G E N E T I C T H E R A P Y

A N D

G E N E T I C E N H A N C E M E N T

________________________________________________________________________

Elaine Hennebeul

ASC 128 – Winter 2001

Dr. Perring

As a result of recent advances in medical science, researchers believe that a gene can be transplanted into human beings who suffer from severe diseases. Such gene transplants may alleviate or perhaps even cure disease for which no adequate treatment now exists. The treatment is called human gene therapy and is one of a series of emerging genetic techniques, commonly called genetic engineering, based on new knowledge about how genes work.

One major goal of gene therapy is to supply cells with healthy copies of missing or flawed genes. Instead of giving a patient a drug to treat or control the symptoms of a genetic disorder, physicians attempt to correct the basic problem by altering the genetic makeup of some of the patients’ cells. Gene therapy has the potential to treat lethal and disabling diseases as well as disease prevention. The rationale for gene therapy lies in our understanding of the genetic basis of human disease. A composite of approximately 150,000 individual genes constitutes a human being. Variation in the structure of a person’s genes collectively helps define us as individuals such as how tall we are to the color of our eyes. Some of this genetic heterogenetics, unfortunately, leads to the development of disease. Each gene acts as a blueprint for making a specific enzyme or other protein. However, only certain genes in a cell are active at any given moment and, as cells mature, many of their genes become permanently inactive. It is the pattern of active and inactive genes in a cell and its resulting protein composition that determines what kind of cell it is and what it can and cannot do. Some genetically inherited diseases are passed from one generation to the next by inheriting a single gene, such as Huntington’s disease. Many other disease and traits are influenced by a collection of genes. The premise of gene therapy is based on correcting disease at its root, the abnormal genes.

For some genetic diseases, there are satisfactory therapies that do exist. Drugs, blood transfusions, changes in diet, or transplantation of body organs can often help to compensate for the incorrect information from the malfunctioning gene. For example, clotting factor can be administered to patients with hemophilia.

The first disease approved to be treated with gene therapy has been adenosine deaminase (ADA) deficiency. ADA deficiency is a rare genetic disease. The normal ADA gene produces an enzyme called adenosine deaminase that is essential for effective immune system function. Patients with ADA deficiency have no intact copies of this gene, and their defective copies do not produce functional ADA. ADA-deficient children are born with severe immunodeficiency and are prone to repeated serious infections. Even the most minor viral illness may pose a dire threat. If untreated, the disease often results in death within the first years of life.

ADA deficiency was selected for the first sanctioned human gene therapy trial for several reasons. The disease is caused by a defect in a single gene, which increases likelihood that gene therapy will succeed. Also, the gene is regulated in a simple fashion, unlike many genes whose regulation is complex. Finally, even small amounts of the enzyme produced by the normal gene are known to be clinically beneficial, while larger amounts do no harm. Thus, the amount of ADA produced does not need to be precisely regulated. The ADA gene therapy trial began in September 1990. Two children were treated, and results to date have been gratifying.

There are two forms of gene therapy, one of which is called somatic gene therapy. Somatic therapy involves the manipulation of gene expression in cells that will be corrective to the patient but not inherited to the next generation. This is the type of gene therapy that is currently being investigated at the Institute for Human Gene Therapy at the University of Pennsylvania, as well as other laboratories across the world. The other form of gene therapy is called germline gene therapy. It involves the insertion of new genes into the nucleus of sperm, eggs, or embryos. The new genes are then passed on from one generation to the next. Raising the question: would this change the evolution of human life? Although scientists do not currently have the technology to safely alter human reproductive cells genetically, such therapy could become technically feasible in the future. In the case of hereditary illness, successful germ-line gene therapy would have the potential to eliminate a genetic defect, such as hemophilia, from an entire family line with a single procedure.

The techniques for isolating human genes and making multiple copies of them in the laboratory are well established. Now scientists are studying how to insert those genes into cells and how to make those genes work properly once inside the cells. One method for inserting genes into cells is to link the genes with a virus that has been crippled and rendered harmless. As part of the modification, such a virus, sometimes called a vector or vehicle, has been deliberately altered so that it can carry genes into cells but cannot then escape to infect other cells. After the cells to be treated have been temporarily removed from a patient’s body, the virus or vector is used to carry the desired gene into them. The final step will be to return the treated cells, which now contain the correct genetic information, to the patient’s body. For example, bone marrow, liver cells, or white blood cells could be removed from the body of patient, treated in the laboratory, and returned to the patient.

