Sustainable Energy Options for Electric Power Generation in Peninsular Malaysia to 2030

ADVISORY REPORT ON STEM CELLS: AGEING AND REGENERATIVE MEDICINE ASM ADVISORY REPORT 4/2013

ASM Advisory Report 4/2013 Advisory Report on Stem Cells Ageing and Regenerative Medicine Academy of Sciences Malaysia 2013 i

Chairman Prof Emeritus Cheong Soon-Keng, FASc (UTAR)Report Editor Dr Loke Seng Cheong (UPM)Taskforce Members Dr Zubaidah Zakaria (IMR) Mr Perumal Chinaya (MMC) Dato' Dr Abdul Hamid Abdul Kadir (MMC) Dr Caroline Jee Siew Yoke (Nottingham U.) Dr Chua Ken Hui (UKM) Prof Dr Ruszymah Idrus (UKM) Associate Prof Tunku Kamarul Zaman Tunku Zainol Abidin (UM) Dr Loke Seng Cheong (UPM) Dr Rajesh Ramasamy (UPM) Associate Prof Lim Yang Mooi (UTAR)Secretariat En P. Loganathan Ms Nurul Hidayah A. Razak ii

Foreword Over the last decade, stem cell research (c) To identify the legal, ethical and religious framework and therapy has attracted much attention already in place and the shortfalls, if any. from the scientific community and the lay public, both because of the d) To ascertain whether the current policy and funding on extraordinary promise and the difficult stem cells and ageing research are adequate; and ethical issues that accompany this field. e) To investigate whether there is a role for traditional and The potential of stem cell therapy and complementary medicine (TCM) in regenerative regenerative medicine to improve the medicine and prevention of ageing. health and function of our senior citizens is tremendous. This is especially The Task Force was headed by Emeritus Prof. Cheong Soon Keng,important given that Malaysia’s population is rapidly ageing and and comprised of subject matter experts from the researchthe cost of healthcare to both individuals and society will institutions active in stem cell research. Findings from the draftcorrespondingly increase. report were presented to various stakeholders in this field at a workshop, and the feedback was incorporated into the final report.Stem cell research locally is being carried out in the private and The Institute of Gerontology at Universiti Putra Malaysia providedpublic sector across multiple institutions, and it is difficult to full access to its research database on the state of the ageingdetermine the current state of progress and research capacity population and hosted the abovementioned workshop.nationally for this field. This is important as an objectiveassessment will enable the government to determine the priority The publication of this Advisory Report is in fulfilment of one offor resource allocation based on the likelihood and magnitude of the Academy’s functions, namely to provide independent advice toreturn on its investment. the Government through dissemination of ideas and suggestions from scientists, engineers, and technologists through identifyingAs such, the Academy of Sciences has commissioned a Task Force where the innovative use of science, engineering, and technologyto prepare an advisory report with the following terms of can provide sound solutions to particular national problems.reference: I am glad that this Advisory Report will be disseminated and (a) To ascertain the current status of the ageing population in made available to the various relevant Ministries, universities, and Malaysia and issues relevant to ageing. research institutes for wider public consumption. (b) To ascertain the current state of art and capacity of stem Tan Sri Dr Ahmad Tajuddin Ali, FASc cell treatment and therapy in Malaysia President, Academy of Sciences Malaysia iii

P r e fa c e Malaysia is currently at a crossroad in its Life sciences and biotechnology is one of the cutting edge areas in development in which important which we should be focusing our attention. In this area, cell decisions must be made which will therapy is projected to become the key research field within the determine whether it is able to realise its next five years. This advisory report aims to give an overview on ambition of becoming a developed the current state of cell therapy research in Malaysia, and provide nation by 2020. We have many policy recommendations which can help to steer its growth in a advantages such as rich natural direction which contributes to our nation’s development. resources, favourable demographics, and a strong scientific tradition. However, the Prof Emeritus Dr Cheong Soon Keng, FASc gulf between developing and developed Chairperson,nations is wide, and this can be bridged only by having a ASM Task Force on Cell Therapy: Ageing and Regenerativeconsistent policy of investment in both our infrastructure and Medicinehuman capital.While funding for research is reasonable considering our currentstage of development, there is a big shortfall in highly qualifiedmanpower. Approximately ten percent of tertiary educatedMalaysians have migrated to other countries, and the figure isworse for researchers, of which about one-third have gone abroad.Moreover, the total research expenditure for Malaysia is less than1% of what the United States spends. If we want to survive as asmall fish in a big pond, we need to think smart and considersolutions that are ‘out of the box’. Our country does not have theresources to do everything, and we will need to pick and choosecarefully to maximise the return on our research investment. Wehave to adopt a ‘blue-ocean’ strategy. iv

Contents Foreword iii iv. Policy and Funding for Stem Cell Research 33 Preface ivi. Evidence on Ageing, Chronic Disease, and Disability Trends 4.1 Policy and Funding for Stem Cell Research Worldwide 34 1.1 Population Ageing 6 7 4.2 Funding for Stem Cell Research in Malaysia 41 1.2 The Importance of the Demographic Window 9 1.3 Chronic Non-communicable Diseases and Disability 12 4.3 References 46 1.4 The Role of Regenerative Medicine in Reversing Disability 15 1.5 References 17 v. TCM, Regenerative Medicine, and Ageing 47ii. Current Status of Stem Cell Research and Services 18 2.1 Stem Cell Research Worldwide 19 5.1 Traditional and Complementary Medicine (TCM) 48 2.2 Stem Cell Research in Malaysia 20 2.3 References 25 5.2 The Role of TCM in Regenerative Medicine 53iii. Ethical and Religious Issues for Stem Cell Research 26 3.1 Ethical and Religious Issues for Stem Cell Research 27 5.3 The Practice of TCM in Malaysia 55 3.2 Regulatory Framework for Stem Cell Research Worldwide 29 3.3 Regulatory Framework for Stem Cell Research in Malaysia 31 5.4 References 56 3.4 References 32 vii. Recommendations 57 6.1 Evidence on Ageing, Chronic Disease, and Disability Trends 63 6.2 Ethical, Religious, and Regulatory Framework 64 6.3 Policy and Funding for Stem Cell Research 66 6.4 TCM, Regenerative Medicine, and Ageing 74 6.5 Overall Recommendations 75 6.6 References 81 viii. Glossary 82 ix. Appendix 84 v

