UNSW Embryology

Week 1 - Cloning

© Dr Mark Hill (2008)

Acknowledgements

Introduction

Cloning has become an important issue in embryonic development both in terms of its practical applications and both the legal and ethical issues that relate to this process. Below are some links to specific sites relating to cloning, including the Roslin Institute, UK where "Dolly" was originally cloned. Currently there are legal and ethical arguments around the world concerning Human cloning and the use/generation of Human Stem Cells (More? Stem Cell Notes).

Dolly, the first cloned sheep

Roslin Institute in the creation of "Dolly" the sheep used four hundred and thirty eggs were extracted from 40 donor sheep, 277 reconstructed eggs were developed, but only 29 embryos resulted. Thirteen surrogate mothers were used, and all of this resulted in the birth (5 July 1996) of only one clone, Dolly.

Page Links: Introduction | Some Recent Findings | News Articles | Sheep | Mouse | WWW Links | References | Glossary

Some Recent Findings

Mouse - Li J, Greco V, Guasch G, Fuchs E, Mombaerts P. Mice cloned from skin cells. Proc Natl Acad Sci U S A. 2007 Feb 13 (More? Mouse Cloning | Stem Cells)

"It has been widely speculated, but largely untested, that their undifferentiated and quiescent state may make stem cells more efficient as donors for cloning by nuclear transfer (NT). Here, we report the use of nuclei from hair follicle stem cells and other skin keratinocytes as NT donors."

Sheep

Dolly, the first cloned sheep

The Roslin Institute in the creation of "Dolly" the sheep used four hundred and thirty eggs were extracted from 40 donor sheep, 277 reconstructed eggs were developed, but only 29 embryos resulted. Thirteen surrogate mothers were used, and all of this resulted in the birth (5 July 1996) of only one clone, Dolly.

The cloned sheep also gave birth (by natural reproduction) to 4 lambs (1998,99).

The six-year-old sheep developed a progressive lung disease and was "euthanased" (14 Feb 2003). (More? BBC News - Dolly Dies)

The name "Dolly" came from Dolly Parton as the sheep was cloned from an adult mammary gland cell.

Links: The Roslin Institute | News Articles | BBC News - Dolly Dies

Mouse

Li J, Greco V, Guasch G, Fuchs E, Mombaerts P. Mice cloned from skin cells. Proc Natl Acad Sci U S A. 2007 Feb 20;104(8):2738-43. (More? PNAS Link | Stem Cells)

"It has been widely speculated, but largely untested, that their undifferentiated and quiescent state may make stem cells more efficient as donors for cloning by nuclear transfer (NT). Here, we report the use of nuclei from hair follicle stem cells and other skin keratinocytes as NT donors."

Mice cloned from adult skin keratinocytes and other cells by nuclear transfer (NT)
(Image: Proc Natl Acad Sci U S A. 2007 Feb 20;104(8):2738-43. © 2007 National Academy of Sciences, U.S.A.)

(A) Cloned blastocysts from oocytes reconstructed by NT of bulge follicle keratinocyte nuclei into unfertilized mouse oocytes. The 6+CD34+ bulge keratinocytes were isolated by FACS from skin of adult female K14-Cre/ROSA-floxed-lacZ mice and used directly in NT. (B) Three mice cloned from the same donor mouse, an adult female. The pup on the left is from an 6+CD34+ bulge follicle keratinocyte nucleus, and the two pups on the right are from CC nuclei. (C) Three mice cloned from the same donor mouse, an adult male. The pup on the left is from an 6+CD34+ bulge follicle keratinocyte nucleus, and the two pups on the right are from 6+CD34– keratinocyte nuclei. (D) Six-week-old mice cloned by NT from 6+CD34+ bulge follicle keratinocytes isolated from an adult male.

