Resource: How to Conquer a Genetic Disease

The map of the human genome has provided far more than a simple list of the three billion letters that make up our genetic code. Scientists are now beginning to understand what certain groups of these letters -- our genes -- actually do. They estimate that about thirty thousand genes in all carry the code for every structure and function in the human body.

An important corollary to understanding proper gene function is that by doing so we gain a better understanding of gene dysfunction. Indeed, scientists have identified the genes responsible for more than two dozen diseases. So far, however, finding the genetic cause of disease has provided little more than the promise of a cure. Fixing broken genes is altogether more difficult.

A decade ago some scientists promised that "gene therapy" would cure a myriad of genetic diseases. Doctors would simply insert normally coded genes in place of malfunctioning ones. The normal genes would override the abnormal genes, produce whichever vital proteins were missing, and the problem would be solved. But several hurdles have stood in the way of what once appeared to be an elegant solution.

Many genetic diseases are caused by more than one gene, or are strongly influenced by environmental factors. These diseases are probably too complex to be cured through gene therapy. In an effort to cure diseases that are caused by the dysfunction of a single gene, however, many scientists are continuing to try to perfect the technique.

For gene therapy to have any long-term effect, replacement genes must be incorporated into the DNA of a huge number of a patient's cells. If this is accomplished the genes will be replicated and passed on when cells divide. None of this can happen, though, unless the genes actually find their way into the cells' nuclei. Herein lies the problem. DNA injected into a patient's bloodstream has little or no chance of ending up inside the nucleus of any cell. So how do doctors get genes inside where they can be of some use? The most promising technique uses viruses as DNA delivery vehicles.

In the late 1980s, geneticists discovered that certain types of viruses, called retroviruses, could be modified to carry replacement genes into the nuclei of cells. These viruses attach whatever genetic material they carry, including the replacement genes, directly to the host's DNA. Because viruses are human pathogens and carry inherent risks, however, progress with gene therapy has been slow.

More often than not, doctors have erred on the side of caution, stripping the viruses of their toxins and their ability to replicate, and injecting only a few thousand into the patient at a time. The effect of such cautious therapy, however, has been marginal because the number of cells receiving replacement DNA in cases like these is quite low. Leaving too much of the virus's own DNA intact or introducing too many viruses into the patient's system, on the other hand, can have deadly consequences.

What are the three phases of conquering a genetic disease?

What are disease "markers" and how do scientists find them for each new disease?

How do scientists decode a defective gene to find out what protein it produces?

Why are both genes and proteins important in developing treatments for genetic diseases?