CHAPTER 1. EVIDENCE ON AGEING, CHRONIC DISEASE, AND DISABILITY TRENDS The population in Malaysia is ageing rapidly This results in a smaller labour force supporting more dependents, thus limiting economic productivity Disability levels are relatively high in Malaysia, which reduces the number of older people in the labour force, while increasing health and social costs for the nation The top four chronic diseases which cause disability are dementia, musculoskeletal diseases, visual-hearing impairments, and cardiovascular diseases Reduction of disability can extend the productive life of older people Stem cell therapy can achieve this by regenerating damaged tissues and organs, thus restoring lost function 6

Population Ageing 4000 Female 9.9 10.0 3500 Male 7.4 9.0 3000 % 8.0 7.0 Number of older persons 60 years or over ('000) 6.2 6.0 Proportion of older persons to total population (%)5.0 2500 5.7 5.5 51.8% 4.0 3.0 5.2 2.0 1.0 2000 0.0 1500 51.6% 1000 52.3% 48.2% 500 50.6% 52.7% 47.7% 48.4% 47.3% 2010 47.8% 49.4% 52.2% 1980 1991 2000 2020 0 Year 1970 Figure 1. Trend of population ageing in Malaysia, 1970 – 2020 (1).Population ageing is said to occur when changes in a country’s The proportion of females in the population is also expected tolife expectancy and birth rate results in a shift in population rise due to a longer lifespan.distribution towards older age groups. This usually arises as anatural consequence of socioeconomic development from a pre- The Demographic Transition (DT) model suggests thatindustrial to an industrialised state. In Malaysia, the proportion of developing countries pass through a series of population stagesolder persons 60 years and above is rapidly increasing and during which mortality and fertility rates both fall as a resultexpected to exceed 10% of the total population by 2020 (Figure 1) of better healthcare, nutrition, education, availability of(1). contraception, and 7

the entrance of women into the labour force (2). The four stages 100+from the DT model can be represented by population pyramids 95-99(Figure 2). 90-94 85-89 80-84 Male Fe m al e 75-7965 70-74 Male 65-69Age Female 60-64 Age group 55-5915 50-54 45-49 Stage 1 - expanding Stage 2 - expanding Stage 3 - stationary Stage 4 - contracting 40-44 35-39 Figure 2. Population pyramids for 4 stages of the demographic 30-34 transition model (2). 25-29 20-24In Stages 1 and 2, the base of the pyramid is broad, with a high 15-19proportion of young people, a small proportion of older people, 10-14and a growing population. In Stage 3, both fertility and mortalityrates are balanced, and population growth is stationary. By Stage 4, 5-9the population is ageing with low fertility and mortality rates, a 0-4small proportion of young people, and a growing proportion ofolder people. Malaysia presently is in stage 2, but is expected to 87 65 43 21 012 34 56 78rapidly progress to Stage 4 by 2050 (Economic Planning Unit 2009) Percent (%)(Figure 3). Male, 2000 Female, 2000 2050 Source: Economic Planning Unit 2009 Figure 3. Population pyramids, Malaysia 2000 and 2050 (3). 8

The Importance of the Demographic WindowPercent of population (%) 80 Demographic Window 0-14 35 Years 15-64 70 65+ 60 50 40 30 20 10 0 1950 1955 1960 1965 1970 1975 1980 1985 1990 1995 2000 2005 2010 2015 2020 2025 2030 2035 2040 2045 2050 Period Source : UNDP 2011; Batelle 2012 Figure 4. Population aged 0 – 14, 15 – 64 and 65+ in Malaysia, 1950 – 2050 (4, 5).As a country progresses through the stages in the DT model, there population t o maintain the economically dependent, such aswill be a period during which the proportion of population within children and the elderly. When a country has a high dependencythe working age group is particularly high. During this period, ratio, a significant proportion of the government’s expenditurewhich is called the Demographic Window (DW), the ratio of will be channelled towards maintaining health services, pensions,population not in the labour force (dependent) to those in it and educational facilities. In contrast, a country with a low(productive) is relatively low. This ratio is called the dependency dependency ratio will have more available resources which can beratio, and indicates the burden on the productive part of the directed towards socioeconomic development. 9

100 Severe disabilityWHODAS-II Score (%) Median disability 80 60 40 20 0 Malaysia Australia Malaysia Australia 8 2 44 21 60–64 15 2 50 25 65–75 27 6 67 31 75–85 Source: National Statistic of HealthFigure 5. Comparison of WHODAS-II scores for median and severe disability between Malaysia and Australia (7)*. * Wellness National Data 2009 – Institute of Gerontology, UPM. Median disability = 50th percentile, Severe disability = 90th percentile.The UN Population Department defines the DW as the period in The standard DW definition presumes that the working populationwhich the proportion of children and youth under 15 years falls is productive up to the age of 65 years old following the trend in developed countries. In Malaysia, there is strong evidence that thebelow 30% and the proportion of people 65 years and older is still productive life of older people is limited by disability and abelow 15%. The DWs for major regions are as follows: Europe relatively early retirement age. For many years, the retirement age1950-2000, North America 1970–2015, China 1990–2025, and for the public sector was set at 55 years, and it is only recently thatIndia 2010–2050. For Malaysia, the DW is expected to last from measures have been taken to increase it to 60 years (6). In addition,2010 – 2045 (Figure 4) (5). 10

Percent of population (%) 80 0-14 15-59 70 60+ 60 Effective Demographic Window 20 Years 50 40 30 20 10 0 1950 1955 1960 1965 1970 1975 1980 1985 1990 1995 2000 2005 2010 2015 2020 2025 2030 2035 2040 2045 2050 Period Source : UNDP 2011; Batelle 2012 Figure 6. Population aged 0 –14, 15–60 and 60+ in Malaysia, 1950–2050.local data has shown that for comparable age cohorts, older people democracies which have had long DWs of about 40–50 years.in Malaysia experience more disability than their peers in other Malaysia needs to make necessary changes now to adapt otherwisecountries such as Australia (Figure 5) (7). the productivity gains from its DW will be lost by mid-century as a result of pressures from an ageing population.If the working population in Malaysia is productive only until theage of 60 years old, this will translate into a shortened effective DWof o n l y 2 0 y e a r s ( Figure 6 ). This i s i n c o n t r a s t t o t h eWestern 11

