Review Article | Published:

Human cloning: can it be made safe?

Nature Reviews Genetics volume 4, pages 855864 (2003) | Download Citation

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Abstract

There are continued claims of attempts to clone humans using nuclear transfer, despite the serious problems that have been encountered in cloning other mammals. It is known that epigenetic and genetic mechanisms are involved in clone failure, but we still do not know exactly how. Human reproductive cloning is unethical, but the production of cells from cloned embryos could offer many potential benefits. So, can human cloning be made safe?

Key points

  • Somatic cell nuclear transfer (SCNT) is the process whereby the nucleus from an adult cell is transferred into a previously enucleated oocyte, followed by oocyte activation and the ultimate production of a clone of the original source (adult) cell.

  • SCNT is an inefficient process and substantial loss occurs throughout development. The precise mechanisms that are involved in these losses remain poorly understood.

  • Nobody has yet provided scientifically peer-reviewed proof of successful SCNT in humans or non-human primates. In rhesus macaques, this failure is the result of a difference in mitotic spindle organization.

  • A range of abnormalities have been shown in species in which cloned animals have been successfully produced; some defects are similar between species, but others are not. These defects include placental abnormalities, and kidney, lung and heart pathology.

  • Genetic and epigenetic effects are involved in cloning failures. DNA methylation, genomic imprinting, gene reprogramming, chromatin structure, X-chromosome inactivation and telomere lengths have all been shown to be influenced by cloning.

  • Interpreting the evidence from abnormal clones (both phenotypic, genetic and epigenetic data) is not straightforward. Some argue that the abnormalities reflect problems that are seen in association with natural reproduction (only at a higher level); others argue that the problems are unique and the mechanisms are poorly understood.

  • Experiments must be designed to examine the molecular, developmental and pathological issues in parallel. Such studies must be prospective and involve single-parameter changes, ideally in a range of species.

  • Although scientists should not condone human reproductive cloning, it is important to address the safety issues of cloning as it pertains to non-reproductive (therapeutic) cloning.

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Acknowledgements

We each acknowledge discussions with colleagues during the development of these ideas and are grateful for funding from the governments, charities and commercial agencies that are acknowledged in our research papers. We apologize to colleagues whose work we have been unable to cite, but limitations of space in many cases limit citations to reviews rather than the source papers.

Author information

Affiliations

  1. Department of Veterinary Pathology, Royal (Dick) School of Veterinary Studies, University of Edinburgh, Easter Bush Veterinary Centre, Roslin, Midlothian EH25 9RG, UK.

    • Susan M. Rhind
  2. Roslin Institute, Roslin, Midlothian EH25 9PS, UK.

    • Jane E. Taylor
    • , Paul A. De Sousa
    • , Tim J. King
    • , Michelle McGarry
    •  & Ian Wilmut

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Corresponding author

Correspondence to Susan M. Rhind.

Glossary

SOMATIC CELL NUCLEAR TRANSFER

(SCNT). The process by which the nucleus from an adult cell is transferred into a previously enucleated cell; the reconstructed oocyte is activated, which initiates subsequent development.

EPIGENETIC

Literally means 'outside conventional genetics'; this term describes any heritable change in gene expression that is not caused by a change in DNA sequence.

G0 PHASE

The resting phase of the cell cycle.

ENUCLEATION

The removal of nuclear material.

BLASTOCYST

A preimplantation embryo that contains a fluid-filled cavity (blastocoel), a focal cluster of cells from which the embryo will develop (inner cell mass) and peripheral trophoblast cells.

LARGE-OFFSPRING SYNDROME

A syndrome that is characterized by fetal oversize and various organ pathologies.

OVERGROWTH

An increase in overall body size and organ size relative to normal controls.

INNER CELL MASS

(ICM). A small group of cells that are present in the blastocyst, which comprise undifferentiated cells.

MORULA

A preimplantation embryo that consists of a solid cluster of cells.

PLACENTOMEGALY

Enlargement of the placenta beyond its normal size.

SPONGIOTROPHOBLAST

The outer structural layer of the placenta.

ZYGOTE

A single-celled fertilized embryo.

EPIGENOTYPE

The state of those mechanisms that regulate gene expression and are transmitted to daughter cells.

GENOMIC IMPRINTING

The epigenetic marking of a gene on the basis of parental origin, which results in monoallelic expression.

TROPHECTODERM

The outer epithelial layer of the blastocyst.

PERINATAL

The period immediately before and after birth.

TELOMERE

A short repeat sequence of DNA at the end of chromosomes, which both protects and ensures the complete replication of chromosome ends.

GRANULOSA CELL

A somatic cell that is found in the ovarian follicles, which supports oocyte growth, maturation and ovulation.

CUMULUS CELL

A cell that is found in the developing ovarian follicles.

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