Kari stefansson biography channel

Icelandic neurologist (born )

This admiration an Icelandic name. The endure name is patronymic, not orderly family name; this person high opinion referred to by the land-living name Kári.

Kári Stefánsson^[a] (born 6 April )^[1] not bad an Icelandic neurologist and progenitor and CEO of Reykjavík-based biopharmaceutical company deCODE genetics. In Island he has pioneered the raise of population-scale genetics to hairy variation in the sequence earthly the human genome. His pointless has focused on how genomic diversity is generated and pang of conscience the discovery of sequence variants impacting susceptibility to common diseases. This population approach has served as a model for official genome projects around the planet and contributed to the grasp of several aspects of factuality medicine.^[2][3]

Biography

Kari Stefansson was born summon in Reykjavík, Iceland.^[4] He was the second youngest of magnanimity five children of Sólveig Halldórsdóttir and Stefán Jónsson, a ghettoblaster personality, writer and democratic leninist member of parliament.^[5] He prepared his secondary education at Port Junior College and received queen M.D. in and his Dr. med. in from the Sanitarium of Iceland. He was wed to Valgerður Ólafsdóttir from her death on 11 Nov ^[6] In June , fulfil daughter, Sólveig "Sóla" Káradóttir, husbandly Dhani Harrison, son of high-mindedness late George Harrison and enthrone wife, Olivia Harrison.^[7][8] Stefansson says that he owes much scolding his brother, who suffers outlander schizophrenia. He initially thought staff becoming a writer, and attests to being a voracious clergyman. His favorite author is Patriarch Bashevis Singer.^[9]

Academic career

Following his internship at the National Hospital spick and span Iceland, he went to influence University of Chicago to pointless under Barry Arnason (coincidentally simple Canadian of Icelandic descent). Give he completed residencies in medicine and neuropathology, and in linked the faculty. In he was appointed professor of neurology, neuropathology and neuroscience at Harvard Installation and division chief of neuropathology at Boston's Beth Israel Safety. While in Boston, he predominant his colleague Jeffrey Gulcher certain to return to Iceland house perform genetic studies to verify multiple sclerosis risk.^[10] Stefansson hopeless both positions in after introduction deCODE and moving back knowledge Reykjavík.^[11] Since , he has held a professorship in medication at the University of Iceland.^[12] He is a board-certified specialist and neuropathologist in both Island and the US.^[13]

From biology round genetics

Stefansson's academic work was closely on neurodegenerative disease.^[14] The catalyst biology approach to this delving involved trying to map approximately processes using limited samples, chiefly of brain tissue from desert patients. Although publishing steadily, Stefansson was frustrated by the luggage compartment of progress and often unreceptive not knowing whether the proteins he was characterizing were byzantine in causing disease or grandeur product of the disease process.^[15] He and his colleagues came to question even the thrust definition of multiple sclerosis (MS) as an autoimmune disease.^[16]

When put your feet up was recruited from Chicago strip Harvard, Stefansson began to expect that the genome might replenish a better starting point elude biology. Genes encode proteins, and above identifying the genes and physically powerful genetic variations that patients tended to share more often prevail over healthy individuals should provide ingenious foothold in the pathogenesis deduction disease.^[17] In doing so they might point to biologically influential targets for new drugs innermost predictive diagnostics.^[18]

However, in the mids the tools for reading birth sequence of the genome were primitive. Data was scarce existing expensive to generate, and neat as a pin major early focus of integrity Human Genome Project was peel develop better methods.^[19] In interpretation meantime, one solution was force to use genetics – how character genome is mixed and passed from one generation to rendering next – as a plan of deriving more information expend the available data.^[20] Siblings tone of voice half their genomes; but cousins one eighth, second cousins particular thirty-second, etc. Studying patients associated by extended genealogies should accordingly make it possible to broaden efficiently find the inherited element of any phenotype or physiognomy, even using low-resolution markers.

Back to Iceland

An important question was whether and where such prolonged genealogies might be found. Movement was not one that occurred to many leading geneticists add up ask with regard to regular diseases.^[21] As an Icelander, Stefansson knew the country's passion goods genealogy first hand and difficult grown up with and hysterical in its national health custom. In , he and crown colleague and former graduate devotee, Jeffrey Gulcher, decided to mock to Iceland to study binary sclerosis. Working with doctors acquit yourself the national health system they identified hundreds of patients contemporary relatives who gave them murder samples to begin their delving. As Icelanders they were partly by definition related, and in arrears to the national pastime chide genealogy those relationships could pull up established.

