Establishing the Taiwan Genetic Data Bank
BY TONY YANG
The completion of the Human Genome Project marked the dawn of a bold new era — the era of the genome in biology and medicine. There has been growing biomedical research on relating population-based genomic analyses to diseases. This is a transformation from investigating a small group of individuals to analyzing the whole population. To optimize the use of biomedical resources in Taiwan, the government has made significant efforts to establish one of the most advanced industrial environments of genomic medicine and pharmacogenomics in the world, via two major projects: a national health information infrastructure by the Health Insurance Bureau1 and a population-based genomic database for diseases (Taiwan Genetic Data Bank) by Academia Sinica2 The idea of the Taiwan Genetic Data Bank is that of a resource center, providing specific genomic information on the Taiwanese population combined with other biomedical data such as epidemiology, genetics, and environmental factors for various diseases. In addition, the Taiwan Genetic Data Bank will also provide useful information for public health units to monitor the most common and complicated inherited diseases. By working with officials and researchers in public health, academia, and private industries, the Taiwan Genetic Data Bank will contribute to improving the practice of disease screening and diagnosis, the surveillance and prediction of drug side effects, the development of new targeted molecular and gene therapy, and ultimately disease prevention.
As an initial step to establish the Taiwan Genetic Data Bank, Taiwanese authorities will conduct a pilot study, which consists of selecting participants according to the distribution characteristic of different ethnic population among Taiwanese residences. There will be three recruitment centers located respectively in Miaoli county (Central Taiwan), Chiayi city (Southern Taiwan), and Hualien county (Eastern Taiwan). Different combinations of ethnic groups are targeted in order to collect biological samples, including in the following areas : (1) Miaoli county, comprising subjects with descent of Fujian (19th century or earlier), Hakka (19th century or earlier), and Mainland (20th century); (2) Chiayi city, with individuals of Fujian and Mainland descent; and (3) Hualien county, with subjects that are of indigenous, Fujian, and Mainland descent. People, 40 to 70 years old, will be recruited by random selection, stratified by different sex, age, and ethnicity. This pilot study aims to collect twenty thousand specimens within the first three years. Furthermore, the Ethical, Legal, and Social Implications (ELSI) research group has been established to explore and analyze various issues involved in building the Taiwan Genetic Data Bank. This group promotes integrative projects, based on theoretical concepts that call for a greater need of adjusting and reconstructing related research fields. For example, one of its initiatives is to modify the current personal data protection laws. The ELSI research group has mapped out policy implementation and plans for the next five years. In During the first year, the group will formulate an ethical, legal, and social infrastructure for building a genetic data bank. The following year, the ELSI research group will set up legal regulations, monitoring mechanisms, and ethical standards vis-à-vis the creation of a genetic data bank. Simultaneously, it will establish interdisciplinary research drawing on the Global Declaration for the need of practical usage, a document issued by the United Nations Educational, Scientific and Cultural Organization. During the third year, the ELSI research group promotes the commercialization and industrialization of genomic research results. During the fourth year, the ELSI group plans to provide concrete suggestions to modify ethical standards and legal infrastructures related to genomic researches. During its last year, the project will be expected to meet the requirements of international bioethical standards and a final evaluation will use the analytical tools established by the ELSI group.
CHARACTERISTICS
Compared with traditional biomedical research, genetic data bank projects of this magnitude have some unprecedented features. First of all, they aim to collect tissue samples and personal genetic data from a substantially large population. For instance, the Taiwan Genetic Data Bank plans to collect blood samples and health data from 200,000 people, the UK genetic data bank forecasts a sample of at least 500,000 men and women aged 45-69 from the United Kingdom population. Moreover, these genetic data bank projects need considerable funding, logistic support and technical collaboration. Suffice it to say that for such an enterprise, the public sector increasingly depends on the private sector to fund and participate in the research. As a case in point, the UK genetic data bank explicitly claims that involvement of the pharmaceutical and biotechnology industry in the project is crucial for its success. In Taiwan, the genetic data bank project includes private capital since the very beginning. In fact, many pharmaceutical and information technology (IT) companies have eagerly pushed the government to establish the Taiwan Genetic Data Bank. Interestingly, the government also clearly underlined that one main purpose of the genetic data bank project was to promote the biotech and IT industry in Taiwan. Last but not least, while commercial involvement is almost inevitable, it is expected that genetic data bank projects will benefit the society as a whole in terms of improving health services and medical research. Considering the large number of participants needed, and given that large-scale genetic data banks are usually backed by public funding and government agencies, there is a general consensus that the success of genetic data bank research greatly depends on public trust and support.
