Sample Essays from Students

Paper 3 -- Ethics/Science: Analysis/Argument, using CBE (Council of Biology Editors) style (numbers in parentheses with references list)

How often can we cure diseases at their very source? Most of the time we have enough difficulty pinpointing the source, much less treating it. As a result, we are left only to alleviate symptoms. For most genetic diseases, this problem is a painful reality. One infant in every hundred is born with a serious genetic defect (1). The damage usually becomes evident in childhood and all too often leads to physical or mental abnormalities, pain, and early death. Of the more than 4,000 known inherited disorders, most lack fully effective therapies (2).

It is no wonder, then, that scientists like the eminent Dr. W. French Anderson have long imagined curing inheritable ills at their source: the genes. Anderson, who researches and practices medicine at the National Institutes of Health, is widely known as "the father of gene therapy." He was the first to devise means for repairing genes that encode for various diseases. According to Anderson, gene therapy could revolutionize medicine. It could eliminate heart disease, diabetes, and some types of cancer and mental disorders. Further, he predicts that five years from now gene therapy will also be used to manage AIDS, hemophilia, and Tay-Sachs (a genetic nervous-system disorder) (5).

What we have in our grasp is a technology with awesome potential to do both tremendous good and devastating harm. Medical, social, and ethical issues must be raised and debated as we journey into what critics may call a "Brave New World" but what supporters believe is the next evolutionary step for mankind.

DNA is the single most important factor that distinguishes living things from non-living matter. If something has DNA, then it is alive or was once alive. DNA stands for deoxyribonucleic acid, which is composed of very simple atoms. It is how the molecule is put together that determines whether we are short or tall, a human being or a tree. It codes for something as complex as the brain or as simple as a strand of hair. It is mind boggling to imagine how chemistry is simply molecules interacting with one another in such a way to produce a human being who can laugh, cry, and think. That is the power of DNA.

In each strand of DNA, there are tens of thousands of genes (3). A gene is a section in the strand that codes for a specific protein. The proteins carry out various life processes, some of which help metabolize the food we eat in order to feed our bodies. Others are involved in the process of reproduction in order to further our genetic inheritance.

A DNA strand can also be called a chromosome. A normal human being has 46 chromosomes or 23 pairs of chromosomes. Within each pair, one chromosome comes from the father and the other from the mother. With the incredibly large number of genes in each of our cells, we must realize there is a finite probability of some of the genes being detective. One example of such a defect involves a case in the 1970's about a young boy named David (1). He became famous for his life-long existence inside a sterile bubble because he suffered from Severe Combined Immune Deficiency (SCID). As a result, he lacked a normal immune system which cause his increased susceptibility to viruses. His parents were normal because within their gene pair, each parent carried a normal gene to make up for the abnormal one that failed to code for an important enzyme, adenosine deaminase (ADA). Receiving both parents' abnormal genes, David was unable to produce ADA. Without this enzyme, poison builds up in the T-cells that make up our immune system and prevents them from dividing. Without T-cells, he could not fight infections. What quality of life is that for a child?

Today, however, physicians can solve this problem by introducing the gene that codes for ADA into the cells deficient in it. Although still in its experimental stage, gene therapy has proven to be successful in treating SCID. In fact, the most recent gene treatment was performed on a newborn infant. On May 15, 1993, Andrew Gobea made medical history by being the first infant to undergo gene therapy (4). Suffering from SCID, he was an excellent candidate for such a treatment. Gene therapy cannot solve a disease that is caused by several defective genes from different chromosomes interacting to manifest the illness. That would be too complicated. But for cases in which only a single gene is dysfunctional, gene therapy is a viable solution. In the case of Andrew, the physicians at Childrens Hospital, Los Angeles, were creative enough to use blood drawn from the umbilical cord that was snipped from the baby at birth. This new technique is important because it allows the physician to treat the stem cells themselves. Stem cells are the cells that give rise to blood and T-cells. With the previous gene treatments, healthy genes were usually inserted into the T-cells because the stem cells are much fewer and virtually impossible to isolate. Often, the removal of bone marrow to extract stem cells is painful and gives low yield. The advantage, however, of correcting the problem at the stem cell level is that T-cells die eventually, and thus gene treatment must be repeated twice every year. Stem cells, on the other hand, live forever, and once they are treated with the healthy gene, they will continue to function normally without requiring further gene treatments. Fortunately, the blood from the umbilical cord has a small number of stem cells. The cells are extracted, treated with the healthy ADA gene, and injected back into the infant. It will then take a couple of months to see if the procedure was successful.

