GENOMICS AND GLOBAL GOVERNANCE - PDF document

1 CHAPTER 3 GENOMICS AND GLOBAL GOVERNANCE
CHAPTER 3 GENOMICS AND GLOBAL GOVERNANCE 38 Worldwide Scientific Capacity for DevelopmentInadequate Governance Contributes to Failure of Diffusion ofGlobal Governance to Promote Global Public GoodsNeed for Global Governance for GenomicsExisting Governance Mechanisms may be InsufficientThe Global Genomics Initiative as a Proposed Global Network toWhat will the GGI do?Summary CHAPTER 4 BUILDING GENOMICS CAPACITY IN DEVELOPING COUNTRIES 46 Transfer of Technology and Science ÐLearning is Key to Building Capacity in Science and Technology:Options for Developing Countries to Build Learning Systems Building a Science Base by Re-energizing Academic Institutions 50 International Collaboration to Adapt Technology to Low-Resources Settings 53 Improving the Policy Environment and Encouraging Regional Cooperation 54 Encouraging Private Enterprise 57 Conclusion GLOSSARY 60 REFERENCES 68 This report will be of interest to actors from several disci-plines,ranging from scientists to policy-makers Ð they willfind that it moves seamlessly from policy to science andback in a highly interdisciplinary way.The completion of the Human Genome Project in April2003 was celebrated with great fa

2 nfare,but its potentialcontribution to d
nfare,but its potentialcontribution to developing countries went unnoticed.Developing countries were conspicuous in their absencefrom Francis CollinsÕagenda in the April 24th,2003 issue Nature .This report brings developing countries into thelimelight,and furthermore focuses on a coherent visionsupported by a policy framework Ð innovation for develop-ment.Given Secretary-General Kofi AnnanÕs call to worldscientists to forge global alliances for achieving develop-ment goals,this is the right time to explore the issues dis-cussed here.As an illustration,this report plays a crucial rolein helping the international and national policy makers,stakeholders and development practitioners understand theways in which science,technology and innovation can con-tribute to long-term improvement of human welfare andeconomic transformation in developing countries. Calestous Juma Co-coordinatorTask Force on Science,Technology and Innovation of theMillennium Project Professor of the Practice of International DevelopmentJohn F.Kennedy School of Government,Harvard University Lee Yee-Cheong Co-coordinatorTask Force on Science,Technology and Innovation of theMillennium Project President of

3 the World Federation of Engineering Org
the World Federation of Engineering Organizations GENOMICS FOR THE UN MILLENNIUM DEVELOPMENT GOALS vi Canadian Program on Genomics and Global HealthUniversity of Toronto Joint Centre for BioethicsISBN:# 0-7727-8762-X© 2004 Joint Centre for Bioethics e thank Calestous Juma,Lee Yee-Cheong,members of the United Nations MillenniumProjectÕs Science and Technology Task Force(Kamel Ayadi,Susan Brandwayn,Norman Clark,DenisGilhooly,Qiheng Hu,Vijaya Kumar,Sanjaya Lall,TonyMarjoram,James Moody,Kenneth Nwabueze,Teresa Poon,Tony Ridley,Francisco Sercovich,Judith Sutz,BrendanTuohy,Caroline Wagner) and Smita Srinivas for providingus with valuable guidance and suggestions in the prepara-tion of this report.We also thank Richard Smith for his rolein developing the concept of genomics as a global publicgood,Basma Abdelgafar,Lynn Mytelka and Uyen Quachfor discussions relating to chapter 4,and Andrew Taylor formaterial relating to chapter 1.Robyn Kennedy andElizabeth Martin participated in the preparation of thereport.We owe special thanks to Archana Bhatt for herwork in the final preparation,design,and execution of thereport.We are also grateful to Douglas K.Martin,ShaunaNast and Alyna

4 Smith for their work on a previous repo
Smith for their work on a previous reporton the ÒTop 10 Biotechnologies to Improve Health inDeveloping CountriesÓ.We thank Michael Keating for hiseditorial support.The CPGGH receives most of its funding from theOntario Research and Development Challenge Fund,andGenome Canada through the Ontario GenomicsInstitute.Matching partners for some of the projectsinclude the Fogarty International Center,FoodBiotechnology Communications Network,Food SystemsBiotechnology Centre,GlaxoSmithKline,The Hospital forSick Children,Indian Council for Medical Research,Industry Canada,International Development ResearchCentre (IDRC),the McLaughlin Centre for MolecularMedicine,Merck and Co,Mount Sinai Hospital,Sunnybrook and WomenÕs College Health Sciences Centre,University of Guelph,University Health Network,University of Toronto,and the World Health Organization.Peter A.Singer is supported by a Distinguished Investigatoraward from the Canadian Institutes of Health Research.ACKNOWLEDGEMENTS ix creation of a global partnership,the Global GenomicsInitiative (GGI),to promote genomics for health.We seethis as a global network of industry leaders,academics,con-cerned citizens,members of NGOs and

5 government offi-cials,with strong repre
government offi-cials,with strong representation from the developing world.Finally,our report tackles the challenge of how to putgenomics and related technologies to work in developingcountries within the next 5-10 years.We feel that develop-ing countries with the scientific capacity and institutionalarrangements that allow creation,utilization,adaptation ordiffusion of genomics are well positioned to harness thisnew science for development.We see examples of strategiesthat some countries have followed to institute learningprocesses that can help them build their national systems ofinnovation in biotechnology.The challenge we face is for industrialized and develop-ing nations,and developing nations themselves,to buildpartnerships that will share the fruits of genomic knowl-edge,and thus help to build a better,healthier and more sta-ble world.The conclusions of our report follow.GENOMICS FOR THE UN MILLENNIUM DEVELOPMENT GOALS xii GENOMICS FOR THE UN MILLENNIUM DEVELOPMENT GOALS xiv ver the last 100 years,innovations in science andtechnology,together with improved socio-eco-nomic conditions,have resulted in improvedhealth,quality of life and a vast increase in peopleÕ

6 s lifeexpectancy worldwide.In light of t
s lifeexpectancy worldwide.In light of this impressive record itis disheartening that the benefits of modern medicine stilldo not reach billions of people in the poorer parts of theworld.Children and adults are undernourished,live inpoor housing with few modern facilities,such as clean,run-ning water,and die from various,often preventable,illness-es in the prime of their lives.While there are many factorsthat come into play in the complex issue of development,it is widely accepted that science and technology plays acritical role in improving health in developing countries.and related biotechnologies constitute anexciting new field of science that possesses tremendouspotential to address health problems in developing coun-tries Ð if we rise to the challenge.The purpose of this reportis to focus on the role of genomics and related healthbiotechnologies as an example of the application of science,technology and innovation (STI) to improve global healthand contribute towards meeting the United NationsMillennium Development Goals.The Millennium Development Goals (MDGs) grew outof the commitment of the United Nations to promote sus-tained development and eliminate poverty a

7 ll over theworld.They help quantify prog
ll over theworld.They help quantify progress by defining targets andindicators to measure them.The first seven MDGs aredirected at specific objectives in promoting developmentand improving peopleÕs lives,while the eighth goal,Ôa glob-al partnership for developmentÕ,focuses on the means toachieve them.Many of the goals address health issuesdirectly,such as improving infant and maternal health andreducing the prevalence of infectious diseases (see Table1.1).The MDGs have become the international standardfor measuring and tracking improvements in development.Therefore,the MDGs have the advantage of (i) agreementand support with the leaders of all UN member states,(ii)offering a comprehensive and multi-dimensional develop-ment framework,and (iii) setting clear quantifiable goals forall countries to meet by 2015.Although the MDGs,espe-cially the health-related ones,have their critics,they do rep-resent a standard by which progress may be measured.The Millennium Project,whose mission is to devise andrecommend operational frameworks to help developingcountries achieve the MDGs,has set up ten thematically-oriented task forces,consisting of experts and leading prac-titioners.T

8 hese task forces have carried out detail
hese task forces have carried out detailed andcomprehensive research in each thematic area on the sci-ence,public health needs and medical interventions,as wellas the social,political and economic issues.The goals of theScience and Technology Task Force are to address how sci-ence and technology can be enhanced and applied to helpall countries achieve the MDGs.Its mission is guided bythe understanding that most of the MDGs cannot bereached without a strong contribution from science andtechnology (Box 1.1). BOX 1.1 THE INTERIM REPORT OF THE SCIENCE ANDTECHNOLOGY TASK FORCE The interim report of the Task Force outlines approaches for usingtion and continuous technological improvement. The reportoffers a conceptual framework under which economic changeis viewed as a learning process by which knowledge is trans- CHAPTER ONE Ð GENOMICS FOR HEALTH AND DEVELOPMENT GENOMICS FOR HEALTH ÒThe scientific communityÕs basic concern for human welfare makes it an indispensable partner of the United NationsÓ -Kofi Annan,2003 Ñ CHAPTER ONE Ñ CHAPTER ONE Ð GENOMICS FOR HEALTH AND DEVELOPMENT 3Goal 1 poverty and hunger Goal 2 primary education Goal 3 : Promote gender equality Goal 4 : Re

9 duce child mortality Goal 5 : Improve ma
duce child mortality Goal 5 : Improve maternal health Goal 6 : Combat HIV/AIDS,malaria and other diseases Goal 7 : Ensure environmentalsustainability Goal 8 : Develop a global part- Target 1: Target 2: Target 3: Target 4: Target 5: Target 6: Target 7: Target 8: Target 9: Target 10: Target 11: Target 12: Target 13:Target 14:Target 15:Target 16:Target 17:Target 18: Halve, between 1990 and 2015, the proportion of people whose income is less thanHalve, between 1990 and 2015, the proportion of people who suffer from hungerEnsure that, by 2015, children everywhere, boys and girls alike, will be able to com-plete a full course of primary schoolingEliminate gender disparity in primary and secondary education, preferably by 2005,Reduce by two-thirds, between 1990 and 2015, the under-five mortality rateReduce by three-quarters, between 1990 and 2015, the maternal mortality ratioIntegrate the principles of sustainable development into country policies and programmesHalve, by 2015, the proportion of people without sustainable access to safe drinkingFurther develop an open, rule-based, predictable, non-discriminatory trading and financialand international measures in order to make

10 debt sustainable in the long termIn co-
debt sustainable in the long termIn co-operation with pharmaceutical companies, provide access to affordable, essentialIn co-operation with the private sector, make available the benefits of new technologies,especially information and communications TABLE 1.1: UNITED NATIONS MILLENNIUM DEVELOPMENT GOALSwww.developmentgoals.org ¥ Countries must create, maintain and continually modernize¥ Countries need research institutions for S&T capacity, includ-¥ For-profit organizations are the worldÕs predominant force inand services. It is important to create an enabling environ-¥ Both industrialized and developing nations need to commit¥ Achieving these goals require collaboration among a widerange of actors at the international level.The report provides a vision for increasing S&T capacity ininnovation systems through: 1) national policies that nurture anationÕs S&T capacity and, 2) an international coalition that pro- http://www.interacademycouncil.net/reports.asp THE NEED FOR GOOD HEALTH Despite the positive influence of modern science and tech-nology on life expectancy and health,in recent years theworld has seen an alarming rise in the incidence of infec-tious diseases,pa

