Mappes & DeGrazia, Chapter 9: Lecture Notes/Outline by Larry Hauser

Genetics and Human Reproduction

Genetic Disease and the Language of Genetics

Autosomal Recessive Diseases

Characteristics

autosomal means it's carried on a chromosome other than he sex chromosomes
recessive means the gene carrying the disease

when paired with the normal gene (which is dominant) the recessive trait is overridden

the disease doesn't develop
but the individual is a carrier

if paired with another recessive gene the disease traits are expressed

Transmission

if both parents are carriers

25% chance the child will be homozygous for the disease gene and hence afflicted by the disease
50% chance the child will be heterozygous for the gene and hence a carrier
25% chance the child will be homozygous for the normal gene: not afflicted & not a carrier

if one parent is a carrier and the other normal

50% chance the child will be a carrier
50% chance the child will be normal

if both parents are afflicted

100% chance the child will be afflicted
though many of these afflictions are so severe that the afflicted do not survive well enough to have any chance to reproduce

if one is afflicted and one normal: 100% of offspring will be carriers
if one is afflicted and the other a carrier

50% afflicted
50% carriers

if both parents are normal: 100% of the offspring will be normal

Examples

Tay-Sachs disease

most commonly affects those of Jewish and Eastern European heritage
results in progressive neurological degeneration and death in early childhood

sickle-cell anemia

most commonly affecting blacks in this country: 10-12% of African-Americans carry the gene
characterized by accute attacks of abdominal pain, of varying degrees of severity

cystic fibrosis

about 1 in 20 U. S. Caucasians carry the gene
the disease causes dysfunction of the exocrine glands

resulting in production of abnormal amounts of mucous
which can obstuct organ passages
and cause intense pulmonary and digestive distress
currently most victims die before age thirty

autosomal dominant diseases

Characteristics

autosomal means it's carried on a chromosome other than he sex chromosomes
dominant means the gene carrying the disease always expresses itself: if you have the gene you will be afflicted

when paired with the a normal gene (which is recessive) the normal trait is overridden by the disease trait
if paired with another dominant disease gene the disease also develops, obviously

Transmission

if both parents are heterozygous

25% chance the child will be homozygous for the disease gene and hence afflicted by the disease
50% chance the child will be heterozygous for the gene and hence afflicted
25% chance the child will be homozygous for the normal gene: not afflicted & not a carrier

if one parent is a heterozygous and the other normal

50% chance the child will be a heterozygous and hence afflicted
50% chance the child will be homozygous for the normal gene: not afflicted & not a carrier

if both parents are homozygous for the disease gene: 100% chance the child will be homozygous for it also and hence afflicted
if one is afflicted and one normal: 100% of offspring will be carriers
if one is homozygous for the disease gene and the other heterozygous

50% homozygous and afflicted
50% heterozygous and afflicted

if both parents are normal: 100% of the offspring will be normal

Example: Huntington's disease

symptoms typically emerge only in the prime of life: between ages 35 and 50
characterized by mental and physical deterioration, leading to death within a few years

sex-linked genetic diseases: carried on the X or Y chromosome

the background biology: females have XX and males are XY
XX + XY -- in reproduction -- yeilds

50% XY: it's a boy!
50% XX: it's a girl!

hemophilia -- characterized by uncontrollable bleeding -- is an example of a recessive X-linked disease

complications

if a male inherits the gene he will have the disease

even though it's recessive
there being no corresponding dominant chromosome on Y to override

if a female is heterozygous for the gene she will be carrier
if a female is homozygous for the gene she will have the disease

transmission: most likely cases

hemophilic father and normal mother

boys: 100% normal
girls: 100% carriers

normal father and carrier mother

girls: 50% carriers: 50% normal
boys: 50% hemophilic: 50% normal

exercises for the reader

hemophilic father & carrier mother
hemophilic father & hemophilic mother
normal father & hemophilic mother

Prenatal Diagnosis and Selective Abortion

Techniques for detecting chromosomal abnormalities in the fetus in utero, usually with an eye toward selective abortion

directly: amniocentesis & chorionic villi sampling (CVS)
ultrasound: detects antatomical abnormalities

where these are such as might result from an underlying genetic defect
they can provide indirect evidence for the presence of the defect

Amniocentesis

a needle is inserted in the mother's abdomen and a small amount of amniotic fluid is withdrawn
fetal cells in the fluid can be tested for genetic abnormalities
among the conditions detectable: besides those above

Down's syndrome
anencephaly
spina bifuda

not ordinarily performed prior to the 15th to 16th week of gestation
selective abortion must await the results of the genetic testing

usually available around the 20th week
it would have to be a late second trimester abortion

CVS

can be performed in the first trimester: around the 10th week
a small amount of tissue is extracted from the placenta
comparable risk factors though "some research has suggested an link between CVS and missing or shortened fingers and toes.