Whether bone marrow cells or some other type of human cells were used, the added genes would be inserted only into somatic (non-reproductive) cells and not into germ line (reproductive) cells. Therefore, newly inserted genes could not be passed to patients’ children. The therapy would be called somatic cell gene therapy and would not attempt to affect the germ line cells, which carry genetic information to the next generation.

The technology of gene therapy is based on strategies for delivering genes. While proponents stress health benefits for the human race, critics worry that germ-line therapy could be a genetic nightmare. Will we see disease eliminated in the future, or will we witness the creation of new and possible more dangerous genetic conditions that cannot be cured once they are unleashed? The Council for Responsible Genetics called for a ban on germ-line manipulation. “They added that inserting foreign DNA into germ cells could have unpredictable repercussions, and could even lead to susceptibility to cancer and other fatal diseases.”[1]

The challenge facing researchers is to remove the disease causing components of the virus and insert recombinant genes that will be therapeutic to the patient. In other words, supply cells with healthy copies of missing or flawed genes. This approach is revolutionary: Instead of giving a patient a drug to treat or control the symptoms of a genetic disorder, physicians attempt to correct the basic problem by altering the genetic makeup of some of the patient’s cells.

Gene therapy could also be used as a drug delivery system. A gene that produces a useful product would be inserted into the DNA of the patient’s cells. For example, during blood vessel surgery, a gene that makes an anticlotting factor could be inserted into the DNA of cells lining blood vessels to help prevent dangerous blood clots from forming. Using gene therapy for drug delivery could shortcut the lengthy and complicated process of collecting large amounts of a gene’s protein product, purifying the product, formulating it as a drug, and administering it to the patient.

There are several risks associated with current gene therapy trials in humans. Viruses usually can infect more than one type of cell. Thus, when viral vectors are used to carry genes into the body, they might alter more than the intended cells. Also, whenever a gene is added to DNA, there is the danger that the new gene could be inserted in the wrong place, possibly causing cancer or other damage. Another possible risk is that when DNA is directly injected into a tumor, or when a liposome delivery system is used, there is a slight chance that foreign genes could unintentionally be introduced into germ cells, sperm or eggs, producing inheritable changes, although this has not occurred in animal tests. Other worries include the possibility that transferred genes could be “over expressed,” producing so much of the missing protein as to be harmful; that the viral vector could cause inflammation or an immune reaction, especially if administered repeatedly; and the virus could be transmitted from the patient to other individuals or into the environment.

Recent reports of problems in gene-transfer trials have brought forward the new pressures facing researchers. In one reported case, the use of gene therapy to transfer healthy genes into the cells of a patient to replace or repair genes linked to disease resulted in the death of the patient. In order to get past the body’s defenses, the genetic material can be delivered attached to a virus, which can cause illness or even death. Last September 2000, 18-year-old Jesse Gelsinger died while participating in a University of Pennsylvania gene therapy for a rare liver disorder. The FDA halted subsequent clinical trials at the institute, citing serious violations of federal research rules. “The Clinton Administration plans to pursue legislation that would allow the FDA to impose civil fines for such violations. The maximum proposed fines are $250,000 for a clinical investigator and $1 million for a research institution.”[2]

Gene therapy could redefine the practice of medicine in the next century. It could be a powerful tool for treating many of the more than 4,000 known genetic disorders, as well as heart disease, cancer, arthritis, and other illnesses. “Gene therapy has the potential to revolutionize health care by enabling more people to remain productive members of society and by eliminating or reducing the need for costly medications and other treatments that alleviate symptoms but do not cure disease.”[3]

Gene therapy has the potential to do more than cure disease involving faulty genes. Gene therapy could be used with patients who have coronary artery disease. Coronary artery disease is a condition in which vessels are partly blocked so that tissue downstream from the blockages doesn’t get enough blood, and therefore, enough oxygen. In such cases, the body will naturally generate more blood vessels, to provide what is known as collateral circulation. Sometimes the body cannot keep up, and oxygen-starved cells generate the pain known as angina. By adding genes that produce an angiogenic growth factor to the body, the collateral circulation can be speeded up and increased.