Chronic Non-Communicable Diseases and Disability30% DEMENTIA 25% CANCER RESPIRATORY20% VISUAL-HEARING MUSCULOSKELETAL RENALVISUAL-HEARING 14% GASTROINTESTINAL 12% CARDIOVASCULAR 11%10% MUSCULOSKELETAL CARDIOVASCULAR DEMENTIA0% Figure 7. Population attributable risk for WHODAS-II disability in older Malaysians. * Combined MHQoL National Data 2006, Psychological Well-Being National Data 2007, Wellness National Data 2009 — Institute of Gerontology, UPM.Based on nationwide data on community-dwelling older people in simultaneously. Usage of all types of healthcare resourcesMalaysia, the top four chronic disease groups which cause increases with degree of disability, with a striking rise in publicdisability are dementia, musculoskeletal diseases, visual-hearing healthcare usage (Figure 8).impairments, and cardiovascular diseases (Figure 7). According to the International Classification of 75% of older people suffer from at least one of these four Functioning, Disability, and Health model from the World Healthchronic disease groups, with 35% having two or more Organisation, disability is said to arise from pre-existing healthdiseases conditions in an 12

Health seeking Behaviour (Mean Visits Past 3 Government Services Months) 3 Private Services Other Services Traditional Medicine (Eastern) Alternative Medicine (Western) Composite Health Seeking Behaviour 2 1 0 5 - 15 16 - 31 32+ Figure 9. Relationship between disability and chronic diseases <= 4 from a lifetime perspective (10). WHODAS-II (Quartiles) predominate. These diseases begin to manifest in adult life, and eventually cause functional impairments which contribute to Figure 8. Healthcare usage by older Malaysians according to disability in old age (Figure 9). degree of disability. When an individual’s level of disability exceeds the* Combined MHQoL National Data 2006, Wellness National Data 2009 — Institute disability threshold for that population, that individual is then of Gerontology, UPM. unable to function independently in society, requires care from others, and becomes what is conventionally known as “disabled”.individual, and can restrict participation in any area of life (8, 9). Local Malaysian data on the Katz basic activities of daily livingAn older person with some level of disability may find difficulty (ADL) supports the concept of a disability threshold (Fig. 10). Thewith formal employment, and be unable to help with looking after implication is that a relatively small change in an individual’s levelyoung family members. Those with a high level of disability of disability who is close to the threshold can render that personbecome dependent, and require care and support from others. either functionally independent or disabled. Most of the disability in an older person occurs as a result ofa lifetime accumulation of impairments from chronic diseases.During early life, risk factors for development of chronic diseases 13

Katz ADL Disability threshold 6 5 4ADL 3 2 1 0 0 20 40 60 80 100 WHODAS-II score (%) Figure 10. Disability threshold based on the Katz activities of daily living. * MHQoL National Data 2006 - Institute of Gerontology, UPM. 14

The Role of Regenerative Medicine in Reversing Disability Policies Retirement AgeProductive Risk FactorsLife Disability Disease Treatment Regenerative Stem Medicine Cell Therapy Figure 11. The hierarchy of factors affecting the productive life of older people in Malaysia.A reduction in disability among older Malaysians coupled with disabled-friendly policies, building designs, and assistiveappropriate policy changes to give them the option to work later technology (Figure 11).in life, can extend the productive lifespan of older people, andlengthen the country’s effective DW. This reduction in disability is Regenerative medicine however provides an alternative avenuetraditionally accomplished by targeting risk factors and better for achieving this, by regenerating damaged tissues and organs,treatment of chronic diseases. Disability can also be mitigated by restoring lost function, and hence reversing existing disability. Stem cell therapy is a sub-set of regenerative medicine, and is a 15

disruptive technology which has the potential to reshape thedisability profile of older Malaysians (Figure 11) (11). Stem cellresearch in Malaysia should be directed towards developingtreatments which target the top local causes of disability, andreducing the costs involved so that they are affordable for a largesegment of the population. 16

REFERENCES1. Department of Statistics Malaysia. Population Distribution 8. Grimby G, Smedby B. ICF approved as the successor of and Basic Demographic Characteristics. Putrajaya: ICIDH. J Rehabil Med. 2001 Sep;33(5):193-4. Department of Statistics Malaysia; 2010. Available from: http://www.statistics.gov.my/portal/download_Popu 9. World Health Organization. World Report on Disability. lation/files/ census2010/Taburan_Penduduk_dan_Ciri- Geneva: World Health Organization 2011. ciri_Asas_Demografi.pdf. 10. Kalache A, Kickbusch I. A global strategy for healthy ageing.2. Contributors. Demographic transition. Wikipedia, The Free World Health-Geneve. 1997;50(4):4-5. Encyclopedia; [12 January 2012]; Available from: http:// 11. Mason C, Brindley DA, Culme-Seymour EJ, Davie NL. Cell en.wikipedia.org/w/index.php?title=Demographic_tr therapy industry: billion dollar global business with ansition&oldid=468935841. unlimited potential. Regen Med. 2011 May;6(3):265-72.3. United Nations Department of Economic and Social Affairs. Institute of Gerontology Raw Data on Population Ageing in Malaysia Population Division, Population Estimates and 1. Nurizan, Y., Tengku Aizan, H., Asnarulkhadi, A. S., Projections Section. 2004 [cited 2012 15/1/2012]; Available from: http:// Mumtazah, O., Afida Mastura, M. A. and Bukryman, esa.un.org/wpp/unpp/panel_population.htm. S. (2010). Patterns of Social Relationship and Psychological Well Being among Older Persons in4. United Nations. World Population Prospects: The 2008 Peninsula Malaysia. Revision, Comprehensive Tables: United Nations; 2010. 2. Tengku Aizan, H., Siti Sa'adiah, H. N., Zaitun, Y., Zaiton, A., Mohmad, S., and Yusuf, M. (2009). Determinants of5. Economic UNDo, Division SAP. World population to 2300: Wellness among Older Malaysians: a Health Promotion United Nations; 2004. Perspective. 3. Tengku Aizan, H., Sarinah Low, A., Rosnah, I., Nurizan, Y.,6. Jabatan Perkhidmatan Awam Malaysia. Saraan Baru Sharifah Norazizan, S. A. R., Asnarulkhadi, A. S., Esther Perkhidmatan Awam. 2012 [cited 2012 15/1/2012]; Gunaseli, E., Suraya, Y., Yau, W. K., Ismail, D. and Shanui, Available from: S. (2006). Mental Health and Quality of Life of Older http://www.jpa.gov.my/kategori.html. Malaysians.7. Andrews G, Kemp A, Sunderland M, Von Korff M, Ustun TB. Normative data for the 12 item WHO Disability Assessment Schedule 2.0. PLoS One. 2009;4(12):e8343. 17

