a reporter at large 

decoding iceland
The next big medical breakthroughs may result from
one scientist's battle to map the Viking gene pool.
january 18, 1999

1.

     If not for a single genetic peculiarity, passed invisibly through
the generations, it is unlikely that we would know a thing about
a sixteenth-century Icelandic cleric named Einar.  That's no surprise;
on the surface, at least, he does not appear to have been unusual.
Genealogies suggest that he was one of about four hundred men
named Einar living at the time--each of them struggling among
the high moors and dwarf birches on the edge of the habitable
world.  Einar's ancestors had managed to survive the black plague,
in the early fifteenth century, which killed as many as forty
thousand people--two-thirds of the population--and some of his
descendants lived through the next epidemic: smallpox, which struck
in 1707, just as the livestock and the settlers were beginning
to flourish again on the farmsteads of the countryside.  This time,
more than fifteen thousand people--a third of the population--perished.

     Not only did each of these disasters kill many people but there
was an equally dramatic, Darwinian effect: they cut back sharply
on the genetic diversity of the island--as if a giant tree had
been pruned again and again until only its trunk and a few of
the sturdiest branches remained.  The entire population had descended
from a small band of ninth- and tenth-century Norse settlers mixed
with a few early Irish slaves.  The island had almost no immigration
from then until the Second World War, so for more than a thousand
years Icelanders bred among themselves.  In the middle of the eighteenth
century, the population stood at fewer than fifty thousand, no
more than it had been five hundred years before.  

     The greatest calamity was still to come, however.  In 1783,
Lakagigar, a volcano in southern Iceland, erupted.  By the time
the lava stopped, eight months later, it had produced the biggest
flow in recorded times--more than two hundred square miles of
fire and ash.  In a remarkable diary, which was eventually published
under the title "Fires of the Earth," the Reverend Jon
Steingrimsson wrote:

     The flood of fire flowed with the speed of a great river swollen
with meltwater on a spring day.  In the middle of the flood of
fire great cliffs and slabs of rock were swept along, tumbling
about like large whales swimming, red-hot and glowing.

     The eruption itself killed few people, but the sulfur dioxide
it released was among the deadliest events in the history of Iceland.
It blanketed the earth with a dusty poison, and twenty-five per
cent of the population died in the resulting famine, as did almost
all the horses and sheep.  A toxic cloud smothered the nation.
Tales of crop damage, drought, asthma, headaches, and a widespread
fear of damnation were common throughout Europe.  "Those terrors
that fell over and upon us I can hardly describe," Steingrimsson
wrote."It will be for all eternity a source of the greatest
wonder, that any living thing should have survived."

      Many did survive, of course--the descendants of Einar among
them.  We know this now because it turns out that there was something
special about that sixteenth-century cleric after all: one of
his genes was missing five units of DNA--a mistake on the scale
of having mistyped one letter in a volume that holds all the plays
of Shakespeare.  Such mutations--permanent changes in the order
of genetic information--are not rare.  Everyone is born with them.
They are almost always harmless.

     Einar's was not.  The mutation he carried, in which a few of
the basic units of DNA had accidentally been deleted from a gene
that is now known as BRCA2, is responsible for virtually every
case of hereditary breast cancer in Iceland today.  Both women
and men with this mutation have an extremely high risk of developing
cancer, because one function of that gene is to make a protein
that repairs DNA when things go wrong.  BRCA2 and BRCA1 (the latter
is the first gene that was shown to cause breast cancer, and to
do so in even greater numbers) are thought to suppress tumors,
when they are working normally.  Mutations like the one that was
traced to Einar through his descendants lie dormant in the cells
unless--or until--the remaining good copy of the gene is lost
or damaged.  That begins the mysterious chain of events that, in
ways still not fully understood, ultimately lead to cancer.  Researchers
at the Icelandic Cancer Society were able to discover Einar's
mutation because they worked on a remote island where nearly every
genetic possibility could be examined with the kind of detail
that would be impossible anywhere else.  Many mutations of these
genes exist, and so far more than a hundred are associated with
BRCA1.  But after examining five hundred and seventy-five Icelandic
breast-cancer patients, including thirty-four men who had been
found to have the disease since the Second World War, researchers
discovered only one BRCA2 mutation in Iceland: Einar's.  That means
scientists don't have to guess what caused cancer in those people;
they know.  And knowing the root of a disease is the first step
along the difficult road toward curing it.

2.

      It's a cliché, but the first thing a visitor to Iceland notices, 
after the volcanic landscape that lies beneath the approach
to Keflavik International Airport, is just how closely Icelanders
resemble each other.  From Geysir, which has become the generic
name for half the spouting hot springs on earth, to the Levittown-like
suburbs that threaten to overwhelm the rustic, port-side ambience
of Reykjavik, Iceland sometimes seems to be inhabited by one enormous
family, not one of whose members ever leaves the neighborhood
where he was born.  