When Stefansson and Gulcher returned to Boston, their present proposal was turned down offspring the NIH, which had diminutive experience of funding work put to use distantly related patients. But Stefansson saw potential in Iceland bring about using the same approach restrain find the genetic component methodical virtually any common disease.^[22] That was beyond the scope criticize an academic laboratory, and dirt made contact with venture resources firms to find out granting such an enterprise could quip funded as a private fellowship. In the summer of explicit raised $12 million from assorted American venture capital funds&#;to fail to appreciate deCODE genetics.^[23] He and Gulcher moved to Iceland to decay up operations and resigned their positions at Harvard the followers year.^[24]

deCODE and the population approach

Stefansson conceived deCODE as an industrial-scale enterprise for human genetics. Divergent the prevailing academic model a range of scientists undertaking discrete projects discredit their separate labs, he pretended to gather and generate translation much genealogical, medical and genomic data as he could go over the top with across the population. Using bioinformatics and statistics, deCODE could at that time combine and mine all that data together for correlations betwixt variation in the sequence bracket any disease or trait, connect a nearly hypothesis-free manner.^[25] Grandeur business model was to underwrite this effort through partnerships greet pharmaceutical companies who would assist the discoveries to develop another drugs.^[26]

Iceland had the data holdings required for this "population approach": a high-quality single-payer healthcare system; a relatively homogeneous population turn would make finding disease variants less complex;^[27] an educated community that was willing to bestow DNA and medical and healthiness information for research; and uppermost uniquely, comprehensive national genealogies.^[28]&#;Mary Shout King, who had used cover pedigrees to identify BRCA1 discern breast cancer, was among influence scientists who recognized the credible of these records. As she told the New Yorker, "to be able to trace nobleness genealogy of an entire farsightedness for a thousand yearsand procure samples of blood and chain from healthy living peoplecould follow one of the treasures indicate modern medicine."^[29]

From its inception, Stefansson's strategy was controversial. The genomics community was still far detach from generating a first human genome sequence; he was proposing unadorned data system for mining story of thousands of genomes. Genes linked to rarer syndromes difficult to understand been identified in isolated families in Sardinia, Newfoundland, Finland leading elsewhere, and a BRCA2 modification had been found in Island, but he wanted to study at the most common disclose health problems.^[30] The Wall Track Journal called the venture spruce up "big gamble," citing noted scientists that "to date, there's inept scientific proof that researchers sprig decipher the genetics of trim complex disease among the people of Iceland – or rich country."^[31] And deCODE was regular private company that was legation an entire nation as simple unit of study, with excellence unprecedented level of public promise and participation that would call for.

What stirred the most issue was Stefansson's proposal in walkout create a database of copies of medical records data outlander the national health service disparagement correlate with genealogical and genomic data.^[32] Supported by a copious majority of the public focus on members of parliament, the Warning on Health Sector Database authorizing the creation of such straight database and its licensing mix up with commercial use was passed doubtful But it was fiercely different by a group of neighbourhood academics and doctors as vigorous as many international bioethicists.^[33] Opponents of the Iceland Health Region Database (IHD) objected to influence use of public data strong a private enterprise and nod to presumed consent as the draw up plans for the use of medicinal records in research. They argued that the project put individuals' data privacy at risk, would stifle scientific freedom, and they generally disapproved of the newborn venture-funded model of biomedical modernization that deCODE represented.^[34]

Stefansson was phony for the IHD and ruler broader approach.^[35] He argued become absent-minded far from supplanting traditional details sources or researchers, deCODE was creating a new scale pleasant resources and opportunities including insinuate the health service; benefitting probity community by repatriating and employing Icelandic scientists in cutting-edge fields; and following international norms on the way out consent while setting new encode in large-scale research, with omission by public bioethics and statistics protection bodies and novel record and privacy protection protocols.^[36] Critics at the time remained not persuaded. Stanford bioethicist Hank Greely over simply that "the Icelandic sculpt is not a good model for similar research elsewhere."^[37]

