Human and Animal cloning John K Heath

Cloning animals The science The history The applications and ethical issues

What is cloning? J.B.S. Haldane coined the word "clone" (from Greek for "twig") Our genes are derived 1/2 from mother and 1/2 from father: We are genetically unique indivduals Cloning is to regenerate a organism asexually by transferring the nucleus of a adult cell into an egg This organism would be genetically identical to the donor of the nucleus In theory it might be possible to generate many replicas of one individual

What scientific question would be answered by cloning? Different cell types in the embryo and adult express different Repertoires of genes Eg Haemoglobin /blood cells, Keratin /skin cells etc. Is this due to loss of genetic information during development? Or selective expression of genetic information? Does the nucleus of an adult cell retain the genetic information Necessary to recreate an entire individual?

Cloning - the history and human drama

Hans Spemann (Germany), proposes a "fantastical experiment” transferring a nucleus from an adult cell to an enucleated egg. Spemann used the nucleus from a 16-cell salamander embryo to create an identical twin Robert Briggs and Thomas King (Philadelphia) clone tadpoles from frog early embryo cells. 27 tadpoles develop from 197 nuclear transfers John Gurdon (Oxford) clones sexually mature frogs from intestinal cells of adult frogs, with a 2% success rate.

Cloning is possible in amphibians Is this a special feature of amphibians? Can mammals be cloned?

David Rorvik, a U.Swriter, publishes IN HIS IMAGE: THE CLONING OF A MAN the purported story of a millionaire who had himself secretly cloned. The book becomes a best seller. In 1982, the publisher admits it was a hoax, after making $730, Karl Illmensee (University of Geneva) claims to have cloned mice, using cells from early mouse embryos Illmensee is accused of fraud and loses his job and research grants Davor Solter (Wistar Institute), after extensive experiments with mice, claims: “Cloning of mammals is biologically impossible”.

Steen Willadsen (Cambridge University) clones sheep from early embryo cells Neal First, Randall Prather and Willard Eysestone clone a cow from a cow early embryo cell (July) Ian Wilmut and Keith Campbell, Roslin, clone identical lambs from differentiated, 9 day old embryo cells. The lambs are named "Megan" and "Morag" (July) Wilmut and Campbell clone "Dolly", using frozen udder cells from an adult ewe.

Dolly the Sheep

Technique of Reproductive Cloning Transfer to the uterus Clone Nuclear transfer (SCNT) Enucleation Egg donor Activation Blastocyst Somatic cell

Cloning by nuclear transfer in mammals

Friday, 14 February, 2003, 20:28 GM Dolly the sheep clone dies young Dolly the sheep, who became famous as the first mammal to be cloned from an adult cell, has died.The news was confirmed on Friday by the Roslin Institute, the Scottish research centre which created her. A decision was taken to "euthanase" six-year-old Dolly after a veterinary examination showed that she had a progressive lung disease, the institute said in a statement.

Premature death is common in cloned sheep

Cloning is very inefficient

Lessons from mammalian cloning Cloned animals can be obtained from adult nuclei The frequency is very low: most cloned embryos die Most (all?) embryos are malformed: overtly or subtly ‘Clonability’ of nuclei is not infinite (cloning a clone) Cloning can be done - but very badly Is this a technical problem or fundamental?

Medical Uses of Cloning

Reproductive cloning The regeneration of a whole organism by cloning techniques Therapeutic cloning The creation of specific cell types from a cloned embryo

Stem cells and totipotency

Stem cells from the Early human embryo can be propagated in culture

The derivation of Stem (hES) cells from the Human preimplantation embryo

RA + Neurotrophin Aggregation Into Embryoid body

Routes to ES cell Differentiation

ES cells form PGCs and Gametes Surani 2004

1.How to direct their differentiation into specific cell types efficiently? 2. How to separate the differentiated cells from undifferentiated cells that might form tumors 3. How to deliver them efficiently for tissue repair. 4. Differentiated cells will not be genetically identical to any patients needing tissue therapies. Problems to be overcome to achieve therapeutic potential of HUMAN EMBRYONIC STEM CELLS

Autologous Regenerative Medicine or ‘Therapeutic cloning’

SCNT for making embryonic stem cells Culture in the laboratory Somatic cell nuclear transfer Enucleation Egg donor Activation Blastocyst Stem cell line

The production of pure differentiated cell types from totipotent stem cell can be achieved Totipotent stem cells can be made from cloned human embryos Can these be used therapeutically? Ethical dilemmas: How do we know they are normal? The production of gametes from stem cells?

Some uses of reproductive cloning

Animal Husbandry The replication of high value agricultural animals ‘Pharming’: replication of animals which express high value proteins in milk Genetically engineered pigs for xeno- transplantation

Preservation of endangered species Noah, the first endangered animal born by inter-species nuclear transfer.

Some Abuses of reproductive cloning?

Human reproductive cloning HUMAN REPRODUCTIVE CLONING ACT 2001 Was given Royal Assent: (Ch 23, 2001) Council of Europe (1997). Additional Protocol to the Convention for the Protection of Human Rights and Dignity of the Human Being with regard to the Application of Biology and Medicine, on the Prohibition of Cloning Human Beings, Strasbourg: Council of Europe

"God does not exist, we were the ones who made all life on earth, "you mistook us for gods and distorted our teachings of love" "we now reveal how to realise your potential and achieve global peace" "- Yahweh The Raelian Revolution, the world's largest Atheist, non-profit UFO related organisation - working towards the first embassy to welcome people from space... Raël has also learned that cloning is the way to immortality: there is no God or soul

cloning