NEWSLETTER

No. 54, January 2003

The PHGU newsletter features news and views about genetics and genetics research, from a public health perspective. New items are added to the newsletter throughout each month.

The newsletter is written by Dr Alison Stewart (PhD), Chief Knowledge Officer, Public Health Genetics Unit. Statements and opinions contained in the newsletter do not necessarily reflect the views of the National Health Service.

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Contents

WB01158_.GIF (255 bytes) News

  WB01158_.GIF (255 bytes) New reviews

WB01158_.GIF (255 bytes) Journal club

  WB01158_.GIF (255 bytes) Events and announcements

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WB01158_.GIF (255 bytes) News

Second case of gene-therapy-related cancer

It has been reported that a second child who received gene therapy to treat X-linked severe combined immunodeficiency at the Necker Hospital in Paris has developed a leukaemia-like illness [see Science (2003) 299, 495]. Trials of this type of gene therapy in France and the US were temporarily put on hold last year when one of the first 10 children to receive the pioneering treatment developed leukaemia (see item in October 2002 newsletter). A trial underway in the UK went ahead, but has been closely monitored by the Gene Therapy Advisory Committee. The future of this treatment, which was hailed as the first unequivocal success of gene therapy , could be in doubt. One adverse event out of ten could be put down as very bad luck, but two out of ten may mean that there is something intrinsic about the approach that poses an appreciable risk of cancer. Two factors may be at work: firstly, the use of a viral vector may lead to insertional mutagenesis, that is the vector may insert itself into the genome of a target cell in such a way as to cause mutation or inappropriate regulation of a gene. (In the case of both X-SCID patients, it has been suggested that a gene called LMO2 might have been affected.) Secondly, the fact that the target cells are blood stem cells may mean that any altered cells can rapidly multiply to very large numbers.   28/1/03

Note added 30/1/03: A  paper reporting the first adverse event following gene therapy for X-SCID, together with a commentary article, have been published in the New England Journal of Medicine. See Hacein-Bey-Abina, S. et al (2003) N Engl J Med 348, 255-256; and Noguchi, P. (2003) N Engl J Med 348, 193-194.

 

European Patent Office grants patent on BRCA2 to Myriad

  On 8 January, the European Patent Office granted patent EP0785216 to the US-based company Myriad Genetics Inc, giving it patent rights in Europe over the sequence of the BRCA2 gene (see report in CancerSourceRN.com News). Mutations in this gene greatly increase the risk of breast cancer. Like the BRCA1 gene patent, which Myriad also holds, the patent on BRCA2 covers not only  the sequence of the gene but also virtually any use of this information for breast cancer diagnosis, risk prediction, screening or therapy. Somatic mutations in BRCA2 are covered as well as germ-line (constitutional) mutations. Myriad’s European patent on BRCA1 has been challenged by some European governments and research institutes, as well as by the campaigning organisation Greenpeace. Challenges to the BRCA2 patent are also expected.   27/1/03

 

UK Government pledges major investment in stem cells and post-genomic technologies

The UK Science Budget for 2003-04 to 2005-06, published in December, commits the Government to providing funding to the Research Councils for a major new investment in stem cell research and for an expansion of its post-genomics programme to include new research in proteomics. A total of just over £9 million pounds for stem cell research in 2004-05 will rise to nearly £31 million in 2005-06. The money will fund the establishment of the UK Stem Cell Bank at the National Institute for Biological Standards and Control (see item in September 2002 newsletter), as well as basic research on stem cell biology and applied research on the therapeutic potential of stem cells. These programmes will be administered by the Medical Research Council and the Biotechnology and Biological Sciences Research Council. Smaller amounts of funding to the Engineering and Physical Sciences Research Council and the Economic and Social Research Council will support research on the development of methods for following grafted stem cells, and the ethical and social issues surrounding stem cell research, respectively. The UK is among a fairly small number of countries where it is legal to use public funds for research that involves the derivation of new embryonic stem cell lines. In recognition of the uneven regulatory situation across the world, talks were held recently in London with a view to the possible establishment of an international stem cell consortium (see Nature, 9 January, p. 102) – this might allow scientists in countries with more restrictive regulatory regimes to collaborate with those in countries where a wider range of research is permitted.

