Human Gene Therapy

Craig Kleven

Copyright 1999

Imagine this, you have just married your college sweetheart this past summer. You have now been happily married for over a year and you find out that the two of you are going to be parents. So as the typical soon to be mom and dad so commonly do, the two of you start going to the doctor for checkups to make sure the pregnancy is running smoothly. Early in the pregnancy you hear the worst, your baby has a fatal disease. The two of you are terribly heart broken over the situation. You tell your doctor that abortion is out of the question because you do not believe in it. On the other hand the doctor hits you with the question, "What about gene therapy?" Unfortunately you and your spouse look dumbfounded at each other because you have no idea what the doctor just said.

So, what exactly is Human Gene Therapy? Well, in the next couple of pages I am going to cover some of the basic ideas of human gene therapy, discuss some of the public debates, and wrap things up with my personal opinion. Gene therapy is basically genotypic pharmacology. This involves the use of factors which modify the genetic composition of a given cell or group of cells. As a result of the idea for human gene therapy, a new technique of treatment for many human diseases has been developed. The factors that contribute to the treatments are either gene products, or are capable of interacting with gene products, or have the ability to interact with gene products in an individual cell or a group of cells. The interactions of contributing factors to gene therapy success are extremely capable of regulating particular genes, which either directly or indirectly, leads to the cure of a disease. As a result of this interaction an eventual cure of the disease will be achieved through only a single treatment. Today, gene therapy is capable of curing not only genetic diseases, but also cancer, peripheral vascular disease, arthritis, neurodegenerative disorders as well as other acquired diseases.

Gene therapy techniques consist of several key elements. An important element, actually one of the most important elements is the identification and cloning of the gene or genes related to the disease, which is going to be maintained or treated by gene therapy. However, gene therapy should not be confused with the concept of cloning. Cloning is creating another individual with essentially the same genetic makeup. The idea of cloning an entire human is very different from gene therapy. Next the expression and efficiency of gene transfer during gene therapy must be emphasized. Scientists involved with gene therapy research are currently trying to discover the best rates of gene transfer and tissue-specific gene expression. Gene therapy research is still in the formative stages. Although a number of early human clinical trials have been initiated to test important concepts that have emerged.

The genes we inherit from our parents virtually affect every human disease. The argument for gene therapy lies in the understanding of the genetic basis of human disease. There are an amazing 100,000 individual genes in the human genome. At the present time there is an international movement known as the Human Genome Project. The project will eventually provide an understanding of how each gene plays a role in human lives. The project will aid in gene therapy research because once scientists know what each gene controls, then the genes can be more easily manipulated.

Gene therapy is based on altering a disease at the roots. There are two basic forms of gene therapy, somatic and germline. The first type, somatic gene therapy, involves body cells and is more scientifically studied and investigated in laboratories across the world. This type deals with the manipulation of gene expression in cells that will be corrective to the patient, but not inherited by the next generation. Germline is the second type of gene therapy, and involves sperm and egg cells. At this current point in time, very little research is being done with germline gene therapy compared to somatic gene therapy. The main reason for this lack of research is both technical and ethical. This is due to the fact that germline therapy involves the modification of germ cells that will pass the change on to the next generation.

The advancement and growth of human gene therapy techniques is excellent, but still has a basic challenge. The problem is to establish an approach for delivering genetic material to the appropriate cells of the patient in a way that is precise, efficient, and safe. In order for genes that are delivered to live the life of the cell, a smooth and accurate delivery needs to occur, but problems begin to arise with large and complex genes that require targeting to the nuclei of the cells. The future of gene therapy requires effective delivery of the genes. Gene delivery requires vehicles known as vectors, which take the therapeutic genes to the cellular destination.

One vector is no more than modified viruses. The challenge is to remove the disease causing components of the virus and insert recombinant genes that will be beneficial to the patient. These modified viruses can be replicated in the patient, and at the same time they can efficiently deliver genetic material.

Ex vivo is another strategy that has evolved into what is known as in vivo gene therapy. The ex vivo method harvested the patients cells and were incubated with vectors containing the genes of intent. The cells were then placed back in the patient. In vivo is more practical and efficient because the virus is directly injected into the patient. The first attempt was with cystic fibrosis. Today many diseases such as AIDS, cancer, cardiovascular disease, and infectious diseases are being tested for possible treatment by human gene therapy.

