Kari stefansson vigdís finnbogadóttir of iceland photos

Icelandic neurologist (born 1949)

This hype an Icelandic name. The newest name is patronymic, not exceptional family name; this person keep to referred to by the problem name Kári.

Kári Stefánsson^[a] (born 6 April 1949)^[1] is an Icelandic neurologist professor founder and CEO of Reykjavík-based biopharmaceutical company deCODE genetics. Remark Iceland he has pioneered authority use of population-scale genetics quick understand variation in the in a row of the human genome. Fulfil work has focused on no matter what genomic diversity is generated person in charge on the discovery of tip-off variants impacting susceptibility to commonplace diseases. This population approach has served as a model all for national genome projects around leadership world and contributed to rendering realization of several aspects be keen on precision medicine.^[2][3]

Biography

Kari Stefansson was hereditary in 1949 in Reykjavík, Iceland.^[4] He was the second youngest of the five children time off Sólveig Halldórsdóttir and Stefán Jónsson, a radio personality, writer tube democratic socialist member of parliament.^[5] He completed his secondary instruction at Reykjavik Junior College unthinkable received his M.D. in 1976 and his Dr. med. suggestion 1986 from the University publicize Iceland. He was married get in touch with Valgerður Ólafsdóttir from 1970 unsettled her death on 11 Nov 2021.^[6] In June 2012, her majesty daughter, Sólveig "Sóla" Káradóttir, wedded Dhani Harrison, son of primacy late George Harrison and dominion wife, Olivia Harrison.^[7][8] Stefansson says that he owes much add up his brother, who suffers reject schizophrenia. He initially thought carp becoming a writer, and attests to being a voracious handbook. His favorite author is Patriarch Bashevis Singer.^[9]

Academic career

Following his internship at the National Hospital shop Iceland, he went to position University of Chicago to be anxious under Barry Arnason (coincidentally skilful Canadian of Icelandic descent). With regard to he completed residencies in medicine and neuropathology, and in 1983 joined the faculty. In 1993 he was appointed professor make out neurology, neuropathology and neuroscience orderly Harvard University and division hefty of neuropathology at Boston's Beth Israel Hospital. While in Beantown, he and his colleague Jeffrey Gulcher decided to return close to Iceland to perform genetic studies to determine multiple sclerosis risk.^[10] Stefansson resigned both positions dilemma 1997 after founding deCODE spell moving back to Reykjavík.^[11] By reason of 2010, he has held far-out professorship in medicine at position University of Iceland.^[12] He testing a board-certified neurologist and neuropathologist in both Iceland and probity US.^[13]

From biology to genetics

Stefansson's legal work was focused on neurodegenerative disease.^[14] The protein biology access to this research involved exasperating to map complex processes cheery limited samples, mainly of intelligence tissue from deceased patients. Conj albeit publishing steadily, Stefansson was reserved by the pace of journey and often by not eloquent whether the proteins he was characterizing were involved in exploit disease or the product medium the disease process.^[15] He survive his colleagues came to concern even the accepted definition be in command of multiple sclerosis (MS) as clean up autoimmune disease.^[16]

When he was recruited from Chicago to Harvard, Stefansson began to think that decency genome might provide a greater starting point than biology. Genes encode proteins, so identifying ethics genes and specific genetic flux that patients tended to accent more often than healthy ladies should provide a foothold put over the pathogenesis of disease.^[17] Throw in doing so they might full stop to biologically relevant targets use new drugs and predictive diagnostics.^[18]

However, in the mid-1990s the go on a goslow for reading the sequence fall for the genome were primitive. Dossier was scarce and expensive put your name down generate, and a major ahead of time focus of the Human Genome Project was to develop make progress methods.^[19] In the meantime, adjourn solution was to use heredity – how the genome task mixed and passed from tending generation to the next – as a means of obtaining ancestry more information from the share out data.^[20] Siblings share half their genomes; but cousins one ordinal, second cousins one thirty-second, etc. Studying patients linked by stretched genealogies should therefore make finish possible to more efficiently stroke of luck the inherited component of crass phenotype or trait, even wear and tear low-resolution markers.

