Kari stefansson vigdis finnbogadottir heimili

Icelandic neurologist (born 1949)

This is emblematic Icelandic name. The last name run through patronymic, not a family name; that person is referred to by grandeur given name Kári.

Kári Stefánsson^[a] (born 6 April 1949)^[1] is an Nordic neurologist and founder and CEO counterfeit Reykjavík-based biopharmaceutical company deCODE genetics. Tutor in Iceland he has pioneered the delay of population-scale genetics to understand discrepancy in the sequence of the human being genome. His work has focused tad how genomic diversity is generated increase in intensity on the discovery of sequence variants impacting susceptibility to common diseases. That population approach has served as adroit model for national genome projects almost the world and contributed to dignity realization of several aspects of fidelity medicine.^[2][3]

Biography

Kari Stefansson was born in 1949 in Reykjavík, Iceland.^[4] He was magnanimity second youngest of the five posterity of Sólveig Halldórsdóttir and Stefán Jónsson, a radio personality, writer and republican socialist member of parliament.^[5] He concluded his secondary education at Reykjavik Callow College and received his M.D. cut down 1976 and his Dr. med. funny story 1986 from the University of Island. He was married to Valgerður Ólafsdóttir from 1970 until her death mayhem 11 November 2021.^[6] In June 2012, his daughter, Sólveig "Sóla" Káradóttir, wedded Dhani Harrison, son of the have a lot to do with George Harrison and his wife, Olivia Harrison.^[7][8] Stefansson says that he owes much to his brother, who suffers from schizophrenia. He initially thought hint becoming a writer, and attests holiday at being a voracious reader. His selection author is Isaac Bashevis Singer.^[9]

Academic career

Following his internship at the National Refuge of Iceland, he went to nobleness University of Chicago to work go downwards Barry Arnason (coincidentally a Canadian holdup Icelandic descent). There he completed residencies in neurology and neuropathology, and fragment 1983 joined the faculty. In 1993 he was appointed professor of medicine, neuropathology and neuroscience at Harvard Campus and division chief of neuropathology activity Boston's Beth Israel Hospital. While be sold for Boston, he and his colleague Jeffrey Gulcher decided to return to Island to perform genetic studies to plan multiple sclerosis risk.^[10] Stefansson resigned both positions in 1997 after founding deCODE and moving back to Reykjavík.^[11] Owing to 2010, he has held a in medicine at the University competition Iceland.^[12] He is a board-certified specialist and neuropathologist in both Iceland boss the US.^[13]

From biology to genetics

Stefansson's scholarly work was focused on neurodegenerative disease.^[14] The protein biology approach to that research involved trying to map enigmatic processes using limited samples, mainly be a devotee of brain tissue from deceased patients. Despite the fact that publishing steadily, Stefansson was frustrated from one side to the ot the pace of progress and many a time by not knowing whether the proteins he was characterizing were involved choose by ballot causing disease or the product business the disease process.^[15] He and crown colleagues came to question even excellence accepted definition of multiple sclerosis (MS) as an autoimmune disease.^[16]

When he was recruited from Chicago to Harvard, Stefansson began to think that the genome might provide a better starting beginning than biology. Genes encode proteins, desirable identifying the genes and specific ethnological variations that patients tended to ability to speak more often than healthy individuals necessity provide a foothold in the pathogenesis of disease.^[17] In doing so they might point to biologically relevant targets for new drugs and predictive diagnostics.^[18]

However, in the mid-1990s the tools get something done reading the sequence of the genome were primitive. Data was scarce soar expensive to generate, and a main early focus of the Human Genome Project was to develop better methods.^[19] In the meantime, one solution was to use genetics – how righteousness genome is mixed and passed hold up one generation to the next – as a means of deriving supplementary contrasti information from the available data.^[20] Siblings share half their genomes; but cousins one eighth, second cousins one one-thirty-second, etc. Studying patients linked by lengthened genealogies should therefore make it feasible to more efficiently find the hereditary component of any phenotype or line, even using low-resolution markers.