11 rticularly HIV/AIDS.In many sub-SaharanA
rticularly HIV/AIDS.In many sub-SaharanAfrican countries life expectancy had been rising duringmost of the last century but has actually fallen in recenttimes due to the AIDS crisis.New technologies to dealwith this,and other infectious diseases,are in high demandbut are still unavailable.It is no surprise that most people in the world view goodhealth as a pre-requisite for quality of life.Good health iscrucial for survival and is essential for productivity andtherefore for social and economic development.TheCommission on Macroeconomics and Health showed thatthe linkages of health to poverty reduction and to long-term economic growth are powerful.Empirical evidencesuggests that countries with low levels of health and educa-tion have a much more difficult time achieving sustainedeconomic growth than countries with higher levels ofhealth and education.Even after controlling for the effectof macroeconomic variables such as structural characteris-tics of the economy,health status continues to explain animportant percentage of the differences in economicgrowth between countries.Investing in health is therefore an effective strategy toboost economic development and contrib

12 ute to the effortsto meet the Millennium
ute to the effortsto meet the Millennium Development Goals.According tothe Commission on Macroeconomics and Health,mostgovernments in developing countries and the internationaldonor community have seriously underestimated the valueof investing in health.To make the case for investing inhealth,it estimated that approximately 330 million disabil-ity-adjusted life years (DALYs - one disability-adjusted life-year is defined as the loss of one year of healthy life to dis-ease) could be saved for every 8 million deaths prevented,generating economic benefit of US$186 billion per year asof 2015.This would require additional annual health out-lays,for all low-income countries and selected middle-income countries,of US $57 billion by 2007 and US $94billion by 2015.Investing in health provides the resources to develop andenhance tools to address health problems of people indeveloping countries.One current obstacle to developingsuch tools is that most ongoing health research is largelyaimed at health problems in richer countries.Ninety per-cent of all health research expenditure is targeted at prob-lems affecting only ten percent of the worldÕs population -the so-called Ò10/90 ga

13 pÓ.As an illustrative example,ofCHAPTER
pÓ.As an illustrative example,ofCHAPTER ONE Ð GENOMICS FOR HEALTH AND DEVELOPMENT 5 GENOMICS FOR THE UN MILLENNIUM DEVELOPMENT GOALS 7 The DNA double helix that carries hereditary information in all of us billion base-pairs of the human genome.Many othergenomes of the plant and animal kingdom have beensequenced,ranging from common yeast to rice,and allthese sequencing achievements promise to enhance scien-tific knowledge.In October 2002,scientists published thesequence of the parasites responsible for human malaria, Plasmodium falciparum ,as well as the mosquito that carries Anopheles gambiae The knowledge of these genomes,together with the knowledge of the human genome,canbe used to develop new drug and vaccine targets againstmalaria.Genomics can be applied in a wide range ofproducts,which we will describe in further detail in BOX 1.4 THE HUMAN GENOME PROJECT teams in 20 different countries, allocated over US $3 billion inal approach to tackle the enormous and complex task ofconcerted effort resulted in the sequencing of 94% of thehuman genome by February 2001, and complete sequencingacceleration was at least partly due to competition fromMaryland. In 1998, Celera ch

14 allenged the Human Genomewithout restric
allenged the Human Genomewithout restrictions within 24 hours of assembly. There may also be direct economic benefits of genomics.It isalready a significant contributor to the biotechnology sec-tor.Despite early setbacks,the genomics-based pharma-ceutical market was expected to grow from US $2.2 billionplayers in the world are not the only ones expected to ben-efit from genomics.Cuba,for example,has invested heavi-ly since the 1980Õs in research infrastructure and manufac-turing in biotechnology.As a result biotechnology is poisedto become a major export industry in Cuba.In order to reap direct economic benefit fromgenomics,countries will have to be active participants inthe development and manufacturing of genomics prod-ucts.Those countries that will benefit the most fromgenomics are those that have appropriate health productsto improve the health of their populations and who areactive in developing and supplying those products.Thiswill involve engaging and stimulating the private sector,without which the production and commercialization ofnew biotechnology products will be a challenge.As high-lighted by the UN Commission on Private Sector andDevelopment report,Ò Un

15 leashing Entrepreneurship:MakingBusiness
leashing Entrepreneurship:MakingBusiness Work for the Poor ,Óthe process of commercializa-tion for development involves the dissemination and facil-itation of knowledge flows between public and privatesectors of both developed and developing markets.report recommends action in both the public and privatespheres,but also emphasizes the linkages between thesespheres,recognizing the importance of cooperation andpartnerships to achieve goals (Box 1.5). BOX 1.5 THE REPORT OF THE UN COMMISSION ONPRIVATE SECTOR AND DEVELOPMENT chaired by Canadian Prime Minister Paul Martin and formerMexican President Ernesto Zedillo) has presented a report titled GENOMICS FOR THE UN MILLENNIUM DEVELOPMENT GOALS 8 One recent initiative that aims to leverage basic scienceand engage the worldÕs best scientific minds in globalhealth is the Grand Challenges in Global Health program,sponsored by the Bill and Melinda Gates Foundation,andadministered by the Foundation for the National Institutesof Health (Box 1.6). BOX 1.6 GRAND CHALLENGES IN GLOBAL HEALTH On January 26, 2003, at the World Economic Forum in Davos,barrier to solving an important health problem in the developingworld with a high likel

16 ihood of global impact and feasibility.Ó
ihood of global impact and feasibility.Ó AThe efforts to identify Grand Challenges in Global Healthboard) of 20 scientists and public health experts from 13 coun-processes, will encourage the participation of developing-coun-try researchers and will be available to advise about organizinginter-institutional or international consortia where appropriate.tinued discussion among members of the board. In the verydesign of its gift, the BMGF has challenged the worldÕs scien- Goals and Grand Challenges To improve childhood vaccines: GC 1 : Create effective single-dose vaccines that can be usedsoon after birth; GC 2 : Prepare vaccines that do not require refrigeration; GC 3 : Develop needle-free delivery systems for vaccines. To create new vaccines: GC 4 : Devise reliable tests in model systems to evaluate live GC 5 : Solve how to design antigens for effective, protective GC 6 : Learn which immunological responses provide protec-tive immunity. To control insects that transmit agents of disease: GC 7 : Develop a genetic strategy to deplete or incapacitate a GENOMICS FOR THE UN MILLENNIUM DEVELOPMENT GOALS 10 Similarly,it is unlikely that achieving good health willsolve all the

17 problems associated with poverty.Develo
problems associated with poverty.Development is not an automatic process but requires acareful,considered approach that stimulates many factorssimultaneously.One such comprehensive approach wouldbe to invest in established indicators of development - edu-cation,living conditions,infrastructure,and improved gov-ernance - as well as new and emerging technologies likegenomics.The dire conditions in developing countriesrequire us to focus on all possible tools to promote healthand development.The potential of genomics and othermodern health biotechnologies are so compelling that theyshould be seriously considered to be an integral part of asound overall development strategy.Therefore,there is goodreason to evaluate the contributions genomics and othermodern health biotechnologies can make to achieving theGENOMICS FOR THE UN MILLENNIUM DEVELOPMENT GOALS 12 GENOMICS FOR THE UN MILLENNIUM DEVELOPMENT GOALS 14 Goal 3 : Promote gender equality and Goal 4 : Reduce child mortality Goal 5 : Improve maternal health Goal 6 : Combat HIV, malaria and Goal 7 Africa were womenAverage HIV infection rates in teenage girlstheir fifth birthdayOver 500,000 maternal deaths per yearto waterb

18 orne diseases¥Female control over STD tr
orne diseases¥Female control over STD transmission¥Vaccine and drug delivery¥Molecular Diagnostics¥Vaccine and drug delivery¥Recombinant vaccines¥Female control over STD transmission¥Nutritionally enriched genetically modi-¥Combinatorial chemistry¥Molecular Diagnostics¥Vaccine and drug delivery¥Recombinant vaccines¥Female control over STD transmission¥Nutritionally enriched GM crops¥Combinatorial chemistry¥Molecular Diagnostics¥Vaccine and drug delivery¥Recombinant vaccines¥Female control over STD transmission¥Bioremediation¥Sequencing pathogen genomes¥Bioinformatics¥Nutritionally enriched GM crops¥Combinatorial chemistry¥Bioremediation TABLE 2.1 HARNESSING THE MDGS WITH BIOTECHNOLOGY MILLENNIUM DEVELOPMENT GOALSTATISTICS / FACTSBIOTECHNOLOGY TO ADDRESS MDG ease.It is not surprising that the scientific panel in theUniversity ofToronto study ranked molecular diagnostics asthe most promising set of technologies for improving healthin developing countries over the next five to ten years.Many of the diagnostic tools currently in use in devel-oping countries are cumbersome,time-consuming andexpensive.In contrast,molecular diagnostics are simple touse,give quick results and

19 can be relatively cheap.In thefollowing
can be relatively cheap.In thefollowing discussion,we focus on a few such technologies:polymerase chain reaction,monoclonal antibodies andrecombinant antigens. polymerase chain reaction (PCR) is a quick way ofThis technology is fast and accurate.It takes advantage ofthe fact that organisms have unique genetic sequences.Amplification and identification of a pathogen-specificDNA sequence in the body fluids or cells of a person iden-tifies infection in that individual.Besides being extremelysensitive,PCR tests can provide results in a few hours asopposed to days for culturing methods.They can also beused to detect infectious organisms that are difficult orimpossible to grow in culture (e.g.tuberculosis,malaria) orare dangerous to handle (e.g.HIV/AIDS). BOX 2.3 BRANCHED DNA TEST Òbranched DNA testÓ, a patientÕs blood sample is treated withpathogenÕs genes, additional compounds that bind to the probeare added, forming a branched structure that emits a detectable In the industrialized world,the use of PCR tests in thediagnosis of infectious diseases is increasing.Tests for HIV-1,gonorrhea,pneumonia and herpes are already available.Recent advances are beginning to bring thi

20 s powerful toolwithin reach of the devel
s powerful toolwithin reach of the developing world.For example,a groupinvolved in the testing of infants for HIV-1 successfullyprocessed and stored blood samples for up to severalmonths on commercially available filter paper.for three complexes of New World Leishmania ( braziliensis , Leishmania mexicana ,and Leishmania donovani ) Ð which cause a spectrum of diseases Ð was developed inNicaragua and uses a technique known as multiplexing totest for more than one disease at once,saving both time andresources.Going a step beyond current practices in PCRare new nanotechnology the molecular level,without the need for DNA amplifica-tion.One nanotechnique uses gold particles complexedwith diagnostic DNA fragments that have the ability tobind to specific pathogen-associated DNA sequences.Asample of the patientÕs blood is placed between two tinyelectrodes in the presence of the probe.When the probeand its target DNA sequence match,the gold particles closethe circuit between the electrodes and produce a detectablesignal.Not only is this approach more sensitive than con-ventional detection methods,it has the potential to be sub-stantially more affordable.While PCR tests are

