Genetics, genomics and the patenting of DNA

Genetics, genomics andthe patenting of DNA

Human Genetics ProgrammeChronic Diseases and Health Promotion

World Health Organization

2005

Review of potential implications forhealth in developing countries

i i

WHO Library Cataloguing-in-Publication Data

Genetics, genomics and the patenting of DNA : review of potential implications for healthin developing countries.

1.Genomics - legislation 2.DNA - therapeutic use 3.Patents - ethics 4.Patents - legislation5.Genetic research - legislation 6.Review literature 7.Developing countries

I.World Health Organization.

ISBN 92 4 159259 1 (LC/NLM classification: QU 33.1)

© World Health Organization 2005

All rights reserved. Publications of the World Health Organization can be obtained fromMarketing and Dissemination, World Health Organization, 20 Avenue Appia, 1211 Geneva27, Switzerland (tel: +41 22 791 2476; fax: +41 22 791 4857; email: [email protected]).Requests for permission to reproduce or translate WHO publications – whether for sale orfor noncommercial distribution – should be addressed to Marketing and Dissemination, atthe above address (fax: +41 22 791 4806; email: [email protected]).

The designations employed and the presentation of the material in this publication do notimply the expression of any opinion whatsoever on the part of the World Health Organizationconcerning the legal status of any country, territory, city or area or of its authorities, orconcerning the delimitation of its frontiers or boundaries. Dotted lines on maps representapproximate border lines for which there may not yet be full agreement.

The mention of specific companies or of certain manufacturers’ products does not imply thatthey are endorsed or recommended by the World Health Organization in preference toothers of a similar nature that are not mentioned. Errors and omissions excepted, the namesof proprietary products are distinguished by initial capital letters.

All reasonable precautions have been taken by WHO to verify the information contained inthis publication. However, the published material is being distributed without warranty ofany kind, either express or implied. The responsibility for the interpretation and use of thematerial lies with the reader. In no event shall the World Health Organization be liable fordamages arising from its use.

Cover by WHO Graphics

Printed in Switzerland

iii

Contents

Acknowledgements v

Foreword vi

Acronyms vii

1Introduction 1

1.1 Goals of this report 11.2 Key issues 21.3 Genomics, genetics and health 21.4 Genetics and health in the developing world 71.5 Patents 8

2The current landscape 15

2.1 Intellectual property systems 152.2 TRIPS and DNA patents 162.3 The genomics industry and patenting 182.4 What some developing countries are doing 242.5 Some early lessons for developing countries 29

3Analysis: impact of DNA patents on access to genetic tests and genomic science 30

3.1 Ethical, legal and social challenges to the patenting of DNA 303.2 Ways in which the patent system may affect access to genetics and genomics 37

4Conclusions 48

4.1 Proposals 494.2 Some final remarks 52

i v

5References 53

6Other reading 61

Articles 61Books 68Proceedings and symposiums 68Reports 69Case Law 71Legislation 72Statements 72

7Notes 74

Appendix 1Glossary of terms 78

Appendix 2Methodology 81

Boxes, figures and tables

Box 1DNA and genes 2

Figure 1Detection rate of cystic fibrosis-causing CFTR mutations 3

Box 2What are DNA genetic tests and what can they tell us? 4

Box 3Genomic medicine in Mexico 6

Box 4Characteristics of the ideal diagnostic test—ASSURED 7

Box 5Australian firm patents “junk” DNA 9

Box 6BRCA—The “Breast Cancer Gene” 13

Box 7Research exemptions 17

Box 8Haemochromatosis 38

Table 1Scientific Review Panel 82

v

Acknowledgements

The present document grew out of a WHOConsultation in April 2002, organized and hostedby the University of Toronto’s Joint Centre forBioethics, a WHO Collaborating Centre. Themeeting was organized to respond to therecommendations of The Advisory Committee onHealth Research (ACHR) report on Genomics andWorld Health (2002), and aimed to develop astrategy to promote genetic services and tostrengthen discussion on genetic ethics. Itsrecommendations emphasized the importance ofan ELSI (ethical, legal and social implications)perspective in considering the implications ofgenomics for health.

This document benefited from the input andguidance of numerous individuals. The HumanGenetics Programme would like to express itsthanks to the University of Toronto Joint Centrefor Bioethics, for its support for this and otherethics-related initiatives of the Programme, as wellas to Louise Bernier, Karen Durell, and E.Richard Gold, of the Centre for IntellectualProperty Policy, McGill University, Montreal,Canada, for drafting the background paper thatformed the basis for the review process, and thedevelopment of this final report. Thanks are alsodue to the following staff from WHOHeadquarters for their helpful feedback on earlierdrafts of this document: Alexander M. Capronand Jason Sigurdson, of the Department of Ethics,Trade Human Rights and Law; and Charles Clift,of the Secretariat for the Commission onIntellectual Property Rights, Innovation and PublicHealth. In addition to members of WHO, several

others generously contributed comments on drafts:R. Cook-Deegan (United States of America),R. Eisenberg (United States), A. Rai (UnitedStates) and P.A. Singer (Canada). A special thankyou also to Eduardo Sabate (Venezuela), for hisvaluable advice and to Rafael Bengoa for hissupport throughout the entire process.

Preparation of the document was undertaken bythe Human Genetics Programme headed byVictor Boulyjenkov. Principal responsibility forwriting and editing rested on Alyna Smith, assistedby Angela Ballantyne. The Programme isparticularly grateful to members of the ScientificReview Panel, for their commentary and advicethroughout the development of this report:Shaikha Al-Arrayed (Bahrain), Amir Attaran(United States), John Barton (United States), KareBerg (Norway), José Maria Cantu (Mexico), Jean-Jacques Cassiman (Belgium), Mildred Cho(United States), Carlos Correa (Argentina),Abdallah Daar (Canada), Prabuddha Ganguli(India), Cathy Garner (United Kingdom of GreatBritain and Northern Ireland), E. Richard Gold(Canada), Vladimir Ivanov (Russian Federation),Patricia Kameri-Mbote (Kenya), Darryl Macer(Japan), Patricia Aguilar-Martinez (France),Sisule Musungu (Switzerland), VictorPenchaszadeh (United States), Sandy Thomas(United Kingdom), Lap-Chee Tsui (China),Ishwar Verma (India), Huanming Yang (China).A complete list of names, including institutionalaffiliations, of the members of the Scientific ReviewPanel can be found in Appendix 2.

v i

Foreword

Rapid advances in genetic technology and humangenome research make it almost certain thatgenetics and genomics will become more and moreimportant for health improvement. If usedappropriately, this knowledge will provide manyexciting future opportunities to achieve betterhealth for all people. However, it is clear that manyindividuals, groups and nations have concernsabout the use and exploitation of genetic data andgenome technology. Biomedical research in humangenetics can lead to the development of diagnosticand pharmaceutical products. Patents may benecessary to raise funding to develop such productscommercially, but patenting also has the potentialto impede access to genetic materials, to theultimate detriment of service delivery to those withgenetic disorders, especially in developingcountries.

While governments have long relied on patentsand other forms of intellectual property to fosterinnovation, in recent years there has been someconcern that patents on genes may hinder researchin the public sector, and push costs too high forwidespread access to medical products and services,particularly for complex diseases such as heartdisease, cancer, diabetes and asthma. However, theextent of the impact of patents on genomicsinnovation and on access to genetic servicescontinues to be a matter about which there is greatdisagreement. The Human Genetics Programme,

with this initiative, aims to draw together existingarguments and evidence to present a picture of thecurrent landscape of the debate, from a pubic healthperspective.

Genetics differs from many areas of research inthat important new knowledge can come from anindividual, a family, or an ethnic group with aparticular genetic variant. Genetic material, andthe information it encodes, therefore has the dualquality of being both personal and communal. Thehuman genome and the segments of DNA thatconstitute it likewise would appear to haveconflicting status of being both proprietary, and acommon heritage. Intellectual property is a systemdeveloped with the ultimate end of promoting thepublic good by fostering the creation of useful newproducts. An important challenge is how to squarethe seemingly competing needs of inventors andcommunities to ensure an equitable distribution ofbenefits.

This report does not look to define policy, but tohighlight areas of contention, suggest avenues forfurther investigation and stimulate dialogue amongdifferent stakeholders. Thus, the report may serveas a point of departure for professionals and publichealth officials to develop policies and appropriatepractices. It expresses the view of the authors anddoes not necessarily represent the policies of theWorld Health Organization.

Dr V. Boulyjenkov, Ph.D, D.Sc.,

Human Genetics Programme

vii

Acronyms

ABS access and benefit sharing

ACHR Advisory Committee on Health Research

AIPPI International Association for the Protection of IntellectualProperty

ARIPO African Regional Industrial Property Organization

BGI Beijing Genomics Institute

BRCA breast cancer gene

CAS Chinese Academy of Science

CBD Convention on Biological Diversity

CHGC Chinese National Human Genome Centre

CVC citrus variegated chlorosis

DMD Duchenne muscular dystrophy

DNA deoxyribonucleic acid

EMR exclusive marketing right

EPO European Patent Office

EU European Union

EST expressed sequence tag

FAPESP State of São Paulo Science Foundation

HGP Human Genome Project

HUGO Human Genome Organisation

IP intellectual property

IPR Commission Commission on Intellectual Property Rights

IPRs intellectual property rights

JPO Japan Patent Office

LDCs least developed countries

MCH Miami Children’s Hospital

OECD Organisation for Economic Cooperation and Development

ONSA Organisation for Nucleotide Sequencing and Analysis

PCR polymerase chain reaction

viii

1

1Introduction

1.1 Goals of this reportAs early as 1963, a World Health Organization(WHO) Expert Committee observed that “geneticconsiderations add a new dimension to public healthwork: a concern not only for the health and well-being of persons now living, but also for (…)generations yet to come” (WHO, 1964).

Nearly 40 years later, WHO’s AdvisoryCommittee for Health Research produced a reporton Genomics and World Health, with the goal ofproviding a realistic picture of the benefits, chal-lenges and limitations of genomics, particularly inrelation to the health needs of the world’s poor.1

The report was published shortly after the comp-letion of the draft sequence of the human genomeand at a time when both expectations and un-certainties about genomics and its likely impacton human health were high. It was therefore timelyto review the science and to wade through thehyperbole surrounding public debate to considerthe realistic possibilities for genomics in terms ofgenerating practical solutions for health. Moreover,the report sought to address widespread concernthat genomics had ushered in new and high-techmethods that would result in both researchapproaches and new interventions beyond the reachof the world’s poor.

The Genomics and World Health report describesthe evolution of genetic science, from Mendeliangenetics and the study of inherited single-genedisorders, to genomics and the comprehensive studyof multiple genes and their interactions. Its authorspostulate that basic molecular genetic methodscould furnish means for developing skills in

genomics, in this way providing a foundation fordeveloping public health-related services (likegenetic tests) while at the same time preparing theground for entry into a growing and promisingfield of biomedical study. Elsewhere it has beensimilarly argued that “most developing countriesnow urgently need to incorporate geneticapproaches (including DNA diagnosis) into theirhealth services. DNA diagnosis is relativelyinexpensive, helps to develop skills in molecularbiology and provides a basis for developingnational expertise in genomics” (Alwan andModell, 2003).

The Advisory Committee on Health Research(ACHR) identifies intellectual property as one ofthe factors affecting the accessibility of the resultsof genomic research and development (WHO,2002). The present report takes up the question ofhow this may be—that is, in what ways intellectualproperty may affect the ability of developingcountries to access genomics, both at the level ofresearch and at the level of health interventions. Itmay be helpful to imagine this report as situated atthe intersection of the ACHR report on Genomicsand World Health, the Nuffield Council onBioethics’ (2002) Ethics of Patenting DNA, andthe United Kingdom Commission on IntellectualProperty Rights (IPR Commission) report (2002)Intellectual Property Rights and DevelopmentPolicy.2 The Nuffield Council on Bioethics report“examine[s] the issues relating to genetics andintellectual property, particularly those thatconcern human healthcare and research related tohealthcare”. Its discussion, however, is in relation

GENETICS, GENOMICS AND THE PATENTING OF DNA2

� the particular needs, both health and tech-nological, of developing countries in rela-tion to genetics, and what this suggests interms of how they should structure theirpatent regimes.

We begin by reviewing briefly the history ofgenomics and its impact on the biomedicalsciences, as well as the relevance of genetics to thehealth needs of developing countries.

1.3 Genomics, genetics andhealth

1.3.1 Mendelian genetics and heritabledisorders

One hundred and fifty years ago Mendel began hisgarden pea experiments, demonstrating that certaintraits are passed from organisms to their progenyaccording to predictable patterns—and, in theprocess, laying the foundations of the field we nowcall genetics.

Disorders that are the product of so-called Mende-lian inheritance are those where a specific trait is

to highly industrialized countries. The last report,on the other hand, explores the relationship betweenintellectual property and development, includingvarious aspects of development that relate to health.But while the concerns of developing countries3

figure prominently, the impact of DNA patents onaccess to effective and affordable products likegenetic tests is not specifically addressed.

This report approaches the issue of intellectualproperty from a public health-centred perspective.It does not look to define policy; rather, its aimsare to shed light on the issues as they exist in thecurrent debate, highlight areas of contention, andsuggest avenues for further investigation. Theproduct of this deliberative process was createdwith the hope that it will stimulate informeddialogue among different stakeholders, and feedusefully into future processes, involving WHO andother entities, to develop policy guidance that isbased on a balanced account of the issues, argumentsand evidence.

1.2 Key issues

The main issues we will consider in our discussionare the following:

� the special ethical, legal, research andmedical challenges raised by DNA pat-ents, with particular reference to genomicindustries;

� the response of different countries, legis-lative and otherwise, to the question ofDNA patents, and the consequences ofthese actions for access to genetic diag-nostics;

� the flexibilities in international frame-works, particularly the Agreement on theTrade Related Aspects of Intellectual Prop-erty Rights (TRIPS), for national policy-making relating to DNA patents; and

Box 1DNA and genes

DNADNADNADNADNA, or deoxyribonucleic acid, is the bio-chemical substance that makes up geneticmaterial. It is a double-stranded moleculecomprising two linear chains made from fourbases (A, C, G and T), together forming a dou-ble helix.

Genes Genes Genes Genes Genes are ordered sequences of nucleotideslocated in a particular position on a particularchromosome that encode a specific functionalproduct, like a protein.

3GENETICS, GENOMICS AND THE PATENTING OF DNA

affected by variations in a single gene inheritedfrom one or both parents. These kinds of disordersare mostly incurable, usually severe, and thoughrelatively rare, taken together affect millions ofpeople globally. It is these kinds of disorders whichare truly “genetic disorders”, and several devel-oping countries are characterized by a high inci-dence of these. According to the Genomics andWorld Health report: “By far the commonest mo-nogenic diseases are those involving human hae-moglobin, the thalassemias, and sickle cell diseaseand its variants, conditions that have a particularlyhigh frequency in sub-Saharan Africa, the Medi-terranean region, the Middle East, the India sub-continent and throughout southeast Asia” (WHO,2002).

Having children with a genetic disorder has a par-ticularly high cost in developing nations becauseparents can rarely rely upon subsidized health careor insurance to pay for often expensive therapies.

Haemoglobinopathies, of which β- and α -thalassaemias are the commonest forms, are themost prevalent genetic disorders affecting humans(WHO, 1996; Clegg and Weatherall, 1999).4

Treatment for thalassaemia requires children toundergo monthly blood transfusions that in turnmay cause an iron overload that could bring aboutdeath in adolescence or in early adulthood. Iron-chelation therapy with deferoxamine to correctthe problem of excess iron is very expensive, and

Figure 1Detection rate of cystic fibrosis-causing CFTR mutations

Source: The molecular genetic epidemiology of cystic fibrosis (WHO/HGN/CF/WG/04.02)

The detection rate of cystic fibrosis (CF)-causing CFTR mutations, i.e. the proportion of CFTR (CF transmembrane conductance regulator) alleles derived from CFpatients on which a mutation can be identified, are given for the different countries of the world. This detection rate for each country from CF patients on which a mutation

can be identified is the maximum detection obtained so far, irrespective of the sensitivity of the screening assays used. A colour code is used for different detectionrates. The countries marked with a dappled screen, represent studies in which less than 100 CFTR genes were studied. They might therefore be less representative. For

the regions coloured white no data are available.

Denmark

Brazil

USA

SaudiArabia

Australia

Algeria

Oman

Tunisia

SouthAfrica

India

ChileArgentina

Uruguay

Ecuador

Colombia

Venezuela

Canada

Mexico

Iceland

Japan

PakistanKuweit

QatarUArabE

Norway

Russian FederationEstoniaLatviaLithuaniaBelarus

Ukraine

SloveniaCroatia

Bosnia & HerzegovenaSerbia & Montenegro

Albania

Hungary

Bulgaria

SlovakiaCzech Rep.

PolandRomania

Turkey

Luxembourg

Bahrain

Cuba

SwedenFinland

BelgiumNetherlands

SpainPortugal

Austria

ItalyGreece

Germany

Ireland

IsraelLebanon

UK

MaltaCyp.

New Zealand

Reunion

Switzerland

Jordan

> 95%90-95%

Detection rate

80-89%70-79%60-69%

<50%50-59%

No data

FYR of Macedonia

France


is therefore out of reach for many poor people, likethose living in Pakistan, where 5% of the healthypopulation carry the gene for β-thalassaemia. Someestimates put the rate of birth of affected infants at1.3 per 1000 live births, which means about 5250Pakistani infants are born each year with β-thalassaemia major (Ahmed et al., 2002).

Simple, inexpensive tests exist for carrier screeningof this disease (WHO, 1994; WHO, 2002). (SeeBox 2.) Genetic testing of the fetus to diagnose thecondition, or of the woman and her partner todetermine their carrier status before conception,can provide critical information to inform choicesabout a condition that may have a dramatic impacton affected lives. Forms of prenatal diagnosis havebeen implemented, at some level, in Nigeria,Pakistan, Cuba and India (Verma et al., 2003).Prenatal diagnosis using the rapid and inexpensivepolymerase chain reaction (PCR) to amplify DNAhas been found to be useful in the diagnosis of sicklecell anaemia, a very serious condition associated

Box 2What are DNA genetic tests and what can they tell us?

DNA genetic testing involves the analysis of DNA in order to determine the presence of a gene associated with aparticular disease. In general, there are four kinds of genetic tests:

Carrier testing Carrier testing Carrier testing Carrier testing Carrier testing determines if the person tested, who does not himself have the disease, carries a gene for the disease.If two carriers have a child together, there is a high probability that their offspring will have the disease.

Prenatal testing Prenatal testing Prenatal testing Prenatal testing Prenatal testing determines whether a foetus is affected with a genetic abnormality causing a particular condition.Embryos may also be tested during in vitro fertilization before being surgically implanted into the womb; this is calledpre-implantation diagnosis. For technical reasons, the latter method is not widely practised.

Diagnostic testing Diagnostic testing Diagnostic testing Diagnostic testing Diagnostic testing determines whether the tested individual in fact has a particular genetic condition or a geneticpredisposition for acquiring the condition later in life.

Predictive testing Predictive testing Predictive testing Predictive testing Predictive testing determines the presence in asymptomatic individuals of an abnormal gene that will lead to a diseasein the future, or of a genetic predisposition for acquiring the condition later in life, in interaction with environmentalfactors.

with a high level of mortality and morbidity. InWest Africa, nearly one in four people is a carrierof the sickle cell gene (Adewole, 1999).

The efficacy of genetic approaches in the manage-ment of genetic conditions has been demonstratedin several Mediterranean countries that have im-plemented public health programmes to curb thedevastating impact of thalassaemia in theirpopulations (WHO, 2000; WHO, 2002; Cao etal., 2002). The enormous success of genetic screen-ing programmes among the Ashkenazi Jewishpopulation in the United States for Tay-Sachs dis-ease (Kaplan, 1998), whose incidence has plum-meted by 90% since testing began in the 1970s(Cohn, 2003), further testifies to the impact of awell-designed preventative strategy that incorpo-rates genetic approaches for genetic diseases.

Because of the life-long burden of many conditionswith a strong genetic component, early diagnosisor identification of carrier status provides valuable


information for making informed life choices—deeply personal choices about marriage,reproduction and lifestyle. Early testing for a rangeof conditions can assist patients in anticipatingchallenges, and in finding supportive structures andguidance early on, which often leads to improvedhealth outcomes. Genetic tests may be particularlyempowering for women, who are the child bearersand generally carry the primary responsibility ofraising children and caring for the sick. But to betruly effective, it is essential that genetic testing beaccompanied by appropriate counselling andsupport services that serve to inform patients, andto protect them from discrimination. Educationalprogrammes are often valuable to improvecommunity awareness, and to reduce the stigmasometimes attached to those identified as carriersof a genetic disorder (WHO, 1998).

But what role can genetic tests play in diagnosingmuch more common conditions, like diabetes andcardiovascular disease? In the following section,we will consider developments in genomics, andhow this has provided the basis for the moreelaborate study of genes and their interactions, andthus for the creation of interventions for much morecomplex human diseases.

1.3.2 The genome projects

Like Mendel’s pea experiments, the 1953 discov-ery by Watson and Crick of the structure of theDNA double helix was a landmark event in thehistory of genetics, and in the history of the bio-logical sciences. The event we will focus on heretook place more than three decades later when,fuelled by advances in molecular biology andinformatics, the Human Genome Project was ini-tiated as an international effort to sequence thecomplete complement of human DNA. The Hu-man Genome Organisation (HUGO) was the co-ordinating body of this effort, and at the First In-ternational Strategy Meeting on Human GenomeSequencing in 1996, partners in this initiative ar-ticulated their commitment to making their resultsrapidly available, and to placing them in the pub-lic domain. In March 2000, British Prime MinisterTony Blair and then-President of the United States

Bill Clinton issued a joint statement, affirming that:“To realize the full promise of this research, rawfundamental data on the human genome includingthe human DNA sequence and its variations,should be made freely available to scientists eve-rywhere” (Lewis, 2000). They did not, however,rule out the patenting of DNA, later adding, “In-tellectual property protection for gene-based in-ventions will also play an important role in stimu-lating the development of important new healthcare products”.

Shortly after the start of the Human GenomeProject (HGP), former president of the not-for-profit Institute for Genomic Research (TIGR)Craig Venter headed up a parallel initiative in theprivate sector, as leader of a new subsidiary ofApplera Corporation, Celera Genomics. In 2001,the private and public sector projects announcedsimultaneously in different journals their respectivecompletion of the draft sequence of the humangenome (Venter et al., 2001; International HumanGenome Mapping Consortium, 2001). Althoughthe aims of the two projects intersected in acommon desire to sequence the human genome,their final goals were different: the Human GenomeProject sought to establish a scientific standard,namely the complete reference genome, whileCelera Genomics sought primarily to sequencecommercially valuable sections of the genome. Thelatter effort used the whole-genome shotgunsequencing method to generate short fragments thatwere pieced together using data from the publicinitiative.

The Human Genome Project, led by scientistsaround the world, was therefore the main driver ofadvances in genomics, an approach to the large-scale sequencing and analysis of DNA that con-tinues to have an enormous impact on how bio-medical research is done in laboratories aroundthe world. Indeed, the Human Genome Projectgave rise to many projects to sequence the genomesof a great many organisms, from useful laboratoryanimals to deadly disease-causing agents. Thesequencing of the mouse (Waterston et al., 2002),rat (Gibbs et al., 2004), yeast, C. elegans (Wilson,1999) and numerous pathogen genomes(Fleischmann et al., 1995; Read et al., 2000; Hall et


al., 2002), have provided vast numbers of potentialnew targets for drug and vaccine development, andidentified genes implicated in common disease.While genetic tests have been available for sometime for a variety of single gene diseases (WHO,1996),5 genomics has led to the creation of tests for“non-Mendelian” disorders, like various cancers,which affect a much larger proportion of peopleworldwide. Marrying genomics and computationhas led to sophisticated microarray technologiesfor the diagnosis of complex disorders, which arethe result of multi-gene interactions. For instance,progress has been made in genetic testing for someconditions, including familial hypercholesterolae-mia, a condition that affects about 10 million peo-ple worldwide, and leads to a more than 50% riskof coronary heart disease by age 50 years in menand at least 30% in women aged 60 years (Markset al., 2003; WHO, 1999). The study of rare butstrongly genetic forms of a common disease (suchas familial hypercholesterolaemia as a cause ofatherosclerosis) not only provides clues about thegenetic disorder, but also provides important

insights into the causal pathways leading to themore common disease (Brown & Goldstein, 1976).

So what, exactly, is the difference between geneticsand genomics? As we have seen, medical geneticstraditionally concerns itself with inherited single-gene (Mendelian) disorders, applying genetic tests,accompanied by non-directive counselling, to helppatients in high-risk groups make decisions basedon their genetic profile. What genomics brings isan approach to the large-scale study of many genesthat permits sophisticated analysis of genes andtheir interactions. This means that genomics hasapplications far beyond simply genetic disorders;it can lead to greater understanding of the functionof genes in more complex, multifactorial diseasesand thereby to better therapies targeted moreprecisely at the root cause of disease.

Genomic medicine introduces a new dimension tohealth care—one that will rely more, rather thanless, on genetic tests to determine susceptibility tovarious conditions and patients’ likely responses

Box 3Genomic medicine in Mexico

In 2004, the Mexican Institute for Genomic Medicine (INMEGEN) was launched. The genomic medicine programme ispart of a strategy to improve the health of Mexicans through the development of cost-effective interventions for theprevention, diagnosis and treatment of disease.

A number of chronic, infectious and degenerative diseases currently represent significant causes of mortality inMexico. In response to this need, the Ministry of Health (SSA), the National Autonomous University of Mexico(UNAM), the Mexican Health Foundation (FUNSALUD) and the National Council of Science and Technology jointlyestablished a plan for the creation of INMEGEN. The Institute, which may ultimately be part of the Mexican NationalInstitutes of Health (M-NIH), consists of an intramural research programme, including on-site laboratories and an in-patient clinical centre, and an extramural programme of collaborative research projects in Mexico and abroad.

In its current state, the Consortium for INMEGEN has already formed partnerships with three institutes in the M-NIH,and has sponsored over 40 lectures and developed three graduate-level courses on genomic medicine. In the first fiveyears following its launch, INMEGEN will cost an estimated US$ 190 million, or 0.82% of Mexico’s annual federalhealth care budget.

Sources: Jimenez-Sanchez (2003), Science Pharmaceutical Executive (2005)


to some medications (Service, 2003). Genomicswill arguably, therefore, make genetic tests morerather than less important as molecular toolsbecome relevant to both diagnosis and prognosisof a much broader range of human diseases(Khoury, 2003; Guttmacher and Collins, 2002).Mexico presents an example of a developingcountry that has made a strategic decision to investin genomic medicine. It would be valuable to assesswhich factors formed the basis for this decision,including the existing competence in traditionalgenetics approaches. Mexico’s efforts over the nextfew years to realize this programme will provide auseful case study of an initiative in a relativelyresource-poor setting to build endogenous researchcapacity in genomics and to generate applicationsrelevant to the local health context.

There continues to be great optimism about thevalue of genomics for creating practical solutionsto health problems. But despite the extraordinarilyintense effort to produce a reference sequencerapidly, the resulting information cannot beimmediately translated into clinical benefit.Sequencing of the human genome, while aremarkable technical achievement, was relativelystraightforward when compared to the workneeded to analyse the growing amount of raw datanow available; this requires a level of analysis thatis not easily automated. The complexity of diseasecausation, which involves gene–gene as well asgene–environment interactions, is particularlychallenging for the study of most common humanafflictions. Identifying relationships betweengenetic characteristics and clinically relevantfeatures has proven extremely difficult.

So, while genomics has unquestionably generatedan enormous volume of data in barely more than adecade, scientists are still in the very early stagesof understanding how to transform this data intouseful health applications. Nevertheless, genomicshas already contributed important insights into themolecular mechanisms behind a range ofconditions (Wickelgren, 2004), and provided newways of approaching old problems, such as thecontrol of disease vectors like mosquitoes (Brower,2001) and vaccine development (Verma andSharma, 2003). It is widely believed that it is only

a matter of time before the promise of genomics isrealized and these approaches begin to yield results(WHO, 2002). But this optimism should betempered by the likelihood that the awaited harvestwill be many years off, and the fact that there remainconsiderable technical and ethical challenges tosurmount—including assuring the equitabledistribution of its benefits.

1.4 Genetics and health in thedeveloping world

We have seen what genetics offers to people withMendelian disorders, and the potential thatgenomics has to offer those who suffer from morecommon human afflictions. But what does all ofthis mean for developing countries, where surelythe issue is more one of the basic provision of healthservices rather than of access to sophisticatedtechnologies?

The major argument of the Genomics and WorldHealth Report is that genetics, and even genomics,should not be considered luxuries beyond the reach

Box 4Characteristics of the idealdiagnostic test—ASSURED

AAAAAffordable by those at risk of infection

SSSSSensitive (few false-negatives)

SSSSSpecific (few false-positives)

UUUUUser-friendly (simple to perform and requiring minimaltraining)

RRRRRapid (to enable treatment at first visit) and Robust (doesnot required refrigerated storage)

EEEEEquipment-free

DDDDDelivered to those who need it

Source: Mabey et al., 2004


of developing countries. Rather they are tools thatpresent opportunities for addressing the specificneeds of the poor, either through technologytransfer or through the development of endogenouscapacity. For example, besides the value of genetictests in providing services of immediate publichealth benefit, the report claims that genetics has asecond advantage: it lays a foundation for thedevelopment of skills and expertise in DNA-basedtechniques like genomics, opening the door to apowerful research platform with potentially wideapplicability in the health sphere and beyond.

