Gene Therapy - An Overview

Altered Genes

In the U.S. and Europe, there are exciting new programs to 'map' the entire human genome - all of our genes. This work will enable scientists and doctors to understand the genes that control all diseases to which the human race is prone, and hopefully develop new therapies to treat and predict diseases.

Diseases of Genetic Origin

On the other hand, if the gene is dominant, it alone can produce the disease, even if its counterpart is normal. Clearly only the children of a parent with the disease can be affected, and then on average only half the children will be affected. Huntington's chorea, a severe disease of the nervous system, which becomes apparent only in adulthood, is an example of a dominant genetic disease.

Finally, there are the X chromosome-linked genetic diseases. As males have only one copy of the genes from this chromosome, there are no others available to fulfill the defective gene's function. Examples of such diseases are Duchenne muscular dystrophy and, perhaps most well known of all, hemophilia.

Queen Victoria was a carrier of the defective gene responsible for hemophilia, and through her it was transmitted to the royal families of Russia, Spain, and Prussia. Minor cuts and bruises, which would do little harm to most people, can prove fatal to hemophiliacs, who lack the proteins (Factors VIII and IX) involved in the clotting of blood, which are coded for by the defective genes. Sadly, before these proteins were made available through genetic engineering, hemophiliacs were treated with proteins isolated from human blood. Some of this blood was contaminated with the AIDS virus, and has resulted in tragic consequences for many hemophiliacs. Use of genetically engineered proteins in therapeutic applications, rather than blood products, will avoid these problems in the future.

Not all defective genes necessarily produce detrimental effects, since the environment in which the gene operates is also of importance. A classic example of a genetic disease having a beneficial effect on survival is illustrated by the relationship between sickle-cell anemia and malaria. Only individuals having two copies of the sickle-cell gene, which produces a defective blood protein, suffer from the disease. Those with one sickle-cell gene and one normal gene are unaffected and, more importantly, are able to resist infection by malarial parasites. The clear advantage, in this case, of having one defective gene explains why this gene is common in populations in those areas of the world where malaria is endemic.

Gene Therapy

The most likely candidates for future gene therapy trials will be rare diseases such as Lesch-Nyhan syndrome, a distressing disease in which the patients are unable to manufacture a particular enzyme. This leads to a bizarre impulse for self-mutilation, including very severe biting of the lips and fingers. The normal version of the defective gene in this disease has now been cloned.

If gene therapy does become practicable, the biggest impact would be on the treatment of diseases where the normal gene needs to be introduced into only one organ. One such disease is phenylketonuria (PKU). PKU affects about one in 12,000 white children, and if not treated early can result in severe mental retardation. The disease is caused by a defect in a gene producing a liver enzyme. If detected early enough, the child can be placed on a special diet for their first few years, but this is very unpleasant and can lead to many problems within the family.

The types of gene therapy described thus far all have one factor in common: that is, that the tissues being treated are somatic (somatic cells include all the cells of the body, excluding sperm cells and egg cells). In contrast to this is the replacement of defective genes in the germline cells (which contribute to the genetic heritage of the offspring). Gene therapy in germline cells has the potential to affect not only the individual being treated, but also his or her children as well. Germline therapy would change the genetic pool of the entire human species, and future generations would have to live with that change. In addition to these ethical problems, a number of technical difficulties would make it unlikely that germline therapy would be tried on humans in the near future.

Before treatment for a genetic disease can begin, an accurate diagnosis of the genetic defect needs to be made. It is here that biotechnology is also likely to have a great impact in the near future. Genetic engineering research has produced a powerful tool for pinpointing specific diseases rapidly and accurately. Short pieces of DNA called DNA probes can be designed to stick very specifically to certain other pieces of DNA. The technique relies upon the fact that complementary pieces of DNA stick together. DNA probes are more specific and have the potential to be more sensitive than conventional diagnostic methods, and it should be possible in the near future to distinguish between defective genes and their normal counterparts, an important development.

The Human Genome Program in the U.S. will provide about $200 million each year to scientists in multidisciplinary research centers who are attempting to determine the makeup of all human genes. Together with similar programs in Europe, it is hoped that in 15 years time we shall be able to identify and treat all diseases to which humans are susceptible. This will revolutionize modern medicine, and hopefully improve the quality of life of all men, women, and children. Already, the genes for Duchenne muscular dystrophy, cystic fibrosis, and retinoblastoma have been identified, and more such information is emerging all the time.

Go to next story: Inheritance of an Illness

Go to Graphics Gallery: Recessive Inheritance - Dominant Inheritance, X-Linked Inheritance - Inheritance of Hemophilia

An update from Oak Ridge National Labs: Gene Therapy