Biotechnology and Genetic Engineering

1
Biotechnology and Genetic Engineering

• Ethics of Human Enhancement
• E 124

2
Birth to DeathEnhancement or Longevity

• In vitro fertilization (germ line engineering)
• Cloning
• Biomedical
• Prevention of disease
• Detection of disease
• Treating disease
• Vitamins
• Steroids

• Genetic analysis
• Pharmaceuticals
• Somatic enhancement
• Gene therapy
• Organ repair
• Organ transplant
• Organ donation
• Physician assisted suicide

3
What is the actual technology?

• Cloning
• Human Germ line Manipulation
• Somatic Cell Genome Manipulation
• Stem Cell Research
• In Vitro Fertilization

4
Cloning

• Cloning uses DNA of existing individual (could be
  dead) to create a new individual that is a
  genetic duplicate.
• Start by creating embryo with the same genes
• Research embryostem cells
• Reproductive cloning if implanted into womans
  uterus and brought to term to produce child.
• Best known example of reproductive cloning is
  Dolly, a sheep that was cloned using DNA from a
  sheep that had been dead for six years.

5
Cloning

• Ethical debate
• Some people against both, others only against
  reproductive cloning because of the uncertainty
  and unnaturalness, playing God and the
  disturbance of evolutionary nature
• US Federal Funds cannot be used for reproductive
  cloning and some states outlaw it, but there is
  no federal law against it.

6
Germ Line Manipulation

• Permanently changes the inheritable
  characteristics passed from one generation to
  another
• Altering sperm or egg cells or altering the embryo

7
Germ Line Manipulation

• Purpose
• Eliminate disease (in which case other means)
• Enhancement-permanently altering germ line
• Eugenics-improve human race
• Similar to breeding dogs and cats?
• Early attempts in 20th Century led to forced
  sterilization and in Nazi Germany to the
  systematic extermination of Jews in order to
  breed a superior race
• Proponents argue that
• we should select for superior individuals and
  individuals more capable of coping with complex
  problems as society gets more complex
• Gen Tech Elite society and worker society

8
Somatic Cell Manipulation

• Altering cells in the body that do not pass DNA
  and sometimes called gene therapy
• Correct genetic component of the disease instead
  of treating with drugs.
• (Ex ways of introducing genes into blood of
  hemophilia or cells of immune system in patients
  with Severe Combined Immune Deficiency (SCID), a
  rare inherited disorder of the immune system.

9
Somatic Cell Manipulation

• Child died at University of Pennsylvania after
  genes introduced into liver of a teenager using a
  modified virus to carry gene to destination.
  (evidence suggests that virus invaded organs
  besides the liver).
• According to FDA poses a threat of insertional
  mutagenesis (disrupt functioning genes) and
  inadvertently introduce altered genes into sperm
  or eggs thereby changing genetic information.
• Reporting research adverse reaction called into
  question and information to FDA is secret.

10
Genetic engineering somatic tissue

• Changing genes in a living human cell. Suppose
  you had a lung disease caused by a defective gene
  in your lung cell. If you change the gene you can
  fix the cell.
• A viral vector carrying a healthy gene can be
  inserted into the nuclei and it repairs the
  tissue.

11
Therapeutic Cloning

• Somatic Cell Nuclear Transfer (SCNT), also called
  therapeutic cloning, is the process by which a
  somatic cell is fused with an enucleated oocyte.
  The nucleus of the somatic cell provides the
  genetic information, while the oocyte provides
  the nutrients and other energy-producing
  materials that are necessary for development of
  an embryo. Once fusion has occurred, the cell
  eventually develops into a blastocyst, at which
  point the inner cell mass is isolated. The
  pluripotent stem cell line is then established
  and is capable of differentiating into all cell
  types.

12
Embryonic Stem Cell Versus Adult Stem Cells

• Embryonic stem cells, derived from human embryos
  differ from adult stem cells in the following
  way
• Embryonic possess the attribute of pluripotency,
  which is to say that they are capable of issuing
  in any cell type except the placenta.
• Cells in the developed human in some cases
  possess multipotency, which is to say they can
  develop into more than one cell type.

13
Embryonic Stem Cells (I)

• Embryonic stem cells (ES) (derived from 5-7 day
  old embryos known as a blastocyst). Where do they
  come from?
• Question of respect for the embryo or does it
  deserve respect because still undifferentiated
  and only a potential human? Does the cluster of
  undifferentiated cells have ethical standing?
  Considered spare embryos and should be used
  with consent of donors?
• Uniting sperm and egg in lab leads to all the
  above concerns and the ethics of using human
  embryos solely and explicitly as a means to some
  end.
• Embryos created through somatic cell nuclear
  transfer (SCNT) allows for creation without
  fertilization-cloning technique.

