In the news

A consortium of 40 organisations and companies involved in genomic research has announced the setting up of a computing platform to help researchers use and analyse the vast amounts of information emerging from the human genome project (see article from Washington Post). The consortium includes major computer companies such as Sun Microsystems and IBM, together with biotechnology companies and research organisations including the US National Cancer Institute. Launching the project, to be known as the Interoperable Informatics Infrastructure Consortium (3IC), consortium members said that the usefulness of current databases is limited by several factors including incompatible formats for data and inconsistent policies on annotation (the addition of information about, for example, the expression pattern of a particular gene). These limitations, they claim, are hindering the use of genomic information for purposes such as drug discovery. The plan is that 3IC would specify the format for data and the rules for searching, analysing and cross-linking it. Whether 3IC will win sufficient support from the whole genomics community to enable it to establish what would essentially be an industry standard for genomic data remains to be seen. 

Australian researchers claim to have successfully fertilised a mouse egg using, not mouse sperm, but a somatic mouse cell (see report in BBC News On-line). When an egg cell matures, it ejects one of its two sets of chromosomes, so that only one set is passed on to the offspring. The egg would normally be fertilised by a sperm cell, which has also shed one set of chromosomes. Fertilisation restores the normal chromosome complement. The researchers fused a somatic mouse cell with a maturing egg cell and succeeded in making the egg cell's machinery work on the somatic cell chromosomes as well, so that one set of them was also ejected. The result was a "fertilised" egg with a normal complement of chromosomes. The researchers claim that embryos produced in this way show normal early development and they now plan to implant these embryos into surrogate mothers to see whether they develop normally, are born healthy, and can themselves produce offspring. The report of this research, which was undertaken with the idea of enabling men who produce no sperm to father children, has prompted fears that, for example, lesbian couples could use such a technique to produce a child that was related genetically to both of them but had no father. Such a possibility still seems some way off, however. It is known that reciprocal modifications to the sperm and egg sets of chromosomes, known as imprinting, are important for normal development; sperm chromosome imprinting would presumably be absent in "fatherless" embryos. Abnormalities in imprinting have also been observed in cloned mouse embryos (see Journal club article below).  

In October last year, it was announced that preimplantation genetic diagnosis had been used successfully to select an embryo that was both free of the genetic disease Fanconi's anaemia (of which both parents were carriers), and a good tissue match for his affected older sister, whose best chance of survival was a cord blood transplant from an HLA-identical donor. The scientific paper reporting this achievement has now been published [Verlinsky, Y. et al (2001) JAMA 285, 3130-3133 (Abstract)]. The couple underwent four IVF cycles, resulting in 33 embryos that were tested for the FANCC gene mutation carried by both parents. 24 were unaffected (19 heterozygous carriers and 5 homozygous normal), of which five heterozygous carriers were HLA-identical to the couple's daughter. Only the single one of these that was transferred in the fourth IVF cycle resulted in a viable pregnancy. Cord blood collected from the baby at birth was transplanted to his older sister, a treatment that appears to have been successful.

Comment: The initial report of this work roused much discussion about its ethical dimension: whether it is right to select a child on the basis of its "usefulness" to another family member. On the other hand, as pointed out by the authors and some commentators, if the technology exists to satisfy simultaneously a couple's desire to have a healthy child and to save a much loved existing child, is it wrong to use it?

Several newspapers recently ran stories with headlines such as "Royal Society condemns human cloning". The report these stories refer to, with the low-key title "Stem cell research - second update", is in fact not focused on reproductive cloning at all. The report does indeed recommend that, on ethical and safety grounds, reproductive cloning should not be allowed, but its main thrust is a discussion of recent advances in stem cell research. There have, for example, been several papers published recently that appeared to show much greater potential for adult stem cells than had previously been thought to be the case, and this work has been cited by those who oppose the use of embryo-derived stem cells. The Royal Society report makes an extremely useful contribution in discussing clearly the claims that have been made for adult stem cells, and explaining their current limitations on both scientific and practical grounds. The report recommends that both adult and embryonic stem cell research should be pursued. In reaching this conclusion, the Royal Society is in tune with recommendations that emerged from a recent US National Academy of Sciences workshop, arguing against placing too much reliance on the potential of adult stem cells and urging legislators to allow stem cell research (see report in Nature 411, page 979).

The Royal Society report, which has been submitted as evidence to the parliamentary committee enquiring into stem cell research and "therapeutic cloning", also deals with questions concerning the effects of globalisation, e-commerce and patenting on the stem cell debate, and the difficulties that would surround any attempt to reach consensus at an international level. These difficulties are highlighted by the deep divisions elsewhere in Europe. The French government proposes allowing research on stem cells derived from "spare" IVF embryos, but has decided not to proceed with proposals to allow therapeutic cloning (see news report in Lancet, 30 June). In Germany, political pressure has forced the main research funding agency to delay further a decision on funding a research project on human embryonic stem cells (see report in Nature, 21 June). For further information on stem cell policy development in the UK and elsewhere, see the stem cells page in the information database.   2/7/01

Note added 3/7/01: The European Science Foundation, a body representing 67 major organisations devoted to scientific research in 24 European countries, has just issued a policy briefing which recommends that research should be allowed on both embryonic stem cells and therapeutic cloning, but that this research should be under strong regulatory control. The document contains a useful summary of the current position with regard to stem cell research across Europe

Developmental biology researchers have warned those who are eager to begin trying to clone human beings that, just as in animals, the success rate would probably be very low and the dangers of producing abnormal babies would be high. Humpherys and colleagues have published evidence, in mice, of some of the sorts of abnormalities that might be expected [Humperys D. et al (2001) Science 293, 95-97]. They looked, in particular, at changes in the expression of imprinted genes: genes that normally show differential expression of the maternal and paternal alleles. Several of these genes are known to be involved in controlling the growth of the embryo and fetus, and changes in their imprinting can lead to excess or restricted growth, along with other abnormalities. Cloned mouse embryos showed widely varying relative levels of expression of several genes that are normally imprinted; variability was also observed in the embryonic stem cells that were used to provide the donor nuclei for the cloning procedure. Cloned mouse pups also tended to be abnormally large, though the degree of overgrowth could not be correlated with the abnormalities in imprinting of any of the genes examined. Even those cloned mice that survived to adulthood showed clear evidence of misregulation of the expression of imprinted genes. There is as yet no way of knowing whether cloned humans would show similar misregulation of imprinted genes, or, if so, what effects these abnormalities might have on their health.

Comment: The potential hazards of human reproductive cloning are, at present, extremely serious, and justify the decision of many governments to ban attempts to carry it out.