What is gene therapy?
Gene therapy is a new approach to treat, cure, and ultimately prevent disease by changing the expression of a person's genes. Gene therapy is in its infancy, and primarily experimental, with most human clinical trials only in the research stages. It is being studied for many different types of cancer and some other diseases.
What are the objectives of gene therapy?
One of the goals of gene therapy is to produce cells with healthy copies of missing or altered genes. Instead of giving a patient a drug, doctors attempting to correct the problem by altering the genetic makeup of some of the patient's cells. Examples of diseases that could be treated in this way include cystic fibrosis and haemophilia.
Gene therapy is also being studied as a way to change how a cell functions; for example, by stimulating immune system cells to attack cancer cells or by introducing resistance to human immunodeficiency virus (HIV), the virus that causes AIDS.
How are genes transferred into cells so that gene therapy can take place?
In general, a gene cannot be directly inserted into a person's cell. It must be delivered to the cell using a carrier known as a "vector”. The most common types of vectors used in gene therapy are viruses. Scientists use viruses because they have a unique ability to enter a cell's DNA. Viruses used as vectors in gene therapy are genetically disabled; they are unable to reproduce themselves.
What are the basic steps involved in gene therapy?
In most gene therapy clinical trials, cells from the patient's blood or bone marrow are removed and grown in the laboratory. The cells are exposed to the virus that is carrying the desired gene. The virus enters the cells, and the desired gene becomes part of the cells' DNA. The cells grow in the laboratory and are then returned to the patient by injection into a vein. This type of gene therapy is called ex vivo, which means "outside the body”. The gene is transferred into the patient's cells during the time the cells are outside the patient's body.
In other studies, vectors or liposomes (fat particles) are used to deliver the desired gene to cells in the patient's body. This form of gene therapy is called in vivo, because the gene is transferred to cells inside the patient's body.
What risks are associated with gene therapy?
Viruses can usually 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. Another danger is that the new gene might be inserted in the wrong location in the DNA, possibly causing cancer or other damage.
In addition, when DNA is injected directly into a tumour, or when a liposome delivery system is used, there is a slight chance that this DNA could unintentionally be introduced into reproductive cells, producing inheritable changes. Other concerns include the possibility that transferred genes could be "overexpressed," producing so much of the missing protein as to be harmful; that the viral vector could cause inflammation or an immune reaction; and that the virus could be transmitted from the patient to other individuals or into the environment.
However, scientists use animal testing and other precautions to identify and avoid these risks before any clinical trials are conducted in humans.
What major problems must scientists overcome before gene therapy becomes a common technique for treating disease?
Scientists need to identify easier and better ways to deliver genes to the body. To treat cancer, AIDS, and other diseases effectively with gene therapy, researchers must develop vectors that can be injected directly into the patient. These vectors must then focus on appropriate target cells (such as cancer cells) throughout the body and successfully integrate the desired gene into the DNA of these cells.
Other advances that are needed include the ability to deliver genes consistently to a precise location in the patient's DNA (thus diminishing the risk of causing cancer), and ensure that transplanted genes are precisely controlled by the body's normal physiologic signals.
What are some of the social and ethical issues surrounding human gene therapy?
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 in the future, when the techniques of gene therapy have become simpler and more accessible, society will need to deal with more complex ethical questions.
One such question is related to the possibility of genetically altering human eggs or sperm, the reproductive cells that pass genes on to future generations. Since reproductive cells are also called germ cells, this type of gene therapy is referred to as germ-line therapy. Another question is related to the potential for enhancing human capabilities—for example, improving memory and intelligence—by genetic intervention. Although both germ-line gene therapy and genetic enhancement have the potential to produce benefits, possible problems with these procedures worry many scientists.
Germ-line gene therapy would forever change the genetic make-up of an individual's descendants. 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, of merely average intelligence. And, justly or not, some people associate all genetic manipulation with past abuses of the concept of "eugenics," or the study of methods of improving genetic qualities through selective breeding.
What is being done to address these social and ethical issues?
Scientists working on the Human Genome Project, which is mapping and sequencing all of the human DNA, have recognized that the information gained from this work will have profound implications for individuals, families, and society. The Ethical, Legal, and Social Implications (ELSI) Programe was established in 1990 to address these issues. The ELSI Programme is designed to identify, analyze, and address the ethical, legal, and social implications of human genetics research at the same time that the basic scientific issues are being studied. In this way, problem areas can be identified and solutions developed before the scientific information becomes part of standard health care practice.