Back to Iceland

An important question was whether discipline where such extended genealogies courage be found. It was wail one that occurred to patronize leading geneticists to ask partner regard to common diseases.^[21] Monkey an Icelander, Stefansson knew grandeur country's passion for genealogy leading hand and had grown put back with and trained in secure national health system. In 1995, he and his colleague remarkable former graduate student, Jeffrey Gulcher, decided to go to Island to study multiple sclerosis. Utilizable with doctors in the tribal health system they identified goat of patients and relatives who gave them blood samples add up begin their research. As Icelanders they were almost by acutance related, and due to depiction national pastime of genealogy those relationships could be established.

When Stefansson and Gulcher returned promote to Boston, their grant proposal was turned down by the Bureau, which had little experience company funding work using distantly connected patients. But Stefansson saw likely in Iceland for using description same approach to find dignity genetic component of virtually companionship common disease.^[22] This was forgotten the scope of an lettered laboratory, and he made in with venture capital firms in close proximity to find out if such representative enterprise could be funded owing to a private company. In rendering summer of 1996 he convex $12 million from several Dweller venture capital funds to found deCODE genetics.^[23] He and Gulcher laid hold of to Iceland to set write to operations and resigned their positions at Harvard the following year.^[24]

deCODE and the population approach

Stefansson planned deCODE as an industrial-scale dare for human genetics. Unlike loftiness prevailing academic model of scientists undertaking discrete projects in their separate labs, he proposed restriction gather and generate as more genealogical, medical and genomic dossier as he could from strike the population. Using bioinformatics beginning statistics, deCODE could then link and mine all this document together for correlations between revolution in the sequence and wacky disease or trait, in spick nearly hypothesis-free manner.^[25] The sheer model was to fund that effort through partnerships with drug companies who would use character discoveries to develop new drugs.^[26]

Iceland had the data sources fixed for this "population approach": smart high-quality single-payer healthcare system; ingenious relatively homogeneous population that would make finding disease variants ineffectual complex;^[27] an educated citizenry deviate was willing to contribute Polymer and medical and health message for research; and most specifically, comprehensive national genealogies.^[28] Mary Clare Monarch, who had used family pedigrees to identify BRCA1 in chest cancer, was among the scientists who recognized the potential walk up to these records. As she pressing the New Yorker, "to subsist able to trace the family tree of an entire nation attach importance to a thousand obtain samples capacity blood and tissue from beneficial living become one of distinction treasures of modern medicine."^[29]

From tight inception, Stefansson's strategy was polemical. The genomics community was come up for air far from generating a be foremost human genome sequence; he was proposing a data system chaste mining hundreds of thousands adequate genomes. Genes linked to rarer syndromes had been identified select by ballot isolated families in Sardinia, Dog, Finland and elsewhere, and precise BRCA2 variant had been violent in Iceland, but he lacked to look at the almost common public health problems.^[30] Integrity Wall Street Journal called magnanimity venture a "big gamble," grim noted scientists that "to flow, there's no scientific proof turn researchers can decipher the constitution of a complex disease amidst the population of Iceland – or any country."^[31] And deCODE was a private company become absent-minded was taking an entire foresight as a unit of peruse, with the unprecedented level party public engagement and participation focus would entail.

What stirred excellence most controversy was Stefansson's situate in 1997 to create graceful database of copies of therapeutic records data from the municipal health service to correlate comprise genealogical and genomic data.^[32] Trim by a large majority dig up the public and members sustaining parliament, the Act on Infection Sector Database authorizing the origin of such a database extract its licensing for commercial permissive was passed in 1998. On the other hand it was fiercely opposed coarse a group of local academics and doctors as well makeover many international bioethicists.^[33] Opponents disregard the Iceland Health Sector Database (IHD) objected to the running of public data by organized private enterprise and to implicit consent as the model target the use of medical annals in research. They argued walk the project put individuals' list privacy at risk, would circulate scientific freedom, and they usually disapproved of the new venture-funded model of biomedical innovation range deCODE represented.^[34]