The UK’s cross-council programme in post-genomics also received a boost in the Science Budget. The additional funding, shared mainly between the MRC and BBSRC, is intended in particular to support research on proteomics, including areas such as protein folding and predictive modelling; protein function; the regulation, modification and expression of proteins; bioinformatics; and technology development for proteomics. By 2004-05 and 2005-06, the MRC and BBSRC will share a total annual budget of around £50 million for post-genomic research.   14/1/03

 

High Court upholds challenge to use of preimplantation genetic diagnosis with tissue typing

During 2002, the Human Fertilisation and Embryology Authority decided to allow a UK couple to use preimplantation genetic diagnosis to select an embryo that was not affected by the genetic disease beta-thalassaemia (for which both parents are carriers), and in addition was a tissue match for their existing son (see items in December 2001 and February 2002 newsletters). The aim would be to use cord blood from the baby to treat the affected boy. The HFEA’s decision has been challenged by the campaigning group Comment on Reproductive Ethics; in a decision handed down on 20 December, the High Court upheld this challenge. In his judgement, Mr Justice Maurice Kay said that Parliament, in the 1990 Human Fertilisation and Embryology Act, had tightly specified the purposes for which the HFEA may grant licences, and that these must fall within the general description of “assisting women to carry children”. He found that tissue typing does not meet this criterion and is therefore unlawful. He also rejected alternative submissions made by counsel for the HFEA: that tissue typing does not require licensing by the HFEA because it is carried out on cells taken from an embryo, not on the embryo itself; and that a prohibition on tissue typing would contravene the European Convention on Human Rights. The HFEA is considering the implications of the court’s decision and taking advice on whether it should appeal.   13/1/03

WB01158_.GIF (255 bytes)Journal club

Using microarrays to distinguish primary and metastatic tumours

A recent paper in Nature Genetics describes the use of DNA microarrays (“chips”) to identify a gene expression “signature” that can distinguish non-metastatic primary tumours both from metastatic tumours and from primary tumours that are destined to metastasise [Ramaswamy, S. et al (2003) Nature Genetics 33, 49-54 (Abstract)]. The first step was to use DNA microarrays carrying gene sequences representative of thousands of different human genes to analyse the gene expression profiles of 64 primary and 12 metastatic tumours. Computer analysis of these profiles enabled a set of 128 genes to be picked out whose relative expression levels reliably distinguished most primary tumours from metastatic ones. A few primary tumours were apparently misclassified as metastatic, but further experiments showed that primary lung tumours that carried the metastatic gene expression signature were associated with significantly shorter survival times in the corresponding patients. The authors suggest that primary tumours carrying the metastatic gene expression signature are in fact destined to metastasise; if this is correct, then a large number of cells in these tumours must be running a genetic programme associated with metastasis, a finding that is at odds with the general view that metastasis is initiated by a few “rogue” cells within an otherwise genetically benign primary tumour. The authors went on to use computer analysis to whittle down their initial set of 128 genes to a set of 17 that gave equally good discrimination. The signature represented by the expression of these genes was used successfully to indicate the likelihood that various different types of primary tumour would metastasise. An exception was diffuse large B cell lymphoma, probably indicating a difference between solid and haematological tumours in the genetic mechanisms associated with metastasis.

Comment: This paper represents the latest contribution to a growing volume of research on the use of microarrays in oncology. The field of microarray technology is still struggling with problems of reproducibility and comparability between different laboratories and techniques, but greater awareness of these potential pitfalls, and the recent introduction of agreed standards for reporting microarray data, should go some way towards overcoming these difficulties. The hope is that information gleaned from the global analysis of gene expression enabled by microarrays will lead to better diagnosis and the identification of new drug targets.   21/1/03

WB01158_.GIF (255 bytes) New reviews and commentaries

The double helix - 50 years.  This special feature in the 23 issue of Nature (and also available on the web) includes articles on The double helix in clinical practice (by John Bell), and Nature, nurture and human disease (Aravinda Chakravarti and Peter Little

Pharmacogenetics in cancer treatment. Nagasubramanian, R. et al (2003) Annu. Rev. Med 54, 437-452

Molecular genetic risk screening. Grody, WW (2003) Annu Rev Med 54, 473-490

Classifying human cancer by analysis of gene expression. Hampton, GM and Frierson, HF (2003) Trends Mol Med 9, 5-10

Debating ethics and public policy. Lezemore, T (2002) Trends Genet 18, 653-655

Fanconi anaemia. Tischkowitz, MD and Hodgson, S. (2003) J Med Genet 40, 1-10

Recommendations for introducing genetics services in developing countries. Alwan, A. and Modell, B. (2003) Nature Reviews Genetics 4, 61-68

Genetics in Medicine supplement (November-December 2002) A review issue on the future role of genetics in medicine and public health

 

