ARTICLE The Human Project

BY STEPHEN SCHERER

RÉSUMÉ ‹ Il existe désormais une séquence préliminaire de ABSTRACT ‹We now have a draft sequence of the entire human l’ensemble du génome humain et de la plupart des gènes encodés. genome and most of the it encodes. Here we explain what Dans le présent article, nous expliquons ce qu’est le génome, ce the genome is, what it means to sequence it, outline how the que représente son séquençage et comment il a été réalisé, avant sequencing was done, and reflect on what this means for the way d’aborder une réflexion sur l’incidence de cette découverte sur we do science and, more fundamentally, how we understand notre façon de faire de la recherche scientifique et, sur un plan plus ourselves. A comprehensive description of the is fondamental, sur notre connaissance de nous-mêmes. La descrip- the foundation of human biology and the essential prerequisite for tion complète du génome humain constitue le fondement de la an in-depth understanding of disease mechanisms. As such, biologie humaine et la condition essentielle à la connaissance information generated by the sequenced human genome will approfondie des mécanismes de la maladie. Comme telle, l’infor- represent a source book for biomedical science in the 21st century. mation découlant du séquençage du génome humain équivaudra à It will help scientists and clinicians to understand, diagnose and un guide de référence pour la science biomédicale XXIe siècle. Elle eventually treat many of the 5000 genetic diseases that afflict aidera les chercheurs et les cliniciens à comprendre, diagnostiquer humankind, including the multifactorial diseases in which genetic et finalement traiter nombre des 5 000 maladies génétiques qui predisposition and environmental cues play an important role. : KATY LEMAY affligent l’humanité, notamment les maladies plurifactorielles dans lesquelles la prédisposition génétique et les éléments environne-

mentaux jouent un rôle important. (Traduction : www.isuma.net) ILLUSTRATIONS isuma 11 the

enes are instructions that contrary to “garbage” which we, and dna was painstakingly slow and give organisms their charac- the cell, throw away). expensive. Sequencing the entire teristics. The instructions are human genome seemed impractical. storedG in each cell of every living The Human Genome Project Others felt it made more sense to organism in a long string-like mole- and DNA sequencing focus research effort and money only cule called Deoxyribonucleic Acid “Sequencing” is the process of deter- on discovering particular genes (dna). dna molecules are subdivided mining the specific order and identity thought to be associated with dis- into finite structures called chromo- of the three billion base pairs in the eases, rather than trying to spell out somes (Figure 1). Each organism has a genome with the ultimate goal of iden- the entire genome. However, even for characteristic number of chromo- tifying all of the genes. “Mapping” is disease projects aimed at finding sin- somes. For humans the number is 46 the process of identifying discrete dna gle disorders (such as that for (23 pairs) and this complete set of segments of known position on a cystic fibrosis) the worldwide cost genetic information is called the which are then used for could often run in the tens of millions genome (Figure 2). sequencing (mapping is a crucial step dollars before success was achieved. for proper reconstruction of the The idea for the human genome pro- DNA, genes and genome; it usually precedes sequenc- ject eventually won support, justified Human dna looks like a twisted lad- ing but is also necessary in post- as an investment in fundamental bio- der with three billion rungs. If sequencing). To give one a sense of the logical infrastructure upon which the unwound, your dna would stretch enormity of the task to decode the scientific community around the over five feet, but it is only 50 tril- human genome, a simple listing of all world would build exciting new lionths of an inch wide. The total of the atcg combinations would fill research that would lead to the diag- amount of dna in the 100 trillion or hundreds of phone books. And hav- nosis and treatment of disease. so cells in the human body laid end to ing the sequence is only a first step in The enormity of the challenge end would run to the sun and back finding the genes, understanding how inspired the creation of an interna- some 20 times. The three billion rungs they operate, and how particular tional, publicly funded research ini- are made up of chemical units, called genetic discrepancies are associated tiative called the Human Genome “base pairs,” of nucleotides — with diseases. Using this dna sequence Project (hgp), officially launched in adenines, thymines, cytosines and gua- information to diagnose, prevent or the early 1990s. The Human Genome nines, represented by the letters A, T, treat those genetic predispositions or Organization (hugo) brings together C and G. Particular combinations of causes of disease is an even more com- over 1000 scientists from 50 countries these dna base pairs (or genes) consti- plex task. worldwide, and has a mandate that tute coded instructions for the forma- When the idea of sequencing the includes promoting international col- tion and functioning of , which human genome was first proposed laboration within the hgp. The earli- make up the body and govern its bio- about 15 years ago, it was highly con- est genome meetings were attended by logical functioning (examples of pro- troversial. For one thing, given the a rag-tag group of usually fewer than teins include insulin, collagen, diges- technology at the time, sequencing 100 biologists of diverse background tive enzymes, etc.). Ribonucleic acid, (rna) is a single stranded copy of dna that acts as an intermediate messenger FIGURE 1 molecule that allows dna sequence to be translated to . This central process, whereby dna transcribes to Gene rna, which in turn transcribes to pro- Nucleus Cell tein, underlies all of life. Some genes are made up of only a DNA few hundred base pairs, others run to a couple of million base pairs. It is now estimated that we have around 30,000 to 40,000 genes (much more work will be required to determine the precise Protein number), but those genes account for less than five percent of our dna, with the rest being filler. For lack of a better term, the non-genic dna is often dubbed “junk” since its role is not ful- ly known (in fact this might be a good Figure 1. The human genome consists of 23 pairs of chromosomes that are comprised of DNA. Approximately 5% of the DNA along the chromosome encodes for genes. Genes make term since just like the cell we often proteins. Proteins provide cellular structure and functional activity within the body. keep our “junk” just in case we need it

