Gene Therapy Essay, Research Paper

“What’s the worst that can happen to me? I die, and it’s for the babies,” said Jessie Gelsinger as he left for the hospital to receive gene therapy treatment. (Stolberg) People risk their lives everyday in the name of science. One such science that people have recently been drawn to is gene therapy. Although, gene therapy may be new and exciting and it may be helping to find cures to diseases we only dreamed of curing, we have to remember it is dangerous. It needs to be done with much supervision. Every new step we take in the advancement of gene therapy should be thought over because the consequences could reach farther then we ever believed they could. There are so many dangers of the techniques used that can lead to consequences as serious as death. The government imposes many guidelines, and it needs to stay that way. The biggest dangers, however, may be in what is to come.

General dangers of the techniques of gene therapy are a large concern. One problem is that the new gene may be inserted in the wrong location in the DNA. Experiments with rats showed this could cause cancer or other damage. In addition, when DNA is directly injected into a tumor there is a chance that the DNA could be introduced by mistake into reproductive cells, producing changes in offspring. The consequences of this are discussed in more detail later on. Another disturbing thing to think about when pondering the safety of gene therapy is the fact that once gene therapy has taken effect it cannot be stopped and is irreversible. It is not like drugs, the genes cannot be stopped from multiplying.

Viral vectors use viruses to transport a modified gene into a patient’s body. They are right now being used all the time in gene therapy trials. These vectors have many dangers associated with them. For example, viruses have a tendency to infect more than one type of cell. Therefore, when viral vectors are used to carry genes into the body, they may alter more than the cells that the scientists intended to change. Another danger is the possibility that the immune system may have severe allergic reactions to the vector itself. Even if the immune system does accept the virus, there is still a concern that it may be possible for transferred genes to be over expressed. This would produce so much of the missing protein that it would become harmful. Also, an immune system reaction could potentially make the viruses less effective when the patient uses them over time.

Since gene therapy is such a new and possibly dangerous field there are many safeguards that the government has tried to set up to regulate it. Before any gene therapy experiment in humans can begin, researchers need to pass many steps of review. They must first demonstrate their ideas in the lab with no live subjects, and then try the treatment on animals. If the animal data looks good then they may consider the therapy for people. The researchers next step is to present their proposal to the review board for their own university or drug company. This board will consider things such as the risks that the patients will be taking while participating in the gene therapy research. Then the experiment may need approval by the National Institutes of Health’s Recombinant DNA Advisory Committee (RAC). The NIH, which includes more than 20 institutes and offices, created this committee in 1974 to consider ethical, scientific and safety issues related to recombinant genetic experiments. The researchers final step is to send their proposals to be reviewed by the Food and Drug Administration. This is slightly controversial because, some people argue that the FDA does not know enough about gene therapy to make proper decisions concerning new trials of it.

Two times, in the history of gene therapy, researchers have gone behind the backs of the government to do gene therapy research. In 1971, Stanfield Rogers of Oak Ridge National Laboratory was the first person to ever transfer animal genes into humans. He used a rabbit virus to try to restore the ability of two German sisters to make their own arginase, an enzyme that breaks down arginine. (The arginine had caused mental disabilities in the sisters.) This experiment did not work and patients were harmed. Martin Cline then became the first person to attempt gene therapy by putting a normal copy of a human gene into people who lacked it. Cline tried to treat beta thalessemia, a blood disease where too much iron builds up in a person’s system. He tried to insert the gene that codes for human hemoglobin. Cline never got permission and went ahead and did the experiments anyways in Israel and in Italy. He hurt people and got into a lot of trouble. No one tried gene therapy again for another ten years.

These examples demonstrate another danger of gene therapy, the race by scientists and drug companies to get money and recognition without much regard for the patient’ safety. “About 40 % of the new studies proposed in the last 3 years have had industry sponsors who hope to commercialize genetic cures.” (www.sandyford.techie.org.uk/gelsinger.htm) It should come as no surprise to us that universities and drug companies withhold information about patient deaths. They have profits and shareholders to protect and answer to.

Unfortunately, this race has caused secrecy to occur even recently. In November of 1999 six deaths went unreported to the NIH. This occurrence was profit driven and involved two competing companies, Isner’s Vascular Genetics and Crystal’s GenVec. These two companies were competing to be the first to grow new blood vessels around blocked ones in the heart. This they hoped would be an alternative to heart bypass surgery. The scientists argued that the patient’s deaths were not related to the gene therapy and therefore did not have to be reported to the NIH. But we will never know whether or not these patients died as a direct effect of their treatment.

The most recent, and most publicized death that occurred because of gene therapy was the death of Jessie Gelsinger. Jessie appeared from the outsider to be a healthy 18-year-old boy. His only brush with death came in 1998 when he fell into a coma. However, Jessie was not entirely healthy. He was on a low protein diet and took a pile of pills every day. He had Ornithine Transcarbamylase Deficiency. This is a genetic disorder caused by a deficiency of one of the enzymes in the urea cycle. The urea cycle involves a series of steps that takes place in the liver, in which nitrogen is removed from the blood and converted into urea. Each step requires a specific enzyme and when one is missing nitrogen builds up and is converted into ammonia, which is highly toxic, instead of urea. Ammonia then can reach the brain through the blood, where it may cause brain damage and even death. Jessie did not die from this disorder though. He died from the treatment he voluntarily received from the University of Pennsylvania.

