Medicine's Future Could Lie in Each Patient's Genome

Two separate scientific teams announced this week that they had successfully sequenced individual genomes to pinpoint precise genetic causes of illness -- breakthroughs that open the door to a future of individualized, genomics-based medicine.

"This is another milestone in the inevitable march towards personalized genetic health," said Dr. Robert Marion, chief of genetics and development medicine and director of the Center for Congenital Disorders at Children's Hospital at Montefiore Medical Center in New York City. "Medicine is going to change from waiting for symptoms to develop to knowing what this person is at risk for and being able to stop that from happening. Eventually, we're talking about prevention."

One day in the future, Marion predicted, doctors will be able to look at all 20,000 or 25,000 genes in a newborn baby and be able to say whether the child has specific genetic disorders, or a twofold increased risk of developing colon cancer or a higher chance of developing childhood asthma.

And the cost to perform such feats has come way down, with experts at one company predicting that genomes could one day be sequenced for as low as $5,000. Right now, the cost hovers closer to $50,000.

"When it gets to the point where it would cost less to sequence the genome using these techniques than it does to send off a sample to test for a few genes, then you can start moving medicine from just seeing people who are sick to trying to prevent people from getting sick," said Dr. Jeffery Vance, director of the Center for Genomic Medicine at the Hussman Institute for Human Genomics, University of Miami Miller School of Medicine. "You can see where things are going. This is showing that it's practical, it can be done and that medicine will start slowly to move toward using this technique as a diagnostic technique for all these individuals and families who have what looks like an inherited disease but not a big family history."

And, Vance pointed out, genes don't change like cholesterol and blood pressure do. These tests would only have to be performed once.

The predictions are based on breakthroughs reported this week in two journals, the New England Journal of Medicine and Science.

Dr. James Lupski, vice chair of molecular and human genetics at Baylor College of Medicine in Houston, was both the lead author and the subject of the NEJM study. Lupski suffers from a genetic disorder, Charcot-Marie-Tooth syndrome, which affects nerve function.

By sequencing his genome, the NEJM authors were able to trace the disorder to mutations in copies of the SH3TC2 gene he and three siblings inherited from healthy parents.

For Lupski, who already knew he had this disease, the findings probably don't come as much of a shock. But suppose people don't know they have this or another single-gene conditon?

In the old days -- meaning last week -- experts would have had to suspect which disease the patient had, then hone in on the area of the genome thought to be associated with the disorder. Even then, the results could be far from certain.

"The breakthrough is that now we would be able to make this diagnosis without having any preconceived idea that the patient had Charcot-Marie-Tooth disease," Marion said.

The second team of researchers sequenced the genomes of two parents and two children from the same family with single-gene diseases. They reported that only 60 of the three billion base pairs in the human genome mutate randomly each generation. That's about half the rate of mutation that was thought to be passed generation to generation.

How were scientists able to make these leaps?

One big factor has been the advent of new technology with the ability to sequence large amounts of DNA very quickly, explained Marion. Previous technology could only analyze bits of material at a time.

For now, the technology is likely to be helpful only with single-gene disorders which, when it comes to genetics, are relatively easy targets.

"It becomes more difficult with complex disorders because these disorders are not due to one single gene but a combination of genetic factors in multiple genes, as well as environmental factors," said Marion, author of Genetic Rounds: A Doctor's Encounters in the Field that Revolutionized Medicine.

"For single-gene disorders, this technology is a breakthrough," he continued. "But for the more complicated polygenomic or multifactorial conditions, which is every condition that affects humans -- diabetes, blood pressure, coronary artery disease and cancer -- there's a complex interplay between multiple genes and the environment. And sorting that out using the technology we have available now is still not possible."

"Right now, it has its biggest effect where one of the 25,000 or so genes we have by itself doesn't work right," Vance agreed. "It won't have much effect on common diseases like cancer and Alzheimer's."

Another expert agreed that the breakthrough could have its limits.

"This showed that there's tremendous variability between individuals, and if you're a cup-is-half-full kind of guy, this creates wonderful possibilities for the concept of personalized medicine," said Richard H. Finnell, professor of environmental and genetic medicine at Texas A&M Health Science Center Institute of Biosciences and Technology in Houston.

"But if you're a cup-is-half-empty kind of guy, we've been treating a lot of disorders with aspirin for a heck of a long time without differentiating individuals or even necessarily knowing what the mechanism of action of a drug is and [still] gotten some benefit," he noted.

But, for many patients, an accurate diagnosis will at least be a move in the right direction.

"If you were the parent of a child with a disorder and you had taken your child to doctor after doctor after doctor and were given either no diagnosis or a vague diagnosis, to even have a clear-cut diagnosis that doesn't come with an intervention, that's a huge step forward and a great relief," Finnell said.

In the meantime, traditional genome-wide association studies, which compared the genomes of people who had a disease with people who didn't have the disease, are going to be "left in the dust," Marion said.