Cloning and Reproductive Control

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Cloning and Reproductive Control

• Dr. Pattle Pun,
• Dept. of Biology, Wheaton College,
• Wheaton, IL 60187
• Pattle.p.pun_at_wheaton.edu

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From Clone to Man
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Technology of cloning
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Mammalian (Non-human)Reproductive Cloning WHY?

• Accomplish animal husbandry goals
• Produce genetically identical animal strains
• Replicate elite farm livestock
• Animal conservation
• To produce transgenic livestock
• Pharming
• Xenotransplantation
• Disease-resistant livestock

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Polly and her sisters secrete human factor IX
in their milka drug needed by hemophiliacs
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Targeted disruption of a key gene causing tissue
rejection A step closer to xenotransplants?
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Developments in Human Cloning

• Abnormal human embryos cloned by embryo
  splittingHall Stillman, 1993
• Establishment of human ES cell lines first
  reported in 1998 from
• BlastocystsThomson et al.
• Germinal tissues of fetusesShamblott, et al.

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Developments in Human Cloning

• Several groups are trying to isolate ES cells
  from cloned human embryos
• Advanced Cell TechnologyCibelli et al., 2001.
• Roger Pedersenformerly of UCSF
• Lu Guangxiu (China)isolated ES cells from human
  blastocysts? 2002
• Advanced Cell Technologyfrom single
  blastomeresKlimanskaya et al., 2006
• Several groups are reportedly trying to produce
  children from adult nuclear donors
• Reproductive Cloning vs Therapeutic Cloning (Stem
  Cells)

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Dr. Severino Antinori and Dr. Panos Zavos
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Dr. Brigitte Boisselier with Rael
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• A human clone has no genetic contribution from
  the mother. If an infertile couple uses human
  cloning to obtain offspring, they will use the
  nucleus of the somatic cells of the husband for
  implantation into the enucleated egg of the
  mother. The resulting clone will always be a male
  who possesses only the characteristics of the
  father

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• In 2001, a few fertility researchers in the
  United States and in Italy have begun
  experimenting on human cloning. Many infertile
  couples have already volunteered their sex cells
  for these experiments. These scientists claim
  that they will have successful results in two
  years and predicted that the expenses of human
  cloning will be comparable to artificial
  insemination.

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• When the somatic cells from an adult individual
  are cultivated in the laboratory, they will only
  divide and develop into the same kind of somatic
  cells. However, when stem cells derived from
  human embryo are established as cell lines that
  can perpetually divide in the laboratory, they
  can develop into various kinds of human tissues.

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• These totipotent characteristics of the human
  stem cells are most promising for medical
  research since these cells can be exploited to
  become potential sources of human transplants to
  replace damaged tissues in many incurable
  diseases.

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Technology of Stem Cell Research
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• Potential benefits of human cloning and stem cell
  research

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•  
• One in 6 couples in developed countries on the
  average is infertile due to genetic or
  environmental causes. Artificial insemination and
  human cloning are amongst the techniques that can
  help these infertile couples to conceive and
  fulfill their desires for procreation.

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• In an animal study, Dr. McKay and his
  colleagues Lorenz Studer, M.D., and Viviane
  Tabar, M.D., took neural stem cells from the
  brains of rat embryos and grew them in culture
  dishes with a protein called basic fibroblast
  growth factor that helps the cells survive and
  divide. After the cells multiplied for 6 to 8
  days, the growth factor was removed and the cells
  were allowed to aggregate into free-floating
  spheres of neurons. The neurons in the spheres
  began to develop functioning connections with
  each other, producing dopamine as well as several
  other kinds of neurotransmitters. When the
  spheres were injected into the brains of rats
  that were missing the dopamine-producing region
  on one side of their brains, the rats
  Parkinsonian symptoms gradually diminished. Most
  showed about a 75 percent improvement in motor
  function 80 days after they received the
  transplants.
•  

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• Stem cells can be one of the sources for human
  transplants. For example, scientists have
  successfully cultivated nerve cells that secret
  dopamine, a neurotransmitter, from embryonic stem
  cells. These cells are transplanted into the
  bodies of patients suffering from Parkinsons
  disease in whom the defective nervous system
  lacks dopamine. Their bodies then acquired the
  ability to secret dopamine and they are cured.
  Despite opposing results and side effects that
  are yet to be totally understood and controlled,
  embryonic stem cells seem to also pose promises
  for other incurable diseases such as diabetes.

