Princeton talk Feb16 2007

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THE NEW ARMS RACE: Making the Case for a Comprehensive International Compact for Infectious Diseases Harvey Rubin, MD, PhD Princeton University February 16, 2007

The problem : 

The problem Recognizing the impact of infectious diseases on national and international health, economic development and security, can a truly comprehensive agreement between states be developed that will limit and control known, newly discovered or deliberately created infectious diseases?

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Emerging Infections: Microbial Threats to Health in the United States 1992, 2003, Institute of Medicine The Global Infectious Disease Threat and Its Implications for the United States” 2000, unclassified report from the National Intelligence Council The Darker Bioweapons Future 2003, unclassified CIA document analyzed the many benefits of modern molecular biology weighed against the danger that “the effects of engineered biological agents could be worse than any disease known to man.” National Security Strategy: 2006, “Public health challenges like pandemics (HIV/AIDS, avian influenza) ... recognize no borders. The risks to social order are so great that traditional public health approaches may be inadequate, necessitating new strategies and responses. ...” (italics added).  The need is well documented

The realities are overwhelming: 

The realities are overwhelming Each year 300 million cases of malaria kill two million people. An estimated 3% of the world’s population - 170 million people- are chronically infected with hepatitis C virus. About four million people are newly infected each year, 80% of whom will progress to a chronic infection associated with cirrhosis in about 20% and liver cancer in about 5%. 2 billion people have been infected with hepatitis B (1 out of 3 people). Approximately 400 million people are chronically infected with the virus and an estimated 1 million people will die each year from hepatitis B and its complications. One third of the world is infected with M. tuberculosis with 10 million cases every year accounting for two million deaths.  Approximately 50 million people worldwide are infected with HIV, which killed 3.9 million people in 2005. Some outbreaks are still relatively unknown to the general public yet represent a serious burden on global health. For example, cholera still causes close to 120,000 deaths per year. 

Dangerous assumption that an agreement exists: 

Dangerous assumption that an agreement exists

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Human Rights 1. International Covenant on Economic, Social and Cultural Rights (New York, 1966) 2. International Covenant on Civil and Political Rights (New York, 1966) 3. Optional Protocol to the International Covenant on Civil and Political Rights (New York, 1966) 4. Convention on the Prevention and Punishment of the Crime of Genocide (New York, 1948) 5. Convention against Torture and Other Cruel, Inhuman or Degrading Treatment or Punishment (New York, 1984) 6. Optional Protocol to the Convention against Torture and Other Cruel, Inhuman or Degrading Treatment or Punishment (New York, 2002) 7. International Convention on the Protection of the Rights of All Migrant Workers and Members of their Families (New York, 1990) 8. Optional Protocol to the Convention on the Rights of the Child on the involvement of children in armed conflict (New York, 2000) 9. Optional Protocol to the Convention on the Rights of the Child on the sale of children, child prostitution and child pornography (New York, 2000)

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Refugees 10. Convention Relating to the Status of Refugees (Geneva, 1951) 11. Protocol Relating to the Status of Refugees (New York, 1967) Penal Matters 12. Rome Statute of the International Criminal Court (Rome, 1998) 13. Agreement on the Privileges and Immunities of the International Criminal Court (New York, 2002) 14. Convention on the Safety of United Nations and Associated Personnel (New York, 1994) Terrorism 15. International Convention for the Suppression of Terrorist Bombings (New York, 1997) 16. International Convention for the Suppression of the Financing of Terrorism (New York,1999) 17. International Convention for the Suppression of Acts of Nuclear Terrorism (New York, 2005)

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Organized Crime and Corruption 18. United Nations Convention against Transnational Organized Crime (New York, 2000) 19. Protocol to Prevent, Suppress and Punish Trafficking in Persons, Especially Women and Children, supplementing the United Nations Convention against Transnational Organized Crime (New York, 2000) 20. Protocol against the Smuggling of Migrants by Land, Sea and Air, supplementing the United Nations Convention against Transnational Organized Crime (New York, 2000) 21. Protocol against the Illicit Manufacturing of and Trafficking in Firearms, Their Parts and Components and Ammunition, supplementing the United Nations Convention against Transnational Organized Crime (New York, 2001) 22. United Nations Convention against Corruption (New York, 2003)