12 Autumn • Automne 2001 the human genome project

FIGURE 2 It will likely take two to three years for the draft 1 23 45form ofthe dna sequence to reach 6 7 8 9 10 11 12 what is considered 181716151413 to be in a finished 19 20 21 22 X Y state.

Figure 2. The 23 pairs of human chromosomes one from each pair being inherited from one parent. Note the interchange of material between chromosomes 7 and 13 which disrupts a gene leading to disease.

and research interests, only a few of dyed nucleotides can attach them- whom had some type of vision of how selves to the dna fragments, but other to accomplish this distant goal (Fig- nucleotides will not adhere to the dyed ure 3). Since 1990, the strategies and nucleotides. Thus the chemical reac- measures of successes of the hgp have tion generates dna fragments of vari- most often been debated at an annual ous length that each terminate at flu- meeting held in Cold Spring Harbor ourescently dyed A, T, C or G Laboratories, New York (directed by nucleotides. The underlying sequence , co-discover of dna). for the range of the dna fragments The most accurate documentation of created in the chemical reaction is then the science and progress behind the determined by an automated sequenc- genome project can be found within ing machine. The synthesized dna the abstracts of this meeting. The ear- fragments are negatively charged. The ly consensus was that before large- sequencing machine sets up an electri- scale and cost-effective sequencing of cal field. The dna fragments move the entire genome could be complet- through a pourous gel toward the pos- ed, numerous technological develop- itive charge, with shorter fragments ments, associated with mapping and moving more quickly through the gel. sequencing processes as well as with The fluorescent, tagged bases at the the computational capacity to make end of the fragments can be detected sense of the resulting information, with the help of a laser, and the result- were essential. ing information stored on a comput- With developments in technology er. As a result, the order in which the over the last few years, the seqencing particular tagged nucleotides are read is now done through a process called reflects their order on the stretch of fluorescence-based dideoxy sequenc- dna that has been replicated in the ing (Figure 4a). Fragments of dna are chemical reaction. first cloned in . They are then Each reaction reveals the sequence put into a chemical reaction with free of about 500 letters (A,T,C,G) of dna nucleotides, some of which are tagged before the process runs its course. Once with fluorescent dyes. Nucleotides these relatively tiny sequences are attach themselves to the dna frag- obtained, their place in the overall ments in a particular order. Similarly, genome dna sequence must be deter- isuma 13 the human genome project

