Genomics and Global Public Health Abdallah S Daar

Genomics and Global Public Health Abdallah S Daar University of Toronto Genomics and Population Health Conference, London Jan. 26, 2006

Global Health Inequities: A key ethical challenge 10/90 GAP Underlying issue: Knowledge Divides (Digital-, Genomic-, Nano-, etc. )

Medical Genetics and Biotechnology: Implications for Public Health unedited draft report, version: 22 December 1999, by Professor A. S. Daar and Professor J-F. Mattei with the assistance and guidance of members of the WHO Working Group on Genetic Manipulations and incorporating modifications suggested at the meeting of the working group of independent and external experts held at WHO headquarters 12 -14 October 1998 © World Health Organization This report is not issued to the general public, and all rights are reserved by the World Health Organization. The report may not be reviewed, abstracted, quoted, reproduced or translated, in part or in whole, without the prior written permission of WHO. No part of this report may be stored in a retrieval system or transmitted in any form or by any means - electronic, mechanical or other - without the prior written permission of WHO. The views expressed are solely the responsibility of the authors.

Collins et al. A Vision for the future of genomics research. Nature, April 14, 2003

Canadian Program on Genomics and Global Health (CPGGH) • • • Main focus is in reducing global health inequities through use of genomics/ biotech knowledge. Not “ethics as usual” The only WHO Collaborating Centre in Bioethics in the world Empirical qualitative research, plus concept development. 40 million Canadian dollars of peer-reviewed research grants; 22 m in 2005 Aiming for major policy impacts International recognition includes 5 prizes this year: UNESCO Avicenna Prize for Ethics in Science; Dales Prize; Anthony Miller Prize; Maud Menten Prize; Yale Award for Excellence in Bioethics

What Do We Mean By Genomics (where is the field going? ) The powerful new wave of health related life sciences (biotechnologies) energized by the human genome project and the knowledge and tools it is spawning (proteomics, transcriptomics, metabolomics, etc)

Avoiding a Genomics Divide Harnessing Genomics and Biotechnology to Improve Global Health Equity Singer PA & AS Daar (2001). Science 294(5540): 87 -89.

Some Projects in Our Program • Promotion of Global Public Goods • Developing New Models of Intellectual Property Regimes • Biotechnologies from Improving Health in Developing Countries (DCs) • Grand Challenges for Global Health • Biotechnologies and the Millennium Development Goals • Health Biotech Innovation Systems of DCs • How Biotechnology Companies Deal with Ethical Challenges • Role of the Private Sector in S&T innovation in DCs and what developed countries can do to help

Projects • • • Diaspora Contributions to Home Country Development Knowledge Societies Global Health Ethics Pharmacogenetics and Geographical Ancestry Genome Policy Courses Nutrigenomics Plant Derived Vaccines Convergent Technologies (e. g. Nanotechnology) Bio-development vs. Bio-security (Bioterrorism) Grand Challenges in Non-Communicable Diseases Regenerative Medicine International Executive Courses on Genomics/Policy

Top 10 Biotechnologies for Improving Health in Developing Countries 1. 2. 3. 4. 5. 6. 7. 8. 9. 10. Molecular diagnostics Recombinant vaccines Drug and Vaccine delivery systems Bioremediation Sequencing pathogen genomes Female-controlled STI protection Bioinformatics Enriched GM crops Recombinant drugs Combinatorial chemistry Daar AS et al (2002). Top 10 biotechnologies for improving health in developing countries. Nature Genetics 32(2).

2. Recombinant Vaccines • • • EXAMPLE: A malaria subunit vaccine recently protected 71% of Gambian adults against natural infection for the first 9 weeks in a test study A broad category of vaccines made by the manipulation of DNA Safer than traditional vaccines, and can be cheaply produced Examples include subunit vaccines, edible vaccines and viral vector vaccines

HIV • • • One of the most rapidly mutating viruses known Great threat to human thriving in developing countries No effective vaccine Almost all approaches will have to take into account HIV genomics Novel approaches e. g. CCR 5 blockers

MALARIA • • • With previous technology no safe vaccine Subunit vaccine, 70% response rate in Gambia Fosmidomycin as new class of antimalarial discovered through partial genome sequence and bioinformatics Now genome of both falciparum and its insect vector has been sequenced Vector control will almost certainly depend on genomics knowledge Synthetic biology to make artesunate

4. Bioremediation • • EXAMPLE: Bioremediation was part of the strategy to clean up the Alaskan shoreline after the Exxon Valdez oil spill in 1989 The use of bacteria and plants to clean up water and soil pollution Much cheaper and more sustainable than waste excavation and disposal

Bangladesh’s Mass Arsenic Poisoning 50 million people exposed • Bacteria convert insoluble arsenic in aquifer wall to soluble arsenic in water • In Australia there are bacteria that do the opposite • We led a coalition with Australian, Canadian, Bangladeshi and US scientists to study genomes of both types of bacteria • Sequencing started in Canada •