21 on their way to finding applicationsin d
on their way to finding applicationsin developing countries,antibody-based applications arealready highly suited to the developing world. Antibodies aremolecules produced by the immune system in response toinfection.They recognize and bind to proteins produced bypathogens.These proteins are known as antigens.Antibodiesare specific,i.e.every antibody recognizes and binds to aspecific type of antigen.This makes them an excellent toolfor the diagnosis of infectious disease.In the last few years,the development of simple and rapid antibody-coated dip-stick tests have increased the relevance of this technologyfor the developing world.Dipsticks can be used anywhere,GENOMICS FOR THE UN MILLENNIUM DEVELOPMENT GOALS 16 without the need for laboratory facilities,running water orelectricity.OptiMAL¨ is one of several antibody-baseddipstick tests for malaria.During a malaria outbreak inHonduras,it rivaled the accuracy of microscopic analysis,the Ògold standardÓof malaria diagnosis.The Program forAppropriate Technology in Health,an international not-for-profit organization committed to improving globalhealth,has developed an HIV dipstick test that is now beingproduced by several p

22 rivate firms in developing countries. De
rivate firms in developing countries. Determine HIV-1/2 can diagnose both HIV-1 and HIV-2based upon a reaction on a nitrocellulose strip betweenrecombinant antigens and patient antibodies.The test isaccurate and sensitive and has been successfully tested in thePATH is also developing dipsticks for thedetection of malaria,TB and hepatitis C,among other dis-eases.Quidel has developed a dipstick test for Streptococcuspneumoniae ,the most common cause of pneumonia.Monoclonal antibodies (mAb) are extremely specificantibodies.They are superior to antibodies harvested fromhuman or animal serum because they are extraordinarilypure,show very high binding specificity and can be grownin large quantities.The drawback is that mammalian cellculture is expensive,so although the sensitivity and speci-ficity of monoclonal antibodies are high,cost issues haveprevented their widespread use in developing countries. CULTURE TECHNIQUE ÔimmortalÕ). Each hybrid cell produces identical antibody mole-clonal antibodiesÓ because they are produced by the identical off- Plantibodies are monoclonal antibodies that are produced ingenetically engineered plants and then extracted for medicaluse.They

23 are a cheaper source of antibodies than
are a cheaper source of antibodies than those pro-duced in mammalian cells.One estimate places the cost of agram of plantibodies at less than 5% that of mammalian cellAnother advantage is that they donot risk spreading animal diseases to humans.Plantibodieshave been patented by Epicyte,a U.S.biotechnology com-pany which plans to begin clinical trials of its anti-HerpesSimplex Virus 1 and 2 plantibody mixture,HX8.pany was recently awarded a grant from the US NationalInstitutes of Health for the development of plantibodiesagainst Human Papilloma Virus (HPV),vical cancer.Other companies have begun human trials ofplantibodies for Hepatitis B,sexually transmitted diseases,and non-HodgkinÕs lymphoma. BOX 2.5 A NEW TEST FOR TUBERCULOSIS testing, the main drawback of which is low specificity. For GENOMICS FOR THE UN MILLENNIUM DEVELOPMENT GOALS 18 methods and,in some cases,because improved storage char-acteristics may not require them to be refrigerated.Muchprogress is being made in recombinant vaccine develop-ment.A major roadblock is the long time it takes for clini-cal trials and regulatory approval.To date,the number ofproducts on the market is quite limited.Researchers a

24 recurrently working to develop technique
recurrently working to develop techniques to overcomesome of the other difficulties too,for example,correct pre-sentation of recombinant antigens to the immune systemand the limited lifetime of the engineered protein in thebody.Several types of recombinant vaccines exist,of whichsome are described below (Box 2.6). BOX 2.6 TYPES OF RECOMBINANT VACCINES Viral vector vaccines consist of a benign virus that has beenattaches to the individualÕs cells and injects its genetic materialinto the cellÕs interior. The foreign genetic material gets incor-porated into the cellÕs genome. The cell follows the geneticalso known, are very similar to viral vector vaccines. The keydifference is that naked DNA vaccines use a different biologi-cal carrier, known as a plasmid, to introduce the antigen genesinto the individualÕs cells. Plasmids are small circular moleculesof DNA that are normally found in bacteria. They can easilyenter cells and recruit the cell to translate their genetic informa-oping naked DNA vaccines is potentially faster, cheaper andmajor cost barrier to efficient vaccine delivery.to. After introducing the pathogen genes into the plantÕs DNA,port and they could be grown

25 locally, making them attractiveseveral
locally, making them attractiveseveral important causes of infant mortality, including infant The examples below illustrate current advances of recom-binant vaccine technology for various diseases. BOX 2.7 RECOMBINANT VACCINES IN DEVELOPMENT involving 24 different vaccines. Of these, 8 are DNA-based,unteers generated antibodies that neutralized HIV-1. Whenportion rose to 94%. Phase III trials began in late 2003. Inprotection conferred by recombinant forms of HIV gp120, afusion protein constructed from HIV regulatory proteins Nef GENOMICS FOR THE UN MILLENNIUM DEVELOPMENT GOALS 20 Closely related to advances in vaccines are improved meth-ods of vaccine and drug delivery.Consequently,these newtechnologies will also serve to meet the fourth,fifth andsixth Millennium Development Goals as mentioned in theprevious section, Reduce child mortality , Improve maternal and Combat HIV/AIDS,malaria and other diseases Thousands of children die each year from vaccine-pre-ventable diseases because the logistics of vaccine deliveryare prohibitively expensive.Refrigerated transport and stor-age (Òthe cold chainÓ) is a major expense in all vaccine pro-grams.Another factor that raises

26 costs is trained medicalpersonnel who ca
costs is trained medicalpersonnel who can deliver vaccinations.Unsanitary drugand vaccine injections are associated with the spread ofblood-borne diseases among the population,particularlyHIV and hepatitis.It is estimated that reuse of needles caus-es 80,000 to 160,000 new cases of HIV/ AIDS,8 to 16 mil-lion new cases of hepatitis B and 2 to 4 million new casesof hepatitis C each year.Long and complicated drug reg-imens are difficult for people to comply with,especially ifthey involve visits to medical facilities.When patients fail tocomplete their treatments,they not only fail to recover,butpartial treatment can lead to the emergence of drug resis-tant strains of disease.Injection-free and controlled-release delivery systemscould help to solve many of these problems.The scientificcommunity is exploring a number of alternatives to needle-based delivery of drugs or vaccines.The skin,for instance,is an attractive route into the body because of its easyaccess.Needle-free injections propel the vaccine or drugthrough the skin and into the body with a high-speed jetof gas.Solutions,rubbing gels and skin patches rely on sim-ple diffusion to introduce agents into the body.Ano

27 theravenue into the body is the mucus me
theravenue into the body is the mucus membrane that lines allof the inner cavities of the body,including the intestinesand the lungs.Mucus membranes are abundant and areclosely associated with the bloodstream (which is importantfor drug absorption).Vaccination in the lung membranesgenerates immunity in the rest of the bodyÕs mucus mem-branes in addition to the systemic immunity generally con-ferred by vaccines.Consequently,the introduction of drugsand vaccines across the respiratory tract through nasal spraysand inhalers is an attractive option.As mentioned earlier,the refrigeration required for stor-ing and transporting conventional vaccines and drugs iscostly.The discovery that some microorganisms can berejuvenated after complete dehydration has led to the excit-ing development of powdered vaccines and drugs that areheat-stable.These organisms contain a non-reactive sugar(trehalose) that stabilizes them while they are desiccated.With this and other stable sugars,researchers have been ableto dehydrate liquid vaccines and drugs and store them atroom temperature for up to several months without affect-ing their potency.Associated injection devices for driedvaccines hav

28 e been developed.Some involve the recons
e been developed.Some involve the reconsti-tution of the dried substance into a liquid just prior toinjection,while others introduce the substance into thebody through the skin as a powder using needles or a high-Improved drug delivery can also help to reduce thelength and complexity of drug treatment regimens.Controlled-release drugs and vaccines can be introducedinto the body in association with a biodegradable polymerthat gradually releases its contents as it is broken down bythe body.One disease for which this would be very usefulis tuberculosis,which has risen to epidemic levels.Sustained-release antibiotic treatments,which automatical-ly release their contents overtime,would lower the num-ber of doses a patient must receive,thereby increasingcompliance and limiting the emergence of drug resistantstrains of TB.Preliminary studies of controlled releaseantibiotics have been promising.Recently a group hasreported the development of temperature-stable,con-trolled-release formulations using oligosaccharide esterderivatives of trehalose and a synthetic peptide analogue ofhepatitis B surface antigen.The ability of these noveldelivery systems to induce strong immune resp

29 onses inGENOMICS FOR THE UN MILLENNIUM D
onses inGENOMICS FOR THE UN MILLENNIUM DEVELOPMENT GOALS 22 solution to this problem.The area is artificially saturatedwith water,plant species are introduced,and these eventual-ly lower the acidity and the metal concentrations at the site.The bacterium Deinococcus radiodurans thrive in environments with 300 times the fatal dose of radi-ation for humans.Researchers have genetically engineered D.radiodurans to express several genes associated with mer-cury detoxification.The recombinant bacterium has beenshown to metabolize mercury while being bombarded byhigh levels of radiation,suggesting that bioremediation maybe able to aid in the process of radioactive waste cleanup.Bioremediation can also help to clean up mosquito-infest-ed water and control the spread of malaria.For example,themalaria-carrying Anopheles mosquito has developed resis-tance to chemical insecticides.Many anti-malarial prophy-lactics that were once effective are now less reliable,not tomention expensive for many people in developing countries.Peru has one of the highest rates of malaria in all of LatinAmerica.CanadaÕs International Development ResearchCentre (IDRC) has supported research at the In

30 stituto deMedicina Tropical ÒAlexander V
stituto deMedicina Tropical ÒAlexander Von HumboldtÓin Lima toexplore the use of coconuts in the fight against malaria.Researchers at the Institute have developed an ingeniousmethod to biologically control mosquitoes that is simple,inexpensive,and an environmentally safe alternative to insec-ticides.It involves the use of coconuts used to culture bacte-ria that are toxic to mosquito larvae but harmless to people Bacillus thuringiensis var. israelensis H-14 Bti ) is a spore-forming bacterium that produces a toxinlethal to mosquito larvae.Imported Bti cultures are expen-sive,but as this project shows Bti can be cultured locally andcheaply using coconuts,which are both cheap and plentifulin many tropical areas. Bti is introduced via cotton swabs intothe coconut and allowed to incubate inside the coconut fora few days.The nut is then broken and tossed into pondswhere mosquitoes breed.The mosquito larvae eat the bacte-ria and are killed.A typical pond needs only two or threecoconuts for each treatment Ð usually lasting 2 months. BOX 2.9 BIOREMEDIATION TO THE RESCUE: a population in historyÓ due to naturally-occurring groundwa-itating skin lesions are believed to have al

31 ready occurredbecause of the seepage of
ready occurredbecause of the seepage of arsenic into the water supply, andat least 50 million people are at risk. Recently discovered ina gold mine in Australia, a bacterium named NT-26 may beNT-26 has the natural ability to transformarsenite, a soluble form of arsenic, into the much less toxicform arsenate. The Australian Research Council is supportingresearch to investigate the potential of NT-26 to reduce thetoxicity of arsenic dissolved in water. Knowledge of thegenomic sequence of NT-26 and other arsenic metabolizingmetabolizing bacteria, including NT-26. This move is part ofa greater Canadian initiative to harness Canadian R&D forbrake fern Pteris vittata harm to itself.The unusually sun-loving fern could be cultivat-filter. The fern collects the arsenic in its fronds, which are easyto harvest, although scientists admit that more work is neededon how to dispose of the plants. Further research is also look-ing into identifying and then splicing the fernÕs arsenic-metabo- GENOMICS FOR THE UN MILLENNIUM DEVELOPMENT GOALS 24 GENOMICS FOR THE UN MILLENNIUM DEVELOPMENT GOALS 26 In addition to spurring novel drug discovery,pathogengenomics has also given a boost to th