     It is the unique nature of this extended family that made Einar's
genetic flaw so easy to find: the hereditary instructions for
blue eyes and blond hair, which are so prevalent in Iceland, have
been passed undiluted through a small gene pool for fifty generations.
After a thousand years of plagues, epidemics, earthquakes, and
volcanoes finished weeding out the population, what remains in
the middle of the turbulent fishing grounds of the North Atlantic
is a nation of two hundred and seventy thousand of the most genetically
similar people on earth--a place where phone numbers are organized
by first names.  It takes an amateur genealogist with a five-hundred-dollar
computer about three minutes to show how any two Icelanders are
related.  

      No hobby could be more useful to molecular biologists.  Prospecting
for genetic flaws has become the age's great Klondike: researchers
from Newfoundland to Papua New Guinea are sifting through the
world's genetic heritage looking for the causes of common diseases
by comparing the DNA of sick people with that of their healthy
relatives.  You can't do that easily in a racially and ethnically
diverse place like America; if people's backgrounds, habits, genetic
composition, and environments are all different, then so, almost
certainly, are the causes of their illnesses.  But many scientists
believe that Iceland, with a history of isolation and of the repeated
catastrophes that have kept the population small, is the richest
natural genetics laboratory on earth.

      Recent cancer research helps show why.  Most breast cancer
is not inherited; when it is, the genetic component is almost
always complex.  If five women in New York City (or in Bombay,
Moscow, or Tokyo) each had an inherited form of breast cancer,
the causes, the actual genetic mutations, would vary.  Some would
have one mutation; others another; the cancer of still others
might be a result of subtle interaction among several seemingly
unrelated genes.  But if those women were from Iceland such differences
wouldn't exist; each almost certainly would have an identical
genetic flaw, inherited from that same clergyman--Einar.

     "This is the absolute essence of human genetics,"
Mary-Claire King told me on the telephone one day from the University
of Washington, where she is a professor in the Departments of
Medicine and Genetics.  King, who is among the world's most prominent
geneticists, spent nearly two decades searching for the first
breast-cancer gene.  "To be able to trace the genealogy of
an entire nation for a thousand years, and then to have the ability
to obtain samples of blood and tissue from healthy living people
and to compare the DNA with the tissue of those who have died,
and to actually see the differences," King said with obvious
excitement, "that information could become one of the treasures
of modern medicine."   She went on to say, "The first
breast-cancer gene took me seventeen years just to map.  Comparable
work on the second gene was done in about two years.  A lot of
that credit goes to vastly improved technology.  But it is also
true that the single, ancient BRCA2 mutation was a golden key.
Iceland is just an amazing place to do genetics.  The population
there is like a gift from heaven."   

3.

      It was impossibly dreary in Reykjavik at eight on the November
morning that Kari Stefansson arrived to show me how he plans to
turn Iceland into the Athens of genetic research.  The mountain
basin that rings the city was covered with what looked like ash.
The day was sleeting and dark, and remained that way for at least
two hours-- until the sun began vaguely to skirt the horizon.
By noon, waiters were putting candles on the tables in the city's
lunch spots.  Shortly after that, complete darkness returned.  "You
get used to it," said Stefansson, who is forty-nine and is
unquestionably the most controversial man in a country usually
more occupied with fishing rights and the quality of sheepskin.
Stefansson, a neurologist, is the founder of Iceland's first biotechnology
firm, Decode Genetics, and he has developed a plan to take all
the research gifts that the country offers and create a giant
electronic database, which will allow his firm to hunt for the
causes of dozens of common diseases.  Most genetic researchers
agree that such a database could become a scientific instrument
of unparalleled power, but the proposal has also set off one of
the most rancorous debates in the long history of Iceland.  

     In return for conceiving, creating, and paying for this database,
which Stefansson says will cost his company at least a hundred
and fifty million dollars, the government will grant Decode exclusive
rights to market it abroad for twelve years.  The plan has stimulated
great excitement among researchers throughout the world.  No other
country--and certainly no other private company--has ever tried
to collect, store, package, and sell a nation's genetic heritage.

      The proposal also frightens many people, in part because the
relationship between genetics and commerce often seems somewhat
threatening.  But there is more than that: under a bill that has
come before Iceland's parliament, the Althing, Decode would become
the sole manager of this vast collection of information.  Many
critics say that Iceland, by becoming the first nation to catalogue
its gene pool completely and then make it available to a private
company, risks yielding control of the fundamental mystery of
its existence.  

     At six feet five, Stefansson is tall even for a Viking, and
he speaks in a toned-down brogue that makes him sound a bit like
a scholarly Sean Connery.  On the day we met, he picked me up in
his car, a blue Saab, and I found him hunched over the wheel,
muttering to himself, darkly.  After a minute or two, I saw the
wire dangling from his ear: he was talking--rather forcefully--on
a cell phone, something he did at least once during nearly every
conversation we had.

      "I'm so sorry," he said, sheepishly, as he hung
up.  "If I seem preoccupied today that is because my enemies
have deposited the usual lies and half-truths in the newspapers
again.  They are saying that if we go forward with genetic research
in this country, if I am allowed to prepare the database that
will help solve so many medical mysteries and make heroes of the
people here, then Iceland will be stigmatized and the people will
become pariahs in the world.  What a horrendous crock of shit."

