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3 October 2002Reporting on its findings from a two-year investigation into research on the genetic basis of behaviour in the normal range (that is, excluding recognised psychiatric illness), a Working Party appointed by the Nuffield Council on Bioethics has concluded that it would not be justified to stifle such research, which, provided it is of high calibre, has the potential to provide important insight into human behaviour. The report points out that the field is still in its infancy, with very few validated findings of genetic variants linked to behavioural traits. The predictive power of any single variants that are found is likely to be very low, though it is possible that combinations of variants – supposing they can be discovered – may be more strongly predictive, especially if their interactions with environmental factors can be understood. The Working Party recommends more careful reporting of behavioural genetics research, both by scientists and by the press (which generally illustrated the problem with sensationalist headlines about the report itself).

Despite the uncertainties, the group decided that is was important to anticipate the potential ethical questions that could arise in the future if it were to become possible, for example, to use prenatal or preimplantation diagnosis to select embryos on the basis of behavioural characteristics such as intelligence, aggressive tendencies or sexual orientation, or to use gene therapy to alter behavioural traits. It concluded (though with some hesitation in the case of preimplantation diagnosis) that these applications would be wrong. The report also expresses concern about the potential for “medicalisation” of behaviour that is currently considered to be within the normal range, and suggests that the Department of Health sets up an agency to monitor and if necessary, control this trend. On the question of criminal responsibility, the Working Party decided that carrying genetic variants linked, say, to heightened aggression that still fell within the normal range could not be said to “absolve individuals from responsibility for their actions”, but that in the future it might be reasonable for such information, together with other information such as social background and circumstances, to be taken into account in sentencing.

The report also notes the potential for the use of behavioural genetics in education, for example to identify children who may need specific educational interventions. It calls for dialogue between scientists and educationalists about this issue, and recommends that until its implications are explored thoroughly, “genetic information about behavioural traits in the normal range should not be used in the context of the provision of education”.  

28 October 2002The European Union Council of Science Ministers has reached an uneasy compromise with the European Parliament on the funding of embryonic stem cell research within the Sixth Framework Research programme. While approving the Framework on 30 September, the Council unexpectedly added a rider that introduced a one-year moratorium on the use of EU funds to support embryonic stem cell research. Vehement objection from the Parliament’s Committee on Industry, External Trade, Research and Energy, which questioned whether the Council’s decision was legal, resulted in negotiations that led to a compromise: “further provisions on the funding of research activities involving the use of human embryos and human embryonic stem cells will be established before the end of 2003, on the basis of a new proposal (based on an in-depth ethical, technical and political study) from the European Commission and in consultation with the European Parliament”. In the meantime, Sixth Framework money can only be used to fund embryonic stem cell work that involves existing cell cultures, and any proposals for such work will have to be approved by a regulatory committee.

9 October 2002Ian Wilmut, the scientist behind the creation of Dolly the sheep, the first cloned mammal, has announced that his team will apply to the UK Human Fertilisation and Embryology Authority for permission to begin attempts to use somatic cell nuclear replacement (SCNR) to create human embryonic stem cells genetically identical to adult donor cells (see report in Science magazine, 4 October issue). The idea is that these stem cells could be used to treat degenerative diseases such as Parkinson’s disease or multiple sclerosis without any problems of immunological rejection – an approach sometimes called “therapeutic cloning”. The UK is so far the first country to have in place legislation and a regulatory regime to enable but control such research. The licensing procedure for Wilmut's research is expected to take at least a year. There have been some previous attempts by private companies in the US to produce cloned human embryos by SCNR, but none has so far succeeded in producing embryos that survived to the stage at which stem cells could be harvested.  

Note added 5/12/02: Professor Wilmut has recently announced that his work will not involve somatic cell nuclear replacement, but rather parthenogenesis: this means activating an egg to begin development without fertilisation. Parthenogenesis has been suggested as an alternative route to obtaining embryonic stem cells that does not involve the use or destruction of viable embryos, as parthenogenetic embryos never develop to term. The potential of this technique, like that of somatic cell nuclear transfer, is controversial.

4 October 2002Doctors at the Necker-Enfants Malades clinic in Paris have revealed that one of the eight children with X-linked severe combined immunodeficiency (X-SCID) whom they treated by gene therapy (see article in April 2002 newsletter) has developed leukaemia (see report in BBC news on-line). The remaining children who responded to the gene therapy treatment are still well, but their health is being closely monitored. A British child who received the pioneering treatment earlier this year is also so far still well. The UK Gene Therapy Advisory Committee (GTAC) has decided not to halt ongoing gene therapy trials for X-SCID at Great Ormond Street Hospital, though extra safeguards are being put in place. Trials have been halted in the US and France. It may be that the same features that made this form of gene therapy so successful - the use of a viral vector and the fact that blood stem cells were the target cells – also increase the risk that some of the altered cells may become cancerous. Nevertheless, in view of the seriousness of the disease and the fact that the only other treatment, bone marrow transplantation, is only possible for a minority of sufferers, the GTAC decision to continue UK trials seems justified. The families of children entering any trials will be fully counselled about the potential risks. The French child who has developed leukaemia is said to be responding well to chemotherapy. 