Although we have considered thus far geneticdiagnostic tests for heritable conditions and othernoncommunicable diseases, genetic tests can alsobe a useful tool for the diagnosis of infectiousdiseases. At present, for most infectious diseases,laboratory-based tests with reasonable sensitivitiesand specificities exist, but they are not available inperipheral health centres, which serve most of thepopulation. Most existing tests depend on theavailability of well-trained and supervisedprofessionals, are time consuming and expensive,and rely on a constant supply of reagents andelectricity. Nucleic-acid amplification technology,like the polymerase chain reaction (PCR), whichcan detect tiny amounts of DNA or RNA in asample, have excellent sensitivity and specificity.This allows the use of non-invasive specimens, suchas urine, for the diagnosis of some infections.Though successes have been achieved in the use ofmodified, simple versions of these assays, they aregenerally expensive and require technical expertiseand equipment (Mabey et al., 2004).

Genetic tests today apply primarily to well-stud-ied heritable conditions like those discussed above.But genomics provides an opportunity to createapplications for much broader use. Because of theircost and simplicity, the use of DNA-based tests islikely to grow, and to prove directly applicable todeveloping countries, and to their health systems.The urgency of developing genetic tests for inher-ited disorders is appropriate in those regions wherethere is heavy burden of haemoglobinopathies orother conditions amenable to existing genetic tests.But the effort to develop technologies that are cheapand well-adapted for use in resource-poor settings

is one that has widespread utility. Achieving thiswill require identifying those applications that arerelevant—whether PCR tests to diagnose Chagasdisease, or microarrays to identify aberrant cellactivity—and adapting them to local settings.Promising areas of research could even includemilitary-driven efforts to develop ways of easilydetecting biological warfare and infectious agentsredirected for use in developing countries. How tobring these applications to the poor is a challenge;it is more a matter of the economics and politics ofhealth research than any innate quality of sciencethat makes it remote to global health challenges.Finding the right political and economic levers toturn advances in genomics into benefits for devel-oping countries requires an open appraisal of in-centives and barriers to research, including pat-ents and other forms of intellectual property.

Genomics is in its formative stages; a great deal ofinformation has been gathered, and the challengeis now to translate it into useful applications.Developing countries could benefit scientifically,economically and in terms of health outcomes,from being part of this foundational, dynamic andoften collaborative research. There are examplesof developing countries (see Box 3, and section1.3) that have made the decision to invest inbuilding capacity in genomics; it would beworthwhile to monitor their progress. Competencyin genetics may, indeed, play a part in some casesin fostering this capacity; in any event, althoughgenetics and genomics have both qualitative andquantitative differences (Khoury, 2003), they bothrely fundamentally on the study and analysis ofgenes and their functions. Factors, includingpatents, that facilitate or hinder access to geneticsequences are likely to have an impact ondevelopments in these two emergent fields.

1.5 Patents

Patents are one of several forms of intellectualproperty. This section will provide an overview ofthe basic features of patents, the rationale for thepatent system, and the patenting of geneticsequences. Some of the issues raised in this section


will be taken up again in the analysis portion ofthis report (see section 3).

1.5.1 What is a patent?

Patents were created as a way to provide financialincentives for inventors to undertake research, byallowing them to exclude competitors fromexploiting their invention for a specified period oftime. This period gives the inventor time tocommercialize her invention and recoup herinvestment, as well as make a profit. The resultingsystem is therefore justified as a means ofencouraging innovation, by rewarding inventors,promoting public disclosure of inventions,inducing investment in the development ofinventions, and providing the public with usefulnew products. The patent system is one method ofaddressing the problem of under-investment inthose areas of innovation where the initial costs of

research and development are high compared tothe costs of copying.

In order to be patentable, an invention must meetthe criteria of novelty, industrial applicability (orutility, in the United States of America), anddemonstrate an inventive step (or non-obviousness,in the United States, arguably a lower thresholdthat is particularly important for sequence-basedpatents). What is already known is called “priorart”, and a patent is intended to reward an inventorfor an advance requiring a step that would not havebeen obvious to someone technically competentin the field.

The rights of a patent holder have been describedas a fence blocking off territory, within which otherparties are not allowed to tread without a licence.Those who cross the fence without permission maybe found to have infringed the patent right of the

Mervyn Jacobson, co-founder and Executive Chairman ofthe small Australian biotechnology firm Genetic Technolo-gies (GTG), claims that he and his colleagues were the firstto realize the value of “junk” DNA, the 98.5% of human DNAthat does not code for genes.

The firm owns four broad patents on non-coding sequences,stretches of “junk” DNA, which today are known to havegreat value in helping researchers to identify and analysecoding regions, and in mapping haplotypes associated withcommon diseases like cancer and diabetes. GTG’s US pat-ents expire between 2010 and 2016. The company has beenheavily criticized in some quarters for what is seen as theaggressive enforcement of its patents, against other firmsas well against academic institutions.

Applera is among three US companies now facing an in-

fringement suit from GTG for its use of non-coding DNA fora diagnostic test for cystic fibrosis. New Zealand’s Depart-ment of Health has been advised to pay US$ 5.7 million inlicence fees.

Dr Jacobson argues that “a lot of academic organizationsare under pressure to generate revenue. Why should they beexempt from the rules of the market?” His company, hesays, wishes to license its inventions widely for reason-able fees. In fact, GTG used its broad patents to make adeal with Myriad Genetics, negotiating the use of GTG’spatented inventions in exchange for control over the licens-ing of Myriad’s rights in Australia. Thanks to this agree-ment, GTG exercises its prerogative to permit free accessto Myriad’s technology for service providers in Australia.

Source: Moukheiber (2003), Forbes.

Box 5Australian firm patents “junk” DNA


patent holder. The text of the patent includes patentclaims that define the subject matter of theinvention, as well as all the elements, features andcritical aspects of the invention, so that a persontrained in the relevant scientific discipline shouldbe able to replicate the invention. Claims definethe scope of the patent, or in other words, the sizeof territory that fits within the protected barrier ofthe fence.

The scope has important implications for how farthe patent reaches, as it were, to encompassunforeseeable uses and applications of the patentedinvention. It is sometimes in the patentee’s interestto draft the claim in very broad language to garnerthe broadest protection possible, though thisstrategy may make the patent more vulnerable tovalidity challenges. It is the role of the patent officeto assure that the language does not encompassprior art, or more than what is warranted by thedescription of the invention. Determining thecorrect limits for the scope of patents for newtechnologies comes about through a gradualprocess of refinement by patent offices, and thenby the courts. Case law plays an important role indefining the boundaries of the rights conferred bypatents.6

One important feature of patents is that they maybe granted on a product, a process, or a use: productpatents to cover, for example, chemicals,formulations, equipment and diagnostic kits;process patents to cover a method for creating aproduct; and use patents to cover a specified use ofa product. An invention covered by a product patentcannot be reproduced without a licence, even if adifferent method is used to make it. A processpatent, on the other hand, does not hinder someoneelse from making the product without a licence, ifa different process is used. What this means,however, is that a patent on a gene within anorganism (like a plant or even a mouse, for instance)can, in effect, confer rights to the organism itself(such as in the case of the Harvard OncoMousereferred to in section 3.1.1).

In general, patents can be claimed for inventions,but not for “discoveries”.7 This dichotomy, whichturns out to be difficult to define precisely, typi-

cally amounts to a distinction between what exists“in nature”, and what is the product of human la-bour, or at a minimum, human intervention.Patenting in biotechnology presents particularchallenges to this distinction, because the subjectmatter in question consists of “natural” entities.Today, the condition of existing “in nature” is un-derstood narrowly in the patent law in many coun-tries, meaning literally what exists in nature; thatis, what exists in its un-isolated form. But despitethe fact that patents have been granted in somejurisdictions for many years, a great deal of debatecontinues to surround the patentability of natu-rally occurring substances that have been isolatedusing laboratory-based approaches (Eisenberg,2002b). This has been the basis of much of the con-troversy surrounding the patentability of DNA andDNA methods, as well as the status of DNA vec-tors, cell lines, embryos, and genetically modifiedorganisms.

According to the United States Patent and Trade-mark Office (USPTO), “a patent on a gene coversthe isolated and purified gene but does not coverthe gene as it occurs in nature” (USPTO, 2001).According to this view, what distinguishes a DNAsequence that exists naturally in a cell or organismfrom a patentable DNA sequence is that the formerowes nothing of its existence to a human inventor,while the latter would not exist without some form,however minimal, of human intervention (Gold,2003). The invention/discovery (or invented/natu-ral) dichotomy is principally relevant to the nov-elty standard of patentability. Once the isolationof a gene sequence has been judged to meet thisstandard, it still must have some distinguishableutility and be shown to have demonstrated an in-ventive step (or non-obviousness). How to accom-modate biotechnology inventions in patent law isstill a hotly debated issue, and countries have notresponded uniformly in the laws they have enactedregarding DNA sequences and other biologicalentities (see section 2.4).

In general, DNA patents claim at least one of thefollowing four applications of DNA sequences:diagnostic testing, research tools or methods, genetherapy or methods, or the production of therapeuticproteins to be used as medicines (Nuffield, 2002).8


However, many patents cover more than onecategory—or simply claim the gene, withoutlimitation as to its use. Various organizations,including professional associations,9 havearticulated their positions on the patenting of humanDNA. HUGO issued a statement in 1995, andlater updates in 2000 and 2003, arguing againstpatents on short sequences of DNA (e.g. expressedsequence tags or ESTs, and single nucleotidepolymorphisms or SNPs), among other things, onthe grounds that they had unproven utility. In 1997,the UNESCO General Assembly unanimouslyadopted a Universal Declaration on the HumanGenome and Human Rights, which stresses theimportance of acknowledging human dignity, andstates that no part of the human being can be subjectto profit in its natural state. Because patent lawstandardly acknowledges that the limits of patentsare entities found “in nature”, the UNESCODeclaration does not in fact challenge the currentpatenting of isolated sequences. In 2002,UNESCO’s International Bioethics Committeealso took up the question of patents and the genome,producing a report addressing a range of ethicalissues. This report proposed the adoption of aninternational convention on ethics, intellectualproperty and genomics, and a Code of Conduct asoptions to address public interest considerationsrelated to TRIPS (Kirby, 2002).

1.5.2 A brief history of the patentsystem

The intellectual property (IP) system has beenaround for a long time. But its history has not beenuniform or without controversy, even in its earlydays. In recent years, this history has been markedby dramatic changes in the way that lawmakersand courts view and interpret the system. In lessthan a decade, subject matter covered by intellectualproperty in several jurisdictions has expanded andthe length of time before work gets into the publicdomain has lengthened. It is not only thatintellectual property has changed; society has alsochanged, becoming increasingly “networked”.This means that copying is easier, but it also meansthat potential markets are considerably enlarged.As one academic has noted: “IP is now implicated

in routine, creative, communicative, and just plainconsumptive acts that each of us perform everyday.The reach of the rights has been expanded just atthe same moment that their practical effect has beentransformed” (Boyle, 2003). The growth ofgenomics has paralleled—and is indeed an elementof—this expansion and strengthening of IP.

The patent system has been compared to a kind ofenclosure movement, not unlike the enclosuremovement of eighteenth century England, whenstate-supported privatization conferred individualproperty rights on what had formerly been landwith communal rights to its use. A major differencewith today’s movement is that its subject is “theintangible commons of the mind”, rather thanagricultural land. The economic rationale for thisformer movement was the need for incentives forlarge-scale investment and to ensure the mostefficient use of resources—in other words, to guardagainst the “tragedies of the commons”, namelyoveruse and under-production (Hardin, 1968). Theequivalent economic argument today is thatintellectual property rights are needed to ensurethat there will be those prepared to invest the time,creativity and capital needed to produce new andneeded products. But the tragedies of the oldcommons do not apply in the same way in thecontext of IP. The “commons of the mind” is non-rival, which means there is no threat of overuse:unlike fisheries, my consumption of an idea doesnot threaten your consumption. In fact, yourconsumption may add value to the idea, rather thansubtract value. It is also non-excludable, like cleanair, which makes it hard to charge money for itsuse.

Today, intellectual property rights have changedfrom being the exception, protecting mostlydownstream industrial inventions and relativelyhard to infringe, to something that the courts oftendefend vigorously, and where courts also tend tofavour property owners more than they did twodecades ago (Boyle, 2003).

The rapid increase in patenting in the last decadeor so is also indicative of a shift in howorganizations do research. According to a recent


report by the Organisation for Economic Co-operation and Development (OECD, 2004):

Not only have new types of inven-tions—software, genetic, and businessmethods—been deemed patentable bysome patent offices, but the ability ofpatent holders to protect and enforcetheir rights has also increased, leadingmany to call the past two decades a pro-patent policy era.

Of course, this is not the first time the patent systemhas had to deal with new technologies. But researchin the twenty-first century is increasingly based onmarkets and knowledge networks, rather than onthe isolated performance of individual firms.Moreover, the biotechnology, pharmaceutical andmedical device markets are among the most patent-sensitive markets in the entire economy, and at thesame time the most dependent on close ties toacademic science for development of new productsand services. These networks are more complexand partnership-dependent, as well as more global.Absorbing these changes has not been easy; indeed,patent offices and courts have struggled to keeppace, build institutional expertise, and evaluateprior art to determine the right standards for thebreadth of granted patents in these rapidly evolvingsectors (Cornish, Llewelyn and Adcock, 2003).

Some have suggested that these changes presentfundamental challenges for the patent system itself:

The patent system is designed as a toolto provide an incentive to technicalprogress. The effectiveness with whichit can do this will depend on the fitbetween the nature of the incentive andthe processes by which technologicaldevelopment takes place. But whereasthe patent system has uniform criteriato judge patent applications, the patternof technical progress may varysignificantly in different fields. Thepatent system fits best a model ofprogress where the patented product,which can be developed for sale to

consumers, is the discrete outcome of alinear research process. The safety razorand the ballpoint pen are examples, andnew drugs also share some of thesecharacteristics. By contrast in manyindustries, and particularly those that areknowledge-based, the process ofinnovation may be cumulative, anditerative, drawing on a range of priorinventions invented independently, andfeeding into further independentresearch processes by others (IPRCommission, 2002).

In the case of new technologies marked by a morecumulative character, there are concerns that patentprotection may impede innovation, in particularby limiting access to essential research tools andmethods. In these instances, “too broad a protectionon basic inventions can discourage follow-oninventors if the holder of a patent for an essentialtechnology refuses access to others underreasonable conditions. This concern has often beenraised for new technologies, most recently forgenetic inventions” (OECD, 2004). In 2003, in itsreport on innovation, competition and patentpolicy, the United States Federal TradeCommission concluded that “in industries withincremental innovation, questionable patents canincrease ‘defensive patenting’ and licensingcomplications”, and moreover that “questionablepatents are a significant competitive concern andcan harm innovation”.

Genomics-based research is inherently of acumulative nature. As we will see in section 3.2,the networked nature of genomic research meansthat exclusive property rights intended to stimulateinnovation may, in some cases, in fact hinder it.Developed countries are increasingly interestedin the debate about genetic patents. Theirexperience may well be a harbinger for developingcountries with relatively advanced scientificcapacity, and could affect research in moredeveloped economies that could generateinterventions for the poor.


A much-cited example is that of Myriad Genetics, and itspatenting and subsequent licensing of two genes (BRCA1and BRCA2) that are implicated in breast and ovarian cancerfor women, and prostate cancer for men. Besides being thesubject of many research initiatives, testing for mutationsof these genes is important for genetic counselling, andrecommending preventative approaches to individuals witha family history for cancer. This example has raised enor-mous controversy around the world, particularly in thosecountries in Europe and North America where patents havebeen issued and exclusive licensing practices exercised.Myriad’s researchers sequenced the two genes and, on thebasis of these discoveries, developed a sophisticated, highlyautomated protocol for the diagnosis of the related condi-tions, which costs US$ 2500. In countries where Myriadholds patents, third parties cannot, without permission fromMyriad, perform research that might refine, improve or vali-date the claimed genetic tests or identify new tests anddiagnostic approaches.

Myriad’s practice of requesting that all samples be sent toits own laboratories for analysis indirectly allows the com-pany to build an exclusive genetic database, which couldserve as a foundation for further research on the two genesand related mutations (possibly to allow some licensing,but data has to be shared). In this way, Myriad is achievingthe ability to store all new information about BRCA1 andBRCA2 in its own laboratories, arguably extending its mo-nopoly beyond what was granted by existing patent laws.

In Europe, numerous institutions filed an opposition to theEuropean patents on the BRCA genes, and in Canada, some

provincial governments have protested by ignoring Myriad’spatents and permitting the use of its patented inventions byCanadian researchers and clinicians. However, Europeanresearchers applauded in February 2004, when the EuropeanPatent Office (EPO) granted a Europe-wide patent on BRCA2to the charity Cancer Research UK, which published itsdiscovery of the gene in 1995. The charity has agreed towaive fees for all public laboratories that apply to use thegene for non-profit research and clinical use.

Myriad’s first patent was revoked entirely by the EPO in2004, because it had filed its sequence with the USPTO ina rough form; by the time the correct sequence was filed,other scientists had already placed it in a public database,making it invalid for patenting. Myriad has filed an appealagainst this decision. On 20 January 2005, the EPO ruledthat the scope of Myriad’s second patent should be dramati-cally limited so that it covers only a single probe, ratherthan any probe or nucleotide sequence that can recognizethe gene. A few days later, following a public hearing, theEPO’s opposition division concluded that Myriad couldmaintain its third patent on BRCA—but amended the patentso that it related only to the gene probe of a defined compo-sition, and no longer included claims for therapeutic anddiagnostic methods.

Sources:Bosch (2004), LancetLecrubier (2002), EMBO ReportsEPO, http://www.european-patent-office.orgAbbott (2005), Nature

Box 6BRCA—The “Breast Cancer Gene”

1.5.3 Licensing patented inventions

Every inventor is faced with the decision of whetheror not to patent his invention (although in manycases, the patent holder and the inventor are notthe same individual, because institutions will oftenclaim rights over their staff’s innovations). Thedecision to patent gives the patent holder at leasttwo options as to how to exercise his rights. First,the patent holder can use the invention herself orhimself and exclude all others from its manufacture,

use or sale. Alternatively, the patent holder cangrant others the right to use the invention underagreed-upon terms through a licence, eitherexclusive to one licensee or non-exclusively tomultiple licensees.10 Exclusive licences can includeexemptions, for example for humanitarian orresearch use. In each of these cases, the patent holderis able to obtain revenue—either through the saleof his own goods and services or through royaltiesobtained from licensees. This is the financialincentive that undergirds patent law.


Decisions as to whether and to whom to license aninvention involve selection, and possibly theexclusion of some from the use of that invention.While this system can promote innovation byproviding a return on investment to earlyinnovators, there is the risk that it could hinderthose conducting important research or providingneeded services downstream, and can inhibitcumulative innovation. A patent holder’s decisionto license may impose constraints on research andeven on clinical practices; if a single protocol isimposed on practitioners, it can obstruct furtherresearch and validation of the inventor’s results.Discretion is left to patent holders whoseprerogative it is to decide how to make use of theinvention. As we will discuss in section 2.3, thereare notable examples of researchers who decidednot to patent their innovations but instead chose tomake them freely available to third parties, andexamples of others who chose to patent, but whoselicensing programmes did not erect barriers toaccess. However, there are also examples ofinstitutions whose patenting and licensing practiceshave been questioned on the grounds that they mayoperate against the wider public interest.

Box 6 (p. 13) describes the example of MyriadGenetics, and the impact of its patents on two genesimplicated in familial breast cancer on access togenetic services.

One should, however, be wary of conclusionsbased on a limited number of case studies. TheMyriad case demonstrates, for example, what canhappen as a result of gene patenting, coupled with

restrictive licensing practices. It is also importantto realize that patent holders do not have unfettereddiscretion. Traditionally, provisions have beenincluded in patent law to safeguard against abuseand anti-competitive behaviour. These includeinstruments like compulsory licenses, which wewill discuss in section 2.1 below.

One question to consider is whether the currentstructure of the patent system tends to encouragebehaviour among patent holders that militatesagainst the objective of promoting innovation forpublicly useful purposes. For example, the natureof industry interactions may create pressure to usepatents as ‘anticompetitive weapons’ to extendmonopolies and block competitors. If this is so,and such practices are widespread, it underminesthe raison d’être of the patent system by inhibitingcumulative innovation.

The United States National Institutes of Health(NIH), in March 2004 introduced draft guidelineson the patenting and licensing of genetic inventions.The guidelines have been criticized by some asbeing based more on anecdote than evidence(Surendran, 2004). In an effort to rectify this, theNIH is sponsoring a number of projects assessingthe impact of university gene patents in order togather relevant facts (Malakoff, 2004). TheNational Academies are, for example, conductinga study on DNA and protein patents. Efforts ofthis kind are valuable for elucidating current trendsin patenting behaviour, and are commendable fortheir attempt to ground policy in empirical work.

15

2The currentlandscape

2.1 Intellectual propertysystems

A patent is valid only within a particularjurisdiction. For instance, a patent granted by theUSPTO provides rights over a given inventionwithin the United States of America. Third partiesare excluded from making, using or selling theinvention within the borders of the United Statesand its territories, including importing theinvention into the country.

An inventor can seek patent protection in multiplejurisdictions through a single application. TheAfrican Regional Industrial Property Office(ARIPO), an organization of eastern and southernAfrican countries, is an example; a singleapplication can provide patent protection acrossall 15 countries that belong to ARIPO, althoughnational offices still need to register patents inaccordance with national law. By contrast, in theAfrican Intellectual Property Organization(OAPI), an organization of West African countries,there is a truly regional patent. In Europe, anapplicant can apply to one or more national patentoffices, or can apply for a patent from the EPO,which is recognized in countries party to theEuropean Patent Convention. A national patent isvalid in that country; an EPO patent can berecognized in multiple countries designated by theinventor. Infringement actions, however, must belitigated in national courts. The EPO is theadministrative body of the European PatentConvention, which covers all European Union

(EU) Member States as well as some non-EUcountries. Since 1975, there has been discussionabout creating a single patent (the CommunityPatent) for the whole of the EU.11 The PatentCooperation Treaty (PCT) permits inventors toapply through the World Intellectual PropertyOrganization (WIPO) for patent protection in 123countries, but patents are only actually granted atthe national level.

Globally, the EPO, USPTO, and Japanese PatentOffice (JPO) are the most influential actors ininternational patent policy, and regularly meet intrilateral discussions.12 WIPO plays a major rolein the administration of international agreements,and the WTO has become a key institution as aresult of the 1995 Agreement on the Trade-RelatedAspects of Intellectual Property Rights, whichemerged from the Uruguay Round of tradenegotiations of 1994 that also established the WorldTrade Organization.

Despite the creation of various internationalframeworks, and the streamlining of patentapplication processing across some jurisdictions,patent legislation is nevertheless designed andapplied principally at the national level. It istherefore important that each country weighdomestic factors when constructing its patentregime. However, national patent regulation isheavily constrained by the requirements of TRIPS.


Under TRIPS, WTO Members are obliged toprovide minimum standards of protection for awide range of intellectual property rights,incorporating many of the provisions from existingagreements administered by WIPO, like the ParisConvention of 1883 and the Berne Convention of1886. With regard to pharmaceutical patentsspecifically, TRIPS requires that all nations (exceptleast developed countries) adopt the practice ofaccepting pharmaceutical product claims aspatentable by 2005 at the latest. The WTO DohaDeclaration of 2001 reaffirmed that the TRIPSAgreement “can and should be interpreted andimplemented in a manner supportive of WTOMembers’ rights to protect public health and, inparticular, to promote access to medicines for all”(WTO, 2001; WT/MIN(01)/DEC/2).

However, the implementation of the DohaDeclaration was contentious, in particularresolving the issue identified in paragraph 6 of theDeclaration. Article 31(f) of TRIPS states thatproducts made under compulsory licensing mustbe “predominantly for the supply of the domesticmarket”. A compulsory license is a government-authorized use of a patented invention without thepatent holder’s consent, and is permissible underArticle 31 of TRIPS, provided that certainconditions are met. In paragraph 6 of Doha, theWTO recognizes that WTO Members withinsufficient or no manufacturing capacity in thepharmaceutical sector could have difficulty makingeffective use of the compulsory licence safeguard,originally expressed in TRIPS and clarified in theDoha Declaration (WTO, 2001; WT/MIN(01)/DEC/2).

On 30 August 2003, after protracted negotiations,member countries finally agreed “to allow anymember country to export pharmaceutical productsmade under compulsory licences” (WTO, 2003;WTO Press/350/Rev.1). Eligible developingcountries now have the option of importing genericdrugs produced under compulsory licencesoverseas, which they would not be in a position toproduce domestically, in order to address localpublic health challenges.16 All compulsory licences

would be required to comply with the agreed termsand it was understood among the members that thedecision would be “used in good faith in order todeal with public health problems and not forindustrial or commercial policy objectives”(WTO, 2003; WTO Press/350/Rev.1).

The present reality is that many developingcountries lack not only sufficient scientific capacityto manufacture patentable products but also thenecessary infrastructure and capacity to constructand implement finely balanced patent systems(Carroll, 1995). There is concern that they may beobliged to institute “TRIPS plus” legislationnationally (e.g. as a result of bilateral tradeagreements), which does not take advantage of theflexibility and public health safeguards withinTRIPS (Musungu and Dutfield, 2003).14

2.2 TRIPS and DNA patents

In relation to DNA patents specifically, there iscontention as to whether TRIPS requires countriesto grant patents on DNA sequences. While theTRIPS Agreement does not explicitly obligate itsmembers to declare DNA sequences to bepatentable inventions, Article 27(3) does not listDNA or genes among the acceptable exceptionsfrom patentability. According to Article 27,“patents shall be available for any inventions,whether products or processes, in all fields oftechnology, provided that they are new, involve aninventive step and are capable of industrialapplication”. However, it stipulates that:

3. Members may also exclude frompatentability:

(a) diagnostic, therapeutic and surgicalmethods for the treatment of hu-mans or animals;


TRIPS, in section 30, states that members can providelimited exceptions to the exclusive rights conferred by apatent. Section 8 of TRIPS permits members to adopt meas-ures necessary to protect public health and nutrition and topromote the public interest in sectors of vital importance totheir socioeconomic and technological development.

Some countries have adopted research exceptions (alsocalled research exemptions) in their patent legislation, whichgrant a limited right to researchers to experiment on a patentedinvention. They may also enable researchers to undertakestudies to gain a fuller understanding of the invention itselfwithout having to pay royalties to the patentee. But there issometimes uncertainty about the scope of a project permittedby a research exception clause, especially in the case ofresearch dealing with genetic material. In the United Statesof America, a recent case (Madey v. Duke, 2002) has severelylimited the research exemption in the country’s universities.

Some developing countries have also integrated a researchexception clause into their patent legislation. For example,the Brazilian Patent Law states that “experimental workingfor scientific or technological research purposes” qualifiesas a research exception (Brazil: Patent Law 9.279 of 1997).

In India, section 47(3) of the Patent Act of 1970 excludesfrom the exclusive patent right “any machine or other articlein respect of which the patent is granted and any process inrespect of which the patent is granted may be made or usedby any person, for the purpose merely of experiment orresearch including the imparting of instructions to pupils”.Amendments to the India Law in 1999 and 2002 have re-tained section 47(3) as crafted in 1970.

The Patent Law of the People’s Republic of China states insection 62 that using the patent concerned solely for thepurposes of scientific research and experimentation is notconsidered to be an infringement of the patent right.

A number of recent reports have expressed the need forgreater clarity regarding what is covered by research ex-emptions, particularly in relation to clinical and preclinicalresearch (OECD, 2004; Nuffield, 2002). This environmentcreates significant uncertainty for researchers who maybecome hesitant to undertake projects where they need torely on ill-defined exemptions. Researchers may rightlyfear having to face patent infringement suits, which couldbe very expensive.

Box 7Research exemptions

(b) plants and animals other than mi-cro-organisms, and essentially bio-logical processes for the productionof plants or animals other than non-biological and microbiologicalprocesses. However, Members shallprovide for the protection of plantvarieties either by patents or by aneffective sui generis system or byany combination thereof. The pro-visions of this sub-paragraph shallbe reviewed four years after the dateof entry into force of the WTOAgreement.

What is relevant for our purposes is that nowherein paragraph 27.3(b) is reference made to genes orDNA. This means that countries are free to judgefor themselves whether the excludability of DNAis inferred, and how strictly to apply the threecriteria of patentability. Brazil, for example, haschosen not to permit the patenting of “the genomeor germ plasm of any natural living being, whenfound in nature or isolated therefrom, and naturalbiological processes” (Section 1, Article 10 IX ofIndustrial Property Law No.9279/96). On theother hand, Brazil will allow use of patents basedon gene sequences.


By contrast, DNA patents have been permitted inEurope and the United States of America for manyyears. The European Parliament and CouncilDirective on the Legal Protection ofBiotechnological Inventions 1998 or the EUBiotechnology Directive (EC, 1998; 98/44/EC),adopted after a 10-year debate in the Council andEuropean Parliament, requires that bio-technological inventions that meet the criteria ofnovelty, utility and non-obviousness be deemedpatentable, with few exceptions. However, mostEU Member States are still to implement theDirective, because of widespread concern aboutthe implications of patenting biological substances.In Article 5, the Directive states:

1. The human body, at the variousstages of its formation and devel-opment, and the simple discoveryof one of its elements, including thesequence or partial sequence of agene, cannot constitute patentableinventions.