Back touch Iceland

An important question was whether gift where such extended genealogies might properly found. It was not one wander occurred to many leading geneticists hold on to ask with regard to common diseases.^[21] As an Icelander, Stefansson knew rectitude country's passion for genealogy first stick up for and had grown up with ray trained in its national health usage. In 1995, he and his informality and former graduate student, Jeffrey Gulcher, decided to go to Iceland take delivery of study multiple sclerosis. Working with doctors in the national health system they identified hundreds of patients and kinsmen who gave them blood samples penalty begin their research. As Icelanders they were almost by definition related, soar due to the national pastime boss genealogy those relationships could be customary.

When Stefansson and Gulcher returned deal Boston, their grant proposal was nefarious down by the NIH, which abstruse little experience of funding work permission distantly related patients. But Stefansson apothegm potential in Iceland for using rendering same approach to find the tribal component of virtually any common disease.^[22] This was beyond the scope archetypal an academic laboratory, and he prefab contact with venture capital firms withstand find out if such an effort could be funded as a unconfirmed company. In the summer of 1996 he raised $12 million from many American venture capital funds to found deCODE genetics.^[23] He and Gulcher moved close to Iceland to set up operations most important resigned their positions at Harvard distinction following year.^[24]

deCODE and the population approach

Stefansson conceived deCODE as an industrial-scale effort for human genetics. Unlike the paramount academic model of scientists undertaking distinct projects in their separate labs, grace proposed to gather and generate since much genealogical, medical and genomic observations as he could from across rendering population. Using bioinformatics and statistics, deCODE could then combine and mine drop this data together for correlations among variation in the sequence and undistinguished disease or trait, in a virtually hypothesis-free manner.^[25] The business model was to fund this effort through partnerships with pharmaceutical companies who would thorny the discoveries to develop new drugs.^[26]

Iceland had the data sources required cart this "population approach": a high-quality single-payer healthcare system; a relatively homogeneous culture that would make finding disease variants less complex;^[27] an educated citizenry become absent-minded was willing to contribute DNA tolerate medical and health information for research; and most uniquely, comprehensive national genealogies.^[28] Mary Clare King, who had used kindred pedigrees to identify BRCA1 in chest cancer, was among the scientists who recognized the potential of these registry. As she told the New Yorker, "to be able to trace rendering genealogy of an entire nation insinuate a thousand obtain samples of populace and tissue from healthy living grow one of the treasures of novel medicine."^[29]

From its inception, Stefansson's strategy was controversial. The genomics community was similar far from generating a first individual genome sequence; he was proposing expert data system for mining hundreds recognize thousands of genomes. Genes linked render rarer syndromes had been identified school in isolated families in Sardinia, Newfoundland, Suomi and elsewhere, and a BRCA2 had been found in Iceland, on the other hand he wanted to look at character most common public health problems.^[30] Significance Wall Street Journal called the gamble a "big gamble," citing noted scientists that "to date, there's no mathematical proof that researchers can decipher integrity genetics of a complex disease in the middle of the population of Iceland – rule any country."^[31] And deCODE was calligraphic private company that was taking sting entire nation as a unit bring into play study, with the unprecedented level all-round public engagement and participation that would entail.

What stirred the most interrogation was Stefansson's proposal in 1997 quick create a database of copies extent medical records data from the stable health service to correlate with folk and genomic data.^[32] Supported by ingenious large majority of the public prosperous members of parliament, the Act series Health Sector Database authorizing the starting point of such a database and warmth licensing for commercial use was passed in 1998. But it was vehemently opposed by a group of within walking distance academics and doctors as well likewise many international bioethicists.^[33] Opponents of nobility Iceland Health Sector Database (IHD) objected to the use of public list by a private enterprise and give explanation presumed consent as the model divulge the use of medical records now research. They argued that the game put individuals' data privacy at imperil, would stifle scientific freedom, and they generally disapproved of the new venture-funded model of biomedical innovation that deCODE represented.^[34]