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Environment 23. Kyoto Protocol to the United Nations Framework Convention on Climate Change (Kyoto, 1997) 24. Rotterdam Convention on the Prior Informed Consent Procedure for Certain Hazardous Chemicals and Pesticides in International Trade (Rotterdam, 1998) 25. Stockholm Convention on Persistent Organic Pollutants (Stockholm, 2001) 26. Cartagena Protocol on Biosafety to the Convention on Biological Diversity (Montreal, 2000) Law of the Sea 27. United Nations Convention on the Law of the Sea (Montego Bay, 1982) and Agreement relating to the implementation of Part XI of the United Nations Convention on the Law of the Sea of 10 December 1982 (New York, 1994)

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Disarmament 28. Comprehensive Nuclear-Test-Ban Treaty (New York, 1996) 29. Convention on the Prohibition of the Use, Stockpiling, Production and Transfer of Anti-Personnel Mines and on their Destruction (Oslo, 1997) Law of Treaties 30. Vienna Convention on the Law of Treaties (Vienna, 1969) Health 31. WHO Framework Convention on Tobacco Control (Geneva, 21 May 2003)

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BUT NO COMPREHENSIVE PROGRAM FOR INFECTIOUS DISEASES

What about the…: 

What about the… International Health Regulations (IHR) of the World Health Organization? The Biological Weapons Convention (BWC)?

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We propose a comprehensive four-part International Compact for Infectious Diseases (the “Compact”) THE SOLUTION

Treaties and Compacts: organizational benefits and drawbacks: 

Treaties and Compacts: organizational benefits and drawbacks Treaty Benefits: Provides an international legal basis for enforcement. Creates a body of durable “hard law” around an issue. Draws on the power of governments to regulate and license within their jurisdiction Treaty Drawbacks: Ratification is slow and may limit action on urgent issues. States may perceive enforcement clauses as an unacceptable burden. Compact Benefits: Quick to set up and provides a framework for action. Brings together a broad coalition of partners around a central issue. Promotes voluntary compliance of laboratories, companies, etc. Compact Drawbacks: Enforcement relies on soft power and voluntary compliance. Soft power may prove ineffective during a health crisis.

A Two-Pronged Approach: 

A Two-Pronged Approach Eligible Parties: States Method of Participation: Ratification Eligible Members: NGOs, academic institutions, corporations, independent research labs Method of Participation: Pledge of Membership and Voluntary Compliance

Treaty and Compact: complementary systems: 

Treaty and Compact: complementary systems By providing parallel frameworks for different parties, the overall project will, over time, achieve the benefits of each. Domestic partners who are signatories to the compact can pressure states to comply with the treaty. Legitimacy and understanding of the overall system will be promoted through involvement of both state and non-state actors

Compacts (soft-law) are effective governance structures : 

Compacts (soft-law) are effective governance structures 1) Human Rights Inter-American Declaration of Human Rights (Organization of American States) Helsinki Accords (Organization of Security and Cooperation in Europe) Labor Rights Laws (International Labor Organization) Sullivan Principles on Apartheid (Private Sector Active in South Africa) McBride Principles (Private Sector Active in Northern Ireland) 2) Environment Prior Informed Consent for Hazardous Chemicals in International Trade Driftnet Fishing (UN General Assembly Series of Resolutions 1989-1992) Antarctica Treaty Recommended Measures Convention on Migratory Species (States were encouraged to create informal agreements within the treaty Memorandums of Understanding) 3) Arms Control/Disarmament Nuclear Safety Measures (The International Atomic Energy Agency) Suppliers Export Controls (Dual Use Technologies) Landmines (Before the Ottawa Treaty) 4) Trade/Finance Money Laundering (World Bank) Standards Harmonization (International Standards Organization) Environmental Soft Law Linkages with Trade (Asian Pacific Economic Community)

The Ottawa Process: 