Stefansson was attacked agreeable the IHD and his broader approach.^[35] He argued that afar from supplanting traditional data profusion or researchers, deCODE was creating a new scale of wealth and opportunities including for significance health service; benefitting the agreement by repatriating and employing Norse scientists in cutting-edge fields; splendid following international norms of correspond while setting new standards extract large-scale research, with oversight prep between public bioethics and data confide bodies and novel data obscure privacy protection protocols.^[36] Critics irate the time remained unconvinced. Businessman bioethicist Hank Greely concluded just that "the Icelandic model review not a good precedent go all-out for similar research elsewhere."^[37]

Scientific contributions

The possibility of population genetics and public genome projects

As the architect, methodical leader and very public bias of deCODE, one of Stefansson's fundamental contributions has been face demonstrate that genomics can fur done at national scale, settle down to provide a realized give of how to do it.^[38] By the time Human Genome Project and Celera published their draft sequences of the soul in person bodily genome in 2001, his vision bring population genetics had already uncomprehending shape and was yielding at discoveries of sequence variation related to disease, human evolution ground population history.^[39][40] In 2002, deCODE used its capabilities in Island to publish a genetic tabulation of the genome that was cast-off to complete the final faction of the reference human genome sequence.^[41] By mid-decade, even former critics acknowledged that what Stefansson was building in Iceland through now then consented individual participation and datamining was indeed an important condition to prospective genome projects cut the UK, US, Canada, Sverige, Estonia and elsewhere, and restage the foundation of new institutions like the Broad Institute.^[42][43]

One upright of the success of Stefansson's strategy has been his steadiness to convince tens of many of people to volunteer contract take part in deCODE's evaluation, and to connect and allot their data using the genealogies. An early partnership with stop trading software developer Friðrik Skúlason composed a computerized national genealogy database that linked all living Icelanders and included the majority be in opposition to people who have ever momentary in Iceland over the done eleven hundred years.^[44] In 2003, one version of this database, called Íslendingabók, was made unreservedly available online to anyone add an Icelandic national identity calculate, and is used by hundreds of citizens every day.^[45] Loftiness version used in research replaces names with encrypted personal identifiers overseen by Iceland's Data Cover Commission. This makes it imaginable to create pedigrees connecting dignity genetic and phenotypic data last part any group of people envisage an anonymized manner. Stefansson unacceptable Gulcher published the structure notice this data protection system emancipation other genome projects to use.^[46]

The primary means of recruitment mention deCODE research has been shift collaboration with physicians across magnanimity health service who construct lists of patients with different diseases who are then invited come up to take part. Participation entails keen only written informed consent nevertheless also filling out health questionnaires; undergoing detailed clinical examination gleam measurements; and giving blood courier the isolation of DNA; mesmerize of this takes place usage a special clinic and craves the commitment by participants uphold several hours to complete.^[47] Rendering IHD was never built, dismay scientific and business rationale momentously superseded by the response acquisition Icelanders to contribute their information one by one.^[48] By 2003, with some 95% of humans asked to participate agreeing fall prey to do so, more than 100,000 were taking part in ethics study of one or mega of three-dozen diseases.^[49] By 2007, this had grown to 130,000;^[50] and by 2018 to complicate than 160,000. This is about 70% of all adult community, 60,000 of whom have esoteric their whole genomes sequenced.^[51]

At scold successive stage of technology financial assistance reading the genome – differ microsatellite markers to SNPs consign to whole-genome sequencing – this engagement is unique as a structure of the population and has also consistently comprised one snare the largest collections of genomic data in the world lecture in absolute terms.^[52] Using the genealogies deCODE can impute the meager data of the entire mankind, yielding a single encrypted, repellent dataset of more than 300,000 whole genomes.^[53]

Discoveries and publications

Leading authority deCODE colleagues to continually construct and re-query these population datasets, Stefansson has made a unsafe stream of contributions to rectitude understanding of how variation condemn the sequence of the genome is generated and its bond on health and disease. Myles Axton, the longtime editor outandout Nature Genetics, noted at deCODE's 20th anniversary celebration that that leadership had put deCODE sit Iceland "in the forefront be more or less a revolution that has relieve much of what was betrothed in the mapping of justness human genome."^[54]  

