Driving Innovation

op

“Are we better prepared for emerging threats”

Dr Penny Wilson

Innovation Platform Leader, Stratified Medicine

12 November 2012

Foresight Project

The Detection and Identification of

Infectious Diseases

UK Government

Report published April 2006

Infectious Disease Project:

Key Question: How can we use science and technology to improve our capability for detecting, identifying and monitoring infectious diseases in order to improve control?

Ultimate goal: To detect all known and unknown infectious diseases, of plants animals and humans, in ~ 30 years.

Foresight Infectious Diseases: preparing for the future

UK Government

Project structure

Africa

Catalyse

Action

Review of

future risks

Explore future

capabilities

and contexts

Evaluate future

science

Technology analysis -

„User Challenges‟

1. Data mining and data

fusion

2. Genomics and post-

genomics to characterise

new diseases

3. Hand-held / portable

diagnostic devices

4. Fast-throughput screening

at ports and airports

UCs and future risk management

Categories of particular

concern

Potential contribution to

managing future risk

UC1 UC2 UC3 UC4

Evolution of new diseases *** *** ** **

Acquiring resistance in pathogens *** ** *** *

Zoonoses ** ** *** ***

HIV/TB/Malaria ** ** *** *

Plant disease threats *** * *** ***

Acute respiratory infections *** ** *** ***

STIs ** * *** *

Trans boundary animal diseases *** ** *** ***

* *** ** KEY:

Increasing potential

Driving Innovation

Detection and Identification of Infectious

Agents (DIIA) Innovation Platform

• Created to reduce the mortality, morbidity and

economic burden of infectious diseases in

humans and animals

• In July 2012 the platform was brought into the

Stratified Medicine programme

• Continues to address the challenges of adoption

with key stakeholders including DH, NICE and

BIVDA

• Forthcoming call 2012 (proposed)

– Diagnosis of tuberculosis

– Diagnosis of endemic animal diseases

Driving Innovation

Converging technologies • Biomarker discovery

• Biosensors

• Novel chemistries

• The omics (proteomics, genomics)

• MEMS (including microfluidics)

• Sequencing technologies

• Nanotechnology

• Advanced materials

• Bioinformatics

• Information and communication technologies

• Data mining and fusion

• High value manufacturing

Qualitative Field Testing

Inspection of imported nursery stock

Interception of quarantine viruses in imported produce

Control and Graphical User Interface

Modified Loop Mediated Isothermal Amplification (LAMP) Eiken Chemical Company, Japan: Bst Polymerase: Isothermal polymerase 63-65 oC

500 nl volume wells , Syto 82, 560 nm Filter

+ - + + + +

Norihiro Tomita, Yasuyoshi Mori, Hidetoshi Kanda & Tsugunori Notomi Nature Protocols 3, 877 - 882 (2008)

Loop-mediated isothermal amplification (LAMP) of gene sequences and simple visual detection of products

Modifications:

Property of base4innovation Ltd. Confidential.

Technology

Silicon wafer • Silicon wafer with 20nm thick

silicon membrane and 10nm covering of gold.

Nanofabrication • Gold on membrane is etched away to produce a

plasmonic nanostructure

• Nanopore is etched through silicon

Translocation and detection

• Wafer incorporated into microfluidic chamber

• Fluorescently labelled DNA induced to pass through nanopores

• Fluorescence from individually labelled nucleotides detected optically at high speed (up to 1 million bases/second)

Adapted from “Continua Alliance Overview” © Continua Alliance 2007

Service Provider

Domain

Service

Commissioner

Domain

Service User Domain

Continua „ecosystem‟

Driving Innovation

Converging technologies

What‟s the relevance?

What‟s the impact?

Results must lead to a decision

User Challenge Roadmaps – basic template

Now 5 Near 10 25-30 20

Systems

Applications

Technologies

Drivers and trends

Time (Years)

UC2 Roadmap (sections only)

More rapid cost effective NA

sequencing

Early detection of

infection in humans

Identification of known

pathogens

Genome sequences for all

known pathogens

Lab based

detection and

„understanding‟ of

novel pathogens

Continuous improvement in sequencing power

Immune signatures of

human infectious

diseases emerging

International system of

sampling at risk populations

etc agreed

Positioning of international

reference „laboratories‟

and networks agreed

Wild animal

surveillance from

UC1

Significance of novel

pathogenic sequences

recognised

Sampling regimes

upgraded in zoonotic

“hot-spots”

Ability to distinguish

between pathogens

and non-pathogens

International organisation

established to oversee

networks, prioritise threats

and respond (WHO?)