The Ottawa Process October 1992 – The International Campaign to Ban Landmines is created at a meeting of NGOs in NYC. The campaign consists of six NGOs: Human Rights Watch, Medico International, Handicap International, Physicians for Human Rights, Vietnam Veterans Association of America and the Mines Advisory Group. May 1993 – The First NGO International Conference on Landmines is held in London. It brings together 50 representatives of 40 NGOs to strategize on building the campaign to ban landmines. The original six NGOs are recognized as the Steering Committee of the Campaign and the Vietnam Veterans Association of America is appointed the coordinator. May, 1994 – ICBL holds its Second International NGO Conference on Landmines in Geneva, with logistical support of UNICEF Geneva, which is attended by more than 110 representatives from more than 75 NGOs. June 1995 – The Cambodia Campaign to Ban Landmines and the NGO Forum on Cambodia host the 3rd international NGO conference on landmines, a three-day event attended by more than 400 people from 42 countries, representing NGOs, governments, the UN, de-mining organizations and landmine victims.

The Ottawa Process: 

The Ottawa Process October 1996 – The historic Ottawa conference brings together 75 governments. It yields three concrete results: 1) a final declaration agreed to by the 50 government participants in the conference, recognizing the urgent need for a ban on AP mines; 2) the conference Chairman's Agenda for Action, an outline of actions for reaching a ban rapidly; and 3) the bold announcement by Canada that it is prepared to hold a treaty-signing conference for a total ban in December 1997. June 1997 – Belgium hosts the second preparatory session for the 'Ottawa Process'. 106 countries sign the Brussels Declaration affirming their commitment to negotiate and sign a ban treaty by December 1998. At a General Meeting of the ICBL, the steering committee is expanded to include Kenyan and South African Campaigns to Ban Landmines. September 1997 – 121 nations negotiate the ban treaty from 1-19 September in Oslo, culminating in adoption of a comprehensive treaty. A parallel NGO Forum attended by more than 130 NGOs produces an action plan for entry into force by the year 2000. October 1997 - Nobel Peace Prize awarded to International Campaign to Ban Landmines

The Compact: Part 1: 

The Compact: Part 1 Establish, maintain and monitor international standards for surveillance and reporting of infectious diseases using advanced information technology to ensure timeliness, interoperability and security

The Compact: Part 2: 

The Compact: Part 2 Establish, maintain and monitor international standards for best laboratory practices

The Compact: Part 3: 

The Compact: Part 3 Expand capabilities for the production of vaccines and therapeutics expressly for emerging and reemerging infections

The Compact: Part 4: 

The Compact: Part 4 Establish, maintain and monitor a network of international research centers for microbial threats.

Part 1Establish, maintain and monitor international standards for surveillance and reporting of infectious diseases: 

Part 1 Establish, maintain and monitor international standards for surveillance and reporting of infectious diseases States parties to the Compact would set up standard, secure computer architectures for biosurveillance information systems Parties would define and continuously refine criteria for surveillance and reporting

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Epidemic and Pandemic Alert and Response Epidemics and pandemics can place sudden and intense demands on health systems. They expose existing weaknesses in these systems and, in addition to their morbidity and mortality, can disrupt economic activity and development. The world requires a global system that can rapidly identify and contain public health emergencies and reduce unneeded panic and disruption of trade, travel and society in general. The revised International Health Regulations, IHR(2005) provide a global framework to address these needs through a collective approach to the prevention, detection, and timely response to any public health emergency of international concern.

IHR issues: 

IHR issues no mechanism for dispute settlement or enforcement fundamental financial burden falls on developed states, not developing nations IHRs do not increase access to therapeutics nor stimulate vaccine development From International Sanitary Conventions to Global Health Security: The New International Health Regulations David P. Fidler Chinese Journal of International Law (2005), 4, 325–392

Challenges for any surveillance and reporting system: 

Challenges for any surveillance and reporting system trust between signatory nations and a willingness to share biosurveillance data developing incentives to share data consequences of non-reporting, or significantly under-reporting the incidence of communicable diseases creation of a common architecture for information systems requires common ontologies developing and validating new algorithms and models of disease spread data flows that will evolve during the developmental process

