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Research in the CBRN domain:

From Mil to extended Civ-Mil cooperation

Royal Higher Institute for Defence, March 2013

Université catholique de Louvain

Pr. Dr. JL Gala

Med Colonel,

Haematologist - Geneticist

Director CTMA / DLD-Bio

Center for Applied Molecular Technologies /

DLD-Bio

UCL-Brussels, Belgium

Plan

• Biological threats at a glance

• Observations

– 1: Biothreats no more « military-restricted»

– 2: Need for Joint Civ-Mil cooperation in CBRN_R&D

– 3: From « reach back » to « on-site CBRN testing »

– 4: Deployability & in-field testing: new Civ-Mil R&D field !

– 5: Room for further improvements: CBRN int. standards !

• Way ahead and conclusion

CBRNE

Threats

Animal Crops Human

Viruses Radiological

Bacteria

Chemical Toxins

EOD

Biological

années

morts

heures Hours Days Years

Dea

ths

C / E

B C / E

B

Biological agents : Mostly covert incidents with delayed lethality

Risk : Likelihood X impact

Copyright 2012 - CTMA/DLD-Bio

Observation 1

B-threats are no more a « Mil restricted topic »

Shift from « Mil» to « Civ-Mil»-driven R&D prompted by

- Globalization (missions, intercontinental trips…)

- Rapidly emerging diseases

- Global risks from remote, poorly accessible areas with

weak health care support

On-going and future research in the CBRN domain:

From Mil-driven R&D to extended Civ-Mil cooperation

Common Mil-Civ Needs:

Joint efforts and cooperation

VIRUSES FUNGI PROTOZOAE BACTERIA PRIONS (?)

Intentional release only

CBRN cases

Natural outbreak –

Endemic zone

Daily infections

Hospital – Ops «in-field»

POTENTIAL THREATS OCCASIONAL THREATS COMMON THREATS

Best validation & trg model

NOT EXPECTED in environment

Risk in war zone (Mil Operations)

PRESENT in natural environment

Risk for Mil Ops in endemic area

COMMON in daily life Risk anytime, anywhere

Rapid, specific and sensitive identification of living pathogens

- Deadly for human beings, animals and crops

- Contaminating the environment

TOXINS

Identification tools and technologies: all alike !

Anthrax : from disease-endemic area to bioterrorism

Accidental (benign) human infection

Deliberate release human infection

Outside «military field» !

Deadly anthrax cases

Countless anthrax copy cat

« Weapanized deadly anthrax»

Major natural outbreaks:... From Variola…. to EBOLA and Monkeypox

Smallpox

Viral Hemorraghic

Fever

Viral Hemorraghic Fever in Africa : 2012

Copyright 2012 - CTMA/DLD-Bio

Copyright 2012 - CTMA/DLD-Bio

Africa

Outbreak 2012

Infected

(confirmed, probable,

suspected)

Deaths Death rate

RDC

Ebola - Jul 2012

Province Orientale 62 34 52%

Uganda

Ebola - Aug 2012

Kibaale 24 17 30%

Luwero 7 4 58%

Uganda

Marburg - Oct 2012

Kabale, Ibanda, Mbarara,

Kampala

12 8 67%

Copyright 2012 - CTMA/DLD-Bio

Monkeypox, Varicella… or Smallpox ?

Need for rapid differencial diagnostic test !

