The Ethics of Genomics

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 • Golden Rice • Biological Plastics • Pharmaceutical Produce • Sterile Fruit • Pest-Resistant Plants • 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? • 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.

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 -5oC without freezing

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.

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.

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

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

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

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.

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 • Privacy and Fairness in the Use and Interpretation of Genetic Information • Clinical Integration of New Genetic Technologies (examines impact of genetic testing on individuals, families, and society) • Issues Surrounding Genetics Research (the design, conduct, participation in, and reporting of genetics research) • 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: • 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

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

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

The Ethics of Genomics