2. An element isolated from the hu-man body or otherwise producedby means of a technical process, in-cluding the sequence or partial se-quence of a gene, may constitute apatentable invention, even if thestructure of that element is identi-cal to that of a natural element.

3. The industrial application of a se-quence or a partial sequence of agene must be disclosed in the pat-ent application.

While some countries’ reluctance to implementthe Directive may, in principle, speak of hesitanceor opposition, it arguably has little consequence inpractice; the majority of patent applications gothrough the EPO, which has incorporated theDirective, and these patents may be validated by

national patent offices, even in those countries thathave not yet implemented the Directive.

This debate reflects a fundamental controversyabout whether DNA ought to be treated specially,or the same as any other molecule. Many naturallyoccurring chemicals, like erythropoietin, have beenpatented by companies that have succeeded inisolating them in the laboratory.15 In section 3.1we will consider some of the concerns about theeligibility of DNA as patentable subject matter.As we saw above with Brazil, developing countrieshave responded differently to the issue of how totreat DNA, in the context of patent law. We willexplore some of these differences in section 2.4.

2.3 The genomics industry andpatenting

Genomic industries are those that employgenomics approaches—namely, sequencing, high-throughput screening, DNA microarrays, otherDNA methods, bioinformatics and data mining—as an important part of their business model. Firmsin this category may be engaged in a range ofactivities, from drug discovery and development,through the creation of diagnostics to producingresearch tools and methods. In this section, we willidentify the major actors in this field, both publicand private, and consider how DNA patents areimplicated in their activities.

2.3.1 Who is doing the work and where

When the Human Genome Project got under wayin the late 1980s, investment in genomics from theprivate sector was very low. However, by 1993,public and private funding of genomics in theUnited States had reached nearly equivalent levels.According to an international survey conducted in2000, the private sector is now the predominantsource of funding for genomics, and the UnitedStates accounts for the lion’s share of thisinvestment. Indeed, the six biggest players in


genomics are United States firms (Cook-Deegan,Chan and Johnson, 2000).

Like biotechnology, genomics is an approach,rather than a specific field. And like biotechnology,genomics has infiltrated many fields that use itslarge-scale, highly automated methods for the studyof DNA. Firms engaged in genomics activitiesinclude service firms that sequence or analyseDNA for research laboratories; firms that carryout genetic testing or forensics; firms that makeinstruments; and firms that develop analyticalsoftware used to analyse entire genomes, mineDNA databases, or interpret data. The top fourgenomics firms in the United States, which includeCelera Genomics, have different business models,and are therefore engaged in varying combinationsof the above activities (Cook-Deegan, Chan andJohnson, 2000). Genomics firms like MyriadGenetics and Quest Diagnostics, for instance, areinvolved in developing genetic tests. In general,“diagnostics firms” invest considerable capital intothe development of highly systematized,automated methods for the accurate diagnosis ofparticular diseases.16

In contrast to companies that are centred on thesequencing and analysis of genomic DNA, somecompanies have complex business strategies thatrequire the large-scale sequencing of genes, as wellas the production of proteins whose medical valuemust be assessed in order to develop new genomicpharmaceutical products. Though their work is“gene-based”, as it were, these companies are inthe business of creating not only diagnostics, butalso therapeutics. They may face, therefore, highfront-end costs of research and developmentsimilar to those confronted by traditionalpharmaceutical firms.

In the pharmaceutical sector, innovation costs aregenerally very high (DiMasi, Harsen andGatowski, 2003), and there may be on average 8 to12 years between patenting a new product andbringing it to market. Average costs are highbecause only a small proportion of investigatedproducts gives rise to marketed drugs. In thissetting, patents are considered a critical factor inproviding incentives for research and development

(R&D), as well as protecting competitiveadvantage. They are also prized by start-ups anduniversity spin-off companies in the biomedicalfield, whose main asset for attracting venture capitalis protected intellectual property (OECD, 2004).

By contrast, in-house genetic tests can often bedeveloped with relatively little expense, usingexisting and accessible methods frombiotechnology, once the relationship between thegene and the disease has been established. Theselaboratories are often proficient at producing low-cost diagnostics based on published information,and do not require the high front-end investmentin product development of commercial firms.Consequently, examples exist of straightforward,reliable methods for testing for genetic disorderslike sickle cell disease and cystic fibrosis. But whilethese tests fill an immediate need, by providingsimple-to-use and inexpensive diagnostic tests forlocally relevant conditions, they vary widely interms of their protocols and safety testing, becausein-house tests are also generally subject to lessrigorous standards (Cox et al., 2003).

The link between diagnostics and therapeutics isincreasingly strong, which could mean that theeconomics of diagnostics and therapeutics willconverge in the coming years. We discussed insection 1.3 the advent of genomic medicine. Thisemploys genomic information to provide morepersonalized care for patients, which is based onevidence that some patients respond more poorlyto certain treatments. In December 2003, theworldwide vice-president of genetics atGlaxoSmithKline stated: “The vast majority ofdrugs—more than 90 per cent—only work in 30or 50 per cent of the people” (Connor, 2003). Somecompanies are already exploiting suchpharmacogenetic indicators to develop genetic teststo determine if patients will benefit from specificdrugs, or will have unusual toxic reactions to them(Service, 2003). For now, this work is directedtowards only a few conditions, including someforms of breast and colon cancer, and some drugclasses for pain control. As understanding of thegenetic basis for drug responses grows, genetic testsmay precede use of many therapies to increase thelikelihood of a positive outcome or to reduce side


effects. This is particularly important for expensivetreatments, and when several possible therapies areavailable, with varying costs and side-effects. The2003 Nuffield Council on Bioethics report onpharmacogenomics claims: “It is not clear that theprivate sector will be motivated to pursuepharmacogenetics research in relation to medicinesnot covered by patent protection”.

The report further recommends that:

Efforts should be made to encouragepharmacogenetics research on existingmedicines, where there is reason to be-lieve that such research could signifi-cantly improve efficacy or safety. Fund-ing within the public sector and public–private partnerships should be encour-aged.

2.3.2 Trends in patenting

Entities from industrialized countries currentlyhold 97% of all patents worldwide. More than 80%of the patents granted in developing countriesbelong to residents of industrialized countries,usually multinational corporations from the mostadvanced economies. 70% of global royalty andlicensing fee payments are made between parentsand affiliates of multinational corporations (UNDP,1999). Developing countries do not represent asignificant percentage of patent applicants. It isestimated that only 0.1% of the total number ofpatents issued by the USPTO, including allvarieties of patents, were filed by sub-SaharanAfrican applicants (Ogbu, 2002).

The rise in patents in biotechnology has beenparticularly dramatic, climbing by 15% per annumfrom 1990 to 2000 at the UPTO and 10.5% perannum at the EPO, compared with a 5% per annumincrease in overall patents (OECD, 2004), thoughthere has been a notable drop in the past three yearsin the number of DNA patents granted. As of 2003,more than 5000 applications for patents on humangenes had been filed with the USPTO and from

those applications more than 1500 patents weregranted (Kluge, 2003). Inventors from the UnitedStates have filed more international patents onDNA sequences than inventors anywhere else inthe world, and more than the combined total ofinventors in the European Union. Japanese andBritish inventors are the next most prolific patenteesin this field (Rausch, 2002).

The public sector has played an important role inthe growth of patents for biotechnologicalinventions. For example, public institutions inEurope and the United States own 30% of all thepatents for DNA sequences filed between 1996and 1999. And start-up companies have a highershare of biotechnology patents than do large,established pharmaceutical companies (OECD,2004). In the United States, the Bayh-Dole Act of1980 introduced incentives to universitiesreceiving federal funding to patent the products oftheir research, in order to encourage technologytransfer, and the commercialization of inventionsinto useful products. The result is that someuniversities today own more DNA patents thando large private firms (Cook-Deegan, Chan andJohnson, 2000). There is ambiguity for those centresthat provide diagnostic testing services. To improveexisting techniques and test efficacy, researchrequires that tests be used on patients, whichamounts to providing clinical services. While anumber of countries provide a research exemption(see section 2.3.3) that permits the use of patentedsubject matter for strictly research purposes, it isnot clear to what extent this exemption applies toinstitutions whose research involves the use ofpatient samples and thus overlaps with clinicalpractice (Walsh, Arora and Cohen, 2003; Cornish,Llewelyn and Adcock, 2003).

One of the difficulties in cases where universitylaboratories are among the chief providers is thatuniversities are increasingly viewed as pursuingcommercial ends, being actively engaged in profit-making activities and in widespread patenting andlicensing (Howard, 2004). Consequently, somehave judged it a double standard that universitieswould be spared having to pay licensing fees for


services provided, when they themselves are likelyholders of rent-earning patents. Although this isnot the case with all universities, their supposedimmunity because of their status as academiccentres may be in danger of disintegrating in theface of increasingly profit-making agendas.

Traditionally, governments have had the role offilling the gaps; of addressing market failure byallocating funds to areas of research that draw lit-tle funding from private sources. However, if thoseinstitutions receiving public funding are increas-ingly tied to the private sector and are licensingtheir inventions exclusively to companies, publicmoney may be generating products that are notreadily accessible to the public (e.g. because of highprices). Products may not be developed for needypopulations as these generally do not constitutelucrative markets. Given that the effectivenes ofthe patent system relies on market mechanisms,this situation, at least in principle, presents a ten-sion between the aims of government-funded re-search and the incentives that underpin the patentsystem; and the further challenge is that publiclyfunded research does not always find its way intothe public domain. However, licensing practicesand policies may in future play an important rolein leaving open avenues of research relevant todeveloping countries. For example, research-useexemptions or humanitarian-use exemptions,which protect from litigation research in areas ofprimarily humanitarian rather than commercialinterest (such as adapted tools for use in low-re-source settings) are being explored by severalgroups. The idea behind such work is to developways of changing norms around licensing, so thatinnovation in areas outside of market interest isnot impeded.

Developing countries stand to gain from takingadvantage of the flexibility within TRIPS thatallows members to protect researchers frominfringing patents used in research. Such clausescan encourage research activity, and foster thedevelopment of scientific capacity. However, theyshould be careful to avoid ambiguity in definingthe scope of the research exemption, because a lackof clarity may chill research. In the face ofuncertainty, researchers are reluctant to risk patent

infringement and possible litigation. It is thereforeparticularly important to clarify how the researchexemption applies to preclinical and clinicalresearch that has the dual aim of advancingknowledge and producing or providing goods andservices.

2.3.3 Opportunities and challenges fordeveloping countries

In most cases, companies do not bother to take outpatents on DNA sequences in developing countries,because the market in those countries is notlucrative enough to warrant protecting. What is atstake is the development of cheap technologiessuitable for use in the developing world, given thecurrent make-up and emphasis of the genomicsindustry. Endogenous research within mostdeveloping countries may not be hindered bypatents; however, research may be hindered in thosecountries with adequate technological capacity andresearch capital to generate the products ofrelevance to their poorer neighbours. Thesecountries include the United States, where, as wehave seen, the bulk of genomics-related research istaking place. They could also include Brazil andIndia, developing countries with well-advancedscience and health technology sectors, which arewell placed to generate appropriate health-relatedproducts to address local and more global needs.

An interesting place where advances are beingmade in genomics is in bioterror-related research.As genomics provides tools for studying pathogensand developing ways of diagnosing them quicklyand simply, it can do the same for “bioterror” agentsand therefore holds great interest for some defenceprogrammes. Platform technologies used forbioterror research can be relatively easily adaptedto create applications relevant to developingcountries. Some academic researchers interestedin creating such tools have capitalized on grantsfor biodefence research to create technologies forthe diagnosis and monitoring of infectious diseases,like HIV/AIDS.

Much of the promise in genomics andbiotechnology for developing countries depends


on using platform tools and technologies, modifiedfor use in poorer settings. The work of Dr EvaHarris is a well known example of technologytransfer of biotechnology tools to low-resourcesettings, primarily in Latin America. She is free toteach local laboratory technicians and health careworkers how to create low-cost alternatives totechnologies used in her own laboratory at theUniversity of California at Berkeley, becausepatents on the technologies do not tend to exist inthose countries. Whether she would have the sameliberty to work in poor countries with more well-developed biotechnology sectors where patents ongenetics tools may be more likely, is less clear. DrHarris must carry out most of her teaching on-sitebecause she risks patent infringement doing thesame work at home. Likewise, work in universitiesusing platform technologies can be modified foruse in developing countries. A research technology,developed through a collaboration between theSustainable Sciences Institute (SSI) and theUniversity of California at Berkeley’s Departmentof Electrical Engineering and its School of PublicHealth, has generated a low-cost point-of-care toolfor diagnosing dengue fever. According to itscreators:

The ImmunoSensor is a platform tech-nology, thus it can be adapted for virtu-ally any disease that is currently diag-nosed by an immunological assay. Theprototype application of theImmunoSensor is diagnosis of dengue,the most prevalent mosquito-borne vi-ral illness, with 100 million cases of den-gue fever annually worldwide. SSI iscoordinating field trials for dengue di-agnosis using the ImmunoSensor inNicaragua, Ecuador and Sri Lanka. Inaddition, efforts are being spearheadedto adapt this technology for HIV diag-nosis. 17

SSI is presently negotiating rights toImmunoSensor technology from the Universityfor use in developing countries, and will develop a

business strategy so that disease-endemic regionscan use and market the product to serve their ownneeds. The underlying IP of platform technologiescould be safeguarded for applications such as this.

As for pharmacogenetic approaches forpersonalized treatment, it will likely be animportant part of the way medicine is practised inthe future. There are a few examples today of itssuccessful use, though there remain big questionsabout when, and if, it will come into widespreaduse. What is important to remark is thatpharmacogenetics presents a further exampleindicating that as medicine continues to evolve, itis likely that the importance of genetic tests willgrow, and their usefulness expand considerablybeyond tests for genetic disease. Competency inthe development and delivery of genetic tests couldtherefore provide a foundation for continuingbenefit from medical advances based on genomics.However, ensuring that personalized medicine willbe an affordable option in general, and fordeveloping countries in particular, presents a majorfuture challenge. Moreover, the application ofpharmacogenomics in developing countries islikely to be quite different from in Europe andJapan, for instance. The disease burden in poorercountries is not identical—for example, infectiousdisease is still a major problem—and healthsystems require adapted methods. The direction ofgenomic research today is the direction that currentincentives encourage—and is one that does notshow any signs today of targeting the needs of thoseoutside of wealthy markets. We will consider inlater sections in more detail the role of patents inguiding the shape of today’s research landscape.

2.3.4 Availability of genomic data

The availability of fundamental genetic data is notsolely dependent on public funding. For example,the SNP Consortium was a collaborative ventureamong 10 private sector companies and theWellcome Trust. It was “founded on the premisethat genetic information related to SNPs isaccelerated when research findings are freely


available to all researchers and companies”(http://snp.cshl.org). The Consortium was a not-for-profit group working to compile a database ofmapped SNP, whose contents are freely availablethrough free public databases. SNPs are commonDNA sequence variations among individuals,which scientists hope will improve their ability tounderstand and treat human disease. According tothe Ontario Ministry of Health and Long-TermCare (2002), this project “treats SNP information(non-patented) as primarily an informational inputfreely available, and yet, still providing a vitalcontribution to downstream product develop-ment”.

One commentator has argued that large companies,in fact, see it as being in their interest to free up rawdata:

Although it may seem extraordinary forfirms that usually sing the praises of thepatent system to collaborate in a con-certed effort to put new discoveries inthe public domain, it makes perfect sensefrom the perspective of the pharmaceu-tical industry. The patents that matter topharmaceutical firms are the drug pat-ents that secure the revenues that fill thepharmaceutical feeding trough. Patentson the many prior discoveries that fa-cilitate drug development look like si-phons, diverting those revenues to thetroughs of other firms (Eisenberg, 2001).

This suggests that big companies may not all beopposed to liberating research tools from patentprotection.

Intellectual property rights covering databasesrepresent the second major way in whichproprietary rights may be exercised over DNAsequences. In some countries, databases areprotected by copyright or sui generis databaserights, though in the United States, unlike in theEU and elsewhere, they are protected mainly bycontract law—agreements signed by users to gainaccess to databases.

As previously noted in section 1.3, the HumanGenome Project exemplifies the fact that by nomeans all genetic inventions are protected by patentrights. In fact, the HGP has been used as an exampleof precisely the kind of scientific effort that did notrequire the incentives of patents to promoteinnovation, and indeed actively discouragedpatenting on the pathway to producing thereference sequence. The project, which wasentirely publicly funded, was characterized by bothopenness with respect to the sharing of results, andcompetition among laboratories.

The HapMap project, which aims to “determinethe common patterns of DNA sequence variationin the human genome and to make this informationfreely available to the public” (InternationalHapMap Consortium, 2003), has adopted adifferent approach, applying the software modelof open-source access, which permits others to useits products on condition that they too agree tokeep them in the public domain (Cukier, 2003).While the HapMap project allows process patents,it does not allow product patents on DNAsequences. It is less open than the HGP, but aims toprotect the products generated from its work frombeing used by private entities that could makeproprietary claims, limiting access to communalresources.

Despite the SNP Consortium and other similarexamples, there were in the late 1990s a number offirms that charged for access to databases ofgenomic sequences. But lately the relative value ofprivate versus public databases has been called intoquestion by the announcement that Incyte Corp.,the largest genomics firm in the United States, isclosing its headquarters and paring more than halfof its workforce. According to a brief in Science:

The gene discovery firm [Incyte] pio-neered the notion of turning profits byselling genetic data to drug discoveryfirms and academics. The strategyseemed promising for a while, and thecompany’s stock bolted to the dizzyinghigh of $144 a share during the technol-


ogy bubble days of 2000. But the com-pany faced the stiffest competition pos-sible: free genomic data supplied bypublic gene-sequencing efforts financedby governments around the globe….Like other one-time genomics compa-nies such as Celera and Myriad Genet-ics, Incyte has refashioned itself as a drugdiscovery firm (Service, 2004).

This suggests not only that efforts to generategenomic data have been highly productive to date,but that the resulting publicly available data isgenerating arguably more useful follow-on researchby companies that have turned to drug discovery,unable to sustain a business model based onprivately-owned data. While the race to sequencethe human genome was a fruitful and largelyefficient one, translating this wealth of knowledgeinto applications has been much slower—though,arguably, it has been facilitated by largely freeaccess to sequence data. Whether the lag ingenerating useful products is due to the unavoidablecomplexity of the work involved, reflectsfundamental flaws in the research and developmentchain, or a combination of both, has yet to beelucidated.

What is clear is that, thanks to the abundant successof the HGP and other initiatives, there is a growingrepository of publicly available genomic data.Researchers in developing countries can benefitfrom access to these resources. Existing strategiesto develop indigenous capacity in bioinformaticsand data mining in low-resource settings, includingthrough international partnerships, should beidentified and assessed, and initiatives consideredto encourage these efforts.

The Human Genome Project was characterizedby competition, openness in the sharing of results,and efficiency. The international HapMap project,for its part, has adopted an open source approachfor providing access to genomic data, whilepreventing third parties from making proprietaryclaims that could restrict access. This approach,while promising, has yet to prove itself; moreover,

while the HGP and HapMap models are arguablyeffective ways for encouraging and sharing thefruits of basic research, it remains very unclearwhether they provide the right kind of incentivesfor the work required to translate this research intoapplications. Large companies have shown theirwillingness, in some instances, to engage in moreopen science when it involves the generation ofraw data.

The open source model for genomics has beenadvanced by several scholars. We will consider it,and various other models, in section 3.2.2 below.

2.4 What some developingcountries are doing

There is great diversity among developingcountries, including wide diversity in scientificcapacity and infrastructure to support healthresearch and health delivery, as well as varyingpatent systems. Although they are different in anumber of respects, Brazil, China and India are allexamples of developing countries withcomparatively well developed gene-basedindustries. In this section, we will consider thecapacity of each of these countries to harness gene-based approaches to address the needs of theirpopulations. We will also look at the patent systemsthat have developed over time and helped to shapetheir present circumstances.

2.4.1 Brazil

Genomics in Brazil

The State of São Paulo Science Foundation orFAPESP, was founded in 1962 in São Paulo, Brazil’srichest and most populous state (37 million people).In 1997, FAPESP, established the Organizationfor Nucleotide Sequencing and Analysis (ONSA),a virtual community including 35 laboratoriesacross the state (Economist, 2000), which wascharged with boosting Brazilian competence ingenomics. ONSA’s first project was to sequence


X. fastidiosa, a bacterium that causes citrusvariegated chlorosis (CVC), which results in fruitthat are small, hard and of no commercial value.CVC was first recorded in Brazil in 1987; it affectsall varieties of sweet orange (Simpson, 2000) andhas a significant economic impact, costingBrazilian growers an estimated US$ 100 millionper year (Economist, 2000).

The successful sequencing of X. fastidiosaprovided FAPESP with both a team of skilledsequencers who were then able to move on tosequencing genes relating to human diseases, andinternational recognition that has resulted inexternal funding for human-related sequencingprojects. The X. fastidiosa genome was the firstcomplete sequence to come from outside the UnitedStates, the United Kingdom or Japan and the firstever sequencing of the complete genome of plant-disease-causing organism (Yoon, 2000). FAPESP’sapproach was novel because it created a virtualresearch community rather than investing inbuilding a physical genomics centre (Trafford,2001). FAPESP’s statute prohibits it fromassembling its own corps of scientists. The institutemust, therefore, invest widely in existing centreswithin the state rather than confining resources toa small subset of the research population. Thisresults in the sharing of knowledge among a largenumber of researchers and a sustainable investmentin the industry.

The virtual network strategy allowed ONSA tomaximize the value of the funding provided byFAPESP, to overcome geographical isolation andto nurture a critical mass of trained geneticists. Thesuccess of the X. fastidiosa project catapulted Brazilinto the international spotlight. As a result ONSAhas developed international partnerships to fundfurther sequencing projects that are expected tomake a significant contribution towards betterunderstanding of leading causes of ill healthglobally. For example, ONSA is sequencinghuman cancer-related genes in collaboration withthe Ludwig Institute in Switzerland (Rother, 2001),which is paying half of the US$ 10 million cost ofthe project (Economist, 2000).

In 2000 the Federal Government of Brazil decidedto expand São Paulo’s genome project to thenational level; it launched the Brazilian GenomeProject, which comprises a network of 25sequencing laboratories. The growth and strengthof genomics industry in Brazil indicate the resultsof these initiatives. For example, the number ofscientific publications from Brazilian researchersincreased 300% between 1987 and 2002, nowaccounting for about 1.2% of global scientificpapers. Brazil is now an undisputed leader in plantgenomics (WHO, 2002).

Brazil’s patent law

In 1809 Brazil became the fourth country in theworld to enact a patent law. Brazil became afounding member of the Paris Convention in 1882(Barbosa, 2004). On 14 May 1996, Brazilintroduced Law No. 9.279 to Regulate Rights andObligations Relating to Industrial Property (BrazilLaw, 1996), which was intended to fulfil Brazil’sobligations under TRIPS to enact minimum patentstandards (Barbosa, 2004).18

Brazil signed the Convention on BiologicalDiversity (CBD) in 1992 and ratified it in 1994.Brazil has been a vocal and active supporter ofbenefit sharing in relation to the commercializationof research based on natural products and ofintroducing an internationally recognizedcertificate of origin for genetic samples (GRAIN,2002). After extensive negotiations at the SeventhMeeting of the Conference of Parties to theConvention on Biological Diversity in KualaLumpur in February 2004, country representativesagreed to include the certificate of origin as a topicto be addressed in the guidelines to be prepared bythe next conference in Brazil in 2006 (Dalton,2004). As we will see in section 3.1.2, CBDspecifically excludes human genetic resources.

In 2001, the United States filed a complaint withthe WTO arguing that Article 68 of Brazil’s patentlaw No. 9.279 was in breach of Articles 27 and 28of TRIPS. Article 68 allows Brazil to issue acompulsory licence to a local producer if, after


three years, the patent holder has not begunmanufacturing the product in Brazil. This measureis designed to encourage technology transfer andsupport a strong domestic generics industry, inaddition to strengthening the BrazilianGovernment’s bargaining position in relation tothe cost of drugs (Oxfam, 2001) and, ultimately,helping the Brazilian Government to ensureaffordable access to vital medicines (Cooper,2001).19 Though the case involving drugs hasbecome the prototype for considering compulsorylicences, particularly in the context of developingcountries, it is important to recognize thatcompulsory licences are not limited to use againstdrug companies. For instance, in France, opponentsto restrictive licensing of genetic tests threatenedto opt for ex officio licences, permitted by Frenchlaw on grounds that practices are contrary to publichealth (Lecrubier, 2002).

Gene patenting

According to a report prepared by the BrazilianGroup of the International Association for theProtection of Intellectual Property (AIPPI), thereis ambiguity as to whether the Brazilian patentlaw No. 9.279 excludes genes from patentability.Both Article 18, item III, and Article 10, item IX,suggest that genes should not be consideredpatentable material. On the other hand, the lawdoes allow for the patenting of chemical products,provided they fulfil the criteria of novelty,inventive activity and industrial application. IfBrazil were to conclude that DNA is not merely alarge polymer, it could permit chemical productpatents while blocking patents on genes.20 At thetime of writing of the Brazilian Group’s reportthere was no case law to resolve this issue ofinterpretation.21 However, a number ofcommentators have concluded that DNA is notpatentable under current Brazilian law—except forcertain specific uses.22

2.4.2 China

Genomics in China

China has adopted a policy of actively supportingand encouraging biotechnology and genomics-related industries. In 1998 the Ministry of Scienceand Technology established both the ChineseNational Human Genome Centres (CHGC) inShanghai and Beijing to specialize in genomesequencing and analysis (WHO, 2002). In 1999,the Chinese Academy of Sciences established theBeijing Genomics Institute (BGI). China was thenin a position to join the International HumanGenome Sequencing Consortium in 1999. Chinanot only played a significant role in the sequencingitself, characterizing 1% of the human genome,but was able to develop advanced bioinformaticsand supercomputing facilities to support furthergenome-sequencing research. This research hasincluded sequencing the silkworm genome,establishing the Super Hybrid Rice GenomeProject and collaboration with Danish scientiststo sequence the pig genome (Porcine GenomeSequencing Project).23

BGI’s latest achievement was announced on1 March 2004, when BGI reported theconstruction of a chicken genome variation map,based on DNA from three strains of chicken andidentifying two million SNPs. This work is part ofa larger project to sequence the chicken genome,conducted by an international team and lead byBGI.

China supports collaboration with foreignresearchers, but recognizes the need to protectChinese genetic resources from exploitation andbiopiracy (WHO, 2002). In 1998 the Ministry ofHealth and the Ministry of Science and Technologyjointly established the Chinese Human Genetic


Resources Management Office. It is responsiblefor managing all matters dealing with Chinesehuman genetic resources, including human genegroups, blood, genes, organs, cells and other DNAmaterials of human beings (Feng, 2003).

China is keen to ensure that some of the benefits ofinternational genetic research, based on Chinesegenetic samples, flow back to the Chinesecommunity. Yu Xiucheng, director of the Divisionof Health Technology Management of theDepartment of Sciences, Technology andEducation of the Ministry of Health has stated thatall cooperative international projects based inChina and working with Chinese human geneticresources should follow the principles of equality,mutual benefit and joint participation; and that theachievements and patents must be owned andshared by both the foreign and domestic researchers(Feng, 2003).

China’s patent law

China first introduced a patent law in 1985, whichwas subsequently revised in 1992. Furtheramendments to bring the patent law in line withinternational standards and TRIPS requirementswere passed at the 17

th Session of the Standing

Committee of the Ninth National People’sCongress, and took effect on 1 July 2003.24 Forexample, the amended law will, in accordance withTRIPS, allow patent holders who believe theirrights are being infringed to ask the courts tointervene.25

During the same period, as China prepared to jointhe WTO, the overall number of patent applicationsincreased. By the end of July 2001, the State

Intellectual Property Office of China had accepted99 550 patent applications from China and abroad,a 24% increase from 2000.26

Gene patents

Chang Mao, an officer from the State IntellectualProperty Office, has stated that China does notallow companies or research institutes to patentlife forms; however patenting genes is permissible(Wang, 2001).

In 2001, Shanghai Joint Gene Technology Co. Ltd,the largest gene technology company in China,applied for more than 3700 gene patents, includingpatents for genes dealing with cancer, obesity, highblood pressure and senile dementia, which areexpected to be of high value for clinical diagnosisand the development of new medicines. “Owningintellectual property is one of our company’sfundamental goals. If we had not owned intellectualproperty, we would not have our own gene industryafter WTO accession”, said Qin Yilong, thecompany’s vice-president in 2001.27

The concept of international patent families 28

provides a basis for comparing the research andtechnological activity of different countries, interms of resulting products intended forinternational use. A patent family consists of allthe patent documents associated with a singleinvention that are published in one country. From1980 to 1999, China, which had filed a total of 145patent families in human DNA sequences, had onlyfiled 17 international patent families.29 The UnitedStates, by comparison, had 5610 internationalpatent families (accounting for 72% of the totalworld figure of 7810).30 Brazil had only 1international patent family.


2.4.3 India

Genomics in India

The growth in the biotechnology industry in Indiais built upon its existing internationally recognizedinformation-technology industry, a large pool oftrained scientists and a dynamic generic pharma-ceutical industry (BioSpectrum, 2003). In the in-ternational market, India’s highly qualified, Eng-lish speaking but comparatively low-costworkforce offers a significant competitive advan-tage (Thorold, 2001). The Indian Government hasinvested substantially in building the industry. TheDepartment of Biotechnology (the Department)was established by the Indian Government in 1986and receives an annual budget of approximatelyUS$ 30 million (WHO, 2002).

