Young researchers, mostly graduate students who trained in Dr. Vogelstein?s lab, are using the detection methods pioneered by Drs. Vogelstein and Kinzler in colon cancer research to study other types of cancer. These young researchers are the troops in any laboratory, and Drs. Vogelstein and Kinzler are quick to note they perform the bulk of experimental work. "In most labs they are responsible for making the discoveries," Dr. Vogelstein said.

Indeed, it is the trainees who decide which chromosome regions to research and which experimental paths to follow. Sometimes their gut feelings and hunches conflict with those of Drs. Vogelstein and Kinzler, sparking long and loud arguments. In the end, though, it is the students who make the call, said Dr. Vogelstein.

 "When push comes to shove, they are encouraged to follow their own gut feelings. We don?t encourage them to follow our hunches, we try to persuade them that our hunches are right. But we prefer they follow their hearts. They work harder," he observed.

Time and resources are always limited. One of the prominent features of  Dr. Vogelstein?s Baltimore lab ? housed in a converted supermarket - is a large sign that reads,  "Focus."

 "It?s not always what you do, it?s what you don?t do," said Dr. Kinzler, who has worked with Dr. Vogelstein for 14 years, an eternity in the scientific world. "What we try to emphasize is when you choose to do something, it prevents you from doing something else. We often choose not to do what other groups do, so we can go on to something that may be harder but more interesting."

And a cancer detective can?t always go by the book. Sometimes they must listen to their instincts.

"My math professor in college told me he had switched from physics to math because his gut feelings about math were better. At the time I didn?t know what he meant, but I do now," said Dr. Vogelstein, who was a math major in college himself.

"You are often faced with a whole variety of paths you could take and no really objective criteria to tell you which path is most likely to be fruitful. Everybody who has achieved some success in science has to have good hunches. And if you have good hunches and you are lucky, you occasionally catch the suspect."

Dr. Vogelstein is tireless when he thinks a gene is in reach, particularly if he believes other researchers are on the same track.

As the work continues in his lab, gene research has made progress on other fronts. It been the beneficiary of new and rapidly evolving technology. State-of-the-art DNA sequencing methods are speeding up the gene mapping process. The biggest roadblock remains the vast uncharted areas of the human genome.

Scientists everywhere are awaiting the results of the Human Genome Project, an ambitious, multi-billion dollar, government-sponsored program begun in 1990 with the objective of mapping the location of every gene. The 15-year project is being run by Francis Collins, MD, PhD, a former cancer detective himself who co-discovered the first gene linked to breast cancer. Once a full map is available, it will speed up the job of linking specific genes to specific diseases.

"It will be much easier to find suspects because there will be a book of them, with history and fingerprints," Dr. Vogelstein added.

But while linking specific genes to specific types of cancer is important, the cancer detectives acknowledge it is only the first step. The next question is what to do with this basic knowledge. How can it be used to benefit the people with cancer?

Part V: Genetic Research Looks Promising ? But Much Work Still Lies Ahead