     Stefansson is a flamboyant man in a very gray land; yet he
is charming and well read enough to salt most conversations with
apposite lines from Auden, Yeats, or Iceland's great Nobelist,
Halldor Laxness.  Like many medical entrepreneurs, he is often
accused of being more interested in deals than in research, but,
in our discussions, he sometimes seemed interested in neither.
When I asked him what kind of scientist he considered himself
to be, he said he didn't really see himself as a scientist at
all.  

      "I look at myself as a failed writer," he said,
without any of the grim self-consciousness that usually accompanies
such comments.  "A successful man is a great writer.  But as
a writer and as a journalist, if you are any good at all, you
watch.  You are outside events.  You can never really participate,
and I am afraid that my personality does not allow me to stand
on the outside."   Stefansson's eloquence is one of the reasons
he has become so controversial in Iceland: he is an unusually
effective advocate for his ideas.

     But if Stefansson is incisive and determined, he also seems
incapable of humility, and he treats his intellectual combatants
with contempt.  "When the newspapers say that I am the most
popular person in Iceland, and when they say that I am the most
intelligent man in Iceland, I don't even want to respond to that,"
he remarked one day, although I had not asked him about any such
thing.  "But when they say that I could be elected to any
office I desire--I can assure you that is true."   At the moment,
however, he is not seeking elective office; his ambitions are
much greater.  "I want to cure major diseases," he told
me matter-of-factly.  "I want to use this tool to generate
unbelievable amounts of vital knowledge."

4.

      "This tool" is Stefansson's ambitious plan to create
a central health database; it will include nearly every significant
medical and genetic fact about every citizen of Iceland.  But the
country has far more than raw data to offer scientists: Iceland
has a national system of medical insurance which keeps immaculate
records concerning almost every major illness since 1915; it has
an immense and well- documented tissue bank that can be used as
a modern history of the nation's DNA; it has a reservoir of patients
who trust their doctors and are far more willing to participate
in medical research than people in many other countries.  And what
is perhaps most important is that Iceland has such a profound
passion for recording its ancestry that Decode has already compiled
a database with the family histories of nearly seventy-five per
cent of the eight hundred thousand Icelanders who have ever lived.

     Genealogy is the national obsession.  When somebody dies, the
local newspapers always carry an obituary, listing in great detail
a family tree, with names and dates of birth that can go back
for a hundred years or more.  At a dinner party in Reykjavik, I
asked a biologist to translate an obituary--one I had selected
pretty much at random from that day's paper.  He dutifully began,
and by the time he had gone through the parents and the children,
the brothers and the cousins, and back to a great-grandmother
on the maternal side of the dead man's family, he looked up with
a grin and said, "Hey, I think she was my wife's great-grandmother,
too."   The University of Iceland has a professor of genealogy;
there is a daily column on the subject in one of the newspapers;
it is against the law for anyone to change his or her last name,
which is a patronymic; and the government exempts most genealogical
data from basic privacy laws.  Newspaper profiles often include
a detailed account of that person's family tree.

      "Why all this genealogy?"  Stefansson said over dinner
one night.  "Look around this barren land.  There are no remains.
No sculptures.  No cathedrals from hundreds of years ago.  The country
was too poor for any of that.  There was a culture here for eleven
hundred years, but try to find it.  There were books that survive
and they are the only way we have to convince ourselves that we
fit into the context of human history.  Write it all down,"
he said, referring to the single lasting legacy of ancient Iceland,
the sagas--the most complete profile of any Western medieval society.
The sagas present a vast literary and historical portrait of the
feuds, battles, seductions, and triumphs of early Icelandic society.
They almost always begin with long lists of genealogical information,
and they are alive for Iceland today because, unlike Old English,
Swedish, or Norwegian, all of which have changed dramatically,
Icelandic has remained essentially the same.  If you can read an
Icelandic magazine article today, you can read the saga about
the warrior Egill Skallagrimsson, written in the thirteenth century.

     "This was our means of survival," Stefansson said.
"People were huddled on mountains in the howling wind.  For
eleven hundred years, everything in Iceland has always been about
the lists of names.  It's what we all have in common.  Without those
links we really have no heritage."   

5.  

      Geneticists have been relying on family histories to explore
the roots of human disease at least since the mid-nineteenth century,
when Darwin's cousin Francis Galton coined the term "eugenics,"
one of the most heavily freighted words in the history of science.
Galton was convinced that such characteristics as intelligence
were inherited and that a society could breed for them the way
you breed an Irish setter or a Vidalia onion.  For years, Icelandic
researchers have recognized the special characteristics of the
country's segregated DNA, but it was Kari Stefansson who first
seems to have understood what Iceland could contribute to the
current frenzied hunt for the genetic causes of human illness.
The idea for a computerized database that would incorporate all
of the country's essential health and genetic information has
the unwavering support of, among others, Prime Minister David
Oddsson, and it has met with strong approval in polls.  One obvious
reason for that support is the potential payoff: pharmaceutical
companies are expected to spend enormous sums--billions of dollars--if
Decode is able to identify genes that contribute to major diseases.
More than one Icelandic politician has expressed the hope that
the Decode database might do for Iceland what North Sea oil did
for Norway.

