Philosophy 302
Sonoma State University
6 July 2004
Introduction
Cloning
for 3 billion years.
Asexual reproduction – simple-cell
bacteria clone themselves
Gene-splicing
for 1.4 billion years – complex cells with internal membranes
DNA gets cut up and packaged for
transport through membranes
Organisms made of complex cells have
sex to reproduce
We
will focus on gene-splicing. Some methods (e.g., protein production) may use
both cloning and splicing.
Terms
- genetic engineering, gene manipulation, genetic modification, recombinant DNA
technology
Powerful
techniques, uncertain effects.
I.
biology
-
A. The Central Dogma of Molecular Biology
<Table 4.2>
Genetic code is basically 4 ‘letters’, and a sequence of 3 DNA
‘letters’ translates to a specific protein ‘building block’ (amino acid).
<Figure 2.8>
Genetic info is transcribed from DNA to RNA, then translated
from RNA to protein. Protein directly affects structure & function of
organism.
<Figure 6.3>
Viruses contain DNA. They specialize in depositing their DNA into
host cells. Humans can take modified DNA, put it in some viruses, and send the
viruses to a group of target cells to deposit the modified DNA. This is called
using the virus as a vector.
B. genotype & phenotype
- phenotype is “what you see”
- reductionist focus on molecular genetics
- there are higher-level organizations of structure & function that determine action of genotype on phenotype
II. applications
A. studies of gene structure & function
- analyze an organism’s genetic sequence
-
find out how genes become proteins (gene
expression)
-
study the interactions between genes and the
proteins they make
-
ethics: world-view of
the researcher
o
“pure science”
o
competition, diffidence, glory
o
team spirit
o
humanitarian spirit
o
profit motive
B. protein engineering
-
compounds like
o
insulin, HGH, interferon,
beta-endorphin
- ethics: conflict of interest
o conflict possible
§ professional duties
§ ethical responsibilities
§ personal gain
· money
· status
· perks
· friendship, connections, favor bank
o trivial or substantial
o examples
§ judge in lawsuit is on Board of Directors
§ physician lunches with pharma rep
C. transgenics:
-
take genes from one organism and put
them in another
1. plants
-
selective breeding ++ (not limited by
sexual compatibility)
-
<Table 8.1> agricultural productivity
-
ethics: danger of introducing modified organisms to
natural environment
o
interbreeding
o
mutations
o
supercompetitor
§
more vigorous
or resistant plant
2. animals
-
technically challenging
-
cell-based applications
o
cancer research
o
protein production from cultured
mammalian cells
-
organismal transgenics
o
frogs, fish, mice, pigs, sheep <Figure 8.11>
o
germ-line modification (covered later)
o
basic research: embryology
o
biotech applications
§
factory farm animal engineering
§
protein production
- ethics: modifying other life forms to suit human needs or desires
D. spin-offs
-
vaccine engineering
o
build special DNA vaccines that eliminate use of
killed viruses
§
flu shot
§
HIV
§
malaria
§
hepatitis
§
Ebola
o
build hybrid viruses that expose multiple antigens
(several inoculations in one shot)
-
medical genetics
o
genetic counseling & early detection
o
gene therapy
-
new & exotic treatments
o
neovascularization
§
heart disease
§
limb regeneration
o
repair damaged nerve tissue
o
prevent transplant rejection
o
treat allergies
IV.
gene therapy
<Table
3.1>
A. Aim is to modify the genetic
profile of a targeted group of cells, in order to correct some malfunction.