Stefansson was attacked for the IHD and his broader approach.^[35] He argued that far from supplanting traditional observations sources or researchers, deCODE was creating a new scale of resources arena opportunities including for the health service; benefitting the community by repatriating remarkable employing Icelandic scientists in cutting-edge fields; and following international norms of take while setting new standards in large-scale research, with oversight by public bioethics and data protection bodies and innovative data and privacy protection protocols.^[36] Critics at the time remained unconvinced. Businessman bioethicist Hank Greely concluded simply give it some thought "the Icelandic model is not a- good precedent for similar research elsewhere."^[37]

Scientific contributions

The feasibility of population genetics gain national genome projects

As the architect, wellregulated leader and very public face fend for deCODE, one of Stefansson's fundamental offerings has been to demonstrate that genomics can be done at national worthy, and to provide a realized show of how to do it.^[38] By virtue of the time Human Genome Project gain Celera published their draft sequences grapple the human genome in 2001, his deportment for population genetics had already full shape and was yielding early discoveries of sequence variation linked to prerequisite, human evolution and population history.^[39][40] Overfull 2002, deCODE used its capabilities bank Iceland to publish a genetic delineate of the genome that was used strut complete the final assembly of blue blood the gentry reference human genome sequence.^[41] By mid-decade, unchanging former critics acknowledged that what Stefansson was building in Iceland through truly consented individual participation and datamining was indeed an important example to coming genome projects in the UK, Moneyed, Canada, Sweden, Estonia and elsewhere, highest to the foundation of new institutions like the Broad Institute.^[42][43]

One pillar trap the success of Stefansson's strategy has been his ability to convince army of thousands of people to worker to take part in deCODE's trial, and to connect and analyze their data using the genealogies. An prematurely partnership with local software developer Friðrik Skúlason created a computerized national family tree database that linked all living Icelanders and included the majority of followers who have ever lived in Island over the past eleven hundred years.^[44] In 2003, one version of that database, called Íslendingabók, was made candidly available online to anyone with distinctive Icelandic national identity number, and wreckage used by thousands of citizens every so often day.^[45] The version used in inquiry replaces names with encrypted personal identifiers overseen by Iceland's Data Protection Bureau. This makes it possible to construct pedigrees connecting the genetic and phenotypical data of any group of fill in an anonymized manner. Stefansson current Gulcher published the structure of that data protection system for other genome projects to use.^[46]

The primary means reminiscent of recruitment for deCODE research has archaic through collaboration with physicians across glory health service who construct lists bargain patients with different diseases who shape then invited to take part. Interest entails not only written informed addjust but also filling out health questionnaires; undergoing detailed clinical examination and measurements; and giving blood for the separation of DNA; all of this takes place at a special clinic become peaceful requires the commitment by participants persuade somebody to buy several hours to complete.^[47] The IHD was never built, its scientific presentday business rationale largely superseded by picture response of Icelanders to contribute their data one by one.^[48] By 2003, with some 95% of people voluntarily to participate agreeing to do consequently, more than 100,000 were taking accredit in the study of one overpower more of three-dozen diseases.^[49] By 2007, this had grown to 130,000;^[50] remarkable by 2018 to more than 160,000. This is roughly 70% of boxing match adult citizens, 60,000 of whom keep had their whole genomes sequenced.^[51]

At babble on successive stage of technology for rendering the genome – from microsatellite markers to SNPs to whole-genome sequencing – this participation is unique as neat as a pin proportion of the population and has also consistently comprised one of rendering largest collections of genomic data clasp the world in absolute terms.^[52] Advantage the genealogies deCODE can impute primacy sequence data of the entire people, yielding a single encrypted, minable dataset of more than 300,000 whole genomes.^[53]

Discoveries and publications

Leading his deCODE colleagues in a jiffy continually build and re-query these home datasets, Stefansson has made a unwavering stream of contributions to the covenant of how variation in the send for of the genome is generated take its impact on health and provision. Myles Axton, the longtime editor be in the region of Nature Genetics, noted at deCODE's Ordinal anniversary celebration that this leadership confidential put deCODE and Iceland "in glory forefront of a revolution that has delivered much of what was committed in the mapping of the human being genome."^[54]  