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• Medical and Ethical Challenges

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• There are web sites offering human sex cells for
  sale. Sperms of Nobel laureates and eggs of
  beautiful models or female students of
  prestigious institutions of higher learning are
  collected and sold to the highest bidders

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Special Egg Donor Needed

• Preferred donor will meet the following criteria
• Height 5-6 or taller
• Caucasian
• High ACT or SAT score
• College student or graduate under 30
• No genetic medical issues
• Extra compensation for gifted athlete,
  science/math student or musician

80,000
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• Molecular biologist Professor Lee Silver of
  Princeton University predicted that the 21st
  century will divide human societies into two
  groups according the cloning technology
• The GeneRich
• those who are able and/or willing to clone
  themselves,
• The Naturals
• those that are unable and/or unwilling to
  clone themselves

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• A brave new world envisioned by the eugenic
  movement will become a reality. Unscrupulous
  entrepreneurs and aggressive politicians will use
  reproductive technologies such as human cloning
  and genetic manipulation to control human
  populations and monopolize market economy. The
  net effect may be the polarization of the rich
  and the poor, the haves and the have-nots.
  Totalitarian regimes can exploit the eugenic
  movement to eliminate the unfit of human
  societies!

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• Are human clones really human?

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• When Dolly was born, she was not an infant sheep
  since she carries the genetic material of the
  nuclear donor. Adult body cells are known to
  gradually lose their telomers (the end sequences
  in the linear chromosomes of most eukaryotic
  cells) because of the lack of telomerase, an
  enzyme found in tumor or embryonic cells which
  can lengthen the telomers during cell division.

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• As a result, the life expectancy of Dolly is
  shorter than a newborn sheep. In addition, Dolly
  has obesity problem. At 6, she was given a lethal
  injection after veterinarians discovered she had
  lung cancer. Normal life span of sheep is 12
  years. These symptoms that are
  associated with premature aging are
  also found in other cloned
  animals.

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Wilmut listed defects occurring regularly in
other cloned animals, including gigantism
(excessive size) in cloned sheep and cattle
placentas of up to four times the normal size in
mice and heart defects in pigs. Despite being
given normal amounts of food, many cloned mice
also become grotesquely fat, while many cloned
cows, sheep and pigs have developmental
difficulties, lung problems and malfunctioning
immune systems. Cloned animals have also shown
a variety of individual defects. A calf cloned in
France appeared to be thriving but suddenly died
at 51 days old after a failure in its ability to
produce white blood cells. Similarly, scientists
at Roslin had to put down a cloned lamb at 12
days old because the muscles around its lungs
were so abnormally thick that it could hardly
breathe.
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• Moreover, the success rate of cloned animals is
  extremely low. Dolly was born after 277
  unsuccessful trials. It will be a horrendous
  waste of human embryos if similar experiments are
  carried out in the attempts to clone humans when
  more than 99 of them are destroyed.

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• Human clones are not only facing health problems,
  they are also faced with psychological pressures.
  He/She always lives under the shadow of his/her
  nuclear donors and will not have the normal self
  image developed in the traditional nuclear family
  with biological parents.

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• Embryonic stems cells can be developed from
  discarded fertilized eggs in fertility clinics,
  aborted or miscarried fetuses. Whenever a human
  fetus is cultivated in the laboratory to develop
  into stem cells, it is no longer viable as a
  human fetus. In other words, the embryo is
  destroyed.
• While a majority of American supports stem cell
  research, a majority of them oppose it if they
  know that it involves embryo destruction.

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• In what stage of embryonic development is the
  fertilized egg accorded the status of a human
  being who is entitled to human right protection?

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• In the context of human transplants, should we
  sacrifice one life in order to save another life?