CHAPTER 2. CURRENT STATUS OF STEM CELL RESEARCH AND SERVICES There are a number of companies and health institutions which provide stem cell therapy services in Malaysia Developed countries are strong in laboratory based stem cell research, while developing countries have an advantage in conducting clinical trials The researchers who are active in stem cell research constitute about 0.5% of the total research manpower in Malaysia The pattern of stem cell research locally is more typical of a developed country 18

Stem Cell Research WorldwideIn recent years, the increasingly globalised nature of healthcareresearch has led to outsourcing of clinical trials from high costdeveloped nations to developing countries where the researchinfrastructure and local technical skills are less advanced. Thisoutsourcing takes advantage of the high disease burden, low costof research, and the varying standard of ethical review andregulation in developing countries (1).In the developed world, regulatory control is usually strict andclinical trials are both expensive and difficult to conduct without astrong base of pre-clinical research. Existing laboratories andfunding infrastructure are usually well developed, and this gives astrong advantage when conducting pre-clinical work. For thedeveloping world, regulatory control is much more permissiveand subjects for clinical trials are readily available in largernumbers. Laboratory work is however more difficult to performas the research infrastructure is usually quite basic, and theresearchers less experienced. 19

Stem Cell Research in MalaysiaTABLE 1. CONFERENCES AND WORKSHOPS ON STEM CELL RESEARCH. Name Date Venue Adult stem cell workshop. 20–23 Oct 2003 HUKM 22–23 July 2008 HUKM2nd National Tissue Engineering and Regenerative Medicine Scientific 10–14 Nov 2008 HUKM Meeting, 2nd MTERMS 2008. 12–13 Dec 2009 IMU Cell based therapy workshop. 13–14 Oct 2010 25–26 Apr 2011 UPMSeminar on Advances in Stem Cell Therapy Current Research & Future Hotel Equatorial Penang Applications ASCT 2009.3rd National Tissue Engineering and Regenerative Medicine Scientific Meeting, 3rd MTERMS 2010. Annual International Conference on Stem Cell Research SCR 2011.Appendix tables 2-IA and 2-IB list the companies and health There are about 110 researchers in local institutions that are activeinstitutions that provide stem cell therapy services in Malaysia. in the field of stem cell research, which is about 0.5% of the totalAbout half of the companies specialise in cord blood banking research manpower in Malaysia (approximately 21,500 full timeservices. equivalent staff) (2) The universities with the largest manpower in this field are Universiti Kebangsaan Malaysia (UKM), UniversitiA number of conferences and workshops have been held on stem Putra Malaysia (UPM), Universiti Malaya (UM), and Universiticell research locally (Table 1). Sains Malaysia (USM), while Stempeutics has the largest research 20

353025201510 5 0 Figure 1. Researchers in the field of stem cell research by institution. * Information compiled from websites and research management centres of the respective institutions. ** See Appendix Tables 2-II and 2-III for the institution abbreviations. 21

80 commercial entities, Stempeutics has the highest output and productivity, and even outperforms the major universities where60 productivity is concerned (Figure 4). This is in part due to a ctive collaboration and funding from the Ministry of Health.40200 CLINICAL OTHERS LAB Figure 2. Journal articles by type.* LAB - pre-clinical and laboratory research, CLINICAL - clinical trials, OTHERS - includes review articles. ** Indexed by Pubmed Medline as of March 2012. Note: the list may not becomprehensive, and includes only articles where the corresponding institution is in Malaysia.contingent amongst the commercial entities (Appendix Table 2-II,Figure 1).A search through Medline turned up about 100 journal articles onstem cell research by Malaysian institutions over the past 10 years,with a cumulative impact factor of 130 (Appendix Table 2-III). Ofthese, 74% are based on pre-clinical research, 6% on clinical trials,and the remaining 20% review articles (Figure 2). From thedistribution of articles, it can be seen that the pattern of researchfollows that of developed countries.Of the universities, UKM, UM, and UPM have the highest outputfor article count and impact factor, with UKM dominating the field(Figure 3). However, when the output is measured per researcher,all three universities perform similarly (Figure 4). Amongthe 22

Article Count Impact Factor5040302010 0 IIU IMR IMU UiTM UKM UM UPM USM Private Not Stated Figure 3. Journal count and cumulative impact factor for articles on stem cell research by institution. * Indexed by Pubmed Medline as of March 2012. All impact factors (IF) from Thomson ISI Web of Knowledge 2011 database. ** Note: the list may not be comprehensive, and includes only articles where the corresponding institution is in Malaysia. See Appendix Tables 2-II and 2-III for the institution abbreviations. 23

Articles / Researcher IF / Researcher543210 IIU IMR IMU UiTM UKM UM UPM USM Private Figure 4. Article count and impact factor (IF) for stem cell research per researcher by institution. * Indexed by Pubmed Medline as of March 2012. All impact factors (IF) from Thomson ISI Web of Knowledge 2011 database. ** Note: the list may not be comprehensive, and includes only articles where the corresponding institution is in Malaysia. See Appendix Tables 2-II and 2-III for the institution abbreviations. 24

REFERENCES1. National Bioethics Advisory Commission. Report and Recommendations of the National Bioethics Advisory Commission. Bethesda: National Bioethics Advisory Commission2001 4/2001.2. Frost & Sullivan. Malaysian Biotechnology: Human Capital Development Report 2009. Kuala Lumpur: Biotechcorp2009. 25

CHAPTER 3. ETHICAL, RELIGIOUS, AND REGULATORY FRAMEWORK Ethical and religious issues arise from embryonic stem cell research and cloning technology Religious and regulatory authorities are more tolerant of therapeutic cloning, in contrast to reproductive cloning Most countries with an established or rapidly growing biotechnology industry allow embryonic stem cell research and therapeutic cloning Malaysian guidelines allow embryonic stem cell research and therapeutic cloning with some restrictions 26

Ethical and Religious Issues for Stem Cell Research TABLE 1. RELIGIOUS VIEWS ON EMBRYONIC STEM CELL RESEARCH AND THERAPEUTIC CLONING (1–8).RELIGION Embryonic research Therapeutic cloning Reproductive cloning Islam Allowed Allowed Not allowed Catholic Christian Not allowed Not allowed Not allowedNon-Catholic Christian Not allowed Not allowed Not allowed Not allowed Buddhism Allowed Allowed Hinduism Allowed Allowed Not Stated Not allowed Not allowed Not allowed Sikh Not allowed Not allowed Not allowed Taoist * Religious views where there is no central authority are diverse, and the above table refers to prevailing opinion among adherents.Most of the controversy surrounding stem cell research centres on The benefits of using embryonic rather than adult stem cells areembryonic stem cell research and cloning technology. There is less that:of an ethical problem with xenotransplantion of animal cells astissues and organs from these sources have already been used for (1) These cells are relatively easy to grow in culturemany years in clinical treatment (e.g. skin substitutes for burns, (2) They are totipotent and can form all cell types found inprosthetic heart valves). the body (3) These cells can be easily isolated from the embryo; and (4) They can be used where adult stem cells are difficult to isolate (e.g. neural tissue) 27