Observation 2

Need for rapid, sensitive, reliable detection and

identification of B-agents

Joint Civ-Mil efforts and R&D cooperation in CBRN

Dual use of CBRN tools and procedures

On-going and future research in the CBRN domain:

From Mil-driven R&D to extended Civ-Mil cooperation

CTMA / DLD-Bio

« Academic - Military - Industrial » Interface

EU

Commission

Bio threats

Biomedical

EU Defense

Agency NATO

networks

Academic hospital &

university support

CTMA DLD-Bio

EU Space

Agency

Military partners

Integrated Mission Group in Security (IMG-S)

Academic partners In

tera

tio

na

l

Nati

on

al

Industrial partnership

and valorisation

(SME’s, industries)

Regional / federal

R&D projects

Copyright 2012 - CTMA/DLD-Bio

OBJECTIVE

Genetic diseases

Biomarkers / Biosensors

B-agents : typing,

virulence & antibiotic

resistance

Toxins

Academic (UCL) &

Clinical pole

(St Luc Univ Hospital)

BE-Defence

(DLD)

RESOURCES

Applied sciences - Technological transfer unit

Clinical

Genetic Testing

DLD-Bio

Genetic

Research

Spin-off

Identification

Diagnosis

CTMA / DLD-Bio

1

Engineering

Biostatistics

Bioinformatics

Biological –

Medical genetics

Copyright 2012 - CTMA/DLD-Bio

Cutting-edge identification tools:

Genetic-based identification

Copyright 2012 - CTMA/DLD-Bio

RHID / IRSD / KHID studies

MED04 Ended 2010 Genetic profile of the B-agents from the CDC “class A” list

MED08 Ended 2011 Specific genetic detection of biothreat agents in difficult sample matrix

LAND06 Ended 2012 CBRN Mixed sample analysis: ultrafiltration and B-agent genetic

identification of nanobiological agents

MED05 ONGOING Rapid DNA- and RNA-based diagnosis of highly contagious viral agents

MED20 ONGOING Multiplex genetic detection of antibiotic resistance (β-lactams and

aminoglycosides)

DLD04 ONGOING Portable DNA-based platfom for multiplex identification of B-agents in

Ops

DLD05 ONGOING Rapid detection and characterization of agents responsible for culture-

negative hospital infections

Optimization of “Mil CBRN-R&D” ?

Last 20 years: No CBRN concepts !

Needs defined by: RHID / ACOS Strat

International consortia

National consortia

Needs Opportunities

Sharing costs (technological watch compulsory…but expensive)

Mutualized benefits Copyright 2012 - CTMA/DLD-Bio

R&D CBRN-Matrix to better support « Mil R&D »

BioEDEP,

JIP-CBRN,

CBRN Cat B

COST, PASR,

FP7

Horizon

2020…

IAP/ARTES20

CBRN-SIBCRA

EDA

Marshall plan

(Biowin), Waleo,

WB Health

FEDER

Erasmus Mundi

Regional/

Federal R&D

projects

BE-MOD

RHID-projects

Interuniv. Attraction Pole

Interuniv. Coop. pole

Brain-Belspo

EC ESA

NATO

IMG-S (CBRN Think tank)

MED

LAND

DLD

BE-Biotech

(SME’s, Industries)

The matrix allows to spread costs, to mutualize the benefits and to decrease the failure rate

CBRN application: Detection of Biological Warfare

Agents (BWA): The "Dirty Dozen" (WHO) Initial Non Specific

Symptoms Pathogen

Bacteria

FLU SYNDROME

NONSPECIFIC SYMPTOMS

[fatigue, myalgia, fever, headache,

nonproductive cough, chest pain, respiratory

distress, high fever, abdominal pain

vomiting, diarrhea]

Inhalation Anthrax Bacillus anthracis

Pneumonic Plague Yersinia pestis

Tularemia Francisella tularensis

(Rabbit Fever)

Brucellosis Brucella suis

Q-Fever Coxiella burnetii

Glanders: Burkholderia mallei

Burkholderia pseudomallei

Viruses Smallpox Variolavirus

Venet. Equine Enzephalitis VEE-Virus

Marburg-Fever (Viral Hemorrh. Fever)

Marburg-Virus

Toxins Botulism Clostridium botulinum

Ricin-Intoxication Ricin

SEB-Intoxication Staphylococcal-Toxin

LUNG INFECTION : Tuberculosis

Innovative dual-use testing: example-1

Copyright 2012 - CTMA/DLD-Bio

Innovative dual-use testing: example-2

Copyright 2012 - CTMA/DLD-Bio

Copyright 2012 - CTMA/DLD-Bio

CTMA/DLD-Bio work validation ?