The Department has established a programme inHuman Genetics and Genomic Analysis, whichincludes projects in genetics diagnosis andcounselling, functional genomics, research intohuman genome diversity, and biocomputing. Thereare 16 Genetic Diagnosis and Counselling Unitsthroughout India, which have provided genetictesting and counselling services for over 18 000patients and families affected by genetic disorderssuch as thalassaemia, sickle cell disease, Duchennemuscular dystrophy(DMD), haemophilia, andcystic fibrosis.31

In recognition of the connection betweeninformation technology and biotechnology, theDepartment initiated a bioinformatics programmein 1986. This programme gave rise to theBiotechnology Information System Network,which operates throughout India, and has resultedin the development of state of the art computationaland communication resources that are used tosupport sophisticated bioinformatics research.India now operates as a “major regional nodal pointfor genomic-related databanks and networks”(WHO, 2002). In addition, the Indian Governmentrecently approved a programme in moleculargenetics and genomics with an annual budget ofUS$ 4 million, to be administered through theIndian Council of Medical Research (WHO, 2002).Furthermore, the Indian Ministry for Science and

Technology has invested in a number of centres ofexcellence in the field with world-classinfrastructure and staff, such as the Plant GenomicsCentre, New Delhi, and the Centre for HumanGenetics, Bangalore.32

States like Andhra Pradesh, Karnataka,Maharashtra, Kerala, Tamil Nadu and HimachalPradesh are developing biotech parks and biotech-friendly policies, which include a number ofconcessions for foreign industry partners.33 Twohighly successful biotech firms are Shanta Biotechand Bharat Biotech. Shanta Biotech producesIndia’s first genetically engineered vaccine calledShanvac (BioSpectrum, 2003), which vaccinatesagainst hepatitis B. Shanvac retails for US$ 4 whichis less than half the price of similar vaccine sold bymultinational companies.

Patent law in India

India’s original Patent Act was passed into law in1970 (Singh and Agarwal, 2003). TRIPS enteredinto force in 1995. The Patent (First Amendment)Act 1999 provides transitional patent protection,as a step towards becoming fully TRIPS compliant,by implementing Exclusive Marketing Rights(EMRs). EMRs are particularly important inrelation to drugs and food, because India will notallow product patents until 2005. EMRs provideexclusive rights to sell one’s patented products,whereas full product patents grant exclusive rightsto both manufacture and sell the products. TheEMRs protection period is five years.34 Under the1999 Amendment, it is now possible to make anapplication for product patents, includingsubstances intended for use or capable of beingused as a medicine or drug, but excluding theintermediate for the preparation of drug. However,because India has until 2005 before its patentlegislation must be fully TRIPS compliant, productclaims for medicines or drugs will not be processeduntil the end of 2004.35

The Patent (Second Amendment) Act 2002 andthe Patent Rules 2003, which came into force on20 May 2003, include provisions for extending thepatent term to 20 years and emergency provisions


to protect public health. These amendments willbring the Indian patent regime further in line withTRIPS. Indian law used to provide a standard periodof 14 years protection (from the date of sealing)and 5 years protection (again from the date ofsealing) for food and medicinal products. This hasbeen increased to a protection period of 20 years.

In order to protect indigenous knowledge, anexemption for products based on Indian systemsof medicine has been granted. Section 3 of thePatents Act explains that an invention that is infact traditional knowledge is not patentable. Nordoes the Indian patent system appear to allowpatents on genes or cells.36

2.5 Some early lessons fordeveloping countries

Each of three countries described above hasachieved a level of competence in gene-basedresearch and its applications. Though there arediverse and complex economic, historical andcultural factors at work, it may be useful tohighlight those features that are common to allthree countries:

� political commitment to building strongnational biotech industries, supported byfinancial resources;

� a clearly defined project, highly relevantto local needs around which to mobilizeefforts;

� an emphasis on building sustainable net-works across the country;37

� capitalizing on international partnerships,and timely entry into the industry; and

� vocal and active participation in interna-tional negotiations on trade and benefitsharing, and domestic structures andpolicy created to protect indigenous re-sources.

One area of divergence of particular relevance tothe present discussion is on the issue of DNApatents; there is no common approach among thethree countries on how to address human DNAwithin patent law.

It is not clear if, and how, the status of DNA asreflected in the patent law of developing countrieshas affected or may in the future affect the abilityof developing countries with relatively strongresearch and technology bases to harness geneticapproaches to improve the health of theirpopulations. It also remains to be seen how theseissues will interact with the overall changes to theirpatent systems as a result of TRIPS coming intoforce in these countries in 2005.

30

3.1 Ethical, legal and socialchallenges to the patentingof DNA

3.1.1 Ethical objections

Despite the fact that patent offices in the UnitedStates and Europe have been granting patents onDNA, there continues to be wide debate about theacceptability of this practice, both on ethical andlegal grounds. In this section, we will sketch someof the broad issues and concerns that have beenconsistently raised in the course of this debate.

Commodification

Intellectual property is a system that confersproprietary rights not on real objects, but on the“intangible commons of the mind” (Boyle, 2003).As we saw in section 1.5.2, the trend in some of themost influential countries over the last two decadeshas been toward a pro-patent policy, one thatfavours patent owners and the expansion of what isdeemed patentable subject matter. Patents ongenetic sequences present a case that falls at theintersection of two controversies: the patenting,and thus the commodification, of biologicalentities, and the patenting of raw data. Concerns

have been expressed about the commodificationof persons and their biological material.38 It hasbeen claimed that it is unacceptable for people tohave “proprietary rights in living beings andtissues” (Gold, 2003), and that market logic nowholds sway over the use of living organisms (ortheir component parts). The court case of Diamondversus Chakrabarty of 1980 in the United Statesconfirmed the patentability of micro-organisms,arguably catalysing the growth of patents in thebiotechnology sector. More recently HarvardUniversity’s successful patenting of theOncoMouse demonstrated that in the United Statesand Europe the courts judge that organisms arelikewise patentable subject matter. Notably, theOncoMouse patent was narrowly rejected by theSupreme Court of Canada, in a 5-4 ruling (Check,2002; Scassa, 2003). And, as we saw in section 2.1,there continues to be much dispute in Europe aboutwhether this is in contradiction to the EU Directiveof 1998 that requires patent protection forbiotechnological inventions. Besides theobjections to the patenting of DNA and otherbiological entities, there are objections that patentsnow permit the commodification of ideas. Bothobjections are argued on two fronts: the first claimsthat extending property rights to biological entitiesor to ideas is wrong in itself; the second isutilitarian, and judges that such practices are wrongbecause they generate unacceptable consequences.

3Analysis: impact of DNA patentson access to genetic tests andgenomic science


Policy debates often tend to focus on the latter typesof argument, because they circumvent difficultdiscussions that often arise from varying worldviews, religious or intellectual. However,objections to the broader patent system and topatenting of genetic sequences should not bebrushed aside; these questions do merit inclusionin policy discourse. Often, decisions about changesto the intellectual property system, which of latehave tended towards strengthening and extendingits reach, have been made on the basis of economicarguments that have not been conclusively proven.Given the lack of definitive economic justificationfor the expansion of IP rights, it is particularlyimportant to take account of objections based on afundamental uneasiness with the system—whichin several cases have been expressed articulatelyand soberly by critics. Though it is doubtless easiersaid than done, this suggests that moves to expandIP into new and controversial territory—particularly in the absence of incontrovertibleeconomic arguments—should not proceed in theabsence of public dialogue.

The TRIPS Agreement leaves space for countriesto do precisely this. According to Article 27 ofTRIPS:

2. Members may exclude frompatentability inventions, the pre-vention within their territory of thecommercial exploitation of whichis necessary to protect ordre publicor morality, including to protecthuman, animal or plant life or healthor to avoid serious prejudice to theenvironment, provided that suchexclusion is not made merely be-cause the exploitation is prohibitedby their law.

Some countries have rejected the patentability ofland mines on these grounds (IPR Commission,2002). But while the ordre public provision, intheory, constitutes a “morality filter” of sorts fordetermining patentable subject matter, andtherefore suggests a route to opponents for

protesting the patentability of DNA, in practice, ithas been invoked only in unusual and extreme cases(Nicol and Nielsen, 2003).

“Common heritage of mankind”

A further position, articulated in UNESCO’sDeclaration on the Human Genome and HumanRights (AIRES/53/152), claims that the humangenome is the common heritage of humankind.This implies that DNA has a special character,beyond that of ordinary biological molecules.Human DNA is common to all human beings(DNA itself is common to all living things), pastand present, and is therefore in some sensefoundational, imbued with not only biological, butalso historical and even moral significance. Onthe other hand, it has been argued that such a viewborders on “genetic essentialism” (Suter, 2001), akind of reductionism that grants exaggerated valueto the contribution of genetics to human behaviour,identity and culture, minimizing the importanceof non-biological factors. UNESCO’s Declarationwas unanimously adopted by the UN Assembly in1997, and has been widely cited. While theDeclaration affirms that “the human genome in itsnatural state shall not give rise to financial gains”(UNESCO, 1997), it does not explicitly precludefinancial gain obtained by the patenting of genes,or of isolated genetic sequences. Despitewidespread controversy, it is noteworthy that, todate, “the shared status of the genome at the‘collective’ universal level has only beenspecifically addressed by international and regionalpolicymaking bodies” (Knoppers, 1999). It is notprecisely clear what this claim amounts to, inpractice. More than likely the argument sets thestage for one of the following assertions.

Public good

A public good is one that is non-rivalrous andinappropriable. A classic example is air: mybreathing it does not stop you from breathing it,and it would be very difficult for anyone to chargemoney for its consumption. It has been argued thatDNA has this character (Devanand et al., 2003).


Genomics is principally about knowl-edge, which is commonly conceived tobe the archetypal public good. Genomicsknowledge is non-rivalrous in con-sumption (not depleted by use), and isusually made public by genomicsdatabases on the internet and journalpublication, as was the case with themalaria and mosquito genome. It is aglobal public good in the sense of theknowledge not being bound by nationalborder, in discovery, transmission, oruse. Further, the global public-good na-ture of genomics is reflected in the wayin which the Human Genome Projectwas funded and undertaken(Thorsteinsdóttir et al., 2003).

To call something a “public good” is not simply todescribe how it is; it is to make a normative claimabout what would be in the public’s interest. In thecase of air, it is a public good because itsappropriation would make everyone worse off. Tosay that genomics, or more specifically genomicdata, is a public good is to say that people would bebetter off if everyone had access to it.

But as we have seen, the generation of genomicdata requires a different set of institutional andanalytic tools than the translation of this data intopractical applications. The latter work looks morelike drug development and less like basic science,and may therefore require the financial incentivesof the patent system to justify the investment oftime and capital. If this is true, then it could well bethe case that permitting some level of appropriationwould introduce more benefits to the public thancosts.

Some commentators have not argued so muchagainst property rights per se—rather they haveargued against the misappropriation of goods fromthose who were their rightful owners. Often thesearguments are a background to further claims aboutdistributive justice, so that the benefits of researchreach back to those who were the “source” of theraw material. In most cases, the source is acommunity whose members share various genetic

traits in common, whose DNA is tapped forscientific, clinical or commercial gain. In essence,such arguments express a concern about thedistribution of benefits, and use the question ofownership as a means of ensuring that those withunequal power but desirable resources, and whocontribute in some way (whether intellectual orbiological) to research that generates useful results,get their due.

3.1.2 Benefit sharing

Some discussion of benefit sharing in relation togenetic resources has taken place within the contextof the United Nations Convention on BiologicalDiversity, adopted at the 1992 Earth Summit inRio de Janeiro. Among the Convention’s threeprimary goals is the fair and equitable sharing ofthe benefits from the use of genetic resources. In2002, the Bonn Guidelines on Access and BenefitSharing were adopted under the CBD;

39 however,

their application to human health is limited because,as section C/9 of the guidelines lays out, the scopeof the guidelines is defined so as to explicitlyexclude human genetic resources.

The earliest discussions of human genomics andfairness arose apart from deliberations in the UN,and were in relation to families of patients withdebilitating genetic illnesses, such as Canavandisease, who participated actively in fruitfulresearch ventures. Indigenous peoples’ rights, incontext of participating in human populationgenetics as opposed to biodiversity, is an issue thatarose later, and was principally catalysed by theHuman Genome Project. In 2000, the HUGOEthics Committee, in its statement on benefitsharing, considered benefit sharing specifically inthe context of research involving the humangenome. The Statement recommends, among otherthings, “that profit-making entities dedicate apercentage (e.g. 1%–3%) of their annual net profitto healthcare infrastructure and/or humanitarianefforts”. In an editorial for Science published inthe same year, members of the HUGO EthicsCommittee offered three arguments to justifybenefit sharing (Berg et al., 2000):


� 99.9% of the human genome is commonto all humans. This entails a responsibil-ity, grounded on human solidarity, to sharein the benefits of research based on thiscommon good.

� There is a long legal history of viewingglobal resources, such as the sea, air andspace, as common goods, to be equitablyavailable to all humans, and protected forfuture generations. The human genomecan equally be regarded as a common her-itage.

� Vast differences in power and wealth be-tween those conducting human geneticresearch and those providing genetic sam-ples for such research, as well as the po-tential for substantial profits, raise con-cerns of exploitation. The HUGO EthicsCommittee sees benefit sharing as a wayto address these concerns.

It has been argued that the discovery of disease-related genes is increasingly the result of fruitfulpartnerships between researchers and thoseafflicted with the condition (Merz et al., 2002). Toa growing extent, research participants not onlytake part in studies; they are also integrally involvedwith broader aspects of the research, includingidentifying and obtaining samples from otheraffected individuals, and even with securingresearch funds. This was the case for the more than150 families worldwide that participated in acollaborative initiative with researchers at MiamiChildren’s Hospital (MCH), which led to the 1993discovery of the gene linked with Canavan disease.Canavan disease is an inherited, fatalneurodegenerative disease largely affectingAshkenazi Jewish people. In 2000, several of thesefamilies as well as various patient associations suedMCH, which had patented the gene without theknowledge of the research participants, for whatthey judged to be an unacceptably restrictive andcostly licensing strategy. Following the issuanceof the patent for the disease-related gene, one infour laboratories in the United States stoppedoffering a test for Canavan disease because of theconditions that MCH attempted to impose on them

(Cahill, 2001; Brower, 2000). The CanavanFoundation had at one time offered genetic testingfree of charge, but ended this practice after it wasadvised that the patentee would require paymentof royalties to MCH, and compliance with specificlicence terms if it wished to continue offering thetest (Marshall, 2000). This case was settled out ofcourt, on terms that have not been made public.

Among the players involved in the developmentof genetic tests—including patients and patientorganizations, universities, companies, andgovernment agencies—some “believe that [patientsand advocacy groups] are the best situated torepresent, protect and serve the interests of thosemost affected” (Merz et al., 2002). Providingcompensation or property interests for those whosesamples are studied, or at the very least giving thema say in how the patented invention should be used,may be strategies for mitigating purely commercialmotives that could hinder access. In some cases,this would mean going against the grain, and seeing“sources” as more than just exploitable founts of“raw” material, with legitimate interests in sharingin the benefit of research in which they have madea contribution, intellectually or materially.40

There are examples of companies that haveincorporated benefit sharing into their strategies,most notably: the Canadian firm NewfoundGenomics, which donates 1% of its net profits to acharitable trust for the general population (http://www.newfound-genomics.com/); deCODEGenetics, which was granted the exclusive use of acentrally compiled population health database inIceland in exchange for paying all related expensesincurred by the government for its building andmaintenance, in addition to an approximatelyUS$ 700 000 annual payment, and 6% of its grossprofit; and the University of Hawaii, whoseresearchers discovered a gene mutation responsiblefor a rare genetic disorder called pseudoxanthomaelasticum (PXE), and subsequently filed for andobtained the first patent in the United States withone of the patients’ parents as co-inventor (Altonn,2002; Marshall, 2004; Terry and Boyd, 2001).According to Patrick Terry, chairman of theadvocacy group PXE International: “With the


heavy stick of holding a patent on the gene, we canaccelerate the research process, control royalty andlicence fees and eliminate turf wars betweenresearchers” (Coghlan, 2001). This presentsanother example of how patents can sometimes beused strategically to secure access to proprietarytechnologies.

The International Treaty on Plant GeneticResources for Food and Agriculture, which tookeffect on 29 June 2004, could prove an importantprecedent for benefit sharing in the context ofhuman genetics. This Treaty is the product of sevenyears of negotiations among governments, farmers’and consumer groups, research organizations andcompanies. According to Article 13.2:

(ii) The Contracting Parties agree thatthe standard Material TransferAgreement referred to in Article12.4 shall include a requirement thata recipient who commercializes aproduct that is a plant genetic re-source for food and agriculture andthat incorporates material accessedfrom the Multilateral System, shallpay to the mechanism referred to inArticle 19.3f, an equitable share ofthe benefits arising from the com-mercialization of that product, ex-cept whenever such a product isavailable without restriction to oth-ers for further research and breed-ing, in which case the recipient whocommercializes shall be encour-aged to make such payment.

Furthermore, Article 12.3 states:

(d) Recipients shall not claim any in-tellectual property or other rightsthat limit the facilitated access tothe plant genetic resources for foodand agriculture, or their geneticparts or components, in the formreceived from the Multilateral Sys-tem (ftp://ext-ftp.fao.org/ag/cgrfa/it/ITPGRe.pdf).

Although its subject matter is plant geneticresources, the Treaty tries to address very similarissues to those raised in the context of humangenetic resources. The Treaty does not attempt tocircumvent existing intellectual property laws, orto confer intellectual property rights to sources;rather it is an effort to generate a more equitabledistribution of benefits through explicit agreementsbetween parties.

Certificates of origin for (non-human) geneticresources are also being discussed as tools for globaldistributive justice. Certificates of origin disclosethe country of origin of genetic material and proofof prior informed consent. Countries rich inbiodiversity and genetic resources like Brazil, theDominican Republic and Peru have insisted thatcertificates of origin be legally enforced. A legalrequirement of informed consent procedures,along the lines of the Bonn Guidelines, could helpensure that developing countries benefit frominternational genetic research by encouraging adiscussion about the distribution of expectedbenefits with the test population prior to theinitiation of research. Such benefits, as suggestedin Appendix II of the Bonn Guidelines, couldinclude technology transfers, joint collaborationsor joint ownership of intellectual property rights,and might contribute to building capacity ingenomic industries. However, the suggestion toinclude certificates of origin as a legal requirementfor patent applications has been fiercely opposedby patent offices in industrialized countries(Dalton, 2004).

It remains contentious whether resolving thequestion of benefit sharing requires makingchanges to the patent system, or whether there maybe other methods of achieving greater equitythrough policies and approaches outside of patentlaw. Ultimately, most commentators arguing forbenefit sharing are not arguing against theownership of genetic knowledge, but against itsmisappropriation and subsequent failure to fairlycompensate sources.


Developing countries should consider establishingpolicies that encourage entities involved incommercial aspects of research to negotiate openlywith foundations and disease-associated advocacygroups or local community leaders for equitablebenefit sharing. These countries shouldcontemplate creating standards to guide suchnegotiation, in addition to carefully assessingmechanisms for negotiating the distribution ofbenefits resulting from international human geneticresearch.

3.1.3 Legal issues

In addition to ethical and social concerns, a numberof commentators have argued that DNA, at leastin certain cases, does not meet the legal criteria ofpatentability when applied strictly, and that it isnot suitable as patentable subject matter.

One set of concerns turns on the view that DNA’svalue lies principally in its informational content,rather than its material qualities. In the case ofdiagnostics, what is discovered is a particularrelationship between the presence of a particulargene or genetic sequence, and a particular illness.41

According to this view, what has been identifiedlooks more like information than physical material(Nuffield, 2002). According to some critics, thisrepresents a departure not only from patentpractice, but from patent doctrine, which is basedon an agreement to disclose information inexchange for giving the inventor rights over thematerial invention. If DNA itself has value notonly as material, but also, if not primarily, asinformation, this moves away from the usual rangeof patentable material and presents a new challengefor those who need access to the information(Eisenberg, 2002a).

A second set of concerns relates more specificallyto the application of the criteria for patentabilityby patent offices. A general worry is that thesecriteria have been interpreted loosely in somejurisdictions in the context of DNA, and moreoverthat patents of broad scope have been granted. Inthe first instance, there has been concern about therequirement of an “inventive step”, given that the

sequencing of DNA, once a laborious manual task,has become a highly automated and routine part oflaboratory practice. In the United States, the Courtof Appeals for the Federal Circuit’s interpretationof the “non-obviousness” standard has explicitlydenied that the difficulty or complexity ofinvention matters at all in the determination ofpatentability (Rai, 1999). According to this ruling,as long as DNA has not been identified before (inother words, is novel), it meets the non-obviousnesstest. This ruling distinguishes the United Statesfrom Europe and Japan, which maintain a morerobust standard (“inventive step”) that considersthe scientific difficulty of the work behind theinvention. Additionally, there has been questioningof the granting of patents for sequences ofquestionable or limited utility. Some of thiscontroversy has abated with the USPTO’s 2001guidelines on expressed sequence tags (ESTs, shortpieces of DNA that help to identify when particulargenes are being expressed in cells), which tightenthe specifications regarding what constitutes“utility”.42

A third set of concerns relates to the traditionaldistinction between inventions and discoveries.While it might be argued that this is an esotericquestion with little import in patent law, for manyit is fundamental to the question of what constitutesgenuine innovation—the very thing intellectualproperty seeks to stimulate. As we have seen, mostlegal documents stipulate that entities, as they existin nature, may not be patented. However, theEuropean Directive, for example, permits thepatenting of biological entities that have beenisolated from their natural state, which have beenshown to have a certain utility, or industrialapplication.

It may be useful to consider an example. We canimagine a researcher who, by experiment, learnsthat a plant growing in its natural habitat is able totake up toxins in the soil. A second researcher takesthe plant and moves it into contaminated soil,demonstrating its utility to clean up theenvironment. At least intuitively, this latter persondid something one might be prepared to call“innovative”; his colleague’s achievement, on theother hand, while useful in generating scientific


knowledge, was less obviously “innovative”.Knowledge is the quintessential public good; inincreasingly knowledge-based industries,innovation in many cases is driven by the verything that typifies common ownership. But whetheror not one is prepared to view the first person’sefforts as truly innovative may well depend on thedegree of creative energy and technical capabilityneeded to acquire the knowledge in question. Inthe case of genetic information, it has been arguedthat the sequencing and isolation of geneticsequences is no longer a demonstration of morethan basic competence. By contrast, identifying thelink between a particular gene (or set of genes) andthe development of disease, depending on thecomplexity of the interactions involved, is unlikelyto be a straightforward matter. What seems clear isthat the question of what is “obvious” depends onthe state of the technology and of the science at agiven point in its evolution.

It is also clear that sometimes the degree ofobviousness is not a good proxy for the social valueof patenting. This has long been the case in smallmolecule patenting for drugs. What this suggestsis that in some cases non-obviousness is becominga place-holder for valuations about the amount oftime and investment behind innovation, rather thanabout the degree of ingenuity behind an invention.Patents, in this case, are principally to induceinvestment rather than to encourage innovation.Though they may both be important, they are notthe same.

As one author notes:

The presumption against patenting ba-sic information about natural phenom-ena might be overcome if the prospectof securing exclusive property rights inscientific discoveries for a limited pe-riod of time served as a necessary orimportant incentive to making invest-ments in scientific research, in particu-lar, if it served to elicit discoveries thatwould not otherwise be made or to ac-celerate the pace at which scientificknowledge advances (Scherer, 2002).

We will explore in section 3.2 below whether ornot these justificatory conditions in fact hold true.

Given the nature and extent of arguments on bothsides of this debate, it is important for developingcountries to recognize the ambiguity in TRIPS,which does not explicitly require that countriesinclude DNA among patentable substances. At thesame time, they should be aware that it cannot beconfidently said that TRIPS permits the exclusionof DNA, because this ambiguity has also beenargued by some to suggest an implicit requirementto grant patent protection on DNA, if the inventionis deemed to meet the standard criteria forpatentability. For the moment, while it may beoptimistic to describe the available room formanoeuvre in TRIPS as flexibility, the presentambiguity arguably permits a degree of manoeuvreand debate for countries on this issue.

Many practical difficulties with the system may bea product of the struggle of patent offices to keeppace with new technologies, and also of courts insome cases lacking the institutional capacity to stayon top of scientific advances (Rai, 1999).Challenges include keeping up with the state-of-the-art of rapidly advancing fields like genomics,and applying the standard criteria appropriatelyso as to reward genuine invention. While it may bethe case that patent offices and courts, left on theirown, will find the appropriate equilibrium, thiswill no doubt be an extraordinarily lengthy process.It may be of benefit for countries with commoninterests and circumstances to share experiences,and work together to strengthen the capacity ofpatent offices to respond to the challenges ofemerging fields.


3.2 Ways in which the patentsystem may affect accessto genetics and genomics

In general, patents can adversely affect access in atleast two ways: by hindering access to the productsof innovation in genomics in the short term; and,indirectly, hindering genomics innovation,particularly in areas relevant to developingcountries, by creating barriers to research. It canalso positively affect access by incitinginvestigation in complex and expensive researchof social value.

3.2.1 Patents and access to genetictests

Patents can affect access to useful genomicsproducts like genetic tests in at least three ways:

� improving incentives to develop usefultests;

� increasing the cost of available services;� imposing transaction costs and inconven-

ience on research and development;� impeding the transfer of existing tools and

technologies.

We will consider each of these effects below.

Improving incentives to developuseful tests

The raison d’être of the patent system is toencourage innovation—or, more precisely, toencourage the investment of the time, creativityand capital necessary to bring about socially usefuladvances. In such industries as pharmaceuticals,where research and development costs arereportedly very high, there is a strong dependencyon patents as a mechanism for recovering up-frontinvestment.

While the HGP is hailed as a success in publicnon-proprietary research, patents may havecontributed indirectly to the pace of researchthrough the competition provided by Celera

Genomics. Even so, while the sequencing efforthas been held up by some as a prototype forcollaborative public initiatives driven primarilyby non-proprietary incentives, it is far from clearthat the work to translate the now-abundant rawgenomic data into clinically useful applications canrely on the same model. The complexity of gene–gene and gene–environment interactions makes thetask of turning promising targets into concreteapplications a challenging one (Wirth, 2001). Thismeans that creating tests for common diseases, andinterventions for some more intractable infectiousdiseases like malaria and HIV/AIDS, will surelyrequire considerable investment of both time andresources. By contrast, simple DNA-baseddiagnostic tests for single-gene disorders and formany infectious diseases depend less on a highfront-end investment because they are relativelyeasy to make.

In the case of common conditions that tend to affectpeople in both economically developed and poorcountries—such as cancers, diabetes and heartdisease—patents will provide an incentive forinvestment, because firms can be assured that ifthey produce a useful product, they will haveprotected access to wealthy markets to repay theirinitial investment. The main question in theseinstances is how to ensure that these products areapplicable and available in low-resource settings.

In the case of diseases that characterize poor pop-ulations, firms have little incentive to invest. Inthese instances, patents will rarely provide an in-centive for research and development. However,patents may still be useful to developing countriesin at least two ways: first, firms within developingcountries that succeed in obtaining patents in lu-crative markets on an endogenous innovationcould earn rents that lift them into viability; andsecond, patents could be used by those doing re-search relevant to developing countries as tools tonegotiate access to other technologies or services(see Box 5, for instance). The latter is preciselywhat is done by many private companies, whichsee patents as assets to be traded in exchange forother assets of value. The possibility of developingcountry institutions obtaining rents from patentedtools and technologies exists, of course, only where


there is a sufficient science and technology base—which is true of relatively few developing coun-tries. And successfully using patents in bargainingfor rights with other institutions requires, for itspart, an ability to negotiate effectively with insti-tutions (multinational companies or universities,for instance) with considerable experience in par-leying and resources to back that up. One possibleoption that we will consider later is to harness theownership of patents by bodies such as universi-ties (which own a substantial proportion of patentson the health biotechnology sector) as a basis forcollective action.

Increasing the cost of available services

There are high-profile examples of patents ondiagnostic tests resulting in the increased cost ofexisting services. Genetic tests for Canavan disease,familial breast cancer, Alzheimer’s disease andhaemochromatosis are among those that havereceived publicity because of the outcry by patientsand clinicians that patents, combined withexclusive licensing practices, have put the price ofdiagnosis beyond the reach of many. MyriadGenetics charges US$ 2500 to test for BRCA1 and

Hereditary haemochromatosis is a genetic disease that re-sults in an overload of iron in the body, and can lead toarthritis, diabetes, liver cirrhosis, liver cancer, and heartfailure. Early diagnosis and treatment can prevent theseserious complications.

Mutations of the HFE gene (C282Y and H63D) have beenlinked to the disease. In 1998, patents were granted onthese mutations in the United States. An exclusive licenceto perform diagnostic genetic testing was issued by thepatent holder to Smith Kline Beecham Clinical Laborato-ries, which subsequently contacted a number of laborato-ries in the United States and offered to issue sub-licensesin exchange for very high up-front fees and royalties.

The combination of additional costs and the fear of beingsued for patent infringement caused insecurity among thosewho had planned to begin conducting similar testing, aswell as among laboratories already performing similar genetictests. In the United States, it has been reported that of 119laboratories surveyed, 30% of those already offeringdiagnostic genetic testing for haemochromatosis stoppedperforming their tests after the patents and exclusive licenses

were granted. Fewer institutions are carrying out genetictests, which means less data are available to researchersseeking to better understand the disease, and fears havebeen expressed that high costs and royalties charged by thepatent holder and licensee to laboratories are likely to trickledown to patients, who will pay more to access genetic testsfor C282Y and H63D, tests that offer a means of obtainingcrucial information about their health status. Patent claimson the HFE gene have also been filed in Europe.

