Gene Therapy

In the early 1970s, scientists proposed what they called "gene surgery" for treating inherited diseases caused by defective genes. In 1983, a group of scientists from Baylor College of Medicine in Houston, Texas, proposed that gene therapy could one day be a viable approach for treating Lesch-Nyhan disease, a rare neurological disorder. The scientists conducted experiments in which an enzyme-producing gene for correcting the disease was injected into a group of cells. The scientists theorized the cells could then be injected into people with Lesch-Nyhan disease.

As the science of genetics advanced throughout the 1980s, gene therapy gained an established foothold in the minds of medical scientists as a viable approach to treatments for specific diseases. However, its promises were more than what it could deliver. One of the major impetuses in the growth of gene therapy was an increasing ability to identify the genetic abnormalities that cause inherited diseases. Interest grew as further studies showed that specific genetic defects in one or more genes occurred in successive generations of certain family members who suffered from diseases like intestinal cancer, manic-depression, Alzheimer disease, heart disease, diabetes, and many more. Although the genes may not be the sole cause of the disease in all cases, they may make certain individuals more susceptible to developing the disease because of environmental influences, such as smoking, pollution, and stress. In fact, many scientists believe that all diseases have a genetic component.

On September 14, 1990, a four-year old girl suffering from a genetic disorder that prevented her body from producing a crucial enzyme became the first person to undergo gene therapy in the United States. Since her body could not produce adenosine deaminase (ADA), she had a weakened immune system, making her extremely susceptible to severe, life-threatening infections. W. French Anderson and colleagues at the National Institutes of Health's Clinical Center in Bethesda, Maryland, took white blood cells (which are crucial for proper immune system functioning) from the girl, inserted ADA producing genes into them, and then transferred the cells back into the patient. Although the young girl continued to show an increased ability to produce ADA, debate arose as to whether the improvement resulted from the gene therapy or from an additional drug treatment she received.

Nevertheless, a new era of gene therapy began as more and more scientists sought to conduct clinical trials in this area. In that same year, gene therapy was tested on patients suffering from melanoma (skin cancer). The goal was to help them produce antibodies (disease fighting substances in the immune system) to battle the cancer.

These experiments have spawned a growing number of attempts to refine develop new gene therapies. For example, gene therapy for cystic fibrosis, a disease that affects the airways, is being developed. However, due to the complications involved in penetrating the natural barriers that impedes viral entry into the airways, it is unlikely that currently used vectors for cystic fibrosis gene therapy represent a plausible approach. Modifications of these vectors by adding compounds that naturally bind to areas on the outermost membranes of the lung and gain entrance into these tissues are currently being investigated. Another approach was developed for treating brain cancer patients, in which the inserted gene was designed to make the cancer cells more likely to respond to drug treatment. Additionally, gene therapy for patients suffering from artery blockage, which can lead to strokes, that induces the growth of new blood vessels near clogged arteries improving normal blood circulation is also being investigated.

In the United States, both DNA-based (in vivo) treatments and cell-based (ex vivo) treatments are being investigated. DNA-based gene therapy uses vectors (like viruses) to deliver modified genes to target cells. Cell-based gene therapy techniques remove cells from the patient, which are genetically altered and then reintroduce them to the patients body. Presently, gene therapies for the following diseases are being developed: cystic fibrosis (using adenoviral vector), HIV infection (cell-based), malignant melanoma (cell-based), kidney cancer (cellbased), Gaucher's Disease (retroviral vector), breast cancer (retroviral vector), and lung cancer (retroviral vector).

The medical has contributed to transgenic research that is supported by government funding. In 1991, the U.S. government provided $58 million for gene therapy research, with increases of $15-40 million dollars a year over the following four years. With fierce competition over the promise of major medical benefit in addition to huge profits, large pharmaceutical corporations moved to the forefront of transgenic research.