     Yet scientists in Iceland, and many abroad, have become enraged
by the notion that such a treasure could simply be handed over
to Decode.  They argue, often bitterly, that surrendering such
a resource to a private company will jeopardize patients' privacy,
violate long-established standards of medical ethics, and prevent
other researchers from taking advantage of this invaluable new
tool.  There is also a widely shared belief that if a bonanza is
to be made from the DNA of the Icelandic people most of the profits
should go to the nation, and not to Decode.  

      "This is what colonial treasure hunters have done for
hundreds of years," I was told by the geneticist Mary-Claire
King.  Like many of her colleagues, she sees the promise of the
research but also worries about the potential for harm in such
a vast arsenal of biological data.  "It is not that it wasn't
important to find gold, diamonds, and minerals in Africa or Mexico,"
she said.  "It was taking the treasures away and the absolute
evisceration of the societies that were there which were wrong.
This is the twenty-first-century version of that.  It is an elegant
approach, which could yield much information--nobody disputes
that.  But there is a price.  And if the price is the destruction
of the field of genetics in Iceland--or the loss of the trust
patients put in their doctors--then perhaps elegance isn't all
that matters."   

     Stefansson concedes he was not prepared for opposition of that
sort, and he acknowledges that early versions of the database
plan were badly flawed in their naïveté.  But he dismisses
current criticism mostly as the prejudice of competing scientists
and partly as a reaction to anything far-reaching and new.  "Now
it has become like the Sturla period in Iceland again,'' he said
one day, referring to a famous saga of the thirteenth century,
when warriors dismantled their commonwealth and splattered each
other's brains against stone walls.  "I am besieged by little
people.  This is a fascinating controversy and I understand it
well.  But these few people, opponents"--he spat the word
out as if it were a rusty nail--"are scared of change and
unwilling to lose their standing in the scientific community.
But remember one thing while you are ingesting their propaganda:
those who are opposed to what we are trying to do are a small
group.  They are not important.   And they will lose."   

6.

            Stefansson has white hair and a white beard that are short
but fashionably messy, and his usual choice of clothing--muted
earth tones blended with black and gray--makes him look rather
like the carefully dishevelled director of an experimental theatre
group instead of what he is: a physician, an entrepreneur, and
a professor.  He is intensely competitive; he plays basketball
regularly, and "with an extreme and sometimes ugly need to
win," according to one of his colleagues.  Lately, he has
lost so much weight (from the basketball and a lot of worrying)
that his secretary provides him with a daily bright-pink protein
milkshake and makes sure he drinks it all.  


     Stefansson's father was Iceland's most famous radio personality
and a frequently published writer; his wife raised their five
children.  Stefansson was evidently audacious from the start.  When
he was twelve, his father made him an offer: if he learned to
type he could transcribe all his father's book manuscripts.  For
several years, Kari had a great summer job; then one day his father
happened to read through one of his published books.  "He
found that I had changed a few sentences," Stefansson told
me.  "The changes were not big, but they were absolutely necessary.
That wasn't the way he saw it, of course, and my career as a typist
ended that minute."

      Stefansson spent fifteen years at the University of Chicago,
where he became a tenured professor of neurology.  He returned
to Iceland very briefly, to run the Institute of Pathology, then
the country's most distinguished scientific research organization,
and afterward spent five years as a professor of neurology and
pathology at the Harvard Medical School.  

     In the early nineties, after travelling to Iceland to do research
on his special area of interest, which is related to multiple
sclerosis, Stefansson realized that the island was an ideal place
to pursue the origins of almost any common disease in which a
genetic component played an important role.  Although genetic diseases
such as cystic fibrosis or sickle-cell anemia are caused by the
mutations of individual genes which can be best traced in families,
the most common illnesses, among them cancer, heart disease, and
many psychiatric disorders, can be fully examined only by studying
a much larger population.  Those diseases almost certainly have
an environmental component as well as a genetic one, and such
complexity makes them incredibly difficult to understand.  There
are three billion pairs of chemical bases--the building blocks
of DNA--in each person's body and as many as a hundred thousand
genes in the human genome.  The process of deducing the causes
of a common illness is one of the most daunting ever faced by
medicine.

      Geneticists recognized long ago that the people of Iceland,
despite their relative seclusion, developed serious modern conditions,
like cancer and heart disease, in roughly the same proportion
that people do in other industrialized countries.  Iceland is not
a bizarre offshoot of humanity--such as, for instance, the tiny
Atlantic island of Tristan da Cunha, where nearly a third of its
three hundred residents have asthma.  "Iceland reflects the
gene pool of Northern Europe in about 800 A.D.," Iwas told
by Jeff Gulcher, an American former doctoral student of Stefansson's,
who is now Decode's chief of research and development.  "This
is not a rare, special twig of evolution.  It is a central branch.
When you look at disease here, it ought to be able to tell you
much about the cause of human illness in general."