Since the structure of DNA was discovered, scientists have gone further in their attempts to manipulate and clone it. Genetic engineering already produces the much-needed insulin for 14 million diabetics (2). Now we are taking DNA manipulation to a higher plateau with gene therapy.

Human genetic engineering is divided into four types (5). The first, which is being practiced today, is somatic cell gene therapy. Somatic cells are the cells in our bodies that are not the egg or sperm cells. Therefore, if a patient were to suffer from melanoma, for instance, somatic gene therapy could cure the skin cancer, but the cure would not extend to his posterity. Germ-line gene therapy, however, involves correcting the genetic defect in the reproductive cells (egg and sperm) of the patient so that his progeny will be cured of melanoma also. The third is enhancement genetic engineering, in which a gene is inserted to enhance a specific characteristic. For example, a gene cording for a growth hormone could be inserted to increase a person's height. The last type is eugenic genetic engineering. It involves the insertion of genes to alter complex human traits that depend on a large number of genes as well as extensive environmental influences. This last type is the most ambitious because it aims at altering a person's intelligence and personality. So far, only somatic cell gene therapy is being performed. The other types involve serious moral and social issues that prevent their being pursued at this time.

There are several methods for inserting the therapeutic gene into the cells. One is integration by chemical means. The target cells (cells that require gene treatment) are treated with a chemical that enables the therapeutic gene to enter the cell. Usually, one in every 100,000 cells is inserted with a gene, which is not very efficient (1). Another way to insert the gene is by injecting it into the cell with a needle. When there are millions of cells to inject, this method can be very laborious. The most successful method involves using a retrovirus as a vehicle for gene transfer. A retrovirus is simply a type of virus that carries RNA (a derivative of DNA) instead of DNA itself as its genetic material. When it injects its RNA into its host cell, the RNA converts back to DNA and the DNA integrates itself into the host's own DNA. This ensures that the viral proteins are made along with the host proteins. The reason that scientists are using retroviruses is that these RNA viruses are better carriers of therapeutic genes than the normal DNA viruses are. The researchers insert the therapeutic gene into the retroviral RNA and have the virus attack and deposit its genetic material into the target cells. The RNA will do the rest.

Cells that are good candidates for this procedure are those of the bone marrow, skin, and liver (1). These types of cells divide all the time, ensuring the replication of the therapeutic gene. They are strong enough to withstand removal, manipulation, and reinsertion into the body.

Using retroviruses for gene transfer, however, has some limitations. The virus cannot simply be injected into the body and expected to find its way to the target cells. The cells themselves must be extracted and isolated. Also, some retroviruses are oncogenic (6). This means that if their DNA is integrated into the cell, the oncogenes can cause tumors in our bodies by a complicated mechanism that need not be explained here. Fortunately, the viruses used in gene therapy are engineered so that they no longer carry the oncogene. These altered viruses have only one purpose and that is to get the therapeutic gene integrated into the cells. Once they accomplish this, they die without reproducing their own progeny. These preliminary steps, however, are not always 100 percent successful. A small percentage of the retroviruses may still be oncogenic.

The last problem that may arise is the activation of our own oncogenes triggered by the insertion of the therapeutic gene. Normally, our oncogenes are dormant or function minimally as a component of the cell replication cycle. However, if one is disturbed by our inserting a gene near it, the oncogene would cause rapid and uncontrollable cell division, resulting in a tumor. According to Dr. French Anderson, no reports of such difficulties have been filed. Fifty-nine patients who have undergone gene therapy at the experimental level have, so far, not suffered from any complications (7). Gene therapies treating SCID, hemophilia, Familial hypercolesterotemia (disease that causes buildup of fatty acids in the blood), and various cancers such as melanoma and leukemia have been performed so far. The first two patients to undergo gene therapy for SCID are now leading normal lives. These two children were given a second chance in life, something David never had. Indeed, this is very exciting news. They are cured of a disease that, in the past, has killed many children before the age of four.