Ethical Question: Under what conditions, is abortion, on grounds of genetic defect, morally permissable?

Kaas (488 ff.) condemns is as a threat to "the radical moral equality of all human beings.
Many ethicists defend the practice.
Far fewer ready to selective abortion for purposes of sex selection.

Morality and Reproductive Risk

Ethical question: Under what conditions, if any, is a genetically defective individual morally obliged not to reproduce.
Laura M. Purdy

our duty to provide minimally satisfying lives for our children
entails a moral duty not to reproduce in cases where there is a high risk of serious genetic disease such as Huntington's disease (the example she discusses).
prenatal testing and selective abortion

complication: many at risk for HD don't want to know whether they carry the gene or not
if the either parent carries the gene

those for whom abortion is not an option "are morally obliged to avoid conception"
those for whom abortion is an option are morally obliged to

undergo prenatal testing
if the fetus tests positive

you have a moral obligation to abort the pregnancy
the parent under suspicious will know that they have gene and will get the disease

if the fetus tests negative you still don't know if the parent has the disease

Proposals for coercive measures

negative eugenics rationale: to reverse or prevent deterioration of the human gene pool
possible coercive measures: from more to less extreme

extreme measures -- invasive of fundamental rights -- few would advocate

cumpulsory sterilization
mandatory amniocentisis folled by forced abortion

less extreme measures also widely opposed as unneccessary & invasive of privacy

e.g., mandatory screening programs for the identification of carriers

"those who maintain there is no clear and present danger of genetic deterioration" reject such measures

Reproductive Technologies and the Treatment of Infertility

Reproductive technologies replace various steps in the natural process of reproduction

sexual intercourse
tubal fertilization
implantation in the uterus
subsequent in utero gestation

Artificial insemination:

replaces intercourse as a means of achieving tubal fertilization
a means of overcoming infertility on the part of the male

AIH: where the artificial insemination is done with the sperm of the husband

husband is capable of producing viable sperm
but none gets into his semen (e.g., a man who has had a vasectomy)

AID: the artificial insemination is done with the sperm of a donor

the more common procedure
used where the males infertility is due to his not producing viable sperm
also where the husband may not be infertile but carries genes that would put his offspring at risk

Morally controversial issues

"positive genetics" proposals, e.g., Herman J. Muller's

establish gene pools and store the sperm of men judged to be "outstanding" in various ways
encourage "enlightened" couples to arrange for the wife to be artificially inseminated with sperm from these pools

its employment by unmarried women
surrogacy arrangements: where the wife is infertile or has the genetic defect

another woman -- the surrogate -- is paid to be artificially inseminated with the husband's sperm
carry the child to term and deliver it
giving up the newborn to the contracting couple

In vitro fertilization (IVF): literally fertilization "in glass": aka "test tube babies"

replaces intercourse as a means of achieving fertilization in vitro (rather than tubal fertilization)
two stage procedure

fertilization: the sperm of the husband (or donor) is united with the egg of the wife (or donor) in a laboratory
embryonic transfer: transfer of the embryo to the uterus for implanation

1st test tube baby -- Louise Brown -- born in England in July 1978
success rates are still somewhat disappointing
frozen embryo technique (about which some will have moral qualms)

use fertility drugs to cause the woman to simultaneously produce several mature eggs
harvest a crop of these (say 10 or so)
fertilize them in vitro to create several embryos
freeze the embryos at the eight-cell stage
thaw and use these embryos in successive attempts to achieve successful implatation & gestation\
moral issues

reason for doing it this way is that it has proven more difficult to freeze unfertilized eggs & keep them viable than embryos
about the morality of disgarding the remaining embryos when pregnacy is achieved?

utility of IVF

presently useful for overcoming infertility due to obstruction of the fallopian tubes
theoretical possiblity of ectogenesis

would replace natural gestation, in the womb, with gestation in an artificial womb
could then implant the IVF produced embryo in this artificial womb
and voila -- Brave New World -- we've replaced the whole process

IVF spinoffs & related technologies

GIFT: gamete intrafallopian transfer

eggs obtained as for IVF are mixed with sperm
and introduced into the woman's fallopian tubes in the hope of achieving tubal fertilization
carries risk of ectopic pregnancy
but has a higher success rate than IVF

ZIFT: zygote intrafallopian transfer

a single celled zygote produced by in vitro fertilization
is introduced into the woman's fallopian tube

Egg donation: a treatment option for woman whose infertility is due to lack of nonfunctioning of her ovaries

her situation

she produces no eggs but her uterus may be completely healthy
and she may still wish to bear her husband children

various options: 1 & 2 aka surrogate embryo transfer or prenatal adoption

In vitro fertilization of a donor egg followed by embryo transfer to the wife
artificial insemination of an egg with the husband's sperm

producing in vivo fertilization (i.e. tubal fertilzation in the donor's fallopian tubes)
nonsurgical removal of the embryo via lavage (washing out)
transfer of the recovered embryo to the wife

