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The Meanin OiThe Double Hdk
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The Meannig OiThe Double
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PHlLlPPE GOUJON
Universite' Catholique de lille
France
World Scientific
Singapore. New Jersey. London Hong Kong
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FROM BIOTECHNOLOGY TO GENOMES
The Meaning of the Double IIelix
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Foreword
At the time of writing this foreword (June 1998), the genome of 15 unicellular
species have been completely sequenced and made available to the scientific
community: ten Eubacteria, four Archaebacteria and yeast, thc only
eucaryotic cell so far.
During the last three years, the amino acid sequences from over 35,000
proteins uiicoded by these genomes have been deciphered. More than 10,OOO
proteins thus unveiled have an unknown fLinction and are members of new
protein families yet to be identified. The sequence of each new bactcrial
genome (with the possible exception of E. coli) provides the microbiologist
with a huge amount of fi-esh metabolic infomation, far in excess of that
already in existence.A surprisingly large biochemical diversity in the bacterial
world has been revealed. If over a million bacterial species exist, of which
only approximately 3,000 have so far been cultured, then the enormous task
of identifying the bacterial world through the sequencing of its geiiomes is
still to be accomplished. Dozens of sequencing centers (rapidly expanding
to become hundreds in number) all over the world are undertaking this task,
which will result in the discovery of thousands of new proteins. These
figures do, however, call into question the exploitation of this data.
Each one of these bacterial genonies forins a tier of biotechnological
information, the exploitation of which will create new catalysts, hopefiilly
inore efficient and more specific, but less detrimental to the environment
than most of the chemical processes currently in use. When the plant and
animal kingdoms have been fully exploited by the human race, the
domestication of a still largely-unexplored and immense world will remain
- that of the Eubacterial and Archebacterial kingdoms.
V
vi From Biofechnology to Genomes:A Meaning for the Double Helix
In the next few years, a considerable portion of the sequencing of bacterial
genomes could be performed in developing countries, where labor costs are
low. It is, however, to be expected that the industrial exploitation of this
newly available knowledge will continue to be carried out primarily by large
multinational corporations. Whatever the outcome, the race for the
identification and exploitation of new microbial enzymes is on; we can only
hope that, in$ne, it will be beneficial to mankind as well as to the preservation
of other living species. Equally important as the production of new industrial
enzymes, newly acquired panoramic knowledge of pathogenic microbial
genonies will considerably speed up the development of new vaccines and
antibiotics.
In addition to harnessing of the bacterial world, it is easy to imagine the
quantitative and qualitative increases in plant productivity which will result
fi-om the complete knowledge of the genomes of some one hundred plant
species, which currently constitute the core of our food source. Moreover,
it is possible to predict the elimination of the potent parasites currently
responsible for the untimely deaths of millions of people each year by
thoroughly understanding of their metabolism. This knowledge will not be
complete until their genomes have been sequenced.
Sa, what will the repercussions on the medical world would be, that will
be brought about by knowing the sequence of all the proteins constituting
over 200 cell types which make up the human body? All the large
pharmaceutical coinpanies are investing heavily in medical genomics, from
which they are hoping to create new drugs, new diagnostic tools and new
genetic treatments. The extent of these investments is somewhat surprising,
as mentioned by Philippe Goujon in his book, since the financial return
appears risky and, at best, will only be obtainable in the long term. I mi,
nevertheless, convinced that the reading of the human genome is a necessary
(though not, of course, the only) step in the molecular biology of all essential
human biological functions, which sooner or later will be used to the benefit
of medical knowledge and ultimately mankind.
This optimism isjustified by my belief in the intrinsic value of scientific
knowledge and by the extraordinary progress in molecular genetics in the
past 25 years. It has flourished from the first genetic transformation of
Foreword vii
bacteria to the first complete sequence of microbial genomes, including
yeast, and will lead to the complete sequence of the human genome, hopefiilly,
by the year 2005.
In the following pages, the science historian Philippe Goujon describes,
in detail, the action talcen by the European Commission in the domain of
biotechnology. He has compiled a comprehensive amount of documentation
and has dug deep into the archives and the ineinories of pioneers such as
Fernand Van Hoeck, Dreux de Nettancourt, Etienne Magnien, Ati Vassarotti
and Mark F. Cantley, who were (or are still) key players in the birth and
development of biotechnology programs at the European Commission.
Philippe Goujon has placed this European effort in a scientific, sociological
and industrial context going back to the beginning of the 20th Century.