The benefits of therapeutic cloning (somatic cell nuclear transfer)are more limited, and come from producing an embryonic stemcell line that is genetically identical to the patient, thus reducingthe chance for graft rejection. In contrast, reproductive cloning hasno clear medical benefits.Regulatory authorities and funding bodies have a duty to weighthe potential benefits from these techniques against the ethical andreligious concerns that arise from their use. The main issue fromembryonic stem cell research and therapeutic cloning is that thesetechniques require the destruction of an embryo that couldpotentially form into a new human being. In addition, therapeuticcloning is seen by some as the first step towards reproductivecloning, which is the generation of a child that is geneticallyidentical to the parent.Religious bodies have diverse views on both these techniques, butin general are more tolerant of therapeutic cloning provided it isdone under regulatory guidance which prohibits crossing over intoreproductive cloning (Table 1). Most religions agree thatreproductive cloning is morally and ethically wrong (1). 28

RegulatoryFrameworkfor Stem Cell ResearchWorldwide TABLE 2. GOVERNMENT POLICIES ON EMBRYONIC STEM CELL RESEARCH AND THERAPEUTIC CLONING (10–12).Country Embryonic research Therapeutic cloning Reproductive cloning VariesUnited States* Varies Varies Not allowedUnited Kingdom Allowed Allowed Not allowed Not allowedChina Allowed Allowed Not allowedIndia Allowed AllowedSingapore Allowed Allowed * No federal regulation has restricted stem cell research of any kind, but state laws varyThe regulatory stance of countries active in stem cell researchgenerally mirrors the religious views of their population.Countries with a strong Catholic Christian tradition have the mostrestrictive policies, while those with secular traditions have themost liberal regulations (Table 2, Figure 1). In addition,countries with a large established o r rapidly growingb i o t e c h n o l o g y industry tend to have more permissivepolicies governing stem cell research (see chapter 4 for moredetails). 29

Permissive policy - embryonic stem cell research permitted, including therapeutic cloning (somatic cell nuclear transfer)Flexible policy - embryonic stem cell research restricted to fertility clinic embryos no longer needed for reproductionRestrictive or no policy - either outright prohibition on embryonic stem cell research or restriction to established cell lines Figure 1. Government policy on embryonic stem cell research and therapeutic cloning (9). 30

RegulatoryFrameworkfor Stem Cell ResearchIn Malaysia TABLE 3. MALAYSIAN GUIDELINES ON EMBRYONIC STEM CELL RESEARCH AND THERAPEUTIC CLONING.Authority Embryonic research Therapeutic cloning Reproductive cloning Not allowedMinistry of Health Allowed* Allowed* Not statedMedical Council Allowed* Not Stated * Some restrictions applyResearch on stem cells in Malaysia is presently not covered by anylegislation. Provision of stem cell therapy services by healthproviders is also similarly not restricted provided that the PrivateHealthcare Facilities and Services Act (1998, Act 586) is compliedwith (13).The Ministry of Health has issued a set of guidelines coveringstem cell therapy, and the Malaysian Medical Council is also in theprocess of finalising its own guidelines (Table 3). While these arenot legally binding legislation, the regulatory authorities will takethese into consideration should any problems arise in the future(14). The Ministry of Health guidelines also prohibitxenotransplantation, except in cases where clear evidence existsfor benefit to the patient. 31

REFERENCES1. Lim S, Ho C. The Ethical Position of Singapore on Embryonic 8. The Editor. Hindu View on Cloning. [cited 2012 9/3/2012]; Stem Cell Research. SMA News. 2003;35(6):21-3. Available from: http://www.hinduismtoday.com/modules/2. Hukum Pengklonan Terapeutik Dan Penyelidikan Sel Stem smartsection/item.php?itemid=5043. (Stem Cell), (2005). 9. University of Minnesota Medical School. MBBNet. Available3. Pontifical Academy for Life. Declaration on the Production from: http://www.mbbnet.umn.edu/. and the Scientific and Therapeutic Use of Human Embryonic Stem Cells. Vatican City2000; Available from: 10. Wikipedia contributors. Stem cell laws. 2012 [cited 2012 http://www.vatican.va/roman_curia/pontifical_academi 10/3/2012]; Available from: http://en.wikipedia.org/w/ es/acdlife/documents/ index.php?title=Stem_cell_laws&oldid=473140858. rc_pa_acdlife_doc_20000824_cellule-staminali_en.html. 11. Wikipedia contributors. Stem cell laws and policy in the4. Pontifical Academy for Life. Document of the Holy See on United States. 2012 [cited 2012 10/3/2012]; Available Human Cloning. 2004 [cited 2012 9/3/2012]; Available from: http://en.wikipedia.org/w/index.php? from:http://www.vatican.va/roman_curia/secretariat title=Stem_cell_laws_and_policy_in_the_United_States& _state/2004/ documents/rc_seg- oldid=480742715. t_20040927_cloning_en.html. 12. Bioethics Advisory Committee Singapore. Ethical, legal, and5. Dalai Lama. When Does a Stem Cell Become a Human social issues in human stem cell research, reproductive, Being? : fpmt Mandala; 2003 [cited 2012 9/3/2012]; and therapeutic cloning. Singapore2000. Available from: http://www.mandalamagazine.org/archives/mandala- 13. Private Healthcare Facilities and Services Act, (1998). issues-for-2003/march/when-does-a-stem-cell-become-a- 14. Malaysian Guidelines for Stem Cell Research and Therapy. human- being/. In: Medical Development Division, editor.2009.6. Dalai Lama. Dalai Lama: Develop mind and heart. The Statesman (India). 2005 30/4/2005. 7. Manickavel V. On Stem Cell Research. 2004; Available from: http://hinduismtoday.com/modules/smartsection/item. php? itemid=1293. 32

