. The three
that will not be on that list in 1980 are tuberculosis, syphilis and gas
tritis. They will be replaced with three others: colonic diseases, liver
diseases and homicide. All of these changes are results of our lifestyle.
An interesting point is that in 1990 suicides, which are decreasing in
actual numbers and in proportion to other causes of death, probably will be
squeezed off the list. Homicide will probably be number nine, and number
ten will be replaced by, of all things, admission to the hospital, which is
a frightening thought. We have reached this point now and I want to ex
plain some of the technical revolutions that have help produced these
changes.
The first was a revolution in chemistry, which originated back in the
19th century in the dye industry of Germany, and, over a short span of two
decades, resulted in many drugs being made available to the public. There
is need to comment on the value of penicillin, antibiotics and sulfona
mides. The polio vaccine wiped out one of the greatest scourges that we
ever had. Every state in the union had a tuberculosis hospital back in the
forties and the fifties; most had more than one. Now there is not a single
one; the last was closed in the seventies. Antipsychotic agents allowed us
to open up the psychiatric hospitals and empty out three-quarters of the
beds.
The chemistry revolution was followed closely by a revolution in
instrumentation, and in fact, overlapped it a little in that span of just
twenty years--the sixties and seventies. Lasers were used for the repair
of the detached retina, and more and more often in surgery. Ultrasound,
non-harmful diagnostic agents, and pacemakers were used to control and
regulate the function of the cardiovascular system. Heart and lung
machines served as a basis for establishment of the open heart surgery;
without these bypass surgery would not have been possible. Dialysis equip
ment extended the life of many people. No one can imagine practicing now
without these ubiquitous patient-monitoring systems. All of these are now
fairly common and literally emerged within two decades.
Now we are moving into the third technical revolution, and in many
ways probably the most dramatic. It will have the most profound and long
lasting impact on the health care system in the nation and the world. We
are in the very early stages of this biotechnological revolution. Already
we have developed six products that are available to patients: Ql, Q2
growth hormones, two alpha-interferon products, hepatitis B vaccine, and
OKT3. These do not seem much for the length of time that the work has been
going on, but in 1986 1200 patents in the United States were issued in
field of biotechnology. Over half of them were products and materials that
were in, or related to, health care. These products are just the forefront
of a wave of new products that will give us new insights into the diagnosis
and treatment of diseases and a better understanding of the disease pro
cess. We have hardly launched these products nor ourselves into biotech
nology before we are faced with the opportunity to map and sequence the
entire human genome, a project that has hardly thought possible a handful
of years ago. Now it is not only possible, but it should be done, and I
would suggest with some sense of urgency. If we expect the U.S. to main
tain its predominant position in the health care field and the pharmaceu
tical industry then we have to fully support this opportunity to map and
sequence the human genome. The first group or institution to achieve
access to the data contained in the human genome will be in a position to
dominate the biotechnology and pharmaceutical industries for decades.
2