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TR: How does a phenotype database help you find the genes behind diseases such as asthma, heart disease or diabetes?

STEFANSSON: You may have someone with diabetes in your grandfather’s generation and it skips the parents and then it affects the children, and so on. And to study these disorders, you have to go to a population, because once a disease begins to skip generations, a nuclear family isn’t a useful unit of society to study.

We can design experiments to mine knowledge out of this [population] data by putting together hypotheses, the old intuitive approach. But as beautiful as that approach is, it is not very powerful. The alternative is to use combinatorial analysis, to take every single data point and compare it to every other data point, looking for the best fit, unblinded by a hypothesis. The unaided human mind cannot handle large numbers of data points; you need the modern computer. It’s an extremely powerful approach. And I’m absolutely convinced that we will revolutionize the ability to develop knowledge about the common diseases by using systematic data mining.

TR: What is deCODE’s advantage in this field?

STEFANSSON: We have the genealogy of the entire nation [of Iceland] on a computer database. When you’re studying the genetics of disease, you’re not only studying the information that goes into making an individual; you’re also studying the flow of this information from one generation to the next. And the genealogy gives you the avenues by which the information flows.

TR: Have you had any success yet?

STEFANSSON: We have indeed had success. We have been able to map genes in incredibly complex diseases, like osteoarthritis, osteoporosis, schizophrenia and psoriasis. Every single complex disease that we have applied significant effort to, we have been able to map by using this process. When we were starting our company, we put most of our effort into development of software systems, of algorithms to analyze data, and we were ahead of the biology that we subsequently began to look at. Making use of informatics, mathematics, and all these genealogical approaches, we have been able to solve problems that others have had difficulties with. Then we are taking the discovered genes and turning them into drug targets. And we are already working on the development of drugs on the basis of those targets.

TR: What kinds of drugs is deCODE working on?

STEFANSSON: We have set up a division to work on drug development, which will probably be located in the States for human resources reasons. It started out as a cell biology division where we work on the biology of the genes we discover. Since we are working on the genetics of 60 diseases now, we have the possibility of selecting the things that are easiest to work on. I honestly cannot tell you which genes we plan to target, because we haven’t made any final decisions. Remember, if you are speaking in terms of drug development based on basic biological discoveries, it takes about 12 to 15 years from the time you make a discovery until you have a drug on the shelves.

TR: How does all this fit into deCODE’s business model?

STEFANSSON: We are basically marketing three lines of business: a discovery service, from discovery of genes to the discovery of drug targets to the discovery of drugs; the service component, which is the database that is based on putting health-care information in the context of genetics; and software systems, not only to use in discovery but also in the delivery of health care. When we started our work and we looked around, there were no software systems that would allow us to do genetics at the scale that we wanted to do it, so we put together a very large informatics section. They have put together algorithms and programs that do spectacular things when it comes to large-scale genetics, for genotyping [finding the individual variations in genetic makeup], for mining genes from raw sequences, for doing statistical analysis.

We have also put together a software system to prevent medication errors, problems due to drug interactions and things of that sort-a very smart, very elegant program. We have put together software systems that protect privacy not only in discovery work but also in the delivery of health care. Now, and particularly in the future, people will be sending medical information to institutions left and right in electronic form. To do that, you need to put a shell around the data so you can protect privacy. We have also been putting together a clinical decision-support system. All of this grew out of our focus on the database.

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