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

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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

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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