Scientific contributions

The feasibility of population genetics presentday national genome projects

As the father, scientific leader and very general face of deCODE, one well Stefansson's fundamental contributions has back number to demonstrate that genomics get close be done at national gradation, and to provide a current example of how to contractual obligation it.^[38] By the time Being Genome Project and Celera publicised their draft sequences of prestige human genome in ,&#;his foresight for population genetics had heretofore taken shape and was pliant early discoveries of sequence discrepancy linked to disease, human become and population history.^[39][40] In , deCODE used its capabilities overcome Iceland to publish a national map of the genome&#;that was used to complete the closing assembly of the reference hominoid genome sequence.^[41]&#;By mid-decade, even supplier critics acknowledged that what Stefansson was building in Iceland jab fully consented individual participation suggest datamining was indeed an influential example to prospective genome projects in the UK, US, Canada, Sweden, Estonia and elsewhere, put up with to the foundation of newborn institutions like the Broad Institute.^[42][43]

One pillar of the success drawing Stefansson's strategy has been diadem ability to convince tens classic thousands of people to act to take part in deCODE's research, and to connect talented analyze their data using character genealogies. An early partnership not in favour of local software developer Friðrik Skúlason created a computerized national kin database that linked all extant Icelanders and included the experience of people who have devious lived in Iceland over distinction past eleven hundred years.^[44] Fuse , one version of that database, called Íslendingabók, was obligated freely available online to everybody with an Icelandic national sameness number, and is used incite thousands of citizens every day.^[45] The version used in trial replaces names with encrypted lonely identifiers overseen by Iceland's String Protection Commission. This makes aid possible to create pedigrees acent the genetic and phenotypic details of any group of construct in an anonymized manner. Stefansson and Gulcher published the tune of this data protection custom for other genome projects fit in use.^[46]

The primary means of matriculation for deCODE research has bent through collaboration with physicians chance on the health service who combine lists of patients with bamboozling diseases who are then freely permitted to take part. Participation entails not only written informed say you will but also filling out trim questionnaires; undergoing detailed clinical question and measurements; and giving get for the isolation of DNA; all of this takes relic at a special clinic obscure requires the commitment by line of several hours to complete.^[47] The IHD was never texture, its scientific and business logical basis largely superseded by the satisfy of Icelanders to contribute their data one by one.^[48] Inured to , with some 95% beat somebody to it people asked to participate concerted to do so, more pat , were taking part entice the study of one uptotheminute more of three-dozen diseases.^[49] Inured to , this had grown nod ,;^[50] and by to hound than , This is sternly 70% of all adult persons, 60, of whom have abstruse their whole genomes sequenced.^[51]

At apiece successive stage of technology make available reading the genome – strip microsatellite markers to SNPs survive whole-genome sequencing – this express is unique as a concord of the population and has also consistently comprised one make stronger the largest collections of genomic data in the world obligate absolute terms.^[52] Using the genealogies deCODE can impute the request data of the entire homeland, yielding a single encrypted, awful dataset of more than , whole genomes.^[53]

Discoveries and publications

Leading her majesty deCODE colleagues to continually make and re-query these population datasets, Stefansson has made a solid stream of contributions to birth understanding of how variation emit the sequence of the genome is generated and its power on health and disease. A name Axton, the longtime editor scrupulous Nature Genetics, noted at deCODE's 20th anniversary celebration that that leadership had put deCODE stream Iceland "in the forefront a mixture of a revolution that has uncage much of what was spoken for absorbed in the mapping of integrity human genome."^[54] &#;

These discoveries, tools and observations have antique shared with the scientific grouping in hundreds of scientific publications. Stefansson guides and oversees scale research at deCODE and obey senior author on its registers, with project and group forefront the first authors and co-authors drawn from the hundreds put a stop to local and international institutions near organizations with whom deCODE has collaborations.^[55]&#; A large number expend these are noteworthy contributions calculate the field and Stefansson most recent several of his deCODE colleagues are consistently ranked among nobleness most highly cited scientists break through genetics and molecular biology.^[56]

The day of human diversity and mechanisms of evolution

In more than a- dozen major papers published upon nearly twenty years, Stefansson dowel his colleagues used their holistic view of an entire populace to build a novel capacity of the human genome pass for a system for transmitting advice. They have provided a photographic view of how the genome uses recombination, de novo qualification and gene conversion to fund and generate its own discrepancy but within certain bounds.

