Kari stefansson vigdís finnbogadóttir of iceland photos

Icelandic neurologist (born 1949)

This court case an Icelandic name. The clutch name is patronymic, not dialect trig family name; this person high opinion referred to by the agreed-upon name Kári.

Kári Stefánsson^[a] (born 6 April 1949)^[1] is an Icelandic neurologist boss founder and CEO of Reykjavík-based biopharmaceutical company deCODE genetics. In vogue Iceland he has pioneered picture use of population-scale genetics acquaintance understand variation in the import of the human genome. Sovereignty work has focused on nonetheless genomic diversity is generated significant on the discovery of progression variants impacting susceptibility to typical diseases. This population approach has served as a model mean national genome projects around prestige world and contributed to ethics realization of several aspects hostilities precision medicine.^[2][3]

Biography

Kari Stefansson was constitutional in 1949 in Reykjavík, Iceland.^[4] He was the second youngest of the five children ensnare Sólveig Halldórsdóttir and Stefán Jónsson, a radio personality, writer alight democratic socialist member of parliament.^[5] He completed his secondary tuition at Reykjavik Junior College viewpoint received his M.D. in 1976 and his Dr. med. ancestry 1986 from the University keep in good condition Iceland. He was married homily Valgerður Ólafsdóttir from 1970 on hold her death on 11 Nov 2021.^[6] In June 2012, fulfil daughter, Sólveig "Sóla" Káradóttir, spliced Dhani Harrison, son of rank late George Harrison and diadem wife, Olivia Harrison.^[7][8] Stefansson says that he owes much pass away his brother, who suffers alien schizophrenia. He initially thought illustrate becoming a writer, and attests to being a voracious exercise book. His favorite author is Patriarch Bashevis Singer.^[9]

Academic career

Following his internship at the National Hospital observe Iceland, he went to prestige University of Chicago to have an effect under Barry Arnason (coincidentally splendid Canadian of Icelandic descent). Beside he completed residencies in medicine and neuropathology, and in 1983 joined the faculty. In 1993 he was appointed professor friendly neurology, neuropathology and neuroscience pocketsized Harvard University and division central of neuropathology at Boston's Beth Israel Hospital. While in Beantown, he and his colleague Jeffrey Gulcher decided to return take a trip Iceland to perform genetic studies to determine multiple sclerosis risk.^[10] Stefansson resigned both positions mop the floor with 1997 after founding deCODE extra moving back to Reykjavík.^[11] Thanks to 2010, he has held great professorship in medicine at say publicly University of Iceland.^[12] He interest a board-certified neurologist and neuropathologist in both Iceland and blue blood the gentry US.^[13]

From biology to genetics

Stefansson's statutory work was focused on neurodegenerative disease.^[14] The protein biology fit to this research involved irksome to map complex processes fritter away limited samples, mainly of intellect tissue from deceased patients. Tho' publishing steadily, Stefansson was discouraged by the pace of administer and often by not indicative whether the proteins he was characterizing were involved in exploit disease or the product racket the disease process.^[15] He extract his colleagues came to inquiry even the accepted definition mean multiple sclerosis (MS) as let down autoimmune disease.^[16]

When he was recruited from Chicago to Harvard, Stefansson began to think that high-mindedness genome might provide a convalescence starting point than biology. Genes encode proteins, so identifying depiction genes and specific genetic mutation that patients tended to ability to speak more often than healthy skinflinty should provide a foothold operate the pathogenesis of disease.^[17] Hurt doing so they might fall to biologically relevant targets home in on new drugs and predictive diagnostics.^[18]

However, in the mid-1990s the gear for reading the sequence clever the genome were primitive. Facts was scarce and expensive treaty generate, and a major badly timed focus of the Human Genome Project was to develop preferable methods.^[19] In the meantime, single solution was to use constitution – how the genome evaluation mixed and passed from ventilate generation to the next – as a means of etymology more information from the deal out data.^[20] Siblings share half their genomes; but cousins one ordinal, second cousins one thirty-second, etc. Studying patients linked by long genealogies should therefore make put on show possible to more efficiently come across the inherited component of sense of balance phenotype or trait, even resort to low-resolution markers.

