In the news

A UK Stem Cell Bank, funded by the Medical Research Council and the Biotechnology and Biological Sciences Research Council, is being set up at the National Institute of Biological Standards and Control. The aim of the Bank is to provide “ethically sourced, quality controlled adult, fetal and embryonic stem cell lines for research and for the development of therapies by the national and international research community”. It will be a condition of licensing by the Human Fertilisation and Embryology Authority that all embryonic stem cell lines created in the UK are deposited in the Stem Cell Bank.

The Bank’s Steering Committee has published, for consultation, a draft Code of Practice for the operation of the Stem Cell Bank. As well as basic operational features such as the management and governance of the Bank, its premises and equipment, personnel and their training, the Code also covers in detail the procedures to be followed for acquisition of new cell lines and the provision of cell lines to researchers and other third parties.

Cell lines offered to the Bank must be screened and validated with respect to their quality (viability, sterility, genetic stability etc), their microbiological safety, their certification as research- or clinical-grade lines, and the medical history of the donor(s). Cell lines will be coded so that they are traceable back to their original donors and to any recipients, but the donors’ and recipients’ identities will be kept confidential. All donors must have provided informed consent, and have been given an opportunity to opt to receive feedback of any information about their health status that arises from tests on the stem cells. The draft Code notes that some aspects of these criteria may need to be revised in the light of the forthcoming EU Human Tissue Directive.

Arrangements for provision of stem cell lines to other researchers cover aspects such as approval of the specific research project by the Bank’s Steering Committee, agreements on rights of exploitation and ownership of intellectual property, negotiation of Materials Use Licences, and audit of research establishments to ensure that they are complying with the regulations and permissions.

Comments on the draft Code of Practice are invited by 31 October 2003. An companion Code of Practice for the Use of Human Stem Cells will also be published for consultation shortly.

The European Group on Ethics in Science and New Technologies (EGE), which advises the European Commission, has published an Opinion on Ethical aspects of genetic testing in the workplace. The group's report considers three aspects of the use of genetic tests in this context: testing to predict the future health of employees, testing to determine susceptibility to specific occupational hazards such as chemical exposure, and "genetic monitoring" to detect any chromosomal damage that may have been caused by the employment environment. "Genetic tests" as defined by the EGE include DNA-based tests, analysis of the protein products of genes, and family histories. The report recommends that, as a general principle, recruitment decisions by employers should be based only on current health and not on attempts to predict future health; there are currently no genetic tests for common disease that have a sufficiently high predictive value to warrant their use. In general, too, employers should attempt to provide a safe workplace for all employees rather than trying to screen out those who may be particularly susceptible to a specific hazard. If a hazard cannot be eliminated, genetic monitoring may be warranted but only with the informed consent of the employee. The EGE concedes that there may be "exceptional cases" in which genetic screening of asymptomatic employees or prospective employees may be "necessary to guarantee health protection of workers or protection of third parties". Its report sets out stringent conditions for such screening, including documented validity of the test used, informed consent of the individual, and protection of the confidentiality of the genetic information itself, which should be provided only to an independent health professional and not to the employer. The EGE's report contains a useful summary of current relevant legislation in European countries, and a discussion of some surveys that have attempted to gauge the extent of employers' interest in, and use of, genetic screening.

A new report on intellectual property rights and genetics recommends that the Department of Health (DH) should recognise its pivotal position as both a provider and a recipient of intellectual property, and should adopt an active approach both to policy development in this area and to routine management of IPR issues. The report is the culmination of a two-year project commissioned by the DH through the Public Health Genetics Unit and undertaken by a project team from the University of Sheffield Institute for Biotechnological Law and Ethics, and Cambridge University's Intellectual Property Unit.

