Human Gene Therapy

Zhou, Jing Kai

Copyright 1997


Each of us carry about half a dozen defective genes. Most of us do not suffer any harmful effects from our defective genes because we carry two copies of nearly all genes, one derived from our mother and the other from our father. Because in the majority of cases, the potentially harmful gene is recessive, its normal counterpart will carry out all the tasks assigned to both. Only if we inherit from our parents two copies of the same recessive gene will a disease develop.

Every year a considerable number of children are born with a genetic disease, a disease that occurs because each of their parents carries a defect in the same gene (Rigby 1995). The most common disease of this sort, with about couple thousand affected children born each year, is cystic fibrosis, which leads to a clogging of the lungs, and to problems with digestion and other functions. Although improvements in care and treatment mean that people with cystic fibrosis can now live for up to twenty-five years, there is no cure. A much rarer but nevertheless well known disease, is severe combined immunodeficiency (SCID). SCID children with this condition have a defect in both copies of a gene which is required for the proper functioning of the immune system. The children can be kept alive but they have to live in sterile plastic bubbles to isolate them from bacteria and viruses. These children would die of infections which would only keep the rest of us in bed for a couple of days. Again, while there are treatments, there is no cure.

However, in simple terms the cure is obvious. If the children are ill because they have two bad copies of a gene, it follows that if we could give them a good copy of the gene they would then be like their parents and be healthy. This very obvious idea is called gene therapy.

Concept of Gene Therapy

Gene therapy is the insertion of a functioning gene into the cells of a patient to correct an inborn error of metabolism or to provide a new function in a cell. This is a very broad definition that includes the potential treatment of essentially all types of human disease through the genetic modification of cells of the human body to prevent or eliminate disease. There are two main types of gene therapy, germinal cell and somatic cell gene therapy (Culver 1996).

Germinal cell gene therapy, which has been performed successfully in several animal studies, involves the insertion of a healthy gene into the fertilized egg of an animal that has a specific genetic defect. At this time, human germinal cell gene therapy, in which the changes would be passed on the successive generations, is neither technically nor ethically resolved.

Somatic cell gene therapy is the technique now considered possible for use in human beings. The insertion of a single gene into the somatic cells of an individual with a life-threatening genetic disease is intended solely to eliminate the clinical consequences of the disease; the inserted gene is not passed on to future generations. This kind of therapy is much different from the germinal cell gene therapy, which pose different technical problems as well as major ethical concerns about experimentation with human embryos and the long-term effects of changing the gene pool of the species..

Technical Aspects of Gene Therapy

Although the highly technical aspects of human gene therapy are somewhat complex, the basic concept is very straight forward. To find the gene that is not functioning right and to insert a portion into the gene. A number of methods have been developed for introducing genes into living cells. Each technique has its own advantages and disadvantages. These include both viral and nonviral methods.

If we wished to use gene therapy to treat someone with an inherited genetic disease, we need firstly a fairly detailed understanding of the disease; why it is that the lack of a particular gene product causes the symptoms. We also need to know in which cells of the body the gene is required. The immunodeficiency disease is an example. Although the gene is active in all the cells of the body, the children only have problems with their immune systems. Either the gene is not needed in other cells or another one can substitute for it. So we only have to get an undamaged copy of the gene into the cell of the immune system, which are in our blood, that make antibodies and kill virus-infected cells. That make things easier because it is very simple to inject thing into blood, or to take blood cells out of a patient, do something to them, and put them back, as is done in blood transfusion centers every day. But we can not simply inject the gene into the bloodstream. Genes are made of DNA, which is quite a fragile chemical, and if one simply injected it into blood it would be destroyed. So we have to construct some kind of carrier, called a vector, that we can use to transfer the good gene into the patient's cells. Fortunately nature has provided us with highly efficient vectors in the form of viruses. Viruses are parasites which can multiply only inside the cells of living organisms and they have therefore evolved extremely efficient ways of inserting their own genes into the cells of the host that they infect. Much of gene therapy research thus far has involved modifying viruses so that instead of introducing their own genes they introduce a therapeutic gene which will cure the patient's disease.

The viruses that have been most commonly used are called retroviruses which, unlike most viruses, do not kill the cells that they infect (Rigby 1995). Gene therapy vectors are made from viruses that normally infect mice. They are turned into vectors by first removing the genes that the virus needs to carry with it to enable it to replicate inside the cells it infects. The genes removed are then replaced in the virus by a perfect copy of the gene which is missing or damaged in the patient. The genes required for virus replication have been removed means that the genetically modified virus can only deliver the therapeutic gene to the first cell that it enters. It can not start an infection and this removes any risk of unwanted side effects.

The vector can now be used to transfer the gene into a patient. This can be done in one of two ways. In most gene therapy treatments that have been done so far, cells are taken out of the patient and then, in the laboratory, are infected with the virus. Once the researchers know that the infection has been successful, the cells can be infused back into the patient where, all being well, the therapeutic gene will be active and the genetic defect will be overcome. In the other type of gene therapy the vector is put directly into the patient. This is much more difficult because the patient's body senses the incoming vector as foreign and thus likely to be dangerous. The immune system will therefore try to destroy it and the immunological responses mounted by the body can be just as bad for the patient as a severe viral infection. Moreover, if we inject the vector into the bloodstream we can not control where it goes and so it is possible that the therapeutic gene will end up in the wrong cells. There have been a number of trials of the first type of gene therapy for SCID and we can say that the treatment does not do the patients any harm; if all of the checks and tests are done properly, it is safe. It also seems that, in some cases at least, the patients improve, but a great deal of work still has to be done before we can be sure of that.