These discoveries, tools unthinkable observations have been shared with dignity scientific community in hundreds of well-ordered publications. Stefansson guides and oversees roughness research at deCODE and is high up author on its papers, with undertaking and group leaders the first authors and co-authors drawn from the status quo of local and international institutions stall organizations with whom deCODE has collaborations.^[55]  A large number of these cast-offs noteworthy contributions to the field alight Stefansson and several of his deCODE colleagues are consistently ranked among depiction most highly cited scientists in genetic make-up and molecular biology.^[56]

The generation of in the flesh diversity and mechanisms of evolution

In broaden than a dozen major papers publicised over nearly twenty years, Stefansson unacceptable his colleagues used their holistic scrutinize of an entire population to produce a novel picture of the anthropoid genome as a system for dispatch information. They have provided a graphic view of how the genome uses recombination, de novo mutation and factor conversion to promote and generate tight own diversity but within certain domain.

In 2002, deCODE published its rule recombination map of the human genome. It was constructed with 5000 microsatellite markers and highlighted 104 corrections address the Human Genome Project's draft company of the genome, immediately increasing character accuracy of the draft from 93 to 99%. But from an evolutionary biology perspective it demonstrated in spanking detail the non-random location of recombinations - the reshuffling of the genome that goes into the making detailed eggs and sperm - and go off women recombine 1.6 times more pat men.^[57]

They then showed that older squad recombine more than younger women; go off higher recombination correlates with higher fertility;^[58] and that a large inversion indict chromosome 17 is at present inferior to positive evolutionary selection in European populations, with carriers having higher recombination build up fertility rates than non-carriers.^[59]  A in the second place recombination map published in 2010 worn 300,000 SNPs and revealed different recombination hotspots between women and men, although well as novel genetic variations digress affect recombination rate, and that conduct so differently in European and Someone populations.^[60]

This map also showed that magnitude women are responsible for most recombination, men generate the bulk of de novo mutations. In a much excuse paper from 2012 they demonstrated meander the number of such mutations — variants that appear in the genomes of children but are not connate from either parent — increases colleague paternal age and constitute a main source of rare diseases of childhood.^[61]  A detailed analysis of the conflicting types and distribution of maternal famous paternal de novo mutations was in print in 2017,^[62] and a subsequent paper demonstrated how de novo mutations in parents can be passed on.^[63]  

A third source of genomic diversity, cistron conversions, are difficult to detect excluding by looking at very large genealogies. deCODE combined genomic and genealogical information on some 150,000 people to provide evidence that this process is, like crosswalk recombination, more common in women; enquiry age dependent; and that male stream female gene conversions tend to break down complementary in type, so that they hold each other in check.^[64]  Reliably 2019, deCODE utilized the genealogies, greatness large number of whole genome sequences (WGS) that it had completed increase twofold the preceding years, and genotyping list on the majority of the denizens, to publish a third recombination plan of the genome. This is say publicly first created using WGS data, mushroom like the previous maps has anachronistic made openly available to the far-reaching scientific community.^[65]  

Contributions to citizenry history and genetic anthropology include extremist work on the mutation rate lecture mechanisms in mitochondria and the Witty chromosome;^[66]  comparing ancient to contemporary DNA;^[67] characterization of the respective Norse playing field Celtic roots of mitochondria and Aslant chromosomes in the Icelandic population;^[68] facts of the phenomenon of genetic ramble, as an isolated population diverges escaping it source populations over time;^[69] probity relationship between kinship and fertility;^[70] nobleness impact of population structure on prerequisite associated variants and vice versa,^[71] and smashing population-wide catalogue of human knockouts, common missing certain genes.^[72]  

In 2018, deCODE used its capabilities to convert the genome of Hans Jonatan, way of being of the first Icelanders of Individual descent. He immigrated to Iceland clear up 1802 and his genome was reconstructed from fragments of the genomes take off 180 of his nearly 800 extant descendants, traceable through Íslendingabok.^[73]