32 e development of vac-cines.Researchers c
e development of vac-cines.Researchers can search the genome of infectiousorganisms for gene sequences characteristic of antigens.Forexample,scientists have discovered vaccine candidates for aparticularly virulent strain of meningitis,a potentially fatalbacterial infection.Of the 570 antigens found,85 showedpromise when used to immunize mice. 6. FEMALE-CONTROLLED PROTECTIONAGAINST SEXUALLY TRANSMITTED ¥Promote gender equality and empower women¥Improve maternal health¥Reduce child mortality Genomics and other biotechnologies are enabling thedevelopment of a number of new forms of female-con-trolled protection against STIs,such as recombinant vac-cines,monoclonal antibodies and new approaches to thedevelopment of vaginal microbicides.These technologies Combat HIV/AIDS,malaria and other diseases and even the third MDG, Promote gender equality and empower women rect effect on other health MDGs:e.g. Reducing child mor- by Improving maternal health The global burden of STIs is felt most heavily by women.A decade ago,the World Bank ranked STIs as the secondmajor cause of ill health among women aged 15 to 44,accounting for 8.9% of their disease burden,compared toFor various r

33 easons Ð socio-economic,cul-tural and bi
easons Ð socio-economic,cul-tural and biological Ð women are more vulnerable to infec-Women with STIs often bear heavy socialstigma,and they often have neither the time nor the moneyto seek health care.Rising infection in women also increas-es the incidence of transmission from mother to newborn.Despite the seriousness of this problem,women possessfew means of protection.The condom requires male con-sent,which many women living in patriarchal societies findhard to negotiate in their relationships.Although the femalecondom has been greeted with enthusiasm by women inpoor countries,its cost and indiscreetness make it a less thanideal option.Vaginal microbicides are one attractive alterna-tive.They are gel or cream formulations of chemical com-pounds that block the transmission of infection across thevaginal wall.Researchers are actively involved in develop-ing safe and effective vaginal microbicides. BOX 2.11 NONOXYNOL-9 The spermicide nonoxynol-9 (N-9) appeared to be very promis-in fact increase a womanÕs susceptibility to infection through itseffect on the vaginal wall.for more effective spermicides.but early laboratory tests suggested that it might be an effec-tive m

34 icrobicide. However, it is now clear tha
icrobicide. However, it is now clear that N-9 does notof infection in women who use it frequently. N-9 is a cytotox-harms the cells that line the vagina and cervix. Studies havewhen used alone, N-9 is only moderately effective in prevent-ing pregnancy.Nonetheless, N-9 spermicides do have some useful character-ing, they do show that similar but less toxic spermicides maybe an effective weapon against the spread of STIs. World Health Organization. 7. BIOINFORMATICS ¥Combat HIV/AIDS, malaria and other diseases As mentioned earlier,bioinformatics is a new tool thatgoes hand-in-hand with genomics,and therefore hasimportant applications to Combat HIV/AIDS,malaria Bioinformatics is the application of computer hardwareand software to store,retrieve and analyze large quantitiesof biological data.The so-called Òhigh throughputÓtech-nologies (DNA sequencers,DNA and RNA microarrays,combinatorial chemistry,2D gel electrophoresis and massspectrometry) have resulted in an explosion in the amountof biological data available.Bioinformatics organizes this seaof biological data into meaningful databases and conductsate answers to research questions.Its importance to the fieldof biotech

35 nology is reflected in its seventh ranki
nology is reflected in its seventh ranking amongthe most promising biotechnologies for improving healthin developing countries within the next five to ten years.Bioinformatics is an indispensable partner for genomics,and together these two technologies are poised to revolu-tionize the way we approach drug and vaccine discovery.Biological databases are central to bioinformatics,andseveral have been established as public resources available toall via the Internet (Box 2.12). BOX 2.12 BIOINFORMATICS DATABASES nizations. Fortunately, much of these resources, as well as theaccessed free of charge over the Internet.tained by the National Center for Biotechnology InformationMolecular Biology Laboratory (EMBL) on a daily basis.groups at the Swiss Institute of Bioinformatics (SIB) and theEuropean Bioinformatics Institute (EBI).information on biological function and the evolutionary historyon anopheline mosquitoes, in particular Anopheles gambiae one of the most important vectors of malaria. Bioinformatics applies computer algorithms to transformlarge-scale biological data into useful information.Forexample,an algorithm could be applied to quickly identifyspecific families of

36 genes in the recently-sequenced Anophele
genes in the recently-sequenced Anopheles gambiae .Without bioinformatics,thistask would be extremely laborious and error-prone,and itwould take scientists several years to realize the potential ofthis genome sequence.Many bioinformatics algorithms areshared worldwide and available free over the Internet alongwith basic tutorials.They can generally be found on thewebsites of public bioinformatics databases.Their accessi-bility to scientists helps to promote R&D.To help meet theworldwide demand for skilled bioinformaticians,a consor-tium of six universities is offering a free accredited web-based course in bioinformatics.One of the key applications of bioinformatics to diseasesis the accelerated discovery of drug targets.A drug target isa biological molecule,most commonly a protein,withwhich a drug interacts to alter its function.Most drug tar-GENOMICS FOR THE UN MILLENNIUM DEVELOPMENT GOALS 28 ated with multiple illnesses attributed to specific nutrientdeficiencies.These include blindness due to Vitamin A defi-ciency,which affects an estimated 500,000 children in devel-oping countries.Anemia is caused by iron deficiency andis one of the leading causes of maternal mort

37 ality.Pregnantwomen with anemia are more
ality.Pregnantwomen with anemia are more likely to give birth to lowbirth weight infants and are at increased risks of death dur-ing childbirth.Malnutrition,which affects approximatelyone in five people living in developing countries,amplifiesthe effects of infectious diseases.Lack of essential vitaminsand minerals impairs the immune system,thereby increasingthe likelihood that infection will develop into disease andimpairing the ability of the body to recover.Genetically modified crops are those whose compositionhas been altered by genetic recombination.This involves theinsertion of a gene Ð either with a gene gun or a carrier organ-ism such as a benign virus Ð into a plant very early on duringdevelopment such that all of the plantÕs cells acquire the gene.Various traits can be introduced into crops through geneticmodification.One application of genetic modification in cropsis to enhance the nutritional value of crops.This type of mod-ification might involve,for example,the insertion of genes thatencode for enzymes that synthesize vitamins.The Top 10study ranked nutritionally enriched GM crops eighthamong the most promising biotechnologies for improvinghealth in deve

38 loping countries in the next five to ten
loping countries in the next five to ten years.The potential advantages of nutritionally-enhanced cropsfor developing countries are difficult to deny.More thanthree million children under five suffer eye damage becauseof Vitamin A deficiency.About 500,000 go blind every year,of whom two-thirds die.Many are children of small farmersor farm workers too poor to afford a highly diversified diet.Some experts maintain that the one effective way of com-bating their Vitamin A deficiency is to increase the VitaminA content of their staple food.Accordingly,Ingo Potrykusand fellow researchers at the Swiss Federal Institute ofTechnology and the University of Freiburg in Germanydeveloped rice enriched in §-carotene,known as ÒGoldenRiceÓ.With grants from Rockefeller Foundation and Swissfunding sources,they worked on this project for eight years,inserting seven genes in all,and establishing for the first timethe feasibility of genetic modification involving multiplegenes.Golden Rice stands apart as a model example of theuse of gene technology to enhance the nutritional value ofa staple food crop.Golden Rice contains elevated levels ofpro-Vitamin A (§-carotene) and iron. BOX 2.13 GOL

39 DEN RICE: IMAGINATIVE USE OFINTELLECTUAL
DEN RICE: IMAGINATIVE USE OFINTELLECTUAL PROPERTY RIGHTS offer their invention free of charge to poor farmers. All 32 com-the world, and Syngenta agreed to allow subsistence farmersto use the rice without charge as long as they earn no moreRockefeller Foundation, WHO and the biotechnology industryworld. In February 2001, the first delivery of Golden Rice wasmade to the International Rice Research Institute (IRRI) in Losalternative ways to address these needs, and establish a frame-iron, it will enable affordable, sustainable, widespread nutrient GENOMICS FOR THE UN MILLENNIUM DEVELOPMENT GOALS 30 recombinant therapeutic proteins was ranked ninth amongthe most promising biotechnologies for improving healthin developing countries within the next five to ten years.This technology is therefore significant for the sixthMillennium Development Goal, Combat HIV/AIDS,malaria and other diseases .As poorer nations move throughthe process of development and associated demographicchange,they face a double burden of disease:infectious dis-eases as well as non-communicable diseases more com-monly associated with the developed world.In fact,non-communicable diseases (including injuri

40 es) now accountfor 60% of all deaths in
es) now accountfor 60% of all deaths in developing countries,and currenttrends suggest this number will reach over 70% by 2020.Affordable and sustainable sources of therapeutic proteinsfor treating these diseases are therefore critical.Since all organisms possess the molecular machinerynecessary to manufacture proteins,in principle they possessthe ability to make any protein.All they would require arethe genetic instructions to do so.Using recombinant tech-nology,researchers can insert a gene or genes for a thera-peutic protein into an organism.As the organism grows,itreads and translates the foreign gene as it does its owngenes,and produces the therapeutic protein,which can beharvested for medical use.Bacteria,particularly Escherichia coli ,were the first organ-isms to be drafted for the production of large quantities oftherapeutic proteins. E.coli is a natural resident of thehuman gut.Under the right conditions,the bacteria growand divide rapidly,producing a new generation every 20minutes.As they grow,they accumulate the recombinantprotein in their interior fluids.Protein purification process-es harvest the protein from the bacterial culture.Bacteria have one main

41 disadvantage as protein facto-ries:they
disadvantage as protein facto-ries:they are extremely simple organisms.Unlike the cellsof more complex organisms,bacterial cells lack the abili-ty to make specific chemical modifications to the proteinsafter the proteins have been translated from the DNAcode.Most human therapeutic proteins require thesetypes of modifications.As more complex organisms,yeastscan carry out many forms of protein modification,and,like bacteria,they reproduce quickly,easily and with sim-ple nutritional requirements.Because of its safety andfamiliarity, S.cerevisiae is the most popular yeast for mak-ing recombinant proteins.Mammalian cells are a more attractive source of recom-binant therapeutic proteins.They possess the ability toperform almost all the post-translational modificationsthat a protein might need in order to function properly.Unfortunately,mammalian cell cultures are more chal-lenging to maintain and have a lower protein yield thanbacteria or yeast.One way around these limitations is theuse of transgenic animals to synthesize recombinant pro-teins.A transgenic animal is a genetically modified animal.These animals are engineered to secrete the protein in aneasily-harvested body

