The Ethics of Genomics

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23 Οκτ 2013 (πριν από 3 χρόνια και 10 μήνες)

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The Ethics of Genomics

Are GMOs Bad?

Is Genetic Testing Good?

How Should the Public Be Informed
of New Discoveries?

Should We Clone Humans?

GMOs
-

Genetically Modified
Organisms


Is the modification of genomes intrinsically
wrong or enormously beneficial?


Many choose to evaluate this question on a
case
-
by
-
case basis

1)
Golden Rice

2)
Biological Plastics

3)
Pharmaceutical Produce

4)
Sterile Fruit

5)
Pest
-
Resistant Plants

6)
Xenotransplants

Golden Rice


Rice is the staple food for 124 million people


Many of these same people suffer from a
vitamin A deficiency
-

which causes blindness


Vitamin pills are not feasible in countries
which lack $ and infrastructure


In Jan 2000, rice was transformed with 3
genes which allow it to make
b
-
carotene


Two of these genes came from daffodil and
one came from bacteria


Testing is being performed in the Philippines,
Africa, China, India, and Latin America


So, What’s the Controversy?


All commercial rights to Golden Rice has been
transferred to Syngenta, the world’s largest
agribusiness


Syngenta has promised to provide Golden Rice
to all subsistence farmers free of charge


Organizations such as Greenpeace believe this
is a ploy to introduce more GMOs into
developing countries where resistance is limited


Syngenta claims that only strains consumed
within the developing country will be bred, not
ones which could then be sold in the West

Biological Plastics


Plastic is usually made from petroleum
products


PHA (polyhydroxyalkanoate) is a naturally
occurring form of polyester


It was 1st described in 1925 by Lemoigne


PHA uses renewable resources and is
biodegradable


GMOs have been modified to produce PHA


Metabolix is one company working with
GMOs in this way

Pharmaceutical Produce


Edible plants have been engineered to
deliver vaccinations


Arntzen and colleagues produced the 1st
prescription potato


Unfortunately, raw potatoes work best to
deliver medicine
-

cooked ones lose 50% of
their potency


Increased consumption may make up for this
loss


Additional trials are underway with bananas

Sterile Fruit


In 1997, a patent was granted for “Terminator”
technology


This can render GM seeds sterile so that they
cannot be re
-
planted by farmers


The technology was designed to protect the
investments of biotech companies


Monsanto has acquired the rights to this
technology


Many farmers, especially subsistence ones, re
-
plant the seeds from the previous crop


It is feared that companies may monopolize
the world’s food supply using this technology

Pest
-
Resistant Plants


Bacillus subtilis toxin (BT) has been
incorporated into plants


The use of this natural pesticide should
reduce the amount of chemicals used


It is feared that the BT gene could be
transferred to other plants via lateral transfer


Initial claims of BT being transferred to milk
weed and killing monarch butterflies have
been unfounded


Like antibiotic resistance, some insects have
become resistant to BT

Xenotransplants


Organs are taken from one species and put into
another


In 1984, a baboon’s heart was transplanted into
Baby Fae, who lived 20 days


Pigs are commonly used as sources of adult
organs


Nextran is one company which genetically
engineers pigs to serve as better donors


The plasma membranes of pig cells have been
inserted with human proteins to reduce rejection


Most concerns center on disease transmission

Why Pigs?

1)
they grow to be the size of a large human and
share certain physiological and anatomical
aspects with humans

2)
they are domesticated and are easy to breed

3)
they have large litters and grow rapidly


The first genetically engineered pig was born
in 1992


By 1994, hundreds of these pigs had been
produced for organ
-
transplant research


In 2003, it was announced that a pig gene that
contributes to human rejection of porcine
organs had been knocked
-
out.

Why Not Pigs?


A number of porcine diseases have the potential to
infect humans


Pigs are known to have PERVs (porcine endogenous
retroviruses)


PERVs have been shown to be able to infect
immunodeficient mice and human cells in culture


It is still unknown whether there are diseases which can
be passed between pigs and humans


As research continues, thousands wait to receive organ
transplants; about 25
-
30% of patients waiting for heart
or lung transplants die before suitable organs became
available to them


Could human cloning be an answer to this shortage
?


Ice
-
Nucleation Bacteria


The damage caused by frost injury in this
country has been estimated to exceed $1
billion/year


In nature, the formation of ice crystals on plants
is often triggered by the growth of bacteria on
the outside of these plants


Some bacteria have proteins on their surfaces
that are particularly effective triggers of ice
-
nucleation


In the absence of these bacteria, plants can
reach an internal temperature of
-
5
o
C without
freezing


How To Keep Plants From Freezing:

1)
warm the air around them or insulate the crops

2)
spray bactericides on the crops to kill the bacteria

3)
spray the crops with bacteria which inhibit the growth of
ice
-
nucleation bacteria


The bacteria responsible for ice
-
nucleation are P. syringae.
These bacteria have been genetically engineered to lack
the protein which causes ice
-
nucleation and are known as
ice
-
minus strains.


