Knowing the sequence of the human genome is the first step toward the development of drugs that can act on specific proteins that cause cancer and other diseases. But much work remains to be done in understanding not just the approximately 30,000 human genes, but also the estimated one million proteins manufactured by those genes.

"The vision is that by knowing the activity, or lack of activity, in cancer cells as opposed to normal cells, we might be able to find specific targets and specific inhibitors," says Dawn Willis, PhD, MPH, scientific program director for the American Cancer Society (ACS).

Drugs could target only the cancer-causing proteins and not healthy cells. One new drug with promising results in clinical trials, Glivec (STI-571), targets an abnormal protein in chronic myelogenous leukemia cells, Willis says. But in that disease, the protein involved is already known. Developing such drugs for other cancers may be far more complex, she says.

The sequence of the genes is now on the record. But the next step is to move from gene sequence to gene function, says Francis S. Collins, MD, PhD, director of the National Human Genome Research Institute. The institute, funded by federal government dollars, published its findings on the genome sequence in a series of articles in the Feb. 15 issue of the journal Nature. The simultaneous and complementary work done by Celera Genomics, a private firm also mapping the human genome, was published in the Feb. 12 issue of the journal Science.

Nobel Laureate James Watson, PhD, referred to DNA as the "play of life," at a press briefing this week on an educational kit to help students and the public understand the Human Genome Project.

Before now, he said, "We didn't have the script or the actors."

The Genome Project scientists divided the work and, from their labs around the world, mapped the sequence of the approximately 30,000 genes -- the "actors" Watson refers to. "But those 30,000 actors can appear in 10 sets of costumes," Watson said. "Then, they can comb their hair or not comb their hair," referring to the many variations possible in proteins encoded by each gene.

It was nearly a half century ago, in 1953, that Watson -- then in his 20s -- and Francis Crick discovered the structure of DNA. While other researchers were looking for much more complicated structures, Watson and Crick discovered the elegant double helix of two strands winding around each other to form DNA. Watson is still active in the National Human Genome Research Institute and served as its first director.

During press briefings this week, Watson suggested it would take another five to seven decades to fully understand the genome that has been mapped.

With the sequencing complete, new scientific disciplines are emerging, such as proteomics -- the study of proteins. And the enormous amount of data will require a whole new field of science in which the researchers are as innovative in technology as they are in biology, according to the ACS's Willis.

The 30,000 genes on the human genome turned out to be significantly fewer than an earlier estimate of 100,000. But that won't make the work any easier, Willis says. Just because there are fewer genes doesn't mean there are fewer proteins, and that?s where scientists believe the action is.

The earliest impact of the genome project may be in prevention and early detection, according to Willis. Cancer is an interaction between genetic and environmental factors, and the goal of genetic researchers is to be able to analyze an individual''s DNA to see whether they have the genetic predisposition to cancer, she says. For those willing to learn that about themselves, it could have a tremendous impact in genetic counseling. As we learn about more genes related to cancer predisposition and how these genes work, we will become better at identifying people at high risk who might benefit from screening exams. And we may be able to predict which lifestyle-related and environmental risks have the greatest impact on each individual.

"For example, roughly 20% of the people who smoke get lung cancer, and we still don't understand what protects those who do not," Willis says. " We suspect a combination of genetics, diet, and random chance, but expect some answers to this question to come from analysis of gene sequences. Of course, this doesn't mean that smoking is safe for anyone, since another 30% of smokers die of heart disease, stroke, chronic lung disease and other diseases caused by smoking."

The potential for gene therapy to cure cancer after it starts is a longer way off, Willis says. Researchers have already discovered and sequenced many cancer-related genes during the past two decades. But, scientists still don't know how to deliver the corrected DNA to every single cancerous cell. Although we expect human genome sequence results to point out additional cancer genes, Willis says, gene therapy will not have a major role in clinical oncology until we develop practical gene delivery techniques. Viruses may play a role, because they're already designed to invade a cell, she says.