A Brief Review on Some of the Major Biobank Developments

(1) deCode in Iceland²³⁵

Iceland appeals to genetic researchers because of its nearly homogeneous population. deCODE Genetics is based in Reykjavik and was incorporated in Delaware in 1996. Its principal aim is to make genetic discoveries that will be useful in drug development. Alliance is with the Swiss pharmaceutical company Hoffman-LaRoche ("Roche"), which agreed to pay deCODE $ 200 million over five years for the genetic identification of 12 diseases. In addition, Roche has promised to give Icelanders free of charge any drugs it may develop as a result of the research. deCODE also has partnership agreements with a number of other

234 Henry T. Greely, Iceland's Plan for Genomics Research: Facts and Implications, 40 Jurimetrics J. 159-160 (1999)

235 Pinto, Ashok M., Corporate Gnomics: Decode's Efforts at Disease Mapping in Iceland for The Advancement of Science and Profits , 2002 U. Ill. J.L. Tech. & Pol'y 467 (Fall, 2002)

pharmaceutical companies and health care institutions, including Genmab, Applied Biosystems, Partners HealthCare (formed by the Massachusetts General Hospital and Brigham and Women's Hospital, both located in Boston), and Affymetrix, Inc.

This Bioank can be taken as one of the most noted and advanced studies so far. First, the Icelandic population of 275,000 inhabitants, spread over roughly 40,000 square miles of land, is a manageable size for researchers. This

population is large enough that several diseases may be found in many different individuals, yet small enough in both population and area that it should be fairly easy to gather and enter all the necessary data to make studies fruitful. Second, Iceland has a rich genealogical tradition; many Icelanders have traced their family roots back to the fourteenth century and beyond. It is well known that genetic variation within a family is much lower than in the general population.

Against a backdrop of genetic similarities within the family, mutations that may be correlated with a disease stand out more readily. Third, Iceland maintains a universal public health system dating back to 1915. In addition, since about 1945, there has been a centralized collection and preservation system for tissue samples.

Thus, the Icelandic public health system provides the research community with strong medical history data for almost the past 100 years. Fourth, Iceland has remained relatively isolated. Aside from its indigenous inhabitants, Iceland has received few immigrants. This means Iceland has a comparatively homogenous genetic pool that has been exposed to very similar environmental influences over its history. Finally, Icelandic citizens demonstrate a willingness to participate in medical research, a willingness bolstered by strong government support of such research efforts.

In 1997, Kari Stefansson, Chief Executive Officer of deCode Genetics, approached the Icelandic government with a proposal to create a centralized database constructed of genetic information of the entire Icelandic population.

The Icelandic parliament, the Althing, saw great potential in allowing such a database to be created. The Althing had discussed plans to centralize and computerize the national health records of its inhabitants in order to improve health care throughout the nation. That plan, however, had been delayed for financial reasons. With active participation from deCode, both legislatively and financially, the plan once again became feasible. Beyond the potential scientific benefits realized through such a project, the Althing also believed that the creation of the database would provide Icelandic scientists and scholars with

employment, allowing them to stay in Iceland rather than seek other

opportunities abroad. However, while generally approving of the deCode project, the Althing expressed some reservations regarding the potential private

"ownership" and "control" of Icelandic medical records created through efforts of the public health system using public funding by a private entity.

In December of 1998, the Althing passed the Act on a Health Sector Database that authorized the creation of a national database consisting of genetic, genealogical and medical history data of all inhabitants of Iceland. The Act provides that the database be operated by a licensee for terms of no greater than twelve years at a time, subject to the Act and special license agreements. Not surprisingly, the first licensee of the database is deCode Genetics.²³⁶

(2) Human Tissue in Singapore

In Singapore, they use theterm “human tissue”to referallkindsofhuman biological materials derived from living or cadaveric donors, including solid body tissue, organs, fortuses, blood and other body fluid and their derivatives, cord blood, embryos, genomates (sperm or eggs) or any part or derivative

thereof.²³⁷ These new life sciences offer enormous promise of potential benefits.

Singapore takes the view that the vast majority of scientists and researchers are responsible and are acutely aware of potential ethical concerns in the work that they do, and in that which they may propose to carry out. Singapore’sview isthat human tissues collections by private individuals should not be encouraged, and that, as far as possible, tissue banks should be held by institutions. Such

institutions may be a public or private character.

In respect of donations of cadaveric tissue, the Medical Act enables people to state in advance their intention to donate their bodies, organs or tissues for research of for transplantation after their death. It also enables the family of a deceased person to donate the body, organs or tissues for research or for transplantation.Besides,when itcomesto apatient’sconsent,itshould be reviewed by an independent ethics review committee or body. They recommend ethical principles that no tissues shall be taken, or shall be accepted, unless the full, free and informed consent of the donor has been obtained. Besides, patients

236 ???????Nts. 69-82 & accompanying texts.