Having the FIGURE 3

sequence is only a DNA cloning and sequencing 1970-80s Concept for human linkage maps Polymerase chain reaction 1985 Discussions of a human genome effort first step in finding Automated DNA sequencing 1986 Human Gene Mapping Workshops Cloning large DNA molecules 1987 First human linkage map the genes, under- Positional cloning 1989-1990 Human Genome Organization forms

New genetic markers 1990-1991 Human Genome Project begins

standing how they Gene prediction algorithms 1992-1996 Genetic maps completed operate, and how Whole genome shotgun 1993-1998 Physical maps completed SNPs and microarrays 1998-2000 DNA sequencing begins particular genetic Comparative DNA sequencing 2000 “Draft” DNA sequence 2000-2005 DNA sequence annotation discrepancies are Figure 3. Timeline of the Human Genome Project (HGP). A historical summary of some of the enabling technologies (on the left) and the achievements (on the right) leading up to and including the associated with HGP are shown. The formal international HGP began around 1990. Other aspects of the HGP are the study of model organisms, analysis of genome variation, and the development of bioinformatics. Establishing training and public education programs, as well as the study of the ethical, legal, and social issues of research in society are also important diseases. priorities.

mined. To achieve a working draft dna the decision to collect only partial ous times in fragments of about 500 sequence of the genome, two approach- data from each dna fragment, hence, base pairs. Identifying where those es were followed. The hgp began by a working or rough draft (the change individual fragments fit in the overall creating a detailed map that would pro- of strategy was partly due to the dna is accomplished through the use vide a framework for the subsequent launching of a privately funded com- of powerful computers that analyze dna sequencing. Numerous dna pany, Celera, which decided to deter- the raw data to find overlaps. “markers,” that is segments with an mine the dna sequence of small pieces The wgs approach was used by sci- identifiable location on the chromo- of human dna totally at random entists at The Institute for Genomic some (Figure 4b), were generated using the “whole genome shotgun” Research to generate the first complete through many worldwide initiatives. (wgs) approach described below). sequence of a self-replicating organism This enabled the hgp to break Working draft dna sequence usually called Haemophilus influenzae as well down the genome into about 30,000 covers 95 percent of the genome as many other single-cell organisms. sections, each containing an average of (maintaining 99% accuracy) but it is The advantage of wgs is that the 100,000 to 200,000 base pairs (Figure divided into many unordered seg- upfront steps of constructing maps are 5). For the actual sequencing, each of ments with gaps between. Additional not needed. For organisms with much these sections was broken down into sequencing is required to generate the larger and more complex genomes, still smaller fragments, of about 2000 finished dna sequence such that there such as the fruitfly Drosophila base pairs. Initially, the plan was to are no gaps or ambiguities, and the melanogaster and humans, assemblies put the fragments to be sequenced in final product is greater than 99.99 of sequences are expected to be com- order, followed by complete sequence percent accurate. At the time of writ- plicated by the presence of a vast num- determination of each fragment in a ing, close to 90 percent of the human ber of repetitive elements (approxi- systematic manner so that the entire genome sequence has been determined mately 50% of human dna is repeats!). human dna sequence would be (approximately 70% of this in work- Notwithstanding, Celera initiated a revealed. This ‘clone-by-clone’ method ing draft and 30% in finished form). wgs project of the Drosophila genome produces highly accurate sequence A second approach to generating a and in doing so, 3.2 million sequence with few gaps. However, the upfront draft sequence of the human genome reads were completed (giving a 12.8 process of building the sequence maps is the whole genome shotgun (wgs) times coverage of the 120 Mb (million is costly, time consuming and there- associated with Celera Corporation. bases) genome). Based on these data, fore can be progress-limiting. In wgs, sufficient dna sequencing is 115 Mb of dna sequence were assem- In 1998, to accelerate progress, a performed so that each nucleotide of bled and, although it was quite com- major deviation from this plan was dna in the genome is covered numer- prehensive, the genome was still divid-