Some laboratories continue to perform molecular diagnos-tic genetic tests they have developed for pre-symptomaticscreening of the haemochromatosis disease. These serv-ices may very well cease should the patent issue. The EPOhas not yet issued a decision on this case, but politicalopposition has been expressed against the type of patentright granted to the patent holder and the exclusive licen-see.

Source: Cogswell et al. (1999). American Journal ofPreventive Medicine

Box 8Haemochromatosis


BRCA2 (for first tests in each family), and does notpermit any laboratory besides its own or a fewlicensed laboratories in other countries to carryout the test. Haemochromatosis (see Box 8) isamong a host of conditions for which laboratoriesacross the United States have stopped providinggenetic tests because of concerns that they areinfringing the rights of patent holders, many ofwhom have been aggressive in sending “cease anddesist” notices to offending institutions (Cho et al.,2003; Merz et al., 2002). In the latter case,laboratories perceived the cost to be excessive andstopped providing services.

As we have noted before (section 1.5.3), it is notclear that patenting DNA, as such, has posed thegreatest problem in these cases, as opposed torestrictive licensing practices. Of course, licensingis only possible because of patenting; but the pointis that the patenting of DNA sequences does not inevery case lead to diminished access. Some of thebenefit-sharing strategies discussed above may beuseful in addressing the fair distribution of benefitsbetween researchers and sources who contributegenetic material, and in a growing number of cases,substantive research support. However, given thatthe affected population is likely to be the principlemarket for the test in question, it is not clear thatcompanies would be willing to make concessionsin prices. In many cases, such as Alzheimer’sdisease, genetic tests are arguably not ready forwidespread clinical use; however, such tests couldbe valuable in conducting research to furtherunderstand the disease. Research exemptions mayalleviate the cost burden on researchers wanting tocarry out studies using the tests for principallyresearch purposes or in order to improve thetechnology.

Imposing transaction costs and inconven-ience on research and development

Patents on research tools can inhibit access toservices, inasmuch as they hinder research thatleads to innovation in these areas. Research tools,broadly, are “any tangible or informational inputinto the process of discovering a drug or any othermedical therapy or method of diagnosing disease”.For example, recombinant DNA, polymerase

chain reaction, genomics databases, micro-arrays,transgenic laboratory animals, and embryonic stemcells are examples of research tools (Walsh, Aroraand Cohen, 2003). Diagnostics are particularlyaffected by patents on research tools because thesame tools are the fundamental building blocks formaking tests.

As we have seen, patents awarded for genes andDNA molecules grant a right to exclude othersfrom using, making, selling or importing that whichincorporates what is covered by the patent claims(Kluge, 2003). Researchers need to use a largenumber of different research tools, and inbiotechnology there is evidence of the cumulativenature of scientific development such that laterinnovation depends heavily on prior iterativeadvancements. The concern is therefore that theexistence of patents on research tools could slowor even block many subsequent research efforts asresearchers are forced to pay high fees to a largenumber of research tool patent holders before evencommencing their projects, or might even bedenied permission for use. The fact that numerousintermediaries are involved in the very early stagesof research projects could significantly increasetheir cost. These high costs will be incurred at astage when the researchers do not even know ifand when they will achieve any feasible result andwhether that research result will be commerciallyviable. The fear is that the cost of basic researchwill increase due to the increasing number ofpatented basic research tools, slowing downbiomedical innovation. This situation has beendubbed the “tragedy of the anticommons” (Hellerand Eisenberg, 1998), and contrasts with thetragedy of the commons feared to result fromleaving valuable resources in the public domain.

A recent report by the National Research Councilof the United States examines, on the basis ofinterviews and archival data, “the changes inpatenting and licensing in recent years and howthese have affected innovation in pharmaceuticalsand related biotech industries” (Walsh, Arora andCohen, 2003). The authors conclude that drugdiscovery has not been significantly hampered bythe increase in patents on research tools. But to thisconclusion they add the following caveat:


“Restrictions on the use of patented geneticdiagnostics, where we see some evidence of patentsinterfering with university research, are animportant exception”. The same report suggeststhat the anticommons effect is worse for smallbusinesses, and those entering the market (Walsh,Arora and Cohen, 2003), which suggestspotentially greater challenges for emerging sectorsin developing countries. The other very importantfinding is that infringement is rampant, amongacademics and companies both. This means that ifnorms shift, then these “gentlemen’s agreements”could collapse.

On the one hand, this study highlights the evidencethat many institutes in the United States havedeveloped workable solutions that allow them tocarry on with research, in the face of the widespreadpatenting of research tools. These includeinfringing the patent, often by informally invokingthe research exception; developing and usingpublic tools; challenging patents in court; andinventing around the patent. On the other hand,not all of these solutions may be viable within thecontext of genetic diagnostics.

For one thing, it has been argued that in the case ofgenetic diagnostics, inventing around patents maybe considerably more difficult than it is with othertypes of invention. There is a finite number of genes,and therefore a limited number of tools, includingplatform technologies, for researchers to employin gene-based research (Nuffield, 2002).Researchers doing work in genetics could have theirhands tied by patents granted on research tools,which are often product rather than method patents,to a greater extent than their counterparts in otherfields. Gene patents are composition of matterpatents on sequences, so making or using them inthe laboratory without permission for any purposerisks infringement. This becomes particularlyproblematic for the development of tests addressingdiseases affected by multiple genes, each of whichis patented.

Because challenging patents in courts is not afeasible option for firms with limited capital(including the majority of those in developing

countries), or for research institutions anduniversities, a more viable long-term solution mayindeed be to clarify the criteria for DNApatentability, and to apply these criteria morestrictly. This could result in fewer DNA patentsbeing granted, but in an overall higher quality ofthe patents and a greater confidence on the part ofinventors and researchers in the validity of grantedpatents, and thus in the credibility of the system.

The bottom line is that these constraints presentobstacles that may be sufficiently high as to createdisincentives for the pursuit of certain lines ofresearch, and could be particularly heavy fordiagnostics, a field in which the raw materials ofgenomics may translate most easily into usefulhealth applications for developing countries.What’s more, these disincentives will chiefly affectinstitutions that have relatively limited capital, suchas research centres and public–private operations,which are often those groups most concerned withresearch in areas relevant to developing countries.

It is significant that the National Academy ofSciences report states:

Our interviews suggested that the mainreasons why projects were not under-taken reflected considerations of tech-nological opportunity, demand, and in-ternal resource constraints, with ex-pected licensing fees or “tangles” ofrights on tools playing a subordinaterole, salient only for those projects whichwere commercially less viable (Walsh,Arora and Cohen, 2003—emphasisadded).

This means that research oriented towards non-lucrative markets, including research addressingdeveloping country health needs, is particularlyvulnerable to the “tangling” effects of obstacles toaccessing research tools.

Countries can learn important lessons from eachother, but should be wary of looking to others forready-made solutions. The United States patentsystem, for instance, has evolved over a period of


more than two hundred years, during which timethe system itself has adjusted to meet the changingscientific and technological needs of the country.United States patent law formerly excluded foreign“prior art” as a deliberate measure to allow UnitedStates patent applicants to obtain a patentdomestically on a copied foreign invention. Thisoption is limited because of TRIPS. Moreover, withreference to new and emerging industries,including biotechnology and genomics, the UnitedStates has evolved a pro-patent court system and aBayh-Dole framework, as well as more expansiveinterpretation of what is patentable (e.g. businessmethods, algorithms), and an unrigorous non-obviousness criterion, which differs from otherjurisdictions such as Japan and the EU. Thequestion of patented research tools is being takenup in several major studies begun in 2004(Malakoff, 2004), in an effort to collect evidence tofill the void in the current debate about their impacton downstream research. This suggests that it maybe of questionable benefit for developing countriesto look to the United States as a model, at least inthe case of biotechnological inventions, since itsown system continues to be assessed and modifiedto accommodate challenges; however, it will beimportant to monitor its progress so that importantlessons may be drawn for others facing similarchallenges.

Developing countries with relatively advancedtechnological capacity need to weigh differentfactors, including: the impact of adopting featuresof a pro-patent system (such as patent protectionfor research tools) on domestic issues such ascompetitiveness within the local industry; foreigndirect investment; access of poor segments of thepopulations to inexpensive healthcare products; theproportion of local innovation directed at domesticneeds versus those directed to overseas market; aswell as its impact on the supply of generics andother cheap products to dependent markets in lessdeveloped countries. China, Brazil and India aredeveloping countries facing these decisions; theyhover on the cusp between developing countriesand the industrialized world, with scientificcapacity that gives them the possibility of self-sufficiency and international competitiveness, butwith a considerable proportion of their population

living in desperate poverty. As we saw in section2.4 above, these countries have not approached IPin the same way; it will be very important tomonitor the impact of TRIPS on the ability of thesecountries, and others in their position, to maintainaccess to affordable healthcare products for theirown citizens, as well as those in other countriesthat rely on their capacity.

A further factor to consider is the need for patentsas incentives for research in genomics. In thecontext of drug development, where patents havebeen argued to be a necessity, the number of drugsmaking their way into the market has slowed(FDA, 2004). The perceived ‘innovation deficit’,in spite of much larger R&D expenditures in recentyears, may be the result of changes in the technologyand methodology used for doing research, and ofunderestimating the scientific challenges inherentin translating fundamental scientific advances intotreatments for specific conditions. The ‘genomicsrevolution’ has indicated the very important partplayed by public initiatives in putting fundamentalgenetic data into the public domain, which can thenbe freely used by other researchers in the publicand private sectors for further applied andtranslational research. It has also demonstrated theneed to balance incentives offered by patenting,with the need to make platform technologies asaccessible as possible to downstream research andpotential applications. Given the complexity of thetask required to move from a gene to a therapeuticproduct or a diagnostic tool, it would be in theinterest of innovation not to place limits on thenumber of institutions that can be engaged in thiswork.

The pharmaceutical industry has been shown torely heavily, more than most other sectors, onpatents (Scherer, 2002). Making it harder to obtainpatents on research tools does not precludecompanies patenting biologically active substancesthat are one or two steps down the developmentchain. The pharmaceutical industry, through itsinvolvement in projects such as the SNPConsortium, has demonstrated the interest it hasin making upstream genetic information freelyavailable as an aid to drug discovery. Patents onDNA sequences cover a range of applications, not


all of them therapeutic; research might thereforebe compromised across these applications if DNApatents were made harder to get. Firms likely to bemost affected by any limits on the patenting ofupstream tools are biotech companies and start-ups, which are widely held to depend heavily onbiotechnology patents to garner venture capital.

In the remainder of this section, we will considerthe question of access from an international pointof view, namely through the lens of technologytransfer.

Impeding the transfer of existing toolsand technologies

The UK Commission on Intellectual PropertyRights, in its report on IP and development,remarks:

In a sense, the crucial issue in respect ofIP is not whether it promotes trade orforeign investment, but how it helps orhinders developing countries to gainaccess to technologies that are requiredfor their development…and whether itencourages or hinders the developmentof technical capacity, including knowl-edge-based industry in that country (IPRCommission, 2002).

In section 2.1, we noted that patents are national inapplication; however, we also noted elsewhere thatresearch, particularly in emerging technologiessuch as genomics, is increasingly global. Thus,while it may be true that patent protection has notbeen obtained for genetic inventions in manycountries in the developing world, it does notnecessarily follow that patents do not affect accessto health products and services in these countries(IPR Commission, 2002).

Most genetic research is performed in industrial-ized countries, and is predictably directed towardsthe health needs of markets in these countries,where patents have been awarded for entire genes,cell lines containing particular DNA sequences,research methods, and other forms of genetic in-

vention. But companies, scientists and universitiesoften refrain from filing patents on genetic com-pounds in the developing world, in large part be-cause the possibility of financial returns for a pat-ented invention in developing countries is likelyto be very small, and not worth the price of filing apatent application and maintaining a patent once itis issued. In the absence of patent rights, develop-ing countries are, in theory, free to use technolo-gies without penalty or the need to pay licensingfees. However, a crucial practical barrier to ac-cessing genetic tools and technologies within de-veloping countries is that most low and middleincome countries do not have the research, testingor manufacturing capacities to make use of the ex-isting tools and technologies. This is the identicalchallenge faced in the context of pharmaceuticalresearch and development, a challenge acknowl-edged by the “paragraph 6 problem” of the DohaDeclaration, discussed in section 2.1 above. Fur-thermore, with few exceptions, developing coun-tries lack facilities required to adapt existing toolsand technologies to their own needs or access non-patented know-how associated with the use of pat-ented DNA sequences.

It is clear, then, that the majority of developingcountries, and particularly the least developed,unable to develop tests themselves, must rely onimports from their more industrially advancedneighbours. In those cases where a geneticdiagnostic tool has been invented and patented indeveloped countries, and where the invention isalso relevant to the health needs of poorercountries, we can draw some conclusions aboutthe impact that the DNA patent may have on accessto the genetic tool in developing countries,particularly in relation to price, by analogy to theaccess issues faced by developing countries in thecase of product patents for drugs.

Furthermore, patents could block the ability ofpotential supplier countries to export patentedgoods to other countries, particularly throughcontrols on distribution channels. This is anotherreason why companies may selectively patent incountries like South Africa, which, thanks to itsrelatively strong manufacturing capacities, is apotential supplier to poorer countries in the region.


At present, drugs-importing countries where thereis no patent protection can import supplies fromgeneric companies, principally in India, becausethese exporters need not have pharmaceuticalproduct patent protection until 2005. Post-2005,India will have to provide product (and not simplyprocess) patent protection on new drugs, and thosefor which patent applications were submitted after1994 will be patentable; the opportunity for theseimports will thus shrink over time (IPRCommission, 2002). There is no direct evidence,to date, that strategic patenting is a threat toaccessing genetic information; as biotechnologyand genomics become increasingly globalized, itwill be important to assess whether this becomes arelevant issue.

The IPR Commission report encourages govern-ments to consider a number of strategies to pro-vide incentives for technology transfer to low andmiddle income countries, including tax breaks forcompanies that license technology to developingcountries, and commitments to ensure open accessto scientific databases. Governments of more in-dustrialized countries can therefore have an im-portant role to play in encouraging the transfer ofbeneficial technologies to less developed econo-mies, including by way of meaningful partnerships.Developing countries, in turn, could benefit fromstudies that assess the impact of their domestic pat-ent regimes and patent protection on the transferof technology for the sustainable development oflocal capacity in genetic technologies.

3.2.2 Some preliminary proposals

A number of proposals have been put forward forsolving the problem of access to health careproducts. In the case of pharmaceuticals, it has beensuggested that developing countries may rely uponcompulsory licensing to gain access to licensedinventions, under certain conditions. While thereis some evidence that compulsory licensingprovides leverage for bargaining in the context ofnegotiating access to therapeutic products, it is lessclear that it is a viable option for preventativeapproaches, such as genetic diagnostics.Compulsory licensing is an important option for

national governments. It is, however, a defensivemechanism that kicks in after a product has beencreated and patented.

Addressing licensing behaviour, by encouragingthe employment of humanitarian use, medical useor research use exemptions could go a considerabledistance toward rectifying the problem of accessingresearch tools. Several commentators advocatesuch changes in norms, which require much greatertransparency in making public the terms oflicensing agreements. One author terms this“publicly-minded licensing” (Benkler, 2004). ThePublic Intellectual Property for Agriculture(PIPRA), is a collaboration among agriculturalresearch universities to share their IP and retainrights to use their technologies for subsistence andspecially for crop development. Groups likePIPRA are formed to give universities much morenegotiating power with biotech and pharmaceuticalindustries. Humanitarian use exemptions, ordeveloping country licenses for their part, wouldpermit research, development, manufacture anddistribution of end products destined for developingcountry markets, or poorer markets withindeveloped countries. Research exemptions wouldpermit the use of a patented technology for researchand education, under certain specified conditions.Such arrangements suggest a change in licensingnorms, rather than changes in legislation or atinkering with the patent system.

Alternatives to patents have also been proposed,including open source approaches that more closelyresemble the loose property arrangements ofcopyright (Maurer, 2002), and the employment ofcompensatory liability rules (Reichman and Lewis,2005). The former model is based largely on theopen source software movement, which operateson distributed innovation and the ingenuity ofnetworked volunteers. The latter model ofcompensatory liability rules takes a well-established method and adapts it to protect know-how under specific circumstances. Liability rulesembody a legal structure that permits third partiesto undertake certain actions without priorpermission, provided that they compensate injuredparties for all or part of the harm they inflict.Liability rules understood in relation to modern


research would operate to manage sub-patentableinnovation—that is, inventions that do not meetthe non-obviousness (or inventive step) standard.They would not be a substitute for the “absolute”property rights of patents, but rather wouldcomplement them, furnishing a means of providingprotection for useful inventions while mitigatingagainst access concerns tied to stronger propertyrights. Proponents of liability rules have arguedthat they provide a viable framework forencouraging small-scale innovation in developingcountries:

[Q]ualified experts have long agreedthat most developing countries wouldbenefit from a special regime to protectsmall-scale innovation. This followsbecause the more limited technical ca-pacities of producers in most of thesecountries are better suited to applica-tions of inventions made elsewhere tolocal conditions than to developing big-ger scale inventions from scratch, espe-cially when these depend on basic re-search, in which most developing coun-tries are deficient (Reichman and Lewis,2005).

Inasmuch as this view of liability rules specificallytargets sub-patentable innovation, it is a crediblemodel for providing property protection forgenetic sequences, one that is somewhere betweenpatents and copyrights in strength. This modelwould require an infrastructure that would permitmediation and the enforcement of rules, and wouldin practice likely function by pooling tools amongowners within a given field, to facilitate access toand the management of research tools. To date,liability rules have not been applied in the contextof research; it is therefore difficult to evaluate theirfeasibility. A good way of testing compensatoryliability rules could be in the context of a specifictechnology, for instance, the development of amalaria vaccine or diagnostic device fortuberculosis.

The open source approach that characterizes thesoftware industry may also prove relevant. Open

source products are made accessible to third partiesby a licensing system that does not require paymentbut does require that any innovation made as aresult of using the invention be placed back intothe public domain. In other words, the cost of accessis the enrichment of the public domain, so that noone individual can control access to genetic tools.The system works best if subsequent inventorsactually acquire rights and then license out theirinventions to all comers on the same conditionsthat were imposed on them. This is a way for geneticknowledge to flow freely into the public domain,much in the same manner as the Human GenomeProject, through copyrights that do not rely upontheir inherent right to exclusivity (Gold, 2003).Open source approaches to genetic informationhave been promoted by an initiative founded in1994, Cambia (www.cambia.org), which has beencalled “a clearinghouse for intellectual propertyissues” (Finkel, 1999). Some industryrepresentatives have been critical, arguing thatopen source undermines the incentive to conductresearch into viable products. And open sourceapproaches have also yet to prove themselves inthe long-term, even in the software industry. Thegrowing intersection between biotechnology andcomputation, as witnessed in the emergence ofbioinformatics and data mining, suggests that themodels and networked framework of the softwareindustry are likely to pervade biomedical sciencesto a growing extent. India, for example, has madeexplicit moves to develop capacity inbioinformatics, to capitalize on its native skills inthe chemical sciences and in informatics.

There nevertheless remains the possibility ofincluding DNA among those entities excludedfrom patentability. In light of current practice inmost economically advanced countries, and thepresent trend towards expansive IP coverage, it isimportant to point out that this is a controversialoption.

Several countries have at different times excludedsome inventions from patent protection, oftenrestricting patents on products and limitingprotection to the processes that make them. Foodstuffs, pharmaceuticals and chemicals are sectorswhere exclusions have typically applied. These


products are essential goods for which the benefitsof free access are perceived to override the potentialstimulus to innovation. In the 19th century, thisapproach was adopted by many countries that arenow considered developed, and some maintainedit until late in the 20th century. This was also thecase in the East Asian countries (such as Taiwanand Korea) until relatively recently. TRIPS nowforbids discrimination in the grant of patentprotection in respect of different fields oftechnology. TRIPS does not, however, stipulateexplicitly that DNA must be subject to patentprotection, insofar as it is not excluded.

Countries deciding to avail themselves of thisambiguity should do so understanding (1) thewidespread view of patent lawyers that DNA isprimarily a chemical compound, (2) the three-decade-long history of permitting DNA patentsin several countries, and (3) the TRIPS requirementto make “patents available for any inventions,whether products or processes, in all fields oftechnology without discrimination, subject to thenormal tests of novelty, inventiveness and industrialapplicability”.43 In any event, complainingmembers of the WTO will have the burden to provethat TRIPS obliges the protection of DNA as an“invention”.

Developing countries are required to grant productpatents on pharmaceuticals by 2005 and leastdeveloped countries, by 2016. However, givenevidence that genomic industries operate on amodel of cumulative development and of the roleof DNA as a foundational tool for further research,developing countries should carefully consider thestandards they apply in permitting (product, orcomposition of matter) patents on DNA, in termsof encouraging innovation in genomics and otherareas. The status of DNA as patentable (orunpatentable) subject matter would, preciselybecause of the “foundational” nature of DNA, haverepercussions not only on basic research involvingthe study of genes, but also on a host of other areasincluding pharmaceutical research.

Developing countries with relatively strong sci-entific capacity need to think carefully about fol-

lowing this option, given that patents for them mayprovide obstacles in some instances, but in otherscould earn them considerable rent on a major in-novation patented worldwide. Developing coun-tries with very limited research and technologicalcapacity have little to gain from providing patentsbecause they do not have sufficient technical skillto attract foreign companies or to incite local in-novation. These countries may, on the other hand,be in a position to be more experimental and to tryoptions such as petty patents, compensatory liabil-ity rules or other systems to encourage small-scaleinnovation.

Excluding DNA from patentability as a chemicalcompound or “composition of matter” may bejudged by some accounts to be incompatible withTRIPS, though there is nothing in the Agreementobligating the grant of patents over substancesexisting in nature (even if isolated). For thosecountries wishing to circumscribe but not tocompletely forbid the patenting of DNA, as analternative to denying patents on genetic materialstout court, the standard of non-obviousness (orinventive step) could be applied more rigorously,in which case genetic sequences are likely to fallshort in most instances. As with USPTO’s revisedguidelines, the utility standard could likewise be atool for diminishing the impact of research toolpatents, by diminishing the number of patentsissued on sequences of dubious industrial value.

For developing countries with sufficienttechnological capacity to develop tools to addresslocal needs, there is limited economic research atthe country level that directly links the IPR regimeto domestic innovation and development,generally. But there is evidence that relatesinnovation in some sectors in Brazil and thePhilippines to the availability of utility models, orpetty patents,44 which offer limited protection forinventions that may not meet the standards of thepatent system. The intellectual property protectionprovided by utility models tends to be more widelyused by local residents than by foreign companies,while in many countries the opposite is the case forfull patents, the majority of which are owned byforeigners (Richards, 2002). This suggests thatutility patents may be useful for stimulating local


innovation. In Japan, the evidence suggests that asystem of weak protection based on utility modelsand industrial designs facilitated incrementalinnovation by small enterprises, and the absorptionand diffusion of technology. This was associated,as in Taiwan and Korea, with an absence of patentprotection for chemical and pharmaceuticalproducts. Japan introduced protection forpharmaceuticals only in 1976. Some com-mentators have recommended a petty patentsystem for developing countries, though othershave argued that the existence of utility modelsalongside the patent system creates confusion andeconomic inefficiencies, and provides opportunitiesfor large companies to gain control of innovationsrepresenting incremental advances (Cornish,Llewelyn and Adcock, 2003). Petty patents differfrom liability rules because the former are stillabsolute rights that forbid the use of the inventionwithout the prior consent of the right holder.Liability rules operate on a “use now, pay later”model that presents no barriers for use, but onlyrequires compensation at a later stage. The role ofpetty patents in encouraging domestic innovationshould be weighed against the possiblemonopolization of particular fields by largecompanies, using petty patents (bearing in mindthat diagnostic firms are typically small).

In some countries, attempts to overcome difficultiesof accessing licensed technologies have led to theuse of so-called “patent pools”, which areagreements between patent owners to license theirinventions to each other or third parties. However,to date the conditions do not seem to havematerialized. In 2000, a report by the USPTO onpatent pools and biotechnology patents concludedthat “the use of patent pools in the biotechnologyfield could serve the interests of both the publicand private industry, a win-win situation” (Clarket al., 2000). Among the benefits cited for thisapproach to licensing were: efficiency in obtainingrights to patented technology through “one stop”licensing mechanisms; the distribution of risks

associated with research and development; and theelimination of “blocking” patents or “stacking”licenses, and the consequent encouragement ofcooperative efforts. Most pools start from a groupof companies with shared market and blockingpatents, with no one player believing it has a clearadvantage. However, such strategies may bedefensive, and therefore not contribute to openingup access to tools but to limiting its use to thoseowning pivotal patents.

As we have seen, a case has been made that patentpools could be most useful for technologiesparticularly relevant to developing countries,because the lack of strong market incentives mayenable agreements that lucrative incentives wouldmake more difficult to engineer. It has been arguedthat such an approach could work for low-marginresearch such as that directed towards problems ofthe poor, because it tends to be conducted byuniversities or non-profit institutions, a relativelyhomogenous group that could be knit togetheraround shared values and a shared goal, withoutthe powerful distractions of powerful financialinterests. PIPRA is precisely this kind of venture.Its members have publicly committed togenerating “best practices” for systematicallyretaining rights that permit public institutions tofreely undertake research oriented towards theneeds of developing countries (Rai, 2004).

Patent pools, liability rules, and open sourceapproaches to accessing genetic research tools,particularly genomics databases, should beexplored as an alternative to patent approaches.Recent work suggests that genomics andbiotechnology are appropriate candidates for theseapproaches, at least at the level of basic research.

Finally, developing countries with an interest indeveloping capacity in genomics might considerthe value of networking. For instance, Brazil andMexico have taken steps at the national level toestablish competence in genomics and related


disciplines. For many countries in the region, aprincipal obstacle to these efforts is a lack of fundsto afford equipment and facilities. This dearth ofresources could be compensated by a “networkingstrategy” that relies on collaboration amonginstitutions in various countries, and thereforemaximizes resources (Ramírez, 2003). A similarapproach was employed nationally across Brazil,which established a virtual network of institutionsto facilitate cooperation across its vast territory.South Africa has recently launched a policy fordeveloping biotechnology and genomics in a reportentitled Biotechnology platforms: strategic reviewand forecast. The policy advocates the

establishment of world-class genomics capacity,through the creation of a national facility andcentres of excellence. The New Partnership forAfrica’s Development (NEPAD) has likewisecommitted to developing regional capacity inscience and technology, including genomics, usingnetworks of centres of excellence. The recentlaunch of the African Biosciences Facility in SouthAfrica is a concrete achievement in this effort tomake possible Africa’s active participation in theadvances of genomics. It may be that such networksfacilitate the development of more “networked”approaches to innovation, such as those describedearlier in this section.

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4Conclusions

Intellectual property has existed, in some countries,for centuries, and biotechnology patents have beengranted in several jurisdictions for years, but it isonly in the past decade that heated controversy hasarisen around the patenting of biological entities(Eisenberg, 2002b). Various theories have beenpromulgated to explain this fact; what is clear isthat the debate has by no means been put to rest.

The patenting of DNA presents an interestingpoint for consideration, because it is a topic aboutwhich there is great polarity in views, not onlyabout its effects on research and access, but alsodue to more basic misgivings about whether DNAis the right sort of thing to patent. Ethical, legaland scientific concerns intermingle to create acomplex milieu for discussions that range fromconsequentialist arguments about possiblepractical implications, to renewed and vigorousdiscussion of the meaning of “innovation”. In thisreport, we have attempted to consider the varioussides of this debate through the lens of public health.

One of the challenges with respect to DNA is thatit is an upstream tool for basic research (e.g. PCR),a medically valuable product (e.g. gene therapy),as well as vital information about the molecularbasis for disease. Some individual patents aretherefore at once the basis for involved studies todevelop therapeutics, and for immediate use inlaboratories as research tools. That is, in somecases, DNA patents can conceivably doconsiderable work to encourage the developmentof therapeutics or diagnostics, and at the same timebe needed for researchers, widely and at low cost.The Human Genome Project, which was itself acase study of innovation, employed incentives for

scientific and medical, but not primarilycommercial, research. There remains, as we haveseen, an unresolved question about whether suchan approach can equally succeed in spurring thework needed to move the fruits of this researchdown the pipeline, to produce benefits for publichealth. In other areas, evidence suggests that aproliferation of patents has not been accompaniedby a proliferation of medical applications—thoughthis tells us only that patents are not solving theproblem, not that they do not matter. While muchof this perceived lag is no doubt owed to technicalissues and the inherent complexity of the science,it is unclear how much is related, if only indirectly,to a failure of incentive mechanisms, includingpatents, to generate new and useful products andservices.

We have seen that one possible exception is thefield of diagnostics, where genetic tests aregenerally considerably easier and cheaper todevelop than treatments or cures. Indeed, medicinehas long been practised on a diagnostic model thatacknowledges the tremendous importance ofidentifying risks, even in the absence of therapies.Diagnostics, then, for developing countries, appearto be a far more achievable application of genomicsin the short term, to fill a very important publichealth need. Building the skills locally to diagnosethese conditions not only addresses a real andpresent need facing many countries with endemicdisease burdens; it can lay the groundwork fordeveloping capacity in genomic applications moregenerally, and contribute to what is an ongoingeffort on the part of researchers worldwide totranslate the wealth of genomic knowledge intobeneficial applications.


