Peer Reviewed Research
Animal reproductive technologies — the forerunners of cloning — have been rigorously studied for decades. The U.S. Food and Drug Administration analyzed over 400 scientific studies on cloning, conducted over many years and encompassing several generations and large families of livestock. The National Academy of Sciences has also scrutinized this topic, publishing reviews in 2002 and 2004.
The animal cloning articles available here comprise the best available scientific research on the topic. Please call us if you are looking for something that you cannot find on this page.
First Reports
Agricultural Sciences
Waddington. 1953. Transplantation of nuclei in newt's eggs. Nature.
First report of cloning by nuclear transfer in newts.
Whittingham. 1972. Survival of mouse embryos frozen to -196 degrees and -269 degrees C. Science.
First report of cryopreservation of mammalian embryos.
Du Pasquier. 1977. Transplantation of nuclei from lymphocytes of adult frogs into enucleated eggs: special focus on technical parameters. Differentiation.
First report of somatic cell nuclear transfer used to produce cloned frogs. It produced tadpoles, but they didn't develop into adults.
Willadsen. 1979. A method for culture of micromanipulated sheep embryos and its use to produce monozygotic twins. Nature.
First report of mammalian cloning by embryo splitting.
McGrath. 1983. Nuclear transplantation in the mouse embryo by microsurgery and cell fusion. Science.
First report of mammalian embryonic nuclear transfer.
Willadsen. 1984. A simple procedure for the production of identical sheep twins. Vetinary Record.
Perfection of high throughput embryonic cloning by embryo splitting.
Willadsen. 1986. Nuclear transplantation in sheep embryos. Nature.
First report of embryonic cell nuclear transfer in an agricultural species (sheep).
Robl. 1987. Nuclear transplantation in bovine embryos. Journal of Animal Science.
First report of embryonic cell nuclear transfer in cattle.
Willadsen. 1989. Cloning of sheep and cow embryos. Genome.
The first time that anyone pointed out that existing NT technology would open the way for large scale cloning in livestock. Published nine years before Dolly was announced.
Stice. 1993. Multiple generational bovine embryo cloning. Biology of Reproduction.
Repeated cycles (multiple generations) of nuclear transfer procedures used to produce a large number of identical animals, thus making Willadsen's prediction of 1989 a reality.
Campbell. 1996. Sheep cloned by nuclear transfer from a cultured cell line. Nature.
First report of a mammal cloned from an embryo-derived cell culture. All prior NT had used cells from embryos rather than from cell lines established from embryos. This made it possible to easily clone an unlimited number of animals from a single embryo.
Wilmut. 1997. Viable offspring derived from fetal and adult mammalian cells. Nature.
Announces the birth of Dolly the sheep, the first mammal cloned by somatic cell nuclear transfer (SCNT).
Cibelli. 1998. Cloned transgenic calves produced from nonquiescent fetal fibroblasts. Science.
First cloning of cattle. Animals were transgenic and derived from fetal fibroblasts.
Wakayama. 1998. Full-term development of mice from enucleated oocytes injected with cumulus cell nuclei. Nature.
First report of cloning in mice.
Baguisi. 1999. Production of goats by somatic cell nuclear transfer. Nature Biotechnology.
First report of cloned goats. Animals were transgenic and derived from fetal somatic cells.
Polejaeva. 2000. Cloned pigs produced by nuclear transfer from adult somatic cells. Nature.
First report of cloned pigs, success achieved using two rounds of nuclear transfer.
Betthauser. 2000. Production of cloned pigs from in vitro systems. Nature.
Third report of cloned pigs, first one using in vitro oocytes.
Wakayama. 2000. Cloning of mice to six generations. Nature.
Cloned mice show no signs of premature aging or unusual telomere shortening, even in clones of clones of clones of clones of clones of clones (6 generations). First report of cloning a clone.
National Academies of Science. 2002. Animal Biotechnology: Science Based Concerns.
Chesne. 2002. Cloned rabbits produced by nuclear transfer from adult somatic cells. Nature Biotechnology.
First report of cloned rabbits, success achieved by modifying procedures to incorporate rabbit's unique oocyte physiology and early embryonic development.