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Cloning will not provide the claimed medical
treatments Unlikely chance of success in clinical
useDr. James Thomson, USAOdorico JS et al.
Multilineage differentiation from human
embryonic stem cell lines, Stem Cells 19,
193-204 2001Dr. Alan Trounson,
AustraliaTrounson AO The derivation and
potential use of human embryonic stem cells,
Reproduction, Fertility, and Development 13,
523-532 2001Dr. Peter Mombaerts, USA,
Therapeutic cloning in the mouse, Proceedings
of the National Academy of Sciences USA 100,
11924-11925 30 Sept 2003 (published online 29
August 2003) Transplant Rejection will still
occur using cells from cloned embryosDr. Irving
Weissman13 February 2002 before the Presidents
Council on BioethicsDr. John Gearhart25 April
2002 before the Presidents Council on
Bioethics. Cloning not commercially viable
Thomas Okarma, CEO, Geron Corporation (Denise
Gellene, Clone Profit? Unlikely, Los Angeles
Times, May 10, 2002) Developing therapeutic
cloning techniques can lead to reproductive
cloningRobert P. Lanza, Arthur L. Caplan, Lee M.
Silver, Jose B. Cibelli, Michael D. West, Ronald
M. Green The ethical validity of using nuclear
transfer in human transplantation The Journal
of the American Medical Association 284,
3175-3179 27 Dec 27 2000American Society for
Reproductive Medicine Ethics Committee Human
somatic cell nuclear transfer (cloning)
Fertility and Sterility 74, 873-876 November
2000Woo Suk Hwang, lead author of the South
Korean human cloning study, admitted that the
technique developed in his lab cannot be
separated from reproductive cloning
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Therapeutic cloning places women at
risk Because both cloning and embryonic stem
cell production are extremely inefficient, a
tremendous number of eggs will be required. For
example, to treat only the 17 million Diabetes
patients in the U.S. Will require at least 1.7
billion human eggs(Optimistically 100 human
eggs/patient, estimated cost US100,000-200,000)M
ombaerts P, Therapeutic cloning in the mouse,
Proceedings of the National Academy of Sciences
USA 100, 11924-11925 30 Sept 2003 Prentice DA,
Stem Cells and Cloning, 1st edition, San
Francisco Pearson Education/Benjamin-Cummings,
July 2002 --Collecting 10 eggs/donorWill
require at least 170 million women - childbearing
age donorsHealth risksHigh-dose hormone therapy
and surgery to obtain eggs risks the donors
health and future reproductive successCommercial
exploitationof women globallySOUTH KOREAN HUMAN
CLONING FRAUDCloned human embryos?? no cells,
faked data, paying women for eggs, coercion of
women students
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• In fact, recent successes with adult stem cells
  make them a non-controversial and promising
  alternative to embryonic stem cells. These
  rapidly dividing adult cells, such as cells
  derived from bone marrow, placenta, cord blood,
  are also capable of developing into totipotent
  cells. They can also pose promises as potential
  source of human transplants.

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Adult stem cell capabilities
Some adult stem cells appear to have the
capability to differentiate into tissues other
than the ones from which they originated this is
referred to as plasticity. Reports of human or
mouse adult stem cells that demonstrate
plasticity and the cells they differentiate or
specialize into include 1) blood and bone marrow
(unpurified hematopoietic) stem cells
differentiate into the 3 major types of brain
cells (neurons, oligodendrocytes, and astrocytes)
ectoderm, skeletal muscle cells, cardiac muscle
cells mesoderm, and liver cells endoderm 2)
bone marrow (stromal) cells differentiate into
cardiac muscle cells, skeletal muscle cells, fat,
bone, and cartilage and 3) brain stem cells
differentiate into blood cells and skeletal
muscle cells. Ibid, Pg. ES-7 emphasis
added
There is no evidence of an adult stem cell that
is pluripotent. It has not been demonstrated that
one adult stem cell can be directed to develop
into any cell type of the body. That is, no adult
stem cell has been shown to be capable of
developing into cells from all three embryonic
germ layers. Stem Cells Scientific Progress and
Future Research Directions, National Institutes
of Health, June 2001 Pg. ES-6 (emphasis added)
Thus, at this stage, any therapies based on the
use of human ES cells are still hypothetical and
highly experimental. Whether embryonic stem
cells will provide advantages over stem cells
derived from cord blood or adult bone marrow
hematopoietic stem cells remains to be
determined. Stem Cells Scientific Progress and
Future Research Directions, National Institutes
of Health, June 2001 Pg. 17, 63
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Diseases Treated in Human Patients
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Nuclear Reprogramming of Somatic Cells After
Fusion with Human Embryonic Stem Cells.
Science2005 vol309 iss5739 pg1369