CHAPTER 4. POLICY AND FUNDING FOR STEM CELL RESEARCH Government support for stem cell research in Malaysia is vital to help it succeed Compared to other countries, policy in Malaysia on embryonic and xenotransplant cell research is relatively restrictive Research funding and human capital development in Malaysia is very poor compared to its economic strength This puts Malaysia at a distinct disadvantage when competing in a knowledge intensive field such as regenerative medicine and stem cell research Stem cell therapy is poised to be the major life science research area within the next five years 33

Policy and Funding For Stem Cell Research WorldwideFigure 1. Status of the biotechnology industry worldwide (2).For a relatively young area of investigation such as stem cell especially important in stem cell research where the physiologicalresearch, success is heavily influenced by the degree of processes that govern its use are still under investigation.government support. This support can be in the form of funds, apermissive regulatory environment, and a good research The use of autologous cells for stem cell therapy is fairly wellinfrastructure. Industry and venture capital grants are more accepted internationally. Embryonic and xenotransplant cellfocused on the later stages of the research cycle where a product is sources however, face varying degrees of regulatory restrictionsalmost ready for commercialisation. In contrast, government depending on jurisdiction, because of the ethical and religioussources of funding predominate in basic research, and this is issues surrounding their use. In Malaysia, the National Guidelines 34

Figure 2. Global biotechnology clusters (3).* Countries in brown rank highly in the Growth Competitiveness Index. Black circles represent biotechnology and life-sciences clusters.for Stem Cell Therapy and Research outline the circumstances in biotechnology i n d u s t r y (Figure 1, 2). Most o f t h e c u t t i n gwhich embryonic and xenotransplant cell research can be e d g e research and development takes place in purpose-builtundertaken, and is relatively restrictive compared to other science parks or research clusters dedicated to life sciences andcountries (see chapter 3 for more details) (1). biotechnology (Figure 2).The research infrastructure for biotechnology in developed nations While Malaysia has a rapidly growing biotechnology industry,is very a d v a n c e d , e s p e c i a l l y t h o s e w i t h a large funding for research and development is relatively poor comparedestablished 35

0.1% China 22.0% 0.3% Indonesia Malaysia 18.0% Thailand Malaysia 0.6%Russian Federation 1.1% Thailand 14.5% China Singapore 14.5% 1.4%Australia 1.8% Taiwan 11.0% Canada 1.9%Singapore 2.0% 2.3% South Korea 10.0% 2.6% India 9.0%Taiwan 2.6% 2.6%EU / UKUSA EU-27 6.5% U.S. 6.0%Korea 3.%2 3.4%Japan 3.5% 0.0% 0.5% 1.0% 1.5% 2.5% 3.0% Japan 5.5% Figure 3. Research and development expenditure as a proportion of Figure 4. Average annual research and development growth, GDP (6). 1996–2007 (7).to the country’s economic strength (Figure 3). This however has and this puts the country at a distinct disadvantage whenbeen increasing rapidly in the last decade, albeit from a small base competing in a knowledge intensive field such as regenerative(Figure 4, Table 1). Under the 9th Malaysia Plan, RM32 million medicine and stem cell research (Figure 7).was allocated over five years to strengthen stem cell and bloodbank activities throughout the country (4). However, this wasdwarfed by the US$5.1 billion that the National Institutes ofHealth in the United States spent on stem cell research for theequivalent period (2006–2010) (5). About 30% of research fundingin Malaysia comes from government grants, which is consistentwith the trend in most countries (Figure 5).Malaysia’s human capital investment for research is one of thelowest in the world, with the number of researchers per populationbeing less than 10% of the equivalent figure in Singapore (Figure6). The overall proportion of scientists and engineers is also verylow, 36

TABLE 1: FORECAST GROSS EXPENDITURE ON RESEARCH AND DEVELOPMENT (GERD) (7) 2010 2011 20121 United States GDP R&D GER GDP R&D GER GDP R&D GER2 China D D D3 Japan PPP as % GDP PPP as % GDP PPP as % GDP4 Germany Bil, US$ PPP Bil, US$ PPP Bil, US$ PPP5 South Korea 14,660 2.83% B4il1, U5.S1$ 15,203 2.81% B4il2, U7.S2$ 15,305 2.85% B4il3, 6U.S0$6 France 10,090 1.48% 149.3 11,283 1.55% 174.9 12,434 1.60% 198.97 United Kingdom 4,310 3.44% 148.3 4,382 3.47% 152.1 4,530 3.48% 157.68 India 2,940 2.82% 3,085 2.85% 3,158 2.87%9 Brazil 1,459 3.36% 82.9 1,549 3.40% 87.9 1,634 3.45% 90.610 Canada 2,145 2.21% 49.0 2,227 2.21% 52.7 2,282 2.24% 56.411 Russia 2,173 1.81% 47.4 2,246 1.81% 49.2 2,305 1.84% 51.112 Italy 4,060 0.80% 39.3 4,472 0.85% 40.7 4,859 0.85% 42.413 Taiwan 2,172 1.10% 32.5 2,294 1.20% 38.0 2,402 1.25% 41.314 Australia 1,330 1.95% 23.9 1,387 1.95% 27.5 1,429 2.00% 30.015 Spain 2,223 1.03% 25.9 2,367 1.05% 27.0 2,491 1.08% 28.616 Sweden 1,774 1.27% 22.9 1,824 1.30% 24.9 1,849 1.32% 26.917 Netherlands 2.30% 22.5 2.35% 23.7 2.38% 24.418 Switzerland 822 2.21% 18.9 883 2.25% 20.7 938 2.28% 22.319 Israel 882 1.38% 19.5 917 1.40% 20.6 958 1.42% 21.820 Austria 1,369 3.62% 18.9 1,409 3.62% 19.7 1,440 3.62% 20.4 355 1.84% 12.9 379 1.87% 13.7 398 1.90% 14.4 677 3.00% 12.5 703 3.00% 13.1 720 3.00% 13.7 324 4.27% 9.7 338 4.20% 10.1 346 4.20% 10.4 219 2.75% 9.4 234 2.75% 9.8 246 2.75% 10.3 332 9.1 350 9.6 359 9.9 37