Shin. 2002. A cat cloned by nuclear transplantation. Nature.
First report of a cloned cat, named CC.
Galli. 2003. A cloned horse is born to its dam twin. Nature.
Healthy cloned horse born to the cell donor (a mother gives birth to her own clone).
Zhou. 2003. Generation of fertile cloned rats by regulating oocyte activation. Science.
First report of cloned rats, highlights the importance of oocyte physiology to the cloning process.
National Academies of Science. 2004. Safety of Genetically Engineered Foods: Approaches to Assessing Unintended Health Effects.
Kubota. 2004. Serial bull cloning by somatic cell nuclear transfer. Nature Biotechnology.
First report of clone of a clone in cattle.
Lee. 2005. Dogs cloned from adult somatic cells. Nature.
First report of a cloned dog, success achieved with in vivo oocytes and brute force.
Telomeres and Clone Aging
Shiels. 1999. Analysis of telomere lengths in cloned sheep. Nature.
The majority of subsequent research refutes the findings in this article (that telomeres in cloned animals are shorter than in conventionally produced animals).
Tian. 2000. Normal telomere lengths found in cloned cattle. Nature Genetics .
The title says it all.
Wakayama. 2000. Cloning of mice to six generations. Nature.
Cloned mice show no signs of premature aging or unusual telomere shortening, even in clones of clones of clones of clones of clones of clones.
Betts. 2001. Reprogramming of telomerase activity and rebuilding of telomere length in cloned cattle.Proceedings of the National Academy of Sciences.
Cells from cloned cattle have normal telomere lengths.
Lanza. 2000. Extension of cell life-span and telomere length in animals cloned from senescent somatic cells. Science.
Cloning by SCNT restored telomere length, cell proliferative lifespan and youthful age-specific genetic markers in cattle.
Clark. 2003. Proliferative life span is conserved after nuclear transfer. Nature Cell Biology.
Underscores that clones have normal telomeres.
Schaetzlein. 2004. Telomere length is reset during early mammalian embryogenesis. Proceedings of the National Academy of Sciences..
Shows that telomere restoration takes place in cloned embryos.
LeJiang. 2004. Telomere lengths in cloned transgenic pigs. Biology of Reproduction.
Cells from cloned pig have normal telomere lengths.
Epigenetics, Reprogramming and Clone Health
Reviews of Clone Health
Cibelli. 2002. The health profile of cloned animals. Nature Biotechnology.
Review of all literature to date concludes "the idea that cloned animals develop abnormally is currently unjustified on scientific grounds."
Lanza. 2001. Cloned cattle can be healthy and normal. Science.
Enright. 2002. Reproductive characteristics of cloned heifers derived from adult somatic cells. Biology of Reproduction.
Clones from an aged, post-reproductive adult have normal reproductive development.
Pace. 2002. Ontogeny of cloned cattle to lactation. Biology of Reproduction.
Summary of basic growth and reproductive characteristics.
Wells. 2003. Cloning in livestock agriculture. Reproduction.
Good overview of the subject.
Young. 1998. Large offspring syndrome in cattle and sheep. Journal of Reproduction and Fertility.
Large offspring syndrome is associated with in vitro culture of embryos, asynchronous embryo transfer, and/or maternal exposure to high urea diets, not just in cloned embryos.
Behboodi. 2001. Transgenic production from in vivo-derived embryos: Effect on calf birth weight and sex ratios. Molecular Reproduction and Development.
Large study showing most of the problems associated with cloning are also common to non-cloned,in vitro-derived embryos.
Young. 2001. Epigenetic change in IGF2R is associated with fetal overgrowth after sheep embryo culture. Nature Genetics.
In vitro culture alone leads to LOS.
Heyman. 2002. Frequency and occurrence of late gestation losses from cattle cloned embryos. Biology of Reproduction.
SCNT and FCNT pregnancies show much higher rates of fetal loss than IVF or natural pregnancies, and this high loss is associated with biomarkers of placental function. Losses may be due to problems with placentation rather than the health of the embryo itself.
Rideout. 2000. Generation of mice from wild-type and targeted ES cells by nuclear cloning. Nature.
Nuclear donor cell type/genetic background has a major influence on cloning efficiency.