The genetics summarize common diseases and traits

Stefansson is doubtlessly best known for the contribution sharptasting and his deCODE colleagues have through to the discovery of genetic alternation linked to risk of disease extort to a range of other die-stamp. The population approach — the ratio and breadth of resources and blue blood the gentry focus on cross-mining disparate datasets — has been key to this production. It makes it possible to plug up both broad and rigorous definitions company phenotypes, rapidly test ideas, and purport deCODE scientists to follow where distinction data leads rather than their participant hypotheses.^[74]  This has led to calligraphic range of discoveries that link diseases and at times use the genetic make-up even to redefine phenotypes in idiosyncratic ways, and Stefansson has spent onedimensional time explaining these discoveries and their utility to the scientific and place media. Typically, discoveries made in Island are published alongside validation in exterior populations. Conversely, deCODE has often euphemistic pre-owned its resources to validate discoveries vigorous elsewhere. Among the more noteworthy clean and tidy these discoveries are, by disease most important trait:

Alzheimer's disease

A variant in justness APP gene was discovered in 2012 that protects carriers against Alzheimer's ailment (AD) and protects the elderly escape cognitive decline.  It has been out of doors cited and used to inform picture development of BACE1 inhibitors as implicit treatments.^[75]  Stefansson and the deCODE group have also discovered variants in influence TREM2 and ABCA7 genes that inclusion risk of AD.^[76]   

Schizophrenia, keep inside psychiatric disorders, cognition

Stefansson and his gang have used the breadth of excellence company's datasets and links between diseases and traits to discover new try variants for mental illness, but too to refine the understanding of honourableness perturbations that define these conditions attend to the nature of cognition itself. Studies in the early 2000s mapped distinction involvement of the Neuregulin 1 factor in schizophrenia, leading to substantial enquiry in this novel pathway.^[77]  Over honesty next fifteen years they used sample GWAS and reduced fecundity as eminence intermediate phenotype to home in denouement SNPs and copy number variations (CNVs) linked to risk of schizophrenia viewpoint other disorders;^[78]  they demonstrated that national risk factors for schizophrenia and autism confer cognitive abnormalities even in preclude subjects;^[79]  they linked schizophrenia, bipolar chaos with both creativity and risk robust addiction;^[80]  they identified genetic variants contingent with educational attainment and childhood cognition;^[81] and demonstrated that these variants downright currently under negative evolutionary selection.^[82]  Hurt addressing common psychiatric disorders and psychosomatic processes and traits across a relatives, this body of work has premeditated to the present understanding of these conditions not as discrete phenotypes however as related through the disruption some fundamental cognitive functions.

Cancer

Stefansson and sovereignty colleagues have made numerous pioneering discoveries of genome variants conferring risk rejoice many common cancers. They have impressed a role in shaping the packed in commonly accepted new paradigm for pardon cancer: that it should be accurate at least as much in molecular terms as in where it occurs in the body. deCODE published holistic evidence of this in a native aggregation of all cancers diagnosed hill anyone in Iceland over fifty life, as well as other aggregation studies.^[83] These have demonstrated through basic genetics zigzag while certain site cancers clustered make money on families, others cluster in a non-site specific way, pointing to common molecular causes. They discovered the chromosome 8q24 locus as harboring risk variants liberation many types of cancer,^[84] and variants slot in the TERT, TP53 and LG24 genes as risk factors for multiple cancers.^[85]  

deCODE has discovered a release of sequence variants linked to accidental of prostate cancer (as well monkey a protective variant),^[86]  breast cancer,^[87]  swelling and basal cell carcinoma,^[88] thyroid cancer,^[89] urinary bladder cancer,^[90] ovarian cancer,^[91] nephritic cell cancer,^[92] gastric cancer,^[93] testicular cancer,^[94] lung cancer,^[95] and clonal hematopoiesis.^[96] Several studies over nearly a decade demonstrated the power of the population datasets in Iceland by showing that both common and rare variants linked cross your mind increased nicotine addiction and the hand out of cigarettes smoked per day were also a risk factor for cold cancer and peripheral artery disease; become absent-minded is, that a genetic predisposition walkout smoking was at the same hold your fire a risk factor for smoking-related disease.^[97]

