The Ethics of Genomics

1
The Ethics of Genomics

• Are GMOs Bad?
• Is Genetic Testing Good?
• How Should the Public Be Informed of New
  Discoveries?
• Should We Clone Humans?

2
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
• Golden Rice
• Biological Plastics
• Pharmaceutical Produce
• Sterile Fruit
• Pest-Resistant Plants
• Xenotransplants

3
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

4
So, Whats the Controversy?

• All commercial rights to Golden Rice has been
  transferred to Syngenta, the worlds 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

5
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

6
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

7
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
  worlds food supply using this technology

8
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

9
Xenotransplants

• Organs are taken from one species and put into
  another
• In 1984, a baboons 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

10
Why Pigs?

• they grow to be the size of a large human and
  share certain physiological and anatomical
  aspects with humans
• they are domesticated and are easy to breed
• 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.

11
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?

12
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 -5oC without
  freezing

13
How To Keep Plants From Freezing

• warm the air around them or insulate the crops
• spray bactericides on the crops to kill the
  bacteria
• 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.

14
Insertion of Modified DNA into Cells

• Vectorless
• 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.
• 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.
• Electroporation uses a strong electric field
  which forces the DNA into the cells. Used on
  plant and fungal cells
• Silicon carbide transformation simply mixes DNA
  with particles which punch small holes in plant
  cells.

15
Retroviruses

• 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
• Retroviruses can only infect dividing cells,
  certain body cells (ie. nerves) do not divide
• Retroviruses insert themselves at random into
  human chromosomes- it is not possible to control
  where they will be inserted
• gene may not be effective as normal if inserted
  into the wrong area
• gene may be inserted into tumor-suppressor genes
  and cause cancer

16
Adenoviruses

• 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

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

17
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

18
History of Biotech the modern era

• 1970s- 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 1st
  death attributed to gene therapy
• 2003- The human genome sequenced Dolly dies at
  an early age

19
Traditional Biotech vs. GMOs

• species which are crossed in traditional
  biotechnology are always closely related, this is
  not so in genetic engineering
• the pace of change in traditional biotechnology
  is much slower than that of genetic engineering,
  working on a scale of years rather than weeks
• 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.

20
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

21
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

22
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?

23
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

24
Life Insurance and Genetic Testing

• British life insurance companies can use data
  from 8 genetic tests, including breast cancer,
  colon cancer, Alzheimers, and (as of 2000)
  Huntingtons 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.)
• Shouldnt those who are free of a disease pay
  lower rates than those who test positive?

25
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
• IPs should be prohibited from using genetic
  information to deny or limit any coverage
• IPs should be prohibited from establishing
  differential rates or premium payments based on
  genetic information
• IPs should be prohibited from requesting or
  requiring collection or disclosure of genetic
  information
• IPs and other holders of genetic information
  should be prohibited from releasing genetic
  information without prior consent of the
  individual

26
Utility of Genetic Tests
A number of factors must be considered to decide
whether an individual test is beneficial to the
patient
27
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

28
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

29
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

30
Icelanders 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

31
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, Alzheimers 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

32
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

33
Arguments Against Human Cloning

• In 2001, Rudolf Jaenisch (an epigeneticist) and
  Ian Wilmut (Dollys cloner) published a paper
  called Dont 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