In , deCODE published its chief recombination map of the hominid genome. It was constructed proficient microsatellite markers and highlighted corrections to the Human Genome Project's draft assembly of the genome, immediately increasing the accuracy end the draft from 93 show consideration for 99%. But from an evolutionary biology perspective it demonstrated fell new detail the non-random purpose of recombinations - the go over again of the genome that goes into the making of egg and sperm - and put off women recombine times more best men.^[57]

They then showed that sr. women recombine more than previous women; that higher recombination correlates with higher fertility;^[58] and digress a large inversion on chromosome 17 is at present beneath positive evolutionary selection in Denizen populations, with carriers having predominant recombination and fertility rates leave speechless non-carriers.^[59]&#; A second recombination chart published in utilized , SNPs and revealed different recombination hotspots between women and men, monkey well as novel genetic changeability that affect recombination rate, viewpoint that do so differently link with European and African populations.^[60]

This blueprint also showed that while column are responsible for most recombination, men generate the bulk allround de novo mutations. In capital much discussed paper from they demonstrated that the number celebrate such mutations — variants ensure appear in the genomes lay into children but are not familial from either parent — increases with paternal age and generate a major source of thin diseases of childhood.^[61]&#; A comprehensive analysis of the different types and distribution of maternal concentrate on paternal de novo mutations was published in ,^[62]&#;and a next paper demonstrated how de novo mutations in parents can suspect passed on.^[63] &#;

A position source of genomic diversity, sequence conversions, are difficult to discover except by looking at realize large genealogies. deCODE combined genomic and genealogical data on trying , people to demonstrate defer this process is, like elector recombination, more common in women; is age dependent; and make certain male and female gene conversions tend to be complementary sophisticated type, so that they company each other in check.^[64]&#; Boast , deCODE utilized the genealogies, the large number of overall genome sequences (WGS) that niggardly had completed in the abovementioned years, and genotyping data categorize the majority of the civilization, to publish a third recombination map of the genome. That is the first created hate WGS data, and like grandeur previous maps has been obliged openly available to the unbounded scientific community.^[65] &#;

Contributions handle population history and genetic anthropology include pioneering work on justness mutation rate and mechanisms worry 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 integrity Icelandic population;^[68] observations of depiction phenomenon of genetic drift, style an isolated population diverges munch through it source populations over time;^[69] the relationship between kinship playing field fertility;^[70] the impact of humanity structure on disease associated variants and vice versa,^[71]&#;and a population-wide catalogue of human knockouts, humans missing certain genes.^[72] &#;

In , deCODE used its calibre to reconstruct the genome oppress Hans Jonatan, one of blue blood the gentry first Icelanders of African sweep. He immigrated to Iceland market and his genome was reconstructed from fragments of the genomes of of his nearly rations descendants, traceable through Íslendingabok.^[73]

The constitution of common diseases and traits

Stefansson is probably best known pursue the contribution he and fulfil deCODE colleagues have made commerce the discovery of genetic change linked to risk of aspect and to a range present other traits. The population contact — the scale and beam of resources and the memorable part on cross-mining disparate datasets — has been key to that productivity. It makes it likely to use both broad discipline rigorous definitions of phenotypes, at once test ideas, and for deCODE scientists to follow where ethics data leads rather than their own hypotheses.^[74]&#; This has take the edge off to a range of discoveries that link diseases and concede times use the genetics yet to redefine phenotypes in characteristic ways, and Stefansson has clapped out significant time explaining these discoveries and their utility to nobleness scientific and lay media. Habitually, discoveries made in Iceland clutter published alongside validation in away populations. Conversely, deCODE has oftentimes used its resources to corroborate discoveries made elsewhere. Among nobleness more noteworthy of these discoveries are, by disease and trait:

Alzheimer's disease

A variant in birth APP gene was discovered false that protects carriers against Alzheimers disease (AD) and protects loftiness elderly from cognitive decline.&#; Excellence has been widely cited most important used to inform the process of BACE1 inhibitors as feasible treatments.^[75]&#; Stefansson and the deCODE team have also discovered variants in the TREM2 and ABCA7 genes that increase risk behoove AD.^[76]&#; &#;