In 1983, field tests were approved for the ice
-
minus
bacteria. Jeremy Rifkin complained that ice
-
nucleation
bacteria could play a role in the climate by triggering ice
-
nucleation events in the atmosphere.


Trials of ice
-
minus bacteria were blocked for many years,
the first test took place in 1987.


Insertion of Modified DNA into Cells

Vectorless:

1)
Biolistic delivery uses a particle gun to shoot DNA
into an organism. DNA of interest is mixed with
particles of metal such as tungsten. Widely used in
plants.

2)
Microinjection into the nucleus involves the use of a
microscope and a very small needle. This method is
used on animal cells (Xenopus oocytes), and
ensures that a large proportion of cells take up the
DNA.

3)
Electroporation uses a strong electric field which
forces the DNA into the cells. Used on plant and
fungal cells

4)
Silicon carbide transformation simply mixes DNA with
particles which punch small holes in plant cells.


Have been used in attempts to insert a copy of a gene into

bone marrow cells, the desired gene is first made into RNA

and then inserted into the retrovirus


Limitations of this technique are:

1)
Retroviruses can only infect dividing cells, certain body
cells (ie. nerves) do not divide

2)
Retroviruses insert themselves at random into human
chromosomes
-

it is not possible to control where they will
be inserted

a)
gene may not be effective as normal if inserted into the
wrong area

b)
gene may be inserted into tumor
-
suppressor genes and
cause cancer


Retroviruses



Do not insert their DNA into host chromosomes


Have been used to attempt gene therapy for CF


Descendents of GM cells do not carry the CF gene


The treatment must be repeated every few months,
but there is no risk of cancer

Adenoviruses

Agrobacterium



Causes crown gall in plants, a disease consisting of
tumors on the stalk of a plant


The bacterium enters wounds on plants and inserts
part of a plasmid (Ti) into the host DNA


Scientists can insert a desired gene into the Ti plasmid
and infect plants with this recombinant plasmid

History of Biotech: the early years


10,000
-
9,000 B.C. (Mesopotamia & Canaan) D. of dogs
9,000
-
8,000 B.C. (Iran & Afghanistan)
D. of goats and
sheep; (Canaan) D. of emmer wheat and barley


8,000
-
7,000 B.C. (Peru) D. of potatoes and beans,
(Indonesia) rice and (North America) pumpkins


7,000
-
6,000 B.C. (East Asia & China)

D. of pig and
water buffalo, (South Asia) chicken, (Turkey) cows,
(Syria) einkorn wheat, (Turkey) macaroni, (New
Guinea) sugarcane, (Indonesia) yams, bananas and
coconuts, (Asia) flax, and (Mexico) maize and peppers;
(Egypt) beer first made from yeast


3,000 B.C. (Iran) Breeding records of domesticated
donkeys recorded on stone tablets


2,000 B.C. (Sumaria) 19 brands of beer available


300 B.C.

Aristotle: concept of speciation




History of Biotech: the modern era



1970’s
-

Restriction enzymes discovered, methods to
determine the sequence of DNA


1975
-

Conference in Asilomar, CA to set guidelines for
genetic engineering


1983
-

PCR developed


1995
-

H. influenzae 1st organism to have its entire
genome sequenced


1996
-

“Dolly” the sheep becomes first mammal to be
cloned by nuclear transfer


1998
-

Mice and cows cloned


1999
-

Monkeys cloned, Jesse Gelsinger becomes 1
st

death attributed to gene therapy


2003
-

The human genome sequenced; Dolly dies at
an early age


Traditional Biotech vs. GMOs

1)
species which are crossed in traditional
biotechnology are always closely related, this is not
so in genetic engineering

2)
the pace of change in traditional biotechnology is
much slower than that of genetic engineering,
working on a scale of years rather than weeks

3)
traditional biotechnology has been applied on a
relatively small number of species, such as crop
plants, farm animals and yeast. Genetic engineering
is more ambitious in scope and seeks to change
these, as well as other, organisms such as those
involved in sewage disposal, pollution control and
drug production.


Is Genetic Testing Good?


Life Insurance


Universal Screening


Genomic Diversity Banks


Who Will Benefit the Most?




At the inception of the HGP in 1990, ELSI
was formed to study Ethical Legal and
Social Issues of genomics

ELSI

1)
Privacy and Fairness in the Use and
Interpretation of Genetic Information

2)
Clinical Integration of New Genetic
Technologies
(examines impact of genetic testing on
individuals, families, and society)

3)
Issues Surrounding Genetics Research
(the design, conduct, participation in, and
reporting of genetics research)

4)
Public and Professional Education


Ethics of Genetic Testing


When a new disease
-
associated gene is
discovered, a genetic test may soon follow


Many people in positions of authority
believe in genetic determinism, that all
human traits are encoded in DNA, this is
an oversimplification of the truth


Is genetic testing a new form of eugenics?