-
Ideal is to insert a complete, fully functional
gene to the precise target with no side effects
-
Long cycles of testing and human trials
B. diseases & conditions
o
cancer
o
AIDS
o
Genetic immune disorders
o
cystic fibrosis
o
hemophilia
o
sickle-cell disease
o
vascular disorders (including heart disease)
o
MS - multiple sclerosis
o
muscular dystrophy
o
ALS (“Lou Gehrig’s disease”)
-
monogenic
o
single identifiable genetic cause
o
aim is permanent cure or correction
o
potential for success considered good
o
considered "lesser risk" to
§
patient
§
environment
§
future generations
o
market considered poor
§
fewer individuals with treatable conditions
§
limited insurance coverage
§
technical factors less available
§
less funding
-
multifactorial
o
multiple causes
§
genetic dysfunction
§
environmental factors
§
infection
§
malignancy
o
more numerous studies
o
more frequent treatments
o
huge, rapidly growing market
D. Somatic (body) cell therapy
-
somatic monogenic
o probably the safest - single-gene and no germ line
o most treated somatic monogenic condition is cystic fibrosis
o continuing problems with
§ vectors
§ reaching correct target
§ gene expression in target
o risk of mutation or recombination
§ potential long-term, poorly-understood risk
-
somatic multifactorial
o aim is to improve patient’s condition
§ not necessarily to fix the problem
§ may be treating symptoms only
o high demand for research and services
o cancer
§ life-threatening, frequently terminal
§ “Do no harm” principle is less relevant
§ risky, expensive, less effective, experimental treatments
· welcomed by patient & by stake-holders
· advancement of science
· using person as means
§ ethics committees & review boards
· set up to protect patients and providers
· vested interest in “moving the ball forward”
E. Germ line therapy
- modify the present generation plus all future generations
o use stem cells and invasive methods on lab mice
o basic method of transgenics.
- regarded as dangerous and unpredictable
o unintended consequences
§ supercompetitor released into environment
§ reduced genetic diversity
· some bad traits are adaptive in special circumstances
o sickle-cell vs. malaria
o efforts to prevent germ-cell exposure in somatic therapy
- potential advantages
o suppress fatal or debilitating disorders in whole population
o enhance desirable traits in food stocks
§ cholesterol-reducing agents
§ insect & rot resistance
· reduce pesticide & fungicide use
§ improved appearance, taste, nutrition
o breed animals to harvest their organs for human transplant
F. Ethical issues related to gene therapy
- basic agency
o fundamentals of life and well-being
o mass genetic treatment for disorders
§ affect on genetic diversity
§ life extension
· population & resources
· human dignity
- secondary enhancement
o what is appropriate?
§ growth therapy for undersize child
§ power therapy for athletes
§ improve intellectual function for disabled person
§ improve art skills
§ designer enhancements
o mass genetic enhancement
§ affect on social & genetic diversity
§ impact on personality
§ traits like obedience, docility, loyalty, diligence, aggressiveness
§ affect on our notions of difference, normality, disability
- Therapy for the elite
o Individuals & families
o Societies
- Questions
o Should we do all we can to cure illness?
o Should we do all we can to improve people’s lives?
VI.
General bioethics and genetic engineering
-
duty to future generations
o don’t leave things worse than we found them
o genetic diversity within species is good
o tinkering should be directed only toward
§ worthwhile cause
§ reasonable expectation of safety
o proceed with caution
-
duty to the environment
o genetic & ecologic diversity
o economic value
o habitat quality
o aesthetics
- “generational” concept takes a strange twist with genetic research
o human genome is part of environment
o human genome belongs to future generations
Jesse
Gelsinger, age 19, had an inherited enzyme deficiency. Nevertheless, he was fit
and lived a fairly normal life.
In
1999, Jesse had a genetically modified virus injected into his liver. The
purpose was to test the virus as a vector for genetic therapy.
Before
the treatment, it was known that:
a. The virus used is toxic to the liver.
b. Successful trials had been conducted on mice.
c. No studies had been conducted on primates.
e. The therapy, if successful, would
probably not help Jesse's condition.
f. The therapy, if successful, could
be of great potential benefit to others.
Jesse
died from liver failure as a direct result of the procedure.
1.
Was it appropriate to use Jesse as a subject?
2.
Should the method have been tested on non-human primates first?
3.
What potential conflicts of interest may have been present?