THE NEW ARMS RACE:
Making the Case for a Comprehensive International Compact for
Infectious Diseases
Harvey Rubin, MD, PhD
Infectious Disease Society of America
Toronto, October 12, 2006
www.istar.upenn.edu/compact
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?
www.istar.upenn.edu/compact
The need is well documented
• 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).
www.istar.upenn.edu/compact
Dangerous assumption that an agreement
exists
www.istar.upenn.edu/compact
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)
www.istar.upenn.edu/compact
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)
www.istar.upenn.edu/compact
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)
www.istar.upenn.edu/compact
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)
www.istar.upenn.edu/compact
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)
www.istar.upenn.edu/compact
BUT NO COMPREHENSIVE PROGRAM
FOR INFECTIOUS DISEASES
www.istar.upenn.edu/compact
What about the…
• International Health
Regulations (IHR) of
the World Health
Organization?
• The Biological
Weapons
Convention (BWC)?
www.istar.upenn.edu/compact
THE SOLUTION
We propose a comprehensive four-part
International Compact for Infectious
Diseases (the “Compact”)
www.istar.upenn.edu/compact
Treaties and Compacts: organizational benefits
and drawbacks
Compact Benefits:
Treaty Benefits:
Provides an international legal basis for
enforcement.
Quick to set up and provides a framework
for action.
Creates a body of durable “hard law” around
an issue.
Brings together a broad coalition of partners
around a central issue.
Draws on the power of governments to
regulate and license within their jurisdiction
Promotes voluntary compliance of
laboratories, companies, etc.
Compact Drawbacks:
Treaty Drawbacks:
Ratification is slow and may limit action on
urgent issues.
Enforcement relies on soft power and
voluntary compliance.
States may perceive enforcement clauses
as an unacceptable burden.
Soft power may prove ineffective during a
health crisis.
www.istar.upenn.edu/compact
A Two-Pronged Approach
Treaty
(Identical in spirit to Compact)
State
State
Compact
State
Eligible Parties: States
Method of Participation: Ratification
Academia
Corporations
NGOs
Eligible Members: NGOs, academic
institutions, corporations,
independent research labs
Method of Participation: Pledge of
Membership and Voluntary
Compliance
www.istar.upenn.edu/compact
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 will 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
www.istar.upenn.edu/compact
Compacts 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)
www.istar.upenn.edu/compact
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
www.istar.upenn.edu/compact
The Compact: Part 2
Establish, maintain and monitor international
standards for best laboratory practices
www.istar.upenn.edu/compact
The Compact: Part 3
Expand capabilities for the production of
vaccines and therapeutics expressly for
emerging and reemerging infections
www.istar.upenn.edu/compact
The Compact: Part 4
Establish, maintain and monitor a network of
international research centers for microbial
threats.
www.istar.upenn.edu/compact
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 reportable agents
using latest information on endemic and
emerging naturally occurring pathogens
www.istar.upenn.edu/compact
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.
www.istar.upenn.edu/compact
Epidemic and Pandemic Alert and Response
(EPR) has six core functions
•
•
•
•
•
•
Support Member States for the implementation of national capacities for
epidemic preparedness and response in the context of the IHR(2005),
including laboratory capacities and early warning alert and response
systems
Support national and international training programmes for epidemic
preparedness and response
Coordinate and support Member States for pandemic and seasonal
influenza preparedness and response
Develop standardized approaches for readiness and response to major
epidemic-prone diseases (e.g. meningitis, yellow fever, plague)
Strengthen biosafety, biosecurity and readiness for outbreaks of dangerous
and emerging pathogens outbreaks (e.g. SARS, viral haemorrhagic fevers)
Maintain and further develop a global operational platform to support
outbreak response and support regional offices in implementation at
regional level.
www.istar.upenn.edu/compact
From International Sanitary
Conventions to Global
Health Security: The New
International Health
Regulations
David P. Fidler
Chinese Journal of International Law
(2005), Vol. 4, No. 2, 325–392
www.istar.upenn.edu/compact
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
www.istar.upenn.edu/compact
Challenges for any surveillance and
reporting system
• trust between signatory nations and a willingness to
share biosurveillance data
• developing incentives to share data
• creation of a common architecture for information
systems requires common ontologies
• developing and validating new algorithms and models of
disease spread
•
consequences of non-reporting, or significantly underreporting the incidence of communicable diseases
www.istar.upenn.edu/compact
Technical solutions
•
integrate current initiatives into a national health IT strategy and
federal architecture to reduce the risk of duplicative efforts
•
develop and adopt consistent interoperability standards
•
create enough flexibility to bring together disparate underlying IT
languages and technologies to provide a common operating picture
•
generate the ability to accept multiple data formats used by agencies
that provide the bio-surveillance information
www.istar.upenn.edu/compact
Technical solutions
• generate the ability to feed information back to the originating
agencies providing bio-surveillance information in a format each
agency can accept
• identify data flows that will evolve during the developmental process
• allow the methods of analysis to evolve and adapt as new data
become available or existing data sets are improved
• know and evaluate the effectiveness of the current underlying
algorithms, methods, and structures for biosurveillance data
analysis.
www.istar.upenn.edu/compact
Governance solutions
The Compact will use “soft” methods to
encourage reporting and discourage noncompliance
• 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
www.istar.upenn.edu/compact
Part 2
International Standards for Best Laboratory Practices
• Bio-safety: at risk
– Laboratory personnel
– Local public health
– National and international public health
• Unavaoidable linkage to bio-security
www.istar.upenn.edu/compact
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
Advanced
China
Hong
Kong
Japan
Korea
Singapore
India
Emerging
Pakistan
Thailand
Taiwan
Malaysia
Developing
Indonesia
Cambodia
Vietnam
Bangladesh
Philippines
Sri Lanka
www.istar.upenn.edu/compact
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.
www.istar.upenn.edu/compact
Another example of best practices: recent publication of 1918 Pandemic
Influenza Virus Papers
“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 highcontainment 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).”
www.istar.upenn.edu/compact
“1918 Flu and Responsible Science”
“I firmly believe that allowing the
publication of this
information was the correct decision in
terms of both national security and
public health.”
