The Global Virome Project
A First Step Toward Ending the
Pandemic Era
Five Take Home Thoughts
• Success will require changing from a culture that is “reactive” to one that is “proactive”
• In the 21st century disease “emergence” is accelerating - driven by population growth
and related impact on the environment
• The world, however, is ill prepared to respond to an emerging threat
• Our capacity to deploy effective “counter measures” is limited by what we “don’t know” about future threats
• The Global Virome Project will transition the sciences of Emerging Viral Diseases into being Big Data sciences – allowing us to think differently about “Problems and Solutions”
If you know your enemies and know yourself, you will not be imperiled in a hundred battles; …..if you do not know your enemies nor yourself, you will be imperiled in every single battle.
Sun Tzu
We are not prepared
• HIV, SARS, H1N1 Influenza, MERS, Ebola, Zika = examples of the futility of developing countermeasures AFTER emergence
• Their emergence and spread have outpaced our ability to develop new countermeasures
• Urgent need to develop countermeasures in ADVANCE of emergence
The Global Virome Project
• The Global Virome Project (GVP) is a global venture to characterize within ten years virtually all of the planet’s threatening viruses
• The GVP will create a data rich field - enabling preventive development of countermeasures
• The GVP will transform the culture – from being Reactive (and ineffective) to one that is Proactive (and effective)
The Global Virome Projects presents a path to the identification of all viruses that can infect humans - so we can prepare for
them before they jump to us
0
50
100
150
200
250
300
194
5
195
5
196
5
197
5
198
5
199
5
200
5
201
5
202
5
203
5
204
5
205
5
Actual
Projected
Decades
Nu
mb
er o
f EV
D E
ven
ts • ~ 3 new Emerging Viral Diseases (EVD) annually
• Driven by population expansion (1.6 billion in 1900 to 11.5 billion people in 2100)
• Increased encroachment into wildlife habitat is accelerating the “spillover” of novel viral threats from wildlife to humans
Source: Jones et al. (2008) Nature
The threat from novel viruses is increasing
HIV
Nip
ah
Avi
an In
fluen
za
SAR
S
Zika
H1N
1Eb
ola
MER
S
MERSSouth Korea
$8-12 bn
2000 2002 2004 2006 2008 2010 2012 2014 2016
$20 bn
$30 bn
$40 bn
$50 bn
$10 bn
$60 bn
SARSChina, Hong Kong,
Singapore, Canada$30-50 bn
H1N1Worldwide
$45-55 bn
H5N1Worldwide
$40 bn
ZikaAmericas
$4-6 bn
EbolaWorldwide
$40 bn
Economic Impact of Recent EVDs
Estimated Annual Inclusive cost of a pandemic ~ $570 billion per year
Fan, Jamison, Summers
Why are there more EVDs?
Drivers for Disease Emergence are Intensifying
Rapidly increasing human population
Drivers for Disease Emergence are Intensifying
Rapidly increasing human population
Increasing domestic animal
production
Increasing crop
production
Increasing natural
resource extraction
Expanding Settlements
+ + +
Drivers for Disease Emergence are Intensifying
Rapidly increasing human populationIncreasing domestic animal
production
Increasing crop
production
Increasing natural
resource extraction
Expanding Settlements
+ + + =Increasing
animal-human
contact and spillover
rate
All Drive Habitat Change
‘Hotspots’ for Disease Emergence during 20th Century
relative
influence
(%)
std.
dev.
population 27.99 2.99
mammal
diversity19.84 3.30
change: pop 13.54 1.54
change:
pasture11.71 1.30
urban extent 9.77 1.62
crop
crop_change
past
urban_land
past_change
pop_change
mamdiv
pop
0 10 20
rel.inf.mean
va
riable
….. But as we consider future risk ….
Likely “Hot Spots” for Viral Diversity
Viral diversity is closely related to mammalian diversity, allowing for geographic targeting
Distribution of Population Change
1950-2100
Developing Countermeasures AFTER Emergence Leaves the World Vulnerable to the Worst
Consequences
We Also Know …..