News Articles

• August 2001- The debate rages on concerning Stem Cells and human Cloning in the News. The external links below to CNN and are videos and require Quicktime
  • Stem Cell Animation
  • Doctor talks about cloning plans- CNN's Elizabeth Cohen interviews Dr. Panos Zavos on his plans to clone humans (6 Aug 2001)
  • Human cloning plan outlined, defended Researchers talk about their plan and defend accusations healthy clones cannot be produced (7 Aug 2001)
  • Illegal to clone humans in U.S. CNN's Kyra Phillips talks to CNN Legal Analyst Roger Cossack about U.S. cloning laws (7 Aug 2001)
• July 2001- Animations
  • Timeline of cloning
  • The cloning process
• March 2001- Italian doctor claims he will carry out first human cloning. Generates enormous furore in Scientific/Medical/Ethical communities. See CNN articles.
• USA considers human embryo research under the new Bush administration, an article from the BBC.
• Transcript of discussion on ABC Radio (Dr. J Kahn , Dr. JWagner) on Genetic Technology And Ethics
• February 2001- The Human Genome was simultaneously published in papers in both Science and Nature journals. While still incomplete it is the most accurate map of the genetic background for development. The sequence was developed by both an international consortium and a commercial group. Note that knowing what genes are present in the genome is only the first step, you then have to know their function. See also introduction to the Human Genome pages.
• A brief article on Cord Blood stem cells and their therapeutic potential from the BBC. (More? about stem cells)
• January 2001- The British parliament passes a law under the 1990 Human Fertilisation and Embryology Act to allow cloning of human embryos. This cloning is to be carried out for scientific research purposes only to human stem cells.
• special article on Cloning from the New Scientist magazine, a good place begin researching this topic.

WWW Links

• Roslin Institute- "Dolly" cloning
  • Cloning and Nuclear Transfer
• Cloning (www.pharma.org/genomics/cloning/index.html)
  • Part of the Genomics: a global resource site provided by PHARMA (Pharmaceutical Research and Manufacturers of America) (www.pharma.org/genomics/)
• United Kingdom- The Royal Society- Whither cloning (1998) (8 pages PDF document)
• Australia- Australian Academy of Science- 3. On human cloning
• France- Reply to the President of the French Republic on the subject of reproductive cloning (N°54 - April 22, 1997)
• Cloning: statements from the Church of Scotland's Science, Technology and Religion Project (dspace.dial.pipex.com/srtscot/srtpage3.shtml)
  • Includes a report to the 1997 General Assembly of the Church of Scotland and a set of continuously updated briefing notes on cloning and related issues. See also the pages dealing with Genetic Engineering and Human Genetics at dspace.dial.pipex.com/srtscot/srtpage3.shtml#Issues
• Cloning and conservation of animal genetic diversity (www.fao.org/news/1997/971209%De.htm)
  • A commentary from the Food and Agriculture Organisation of the United Nations (FAO) (www,fao.org) on the potential impact of cloning on the effort to preserve the genetic diversity of domestic animal species (December 1997)
• Cloning issues in reproduction, science and medicine (www.dti.gov.uk/hgac/papers/papers_c.htm)
  • A consultation paper prepared in January 1998 by the Human Genetics Advisory Commission as part of a joint UK wide exercise with the Human Fertilisation and Embryology Authority, with a particular emphasis on implications for human medicine (January 1998).
  • The final report, also entitled Cloning issues in reproduction, science and medicine (www.dti.gov.uk/hgac/papers/paperd1.htm) was issued in December 1998.
• Council of Europe (www.coe.fr)
  • Includes the text and background notes to the Protocol banning human cloning in Europe (January 1998), developed under the Convention on Bioethics (See: www.coe.fr/eng/legaltxt/e-bio.htm).
• Home Office, Animals, Byelaws and Coroners Unit (ABCU) (www.homeoffice.gov.uk/ccpd/abcu.htm)
  • Links to the part of the UK Government responsible for the operation of animal welfare law and for the licencing of scientific procedures involving animals
• Ifgene: International Forum for Genetic Engineering
  • An international forum to promote discussion about the moral and ethical aspects of genetic engineering, includes a list of further sources.
• New Scientist special report (www.newscientist.com/nsplus/insight/clone/clone.html)
  • Special report from the weekly science magazine with further links and a discussion site
• Nuffield Council on Bioethics (www.nuffieldfoundation.org/bioethics/)
  • An advisory body sponsored by the Nuffield Foundation to examine ethical issues arising from recent advances in biological and medical research.
• The cloning of Dolly (www.synapse.ndo.co.uk/science/clone/index.html)
  • A readable explanation from Science Explained (January 1998)
• (US) Biotechnology Information Center (www.nal.usda.gov/bic/)
  • A useful starting point for information on all aspects of biotechnology provided by the (US) National Agricultural Library
• (US) National Biotechnology Advisory Committee (www.nih.gov/nbac/nbac.html)
  • Web site for the body advising the US government on biotechnology issues
• (US) National Bioethics Advisory Commission (bioethics.org)
  • An advisory body set up by President Clinton in 1995 to deal with the implications of recent advances in biological and medical research. See Reports for their report on human cloning (June 1997).
• (US) National Reference Center for Bioethics Literature (guweb.georgetown.edu/nrcbl)
  • A US national resource for literature and resources relating bioethics.
• Reflections on cloning (www.vatican.va/roman_curia/pontifical_academies/acdlife/documents/en_rc_pa_acdlife_doc_30091997_clon_en.html)
  • A commentary by the Vatican sponsored Academy for Life (www.vatican.va/roman_curia/pontifical_academies/acdlife/index.html) (September 1997)
• Yahoo Science and Technology, full coverage: cloning debate (www.headlines.yahoo.com/full_coverage/tech/cloning/
  • A collection of (mainly US) Web resources from one of the major Web directory services