Science Editorial
Vol.
310, 7 October 2005
Philip A. Sharp
www.istar.upenn.edu/compact
“The 1918 flu genome: Recipe for
Destruction”
“This is extremely foolish.
The genome is essentially
the design of a weapon of
mass destruction.”
New York Times Op-Ed
October 17, 2005
Ray Kurzweil and Bill Joy
contributors
www.istar.upenn.edu/compact
Best Lab Practices Model
Compact / Treaty Organization
Private Sector Signatory
State Certification Body
Public/Private Universities
Research Labs
State Labs
University Labs
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.
www.istar.upenn.edu/compact
Part 3
Expansion of capabilities for the production of vaccines and
therapeutics expressly for emerging and reemerging infections
1.
An innovative solution for the limited base of manufacturing and
distribution of therapeutics and vaccines has to be achieved
2.
Government as well as large, multi-national pharmaceutical concerns
and the biotechnology industry need to engage in a commitment to
expand the manufacturing base
3.
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.
4.
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.
www.istar.upenn.edu/compact
Challenges
1.
The market for therapeutics and vaccines in the developing world
is too small to attract serious commercial research investment
2.
Even in the developed world, vaccine markets generally suffer
from high up-front costs relating to research and regulation, and
uncertain demand over time
3.
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
4.
The enterprise requires high levels of transparency, oversight and
acceptance of international standards for licensure
5.
Incentives and enforcement must be considered
www.istar.upenn.edu/compact
Editorial
September 6, 2006
Vaccine Futures
One of the big reasons that companies don’t try to develop vaccinations for poor-country diseases is
that they fear there won’t be a market for them. So what if rich countries promised to buy them?
That’s the very simple idea behind a new plan to entice companies into making vaccines for illnesses
that mostly kill poor people, like malaria and tuberculosis. The program will be discussed by
finance officials from wealthy nations at a meeting in Rome tomorrow. It works like this: Rich
countries commit to pay a specific amount to help poor countries buy a guaranteed supply of a
needed, effective vaccine. The subsidy would allow the manufacturer to recoup its investment and
earn a profit. The company agrees that after it has received the pledged amount, it will sell to poor
countries cheaply.
A panel of experts recommended that the idea be tried first to promote a vaccine against
pneumococcal disease, which kills about 1.6 million people a year, making it the leading vaccinepreventable cause of death. AIDS is making this kind of infection more common, and the bacteria
are increasingly resistant to the antibiotics used to treat them.
In the last few years, researchers have tried several novel financing ideas. Many combine government
and charitable financing with industrial know-how. This idea would complement the others. The
Bush administration has been reluctant to join international financing mechanisms. But it has no
reason not to jump on this plan, which will benefit American companies and is a private-sector,
market-driven program that pays only for success.
www.istar.upenn.edu/compact
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
www.istar.upenn.edu/compact
Among the many benefits
1. The Compact equitably spreads the high cost of
manufacturing and distribution of drugs and vaccines across a
group of nations.
2. It creates a structure with which to develop incentives for
large pharmaceutical corporations to undertake the
development of vaccines and therapeutics.
3. It provides the mechanism to achieve the common goal of
providing the world with standardized and authenticated
agents.
4. It will address the legal issues of international pharmaceutical
licensing.
www.istar.upenn.edu/compact
Part 4
Establishment, maintenance and monitoring of a network of
international research centers for microbial threats.
1.
The research centers should have a permanent faculty and staff as well
as visiting fellowships and studentships.
2.
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.
3.
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
1.
www.istar.upenn.edu/compact
The Compact: 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.
•
Furthermore, the Compact uses both 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.
www.istar.upenn.edu/compact
Benefits: the whole is greater than the sum of
its parts
1. Provide access to specific therapeutics and vaccines that are relevant to
the signatories.
2. Provide access to cheaper and more highly standardized therapeutics
and vaccines.
3. Ensure better quality control of vaccines, therapeutics and diagnostics in
the developing world, leading to fewer expired or counterfeit agents.
4. Provide access to and participation in high-level research.
5. Provide developing and developed states with a voice in the direction of
research and development.
www.istar.upenn.edu/compact
Benefits: the whole is greater than the sum
of its parts
6. Distribute the costs and risks of research and development across a
number of countries
7. Provide more complete datasets on emerging infections and
potential pandemics.
8. Create a more competitive market for vaccine and therapeutic
development targeting diseases of relevance to signatory nations.
9. Enhance and enable human health and well being, economic
development, and basic biological research.
www.istar.upenn.edu/compact
Global Collaborators
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
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
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.
www.istar.upenn.edu/compact
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.
www.istar.upenn.edu/compact
Next steps
1.
•
•
•
•
2.
3.
Complete the legal, business and research cases by
engaging
the pharmaceutical industry
the information technology industry
NGOs
Academia
Feedback and suggestions from you, log on to:
www.istar.upenn.edu/compact
Present plans to the appropriate national and
international government agencies
www.istar.upenn.edu/compact
www.istar.upenn.edu/compact
Thanks to the University of
Pennsylvania students
•
•
•
•
•
Adrian Arroyo
Dr. Jian Shin Teh
Joanna Johnston
Daniel Milich
Jon Stott
www.istar.upenn.edu/compact
“ 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
www.istar.upenn.edu/compact