6. Female-Controlled STD Protection • • EXAMPLE: Antibodies bind to and disable pathogens. Monoclonal antibodies applied as a vaginal gel have been effective at preventing STDs. Women lack ways of protecting themselves against STDs without needing their partner’s consent Biotechnology may help by providing vaccines, vaginal microbicides or blockers of viral receptors e. g. CCR 5

UN MILLENNIUM DEVELOPMENT GOALS • • Eradicate extreme poverty and hunger Achieve universal primary education Promote gender quality and empower women Reduce child mortality Improve maternal health Combat HIV/AIDS, malaria and other diseases Ensure environmental sustainability Develop a global partnership for development

Bill and Melinda Gates Foundation $437 M Grand Challenges in Global Health * Elias Zerhouni, Director of NIH Budget: 28 billion $ www. grandchallengesgh. org

What is a Grand Challenge? “A specific scientific or technological innovation that would remove a critical barrier to solving an important health problem in the developing world with a high likelihood of global impact and feasibility. ”

Goals and Grand Challenges GOAL 1: To improve childhood vaccines: GC 1: Create effective single-dose vaccines that can be used soon after birth; GC 2: Prepare vaccines that do not require refrigeration; GC 3: Develop needle-free delivery systems for vaccines. GOAL 2: To create new vaccines: GC 4: Devise reliable tests in model systems to evaluate live attenuated vaccines; GC 5: Solve how to design antigens for effective, protective immunity; GC 6: Learn which immunological responses provide protective immunity. GOAL 3: To control insects that transmit agents of disease: GC 7: Develop a genetic strategy to deplete or incapacitate a disease-transmitting insect population; GC 8: Develop a chemical strategy to deplete or incapacitate a diseasetransmitting insect population.

GOAL 4: To improve nutrition to promote health: GC 9: Create a full range of optimal bioavailable nutrients in a single staple plant species. GOAL 5: To improve drug treatment of infectious diseases: GC 10: Discover drugs and delivery systems that minimize the likelihood of drug resistant microorganisms. GOAL 6: To cure latent and chronic infections: GC 11: Create therapies that can cure latent infections; GC 12: Create immunological methods that can cure chronic infections. GOAL 7: To measure disease and health status accurately and economically in poor countries: GC 13: Develop technologies that permit quantitative assessment of population health status; GC 14: Develop technologies that allow assessment of individuals for multiple conditions or pathogens at point-of-care.

Genetically Modify Mosquito Populations To Make Them Incapable Of Transmitting Dengue Virus (O’Neill) • • Targets insect age, one of the most sensitive parameters influencing the epidemiology of insect-transmitted diseases. By introducing known life-shortening strains of inherited Wolbachia endosymbionts into mosquitoes we can selectively eliminate old mosquito adults in the population. Because of the length of the extrinsic incubation period of dengue virus within a mosquito, the removal of old individuals can stop disease transmission to humans. Moreover, the inherited Wolbachia endosymbionts that are capable of shortening lifespan provide their own genetic drive mechanism that allows them to spread throughout the host population.

Learning From the Human Genome How Protective Immunity Against Malaria Works (GC#6 Kwiatkowski) • • • To identify critical mechanisms of protective immunity against malaria by combining state-of-the art human genome technologies with large-scale epidemiological studies in malaria-endemic regions. To answer: How do people naturally clear malaria parasites from the blood stream? Why some people and not others get severe malaria? Most human genes show variation between individuals. By investigating how this natural genetic variation affects disease susceptibility, we can build a catalogue of host molecules that are critical for protective immunity.

“Engineered Immunity” (David Baltimore’s Grand Challenge in Global Health) • • New method using genetic engineering and cell transplantation methods to deal with infectious diseases of developing countries Antibody repertoire in humans is altered to direct life-long production of specified antibodies with desired properties The antibodies are produced in vivo by infecting autologous haematopoietic stem cells with lentiviral vectors bearing specific antibody genes and injecting the cells back into the patient. Initial focus on HIV, but the method is applicable to other infectious diseases.

Health Biotechnology Innovation in Developing Countries (Nature Biotechnology) Case studies: 1. Brazil 2. China 3. Cuba 4. Egypt 5. India 6. S Africa 7. S Korea

The only Meningitis B Vaccine

IMPACT: Some Examples • • • Canadian Prime Ministers’ 5% commitment Argentina bill on nanotechnology Nigerian Health Minister United Nations Task Force High Level Africa Biotechnology Panel etc

UNITED NATIONS

Nigerian Health Minister Eyitayo Lambo – London 2005 “Tells me what to do” “Tells me how to do it”

It's a miracle: mice regrow hearts 29 August 2005 SCIENTISTS (at Wistar Institute) have created "miracle mice" that can regenerate amputated limbs or damaged vital organs, making them able to recover from injuries that would kill or permanently disable normal animals.

“There can be no peace, no security, when a few rich countries with a small minority of the world’s people alone have access to the brave, and frightening, new world of technology and science, while the large majority live in deprivation and want, shut off from opportunities of full economic development; but with expectations and aspirations aroused beyond the hope of realizing them. ” Prime Minister Lester B. Pearson