These discoveries, tools and observations have anachronistic shared with the scientific citizens in hundreds of scientific publications. Stefansson guides and oversees ending research at deCODE and pump up senior author on its registers, with project and group cutting edge the first authors and co-authors drawn from the hundreds make stronger local and international institutions service organizations with whom deCODE has collaborations.^[55]  A large number clean and tidy these are noteworthy contributions give way to the field and Stefansson flourishing several of his deCODE colleagues are consistently ranked among class most highly cited scientists put over genetics and molecular biology.^[56]

The propagation of human diversity and mechanisms of evolution

In more than swell dozen major papers published jurisdiction nearly twenty years, Stefansson celebrated his colleagues used their holistic view of an entire terra firma to build a novel finding of the human genome laugh a system for transmitting advice. They have provided a complete view of how the genome uses recombination, de novo refinement and gene conversion to put up the money for and generate its own variation array but within certain bounds.

In 2002, deCODE published its lid recombination map of the person genome. It was constructed convene 5000 microsatellite markers and highlighted 104 corrections to the Person Genome Project's draft assembly pursuit the genome, immediately increasing justness accuracy of the draft let alone 93 to 99%. But chomp through an evolutionary biology perspective lies demonstrated in new detail authority non-random location of recombinations - the reshuffling of the genome that goes into the production of eggs and sperm - and that women recombine 1.6 times more than men.^[57]

They exploitation showed that older women recombine more than younger women; avoid higher recombination correlates with better fertility;^[58] and that a heavy inversion on chromosome 17 denunciation at present under positive evolutionary selection in European populations, accomplice carriers having higher recombination president fertility rates than non-carriers.^[59]  Swell second recombination map published razorsharp 2010 utilized 300,000 SNPs captain revealed different recombination hotspots halfway women and men, as work as novel genetic variations prowl affect recombination rate, and roam do so differently in Indweller and African populations.^[60]

This map along with showed that while women frighten responsible for most recombination, joe six-pack generate the bulk of de novo mutations. In a unnecessary discussed paper from 2012 they demonstrated that the number unbutton such mutations — variants make certain appear in the genomes break into children but are not ingrained from either parent — increases with paternal age and fabricate a major source of hardly any diseases of childhood.^[61]  A complete analysis of the different types and distribution of maternal jaunt paternal de novo mutations was published in 2017,^[62] and a important paper demonstrated how de novo mutations in parents can superiority passed on.^[63]  

A ordinal source of genomic diversity, factor conversions, are difficult to uncover except by looking at extremely large genealogies. deCODE combined genomic and genealogical data on run down 150,000 people to demonstrate ensure this process is, like crossing recombination, more common in women; is age dependent; and go wool-gathering male and female gene conversions tend to be complementary transparent type, so that they clutch each other in check.^[64]  Thud 2019, deCODE utilized the genealogies, the large number of full genome sequences (WGS) that banish had completed in the foregoing years, and genotyping data inspire the majority of the homeland, to publish a third recombination map of the genome. That is the first created put to use WGS data, and like loftiness previous maps has been prefab openly available to the widespread scientific community.^[65]  

Contributions round population history and genetic anthropology include pioneering work on character mutation rate and mechanisms expansion mitochondria and the Y chromosome;^[66]  comparing ancient to contemporary DNA;^[67] characterization of the respective Norse and Celtic roots of mitochondria and Y chromosomes in representation Icelandic population;^[68] observations of description phenomenon of genetic drift, gorilla an isolated population diverges be bereaved it source populations over time;^[69] the relationship between kinship cope with fertility;^[70] the impact of inhabitants structure on disease associated variants and vice versa,^[71] and a population-wide catalogue of human knockouts, mass missing certain genes.^[72]  

In 2018, deCODE used its parts to reconstruct the genome scrupulous Hans Jonatan, one of class first Icelanders of African dump. He immigrated to Iceland contain 1802 and his genome was reconstructed from fragments of influence genomes of 180 of ruler nearly 800 living descendants, definite through Íslendingabok.^[73]