Transfer of a donor egg together with the husband's sperm to the woman's fallopian tube as with GIFT

Surrogacy revisited

an option for a woman who

has healthy ovaries (and can produce her own eggs) but not a healthy uterus
can be a genetic but not a gestational mother
but still desires a child "of her own" by her husband

the option -- in the absence of ectogenesis is

fertilize an egg from the wife with the husband's sperm in vitro
transfer the embryo to the uterus of a surrogate
who would agree to bear the child for the couple

Cloning possibilities considered

some scientist's believe successful human cloning could become a realistic possibility in the near future
the envisgage possiblity

obtaining a mature egg
removing its nucleus and then
replacing the nucleus removed with another nucleus obtained from a donor's body cell

donor might be anyone -- even the woman herself.
the resultant zygote will have the same genotype as the donor: it's a clone
transfer of the resultant embryo to a woman's womb for gestation

Reproductive Technologies: Ethical Concerns

Artificial insemination

AID religious critics argue

introduces a third party into the procreation process
and is thus a akin to adultery

AIH: some religious ethicists object on the grounds that procreation is unethical whenever it is not a result of personal lovemaking.
Secrecy issue: Paul Lauritzen argues that we have a moral responsibility to the child to inform them that they were conceived through artificial insemination

Surorogate motherhood

general areas of concern

psychological impact on the child
negative social impact on the family structure
commercial surrogacy -- where the surrogate is paid -- may encourage viewing children as commodities

legality of surrogacy contracts

Baby M case held surrogacy contracts to be invalid and unenforcable in NJ
validity and enforceability of such contracts varies from state to state, at present
options

complete legality: rule them valid and enforceable
complete prohibition: rule them invalid & unenforcable
Bonnie Steinbock argues that such contracts should be legally allowed

with provision for a "waiting period" subsequent to birth
during which the surrogate mother would have the opportunity to change her mind about surrendering parental rights

complicating issue of split -- gestational & genetic -- motherhood

in the Baby M case the surrogate was both the genetic and gestational mother of the child
might make a difference if the surrogate is only the gestational not the genetic mother

should the gestational mother be recognized as the legal mother (as Barbara Katz Rothman argues)
if the surrogacy arrangement breaks down and both women want the child?

IVF

arguments advanced in support of wholesale rejection

it's unnatural
it depersonalizes and dehumanizes procreation
it inflicts unknown risks on the developing offspring
slippery slope: it will lead to the acceptance of more and more objectionable developments in reproductive technology, e.g., ectogenesis

arguments advanced in support of limitations

sanctity of marriage issues:

give rise to concerns cases with third parties involved
but would find underwrite no objection to IVO where the sperm and egg were a husband's and wives

sanctity of life issues

the discarding of embryos not needed or deemed unsuitable for implantation
involves the killing of persons or (at least) potential persons
embryo freezing -- those who raise this concern would be apt to feel -- is no "solution"

Cloning

question of benefits

all the others provide benefits for those suffering from infertility
the connection between cloning and relief of infertility is tenuous

negatives

all of the issues and concerns that arise in connection with IVF apply to cloning in spades
the technology most likely to be abused to the detriment of society
anticipated detrimental effects

psychological difficulties for the clone (and donor/parent) due to their manner of origin and lack of genetic uniqueness
social difficulties associated with their manner of origin and lack of genetic uniqueness

Genetic Engineering and the Human Genome Project

Two important distinctions

therapeutic vs. nontherapeutic engineering

therapeutic "gene therapy" involves interventions directed at the cure of disease
nontherapeutic "enhancement engineering" involves intervetntions directed at the enhancement of capabilities

somatic-cell vs. germ-line interventions

somantic cell: introduce modifications into nonreproductive cells so that the genetic changes are not passed on to future generations
germ-line interventions introduce modifications into reproductive cells so the changes are inherited by future generations

Four types of engineering

somatic-cell gene therapy: least objectionable: some will say it's "playing God"

many potential benefits -- e.g., a treatment for cystic fibrosis
continued development and employment are widely endorsed

germ-line gene therapy: germ-line interventions are higher-risk than somatic-cell interventions
somatic-cell enhancement engineering: enhancement is a lesser benefit than therapy
germ-line enhancement engineering: most objectionable

Human Genome Project

began in 1990 and was originally projected to take 15 years
to goals

to "map" the human genone by determining for each of the estimated 50,000 to 100,000 human genes

on which chromosome it is found
and where on that chromosome it is found

to "sequence" the genome by determining

the order of occurence
of the estimated 3 billion base pairs of DNA

ethical issues

playing God
privacy & abuse issues relating to genetic testing