CASES
TIME
Detection
Lab Confirmation
Response
First Case
Standard Model for Detection and Response
April 10, 2009April 20, 2009May 1, 2009H1N1 Spread May 18, 2009June 11, 2009September 20, 2009April 10, 2010
Nearly 2 billion people infected73 countries reporting H1N1 cases
*Data provided by WHO Report of the Review Committee on the Functioning of the IHR Regulations in relation to Pandemic (H1N1) 2009. 5 May 2011.
April 10, 2009April 20, 2009May 1, 2009May 18, 2009June 11, 2009September 20, 2009April 10, 2010
Nearly 2 billion people infected73 countries reporting H1N1 cases
0
200
400
600
800
1000
1200
1400
Apr-09 Jun Sept Dec Apr-10
Global Vaccine Production% Global
Population
Millions of Doses
20
107%
(6 months)
17%(1 year)
First Detection
Seed Strain
Vaccine Production
H1N1 Spread vs Vaccine Development
Animal Amplification
CASES
TIME
The “ecology” of disease emergence …..
…at the “animal-human-ecosystem” interface”
Animal Amplification
CASES
TIME
Characterizing Determinants of
Pathogen Emergence –biological and
behavioral
Targeting “Behaviors and Practices” that trigger
“spill-over and amplification”
“DETECT” “PREVENT”
“Respond”
Building a
response “toolbox”
before emergence
Moving Preparedness to the “Left”
We also know…….
Global Travel can turn local epidemics into “global epidemics”
GVP: “Proof of Concept”
Feasibility: Large scale “Proof of Concept”
➢ Spanning >30 countries
➢ Over $120 million invested to date
➢ Seven years +
➢ Another approx. $90 million obligated for activities over next 3 years
The feasibility of GVP was validated through USAID’s PREDICT Project
Zoonotic disease surveillance - from how to safely collect and handle samples, laboratory diagnostics, and data management and
interpretation.
Trained
field & lab staff
Optimized Sampled
labs wild animals
Viruses detectedSystems and Capacities Built
Targeting “High Risk” Species
Bat Guano Farms
Vietnam, Cambodia & Thailand
Smiley Evans et al. PLoS Neglected Tropical Diseases, 2015
Viruses Detected in 28 Viral Families
Li et al. Science, 2005; Ge et al. Nature, 2013
MERS-CoV, Saudi Arabia
Wacharapluesadee et al. Emerging Infectious Diseases, 2013
Thailand bat CoV
Novel beta CoVs from bat guano
Ranking Which Viruses Are Most “Risky”
Mortalities caused by Human Metapneumovirus & Human Respiratory Syncytial Virus
Palacios et al. Emerging Infectious Diseases, 2011Gilardi et al. Emerging Infectious Diseases, 2014
Feasibility: Extrapolating from PREDICT
Discovery Curves Show the Number of Samples Requiredmber of
samples required to discover most of the unknown viruses
• PREDICT research has demonstrated that far fewer samples than previously expected are required to identify most threatening viruses
• These viral discovery curve studies provide a roadmap to sampling needs for GVP
Making the unknown known
• There are ~700,000 viruses spanning 24 viral families in wildlife that have the potential to cause human infection
• This means, for every “known” corona virus there are likely 20,000 distinct “unknown” viruses of the same coronavirus family circulating among an “unknown” pool of wild animals
• The same holds for HIV and retroviruses, filoviruses, etc.
111 viral families recognized to-date infecting all hosts around the globe
24 of these families likely contain species capable of infecting humans
~1.6 million viral species spanning the 23 viral families are estimated to be circulating in mammals and water fowl
Of these 650,000 - 840,000 viral species are likely to be of human pandemic /epidemic potential
To-date a total of 385 viruses are known to have infected humans
GVP: Strategic Underpinnings
Feasibility: Extrapolating from PREDICT
Discovery Curves Show the Number of Samples Requiredmber of
samples required to discover most of the unknown viruses
• Extrapolating from each of 21 viral families tested in 2 studies, we estimate there are 1.6 million unknown viruses in 24 viral families in mammals and water birds.