Scientists at the University of Pennsylvania Medical Center have developed a novel gene therapy treatment that permanently blocks the age-related loss of muscle size and strength in mice. Mice, like humans and all mammals, lose up to a third of their muscle mass and power with age. In humans, the result is an advancing weakness in the elderly that can lead to unsteadiness and impaired mobility, increased susceptibility to falls and injury, and joint stress and degeneration.

Even in young adult mice, the new treatment increased muscle strength by a dramatic 15 percent over untreated muscle. But in older mice, the improvement was even more remarkable. The researchers documented a 27 percent increase in strength over untreated muscle in these mice. This fully restored their strength to what it was in young adulthood.

The technique suggests human therapies that could reverse the feebleness associated with old age or counter the muscle-wasting effects of muscular dystrophies and related diseases. It also raises the possibility, however, that the technique could be used, or abused, for athletic or cosmetic enhancements.

Results from the experimental study showed that it might be possible to preserve muscle size and strength in old age using this approach. Researchers are now looking to see whether the technique might also be used to increase muscle strength in diseases such as muscular dystrophy.

Biologists studying aging at the level of cells and genes are finding that life span is far easier to manipulate than they had expected, at least, in certain laboratory organisms. Some eight genes have now been found that can lengthen the life span of the laboratory roundworm, C. elegans, in one instance by fourfold. That is equivalent to making a person live 340 years.

Biologists at the Massachusetts Institute of Technology recently announced that they had discovered a basic mechanism that causes yeast cells to age. The mechanism can be triggered by failures in a gene whose counterpart in humans causes Werner’s syndrome, a disease with symptoms that strongly resemble premature aging.

Roundworms and even yeast are much closer to humans genetically than their outward forms suggest. The importance of the new findings is that they seem to contradict in several ways the long-standing theory of aging developed by evolutionary biologists. “Their theory says that there is no basic mechanism of aging, just a lot of things that go wrong at about the same time. They believe aging is controlled by a multitude of genes, with not one single gene having any big effect. Dr. Thomas E. Johnson, a biologist at the University of Colorado, said, “The identification of genes that slow the rate of aging has made people recognize that the fundamental aging process, even in higher organisms, could be under genetic control and can and may be modulated.”[4]

Gene therapy is currently focused on correcting genetic flaws and curing life-threatening disease, and regulations are in place for conducting these types of studies. But society will need to deal with more complex issues regarding gene therapy. One issue is the possibility of genetically altering human eggs or sperm, thereby permanently (though potentially reversibly) changing the human genetic inheritance. Another relates to the potential for enhancing human capabilities, for example, improving memory and intelligence, by genetic intervention. From that kind of enhancement, however, it is an easy jump to introducing genes that will improve a perfectly healthy body.

The term applied to the uses of gene transfer for purposes other than treating disease is called gene enhancement. It is very difficult to come to any consensus about what people deem as enhancement. There are many different types of enhancement, which have a different level of appeal to different people. This is very distinctive from disease where a group of medical experts can convene and come to some definitive conclusions about malfunctions in the body. Diseases can be placed in a spectrum ranging from mild to serious to fatal; whereas, the market for enhancement is thought to be largely driven by desire.

There are many common cosmetic enhancements that might be targeted for research in the area of genetic enhancement. The use of genes to correct pattern baldness and the use of genes to affect skin color or hair color or physical appearance are among the most common types of physical enhancement. Another area that could be open to research, but is a little more far fetched, is the matter of improving intelligence; because intelligence is a multigenic function which involves hundreds or even thousands of genes. Even if they were identified, this would not be sufficient since the interactions among such genes would also have to be known as well. However, it is not likely that the genetic definition of intelligence may be understood in the near future.