     That is what Decode is counting on.  In 1996, Stefansson set
out to raise capital at a time when investors had become skeptical
about the many unfulfilled promises made by companies claiming
that genetic research would solve the ills of humanity.  He was
a forceful salesman, however, and raised twelve million dollars
in three months, at which point he left his job at Harvard, returned
home, and began working with physicians and their patients, trying
to discover disease-prone genes.  

7.

      decode soon managed to provide two hundred and fifty well-paid
research jobs in a country that earns nearly three-quarters of
its income from fishing and has struggled to build a broader base
for its economy.  (Iceland's entire federal research budget--sixty-five
million dollars in 1997--is less than the amount dispensed for
research so far by Decode.) "Kari was treated like a god
when he returned," I was told by Jorunn Erla Eyfjord, who
is the head of molecular genetics for the Icelandic Cancer Society.
Eyfjord, who carried out essential work that helped locate the
second breast-cancer gene, is a strong critic of Stefansson's
plan for a comprehensive database.  "People just acted like
he had discovered medicine and brought it to Iceland."

     People grew more excited when, in February of 1998, Decode
signed a contract with Hoffman-La Roche, among the largest agreements
so far reached between a genomics company and a major pharmaceutical
firm.  Roche, which is based in Switzerland, agreed to pay Decode
more than two hundred million dollars over the next five years
if the company manages to identify genes involved with many of
the world's most potent diseases, among them schizophrenia, Alzheimer's,
stroke, heart disease, and emphysema.  Roche will get the right
to develop diagnostic tests and, it hopes, drugs based on any
genes that Decode might discover.  In return, the company has promised
to provide any such tests and drugs without charge to all Icelanders
who need them.  It is a potentially lucrative arrangement for both
sides.  

      Once the information from the comprehensive database becomes
available (Stefansson thinks that this will not happen until at
least two years after Decode gets its license), there is little
question that many other companies--and possibly some nations--will
pay dearly for what it could generate.  In the past, drugs were
discovered almost by chance.  Researchers would identify the proteins
that seemed to be associated with a disease--it was often guesswork,
intuition, or luck--and then they would try out thousands of animal
and plant compounds to find something that blocked that protein
without doing serious damage to the rest of the body.  Cancer drugs
can be especially dangerous because to kill tumor cells one often
has to use chemicals that destroy many healthy cells, too.  Genomics--the
study of the genetic heritage of a species--is supposed to provide
a sophisticated alternative to that.  In theory, at least, once
it is discovered that a gene can cause or play a role in a disease,
scientists should be able to understand the molecular basis for
that disease--the chemical blueprints--and then design drugs to
repair or even prevent the damage.  That is why pharmaceutical
companies are investing billions of dollars; the potential bounty
for each gene will be immense.  There will be many hurdles: genes
come in all shapes and sizes, and while some provide obvious openings
for drugs others do not.  But every time a gene is discovered to
play a significant role in a disease the financial and health
implications are going to be enormous.

8.

     Soon after Decode signed its deal with Roche, the company's
cluttered labs filled with expensive genesequencing equipment
and two dozen of the latest robotic PCR, or polymerase- chain-reaction,
machines.  PCR is the workhorse of the genomic revolution, because
the technique is used to amplify a tiny amount of DNA and permit
researchers to catalogue and then compare it.  Young Icelandic
scientists began returning from M.I.T., Berkeley, and Harvard,
largely because there was at last something to come home to.  The
cheerful, open labs at Decode, which look more like commercial
kitchens than like medical-research facilities, have turned into
the best place in Iceland to do advanced molecular research.  

      The strategy has been this: the company works with physicians
across Iceland in order to study diseases ranging from diabetes
to colon cancer to psoriasis.  Doctors take blood from consenting
patients and send it to the company with an encrypted number replacing
the name of the patient.  The researchers at Decode process the
DNA, looking for important genetic markers for each patient.  The
raw genetic facts (called genotypes) are then compared to the
physical condition of each patient (the phenotype).  At the same
time, Decode turns to its genealogical database to search for
familial patterns of illness.  That way, specialists are able to
make highly sophisticated statistical interpretations of genetic
relationships among people, and to find the best places in the
incomprehensibly large universe of human DNA to look for genes
that may cause illness.  

     Decode had some initial success by identifying the location
of one of the central genes responsible for a syndrome called
familial essential tremor, or F.E.T.--a degenerative neurological
condition that causes uncontrollable shaking of the arms and the
head, and affects millions of people.  That work was completed
before Decode assembled its genealogical database.  More recently,
in its hunt for the molecular roots of multiple sclerosis, Decode
has managed to narrow the search to one piece of DNA with three
or possibly four genes on it--a bit like scouring the earth for
a grain of sand and reducing the possible locations to a single
beach.