Specifically, the report recommends moving the argument on the patents issue away from what types of genetic material should be patentable, and towards implementing more robust criteria for granting patents, along the general lines suggested by a recent report from the Nuffield Council on Bioethics. The DH could influence this process by having mechanisms for making representations to the UK or European Patent Office to restrict the scope of particular patents, to challenge patent validity where it thinks this would be appropriate, and to prevent patent holders from abusing their monopoly rights. It should also encourage the negotiation of fair licensing agreements (both "licensing in" from other patent holders and "licensing out" its own inventions) and should work with other relevant Government departments, such as the Department of Trade and Industry, towards developing a shared policy framework for intellectual property rights in biotechnology and genetics. The DH should also support efforts to clarify the exemption from patent infringement that applies to research on patented inventions; this "research exception" is currently ill-defined and is particularly problematic in the area of clinical trials.

The report acknowledges issues of ethics and human rights that are raised by intellectual property rights, discusses these in outline and recommends that the DH supports initiatives by groups such as the Human Genetics Commission to tackle such issues as they arise.

Overall, the project team believes that, by taking a proactive stance on intellectual property rights issues and using its influence to ensure that policy is developed in a rational way, the DH can help to ensure that a balance is achieved between "just rewards for innovation and a fair price for health care".

Nephronophthisis (NPHP) is a form of cystic kidney disease and the most common inherited cause of chronic renal failure in children. Four genetically and clinically distinct forms of this autosomal recessive disorder have been identified (NPHP1 - 4); the associated genetic loci have been mapped and the genes mutated in NPHP1 and NPHP4 identified. It has long been assumed that the different genetic defects associated with the disease must contribute to a single pathogenic mechanism, resulting in the common outcome of cystic renal failure. Two reports in the August edition of Nature Genetics each identify one of the genes underlying the remaining two forms of the disease, NPHP2 [Otto, E.A. et al. (2003) Nat. Genet. 34, 413-420 (Abstract)] and NPHP3 [Olbrich, H. et al. (2003) Nat. Genet. 34, 455-459 (Abstract)].Together these studies provide compelling evidence for a single underlying pathogenic mechanism for cystic kidney disease: defects in the cilia. Cilia are fine, hair-like cellular projections that beat constantly in a single direction. The products of the genes mutated in NPHP2 and NPHP3 are shown to interact with the product of the gene mutated in NPHP1, nephrocystin, which in turn interacts with ß-tubulin, the major component of renal cilia. The product of the gene mutated in NPHP4, nephroretinin, also interacts with nephrocystin.

Comment: These studies contribute substantially to the evidence that genetic forms of cystic kidney disease have a universal underlying pathology related to dysfunction of the renal cilia. Understanding of the pathological basis of disease is essential for the development of treatments to cure or alleviate the disorder. However, a review of the two reports by Watnick and Germino notes that, although the model of cilial dysfunction as a cause of cyst formation and renal failure is attractive, a definitive causal connection has yet to be established. The model must also explain the clinical heterogeneity of the different forms of genetic kidney disease.

Chemotherapy following surgery for breast cancer is a key factor in reducing death rates, but as yet there is no way to predict how patients will respond. A recent paper [Chang, J.C. et al. (2003) Lancet 362, 362-369 (Abstract)] reports the use of microarray technology to analyse gene expression in samples from breast tumours treated with the chemotherapeutic agent docetaxel. Tissue samples from 24 patients were removed before treatment and cDNA from the tumours examined for patterns of gene expression. A set of 92 genes were identified whose expression correlated closely with the outcome of chemotherapy, as determined by changes in tumour size following therapy. Tumours were classified as sensitive or resistant to docetaxel based on their decrease in size following treatment; the profile of 92 genes correctly classified sensitivity or resistance of the tumour to docetaxel with an accuracy of 92% and 83% respectively. The authors propose that genetic profiling of tumours could identify those patients likely to respond to treatment with docetaxel before chemotherapy is started; patients whose tumours are unlikely to respond well should receive alternative treatment.

Comment: This study provides the first evidence that genetic profiling of tumours can predict the outcome of therapy with a specific drug; however, the sample size of patients involved in the study was very small and considerably more evidence would be required to validate the results. An article by Brenton and Caldas commenting on the report observes that the authors' measure of tumour response was an arbitrary one, and may not have any clinical value, unlike absolute measures such as survival outcomes, but the value of exploratory clinical studies such as this one to guide and contribute to more rigorous studies of chemosensitivity is noted.