Renard. 2002. Nuclear transfer technologies: between successes and doubts. Theriogenology.
Review of all problems known to be found in cloned animals by species and evidence suggesting that they are due to epigenetic remodeling of the somatic cell nucleus.
Kolber-Simmonds. 2004. Production of alpha 1,3 galactotransferase null pigs by means of nuclear transfer with fibroblasts bearing loss of heterozygosity mutations. Proceedings of the National Academy of Sciences.
When cloned animals with epigenetic abnormalities were re-cloned (clones of clones), the resulting animals were normal.
Smith. 2005. Global gene expression profiles reveal significant nuclear reprogramming by the blastocyst stage after cloning. Proceedings of the National Academy of Sciences.
Shows that cloned embryos can successfully reprogram themselves to resemble the equivalent of a nucleus of a naturally fertilized embryo.
Analyses of Epigenetics in Clones
Rideout. 2001. Nuclear cloning and epigenetic reprogramming of the genome.Science.
Discusses epigenetic reprogramming issues.
Kang. 2001a. Typical demethylation events in cloned pig embryos. Journal of Biological Chemistry.
Cloned pig embryos undergo typical demethylation process.
Kang. 2001b. Aberrant methylation of donor genome in cloned bovine embryos. Nature Genetics.
DNA methylation patterns in cloned bovine embryos are very different from natural embryos and may be the cause of epigenetic problems associated with clones.
Inoue. 2002. Faithful expression of imprinted genes in cloned mice. Science.
Shows faithful expression of imprinted genes in cloned mice.
Improvements in Cloning Efficiency (CT and Aggregation)
Houdebine. 2003. Cloning by numbers. Nature Biotechnology.
Editorial review discussing the importance of aggregation technology.
Boiani. 2003. Pluripotency deficit in clones overcome by clone-clone aggregation: epigenetic complementation? EMBO Journal.
Aggregation of cloned mouse embryos improves developmental rates of cloned embryos.
Sullivan. 2004. Cloned calves from chromatin remodeled in vitro. Biology of Reproduction.
Shows that somatic nuclei can be remodeled using mitotic cell extract prior to SCNT, resulting in a trend for higher rates of survival of calves at one month of age.
Meat and Milk from Clones
Walkera, Christensonb, Ruizc, Reevesd, Pratte, Arenivasa, Williamsa, Brunera, and Polejaevaa. 2007.Comparison of meat composition from offspring of cloned and conventionally produced boars.Theriogenology.
Laible, Brophya, Knightona, and Wells. 2007. Compositional analysis of dairy products derived from clones and cloned transgenic cattle. Theriogenology.
Yamaguchi, Ito, & Takahashi. 2006. Fourteen-week feeding test of meat and milk derived from cloned cattle in the rat. Theriogenology. (pdf)
Concludes that the physiologic conditions of rats were not affected by consumption of meat and milk from bovine clones.
Norman, Lawlor, Wright, and Powell. 2004. Performance of Holstein clones in the United States.Journal of Dairy Science.
Milk composition for cloned cows was not different from that for the population.
Takahashi and Ito. 2004. Evaluation of meat products from cloned cattle: biological and biochemical properties. Cloning and Stem Cells.
This study showed for the first time that the biological/biochemical properties of meat of cloned cattle are similar to those of non-cloned cattle.
Tome, Dubarry, and Fromentin. 2004. Nutritional value of milk and meat products derived from cloning. Cloning and Stem Cells.
Preliminary results obtained in rats fed cow's milk or meat-based diets prepared from control animals or from animals derived from cloning did not show any difference between control and cloning-derived products.
Heyman et al.. 2004. Zootechnical performance of cloned cattle and offspring: preliminary results.Cloning and Stem Cells.
Concerning the offspring of both female and male clones, the phenotypical and clinical observation of the calves in the first week of age did not reveal any clinical abnormality, suggesting that the deviations observed in clones are not transmitted to the progeny.
Walsh. 2003. Comparison of milk produced by cows cloned by nuclear transfer with milk from non-cloned cows. Cloning and Stem Cells.
Chemical composition analyses of milk revealed no differences between cloned cows and non-cloned cows.