References

• Campbell, K.H.S., McWhir, J., Ritchie, W.A., & Wilmut, I. (1996) Sheep cloned by nuclear transfer from a cultured cell line. Nature 380 64-66
• Wilmut, I., Schnieke, A.E., McWhir, J., Kind, A.J., & Campbell, K.H.S. (1997) Viable offspring derived from fetal and adult mammalian cells. Nature 385 810-813
• Schneike, A.E., Kind, A.J., Ritchie, W.A., Mycock, K., Scott, A.R., Ritchie, M., Wilmut, I., Colman, A., & Campbell, K.H.S. (1997) Human factor IX transgenic sheep produced by transfer of nuclei from fetal fibroblasts. Science 278 2130-2133
• Ashworth, D., Bishop, M., Campbell, K., Colman, A., Kind, A., Schnieke, A., Blott, S., Griffin, H., Haley, C., McWhir, J. & Wilmut, I. (1998) DNA microsatellite analysis of Dolly Nature 394 329
• Sheils, P. G., Kind, A. J., Campbell, K. H. S., Waddington, D., Wilmut, I., Colman, A., & Schnieke, A. E. (1999) Analysis of telomere length in cloned sheep. Nature 399 316-317
• Evans, M. J., Gurer, C., Loike, J. D., Wilmut, I., Schneike, A. E., & Schon, E. A. (1999) Mitochondrial DNA genotypes in nuclear transfer-derived cloned sheep Nature Genetics 23 90-93
• Judy Siegel-Itzkovich Israel bans imports of fertilised ova BMJ 2001; 323: 532e.

Glossary of Terms

A | B | C | D | E | F | G | H | I | J | K | L | M | N | O | P | Q | R | S | T | U | V | W | X | Y | Z

Quick Links

Week 1 Pages:

Introduction | Abnormalities | Gamete formation | Cell division | Fertilization | Zygote | Blastocyst | Male sex determination| X inactivation | References | Text only page | WWW Links |

Development Notes ----------------- Menstrual Cycle Week 1 Week 2 Week 3 Week 4 Placenta Serial Images Genes/DNA Molecular Dev Abnormal Dev Postnatal Dev Notes Index

System Notes ----------------- Heart/Cardiovascular Respiratory Coelomic cavity Gastrointestinal Tract Head and Neck Neural Neural Crest Eye Ear Nose Endocrine Urogenital Musculoskeletal Integumentary

Movies ----------------- Embryo Growth Ultrasound Week 1 Week 2 Week 3 Week 4 Stage 13/14 Stage 22 Neural Head and Neck Heart Vasculature Gastrointestinal Urogenital Other Embryos Larsen Internet

Other Embryos ----------------- Chicken Fly Frog Mouse Rabbit Rat Worm Zebrafish Guinea Pig

UNSW Embryology ISBN: 978 0 7334 2436 6

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