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genome is not an end in itself, merely the end ofthe beginning – and the start of the next excit-ing chapter in genomics and genetics.

Already the availability of genetic and physi-cal maps produced by the HGP has dramaticallyaccelerated the successful identification ofgenes involved in relatively rare, single-genedisorders. The next challenge is to apply information about the human genomesequence and its variants to identify genes thatplay a significant role in common human dis-eases, such as cancer, diabetes, heart diseaseand schizophrenia.

Although humans around the globe are99.9% identical in their genetic make-up, the0.1% difference is thought to hold key clues toindividual differences in susceptibility to disease. Taking aim at that critical 0.1%, a five-nation coalition recently launched a highly ambitious, $100 million public-privateventure, called the International HapMap Project, to construct a catalogue of humangenetic variations and how they are organizedalong chromosomes.

Among those playing a pivotal role in thatendeavour is The SNP Consortium (TSC), acollaborative genomics effort of major phar-maceutical companies, the Wellcome Trust andacademic centres. TSC was the major forcebehind the creation of an existing public data-base (dbSNP) which describes 2.8 milliongenetic variants called single nucleotide poly-morphisms (SNPs).

Following the lead of the Human GenomeProject, the HapMap team has enlisted the helpof ethical, legal and social experts to maintainand strengthen the delicate threads of societaltrust, which are likely to come under strain asgenetic and genomic research begin to intersectwith the daily lives of people worldwide.

When completed, the HapMap will serve as atool for researchers trying to discover the genet-ic variations associated with common diseases,as well as variations associated with differencesin drug metabolism and with hallmarks of goodhealth, such as longevity.

The development of new technologies andstrategies for the large-scale, high-throughputgeneration of biological data at relatively lowcost has been crucial to the success of genomicsresearch in the past 15 years. However, there isstill an urgent need to improve and add to ourexisting tool kit of technologies for performinghigh-throughput analysis of the human

For nearly 100 years the medicalcommunity has been aware ofheredity’s powerful role inhuman health and disease. Yet awide chasm filled with scientificuncertainties has stood betweenthat understanding of the princi-ples of human genetics and medicine’s ultimate aim of allevi-

ating human suffering. A bridge is now on thehorizon. Equipped with our new-found knowl-edge of the genetic Book of Life – the humangenome – the world’s leading scientists are lay-ing the foundation for a genomics revolutionthat will change the face of medicine in the21st century.

This is one revolution that should take no oneby surprise. In contrast to most other ambi-tious scientific undertakings, the HumanGenome Project (HGP) has been internationalsince its inception. Although the US investedthe largest amount in HGP, many nations –including the UK, France, China, Germany andJapan – have made critical contributions.

HGP leaders also agreed at the outset torelease all mapping and sequencing data intothe public domain immediately, making theinformation freely available to the worldwidescientific and pharmaceutical communitieswithout restrictions on access or use.

Furthermore, in a highly unusual step for abasic science enterprise, the US HGP set aside3-5% of its budget for research on the ethical,legal and social implications of this exponentialincrease in knowledge about humans’ geneticmake-up. In the past, analysis of the ethical,legal and social consequences of a scientificrevolution were often not addressed until aftera crisis had arisen.

Taking full advantage of this multidiscipli-nary, multi-institutional, internationalapproach, the HGP has attained historic mile-stones, while consistently running ahead ofschedule and under budget. HGP scientists arecurrently on target to finish the sequence of all3 billion base pairs of human DNA by April2003 – more than two years ahead of scheduleand coinciding with the 50th anniversary ofJames Watson and Francis Crick’s seminal pub-lication of the double-helix structure of DNA.

However, now is not the time for leaders inthe scientific, economic and political arenas torest upon the HGP’s monumental achieve-ments. Obtaining the sequence of the human

Genomics: the comingrevolution in medicine

Sequencing the human genome is not an end in itself, saysFrancis Collins.It is just the startof a revolution in genomics andgenetics that willchange the face of medicine in the 21st century

GENETIC RESEARCH TECHNOLOGY & SCIENCE

GLOBAL AGENDA 2003 153Alfred Pasieka/SCIENCE PHOTO LIBRARY

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genome, along with the wide array of proteinsproduced by these genes. Indeed, one of myinstitution’s most audacious goals for the nextdecade is to establish technologies that willallow us to sequence a person’s entire genomefor $1,000 or less.

Bear in mind that it will do people little goodto learn about the genetic variations that pre-dispose them to illness if medicine can offer noassistance in averting or treating such suffering.Identification of a gene or collection of genesthat contributes to disease represents the initialstep in a multipronged process of moving basicgenetic and genomic knowledge into the med-ical mainstream (see diagram, right).

Typically, the first practical payoffs of a genet-ic discovery are new or improved diagnostictests. By 2010 it is expected that validated, pre-dictive genetic tests will be available for asmany as a dozen common conditions. Thesetests will enable individuals who wish to learnmore about their personal disease susceptibil-ities to take preventive steps to reduce the riskof their developing a condition.

Such steps could take the form of close med-ical surveillance such as more frequent mam-mography or colonoscopy screening, lifestylemodifications such as changing diet, avoidingenvironmental triggers or increasing exercise,or preventive drug therapy similar to the cur-rent use of cholesterol-lowering agents in peo-ple at risk of coronary artery disease.