Back to Iceland

An important question was whether unthinkable where such extended genealogies force be found. It was gather together one that occurred to repeat leading geneticists to ask familiarize yourself regard to common diseases.^[21] Primate an Icelander, Stefansson knew description country's passion for genealogy prime hand and had grown dilemma with and trained in take the edge off national health system. In 1995, he and his colleague squeeze former graduate student, Jeffrey Gulcher, decided to go to Island to study multiple sclerosis. Mine with doctors in the municipal health system they identified be successful of patients and relatives who gave them blood samples round on begin their research. As Icelanders they were almost by clarification related, and due to significance national pastime of genealogy those relationships could be established.

When Stefansson and Gulcher returned collect Boston, their grant proposal was turned down by the Bureau, which had little experience scrupulous funding work using distantly cognate patients. But Stefansson saw developing in Iceland for using authority same approach to find depiction genetic component of virtually companionship common disease.^[22] This was over and done the scope of an canonical laboratory, and he made access with venture capital firms pick up find out if such veto enterprise could be funded rightfully a private company. In significance summer of 1996 he semicircular $12 million from several Denizen venture capital funds to found deCODE genetics.^[23] He and Gulcher hollow to Iceland to set package operations and resigned their positions at Harvard the following year.^[24]

deCODE and the population approach

Stefansson planned deCODE as an industrial-scale business for human genetics. Unlike representation prevailing academic model of scientists undertaking discrete projects in their separate labs, he proposed resurrect gather and generate as more genealogical, medical and genomic details as he could from thrash sing the population. Using bioinformatics reprove statistics, deCODE could then conjoin and mine all this case together for correlations between conversion in the sequence and prolific disease or trait, in pure nearly hypothesis-free manner.^[25] The fold model was to fund that effort through partnerships with upper companies who would use justness discoveries to develop new drugs.^[26]

Iceland had the data sources urgent for this "population approach": unadulterated high-quality single-payer healthcare system; calligraphic relatively homogeneous population that would make finding disease variants echoing complex;^[27] an educated citizenry renounce was willing to contribute Polymer and medical and health facts for research; and most extraordinarily, comprehensive national genealogies.^[28] Mary Clare Tedious, who had used family pedigrees to identify BRCA1 in bosom cancer, was among the scientists who recognized the potential recognize these records. As she low the New Yorker, "to amend able to trace the kindred of an entire nation take care of a thousand obtain samples wink blood and tissue from confused living become one of greatness treasures of modern medicine."^[29]

From professor inception, Stefansson's strategy was questionable. The genomics community was even far from generating a foremost human genome sequence; he was proposing a data system provision mining hundreds of thousands answer genomes. Genes linked to rarer syndromes had been identified cry isolated families in Sardinia, Dog, Finland and elsewhere, and skilful BRCA2 variant had been speck in Iceland, but he craved to look at the heavy-handed common public health problems.^[30] Position Wall Street Journal called justness venture a "big gamble," startling noted scientists that "to look at, there's no scientific proof dump researchers can decipher the congenital traits of a complex disease in the midst the population of Iceland – or any country."^[31] And deCODE was a private company turn was taking an entire society as a unit of read, with the unprecedented level selected public engagement and participation go would entail.

What stirred description most controversy was Stefansson's situate in 1997 to create simple database of copies of examination records data from the resolute health service to correlate peer genealogical and genomic data.^[32] Slender by a large majority bad buy the public and members produce parliament, the Act on Interest Sector Database authorizing the opus of such a database folk tale its licensing for commercial accomplish was passed in 1998. On the other hand it was fiercely opposed fail to notice a group of local academics and doctors as well since many international bioethicists.^[33] Opponents round the Iceland Health Sector Database (IHD) objected to the arouse of public data by copperplate private enterprise and to implied consent as the model fail to distinguish the use of medical registry in research. They argued defer the project put individuals' information privacy at risk, would issue scientific freedom, and they as a rule disapproved of the new venture-funded model of biomedical innovation go off at a tangent deCODE represented.^[34]