A very important question is raised: Can genetic enhancement be prevented or should it be prevented? The regulatory agency that will be the first to face this issue is the Food and Drug Administration (FDA). Two main questions will have to be answered by the FDA. One is does the product do what it is alleged to do? And the second, is the product safe? The second can be very complicated because it involves a risk/benefit ratio. One can justify certain kinds of risks when treating a serious or fatal illness, especially if there is a reasonable chance of benefit. The tolerance of risk for a “cosmetic” may be difficult to determine, particularly if there are potential genetic side effects that are impossible to predict. On the other hand, if the enhancement product is deemed to be safe by all the measures available, then the FDA may proceed to make approval. There is no obligation for the FDA to conduct an “ethical” review although the agency retains the right to convene public advisory conferences when it is deemed necessary. A conference, however, would guarantee press attention.

Genetic enhancement raises many issues. There is the anxiety that such manipulation could become a luxury available only to the rich and powerful. Some also fear that widespread use of this technology could lead to new definitions of “normal” that would exclude individuals who are, for example, short, unattractive, or of merely average intelligence. Some people associate all genetic manipulation with past abuses of the concept of “eugenics.” Still another concern is that technologies can accomplish great good, but they can also result in great harm, either inadvertently or because of deliberate misuse.

A proposed experiment, or protocol, must pass through at least two review boards at the scientists’ institution and must be approved by that institution. The protocol must then be approved by the Recombinant DNA Advisory Committee (RAC) of the National Institutes of Health (NIH) and be signed by the NIH director. All protocols must also receive the approval of the U.S. Food and Drug Administration.

Government-funded experiments involving gene therapy for human patients occur at both the local and national levels. At the local level, facilities at which experiments would take place are required to have two types of committees. First, hospitals and universities involved in experiments with human subjects are required to have Institutional Review Boards (IRB) to ensure that the research complies with Department of Health and Human Services (DHHS) regulations for protection of human subjects. Second, experiments that involve gene insertion must be approved in advance by an Institutional Biosafety Committee (IBC).

These local review boards provide an opportunity for the general public to become involved in the decisions made about research involving gene therapy for human patients. The DHHS regulations require that at least one nonscientist serve as a member of each IRB. Further, the NIH Guidelines for Research Involving Recombinant DNA Molecules encourage research facilities to open their IBC meetings to the public.

At the national level, the Director of the National Institute for Health (NIH) must approve each human gene therapy proposal. In making this decision, the Director seeks advice from the Recombinant DNA Advisory Committee (RAC). The initial review of the proposal is performed by the RAC’s Human Gene Therapy Subcommittee, which is guided by the Points to Consider in the Design and Submission of Protocols for the Transfer of Recombinant DNA into Genome of Human Subjects.

The general public is represented on the RAC and the Human Gene Therapy Subcommittee, as well as on the local review boards. The membership of the RAC (25 people), and the Human Gene Therapy Subcommittee (15 people), includes scientists, physicians, lawyers, ethicists, and several laypeople.

The Food and Drug Administration (FDA) has two main questions to answer: Does the product do what it is alleged to do? And is the product safe? The second question can be very complicated because it involves a risk/benefit ratio. One can justify certain kinds of risks when treating a serious or fatal illness, especially if there is a reasonable chance of benefit. The tolerance of risk for a “cosmetic” may be difficult to determine, particularly if there are potential genetic side effects that are impossible to predict. On the other hand, if the enhancement product is deemed to be safe by all the measures available, then the FDA may proceed to make approval.

Michael S. Langan, Vice President of Public Policy for the National Institute of Health during the Gene Therapy Policy Conference stated, “Give Americans with Genetic Diseases a Chance to Live.”[5] “The National Organization for Rare Disorders’ (NORD) observation of the Field thus far indicates that gene therapy will continue to move in the direction of the most profitable human conditions because there is even far more money to be made in curing baldness and wrinkles than there ever will be in cancer or HIV/AIDS.”[6] NORD believes that barriers should be erected stating the point beyond which scientists should not go. This should be enforced for federally funded research as well as private funded research. There is the issue of the “absence” of regulations over moral and ethical issues. If “enhancement” protocols move forward, to make a person taller, or thinner, or to change the color of their eyes or skin, there will be no way to stop them as long as the FDA determines that they are safe and effective.