Beyond diagnosis and screeningGene-based tests will by no means be limited todiagnosing disease or screening for diseasesusceptibility. The discovery of genes for drugresponsiveness is likely to lead to predictivetests to determine whether a person is likely tohave a good or bad reaction to a specific phar-maceutical agent.

The expectation is that many such gene-drugcorrelations will be found over the next decades,fuelling the growth of a rapidly emerging fieldknown as pharmacogenomics and eventuallyenabling doctors to tailor their prescribing practices to each person’s genetic profile. Inshort, medicine’s current “one size fits all”approach to managing patients will become athing of the past.

One much-publicized application of geneticknowledge – gene therapy – burst on to thescene in the early 1990s, generating hopeamong patients that it could provide quick solu-tions to a long list of medical problems.

However, this strategy, which uses geneti-cally engineered viruses or other vectors toinsert a “healthy” copy of the gene into anaffected person’s cells, has suffered a series ofdisappointments over the past few years. Theseincluded the death of a young man in a USmedical trial in 1999 and the development ofvector-induced cancer in a child in a French trialin 2002.

Still, it remains likely – after researchers havespent more time at the bench answering basicscience questions more thoroughly and devel-oping safer, more effective vectors – that genetherapy will re-emerge to play a significant rolein the treatment of some diseases.

Although grabbing fewer headlines thangene therapy, an equally promising or even

common drugs and disorders. More predictivegenetic tests for disease susceptibility willbecome available, to be used not only for peoplewith a strong family history of a disorder butalso for healthy people who are seeking toenhance their chances of staying well.

Despite these exciting projections, there willbe tensions. Antitechnology movements,already active in the US and elsewhere, are like-ly to gain momentum as the focus of geneticsturns even more intensely towards humanapplications. Efforts at public education need to start now to explain the potential benefits of genetic medicine and to be honest about the risks.

The public also remains deeply concerned,about the possibility that genetic informationwill be misused in a discriminatory manner –an issue that must be dealt with effectively bygovernments worldwide. Even the most excit-ing clinical breakthroughs generated by genom-ic science will come to nought if they are metwith a societal backlash.

As is the case with most other hi-tech medicaladvances, access to health care is a major issue.It is clear that millions of people in both indus-trial and developing nations will be deprived ofnew genetics and genomics advances unlessmany medical care systems change in signifi-cant ways.

Some observers also discount the importanceof genomics to the developing world. However,a better understanding of the genetic factorsthat influence susceptibility and/or responseto various infectious diseases, including malar-ia, tuberculosis and AIDS, could have a greatimpact on health in the developing world.

Furthermore, genomics holds the promise ofreducing the research and development costs ofvaccines and pharmaceutical agents, whichshould help make such products more availablethroughout the world. The continued vigoroussupport of science is critical to realizing thispromise of a revolution in medical practice.

But science alone is no match for all thesedaunting global challenges. Sustained partner-ships must be developed between leaders inthe field of genetics and their counterparts in allrealms of society – from public policy to inter-national economics, from corporate decision-making to elementary education.

The World Economic Forum provides astrategic opportunity for such partnerships tobe formed and strengthened. GA

more promising therapeutic approach isgrounded in using new-found genetic andgenomic knowledge to gain a better under-standing of the underlying biology of disease.

Identification of each genetic variant confer-ring disease risk will point towards a criticalpathway for that illness, often immediately sug-gesting targets for pharmaceutical therapy.Many of these pathways will come as a sur-prise, given our limited understanding of themolecular basis of most common diseases.

In response to the dominant role thatgenomics is likely to play in future drug devel-opment, the pharmaceutical industry is alreadygearing up to put in place efficient, high-volumemethods of developing and designing thesmall-molecule drugs needed to target biolog-ical pathways.

At the same time, basic scientists are contemplating ways of using small-moleculecompounds as probes in their efforts to chart more precisely the complex pathwaysaffected by different genetic variations and gene mutations.

This area of activity is just one of severalexamples that highlight the potential forincreased interactions between academic sci-entists and the private sector in the genome era.

Such efforts are already starting to pay off, asindicated by the development in 2000 of the tar-geted drug STI-571, or Gleevec, which has pro-duced dramatic responses in people sufferingfrom otherwise untreatable chronic myeloge-nous leukaemia.

Gleevec was discovered using informationabout an abnormal protein produced because ofa genomic rearrangement found to occur inleukaemic cells.

Given the large amount of genetic andgenomic information already collected aboutvarious types of cancer, it is likely that withinthe next two decades all cancer patients willhave their malignancies genetically “finger-printed” and their therapies will be individual-ly targeted to those fingerprints.

In fact, by 2020 the impact of genetics andgenomics on medicine is likely to be far moresweeping than any of us can envisage today.Among the developments we can expect arethe introduction of new gene-based designerdrugs for diabetes, high blood pressure, mentalillness and many other conditions that cur-rently take such a high toll on individual lives,as well as economic productivity.

We can also expect that the pharmacoge-nomics approach for predicting drug respon-siveness will be standard practice for many

CV FRANCIS COLLINSFrancis Collins, MD, PhD is director of the US National Human GenomeResearch Institute.

Genetics leads to a range of treatment strategies