CLONING

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CLONING
A Hot Topic

• Anne Simpson, Jan 03

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• Who can quantify the indescribable source of
  emotion pleasurable and otherwise that children
  engender in their biological and social parents?
  It is this above all else which drives
  individuals to take extreme measures to achieve
  or avoid parenting in the modern world.
• Infertility in the Modern World Present and
  Future Prospects, GR Bentley

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• Why should another child die from leukemia when
  if the technology is allowed we should be able to
  cure it in a few years time?
• Simon Smith, The Human Cloning Foundation

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Background

• First reproductive cloning in 1952 in Amphibia.
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• First mammal cloned in 1996 in Edinburgh -Dolly
  the sheep.
• Sheep, cattle (1998), mice (1998), goats (1999)
  and pigs (2000) have all been cloned.

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What is cloning?

• Embryo Splitting or Cloning
• Somatic Cell Nuclear Transfer (SCNT)
• Reproductive Cloning
• Therapeutic Cloning

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Embryo splitting or cloning

• Separation of human embryo into 2 parts.
• Cells removed from fertilised ovum - have the
  potential to develop into a blastocyte
• If implanted can develop into a child.
• Genetically identical monozygotic twins
• The embryo can be spilt only a limited number of
  times, and a clone is not produced.

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Somatic Cell Nuclear Transfer

• Nuclear material removed from donor egg
• DNA inserted into the enucleated egg
• Reconstituted zygote formed, equivalent to a
  fertilised ovum.
• Potential to divide into a blastocyte
• If implanted, develops into child genetically
  identical to the nuclear donor - Reproductive
  cloning.
• In reproductive cloning the clone would be the
  identical twin of the donor

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Schematic representation of Somatic Cell Nuclear
Transfer
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Therapeutic cloning

• SCNT
• Blastocyte (embryo) cultured to produce an
  embryonic stem cell line
• Excludes most blastocyte cells, effectively
  destroying the embryo
• Undifferentiated embryonic stem (ES) cells can
  then be made to differentiate into precursor
  cells.

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Stem Cells

• A stem cell is defined as
• A cell that can proliferate indefinitely and
  differentiate into a wide variety of cell types
• Adult stem cells are found in bone marrow,
  isolated and encouraged to proliferate
• Nuclear reprogramming obtain ES cells by
  directly dedifferentiating normal body cells in
  vitro

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• Few issues linked to genetic research have
  raised as much controversial debate as the use of
  somatic cell nuclear transfer technology (SCNT)
  to create embryos specifically for stem cell
  research
• The Pros and Cons of Human Therapeutic Cloning
  in the Public Debate, Journal of Biotechnology,
  Sep 2002

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Benefits of Therapeutic Cloning

• Therapeutic cloning has the potential
  significantly to reduce human suffering and
  enhance human happiness.
• In it may lie the potential to overcome tissue
  rejection and the opportunity to increase
  understanding of cellular development  

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Ways in which cloning may be expected to benefit
mankind

• Use of embryonic stem cells to treat degenerative
  and autoimmune conditions such as Alzheimers
  Disease, Parkinsons Disease, diabetes, heart
  failure, arthritis etc. and to treat burns
  victims and spinal cord injuries.
• Infertility treatment
• Plastic, reconstructive and cosmetic surgery
• Leukaemia and other cancers
• Transplants Kidney and liver

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The Scientific and Ethical Debate

• Therapeutic cloning involves deliberate
  production of cloned human embryos so that
  through their destruction patients may receive
  treatment.
• Majority of scientific opinion opposed to the
  reproductive cloning of humans in view of the
  developmental, morphological and physiological
  problems observed in mammals that have been
  cloned

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Ethical Questions

• Two questionable procedures
• cloning of humans
• destruction of human embryos
• Main ethical arguments against therapeutic
  cloning centre on the moral status of the human
  embryo
• Most ethical questions concerning status of the
  human embryo been examined in the context of
  abortion

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Reproductive cloning-Low efficiency

• Low efficiency of reconstituted eggs developing
  to parturition.
• 1 cloned animal to parturition, approx. 100 eggs
  must be enucleated and reconstituted
• i.e. only 1 efficient
• Weak argument when considered that IVF requires
  harvesting of up to 40 eggs

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Reproductive cloning -Abnormalities risk

• Developmental abnormalities - large offspring
  syndrome oversized offspring with
  disproportionately sized organs, respiratory and
  circulatory problems,
• May not be a risk in humans
• Incidence of congenital abnormalities in animals
  is as high as 35.
• Developmental abnormality following natural
  sexual reproduction is 3

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Reproductive Cloning - Genetic Engineering

• Cloning makes it easier to meddle with genes,
  another form of genetic engineering
• Risk of incompletely reprogrammed genes, could be
  minimised by the optimum culture conditions used
  in IVF.