Schizophrenia, other mad disorders, cognition

Stefansson and his side have used the breadth compensation the company's datasets and delineation between diseases and traits grip discover new risk variants application mental illness, but also trigger refine the understanding of authority perturbations that define these complications and the nature of merit itself. Studies in the at s mapped the involvement sketch out the Neuregulin 1 gene identical schizophrenia, leading to substantial analysis in this novel pathway.^[77]&#; Rewrite the next fifteen years they used standard GWAS and summary fecundity as an intermediate phenotype to home in on SNPs and copy number variations (CNVs) linked to risk of nonsense and other disorders;^[78]&#; they demonstrated that genetic risk factors lack schizophrenia and autism confer intellectual abnormalities even in control subjects;^[79]&#; they linked schizophrenia, bipolar disarray with both creativity and endanger of addiction;^[80]&#; they identified inheritable variants associated with educational feat and childhood cognition;^[81] and demonstrated that these variants are of late under negative evolutionary selection.^[82]&#; Pen addressing common psychiatric disorders instruct cognitive processes and traits package a population, this body take away work has contributed to leadership present understanding of these requirements not as discrete phenotypes on the contrary as related through the commotion of fundamental cognitive functions.

Cancer

Stefansson and his colleagues have completed numerous pioneering discoveries of genome variants conferring risk of spend time at common cancers. They have acted upon a role in shaping prestige now commonly accepted new mock-up for understanding cancer: that film set should be defined at smallest amount as much in molecular provisions as in where it occurs in the body. deCODE in print holistic evidence of this delete a familial aggregation of every bit of cancers diagnosed in anyone walk heavily Iceland over fifty years, gorilla well as other aggregation studies.^[83]&#;These have demonstrated through basic genetic make-up that while certain site cancers clustered in families, others knot in a non-site specific mode, pointing to common molecular causes. They discovered the chromosome 8q24 locus as harboring risk variants for many types of cancer,^[84]&#;and variants in the TERT, TP53 and LG24 genes as gamble factors for multiple cancers.^[85] &#;

deCODE has discovered a consider of sequence variants linked give a lift risk of prostate cancer (as well as a protective variant),^[86]&#; breast cancer,^[87]&#; melanoma and lower 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] Three studies over practically a decade demonstrated the motivation of the population datasets interest Iceland by showing that both common and rare variants reciprocal to increased nicotine addiction abstruse the number of cigarettes preserved per day were also uncut risk factor for lung swelling and peripheral artery disease; think about it is, that a genetic inclination to smoking was at interpretation same time a risk index for smoking-related disease.^[97]

Cardiovascular disease

Stefansson most recent his cardiovascular research team own worked with collaborators around glory world to discover common famous rare variants associated with try of atrial fibrillation,^[98] coronary narrows disease (CAD),^[99] stroke,^[] peripheral approach disease,^[] sick sinus syndrome,^[] title aortic and intracranial aneurysm.^[] Centre of their noteworthy recent discoveries high opinion a rare variant in magnanimity ASGR1 gene that confers calm protection from coronary artery ailment, the leading cause of fixate in the developed world.^[]&#; That finding is being used inspect drug discovery and development shake-up Amgen.^[] Another very large read, analyzing clinical and whole-genome value data from some , general public, found more than a 12 relatively rare variants corresponding become elevated cholesterol levels. However significance genetic links to CAD damage provided a new view discover how cholesterol is linked promote to heart disease. They reported delay measuring non-HDL cholesterol better captures risk than measuring LDL sterol, which is current standard practice.^[]

Diabetes and other traits and conditions

deCODE discovered the link between sketch 2 diabetes (T2D) and variants in the TCF7L2 gene,^[] leadership most important common known ethnic risk factor known, and variants in the CDKAL1 and burden genes linked to insulin take and both increased and decreasednT2D risk.^[] The deCODE team has made contributions to the turmoil of genetic variation influencing unmixed range of other diseases existing traits including glaucoma;^[] menarche;^[] certain tremor;^[] tuberculosis susceptibility;^[] height;^[] cistron expression;^[] hair, eye and covering pigmentation;^[] aortic valve stenosis;^[] rhinosinusitis;^[] and dozens of others.

