Finland is a land of lakes and forests and rushing wind. Helsinki, the capital, on the southern coast, lies on the same latitude as Anchorage, Alaska. Finland extends as far north as Alaska, but the influence of the Gulf Stream makes Finland milder. Helsinki is not too different in appearance from other great cities of Europe. Its pool of DNA must be the most heterogeneous in Finland because Helsinki is a crossroads, past and present, to and from other peoples of Europe.
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Most population geneticists agree that the main migratory stem, well before the budding of the Finns, has its roots in Africa. They also agree, if with less unanimity, that the most common genetic variants found in contemporary human beings are ancient in origin—at least 50,000 years old. It follows that the pioneers of Finland carried with them the propensities for all the common diseases plaguing people today, such as heart disease, arthritis, Parkinson’s, and asthma. These are called complex conditions because their genetic and environmental causes are multiple and murky. According to the “common disease/common variant” theory, it’s not necessary that the diseases themselves be old, just that the alleles, the predisposing variants, are old.
Two thousand years ago farmers inhabited the southern and western coasts of Finland. Then, as now, meat and dairy foods were the mainstays of the diet, all the more so in a land where raising crops was hit-or-miss. Then, as now, a minority of Finns would have trouble digesting the milk and cheese because of a gastrointestinal condition known as lactose intolerance. It’s caused by a gene variant that makes too little LPH, an enzyme that breaks down lactose.
Lactose intolerance occurs in populations around the world. In Asia and Africa rates are as high as 80 percent. The most frequent form of the disorder develops in adulthood. Nursing children are seldom affected because mother’s milk is vital for survival. By the same reasoning, northern people need the benefits of milk proteins more than other groups and therefore show relatively low rates of lactose intolerance—in Finland it’s about 18 percent.
In the late 1990s Leena Peltonen and her team, capitalizing on Finnish homogeneity, unlocked the key to the condition. They found that a tiny change in the sequence of DNA, a change of a single letter, from a C to a T, causes the gene to lose its capacity to make the enzyme. Peltonen found the identical alteration in groups and races who by geography were far apart. That finding suggested that the allele occurred before human populations branched out from Africa.
Adult lactose intolerance appears to have been the normal condition for Homo sapiens 100,000 years ago. The mutation that the majority of Europeans carry, the version of the gene that allows them to eat ice cream and crème brûlée without distress, emerged later. Initially the people who drank milk from cows had something unusual about them, but by chance the new allele improved the welfare of human beings on their way north. The gene helped a pale-skinned strain of farmers adapt to the European winter, when agriculture failed.
Peltonen likes this story because it shows how DNA drawn from a small corner of the world contains a message of universal significance. The story also demonstrates, with a twist, the common disease/common variant theory. The alleles for lactose intolerance and lactose tolerance represent time-tested genes of the human race, just the opposite of the alleles of the Finnish Disease Heritage, which are native born and recent.
During the 1500s about 250,000 Finns inhabited the coastal zone of what was then Swedish territory. Concerned about the unguarded border with Russia, King Gustav of Sweden induced Finns to migrate north and east into the pine forest. After the colonists established small farms and villages along the eastern frontier, immigration stopped, and the region remained isolated from the rest of Finland for centuries.
With an initial population in the several hundreds, the situation was ideal for what geneticists call genetic drift and founder effects. Mutations that were too scarce to make a dent on a larger population were enriched in the small but expanding group of people in East Finland. Most of the disorders that transpired were recessive, meaning that two copies of a flawed gene had to be inherited, one from each parent. Although people did avoid marrying their relatives, after 5 to 10 generations it was almost impossible that bloodlines would not have crossed in spouses from the same area.
From Helsinki to the Kainuu district in East Finland the distance is some 300 miles, pleasantly covered on smooth highways. In the last half of the journey the road passes banks of purple lupine, thick stands of conifer and birch, big clean lakes with a cottage or two on the shore, fields with little hay sheds in the center, then more woods and more lakes and more fields. The landscape, like the DNA, is homogeneous. The only exclamation points are the tall steeples of the churches, one for each widely spaced town.