Who has the right to know the results of
your test?


Who has the right to obtain your DNA for
genetic testing?


Screening for G6PD Deficiency


In addition to sensitivity to fava beans, deficiency in
G6PD puts employees exposed to certain oxidizing
agents at higher risk


A simple and inexpensive test can detect G6PD
deficiency


A number of companies have screened workers for
this deficiency as part of their hiring process when the
work entails exposure to oxidizing agents


It could be argued that this practice provides a type of
discrimination, but companies argue that they are
simply fulfilling their legal and moral obligation to
prevent injuries and damage to worker health

Life Insurance and
Genetic Testing


British life insurance companies can use
data from 8 genetic tests, including breast
cancer, colon cancer, Alzheimer’s, and (as
of 2000) Huntington’s disease


In the latter case, people who test positive
can be denied insurance (with the
exception of the basic life insurance
needed to buy a house in the U.K.)


Shouldn’t those who are free of a disease
pay lower rates than those who test
positive?


U.S. Insurance Providers


Some have recommended legislation be passed that
would prevent insurance companies from
discriminating on the basis of genetic information.
Some of the main stipulations of this proposal are:

1)
IPs should be prohibited from using genetic
information to deny or limit any coverage

2)
IPs should be prohibited from establishing differential
rates or premium payments based on genetic
information

3)
IPs should be prohibited from requesting or requiring
collection or disclosure of genetic information

4)
IPs and other holders of genetic information should
be prohibited from releasing genetic information
without prior consent of the individual


A number of factors must be considered to decide
whether an individual test is beneficial to the
patient

Utility of Genetic Tests

Universal Screening for a Disease


Every pregnant woman in America is informed
of the availability of a test for Cystic Fibrosis


This is the 1st of nearly 400 genetic tests to be
implemented nationally


CF is the most common genetic disease for
Caucasians but not other populations


CF occurs in 1 out of 2,500 Caucasian births
but only 1 out of 17,000 African American ones


Moreover, the efficiency of detection is 85% in
Caucasians but ranges between 30
-
69% for
non
-
Caucasian populations

Screening for Cystic Fibrosis


Most experts agree that a universal test for CF
does not make sense


Nevertheless, the HMO Kaiser Permanente
conducted a pilot test


They offered the test to all Caucasian patients


1st, both parents were tested
-

if they were
heterozygous
-

the fetus could be tested


About 18,000 women have been screened to
date
-

90% of these have terminated their
pregnancy if the fetus was homozygous for CF

Genomic Diversity Banks


In 1996, Kari Stefansson started a company
called deCODE


Their goal is to create genomic fingerprints for
the entire population of Iceland
-

275,000
people!


Iceland is ideal for such a venture since the
majority of the population is descended from a
few European explorers and the people have
kept detailed family trees


Differences which lead to medical conditions
should be easier to find in such a population

Icelander’s Right to Privacy?


Iceland has a single medical provider, all
records are kept in the same database


deCODE purchased the medical records and
has correlated family relationships with medical
records


Every citizen will give blood to determine a
genetic fingerprint unless they opt out


Some physicians worry that patient
-
physician
trust has been broken and that patients may be
less forth
-
coming with medical information


Estonia has expressed interest in forming
similar program



How Should the Public Be
Informed of New Discoveries?



News media outlets tend to over
-
simplify
findings, but most Americans do not
understand the scientific literature


The media has recently reported on the
discovery of a: “gay gene”, “smart gene”, “fat
gene”, “worry gene”, “Alzheimer’s gene”,
“cancer gene”, and “fountain
-
of
-
youth” gene


Most of the time, the fact that these are just
one of many genes affecting a given condition
or that environmental factors exist is buried in
the story of left out completely


Should We Clone Humans?


In 2001, a number of groups announced
that they would clone a human by 2003


However, these groups have little
credibility within the scientific community
and include the Raelian cult (who believe
life was produced by extra
-
terrestrials)


In Jan. of 2003 it was claimed that a clone
had been born but this is now thought to
have been a hoax


Despite this, it is likely that some group will
attempt to clone a human in the future

Arguments Against Human Cloning


In 2001, Rudolf Jaenisch (an epigeneticist) and
Ian Wilmut (Dolly’s cloner) published a paper
called “Don’t Clone Humans!”


In it they described a number of failed attempted
to clone animals and health problems associated
with clones


In 2003, Dolly died at half the expected age


Epigenetic factors which may be altered in clones
include CpG methylation, chromatin structure,
and telomere length


Most have denounced human cloning at this time