RATIONALE
In the past, genetic databases in Taiwan were all small-scale specimen collection projects that lacked complete information such as environmental factor exposures. Without extensive collection and proper statistical methods to control various factors, the results from those small-scale specimen collection projects could be misleading and unreliable with significant bias. On the contrary, the establishment of population based genetic data bank could provide substantially better and large-scale data for cross sectional studies between individual genetic component and various environment factors in the near future. Furthermore, to set up a special pharmacogenomic data bank or to build a DNA data bank to prevent and diagnose diseases or to predict drug side-effects all require the establishment of population based-genetic data banks in order to create reliable results with clinical significance. By combining the bio-information technology with population-based genetic resources, it is expected to see rapidly progressing and prosperous biomedical industries. That is the reason why many countries or big biomedical companies are organizing and establishing population based genetic data banks.
Genetic data bank research in the past has been characterized by small specimen size, incomplete or inadequate measures of exposure, lack of formal statistical controlling of effects and the use of retrospective case-control design. To translate recent advances in genetics and reliable information of direct clinical, etiological and public health relevance, there is a pressing need for comprehensive and reliable large-scale, data on how both, genotype and environmental factors affect the risk of disease. A large population-based prospective study would provide such data including a wide range of conditions, environmental factors and genotype and would therefore constitute an important resource for future health research.
To establish a pharmacogenomic DNA bank and a single nucleotide polymorphisms library3 could be a millstone for Taiwan to develop biomedical and biopharmaceutical industries and then become the main Asian center for clinical trial and drug testing for Chinese populations. To achieve this goal, setting up a population-based DNA bank represents the first critical step because only data from population-based genetic data banks are the foundation for comprehensive analyses and comparisons.
Biomedical investigation focusing on genetics is a feasible and desirable next step to help translate recent basic research advances into practical applications. The newly gained knowledge by mapping the human genome, thus directly applies to public health issues. Additionally, progress in information technology has improved the feasibility and cost-effectiveness of conducting large-scale epidemiological studies.
In the past, studies, which consisted of building small-scale genetic databases, were only approved by institutional review boards4 in different institutes and followed by individual regulations without much consistency and uniformity. Besides, the degree of compliance, and the power of execution and enforcement for these regulations were always questionable.
Integrating data from different small-scale genetic databases would therefore not be appropriate for future studies, especially for those with clinical implications, because of the lack of well-organized and well-designed legal mechanism for informed consent and confidentiality protection in existing small scale studies.
CHALLENGES
Large-scale genetic data bank projects and population genetics have triggered a number of controversies at both national and international levels. Most attention has been focused on issues of informed consent, privacy, and data security. However, there are also issues stemming from the dichotomy between commercial interest and public trust.
Many people have concerns about private sector interests in biomedical research, and empirical data show that these concerns may affect public trust and support. For example, in the UK, a survey by the Human Genetics Commission found a clear aversion to the use of personal genetic information for commercial purposes. The same survey also shows that participants overwhelmingly favored public ownership of new products developed from using genetic information. Public opinion data from Canada suggest that the public generally lacks trust in corporate responsibility in the biotechnology field and that it tends to mistrust researchers if they are collaborating with for-profit companies. In Taiwan, according to a survey conducted in 2005, about 78% of the interviewees worried about the possibility that their genetic information may be released for commercial purposes.
It goes perhaps without saying that donors may feel cheated if they find that researchers or private companies appeal to altruism to collect their samples on the one hand, but make profit and do not actually return a reasonable portion of the profit to the public on the other. The recent lawsuit against a researcher and Miami Children’s Hospital (MCH) filed by families afflicted with Canavan disease5 and the Canavan Foundation can serve as a good example. This case involves an alliance between parents and not-for-profit organizations that sought the help of researchers to develop prenatal testing for Canavan disease, and hoped that the testing could be made accessible and affordable to the public. From the beginning, it was obvious that they donated their blood samples and money for the common good. That was exactly why they felt betrayed when they learned that the researcher and his employer, MCH, secretly obtained a patent for the Canavan disease gene they discovered, and began to charge royalties and limit the availability of tests.