14 Autumn • Automne 2001 the human genome project

FIGURE 4 If a segment of dna

A. B. 7 has been conserved 22 GACACCCGG 21 15.3 G A C A CC C GG 15.2 throughout 15.1 14 13 12 11.2 11.1 evolution, it almost 11.1 11.21 11.22 11.23 GACATCCGG 21.1 always encodes a 21.2 G A C A TC C GG 21.3 22 31.1 31.2 gene or a regulatory 31.3

32 33 34 CASPR2 element controlling 35 36 the expression of Figure 4. Techniques of the HGP. (A) DNA sequencing and (B) positioning a gene on a chromosome, in this case the CASPR2 gene on human . that gene.

ed by 1630 gaps. Closure of the gaps is using the dna markers and maps from being completed with the help of the the hgp. maps generated by the hgp. It will likely take another two to Following the experience gained three years for the draft form of the from the Drosophila melanogaster dna sequence to reach what is con- project, Celera planned a whole sidered to be in a finished state. This genome assembly of human dna. The work is ongoing around the world in aim of the project was to produce big and small laboratories alike. The highly accurate, ordered sequence completeness and accuracy of these spanning more than 99.9 percent of versions of the human genome the human genome. Based on the size sequence will be tested by many types of the human genome and the results of experimentation over the next from the Drosophila experiment, it decade. In future dna sequencing pro- was predicted that over 70 million jects, as is currently ongoing for the sequencing reactions would need to be mouse genome, a combination of the completed. The alignment of the clone-by-clone and wgs strategies will resulting sequence assemblies along likely become the standard because the genome would be accomplished they are largely complementary. using the large number of dna mark- ers (including genes, see figures 4b and Annotation of the 5) and physical maps generated by the human genome DNA sequence ongoing hgp. Since sequencing efforts Ascribing functional meaning to all were escalated by the publicly funded the genes and other important biolog- hgp (and released each night on the ical information encoded by the dna Web) using its approach, Celera could in our genome will be the ultimate also easily integrate this data into their goal of the hgp. This process is often assemblies thereby greatly reducing the called “annotation.” With this infor- amount of sequencing required. In the mation, it will be possible to investi- end, Celera completed approximately gate the roles of all of the gene prod- 28 million reads and merged these ucts, how they are controlled, how data with dna sequence in public they interact, and how they might be databases. The final sequence assem- involved in disease. The process of blies were ordered along chromosomes annotating the human dna sequence isuma 15 the human genome project

About 5,000 FIGURE 5 human diseases are Chromosome

Chromosome region known to have a Genetic marker Expressed sequence tag genetic component, Gene

YAC clones and 1,000 disease- (1,000,000 bp)

BAC clones associated markers (100,000 bp)

or genes have Sub-clones for DNA sequencing ATCGGGTCTTTCGGAACGT already been (1000 bp)

Figure 5. Systematic mapping and sequencing of human chromosomes using a clone-by-clone approach. DNA markers from a chromosome region are positioned and simultaneously used isolated. to order large cloned DNA molecules (called YACs and BACs). BACs are broken down in ‘sub- clones’ for DNA sequencing. Obtaining partial sequence of the BACs represents ‘draft’ sequence. In the whole genome shotgun approach (WGS) the intermediate steps of cloning and mapping BACs and YACs are not completed. It is estimated there are 3 billion A,T,C,and G’s in the human genome.