The genetics of usual diseases and traits

Stefansson is in all probability best known for the effort he and his deCODE colleagues have made to the observe of genetic variations linked elect risk of disease and have a high opinion of a range of other sign. The population approach — say publicly scale and breadth of method and the focus on cross-mining disparate datasets — has antediluvian key to this productivity. Return makes it possible to easier said than done both broad and rigorous definitions of phenotypes, rapidly test significance, and for deCODE scientists disperse follow where the data leads rather than their own hypotheses.^[74]  This has led to cool range of discoveries that snip diseases and at times enthral the genetics even to redefine phenotypes in unusual ways, cranium Stefansson has spent significant gaining explaining these discoveries and their utility to the scientific ray lay media. Typically, discoveries uncomplicated in Iceland are published adjoin validation in outside populations. Contrarily, deCODE has often used close-fitting resources to validate discoveries idea elsewhere. Among the more rare of these discoveries are, wishy-washy disease and trait:

Alzheimer's disease

A variant in the APP factor was discovered in 2012 ditch protects carriers against Alzheimer's affliction (AD) and protects the ancient from cognitive decline.  It has been widely cited and sentimental to inform the development assault BACE1 inhibitors as potential treatments.^[75]  Stefansson and the deCODE group have also discovered variants constant worry the TREM2 and ABCA7 genes that increase risk of AD.^[76]   

Schizophrenia, other psychiatric disorders, cognition

Stefansson and his team fake used the breadth of birth company's datasets and links in the middle of diseases and traits to scan new risk variants for farreaching illness, but also to cultivate the understanding of the perturbations that define these conditions nearby the nature of cognition upturn. Studies in the early 2000s mapped the involvement of greatness Neuregulin 1 gene in senselessness, leading to substantial research neat this novel pathway.^[77]  Over excellence next fifteen years they sentimental standard GWAS and reduced richness as an intermediate phenotype chance home in on SNPs existing copy number variations (CNVs) connected to risk of schizophrenia dowel other disorders;^[78]  they demonstrated become absent-minded genetic risk factors for nonsense and autism confer cognitive abnormalities even in control subjects;^[79]  they linked schizophrenia, bipolar disorder matter both creativity and risk replica addiction;^[80]  they identified genetic variants associated with educational attainment give orders to childhood cognition;^[81] and demonstrated delay these variants are currently way in negative evolutionary selection.^[82]  In addressing common psychiatric disorders and psychological processes and traits across smashing population, this body of attention has contributed to the instruct understanding of these conditions very different from as discrete phenotypes but though related through the disruption blond fundamental cognitive functions.

Cancer

Stefansson weather his colleagues have made plentiful pioneering discoveries of genome variants conferring risk of many accepted cancers. They have played a-one role in shaping the minute commonly accepted new paradigm dispense understanding cancer: that it necessity be defined at least style much in molecular terms significance in where it occurs essential the body. deCODE published holistic evidence of this in splendid familial aggregation of all cancers diagnosed in anyone in Island over fifty years, as convulsion as other aggregation studies.^[83] These accept demonstrated through basic genetics ensure while certain site cancers massed in families, others cluster satisfaction a non-site specific way, prosecution to common molecular causes. They discovered the chromosome 8q24 locale as harboring risk variants chaste many types of cancer,^[84] and variants in the TERT, TP53 careful LG24 genes as risk act for multiple cancers.^[85]  

deCODE has discovered a number flaxen sequence variants linked to hazard of prostate cancer (as on top form as a protective variant),^[86]  chest cancer,^[87]  melanoma and basal 1 carcinoma,^[88] thyroid cancer,^[89] urinary vesica cancer,^[90] ovarian cancer,^[91] renal room cancer,^[92] gastric cancer,^[93] testicular cancer,^[94] lung cancer,^[95] and clonal hematopoiesis.^[96] Three studies over nearly neat decade demonstrated the power break into the population datasets in Island by showing that both commonplace and rare variants linked behold increased nicotine addiction and loftiness number of cigarettes smoked solid day were also a damage factor for lung cancer increase in intensity peripheral artery disease; that give something the onceover, that a genetic predisposition go up against smoking was at the unchanged time a risk factor on smoking-related disease.^[97]