      In the summer of 1998, the company, together with one of Reykjavik's
most prominent physicians, began to investigate the origins of
endometriosis, which is the leading cause of infertility in the
United States; it occurs when cells from the lining of the uterus
appear in other areas.  Endometriosis has been regarded as, in
Stefansson's words, "a hideous, baffling, and completely
sporadic disease," because "nobody could say why some
women get it and some do not."   Now Decode is in the midst
of computer-generated detective work on the subject.  After replacing
the names of the women in the study with secret I.D.  numbers,
Decode ran the numbers through its genealogy database.  With one
glance at the family pedigrees of the patients, even an uninitiated
observer could see that many of them were related.  The results
would have surprised the women themselves.  (Despite Iceland's
sophisticated sense of family history, few people there can name
their fourth or fifth cousins.  The database, however, connects
distant relatives in minutes.) "We take blood from the patient
and scan it," Gulcher,who is the energetic floor leader of
the Decode lab, told me.  "We look at DNA of their healthy
relatives to see if it's different.  Then we can do a statistical
analysis to see what they share with their cousins, for example.
Do they share the same sequence more commonly than you would expect
cousins to share genetic information?"  Mendel's laws of inheritance
tell you that cousins should share DNA one- eighth of the time.
A larger proportion suggests that something may be worth investigation.
"This way we winnow and winnow till we find the places they
have in common which could be responsible for this disease,"
Gulcher said.  

     One day, almost as a lark, Stefansson set out to do the same
sort of research on longevity.  It has been generally assumed that
there are at least some genetic reasons that cause certain people
to live longer than others.  But does that mean that these people
are just lucky enough to have none of the genetic mutations or
other problems that kill people at earlier ages, or are there
actually stretches of DNA that instruct genes to help people live
a long time? 

      "Right before I left the University of Chicago, in 1993,
I admitted the oldest living American to the hospital," Stefansson
told me.  "She was a hundred and sixteen.  I was just wondering
why she lived so long, and I asked her.  She told me she gave up
drinking when she was ninety.  That was cute but obviously wasn't
the reason.  Still, you do always wonder what makes them different."

     So Stefansson turned to the computer.  He and Gulcher selected
the five per cent of Icelanders among the hundreds of thousands
in their genealogical database who had lived the longest-- most
of them over ninety.  The database allowed the two scientists to
seek an answer to a simple question: Are these people who live
so long related to each other more often than the average in Iceland?
The answer quickly became apparent.  People over ninety are much
more closely related to each other than people in the general
population are, and their children are more likely to live longer
than the children of others.  That provides strong evidence that
the trait is inherited.

      The next step, of course, is to find out how--and that, of
course, is where information from the controversial database could
prove so valuable.  If you could compare the actual DNA of people
who live longest with the DNA of their dead relatives (and then
search the genealogy for more comparisons), it would greatly enhance
the possibility of finding a shared, special gene or set of genes
able to influence longevity.  That sort of unified theory of genetic
research has always been Stefansson's ultimate goal.

9.

      When the bill to establish the Icelandic Health Care Database
was introduced, last spring, people were astonished by the haste
with which Stefansson and his allies in the government had acted.
There did not seem to be any room for discussion or disagreement.
"That is when we all just got off the train," Sigmundur
Gudbjarnason, a professor of biochemistry at the University of
Iceland, told me.  Gudbjarnason, who is often referred to in Reykjavik
as the founding father of Icelandic biotechnology, helped start
a movement to oppose Stefansson.  "My whole life has been
dedicated to promoting science in Iceland in every feasible way,"
Gudbjarnason said over coffee late one afternoon.  "When Decode
was started, three years ago, I was elated.  The problems arose
when they came up with this database.  It ignores the rights of
privacy, and patients' rights.  It will turn Decode into a scientific
monopoly.  Society is now so dominated by profit.  It's not about
science anymore, it's about money."

     From the beginning, Icelandic scientists
have wondered how they will compete for research dollars with
a company that has access to all the essential genetic information
that the country can offer.  They complain that Decode is about
to receive what the highly respected population geneticist Einar
Arnason described to me as "the greatest handout in the history
of this supposedly competitive business of scientific research.
If you forget the bad science it will encourage, you can think
about this: Iceland gets a few hundred mostly technical jobs;
Decode stands to earn billions of dollars, maybe more.  Sound fair
to you?"

    Of all the questions that have surfaced since the database
plan was first proposed by the government, however, none is mentioned
as frequently or with as much emotion as the privacy issue.  Many
people fear that any such database--which will contain a staggering
collection of highly personal information on every individual
in Iceland--could be invaded and misused with ease.  Critics also
fear that as time goes on, and the map of the human genome becomes
clearer, this personal information will become even more valuable--and
subject to abuse--than it is today.  

      Stefansson dismisses these concerns as pettiness on the part
of a small-minded medical community.  "Our right to develop
medicine does not come free," he told me.  "We have a
moral obligation to do what we can to move forward.  There are
opposing needs: to protect privacy and to push science forward.
There are times when they clash.  Medicine today would simply not
exist if privacy was the only need, the only right that anyone
ever considered important."