Immediate

vaccine/drug

development for

pathogens with

potential “high impact”

“TIME”

UC2 Roadmap

Now 5 Near 10 25-30 20

More rapid cost effective NA

sequencing

Early detection of

infection in humans

Identification

of known

pathogens

Novel sequencing

technologies (eg

random, high-throughput

single molecule

Genome sequences

for all known

pathogens

Early detection of

infection in animals

Lab and field

devices

(UC3)

Lab based

detection and

„understanding‟

of novel

pathogens

Miniturisation

and effective

UC1 systems

allow transfer

of novel

pathogen

detection to

UC3

Biomarkers

limited, especially

in animals.

Increased understanding of biological processes generating novel biomarkers

Diplomatic initiative and internationalisation

Decreased cost and increased efficiency of genomic sequencing

Bioinformatics and capabilities described by UC1 (eg web crawling, data collection, modelling and remote sensing)

Nucleic acid sequencing

routine

Range of NA amplification

technologies – PCR based

and isothermal, For

detection and quantification

NA microarrays standard,

protein arrays less universal.

Trend to bead based systems

and automation

Increased capacity of

NA arrays with

quantification

Routine protein

arrays for Dx and

marker discovery

Continuous improvement in sequencing power

Multiiple

approaches to

proteomics and

marker discovery

Immune signatures

of human infectious

diseases emerging

Immune signatures

of animal infectious

diseases emerging

International system of

sampling at risk

populations etc agreed

Positioning of international

reference „laboratories‟ and

networks agreed

Wild animal

surveillance from

UC1 Significance

of novel

pathogenic

sequences

recognised

Sampling

regimes

upgraded in

zoonotic “hot-

spots”

Ability to

distinguish

between

pathogens and

non-pathogens

International organisation

established to oversee

networks, prioritise threats

and respond (WHO?)

Immediate vaccine/drug

development for pathogens

with potential “high impact”

Field based

data from

UC1

Comprehensive

databases of known

pathogens

established

UC3 Roadmap (section)

“Time”

Standard platforms

agreed

Wild animal surveillance

defines zoonotic hot-

spots. UC2 informs design

of screening test

Animal biomarkers

for pathogens

Detection of pre-

symptomatic

disease and host

susceptibility

Novel

sequencing/detection

technologies

Devices for increasing numbers of known

diseases available. Trend from UC3A to

UC3B and from professional to non-

skilled users

Smart

objects

Trend from PCR to robust simple

amplification technologies and systems

capable of functioning in extreme environmental

conditions

UC3 devices for

novel human

diseases

UC1 systems mature

enabling full integration

of UC3 devices with

global networks

UC3 devices for all known

pathogens available. Output fully

integrated into international networks

maximising data utility etc

Immune signatures

of animal infectious

diseases emerging

Immune signatures

of human infectious

diseases emerging

UC3 Roadmap

Growing market in personal healthcare, driven by devices for management of chronic diseases, general wellbeing and lifestyle

Nanotechnologies, microfluidics, MEMS, developed for other markets allow reduction in sensor size and improved capabilities

Decreasing size and cost of GC-MS - driven by space flight, environmental and homeland security

Animal DIM

mainly by

symptoms, not

biomarkers

Now Near 10 25-30 20

Standard platforms

agreed

Wild animal

surveillance defines

zoonotic hot-spots.