42 fluid,such as milk,urine or semen.To lim
fluid,such as milk,urine or semen.To limit the secretion of the protein to a particular tissue,researchers link the gene of interest to another geneticelement that promotes the expression of the gene only inthe target tissue.It is estimated that the use of transgenicanimals to synthesize recombinant therapeutic proteinswould be four to five times cheaper than using mam-malian cell cultures.Plants,particularly corn,have also been explored for theirability to function as recombinant protein factories.Plantsoffer many advantages over the use of animals to producerecombinant proteins.Like yeast,plants have the ability toperform many of the steps required to refine complex pro-teins.They can also be grown in large quantities at low cost.Using plants also minimizes certain ethical concerns related toanimal experimentation and use,as well as risks associatedwith animal viruses and bacterial toxins.However,transgenicplant expression systems have a relatively low protein yield.Another disadvantage limiting the therapeutic value of theplant-derived product is the difference between plant andmammalian post-translational modifications.For instance,many human proteins are glycosyl

43 ated Ð i.e.after the proteins 33 CHAPTER
ated Ð i.e.after the proteins 33 CHAPTER TWO Ð GENOMICS AND THE MILLENNIUM DEVELOPMENT GOALS Although the drug has been found to be effective against malariaproduction of artemisinin currently relies on its extraction and purifi-cation from plant material, the yields of which are low. This hasÐ until recently. In a major breakthrough, a research group atUniversity of California, Berkeley has genetically engineered E. to produce yeast and plant enzymes that perform quick andefficient synthesis of artemisinin.artemisinin belongs to an extremely important family of plantimportant drugs, commercial flavorings and fragrances. ForIsoprenoids are currently expensive for the chemical industry to 10. COMBINATORIAL CHEMISTRY ¥Combat HIV/AIDS, malaria and other diseases Combinatorial chemistry has bearing on the health-relatedMillennium Development Goals,particularly CombatHIV/AIDS,malaria and other diseases .There are manydiseases prevalent in the developing world for which effec-tive and affordable treatments are lacking.Some pathogens,such as those that cause malaria and tuberculosis,areacquiring resistance to the only treatments available.Childmortalityis caused in large p

44 art by pneumonia,diarrhea andmalaria,thr
art by pneumonia,diarrhea andmalaria,three diseases that are acquiring drug resistance.Combinatorial chemistry can be used to provide new ormore effective medications for these diseases.It may alsopromote enterprise by helping industries in developingcountries become competitive and economically viable inthe global market.The increase in efficiency also potential-ly decreases costs,wastes less material and creates fewer by-products Ð all of which serve to protect the environment.Combinatorial methods are easily automated techniquesfor making many different kinds of chemical compounds.The resulting collection of compounds,known as a library,is biologically screened to select the compounds with themost therapeutic promise.Developed first in the early1980s,combinatorial chemistry has become a mainstay ofdrug discovery and development in industrialized nations.In many cases,it replaces the much more costly and time-consuming one-compound-at-a-time method.The scien-tific panel ranked combinatorial chemistry as the tenthmost promising biotechnology for improving health indeveloping countries within the next five to ten years.Two features make combinatorial chemistry excepti

45 on-ally efficient for drug discovery and
on-ally efficient for drug discovery and development:first,it isamenable to automation with robots doing most of thepreparation and screening of compounds.Second,it alsomakes it possible to prepare many unique compounds fromfewer experiments.For example,suppose a chemist wantedto improve upon a drug by varying its basic structure.If thisdrug had three chemical parts,with each part potentiallyvaried in three different ways,this would representFor instance,two new classes of drugs against leishma-niasis were discovered using a combinatorial process thatproduced over 150,000 different compounds.Leishmaniasis is a potentially fatal disease that is estimatedto affect 12 million people around the globe.Researchersalso used combinatorial chemistry to focus in on a morepotent version of vancomycin,an antibody of last resortagainst which many diseases are acquiring resistance.most successful compounds in the library outperformed 35 CHAPTER TWO Ð GENOMICS AND THE MILLENNIUM DEVELOPMENT GOALS 37 CHAPTER TWO Ð GENOMICS AND THE MILLENNIUM DEVELOPMENT GOALS GENOMICS FOR THE UN MILLENNIUM DEVELOPMENT GOALS 38 oped world to see the value of ensuring the distribution ofbenefits of new

46 technologies that can address developin
technologies that can address developingcountriesÕneeds and you have a recipe for inequity.Arguablythe fundamental reason why new technologies are notimplemented is inattention to governance and failure tounderstand the interplay between these complex issues. Global Governance to PromoteGlobal Public Goods Governance for genomics is a challenge not just because ofthe complexity of ethical,social and legal issues involved,butalso because of the rapid evolution of the science.Globalization increases this complexity.So do the significantglobal public goods characteristics of genomics knowl-edge.145, 146Goods can be defined along a spectrum from pureÔprivateÕto pure ÔpublicÕgoods.The benefits of public goodssuch as the ozone layer are enjoyed by all.They are non-excludable and non-rivalrous in consumption. Global publicgoods exhibit a significant degree of ÒpublicnessÓacrossnational boundaries.The ozone layer is an example -available to all across national boundaries,and not depletedthrough individual ÒuseÓ.Externalities caused by otheractivities can have an impact on both quality and quantity ofpublic goods (e.g.chlorofluorocarbons,or CFCs,thatdeplete ozone).Public good

47 s require some form of gover-nance to ma
s require some form of gover-nance to maintain them,typically one that transcends BOX 3.1 PUBLIC AND PRIVATE ASPECTS The recent worldwide SARS (severe acute respiratory syn-Internet. These scientists were able to download and analyzethe data directly, and apply it towards their epidemiologicalinvestigations in situ, highlighting the importance of sharing theinformation globally towards local solutions. (This unprecedent-gence of genomics and information technology in the interestof global public health). Going a step further into the realm ofprivate goods, the California-based biotechnology companyAffymetrix Inc. was able to use the public genome to create atrum and private goods emerging at the other. In this stepwisesector to create a specialized, value-added product. www.bcgsc.ca/bioinfo/SARS/ GENOMICS FOR THE UN MILLENNIUM DEVELOPMENT GOALS 40 The SARS virus belongs to the family of coronaviruses,which are namedfortheir striking corona (crown) of spikes Genomics is fundamentally about knowledge,which,according to Stiglitz,is the archetypal public good.Genomics knowledge (sequences and databases) is in thepublic domain.In fact,in a symbolic sense the humangenome ha

48 s been declared a common global heritage
s been declared a common global heritage ofhumanity.ketable product (such as,for instance,a diagnostic tool formalaria) has characteristics of a private good (see Box 3.1).We need a governance mechanism that fosters a balancebetween the global public goods characteristics ofgenomics knowledge and the private goods nature of itsapplication.The market is already a major driving force forhuman health,and most goods and services,and thereforemost research and development in health,are geared to theneeds of the developed world.If this continues,there is areal danger that the majority of the worldÕs 6 billion people- who do not present profitable market opportunities - willnot see the benefits of genomics.We need new mechanismsto address such market failures,perhaps some form of stew-ardship to maintain the GPG characteristics of genomics.The GPG characteristics of genomics knowledgeinevitably raise issues about access to this emergingresource.This gives us new opportunities to solve globalhealth problems,but it also tests our skills in the evolutionand management of international relations,foreign policy,financing,regulation and intellectual property rights.Agovernance mec

49 hanism that can successfully harness the
hanism that can successfully harness theseGPG characteristics could be highly effective in promotingOther global public goods that have had challenging gov-ernance issues and might have relevance to the governanceof genomics are biodiversity and the ozone layer (Table 3.1).Depletion of the ozone layer was the major impetus for theMontreal Protocol.The Convention for Biodiversity (CBD)prioritized taking action to deal with biodiversity loss andthe potential global public benefits of maintaining biodiver-sity at various levels.Genomics has similar needs - theoption value (enormous potential benefits to global health),as well as the potential misuse of genomics knowledge.Aquick look at these GPGs (in Table 3.1) shows certain sim- 41 CHAPTER THREE Ð GENOMICS AND GLOBAL GOVERNANCE TABLE 3.1 GPGS AND THEIR GOVERNANCE GPGDRIVING FORCE FOR GOVERNANCEPRIORITYGOVERNANCE STRUCTURESOzone LayerThinning of the layer ÐReduction of Global conventioneffect on human healthChorofluorocarbons(Montreal Protocol) BiodiversityLoss of diversitySpecies and PPPs Potential useecosystemGlobal convention (CBD) conservationNational targetsGenomicsPotential useImproving PPPsRisk of misuseGlobal Hea

50 lth Global networks have the advantage o
lth Global networks have the advantage of speed - they can belaunched quickly,and are responsive to rapidly-evolvingThey are inclusive and non-restrictive in member-ship (unlike more conventional mechanisms that can takeon a Òclub-likeÓcharacter).Because of their diverse mem-bership,they can put constructive pressure on governinginstitutions.They encourage participation from developingcountries,and also allow for initiation and leadership fromthe South.Developing countries with strong biotechnolo-gy sectors can take the lead in driving the agenda forhealth equity.In short,networks encourage speed,equi-table participation and flexibility while minimizingbureaucracy and hierarchy. The Global Genomics Initiative as a ProposedGlobal Network to Promote Genomics for We at the University of Toronto Joint Centre for Bioethicspropose the Global Genomics Initiative (GGI) as a globalnetwork to promote genomics for health.The GGI willfoster international dialogue for access to and sharing ofgenomics knowledge;prioritizing health needs in partici-pating countries;and providing the network to help mem-bers optimize funding and facilities.It can help countriesundertake and achieve s

51 pecific tasks to implementgenomics for h
pecific tasks to implementgenomics for health in developing countries.It could coor-dinate the assortment of existing alliances,partnerships,agreements into a global governance network,and helpbridge the gap between bilateral partnerships,PPPs,andalliances at one level and the higher-level governance struc-tures and international organizations like the UnitedNations and the World Health Organization.What sets the GGI apart from a risk-focused vision ofbiotechnology governance is our recognition of,and focuson,the GPG nature of genomics knowledge and its enor-mous potential for improving health.The use and applica-tion of this knowledge towards health and developmentshould be an incentive to people worldwide.A major roleof the GGI must be to safeguard genomics knowledge,make it openly accessible and promote its application fordeveloping countries,while minimizing risk of misuse. What will the GGI do? The GGI is foreseen to be a global network of concernedcitizens,industry leaders,academics,representatives fromNGOs,and government officials,with particular emphasison developing world representation.We are now in theprocess of bringing together some of the best creativemi

52 nds from these fields to begin the dialo
nds from these fields to begin the dialogue and to learnfrom their experiences so that any decision-making willcome from the bottom up - shaped through consultations.Existing public-private partnerships,alliances,networks andcoalitions in the arena of genomics and health (such asNEPAD,BIOPAD,the Malaysia-MIT biotechnology part-nership) could feed into this network.There is considerableadvantage for these partnerships in forging links within aglobal network - access to knowledge,expansion of part-nerships and creation of new scientific capacity throughshared resources are obvious benefits.This group will move forward quickly to set the agendaand define concrete goals for the GGI,both long-term andshort-term (Box 3.2): BOX 3.2 GOALS AND OBJECTIVES OF THE GGI Overall Mission of GGI: To promote and facilitate broad-based, informed and ethical decision-making about the use ofgenomic technologies to contribute to global health equity.¥Promote genomics as a GPG - In this crucial move, the GGImust try to ensure rapid and reliable global access to theworldÕs expanding resources in genomics knowledge¥Encourage equitable participation - The GGI represents a 43 CHAPTER THREE Ð GE