• The Harvard University team fused lab-grown
  embryonic stem cells with the adult cells to
  create the new stem cell. Researchers believe
  these hybrid embryonic stem cells could help
  disease research without using human embryos.
• We have explored the use of embryonic stem cells
  as an alternative to oocytes for reprogramming
  human somatic nuclei. Human embryonic stem (hES)
  cells were fused with human fibroblasts,
  resulting in hybrid cells that maintain a stable
  tetraploid DMA content and have morphology,
  growth rate, and antigen expression patterns
  characteristic of hES cells. Differentiation of
  hybrid cells in vitro and in vivo yielded cell
  types from each embryonic germ layer. Analysis of
  genome-wide transcriptional activity, reporter
  gene activation, allele-specific gene expression,
  and DMA methylation showed that the somatic
  genome was reprogrammed to an embryonic state.
  These results establish that hES cells can
  reprogram the transcriptional state of somatic
  nuclei and provide a system for investigating the
  underlying mechanisms

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In 2006, using PGD, scientists generated two new
stem-cell lines while the embryos survived and
continued to develop

• pre-implantation genetic diagnosis, or PGD,
  allows doctors to implant in a woman only the
  healthiest embryos that have been conceived
  through in vitro fertilization

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Isolation of amniotic stem cell lines with
potential for therapyNature Biotechnology 25,
100 - 106 (2007) Published online 7 January
2007 doi10.1038/nbt1274

• Stem cells capable of differentiating to multiple
  lineages may be valuable for therapy. We report
  the isolation of human and rodent amniotic
  fluidderived stem (AFS) cells that express
  embryonic and adult stem cell markers.
  Undifferentiated AFS cells expand extensively
  without feeders, double in 36 h and are not
  tumorigenic. Lines maintained for over 250
  population doublings retained long telomeres and
  a normal karyotype. AFS cells are broadly
  multipotent. Clonal human lines verified by
  retroviral marking were induced to differentiate
  into cell types representing each embryonic germ
  layer, including cells of adipogenic, osteogenic,
  myogenic, endothelial, neuronal and hepatic
  lineages. Examples of differentiated cells
  derived from human AFS cells and displaying
  specialized functions include neuronal lineage
  cells secreting the neurotransmitter L-glutamate
  or expressing G-protein-gated inwardly rectifying
  potassium channels, hepatic lineage cells
  producing urea, and osteogenic lineage cells
  forming tissue-engineered bone.

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• The United States House of Representatives have
  voted to ban research on human cloning.
• The President of the United States has also
  recently decided that federal support will not be
  available to support any research based on
  embryonic stem cells created after August 9,
  2001. In September 2006, He also vetoed a bill
  which allows couples who have had embryos frozen
  for fertility treatments to donate them to
  researchers rather than let them be destroyed.
• September 2006, Two companion bills -- one to
  promote alternative means of developing stem-cell
  lines from sources such as placental blood and
  another to ban the commercial production of human
  fetal tissue were passed unanimously in the US
  Senate. The former bill was rejected by the
  House.
• UNITED NATIONS, March 8, 2005 -- The U.N. General
  Assembly adopted a declaration that calls on
  governments to ban all forms of human cloning
  that are "incompatible with human dignity and the
  protection of human life." (Opposed by UK,
  Belgium and China.)

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Ethics of Reproductive Control

• Utilitarian Views
• Rosss theory of Beneficence
• Kantian Categorical Imperatives
• Natural Law

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Utilitarian Views

• 1. Does Reproductive Technology bring more
  happiness?
• 2. Does Reproductive Technology affect society
  adversely?

