The Future of Medicine

Some experts say the world is on the cusp of a “golden age” of genomics By Maggie Fox, Julie Steenhuysen and Ben Hirschler

Francis Collins, who helped map the human genome, did not get around to having his own genes analyzed until last summer. And he was surprised by what he learned.

Collins has a predisposition for type 2 diabetes, something he had never suspected. The lanky, former director of the National Human Genome Research Institute (NHGRI) discovered this through tests offered by Navigenics, 23andMe and DecodeMe • companies that charge customers a few hundred dollars for a peek at their genetic makeup. “I signed up for all three because I wanted to see if they gave the same answer,” he said. “They all agreed my diabetes risk is higher.”

Armed with that information, he eventually lost 25 pounds. But as a rule, he doesn’t consider such tests especially useful • at least not yet. “Admittedly, right now your family history may be your best bet and it doesn’t cost anything,” he said. And so it goes in the fledgling genome field. Some experts say the world is on the cusp of a “golden age” of genomics, when a look at the DNA code will reveal your risk of cancer, diabetes or heart disease, and predict which drugs will work for you. Yet the $3 billion international Human Genome Project, whose first phase was completed a decade ago, has not led to a single blockbuster diagnosis or product.
Still, Collins describes this as low-hanging fruit. He says the hard work is only just beginning. In a sense, the field is a victim of its own success. Companies are beating down the price of genetic sequencing, competing to make the machine that every biotech lab will have as standard equipment to sequence a person’s entire genome on the spot.

But all this genome sequencing is creating what current NHGRI director Dr. Eric Green calls a “tsunami of information” that is overloading the brains of scientists and the capacity of computers. Paradoxically, this reflects the fact that people have relatively few actual genes, the stretches of DNA that instruct a cell to make a protein, or what Green refers to as “bricks and mortar.” Humans have just 20,500 of them, compared with up to 30,000 for mice and 50,000 in rice. That was one of the big surprises from the Human Genome Project.

As a result, much of the most important information lies in what used to be called “junk DNA,” which makes up two-thirds of the human genetic code. “There is this dark matter of the genome that is lurking out there, waiting to be uncovered,” says Collins. GENES AND CANCER For many cancer patients, a major fear is that their surgeon missed something and their cancer will grow back. The only way to tell now is to wait until tumors are big enough to be spotted by imaging machines.

That could soon change. A gene-based test that can search a patient’s blood for tiny bits of DNA shed from tumors may soon give doctors an early warning that they may have missed something. “That’s only become possible through the advent of so-called next-generation sequencing technology,” said Dr. Vogelstein, who is developing the blood test.

The test takes advantage of rapid advances in the technology to sequence whole genomes. The latest machines from companies like Illumina Inc and Life Technologies Corp can map out a patient’s whole DNA code in just a few weeks for as little as $5,000, a far cry from 13 years and $3 billion it took Collins and his international collaborators to get the first human genome.

Vogelstein said the rapidly falling cost of genome sequencing means the blood test could be affordable enough to be on the market within two years. Before long, all cancer patients could have their tumors sequenced routinely to find the genetic defects that cause them to grow. “Cancer is maybe the best disease to cut our teeth on,” said Yale MedicalSchool geneticist Richard Lifton. “The reason for that is we know that cancer is largely a disease in changes of DNA sequence.”

Matthew Meyerson of the Dana-Farber Cancer Institute and the Broad Institute of Harvard and the Massachusetts Institute of Technology said he is impressed by the pace of change. “The first cancer gene sequence was reported in 2008. There were probably 100 done last year. Maybe there will be many hundreds or even 1,000 this year,” he said.

Lifton predicts that within the next two years, scientists will have the genetic sequence of every major human cancer. “Many of these will identify new genes that we had not previously known about with a role in cancer,” he said. “Some of these will turn out to be incredibly important new drug targets.”