“It takes a long time to understand a new human molecule,” cautioned Tarja Laitinen, the chief scientific officer of GeneOS. Opening a freezer in the company’s small laboratory, she pulled out a test tube containing a grayish substance. It was pure frozen DNA—concentrated copies of the Kainuu asthma gene. “Investors are sometimes concerned that we [Finns] might be different,” Laitinen said. “Sometimes they ask: ‘Will a drug that works here also work in the U.S.? Shouldn’t we do the studies in the U.S.?’ So when we find the same haplotypes [blocks of DNA sequence around the gene] in Quebec, we are proving the common European root.
“Besides,” she added, “we’re too young as a species to be different. What’s different are the environmental factors.” What sparks asthma attacks in one society may not be the same in another.
Laitinen pointed out yet another advantage of doing science in Finland. “The strength for the Finns is both the homogeneous genes and the homogeneous environment,” she said. “Diets are similar. The same supermarkets are everywhere. In health care, people are treated the same everywhere.” This is useful because when environmental factors can be held constant in a study, genetic factors may surface more readily.
“When we were collecting blood samples in Kainuu,” Laitinen continued, “people knew that the benefits would be a long time coming. But Finland is a good place for medical research because people feel positive about it. . . . So as a scientist I value the environment of Finland more than the genes.”
It’s a short walk from the GeneOS office to the National Public Health Institute of Finland, where Jaakko Tuomilehto heads the Diabetes and Genetic Epidemiology Unit. For 10 years Tuomilehto has collaborated with American investigators at the University of Southern California and the University of Michigan on a gene-mapping project for type 2 diabetes, formerly known as adult-onset diabetes. It’s a worldwide disease. Patients have numerous health problems because their blood-sugar levels are too high. Many eventually need insulin shots, like the children and young people who have the harsher type 1 diabetes.
The big-ticket item in the budget—$1 million a year—is to scan Finnish DNA for promising gene variants. That job is performed at the National Human Genome Research Institute in Bethesda, Maryland. Tuomilehto’s researchers enrolled subjects and collected blood from families throughout Finland.
“In the United States you are so heterogeneous you can forget about genetic studies,” he said. “There’s less of that here.
“Second, our records are the best. In most other countries the records are lousy if you want to trace back relatives. On my computer I can get, with the permissions that I have for each patient, the records on all past diagnoses, all hospitalizations and prescriptions. Also socioeconomic information like taxable income, ownership of a car, education, and marital status.”
Nonetheless, because diabetes is an extremely complicated disease, the results have been disappointing. “It’s difficult,” said Tuomilehto. “We realize we won’t get major genes quickly.” The gene variants that have been identified so far contribute only weakly to the risk of contracting the disorder. In other words, type 2 diabetes could never make it into the Finnish Disease Heritage, where a change in a single gene is decisive.
Given that the gene variants for diabetes may remain elusive for a while, Tuomilehto has concentrated on the environmental aspects of the disease. Obesity, he pointed out, is the leading risk factor for the condition. Genes interact with the environment. According to this view, whenever susceptible genes meet too many calories, weight goes up and diabetes follows.
That might help explain the postcard Tuomilehto has pinned to the wall behind his desk. It shows an enormous young man lying on his side on a beach. “Come to California,” it reads, “the Food is #1.”
When Finns brood over their history, their dark thoughts turn east, to the monolith of Russia. Throughout the 19th century, czars ruled the Finns. Under cover of World War I and the upheaval of the Russian Revolution, Finns declared their independence and made it stick, but the Soviets grabbed back a slice of territory after World War II. Only since the fall of communism have Finns been able to relax.
The border between Russia and Finland divides a region known as Karelia. Historians say the line has shifted nine times during the past 1,000 years, and no doubt genes have flowed freely as well. Compared with the Nordic-looking Finns, the Karelian type of Finn, according a source, is “shorter limbed, rounder faced, fair haired, gray eyed.” That could well describe a man named Aimo, who lives in the Kainuu district of East Finland.