14
Embryonic Stem Cells (II)

• Embryonic germ cells (EG) (derived from immature
  aborted fetuses).
• Enmeshes stem cell research in the ongoing,
  emotionally charged abortion debate.

15
Evidence of a Pluripotent Human Embryonic Stem
Cell Line Derived From a Cloned Blastocyst
Seoul National University

• Generation of pluripotent embryonic stem (ES)
  cell line from a cloned human blastocyst with
  potential applications in tissue repair and
  transplantation.
• Oosytes cytoplasm would reprogram the
  transferred nucleus by silencing somatic cell
  genes and activating the embryonic ones.

16
Evidence of a Pluripotent Human Embryonic Stem
Cell Line Derived From a Cloned Blastocyst
Seoul National University

• Method
• Oocytes and cumulus cells donated (242)
• Enucleation
• Somatic cells injected
• Artificial stimulus is needed to initiate
  development because sperm isnt involved
• Grows into blastocyst and stem cells removed and
  tested

17
Is Biomedical Research Too Dangerous to Pursue?

• Chair of President Bushs Council on Bioethics,
  Dr. Leon R. Kass, is concerned with ways in which
  biotech might undermine or shift our
  understanding of the nature of family, marriage,
  sexual relations, aging and parenting.
• Slippery slope from cloned blastocyst first
  used for disease research and enhancement to baby
  making.

18
Stem Cell Research

• Bush Administration limited federal grants
  administered by the NIH for research only on stem
  cells created before Aug 2001.
• These cells may be good for generating
  hypotheses, but most lines were not generated
  consistently enough to compare results from one
  cell group to another, allowing for consistent
  scientific research.

19
Ethical Arguments Somatic Cell and Germ Line
Manipulation

• Advocates
• Lee Silver of Princeton (Remaking Eden Cloning
  and Beyond in a Brave New World) looks forward to
  a future in which health, appearance,
  personality, cognitive ability, sensory capacity
  and life span of our children become artifacts of
  genetic modification.
• Evolution can be cruel why not alter it? (James
  Watson)
• Comparison to choosing a family dog. (

20
Ethical Arguments Somatic Cell and Germ Line
Manipulation

• Critiques.
• Irrevocably alter the genes we pass to our
  children.
• Destabilize human biology.
• Put into play unprecedented social, psychological
  and political forces that would feed back upon
  themselves with impacts beyond our ability to
  foresee.
• Implications for individual integrity and
  autonomy, for family and community life, social
  and economic justice and world peace (instead of
  arms race wed have a techno-eugenics race).

21
Critics of Biotechnology

• Biomedical research cannot continue on its
  present course without significantly altering
  human nature.
• Human nature has already changed drastically in
  response to technology.
• Human nature is not static It lacks any
  recognized essence.

22
Critics of Biotechnology

• In the name of more cures, longer life and
  improved quality of life, we will commodify and
  objectify human life.
• Although we may imperil the value of humanity by
  objectifying and commodifying ourselves, it is
  not an inevitable result of biomedical progress.
  Social and political choices, rather than
  scientific advances, will determine how our
  dignity and autonomy are to be squared with the
  prospect of birthing artificially or enhancing
  mental capabilities, etc.

23
Critics of Biotechnology

• Will produce a loss of authenticity and meaning
  in human experience. Our sense of well-being will
  become programmed , artificial, and inauthentic.
• Doesnt seem to square with what we have already
  experienced in the wake of biomedical progress,
• i.e. eye glasses, insulin injections,
  wheelchairs, inhalers, oxygen tanks, etc.
• Compared to use of a calculator, computer or the
  Internet to solve a problem.

24
Current Policy Landscape

• 1997 Roslin institute (Scotland) announced
  successful cloned sheep.
• UNESCO, council of Europe, European Parliament,
  World Health Assembly took strong stand against.
• Banned in Australia, Argentina, Brazil, Costa
  Rica, Finland, France, Germany, India, Israel,
  Italy, Japan, Mexico, Norway, Peru, South Africa,
  Sweden, Switzerland,Trinidad, Tobago and the UK.
• December 2003 Canadian based sect claim
  successful cloning attempt of a human.
• US House of Representative passed a bill banning
  both reproductive and research cloning, however,
  it hasnt passed in the Senate.
• FDA has jurisdiction over cloning and can only
  ban it on grounds of safety and efficiency rather
  than ethical issues.

25
Is Biomedical Research Too Dangerous to Pursue?

• Should we accept framing the issues in
  Utilitarian terms such as progress, cures,
  and a better life?
• Or will we be creating a genetic or biotech
  caste system in which only the most privileged
  will be able to afford biotechnical enhancement?