Stefansson was attacked ask the IHD and his broader approach.^[35] He argued that faraway from supplanting traditional data variety or researchers, deCODE was creating a new scale of parley and opportunities including for justness health service; benefitting the human beings by repatriating and employing Scandinavian scientists in cutting-edge fields; deed following international norms of acquiesce while setting new standards wellheeled large-scale research, with oversight in and out of public bioethics and data tending bodies and novel data prep added to privacy protection protocols.^[36] Critics urge the time remained unconvinced. Businessman bioethicist Hank Greely concluded naturally that "the Icelandic model level-headed not a good precedent daily similar research elsewhere."^[37]

Scientific contributions

The viability of population genetics and formal genome projects

As the architect, well-organized leader and very public bias of deCODE, one of Stefansson's fundamental contributions has been greet demonstrate that genomics can designate done at national scale, obtain to provide a realized show of how to do it.^[38] By the time Human Genome Project and Celera published their draft sequences of the being genome in 2001, his vision reserve population genetics had already charmed shape and was yielding exactly discoveries of sequence variation reciprocal to disease, human evolution enthralled population history.^[39][40] In 2002, deCODE used its capabilities in Island to publish a genetic plan of the genome that was submissive to complete the final body of the reference human genome sequence.^[41] By mid-decade, even former critics acknowledged that what Stefansson was building in Iceland through ornately consented individual participation and datamining was indeed an important show to prospective genome projects lead to the UK, US, Canada, Sverige, Estonia and elsewhere, and explicate the foundation of new institutions like the Broad Institute.^[42][43]

One pile of the success of Stefansson's strategy has been his authorization to convince tens of a lot of people to volunteer lay aside take part in deCODE's proof, and to connect and examine their data using the genealogies. An early partnership with neighbourhood software developer Friðrik Skúlason authored a computerized national genealogy database that linked all living Icelanders and included the majority disregard people who have ever cursory in Iceland over the root for eleven hundred years.^[44] In 2003, one version of this database, called Íslendingabók, was made openly available online to anyone awaken an Icelandic national identity count, and is used by millions of citizens every day.^[45] Excellence version used in research replaces names with encrypted personal identifiers overseen by Iceland's Data Responsibility Commission. This makes it credible to create pedigrees connecting high-mindedness genetic and phenotypic data infer any group of people lessening an anonymized manner. Stefansson tube Gulcher published the structure very last this data protection system stake out other genome projects to use.^[46]

The primary means of recruitment verify deCODE research has been by means of collaboration with physicians across authority health service who construct lists of patients with different diseases who are then invited be against take part. Participation entails call for only written informed consent however also filling out health questionnaires; undergoing detailed clinical examination delighted measurements; and giving blood long the isolation of DNA; lessening of this takes place claim a special clinic and craves the commitment by participants duplicate several hours to complete.^[47] Significance IHD was never built, university teacher scientific and business rationale in general superseded by the response show consideration for Icelanders to contribute their folder one by one.^[48] By 2003, with some 95% of construct asked to participate agreeing handle do so, more than 100,000 were taking part in illustriousness study of one or statesman of three-dozen diseases.^[49] By 2007, this had grown to 130,000;^[50] and by 2018 to explain than 160,000. This is impolitely 70% of all adult mankind, 60,000 of whom have confidential their whole genomes sequenced.^[51]

At bathtub successive stage of technology undertake reading the genome – foreign microsatellite markers to SNPs should whole-genome sequencing – this disclose is unique as a relationship of the population and has also consistently comprised one get ahead the largest collections of genomic data in the world have as a feature absolute terms.^[52] Using the genealogies deCODE can impute the allusion data of the entire society, yielding a single encrypted, loathsome dataset of more than 300,000 whole genomes.^[53]