• Using ICTV data, we expect 650,000 - 840,000 have zoonotic potential.• Folllowing the cost of PREDICT sampling and testing, a GVP that discovers 85% of
these viruses would cost $1.7 billion, or $170 million per year over a decade
GVP: The Approach – Get to the Source
Mammals and water birds are key viral reservoirs
Mammalian diversity hotspots Water bird breeding hotspots
Tracking mammalian diversity for geographic targeting
- 319 Mammal species
- Up to 638K mammal samples
- 560 Mammal species and 120 waterbird species
- Up to 1.4 million total samples
- 648 Mammal species
- Up to 1.3 million mammal samples
Targeting Rich Mammalian Diversity
Brazil
UgandaChina
Optimizing the targeting strategy
Minimize cost
Global mammalian biodiversityAccess costs (days to location)
…while maximizing biodiversity
Country-level optimization: China
Number of planning units: 573 Number of species: 572
Unique wildlife assemblages - counterintuitive site choice
Calculating Return on Investment (ROI) for the
Global Virome Project
From Holt et al. 2013, Science
Zoogeographic areas
Minimizing duplication of sites in adjacent countries
East Neotropical Zoogeographic Area
Number of planning units: 1225 Number of species: 853
Potential First Wave of High-Yield Targets
Funding Strategies
Latin America
Brazil: $80M
Costa Rica: $29M
South Asia
Bangladesh:
$18M
West/Central Africa
Ghana: $39M
Cameroon: $35M
East/Central Africa
DR Congo $57M
Cameroon: $43M
Southeast Asia
Thailand: $38M
Cambodia: $26M
Indonesia: $90M
Could capture a huge amount of viral
diversity and associated benefits with less
than $500M in approximately 5 years
Potential Countries of Opportunity
Mammal biodiversity hotspots Water bird breeding hotspots
Canadaa Norway ChinaChina, Costa Rica, Australia
Funding Strategies
The Global Virome Project
The Global Virome Project
• The Global Virome Project (GVP) is a global venture to document and characterize virtually all of the planet’s viruses in wildlife that could pose a threat to humans
• The GVP aims to convert virology into a data rich field
• The GVP will transform the culture – from being Reactive (and ineffective) to one that is Proactive (and effective)
Global Virome Project
parallels to the
Human Genome Project
• An audacious but doable visionary project
• Clear metrics and goals
• The potential to change the way we do science
MERSSARS
Convert Virology into a data rich field:
Thousands of other Corona Viruses
The Next-Gen of Broad Spectrum Countermeasures
Universal Corona Virus Vaccine
The Impact– Disruptive & Transformative
Minimizing the Risk of Spillover
Targeted, High Impact Risk Mitigation
Detailed characterization of virus's ecologic profile - spanning host range, geographic distribution, and epidemiology – will enable the identification of viruses that pose the greatest potential threat - and the targeting of measures to prevent spillover
The Impact– Disruptive & Transformative
The Impact– Disruptive & Transformative
• GVP’s surveillance and laboratory platforms have the potential to remain beyond the GVP as a long term system for monitoring evolving viral threats – ensuring early and effective deployment of biomedical and preventive countermeasures
• GVP database will serve as a critically important “snap shot in time” on viral ecology, epidemiology, and genetics
• An inherent characteristic of the most dangerous emerging viral diseases is that their host range, epidemiology, and genetic profiles will evolve over time
The “Halo Effect”
• As in the Human Genome Project, the GVP will dramatically accelerate the development of new diagnostic & analytic tools
• Data generated will have unanticipated impact –
• GVP’s surveillance and lab platforms will remain after GVP is completed as a long term system for monitoring evolving viral threats
The Impact– Disruptive & Transformative
HOW WOULD JOHN SNOW VIEW TODAY’S WORLD?
JOHN SNOW’S GHOST MAP 1854 LONDON
“Insanity is doing the same thing over and over again and expecting different results”
Albert Einstein