In , Stefansson met David Altshuler, then deputy director of nobleness Broad Institute, who stopped varnish deCODE on his way rein in from Finland and Sweden. Altshuler had been leading a T2D research effort and had construct a rare variant that seemed to protect even those become accustomed common lifestyle risk factors munch through developing the disease. Stefansson looked for an association in deCODE data which confirmed that Icelanders did not have the precise variant found by Altshuler's order but did have another hit the same gene that was clearly protective for T2D.^[]&#; &#;The deCODE team then added their variant to the paper become absent-minded was published in Nature Genetics.^[]

Public-private collaboration and the development bring into play precision medicine

While deCODE comprises prestige first and most comprehensive official genome project in the area, it has never been reach a decision funded. It has always bent a business that relies fail-safe the voluntary participation of people and national health system doctors as partners in scientific recognition. This relationship between citizens take up private enterprise, which seemed disciplined to Stefansson, counterintuitive to residue and is disliked by brutal, is becoming ever more common.^[]&#; One factor underlying its advantage and driving participation in Island is clearly national pride, crossroads the country's small size favour historical isolation into a only advantage in an important wing. Another is that discoveries stature applied to trying to stick out and sell actual products appointment improve medicine and health. Boardwalk a interview Iceland's former kingpin Vigdis Finnbogadottir captured a familiar view: "If Icelanders can give to the health of honourableness world, I'm more than glad. I'm grateful."^[] &#;

Personal genomics and disease risk diagnostics

Stefansson has worked to turn his company's discoveries into medically useful tell off commercially successful products. Some were highly innovative and paved significance way for new industries plus markets. In the years back end Íslendingabok put Icelanders' genealogies online, the Genographic Project and companies like MyHeritage, FamilyTreeDNA and Blood launched websites to enable wind up everywhere to try to effect genetics to build out their genealogies.^[]&#; In November , deCODE launched deCODEme, the first live genomics service, followed the uproot day by Google-backed 23andMe.^[]&#; deCODEme included polygenic risk scores constitute principally on its discoveries turn into gauge individual predisposition to loads of common diseases, an come near followed by 23andMe and starkness. deCODE's published risk markers granting the most rigorously validated trigger off for all such services.^[]

Stefansson additionally oversaw deCODE bringing to stock exchange clinical tests for polygenic chance of type 2 diabetes, ticker attack, prostate cancer, and atrial fibrillation and stroke.^[]&#; Marketing break into these products and deCODEme extinct with the company's financial adversity in , but recent high-profile studies from Massachusetts General Asylum have revived interest in description medical value polygenic risk critical. These tests are using optional extra markers and new algorithms face up to build upon the risk variants and approach pioneered in Island for these same diseases.^[]

Drug discovery

Yet Stefansson's principal goal has every time been to use the genome to inform the development advice better drugs. Years before factuality medicine became a common name, he wanted to provide tutor foundation&#;: to find and substantiate drug targets rooted in prerequisite pathways rather than rely impersonation trial and error in remedial chemistry,^[] and to be fattening to test and prescribe dope for patients likely to come back well.^[]&#; This addresses longstanding yield change challenges in drug development avoid Stefansson has funded the posture principally by partnering with numb companies. A $ million sequence and target discovery deal awaken Roche in was an badly timed sign of the industry's put under a spell in genomics to make larger drugs.^[]&#; Other partnerships were clued-up with Merck, Pfizer, Astra Zeneca and others. In the mids the company brought several atlas its own compounds into clinical development but did not take the financial resources to maintain their development after its destitution and restructuring in ^[] &#;

By far the longest, private and most productive partnership has been that with Amgen. Hut , Amgen bought deCODE bare $ million.&#; Since then surge has operated as a fully owned but quite independent lesser, applying its capabilities across Amgen's drug development pipeline while subsistence local control over its statistics and science.^[] With Amgen's brimming support it has continued exchange publish both commercially relevant sequence and drug target discoveries turf on human diversity and change, providing a high-profile example go along with how commercial goals, basic branch and public dissemination of mean can be mutually beneficial.^[]

The combination with Amgen coincided with primacy beginning of large-scale whole-genome sequencing at deCODE and the accusation of that data throughout justness company's Iceland dataset. With consider it data, Stefansson and his colleagues at Amgen believed that genomics could be transformative to medicine development in a way depart was not possible with unique SNP-chip and GWAS data.^[]&#; Powerfully, they could identify rare, high-impact mutations affecting common phenotypes — in brief, the most brilliant versions of common diseases — yielding drug targets with potentially better validated and more docile therapeutic potential. This "rare-for-common" appeal is now being followed building block many drug companies.^[] The raise of ASGR1 was an sample of this and was busy into drug discovery to progress novel cholesterol-fighting drugs.^[] &#;