will take several forms including the the sequence atg, end with tag, tga unique functions such as specific fer- catalogue of the genes; the identifica- or taa, and the boundaries between tilization (Figure 7). tion of the genes and dna sequence introns and exons are often defined by Current estimates put the number of variations that either directly cause or the dinucleotides at and cg, respec- genes in the human genome at between are associated with disease; and the tively (Figure 6). 30,000 and 40,000. The precise num- study of variation between individu- Another powerful approach to find- ber continues to be hotly debated, and als in the population. ing genes is to compare the dna it could very well be that there are Cataloguing the genes: Just as diffi- sequence between two organisms to upwards of 50,000 to 60,000 or more cult as constructing maps or determin- search for shared elements (Figure 7). genes in the genome. Discrepancy in ing the dna sequence of the human If a segment of dna has been con- numbers can be attributed to different genome will be identifying all of the served throughout evolution it almost interpretations in the definitions, and genes it encodes. As mentioned earli- always encodes a gene or a regulatory the use of different datasets which, in er, the genes comprise less than five element controlling the expression of every case, are still largely incomplete. percent of the dna scattered through- that gene. Almost every human gene For example, at present we only know out the three billion nucleotides of known can also be found in the the complete sequence from start to genetic information. To complicate genomes of other mammalian species end of about 25 percent of the 30,000 matters, human genes almost always (e.g., mice and dogs) with the similar- to 40,000 genes that have been pre- appear as discontinuous segments of ity of the two sequences often exceed- dicted using computer algorithms. dna along a chromosome divided into ing 85 percent. The genomes of One of the most interesting obser- gene-coding regions (exons) and non- humans and chimpanzees are 98.5 vations to come out of genome coding regions (introns) (Figure 6). To percent identical. Some genes, includ- sequencing is that the number of genes complicate matters further, there are ing those that encode proteins involved does not necessarily correlate with dna stretches that do not encode for in replicating dna (and are thus organism complexity or its place in the proteins but, instead, the rna molecule absolutely crucial to survival of every evolutionary hierarchy. For example, performs a biological function within organism), are highly conserved in the fruitfly Drosophila melanogaster the cell. Notwithstanding, most genes every species from human all the way has 13,000 genes and comprises 10 have characteristic features that can be down the evolutionary tree to yeast times more cells than the worm C. ele- identified using computer programs and bacteria. Other genes that origi- gans, which has 19,000 genes. trained to search for these identifiers. nated from a common progenitor have Disease gene identification: The For example, genes usually start with evolved between species to have immediate medical application of

16 Autumn • Automne 2001 the human genome project

human genome information is in iden- FIGURE 6 tification of genes associated with dis- ease, and the pursuit of new diagnos- tics and treatments for these diseases promoter exons intron (Figure 8). About 5,000 human dis- ATG TAA GTAG GT AG eases are known to have a genetic DNA component, and 1,000 disease-associ- ated markers or genes have already Transcription been isolated over the years. Until the RNA 1980s, the primary strategy for iden- tifying human genetic disease genes Processing was to focus on biochemical and phys- iological differences between normal AAAAAAAAA mRNA and affected individuals. However, for the vast majority of inherited single- gene disorders in humans, biochemi- cal information was either insufficient protein or too complicated to give insight into the basic biological defect. In the early 1980s an alternative Figure 6. Anatomy of a gene. While genes occupy less than 5% of the DNA on a chromosome they strategy was introduced that suggest- often have characteristic features that allow them to be identified amongst the so-called ‘junk’ DNA. Promoters are the regions of DNA that turn genes on and off. Most genes start ed disease genes could be isolated sole- with ATG and end with TAA, TGA, or TAG. The GT and AG di-nucleotides usually flank the parts ly on their location along the chromo- of genes (exons) that code for proteins. RNA and messenger RNA (mRNA) are intermediates to the production of proteins. some. This approach, now called “positional cloning,” consists of first determining which of the 23 chromo- somes the disease gene resides on. Then genes on the chromosome are systematically tested for dna sequence FIGURE 7 changes (or mutations) that occur only in the family members having the dis- Mouse gene ease but which are not found in unaf- fected individuals. Prior to the initiation of the hgp, Trip6 ZAN Cip1 Eph4b Epo Rpp20 Tfr2 Gnb2 Baf53b PerQ1 Ache Hs.157779 ASR2 the disease gene for Duchenne/Becker 1 250,000 muscular dystrophy, cystic fibrosis and TFR2 a few others were identified. With the BAF53B development of new mapping resources GNB2 and technologies generated by the hgp, PERQ1 the positional cloning process was RPP20 greatly simplified. This has accelerated EPO the pace of discovery of new disease ZAN genes including those for fragile x syn- drome, Huntington disease, inherited