Indeed, given the complexity of the work totranslate the wealth of raw genomic data intopractical solutions, it would be preferable to permitas many researchers as possible to take up thischallenge. Tying patent protection to productsfurther down the development pipeline linksinnovation with socially valuable inventions thatshould give evidence of real-world utility.Facilitating widespread access to gene sequencesand other upstream discoveries useful as researchtools could encourage a large number ofresearchers and institutions to undertake the muchtrickier work to develop end-products—particularly if those products are assured of patentprotection, or other reward. Patent standards arecurrently being stretched to accommodatearguably sub-patentable items such as genesequences. While these useful discoveries maymerit some protection of some kind, they in mostcases may not deserve the absolute protectionprovided by patents that exclude access.

In developed countries, where the science is moreadvanced, there is talk of a transition fromtraditional medical genetics, which focusesnarrowly but effectively on heritable conditions,to genomic medicine, which integrates geneticinformation into everyday clinical practice. Indeed,according to proponents of genomic medicine, itis knowledge that will transform medical practicein the long-term—knowledge of how genesinteract with each other and with the environmentto cause disease. In the foreseeable future, then,genetic tests will play an increasing—not adiminishing—role in the diagnosis and prognosisof a range of conditions of great public healthconcern in all countries. But even before we havethe tools to treat or cure these conditions, we canmake important strides in the areas of earlydetection and prevention.

In this report, the aim has been to evaluate thecurrent landscape of issues and evidence. Here, wepresent the major conclusions of this report, and ineach case offer proposals for avenues of fruitfulinvestigation that could usefully inform policy-making in the future.

4.1 Proposals

— Ongoing ethical, legal and socialcontroversy regarding thepatentability of human DNA

The controversy about the patenting of DNAremains unabated. This controversy is at severallevels, from moral and legal claims, toconsequentialist arguments about social benefit.Questions of benefit sharing also arise in relationto human genetics research, particularly regardingthe obligations of inventors or researchers towardsthose who provide genetic samples. Many of theseissues are parallel to those currently being debatedwithin the context of biodiversity, plant geneticresources and traditional knowledge. In both cases,there is arguably a similar claim that the resourcein question is both communal and “cultural”, andat the same time commercially valuable,suggesting that it is both “person” and “property”to those who have been its caretakers. Oneparticular area where WHO with other agenciesmight make a useful contribution is in suggestinghow policy-making around ethically thorny subjectmatter, such as DNA, might take better account ofthe legitimate concerns of the public. Somepossible avenues of inquiry are as follows.

� Explore possible mechanisms for solicit-ing public input into policy changes relat-ing to IP, including making use of the ordrepublic clause within TRIPS. Examine howsuch input might contribute constructivelyto the development of policy, particularlyin relation to issues of widespread contro-versy (e.g. the patenting of biological or-ganisms, like DNA and stem cells, andwhat kinds of innovation are judged to beof social value).

� Explore policies that encourage entitiesinvolved in commercial aspects of researchto openly negotiate with community lead-ers (including disease-associated advocacygroups, in the case of genetic diseases) for


equitable benefit sharing, and create stand-ards to guide such negotiations. Moreo-ver, carefully assess the value of certifi-cates of origin, or similar mechanisms, fornegotiating benefits for the results of in-ternational genetic research.

� Assess the relevant similarities and differ-ences of benefit-sharing issues relating togenetic resources derived from humans,and those derived from the environment,i.e. biodiversity. Explore what these con-trasts suggest for the synergistic develop-ment of policy in these areas.

� Consider strategies for increasing thetransparency of funding sources that sup-port both public and private R&D initia-tives in genomics and related fields in se-lected developed and developing coun-tries, in order that there might be greateraccountability for publicly supported ven-tures. Likewise examine ways of increas-ing the transparency of licensing inven-tions arising from federal and non-profitfunding, in order to better track how in-ventions are being used.

— Ambiguity in TRIPS regardingwhether DNA may be excludedfrom patentability

National legislation is constrained by provisionswithin international agreements. TRIPS, inparticular, requires that WTO Members adoptminimal standards of intellectual propertyprotection, though countries may take advantageof certain flexibilities to protect the health and safetyof their populations. In relation to DNA patentsspecifically, however, there is ambiguity as towhether TRIPS requires countries to grant patentson DNA sequences. DNA patents have beenwidely permitted in Europe and the United States,but not all countries have responded in like manner.In light of this, it would be useful to undertake thefollowing.

� Conduct comparative studies of se-lected developing countries to identifyways in which they have employedflexibilities in TRIPS for the protec-tion of health-related interests (e.g.ambiguity about some types of patent-able subject matter; compulsory li-cences; etc.) to advance health priori-ties, particularly in relation togenomics.

� Compare the status of DNA as re-flected in the patent law of differentdeveloping countries, and analyse howthis has affected (or will in the futureaffect) the ability of developing coun-tries with relatively strong research andtechnology bases to harness gene-basedapproaches to improve the health oftheir populations. Furthermore, evalu-ate how these issues intersect with theoverall changes to these countries’ pat-ent systems as a result of TRIPS com-ing into force in these countries in2005, with a view to providing guid-ance for least developed countries thatmust make the same transition in 2016.

� Clarify the impact of current researchexemption clauses on clinical researchin selected countries (both developedand developing), and particularly ongenomic research. This work couldhelp to guide developing countries indevising clear and effective methodsof fostering research. In particular, is-sues to consider include whether theexemption should be statutory, and ifso, how to define so it does not destroyreagent, instrument and other “re-search tool” industries aimed towardsresearch laboratories; whether it bemade explicit for non-profit and gov-ernment-funded research, mandating“research use” exemptions in licens-ing practices; and whether it should


emerge from norms and practices (i.e. self-regulation) in technology licensing, suchas through humanitarian-use licensing.

� Assess the role of petty patents/utilitymodels in encouraging domestic innova-tion and weigh their use against the possi-ble monopolization of particular fields bylarge companies, using petty patents. Theparticular value of petty patents in cumu-lative sectors, such as biotechnology andgenomics, should also be evaluated, espe-cially in relation to encouraging domesticinnovation.

— Developing countries stand tobenefit from genomics

There is a body of epidemiological data that atteststo the not inconsiderable burden of debilitatinggenetic diseases, particularly blood disorders, indeveloping countries. Moreover, other conditionswith a significant genetic component, includingheart disease, cancer and diabetes, contribute to agrowing burden of common conditions among allcountries. DNA-based diagnostics, which can beapplied to diagnosis of both infectious andnoncommunicable diseases, are generallyinexpensive to manufacture. Building on theGenomics and World Health report, WHO and itspartners can work to build a global strategy onhow innovation in genomics can better serve thehealth needs of the world’s poor. This would includeconsidering how developing countries at theleading edge of technological development ingenomics and biotechnology, such as Brazil, China,India and South Africa, could provide leadershipby sharing experiences and expertise relating tothe development of endogenous research capacity,as well as the development of infrastructure andcapacity for appropriately evaluating, processingand enforcing patents. Questions whose answersmight usefully inform such a process include thefollowing.

� Consider how the development of low-cost, effective gene tests for use in devel-oping countries could form a case study

for the application of a compensatory li-ability rules system.

� Identify platform genomic technologies,such as microarrays, that could be easilyadapted for application in poor settings, asa basis for pinpointing research opportu-nities. For example, for infectious diseasesDNA analysis could mean making linkswith the biodefence research establish-ment, particularly academic and companygroups developing portable detectionmethods.

� Undertake studies to systematically iden-tify genetic tests of specific importance todeveloping countries (particularly geneticdisorders and infectious diseases), and todetermine which patents exist on thesetests, by whom and in which countries.These studies would also assess the cur-rent licensing agreements surrounding theuse of these tests. This will fill an impor-tant lacuna of knowledge, and provide astarting point for determining concretepolicy steps, where necessary.

� Study cases such as Mexico, which hasadopted a national strategy for the inte-gration of genomics into medicine, to dis-cover the factors underlying this move,including existing capacity in molecularscience and biotechnology, and to shedlight on the role of patents in the innova-tion process in these areas.

� Assess the extent to which researchers indeveloping countries make use of thegrowing repository of publicly availablegenomics data, and current strategies todevelop indigenous capacity inbioinformatics and data mining in low-resource settings.

� Explore mechanisms for developing coun-tries to share experiences, and work to-gether to strengthen the capacity of patentoffices and courts to respond to the chal-lenges of newcomer fields, like genomic


industries. In particular, develop strategiesfor building capacity among policy-mak-ers in developing countries to permit themto recognize and avail themselves of theflexibilities in TRIPS.

� Explore policies in OECD countries thatfoster indigenous technical development,particularly in biotechnology andgenomics, and assess to what extent thesehave been effective in generating healthapplications of local relevance.

� Explore patent pooling, as well as opensource approaches to licensing genetic re-search tools, particularly genomicsdatabases, as an alternative to proprietaryapproaches. In particular, assess their vi-ability for providing incentives for thedevelopment of medical applications, suchas diagnostics and therapeutics (being care-ful to consider relevant differences be-tween these fields) for populations withno ability to pay.

4.2 Some final remarks

Research networks, and particularly those in thebiotech sector, are increasingly complex;understanding how they affect, and are affected by,the patent system is by no means a straightforwardproject, particularly when one tries to assess theimplications for countries that are behind the waveof technological development. The mostproductive way to move forward is undoubtedlyfor countries, to the greatest extent possible, to sharetheir experiences and challenges with each other,and to work together to create best practices thatcan also usefully guide those likely to face similarchallenges in the future. Many industrializedcountries have valuable experiences at both thetechnical and policy levels, and internationalbodies should double their efforts to encouragesupportive networks for information sharing andcapacity building in these areas.

WHO can, as an international body principallyconcerned with public health, play an important

role, as it has in the past, by focusing a health-centred lens on the debate around intellectualproperty and in fostering dialogue in this area. Itcan also facilitate the studies that are needed to fillthe remaining gaps in our knowledge about thetrue impact of intellectual property systems onhealth outcomes, particularly in developingcountries. Indeed, in 2003 the World HealthOrganization, at the request of its membership,established a Commission on Intellectual PropertyRights, Innovation and Public Health to considerIP in addition to broader issues impinging onhealth-related R&D.

It is clear that a discussion of patents does notpresent a complete picture of all the issues relevantto the discussion of access. The notion of innovationitself is a complex one; to the extent that patentsimpact on this process, they are certainly one factoramong many. Education, scientific capacity,physical infrastructure, and appropriate regulatoryand safety standards are among an array ofcomponents needed to ensure a functioninginnovation system.

Finally, it is important to maintain a realistic andmoderate view of the impact of genetics andgenomics on health outcomes. The reality isunlikely to involve dramatic shifts in the short term,or even the longer term; rather, what we have seenso far suggests an evolution of practice rather thana revolution. The work of sequencing the humangenome was a landmark achievement, but only afirst step along a process that will inevitably takemany years to achieve its full potential.Nevertheless, it is at the beginning of the processthat timely consideration can be given to thepossible incentives and barriers that could mouldthe directions of research, and affect access to itsresults.

Clarifying the interplay among patents, innovationand genomics could suggest one set of strategiesfor encouraging the right kinds of research, and amore equitable distribution of benefits.

53

5References

Abbott A (2005). Europe pares down doublepatents on breast-cancer gene. Nature, 26January 2005, 433(7024):344.

Adewole TA, et al.(1999). Application ofpolymerase chain reaction to the prenataldiagnosis of sickle cell anaemia in Nigeria.West African Journal of Medicine, 1999,18(3):160–165.

Ahmed S, et al. (2002). Screening extended familiesfor genetic haemoglobin disorders in Pakistan.New England Journal of Medicine,347(15):1162–1168.

Altonn H (2002). UH makes gene patent history.Star-bulletin, 23 December 2002 (http://s tarbul le t in .com/2002/12/23/news/story7.html, accessed 7 March 2004).

Alwan A, Modell B (2003). Opinion:Recommendations for introducing geneticsservices in developing countries. NatureReviews: Genetics, 2003, 4(1):61–68.

Andrews LB, Mehlman MJ, Rothstein MA, eds(2002). Chapter 5: Commercialization ofgenetic research: Property, patents, andconflicts of interest. In: Genetics: Ethics, Lawand Policy. St. Paul, Mn., West Group, 2002.

Barbosa DB (2004). The New Brazilian PatentLaw (http://www.nbb.com.br/public/memos5.htm, accessed 2 March 2004).

Bar-Shalom A, Cook-Deegan R (2002). Patentsand innovation in cancer therapeutics: Lessonsfrom CellPro. The Milbank Quarterly, 2002,80(4)637–676.

Benkler Y (2004). Commons-based strategies andthe problems of patents. Science,305(5687):1110–1111.

Berg K et al. (2000) Genetic benefit sharing.Science, 6 October 2000:49.

Berne Declaration (2003).

Biological Procedures Online (2004).Announcement of the chicken genomesequence and genome variation maps.Biological Procedures Online (http://www.biologicalprocedures.com/bpo/general/news/040301/05.htm, accessed 5 March 2004).

BioSpectrum (2003). Biotech industry outlook.Biospectrum India (http://www.biospectrumindia.com/advertising/bs.asp accessed 22 February 2005).

Bosch X (2004). Myriad loses rights to breast cancergene patent. Lancet, 2004, 363(9423):1780.

Boyle J (2003). The second enclosure movementand the construction of the public domain.Law and Contemporary Problems. Winter/Spring, 66(1&2):33–74.

Brazil Law (1996). Law No.9.279/96.

Brower V (2000). Canavan families slam scientistsover test patent profits. BiotechnologyNewswatch, 2000:1.

Brower V (2001). Tackling the most difficultdiseases: Genetics and genomics open newstrategies to fight vector-borne diseases.


EMBO Reports, 2001, October, 2(10):875–877.

Brown MS, Ho YK, Goldstein JL (1976). The low-density lipoprotein pathway in humanfibroblasts: relation between cell surfacereceptor binding and endocytosis of low-density lipoprotein. Annals of the New YorkAcademy of Sciences, 1976, 275:244–257.

Cahill LS (2001). Genetics, commodification, andsocial justice in the globalisation era. KennedyInstitute of Ethics Journal, 2001, 11(3)221.

Cao A et al. (2002). Screening for thalassemia: Amodel of success. Obstetric and GynecologyClinics of North America, June 2002,29(2):305–28 (vi–vii).

Carroll AE (1995). A review of recent decisions ofthe United States Court of Appeals for theFederal Circuit: Comment: Not always thebest medicine: Biotechnology and the globalimpact of U.S. Patent Law. The AmericanUniversity Law Review, 1995, 44:2433.

Check E (2002). Canada stops Harvard’soncomouse in its tracks. Nature, 12 December,420(6916):593.

China Daily (2002). New patent rules to upstandards. 2 September 2002 (http://www.china.org.cn/english/MATERIAL/21876.htm, accessed 6 March 2004).

Cho MK et al. (2003). Effects of patents and licenseson the provision of clinical genetic testingservices. Journal of Molecular Diagnosis,February 2003, 5(1)3–8.

Clark J, et al (2000). Patent pools: A solution to theproblem of access in biotechnology patents? 5December 2000:1–16 (http://www.uspto.gov/offices/pac/dapp/opla/patentpool.pdf,accessed 2 July 2004).

Clegg JB, Weatherall DJ (1999). Thalassemia andmalaria: New insights into an old problem.Proceedings of the Association of AmericanPhysicians, 1999, July–August, 111(4):278–282.

Coghlan A (2001). Patient power. New Scientist,2001, 24 February 24 (http://www.pxe.org/news/newscientist_022401.html, accessed 9July 2004).

Cogswell ME et al. (1999). Screening forhemochromatosis: A public healthperspective. American Journal of PreventiveMedicine, February, 16(2):134:140.

Cohn A (2003). Now more common in non-Jews:Years of genetic testing virtually erase Tay-Sachs. Jewish Bulleting News, June 2003(http://www.jewishsf.com/bk030613/1b.shtml, accessed 7 March 2004).

Connor S (2003). Glaxo chief: Our drugs do notwork on most patients. Independent, 8December 2003 (http://209.157.64.200/focus/f-news/1035880/posts, accessed 19February 2005).

Cook-Deegan R, Chan C, A Johnson (2000). Worldsurvey on funding for genomics research.September 2000 (http://www.stanford.edu/class/siw198q/websites/genomics/entry.htm,accessed 9 March 2004).

Cooper H (2001). White House drops WTO claimagainst Brazilian Patent Law. Wall StreetJournal, 26 June 2001.

Cornish WR, Llewelyn M, Adcock M (2003).Intellectual Property Rights (IPRs) andgenetics: A study into the impact andmanagement of Intellectual Property Rightswith the healthcare sector. Cambridge, PublicHealth Genetics Unit, 2003.

Cox SM et al. (2003). International genetic testing.Genetic Medicine, 2003, May–June, 5(3):176–182.

Cukier KN (2003). Open source biotech. AcumenJournal of Life Sciences, 2003, I:3.

da Graça Derengowski Fonseca M, da SilveiraJMFJ (2002). Frontiers of Innovation Researchand Policy (a Workshop between the Institutode Economia—UFRJ, Brazil and CRIC/University of Manchester), September 2002,


Rio de Janeiro, Brazil (http://les1.man.ac.uk/cric/workshops/frontiers/papers.htm,accessed 3 March 2004; paper available athttp://les1.man.ac.uk/cric/workshops/frontiers/papers/fonseca.pdf, accessed 3March 2004).

Dalton R (2004). Bioprospectors edge towards dealwith developing countries. Nature, 26February 2004, 427:769.

Devanand CJ, Schlich GW (2003). Is there a futurefor “speculative” gene patents in Europe?Nature Reviews, May 2003, 2:407.

Diamond v. Chakrabarty (1980), 447 U.S.

DiMasi JA, Harsen RW, Gatowski HG (2003). Theprice of innovation, new estimates of drugdevelopment costs. Journal of HealthEconomics, 2003, 885:1–35.

EC (1998). European Parliament and Council ofEuropean Union. Directive 98/44/EC of theEuropean Parliament and of the Council.Official Journal of the EuropeanCommunities, L 213/13, 30.7.98.

EC (2004). Results of the Competitiveness Councilof Ministers. Brussels, 11th March 2004,Internal Market, Enterprise and ConsumerProtection issues. Brussels, 12 March 2004( h t t p : / / e u r o p a . e u . i n t / r a p i d /pressReleasesAction.do?reference=MEMO/04/58&format=HTML&aged=0&language=EN&guiLanguage=en accessed 22 June2004).

Economic and Social Council (2002). Capacity ofthe public sector to support the creation andapplication of knowledge, innovation andtechnology for development. Report of theSecretariat. 10 May 2002 (E/C.16/2002/5).

Economist (2000). Science and technology: Fruitsof co-operation. The Economist (London), 22July 2000, 356(8180):79.

Eisenberg R (2001). The shifting functionalbalance of patents and drug regulation. HealthAffairs, September–October 2001.

Eisenberg RS (2002a). Concerns about thepatenting of genes. In: Andrews LB, MehlmanMJ, Rothstein MA, eds, Genetics: Ethics, Lawand Policy. St. Paul, Mn., West Group,2002:169–172.

Eisenberg RS (2002b). Why the gene patentingcontroversy persists. Academic Medicine,2002, 77(12):1381–1387.

ETC Group (2004). From global enclosure to selfenclosure: Ten years after – A critique of theCBD and the Bonn Guidelines on Access andBenefit Sharing. Communiqué, Issue 83,February 2004 (http://www.etcgroup.org/d o c u m e n t s / C o m m 8 3 _ C O P 7 _CBDCBonn.pdf accessed 20 March 2004).

FDA (2004). Challenge and opportunity on thecritical path to new medical products.Washington, DC, United States Departmentof Health and Human Services, Food andDrug Administration, 16 March 2004.

Feng Z (2003). Rules set for study on geneticresources. China Daily (HK Edition), 25November 2003.

Finkel E (1999). Australian center develops toolsfor the developing world. Science, September1999, 285:3.

Fleishmann RD et al. (1995). Whole-genomerandom sequencing and assembly ofHaemophilus influenza. Science, 28 July 1995,269:496–512.

Gibbs RA, et al. (2004). Genome sequence of thebrown Norway rat yields insights intomammalian evolution. Nature, 2004,428(6982):493–521.

Gold ER (2003). Exclusive rights in life:Biotechnology, genetic manipulation, andIntellectual Property Rights. In: Jackson JF,Linskens, HF, eds, Molecular methods of plantanalysis, vol. 23, Genetic transformation ofplants. New York, Springer, 2003:1–22.


GRAIN (2002). WIPO moves towards “World”patent. Genetic Resource Action International(GRAIN), July 2002 (http://www.grain.org/publications/wipo-patent-2002-en.cfm,accessed 2 March 2004).

Guttmacher AE, Collins FS (2002). Genomicmedicine—a primer. New England Journal ofMedicine, 7 November 2002, 347(19):1512–1520.

Hall N et al. (2002). Sequence of Plasmodiumfalciparum chromosomes 1, 3–9 and 13.Nature, 2002, 419(6906):527–531.

Hardin G (1968). The tragedy of the commons.Science, 162:1243–1248.

Heller MA, Eisenberg RS (1998). Can patents deterinnovation? The Anticommons in biomedicalresearch. Science, 1 May 1998, 280:698–701.

Howard K (2004). University entrepreneurinitiatives on the rise. Nature Biotechnology,2004, 22(5):625–626.

International Human Genome MappingConsortium (2001). A physical map of thehuman genome. Nature, 15 February 2001,409(6822):934–41.

IPR Commission (2002). Integrating IntellectualProperty Rights and Development Policy.London, United Kingdom, Commission onIntellectual Property Rights, 2002:127 (http://www.iprcommission.org/papers/pdfs/final_report/CIPRfullfinal.pdf, accessed 29December 2003.

Jimenez-Sanchez G (2003). Developing a platformfor genomic medicine in Mexico. Science, 11April 2003, 300(5617):295–296.

Kaplan F (1998). Tay-Sachs disease carrierscreening: A model for prevention of geneticdisease. Genetic Testing, 1998, 2(4):271–292.

Khoury MJ (2003). Genetics and genomics inpractice: The continuum from genetic diseaseto genetic information in health and disease.Genetic Medicine, July–August 2003,5(4):261–268.

Kirby M (2002). Report of the IBC on ethics,intellectual property and genomics. Paris,International Bioethics Committee,UNESCO, January 2002 (http://portal.unesco.org/shs/en/file_download.php/0f8d8bed17083342b45db84beef431acFinalReportIP_en.pdf, accessed 4 January2004).

Kluge E-HW (2003). Patenting human genes:When economic interests trump logic andethic. Health Care Analysis, June 2003,11(2):119–130.

Knoppers BM (1999). Status, sale and patenting ofhuman genetic material: An internationalsurvey. Nature Genetics, May 1999, 22:23–26.

Lecrubier A (2002). Patents and public health.European Molecular Biology OrganizationReports, 2002, 3(12):1120–1122.

Lewis R (2000). Clinton, Blair stoke debate on genedata: US–UK joint statement creates initial stiramong commercial interests. The Scientist, 3April 2000, 14(7):1.

Mabey D et al. (2004). Diagnostics for thedeveloping world. Nature Reviews, March2004, 2:231–240.

Madey v. Duke University (2002). 307 F3d 1351(Federal Circuit Court of Appeal 2002).

Malakoff D (2004). NIH roils academe with adviceon licensing DNA patents. Science, 2004,303:1757–1758.


Marks D, Thorogood M et al. (2003). A review onthe diagnosis, natural history, and treatmentof familial hypercholesterolaemia.Atherosclerosis, May 2003, 168(1):1–14.

Marshall E (2000). Families sue hospital, scientistfor control of Canavan gene. Science, 2000,290(5494):1062.

Marshall E (2004). Patient advocate named co-inventor on patent for the PXE disease gene.Science, 27 August 2004, 305:1226.

Merz JF et al. (2002). Diagnostic testing fails thetest: The pitfalls of patents are illustrated bythe case of haemochromatosis. Nature, 7February 2002, 415:577–579.

Ministry of Health and Long-Term Care (2002).Genetic, testing and gene patenting: Chartingnew territory in healthcare. Toronto, Ontario,Ministry of Health and Long-Term Care, 2002(http://www.health.gov.on.ca/english/public/pub/ministry_reports/geneticsrep02/report_e.pdf, accessed 29 December 2003).

Moukheiber Z (2003). Junkyard dogs. Forbes, 6October 2003.

Musungu SF, Dutfield G (2003). Multilateralagreements and a TRIPS-plus world. TheWorld Intellectual Property Organisation(WIPO), Ottawa, 2003 (TRIPS Issues PaperNo. 3).

Nuffield (2002). The ethics of patenting DNA, Adiscussion paper. London, Nuffield Council onBioethics, July 2002 (http://www.nuffieldbioethics.org/filelibrary/pdf/theethicsofpatentingdna.pdf, accessed 29December 2003).

OECD (2004). Patents and innovation: Trends andpolicy challenges. Paris, Organisation forEconomic Co-operation and Development(http://www.oecd.org/dataoecd/48/12/24508541.pdf accessed 18 February 2005).

Ogbu O (2002). African Science and TechnologyDay: Has Africa surrendered in the field ofscience and technology? Science andDevelopment in Africa, 2002 (http://www.sciencenewsdev.co.ke/special-f.htm,accessed 19 December 2003).

Oxfam (2001). WTO patent rules and access tomedicines: The pressure mounts. Oxford, June2001 (http://www.oxfam.org.uk/w h a t _ w e _ d o / i s s u e s / h e a l t h /wto_patentrules.htm, accessed 19 February2005).

People’s Daily (2001). Chinese firms keen on patentapplication for WTO entry. People’s Daily,15 August 2001 (http://fpeng.peopledaily.com.cn/200108/15/eng20010815_77382.html, accessed 6 March2004).

Pharmaceutical Executive (2005). January 2005:S5(http://www.inmegen.org.mx/Portal/P h a r m a c e u t i c a l _ E x e c u t i v e /Articulo_P_E.pdf, accessed 29 Maarch 2005).

Rai AK (1999). Intellectual property rights inbiotechnology: Addressing new technology.Wake Forest Law Review, Fall 1999, 34:827–847.

Rai AK (2004). Proprietary rights and collectiveaction: The case of biotechnology researchwith low commercial value. Manuscriptprovided by author, 2004.

Ramírez JL, Holmes D (2003). The need forgenomics networking in Latin America.SciDevNet, 14 August 2003.

Rausch LM (2002). International patenting ofhuman DNA sequences. InfoBrief. NationalScience Foundation, August 2002.


Read TD et al. (2000). Genome sequences ofChlamydia trachomatis MoPn andChlamydia pneumoniae AR39. Nucleic AcidsResearch, 2000, 28:137–1406.

Reichman JH, Lewis T (2005). Using liability rulesto stimulate innovation in developingcountries: Application to traditionalknowledge. In: Maskus KE, Reichman JH, eds,International public goods and transfer oftechnology under a globalized intellectualproperty regime. Cambridge University Press(forthcoming 2005).

Richards J (2002). Introduction. Petty patentprotection. Ladas & Perry, 2002 (http://www.ladas.com/Patents/PatentPractice/PettyPatents/PettyP_c.html, accessed 3 March2004).

Rother L (2001). Model for research rises in a ThirdWorld city. New York Times, 1 May 2001.

Scassa T (2003). A mouse is a mouse is a mouse: Acomment on the Supreme Court of Canada’sdecision on the Harvard Mouse Patent. OxfordUniversity Commonwealth Law Journal,2003, Summer.

Scherer FM (2002). The economics of human genepatents. Academic Medicine, December 2002,77(12 Pt 2):1348–1367.

Science and Engineering Indicators (2002a).International patenting trends in two newtechnology areas (http://www.nsf.gov/sbe/srs/seind02/c6/c6s5.htm#fn37, accessed 6 March2004).

Science and Engineering Indicators (2002b). Hu-man DNA sequence patents: Number ofinternational patent families,by priority country and priority year(http://www.nsf.gov/sbe/srs/seind02/append/c6/at06-15.xls, accessed 6 March 2004).

Secretary’s Advisory Committee on GeneticTesting (2000). Summary of Panel Session onHuman Gene Patenting and LicensingPractices and Access to Genetic Tests, 7 June2000, vol. 3 (http://www4.od.nih.gov/oba/sacgt/reports/patent_panel_sum.pdf accessed18 February 2005).

Service R (2003). Genetics and medicine:Recruiting genes, proteins for a revolution indiagnostics. Science, 11 April 2003,300(5617):236–239.

Service R (2004). Incyte throws in the towel ongenomics, trims workforce. Science, 13February 2004, 303:941.

Simpson A et al. (2000). The genome sequence ofthe plant pathogen Xylella fastidiosa. Nature,13 July 2000, 406(6792):151–157.

Singh G, Agarwal P (2003). Forward andbackwards on patent law. The Hindu BusinessLine, 4 October 2003 (http://www.blonet.com/2003/10/04/stories/2003100400090800.htm, accessed 18February 2004).

Surendran A (2004). US NIH draft guidelinesthreaten diagnostics sector. NatureBiotechnology, 2004, 22(5):496.

Suter SM (2001). The allure and peril of geneticsexceptionalism: Do we need special geneticslegislation? Washington University LawQuarterly, Fall 2001, 79(3):669–748.

Terry SF, Boyd CD (2001). Researching thebiology of PXE: Partnering in the process.American Journal of Medical Genetics, Fall2001, 106(3):177–184.