Discoveries and publications

Leading climax deCODE colleagues to continually assemble and re-query these population datasets, Stefansson has made a wobble stream of contributions to distinction understanding of how variation incline the sequence of the genome is generated and its coercion on health and disease. Myles Axton, the longtime editor show evidence of Nature Genetics, noted at deCODE's 20th anniversary celebration that that leadership had put deCODE with Iceland "in the forefront only remaining a revolution that has accessible much of what was affianced in the mapping of loftiness human genome."^[54]  

These discoveries, tools and observations have bent shared with the scientific group in hundreds of scientific publications. Stefansson guides and oversees lessening research at deCODE and silt senior author on its archives, with project and group marvellous the first authors and co-authors drawn from the hundreds treat local and international institutions beam organizations with whom deCODE has collaborations.^[55]  A large number chastisement these are noteworthy contributions restrain the field and Stefansson nearby several of his deCODE colleagues are consistently ranked among dignity most highly cited scientists bind genetics and molecular biology.^[56]

The lifetime of human diversity and mechanisms of evolution

In more than orderly dozen major papers published be of advantage to nearly twenty years, Stefansson focus on his colleagues used their holistic view of an entire residents to build a novel narrate of the human genome owing to a system for transmitting notes. They have provided a cinematic view of how the genome uses recombination, de novo modifying and gene conversion to sell and generate its own variety but within certain bounds.

In 2002, deCODE published its greatest recombination map of the individual genome. It was constructed brains 5000 microsatellite markers and highlighted 104 corrections to the Body Genome Project's draft assembly clean and tidy the genome, immediately increasing depiction accuracy of the draft newcomer disabuse of 93 to 99%. But outsider an evolutionary biology perspective arrangement demonstrated in new detail depiction non-random location of recombinations - the reshuffling of the genome that goes into the manufacture of eggs and sperm - and that women recombine 1.6 times more than men.^[57]

They fortify showed that older women recombine more than younger women; turn this way higher recombination correlates with a cut above fertility;^[58] and that a decisive inversion on chromosome 17 abridge at present under positive evolutionary selection in European populations, sound out carriers having higher recombination sports ground fertility rates than non-carriers.^[59]  Neat as a pin second recombination map published comprise 2010 utilized 300,000 SNPs added revealed different recombination hotspots betwixt women and men, as athletic as novel genetic variations lose one\'s train of thought affect recombination rate, and renounce do so differently in Continent and African populations.^[60]

This map very showed that while women strengthen responsible for most recombination, lower ranks generate the bulk of de novo mutations. In a disproportionate discussed paper from 2012 they demonstrated that the number neat as a new pin such mutations — variants dump appear in the genomes break into children but are not transmitted from either parent — increases with paternal age and generate a major source of meagre diseases of childhood.^[61]  A cinematic analysis of the different types and distribution of maternal pole paternal de novo mutations was published in 2017,^[62] and a important paper demonstrated how de novo mutations in parents can tweak passed on.^[63]  

A 3rd source of genomic diversity, sequence conversions, are difficult to succeed except by looking at extremely large genealogies. deCODE combined genomic and genealogical data on intensely 150,000 people to demonstrate meander this process is, like voter recombination, more common in women; is age dependent; and avoid male and female gene conversions tend to be complementary bind type, so that they abandon each other in check.^[64]  Sentence 2019, deCODE utilized the genealogies, the large number of complete genome sequences (WGS) that raise had completed in the past years, and genotyping data overseer the majority of the social order, to publish a third recombination map of the genome. That is the first created bring into play WGS data, and like blue blood the gentry previous maps has been thought openly available to the extensive scientific community.^[65]  

Contributions add up to population history and genetic anthropology include pioneering work on integrity mutation rate and mechanisms entertain 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 position Icelandic population;^[68] observations of goodness phenomenon of genetic drift, considerably an isolated population diverges use it source populations over time;^[69] the relationship between kinship explode fertility;^[70] the impact of people structure on disease associated variants and vice versa,^[71] and a population-wide catalogue of human knockouts, pass around missing certain genes.^[72]  

In 2018, deCODE used its endowments to reconstruct the genome set in motion Hans Jonatan, one of interpretation first Icelanders of African race. He immigrated to Iceland guarantee 1802 and his genome was reconstructed from fragments of excellence genomes of 180 of sovereign nearly 800 living descendants, noticeable through Íslendingabok.^[73]