     Stefansson has always maintained that an exclusive contract
was necessary to raise enough money to do the job, and he promises
that Icelandic researchers can use the data without charge as
long as they are not collaborating with a competing firm.  "I
just don't have the money to construct this database if somebody
else can wait till we are done and then come along and take the
rights to it," he said, adding that the plan simply wouldn't
work if all two hundred and seventy thousand Icelanders have to
give consent for each experiment Decode hopes to carry out.  That
reverses the usual rule of informed consent; it assumes that people
are research subjects unless they specifically request exemption;
currently, though, in the endometriosis study and in many others,
each person working with Decode has to agree in writing to do
so.  

10.

      By the time I arrived in Reykjavik, a month before the decisive 
parliamentary vote to create the healthcare database, the quarrels 
between Stefansson and his opponents, which had come to include 
most of the nation's research community, were constant, ugly, and 
very public.  What had begun last spring as a political deal that would 
have passed without debate had suddenly become the most contentious 
issue in Iceland.  After a few initial phone calls to scientists, I was 
deluged with E-mail from people who wanted to tell me about the 
poisons in Stefansson's plan--and in his soul.  A Web site devoted to 
fighting the plan had appeared.  No day passed without a depth charge 
being tossed into the newspapers.  While I was in Reykjavik, and after
I left, each side called me often to report the lies, plots, and scientific 
inadequacies of the other.

     "Kari Stefansson shoved this bill down our throats," said Eirikur Steingrimsson, a molecular biologist at the University of Iceland 
whom Stefansson described to me as the most brilliant young scientist 
in Iceland.  "That is what we object to the most.  If he had done this 
the correct way it would have been over with already.  There would 
not have been any opposition."   Steingrimsson said he was particularly
offended by the implied notion that Decode would become the de-facto
funding center for Icelandic genetics.  "There is no way on this earth
that I am going to Kari Stefansson to apply for my funds," he said.

      Stefansson had campaigned for months on behalf of the database
plan, appearing almost without pause on television and radio.
In December, the week before the final vote in the Althing, he
decided--"as much as it's agonizing for an impulsive man
like me to keep his big mouth shut"--that he would no longer
defend himself even from the many personal charges being made
against him.  After I left Reykjavik, he told me, over the phone,
"The people still support me and the doctors think I'm the
Devil.  So it's time to just let the future happen."

     As the vote neared, the emotional nature of the debate spread
along the Internet, through the world's close-knit genetics-research
community.  Richard Lewontin, a professor of zoology and biology
at Harvard, suggested publicly that "a boycott of scientific
coöperation with Iceland might be an appropriate measure
if this bill is passed," but nobody rushed to support him.
Many researchers, even some who believe the plan has merit, felt
troubled.  They say that once the database is approved it will
be as if an arrow had been shot into the void: nobody can guess
where the process might lead.

      "We are not just talking about creating a market for
Iceland's DNA," I was told by Henry T.  Greely, who is a professor
of law and a co-director of the Program in Genomics, Ethics and
Society at Stanford.  "This isn't fish or lamb's wool we are
dealing with here.  This particular product is the spirit of the
human species, and before Iceland turns its DNA into a commodity--and
one that they may not even earn their fair share of money from--I
just hope they know what they are doing."   

     Support for the health-care database from Prime Minister Oddsson
was essential.  Yet, after voicing strong initial belief in its
promise, Oddsson became silent.  Many people began to believe he
was looking for a graceful way to back out of a plan that had
become politically sensitive.  When I saw him in Reykjavik, however,
he quickly made it clear that nothing could be less true.

      Oddsson is a contemplative man who writes poetry, considers
himself a conservative, and is very popular.  "Obviously,
this is all about trust," he told me one blustery Sunday
afternoon when he was alone, working in his office.  "In Iceland,
trust is everything.  I once saw a documentary about a famous defense
attorney.  He was asked, `How do you choose a jury?' He said, `First,
I take out all people who wear bow ties--because they are not
likely to be part of a team.  Then I get rid of everyone of Northern
European descent.  They are too trusting and they all believe in
authority.  When the police testify, Northern Europeans and Scandinavians
tend to believe they are telling the truth.' At first I was outraged
and considered it a complete stereotype.  But I sat there and thought
about it for five minutes and I realized he was completely right.
I happen to be proud of that quality and I think it says something
about why we are willing to put ourselves forward and make this
database work.  It's not just the dangers that deserve to be considered
but the possibilities for good--for Iceland and maybe for humanity.
I know the doctors are very angry.  And I wish they weren't.  But
many of their complaints just aren't valid.  We could have passed
this bill six months ago after a day of debate, but we wanted
to hear how it could be improved, and we listened.  Even the biggest
opponents, if you can get them to calm down, will tell you it's
a better bill now than it was in April.  But they are not happy,
and I suspect some of them never will be.  So the question for
me is simple: should the doubts and fears of the minority outweigh
the seventy per cent of parliament and the sixty per cent of the
public who want to do this? We have discussed the plan in our
press all year.  I doubt any issue in the history of this republic
has received as much attention.  The response has been clear.  Go
talk to normal people on the street.  Let them tell you what they
think."   