The International HapMap Consortium (2003).The International HapMap Project. Nature,2003, 426:789–96.


Thorold C (2001). Indian firms embracebiotechnology. BBC News Online, 6 April2001 (http://news.bbc.co.uk/1/low/world/south_asia/1264569.stm, accessed 20February 2004).

Thorsteinsdóttir H et al. (2003). Genomics—aglobal public good? Lancet, 2003, 361:891–2.

Trafford A (2001). California vintners put hopesin Brazil’s labs. Washington Post, 29 December2001:A01.

UNDP (1999). Globalization with a human face.New York, United Nations DevelopmentProgramme, 1999.

UNESCO (1997). Universal Declaration onHuman Rights and the Human Genome.UNESCO, Paris, 1997.

USPTO (2004). Revised interim utility guidelinestraining materials, 2004. United States Patentand Trademark Office (http://www.uspto.gov/web/menu/utility.pdf,accessed 8 July 2004).

Venter C et al. (2001). The sequence of the humangenome. Science, 16 February 2001,291(5507):1304–1351.

Verma IC et al. (2003). Genetic counselling andprenatal diagnosis in India—Experience at SirGanga Ram Hospital. Indian Journal ofPediatrics, April 2003, 70(4):293–297.

Verma P, Sharma YD (2003). Malaria genomeproject and its impact on disease. Journal ofVector Borne Diseases, March–June 2003,40(1–2):9–15.

Walsh JP, Arora A, Cohen WM (2003). Effects ofresearch tool patents and licensing onbiomedical innovation. In: Cohen WM, AMerrill, eds, Patents in the knowledge-basedeconomy. Washington, DC, The NationalAcademies Press, 2003:285–340.

Wang Y (2001). Monsanto under fire for “pirating”Chinese soy strain. China Daily, 30 October2001.

Waterston RH et al. (2002). Initial sequencing andcomparative analysis of the mouse genome.Nature, 2002, 420(6915):520–562.

WHO (1964). Human genetics and public health.Second report of the WHO Expert Committeeon Human Genetics. Geneva, World HealthOrganization (WHO Technical Report SeriesNo. 282).

WHO (1994). Guidelines for the control ofhaemoglobin disorder. Geneva, World HealthOrganization (WHO/HDP/HB/GL/94.1).

WHO (1996). Control of hereditary diseases.Geneva, World Health Organization (WHOTSR, no. 865:1–86).

WHO (1998). Proposed international guidelineson ethical issues in medical genetics and geneticservices. Geneva, World Health Organization(WHO/HGN/GL/ETH/98.1).

WHO (1999). Report of a WHO/WAO meetingon prevention and care of genetic disease andbirth defects in developing countries. Geneva,World Health Organization (WHO/HGN/WAOPBD/99/1).

WHO (2000). Report of a WHO meeting onpublic health approaches for the control ofgenetic disorders. Geneva, World HealthOrganization (WHO/HGN/WG/00.1).

WHO (2002). Genomics and World Health.Geneva, The Advisory Committee on HealthResearch of the World Health Organization,2002 (http://www3.who.int/whosis/genomics/pdf/genomics_report.pdf, accessed12 January 2004).


Wickelgren I (2004). Heart disease: Gene suggestsasthma drugs may ease cardiovascularinflammation. Science, 13 February 2004,303(5660):941.

Wilson RK (1999). How the worm was won. TheC. elegans genome sequencing project. Trendsin Genetics, 1999, 15(2):51–58.

Wirth D (2001). A harvest not yet reaped:Genomics to new drugs in Leishmania andTrypanosomes. Boston, MSF/DND WorkingGroup, September 2001.

WTO (2001). Ministerial Declaration. WTO/MIN(01)/DEC/2, 20 Nov 2001. Doha, Qatar(http://www.wto.org/english/thewto_e/minist_e/min01_e/mindecl_e.pdf).

WTO (2003). Decision removes final patentobstacle to cheap drug imports. WTO PressRelease, 30 August 2003 (Press/350/Rev.1).

Yoon CK (2000). Agriculture takes its turn in thegenome spotlight. New York Times, 18 July2000.

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6Other reading

Articles

Agarwal MB. Advances in management of sicklecell disease. Indian Journal of Pediatrics,August 2003, 70(8)649–654.

Akinyanju OO et al. Initiation of prenataldiagnosis of sickle-cell disorders in Africa.Prenatal Diagnosis, 1999, 19:299–304.

Alwan A, Modell B. Community control of geneticand congenital disorders. Cairo, World HealthOrganization, Regional Office for the EasternMediterranean, 1997 (EMRO TechnicalPublications Series 24).

Arzberger P et al. An international framework topromote access to data. Science, 2004,303:1777–1778.

Attaran A, Gillespie-White L. Do patents forantiretroviral drugs constrain access to AIDStreatments in Africa? JAMA: Journal of theAmerican Medical Association , 2001,286(15):1886–1892.

Barton JH. Patents, genomics, research, anddiagnostics. Academic Medicine, 2002,77(12):1339–1347.

Barton JH. Research-tool patents: Issues for healthin the developing World. Bulletin of the WorldHealth Organization, 2002, 80(2):121.

Barton JH, Strauss J. How can the developingworld protect itself from biotech patent-holders? Nature, 2000, 406:455.

Beck IA et al. Simple, sensitive, and specificdetection of human immunodeficiency virustype 1 (HIV-1) subtype B DNA in dried bloodsamples for diagnosis in infants in the field.Journal of Clinical Microbiology, 2001,39(1):29–33.

Beitz C. Social and cosmopolitanism liberalism.International Affairs, 1999, 75(3):515.

Bendekgey L, Hamlet-Cox D. Gene patents andinnovation. Academic Medicine, 2002,77(12):1373–1380.

Benenson Y, et al. An autonomous molecularcomputer for logical control of geneexpression. Nature, 2004, 429(6990):423–429.

Black J. Regulation as facilitation: Negotiating thegenetic revolution. Modern Law Review, 1998,61:621–660.

Bobrow M, Thomas S. Patents in a genetic age:The present patent system risks becoming abarrier to medical progress. Nature, 2001,409:763.

Bounpheng M et al. Rapid, inexpensive scanningfor all possible BRCA1 and BRCA2 genesequence variants in a single assay:Implications for genetic testing. Journal ofMedical Genetics, 2003, 40(4):e33.


Boyle J. Enclosing the genome: What the squabblesover genetic patents could teach us. 2003 (http://www. law.duke .edu/boyles i t e / low/genome.pdf accessed 19 February 2005).

Broder S et al. Cures for the Third Word’sproblems. EMBO Reports, 2002, 3(9):806.

Buchanan A. Rawls’s Law of Peoples: Rules for avanished Westphalian world. Ethics, July2000:697.

Burch RK et al. Divergent incentives to protectIntellectual Property: A political economyanalysis of North–South welfare. Journal ofWorld Intellectual Property, March 2001,3:169–195.

Burke W et al. Recommendations for follow-upcare of individuals with an inheritedpredisposition to cancer. JAMA: Journal of theAmerican Medical Association, 1997,277(12):997–1003.

Butler D. Genetic diversity proposal fails toimpress international ethics panel. Nature,1995, 377:373.

Cantu JM, Figuera LE. Virtual molecular medicinein developing countries: The MexicanInitiative. Molecular Medicine Today, 2000,6:190–192.

Caplan A, Merz J. Patenting gene sequences.British Medical Journal, 13 April 1996,312(7036):926.

Carey NH, Crawley PE. Commercial exploitationof the human genome: What are the problems?Human Genetic Information: Science, Lawand Ethics. Toronto, John Wiley and Sons,1990:133–147.

Caulfield T. Globalization, conflicts of interestsand clinical research: An overview of trendsand issues. Widener Law Symposium Journal,2001, 8:31.

Caulfield TA et al. Genetic technologies, healthcare policy and the patent bargain. ClinicalGenetics, January 2003, 63(1):15–18.

Caulfield TA, Gold ER. Genetic testing, ethicalconcerns, and the role of Patent Law. ClinicalGenetics, 2000, 57:370–375.

Cherniawsky K. Commercialization/Patents. In:Knoppers BM, eds, Human DNA: Law andPolicy, International and ComparativePerspectives. Kluwer Law International, TheHague, 1997:385.

Chong SS et al. Single-tube multiplex-PCR screenfor common deletional determinants of alpha-thalassemia. Blood, 2000, 95(1):3602.

Clavel C et al. Hybrid Capture II-based humanpapillomavirus detection, a sensitive test todetect in routine high-grade cervical lesions:A preliminary study on 1518 women. BritishJournal of Cancer, 1999, 80(9):1306–1311.

Cook-Deegan RM, McCormack SJ. Intellectualproperty: Patents, secrecy, and DNA. Science,2001, 293(5528):217.

Correa CM. Integrating public health concerns intopatent legislation in developing countries.Geneva, South Centre, October 2000 (http://www.netamericas.net/Researchpapers/Documents/Ccorrea/Ccorrea1.pdf, accessed 5January 2004).

Correa CM. Public health and patent legislation indeveloping countries. Tulane Journal ofTechnology and Intellectual Property, 2001,3:1.

Couzin J. Cancer sharpshooters rely on DNA testsfor better aim. Science, 27 August 2004,305:1222–1223.

Crigger BJ. The West knows best? Hastings CenterReport, March/April 1996, 26(2)50.

Cullet P. Patent and medicines: The relationshipbetween TRIPS and the human right to health.International Affairs, 2003 79(1):139.


D’Amato RF et al. Rapid diagnosis of pulmonarytuberculosis by using Roche AMPLICORMycobacterium tuberculosis PCR test. Journalof Clinical Microbiology, 1995, 33(7):1832–1834.

Daniels N. Just Health Care. Cambridge and NewYork, Cambridge University Press, 1985.

Davies K. Playing by Aussie rules (Conversation:Mervyn Jacobson). Bio·IT World (www.bio-itworld.com), 13 August, 2003.

Dennis C. Geneticists question fees for use ofpatented “junk” DNA. Nature, 8 May 2003,423:105.

Dickson D. Open access to sequence data will boosthunt for breast cancer gene. Nature, 1995,378:425.

Drahos P, Braithwite J. Intellectual property,corporate strategy, globalization: TRIPS incontext. Wisconsin International LawJournal, 2002, 20:451 (Proceedings of 2002Conference Access to Medicines in theDeveloping World).

Dryer O. US awards patent for tribesman’s DNA.British Medical Journal, 1995,311(7018):1452a.

Eisenberg RS, Nelson RR. Public vs. proprietaryscience: A fruitful tension? AcademicMedicine, 2002, 77(12):1392–1399.

Eisenberg RS. Patent swords and shields. Science,2003, 299:1018–1019.

Enriquez J, Martinez R. The next revolution: Who’sready? Who’s not. Perspectives in HealthMagazine (The Magazine of the Pan AmericanHealth Organization), Special CentennialEdition, 2002, 7:1 (http://www.paho.org/English/DPI/Number14_article4_5.htm,accessed 15 December 2003).

Ergenziger E, Spruill M. Basic science in USuniversities can infringe patents. TheScientist,10 March 2003, 17(5):43.

Fidle DP. Racism or realpolitik? U.S. foreignpolicy and the HIV/AIDS catastrophe in sub-Saharan Africa. Journal of Gender, Race andJustice, 2003, 7:97.

Friedman MA et al. Out-licensing: A practicalapproach of improvement of access tomedicines in poor countries. Lancet, 2003,361:341–44.

Genetic diversity proposal fails to impress interna-tional ethics panel. Nature, 5 October 1995.

Gitter D. International conflicts over patentinghuman DNA sequences in the United Statesand the European Union: An argument forcompulsory licensing and a fair-use exemption.New York University Law Review, 2001,76:1623–1691.

Gold ER. From theory to practice: Health careand the patent system. Health Law Journal,September 2003, Special Edition 2003:Precedent & Innovation: Health Law in the21st Century.

Gold ER. Gene patents and medical access.Intellectual Property Forum, 2000, 49:20–27.

Gold ER. Making room, Integrating basic research,health policy and ethics into patent law. In:Caulfield T, Williams-Jones B, eds, TheCommercialisation of genetic research,Ethical, legal and policy issues. New York,Kluwer Academic/Plenum Publishers,1999:63–78.

Gold ER. Moving the gene patent debate forward:A framework for achieving compromisebetween industry and civil society. NatureBiotechnology, 2000, 18:1319–1320.

Gold ER. Owning our bodies: An examination ofproperty law and biotechnology. San DiegoLaw Review, 1995, 32(4):1167–1247.

Gold ER. SARS genome patent: Symptom ordisease? Lancet, 2003, 361:2002–2003.


Gold ER et al. Gene patents and the standard ofcare. Canadian Medical Association Journal,6 August 2003, 167(3):256–57.

Gold ER, Caulfield TM. The moral tollbooth: Amethod that makes use of the patent system toaddress ethical concerns in biotechnology.Lancet, 2002, 350:2268–2270.

Gold ER, Gallochat A. The European directive:Past and prologue. European Law Journal,September 2001, 7(3):331–366.

Gold ER, Lam DK. Balancing trade in patents:Public non-commercial use and compulsorylicensing. Journal of World IntellectualProperty, 2003, 6(1):5–31.

Granda H et al. Cuban program for prevention ofsickle cell disease. Lancet, 1991, 337:152–153.

Greco A. From bench to boardroom: PromotingBrazilian biotech (Profile: Fernando Reinach).Science, 2003, 300:1366–1367.

Hanson MJ. Biotechnology and commodificationwithin health care. Journal of Medicine andPhilosophy,1999, 24:267.

Herdegen M. Patenting human genes and otherparts of the human body under ECbiotechnology directive. Bio-Science LawReview, 2001:13.

Heredero L. Comprehensive national geneticprogram in a developing country—Cuba. BirthDefects Original Article Series, 1992,28(3):52–57.

Hill AV. Molecular epidemiology of thethalassaemias (including haemoglobin E).Baillieres Clinical Haematology, January1992, 5(1):209–38.

Hoffman SL. Research (Genomics) is crucial toattacking malaria. Science, November 2000,290:5496, 1509.

Human Genetic Organisation Ethics Committee.HUGO urges genetics benefit-sharing.Community Genetics, 2000, 3:88–92.

Ida R. Human genome as the common heritage ofmankind. Bioethics in Asia, 1998:59–63 (http://www.biol.tsukuba.ac.jp/~macer/asiae/biae59.html, accessed 5 January 2004).

James JS. India research opportunities, price andpatent problems. AIDS Treatment News Issue,1999:321.

Jia H. IP litigation in China could driveinnovation. Nature Biotechnology, 2004,22(4):368.

Jones JS. Biotechnology “roadmap” for SouthAfrica unveiled. SciDevNet, 17 September2004.

Kass LT, Nitabach MN. A roadmap forbiotechnology patents? Federal Circuitprecedent and the PTO’s new examinationguidelines. American Intellectual PropertyLaw Association Quarterly Journal, 2002,30:233–265.

Kent A. BC sidesteps patent claim, Transfers BRCAgene testing to Ontario. Canadian MedicalAssociation Journal, 21 January 2003, 68:2.

Knoppers BM. Biotechnology: Sovereignty andsharing. In: Caulfield T, Williams-Jones B,eds., The Commercialisation of geneticresearch, ethical, legal and policy issues. NewYork, Kluwer Academic/ Plenum Publishers,1999:1–11.

Koch WH. Technology platforms forpharmacogenomic diagnostic assays. NatureReviews: Drug Discovery, 2004, 3:749–761.

Kongolo T. The African Intellectual PropertyOrganizations: The necessity of adopting oneuniform system for all Africa. Journal of WorldIntellectual Property, 2000:265–288.

Lanjouw JO. A new global patent regime fordiseases: US and international legal issues.Harvard Journal of Law & Technology,2002:16:85.


Lazzarini Z. Making access to pharmaceuticals areality: Legal options under TRIPS and thecase of Brazil. Yale Human Rights &Development Law Journal, 2003, 6:103.

Le Saux O et al. A spectrum of ABCC6 mutationsis responsible for pseudoxanthoma. AmericanJournal of Human Genetics, 2001, 69:749–764.

Lesko JL, Woodcock J. Translation ofpharmacogenomics and pharmacogenetics: Aregulatory perspective. Nature Reviews,September 2004, 3:763–769.

Lichtman MA, Hunter MD, Liders GJ. Intellectualproperty—the dispute between researchinstitutions and voluntary health agencies.Nature Biotechnology, 2004, 22(4):385–386.

Lindpaintner K. Genetics and genomics: Impacton drug discovery and development. AnnualConference on Research in ComputationalMolecular Biology, Proceedings of the fifthannual international conference onComputational Biology . Basel, GSIA,2000:221–222.

Lock M. The Human Genome Diversity Project:A perspective from cultural anthropology. In:Knoppers BM, ed., Human DNA: Law andPolicy, International and ComparativePerspectives. The Hague, Kluwer LawInternational, 1997.

Macklin R. The ethics of gene patenting. In:Thompson AK, Chadwick R, eds. GeneticInformation. New York, Kluwer Academic/Plenum Publishing, 1999:129–37.

Marks SP. Health and human rights: Theexpanding international agenda. AmericanSociety of International Law Proceedings,2001, 95:64.

Marks SP. Tying Prometheus down: TheInternational Law of Human GeneticManipulation. Chicago Journal ofInternational Law, 2002, 3:115.

Martinez PA et al. Simple and rapid detection ofthe newly described mutations in the HLA-HGene. Blood, 1997, 89:1835–1836.

Martone M. The ethics of the economics ofpatenting the human genome. Journal ofBusiness Ethics, 1998, 17:1679.

Maskus K. Intellectual property rights in the globaleconomy. Institute for InternationalEconomics, 2000 (http://www.iie.com/p u b l i c a t i o n s / b o o k s t o r e /publication.cfm?Pub_ID=99, accessed 15January 2003).

Matthijs G, Halley D. European-wide oppositionagainst the breast cancer gene patents.European Journal of Human Genetics, 2002,10:783–784.

Mayor S. Charity makes cancer gene freelyavailable across Europe. British MedicalJournal, 21 February 2004, 328:423.

McCabe KW. The January 1999 Review of Article27 of the TRIPs Agreement: Diverging viewsof developed and developing countries towardthe patentability of biotechnology. Journal ofIntellectual Property Law, 1998, 6(41):41–67.

McLeland L, O’Toole JH. Patent systems in lessdeveloped countries: The Cases of India andthe Andean Pact countries. Journal of LawTechnology, 1987:226–247.

McManis CR. Intellectual property, geneticresources and traditional knowledgeprotection: Thinking globally, acting locally.Cardozo Journal of International andComparative Law, 2003, 11:547.

Merz JF. Disease gene patents: Overcomingunethical constraints on clinical laboratorymedicine. Clinical Chemistry, 1999,45(3)324–330.

Merz JF et al. Protecting subjects’ interests ingenetics research. American Journal ofHuman Genetics, 2002, 70:965–971.


Morgan S et al. Predictive genetic tests and healthsystem costs. Canadian Medical AssociationJournal, 15 April 2003, 168(8):989–991.

Mugabe J. Centers of Excellence in Science andTechnology for Africa’s sustainabledevelopment: Towards new forms of regionaland sub-regional networks. For AfricanMinisterial Conference on Science andTechnology for Development (http://www.touchtech.biz/nepad/files/documents/126.pdf, accessed 15 January 2004).

Mugabe J. Intellectual property protection andtraditional knowledge: An exploration ininternational policy discourse. For WorldIntellectual Property Organization on behalfof African Centre for Technology Studies.African Centre for Technology Studies,Kenya,1998.

Nau JY. Une Pétition Lancée par le Prof. MatteiS’oppose aux Brevets sur les Gènes Humains.Le Monde, 26 May 2000.

Nelsen L. The role of university technologytransfer operations in assuring access tomedicines and vaccines in developingcountries. Yale Journal of Health Policy Lawand Ethics, January 2003, 3(2):301–308.

Nerozzi MN. The battle over life-savingpharmaceuticals: Are developing countriesbeing ‘TRIPped’ by developed countries?Villanova Law Review, 2002, 47:605.

Nolff M. Compulsory patent licensing in view ofthe WTO Ministerial Conference Declarationon the TRIPS Agreement and Public Health.Journal of the Patent and Trademark OfficeSociety, 2002, 84:133.

Nwabueze RN. Ethnopharmacology, patents andthe politics of plants’ genetic resources.Cardozo Journal of International andComparative Law, 2003, 11:585.

Page AK. Prior agreements in international clinicaltrials: Ensuring the benefits of research todeveloping countries. Yale Journal of HealthPolicy, Law, and Ethics, 2002, 3:35.

Perkel C. Ontario defying American genecompany by using new breast-cancer test.Canadian Press, 6 January 2003 (http://mediresource.sympatico.ca/health_news_detail.asp?channel_id=12&news_id=578,accessed 5 January 2003).

Petrou M, Modell B. Prenatal screening forhaemoglobin disorders. Prenatal Diagnosis,1995, 15:1275–1295.

Poste G. The case for genomic patenting. Nature,1995, 387:534.

Pridan-Frank S. Human-genomics: A challengeto the rules of the game of international law.Columbia Journal of International andComparative Law, 2002, 40:619.

Ragavan S. Can’t we all get along?: A case for aworkable patent. Arizona State Law Journal,2003, 35:117.

Ragavan S. Protection of traditional knowledge.Minnesota Intellectual Property Review, 2001,2:1.

Ramirez JL, Holmes D. The need for genomicsnetworking in Latin America. Science andDevelopment Network (www.SciDev.net), 14August 2003.

Rapp RT, Rozer RP. Benefits and costs ofIntellectual Property protection in developingcountries. Journal of World Trade, 1990,24:75–102.

Raskins S et al. DNA analysis of cystic fibrosis inBrazil by direct PCR amplification fromGuthrie cards. American Journal of MedicalGenetics, 1 July 1993, 46(6):665–659.

Rosendal GK. The politics of patent legislation inbiotechnology: An international view.Biotechnology Annual Review, 1995, 1:453.

Roses AD. Pharmacogenetics and drugdevelopment: The path to safer and moreeffective drugs. Nature Reviews, September2004, 5:645–656.


Russo E. Merging IT and biology. The Scientist,2000, 14(23):8.

Salotra P et al. Development of a species-specificPCR assay for detection of Leishmaniadonovani in clinical samples from patientswith kala-azar and post-kala-azar dermalleishmaniasis. Journal of ClinicalMicrobiology, 2001, 39(3):849–854.

Savithri HS et al. Predictive testing for familialadenomatous polyposis in a rural South Indiancommunity. Clinical Genetics, 2000, 58(1):57–60.

Service RS. Gene and protein patents get ready togo head to head. Science, 7 December 2001,294(5549): 2082.

Shattuck-Eidens D et al. BRCA1 sequence analysisin women at high risk for susceptibilitymutations. Risk factor analysis andimplications for genetic testing. JAMA:Journal of the American Medical Association,1997, 278(15):1242–1250.

Sheremeta L, Gold ER. Creating a patentclearinghouse in Canada: A solution toproblems of equity and access. Health LawReview, 2003, 11(3):17–19.

Spectar JM. Patent necessity: Intellectual propertydilemmas in the biotech dominant treatmentequity for developing countries. HoustonJournal of International Law, 2001, 24:227.

Streit C et al. CFTR gene: Molecular analysis inpatients from South Brazil. MolecularGenetics and Metabolism, April 2003,78(4):259–264.

Streit C et al. CFTR gene: Molecular analysis inpatients from South–Brazil. MolecularGenetics and Metabolism, 2003, 78:259.

Taubes G. Scientists attacked for patenting Pacifictribe. Science, 17 November 1995, 270(5239).

Taylor AL. Globalization and biotechnology:Unesco and an international strategy toadvance human rights and public health.American Journal of Law & Medicine,1999:479.

Thomas SM et al. Ownership of the humangenome. Nature, 1996, 380:387–388.

Thomas SM et al. Public-sector patents on humanDNA. Nature, 1997, 388:709.

Verma IC. Burden of genetic disorders in India.Symposium: Genetics for Pediatricians-I.Indian Journal of Pediatrics, 2000,67(12):893–98.

Wadman M. Ethical terms set for breast cancer test.Nature, 27 November 1997, 390:324.

Warner JP, Barron LH, Brock DJ. A newpolymerase chain reaction (PCR) assay for thetrinucleotide repeat that is unstable andexpanded on Huntington’s diseasechromosomes. Molecular and CellularProbes, 1993, 7(3):235–9.

Warner S. Diagnostics + therapy = theranostics.The Scientist, 30 August 2004, 18(16):38.

Weinshilboum R, Wang L. Pharmacogenomics:Bench to bedside. Nature Reviews: DrugDiscovery, 2004, 3(9):739–748.

Wheeler C, Berkley S. Initial lessons from public-private partnerships in drug and vaccinedevelopment. Bulletin of the World HealthOrganization, 2001, 79:728.

Williamson AR. Gene patents: Are they sociallyacceptable monopolies or an unnecessaryhindrance to research. Drug Discovery Today,November 2001, 6(21):1092–1093.


Willison DJ, Macleod SM. Patenting of geneticmaterial: Are the benefits to society beingrealised? Canadian Medical AssociationJournal, 6 August 2002, 167(3):259–262.

Winnick E. DNA sequencing industry sets itssights on the future. The Scientist, 27September 2004, 18(18):44.

Wolfson JR. Social and ethical issues innanotechnology: Lessons from biotechnologyand other high technologies. BiotechnologyLaw Report, 2003, 22:376.

Books

Boyle J. Shamans, software & spleens: Law andthe construction of the information society.Cambridge, Massachusetts and London,Harvard University Press, 1996.

Cain B. Legal aspects of gene technology. London,Thompson, 2003.

Gold ER. Body parts: Property rights and theownership of human biological materials.Washington, D.C., Georgetown UniversityPress, 1996.

Greider G. One world, ready or not: The maniclogic of global capitalism. New York, Simonand Shuster, 1997.

Knoppers BM, ed. Human DNA: Law and policy,international and comparative perspectives.New York, Kluwer, 1997.

Laurie G. Genetic privacy: A challenge to medico-legal norms. Cambridge, CambridgeUniversity Press, 2002.

Mason S, Megone C, eds. European neonatalresearch: Consent, ethics committees and law.Aldershot, Ashgate, 2001.

Radin M. Contested commodities. Cambridge,Harvard University Press, 1996.

Silver LM. Remaking Eden. New York, AvonBooks, 1997.

Proceedings and symposiums

Fidler DP. Introduction to written symposium onPublic Health and International Law. ChicagoJournal of International Law, 2002:3.

Fifth Meeting of the Secretary’s Committee onGenetic Testing, Volume III. United States,Secretary’s Advisory Committee on GeneticTesting (SACGT), 7 June 2000 (http://www4.od.nih.gov/oba/sacgt/sacgtmtg.htm,accessed 9 March 2004).

Nelkin D. A Brief history of the political work ofgenetics. Symposium: Legal & Ethical Issuesin Genetic Research or IndigenousPopulations. Jurimetrics, 2002, 42:121.

Pai GS et al. Challenges in human genetics in Indiain the new millennium. Symposium: Geneticsfor Pediatricians-I. Indian Journal ofPediatrics, 2000, 67(11):809–811.

Report of a WHO meeting on collaboration inmedical genetics. Geneva, World HealthOrganization, 2002 (WHO/HGN/WG/02.2).

Scidev. Africa’s Scientific Revival Day nowrecognized. Scidev Workshop, Uganda, 29September to 3 October 2002 (http://www.sciencenewsdev.co.ke/special-f.htm,accessed 15 January 2004).

Sheremeta L, Gold ER. Creating a patentclearinghouse in Canada: A solution toproblems of equity and access? posterpresentation, GELS Winter Symposium 2003,6–8 February 2003, Montreal, Quebec.

Verma IC. Burden of genetic disorders in India.Symposium: Genetics for Pediatricians-I.Indian Journal of Pediatrics, 2000,67(12):893–98.


Verma IC et al. Genetic counseling and prenataldiagnosis in India—Experience at Sir GangaRam Hospital. Indian Journal of Pediatrics,2003, 70:293–97.

World Health Assembly Resolution WHA56.27.Intellectual property rights, innovation andpublic health. Fifty-sixth World HealthAssembly, 28 May 2003 (http://www.who.int/gb/ebwha/pdf_files/WHA56/ea56r27.pdfaccessed February 2005).

Reports

American College of Obstetricians andGynaecologists

Screening for Canavan Disease, fact sheet number212. American College of Obstetricians andGynaecologists, November 1998 (http://www.tay-sachs.org/medical.php accessed 5January 2004).

British Society for Human Genetics (BSHG)

Statement on patenting and clinical genetics.United Kingdom, British Society for HumanGenetics, 1 February 1998.

Canada Department of Justice

Gold ER, Caulfield TA. Human genetic inventions,patenting and human rights. Ottawa,Department of Justice, Government ofCanada, 2003.

Canadian Cancer Society

The patenting of BRCA1 and 2 genes facts sheet.Canada, The Canadian Cancer Society (http://www.cancer.ca/ccs/internet/standard/0,3182,3172_31282995_32777862_langId-en,00.html, accessed 30 December 2003).

Patenting of genes and gene sequences. Canada,The Canadian Cancer Society, 17 June 2003(http://www.cancer.ca/ccs/internet/standard/0,3182,3172_61901275__langId-en,00.html,accessed 15 December 2003).

Center for Advanced Studies at the Universityof Buenos Aires

Carlos M Correa. Intellectual property rights andthe use of compulsory licenses: Options fordeveloping countries [Working Paper]. BuenosAires, Center for Advanced Studies at theUniversity of Buenos Aires, A, 1999.