2010 2011 201221 Turkey GDP R&D GERD GDP R&D GERD GDP R&D GERD22 Singapore23 Belgium PPP as % GDP PPP PPP as % GDP PPP PPP as % GDP PPP24 Finland Bil, US$ Bil, US$ Bil, US$ Bil, US$ Bil, US$ Bil, US$25 Mexico 0.85% 1,045 0.90% 1,080 0.90%26 Denmark 960 2.52% 8.2 2.60% 9.4 2.65% 9.727 Poland 292 1.96% 7.4 314 2.00% 8.2 331 2.03% 8.828 South Africa 394 3.87% 7.7 412 3.83% 8.2 423 3.80% 8.629 Norway 186 0.37% 7.2 196 0.38% 7.5 203 0.39% 7.730 Czech Republic 1,567 3.02% 5.8 1,663 3.05% 6.3 1,741 3.08% 6.831 Argentina 202 0.68% 6.1 209 0.72% 6.4 215 0.72% 6.632 Portugal 721 0.93% 4.9 765 0.95% 5.5 796 0.95% 5.733 Malaysia 524 1.80% 4.9 553 1.85% 5.3 579 1.85% 5.534 Ireland 255 1.53% 4.6 265 1.55% 4.9 274 1.55% 5.135 Hungary 261 0.51% 4.0 272 0.58% 4.2 280 0.61% 4.336 Indonesia 596 1.66% 3.0 658 1.65% 3.8 695 1.67% 4.237 Romania 247 0.64% 4.1 247 0.70% 4.1 245 0.70% 4.138 Saudi Arabia 414 1.77% 2.6 445 1.75% 3.1 472 1.75% 3.339 Greece 172 1.15% 3.0 176 1.20% 3.1 181 1.20% 3.240 New Zealand 188 0.10% 2.2 195 0.15% 2.3 201 0.20% 2.4 1,030 0.59% 1.0 1,120 0.65% 1.7 1,203 0.66% 2.4 254 0.10% 1.5 263 0.20% 1.7 275 0.25% 1.8 622 0.58% 0.6 677 0.55% 1.4 708 0.50% 1.8 318 1.18% 1.8 314 1.20% 1.7 311 1.22% 1.6 118 1.4 123 1.5 129 1.6 38

Malaysia 52 32 5 12 G-8 Singapore 58 36 1 6 Nations South Korea 75 23 11 67 26 6 1 China 75 18 7 JapanRussian Federation 30 62 1 8 France 52 38 2 9 Germany 67 30 3 United Kingdom Canada 44 33 6 17 United States 47 34 9 66 29 6 Industry Government Other Domestic OverseasFigure 5. Source of research and development funding by country (6). Malaysia 4.0 EU / UK 9.1Russian Federation South Korea 25.5 55.0 Canada 33.3 66.6 Taiwan 32.3 68.2 United States 34.9 70.9 Singapore 38.8 Japan 45.4 87.0 91.1 53.8 109.1 61.8 118.1 0 20 40 60 80 100 120 140 FTE Researchers to 10,000 Workforce FTE Researchers to 10,000 Population Figure 6 Full time equivalent researchers (FTE) by country (6). 39

8000 Americ Finland as Asia7000 Europe Singapo Other re6000 Norway Denmar5000 k40003000 Greec New United South Sweden e Zealan States Korea Israel2000 Poland d Taiwa n Canad Australia Austri Japa a a n Portug Belgiu Germa al m ny Spai Russi Franc Switzerland n a e Ireland Netherlan UK ds Czec h Republi c Italy Argentina Hungar y1000 Turke Chin Brazil a y Saudi Mexic Romani Arabia o a I o sia 0 nn 40 de

Malaysia India S 0.5 oScientists & Engineers/Million People u t h A f r i c a 1.0 1.5 2.0 2.5 3.0 3.5 4.0 4.5 R & D a s % G D P 41

Funding for stem cell researchin Malaysia Stem cell applications 54% Biologics 22% Detecting / monitoring 44% Surgical procedures 22% 34% 18% the human body 33% Carcinogens 15% Genetically 29% Proteomics 14% 28% 12% Biomarkers 24% Enzymes 12% 24% Genetically 11% Surgical implants MetabolomicsPharmaceutical products Food and beverage Cell biology processing Neuroscience Figure 8. Predicted key life sciences research areas by 2014 (7).Stem cell therapy is poised to be the major life science research There are several local sources which can provide funding forarea within the next five years, with a very high growth rate stem cell research. The Ministry of Higher Education (MoHE)(CAGR of 23% from 2006-2010) (Figure 8) (8). Currently, mainly provides grants for universities and other institutions oforthopaedic applications of stem cell therapy are the most higher learning (Table 2). The Malaysian Biotechnologydeveloped in Malaysia, but research on neurological, dental, and Corporation (BiotechCorp), Ministry of Science, Technology anddermatological use is ongoing (Figure 9, Appendix Table 4-I). Innovation (MOSTI), and Malaysian Technology DevelopmentTissue engineering is an emerging field where cultured cells are Corporation (MTDC) also allow industry based researchers tointegrated with suitable biomaterial scaffolds to create artificial apply (Table 3).tissues. Locally, there is significant research interest in this areawith a number of projects across the major universities (AppendixTable 4-I). 42

Priority of Biological Therapeutics1 Area of prevention, diagnostic and treatment Colorectal cancer, Parkinson's and Cardiovascular disease, prostate cancer Alzheimer's diseases leukemia, transplant Stem cell rejection therapy Pancreatic cancer, Spinal cord injury, breast cancer stroke, burns Inflammatory diseases,2 radioimmunotherapy Myocardial ischemia, Heart disease, diabetes Biomarkers myocardial infarction Macular degeneration, Osteoarthritis and multiple sclerosis3 Acute coronary syndrome, rheumatoid arthritis heart failure Cancer, viral Monoclonal infection antibodies Atherosclerosis, thrombosis Antibody-directed enzyme prodrug theraphy (ADEPT) Radioimmunotherapy Segment Areas Biomarkers Stem Cell Therapy Monoclonal Antibodies Low-hanging Mid-term Long-term Non conventional conventional conventional Figure 9. Priorities for life sciences research (8). 43

TABLE 2. AVAILABLE MOHE FUNDING SOURCES IN MALAYSIA.Type of Fund Details AmountFundemental research Why and how Ceiling amount RM250Kgrant scheme (FRGS) Maximum RM125K annually Research that can produce new theories or conceptsExploratory and Discipline-based researchexperimental Duration: 2–3 yearsresearch grant scheme Ceiling amount RM250K and maximum RM125K annually(ERGS) What and where Ceiling amount RM300KLong-term research Problem-based research, inter-disciplinary (within institution) Maximum RM100K annuallygrant scheme (LRGS) Expansion of ideas from the fundamental concept Findings can be further developed into applicationsPrototype research Duration: 2–3 yearsgrant scheme (PRGS) Ceiling amount RM300k and maximum RM100k annually Fundamental research that needs more than 3 years Ceiling amount RM15 million Must be multi-institutional and multi-disciplinary Maximum RM3 million annually Problem-based research Programme / cluster-based Duration: 3–5 years (at least 3 years) Ceiling amount RM15mil and maximum RM3mil annually Prototype development for pre-commercialisation Ceiling amount RM500K Duration: 1–2 years Ceiling amount RM500k * MoHE - Ministry of Higher Education 44

