Kári Stefánsson

Following his internship at the National Hospital of Iceland, he went to the University of Chicago to work under Barry Arnason (coincidentally a Canadian of Icelandic descent). There he completed residencies in neurology and neuropathology, and in 1983 joined the faculty. In 1993 he was appointed professor of neurology, neuropathology and neuroscience at Harvard University and division chief of neuropathology at Boston's Beth Israel Hospital. While in Boston, he and his colleague Jeffrey Gulcher decided to return to Iceland to perform genetic studies to determine multiple sclerosis risk. Stefansson resigned both positions in 1997 after founding deCODE and moving back to Reykjavík. Since 2010, he has held a professorship in medicine at the University of Iceland. He is a board-certified neurologist and neuropathologist in both Iceland and the US.

From biology to genetics

Stefansson's academic work was focused on neurodegenerative disease. The protein biology approach to this research involved trying to map complex processes using limited samples, mainly of brain tissue from deceased patients. Although publishing steadily, Stefansson was frustrated by the pace of progress and often by not knowing whether the proteins he was characterizing were involved in causing disease or the product of the disease process. He and his colleagues came to question even the accepted definition of multiple sclerosis (MS) as an autoimmune disease.

When he was recruited from Chicago to Harvard, Stefansson began to think that the genome might provide a better starting point than biology. Genes encode proteins, so identifying the genes and specific genetic variations that patients tended to share more often than healthy individuals should provide a foothold in the pathogenesis of disease. In doing so they might point to biologically relevant targets for new drugs and predictive diagnostics.

However, in the mid-1990s the tools for reading the sequence of the genome were primitive. Data was scarce and expensive to generate, and a major early focus of the Human Genome Project was to develop better methods. In the meantime, one solution was to use genetics – how the genome is mixed and passed from one generation to the next – as a means of deriving more information from the available data. Siblings share half their genomes; but cousins one eighth, second cousins one thirty-second, etc. Studying patients linked by extended genealogies should therefore make it possible to more efficiently find the inherited component of any phenotype or trait, even using low-resolution markers.

Public health: BRCA2 screening

In 2018, deCODE launched a website that enables Icelanders to request the analysis of their sequence data to determine whether they carry a SNP in the BRCA2 gene linked to significantly increased risk of breast and prostate cancer in Icelanders. This was the first time that deCODE, which is primarily a research organization, returned information from its research data to participants. Stefansson had tried for many years to convince the Icelandic Ministry of Health that this was a serious public health issue that deCODE's data could address at virtually no cost, and it was but one of the clearest-cut of many such possible precision medicine applications to healthcare in Iceland.

With no response from the health system, Stefansson went ahead and put the matter in the hands of citizens. As of late 2018, some 40,000 people, more than ten percent of the population, had utilized the site to learn their BRCA2 status. Hundreds of people have been able to learn that they are carriers and the National Hospital has built up its counseling and other services to help those decide how they wish to use this information to protect their health. Given the disease and mortality rates from breast and prostate cancer associated with BRCA2, the availability of this information should enable the prevention and early detection of hundreds of cancers and save dozens of lives.