Few examples….

• Tomaso H, Jacob D, Eickhoff M, Scholz HC, Al Dahouk S, Kattar MM, Reischl U,

Plicka H, Strand JO, Nikkari S, Matero P, Beuret C, Lista F, Gala JL, Broll H,

Appel B, Sellek Cano RC, del Carmen Ybarra de Villavicencio M, Broekhuijsen M,

Indra A, Petersen R, Neubauer H. A multicenter evaluation of real-time PCR

assays for the identification of Yersinia pestis. Clin Chem Lab Med, 2008;46:1139-

44.

• Irenge LM, Walravens K, Govaerts M, Godfroid J, Rosseels V, Huygen K, Gala

JL. Rapid detection and specific identification M. avium subsp. paratuberculosis in

fecal samples from experimentally infected, subclinically affected cattle by a triplex

real-time PCR: comparison with conventional methods. Vet Microbiol,

2009;136:166-172.

• Irenge LM, Durant JF, Tomaso H, Pilo P, Olsen JS, Ramisse V, Mahillon J, Gala

JL. Development and validation of a real-time quantitative PCR assay for rapid

identification of Bacillus anthracis in environmental samples. Appl Microbiol

Biotechnol, 2010;88:1179-92.

• Irenge L, Gala JL. Current B. Rapid detection methods for Bacillus anthracis in

environmental samples : a review. Appl Microbiol Biotechnol. 2012;4:1411-1422.

Response

time

Selectivity Sensitivity Warning Detection Identifi-

cation

Monito-

ring

Survey /

recce

Molecular

Genetics --- + +++ + +

Immuno - ++ - + -

Optical

detection ? ? +++ ? ? + +

Physical

detection ++ + - ++ +

Hybrid

technologies

Ongoing-CBRN Research

Integration of Hybrid identification methods

Copyright 2012 - CTMA/DLD-Bio

Observation 3

CBRN threats require « rapid on-site testing»:

The concept «Light Fiedable Laboratory or LiFi »

Size ? Specificity ? Sensitivity ? Type of Samples?

Tools (analytical, communication, GIS/EO, Sat Navigation [GPS/GNSS], robots) ?

On-going and future research in the CBRN domain:

From Mil-driven R&D to extended Civ-Mil cooperation

Interoperable platform

for CRBN or Health crisis

Identical HEART

CIVILIAN

specifications

MILITARY

specifications

• Civilian-specificity

– B-specific

– Light Fieldable

– First responders (nurses,

MD)

– GOARN / WHO

• Common Civ-Mil specifications

– Analytical equipement

– Communication, site selection,

georeferencing

– Expertise (human resources)

• Military-specificity

– Full CBRN protection (heavy

shelter??)

– Heavy slowly deployable

– Sampling team

– Ops military C2

Copyright 2012 - CTMA/DLD-Bio

Observation 4

« Increased deployability » and « on-site testing »

implies facing new constraints (preparation,

communication, technologies, logistics, …) !

New field for « Civ-Mil oriented-CBRN research »

On-going and future research in the CBRN domain:

From Mil-driven R&D to extended Civ-Mil cooperation

Trigger for BE-LiFi

deployement in Africa ?

240 Km

Monkeypox MWEKA

Outbreaks 2007 & 2008

RESISTANT TUBERCULOSIS

MALARIA

DREPANOCYTOSIS...etc...

EBOLA

Endemic Monkeypox

area

Copyright 2012 - CTMA/DLD-Bio

Deployment prerequisites ?

• Rapid and easy deployment: Balance the volume/weight of the

equipments with the technical /logistic needs and constraints

(no dedicated container nor transporter).

• Robust /portable “cutting edge” technologies: avoid the loss or

damage of often sensitive equipments during the journey and

deployment.