Center for International Environmental Law

Downes D. The 1999 WTO review of lifepatenting under TRIPS [Revised discussionpaper]. Washington, D.C, Center forInternational Environmental Law, September1998:1.

Centre for Law and Genetics

Nicol D, Nielsen J. Patents and medicalbiotechnology: An empirical analysis of theissues facing the Australian industry. Tasmania,Australia, Centre for Law and Genetics, 2003(Occasional Paper No. 6).

Centre for Management of IntellectualProperty in Health Research and Development

Mahoney RT ed. Handbook of best practices formanagement of intellectual property in healthresearch and development. Oxford, UK,Centre for Management of IntellectualProperty in Health Research andDevelopment, November 2003.

Conference of the Parties to the Convention onBiological Diversity

Sixth Meeting of the Conference of the Parties tothe Convention on Biological Diversity,Decision VI/24, Access and benefit-sharing asrelated to genetic resources. The Hague, April2002 (http://www.biodiv.org/welcome.aspx,accessed 5 January 2004).


Econexus and GeneWatch UK

Patenting genes—Stifling research andjeopardising healthcare. United Kingdom,Econexus and GeneWatch UK, 1 April 2001(http://www.genewatch.org/Publications/Patenting/Patents.pdf, accessed 3 January2004).

Economic and Social Research Council

ESRC Genomics Scenarios Project: 3. Key driversof genomics: forecasts for 2015. Economic andSocial Research Council, January 2002.

Global Forum for Health Research

The 10/90 Report on Health Research. Geneva,Global Forum for Health Research, 2000.

International Association for the Protection ofIntellectual Property

Patentability requirements and scope of protectionof Expressed Sequence Tags (ESTs), SingleNucleotide Polymorphisms (SNPs) and entiregenome. Sorrento, International Associationfor the Protection of Intellectual Property, 14April 2000 (http://www.aippi.org/reports/resolutions/res-q150-e-exco-2000.htm,accessed 5 January 2004).

International Intellectual Property Institute

Patent protection and access to HIV/AIDSpharmaceuticals in sub-Saharan Africa.Washington DC, International IntellectualProperty Institute, 2000 (http://www.iipi.org/a c t i v i t i e s / R e s e a r c h /HIV%20AIDS%20Report.pdf accessed 21January 2004).

Medical Research Council of South Africa

Guidelines on ethics for medical research:Reproductive biology and genetic research.Tygerberg, The Medical Research Council ofSouth Africa, 1 April 2002 (http://www.sahealthinfo.org/ethics/ethicsbook2.pdf,accessed 15 December 2003).

National Institute for Health CareManagement Research and EducationalFoundation

Changing patterns of pharmaceutical innovation.Washington, DC, The National Institute forHealth Care Management Research andEducational Foundation, May 2002.

National Research Council

Patents in the knowledge-based economy. NationalResearch Council, USA, 2003 (http://books.nap.edu/books/0309086361/html/297.html#pagetop accessed 21 January 2003).

Organisation for Economic Development andCooperation

Genetic inventions, intellectual property rights andlicensing practices: Evidence and policies.Paris, Organisation for EconomicDevelopment and Cooperation (OECD),2002:50.

Royal Society

Needham R et al. Keeping science open: The effectsof intellectual property policy on the conductof science. London, The Royal Society, April2003.

United Nations Commission on Human Rights

Motoc A. Specific human rights issues. UniversalDeclaration on the Human Genome andHuman Rights. Geneva, UN Commission onHuman Rights, 2002 (doc.E/CN.4/sub.2/2002/37).

United Nations Educational Social andCultural Organization

Report of the IBC on ethics, intellectual propertyand genomics. UNESCO, InternationalBioethics Committee (IBC), 10 January 2002.


United States Federal Trade Commission

To promote innovation: The proper balance ofcompetition and patent law and policy.Washington, DC, Federal Trade Commission,October 2003.

University of Toronto Joint Center for Bioethics

Top 10 biotechnologies for improving health indeveloping countries. Toronto, Program inApplied Ethics and Biotechnology andCanadian Program on Genomics and GlobalHealth, University of Toronto Joint Centerfor Bioethics, 2003 (http://www.utoronto.ca/jcb/pdf/top10biotechnologies.pdf, accessed 30December 2004).

World Bank

Fink C. How stronger patent protection in Indiamight affect the behavior or transnationalpharmaceutical industries. DevelopmentResearch Group, World Bank, 2000 (http://econ.worldbank.org/docs/1106.pdf, accessed15 January 2004).

Yang G, Maskus KE. Intellectual property rights,licensing, and innovation. World Bank, 2003(Policy Research Working Paper 2973).

World Health Organization

Berg K, Boulyjenkov V, Christen Y. Geneticapproaches to noncommunicable diseases.Geneva, World Health Organization andFondation IPSEN, Springer-Verlag, 1996:1–155.

Fifty facts from the World Health report 1998,Global health situation and trends 1955–2025.Geneva, World Health Organization, 1998(http://www.who.int/whr2001/2001/archives/1998/pdf/factse.pdf, accessed 30December 2003).

Genomics and World Health: Report of theAdvisory Committee on Health Research.Geneva, World Health Organization, 2002(EB112/4).

Guidelines for control of haemoglobin disorders.Geneva, World Health Organization, 1994(WHO/HDP/HB/GL/94.1).

Human genetic technologies: implications forpreventative care. Geneva, World HealthOrganization, 2001 (WHO/HGN/Rep/02.1).

Report of a WHO meeting on collaboration inmedical genetics. Geneva, World HealthOrganization, 2002 (WHO/HGN/WG/02.2).

The molecular genetic epidemiology of cysticfibrosis. Geneva, World Health Organization,2004 (WHO/HGN/CF/WG/04.02).

World Health Report 1999: Making a difference,Part I. Geneva, World Health Organization,1999 (http://www.who.int/whr2001/2001/archives/1999/en/pdf/whr99.pdf, accessed 29December 2003).

Patent office publications

India Patents Office. Exclusive Market Rights(http://www.patentoffice.nic.in/ipr/patent/emr.htm, accessed 26 February 2004)

United States Patent and Trademark Office, UtilityExamination Guidelines. 66:4 FederalRegister, 5 January 2001, 1092.

Case Law

Canada

Schmeiser v. Monsanto Canada Inc. [2002] 21C.P.R. (4th) 1 affirming 12 C.P.R. (4th) 204(FCA).

Harvard College v. Canada (Commissioner ofPatents), (2002) SCC 76.


United States of America

Chou v. Univ. of Chicago, 254 F.3d 1347, 1363(Fed. Cir. 2001).

Greenberg v. Miami Children’s Hospital ResearchInstitute, Inc 16 Fla.L. Weekly Fed D 417.

Legislation

Agreement on Trade-Related Aspects ofIntellectual Property Rights, being Annex 1Cof the Marrakesh Agreement Establishing theWorld Trade Organization, 33 I.L.R. 1197(1993).

Brazil. Patent Law 9.279 of 1997.

China. Patent Law 1985, amended in 1992 and in2003.

Convention on Biological Diversity, Rio de Janeiro,5 June 1992 (http://www.biodiv.org/doc/legal/cbd-en.pdf, accessed 5 January 2004).

France. Projet de loi relatif à la protection desinventions biotechnologiques. France: Sénat.Session ordinaire de 2001–2002; 2001 Nov 6.No 55. Art. 11. (www.senat.fr/leg/pjl01-055.html, accessed 6 January 2004).

Genomic Research and Diagnostic AccessibilityAct of 2002, H.R. 3967, 107th Cong., 2nd Sess.(2002).

India. Patents Act 1970.

International Treaty on Plant Genetic Resourcesfor Food and Agriculture (ITPGRFA), FAO,November 2001 (ftp://ext-ftp.fao.org/ag/cgrfa/it/ITPGRe.pdf, accessed 5 January2004).

United Nations Convention on the Law of the Sea.Montego Bay, 1982 (http://www.un.org/Depts/los/convention_agreements/texts/unclos/closindx.htm, accessed 5 January2004).

Statements

European Group on Ethics in Science and NewTechnologies

Opinion No. 16, Ethical aspects of patentinginventions involving human stemcells. Brussels, European Group on Ethics inScience and New Technologies, 7 May 2002( h t t p : / / e u r o p a . e u . i n t / c o m m /european_group_ethics/avis3_en.htm,accessed 14 January 2004).

European Council

Council agreement relating to Community patents.Luxembourg, European Council, 15December 1989 (89/695/EEC) (http://e u r o p a . e u . i n t / s m a r t a p i / c g i /sga_doc?smartapi!celexapi!prod!CELEXnumdoc&lg=en&numdoc=41989A0695(01)&model=guichett, accessed 25 January 2004).

Government of India

Ethical policies on the human genome, geneticresearch and services. New Delhi, Departmentof Biotechnology—Government of India, June2001 (http://dbtindia.nic.in/publication/publicmain.html, accessed 13 January 2004).

Human Genome Organisation

Statement on benefit sharing. HUGO, 2000 (http://www.gene.ucl.ac.uk/hugo/benefit.html,accessed 5 January 2004).

Statement on patenting DNA sequences. HUGO,April 2000 (http://www.hugo-international.org/hugo/patent2000.html,accessed 12 January 2004).

Statement on patenting issues related to earlyrelease of raw sequence data. HUGO, 1997( h t t p : / / w w w. g e n e . u c l . a c . u k / h u g o /ip1997.htm, accessed 13 January 2004).


Indigenous Peoples Council on Biocolonialism

A resolution to oppose the human genome diversityproject and condemning unethical geneticresearch on indigenous peoples. Wadsworth,Indigenous People Council on Biocolonialism(IPCB), 15 January 1998 (http://w w w. i p c b . o r g / r e s o l u t i o n s / h t m l s /model_resolution_hgdp.html, accessed 13January 2004).

The “Heart of the Peoples” Declaration. FortBelknap Reservation, Indigenous PeoplesCouncil on Biocolonialism (IPCB), 7 August1997 (http://www.ipcb.org/resolutions/htmls/dec_heartopeoples.html, accessed 13 January2004).

International Federation of Gynecology andObstetrics

Recommendations on ethical issues in obstetrics andgynaecology-patenting human genes. FIGOCommittee on the Study of Ethical Aspects ofHuman Reproduction. International Digest ofHealth Legislation, 1997, 48:447.

United Nations

UN Agreement governing the activities of Stateson the Moon and other celestial bodies. NewYork, 18 December 1979.

74

7Notes

1 In 2004, the World Health Assembly officiallyadopted the following definition of “genomics”:the study of genes and their functions, and re-lated techniques (WHA 2004, a57.16). See theGlossary for definitions of terms used in thisreport.

2 This is not to say that it accepts all of the con-clusions of these reports. Rather, in terms of itsaims and the subject matter with which it is con-cerned, the present report can be said to find itsplace at the intersection of these three docu-ments.

3 In this report, when we refer to developing coun-tries, we refer broadly to countries, primarily insub-Saharan Africa, Latin America and Asia,with a weak industrial base, and where a con-siderable proportion of the population lives nearsubsistence level. We acknowledge the short-coming of this terminology, in light of the greatdiversity among countries in this category—diversity in health needs, economic develop-ment and scientific capacity. Where possible,we will try to point out where these factors makea difference in terms of the impact of DNA pat-ents.

4 As Clegg and Weatherall’s review points out,there is a hypothesized relationship, with grow-ing empirical support, between thehaemoglobinopathies and protection againstmalaria, which provides clues about why theseconditions are prevalent in malaria endemicareas.

5 See, for instance, the USA Department of En-ergy Office of Science’s human genome projectinformation website, for a list of available ge-netic tests: http://www.ornl.gov/sci/

techresources/Human_Genome/medicine/genetest.shtml#testsavailable (accessed 8 March2004).

6 Civil law does not take prior cases to be prec-edent in the same way as the common law sys-tem. While judges do refer to previous cases,commentary plays a much more important rolein the civil law. So, while precedent is impor-tant for common law system, doctrine is impor-tant for civilians.

7 This being said, neither the United States Con-stitution (Article I, Section 8) nor the UnitedStates Code (Title 35, Part II, Chapter 10, Sec-tion 101) distinguishes inventions from discov-eries. The latter document states that: “Who-ever invents or discovers any new and usefulprocess, machine, manufacture, or compositionof matter, or any new and useful improvementthereof, may obtain a patent therefore, subjectto the conditions and requirements of this ti-tle.” Courts have consistently interpreted Arti-cle 101 as excluding natural phenomena, suchas principles, powers and products of nature.O’Reilly v. Morse [56 U.S. (15 How.) 62 (1853)]rejected Samuel Morse’s claim seeking a patenton electromagnetism. Though he was the firstto harness it in inventing the telegraph, the courtargued that he had not invented electromagnet-ism, which is a force of nature and thus not pat-entable subject matter.

8 More specifically, they cover purified or iso-lated genes, the protein coded for by a gene,cells engineered to express the gene or proteinto detect or treat disease (Andrews, Mehlmanand Rothstein, 2002).


9 For example, the British Society of HumanGenetics, the American College of MedicalGeneticists, the Human Genetics Society ofAustralasia.

10 The patent holder may also opt not to use thepatented invention in countries where local lawsdo not impose a working obligation. “Exclu-sive” licenses do not always confer rights for alluses. Sometimes an invention is exclusively li-censed to multiple groups under different con-ditions.

11 An agreement on a “common political ap-proach” regarding the Community Patent,reached at the Competitiveness Council of Min-isters in Brussels on 3 March 2003, brought thisone step closer to realization. However, at theirmeeting in March 2004, the Ministers failed toreach agreement on the proposed Regulation,primarily due to a lack of consensus on how totreat infringements of patents that could arisedue to mistranslations. See Results of the Com-petitiveness Council of Ministers (EC, 2004).

12 See USPTO website on Trilateral Studies,http://www.uspto.gov/web/tws/sr-3.htm(accessed 29 September 2004).

13 All WTO Member States are eligible to importpharmaceuticals made under compulsory li-cences abroad, but 23 developed countries havealready stated that they will not use this provi-sion. All other members are eligible if they no-tify the Council for TRIPS of their intention touse the system as an importer.

14 TRIPS, as noted earlier, sets minimum stand-ards for countries; it offers relatively little di-rection on how to implement these norms. Any-thing above these minimum standards fallswithin a zone of “flexibility” (see South Cen-tre, http://www.southcentre.org/info/southbulletin/bulletin63/bulletin63-09.htm,accessed 14 May 2004). In bilateral negotiations,pressure has been brought to bear on develop-ing countries to extend stronger IP protectionthan what is required in TRIPS, i.e. so-calledTRIPS-plus provisions.

15 See, for example, http://www.bio.org/ip/primer/patentsay.asp, accessed 1 April 2004.

16 In 2000, Myriad Genetics claimed to have in-vested the equivalent of about 150 person-yearsof effort and tens of millions of dollars into thediscoveries of these genes, and the developmentof a highly automated and accurate clinical test.The company has argued that this investmentwould not have been possible without the po-tential for patent protection on these discover-ies. See Secretary’s Advisory Committee onGenetic Testing (Vol. III), 7 June 2000. It is notclear whether such figures would apply today,several years after the initial identification andsequencing of BRCA1 and BRCA2.

17 See Cutting-edge technology for low-cost di-agnosis. Sustainable Sciences Institute(www.ssilink.org/immunosensorhistory.html,accessed 14 May 2004).

18 Law No. 9.279 increases the patent term to 20years for all products and processes, and re-moves prior prohibitions on the granting of pat-ents for chemical products and processes for theproduction of pharmaceuticals and foods. LawNo. 9.279 has an important affect on Brazil’sability to manufacture generics. Brazil can nolonger freely produce generic versions of phar-maceuticals that are patented overseas. The ge-nerics industry can, however, continue to pro-duce generics based on products patented over-seas before 1996. In addition Brazil has the op-tion of issuing compulsory licences (see Glos-sary, Appendix 1) to produce generics undercertain conditions.

19 Oxfam and the Consumer Project on Technol-ogy defended Brazil’s position and contendedthat the complaint threatened the most success-ful AIDS treatment programme in the develop-ing world. In June 2001, a compromise wasreached, where the United States agreed to dropthe complaint and Brazil agreed to give UnitedStates officials advance notice before invokingthe provision.


20 Article 18, item III, states that living beings, inwhole or in part, are not considered patentable.Article 10, item IX, states that natural livingbeings, in whole or in part, and biological ma-terial encountered in nature or isolated includ-ing the genome or germplasm of any naturalliving being, are not considered as inventions.The Brazilian Group states that if sequences ofDNA are interpreted as chemical products theymay be patentable.

21 Ibid.

22 For instance, New Zealand’s Ministry ofHealth, in a report to the Cabinet Policy Com-mittee, concluded that Brazilian patent law con-siders genetic material, even in a purified andisolated state, as a discovery and therefore notpatentable; and in a paper presented for the Fron-tiers of Innovation Research and Policy, Mariada Graça Derengowski Fonseca and José MariaF.J. da Silveira state that Brazilian legislatorshave decided to allow patenting for geneticallymodified organisms only (Fonseca & Silviera,2002). Ladas & Perry LLP also state that thepatent law makes it clear that transgenic micro-organisms are patentable. But they do notspecify whether genes and DNA sequences areexcluded from patenting.

23 See the Beijing Genomics Institute website(http://www.genomics.org.cn/bgi/english/1.htm, accessed 5 March 2004).

24 See China Daily, 2002.

25 Ibid.

26 See Chinese firms keen on patent applicationfor WTO entry, People’s Daily (2001).

27 Ibid.

28 Counting patent families can only provide arough guide of a nation’s technological activityrelative to other countries, because differingnational patent laws and customs can result inhigher levels of patenting in some countries thanin others. Because a patent generally offers pro-tection only in the country in which it is issued,

and because it can be very expensive to applyfor patent protection in multiple countries, or-ganizations are assumed to seek patent protec-tion abroad only for those inventions they be-lieve will have significant commercial value.Comparing international patent families (in-ventions for which patent protection has beensought in more than one country) makes inter-national comparisons more accurate and pro-vides a more precise measure of technologicalactivity. A priority application refers to the firstapplication filed anywhere in the world and it isgenerally assumed that the country in which thepriority application was filed is the country inwhich the invention was developed.

29 See Science and engineering indicators, 2002a.

30 See Appendix table 6-15, Human DNA se-quence patents: Number of international patentfamilies, by priority country and priority year.Science and Engineering Indicators, 2002b.

31 See Achievements, Human Genetics and Ge-nome Analysis (http://dbtindia.nic.in/programmemes/progmain.html, accessed 26February 2004).

32 See Biotech Desk. Biotechnology in India –Initiatives by the Government (http://www.biotechdesk.com/market4.php, accessed24 February 2004).

33 Ibid.

34 See Patents Office India. Exclusive MarketRights (http://www.patentoffice.nic.in/ipr/patent/emr.htm, accessed 26 February 2004).

35 Ibid.

36 See Gene Campaign. International TradePolicy (http://www.genecampaign.org/about_us/impact_efforts.html, accessed 24 Feb-ruary 2004).

37 Although, as with Chinese and Indian pro-grammes, there are aspects mainly aimed at ex-port markets.


38 The human genome, itself, is not currently pat-entable. Some have claimed that the human ge-nome is therefore safeguarded from the chargeof commodification, because it is only specificsequences that are subject to patents. But thisprotection is currently de facto, and is not thebasis of any principled distinction; there is noth-ing within the current system that prohibits theeventual allowance of large-scale patenting ofportions of the genome, or the genome in itsentirety. Moreover, since the genome just sim-ply is composed of DNA sequences, a princi-pled objection to the patenting of the genomewould seem to impose similar constraints onthe patenting of its components.

39 Groups such as the Action Group on Erosion,Technology and Concentration (ETC Group),however, have raised concerns that such guide-lines establish national sovereignty over geneticresources, thus reducing the rights of indigenouspeoples and rural communities and their deci-sion-making capacity. According to the ETCGroup, a national level approach to benefit shar-ing undermines customary systems of resourceexchange (for example seed exchange betweenindigenous farmers). In response they call forthe reformulation of the Bonn guidelines to en-courage governments to establish non-propri-etary systems of benefit sharing, and for the CBDto facilitate the establishment of a globalbiodiversity fund to support the conservationand development of biodiversity in a mannerindependent of IP rights (ETC, 2004).

40 In 1984, John Moore filed a lawsuit against theUniversity of California. While he was under-going treatment for leukemia, his physician de-veloped a medically useful cell-line against can-cer, on the basis of which a patent was later ob-tained and commercial profits earned on thesubsequently developed therapies. The Califor-nia Supreme Court, in 1990, stated that donors

do not have “property rights” in the tissueearned from their bodies, and that in fact such aposition would hinder research and access toraw materials (Moore v. Regents of the Univer-sity of California, 793 P.2d 479 [Cal. 1990])

41 In one respect, this represents a more technicalbasis for arguing for the special status of DNA.One version, as stated above, rests on DNA’sessential difference from other natural products,even those molecules that are similarly situatedin the human body. What this argument seemsto suppose, like the more technical argument, isthat DNA is fundamentally valuable, in a“moral” sense, because it has a kind of “infor-mational content” that separates it from otherkinds of chemicals. It is a molecule that encodesinstructions for every aspect of a cell’s function,and for yet-unknown aspects of a person’s be-haviour and identity. It is therefore the so-calledinformational value of DNA that lends it itsspecial-ness.

42 See USPTO’s announcement of its new guide-lines for assessing utility of genetic inventions(http://www.uspto.gov/web/offices/com/speeches/01-01.htm, accessed 8 March 2004).

43 See WTO (http://www.wto.org/english/tratop_e/trips_e/intel2_e.htm, accessed May 12,2004).

44 Countries where there are significant differencesin standards of invention between full patentsand petty patents tend to grant more petty pat-ents. According to WIPO statistics, in 1999, forexample, China received 44 369 applicationsfor utility model patents, Korea received 30 650,Germany received 23 584 and Taiwan received17 954.

78

Appendix 1Glossary of terms

Benefit sharing the fair and equitable sharing of the benefits arising from the use ofgenetic resources

Biopiracy the appropriation of the knowledge and genetic resources of farmingand indigenous communities by individuals or institutions seekingexclusive monopoly control (usually patents or plant breeders’ rights)over these resources and knowledge

Compulsory licensing a state-granted licence to a third party, not requiring approval fromthe patent holder, allowing the licensee to exploit the patented inven-tion

DNA (deoxyribonucleic acid); the biochemical substance that makes upgenetic material; a double-stranded molecule comprising two linearchains made from four bases (A, C, G and T), together forming adouble helix

EST (expressed sequence tag); a short section of complementary DNAsequence, where location and nucleotide sequences are known. ESTshave applications in the discovery of new human genes, mapping ofthe human genome, and identification of coding regions in genomicsequences

Gene an ordered sequence of nucleotides located in a particular position ona particular chromosome that encodes a specific functional product,i.e. a protein or RNA molecule

Genetic patent (or DNA patent); a patent issued by any national patent office, whichclaims subject matter relating to specific sequences of DNA, includ-ing isolated genes, modified genes, etc., or any use or application ofsuch

Genetic testing DNA analysis to determine the carrier status of an individual; to di-agnose a present disease in the individual; or to determine the indi-vidual’s genetic predisposition to developing a particular conditionin the future


International patent family a patent family consists of all the patent documents associated with asingle invention that are published in one country. An internationalpatent family consists of all the patent documents relating to an in-vention for which patent protection has been sought in more than onecountry. Counting patent families can only provide a rough guide of anation’s technological activity relative to other countries, because dif-fering national patent laws and customs can result in higher levels ofpatenting in some countries than in others. The comparison of inter-national patent families (based on the assumption that organizationsseek patent protection abroad only for those inventions they believewill have significant commercial value) makes international com-parisons more accurate and provides a more precise measure of rela-tive technological activity

Licence the exclusive or non-exclusive transfer (not assignment) of patentrights to a third party, permitting the third party, under negotiatedconditions, to make, use or sell the patented invention

Patent a legal document providing an exclusive right to the owner for themanufacture, use or sale of the invention claimed therein

Patent claim the text within a patent that specifies all the elements, features andcritical aspects of the invention

Patent scope the interpretation that is given to the patent claim, which determinesthe boundaries or limitations of legal protection over the invention

Penetrance the probability that a genetic trait will be expressed. A genetic variantmay have “complete” or “incomplete” penetrance. The latter refersto cases where having the particular genetic variant leads to a less than100% likelihood of manifesting the condition

Research exemption (or research exception); a doctrine that enables the unlicensed use of apatented invention in pure research, which is usually interpreted asnon-commercial in its aim

Research tool(s) the full range of resources that scientists use in the laboratory, e.g. celllines, monoclonal antibodies, reagents, animal models, growth fac-tors, combinatorial chemistry libraries, drugs and drug targets, clonesand cloning tools, laboratory equipment and machines, databases andcomputer software

RNA (ribonucleic acid); a single-stranded nucleic acid molecule compris-ing a linear chain made from four bases (A, C, G and U). There arethree types of RNA: messenger (mRNA), transfer (tRNA) and ribos-omal (rRNA)

SNP (single nucleotide polymorphism); DNA sequence variation that oc-curs when a single nucleotide (A, T, C or G) in the genome sequenceis altered


TRIPS-plus intellectual property systems that go beyond the minimum standardrequired by TRIPS, i.e. systems that provide stronger intellectual prop-erty protection to inventors than what is explicitly required underTRIPS

Utility model (or petty patent); like a patent, grants a registered exclusive right tothe inventor to manufacture, sell or use an invention; the standardsrequired for protection (inventive step, novelty, industrial applica-tion) and the level of protection offered are generally lower than withpatents; however, the application process is usually cheaper and quickerbecause utility models may be granted without prior examination toestablish that above conditions have been met

81

Appendix 2Methodology

In November 2003, the Human GeneticsProgramme commissioned the writing of abackground paper on the “impact of DNA patentson access to genetic technologies and services forthe control and management of non-communicable diseases in low to middle incomecountries”, by McGill University’s Centre forIntellectual Property Policy, Montreal, Canada.

This background document formed the basis for athree-round electronic review process, initiated inJanuary 2004. Twenty-two individuals wereselected as Scientific Review Panellists, on the basisof recommendations, demonstrated expertise, andtheir record of publications in the area of geneticsor intellectual property rights. This work soughtto explore and to highlight the crucial issuesrelating to intellectual property (particularlypatents) through the lens of public health, ratherthan to produce official policy; the ScientificReview Panel therefore comprises chieflyacademics, rather than policy-makers. Each of theseindividuals formally agreed to participate in thereview process, and submitted a Declaration ofInterests form. Table 1 presents a complete list ofthe members of the Panel.

The goal of the review process was to obtain criticalfeedback from academics, representing a balanceddistribution across regions, and between sexes, onthe document. During the first round of the review

process, extensive feedback was received fromseveral reviewers, which led to a dramatic re-shaping of the document. In general, the first roundof comments reflected a desire for a more detailedexploration of the ethical issues relating to thepatenting of DNA sequences, and concretelinkages between the issues addressed and thespecific needs of developing countries. The aim ofthe review was not to achieve consensus at all costs,or to privilege particular viewpoints; rather, it was,as much as possible, to present the important issues,including points of ongoing disagreement. Thereport was re-drafted in line with the commentsreceived during the first round, and was sent backto the reviewers. The second round of commentswere, in general, more specific—for example,pointing to technical matters, and to the need toclarify various arguments, as well as suggestionsfor the inclusion of a glossary and list ofacronyms—rather than proposing the re-framingor substantial alteration to the report. Changes wereagain made by the editors on the basis of thisfeedback, and a third version of the document wassent out electronically for final review, includingto several WHO staff. This third and last wave ofcomments comprised largely minor proposals forclarification of terms, and alternative language forsome portions of text. These comments wereincorporated, and the final report underwentprofessional editing and publication.


Table 1Scientific Review Panel

Name Institutional affiliation

Shaikha Al-Arrayed Gulf Genetic Center, Ign Al Nafees Hospital, Kingdom of Bahrain

Amir Attaran Centre for International Development & Kennedy School of Government, Harvard University,United States of America

John Barton Law School, Stanford University, United States of America

Kare Berg Institute of Medical Genetics, University of Oslo, Norway

José Maria Cantu Genetics Division, Centro de Investigacion Biomédica de Occidente, Mexico

Jean-Jacques Cassiman Center for Human Genetics, Campus Gasthuisberg, Belgium

Mildred Cho Center for Biomedical Ethics, Stanford University, United States of America

Carlos Correa University of Buenos Aires, Argentina

Abdallah Daar Joint Centre for Bioethics, University of Toronto, Canada

Prabuddha Ganguli “Vision-IPR”, India

Cathy Garner Centre for the Management of IP in Health R&D, United Kingdom

E. Richard Gold Centre for Intellectual Property Policy, McGill University, Canada

Vladimir Ivanov Research Institute for Medical Genetics, Russian Federation

Patricia Kameri-Mbote International Environmental Law Research Centre, Kenya

Darryl Macer Eubios Ethics Institute, Japan

Patricia Aguilar-Martinez Laboratoire d’Hématologie, Hôpital Saint Eloi, France

Sisule Musungu South Centre, Switzerland

Victor Penchaszadeh Mailman School of Public Health, Columbia University, United States of America

Sandy Thomas Nuffield Council on Bioethics, United Kingdom

Lap-Chee Tsui University of Hong Kong, China

Ishwar Verma Department of Medical Genetics, Sir Ganga Ram Hospital, India

Huanming Yang Beijing Genomics Institute, Chinese Academy of Sciences, China

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