When Steven Smit opens the freezer, liquid nitrogen pours into the room, cascading dramatically over the sides of the container before spilling across the floor. He pulls out a cylindrical goblet containing 168 straws full of genetic material. Even if the building lost electricity, he tells me, these samples would remain frozen for a month before thawing. As long as they stay frozen, they’ll last at least 50 years, maybe more.
Smit and I are in the basement of the Estonian Genome Center at the University of Tartu, which holds more than 1 million of these straws, filled with DNA, white blood cells, and plasma of more than 52,000 Estonians. These samples comprise the country’s national biobank, a program that began in 2000 to collect DNA samples from a quarter of the country’s population. These samples are used for clinical research, but equally as important, they also form the backbone of the small Baltic nation’s plans to revamp its health-care system to provide more personalized care. Already, the Estonian government has begun developing a system to making this genetic data available to citizens (and their doctors), free of charge, with plans to launch by the end of 2015.
For a country with a population of only 1.3 million people, the 52,000-strong dataset represents just 5 percent of the population, a far cry from the target of 25 percent. But Estonia’s small size, sophisticated technological infrastructure, and relatively homogenous populace make it an ideal place to put this ambitious idea to the test.
Smit tells me that there’s enough space for 15,000 more participants in this room—it holds 15 freezers, called cryovessels, each of which can hold 720 goblets. In the adjacent room, another freezer has space for up to 48,000 more DNA samples. The complex bar-coding system attached to the freezer can select, thaw, and prepare up to 5,000 samples, all stored to be ready for analysis within 24 hours.
There are currently more than 120 biobanks worldwide, but the majority of them focus on genomic research rather than personalized medicine. In Iceland, for example, the biobanks are privately owned—so while around 40 percent of the country’s population has contributed DNA, that information isn’t integrated into personal health on a national scale. The U.S. similarly lacks a means to integrate large amounts of data from companies like 23andMe into its health-care system. Americans also remain suspicious of the ways such companies are using their data: 23andMe, which has genotyped more than one million customers as of June 18, has been accused of selling its customers’ genetic data for profit.
The Estonian biobanking system, by contrast, is built on a law that fundamentally protects gene donors’ privacy and establishes their rights. Passed in 1999, the Estonian Human Genes Research Act governs the activities of the biobanking project: It establishes anonymity in clinical research, enables donors to decide which studies they want to participate in, and gives donors full control over who has access to their data. By default, a donor’s doctor is the only other person who can look at his or her genetic information through the portal, unless the donor authorizes more people. By the end of this year, citizens will be able to log on to a central online portal to see which research studies have used their DNA. The portal is also the hub through which the Estonian government communicates with its citizens, meaning the online space where Estonians check their genetic data is also where they pay their taxes, fill prescriptions, and open a business, among other things.
The 1999 law “is the cornerstone of the Estonian Biobank Project,” says Andres Metspalu, the Genome Center’s director and a professor of biology at the University of Tartu. He’s also a gene donor himself. “It protects the people.” By placing control over their data in donors’ hands, the law has encouraged the public’s trust in the project: In a 2011 survey by the Baltic market-research firm TNS Emor, 70 percent of Estonians strongly supported the national biobank, and less than 5 percent opposed it.
By studying the genetic data of such an unvaried population, scientists can improve their understanding of hereditary diseases and the interaction of genetic and environmental factors. But the biobank also offers international researchers an extensive pool of samples they can analyze by age, gender, education, and lifestyle. And while the samples cannot be considered completely random and may be subject to recruitment bias, the size of the biobank means its contents can be considered representative of Estonia's population. Research groups from around the world have already submitted dozens of requests for samples that range in number from 20 to 10,000. Requests can be very specific: For example, a researcher could ask for a sample of 1,000 men and 1,000 women, ages 51-74 years old, all with a BMI over 30.
It currently costs 5,000 euros and takes one week to sequence one genome on site at the center in Estonia, so much of the sequencing has been outsourced to the Broad Institute of MIT and Harvard, where it costs 1,000 euros per donor. Genotyping, which involves taking 1 million chunks of the most important genetic data from the donor, costs 10 times less and is 10 times faster than harvesting the entire genetic code. Thus far, 20,000 of Estonia’s DNA samples have been genotyped and 2,300 have been fully sequenced. Because the country’s population is fairly homogenous—95 percent of people are ethnically Estonian or Russian—scientists can fill in the gaps for those who have been genotyped using information from people who have been fully sequenced.
Despite the program’s cost, its leaders are optimistic. “I am absolutely positive that in a foreseeable future, every individual will have their genetic information known, at least to their doctor,” says Ain Aaviksoo, who works for Estonia's Ministry of Social Affairs and is spearheading the project from the governmental side. Aaviksoo’s more immediate goal is to have 250,000 individuals in Estonia either genotyped or fully sequenced in the next two to three years. During the first recruitment round, which lasted from 2002 to 2011, more than half of all Estonian medical professionals cooperated with the biobank, agreeing to integrate the process of donating into normal doctors’ visits for those who were interested. By 2020, Aaviksoo tells me, everyone with an Estonian ID card might have the chance to opt in to the biobank if they want to do so.
Some are skeptical as to how valuable the predictions from the data will actually be in helping doctors improve their patients’ health. In a 2012 article in The Atlantic, David Ewing Duncan discusses the two primary schools of thought: Some people consider genes to be “near-magical fortune-tellers about a person’s health future,” he says, while others claim that the “genes as crystal balls” line of thinking is unrealistic because it doesn’t take environmental factors into account. Both sides are right, Duncan concludes, because genes are “just part of the equation telling us what is happening, or might happen, to our bodies in time.” Ultimately, the use of genomics to study diseases is a practice of probability.
Nevertheless, Metspalu believes that the predictive power of the genetic data will enable the Estonian health-care system to shift from reactive to more preventative. “Today we are mostly treating the patients,” he tells me in an email. “But we should keep them healthy instead.” When a person knows about his or her personal genetic tendencies, it can motivate him or her towards a healthy lifestyle. The knowledge can also serve as another factor for doctors to consider in diagnoses. Metspalu estimates that the Genome Center will be able to begin providing information to its gene donors (and their doctors) through the e-Health portal within the next six months.
“It’s like basic education. [The government] provides the infrastructure, the people, the methods, and procedure and everybody gets access to that,” Aaviksoo says. “By and large this is a system that is there to support you in the most important role, which is behaving on behalf of your own health.” He foresees a future of medicine where patients are able to use all kinds of technology—parsed genetic data, but also things like wearables—to take a larger and more important role in managing their health.
Over at the Broad Institute, the institute’s president and MIT biology professor Eric Lander also believes Estonia is a model of what the future might look like, despite its imperfections.
“Everyone should have the right and ability to donate their data,” Lander said. “We owe it to our children to not let medical experiences go to waste, at least for the people who want to contribute.” Lander argues that the Estonian system’s technical infrastructure, the core of Estonia’s entire e-government, is what makes the Estonian Genome Project “a model system for how the world should do things.”
“Think of the amazing opportunities that come from combining the IT infrastructure and the public trust in it with the information that can be learned from the genome,” Lander said during a talk at the University of Tartu in 2014. “There is so much opportunity to turn medicine into a learning system.”