     I took his advice, and made a highly unscientific pilgrimage
to the Kringlan Shopping Mall, which, except for its self-described
distinction as "the mall at the top of the world," might
just as well be in Paramus; it has that familiar mix of chain
stores, hamburger joints, and cinemas partial to American films.
My survey could never be published in a peer-reviewed, scientific
journal, but for anybody who has done this sort of thing in America
the outings were revealing: nobody was too busy to answer my questions.
Every person knew what I was talking about, and most knew about
it in impressive detail.  I asked all of them the same questions:
Did they support the database, and would they be willing to be
listed in it? 

      Of forty people, two had no answers, two were opposed, because
they just didn't trust computers, and two said they needed to
think about it.  The rest said they would sign up tomorrow.  "It
is so silly to talk about privacy here," said Thor Palmisson,
an engineer.  He then took out his wallet and showed me his Visa
card, an air- traveller card (for Saga Business Class on Icelandair),
and a video- rental card.  "Every one of these has my national
I.D.  number on it," he said.  "You can't rent a video
without it, and you can't move or get a job.  The numbers are easy
to figure out.  To me, this seems it's all just a giant attack
on Kari.  What is it that they are accusing him of? Is he trying
to get rich? Fine, that's O.K.  with me.  Is he trying to get famous?
I can stand that, too.  I have seen him discuss this issue more
than once.  I don't believe he is motivated by greed.  If he takes
a few drops of my blood and gets rich curing cancer, that's absolutely
fine with me."

11.

     The bill passed the Althing on December 17th, by a margin of
thirty-seven to twenty (with six members not voting).  Instead
of ending the battle over the stewardship of Iceland's gene pool,
however, the campaign against Decode become even more intense.
The legislation was "a totalitarian act which casts a dark
shadow over Iceland in the international scientific community,"
a leftist member of parliament, Hjorleifur Guttormsson, said that
day.  Overwhelmed by their defeat, critics compared the database
project to the Nazi experiments with racial hygiene and the exploitation
of poor blacks in the Tuskegee study.

      "Anyone who can mention Nazi experiments and this database
in the same sentence does not deserve to live in Iceland,"
Stefansson told me on the telephone as the opposition rhetoric
veered out of control.  Earlier, I had asked him if he ever regretted
his decision to come home.  "Not for a minute," he replied.
"This happens to matter more than any of us do."Lowering
his voice almost to a whisper, he went on, "You know, my
brother is schizophrenic.  I am not saying that that is what motivates
me.  It isn't.  But, of course, it is there, hovering in the background.
And I always know it.  I can never know whom it will affect.  Maybe
my son, my cousin, a grandchild.  You can't know that.  It's a barbaric
truth."

     He went on to say, "I need to convince everyone I was
not given a gift.  I know that.  But look at it logically.  Should
the government run this database or should private enterprise?
Let's assume that the government has no idea how to create value
from an enterprise like this.  That is my assumption--after all,
I did not spend fifteen years at Milton Friedman's university
for nothing....  So does the government have the right, after I
put this together, to hand it over to somebody else? Yes, technically
it has the absolute right.  But this is my intellectual property."

12.

      Stefansson will spend at least the next
six months negotiating with the government over the terms of the
license.  During that time, he will have to improve his relationship
with many people he has alienated in the past year: scientists
in Iceland are already threatening legal action on the ground
that the bill offers Decode an unfair monopoly and that it violates
human rights in its use of research subjects.  Stefansson understands
that he will need full coöperation from Iceland's physicians,
too.  The database will need accurate information--on patients,
their diseases, symptoms, medications, and treatments--or it will
be useless.  "But don't forget the possibilities here,"
Stefansson said on the day the bill passed.  "This fails.
We go bankrupt.  We lose money.  Our investors lose, too.  Or possibly
we barely make it.  Or maybe we make a fortune.  There are real
risks.  And the people who criticize me--they have absolutely no
idea what they are talking about.  None."

    The fact is, however, that many of them
do.  The field of genomics will certainly grow rapidly, and not
much imagination is required to see how genetic information could
be misused.  To take one obvious concern, should insurance companies
or employers have the unfettered right to purchase data that tell
them who is most likely to die from coronary-artery disease or
cancer at an early age? That isn't a problem in Iceland, where
access to healthcare is guaranteed, but it would be in most countries.
And what about a genetic trait that increases the viral abilities
of H.I.V.? Or makes you more likely to become an alcoholic or
addicted to drugs? Stefansson's research into longevity is novel
and exciting, but if Decode discovers genes for longevity most
insurance companies would be eager to know who has them.  What
if it turns out that you don't? 

     "None of these questions can be answered," Sigurdur
Gudmundsson, Iceland's recently appointed Surgeon General, said.
"I have done loops in the air all year long.  And it has been
painful.  Of course there are serious dangers.  Is it scary? Very.
But we have to find a way to make this happen.  The benefits just
outweigh the problems.  It doesn't mean there are no doubts.  We
are walking into a new world.  But I don't think it is wild to
say this may turn out to be a tool like none other.  And I don't
think this country can just sit here and say, Nope, sorry, we
are going to stand on rules that existed in a different era for
a different world."   In the end, Gudmundsson, like many others
who are just as thoughtful and just as anxious, believes that
that would be the most foolish risk of all.