Governance solutions: 

Governance solutions The Compact will use “soft” methods to encourage reporting and discourage non-compliance Compliance status will be made public Parties not reporting or under-reporting disease incidence will have lower priority to vaccines and therapeutics research done through the Compact

Part 2  International Standards for Best Laboratory Practices: 

Part 2 International Standards for Best Laboratory Practices Bio-safety: at risk Laboratory personnel Local public health National and international public health Linkage to bio-security April 2, 1979, unusual anthrax outbreak affected 94 people and killed at least 64

Example of International Standards for Best Laboratory Practices: 

Example of International Standards for Best Laboratory Practices Survey of 300 Asian life scientists engaged in research with over 60 different infectious agents and/or toxins. 1. examine the policies and standards employed to advance biosafety and biosecurity 2. understand the practices, equipment and facilities used by these researchers 3. examine existing regulations in the context of the infectious pathogens they study 4. identify and address gaps in the development and implementation of policies related to laboratory biosafety and biosecurity Emerging Pakistan Thailand Taiwan Malaysia Advanced China Hong Kong Japan Korea Singapore India Developing Indonesia Cambodia Vietnam Bangladesh Philippines Sri Lanka

Results of the Sandia survey: 

Results of the Sandia survey Most of the laboratories profiled in the study perform risk assessments as the antecedent to instituting a biosafety plan. These plans, along with a laboratory’s biosecurity practices are highly influenced by each country’s national government. Five of the top nine infectious agents identified by respondents should be studied under biosafety level (BSL) 3 conditions, however almost two-thirds of researchers state they are working only with BSL 2 practices.

Council for Responsible Genetics: ongoing survey of accidents and security breakdowns at high-security biological research facilities : 

Council for Responsible Genetics: ongoing survey of accidents and security breakdowns at high-security biological research facilities loss of (or inability to account for) significant quantities of bioterrorism agents stored in biocontainment laboratories infection of laboratory personnel with a dangerous pathogen, resulting in serious illness or death failure of key safeguards and containment measures following a security inspection or power failure use of bioterrorism agents removed from a biocontainment facility for the purposes of causing indiscriminate harm to civilians

It happens… : 

It happens…

What if?  1918 Pandemic Influenza Virus : 

What if? 1918 Pandemic Influenza Virus “The 1918 virus and recombinant H1N1 influenza viruses were generated using the previously described reverse genetics system (8, 14). All viruses containing one or more gene segments from the 1918 influenza virus were generated and handled under high-containment biosafety level 3 enhanced (BSL3) laboratory conditions in accordance with guidelines of the National Institutes of Health and the Centers for Disease Control and Prevention (15).”

Is it worth it?: 

Is it worth it? Feb 2, 2007

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“1918 Flu and Responsible Science” Science Editorial Vol. 310, 7 October 2005 Philip A. Sharp “I firmly believe that allowing the publication of this information was the correct decision in terms of both national security and public health.”

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New York Times Op-Ed October 17, 2005 Ray Kurzweil and Bill Joy “The 1918 flu genome: Recipe for Destruction” “This is extremely foolish. The genome is essentially the design of a weapon of mass destruction.”

Best Lab Practices Model: 

Best Lab Practices Model 1. The Compact develops and adopts best laboratory practices with input from signatories. 2. Signatories set up internal certification bodies responsible for ensuring compliance with BLPs. 3. Signatories submit annual reports to expert panel within Compact verifying compliance with BLPs. 4. Signatories that do not comply with BLPs suffer reduced access to compact institutions and data, and their non-compliance in publicized.

Part 3 Expansion of capabilities for the production of vaccines and therapeutics expressly for emerging and reemerging infections: 

Part 3 Expansion of capabilities for the production of vaccines and therapeutics expressly for emerging and reemerging infections An innovative solution for the limited base of manufacturing and distribution of therapeutics and vaccines has to be achieved Government as well as large, multi-national pharmaceutical concerns and the biotechnology industry need to engage in a commitment to expand the manufacturing base Manufacturing contracts would be awarded to the countries or organizations with the most compelling offer, including commitments to assurance of continuity of supply and operations, safety, security and infrastructure. The signatories to the Compact would agree to fund the efforts sufficiently, perhaps representing a percentage of their GDP, thereby pooling the resources of many nations to create assured supplies of drugs and vaccines on a global scale as well as for specific local use.