About 400 years ago a new gene arose in the Kainuu district, an allele with no ill effect on its bearer, who was either a man named Matti or possibly Matti’s wife. In later generations, when a child received a copy of the gene from each parent, it seeded a disease called Northern epilepsy. Reijo Norio, a physician who has chronicled the Finnish Disease Heritage, refers rather fondly to Northern epilepsy as “an extremely Finnish disease.” Its symptoms were first described in a 1935 novel that takes place in Kainuu. A character, a beautiful and intelligent boy, developed “falling sickness” and “lost his wits.”
When Aune Hirvasniemi, a pediatric neurologist at the local hospital, began to track the disease in the late 1980s, she found 19 patients in a handful of families. No one had connected the cases before. Hirvasniemi consulted the records of the Lutheran Church, which for 250 years had written down the comings and goings of Finns in each parish. Creating a medical pedigree for Northern epilepsy, she followed it all the way back to its founder, Matti. She published her discovery of the epilepsy in 1994, the same year that researchers in Finland identified its gene on chromosome 8.
Hirvasniemi is a smiling woman with penetrating blue eyes. “I studied this because I wanted to show something new,” she said modestly. “It was not my daily work.” Indeed, after earning her Ph.D. in medical genetics on the strength of the find, the doctor resumed her pediatric rounds, shunning awards and speaking invitations. She had not heard of any new cases of Northern epilepsy in more than a decade, which she believed was partly because Finns now migrate out of Kainuu, an economically depressed region. At least half the hay sheds in the fields are abandoned and crumbling.
“But the gene is still alive in Finland,” Hirvasniemi said. About one in seven Finns is a carrier of at least one of the special disorders. Partly because of genetic counseling, but mainly because of luck, only 10 newborns a year are stricken with the distinctive conditions.
Norio, a medical geneticist, was an early investigator of the disease heritage. In the late 1950s he was a pediatrician like Hirvasniemi and curious about a lethal kidney condition that he named congenital nephrotic syndrome. Traveling around the country, Norio deduced its genealogy from family accounts and church records. Afterward he became a genetics counselor in Helsinki. Now semiretired, Norio receives visitors in his book-lined office and, over coffee and pastries, muses on the diseases that he calls “rare flora in rare soil.” He has written a book titled The Genes of Maiden Finland.
Other people might feel stigmatized by an unusual genetic heritage, but Finns take pride in it. That is something of a psychological turnabout. Like many people identified as belonging to a racial group, Finns used to be defensive about their biological identity, which was disparaged by their domineering neighbors. About the Mongol racial designation Norio wrote: “This characterization was then used as an abuse by those who wanted to repress the Finns into a lower caste. Today speaking about races is genetically out of date.”
Norio refused even to entertain the notion that Finns could be called a race of people because of their genetic idiosyncrasies. “Finns are just Finns,” he insisted, “a marginal population at the inhabited edge of the world.”
Finland’s genetic uniformity, which facilitates finding disease genes, has served science far beyond its borders. In an approach similar to Peltonen’s discovery of the allele for lactose intolerance, Juha Kere of the University of Helsinki and his colleagues have linked versions of Kainuu genes to asthma. A paper they published in the journal Science several months ago has gotten a lot of attention, because after detecting a suspect allele in Finnish families with asthma, the researchers found the same gene in families with asthma in Quebec.
Even more interesting, the allele is a variant of a gene that might actually be part of the disease process. In exploring complex disorders like asthma, diabetes, cancer, and heart disease, scientists can find genes that are associated with the condition: Such and such a gene is plucked out by computer analysis on the basis of its frequency. But that isn’t always terribly helpful, and it doesn’t necessarily grab the attention of pharmaceutical companies. Usually it’s but one of many genes associated with the disease, and often its function is unclear. The gene may be useful for diagnosing the condition or projecting the risk of disease in people who are healthy, but there isn’t a lot of profit in testing people.
The asthma gene found by Kere and his colleagues—which they immediately patented—is different because it expresses in bronchial tissue, where drugs might reach it. Investors and pharmaceutical companies noticed because asthma medications are a big business. With funding from foreign backers and the Finnish government, the scientists formed a small company, GeneOS, in Helsinki, where they are working on how the gene and its protein work.
