Large genome databases are starting to reveal critical health
information—even about people who have not contributed their DNA.
Maps show how common certain risk-causing DNA mutations are around Iceland.
The
CEO of an Icelandic gene-hunting company says he is able to identify
everyone from that country who has a deadly cancer risk, but has been
unable to warn people of the danger because of ethics rules governing
DNA research.
The company, DeCode Genetics,
based in Reykjavík, says it has collected full DNA sequences on 10,000
individuals. And because people on the island are closely related,
DeCode says it can now also extrapolate to accurately guess the DNA
makeup of nearly all other 320,000 citizens of that country, including
those who never participated in its studies.
That’s
raising complex medical and ethical issues about whether DeCode, which
is owned by the U.S. biotechnology company Amgen, will be able to inform
members of the public if they are at risk for fatal diseases.
Kári
Stefánsson, the doctor who is founder and CEO of DeCode, says he is
worried about mutations in a gene called BRCA2 that convey a sharply
increased risk of breast and ovarian cancers. DeCode’s data can now
identify about 2,000 people with the gene mutation across Iceland’s
population, and Stefánsson said that the company has been in negotiations with health authorities about whether to alert them.
“We
could save these people from dying prematurely, but we are not, because
we as a society haven’t agreed on that,” says Stefánsson. “I personally
think that not saving people with these mutations is a crime. This is
an enormous risk to a large number of people.”
The
Icelandic Ministry of Welfare said a special committee had been formed
to regulate such “incidental” findings and would propose regulations by
the end of the year.
The
technique used by DeCode to predict people’s genes offers clues to the
future of so-called precision medicine in other countries, including the
U.S., where this year President Barack Obama called for researchers to
assemble a giant database of one million people (see “U.S to Develop DNA Study of One Million People”).
A large enough U.S. database could also be used to infer genes of
people whether or not they had joined it, says Stefánsson, and could
raise similar questions about whether and how to report health hazards
to the public.
“This technique can be applied to any population,” says Myles Axton, chief editor of Nature Genetics,
the journal in which DeCode today presented some of its findings. He
said the tiny island’s detailed genealogical records are why “it was
achieved first in Iceland.”
Various
legal and ethical obstacles currently prevent DeCode from warning
people who are at risk. Volunteers who signed up for DeCode’s studies
were promised anonymity, and also that they wouldn’t learn of research
findings. Bioethicists recognize that people have a right “not to know”
of genetic hazards, which means they can’t simply be told.
“The rule is that you can only use and expose genetic data if you have the permission from the individual in question,” says Gísli Pálsson,
an anthropologist at the University of Iceland. “But this is beyond
informed consent. People are not even in the studies, they haven’t
submitted any consent or even a sample, yet the company claims to have
knowledge about these people and that there is a health risk.”
Pálsson
says traditional notions of medical ethics are now in open conflict
with the aims and capabilities of precision medicine. He believes such
standards will need to be adjusted in fundamental ways in the future, so
that more weight is given to public health benefits over individual
privacy rights.
The
life expectancy of women with the BRAC2 mutation is 12 years less than
for women without it because 86 percent of those who have it will
develop cancer. Men are also affected because the mutation raises the
chance of prostate cancer. Stefansson says many of those deaths could be
avoided by preventive surgery, like a mastectomy.
“We
could in Iceland, at the push of a button, find all women with a
mutation in the BRCA2 gene,” says Stefánsson. “It is one tiny little
example of what you can do. You can use this in preventive medicine like
never before.”
DeCode’s
data might also be able to predict who in the population is at elevated
relative risk for Alzheimer’s disease or who has an undiagnosed
learning disability.
DeCode was started in 1996 with the idea of linking DNA research to Iceland’s national health system (see “Population Inc.”).
The country’s situation is unique because of its carefully kept
genealogical records, which go back to the Ninth Century, when the
island was settled. That also means most Icelanders are at least distant
cousins.
DeCode
has generated rough gene maps, called genotypes, on about 150,000
Icelanders. More recently, advances in DNA sequencing technology have
allowed it to obtain complete genome sequences of about 10,000 people,
Stefánsson says, or about one in 30 Icelanders. Results from the first
2,636 full genomes were reported by the company today in Nature Genetics.
Combined
with genealogical tables, these data are what allow DeCode to “impute”
the genomes of nearly everyone born of Icelandic parents. That is
because once the full genome of some people in a family tree is known,
the genes of the others can be inferred.
Sean
Harper, head of R&D at Amgen, calls DeCode’s ability to guess
people’s DNA a “conundrum.” He says it is not an unfamiliar problem to
geneticists, however, since routine DNA tests of one person often reveal
information about close relatives. But it has never before occurred at
the level of an entire nation.
“It’s
a gray area from a bioethics perspective, but we would be inclined to
provide the data or at least a notice,” says Harper. He says Amgen,
which uses gene information from DeCode to guide its drug research, had
no plans to charge anyone for the risk information it has developed. “It
would not be appropriate [to] try to make it a commercial process,” he
says.
The
U.S. lacks a similar national database, although some private
companies, like 23andMe and Ancestry.com, have generated rough gene maps
of several million people altogether. The National Institutes of Health
is planning to spend millions in the coming years on accumulating full
genome data on tens of thousands of people.
That
means the entire world will soon confront the same types of ethical
dilemmas that Iceland now faces, says Pálsson. “Do you have the right to
fiddle with people’s lives on a massive scale? You can tell your
neighbor, ‘You are smoking too much.’ But it’s another thing to approach
1,000 people and say, ‘You have the BRCA2 mutation,’ ” he says.