Much of the research in genetic therapy today is concerned with the treatment of cancer. It has long been thought that when a cell in the body becomes cancerous it activates genes that it ought not to and should be recognized by the body's immune system as if it were foreign. If that were so, and the immune system worked properly, then none of us would get cancer, so things clearly do not work quite like that. A very popular idea at present is that the cells of our immune system can recognize the cancerous cell as foreign but that for some reason they do not do what they are supposed to do and the cancerous cell is not killed. In most cases gene therapy for cancer involves transferring genes which are thought likely to improve the immunological response to the cancer into either the cancerous cells themselves or the cells of the patient's immune system. In experiments with laboratory animals that have tumors these approaches are spectacularly successful, and the tumors are completely cured. There are now a number of clinical trials which researchers around the world are trying to find out if the same things happen in humans who have incurable cancers.

Argument of Human Gene Therapy

Gene therapy technologies are now making it possible to provide treatments that 20 years ago were hardly dreamed possible. These new technologies will bring about a whole new era in medicine. The answers to many medical problems people thought were incurable are new becoming possible. Like other new forms of therapy, gene therapy raises ethical and social issues.

Most people feel that it is fine to use gene therapy to treat human genetic disease. Even the Catholic Church has taken a stand for the use of gene therapy (Murray 1990). Others worry that one step into the arena of gene therapy will lead inexorably to practices that reduce the human species to a technologically designed product. They argue, if we can change somebody's gene in order to cure threaten disease then, we could change their genes to make them taller, or cleaver, or to give them blue eyes.

Four issues have been paramount in the ethical debate about human gene therapy: (1) the ethics of human experimentation as applied to somatic cell and germinal cell gene therapy, (2) whether there is an ethical obligation to future generations to prevent transmission of genetic diseases, (3) whether reasonable moral lines can be drawn now and in the future between the use of genetic knowledge to treat of prevent genetic diseases and uses for enhancement genetic engineering, and (4) whether modern societies have the capacity to direct the uses of human genetic knowledge to ethically acceptable ends and still maintain scientific and academic freedom (Fletcher 1990).

Today, in many countries governments set up committees which included not only scientists and doctors but also religious leaders, lawyers and ethicist, to consider the matter (Nichols 1988). A distinction should be drawn between making genetic changes in somatic cells and in germinal cells. The purpose of somatic gene therapy is to treat an individual patient, e.g., by inserting a properly functioning gene into a patient's bone marrow cells in vitro and then reintroducing the cells into the patient's body. They differ, however, in that gene therapy involves an inherent and probably permanent change in the body rather than requiring repeated applications of an outside force or substance. An analogy is organ transplantation, which also involves the incorporation into an individual of cells containing DNA of foreign origin. Germinal gene therapy, in which the changes would be made in germ cells and so would be passed on to the offspring, is not allowed.

My personal opinion is that the gene therapy is both beneficial and potentially harmful, depending on how it is applied. Somatic cell gene therapy will have great benefits for some of the disease that human beings suffer. Even germinal cell gene therapy should be used, if it can be guaranteed to use at eliminate life-threatening and incurable human diseases, such as cancers and AIDS.

I believe that somatic gene therapy should be utilized to its fullest potential for diseases in humans with the strictest consideration of all guidelines that have been developed. Everyone, regardless of sex, race, wealth and so on should have the same opportunity to have the human gene therapy techniques performed. Children should have the upmost consideration for somatic. In no way should gene therapy be used to improve an already healthy adult or child by increasing intelligence, strength or physical attributes. This can only occur if the scientific community, public groups and government participate in deciding the limitations on gene therapy. The government needs to work closely with the scientists to develop basic laws which prohibit the application of these therapies for use other than those that are deemed medically necessary. They should make sure that these guidelines pertain to large companies as well as the bio-technical science and medical groups.

The advantage of the gene therapy technique, is to give someone that is born with a genetic disease or who develops cancer a chance at a normal life. This technique has the ability to cure many of the diseases that have effected out society for years. I think this is an advantage that far outweighs any of the disadvantages that have been presented against gene therapy. I believe that people opposed to gene therapy do not understand the technique. In the coming future, gene therapy will play an important part in many people's lives. Gene therapy will revolutionize the practice of medicine. The role of doctors and patients will be changing in the coming years, and it will all be due to gene therapy. I believe gene therapy is going to be a great advancement for science.

It is crucial that regulation be a necessary component of gene therapy research and applications. I hope that the government can regulate who can receive this treatment, and restricts it to people that have serious genetic diseases. I also hope all countries of the world cooperate to regulate the gene therapy research and application. I prey this technique will not be abused by people for cosmetic reasons or even the worse for war. Gene therapy will change the field of medicine from what it is today. As scientist discover more genes and their functions, the potential of this treatment is limitless. Government regulators and scientist must take a lead role in adopting a practical approach to address these issues and determining the correct procedures for dealing with them. It must be remembered that a lack of knowledge breeds ignorance and fear.


1. Greenwood, M.R.C. 1994. "Gere Therapy Status, Prospects for the Future, and Government Policy Implications". Obtained from the WWW:

2. Rigby, P. 1995. Gene Therapy: Simple in Theory but Difficult in Practice. Obtained from the WWW:

3. Culver, K.W. 1996. P. xv - xvii in Gene Therapy A Primer for Physicians. Mary Ann Liebert, Inc. Publishers, Larchmont, New York.

4. Fletcher, J.C. 1990. Evolution of Ethical Debate about Human Gene Therapy. Human Gene Therapy 1:55-68.

5. Murray, T.H. 1990. Human Gene Therapy, the Public, and Public Policy. Human Gene Therapy 1:49-54.

6. Nichols, E.K., 1988. P. 162 -173 in Human Gene Therapy, Harvard University Press, Cambridge, Massachusette.

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