The treatment began in September of 1999. It included directly inserting an adenovirus into the hepatic artery that leads directly into the liver. This specific treatment was much looked down upon by the NIH because it was dangerous. But, after many public discussions between the University of Pennsylvania researchers and the NIH, the NIH eventually voted for approval of the study. Jessie died only four days after the start of his treatment. His organs failed one at a time, starting with jaundice and then blood clots, kidney failure, lung failure and lastly, brain death.

Since Jessie was the supposedly the first patient to have ever died as a direct result of gene therapy, his death sent out a lot of alarming messages about this treatment that was new to much of the public. The news reporters went wild in the weeks following Jessie’s death. Many scientists believed that the boy was healthy enough where he should not have needed gene therapy at all. Therefore a “healthy” teenaged boy had just died from an “unnecessary” treatment.

The FDA began their investigation immediately. They found many problems associated with the way the University of Pennsylvania conducted the Gelsinger gene therapy trial. Before Gelsinger began the treatments his ammonia levels were too high. The researchers should have waited until they got lower to begin the trial. A second thing that the University did wrong was that they failed to report that two other patients had had serious side effects from the Gelsinger type gene therapy. Lastly, the scientists failed to mention in the consent discussion that they had with the Gelsinger family about the deaths of monkeys given similar treatment.

In response to the Gelsinger case there was much talk about whether the safeguards surrounding gene therapy were good enough. The NIH Director, Dr. Harold Varmus, established the Advisory Committee to the Director Working Group on NIH Oversight of Clinical Gene Transfer Research (the Working Group) to review the role of NIH in oversight of clinical gene transfer research. The Working Group includes people from scientists to bioethicists to representatives of the general public. They met in May 2000 to decide if there needed to be any additional NIH measures taken to minimize risk associated with gene therapy. They came to the conclusion that research in the field of human gene transfer should be kept under a close watch and patients should be extremely protected. Hopefully, committees such as the NIH and FDA will continue to regulate and watch over the advancement of gene therapy. This field is advancing quickly and the government regulations need to advance with it.

Perhaps the biggest danger of gene therapy may not lie in what is happening right now, but may lie in what is to come. Germ-line therapy is a type of therapy we may see in the near future. So far, all gene therapy trials now are somatic. Somatic therapy only introduces genes into regular body cells, not sperm or egg cells. The genetic material added to these cells can help patients only during their lifetimes, but will never be passed on to their children. Germ-line gene therapy on the other hand involves genetic manipulations of sperm, egg, or early embryonic cells. These cells can create a whole person all by themselves, therefore, if their genes are altered, the change will be passed on to future generations. Many researchers praise germ-line gene therapy and say that it is good because it will not only eliminate the disease in the patient, but the “fixed” gene will be passed on to the children, therefore preventing them from having the disease. Advocates also say, the germ-line approach might be less expensive than somatic gene therapy or traditional treatments for genetic diseases. However, there are large risks involved. First, there is a large risk for the developing embryo. This is because scientists lack the technical skills to insure precise insertion of a gene without disrupting other genes. Also the genes would be passed on to future generations therefore changing the human gene pool. Although these changes are thought to be for the better, an error in current technology or judgment could have long lasting consequences.

Another issue surrounding Germ-line gene therapy is that it could eventually lead to eugenics, or reproductive policies that are intended to promote preferred characteristics. We may be working on life threatening illnesses today but tomorrow we could be concerned about baldness or height. One last item that many are disturbed about is the fact that the patients involved are fetuses and future people that have not been born. They have no say in whether they want to be treated and they will never learn of the risks and benefits of the treatments.

Gene therapy, therefore, raises ethical questions: where can the line be drawn between a necessity to someone’s life, such as finding a cure for cancer, and a admirable trait that someone would like to have, such as skin color? In January of 1993, it was reported in USA Today that an 11 year-old boy was receiving gene therapy treatments at a cost of $150,000 per year to increase his height. He was 4 feet 11 inches, four inches below average height. He was tired of being picked on at school for being short. His father was quoted in the article as saying, “You want to give your child that edge no matter what. I think you’d do just about anything.” (Ruggles) The Ethical, Legal, and Social Implications (ELSI) Program was established in 1990 to address issues such as these. The ELSI Program is designed to address the ethical, legal, and social part of human genetics research.

Many are wary of gene therapy because it is so futuristic. People raise religious and moral concerns about messing around with our complex bodies and their natural processes. We may never fully understand these things. The treatments we do now to help people may, in the long run, hurt our society as a whole. This is why researchers must be constantly watched over by the government. We do not need them racing carelessly for profit and fame. Deaths like Jessie Gelsinger are unnecessary and should not happen. Gene therapy has a potential to save many lives. Let us realize, however, that we need to understand the dangers and proceed with research with caution.

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