29 October 2002The UK Human Fertilisation and Embryology Authority (HFEA), which regulates assisted reproduction technology that involves the use of donor gametes or in vitro fertilisation, has launched a consultation on sex selection in human reproduction. At present, the HFEA has the power to regulate the use of preimplantation genetic diagnosis (PGD) for sex selection, and the current position is that PGD for this purpose is only permitted in order to avoid the birth of a child with a serious sex-linked genetic disease. A recent application to use PGD for “family balancing” by a couple with several sons but no living daughter was refused. Sex-selection techniques that involve only the sorting of sperm before conception are currently not regulated in the UK. This technology has to date been notoriously unreliable, but there are indications that its accuracy is improving and the HFEA has decided that the time is ripe to re-examine the issue of sex selection. The consultation, which runs until 22 January 2003, covers questions such as whether sperm sorting should come under the regulatory remit of the HFEA and, if so, in what circumstances it should be permitted. It also asks whether the use of PGD should continue to be allowed only for medical reasons or should also be permitted for family balancing or other non-medical reasons. 

30 October 2002US Department of Health and Human Services has announced plans to establish a Secretary’s Advisory Committee on Genetics, Health and Society. This follows the decision not to renew the charter of the Secretary’s Advisory Committee on Genetic Testing, established during the Clinton presidency (see item in September 2002 newsletter). The new Committee will provide a forum for discussion and make policy recommendations on the “complex and sensitive medical, ethical, legal and social issues raised by new technological developments in human genetics”, including medical and non-medical uses of genetic information, patent policy and licensing practices, and the potential use of genetics in bioterrorism. A core of 13 members, selected by the Secretary for Health and Human Services, will bring expertise in areas including human genetics, public health, forensics, bioterrorism, ethics, law and occupational health. The Committee’s initial charter will run for two years. It remains to be seen whether the new Committee will attract criticism similar to that directed at some other scientific advisory committees established by the Bush administration: that they are dominated by members whose views are known to coincide with those of the administration. [A particularly critical editorial appeared in the 25 October issue of Science magazine: see "Advice without dissent", Michaels, D et al (2002) Science 298, 703].  

8 October 2002The British Society of Gastroenterology and the Association of Coloproctology for Great Britain and Ireland have published guidelines for the management of families affected by high-penetrance inherited colorectal cancer syndromes, and of individuals at moderately increased risk of colorectal cancer on the basis of their family history. People at moderate risk, estimated as about 0.5% of people in the age group 40-75 (a total of around 750 people in a population served by a typical district general hospital), are defined as those with two affected first-degree relatives or one first degree relative diagnosed under the age of 45 [Dunlop, MG (2002) Gut 51 (Suppl V), v17-v20]. This group has a lifetime risk of about 10-15%, compared with 2% for the general population. The recommendation is that these people should be offered a maximum of two complete colonoscopies, one at age 35-40 and the second at age 55. The additional workload for an average health district population of 300,000 is estimated to be 35 colonoscopies annually. A strong recommendation is made for audit of numbers and outcomes, including total number of referrals; proportion recommended surveillance; surveillance-related morbidity/mortality; and cancers in those fulfilling and not fulfilling the referral criteria.

A second paper deals with families affected by hereditary colorectal cancer syndromes: hereditary non-polyposis colorectal cancer (HNPCC), familial adenomatous polyposis (FAP), juvenile polyposis and Peutz-Jeghers syndrome [Dunlop MG (2002) Gut 51 (Suppl V), v21-v27]. These syndromes are rare (1-3% of colorectal cancers for HNPCC and less than 1% for FAP) but the risks to mutation carriers are high. HNPCC is defined both genetically as possession of a causative mutation in a mismatch repair gene, and empirically on the basis of a family history fulfilling the modified “Amsterdam criteria”. Those at risk should be offered colonoscopy every two years from age 25, or five years earlier than the earliest age of onset in that family, whichever is the earlier. For FAP, mutation carriers should be advised to have prophylactic colorectal surgery at age 16-20 years. In the minority  of FAP families where no mutation can be identified, annual flexible sigmoidoscopy surveillance should begin at age 13-15 years, and prophylactic surgery should be offered to those in whom multiple polyps are detected. Cost/benefit calculations show a clear balance of benefit in favour of screening for these high-penetrance syndromes. Recommendations are also made for the establishment of family registries and for audit of outcomes.

1 October 2002The penetrance of mutations in the BRCA1 and BRCA2 genes depends on the population surveyed. Original penetrance estimates based on highly selected families with multiple affected members are substantially higher than estimates based on mutation carriers identified from populations of unselected breast cancer cases. What are the appropriate figures to use when counselling women? Most BRCA1/2 testing is done after referral to genetics services on the basis of concerns about a family history of breast cancer. Brose et al argue that penetrance estimates for mutations identified in this context are likely to be the most clinically relevant [Brose, MS et al (2002) J Natl Cancer Inst 94, 1365-1372 (Abstract). They analysed cancer incidence over 10-year age intervals in 483 BRCA1 mutation carriers from 147 families referred to a breast/ovarian cancer risk evaluation clinic. The cumulative female breast cancer risk to age 70 was approximately 70% and the ovarian cancer risk was 40%. They also found evidence for increased risk of other cancers in BRCA1 mutation carriers. However, Thompson and Easton, reporting the results of a much larger study, found that only female BRCA1 mutation carriers were at significantly increased risk of primary cancers other than breast or ovarian; they calculate a relative risk of 2.3 for other gynaecological cancers and for cancers at some other abdominal sites [Thompson, D and Easton, DF (2002) J Natl Cancer Inst 94, 1358-1365 (Abstract).