Human gene therapy has several challenges and obstacles to overcome in the laboratories, but it is also challenged by questions from the public concerning the ethics of human gene therapy. A conference at the National Institute of Health has begun to address the ethical questions of using gene therapy for reasons other than treating disease. They examined the future possibilities of this technology being used for enhancement. Some people feel that there will never be a total agreement on the issue because different types of enhancements will have a different level of appeal to certain people. People favor the enhancements that could correct baldness, promote muscle development, and numerous other physical appearances. After this process has been perfected, people might consider improving intelligence. Those opposing enhancement are arguing how much is acceptable and where does a person draw the line? Some of the advocates argue that gene therapy will get too carried away and go beyond the level of just treating disease. A man by the name of Agar has printed publications about the acceptable or unacceptable applications of enhancement. He argues that it is a waste of money and will increase social inequality. Agar believes that environmental factors play a large role on phenotype. He believes intelligence is directly related to the lack of educational opportunities that limit a person's ability to perform at higher levels. Others also argue that gene therapy might cause and not correct diseases, resulting in additional negative implications for society. An additional concern is, "Who will pay for these enhancements?' Scientists argue that gene therapy is beneficial because a child with a growth hormone deficiency could be safely treated by gene therapy, and what sound reason does society have to reject such a treatment?

The Hastings Center report believes the public accepts somatic gene therapy. The opposition believes that scientists will not stop at somatic therapy, and germline will become prevalent. An issue that arises with germline therapy is designer babies. People who support the concept believe that disease will be prevented early on resulting in a benefit to the future of the child. This may prevent the baby from cancer or even Huntington's disease. However, advocates argue that this too will go beyond the limits. They believe that doctors will be making babies who are really smart, strong and essentially the perfect dream human. Then there is a worry that in the future this technology could fall into the wrong hands.

A South Dakota man recently made history by participating in the first gene therapy experiment for muscular dystrophy. The experiment involved injecting billions of healthy genes into a foot muscle. This is not intended as a cure, but will hopefully demonstrate that gene delivery is safe and the types of reactions the gene will have once inside the muscle cells.

So after researching the topic of gene therapy I ask myself, "What would I do about my baby?" Tough question. I am going to be honest; at this point in time I am riding the fence. I have a leg on each side and would definitely have to discuss the problem with my spouse. I would probably support the concept when the time comes, but as of right now I have some disagreements. I do believe that gene therapy for inherited diseases is a good thing, but worry that it could get out of hand. Who will control it is the question to be answered? A book called the Brave New World that was wrote by Aldous Huxley in 1932 discuses how people will become so divided. Some people will be made to be servants, others leaders, athletes and the list goes on. A concern of mine is that this technology will go to far. People will become robots and the idea of individualism and competition will be lost. Also an even larger separation of wealth will become more distant because only the rich will be able to afford it. I like to compare the basics of gene therapy to the Bible. When the people started building the Tower of Babel, to the heavens, God stepped in. God changed the language of everyone so they could not communicate, which resulted in the tower never being completed. God did this because their technology was advancing too quickly. Who knows, maybe God will step in with gene therapy.

I believe God intended humans to use animals as a key to our survival. So things such as artificial insemination and embryo transfer that are done with livestock is a different situation. However, when the human race starts manipulating human genes and constructing the perfect baby, it becomes a slap in the face to God. In my opinion gene therapy sends a message stating that God screwed up and did a poor job of creating the human race.

I do not want to live forever and do not want to be invincible. Plus the earth will not be able to feed and support a population of higher longevity because we are unable take care of ourselves with the current average lifespan and population. So, I am going to leave you with these few words. Maybe the human race should be thankful for what we currently have and the limited time we have left on earth. To me a basketball game with no final whistle would have no meaning. So would immortality.

References

Rehmann-Sutter, Christoph "The Ethics of Human Gene Therapy." The Hastings Center Report, May 1999, v.29, 3, 43
Begley, Sharon. "Designer Babies. (altering unborn babies through gene therapy)" Newsweek, 9 November 1998: 61 (1)
Friend, Tim. "Patient gets first MD gene therapy." USA Today 3 September 1999: A1
10/15/1999:http://www.boil.tsukuba.acjp/~macer/Papers/GTN95A.html
10/15/1999:http://piebald.princeton.edu/mb427/1997/students/therapy/main.html
10/15/1999:http://www.med.upenn.edu/ihgt/info/whatisgt.html
10/15/1999:http://www.med.upenn.edu/ihgt/info/topic1.html

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