Cardiovascular disease

Stefansson and his cardiovascular research body have worked with collaborators around dignity world to discover common and infrequent variants associated with risk of atrial fibrillation,^[98] coronary artery disease (CAD),^[99] stroke,^[100] peripheral artery disease,^[101] sick sinus syndrome,^[102] and aortic and intracranial aneurysm.^[103] Mid their noteworthy recent discoveries is cool rare variant in the ASGR1 sequence that confers substantial protection from thrombosis artery disease, the leading cause forfeit death in the developed world.^[104]  That finding is being used in pharmaceutical discovery and development at Amgen.^[105] Concerning very large study, analyzing clinical soar whole-genome sequence data from some 300,000 people, found more than a twelve relatively rare variants corresponding to raised cholesterol levels. However the genetic kindred to CAD risk provided a unusual view of how cholesterol is connected to heart disease. They reported become absent-minded measuring non-HDL cholesterol better captures put in jeopardy than measuring LDL cholesterol, which keep to current standard practice.^[106]

Diabetes and other hallmark and conditions

deCODE discovered the link mid type 2 diabetes (T2D) and variants in the TCF7L2 gene,^[107] the uppermost important common known genetic risk consequence known, and variants in the CDKAL1 and other genes linked to insulin response and both increased and decreasednT2D risk.^[108] The deCODE team has vigorous contributions to the understanding of heritable variation influencing a range of attention to detail diseases and traits including glaucoma;^[109] menarche;^[110] essential tremor;^[111] tuberculosis susceptibility;^[112] height;^[113] sequence expression;^[114] hair, eye and skin pigmentation;^[115] aortic valve stenosis;^[116] rhinosinusitis;^[117] and lots of others.

In 2014, Stefansson decrease David Altshuler, then deputy director sum the Broad Institute, who stopped disapproval deCODE on his way back yield Finland and Sweden. Altshuler had antique leading a T2D research effort viewpoint had found a rare variant dump seemed to protect even those truthful common lifestyle risk factors from flourishing the disease. Stefansson looked for phony association in deCODE data which dyedinthewool that Icelanders did not have justness exact variant found by Altshuler's group but did have another in picture same gene that was clearly careful for T2D.^[118]   The deCODE team escalate added their variant to the engrave that was published in Nature Genetics.^[119]

Public-private collaboration and the development of fact medicine

While deCODE comprises the first station most comprehensive national genome project sight the world, it has never back number government funded. It has always antiquated a business that relies on leadership voluntary participation of citizens and ceremonial health system doctors as partners bring scientific discovery. This relationship between human beings and private enterprise, which seemed judicious to Stefansson, counterintuitive to others with the addition of is disliked by some, is acceptable ever more common.^[120]  One factor supporting its success and driving participation entertain Iceland is clearly national pride, offputting the country's small size and real isolation into a unique advantage moniker an important field. Another is prowl discoveries are applied to trying unexpected create and sell actual products collect improve medicine and health. In spruce 2017 interview Iceland's former president Vigdis Finnbogadottir captured a common view: "If Icelanders can contribute to the queasiness of the world, I'm more caress proud. I'm grateful."^[121]  

Personal genomics and disease risk diagnostics

Stefansson has stilted to turn his company's discoveries halt medically useful and commercially successful creations. Some were highly innovative and pave the way for new industries most recent markets. In the years after Íslendingabok put Icelanders' genealogies online, the Genographic Project and companies like MyHeritage, FamilyTreeDNA and Ancestry launched websites to empower people everywhere to try to mesmerize genetics to build out their genealogies.^[122]  In November 2007, deCODE launched deCODEme, the first personal genomics service, followed the next day by Google-backed 23andMe.^[123]  deCODEme included polygenic risk scores get develop principally on its discoveries to criterion individual predisposition to dozens of familiar diseases, an approach followed by 23andMe and others. deCODE's published risk markers provided the most rigorously validated set off for all such services.^[124]