Human gene EPHB4 breast cancer, early onset Alzheimer disease and many others. CIP1 With the hgp sequence now well TRIP6 ASR2 advanced, it becomes possible to dis- Hs.157779 sect the molecular genetics of multi- ACHE 1 250,000 factorial diseases such as cancer and cardiovascular disease which involve Figure 7. Genes conserved between species. Thirteen human genes on human chromosome 7 are multiple combinations of genes and compared to the equivalent genes in the mouse genome. A 45 degree line between indicates strong environmental components. the DNA sequence of the human and equivalent mouse gene is >85% identical. The deviation at the intersection of the zonadhesin (ZAN) genes occurs because each encodes a protein The study of these common diseases that is involved in the process of species-specific fertilization of sperm to egg. Therefore, will require careful patient and family during evolution the DNA sequences of these genes diverged from each other to fulfill the role of making a protein unique to the survival of that organism. data collection, thorough clinical examination, systematic dna analysis and complex statistical modeling. isuma 17 the human genome project

We now face the FIGURE 8

more daunting Diagnostic tests Carrier tests Population screening Basic defect responsibility of Disease pathology having power Gene/Protein therapy over the genetic cure Figure 8. Applications of the Human Genome Project. The immediate application of the human genome information are identification of genes associated with disease, and development of diagnostic and predictive tests. Based on this information the pursuit of new treatments for destiny of our these diseases can be pursued. own species. Human genome sequence variation: grasp of human history, evolution of There are many types of variation in the human gene pool and our basic the human genome with single understanding of genome evolution. nucleotide changes (snps) being the For example, studies of dna variation most frequent occurring in one of have revealed that the vast majority of 1000 nucleotides. Therefore, on aver- genetic diversity (>80%) occurs age, each genome contains approxi- between individuals in the same popu- mately three million snps. Other dna lation even in small or geographically sequence variations include copy num- isolated groups. Moreover, most vari- ber changes, insertions, deletions, ation seems to predate the time when duplications, translocations, inver- humans migrated out of Africa around sions and more complex rearrange- 200,000 years ago. Therefore, the con- ments, but these are not as frequent. cept of homogeneous groups (or races) There are, thus, significant differences having major biological differences is between the genome of the two par- not consistent with genetic evidence. ents whose chromosomes come together to form new life. This genet- The Human Genome Project ic variation is the basis of evolution. and society It is this genetic variation that con- With the success of the hgp, we have tributes, in part, to health and to each overcome the psychological barrier of individual’s unique traits. However, cracking nature’s code and now face when dna sequence variants occur the more daunting responsibility of within genes or affect their expression, having power over the genetic destiny disease can sometimes result. of our own species. As such, the hgp Technological advances, availabili- joins the ranks of the other massive ty of genetic markers and higher reso- scientific undertakings of the 20th lution snp maps generated by the hgp century — splitting of the atom and have revolutionized the study of the conquest of space—in transform- human genetic variation. The bio- ing civilization. And, just as Galileo’s medical applications include identify- work was foundational to proving the ing variations within specific genes Copernican theory which debunked that cause or predispose to disease, the notion that the earth was the cen- finding gene-environment interactions tre of the universe, the hgp proves that might have toxologic implications there are human-to-animal dna and identifying variations in immune sequence links, thus substantiating response genes that will have implica- Darwin’s theory that we are not a tions for transplantation and vaccine unique life form. With this informa- development. tion, the hgp promises to give us pro- The study of human genome vari- found knowledge as the basis to ability has also greatly improved our understanding how our minds work,

