A decade before the term was in common use, deCODE's premise was that this was a big data problem: finding variants impacting risk in dynamic interaction with lifestyle and other factors would require studies not at the family level, but at the scale of public health.

It made rapid progress in creating a national genealogy database; developed a novel privacy protection system with government-supervised identity encryption; signed a landmark partnership with Swiss pharmaceutical company Roche; and mapped putative disease genes in a handful of conditions.

[15] Widely supported by the public and parliament, the IHD's openly commercial aims, and proposed inclusion of medical records data unless individuals opted out, unleashed vehement opposition played out in the local and international media, led by a group of Icelandic activists as well as a number of foreign bioethicists.

[18] By the time Bill Clinton and Tony Blair announced the completion of the first rough draft of the human genome sequence in June 2000,[19] deCODE was busily scaling up its gene-hunting in dozens of diseases and publishing its first discoveries.

[20] The company used the most scalable DNA-reading technology of the time - microsatellite genotyping - to place and measure highly variable and therefore informative markers at hundreds of points along the genome.

Geneticist Mary Claire King, whose family-based research in the early 1990s led to the discovery of the BRCA1 and BRCA2 breast cancer genes, predicted not long after deCODE's founding that the ability "to trace the genealogy of an entire nation...could become one of the treasures of modern medicine.

[33] In a country that is essentially a huge extended family with a correspondingly keen interest in how its members are related, Islendingabok has become a constant in national life and a daily and direct means of social engagement with deCODE's work.

But in scientific terms, the ability to understand the precise genealogical relationships of all participants in its research projects has given deCODE an abiding advantage as a discovery enterprise, ensuring that its genomic and medical datasets have remained among the largest and best powered collections anywhere.

In common diseases, as with many traits or phenotypes such as drug response, the difference is not one of causal certainty but of statistical odds representing increased or decreased risk versus the population average.

[43] Stefansson, deCODE's research chief Unnur Thorsteinsdottir, and statistician Gudmar Thorleifsson were respectively ranked the first-, second- and sixth-highest impact GWAS authors in the world.

[45] The value of this approach is best known from the model of PCSK9, in which the study of families with extremely high cholesterol levels and early-onset heart disease led to an understanding of the key role of this gene and the development of a new class of cholesterol-fighting drugs.

Over fifteen years deCODE has published a series of breakthrough papers detailing in a real human population how recombination rate varies according to sex, age and other characteristics, and how these differences impact the generation of genomic diversity and variation of many kinds.

[citation needed] deCODE's scientific leadership over more than twenty years has enabled it repeatedly to pioneer new types of partnerships, products and applications for many aspects of precision medicine.

[59] Over the next few years the company initiated and completed several early-stage clinical trials for potential new treatments for heart attack, peripheral artery disease, and conducted work with partners on asthma and SMA.

The idea was to make screening and prevention strategies and therapies more specific and more effective for those at higher risk, and hopefully to provide new incentive for individuals to follow through with well understood lifestyle modification such as weight loss, smoking cessation, etc.

In late 2007, the company effectively launched the field of personal genomics with its deCODEme[69] direct-to-consumer (DTC) scan aimed at enabling people to better understand their risk of common diseases and use this information to stay healthy.

[70] deCODEme's marketing emphasized its pedigree, seriousness and scientific rigor: "provided by a world leader in the discovery of genetic risk factors for disease...[so that its customers] benefit directly from the knowledge and experience of scientists carrying out internationally renowned research" (its competitors used deCODE's published variants as the basis for many of their results); with the scan processed in the same labs that had found them.

Within months, ten percent of the population had requested their BRCA2 status, and the National Hospital has built up its counseling and other services to help people follow up on their preliminary results and use the information to protect their health.

Its early pharmaceutical alliances, particularly that with Roche, further helped to fund the enrollment of most of the adults in the country in the first decade of its research, and the rapid expansion of both its discovery capabilities and its product development efforts in drugs, diagnostics and personal genomics.

[citation needed] A key rationale for the acquisition was deCODE's unique ability to use WGS data to discover rare coding variants and cause extreme versions of more common diseases.

[94] Introducing Stefansson for the organizations at the American Society of Human Genetics annual meeting in 2017, the Broad Institute's Mark Daly observed that the meeting and the field were dominated by "a pervasive paradigm involving biobanks recruited with full population engagement, historical medical registry data, investments in large-scale genetic data collection and statistical methodology, and collaborative follow-up across academic and industry boundaries...[and] deCODE provided the template for this discovery engine.

"[95] From its early days, deCODE's example gave fresh impetus to others hunting for disease genes in isolated communities and small populations in Sardinia, Quebec, Newfoundland, northern Sweden, Finland, and elsewhere.

[97] Iceland's experience, behind the scientific and medical value of applying the NHS's vast reach and resources to one of the most diverse populations in the world,[98] informed the authorization of the UK Biobank in 2003[99] and then Genomics England in 2013.

These include Regeneron's with the Geisinger health system in the US,[104] and Astra Zeneca's hybrid public/private/academic partnership with the Wellcome Trust in the UK, Craig Venter's Human Longevity in California, and Finngen in Helsinki.

[105] The latter, founded by Broad Institute leaders and Finnish universities, the health ministry, and biobanks to drive drug discovery,[106] is remarkably close to deCODE's original vision in Iceland but with academics and government bodies as equity partners in the business.

This effort marked the company's deepest and most direct ever involvement in public health and constitutes an important component of one of the most intensive and successful containment strategies of any country in the early months of the global pandemic.

In late January 2020, the National Directorate of Health began testing people arriving in Iceland from high-risk areas or showing possible symptoms of infection, and, with the Department of Civil Protection and Emergency Management, activated a system to isolate anyone diagnosed with the virus and to trace and quarantine all of their contacts.

In early March, deCODE's CEO Kari Stefansson became concerned that without also screening the population at large there was no way to understand the virus' spread or its fatality rate, crucial information for holistically addressing the epidemic.

Powered by this combined testing strategy and tracing and isolation follow up, the number of infections in Iceland peaked in the first week of April and dropped steeply off by the end of the month.

[125][non-primary source needed] In April 2020, with colleagues from the Directorate of Health and the national hospital, the company published in the New England Journal of Medicine a paper detailing what the spread of COVID-19 looks like across a population, and how a robust policy of testing, tracing and isolation could effectively contain it.