Available funding sources for healthcare biotechnology Type of Fund Details Source Amount Seed Fund To fund seed or start-up costs in setting up biotech BiotechCorp Up to RM2.5 companies and to assist towards the development and BiotechCorp million perResearch & Development commercialization of biotechnology projects and R&D BiotechCorp company Matching Fund findings of priority and core areas. MOSTI Maximum of International Business To provide matching fund for R&D projects which c a n RM1.0 million Development Matching develop new o r improved products and/or processes MOSTI and/or t echnologi es and lead to further development and per project Fund commercialization within the Malaysia's Biotechnology Focus Areas. Maximum of Type A: RM1.25 million Pre-commercialization To promote the expansion of BioNexus Status Companies into the global market. per project Type B : IP Acquisition Pre-commercialization activities comprise development Up to (Laboratory Scale) of pilot plant/up-scaling of laboratory prototype or RM 5 million development of commercial ready prototype/pre-clinical or clinical t r i a l s /field t r i a l s for demonstration and Up to t e s t i n g purposes and not for commercial production RM 2 million purposes. Type B comprises acquisition of IP (academic/laboratory scale prototype) from overseas or local sources and must be f u r t h e r developed to p r e -commercialization stage (Type A). 44

TABLE 3: AVAILABLE NON-MOHE FUNDING SOURCES IN MALAYSIA (8). Available funding sources for healthcare biotechnologyType of Fund Details Source Amount INNOFUND — To assist individuals / sole-proprietors, micro and small MOSTI Up toEnterprise Innovative Fund businesses/ enterprises to develop new or improve RM250,000 existing products, process or services with elements of MOSTI INNOFUND — innovation for commercialization. MTDC Up to Community Innovative MTDC RM500,000 To assist community groups to convert knowledge/idea Fund into prodcts / processes / services that improves the N/A – quality of life of communities. on case basisCRDF 1 Feasibility Study on public sector R&D results for Up toCRDF 2 university/research institution's commercialization office. RM 500,000 Commercialization of Public Sector R&D Results via Up to University/Research Institution's Spin-Off Company. RM 500,000CRDF 3 Commercialization of Public Sector R&D Results via MTDC Up toCRDF 4 Start-up Company MTDC RM 4 million Commercial Production of Any Locally Generated Up to R&D Results by SME RM 2 millionTechnology acquisition Technology Acquisition Fund (TAF) provides partial grant to MTDC Up to fund (TAF) further promote efforts by the private sector to enhance RM 300,000 their technology level and production processes.Science and technology research grant To help in research activities Malaysia Toray Science Foundation (MTSF)* BiotechCorp - Malaysian Biotechnology Corporation; MoHE - Ministry of Higher Education; MOSTI - Ministry of Science, Technology and Innovation; MTDC - Malaysian Technology Development Corporation 45

REFERENCES1. Malaysian Guidelines for Stem Cell Research and Therapy. In: Medical Development Division, editor.2009.2. University of Minnesota Medical School. MBBNet. Available from: http://www.mbbnet.umn.edu/.3. Rinaldi A. More than the sum of their parts? Clustering is becoming more prevalent in the biosciences, despite concerns over the sustainability and economic effectiveness of science parks and hubs. EMBO Rep. 2006 Feb;7(2):133-6.4. Malaysia Biotechnology Information Centre. News at Home. Petaling Jaya: Monash University Malaysia; 2012 [cited 2012]; Available from: http://www.bic.org.my/BICalert/0608/p2.html.5. National Institutes of Health. Stem Cell Information. Bethesda, MD: U.S. Department of Health and Human Services;2012 [cited 2012 28/2/2012]; Available from: http:// stemcells.nih.gov/research/funding/funding.6. Frost & Sullivan. Malaysian Biotechnology: Human Capital Development Report 2009. Kuala Lumpur: Biotechcorp2009.7. Battelle. 2012 Global R&D Funding Forecast2011.8. Frost & Sullivan. Overview: Malaysian Healthcare Biotechnology. Kuala Lumpur: Biotechcorp2009. 46

CHAPTER 5: TCM, REGENERATIVE MEDICINE, AND AGEING TCM is used in Malaysia by 50%–80% of the population The predominant forms of TCM locally are biologically based therapies such as herbal medicine TCM use rises with disability, although to a lesser extent than Western medicine The role of TCM in stem cell therapy is primarily as an adjuvant treatment Published research in this field is currently sparse Asian countries have a strong tradition of using herbs for anti-ageing TCM practice in Malaysia is monitored by the TCM division of the Ministry of Health, and supported by professional bodies 47

TRADITIONAL AND COMPLEMENTARY MEDICINE (TCM)100% 100%80% 80%60% 60%40% 40%20% 20%0% 0% Mind body Biologically Manipula!ve Whole medical Mind body Biologically Manipula!ve Whole medical medicine based therapies and body based system medicine based therapies and body based system Figure 1. Prevalence of TCM modalities in Malaysia for Figure 2. Prevalence of TCM modalities in Malaysia for health treatment (1). maintenance (1).TCM has been defined by the World Health Organization (WHO) TCM is broadly classified into four categories: mind-bodyas the sum total of the knowledge, skills, and practices based on medicine, biologically based therapies, manipulative and bodythe theories, beliefs and experiences indigenous to different based treatments, and whole medical systems (Table 1). It can becultures, whether explicable or not, used in the maintenance of used both for treatment of disease and maintenance of goodhealth as well as prevention, diagnosis, improvement, or health. Usage of TCM in Malaysia is widespread, and biologicallytreatment of physical and mental illness. According to the WHO, based therapies, particularly herbal medicine, account for most ofapproximately 65% and 50-80% of the population of developed the TCM used locally (Figure 1–2, Table 2–3).and developing countries respectively use TCM. The WHO hasalso recognised the importance of TCM in health promotion for a The overall prevalence of TCM usage in Malaysia is betweenlarge segment of the population, especially in developing 50-80%, which is similar to the WHO figures for other developingcountries. countries (1). Usage of TCM increases with the degree of disability, although not to the same extent as Western medicine (Figure 3). 48