Science in the Triangle

To treat each patient according to his or her genetic disease triggers is an idea researchers have pursued for nearly two decades. Tests and a few medicines have resulted from the pursuit, mostly to target some cancers and to prevent side effects from genetic drug sensitivities. But putting personalized medicine into practice has proven to be a lot more complicated than originally thought.

Patients, doctors and researchers have been particularly frustrated by how difficult it is to figure out the genetic nature of complex diseases such as diabetes, heart disease and Alzheimer’s, diseases that are costly because they are chronic and affect an increasing number of people.

A Personal Genomics Symposium that Duke University’s Institute for Genome Sciences and Policy held Wednesday took stock of how far science has yet to go seven years after researchers completed mapping of the human genome and how bumpy the road can be.

Dietrich Stephan

Dietrich Stephan, one of four presenters at the symposium, said the goal is to pinpoint hard-wired susceptibilities to diseases early on by sequencing the genome of each newborn. Once the risks are known for each person, medicine can intervene to keep people healthy longer by preventing or delaying disease. Stephan, a personalized medicine pioneer and chief executive of the Ignite Institute in Herndon, Va., called that approach “managing people from birth to death individually.”

It’s an approach, Stephan suggested, that is necessary to get a handle on run-away health care costs.

The U.S. spent 17.3 percent of its gross domestic product on health care last year, according to a recent report from the Centers for Medicare and Medicaid Services. The CMS estimated that by 2019 U.S. health care costs could nearly double.

The potential benefits are alluring, but personalized medicine also raises questions that go beyond how long it will take researchers to pin down genetic disease triggers.

How much control do patients have over the massive amounts of sensitive, individual data that would be collected? Should the search for gene-based tests and treatments be driven by patients, by institutions, by industry or by the government? Does the entity that pays for the research own parts of the human genome? How much of the data should be made public?

Misha Angrist

Already, patients are bringing results of gene-based tests to doctor visits, said Misha Angrist, an assistant professor at Duke’s Institute for Genome Sciences and Policy who’s interested in ethical and social issues that personalized medicine raises. But “the infrastructure for this stuff isn’t there yet,” Angrist said.

Three years ago, Angrist became the fourth person whose entire genome was sequenced, linked to disease risks and made public as part of the Personal Genome Project.

While the ethical and social implications of personalized medicine remain open questions, researchers are discovering genetic links to one disease after another.

Variations in one specific gene may be common to as many as half of those with age-related macular degeneration, a leading cause of vision loss in older Americans. One version of the apolipoprotein E gene increases the risk of late-onset Alzheimer’s disease. Up to 10 percent of thyroid cancer patients carry a mutation they inherited from a parent. Genetic variations increase the risk for urinary bladder cancer and skin cancer. A group of researchers has even discovered genetic variants that are associated with an increased risk of heart attack.

To pinpoint genetic traits that can be matched to diseases is like finding needles in a haystack. One company, deCODE Genetics, is collecting genetic information in Iceland, a country where residents can trace their lineage particularly well.

Dr. Kari Stefansson

At the Duke symposium, Dr. Kari Stefansson, co-founder and CEO of deCODE, spoke about the population-based approached his company has taken. Using the Icelandic database, DeCODE researchers have found genetic links to schizophrenia, diabetes and prostate cancer, Stefansson said.

DeCODE researchers also discovered that African-Americans who carry a particular gene are 3.5 times more likely to suffer a heart attack than people of European descent who carry the same gene.

David Goldstein

David Goldstein, director of Duke University’s Center for Human Genome Variation, used a similar approach to discover two genetic variants that explain why patients of European descent are more than twice as likely to be cured from chronic hepatits C than patients of African descent.

The two variants protect from anemia, a side effect from the standard treatment for chronic hepatitis C infections that can be severe.

“You can personalize the treatment of patients with hepatitis C,” Goldstein said.

But to find genetic triggers for most common diseases, Goldstein favors another approach. He has argued that only a few rare diseases can be linked to changes that affect one common gene, or two, or three. Goldstein suggests that complex diseases are caused by a combination of many rare genetic variants - missing genes as he calls them, because they are so difficult to find.

He’s using the approach to look into epilepsy, schizophrenia that runs in families and resistance to HIV/AIDS.