February 16, 1999
By SARAH LYALL
REYKJAVIK, Iceland -- This remote island is known around the world for its eerily beautiful but spectacularly punishing landscape, carved almost beyond reason from volcanoes and ice. It is known for winters that are shrouded in darkness and summers that are punch-drunk with light. It is known for the fish, particularly cod and shrimp, that make up 75 percent of its exports.
But Iceland has another precious resource. It has a nearly homogeneous population, whittled down over the years by natural disaster and disease, carrying nearly the same genetic codes as the Viking explorers who settled here more than 1,100 years ago.
Such homogeneity is greatly prized by researchers, because it means that genetic anomalies can be more easily identified in studies of the origin of diseases. And now, in a brave new experiment that is being closely watched around the world, Iceland's 270,000 residents are poised to share the genealogical, genetic and medical information that makes them who they are for the goal of advancing science.
But the audacity of the plan -- and what it bodes for the future -- has provoked a bitter battle both within and outside of Iceland, a country smaller than Kentucky that has suddenly found itself at the forefront of a world debate over the ethics and uses of genetic research.
In December, after a fierce public discussion that raged for months, Iceland's Parliament passed a law giving an Icelandic biotechnology concern the right to develop a giant database combining the health records, genealogical backgrounds, and DNA profiles of every person in Iceland. The concern, Decode Genetics, which is to have exclusive rights to market the database abroad for 12 years, says the information will be used to answer a host of questions about the nature and origins of hundreds of diseases.
Supporters of the plan, including the Icelandic Government and many scientists, say it may produce a wealth of knowledge that is too exciting to pass up. But opponents, including many prominent researchers in Iceland and the United States, contend that it is a terrifying example of how science can become so carried away by dreams of glory and profits that it abandons good research practice and runs roughshod over the rights of individuals.
"I see Iceland as a precedent for a new style of medical research that will involve not just Icelanders, but people around the world," said Hank Greely, a professor of law at Stanford University, who studies the ethical, legal and social issues of genetics, and who has deep reservations about how Decode intends to collect and use its data.
"Advances in the speed and cost of genetic analysis are about to make it possible to collect huge amounts of clinical and genetic data from hundreds of thousands of people and process it through powerful computers. Iceland is the first example we've got of this kind of large-scale correlation of data, and I'd like it to be done in a way that was ethically right."
Many Icelanders, however, resent the meddling of outsiders who think they know what is good for Iceland, the world's oldest democracy. "People adopt a view from afar and think they understand what's going on in a place that's culturally very different from their own," said Gisli Palsson, director of the Institute of Anthropology at the University of Iceland, who supports the database. "But there was a fierce debate for months, with public participation, and one has to conclude that it has been an informed and lengthy discussion, a democratic process."
Decode's project is simple and breath-takingly ambitious, relying on a happy confluence of factors.
First, Iceland comes close to having what is known as a closed population, meaning that there has been little immigration to muddy the genetic pool over the centuries. As the islanders' language has remained virtually unchanged for 1,000 years, so has their genetic makeup. "All Icelanders are walking around with a large segment of the DNA that their ancestors had," said Kari Stefansson, Decode's exuberant president and chief executive officer.
Mr. Stefansson, a former professor of neurology and pathology at the
Harvard Medical School, has a
larger-than-life personality and grand vision that have drawn almost as much attention as the work his company is doing. "When someone has a genetic disease here," Mr. Stefansson said, "you can almost invariably trace it back to one individual who brought the disease into the community."
The country also has a passion for genealogical record-keeping, so much so that many residents can trace their family trees back 500 years or more. And it has a universal, state-financed health-care system that since 1915 has kept comprehensive records of every patient's medical history. All this information -- along with the DNA samples of willing Icelanders -- is to be gathered together in Decode's gigantic database.
"A homogeneous population with great genealogical and medical records is the scarcest resource in human genetics today," said Jeffrey Gulcher, Decode's vice president for research and development. "The notion that you can actually take a list of patients and link them together with genealogy to begin a study is one of the most powerful aspects of the work we're doing.
"For instance, when you look at people who've lived over the age of 95 and ask how they are clustered together in the population, it's amazing how you can see that longevity is passed down from generation to generation. In Iceland, we have the opportunity of looking at every single individual who lived to a certain age. We know when they were born and when they died, and it allows us to do, for the first time, a population-based study of longevity."
Critics, however, say they are alarmed at the prospect of concentrating so much information in one place and worried that the Icelandic people do not understand what they are getting themselves into. It is not clear what the benefits of Decode's research will actually be, they say, and it is very dangerous for a nation to give so much of itself away when it is not sure of what it will get in return.
"It is not right to use a population as a commodity in this way," said Jorunn Erla Eyjfjord, the head of molecular genetics at the Icelandic Cancer Society. "What they're doing probably won't hurt me personally, or Iceland now, but I fear that we could be used as a well-defined guinea pig population in the future."
