Late last month, researchers out of Iceland announced that they’d made a major leap in the field of genetics: They’d mapped the entire genetic code of their nation, the largest genomic study ever. This project, detailed in four interconnected papers in the current issue of the scientific journal Nature Genetics, was the culmination of 18 years of work by deCode, a local private research company (purchased by California’s Amgen after declaring bankruptcy in 2009). And according to these papers, the firm’s research isn’t just cool in abstract. As a roadmap for further studies, it has the potential to revolutionize the way we develop and target medical treatments, from drugs to surgical interventions.
At first blush, this Icelandic research may sound like an effort of unbelievable blunt-force science, sequencing the multi-billion-component genetic code of a nation’s every resident. But rather than sequence every individual person’s DNA, from 2013 on, deCode sequenced about 2,636 people’s genomes in full. Then for more than 100,000 other Icelanders, they performed more basic genetic analysis, looking at every 10,000 or so parts of their DNA (much the same as a service like 23andMe does). The result was a total genetic map of about one percent of the population and a partial map of a third of the population.
Due to the very specific genetic history of Iceland, this data was enough to extrapolate a wider genetic map of the country. Settled in the late 9th and early 10th century by between 8,000 and 20,000 individuals, Iceland’s gene pool has remained largely isolated and become increasingly homogenous over the past 1,100 years. This means that computer programs could stretch researchers’ sliver of genomic information into a rough yet useful genetic sketch. “By using these tricks we can predict, with substantial accuracy, the genome of the entire nation,” deCode founder and CEO Dr. Kári Stefansson told the BBC.
Even if the map is more predictive than perfect, it can still help scientists envision new ways of researching disease and treatments. In the past, we’ve focused on finding people with diseases and then looking at their genomes to try to find oddities that might explain their disorders. But given all the confusing gunk and confounding mutations in a massive human genome, that approach becomes something of a hit-or-miss, needle-in-haystack strategy. By creating a national genome map, however, scientists can identify people with similar genetic anomalies and then investigate their medical records. Controlling for other factors, they can then try to isolate a common effect of that genetic anomaly across multiple individuals. Identifying disorders in this inverted fashion then makes it easier to target the problems with drugs and therapies.
To prove the potential of this new approach, deCode’s papers identified 20 million new genetic variations and linked several specific genes to Alzheimer’s, liver disease, thyroid disorders, and irregular heart rates (as well as, for fun, tracing back humanity’s oldest common genetic ancestor—who they say lived 174,000 to 321,000 years ago). Their findings are hardly definitive guidelines for how to treat these disorders, but they create uncannily precise targets for future research.
Beyond the potential for new research into the origins of specific medical conditions, Iceland’s genetic mapping makes it easier to predict where diseases with already known causes might pop up, and to focus preventative treatments on those regions or populations. In their research, deCode demonstrated this application by focusing on a mutation in the BRCA2 gene, which makes people drastically more prone to breast and ovarian cancers. They have been able to estimate that 2,000 men and women may carry this mutation in Iceland, and can now locate them fairly precisely. This potentially means that these patients could be called in, have this specific gene checked for a specific mutation, and then know for sure if they should consider prophylactic treatments.
“The risk [of these cancers] could basically be nullified by preventative mastectomies and ovariectomies,” says Dr. Stefansson. “It would be criminal not to take advantage [of this data] and I am convinced that my fellow countrymen will begin to use it pretty soon.”
Yet currently, Steffanson’s countrymen cannot access and act on his data, because—due to a host of data privacy problems posed by their techniques—deCode has been forced to withhold its findings for the time being. Under European and Icelandic law, all medical data must be anonymous and collected with the consent of each patient. Yet the predictive modeling at work here essentially allowed deCode access to personal genetic data without individuals’ consent, and could easily be used to locate and identify individuals with a certain genetic profile or defect.
DeCode managed to overcome concerns about privacy in 2004 and 2013, earning the right to access medical records and run modeling tests. But attempting to release the information to citizens or drug companies will likely be more ethically complicated than just performing the research. Icelanders have also become increasingly uncomfortable with deCode—many believe the project sprung their tests on the population, trying to guilt them into participation by promising charitable donations to local non-profits in exchange for the public’s genetic samples. This heightened wariness, and the company’s history of collapse and ties to drug manufacturers, make it seem fairly likely that their data will be tied up for quite some time.
In any case, this roadblock will likely result in some productive global debates on medical privacy, genetic research, and predictive medicine. It will also likely inform future research modeled on the deCode template. “You can basically trace all human diversity, the risk of disease and the response to treatment,” said Dr. Steffanson to ZME Science, on the ideal implications of his research.
Making these kinds of models will likely not be as easy beyond Iceland or for other diseases. The increased diversity, and thus the increased genetic background noise, of less homogenous populations makes similar projections more complicated in the wider world. Yet despite the incredible amount of data and statistical wizardry it would take to do anything like deCode’s project outside of Iceland, the potential of this method is still alluring enough to drive research towards how to scale up such investigations. And as the research becomes more robust in its tactics, powerful in its predictive abilities, and considerate in its privacy safeguards, the radical transformations of medicine it promises will come closer to being a reality. That’s all many years away. But the hopefully those prospects will be tantalizing enough to drive us through all those troublesome hoops and roadblocks and into a brighter genetic future.