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Rosss theory of Beneficence

• Does Reproductive Technology promote the
  well-being of others?

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Kantian Categorical Imperative

• Can Reproductive Technology be universalized in
  all circumstances?

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http//www.bioethics.gov/
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Kantian Categorical Imperative Autonomy
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Human Cloning and Human Dignity An Ethical
InquiryThe President's Council on Bioethics,
Washington, D.C.,July 2002
We believe that a permanent ban on
cloning-to-produce-children coupled with a
four-year moratorium on cloning-for-biomedical-res
earch would be the best way for our society to
express its firm position on the former, and to
engage in a properly informed and open democratic
deliberation on the latter.
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David King Savior Sibling Illicit

• 1. Human beings an end, not a means.
• 2. Tissue Farms?
• http//lime.theisland-themovie.com/trailer/interna
  tional_1.html
• 3. Born to be donors second class?

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Recent Controversies

• Embryo Adoption?
• http//www.nightlight.org/snowflakeadoption.htm
• State Funding for Stem Cell Research?
• http//www.ncsl.org/programs/health/genetics/embfe
  t.htm
• California's stem-cell initiative on hold
• http//www.csmonitor.com/2006/0308/p03s03-stss.htm
  l

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Natural Law

• Part 1 Respect for Human Embryos

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Natural Law

• 2. Is Prenatal Diagnosis Licit?
• Not if Abortion is an alternative outcome.

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Natural Law

• 1. What Respect is Due to the Human Embryo,
  Taking Into Account His Nature and Identity?
• The human being must be respected as a person
  from the very first instant of his existence.

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Natural Law

• 3. Are Therapeutic Procedures Carried Out on the
  Human Embryo Licit?
• Yes if they are for the benefits for the embryos
  at minimal risks.

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Natural Law

• 4. How Is One to Evaluate Morally Research and
  Experimentation on Human Embryos and Fetuses?
• Integrity of the Human Embryos
• Informed and Free Parental Consent

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Natural Law

• 5. How is One to Evaluate Morally the Use for
  Research Purposes of Embryos Obtained by IVF?
• Voluntary destruction of human embryos for the
  purpose of research created by IVF is morally
  wrong.

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Natural Law

• 6. What Judgment Should be Made on Other
  Procedures of Manipulating Embryos Connected with
  Reproductive Technology?
• They are contrary to the dignity of the human
  embryos and are immoral.

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Natural Law

• Part II. Intervention upon Human Procreation

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Natural Law

• A. Heterologous Artificial Fertilization and
  Surrogate Motherhood
• Why Must Human Procreation Take Place in
  Marriage?
• Respect for the fidelity of married couples.
• Respect God for the gift of children.
• Violation of the One Flesh essence of marriage

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Natural Law

• B. Homologous Artificial Insemination
• Because it is in opposition to the dignity of
  procreation and of the conjugal union even though
  everything is done to insure the integrity of the
  embryos, it is immoral.
• Possible exceptions cases for miscarriages?

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• Congregation for the Doctrine of the Faith 1987
• Respect for the humanity and dignity of the
  embryo, and the nature of marriage, provide moral
  grounds to evaluate recent developments in
  assisted reproduction
• Impermissible
• Prenatal diagnosis for abortion.
• Risky therapeutic intervention in utero.
• Nontherapeutic research on embryos.
• Creating and maintaining embryos for research or
  sale, as well as destroying them.
• Cross species fertilization.
• Gestation of a human embryo other than in a human
  womb.
• Use of human genetic material in procedures like
  cloning, parthenogenesis, and twin fission.
• Manipulation of genetic material for sex
  selection or positive eugenics.
• AI for unmarried persons or widows.
• Acquiring sperm by masturbation.
• Surrogate motherhood.
• Permissible
• Medical and drug therapy to promote fertility.
• Prenatal diagnosis for fetuss benefit.
• Prenatal therapeutic intervention and genetic
  manipulation to heal the developing unborn child.

