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SCIENCE FILE / Q & A

Gene decoder sets his sights on cancer

December 15, 2007|Karen Kaplan | Times Staff Writer

Dr. Francis Collins is a gene hunter. Early in his career, he found the genes responsible for cystic fibrosis and Huntington's disease, among others. Then he took over the Human Genome Project, which, in 2000, presented the first draft of the roughly 22,000 genes contained in human DNA. More recently, he published "The Language of God," a book that reconciles scientific conviction with religious faith. Collins, now director of the National Human Genome Research Institute in Bethesda, Md., was recently in Los Angeles to receive the Will Rogers Institute's inaugural annual prize for lung research.

After decoding the human genome, what do you do for an encore?

The Human Genome Project birthed a long list of other projects, one of which is the Cancer Genome Atlas. It's an effort to try to find all of the culprits in particular types of cancer. Cancer is a disease of the genome -- you get it because of mistakes in your DNA, some of them inherited, most of them acquired during life. The way we classify cancer right now is based upon two questions: What part of your body did it arise in? And what did it look like when you peered through a microscope? It is so last century. We'd like to look at perhaps the 50 most common cancers.

Where do you start?

We're starting with glioblastoma multiforme, which is the most malignant, most awful brain tumor there is. Survival is generally a year or less. That makes it a very high priority to try to learn something about it as fast as we can.

How do you pick which diseases to study?

It's a combination of factors. Sometimes you develop a passion for something because of some personal experience. I took care of young adults with cystic fibrosis when I was in my residency training and found this to be a disease that was desperately in need of some explanation. So it made for a very appealing place to go when I was setting up my first research lab.

Do you ever find genetic links to diseases that surprise you?

A good example of that is macular degeneration, which is the most common cause of blindness. It doesn't hit you until you're 80 or 90 years old. It doesn't sound like a genetic condition. Well, guess what? There's two genes, and if you combine them with smoking they account for about 80% of the risk. The genes are in the pathway that we would call inflammation, so that suggests possible preventions. We have lots of drugs that block inflammation, we just never tried them on this disease. And now we have a pretty good idea they might work.

Do genes often help you find therapies?

Another disease my lab works on is a very rare and dramatic form of premature aging called progeria. These kids age at about seven times the normal rate and die usually by the age of 12 or 13 of heart attacks and strokes. It's a very, very tragic situation.

We found the genetic glitch in that condition in 2003 and figured out what the gene's normal function is. Then we realized there was a drug in Phase III trials for cancer that actually had exactly the right properties. We showed that the drug would cure the disease in a mouse model, and now there is a clinical trial underway. We've got our fingers crossed.

It seems like every week, they're finding a gene for another disease.

These discoveries now have happened for diabetes, for breast cancer, for prostate cancer, for asthma, for heart disease, for multiple sclerosis, for gallstones, for Crohn's disease -- I've sort of lost track. Most of them have a modest effect -- maybe your likelihood of getting the disease goes up by 20% or 30%. That has not stopped the marketplace from getting very interested in this new opportunity. You've probably seen the launch of 23andMe [a company that will analyze hundreds of thousands of common genetic variants for $999]. Navigenics will launch early next year. Decode has their own personalized genetic analysis available, and a company called Knome will look at the whole genome as long as you're willing to pay $350,000. I suspect they will all get curious customers.

Will people know how to use this information?

I predict it's going to be a tumultuous year. People will get confused. They're going to get a printout that says, "Your risk of diabetes is 30% higher than somebody else's," and they'll take it to their physician and say, "What should I do?" Most medical professionals aren't ready for this. It's not yes-no stuff. It's statistical risk.

You used to be an atheist. What made you a believer?

I was raised to be nothing. My parents were wonderfully creative people who were very much into music and theater and the arts, but faith just wasn't important. Then I decided to go to medical school. I arrived there as an atheist and I left as a believer. That happened to me because of being put face-to-face with suffering and death. Challenged by one of my patients, who asked me one afternoon what I believed, I realized I didn't have a good answer.

Did faith change your views about science?

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