Although the European effort has become much more prolific than initially
predicted, Philippe Goujon highlights the still dominant contributions of the
United States of America and multinational corporations to the massive
industrial exploitation of molecular biotechnology which, after a first half-
century of progressive iinplementation, will undoubtedly triumph during the
21st Century. Philippe Goujon, an informed observer, incticulously describes
the succession of scientific discoveries which have resulted in the recent
discovery of the complete sequence of genomes. Finally, as a scientific
philosopher, he makes his position clear on the future of genomics and its
possible implications. He also gives a concluding analysis of the role of
science in our society.
This coinprchcnsivc analysis, based on remarkable documentation, is a
massive and unique undertaking. I am pleased to have been able to foster
the writing of a book which, I believe, will become a classic in the
contemporary History of Science.
Professor Andrk Goffeau
UniversitC catholique dc Louvain
Unit6 dc Biochimie Pysiologiquc
2, Place Croix du Sud
1348 Louvain-la-Neuve
Belgium
Contents
Foreword
Introduction: The Essence of Life and the Labyrinth of
...
the Genome Xlll
1 The Invention of Biotechnology 1
1.1 The Origins of Biotechnology 5
1.2 The Emergence of a New Concept of Life 11
1.3 From Zymotechnology to Biotechnology 13
1.4 The Engineering of Nature -Towards thc Best of all
Possible Worlds 21
1.5 Technique, Biology and the Development of Biotechnics 23
1.6 The Recognition of Biotechnology by the Institutions 43
2 Political Interpretations of Biotechnology and the Birth of
the First Research Programs 62
2.1 The Example of the United States 64
2.2 Biotechnology in Japan: Economic Success and
Ecological Failure 73
2.3 Germany and the Political Aspect of Biotcchnology 78
2.4 The British Development of Biotechnology : Delayed
Political Reaction 84
2.5 Thc French Reaction 90
2.6 The European Community and Biotechnology -The
Emergence of the First European Biotechnology Programs 92
ix
x From Biotechnologyto Genomes:A Meaning for the Double Helix
3 The Foundations of the Heralded Revolution 116
3.1 From the Frontiers of Genetics to the Birth of
Molecular Biology 116
3.2 The Secret of Life: DNA 126
3.3 The First sequencing of a Protein: Insulin 135
3.4 Techniques of DNA Sequencing 139
3.5 Gene Money, or the Miracles Expected of Biotechnology 161
3.6 The Japanese Threat and the Human Frontier
Science Program 174
4 Attack on the Genomes: The First Genetic and Physical Maps 182
4.1 The Problem of Gene Localization 182
4.2 Polymorphic Markers, Gene Mapping and the
Great Gene Hunt 185
4.3 Towards a Complete Linkage Map 194
4.4 Physical Genome Mapping: The Reconstruction of a
Complicatedhzzle 202
4.5 The First Physical Maps of Large Genonies 205
4.6 Towards a Physical Map of the Human Genome 215
5 The Human Genome Project and the Interiiational
Sequencing Prograins 217
5.1 The Ultimate Challenge: The Human Genome Project 218
5.2 The Department of Energy Initiative 230
5.3 The NIH Genome Project 245
5.4 HUGO, or the Difficulties of International Coordination 252
5.5 The Iniportance of Model Organisms 267
5.6 The International Dimensions of Genome Research:
The First Stirrings in other Countries 273
6 European Bioteclinology Stratcgy and Sequencing
the Yeast Genome 327
6.1 Towards a New European Research Policy for
Biotcchnology 328
Contents xi
6.2 The 1980s: An Implenientationof the 1983 Strategy? 34 1
6.3 3AP’s First Year 353
6.4 The Revision of the BAP Program 359
6.5 The Origins andNature of the Yeast Genome
Sequencing Project 369
6.6 Critical Discussions and the Adoption of the Yeast
Genome Sequencing Project 382
7 The Decryption of Life 42 1
7.1 The Structure and Organization of the European
Yeast Genome Sequencing Network 421
7.2 A World First -The Sequence for a Whole Eucaryote
Chromosome: Chromosome111 of the Yeast
Succhuro~~iycc~eerse visiue 434
7.3 The Complete Sequence of the Genome and the
Intensification of European Efforts 45 1
7.4 After the Sequence -The Challenge of Functional
Analysis 487
7.5 Sequences, Sequences and More Sequences 511
7.6 From Science to Economics 606
8 Conclusion: The Dreams of Reason or the New Biology’s
Dangerous Liaisons 643
8.1 Fascination but Anxiety Concerning Progress in the
Life Sciences 643
8.2 Reductionism vis-u-vis the Complexity of Life 648
8.3 Froni Science to Ideology -The Dangers of
“The Genetic All” 658
8.4 The Health Excuse -A New Utopia? 666
8.5 Behind Gene Therapy - The Dangerous Liaisons
of the New Biology 676
8.6 Convenient Reductionism 683
8.7 The Reasons Behind an Ideology 684
