The Year of Miracles

To make it all harder to fathom, each bit of DNA is susceptible to mutation and variation among individuals. Of the 3 billion DNA bases in the human genome, geneticists identified about one tenth of one percent (millions) that differ from one person to another. Variations in these particular letters—called "snips," or SNPs, for single nucleotide polymorphisms—have replaced genes as the unit of heredity.

Many scientists responded to this devastating realization by going into a funk. "It will be difficult, if not impossible, to find the genes involved [in common diseases] or develop useful and reliable predictive tests for them," Dr. Neil Holtzman, director of genetics and public policy at Johns Hopkins University, said in 2001.

Fortunately, another visionary scientist, Kari Stefansson of Iceland, was already blazing a trail out of this thicket. If the genome was far more complex than scientists had thought, they would need to test for many more variables, and to do that they would need more test subjects. To find the cause of diseases would now require the participation of very large groups of genetically related people.

Like Hood and Venter, Stefansson was originally motivated by frustration with the pace of research. In the United States, where most of the disease-gene-discovery projects were being conducted, most people cannot trace their ancestors back more than a few generations, and the largest families consist of a few hundred living subjects at most. Subject panels of this size failed to provide sufficient data to identify the genetic bases for complicated and variable common diseases. Stefansson decided to solve this problem by taking aim at the largest well-documented extended family that he knew—his own.

Nearly all the 300,000 citizens of Iceland can trace their ancestors back, through detailed, public genealogical records, to the Vikings who settled this desolate European island more than 1,000 years ago. Stefansson gave up his faculty position at Harvard Medical School to return to Iceland, where he founded the company deCODE Genetics in 1996. He persuaded the Icelandic government to provide deCODE with exclusive access to the health records of its citizens in return for bringing investment capital and high-tech jobs to the capital, Reykjavik. So far, more than 100,000 Icelandic volunteers have donated their DNA to deCODE.

Stefansson's project was roundly criticized by international bioethicists and other geneticists for violating the privacy of Icelanders (even though 90 percent of the population approved). Nevertheless, he persevered, placing "the genealogy of the entire nation on a computer database," together with the health and DNA records of still-living individuals. The power of large numbers was soon apparent. In a study of obesity, he directed his software to look for SNPs associated with subsets of the population who were either extremely overweight or very thin. Within just a few hours, it began finding evidence that variations among particular DNA letters indeed played a causative role, confirming SNPs as the new unit of inheritance.