• Specific, sensitive, reliable and validated identification of

health-threatening B-agents in a large range of samples

(flexible universal platform for complex matrixes; wide range of

B-agents)

• Compliant with biosecurity and biosafety standards (expertise,

daily training)

Deployment in Ops

conditions

No dedicated aircraft !

C130 normal rotation: 3days

Copyright 2012 - CTMA/DLD-Bio

A simple tent or even a

wooden hut…..

KUYA KUMPALA CAMP

Copyright 2012 - CTMA/DLD-Bio

• Heat

• Storms with water flood

• Lightening with power cut

Some

challenges

Copyright 2012 - CTMA/DLD-Bio

Light Fieldable Detection Laboratory

Kananga, RDC, April 2009

Modular structure : scalability – joint intervention

Copyright 2012 - CTMA/DLD-Bio

Successful monitoring of health-threatening

agents nearby a Military settlement

• Monkeypox outbreak

• Ebola outbreak

Real-time PCR

• Resistant Tuberculosis

Endpoint-PCR

Copyright 2013 - CTMA/DLD-Bio

Observation 5

Light fieldable laboratory:

Room for continous improvement –

Needs for international CBRN integration &

standards

On-going and future research in the CBRN domain:

From Mil-driven R&D to extended Civ-Mil cooperation

Copyright 2012 - CTMA/DLD-Bio

Copyright 2012 - CTMA/DLD-Bio

Copyright 2012 - CTMA/DLD-Bio

B-LiFE Proof of Concept

(Anthrax spread in EC premises in Brussels)

29 Nov 2012

Integration of Space-based technologies/ tools : Sat Communications, Sat Navigation (GPS/GNSS), GIS/Earth observation

B – LiFE ESA-

IAP/ARTES20

Biological

Light Fieldable

Laboratory for Emergencies

Data Relay Satellite

Georeferencing Sampling team:

Earth Observation: Site selection

Candidate sites 50-500m

Soccer field RMS

Copyright 2012 - CTMA/DLD-Bio

Copyright 2012 - CTMA/DLD-Bio

B-LiFE Communication flow

Wireless Optic Fiber Optic Fiber

Optic Fiber Sat Com

Wi-Fi

3G

Central Server

SES Bedzdörf Emergency.Lu antenna

Mobile lab

Sampling team

Crisis Center

Copyright 2012 - CTMA/DLD-Bio

Plan

• Biological threats at a glance

• Observations

– 1: Biothreats no more « military-restricted»

– 2: Need for Joint Civ-Mil cooperation in CBRN_R&D

– 3: From « reach back » to « on-site CBRN testing »

– 4: Deployability & in-field testing: new Civ-Mil R&D field !

– 5: Room for further improvements: CBRN int. standards !

• Way ahead and conclusion

B-LiFE supported by new projects in « R&D CBRN-Matrix »

EDA

Regional/

Federal R&D

projects

BE-MOD

RHID-projects

EC ESA

NATO

IMG-S (CBRN Think tank)

BE-Biotech

(SME’s, Industries)

• B-LiFE - IAP/ARTES20:

Biological Light Fieldable

laboratory for Emergencies

(CTMA Coordination)

• FP7-SEC-PRACTICE: Preparedness and

Resilience against CBRN Terrorism using

Integrated Concepts and Equipment

• FP7- SEC-MIRACLE: MobIle Laboratory

for the Rapid Assessment of CBRN

Threats Located within and outside the

EU (CTMA Coordination)

• BioEDEP: 2d generation

deployable tactical field

analysis (project n°6)

• Sampling

(SIBCRA) team

Copyright 2012 - CTMA/DLD-Bio

Mil R&D: Luxury or Need ?

…a clear answer is now provided by the EU institutions themselves !

But maybe no mopre as « stand alone »

Mil R&D needs to intergrate / Meet in « wider societal needs «

END

Copyright 2012 - CTMA/DLD-Bio

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