Editing DeCODE genetics (section)

== Iceland and the population approach ==
In 1996, when Stefansson left a tenured position at [[Harvard Medical School]] to return to Iceland to found a genomics enterprise, nearly everything in his thinking was unproven or controversial. At the time, the causes of some rare diseases - often variations in single genes that could be found by studying small families - were beginning to be uncovered.<ref>See for example Francesco Cuca ''et al.'', "The distribution of DR4 haplotypes in Sardinia suggests a primary association of type I diabetes with DRB1 and DQB1 loci," ''[https://www.sciencedirect.com/science/article/pii/0198885995000423?via%3Dihub Human Immunology]'', Vol 43, Issue 4, pp 301-308 (August 1995); EM Petty ''et al.'', "Mapping the gene for hereditary hyperparathyroidism and prolactinoma (MEN1Burin) to chromosome 11q: evidence for a founder effect in patients from Newfoundland," ''[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1918205/ American Journal of Human Genetics]'', Vol 54, Number 6, pp 1060–1066 (June 1994); Melanie M Mahtani ''et al.'', "Mapping of a gene for type 2 diabetes associated with an insulin secretion defect by a genome scan in Finnish families," ''[https://www.nature.com/articles/ng0996-90 Nature Genetics]'' (subscription required), Volume 14, pp 90–94, (September 1996); Steinnun Thorlacius ''et al.'', "A single BRCA2 mutation in male and female breast cancer families from Iceland with varied cancer phenotypes," ''[https://www.nature.com/articles/ng0596-117 Nature Genetics]'' (subscription required), Vol 13, pp 117–119 (May 1996)</ref> Yet it was far from universally accepted that there was any significant genetic component to common/complex diseases like heart disease or type 2 diabetes with well-known behavioral and environmental risk factors; nor, even if there were, whether such variations could be found given the rudimentary technology for reading DNA.<ref>On the approach, and its doubters, see Stephen D. Moore, "Biotech firm turns Iceland into a giant genetics lab," ''[https://www.wsj.com/articles/SB867882460839119500 Wall Street Journal]'' (subscription required), 3 July 1997</ref>

Stefansson was convinced that these existed and could be identified, but only by working at industrial scale. 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. As a discovery venture in uncharted territory, the strategy was to assemble and query as much data as possible: DNA contributed by tens of thousands of people; both broad and deep medical and health data; and, crucially, comprehensive genealogies linking all these participants together.<ref>An early description of the discovery model by Stefansson and his laboratory director, Jeffrey Gulcher, in "Population genomics: laying the groundwork for genetic disease modeling and targeting," ''[https://www.degruyter.com/view/j/cclm.1998.36.issue-8/cclm.1998.089/cclm.1998.089.xml Clinical Chemistry and Laboratory Medicine]'' (subscription required) vol 36, number 8, pp 523-7 (August 1998)</ref> In short, this required a population, with people willing to take part in research, a modern healthcare system with meaningful numbers of cases of most common diseases, and much genealogical data. Iceland, Stefansson's native country, with 270,000 people at the time, fit this description better than any other.<ref>Population and other statistics at [https://statice.is/statistics/population/inhabitants/overview/ Statistics Iceland]</ref>

In 1996, funded by $12 million in American venture capital, deCODE set up a laboratory and began operations.<ref>First major interview with Stefansson on the company, now up and running, in [https://timarit.is/page/1866979#page/n17/mode/2up ''Morgunblaðið''], 24 November 1996</ref> Within its first few years it recruited and genotyped tens of thousands of participants. 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.<ref>For an overview of the company's activities and achievements in these early years, see the years 1997-2003 in the [https://www.decode.com/news-events/ news section of its website].</ref>