53 NOMICS AND GLOBAL GOVERNANCE We have des
NOMICS AND GLOBAL GOVERNANCE We have described the Global Genomics Initiative as aence and technology to help achieve the MDGs.As out-lined in box 3.2,the GGI has several objectives,amongthem improving global genomics policy,encouraging theidea of investment in human capacity and R&D,promotingentrepreneurial activities in the area of biotechnology andgenomics and playing an active role in forecasting activities.Science and technology can contribute to economic devel-opment in developing countries.Developing countries canestablish and strengthen scientific institutions throughimproving the science policy environment.One way toimprove science policy is through exchange of informationwith other countries,especially those with success stories toshare.A global science and technology network,based onthe model provided by the Global Genomics Initiative,mayhelp countries use multi-sectoral dialogue to develop for-ward-thinking global science policy for development. The Role of the United Nations in the GlobalGenomics Initiative The Global Genomics Initiative aligns well with KofiAnnanÕs announcement of the UNÕs intention to convenea global policy network on biotechnology.anno

54 uncement confirms the prominence of biot
uncement confirms the prominence of biotechnolo-gy as a global force of change.It underscores both theurgency for a global network for biotechnology as well asshows evidence of the UNÕs initiative and leadership inbiotechnology.Others have noted that by facilitating theemergence of global policy networks,the UN can helpstrengthen the capacity of state and non-state actors todevelop global public policy,while increasing its owneffectiveness and credibility.We now extend these argu-ments to apply to the Global Genomics Initiative,and callattention to the UNÕs potential role in helping the GGIachieve its goals Ð and thereby helping to achieve theMillennium Development Goals.Just as the World HealthOrganization can promote the production of health as aglobal public good,we envision the UNsystemas pro-moting genomics as a global public good.TheGGIcanassist byplaying the role of facilitatoramong multi-sectoralpartners,including international agencies through provid-ing a platform for reliable and freely accessible informa-tionfor genomics knowledge. Summary An interdependent world in which the greatest majoritythe minority continues to improve is a recipe for socialconfront

55 ation.The UN Millennium Development Goal
ation.The UN Millennium Development Goalsaim to decrease these development gaps,and achievingthem is well within human capacities.The GlobalGenomics Initiative could be instrumental in developingcommon understandings among governments and their cit-izens,corporations,and non-governmental organizations,setting a strategic direction and mobilizing commitment toa healthier,more equitable world.The GGI can help torealize the benefits of genomics and biotechnology for theUN Millennium Development Goals. 45 CHAPTER THREE Ð GENOMICS AND GLOBAL GOVERNANCE enomics holds clear benefits for developing coun-tries,and chapter 2 of this report indicated theways in which genomics and related biotechnolo-gies can serve the Millennium Development Goals.Thechallenge is how to implement these technologies in devel-oping countries within the next five or ten years.The abil-ity of a country to solve development problems and sustaineconomic growth depends to some extent on its institu-tional structures and capabilities in science and technology.In this final chapter of this report,we assert that developingcountries with the scientific capacity and institutionalarrangements that allow creat

56 ion,utilization,adaptation ordiffusion o
ion,utilization,adaptation ordiffusion of this new field of science and technology arewell-positioned to harness genomics for development.Wesupport our argument with examples of strategies thatsome countries have followed to institute learning process-es that can help them build their national systems of inno-vation in biotechnology,and conclude with lessons learnedand recommendations. Transfer of Technology and Science Ð BuildingScience Capacity in Developing Countries After the Second World War,technologies were transferredfrom the United States to reconstruct war-torn WesternEurope.EuropeÕs success led naturally to the mistakeneconomic development in developing countries.156, 157was believed that technology transfer would kick-start theengine of growth,the benefits would trickle downthroughout the economy and result in further develop-ment of technological capacity.It was considered unneces-sary,even extravagant,for poorer income countries to dofundamental research since they were primarily seen astechnology users and dependent on imports from technol-ogy producers.Today the growing view is that mere technology trans-fer does not always guarantee solutions to prob

57 lems indeveloping countries,especially i
lems indeveloping countries,especially if they are not of relevanceto industrially advanced countries.For example,diseaseprofiles and health needs vary the world over,and the phar-maceutical companies in the industrialized world typicallytarget health problems in higher-income countries.Themarket-driven strategies of the pharmaceutical industry arenot sufficient to steer technological innovation to solvedevelopment problems.Research on treatments for diseasesof the poor,which generally have higher incidence andprevalence rates in lower-income countries,remainsThe imbalance in global R&D efforts strength-ens the case for developing countries to invest in indige-nous scientific capacity to help meet their own health anddevelopment needs.Contrary to expectations,technology transfer initiativesin developing countries have met with limited success.Indeed,research has shown that the benefits of technologytransfer are best harnessed by those countries that have builtthe capacity to absorb,use and even adapt technology.159, 160Countries need to build capacity in high quality basicresearch in order to benefit economically from science andtechnology.This includes trained human

58 capital,as well asinvestment in institut
capital,as well asinvestment in institutions,equipment,and networks.Countries like Brazil,China and Cuba have invested in sci-ence and technology for decades and have consequentlycreated a strong science base.These scientifically proficientcountries have to some extent been able to absorb and keepup with the advances that the genomics revolution bringsby building upon their strong scientific foundations.Someof these countries are even beginning to enjoy private sec-tor successes in this new field.It follows,therefore,that genomics and biotechnologywill probably make the most sustainable and effective con-tributions to development in those developing countriesthat possess capacity in these fields.Developing countriescan best benefit from these technologies if they are activeparticipants not just in the use of technology but indeed inall stages of innovation including research,development,and production.For example,several international public- 47 CHAPTER FOUR Ð BUILDING GENOMICS CAPACITY IN DEVELOPING COUNTRIES BUILDING GENOMICS CAPACITY Ñ CHAPTER FOUR Ñ Learning is Key to Building Capacity inScience and Technology: National InnovationSystems in Developing Countries On

59 e way to think about building scientific
e way to think about building scientific capacity is as aprocess of learning and innovation Ð a sustainable approachto enable developing countries to capture the benefits ofgenomics for the MDGs.Creating synergistic inter-linkagesbetween the learning processes that occur within all eco-nomic activities including R&D,marketing,production,and development is essential to spur innovation.This net-work of interactions is the foundation of a national systemof innovation.The national system of innovation (NSI) represents theinstitutions that contribute to the creation,diffusion,anduse of new economically useful knowledge in a specificcountry and the linkages and synergies between the insti-These institutions include not only formal oneslike firms,universities,research centers and government,but also institutions in a wider sense,such as social normsand laws (for example intellectual property rights).Knowledge creation,diffusion and use are at the core ofinnovation systems frameworks.This involves non-linear,multidirectional flows between the various actors.There arevarious ways in which the elements of the NSI can inter-act for knowledge creation,diffusion and use.For exampl

60 e,they can involve technical,commercial,
e,they can involve technical,commercial,legal,developmen-tal,social,financial,or regulatory interactions.Although the NSI concept has been studied for over adecade,its application to developing countries is relativelyrecent.Some researchers have concerns about the applica-bility of the NSI framework in developing countries.aspect that Arocena and Sutz emphasize is that innovationin developing countries is often within micro-realmsinstead of being systemic.They warn against importingÒturn-keyÓinstitutions and policies from industriallyadvanced countries to developing countries based on tacitassumptions,which may not be true in these countries.Intheir study on innovation systems in Thailand,Intrakamnerd et al.stress the need to examine factors thathinder technological learning.The perception is thatinnovation systems in developing countries are weak andfragmented.Lundvall and colleaguesalso agree with thisnotion that NSI studies in developing countries should beadjusted to accomodate different learning environments.They argue that in the context of developing countries it isimportant to shift the emphasis of NSI studies to systemconstruction and promotion.They also poin

61 t out that thereis a need to apply a bro
t out that thereis a need to apply a broader concept of innovation when itis used in the context of developing countries.For instance,developing countries may more often (relative to higherincome countries) be able to leverage the richness of theirlocal and traditional knowledge.Therefore,the innovativelearning that takes place in many developing countries isnot always in the realm of science-intensive endeavors or inhigh-tech activities.Other analysts have observed that,when applied to developing countries,innovation can beperceived as the process that companies use in their learn-ing of design and production that is new to them.Imitations and incremental improvements in productdesign and production processes may form a significant partof local innovation in developing countries.Developing countries that are now overcoming barriersand are fostering learning processes in their institutionsand building scientific capacity are of particular relevanceto the question of how a country can build its NSI.TheCanadian Program on Genomics and Global Health is inthe process of conducting a study of the health biotech-nology innovation systems of Brazil,China,Cuba,Egypt,India,Sou

62 th Africa and South Korea,all of which h
th Africa and South Korea,all of which have rel-atively active biotechnology industries.identifying the main actors in the health biotechnologyinnovation systems under study,i.e.by examining the rolesof government,private firms,R&D system,the educationsystem etc in the health biotechnology innovation process.The study has also explored the extent and patterns oflinkages between all the actors in the NSI systems.Where 49 CHAPTER FOUR Ð BUILDING GENOMICS CAPACITY IN DEVELOPING COUNTRIES Learning Systems The health biotechnology innovation country case studiesdiscussed in the previous section should yield useful infor-mation that could help identify factors and policies thatfoster biotechnology innovation in the developing world.They may also provide insights into potential barriers todevelopment.Other developing countries could apply theexperiences of these countries,within limits,to helpdevelop their own innovations systems and reap the ben-efits of biotechnology.While there is no Òone-size-fits-allÓmodel,there are lessons to be learned from these coun-tries that have already had some successes in creatingstrong and vibrant biotechnology sectors.And evenwhere the NSI f

63 ramework is not clearly spelled out,deve
ramework is not clearly spelled out,developing countries can work on particular elements ofthe framework in their effort to build capacity in biotech-nology.For instance,they could focus on building humanresources by training scientists in genomics and bioinfor-matics.Alternatively,they could explore ways of adaptingexisting biotechnologies to low-resource settings.The fol-lowing examples illustrate how developing countries cantake advantage of existing programs with organizationsthat carry out these functions. Building a Science Base by Re-energizingAcademic Institutions Strengthening academic institutions and improving theircapabilities in the new life sciences is an essential compo-nent of the National System of Innovation,as is the cre-ation of a pool of trained scientists.Governments of devel-oping countries will have to invest in higher education,with a focus on the sciences,in order to create the humancapital and knowledge base to enable research and develop-ment.Given the paucity of financial resources,most devel-oping countries agree that this investment has to be carefuland measured.One way forward for these countries in theshort term may be to invest in spe

64 cialized departments orresearch centers,
cialized departments orresearch centers,perhaps within existing universities,thatfocus on particular research areas and have clearly definedresearch goals Ð such as the development of technology forbioremediation.In Thailand,the National Centre forGenetic Engineering and Biotechnology (BIOTEC) wasinstrumental in setting up the new Microbial GeneticEngineering Unit at Mahidol University,which focuses onthe study of microorganisms and also shares and dissemi-nates genetic engineering techniques through training andeducation.One of the projects the Unit is currently con-ducting is the development of a strain of A.quadruplicatum bacteria genetically engineered to be capable of controllingand eliminating disease-carrying mosquito larvae in conta-minated water.BIOTEC allocates approximately 70% of itsR&D budget to universities and research institutes,oneaspect of which is creating biotechnology-focused depart-ments at universities in Thailand;the remaining 30% is usedfor in-house research projects.Its overall mandate is to pro-vide the resources for the country to develop the criticalmass of researchers necessary to achieve ThailandÕs nationalR&D targets in biotechnology.A