Aimo’s last name is Karjalainen (“the Karelian”). He is 43 years old. He had a heart attack a year ago and a triple bypass operation last May, in which his prematurely diseased arteries were replaced by veins in his leg. In July he went for a checkup. An affable, muscular fellow, he indicated that he was recovering fast.
“Feels good,” Aimo said, which was the extent of his English. He unbuttoned his shirt to show the pink scar running down his chest. His mother’s family is from the Finnish side, and his father is from East Karelia, in what is now Russia.
In the 1970s the health authorities in Finland addressed an alarming statistic: Their country has the highest rate of mortality from heart attacks in the Western world. An intense public education campaign targeting the North Karelia district, just south of Kainuu, introduced Finns to low-fat diets. The campaign succeeded in lowering both cholesterol levels and heart fatalities. Yet the country’s physicians and researchers knew more had to be done.
“It’s my life’s work to solve the problem of heart disease,” said Jukka Salonen, an epidemiologist and gene hunter at the University of Kuopio. “Why do eastern Finns have the highest heart-attack mortality rate—in males—in the world? We still do. It’s come down, but . . . ”
Salonen went to an easel and with markers charted the rise of deaths in the 1950s, their peak in the late 1970s, and then a decline to 2000. He drew the same curve lower down for the rates in southwestern Finland. Still lower down on the chart was a parallel curve for mortality over the same period in the United States.
“In eastern Finnish men there are risk factors—smoking, high-fat diet, high cholesterol and blood pressure, but they’re not that high,” he said. “We knew that in the 1970s. Today the differences between eastern and western Finns, in terms of diet, have disappeared.” Yet mortality from the disease in the east is still 1.5 to 2 percent higher. “More than half of the heart-attack risk is explained by other things,” Salonen said. “We think it’s genetic.”
As many as 500 genes might be involved in coronary heart disease, he said. “Half of them will be silent—they would have to be environmentally tripped.” That is, there would be interactions with changes in lifestyle, just as Tuomilehto’s diabetes genes have to be environmentally tripped. Many of the vulnerable genes—variants—may be the same for both conditions.
Salonen has led a 20-year study of coronary heart disease in Kuopio. With patented DNA chips and corporate backers, he is looking for alleles that distinguish healthy Finns from patients with a family history of heart disease.
In Kajaani, Aimo’s hometown, a squadron of public-health nurses is trying to get people to lead healthier lives. Also under way is a long-term study of 500 high-risk children to see if counseling parents about healthy cooking and exercise will reduce the death rates of the subjects when they become adults. To be high risk in the study is to have a father or grandfather who had a heart attack before age 55 or a mother or grandmother who had a heart attack before 65.
Aimo told the story of his health through his doctor, Juha Rantonen. The story was full of twists and turns.
Aimo had two jobs: one as a bouncer in a bar at night and the other as the owner of a gym. His heart attack was misdiagnosed at first as pain from a pulled muscle following an incident in the bar (Aimo had subdued a knife-wielding patron). But a friend took him in for tests. The cardiologists thought he might need only drug therapy, but after further review they called him back for the bypass operation.
Aimo had not known his heart was failing. He watched his weight and was not a smoker. His cholesterol was low. But he had been feeling weak and fatigued for three years. His father had a heart attack at age 50, and his grandmother died at age 70 from her heart condition.
Still, Aimo didn’t seem anxious. He was feeling better than he had for a while. What did he think about Finnish genes?
From his measured replies, it seemed that genes interested him more as wellsprings of the national character than as vehicles for illness.
“Finnish self-esteem,” Aimo said through his doctor, “is not good because we are squeezed between Sweden and Russia. But our language, our culture, our genes are unique. We should be more proud of ourselves.
“One black cloud only,” he stressed, opening his hands. “The disease genes. The rest is good.”