DeCode Genetics, an Icelandic biotech and genomics company, is best known for its unique approach to gene discovery. Scientists use the extensive genealogical records of the Icelandic community to hunt down genetic variations that boost risk for common diseases, such as heart disease, asthma, and diabetes.
In its 10-year history, deCode has developed research programs for 50 diseases and isolated 15 genes linked to common diseases. The company is now translating its genomics success into drug development. Currently, it is testing in clinical trials compounds to treat heart attacks, asthma, and peripheral arterial disease.
Kari Stefansson, deCode’s chief executive officer, tells Technology Review why gene hunting is so well-suited to drug discovery and describes why he thinks big pharma will soon jump on the bandwagon.
Technology Review: DeCode has now isolated many gene variants that have an impact on risk for common diseases. Do they have anything in common?
Kari Stefansson: These gene variants almost always influence where you fall on the disease spectrum – whether you are at risk for a disease or whether you are protected. For example, we found one variant that increases risk for stroke and another that confers protection against stroke. So these two variants influence gene expression in the opposite direction.
This discovery has some interesting implications. You can develop an inhibitor of the enzyme [coded by the gene] – but do you take it to the norm of the general population or to the norm that confers protection? We must be cognizant of the fact that this likely will confer risk of some other problem. Evolution has left that variation for a reason.
TR: So how does that affect the way you study disease genes?
KS: The key to the understanding of common diseases is to study them in the context of evolution and population history. Gene variants involved in common diseases are almost always under selection. That’s important because there is a difference in the variants between, say, Iceland and Africa.
[In a study published last year,] we found a gene variant that boosts risk for heart attacks in African Americans by 250 percent, but increases risk in Caucasians by only 16 percent. This variant is not found in Africa, so it must have [evolved in people after the migration out of Africa.]
[The gene is involved in the leukotriene pathway, which is part of the body’s immune response.] My hypothesis is that when people left Africa 60,000 years ago, they were exposed to different bacteria. So evolution increased the leukotriene pathway, which also increased risk of heart attack. At that time, though, the risk didn’t matter because life expectancy was so low.
But as life expectancy began to increase, Caucasians had many generations to evolve other gene mutations to compensate for the negative effect of the variant. But African Americans, who acquired the gene variant more recently through admixture, have not had the same amount of time to develop compensatory variants.