At the same time as it was beginning to prove its science, the company ignited a huge controversy with the proposal to create a research database - the Iceland Health Sector Database (or IHD for short) - containing copies of medical records from across the country's national health service.<ref>Gulcher and Stefansson cited polls showing public support for the IHD of 75% in "An Icelandic saga on a centralized healthcare database and democratic decision making," ''[https://www.nature.com/articles/nbt0799_620 Nature Biotechnology]'' (subscription required), volume 17, p 620, July 1999.</ref> In December 1998, with lobbying from deCODE, the [[Icelandic Parliament]] passed the [[Act on Health Sector Database]] which permitted public bidding for the right of a company to create this health database and use it for commercial research and to support the national health system.<ref>J Gulcher and K Stefansson, "The Icelandic Healthcare Database and Informed Consent," ''[https://www.nejm.org/doi/full/10.1056/NEJM200006153422411 New England Journal of Medicine]'', vol 342, pp 1827-1830 (June 2000)</ref> The parliament shortly thereafter granted deCODE the right to create this database after the company made a successful bid to do so.<ref>Chadwick, R. (1999). "The Icelandic database—do modern times need modern sagas?". ''BMJ''. '''319''' (7207): 441–444. [[Digital object identifier|doi]]:10.1136/bmj.319.7207.441. [[PubMed Central|PMC]]&nbsp;1127047. [[PubMed Identifier|PMID]]&nbsp;10445931.</ref> 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.<ref>Opponents of the IHD created an organization called Mannvernd to fight it and to encourage people to exercise their right to opt-out. The number of opt-outs provides one concrete measure of opposition to the idea as well as, conversely, a measure of how many people either favored the idea or held no strong opinion. According to an [https://web.archive.org/web/20030920233821/http://www.mannvernd.is/ archived snapshot of Mannvernd's website from September 2003], in the five years following the passage of the law authorizing the IHD, just over 20,000 people had opted out, or 7% of a 2003 population of 288,000.</ref> Although the IHD was never built, the debate underscored the political challenges involved in enlisting an entire society in a scientific enterprise, especially one with the explicit aim of commercializing its discoveries.<ref>Books and major research articles by bioethicists and other opponents of the IHD and commercial genomics include: Mike Fortun, ''Promising genomics: Iceland and deCODE genetics in a World of speculation'' (Berkeley: University of California Press, 2008); David Winickoff, "Genome and nation: Iceland's Health Sector Database and its legacy,"  ''[https://www.researchgate.net/publication/24089987_Genome_and_Nation_Iceland's_Health_Sector_Database_and_its_Legacy Innovations: Technology Governance Globalization],'' vol 1, number 2, pp 80-105 (February 2006); Henry T. Greely, "Iceland's plan for genomics research: Facts and implications," ''[https://www.jstor.org/stable/29762639?seq=1#page_scan_tab_contents Jurimetrics]'' (subscription required) vol 40, number 2, pp 153-91 (Winter 2000); and Jon Merz, "Iceland, Inc?: On the ethics of commercial population genomics", ''[https://www.sciencedirect.com/science/article/pii/S0277953603002569?via%3Dihub Social Science & Medicine]'' vol 58, number 6, pp 1201-9 (April 2004). Apart from Mannvernd's, [http://www.lib.berkeley.edu/iceland/ another website] hosted in Berkeley, California was devoted to the anthropological implications of deCODE and genetics research in Iceland.</ref> It also ensured that deCODE and its approach went from being a peripheral curiosity to one of the highest profile enterprises in the global effort to understand the human genome.<ref>Hundreds of articles were written for and against the IHD and deCODE and its approach. A glimpse of the tenor and sheer number of these can be found in an [https://web.archive.org/web/19990508201348/http://www.mannvernd.is/ archived view from May 1999] of the website of Mannvernd, the Icelandic organization formed to oppose the IHD, and in a [https://notendur.hi.is/sksi/hsd_dec_bib.html highly detailed bibliography] {{Webarchive|url=https://web.archive.org/web/20190507185834/https://notendur.hi.is/sksi/hsd_dec_bib.html |date=7 May 2019 }} created by Dr Skúli Sigurðsson, a leading member of Mannvernd.</ref>