There are some enhancements, which are widely acceptable in our society, such as cosmetic surgery to modify appearance. Then there are several controversial medical “enhancements” found in our society today. Prozac and other antidepressants have been increasingly reported to be performance-enhancers, and they are prescribed for that purpose. There has also been an increase use of the stimulant Ritalin for enhancement purposes. A drug previously used primarily prescribed to combat attention deficit disorder. Then there are still others, which are not even considered a form of enhancement at all, such as the use of private schools, vaccinations, and vitamin supplements.

Certain kinds of enhancement are more acceptable than others. Education is conventional and appropriate improvement for our offspring. Unlike the enhancement of our offspring through drugs or genetics, because education allows children to fulfill their “innate capacities,” without changing the child’s “natural state.” An issue, which is raised, lies in how our society views education and how our society views genetic enhancement. “Education allows our children to “fulfill their potential.” Genetic enhancement is viewed as potentially dangerous because, in part, it would modify potential itself.”[7]

Objections to genetic enhancement are raised because critic’s point to the fear of a slippery slope that begins with reproductive genetic testing for diseases and culminates in “an expectation of a perfect baby.” “Once parents have crossed over into modification of the natural state as a part of parenthood, it will be easy to modify that state for less merit

worthy reasons.”[8]

There are many environmental factors, which affect your genetic makeup. Walking in the sun ages your skin because it affects your genetic makeup. Radiation and the chemicals in the water effect changes in germ-line and somatic cells. “There is simply no such think as a genetic model that functions ideally in an ideal environment.”[9] Genes are affected by the environment, and the genome is our shorthand way of saying that we believe that most of the cells in our bodies have roughly the same genetic information, much of which we inherited. Therefore, shouldn’t we place significant importance on environmental factors as well as genetic factors when dealing with a person’s makeup? The term genome could then be hereditary information that is constantly modified in significant and not-so-significant ways by our environment as opposed to meaning a “code of codes.”

It is extraordinarily difficult to know what actions and words will register in the minds of our children. How will the whole package fit together: the way we treat them, the food we feed them, the genes we give them, and the rules we set for them? “The most complex and sophisticated plans for a child’s future can turn out to be the least effective, and we may send messages that are much more mixed than we know.”[10]

There is concern that there will be many wealthy people willing and eager to pay the price of making their child taller or more beautiful. Eventually, there will be discrimination against those who look “different” because their genes were not altered. The absence of ethical restraints could mean that crooked noses and teeth, or acne, or even baldness will become the target for discrimination. Many questions arise over the issue of gene enhancement: Should we allow human gene therapy to be diverted from its important therapeutic path of disease prevention to unnecessary “enhancement” therapy? Some say, such as the National Institute of Health, that it is inevitable. “Unfortunately, however, without veto power for the RAC, and without a statutory ethical mandate for the FDA, you can rely on “enhancement” experiments moving forward because there is just too much money to ignore. Without public oversight of private industry’s clinical trials, these experiments will go forward in utter secrecy because the FDA is not allowed to reveal any information about them without the sponsor’s permission.”[11] Other questions arising from this debate are: Do we as a society have the responsibility to safeguard the human gene pool? Is diversity necessary? Some feel that biotechnology companies and scientists should not decide these monumental questions for us. They feel that Institutional Review Boards (IRBs), which have a conflict of interest, will not be able to resist the dollars attracted to their universities through clinical trials for “enhancement” therapies.

The following is a list of “Points to Consider” from the National Institute of Health:

· What are the probable benefits and harms of the proposed treatment, both to the patient and to others?

· If there are several patients who need gene therapy but only one of them can be treated initially, how will selection be made in a way that treats all patients fairly?

· How will patients - or, in the case of young children, the parents of patients - be properly informed about the possible benefits and risks of gene therapy?

· What steps will be taken to protect the privacy of the patient and the patient’s family, while at the same time informing the public about the results of gene therapy? Two possible undesirable or unintentional consequences of somatic cell gene therapy: transmission of altered genes to a patient’s offspring, and viral infection of persons who come in contact with the patient. What actions will be taken to prevent either event from occurring?

· “Civic, religious, scientific, and medical groups have all accepted, in principle, the appropriateness of gene therapy of somatic cells in humans for specific genetic diseases. Somatic cell gene therapy is seen as an extension of present methods of therapy that might be preferable to other technologies.”