237 Actually, when the Singapore name it “human tissue,”still, the samples they collect can still be recognized by the scientist as the object to be collected for Biobank. For the detail, please refer to partv3 of this paper, titled by “III The Characterization of Bio Bank Related Property Right Issues.”

should be informed when material left over following diagnosis or treatment, might be used for research. ²³⁸

In Singapore, the tissue collection plan is geared by the government agency, known as A*STAR²³⁹ The agency mandate is aimed to promote the knowledge creation and exploitation of scientific discoveries for a better world. Just like this authormentioned atvery beginning,normally,it’salmostimpossibleto establish aBiobank withoutgovernment’sblessing orsupports.

(3) Biobank in UK

In the United Kingdom, the National Health Service ("NHS") possesses 50 years of data, including patient records and tissue samples, which have enormous potential value for genetic research. However, British scientists and lawmakers have been cautious to avoid the notoriety that has plagued Iceland. The Human Genetics Commission also emphasized public awareness by publishing a document discussing the basics of genetic research and its implications. In addition, privacy and consent are major concerns. A government report found that the Data Protection Act of 1998, which makes it illegal to identify specific patients without their personal consent, provided adequate safeguards for processing personal genetic data and did not deem further protection necessary.²⁴⁰

238 The Bioethics Advisory Committee Singapore, Human Tissue Research, 27^thFeb. 2002.

239 A*STAR is a luminous Constellation, charting the course for Singapore's Science and Technology.

It comprises the Biomedical Research Council (BMRC), the Science and Engineering Research Council (SERC), Exploit Technologies Pte Ltd (ETPL) and the Corporate Planning and Administration Division (CPAD). Both BMRC and SERC promote, support and oversee the public sector R&D research activities in Singapore. Both Councils fund the A*STAR public research institutes which conduct cutting-edge research in specific niche areas in Science, Engineering and Biomedical Science.

The following R&D Capability Diamonds show clearly how the research capabilities of A*STAR Research Institutes strengthen the key industries in Singapore. Agency of Science, technology and Research, http://www.a-star.edu.sg/astar/index.do.

240 Following the research protocol, all men and women aged 45 to 69 and registered at participating general practices will be sent an explanation of the study and an invitation to take part, signed by their general practitioner, accompanied by the study questionnaire and consent form.

Participants will be asked to bring the completed questionnaire to their appointment with the research nurse. At this appointment the statement of consent will be discussed and those wishing to take part will provide written consent to do so.

He or she will be reminded that participation in the study is purely voluntary and that he or she is free to withdraw from the study at any stage. It will also be made clear that any decision regarding

participation will not affect his or her health care in any way. Potential participants will also be assured of the confidentiality of all personal data and that such data will be treated in full accordance with the Data Protection Act and will be used for medical research only.

Besides, the storage system used for the biological samples will ensure access for future studies nested within the overall cohort.

These databases therefore provide a reliable, unbiased and accessible electronic source of data on

UK Biobank is expected to contribute substantially to international

knowledge regarding the combined effects of genotype and exposure on the risk of disease. Its design means that the study will provide a structure and resources for future research, and will enable researchers to address current and unforeseen scientific questions.

Potential participants will have been informed of several questions in

writing;including “thatparticipation ispurely voluntary and thatthey arefreeto withdraw from thestudy atany time,”“thatthey willnotreceiveany individual feedback about their blood results or any other aspect of their data, apart from theimmediateresultoftheirphysicalexamination,”“thattheirblood samples willbestored indefinitely;”²⁴¹and will have had the opportunity to discuss them with a research nurse and via the freephone helpline.

Involvement of the pharmaceutical and biotechnology industry in the project is therefore essential to maximize delivery of potential health benefits.Potential participants will be informed of the likely involvement of commercial bodies, along with the reasons underlying their involvement.

The Department of Health and the appropriate regulatory body will be informed at the earliest possible stage of any relevant findings. Overall relevant findings will be conveyed to study participants via regular newsletters and, where appropriate, web-based media will be used to make findings available to the public.

prescription of medication to participants which can be updated regularly. For the detail of UK Biobank, please refer to Medical Research Council & Department of Health, The UK Biobank Protocol－－ a atudy of genes, environment and health, Feb. 2002.

241 For others, include the followings;

1. the purpose and nature of the study;

2. the study methods and what participation would involve;

3. that any decision they make about participation will not affect their future health care in any way;

4. that their data will be kept strictly confidential in accordance with the Data Protection Act, used for medical research only and will never be used in a way which would identify them personally;

5. that the study will be important for future research and that many of the tests and analyses which will be conducted in the future cannot be specified at present;

6. that their future health will be tracked through a number of different National Health service sources;

7. that they are likely to be asked to provide more information for the study in the future;

8. that the research has been approved by the appropriate Multi-centre Research Ethics Committee and that all research carried out within the study will conform to strict ethical guidelines;

9. that there will be a committee to monitor the conduct of the study which is independent of the study investigators and will ensure that the public interest is served by the study.