Discovering New Antibiotics: A Matter of National Security : 

Discovering New Antibiotics: A Matter of National Security “…nearly 2 million people in the United States will acquire bacterial infections while in the hospital, and about 90,000 of them will die, according to CDC estimates. More than 70 percent of the bacteria that cause these infections will be resistant to at least one of the drugs commonly used to fight them. In a growing and frightening number of cases, these bacteria are resistant to many approved drugs, and patients have to be treated with new, investigational compounds or older, toxic alternatives. For many patients, there simply are no drugs that work.” Resistant bacterial infections are not only a public health problem; they have national and global security implications as well. The Institute of Medicine and federal officials have identified antibiotic resistance and the dearth of antibiotic R&D as increasing threats to U.S. public health. (italics added).” Infectious Diseases Society of America, 2004

Discovering New Antibiotics: A Matter of National Security: 

Discovering New Antibiotics: A Matter of National Security “American national security in the 21st century – as at virtually any time in our history until the age of vaccines and antibiotics – is likely to be threatened by pathogens as much as people. New diseases and antibiotic-resistant strains of old ones are on the rise…” FORGING A WORLD OF LIBERTY UNDER LAW: U.S. NATIONAL SECURITY IN THE 21ST CENTURY. G. John Ikenberry and Anne-Marie Slaughter, Co-Directors September 27, 2006, The Princeton Project Papers Published by The Woodrow Wilson School of Public and International Affairs, Princeton University, Final Paper of the Princeton Project on National Security

Challenges: 

Challenges The market for therapeutics and vaccines in the developing world is too small to attract serious commercial research investment Even in the developed world, vaccine markets generally suffer from high up-front costs relating to research and regulation, and uncertain demand over time Vaccines against potential biological weapons will suffer from high demand uncertainties and, should a bioterror event occur, may be requisitioned rather than purchased at market price The enterprise requires high levels of transparency, oversight and acceptance of international standards for licensure Incentives and enforcement must be considered

Potential Financial Models: 

Potential Financial Models 1. Advance Market Commitments 2. International Finance Facility for Immunization (IFFIm)- bond mechanism to pay for vaccines borrowing operating funds in the international capital markets over 10 years, expecting a triple-A credit rating 3. International drug purchase facility (IDPF) –French plan to levy tax on airline tickets

Among the many benefits: 

Among the many benefits The Compact equitably spreads the high cost of manufacturing and distribution of drugs and vaccines across a group of nations. It enables a structure with which to develop incentives for large pharmaceutical corporations to undertake the development of vaccines and therapeutics. It provides the mechanism to achieve the common goal of providing the world with standardized and authenticated agents. It will address harmonizing legal issues of international pharmaceutical licensing.

Part 4Establishment, maintenance and monitoring of a network of international research centers for microbial threats.: 

Part 4 Establishment, maintenance and monitoring of a network of international research centers for microbial threats. The research centers should have a permanent faculty and staff as well as visiting fellowships and studentships. The lasting positive impacts of international research centers include fostering long-term relationships between scientists, establishing a culture of research responsibility and serving as the nucleus for safe applications of interdisciplinary sciences globally. The example of the "Rice Institutes" funded by the Rockefeller Foundation for fifteen years and sustained by the Consultative Group in International Agricultural Research, provides an example. RICE BIOTECHNOLOGY: Rockefeller to End Network After 15 Years of Success. Dennis Normile Science 19 Nov. 1999:286, 1468 – 1469

The Compact: novel set of incentives and enforcements: 

The Compact: novel set of incentives and enforcements These recommendations are made with full awareness of the inherent legal, political, diplomatic and economic challenges of multilateral compacts.  We believe that a major strength of linking the production and distribution of therapeutics and vaccines with biosafety, biosecurity and improved access to and participation in research programs creates a global incentive of compassion, maximization of human health and welfare and economic and scientific development. The Compact uses incentives and penalties to create a cohesive international body that does not challenge sovereignty, but pools resources. Non-participation by any given state would lower its priority to receive the cost benefits of therapeutics and vaccines. The non-participating state would have lower priority in the research center.

