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A Genetics Company Fails, Its Research Too Complex

DeCode Genetics, a pioneering company that used the Icelandic population as its guinea pigs in detecting disease-causing mutations, filed for bankruptcy on Tuesday.

The company’s demise suggests that the medical promise of the human genome may take much longer to be fulfilled than its sponsors had hoped. Based in Reykjavik, Islandia, it was founded in 1996 by Dr. Kari Stefansson, a research neurologist who worked at the University of Chicago and at Harvard. After the human genome sequence was achieved in 2003, Dr. Stefansson quickly realized that Iceland’s excellent medical records, combined with the genealogical information available on its close-knit population, provided a fine test bed for seeking the roots of genetically complex diseases like cancer, diabetes i schizophrenia.

DeCode quickly became the leader in the worldwide race to identify the causes of common disease. The company’s researchers discovered mutations linked to schizophrenia, heart disease, diabetes, prostate cancer and many other illnesses. Its approach was to identify the mutations first in Icelanders and then to confirm them in other populations.

Whatever business errors deCode may have made, a principal reason for its downfall is scientific — the genetic nature of human disease has turned out to be far more complex than thought.

Many researchers expected that just a handful of genetic mutations would explain most cases of any given major disease. But the mutations that deCode and others detected in each disease turned out to account for a small fraction of the overall incidence. Natural selection seems to be much more efficient than expected at ridding the population of dangerous genes, even of those that act well after the age of reproduction. That leaves thousands of different mutations, each very rare in the population, as the probable culprit. And because most of the mutations are rare, they are extremely hard to find.

The mutations that deCode detected in each major disease were responsible for too few cases to support the development of widely used diagnostic tests or blockbuster drugs.

Today’s bankruptcy affects deCode Genetics, the parent company based in the United States that owns the Icelandic operation, called Íslensk Erfagreining. That operation is being put up for auction and, depending on the wishes of its new owners, could continue its gene-hunting efforts much as before.

“It’s not a happy day but it would be worse if the genetics operation were not to continue,” said Edward Farmer, deCode’s chief communications officer. The discovery that major diseases do not have any simple genetic pattern of causation has dealt a serious setback to the gene-hunting field as a whole, and researchers are trying to figure out their next move.

“DeCode has been very successful using genome-wide association studies, and among the first to publish many discoveries,” said Dr. David Altshuler, a medical geneticist at the Massachusetts General Hospital. But he expressed optimism that the human genome project would succeed despite deCode’s stumble.

“It would be a mistake to draw any connection between the medical promise of the human genome and the success of a specific company and business model,” he said.

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