65 nother way forward is to take advantage
nother way forward is to take advantage of trainingopportunities in partnership with academic institutions inthe industrialized world.Such programs are offered bymany organizations.One such organization is the FogartyInternational Center (FIC) of the National Institutes ofHealth (NIH).In October 2002,FIC and seven partnersannounced six new research and training grants to supportinternational collaborations in human genetic sciences foran International Collaborative Genetics Research TrainingProgram.FICÕs partners included the World HealthOrganization,the National Human Genome ResearchInstitute (NHGRI),the National Institute of MentalHealth (NIMH),the National Institute of NeurologicalDisorders and Stroke (NINDS),the National Institute onAging (NIA),the National Institute on Drug Abuse(NIDA),and the National Institute of Environmental 51 CHAPTER FOUR Ð BUILDING GENOMICS CAPACITY IN DEVELOPING COUNTRIES Bioinformatics can allow developing countries to participatein quality research with relatively few resources.The UNScience and Technology Task Force has identified bioinfor-matics as one field of biotechnology that would encouragelocal research.There are several trainin

66 g opportunities in thisfield for develop
g opportunities in thisfield for developing country scientists (Box 4.4). BIOINFORMATICS Ð A SPECIAL FOCUS ways using genomics and bioinformatics. Most bioinformaticsfreely available on the Internet. The Special Program forResearch and Training in Tropical Diseases (TDR) provides train-ing opportunities for scientists. It is an independent global pro-sponsored by the United Nations Development Program(UNDP), the World Bank, and the World Health Organization(WHO). In 1994, TDR helped establish five international par-asite genome networks to provide the opportunity for scientistsfrom disease endemic countries to participate and collaborateinitiative on developing capacity in bioinformatics wascenters for ÒBioinformatics and Applied GenomicsÓ located inthat capacity in bioinformatics is required for both basic- Train 20-30 disease-endemic country (DEC) scientists (Ôtrain-ersÕ) in bioinformatics in order for them to conduct local bioin-formatics training in Africa, Asia and Latin America in the next- Establish sustainable regional networks of centres and expertisefor the promotion and integration of bioinformatics and DNA- Establish a distance-learning program for bioinfo

67 rmatics inAs a first step Ð Òtraining th
rmatics inAs a first step Ð Òtraining the trainersÓ Ð the InternationalTraining Course on Bioinformatics and Computational Biologyobjective was to develop a multi-disciplinary and internationalnetwork for bioinformatics applied to pathogen genomeresearch and to prepare participants to teach similar coursesBioinformatics Career Development Grant for exceptional sci-entists identified from these courses. In the longer term,vide regional training courses in bioinformatics. Despite thefact that TDRÕs bioinformatics initiative is quite young, consid-helping them to reach self-reliance in this field of modern bio-A similar effort has been initiated at the South African NationalBioinformatics Institute (SANBI) at the University of the WesternCape, South Africa: the Bioinformatics Capacity Developmenttunities in bioinformatics for smaller, less developed countriessince bioinformatics does not require prohibitively costly infra-located in and focused on Africa and African concerns. Its goalsgenomics and genome informatics; capacity development ingenomics and bioinformatics in South Africa; and the develop- 53 CHAPTER FOUR Ð BUILDING GENOMICS CAPACITY IN DEVELOPING COUNTRIES Ec

68 uador and Sri Lanka in partnership with
uador and Sri Lanka in partnership with local scientists. The firstthe ImmunoSensor platform. SSI and UC Berkeley are planning www.ssilink.org Improving the Policy Environment andEncouraging Regional Cooperation Governments can promote innovative learning throughvisionary technology or economic policies.Alvaro D’az,ChileÕs deputy economy minister,has recently unveiled apolicy ÒBiotechnology as a tool for development and well-beingÓthat aims to boost biotech research and to help com-panies use biotechnology to strengthen the countryÕs econ-omy.The policy has four main objectives:updating lawsthat concern biotechnological activities;creating an overar-ching regulatory body;developing scientific and techno-logical capacity;and promoting entrepreneurial innovationin biotechnology.Although many have welcomed this pol-icy as a step in the right direction,others fear that it doesnot sufficiently reflect the concerns of small and medium-size biotechnology companies and consequently may notfoster innovation on a large scale.A somewhat more focused policy in Cuba provided polit-ical support for biotechnology over the last few decades thatallowed for government investment in dev

69 eloping modernlaboratories and incubatio
eloping modernlaboratories and incubation centers.These research centersworked primarily on health biotechnology.This investmenthas paid off,with the discovery and patenting of meningitis-B vaccine in the late 1980s.The vaccine has now beenlicensed to GlaxoSmithKline,which will market it in Europeand the USA.Scientists in Cuba tend to play an active rolein national policy-making,and this in turn strengthens sci-entific research institutions.For example,the directors of theCentro de Ingenier’a GenŽtica y Biotecnolog’a (CIGB),andof the Carlos Finlay Institute,are members of the StateCouncil.The fact that they play an influential role in deci-sion-making underscores the importance of informed poli-cy-making in fostering innovation.Creating the appropriate policy environment for learningand innovation requires multi-disciplinary dialogue.In part-nership with other institutions,the University of TorontoÕsJoint Centre for Bioethics is in the process of conducting aseries of Genomics Policy Executive Courses in developingcountries,with funding from Genome Canada and theInternational Development Research Centre (IDRC).Thepurpose of these courses is to help draw necessary atte

70 ntionto genomics policy in these countri
ntionto genomics policy in these countries in order to better pre-pare them to assimilate and apply genomics technologies totheir needs.The main objectives are:¥To familiarize participants with the current status andimplications of genomics and biotechnology for healthin their country,and to provide information relevant topublic policy¥To provide frameworks for analyzing and debating thepolicy issues and related ethical questions,and to helpunderstand,anticipate and possibly influence the legaland regulatory frameworks which will operate,bothnationally and internationally¥To begin developing an opinion leadersÕnetwork acrossdifferent sectors (industry,academic,government,andvoluntary organizations) by sharing perspectives andbuilding relationshipsA wide range of topics is covered,starting with recentscientific advances in genomics,followed by discussions onbusiness models in genomics and biotechnology,intellectu- 55 CHAPTER FOUR Ð BUILDING GENOMICS CAPACITY IN DEVELOPING COUNTRIES should be particular emphasis on information and communica-tion technologies (ICT) and bioinformatics.The National Biotechnology Body, in collaboration with the rel-health of the poor.well b

71 eing of people in the EMRO Region. Works
eing of people in the EMRO Region. Workshop partici-pants, as well as other concerned individuals, are encouraged to A common sentiment among the participants in all thecourses held so far was that a key requirement for buildingscientific capacity is access to scientific knowledge.It isimportant to achieve a balance between the requirementsof the scientific and technological research community foropen access to the most current scientific information andacknowledging and maintaining a healthy intellectual prop-erty rights regime that provides incentives to various stake-holders.Understanding,interpreting and effectivelyleveraging international agreements on intellectual proper-ty rights and trade is an essential component of the learn-ing process to build scientific capacity.Furthermore,foreigninvestment rises when countries can ensure intellectualproperty protection.In the last decade,a number of devel-oping countries have expressed discontent with interna-tional intellectual property rights and their perceived biastowards the industrialized world.But interestingly manyobservers feel that developing countries are moving towardsa paradigm in which they are not only ad

72 opting,but alsoadapting,intellectual pro
opting,but alsoadapting,intellectual property laws to serve their ownneeds.The recent failure of the Cancun talks,in mid-2003,points in fact to success when viewed from an alternativeperspective Ð the recognition by Brazil,China and Indiathat developing countries can use international trade lawsto their advantage to strengthen their negotiating positions.Almost all Ministers from the developing countries havereaffirmed their faith and confidence in the multilateraltrading system and appear to support the sentiment reflect-ed in the statement made by Celso Amorim,ForeignMinister of Brazil:Òthe WTO is irreplaceable not only forBrazil,or for members of G-20,but also for all developingcountries.ÓMany developing countries and international organiza-tions agree that training in patent law and intellectual prop-erty protection is urgently needed.In 2002,the RockefellerFoundation launched the Centre for the Management ofIntellectual Property in Health Research and Development(MIHR).The aim of MIHR is to help build technologymanagement capacity in developing countries,and espe-cially to conduct research and share best practices in themanagement of intellectual property to prom

73 ote globalhealth.This international orga
ote globalhealth.This international organization is based in Oxford,United Kingdom,but has linkages and activities all over theworld.MIHR has developed a handbook of best practices,conducted workshops in South Africa,Egypt and India,andis now exploring partnerships with the Indian Council forMedical Research,South AfricaÕs Medical ResearchCouncil and other technical agencies in developing coun-tries.One of MIHRÕs primary goals is to raise the statureand build capacity of technology managers and technologymanagement offices in publicly funded health researchinstitutions in developing countries Ð so they can enter intosound,viable ÒindigenousÓpublic-private partnerships thatare accountable to the public interest.183, 184lenge that still remains,and that is relevant to many devel- 57 CHAPTER FOUR Ð BUILDING GENOMICS CAPACITY IN DEVELOPING COUNTRIES Biopad (Biotechnology Partnership for Development),itselfcharged with stimulating economic development,con-tributing to job creation,and building world-class skills andtechnology platforms to sustain and continue development.Creating incentives for private enterprise is not likely tobe sufficient for private sector growth with

74 out simultane-ous growth in human capita
out simultane-ous growth in human capital.China,for instance,has beentrying to attract back its scientists trained overseas throughvarious incentives (some of these somewhat controversial Ðsuch as limiting the time spent abroad during post-doctor-al training).Critical factors to consider for the growth ofprivate firms in developing countries include the relativelysmall academic base,the lack of human capital and financialresources,the absence of a market-oriented research cul-ture,few large national (or even international Ð althoughthis is changing gradually) biotechnology companies,andinexperience by academic institutions in mechanisms totransfer research findings to companies.Finally,the linkage between basic/applied research activ-ities and commercial enterprise continues to be criticallyweak in most developing countries.Strengthening this linkcould help to provide fresh stimulus to academic researchand re-energize universities and could also be instrumentalin the translation of basic research into important commer-cial products for local use Ð such as molecular diagnostictools.This link between academia and private sector issomething many countries,even in the ind

75 ustrializedworld,have struggled with Ð c
ustrializedworld,have struggled with Ð countries like France andGermany,for instance,have had limited success in thissphere.Perhaps the country that has most effectivelystrengthened the interaction between academia and indus-try is the United States.In 1980,the Bayh-Dole act creat-ed incentives for U.S.universities to translate academicresearch discoveries into innovative commercial products.Itgranted them ownership of patents arising from federallyfunded research,as a consequence of which universitieshave licensed many thousands of patents to the private sec-tor.Although some analysts are skeptical about the impactothers feel this legislation has been instrumen-tal in energizing universities and strengthening the linkbetween academia and the private sector.Over the lastfew decades there has been a gradual but perceptiblechange in the role of U.S.universities as Òivory towersÓofresearch to active participants in economic growth. Conclusion The processes and initiatives described in this chapterdemonstrate some ways in which countries are developingcapacity in genomics and biotechnology.There is evidencethat mechanisms that foster learning and national systems ofinnova