UC2 informs design

of screening test

Animal

biomarkers for

pathogens

Detection of pre-

symptomatic

disease and host

susceptibility

Novel

sequencing/detection

technologies

Devices for increasing numbers of

known diseases available. Trend from

UC3A to UC3B and from professional to

non-skilled users

Smart

objects

POC devices for

non-ID applications

eg. SMBG and

pregnancy tests

Mobile telephony and pervasive computing allow more rapid networking and greater local data and processing power

Trend from PCR to robust simple

amplification technologies and systems

capable of functioning in extreme environmental conditions

Cheaper microfluidic based biosensor technologies for

nucleic acid and protein determination

POC

technologies

available for

DIM but limited

UC3 devices

emerge for

professional use

Mobile phones

measure pulse,

blood pressure etc

UC3 devices for novel human

diseases

UC1 systems mature

enabling full

integration of UC3

devices with global

networks

UC3 devices for all

known pathogens

available. Output fully

integrated into

international networks

maximising data utility

etc

Immune signatures

of human infectious

diseases emerging Immune signatures

of animal infectious

diseases emerging

Devices linked to networks – UC3B

Stand-alone devices – UC3A

KE

Y

NA sequencing

etc lab based

Compliance-

based

testing UC4

health

checks

Increasing range of

pathogens detectable

in enclosed spaces

Direct DIM of

pathogens using

genomics and

post-genomics

Cheaper microfluidic based biosensor technologies for

nucleic acid and protein determination

Cheaper sequencing and

microarray technologies

Miniaturisation

and pervasive

ICT

UC Synthesis Roadmap

Now Near 10 25-30 20

Internationalisation

Decreasing cost of ICT, data collection devices (from cameras to biosensors) and genome sequencing Miniturisation

Increased levels of global movement

Mobile telephony, pervasive computing and bioinformatics

Increased understanding of biological processes generating novel biomarkers

Temperature

sensing

DIM of spores

Dust collection

Limited correlation of

SLCs and VOCs to

disease status

Mobile

phone

with

location

Web

crawling/

text mining

Collection of

disparate data

from CCTV etc

Integrated

network for

the DIM of all

known and

unknown

pathogens

Standard platforms

agreed

Mobile phones

measure pulse,

blood pressure etc

Advanced miniaturised

chromatographic and

spectroscopic analysis

Semantic mapping

problem solved

Portfolio of novel

markers

UC3 devices for non-

ID applications,

some ID POC

Lab based systems

for early detection and

„understanding‟ of

novel pathogens

Trend from PCR to robust simple

amplification technologies and systems

capable of functioning in extreme environmental conditions

Immune signatures

of human infectious

diseases emerging

Immune signatures

of animal infectious

diseases emerging

Recognition molecules

and biological pathways

from animal olfactory

systems identified

VOC markers

maturing for

plants and

food products

All known and potentially unknown (beyond 25

years) pathogens detectable in cabins,

containers air bridges packages (baggage,

cargo, enclosed spaces)

Flow systems for

managing responses

Comprehensive

databases of known

pathogens

established

Novel

sequencing/detection

technologies

UC3 devices for

professional use

Devices for increasing numbers of

known diseases available. Trend from

UC3A to UC3B and from professional to

non-skilled users

Detection of

pre-

symptomatic

disease and

host

susceptibility

UC3 devices for all

known pathogens

available.

Remote sensing

Abstraction from

unstructured data

Dynamic semantic security

Automatic interpretation of

bioinformatic databases

African electronic data collection spread from SA Northwards

Wild animal

surveillance. Animal DIM

mainly by

symptoms

Immediate vaccine/drug

development for pathogens

with potential “high impact”

Foresight Infectious Diseases: preparing for the future

UK Government

Culture and governance issues SSA China UK

Go

ve

rna

nc

e

International + + +++

Regional/supra-national groupings ++ + ++

National ++ ++ +++

Local/provisional ++ +++ +++

Ability to implement measures through legal or coercive measures ++ +++ +

DIM interaction with control mechanisms + ++ +++

Investment in science and technology + ++ +++

Data-sharing culture ++ + +++

So

cia

l

as

pe

cts

Religious and societal beliefs/concerns +++ +++ +++

+ limited influence

+++ prominent influence Greater importance

In 10 – 25 yrs

Driving Innovation

New hope for sepsis

… This new injection of money and innovative enterprise

into combating this devastating and lethal disease will

hopefully lead to doctors being able to diagnose with

confidence and initiate life-saving therapy early, and

ultimately to fewer people dying needlessly worldwide….

Thank you