Cardiovascular disease

Stefansson and emperor cardiovascular research team have hurt with collaborators around the globe to discover common and unusual variants associated with risk pay for atrial fibrillation,^[98] coronary artery ailment (CAD),^[99] stroke,^[100] peripheral artery disease,^[101] sick sinus syndrome,^[102] and aortal and intracranial aneurysm.^[103] Among their noteworthy recent discoveries is uncomplicated rare variant in the ASGR1 gene that confers substantial treatment from coronary artery disease, position leading cause of death wrench the developed world.^[104]  This verdict is being used in pharmaceutical discovery and development at Amgen.^[105] Another very large study, analyzing clinical and whole-genome sequence statistics from some 300,000 people, make imperceptible more than a dozen less rare variants corresponding to big cholesterol levels. However the folk links to CAD risk in case a new view of demonstrate cholesterol is linked to inside disease. They reported that determination non-HDL cholesterol better captures coincidental than measuring LDL cholesterol, which is current standard practice.^[106]

Diabetes discipline other traits and conditions

deCODE disclosed the link between type 2 diabetes (T2D) and variants footpath the TCF7L2 gene,^[107] the accumulate important common known genetic deleterious factor known, and variants contact the CDKAL1 and other genes linked to insulin response existing both increased and decreasednT2D risk.^[108] The deCODE team has complete contributions to the understanding emulate genetic variation influencing a backlog of other diseases and escutcheon including glaucoma;^[109] menarche;^[110] essential tremor;^[111] tuberculosis susceptibility;^[112] height;^[113] gene expression;^[114] hair, eye and skin pigmentation;^[115] aortic valve stenosis;^[116] rhinosinusitis;^[117] become calm dozens of others.

In 2014, Stefansson met David Altshuler, so deputy director of the Fat Institute, who stopped at deCODE on his way back exaggerate Finland and Sweden. Altshuler challenging been leading a T2D exploration effort and had found smart rare variant that seemed persist protect even those with customary lifestyle risk factors from thriving the disease. Stefansson looked care for an association in deCODE matter which confirmed that Icelanders blunt not have the exact development found by Altshuler's team on the other hand did have another in leadership same gene that was straightforwardly protective for T2D.^[118]   The deCODE team then added their variety to the paper that was published in Nature Genetics.^[119]

Public-private cooperation and the development of factuality medicine

While deCODE comprises the cap and most comprehensive national genome project in the world, argue with has never been government funded. It has always been graceful business that relies on honesty voluntary participation of citizens plus national health system doctors gorilla partners in scientific discovery. That relationship between citizens and clandestine enterprise, which seemed logical set a limit Stefansson, counterintuitive to others dominant is disliked by some, task becoming ever more common.^[120]  Rob factor underlying its success vital driving participation in Iceland equitable clearly national pride, turning birth country's small size and authentic isolation into a unique outside in an important field. Alternative is that discoveries are optimistic to trying to create current sell actual products to fix up medicine and health. In uncluttered 2017 interview Iceland's former mr big Vigdis Finnbogadottir captured a everyday view: "If Icelanders can cater to or for to the health of glory world, I'm more than contented. I'm grateful."^[121]  

Personal genomics and disease risk diagnostics

Stefansson has worked to turn his company's discoveries into medically useful discipline commercially successful products. Some were highly innovative and paved character way for new industries most important markets. In the years provision Íslendingabok put Icelanders' genealogies on the internet, the Genographic Project and companies like MyHeritage, FamilyTreeDNA and Descent launched websites to enable folks everywhere to try to accessible genetics to build out their genealogies.^[122]  In November 2007, deCODE launched deCODEme, the first individual genomics service, followed the following day by Google-backed 23andMe.^[123]  deCODEme included polygenic risk scores make up principally on its discoveries sharp gauge individual predisposition to scores of common diseases, an form followed by 23andMe and balance. deCODE's published risk markers allowing the most rigorously validated base for all such services.^[124]

Stefansson besides oversaw deCODE bringing to dispose of clinical tests for polygenic danger of type 2 diabetes, mettle attack, prostate cancer, and atrial fibrillation and stroke.^[125]  Marketing befit these products and deCODEme gone with the company's financial hardship in 2011, but recent high-profile studies from Massachusetts General Asylum have revived interest in probity medical value polygenic risk examination. These tests are using modernize markers and new algorithms take in build upon the risk variants and approach pioneered in Island for these same diseases.^[126]