Slide48: 

Martin J. Blaser, M.D., Frederick H. King Professor of Internal Medicine, Chair, Department of Medicine, Professor of Microbiology, New York University School of Medicine Baruch Blumberg, M.D., Distinguished Scientist at Fox Chase Cancer Center, President, American Philosophical Society, Nobel Prize 1976 William W. Burke-White, Assistant Professor of Law, University of Pennsylvania, Member, Government of Rwanda, Constitutional Commission, Member, International Criminal Tribunal for Yugoslavia, The Hague. Arturo Casadevall, MD, PhD. Professor, Medicine, Microbiology, & Immunology, Chair, Department of Microbiology & Immunology, Leo and Julia Forchheimer Professor of Microbiology & Immunology Abdallah S. Daar D.PHIL(OXON), FRCP(LON), FRCS(ENG.&ED.), FRCSC, FRS(C). Professor of Public Health Sciences and of Surgery at the University of Toronto, Director of the Program in Applied Ethics and Biotechnology, co-Director of the Canadian Program on Genomics and Global Health and Director of Ethics and Policy at the McLaughlin Centre for Molecular Medicine. David Franz, DVM. PhD, Senior Biological Scientist, Midwest Research Institute and Director of the National Agricultural Biosecurity Center at Kansas State University Sir Lawrence Freedman, Professor of War Studies and Vice Principal (Research), King's College London Malcolm Gillis, PhD. Zingler Professor of Economics and University Professor, Rice University Global Collaborators

Slide49: 

Manfred S Green MD, PhD. Director, Israel Center for Disease Control , Professor of Epidemiology and Preventive Medicine in the Sackler Faculty of Medicine at Tel Aviv University Dr. Green’s views do not necessarily reflect the views of the Israel Ministry of Health. Phillip A. Griffiths, PhD. Professor, School of Mathematics, Institute for Advanced Study, Princeton NJ. Former Director, Institute for Advanced Study, Princeton. J. Tomas Hexner, MBA. Director Science Initiative Group. Cambridge, Massachusetts Chung W. Kim, PhD. Director Emeritus, Korea Institute for Advanced Studies, Emeritus Professor, Physics and Astronomy, Johns Hopkins University Stuart B. Levy M.D., Professor of Molecular Biology and Microbiology and of Medicine and the Director of the Center for Adaptation Genetics and Drug Resistance at Tufts University, School of Medicine, Boston, Massachusetts Dr. Adel Mahmoud M.D. PhD., President of Merck Vaccines (retired). Erwann Michel-Kerjan, PhD., Managing Director of the Risk Management and Decision Processes Center at the Wharton School, University of Pennsylvania Peter A. Singer, MD, MPH, FRCPC , Co-Director of the Canadian Program in Genomics and Global Health; Senior Scientist at the McLaughlin Centre for Molecular Medicine; Professor of Medicine at University of Toronto and University Health Network; and a Distinguished Investigator of the Canadian Institutes of Health Research.

Next steps: 

Next steps Feedback and suggestions from international community: www.istar.upenn.edu/compact Draft the legal, business and research cases engaging the pharmaceutical industry the information technology industry NGOs Academia 3. Present plans to the appropriate national and international governmental agencies

Thanks to the University of Pennsylvania students: 

Thanks to the University of Pennsylvania students Adrian Arroyo Dr. Jian Shin Teh Joanna Johnston Daniel Milich Jon Stott Simran Dhillon

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“ We choose to go to the moon in this decade and do the other things, not because they are easy, but because they are hard, because that goal will serve to organize and measure the best of our energies and skills, because that challenge is one that we are willing to accept, one we are unwilling to postpone, and one which we intend to win…” John F. Kennedy Rice University September 12, 1962