Tian. 2005. Meat and milk compositions of bovine clones. Proceedings of the National Academy of Sciences.
Chemical composition analyses of milk and meat reveal largely no statistical differences between cloned cows and non-cloned cows.
National Academies of Science. 2002. Animal Biotechnology: Science Based Concerns.
National Academies of Science. 2004. Safety of Genetically Engineered Foods: Approaches to Assessing Unintended Health Effects.
Heyman, Chavatte-Palmer, Berthlot et al. 2007. Studied a clone and control group of cows and found the health and development of the animals, as well as their meat and milk products to be within the normal range for the breed. Theriogenology.
Yamaguchi, Ito, Takahashi. 2007. Conducted long-term rat feed studies and found no significant differences in the animals from being given diets of meat and milk powder from SCNT and embryonic clones. Theriogenology
Laible, Brophy, Knighton et al. 2007. Examined milk and cheese derived from cloned and transgenic cows and found them to be essentially the same as those from conventional dairy cows.Theriogenology.
Walker, Christenson, Reeves et al. 2007. Compared the meat composition from the offspring of cloned and conventionally produced boars [pigs].. The researchers found the meat was not chemically different than the control animals. Theriogenology.
Offspring of Clones
Martin. 2004. Pre-weaning performance and health of pigs born to cloned (fetal cell derived) swine versus non-cloned swine. Theriogenology.
Litters produced by breeding cloned boars with cloned gilts had the same health and performance as litters produced by conventional pigs of similar genetic backgrounds.
Mir. 2005. Progeny of somatic cell nuclear transfer (SCNT) pig clones are phenotypically similar to non-cloned pigs. Cloning Stem Cells.
Study strongly supports the hypothesis that offspring of clones are similar to offspring of naturally bred animals, and as such there should not be any increased risks associated with consumption of products from these animals.
Ortegon, Betts, Lin et al. 2007. Examined the offspring of a cloned bull and found it had normal chromosomal stability, growth, physical, blood and reproductive parameters. Theriogenology.
Panarace, Aguero, Garrote et al. 2007. Examined five years of clone data and concluded cloning had no qualitative risks different from those of any other animals in modern agricultural practices; there was some indication that risks were increased in cattle during the early life cycle of the clones.Theriogenology.
Cloning and Conservation
Roosen. 2005. Economic evaluation for conservation of farm animal genetic resources. Journal of Animal Breeding and Genetics.
Thibier. 2005. The zootechnical applications of biotechnology in animal reproduction: current methods and perspectives. Reproduction Nutrition Development.
Reist-Marti. 2005. Conservation programmes for African cattle: design, cost and benefits. Journal of Animal Breeding and Genetics.
Madan. 2005. Animal biotechnology: applications and economic implications in developing countries.Scientific and Technical Review.
Basrur. 2005. Genetics then and now: breeding the best and biotechnology. Scientific and Technical Review.
Swanson. International training programs in reproductive sciences for conservation of Latin American felids. Animal Reproduction Science.
Holt. 2004. Wildlife conservation and reproductive cloning. Reproduction.
Paris. 2004. Xenotransplantation: a tool for reproductive biology and animal conservation?Theriogenology.
Pukazhenthi. 2004. Which reproductive technologies are most relevant to studying, managing and conserving wildlife? Reproduction, Fertility and Development.
Shivaji. 2004. Conservation of wild animals by assisted reproduction and molecular marker technology.Indian Journal Experimental Biology.
Swanson. 2003. Research in nondomestic species: experiences in reproductive physiology research for conservation of endangered felids. ILAR Journal.
Endangered Species
Loi. 2001. Genetic rescue of an endangered mammal by cross-species nuclear transfer using post-mortem somatic cells. Nature Biotechnology.
First report of using cloning to preserve an endangered species — a Mouflon, a type of sheep. The authors say: "Our findings support the use of cloning for the expansion of critically endangered populations."
General Studies on Cloning
Wells. 2003. Cloning in livestock agriculture. Reproduction Supplement. 61, 131–150.
Bousquet & Blondin . 2004. Potential Uses of Cloning in Breeding Schemes: Dairy Cattle. Cloning and Stem Cells. Volume 6, Number 2.