But Ragnheidur Haraldsdottir, deputy permanent secretary of Iceland's Ministry of Health, said that the data base would prove invaluable to Iceland. "This will enable us to build up an outstanding computerized health-care record system for every health care institution in this country," she said. And, in a country that routinely loses scientists to foreign institutions, the company has worked to reverse the brain-drain by luring researchers back home.
Debate over the plan, continuing among researchers in spite of the new legislation, broadly focuses on three points: privacy, consent and the still uneasy intersection between genetics and commerce.
Many critics say they fear that it will be impossible for the database to guarantee people's privacy, even with sophisticated computer protections. They worry that sensitive information could be traced back to people and used against them, in hiring, for instance.
"I'm sure they will have a lot of safeguards, but it will be relatively easy to break the codes when you have so much genetic and genealogical and health information tied together," said Tomas Zoega, chairman of the ethical council at the Icelandic Medical Association.
Not likely, Mr. Stefansson says, asserting that the company will "use every single method that exists in the world to maintain the privacy of the database." That includes removing identifying features like people's names, encrypting the data three separate times, making it impossible to winnow information down to groups smaller than 10 people, and limiting access to the database.
Opponents have also criticized Decode's plans to collect its medical data from everyone who does not explicitly opt out of the program. The ethical approach, they say, would be to use informed consent, in which participants actively agree to take part in specific studies, rather than ceding their records for whatever purpose the researchers want.
"It's akin to treating people as objects rather than human beings," said Jon Johannes Jonsson, an associate professor in the department of biochemistry and molecular biology at the University of Iceland Medical School. "I flatly reject the notion that you have to make concessions on patients' rights in order to do human genetic research."
But Decode says that its research conforms to internationally accepted ethical standards. And while the medical records are to be gathered on the basis of presumed consent, the far more sensitive genetic information -- DNA obtained through Icelanders' blood samples -- will be gathered only with the explicit permission of the subjects.
Finally, the opponents worry about how the other companies will use the data they buy from Decode. "Science has a lot at stake in making sure that people don't feel cheated and embittered when they take part in research," said Professor Greely of Stanford. "I worry that there will be an episode which leaves the research subjects feeling unhappy, mistreated, resentful and burned."
With a staff of 250 and $12 million in venture capital money, mostly from the United States, Decode is already Iceland's biggest biotechnology company, stirring fears from rivals that it will soak up most of the country's research money and make it harder for them to compete. While it waits for the government to grant a license for its database this spring, Decode has already begun a host of genetic studies that are seeking to identify the genes -- or combinations of genes -- responsible for 20 diseases, including multiple sclerosis, endometriosis, hypertension, Alzheimer's disease and osteo-arthritis.
To that end, it is using blood samples from more than 10,000 Icelandic volunteers, as well as the genealogical histories of 580,000 of the 750,000 or so Icelanders who have ever lived, including everyone alive today. Its research is being supported by the pharmaceutical company Hoffman-La Roche, which has agreed to pay the company as much as $200 million over five years if Decode can identify the genes for a list of 12 of those 20 diseases. As part of this agreement, Hoffman-La Roche has pledged to provide free to Iceland any medicine it may develop from Decode's work.
Already, Mr. Gulcher said, the company has begun to make progress toward finding the genes associated with multiple sclerosis, schizophrenia, arthritis, manic depression, and essential tremor, a disease that causes involuntary shaking.
"All we're doing is extending the age-old practice of understanding familial risk factors to bring a greater precision to health care," said Jonathan K.C. Knowles, the head of global pharmaceutical research for Hoffman-La Roche. Saying that research carried out by companies like Decode represents "the paradigm shift in medicine," Mr. Knowles added that by finding the genetic underpinnings of various diseases, researchers could begin to develop treatments for people who were not sick, but who had a higher risk of falling ill.
It remains to be seen what will happen when Decode begins collecting the medical data and blood samples, a process it hopes to begin next fall. While Decode says that the overwhelming majority of Icelandic doctors support its efforts, pointing to a petition against the database that was signed by only a fifth of the island's 700 physicians, the Icelandic Medical Association says that opposition is much more widespread.
But the country is determined to go forward. "We feel that we might
be able to contribute something to the world," said Mrs. Haraldsdottir.
"Some people would maintain that it would be unethical not to try to use
the unique resources that we have in Iceland to try to improve the health
of Icelanders, and hopefully of others." [Image]
Siguleil Siguljonson for The New York Times Kari Stefansson at Decode Genetics, which he heads, wants to build a vast database of health records, genealogical backgrounds and DNA profiles of every person in Iceland.
Siguleil Siguljonson for The New York Times
Jon Johannes Jonsson of the University of Iceland Medical School, an opponent of the genetic research project, is troubled by ethical issues.
Copyright 1998 The New York Times Company