Of the four categories of human genetic engineering, only somatic cell gene therapy is being performed on human beings. Ethical debate over this procedure appears to have ended, only to be replaced by germ-line therapy. Both germ-line and enhancement genetic engineering are being carried out in laboratory and farm animals. Therefore, the technical ability exists. The reason we haven't applied these to human beings is that we must first consider their social and moral implications. It is critical that serious ethical reflection by both experts and the general public begin on germ-line and enhancement engineering. As mentioned earlier, eugenic genetic engineering is far beyond our technical capabilities and thus need not be considered at this time. Enhancement genetic engineering is mostly opposed by the public, as well as by scientists, which is as it should be in a responsible society. Enhancement engineering would threaten important human values in two ways. First, the medical risks exceed the potential benefits. And second, it would be morally precarious. Our society is not yet prepared to make such moral decisions, ones which could lead to an increase in discrimination. It is frightening to think that children like Toni Morrison's fictional character, Pecola, could actually obtain blue eyes. The media already toys with our self-esteem, reminding us constantly that we flawed in all aspects of our lives. With enhancement engineering, we are doomed to lose more than our self-esteem; we would lose our individuality.

Germ-line therapy, however, is a different matter. As caring human beings we have a moral responsibility to cure diseases and prevent suffering whenever possible. Germ-line therapy results in the therapeutic gene being passed on to the recipient's offspring and to all subsequent generations. This notion of having future posterity affected raises ethical issues. Some ethicists critically point out that "it is the prospect of making inheritable changes in genes that leads many to feel that we have indeed crossed the barrier separating the permissible imitation of the divine with the usurpation of God's prerogatives" (7). Also, germ-line gene therapy would violate the rights of subsequent generations to inherit a genetic endowment that has not been intentionally modified (8). These are strong arguments.

However, if we are to argue about the "rights" of future generations, then we must parallel that with the complaints of not being able to receive smallpox now that medicine has essentially eliminated it. It is preposterous to demand the right to inherit diseases that can hurt and kill us. Furthermore, we are not trying to play God; we are simply following the fundamental moral principle of relieving human suffering. When germ-line therapy is accepted as a moral good (and I believe it to be "when" and not "if"), certain criteria must be met before initiating this procedure (7). First, there should be considerable experience with somatic cell gene therapy that clearly establishes the effectiveness and safety of treatment of somatic cells. Second, there should be adequate animal studies that establish the reproducibility, reliability, and safety of germ-line therapy, using the same procedures that would be used in humans. And last, there should be public awareness and approval of the procedure since unborn generations will be affected. The gene pool is a joint possession of all members of society. Since germ-line therapy will affect the gene pool, the public should have a thorough understanding of this form of treatment. Only when an informed public has indicated support should clinical trials begin.

As long as we are an informed and responsible society, we have no danger of heading toward that "Brave New World." Gene therapy, somatic cell and germ-line, has the potential for providing mankind with enormous good. It is imperative that we do not deny ourselves, our children, and their children the benefits of this technology simply because we fear its potential for misuse. It is our responsibility to establish adequate safeguards to prevent the abuses so that the full power of gene therapy can be realize and we can live longer and healthier lives.

1. Aehrman, Sally. Breaking genetic barriers. Image 19 May: 18-24; 1991.

2. Alman, Inder. Gene therapy. Sci. Am. November: 68-83; 1990.

3. Darnell, James. Molecular biology. New York: Freeman & Co., 1990.

4. Dolberg, Sheryl. Baby 1st to receive gene treatment. Los Angeles Times 1993 May 16: Sect. A, 2.

5. Anderson, W. French. Uses and abuses of human gene transfer. Human Gene Therapy February, 1; 1992.

6. Larhop, Michael. Oncogenes. Sci. Am. January: 3-8; 1982.

7. Mungst, Eric. Germ-line therapy: back to basics. Human Gene Therapy February'. 45-47; 1992.

8. Paver, Bernard. Germ-line therapy., evolution and moral consideration. Human Gene Therapy August: 361; 1992.