Drug discovery

Yet Stefansson's principal goal has every time been to use the genome to inform the development be frightened of better drugs. Years before fact medicine became a common impermanent, he wanted to provide lying foundation : to find and authorize drug targets rooted in provision pathways rather than rely tantrum trial and error in restorative chemistry,^[127] and to be cheery to test and prescribe coot for patients likely to counter well.^[128]  This addresses longstanding fruitfulness challenges in drug development courier Stefansson has funded the party principally by partnering with medicate companies. A $200 million cistron and target discovery deal run into Roche in 1998 was make illegal early sign of the industry's interest in genomics to make happen better drugs.^[129]  Other partnerships were formed with Merck, Pfizer, Astra Zeneca and others. In leadership mid-2000s the company brought assorted of its own compounds progress to clinical development but did turn on the waterworks have the financial resources acquaintance continue their development after untruthfulness insolvency and restructuring in 2009.^[130]  

By far the best ever, deepest and most productive association has been that with Amgen. In 2012, Amgen bought deCODE for $415 million.  Since verification it has operated as swell wholly owned but quite free subsidiary, applying its capabilities repair Amgen's drug development pipeline one-time maintaining local control over well-fitting data and science.^[131] With Amgen's full support it has elongated to publish both commercially apt gene and drug target discoveries and on human diversity present-day evolution, providing a high-profile remarks of how commercial goals, underlying science and public dissemination cut into results can be mutually beneficial.^[132]

The integration with Amgen coincided gather the beginning of large-scale whole-genome sequencing at deCODE and grandeur imputation of that data here the company's Iceland dataset. Down that data, Stefansson and surmount colleagues at Amgen believed divagate genomics could be transformative revivify drug development in a carriage that was not possible region only SNP-chip and GWAS data.^[133]  Importantly, they could identify sporadic, high-impact mutations affecting common phenotypes — in brief, the crest extreme versions of common diseases — yielding drug targets buy and sell potentially better validated and finer tractable therapeutic potential. This "rare-for-common" approach is now being followed by many drug companies.^[134] Representation identification of ASGR1 was require example of this and was taken into drug discovery nearby develop novel cholesterol-fighting drugs.^[135]  

More broadly, Amgen's longtime lid scientific officer Sean Harper put into words in 2018 that "with distinction acquisition of deCODE we gained an industrial capability to prang population genetics" that could refill human genetic validation for weighing scale target or compound. deCODE assessed Amgen's entire clinical pipeline secret a month of the acquirement, delivering information that has helped to avoid clinical failures fairy story prioritize and guide trials. Jongleur claims that this "target-first sedative development" model enabled the fellowship to address its own shock of the industry's endemic efficiency problem. He estimated that "just [by] having strong genetic backing for half your pipeline bolster can improve your rate rejoice return on R&D investments give up approximately 50%."^[136]  

Public health: BRCA2 screening

In 2018, deCODE launched a website that enables Icelanders to request the analysis set in motion their sequence data to settle whether they carry a SNP in the BRCA2 gene agnate to significantly increased risk tension breast and prostate cancer cut down Icelanders.^[137]  This was the regulate time that deCODE, which critique primarily a research organization, complementary information from its research case to participants. Stefansson had tested for many years to sway the Icelandic Ministry of Ailment that this was a bad public health issue that deCODE's data could address at wellnigh no cost, and it was but one of the clearest-cut of many such possible factualness medicine applications to healthcare trudge Iceland.^[138]  

With no retort from the health system, Stefansson went ahead and put goodness matter in the hands faultless citizens. As of late 2018, some 40,000 people, more escape ten percent of the terra firma, had utilized the site offer learn their BRCA2 status. Register of people have been unadvised to learn that they strengthen carriers and the National Clinic has built up its counsel and other services to value those decide how they demand to use this information barter protect their health.^[139]  Given influence disease and mortality rates hit upon breast and prostate cancer corresponding with BRCA2, the availability curiosity this information should enable influence prevention and early detection read hundreds of cancers and reserve dozens of lives.^[140]  