· While the RAC and its Subcommittee believe that gene therapy for non-reproductive, or somatic, cells holds promise for patients suffering from certain genetic and other diseases, they will seek to ensure that patients are not subjected to unreasonable risk of harm, excessive discomfort, or unwanted invasion of privacy and that they will receive special care, monitoring, and consideration. The public will be informed about every step that is taken with this new technique.

· Germ-line gene therapy would change the genetic endowment of an individual’s descendants in perpetuity. Thus, the human gene pool would be permanently affected. Although these changes would presumably be for the better, an error in technology or judgment could have far-reaching consequences.

· In the case of genetic enhancement, there is anxiety that such manipulation could become a luxury available only to the rich and powerful. Some also fear that widespread use of this technology could lead to new definitions of “normal” that would exclude individuals who are, for example, short, unattractive, or of merely average intelligence. And, justly or not, some people associate all genetic manipulation with past abuses of the concept of “eugenics.”

Then there are issues about a person’s “right to privacy.” President Clinton made several statements while at a conference held at the National Human Genome Research Institute regarding “protecting people’s privacy.”

The President was quoted saying, “But, clearly, people’s medical records, their financial records and their genetic records are among the most important things that we have to protect. Last year we proposed rules to protect the sanctity of medical records; we’ll finalize them this year. Soon I will send legislation to complete the job we started in protecting citizen’s financial records. Today, we move forward to try to make sure we do what we can to protect, in an important way, genetic privacy.” “We cannot allow our remarkable progress in genomic research to be undermined by concerns over the privacy of genetic data or the safety of gene therapies. Instead, we must do whatever it takes to address these legitimate concerns. We know if we do, the positive possibilities are absolutely endless.”[12]

It is hard to debate the statement that human genetic information will provide knowledge. “It is generally accepted that knowledge about oneself represents power to determine appropriate outcomes that are consistent with your own personal beliefs in a more rational and positive way. For a liberal society such as ours, this is a positive outcome that enhances our autonomy and allows realistic choices to be made, provided that they do not interfere with the rights of others.”[13] However, genetic information could interfere with the rights of others, where sharing genetic material could include parents, siblings, offspring, cousins, aunts, and uncles who may not want to know about their genetic background. The power to use knowledge may be wanted by some and not be others. It also may be given to some who do not want it, either inadvertently or deliberately. Realistically, genetic knowledge affects more than just one individual. However, is this knowledge significantly different from any other information that is available to a group who share a situation?

There is no doubt that gene therapy could enhance our lives, giving people with diseases a better quality of life and also providing more enrichment Yet, there remain almost an infinite number of unanswered issues that surround genetic therapy and even more controversial, genetic enhancement. Surely, regulations are needed to protect and ensure “safety” but just “how much” or “how little” at both the local and national levels as well as in the public and private sector still remains open. The debate over genetic therapy and genetic enhancement has begun and still remains a debate regarding many “issues.” Consensus will be very hard to achieve on many issues, but justifiably so.

B I B L I O G R A P H Y

______________________________________________________________________

McGee, Glenn, THE PERFECT BABY, Second Edition, Rowman and Littlefield Publishers, Inc., U.S.A., 2000.

Nichols, Eve K., HUMAN GENE THERAPY, Harvard University Press, Cambridge, Massachusetts, London, England, 1988.

Tagliaferro, Linda, GENETIC ENGINEERING, PROGRESS OR PERIL?, Lerner Publications Company, 1997.

Wade, Nicholas, THE SCIENCE TIMES BOOK OF GENETICS, The Lyons Press, 1998.

Yount, Lisa, GENETICS AND GENETIC ENGINEERING, Facts On File, Inc., 1997.