76 tion can create the scientific capacity
tion can create the scientific capacity countries needto absorb and use biotechnologies to address their heathand development needs.This report on the contribution of genomics to theMDGs follows those of the UN Science and TechnologyTask Force,the Inter-Academy Council on Science andTechnology Capacity and the UN Commission on PrivateSector and Development to outline strategies that develop-ing countries can adopt to develop their science base forhealth and economic development.It brings greater focusto elements of this strategy,using the example of genomicsand related biotechnologies and their potential influenceon efforts to achieve the Millennium Development Goals.It describes the need for a global international partnershipthat can shepherd the process of knowledge-sharing to fos-ter capacity-building in the developing world.It specifiesthe ways in which genomics can help to address the health-related MDGs,and stresses the need for developing coun-tries to build capacity in genomics in order fully to harnessthe potential of this exciting and promising field of life sci-ences.The report echoes the findings of the reports of theUN Science and Technology Task Force,th

77 e Inter-Academy Council and the UN Commi
e Inter-Academy Council and the UN Commission on PrivateSector and Development.We present in Box 4.7 the main conclusions from thisreport. 59 CHAPTER FOUR Ð BUILDING GENOMICS CAPACITY IN DEVELOPING COUNTRIES A, T, G, C The four bases of DNA,Adenine,Thymine,Guanine andCytosine.These are organic molecules made up of carbon,nitrogen,oxygen and hydrogen and they form the ÔrungsÕofthe DNA ladder.Typically,A pairs with T,and G pairs with C. Amino acid One of a class of 20 molecules that form the ÔbuildingblocksÕof proteins in all living organisms.The sequence ofamino acids in a protein and hence protein function aredetermined by the sequence of bases in the corresponding Amplification An increase in the number of copies of a specific DNAfragment;amplification can be in vivo (in an organism,suchas bacteria or yeast) or in vitro. See also:cloning,polymerase chain reaction Annotation Addition of pertinent information such as the gene codedfor,or the corresponding amino acid sequence or other rel-evant commentary to raw DNA sequences in databases. See also:bioinformatics Antibody A protein that is produced by the immune system inresponse to,and counteracts,an antigen. Antigen A

78 molecule that triggers an immune respon
molecule that triggers an immune response in the body.It induces the formation of antibodies because it is recog-nized by the immune system as a threat.It may be a foreign(non-native) substance from the environment (such aschemicals) or formed within the body (such as bacterial orviral toxins). Base One of the molecules that form DNA and RNA,alongwith a sugar (either deoxyribose or ribose) and phosphategroups.In DNA,these are adenine,thymine,guanine andcytosine,while in RNA thymine is replaced with uracil. See also:A,T,G,C,base pair,base sequence,nucleotide Base pair Two nitrogenous bases (in DNA,adenine-thymine andguanine-cytosine) held together by weak bonds.The twostrands of DNA double helix are held together by thebonds between base pairs (bp). Bioinformatics The science of managing,storing,and analyzing large-scalebiological data,such as genomic sequences,using advanced Bioremediation The use of biological organisms such as plants or microbesto aid in removing hazardous substances from the environ- Biotechnology Technology that uses biological organisms and processes inthe industrial production of goods and services. Cancer Diseases in which abnormal cells divid

79 e and growunchecked.Cancer can spread fr
e and growunchecked.Cancer can spread from its original site to otherparts of the body and can be fatal. See also:hereditary cancer,sporadic cancer Cell The basic unit of any living organism that performs bio-chemical processes of life. See also:genome,nucleus 61 GLOSSARY GLOSSARY Double helix The Ôspiral ladderÕstructure that two linear strands of DNAassume when complementary nucleotides on opposingstrands bond together. Drug target A biological molecule that interacts with an exogenousmolecule (the drug) in such a way that its activity is altered,and consequently,changing an outcome.For example,sev-called cyclooxygenase-2 (COX-2) which triggers therelease of prostaglandins that cause inflammation. ELISA (enzyme-linked immunoabsorbant assay) Enzyme-linked Immunosorbent Assays (ELISAs) combinethe specificity of monoclonal antibodies with the sensitivi-ty of simple enzyme assays,by using antibodies or antigenscoupled to an easily-assayed enzyme (an enzyme whoseactivity can be easily measured).ELISAs can provide a use-ful measurement of antigen or antibody concentration. Embryonic stem (ES) cells An embryonic cell that can replicate indefinitely,transforminto other type

80 s of cells,and serve as a continuous sou
s of cells,and serve as a continuous source ofnew cells. Enzyme A protein that acts as a catalyst,speeding the rate at whicha biochemical reaction proceeds but not altering the direc-tion or nature of the reaction. Escherichia coli Common bacterium that has been studied intensively bygeneticists because of its small genome size,normal lack ofpathogenicity,and ease of growth in the laboratory. Gel electrophoresis Gel electrophoresis is a method that separates biologicalmacromolecules - either nucleic acids or proteins - on thebasis of their size,electric charge,and other physical prop-erties.An electric current is applied across the gel mediumand the molecules travel at different speeds through themedium towards the oppositely charged pole.For instance,DNA is negatively charged,and large pieces of DNA moveless rapidly through a gel than small pieces.Two-dimen-sional (2D) gel electrophoresis separates proteins in onedirection based on their charge (isoelectric point) and in Gene The fundamental physical and functional unit of heredity.Agene is an ordered sequence of nucleotides located in a par-ticular position on a particular chromosome that encodes aspecific functiona

81 l product (i.e.,a protein or RNA molecul
l product (i.e.,a protein or RNA molecule). Gene-gun A device used for insertion of foreign DNA into plant cellsby propulsion.In the original gene-guns (invented by JohnSanford,Cornell University) the foreign gene is coated ona pellet that is shot into a cell.The gene inserts itself ran-domly into the genome of the cell.Newer models are moreefficient at gene incorporation. Gene mapping Determination of the relative positions of genes on achromosome and of the distance between them. Gene product The biochemical material,either RNA or protein,resultingfrom expression of a gene. Gene therapy An experimental procedure to replace,manipulate,or sup-healthy genes in living tissue.Typically,a carrier moleculecalled a vector must be used to deliver the therapeutic gene 63 GLOSSARY their mass and charge.One application has been in pro-teomics to determine the amino acid sequence of proteins. Megabase nucleotides. Messenger RNA (mRNA) RNA that is encoded from DNA and serves as a templatefor protein synthesis. Microarray Set of miniaturized chemical reaction areas (wells) that mayalso be used to test DNA fragments,antibodies,or proteins. Microbicide A substance that can reduce or

82 prevent infection.Vaginalmicrobicides c
prevent infection.Vaginalmicrobicides can prevent sexually-transmitted infection andmay or may not act as a contraceptive. Microinjection tiny needle. Mitochondria Organelles in cells that convert food into energy. Model organisms A laboratory animal or other organism useful for research. Molecular biology The study of the structure,function,and makeup of bio-logically important molecules. Molecular pharming The development of transgenic plants or animals to pro-duce human proteins for medical use. Molecular genetics The study of molecules important in biological inheritance. Molecular medicine The treatment of injury or disease at the molecular level.medicine derived from DNA sequence information. Monoclonal antibodies Antibodies of exceptional purity and specificity that areable to recognize and bind to a specific antigen.They arederived from the progeny of a single immune cell. Multiplexing A laboratory approach that performs multiple sets of reac-tions simultaneously;this increases speed and throughput. Mutagen An agent that causes a permanent genetic change in a cell.Does not include changes occurring during normal genet-ic recombination. Mutation Any change in

83 normal DNA sequence. Nitrogenous base A
normal DNA sequence. Nitrogenous base A nitrogen-containing molecule with the chemical proper-ties of a base (such as ammonia).DNA contains thenitrogenous bases adenine (A),guanine (G),cytosine (C),and thymine (T). Non-communicable diseases Generally refers to chronic diseases that cannot be transmittedhorizontally from person to person,as opposed to communi-cable or infectious diseases such as malaria or tuberculosis.Theymay or may not have a hereditary component (and thereforecould be transmitted vertically from one generation to thenext).Examples include cancer,diabetes and heart disease. 65 GLOSSARY Proteome All the proteins expressed by a cell or a tissue at a particu-lar time and under specific conditions.Unlike the genome,which is constant and identical in all the body cells,theproteome changes constantly depending on the require-ments of the organism at a given time. Proteomics The study of the proteome. Recombinant DNA molecules A combination of DNA molecules of different originjoined using recombinant DNA technologies (see below) . Recombinant DNA technology Any procedure for combining DNA from two or more dif-ferent sources.It makes use of restriction enzy

84 mes to cutand introduce foreign DNA into
mes to cutand introduce foreign DNA into a plasmid or other vector.Under appropriate conditions,a recombinant DNA mole-cule can enter a cell and replicate there (using,for instance,a gene gun).The function of the isolated foreign DNA canbe studied using this technique,or the expressed proteincan be harvested,as in molecular pharming. Restriction enzyme Bacterial enzymes used in recombinant DNA technolo-gy to cut DNA for insertion of foreign DNA.(Their pur-pose in nature is to protect bacteria against intrudingDNA from other organisms).They are very specific,rec-ognizing short,specific nucleotide sequences in DNAsequences.Bacteria contain over 400 such enzymes thatrecognize and cut more than 100 different DNAsequences.Once the DNA is cut and the foreign DNAintroduced,the enzyme ligase seals the ends to make acontinuous DNA molecule. Ribose A five-carbon sugar that is a component of RNA.Deoxyribose is the corresponding sugar in DNA.The pres-ence of an extra O atom in RNA makes this moleculemore reactive than DNA,which is why DNA is the formin which hereditary information is stored and RNA is theform in which information is decoded to form proteins. RNA (Ribonucleic acid

85 ) A biological macromolecule found in th
) A biological macromolecule found in the nucleus andcytoplasm of cells;it plays an important role in protein syn-thesis and other chemical activities of the cell.The structureof RNA is similar to that of DNA.It is also made up ofnitrogenous bases:adenine,uracil,guanine and cytosine.There are many kinds of RNA molecules,including mes-senger RNA,transfer RNA,ribosomal RNA,and othersmall RNAs,each serving a different purpose. Sanger sequencing A widely used method of determining the order of bases Sequencing Determination of the order of nucleotides (base sequences)in a DNA or RNA molecule or the order of amino acidsin a protein. Shotgun sequencing Sequencing method that involves randomly sequencedcloned pieces of the genome,with no foreknowledge ofwhere the piece originally came from.This can be con-trasted with ÒdirectedÓstrategies,in which pieces of DNAfrom known chromosomal locations are sequenced.Because there are advantages to both strategies,researchershave used both random (or shotgun) and directed strategies 67 GLOSSARY 69 1.WHO (1999).World Health Report 1999 Ð Makinga Difference.(Geneva).2.Annan K (2003).A Challenge to the WorldÕs Science. 299:1485.3.In this

86 report,we use the term genomics to descr
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