Ethics before science. This is the strong message that Singapore's Bioethics Advisory Committee ( BAC ) is sending to the biomedical research community here. However, researchers need not be too concerned. BAC's chair, Professor Lim Pin (pictured left) assures us that the objective is to make "research more formal and not more difficult."
Tasked to conduct a thorough review of the issues associated with biomedical research, BAC recently set out its first national guidelines for human tissue banking and for biomedical research that involves the use of human tissue samples. Balancing ethical and medical considerations, the guidelines governing the collection, storage, and use of human tissue samples for research were put together after extensive consultations with expert scientists, as well as local religious, professional, and civic organizations.
"We must make sure the recommendations are accepted by the community at large and are consistent with best practices around the world," says Lim. The committee maintains that establishing a national bioethics framework "signals that Singapore is being transparent in an important and sometimes controversial area of life sciences research."
Of foremost significance, perhaps, is BAC's recommendation that all research tissue banks be statutorily approved and licensed. A new statutory board will regulate and supervise all human tissue research in the republic. Hereafter, researchers using human tissues (see sidebar) will have to get their proposals approved by an appropriately constituted research ethics committee or institutional review board before they can embark on their work. The new guidelines further stipulate that tissue banks that permit research access may be set up only by or through institutions that are approved by the appropriate authorities to do so and not by private individuals.
BAC defines human tissues as all kinds of human biological materials derived from living or cadaveric donors, including solid body tissues, organs, foetuses, blood and other bodily fluids and their derivatives, cord blood, embryos, gametes (sperm or eggs), or any part or derivative thereof.
In effect, it will be illegal to engage in human tissue research privately and independently. Private individual researchers who are working independently will now have to work through approved research centres such as hospitals, research institutes, or academic institutions. "Individuals are encouraged to work with approved institutions that have established ethics review boards," says Lim. Associate Professor Terry Kaan, who heads BAC's subcommittee on human genetics, adds: "For practical purposes, these researchers should work within the framework of an approved organization with sufficient resources to ensure that there is proper ethical review." Lim points out that the guidelines are not intended to preclude eligible private organizations from applying to be tissue bankers; they simply need to meet all the requirements.
Fundamentally, the new guidelines stress the importance of the welfare and safety of the donor. "There are two key issues: the dignity, safety, and welfare of the donor, and confidentiality," says Lim. Under the guidelines, researchers and tissue banks are required to obtain the donor's informed consent before taking any tissue, and they are obliged to ensure confidentiality of the donor's personal information. Prospective donors should also be given sufficient information to enable them to exercise their choices and, in so doing, be allowed to specify if they are giving away their tissues for a specific research purpose or for general use.
"Donations of tissues have to be outright gifts," says Kaan. As a corollary to this principle, researchers should make clear to donors that they should not expect any personal or direct benefit from the donation, including information on any medical condition or predisposition discovered in the course of the research, unless it has been agreed upon in advance of the donation. Likewise, researchers cannot disclose such information to donors. One may not induce patients with financial incentives either. "However, research subjects may be reimbursed for traveling expenses and time spent," says Professor Tan Chor Chuan, director of medical services at the Ministry of Health .
On the use of human tissue in clinical trials--an area in which pharmaceutical companies are actively involved, Tan says--"trials involving human tissue have to be approved by the ethics committee of the institution involved. There is an existing regulatory guideline for clinical trials, but if pharmaceutical companies wish to make use of existing tissue samples, they have to approach the institution concerned for approval." Currently, it is usually the hospital ethics committees that monitor in-house clinical trials.
A patient's consent to clinical care versus research will be two separate issues. According to Lim, in situations in which the primary purpose or objective for taking a tissue sample is research, the consent form should be separate from that used before taking tissue for therapeutic or diagnostic purposes. "The purpose has to be clear, " explains Lim. "If the patient is treated for a boil problem, you don't use his tissue for liver research." In cases in which tissue left over following diagnosis or treatment might be used for research, patients should also be duly informed and their consent for that additional activity sought and obtained.
BAC has noted that hospitals and institutions here have been collecting and storing tissue samples from patients over many decades. "Working under their own ethical bodies, they are already doing a satisfactory job," says Kaan. "We're building on what has already been done. With the new national framework, we are making it formal, so there will be uniform standards applied by everyone across the board." Some realignment might be necessary on a case-by-case basis, though, and "individual institutions will have to see how they can refine their own systems," says Tan.
According to Professor Yap Hui Kim, vice dean of research at the National University of Singapore's faculty of medicine , tissue banks here have collected thousands of samples over many decades, approximately 30% of which might be useful for research. Legacy tissue samples--usually small tissues from diagnostics--are stored in liquid nitrogen or paraffin blocks. For these valuable collections that were built up by institutions before formal consent guidelines were in place, BAC recommends that a national ethical policy be formulated to govern research access.
The committee realizes the difficulty of enforcing current rules on such legacy samples. "If we apply today's standards to all samples, a lot of legacy samples will have to be discarded," says Lim. Hence, old biomaterials from legacy collections--regardless of how they were obtained--may be put to reasonable and respectful use for the greater public good. The committee, however, suggests that anonymised data arrangements such as coding of samples be facilitated to allow names and other identifiers to be removed to safeguard donors' privacy.
Given the current pace of developments in the genetic and genomic sciences, and the rapidly evolving field of bioethics, legal rules, and opinions governing human tissue research and banking, BAC would rather not hard-code specific rules for regulating research and commercial activities in legislative form. But the committee is prepared for a "continuing professional and public dialogue ... with a view towards ensuring the harmonization of its laws with accepted international best practice and consensus on relevant legal doctrines and principles, such as are being developed in the leading jurisdictions around the world."
"This is a living document," says Lim. "We are prepared to modify it through continued dialogue."