B I B L I O G R A P H Y - W E B S I T E S

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Gene Therapy for Human Patients, Information For The General Public, RAC, National

Institutes of Health, Public Health Service, Department of Health and Human Services

http://www4.od.nih.gov/oba/cover.htm

National Human Genome Research Institute, News Conference with President Clinton,

Story Filed: Wednesday, February 9, 2000.

http://www.nhgri.nih.gov/NEWS/Executive_order/clinton.html

The National Organization for Rare Disorders, Inc., Gene Therapy Policy Conference,

Updated February 16, 1998, “Prohibit Unethical “Enhancement” Gene Therapy.”

http://www.rarediseases.org/new/nihgene.htm

Academic Press, Daily Inscight, “Not-So-Mighty Mice,“ July 1, 1997.

http://www.apnet.com/inscight/06301997/grapha/htm

Science Updates, Access Excellence, What’s News, “Mighty Muscular Mice Cloned”,

By Sean Henahan, May 7, 1997.

http://www.acessexcellence.org/WN/SUA10/mouse597.html

Smithsonian Magazine, “Betting On Designer Genes,” January 2001.

http://www.smithsonianmag.si.edu/smithsonian/issues01/jan01/gene.html

University of Pennsylvania Cancer Center, NCI Fact Sheet: Questions and Answers About Gene Therapy - Updated 08/1993. http://oncolink.upenn.edu/pdq_html/6/engl/600718.html

University of Pennsylvania Health System, The Institute for Human Gene Therapy, (IHGT), What Is Gene Therapy? http://www.med.upenn.edu/ihgt/info/whatisgt.html

University of Pennsylvania Health System, The Institute for Human Gene Therapy, (IHGT), Prospects in Gene Therapy. http://www.health.upenn.edu/ihgt/info/prospects.html

University of Pennsylvania Health System, The Institute for Human Gene Therapy, (IHGT), Hot Topics, #1, Gene Transfer for Enhancement http://health.upenn.edu/ihgt/info/topic1.html

University of Pennsylvania Health System, News and Periodicals: New Gene Therapy Keeps Muscles Strong in Old Age: Possibilities Seen for Disease Treatment, But Also for Athletic or Cosmetic Enhancements, December 14, 1998. http://health.upenn.edu/news/NEWS_Releases/dec98/strong.shtml

CNN Cable News Network 2001, Health Administration, May 24, 2000,

“Gene Therapy Controversy Cited.”

http://www.cnn.com/2000/HEALTH/05/24/gene.therapy.trials/index.html

The Gene CRC, The Cooperative Research Centre for Discovery of Genes for Common Human Diseases, “What is New About Genetics?,” by Professor Bob Williamson, Chair of the Education and Ethics Group of the Gene CRC,

http://www.genecrc.org/site/ge/ge6.htm

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[1] Tagliaferro, Linda; GENETIC ENGINEERING, Progress or Peril?; Lerner Publications Company, 1997.

[2] CNN Cable News Network 2001, Health Administration May 24, 2000. http://www.cnn.com/2000/HEALTH/05/24/gene.therapy.trials/index.html

[3] The University of Pennsylvania Health System, Press Release, December 14, 1998. http://health.upenn.edu/news/NEWS_Releases/dec/strong.shtml

[4] Wade, Nicholas, THE SCIENCE TIMES BOOK OF GENETICS, The Lyons Press, 1998.

[5] The National Organization for Rare Disorders, Inc., Gene Therapy Policy Conference, February 1998. http://www.rarediseases.org/new/nihgene.htm

[6] The National Organization for Rare Disorders, Inc., Gene Therapy Policy Conference, February 1998. http://www.rarediseases.org/new/nihgene.htm

[7] McGee, Glenn; THE PERFECT BABY, Second Edition, Rowman and Littlefield Publishers, Inc., 2000.

[8] McGee, Glenn; THE PERFECT BABY, Second Edition, Rowman and Littlefield Publishers, Inc., 2000.

[9] McGee, Glenn; THE PERFECT BABY, Second Edition, Rowman and Littlefield Publishers, Inc., 2000.

[10] McGee, Glenn; THE PERFECT BABY, Second Edition, Rowman and Littlefield Publishers, Inc. 2000.

[11] The National Organization for Rare Disorders, Inc., Gene Therapy Policy Conference, February 1998. http://www.rarediseases.org/new/nihgene.htm

[12] National Human Genome Research Institute, News Conf. with President Clinton, February 9, 2000. http://www.nhgri.nih.gov/NEWS/Executive_order/clinton.html

[13] The Gene CRC, The Cooperative Research Centre for Discovery of Genes for Common Human Diseases, http://www.genecrc.org/site/ge/ge6.htm