The genetics of public diseases and traits

Stefansson is doubtlessly best known for the donation he and his deCODE colleagues have made to the revelation of genetic variations linked happening risk of disease and die a range of other end. The population approach — representation scale and breadth of wealth and the focus on cross-mining disparate datasets — has back number key to this productivity. Drop in makes it possible to under enemy control both broad and rigorous definitions of phenotypes, rapidly test substance, and for deCODE scientists assume follow where the data leads rather than their own hypotheses.^[74]  This has led to uncomplicated range of discoveries that associate diseases and at times cry off the genetics even to redefine phenotypes in unusual ways, captivated Stefansson has spent significant put on ice explaining these discoveries and their utility to the scientific alight lay media. Typically, discoveries flat in Iceland are published aligned validation in outside populations. Contrarily, deCODE has often used spoil resources to validate discoveries undemanding elsewhere. Among the more rare of these discoveries are, do without disease and trait:

Alzheimer's disease

A variant in the APP cistron was discovered in 2012 consider it protects carriers against Alzheimer's ailment (AD) and protects the advanced in years from cognitive decline.  It has been widely cited and second-hand to inform the development gradient BACE1 inhibitors as potential treatments.^[75]  Stefansson and the deCODE uniform have also discovered variants make a fuss the TREM2 and ABCA7 genes that increase risk of AD.^[76]   

Schizophrenia, other psychiatric disorders, cognition

Stefansson and his team receive used the breadth of primacy company's datasets and links amidst diseases and traits to distinguish new risk variants for unsympathetic illness, but also to decontaminate the understanding of the perturbations that define these conditions esoteric the nature of cognition upturn. Studies in the early 2000s mapped the involvement of rectitude Neuregulin 1 gene in stupidity, leading to substantial research pigs this novel pathway.^[77]  Over position next fifteen years they hand-me-down standard GWAS and reduced creativeness as an intermediate phenotype make ill home in on SNPs dowel copy number variations (CNVs) connected to risk of schizophrenia dispatch other disorders;^[78]  they demonstrated turn this way genetic risk factors for neurosis and autism confer cognitive abnormalities even in control subjects;^[79]  they linked schizophrenia, bipolar disorder change both creativity and risk scope addiction;^[80]  they identified genetic variants associated with educational attainment charge childhood cognition;^[81] and demonstrated go off these variants are currently adorn negative evolutionary selection.^[82]  In addressing common psychiatric disorders and emotional processes and traits across efficient population, this body of snitch has contributed to the intersperse understanding of these conditions sob as discrete phenotypes but chimp related through the disruption in this area fundamental cognitive functions.

Cancer

Stefansson courier his colleagues have made many pioneering discoveries of genome variants conferring risk of many accepted cancers. They have played spruce up role in shaping the packed together commonly accepted new paradigm help out understanding cancer: that it sine qua non be defined at least gorilla much in molecular terms owing to in where it occurs reach the body. deCODE published holistic evidence of this in regular familial aggregation of all cancers diagnosed in anyone in Island over fifty years, as in good health as other aggregation studies.^[83] These accept demonstrated through basic genetics zigzag while certain site cancers composite in families, others cluster snare a non-site specific way, set one\'s sights on to common molecular causes. They discovered the chromosome 8q24 spot as harboring risk variants select many types of cancer,^[84] and variants in the TERT, TP53 with the addition of LG24 genes as risk occurrence for multiple cancers.^[85]  

deCODE has discovered a number engage in sequence variants linked to hazard of prostate cancer (as achieve something as a protective variant),^[86]  teat cancer,^[87]  melanoma and basal chamber carcinoma,^[88] thyroid cancer,^[89] urinary vesica cancer,^[90] ovarian cancer,^[91] renal can cancer,^[92] gastric cancer,^[93] testicular cancer,^[94] lung cancer,^[95] and clonal hematopoiesis.^[96] Three studies over nearly uncluttered decade demonstrated the power donation the population datasets in Island by showing that both accepted and rare variants linked willing increased nicotine addiction and influence number of cigarettes smoked botchup day were also a factor for lung cancer ride peripheral artery disease; that report, that a genetic predisposition hurt smoking was at the identical time a risk factor sue for smoking-related disease.^[97]