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Statement by the Vatican on Cloned Human Embryo ,
Nov. 27, 2001

• "Therefore, notwithstanding the declared
  'humanistic' intentions of those who announce
  amazing cures through this method, that will go
  via the cloning industry, a calm but firm
  evaluation is necessary that will show the moral
  gravity of this project and motivate its
  unequivocal condemnation. The principle that de
  facto has been introduced, in the name of health
  and well- being, sanctions, in fact, a true and
  proper discrimination among human beings based on
  the measure of time of their development (thus an
  embryo is worth less than a fetus, and a fetus
  less than a child, a child less than an adult),
  overturning the moral imperative that imposes,
  instead, the greatest care and maximum respect
  precisely of those who are not in a condition to
  defend themselves and to show their intrinsic
  dignity.
• "On the other hand, stem cell research shows that
  other paths are available, morally licit and
  valid from a scientific point of view, such as
  the utilization of stem cells that have been
  taken, for example, from an adult individual
  (there are many in each one of us), from maternal
  blood or from fetuses that were aborted
  spontaneously. This is the path that every honest
  scientist must follow to the end of reserving
  maximum respect for man, that is, for himself."

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• Guidelines according to the Scriptures

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• After the first human couple sinned, the human
  race has been subject to death, disease and pain
  (Gen. 3). The paradox of a loving Creator
  allowing human suffering is only resolved in the
  Incarnation, Crucifixion and Resurrection of our
  Lord Jesus Christ.

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• (A) The purpose of human life is for the glory
  of God. God created us for His glory. (Is. 437).

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• While eliminating human suffering is a noble
  cause, there may be a higher purpose for some
  incurable diseases after all human efforts are
  exhausted, as Paul has experienced from the thorn
  in his flesh. (II Cor. 127-9) Jesus did not
  confront the origins of congenital diseases. Yet
  He made it clear that the ultimate purpose of the
  healing of the man blind from birth was that the
  works of God might be displayed in him (Jn.
  93).

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• Infertile couples should not pursue human cloning
  that risks the destruction of potential lives or
  creating defective human embryos in their
  attempts to have biological offspring. This is
  exactly the reason used by the mainstream
  scientific establishment to oppose
  experimentation on human cloning. Infertile
  couples should explore other avenues of having
  children such as adoption of unwanted children or
  embryo adoption.

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• (B) Human Being, Created in the Image of God,
  Became a Living Being by the Direct Involvement
  of God.

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• Humans were created in the Image of God. (Gen. 1
  26-27). Gods act of the breathing into the
  nostrils of man the breath of life to make him a
  living being (Gen. 27) strongly suggests a
  direct involvement of God in mans life. After
  the creation of the first couple, the capability
  for procreation or the potentials of the human
  gene pool that generated the entire human race is
  also divinely endowed. (Gen. 128, 2 24).

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• The Scriptures emphasize children are the
  inheritance given by God (Ps. 1273). Invitro
  fertilization using the sex cells of an infertile
  couple and implantation of these artificially
  inseminated embryos into the wifes uterus has
  been successfully carried out. These children can
  be a gift of God made possible by good
  stewardship on the parts of scientists who
  develop these technologies. Preimplantation
  Genetic Diagnosis may be a way to produce normal
  children by IVF from disease carriers.

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• However, if the sole purpose of artificial
  insemination is to create human embryos for
  experiments in human cloning, then the line of
  violation of human rights may have been crossed.
  Human clones are products of asexual reproduction
  which lacks the normal process of genetic
  recombination during meiosis characteristic of
  sexual reproduction that gives rise to variations
  amongst the offspring of a couple. In addition,
  human clones will have shorter life spans. Even
  though the technology of human cloning can be
  improved, the human clones will live in the
  perpetuate shadow of identity crisis. They will
  always be second-class citizens. Humans are
  always an end in themselves, never a means.
•  

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Conclusion

• Establishment of Scriptural principles that
  will safeguard human dignity and prevent abuse of
  human rights for reproductive technologies.

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Baby Hope born as a means to an end?

• CBS News A Miracle 'Baby Hope' July 14,
  2003 171639

Miracle of Life http//abcnews.go.com/search?searc
htextmiracle20of20lifetype