(4) Other Proposals for Population-Based Genetic Studies A. Estonian Gene Bank

While the Icelandic project is the furthest along, similar projects are at various stages of development throughout the world. In 1999, Estonia created the Eesti Geenikeskus, or Estonian Genome Foundation, which plans to create the Estonian Gene Bank. Unlike Iceland, Estonia is not an isolated population with a fairly homogenous gene pool. Nevertheless, Estonians are genetically similar to inhabitants of mainland Europe. Therefore, Estonia's larger population will facilitate the detection and study of rare diseases expressed in a very small number of individuals. A draft proposal on the project was presented to the Ministry of Social Affairs in April 2000 and the Human Genes Research Act was passed in December 2000. Specific provisions of the Act will be discussed in Section V, but it is expected that about one half of the funding necessary will be provided by the government with the remainder supplied by companies wishing to have access to the information. In fact, the Estonian Genome Foundation launched a website in November 2000 to attract investors to its project. When completed, the government hopes the database will contain DNA and medical records of at least two-thirds of the 1.4 million Estonians.

B. Proposed Studies in Italy and Tonga

In October 2000, ten remote villages grouped in southern Italy were targeted for populational genetic studies based on their unique gene pool. These villages have existed relatively undisturbed for thousands of years. In fact, many of them had no roads or electricity until fairly recently. Their isolation has created an extremely homogenous gene pool that researchers trust is very valuable. A team from the International Institute of Genetics and Biophysics, a division of the Italian National Research Council, has already begun the

collection of genealogical data in Gioi, Cilento, and other remote Italian villages, and the collection of DNA samples will commence soon. Unlike other targeted populations, the residents of this remote region have not raised concerns over their privacy or the manner in which their data will be used. Instead, the residents have embraced the project in hopes of increasing tourism and employment opportunities for local residents. Like several other projects, the Italian National Research Council is contributing only part of the funding for the project. It is

hoped that private companies interested in the data will provide additional financing to complete the project.

In late November 2000, it was announced that an Australian based company, Autogen, acquired the exclusive right to a database being developed in the South Pacific nation of Tonga. The Tongans have also enjoyed relative isolation for many years and their population of 108,000 inhabitants consists primarily of Polynesian descendants. Autogen said that under its deal with the Tongan government, participation in the study will be strictly voluntary and all data collected will remain government property. In exchange for use of the data, Autogen will also set up a major research facility on Tonga that will provide the local residents with jobs and the company agreed to pay royalties to the

government on any discoveries that eventually may be commercialized.

C. Proposed Studies in the United States

Several similar projects have been proposed or begun in the United States as well. One failed proposal would have expanded the research data already

collected by the Framingham Heart Study, which has been collecting medical data on the residents of Framingham, Massachusetts since 1948. Boston

University, in partnership with a group of venture capitalists, founded a company called Framingham Genomic Medicine to reorganize the data already collected from over 10,000 participants and supplement it with additional DNA

information. However, the deal was cancelled in December 2000 after negotiations broke down. One major point of contention was the University's desire to continue making its research data, which was collected using public funds, freely available to nonprofit researchers, whereas the company planned to generate profits by selling access to the data to commercial enterprises. The two sides were unable to reach an agreement satisfying both goals, thus highlighting one common battle in population-based studies relying on both public and private funding.

In August 2000, a California company, DNA Sciences, launched a Web site designed to attract potential participants for its research efforts. The company relies on altruistically motivated volunteers to participate. Under the DNA Sciences approach, volunteers are asked to answer a series of on-line questions about family and medical history. Following completion of the survey, the volunteer is contacted if his or her profile matches any of DNA Sciences' current

studies so that a blood sample may be collected. DNA Sciences hopes to attract between 50,000 and 100,000 volunteers through its on-line efforts. Information collected from the volunteers will then be available to various pharmaceutical and biotechnology companies willing to purchase access to the data for use in their own research projects.

In a similar venture, but using a different appeal, a Chicago-based company, First Genetic Trust, opened its doors in October 2000. Rather than appealing to a participant's altruism, First Genetic Trust stresses its commitment to maintaining the privacy and confidentiality of genetic information by leaving the power to control the data and its use in the hands of each individual participant. The company plans to function as an intermediary between researchers, healthcare providers, and patients by supplying educational and counseling services, as well as a secure DNA "banking," or storage service, thus balancing the privacy of the individual with the need for researchers to have access to crucial populational data.

Other similar projects in the earliest stages of development are announced almost monthly. Each study is aimed at developing immense databases of information that may be used by researchers to understand the intricacies of genetic diseases. This information will also be used by pharmaceutical

companies to develop more accurate genetic tests, more effective gene therapies directed at treating and curing various disorders, and, eventually, the

development of drugs and treatments specifically designed for individual patients based on their unique genetic makeup. To reach that goal, mountains of data will need to be collected and analyzed. Understandably, genomic research represents billions of dollars in both investment costs to create the databanks and potential profits for the companies who maintain and access the databanks.