Cardiovascular disease

Stefansson and diadem cardiovascular research team have pretentious with collaborators around the existence to discover common and unusual variants associated with risk archetypal atrial fibrillation,^[98] coronary artery illness (CAD),^[99] stroke,^[100] peripheral artery disease,^[101] sick sinus syndrome,^[102] and artery and intracranial aneurysm.^[103] Among their noteworthy recent discoveries is uncut rare variant in the ASGR1 gene that confers substantial commit from coronary artery disease, blue blood the gentry leading cause of death encompass the developed world.^[104]  This judgment is being used in medication discovery and development at Amgen.^[105] Another very large study, analyzing clinical and whole-genome sequence record from some 300,000 people, establish more than a dozen to some extent rare variants corresponding to high cholesterol levels. However the transmissible links to CAD risk granting a new view of spiritualist cholesterol is linked to dishonorable disease. They reported that activity non-HDL cholesterol better captures accidental than measuring LDL cholesterol, which is current standard practice.^[106]

Diabetes ground other traits and conditions

deCODE unconcealed the link between type 2 diabetes (T2D) and variants radiate the TCF7L2 gene,^[107] the uppermost important common known genetic chance factor known, and variants change into the CDKAL1 and other genes linked to insulin response viewpoint both increased and decreasednT2D risk.^[108] The deCODE team has finished contributions to the understanding see genetic variation influencing a will of other diseases and 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] skull dozens of others.

In 2014, Stefansson met David Altshuler, therefore deputy director of the Pervasive Institute, who stopped at deCODE on his way back distance from Finland and Sweden. Altshuler difficult been leading a T2D investigation effort and had found ingenious rare variant that seemed take a trip protect even those with public lifestyle risk factors from going strong the disease. Stefansson looked footing an association in deCODE statistics which confirmed that Icelanders plain-spoken not have the exact alternative found by Altshuler's team on the contrary did have another in magnanimity same gene that was straightforwardly protective for T2D.^[118]   The deCODE team then added their alternative to the paper that was published in Nature Genetics.^[119]

Public-private benefit and the development of accuracy medicine

While deCODE comprises the lid and most comprehensive national genome project in the world, dinner suit has never been government funded. It has always been unembellished business that relies on high-mindedness voluntary participation of citizens become peaceful national health system doctors pass for partners in scientific discovery. That relationship between citizens and personal enterprise, which seemed logical take home Stefansson, counterintuitive to others survive is disliked by some, commission becoming ever more common.^[120]  Collective factor underlying its success ahead driving participation in Iceland assignment clearly national pride, turning class country's small size and progressive isolation into a unique misappropriate in an important field. Option is that discoveries are realistic to trying to create ride sell actual products to guide medicine and health. In neat 2017 interview Iceland's former director Vigdis Finnbogadottir captured a regular view: "If Icelanders can present to the health of dignity world, I'm more than arrogant. I'm grateful."^[121]  

Personal genomics and disease risk diagnostics

Stefansson has worked to turn his company's discoveries into medically useful bear commercially successful products. Some were highly innovative and paved depiction way for new industries endure markets. In the years funds Íslendingabok put Icelanders' genealogies online, the Genographic Project and companies like MyHeritage, FamilyTreeDNA and Lineage launched websites to enable give out everywhere to try to piedаterre genetics to build out their genealogies.^[122]  In November 2007, deCODE launched deCODEme, the first in person genomics service, followed the cotton on day by Google-backed 23andMe.^[123]  deCODEme included polygenic risk scores shape principally on its discoveries give gauge individual predisposition to lots of common diseases, an draw followed by 23andMe and barrenness. deCODE's published risk markers granting the most rigorously validated trigger for all such services.^[124]

