Iceland faces a DNA dilemma: Whether to notify people carrying cancer genes


Iceland faces ethical DNA dilemma

Iceland, with extensive DNA databases, has the ability to identify citizens with deadly breast-cancer genes, and notify them. But government so far refuses to do so.

By Stuart Leavenworth and Alexa Ard June 14, 2018 05:00 AM

REYKJAVÍK, ICELAND - Sometime in the future, U.S. researchers will be able to press a button and reliably identify the thousands of people who carry cancer-causing genes, including those that trigger breast cancer.

In Iceland, that day is already here. With a relatively uniform population and extensive DNA databases, Iceland could easily pinpoint which of its people are predisposed to certain diseases, and notify them immediately. So far, the government has refused to do so. Why? Iceland confronts legal and ethical obstacles that have divided the nation and foreshadow what larger countries may soon face.

Since the late 1990s, tens of thousands of Icelanders have agreed to contribute their DNA to a public-private science projects aimed at delivering medical breakthroughs. But in contributing their DNA — and in many cases, their medical records — these people never explicitly consented to be notified of personal health risks that scientists might discover.

Icelandic regulators have determined that without that explicit consent, neither the government nor private industry can notify people of these risks.

"That is utter, thorough bulls--t," Dr. Kári Stefánsson, a world-renowned Icelandic neurologist and biotech leader who has been at the center of the nation's DNA debate, told McClatchy in an interview in his Reykjavík office. "There is a tradition in American society, there is a tradition in Icelandic society, to save people who are in life-threatening situations, without asking them for informed consent. Should there be a different rule if the danger is because of a mutated gene?"

In Iceland more than anywhere, the promises of technology and "personalized medicine" are clashing with concerns over privacy and medical norms. In the United States and elsewhere, scientists and doctors will soon have the capability to tell people about their predispositions to diseases. But at what age should they be told, and with what caveats? Should researchers only tell individuals about diseases that can be prevented — such as with a mastectomy — as opposed to those they can't stop, such as Alzheimer's? And what if people don't want to know?

For government critics such as Stefánsson, the answers are straightforward. He compares Iceland's situation to an individual's day-to-day obligation to act if they see another in peril. "If someone falls into the harbor, does he need to sign an informed consent before you pull him out of the sea?," he asked incredulously.

It is hardly surprising that Iceland, with a mere 330,000 people, has become a living laboratory for DNA testing and the privacy issues that surround it. Nearly everyone here traces their lineage back to the original Viking settlers, a mix of Norsk and Celtic peoples. Iceland's gene pool has varied little over the centuries, in part because of its isolation.

This homogeneity makes it easier for researchers to isolate genes that trigger diseases. For example, Icelanders carry just one mutation of BRCA2, a gene that causes breast cancer. Only 0.8 percent of Icelandic people possess the gene, but it holds an 86 percent probability of causing cancer in women who carry it, Stefánsson said. It also threatens male carriers with a higher risk of untreatable prostate cancer.

Since the mid-1990s, Stefánsson's company deCODE Genetics Inc., has dominated the nation's genomic research. Stefánsson claims the company now can access a DNA database of 60,000 fully sequenced individuals, and another 180,000 whose genetic code has been partially sequenced.

The biotech company declared bankruptcy in 2009 amid Iceland's financial crisis, but has since bounced back, with the help of Amgen, which purchased deCODE in 2012 for $415 million. Over the last six years, deCODE has helped identify a gene variant linked to late-onset Alzheimer's and another one that increases risk of osteoporosis and certain cancers.

With his slashing style and media charisma, Stefánsson has become one of Iceland's most well-known figures, said Dr. Bogi Andersen, an Iceland native and medical professor at the University of California, Irvine. "In Iceland, Kari is more prominent than Björk," he said, referring to the Icelandic pop singer.

But Stefánsson is also enormously controversial. Outspoken, contemptuous of ethics purists, Stefánsson has built a career on lobbying and sometimes bullying the Icelandic government. "It is outside the norms the way he has manipulated the agencies," said Andersen.

Two years after founding deCODE, Stefánsson and others in the company persuaded Iceland's parliament to pass the Health Sector Database Act, an effort to create a vast database of Icelanders' genetic information and medical records, in an encrypted form, for scientific research. The law also allowed a private licensee to control and access this data. Stefánsson's deCODE became that licensee.

Icelanders generally supported the law, but one of its lesser-known provisions soon caused an uproar, both in Iceland and beyond. Under the law, personal data of Icelanders was excluded from the database only if a person asked to opt out. Under normal research protocols, people are only included in a study if they explicitly consent.

"When deCODE was founded, it broke every bioethics norm," said Michael Malinowski, a Louisiana State University law professor who specializes in biotechnology issues. "It was a complete flip on the idea of informed consent."

Iceland's use of "presumed consent" with the database was ultimately deemed unconstitutional. In 2003, Iceland's Supreme Court ruled in favor of an Icelandic woman who challenged the inclusion of her father's medical records in the database. The decision effectively ended the Health Sector Database, forcing deCODE to use other means to build its data sets.

Over the years, deCODE has encouraged tens of thousands of Icelanders to voluntarily share their genetic codes. Stefánsson said the company now could identify carriers of the BRCA2 gene in the 60,000 Icelanders whose DNA has been fully sequenced, and extrapolate to pinpoint others. But Icelandic regulators have repeatedly refused to let deCODE de-encrypt the data to identify these carriers, and notify them.

"The legal experts working for the government have come to the conclusion the government cannot approach women with this mutation and warn them," Stefánsson said. As a stop-gap measure, deCODE last month established a web site where people could sign up to be notified if they were carriers of the BRCA2 gene.

Stefánsson, who served on the faculty of University of Chicago and Harvard University before starting deCODE, said he expects the United States to face similar conundrums as DNA testing evolves. Currently, the National Institutes of Health is seeking to recruit 1 million Americans to contribute DNA and medical data — in an anonymous form — to the "All of Us" national research project.

Stephanie Devaney, a geneticist and deputy director of All of Us, said the NIH is taking several steps to avoid the kind of dilemma Iceland is facing. Roughly 72,000 people have so far signed consent forms to participate in All of Us, with the expectation they will receive personal information from the study, if they want it, she said.

The NIH is preparing to select a genetic counseling service to help participants understand their results, and will likely ask them to sign separate consent forms before receiving personal health data and interpretations. "We've been thinking about this from the embryonic stages of this program," said Devaney.

Informed consent protocols are partly a response to history's most notorious scientific abuses. During World War II, the Nazis conducted numerous experiments on prisoners, in part to advance the Nazi racial ideology. In the United States during the early 20th century, more than 30 states passed compulsory sterilization laws, part of a eugenics push that led to the sterilization, without consent, of tens of thousands of people.

Stefánsson said he understands concerns about bio-ethics, but argues that Iceland is overreacting. He blames the dilemma partly on German dominance of Europe's research protocols, which he thinks are excessively sensitive.

"The Germans, for whom I have great admiration, are still dealing with their bad conscience from the Second World War," he said. "They have an extraordinarily ambivalent view of any instruments that allow you to approach a lot of people for any particular purpose."

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