18 Autumn • Automne 2001 the human genome project to be able to quantitate nature and through all of this information we will the past, our biological evolution nurture, and increasingly, to be able design even more massive computers (based on genes) was slow and ran- to alter our genetic constitution. and newer technologies. And the time dom caused by the changes in the Our preoccupation with dna has between acceptance of a new technol- environment, whereas, our cultural already shed light on historical puzzles ogy and its application will only evolution (based on ideas) was fast such as the roots and migrations of become shorter. To keep up with this and purposeful due to frequent for- ancient peoples, historical demography revolution we may be forced to mation of new ideas and technologies of cultures and human genetic diversi- redesign ourselves using the same to disseminate them. In the future, we ty. We now know that the age-old prej- tools that brought on the change. may be able to catalyze evolution in udices of caste, race or royalty, which It took less than 50 years from the the same way as cultural change has granted undue importance to biologi- discovery of the structure of the dna occurred. It will be the responsibility cal inheritance, have no substantial molecule in 1953 to the cracking of of all in society to ensure that there is genetic basis. The hgp gives the scien- the human genetic code. In the proper education and adequate dis- tific basis for promoting the concept of upcoming years, scientists will work cussion of these topics to ensure the one race and of equal opportunity for vigorously on the hgp to find new best decisions are made for our all at the beginning of life. Sadly, this genes, to determine the function of the species as a whole as we move for- knowledge, on its own, is unlikely to gene products and to apply all of this ward. Therefore, programs studying be enough to overcome deeply embed- information to the study of common ethical, legal and societal implications ded racial and other prejudices. diseases. While the hgp will not be a of genetic information will be as Each success of the hgp, from con- cure-all, for some diseases there will important to success in applying the ceptualization through to mapping be cures in our lifetime. And because hgp knowledge as continued support and dna sequencing, followed close of the hgp, preventive medicine of the science. behind advances in technology and through early diagnosis and directive implementation of new strategies, one genetic counselling will, over time, Stephen W. Scherer is a Senior Scientist in building on the other. This large-scale, move to the forefront of health care, Genetics and Genomic Biology and Associate technology-driven approach will epit- replacing our current reactive system. Director of The Centre for Applied Genomics at The omize how science is to be conducted Perhaps more difficult than the Hospital for Sick Children in Toronto. He is also in the 21st century. To identify genes genetic science will be the social and Associate Professor in Molecular and Medical involved in disease we will determine moral implications of this knowledge. Genetics at the University of Toronto. His labora- tory has contributed to mapping, sequencing and the differences in dna specific to those It raises issues of genetic privacy and gene identification studies on human chromosome afflicted. To identify traits unique to ownership of our genome, not to 7 as part of the HGP. He is currently Chair of the Homo sapiens we will study differ- mention human cloning, social Dar- Human Genome Organization (HUGO) Annotation ences in dna between species. To sort winism and perhaps even eugenics. In Committee.

INTRODUCTION GÉNÉRALE À LA BIOÉTHIQUE Histoire, concepts et outils guy durand

Unique en son genre, cet ouvrage constitue une initiation au vaste et complexe domaine de la bioéthique. S’adressant aux professionnels de la santé comme aux généralistes, Guy Durand étudie les concepts de base, les principes et les grilles d’analyse des principaux auteurs et courants contemporains.

Il s’agit d’une entreprise d’envergure, d’un travail titanesque, «d’une œuvre majeure qui aura un impact considérable. Ce livre sera probablement la référence en bioéthique pendant de nombreuses années, la bible de la bioéthique. Il n’est pas 576 pages • 39,95 $ demain le jour où un autre reprendra cette entreprise… Fides cerf Michelle Dallaire, médecin» • fides isuma 19