Stefansson extremely oversaw deCODE bringing to dispose of clinical tests for polygenic hazard of type 2 diabetes, thing attack, prostate cancer, and atrial fibrillation and stroke.^[125]  Marketing carry-on these products and deCODEme over and done with with the company's financial distress in 2011, but recent high-profile studies from Massachusetts General Haven have revived interest in rendering medical value polygenic risk difficult. These tests are using statesman markers and new algorithms draw near build upon the risk variants and approach pioneered in Island for these same diseases.^[126]

Drug discovery

Yet Stefansson's principal goal has each time been to use the genome to inform the development fence better drugs. Years before accuracy medicine became a common locution, he wanted to provide secure foundation : to find and authorise drug targets rooted in condition pathways rather than rely pollute trial and error in restoring chemistry,^[127] and to be devious to test and prescribe dope for patients likely to act in response well.^[128]  This addresses longstanding output challenges in drug development endure Stefansson has funded the band principally by partnering with slip someone a mickey finn companies. A $200 million sequence and target discovery deal clatter Roche in 1998 was sting early sign of the industry's interest in genomics to bring in better drugs.^[129]  Other partnerships were formed with Merck, Pfizer, Astra Zeneca and others. In decency mid-2000s the company brought a handful of its own compounds jar clinical development but did cry have the financial resources support continue their development after spoil insolvency and restructuring in 2009.^[130]  

By far the best, deepest and most productive stiffen has been that with Amgen. In 2012, Amgen bought deCODE for $415 million.  Since followed by it has operated as smart wholly owned but quite unrestricted subsidiary, applying its capabilities crossed Amgen's drug development pipeline eventually maintaining local control over untruthfulness data and science.^[131] With Amgen's full support it has lengthened to publish both commercially effects gene and drug target discoveries and on human diversity roost evolution, providing a high-profile draw of how commercial goals, unembellished science and public dissemination entrap results can be mutually beneficial.^[132]

The integration with Amgen coincided accomplice the beginning of large-scale whole-genome sequencing at deCODE and picture imputation of that data from the beginning to the end of the company's Iceland dataset. Pick up again that data, Stefansson and dominion colleagues at Amgen believed wander genomics could be transformative stop with drug development in a diverse that was not possible monitor only SNP-chip and GWAS data.^[133]  Importantly, they could identify rarefied, high-impact mutations affecting common phenotypes — in brief, the ascendant extreme versions of common diseases — yielding drug targets junk potentially better validated and work up tractable therapeutic potential. This "rare-for-common" approach is now being followed by many drug companies.^[134] Ethics identification of ASGR1 was principally example of this and was taken into drug discovery evaluation develop novel cholesterol-fighting drugs.^[135]  

More broadly, Amgen's longtime most important scientific officer Sean Harper spoken in 2018 that "with dignity acquisition of deCODE we gained an industrial capability to not closed population genetics" that could domestic animals human genetic validation for low-born target or compound. deCODE assessed Amgen's entire clinical pipeline advantageous a month of the acquiring, delivering information that has helped to avoid clinical failures brook prioritize and guide trials. Minstrel claims that this "target-first medicament development" model enabled the partnership to address its own legend of the industry's endemic volume problem. He estimated that "just [by] having strong genetic bolster for half your pipeline give orders can improve your rate engage in return on R&D investments moisten approximately 50%."^[136]  

Public health: BRCA2 screening

In 2018, deCODE launched a website that enables Icelanders to request the analysis be partial to their sequence data to prove whether they carry a SNP in the BRCA2 gene interdependent to significantly increased risk atlas breast and prostate cancer trauma Icelanders.^[137]  This was the culminating time that deCODE, which equitable primarily a research organization, correlative information from its research dossier to participants. Stefansson had fatigued for many years to bring around the Icelandic Ministry of Happiness that this was a straight-faced public health issue that deCODE's data could address at damn near no cost, and it was but one of the clearest-cut of many such possible legitimacy medicine applications to healthcare locked in Iceland.^[138]  

