The Ethics of Embryonic Stem Cell Research

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					The Ethics of Embryonic
  Stem Cell Research

         Louis DeVoe
        Jenny Gilbreath
        Matt McCumber
          Liz Moore

                Stem Cells

S Stem cells have capacity to divide for indefinite
  period of time
S At division give rise to similar stem cells or a
  more specialized cell type
           Adult Stem Cells

S Found in cell types that are constantly being
      - red blood cells (2 million per second)
      - epidermis of skin (1 gram per day)
      - hair follicles to replace hair shaft
      - male germinal stem cells (sperm)
      - neural stem cell in brain
      - muscle stem cells lining muscles
       Biology of Stem Cells

S Cells of Morula

    - Totipotent stem cell
    - Can become every cell type of the body or

S Inner cell mass cells of Blastocyst

    - Pluripotent stem cells
    - Can become every type of cell in embryo
    - Embryonic Stem cells
  Stem Cells

Stem cells become more restricted
-committed stem cell
-progenitor cell
-differentiated cell

When stem cells divide they form both a
more committed cell and another stem cell
  Lineage restricted stem cells

S Become restricted to germ layers followed by further
S Ectoderm becomes further restricted to epidermal or
  neural types
S Mesoderm becomes mesodermal derived tissue and
  organs - heart, blood, immune cells, bone, muscles,
  dermis, kidney, gonads
S Endoderm becomes gut derived tissues including the
           Progenitor cells

S Are not multipotent stem cells

S Each of two daughter cells will be a specific
  type of differentiated cell
         Cell Differentiation

S Cell specification involved the successive
  restriction of what a cell can become

S Caused by cell-cell interactions - cells tell each
  other what to become
          Paracrine Factors

S Also called growth factors

S Molecules that mediate communication
  between cells

S Usually proteins secreted by one cell and
  received by neighboring cells- act locally

S Cell receiving the paracrine signal must have a
  receptor for that factor

S Type of cell development where cells are
  instructed by their neighbors to differentiate

S The most common ways that cell fates are
  determined in vertebrate embryos
Mechanism of paracrine induction

S Paracrine factor binds to the outside domain of
  the receptor
S This causes the inside domain of the receptor
  to change shape
S The inside domain now acts as an enzyme in
  specific chemical reactions
S One reaction is to phosphorylate transcription
  factors which than become active and enter the
  cell nucleus
       Paracrine Factor Signaling
A receptor protein spans the
cell membrane

The receptor binds a paracrine
factor outside the cell which
causes the internal domain to
change its structure and become
enzymatically active

The reaction adds phosphate
groups to transcripton factors
which then enter the cell nucleus
and stimulate or repress the
activity of a specific gene
       Transcription Factors

S Once active and in the nucleus they bind to an
  area of a gene called the enhancer
S This turns the gene on or off and determines
  what genes will be expressed inside a given cell
       Reciprocal Induction

S Genes activated by transcription factors can
  make other paracrine factors
S These paracrine factors can act on the cell that
  produced the original paracrine factor
S In this way adjacent cells interact with
S Critical for organ development
  Stem Cells and Paracrine Signaling

S If all the correct paracrine
  factors were applied to an
  embryonic stem cell a
  particular cell type could
  be produced

S The new cells could be
  transplanted to replace
  diseased or missing tissue
       Potential Importance of
        Embryonic Stem Cells

S Neuron cells to treat
  brain disorders
S Pancreatic cells for
S Blood cells for people
  suffering from anemias
   Stem Cells Used in Research

S Pluripotent
S Can be kept
  undifferentiated for
  long periods of time
S Two major sources
  and two minor
                  1st    Major Source

S   Blastocyst-stage embryo cells

S   Individual cells taken from the
    inner cell mast

S   Cultured

S   Become pluripotent

S   Usually from embryos leftover
    from in vitro fertilization
             2nd    Major Source

