Influence of Technology on Scientific Collaboration – Indonesia Experience

Herawati Sudoyo MD PhD

Eijkman Institute for Molecular BiologyIndonesian National Academy of Sciences

Trends in Science and Technology Relevant to the Biological and Toxin Weapon Conventions – Beijing, 31 October – 3 November 2010

Mission - To advance fundamental knowledge in the field of molecular cell biology, and to apply such knowledge to the understanding, and the

prevention of and treatment of human diseases

Eijkman Institute for Molecular Biology

Christiaan Eijkman 1858-1930

• Re-opened in 1992, as response to urgent need of Indonesia for a biomedical research institute capable of tapping the substantial growth of knowledge and technical development in molecular cell biology

• Continuing the proud tradition of the Eijkman Institute which was initially founded in 1888 with Christiaan Eijkman, a Nobel Laureate, as the foundation Director

Indonesia and Infectious Diseases – a Great Challenge to Mitigate Biorisk

Problems with emerging and reemerging infectious diseases

Most caused mainly by environmental, ecological or demographic factors spread by travel and trade – Indonesia is a maritime country with 17.504 islands, 700 languages, 33 provinces, 220 million population

Problems with people movementRecognize the need to develop, strengthen and maintained the capacity to detect, report and respond to public health events

Mount Merapi Volcanic Eruption – 26 October 2010

Indonesia Tsunami Kills More than 340October 27, 2010 |

Indonesia – A very diverse populations – vast genome diversity – disease management complex Indonesia - A rapidly developing country with serious challenges in infectious (emerging and re-emerging) and zoonotic diseases

WHAT ARE WE FACING?

Indonesia –problems in Infectious disease

Dengue: Most important viral borne diseaseIn 2004: 78,690 cases (CFR- 1.2%)In 2007: 123,174 cases,1,251 deaths

Hepatitis B:10% of population are carriersModerate-to-high endemic (WHO)

Avian Influenza: 133 positive cases (CFR: 80%) - highest case number and fatality rate in the world

Malaria:15 million cases and 42,000 deaths/year (2005) - highest case number and fatality rate in the world; increasing drug resistant parasites

Tuberculosis:ranked third in TB burden following India and China

- TB is third major causes of mortalityEstimation: 529.000 TB cases (2007)

Toraja

Ambon

DiliKupangJavanese

Chinese Indon

Sumba

Karo

Alor

Medan

P"bang

Padang

Jakarta

S'baya

Pontianak

Mandar

B'masin

B'papan

M'kassar

Manado Ternate Daruba

S'raja

M'taram

S'bawa

M'mereW'ngapu

Sorong

J'puraNabire

Merauke

Japan

Taiwan

ShanghaiNanning

Hongkong

Korea

Bangkok

C East AsiaB1 JapanB2 ChinaB3 West IndonesiaB6 East Indonesia

Population related HBV subgenotypes

Eijkman Institute

Toraja

Ambon

DiliKupangJavanese

Chinese Indon

Sumba

Karo

Alor

Medan

P"bang

Padang

Jakarta

S'baya

Pontianak

Mandar

B'masin

B'papan

M'kassar

Manado Ternate Daruba

S'raja

M'taram

S'bawa

M'mereW'ngapu

Sorong

J'puraNabire

Merauke

Japan

Taiwan

ShanghaiNanning

Hongkong

Korea

Bangkok

Population Structure and Disease – Hepatitis B Virus

HB/C major genotype in mainland Asia and Papua

HBV/B dominant in Austronesian speakers

Serotype Legend

4 13 2

42%

30%

8%

20%41%

32%

19%

8%

Makassar 2007-2008N = 111

Merauke 2001

Palembang 1998

Bandung 2002

Yogyakarta 1996

Jayapura 1994Jakarta 2004

Corwin 2001; Suwandono 2006; Porter 2005; Graham 1999; Richards 1997; Sukri 2003

DENV serotype distribution in Indonesia DENV serotype distribution in Indonesia –– showed diversity showed diversity

Four antigenically distinct serotypes: infection with one serotype does not provide protection to the other three

Management of Disease is not Simple, Need a Strong Disease Surveillance and Fundamental Research

Role of Research Institution i.e. Eijkman Institute in national response to Emerging Infectious Disease•

To provide scientific and technological support to the national diagnostic laboratory network, including capacity building

•

As the leading research laboratory, in particular in genomic research (viral as well as host) and pathology

•

As the major back up diagnostic facility in emergency situation,

such as in pandemic response

Prepare for future emerging infectious disease threat

Research is an Essential Component of Response to Emerging Infectious Diseases – Maximize Existing Resources and Facilities to Enhance Effectiveness

Building Capacity in Detection, Diagnosis and Tracking Outbreaks of Infectious Diseases