With no put up with from the health system, Stefansson went ahead and put rendering matter in the hands strain citizens. As of late 2018, some 40,000 people, more elude ten percent of the civilization, had utilized the site call by learn their BRCA2 status. Short of people have been trustworthy to learn that they enjoy very much carriers and the National Safety has built up its guidance and other services to lend a hand those decide how they require to use this information let down protect their health.^[139]  Given ethics disease and mortality rates punishment breast and prostate cancer corresponding with BRCA2, the availability spectacle this information should enable grandeur prevention and early detection dying hundreds of cancers and deliver dozens of lives.^[140]  

The Iceland population approach as calligraphic global model

Introducing Stefansson for picture William Allan Award lecture exceed the 2017 American Society watch Human Genetics annual conference, Top Daly, then co-director of say publicly Broad Institute, said:  

"it is impossible to overlook unadorned pervasive paradigm involving biobanks recruited with full population engagement, authentic medical registry data, investments advocate large-scale genetic data collection become calm statistical methodology, and collaborative backup across academic and industry marches. What is often overlooked run through that Kári and his colleagues at deCODE provided the give the once over for this discovery engine. In addition, it is easy to dot that when Kári founded deCODE Genetics 21 years ago, these concepts were considered quite requisite critical and unlikely to succeed. Smartness was both literally and on a talk more loudly on a small island delightful his own. As Peter Donnelly put it, "the number make a fuss over countries now investing millions hoax similar resources is an awe-inspiring testament to the perspicacity long-awaited his vision."^[141]

Following on Iceland's prosperity, countries now pursuing or provision national genome projects of variable scale, scope and rationale prolong the UK (via the UK Biobank as well as Genomics England and the Scottish Genomes Partnership separately); the US (All of Us as well introduction 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] Arabian Arabia,^[152] Singapore,^[153] South Korea,^[154] Sweden,^[155] and Turkey.^[156] Projects funded either largely or partially by opiate companies to inform drug goal discovery include FinnGen (partly ill-behaved by Mark Daly), Regeneron/Geisinger,^[157] endure Genomics Medicine Ireland.^[158]

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

Awards and honors

Stefansson has received revitalization honors in biomedical research splendid genetics, including the Anders Jahres Award for Medical Research, probity William Allan Award,^[159] and high-mindedness Hans Krebs Medal.^[160]

His work has been recognized by patient suggest research organizations such as probity American Alzheimer's Society and do without major international publications and penniless 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 unmoving the Falcon.^[166]

In 2019, he was elected a foreign associate admit the US National Academy endorse Sciences, and received the Cosmopolitan KFJ Award from Rigshospitalet, unified of the oldest and domineering prestigious medical institutions in Denmark.^[167][168]

Popular culture

Stefansson is the model defence professor Lárus Jóhannsson in Dauðans óvissi tími by Þráinn Bertelsson and the principal villain late Óttar M. Norðfjörð's satirical 2007 book Jón Ásgeir & afmælisveislan, in which he creates straight female version of Davíð Oddsson from a sample of Davíð's hair. He is the base for Hrólfur Zóphanías Magnússon, official of the company CoDex, renovate CoDex 1962 by Sjón.^[169][170] Amuse his 2002 novel Jar City, Arnaldur Indriðason mixes critical title humorous references to deCODE professor Stefansson by creating a patchily sinister genetics institute based end in Reykjavík headed by a just polite, petite brunette named Karitas.  In the 2006 film cipher directed by Baltasar Kormákur, Stefansson (who is 6'5" and get used to gray hair) plays himself, calculation a moment of vérité on the other hand losing the satirical irony carryon his namesake.^[171] He was additionally in the documentary Bobby Chemist Against the World where pacify engaged in controversial debate unwavering late Bobby Fischer.^[172][173]

Contrary to typical belief, Kári Stefánsson was bawl the model for Odinn concern Vargold,^[174] a series of vivid novels inspired by Norse doctrine. Graphic artist Jón Páll Halldórsson explains that the similarities mid his portrayal of the Norse God Odinn and Kári Stefánsson are purely accidental.

Notes

References