S Primordial germ cells

S Derived from miscarried fetuses

S Most commonly pictured source of stem cells
                   Minor Sources

       Adult Stem Cells                Therapeutic Cloning
S   Can be obtained from certain   S   Nucleus from a somatic cell is
    organs                             implanted into an enucleated

                                   S   Gives rise to a blastocyst contains
                                       an inner cell mass
              Tests Done on Mice

S   Scientists have been able to form
    lineage-specific cells which are
    then able to form specific cells
    (insulin secreting cells, muscle
    cells, glial cells, and neural cells)

S   The glial and neural cells were
    functional and were able to
    reduce symptoms of Parkinson-
    like disease in mice (Bjorkland et
    al 2002: Kim et al 2002)
Major Histocompatibility Complex

S The experiments were done on genetically identical mice

S Human stem cells would cause an immune reaction

S Overcome by using the nucleus of a somatic cell and an
  enucleated oocyte (Therapeutic cloning)
         Potential Case to Cure

S Implant the nucleus of a somatic cell into an enucleated oocyte

S Allow it to develop into a blastocyst and remove the inner cell mass

S Produce embryonic stem cells from the inner cell mass

S The stem cells are cultured in paracrine factors inducing them to
   become dopaminergic neurons

S The dopaminergic neurons would be transplanted into the brain

S Successful in both mice and monkeys
             Adult Stem Cells

S The body contains stores of stem cells in areas such as bone

S Bone marrow stem cell transplants worked in mice

S A scare for adult stem cell transplants would be the
  development of tumors from incorrect transplant dosage

S As of 2004, embryonic cells were able to be frozen and
  differentiation was able to be induced later
Primum non nocere

    …first, do no harm
        3 Main Ethical Issues

S Source: Is an embryonic stem cell considered a human life?

S Egg donation: Who will supply the eggs, how might the
  suppliers be paid, do these donors have rights?

S Life Extension: Would it be a good thing to allow people to
  extend their natural life span?
Sources of Embryonic Stem Cells

 S Embryonic stem cells (ESCs) come from frozen zygotes,
   “fresh” zygotes, or aborted fetuses.

 S Are these human beings?

 S What constitutes a human life?

 S What defines the beginning of human life?

 S When does one acquire value, human dignity, and rights?
                    Pros & Cons

S 1) “Left over” after in vitro fertilization (IVF)- frozen embryos
  S (+) Does not risk objectifying the embryo as a source for
     commercial use
   S (no money should be given to the donating couples)
   S (-) Some say this is not a broad enough range of genetic types

S 2) Embryos created solely for obtaining stem cells
  S (+) Can direct and manage specific cell lines
  S (-) May objective embryos as product or commercial good instead
      of a human being
                     Pros & Cons

S 3) Aborted Fetuses
   S (+) Does not objectify the embryo or directly kill the embryo
   S (-) May be difficult to obtain

S 4) (Potentially) Fused human nuclei with enucleated cow oocytes
   S Only a potential source of embryonic stem cells
   S (+) May avoid some of the legal & ethical constraints
   S (-) fear of creating viable chimeras
   S (-) fear of transferring viruses
              Therapeutic Cloning

S Not exactly the same debate as ESC research but is closely tied

S Support:
  S Tissues- not people- are the intended result and thus their destruction is not
  S Viability as an embryo is already severely compromised because its
    nucleus was transferred from an already differentiated cell
  S Destruction of a cloned embryo to make ESCs is a less ethical problem
    than the destruction of frozen embryos in the IVF clinic

S Against:
  S May increase the likelihood of a successful attempt at human reproductive
  S too much of a risk…
     Therapeutic Cloning (cont)

S Conception technically never takes place because there is not a
  joining of an egg and sperm…but the cloned embryo does have
  potential to grow into a fetus and thus is not supported by some
S Can they modify the genetic material in such a way that the
  embryo could only give rise to stem cells? (so even if implanted it
  would not develop into a fetus)
  S Ex) knocking out the CDX2 gene that is essential for development of the
    trophoblast in mice
  S But some argue there is no basis for concluding that a gene represents a
    transition point at which a human embryo acquires moral status
 Do the benefits outweigh the
S “Does the destruction of a human embryo at the very earliest
   stages of development constitute harm that is morally
   unacceptable when weighed against the potentially monumental
   gains in the war against human suffering” (p.159).

