Cloning-derived technologies warrant intensive research

David H. Barlow, Editor-in-Chief


    Introduction
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 Introduction
 References
 
The field of assisted reproduction has been consistently innovative since its inception more than 20 years ago. The field in 2002 looks quite different from the same field in 1992, which in turn bears only a superficial resemblance to that in 1982. At each stage it has been possible to follow innovation in animal models through into human research and development, and then to therapy. The people who have gained from this are the thousands of couples who have been helped by the progressive extension of therapy options. Happily, the major innovations which have reached the clinical sphere have proved to be generally safe as far as the health of the resulting offspring is concerned and in areas where concern exists there is good evidence of follow-up activity to monitor the health of offspring.

Innovative technologies have stimulated a range of clinical interventions which endeavour to extend their usefulness. Examples include the many options which are based on gonadotrophin stimulation of multiple follicular development, the treatment options which were made possible by micromanipulative fertilization, the strategies made possible by oocyte or embryo cryopreservation, and finally the expanding options centred on embryo biopsy for genetic analysis. The first example of reproductive cloning, achieved in Dolly the sheep, generated huge interest, and again, the scientific avenues that opened up continue to multiply. The most obvious avenue is therapeutic cloning, aimed at embryonic stem cell generation with immune-compatibility with a specific adult whose somatic cell was used for the nuclear replacement. Reproductive cloning remains restricted to the animal field pending further research on imprinting and the potential for developmental pathologies, and because of ethical concerns internationally. On the other hand, the translation of therapeutic cloning into human medicine is going forward under close control, as in the UK, because of the potential benefit for human medicine.

Cloning technologies have raised international ethical concerns over the generation of identical cloned humans. One alternate option arising from cloning technology is the possibility of a somatic cell being converted to a haploid state. Similar to normal conception, such a reconstituted ‘germ cell’ would permit an individual without their own gametes to contribute to a conception with the germ cells of their partner. Reports concerned with haploidization appeared last year (Lacham-Kaplan et al., 2001Go; Tesarik et al., 2001Go) and interest in the possibility continues, as evidenced by posters presented at the recent ESHRE meeting in Vienna in July (Heindryckx et al., 2002; Takeuchi et al., 2002Go). It is therefore appropriate that the subject is discussed in the pages of this journal, but this discussion must be from an objective standpoint. We have noted that scientific opinion on this topic is diverse and there is a body of opinion that considers that the advocates of haploidization have yet to provide clear evidence that accurate chromosome segregation has been satisfactorily achieved, particularly against a background of current genetic studies showing that pairing and recombination are essential features of reductional chromosome segregation. With the likely enthusiasm of both possible patients and the media in the treatment implications of gamete reconstitution, it is important that the burden of proof remains with the advocates of haploidization at this stage and it is also important that the subject is discussed and debated openly, especially with reference to the potential for impaired imprinting and developmental disorders.

In this issue of Human Reproduction we publish a debate article by Professor Tesarik in which he reviews the subject so far (Tesarik, 2002Go) and we also publish two research papers which report different experiences (Fulka et al., 2002Go; Palermo et al., 2002Go). As indicated by Professor Tesarik, those reporting on haploidization experiments have much work to do and the subject is not yet at a stage of being relevant to clinical practice.


    References
 Top
 Introduction
 References
 
Fulka, J., Martinez, F., Tepla, O., Mrazek, M. and Tesarik, J. (2002) Somatic and embryonic cell nucleus transfer into intact and enucleated immature mouse oocytes. Hum. Reprod., 17, XXX–XXX.

Heindryckx, B., Lierman, S., Rybouchkin, A., Van der Elst, J. and Dhont, M. (2001) Ploidy of artificial mouse oocytes and zygotes. Hum. Reprod., 17 (Abstract Book 1), P-350.

Lacham-Kaplan, O., Daniels, R. and Trounson, A. (2001) Fertilization of mouse oocytes using somatic cells as male germ cells. RBM online, 3, 205–211.[Medline]

Palermo, G.D., Takeuchi, T. and Rosenwaks, Z. (2002) Technical approaches to correction of oocyte aneuploidy. Hum. Reprod., 17, 2165–2173.[Abstract/Free Full Text]

Takeuchi, T., Rosenwaks, Z. and Palermo, G.D. (2002) Developmental potential of ‘cloned’ oocytes. Hum. Reprod., 17 (Abstract Book 1), P-351.

Tesarik, J. (2002) Embryos from syngamy between a gamete and a haploidized somatic cell: reproductive semi-cloning respecting biparental embryo origin. Hum. Reprod., 17, 1933–1937.[Abstract/Free Full Text]

Tesarik, J., Nagy, Z.P., Sousa, M., Mendoza, C. and Abdelmassih, R. (2001) Fertilizable oocytes reconstructed from patient’s somatic cell nuclei and donor ooplasts. RBM online, 2, 160–164.[Medline]





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