26
Ethics of Stem Cell, Human Genome and Genetic
Therapy

• Moral treatment of embryos (consumption of human
  embryos or humanitarian embryo use).

27
Ethics of Stem Cell, Human Genome and Genetic
Therapy

• Who owns your genetic information?
• Volunteers loose economic rights over their own
  genetic material?
• Academic research and pharmaceutical companies
  get the patents.

28
Ethics of Stem Cell, Human Genome and Genetic
Therapy

• Fallacy and implication of genetic determinism
• Genome isnt linear but complex relying on
  interrelationship of genes.
• Genetic factors only portion of the picture.
• Human genome project could be too big for the
  biotech and pharmaceutical companies to handle
  and could bankrupt the industry. (Lehman Brothers
  McKinsey)
• Increase cost of drugs and billions of medical
  research dollars when healthcare system in
  crisis.
• Ownership of cell lines (ex gene line of Iceland
  and Tonga have been sold to private companies
• Healthy people tested genetically face employment
  and insurance ramification

29
(No Transcript)
30
Percentages and Costs/Cycle

• From a 1998 Center for Disease Control Report
• 7,800
• 30 pregnancy rate
• 3-4 embryos transferred

31
PGD Genetic testing performed prior to embryo
transfer
32
Commonly, more than 100 diseases can be detected
through testing, including

• Hemophilia A
• Muscular Dystrophy
• Tay-Sachs Disease
• Cystic Fibrosis
• Down Syndrome

Removal of one cell for testing
33
Result of PGD

• Viability Desirability

• Applications for discarded embryos

34
Impact (Part I)
35
Impact (Part II)
36
(No Transcript)
37
(No Transcript)
38
(No Transcript)
39
(No Transcript)
40
Fate of Embryos at IVF Clinics

• Since 1978 over 100,000 embryos have been
  destroyed at IVF clinics.
• Currently there could be 1,000,000 embryos in
  storage in the united states (e.g. at UCSF clinic
  3,300 are in storage)
• Survey of 239 IVF clinics in the united states
  reveals
• 27 clinics donate to diagnostic tests mostly
  with the mothers permission
• 55 donate embryos to research
• 115 immediately discard unused embryos

41
Sources of Stem Cells
Uncontroversial Sources
Umbilical Cords
These are currently desired for many uses
Cord blood is frequently not stored
Adult Stem Cells
These do not seem as clinically effective
Controversial Sources
Aborted Fetuses
Frozen Spare Embryos
Cloned Human Embryo
Sources That Should Not be Controversial
Designed Stem Cell
From Modified Female Egg
42
Organ Tissue Replacement
Animal
Cadaver
Living
Stem Cell
Organs
Organs
Donor



e.g., pig organ
e.g., cornea
e.g., kidney
Fetal stem
Stem cells
Stem cells
cells taken
from your
from your
after
blood
organ
child-birth
death
Umbilical
Umbilical
Stem cells
Stem cells
stem cells
stem cells
grown
from pre-
at your
from
from a
implanted
birth
others'
discarded
embryo
birth
aborted
which is
fetus
to be
discarded
43
Federal Ethical Guidelines
The Belmont Report 1979
Now 22 years old
The principles are still sound, however, current
extrapolations and recommended implementations
are controversial
Basic Principles
Autonomy - self governing / self directed
Beneficence - doing or producing good
Justice - equal burden / equal benefit
e.g. Do no harm, maximize benefits, minimize risk
No guidance for
Intergenerational risks
Stem cell uses
44
Informed Consent Knowledge of and consent to a
particular form of treatment and experiment
Four Elements
Three Standards

• Make a decision
• Select a choice
• Selected choice is reasonable

1. Competence 2. Disclosure 3.
Comprehension 4. Voluntariness

• What others would tell patient?
• What a reasonable person would want to know?
• What would this patient really want to know?

• Fully informed vs. adequately informed
• Translation to what the patient can comprehend
• Varies with patient

• Free from undue pressure
• But we all have some pressures and they vary
  with the individual.

45
Eugenics is a term presented by Galton good
genes

• This philosophy deals with all influences that
  improve the inborn qualities of a race either by
  enhancing good attributes (positive eugenics) of
  an individual or by removing unwanted attributes
  (negative eugenics).

46
Ethical and Political Issues Regarding Embryonic
Stem Cell Research

• Moral treatment of embryos human and animal.
• Human
• Bush Administration banned use of federally
  funded research on embryonic stem cells unless
  embryos secured before 8/01.
• How many human embryos are we prepared to
  sacrifice?
• Animal
• Uncertainty regarding the hybrid of cellular
  components (nucleus epigenetic material).
• Potential health risks but high profits.
• Infectious gene transfer vectors that can easily
  recombine to create new pathogenic viruses.