S Pros:
   S   Could possibly alleviate or eliminate diseases such as Parkinson’s,
       Alzheimer’s, multiple sclerosis, diabetes, spinal cord injuries, etc.

S Cons:
   S   If one defines an embryo to be human than is killing one human to
       alleviate the pain and suffering of another justified?
           Humans are Unique

S 1) There is something unique about human beings that
  make them different than other animals
  S Ex) rationality, ability to communicate, human soul, etc
  S Laws against slavery and cannibalism

S 2) Part of our human dignity is found in using one’s brain
  S ESC research has the potential to restore human dignity to
    those who suffer (Alzheimer’s patient can dress himself)
  S Both sides fight for their “moral obligation
     S   Supporters- obligation to fight for the patient
     S   Opposition- obligation to fight for the embryo
         Religious Perspectives

S Largely revolves around the definition of life and when
   life begins.
S Jewish:
  S Fertilized egg does not have “personhood” and is without legal
  S Humans have an obligation to heal should further pursue ESC

S Islamic
  S Embryo doesn’t have full human rights until “ensoulment” which
     is 120 days after conception (some say 40 days)
  S Acceptable to do ESC research prior to this day
  Religious Perspectives (cont)

S Roman Catholic & Eastern Orthodox
  S Embryo is an individualized human entity from the moment of
  S Prohibits all human embryonic stem cell research except that from
    a spontaneously aborted (miscarried) fetus

S Christian Protestant
  S Very diverse perspectives
  S Totally unacceptable because embryo has equal moral status of a
    human and should be protected
  S Some support cells from supernumerary embryos from IVF and
    fetuses aborted for therapeutic reasons
                    Oocyte Donation

Ethics against it:

S   1) Poses unfair risks to women
    S   –hormones for superovulation
    S   –cancer
    S   –Ovarian hyperstimulation syndrome (5%)

S   2) Exploitation of poor women
    S   -pressured into selling their oocytes to commercial suppliers

Discoveries that may reduce the number of oocytes needed from women:

S   1) # needed for stem cells may be less than that for cloned animals

S   2) ESCs may be able to generate more oocytes and then be the source, not women
    S   -does it represent the beginning of life? Could/should they be used to create viable

S Life extension

S Age retardation

S Stem cells have the potential to do both

S Against:
   S   Would our lifestyles be less committed and less motivated?
   S   Society is renewed by teaching its principles to children, would it be sustained?
   S   One generation wouldn’t make way for the next (jobs) could lead to lack of
       innovation and adaption
   S   Economically the wealth may be concentrated in the hands of the elderly

S So…These therapies may need to be restricted to the young

S Bill Clinton George Bush Barack Obama

S Now embryonic stem cell research is federally funded in the US

S National Academies previously advised setting up guidelines:
   S   Ethics committee, full consent, no payment, anonymity, no culturing past
       14 days, no cloning, etc.

S 1st Clinical Trials have begun in the US

S Federal funding must be published so it is shared with the public

S Over 200 patents (10 involving human ESCs)
   S   Should human cells be considered patentable subject material?
Equal Opportunity vs.
   S Will cures be equally available to all?

   S Should we use public money to develop
     treatments that will presumably only
     benefit the well-off ? (This money could
     otherwise go towards expanded basic
     health care for the disadvantaged).
     S It may initially only benefit the wealthy but
       overtime may level out.
     S There is a great economic cost in maintaining
       victims of diseases such as Parkinson’s and

S What constitutes a human life?

S What dignity and value do human embryos have, if any?

S Will the need for oocytes bring harm to women?

S Is the extension of life something we really want?

S How will this effect society and the economy?

S Who is your patient and what is harm?
     The End

Primum non



S Bioethics and the New Embryology; Chapters 9 & 10


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