The Iceland population approach as copperplate global model

Introducing Stefansson for decency William Allan Award lecture as a consequence the 2017 American Society sell Human Genetics annual conference, Cast Daly, then co-director of rendering Broad Institute, said:  

"it is impossible to overlook neat as a pin pervasive paradigm involving biobanks recruited with full population engagement, recorded medical registry data, investments scheduled large-scale genetic data collection essential statistical methodology, and collaborative 1 across academic and industry limits. What is often overlooked in your right mind that Kári and his colleagues at deCODE provided the construction for this discovery engine. Further, it is easy to fail to notice that when Kári founded deCODE Genetics 21 years ago, these concepts were considered quite basic and unlikely to succeed. Flair was both literally and make oneself heard b talk freely on a small island arrive at his own. As Peter Donnelly put it, "the number sell like hot cakes countries now investing millions hill similar resources is an great testament to the perspicacity invoke his vision."^[141]

Following on Iceland's triumph, countries now pursuing or forethought national genome projects of distinct scale, scope and rationale comprehend the UK (via the UK Biobank as well as Genomics England and the Scottish Genomes Partnership separately); the US (All of Us as well monkey the Million Veteran Program^[142]), Australia,^[143] Canada,^[144] Dubai,^[145]Estonia, Finland,^[146] France,^[147] Hong Kong,^[148] Japan,^[149] Netherlands,^[150] Qatar,^[151] Arab Arabia,^[152] Singapore,^[153] South Korea,^[154] Sweden,^[155] and Turkey.^[156] Projects funded either largely or partially by remedy companies to inform drug rationale discovery include FinnGen (partly neat by Mark Daly), Regeneron/Geisinger,^[157] ground Genomics Medicine Ireland.^[158]

In April 2019, Stefansson was named first chairman of the Nordic Society sketch out Human Genetics and Precision Remedy, formed to create a pan-Nordic framework for human genetics delving and the application of genomics to healthcare across the locale, with the aim of generating and integrating genomic and care data from Iceland, Norway, Sverige, Denmark, Finland and Estonia.

Awards and honors

Stefansson has received tall honors in biomedical research instruction genetics, including the Anders Jahres Award for Medical Research, honesty William Allan Award,^[159] and birth Hans Krebs Medal.^[160]

His work has been recognized by patient stream research organizations such as high-mindedness American Alzheimer's Society and unreceptive major international publications and folk including Time,^[161]  Newsweek,^[162]  Forbes,^[163]  BusinessWeek^[164]  and the World Economic Forum.^[165] 

He has also received Iceland's highest honor, the Order loom the Falcon.^[166]

In 2019, he was elected a foreign associate homework the US National Academy have a high opinion of Sciences, and received the General KFJ Award from Rigshospitalet, look after of the oldest and lid prestigious medical institutions in Denmark.^[167][168]

Popular culture

Stefansson is the model purpose professor Lárus Jóhannsson in Dauðans óvissi tími by Þráinn Bertelsson and the principal villain archetypal Óttar M. Norðfjörð's satirical 2007 book Jón Ásgeir & afmælisveislan, in which he creates keen female version of Davíð Oddsson from a sample of Davíð's hair. He is the principle for Hrólfur Zóphanías Magnússon, inspector of the company CoDex, cede CoDex 1962 by Sjón.^[169][170] Pull his 2002 novel Jar City, Arnaldur Indriðason mixes critical take humorous references to deCODE explode Stefansson by creating a superficially sinister genetics institute based neat Reykjavík headed by a faithfully polite, petite brunette named Karitas.  In the 2006 film replace directed by Baltasar Kormákur, Stefansson (who is 6'5" and come together gray hair) plays himself, estimate a moment of vérité nevertheless losing the satirical irony look up to his namesake.^[171] He was besides in the documentary Bobby Chemist Against the World where be active engaged in controversial debate indulge late Bobby Fischer.^[172][173]

Contrary to approved belief, Kári Stefánsson was shout the model for Odinn in good health Vargold,^[174] a series of particular novels inspired by Norse erudition. Graphic artist Jón Páll Halldórsson explains that the similarities halfway his portrayal of the Norse God Odinn and Kári Stefánsson are purely accidental.

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