In addition to its possible adverse effects on public trust, the commercial involvement may harm scientific integrity as well. For instance, many empirical studies show that objectivity—which is central to the scientific pursuit of truth—has been eroding because of commercialization trends. Studies found that when a researcher is funded by a company, results of the research tend to favor the sponsor’s products. Additionally, many sponsors, especially pharmaceutical companies, require their researchers to withhold data and findings from colleagues because of commercial secrets or competition. In the end, the decline of scientific integrity may further hurt the public trust in biomedical research.
In order to overcome this dichotomy or at least lessen in an acceptable way, benefit sharing mechanisms with concerned populations is essential to ensure public trust and support. In the future, the administrators of the Taiwan Genetic Data Bank should consider reaching a benefit-sharing agreement with each company that applies for using the data, and the agreement should specifically stipulate that the company should share the benefits with Taiwanese society as a whole, to ensure that Taiwanese people receive the common good they have been promised.
REFERENCES
Daniel Fu-Chang Tsai Conflict of Interest in Medical Healthcare, 48 JOURNAL OF TAIPEI MEDICAL ASSOCIATION 35 (2004).
Eric G. Campbell, Data Withholding in Academic Genetics: Evidence from a National Survey, 287 JAMA 411 (2002).
Jocelyn Kaiser, Population Databases Boom, From Iceland to the U.S., 298 SCIENCE 1158 (2002).
Justin E. Bekelman et al., Scope and Impact of Financial Conflicts of Interest in Biomedical Research, 289 JAMA 454 (2003).
Lorraine Sheremeta, Population Biobanking in Canada: Ethical, Legal and Social Issues, http://cbac-cccb.ca.
M. G. Hansson, Building on Relationships of Trust in Biobank Research, 31 J.MED. ETHICS 415 (2005).
Mary R. Anderlik, Commercial Biobanks and Genetic Research: Ethical and Legal Issues, 3 AM. J. PHARMACOGENOMICS 203, 210 (2003).
Michael Yeo, Biobank Research: The Conflict Between Privacy and Access Made Explicit,http://cbac-cccb.ca.
Mylène Deschênes & Geneviève Cardinal, Survey of National Approaches to the Development of Population Genetic Biobanks, http://cbac-cccb.ca.
Timothy Caulfield & Glenn Griener, Conflicts of Interests in Clinical Research: Addressing the Issue of Physician Remuneration, 30 JOURNAL OF LAW, MEDICINE ÐICS 305 (2002).
UK Biobank, Protocol for the UK Biobank, http://www.ukbiobank.ac.uk.
ENDNOTES
- The current health care system in Taiwan, known as National Health Insurance (NHI), was instituted in 1995. NHI is a single-payer compulsory social insurance plan which centralizes the disbursement of health-care funds, organized by Taiwan’s National Health Insurance Bureau. [↩]
- The Academia Sinica (“Chinese Academy” in Latin, literally Central Research Academy”) is the national academy of the Republic of China (Taiwan). It supports research activities in a wide variety of disciplines, ranging from mathematical and physical sciences, to life sciences, and to humanities and social sciences. [↩]
- Single nucleotide polymorphisms (SNPs) are a type of polymorphism involving variation of a single base pair. Scientists are studying how single nucleotide polymorphisms, or SNPs (pronounced “snips”), in the human genome correlate with disease, drug response, and other phenotypes. [↩]
- An institutional review board (IRB), also known as an independent ethics committee (IEC) or ethical review board (ERB) is a committee that has been formally designated to approve, monitor, and review biomedical and behavioral research involving humans with the aim to protect the rights and welfare of the research subjects. [↩]
- Canavan disease, one of the most common cerebral degenerative diseases of infancy, is a gene-linked, neurological birth disorder. Symptoms of Canavan disease, which appear in early infancy and progress rapidly, may include: mental retardation, loss of previously acquired motor skills, feeding difficulties, abnormal muscle tone (floppiness or stiffness), and an abnormally large, poorly controlled head. Paralysis, blindness, or hearing loss may also occur. [↩]