Development of diagnostic tests (AI)Hemaglutinating activity indicates the presence of influenza virusReverse Transcription-PCR assay for molecular identificationPositive test by RT-PCR should be confirmed by the second Institution - confirmation by sequencing analysisRT- PCR and antigen testing carried out in BSL2

Tracking outbreaks

BSL3 laboratory conditions are required for HPAI viruses

culture - detection of viral sequence changes (infection with other subtypes have been associated with outbreaks in other species)

The Role of Science and Technology in Health Security – Preparedness for Pandemic

Risk Assessments carried out by:

Molecular Epidemiology study

•

Grouping of viral in clades or subclades –

•

Surveilance -

tracing sources of infection

Molecular Characterisation of Virus

• Alteration of interaction with host receptors i.e. pandemic need changing in specificity of avian type receptor into human-type

• Change of virulence • Drug resistance – no sign

Message: Accurate diagnosis and pathogen characterization is a cornerstone in the control of disease. Improvements to detection and diagnostic capabilities are important.

Preparedness for New Emerging Infectious Diseases

FROM BENCH TO BEDSIDE -

the capability to respond to a new

emerging infectious diseases –

i.e. designing new detection method

for A/H1N1 on HA, NA and PB2 genes based on 133 sequences deposited at GISAID

Adopt new detection protocol (CDC and SEARN – Oxford)

Message – Strong Basic Research Support the Capability to Respond to New Emerging or Reemerging Diseases

SEA Infectious Diseases Clinical Research Network is a collaborative partnership of hospitals and research institutions in Thailand, Vietnam, Indonesia

Focus on human and avian influenza and other infectious diseases of public health importance in the region

The international institute partners are NIAID, Oxford University, Wellcome Trust, and WHO.

provides technical leadership and administrative support.

University of Oxford, Center for Tropical Medicine, Nuffield Department of Medicine

The aim is to build a multilateral, collaborativenetwork based on shared principles of respect, sharing

and commitment to improve patient management through quality clinical research

Network offers short and long term scholarships, academic and clinical centered, locally or abroad to strengthen research capacity

Participation in study-specific seminars and workshops and trainings for conducting studies according to international guidelines; developing laboratory and diagnostic expertise; enhancing institutional support structures for conducting and overseeing studies; and, establishment of internal quality assurance and quality control system.

Collaboration, Commitment, Coordination and Sharing

New Technology Boost More Scientific Collaboration – an Asian Experience

• Consortium of 40 institutions in 11 countries - Singapore, Indonesia, Japan, China, Korea, Thailand, Malaysia, Philippines, Taiwan, India

• 1953 individuals - 73 pre-defined populations, 11 language families• Affymatrix 50K chips

118155

359

215

95

217165

90 80

246

13 8 9 4 1 6 9 3 2 13

178

140

50100150200250300350400

Affymetr

ix Data

China

India

Indon

esia

Japa

n

Korea

Malays

iaPhil

lipine

sSing

apore

Taiwan

Thaila

nd

Samples Populations

Steering Committee (Scientific Management):E. Liu (Singapore), Y. Sakaki (Japan); S. Marzuki (Indonesia), G. Zhao (China).

Pan-Asian SNP Initiatives Science 306; 1667 (2004)

Japan, Singapore, China and Korea provide technical and scientific training for scientists in less developed countries

Benefit for Indonesia…..we can access state-of the art technology which is currently out of reach………..

Some researchers have to reconcile the work with local regulations prohibiting the export of DNA materials – prepare DNA for chip hybridization at home or participating scientist s may be able to hand deliver samples to one of the technology centers and bring the remaining samples home

Holocene colonization

4,500 ybp

3,500 ybp4,000 ybp

Pleistocene colonization

60,000 ybp?

55,000 ybp

40-60,000 ybp

MIGRATORY ORIGINS OF THE INDONESIAN POPULATIONS – OUT OF AFRICA

AUSTRONESIAN SPEAKERS

PAPUAN SPEAKERS

Papuan speaking population

Austronesian

Austro-asiatic

Science, 326, 1470, 2009

Massive effort concluded that Asia was initially settled by single wave of migration along coast

Southern route more important contribution to east and SEA populations

Future Project – analyzing more genetic markers to map diversity and to extend work to genomic medicine, identifying genetic characteristics associated with certain diseases

Uniqueness:Comprises 93 researchers in 11 countries – a grass rootConceived by Asians in Asia and executed, funded and completed by Asian Consortium

Expanding the use of safe and modern diagnostics – National capacity building in fundamental and translational research

Participation in infectious disease surveillance networks

Scientific enterprise has become highly collaborative within and across countries – efforts successful if community function in more global integrated way – scientist can work together with full trust and confidence

Conclusion – Together, We can

Thank you and greetings from Indonesia