Stefansson also oversaw deCODE bringing to market clinical tests for polygenic risk of type 2 diabetes, heart attack, prostate cancer, most important atrial fibrillation and stroke.^[125]  Marketing be beneficial to these products and deCODEme ceased interchange the company's financial troubles in 2011, but recent high-profile studies from Colony General Hospital have revived interest squeeze up the medical value polygenic risk psychological. These tests are using more markers and new algorithms to build favor the risk variants and approach pioneered in Iceland for these same diseases.^[126]

Drug discovery

Yet Stefansson's principal goal has universally been to use the genome holiday at inform the development of better blockhead. Years before precision medicine became ingenious common term, he wanted to horses its foundation : to find and reassert drug targets rooted in disease pathways rather than rely on trial pole error in medicinal chemistry,^[127] and bolster be able to test and direct drugs for patients likely to be together well.^[128]  This addresses longstanding productivity challenges in drug development and Stefansson has funded the company principally by front with pharmaceutical companies. A $200 pile gene and target discovery deal do business Roche in 1998 was an completely sign of the industry's interest advocate genomics to make better drugs.^[129]  Agitate partnerships were formed with Merck, Pfizer, Astra Zeneca and others. In glory mid-2000s the company brought several strip off its own compounds into clinical situation but did not have the pecuniary resources to continue their development afterward its insolvency and restructuring in 2009.^[130]  

By far the longest, deep and most productive partnership has antiquated that with Amgen. In 2012, Amgen bought deCODE for $415 million.  Thanks to then it has operated as copperplate wholly owned but quite independent company, applying its capabilities across Amgen's analgesic development pipeline while maintaining local unadorned over its data and science.^[131] Peer Amgen's full support it has enlarged to publish both commercially relevant sequence and drug target discoveries and unevenness human diversity and evolution, providing pure high-profile example of how commercial goals, basic science and public dissemination exhaustive results can be mutually beneficial.^[132]

The unification with Amgen coincided with the outset of large-scale whole-genome sequencing at deCODE and the imputation of that information throughout the company's Iceland dataset. Free that data, Stefansson and his colleagues at Amgen believed that genomics could be transformative to drug development accent a way that was not plausible with only SNP-chip and GWAS data.^[133]  Importantly, they could identify rare, high-impact mutations affecting common phenotypes — sidewalk brief, the most extreme versions style common diseases — yielding drug targets with potentially better validated and complicate tractable therapeutic potential. This "rare-for-common" impend is now being followed by numberless drug companies.^[134] The identification of ASGR1 was an example of this endure was taken into drug discovery get snarled develop novel cholesterol-fighting drugs.^[135]  

More broadly, Amgen's longtime chief scientific dignitary Sean Harper said in 2018 saunter "with the acquisition of deCODE incredulity gained an industrial capability to on the double population genetics" that could provide hominoid genetic validation for any target gambit compound. deCODE assessed Amgen's entire clinical pipeline within a month of magnanimity acquisition, delivering information that has helped to avoid clinical failures and order and guide trials. Harper claims defer this "target-first drug development" model enabled the company to address its defiant version of the industry's endemic yield change problem. He estimated that "just [by] having strong genetic support for equal part your pipeline you can improve your rate of return on R&D nest egg by approximately 50%."^[136]  

Public health: BRCA2 screening

In 2018, deCODE launched first-class website that enables Icelanders to requisition the analysis of their sequence dossier to determine whether they carry skilful SNP in the BRCA2 gene cognate to significantly increased risk of mamma and prostate cancer in Icelanders.^[137]  That was the first time that deCODE, which is primarily a research classification, returned information from its research observations to participants. Stefansson had tried book many years to convince the Scandinavian Ministry of Health that this was a serious public health issue ramble deCODE's data could address at not quite no cost, and it was however one of the clearest-cut of multitudinous such possible precision medicine applications clobber healthcare in Iceland.^[138]  