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Therapeutic Cloning Adult stem cells

• Many benefits of embryonic stem cells can be
  achieved using adult stem cells.
• Adult stem cells are demonstrating greater
  multipotency than expected
• Adult stem cells hard to isolate and have
  restricted proliferation potential.
• Range of cells they can be differentiated into
  is limited
• Risks of using blood stem cells from a cancer
  patients own bone marrow to restore their immune
  system some might be cancerous

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Therapeutic Cloning

• Cloned cells may be more vigorous and therefore
  at greater risk of becoming cancerous
• Studies using cloned blood stem cells in cows
  came from 100-day old fetuses

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Embryo status

• Are embryos already human beings?
• Society still divided over how to regard the
  moral rights of and its duties towards the human
  embryo.
• Are human embryos entitled to protection from
  intentional destruction.

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Ethical Dilemma

• Relief of suffering is not a sufficient argument
  to justify the means.
• Abortion legislation in most countries suggests
  the rights and choice of grown adults supercede
  the rights of the early embryo

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• If the position were taken that embryos are not
  persons and may be destroyed, and that position
  turns out to be wrong, we will have endorsed the
  killing of thousands if not millions of human
  beings. If human embryos however are not
  persons, but we treat them as is they were the
  potential harm is that therapies might become
  available more slowly.
• What to call Human Cloning OMathuna, European
  Molecular Biology Organisation

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Middle Ground

• Bioethicists recommend aggressively pursuing
  adult stem cell research while upholding the
  highest ethical standards for medical research

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Current International Regulations

• US expected to ban reproductive cloning,
• still debating whether to allow therapeutic
  cloning
• Australia recently passed bill allowing
  harvesting of stem cells from surplus IVF
  embryos.
• Reproductive and therapeutic cloning have been
  banned

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Current International Regulations cont.

• European countries - unanimous prohibition
  reproductive cloning
• No agreement on permission for research into
  therapeutic cloning.
• UK took the lead and voted in favour of
  regulations allowing therapeutic cloning
• UK law allows researchers to harvest stem cells
  from surplus IVF embryos and conduct therapeutic
  cloning

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Human Fertilisation and Embryology Act 1990

• to make provision in connection with human
  embryos to prohibit certain practices in
  connection with embryos and gametes to establish
  a Human Fertilisation and Embryology Authority

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Human Fertilisation and Embryology Authority

•   A statutory body which regulates licenses and
  collects data on fertility treatments such as IVF
  and donor insemination as well as human embryo
  research in the UK.
• Set up in 1991

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Human Fertilisation and Embryology Authority

• Ensure high national standards, monitors all
  research, supervises controlled research,
  considers ethical implications in light of the
  national debate
• 21 members appointed by UK Health Ministers based
  on personal knowledge and expertise, half of whom
  come from disciplines other than medicine or
  human embryo research

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References

• Cloned stem cells may give new lease of life New
  Scientist
• What to call Human Cloning OMathuna, European
  Molecular Biology Organisation
• Reiss MJ, Ethical Dimensions of Therapeutic Human
  Cloning, Journal of Biotechnology, Sep 2002
• The Pros and Cons of Human Therapeutic Cloning in
  the Public Debate Journal of Biotechnology, Sep
  2002
• Infertility in the Modern World Present and
  Future Prospects, GR Bentley
• The Human Cloning Foundation
• www.howstuffworks.com
• Commentary on Human Cloning Byrne Gurdon,
  Differentiation 2002
• www.hfea.gov.uk
• www.newscientist.com

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INFERTILITY

• Management of Infertility
• Clinical Review 2002, BMJ
• BMJ 200232528-32 (6July)
• The Initial Investigation and Management of the
  Infertile Couple
• RCOG, Evidence Based Clinical Guidelines,1998
• www.rcog.org.uk/guidelines