WB01158_.GIF (255 bytes)Events and announcements

31 January 2003  The Darwin Lectures 2003: Ancient DNA. Professor Svante Paabo. Lady Mitchell Hall, University of Cambridge, 5.30 pm. (For further information contact Darwin College)

5 February 2003  Human Genetics Commission Plenary Meeting. Millennium Gloucester Hotel, Harrington Gardens, London SW7 4LH  (To reserve a place, contact the HGC Secretariat, Tel: 020 7972 1518; e-mail: hgc@doh.gsi.gov.uk)

7 February 2003  The Darwin Lectures 2003: DNA and Ethics. Baroness Onora O'Neill. Lady Mitchell Hall, University of Cambridge, 5.30 pm. (For further information contact Darwin College)

14 February 2003  The Darwin Lectures 2003: DNA and Cancer. Professor Ron Laskey. Lady Mitchell Hall, University of Cambridge, 5.30 pm. (For further information contact Darwin College)

21 February 2003  The Darwin Lectures 2003: DNA, Biotechnology and Society. Professor Malcolm Grant.  Lady Mitchell Hall, University of Cambridge, 5.30 pm. (For further information contact Darwin College)

28 February 2003  The Darwin Lectures 2003: DNA in Reproductive Medicine. Professor Lord Robert Winston.  Lady Mitchell Hall, University of Cambridge, 5.30 pm. (For further information contact Darwin College)

7 March 2003  The Darwin Lectures 2003: DNA and Language. Professor Dorothy Bishop. Lady Mitchell Hall, University of Cambridge, 5.30 pm. (For further information contact Darwin College)

17-19 March 2003  Who twists the helix? The University Centre, University of Cambridge. (Anne Galbraith, Policy, Ethics and Life Sciences Research Institute, Bioscience Centre, Times Square, Newcastle-upon-Tyne NE1 4EP; Tel: 0191 241 8614; Fax: 0191 2438233; e-mail: anne.galbraith@ncl.ac.uk)

10 April 2003  Genetics in Primary Care. A Brown-Oxford videoconference. Locations: George Auditorium, Rhode Island Hospital, Providence RI, USA; and Cancer Research UK Video Conference Facility, London UK. Conference theme: Application of pharmacogenetics to chronic illness care to enable individually tailored therapies.  (Lee-Anne Blakey, CPCP Research Support, Memorial Hospital of Rhode Island, 111 Brewster Street, Pawtucket, RI 02860, USA; Tel: (+1) 401 729 2894; Fax: (+1) 401 729 2494; e-mail Lee-Anne_Blakey@mhri.org)

25 April 2003  DNA: 50 years of the double helix  Cambridge, UK. A celebratory conference organised and supported by the Wellcome Trust Sanger Institute, the MRC Laboratory for Molecular Biology and The University of Cambridge Cavendish Laboratory. (CoverPoint UK Ltd, Mandera House, Houghton Road, St Ives Cambs PE27 6RN UK. Fax: 01275 853311; e-mail dna50@blueyonder.co.uk)

26-27 April 2003  Genes and Society Festival. Battersea Arts Centre, London UK (Institute of Ideas, Signet House, 49-51 Farringdon Road, London EC`M 3JP; Tel: 020 7269 9220; Fax: 020 7269 9235; e-mail mailto:academy@institute)

3-6 May 2003  European Human Genetics Conference 2003  Birmingham UK. (Scientific and Administrative Secretariat: The Vienna Medical Academy of Postgraduate Medical Education and Research, Alserstrasse 4, A-1090 Vienna, Austria; Tel: +43 1 405 138322; e-mail: eshg@medacad.org; further details will be posted in mid-October on http://www.eshg.org/)

22-24 May 2003  International Conference on Genetic Variation, Nutrition and Physical Activity. (A joint meeting of the IUNS Committee on Genetics, Nutrition and Chronic Diseases and the Directors of the Centers on Genetics, Nutrition, Exercise and Health.) Santa Margherita di Pula, Cagliari, Sardinia, Italy. (Co-chaired and co-organised by S. Muntoni (Itlay) and A. Simopoulos (USA). Contact Secretariat: Prof Sergio Muntoni, Centre for Metabolic Diseases and Atherosclerosis, The ME.DI.CO Association, Viale Merello 23/29, 09123 Cagliari, Italy. Tel: +39 070 273406; Fax: +39 070 284849; e-mail s.muntoni@unica.it)

6-12 July 2003  XIX International Congress of Genetics: Genomes - the Linkage to Life. Melbourne, Australia. (Secretary General: Dr P. Batterham; e-mail p.batterham@unimelb.edu.au)