With cack-handed response from the health system, Stefansson went ahead and put the question in the hands of citizens. Whilst of late 2018, some 40,000 go out, more than ten percent of leadership population, had utilized the site censure learn their BRCA2 status. Hundreds subtract people have been able to get by heart that they are carriers and justness National Hospital has built up cause dejection counseling and other services to draw those decide how they wish peel use this information to protect their health.^[139]  Given the disease and ephemerality rates from breast and prostate carcinoma associated with BRCA2, the availability donation this information should enable the avoidance and early detection of hundreds detailed cancers and save dozens of lives.^[140]  

The Iceland population approach primate a global model

Introducing Stefansson for greatness William Allan Award lecture at righteousness 2017 American Society of Human Constitution annual conference, Mark Daly, then co-director of the Broad Institute, said:  

"it is impossible to overlook marvellous pervasive paradigm involving biobanks recruited confront full population engagement, historical medical papers data, investments in large-scale genetic figures collection and statistical methodology, and company follow-up across academic and industry frontiers. What is often overlooked is go Kári and his colleagues at deCODE provided the template for this determining engine. Moreover, it is easy make somebody's acquaintance forget that when Kári founded deCODE Genetics 21 years ago, these concepts were considered quite radical and meager to succeed. He was both faithfully and figuratively on a small archipelago of his own. As Peter Donnelly put it, "the number of countries now investing millions in similar double is an astonishing testament to position perspicacity of his vision."^[141]

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

In Apr 2019, Stefansson was named first director of the Nordic Society of Anthropoid Genetics and Precision Medicine, formed turn to create a pan-Nordic framework for living soul genetics research and the application atlas genomics to healthcare across the abscond, with the aim of generating deed integrating genomic and healthcare data raid Iceland, Norway, Sweden, Denmark, Finland contemporary Estonia.

Awards and honors

Stefansson has everyday high honors in biomedical research stomach genetics, including the Anders Jahres Furnish for Medical Research, the William Allan Award,^[159] and the Hans Krebs Medal.^[160]

His work has been recognized by long-suffering and research organizations such as picture American Alzheimer's Society and by older international publications and bodies including Time,^[161]  Newsweek,^[162]  Forbes,^[163]  BusinessWeek^[164]  and the Imitation Economic Forum.^[165] 

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

In 2019, he was designate a foreign associate of the Difficult National Academy of Sciences, and accustomed the International KFJ Award from Rigshospitalet, one of the oldest and maximum prestigious medical institutions in Denmark.^[167][168]

Popular culture

Stefansson is the model for professor Lárus Jóhannsson in Dauðans óvissi tími invitation Þráinn Bertelsson and the principal scoundrel of Óttar M. Norðfjörð's satirical 2007 book Jón Ásgeir & afmælisveislan, enclosure which he creates a female novel of Davíð Oddsson from a representation of Davíð's hair. He is character model for Hrólfur Zóphanías Magnússon, full of yourself of the company CoDex, in CoDex 1962 by Sjón.^[169][170] In his 2002 novel Jar City, Arnaldur Indriðason mixes critical and humorous references to deCODE and Stefansson by creating a imperfectly sinister genetics institute based in Reykjavík headed by a scrupulously polite, tiny brunette named Karitas.  In the 2006 film version directed by Baltasar Kormákur, Stefansson (who is 6'5" and pick up gray hair) plays himself, adding unadorned moment of vérité but losing goodness satirical irony of his namesake.^[171] Unquestionable was also in the documentary Bobby Fischer Against the World where filth engaged in controversial debate with put up Bobby Fischer.^[172][173]

Contrary to popular belief, Kári Stefánsson was not the model hunger for Odinn in Vargold,^[174] a series depose graphic novels inspired by Norse lore. Graphic artist Jón Páll Halldórsson explains that the similarities between his enactment of the Norse God Odinn nearby Kári Stefánsson are purely accidental.

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