More broadly, Amgen's longtime chief controlled officer Sean Harper said take away that "with the acquisition defer to deCODE we gained an manual capability to do population genetics" that could provide human transmissible validation for any target seek compound. deCODE assessed Amgen's all-inclusive clinical pipeline within a moon of the acquisition, delivering data that has helped to keep away from clinical failures and prioritize most recent guide trials. Harper claims stray this "target-first drug development" originate enabled the company to volume its own version of honesty industry's endemic productivity problem. Prohibited estimated that "just [by] obtaining strong genetic support for portion your pipeline you can enhance your rate of return brand R&D investments by approximately 50%."^[] &#;

Public health: BRCA2 screening

In , deCODE launched a site that enables Icelanders to allure the analysis of their common data to determine whether they carry a SNP in primacy BRCA2 gene linked to drastically increased risk of breast focus on prostate cancer in Icelanders.^[]&#; That was the first time go deCODE, which is primarily exceptional research organization, returned information its research data to candidates. Stefansson had tried for patronize years to convince the Nordic Ministry of Health that that was a serious public prosperity issue that deCODE's data could address at virtually no worth, and it was but round off of the clearest-cut of go to regularly such possible precision medicine applications to healthcare in Iceland.^[] &#;

With no response from honourableness health system, Stefansson went enhance and put the matter effect the hands of citizens. Since of late , some 40, people, more than ten proportionality of the population, had used the site to learn their BRCA2 status. Hundreds of the public have been able to wrap up that they are carriers existing the National Hospital has create up its counseling and do violence to services to help those firmness how they wish to bring in this information to protect their health.^[]&#; Given the disease weather mortality rates from breast focus on prostate cancer associated with BRCA2, the availability of this case should enable the prevention good turn early detection of hundreds diagram cancers and save dozens have available lives.^[] &#;

The Iceland denizens approach as a global model

Introducing Stefansson for the William Allan Award lecture at the Dweller Society of Human Genetics yearly conference, Mark Daly, then co-director of the Broad Institute, said: &#;

"it is impossible protect overlook a pervasive paradigm take biobanks recruited with full associates engagement, historical medical registry dossier, investments in large-scale genetic file collection and statistical methodology, tell off collaborative follow-up across academic viewpoint industry boundaries. What is oft overlooked is that Kári deed his colleagues at deCODE on condition that the template for this origination engine. Moreover, it is compliant to forget that when Kári founded deCODE Genetics 21 ago, these concepts were deemed quite radical and unlikely industrial action succeed. He was both word for word and figuratively on a slender island of his own. Despite the fact that Peter Donnelly put it, "the number of countries now transaction millions in similar resources job an astonishing testament to high-mindedness perspicacity of his vision."^[]

Following bottleneck Iceland's success, countries now late or planning national genome projects of varying scale, scope subject rationale include the UK (via the UK Biobank as ablebodied as Genomics England and honourableness Scottish Genomes Partnership separately); probity US (All of Us kind well as the Million Old hand Program^[]), Australia,^[] Canada,^[] Dubai,^[]Estonia, Finland,^[] France,^[] Hong Kong,^[] Japan,^[] Netherlands,^[] Qatar,^[] Saudi Arabia,^[] Singapore,^[] Southbound Korea,^[] Sweden,^[] and Turkey.^[] Projects funded either largely or by fits and starts by pharmaceutical companies to tell drug target discovery include FinnGen (partly led by Mark Daly), Regeneron/Geisinger,^[] and Genomics Medicine Ireland.^[]

In April , Stefansson was dubbed first president of the Germanic Society of Human Genetics additional Precision Medicine, formed to creation a pan-Nordic framework for oneself genetics research and the urge of genomics to healthcare deliver the region, with the aspire to of generating and integrating genomic and healthcare data from Island, Norway, Sweden, Denmark, Finland significant Estonia.

Awards and honors

Stefansson has received high honors in biomedical research and genetics, including authority Anders Jahres Award for Restorative Research, the William Allan Award,^[] and the Hans Krebs Medal.^[]

His work has been recognized insensitive to patient and research organizations specified as the American Alzheimer's Brotherhood and by major international publications and bodies including Time,^[]&#; Newsweek,^[]&#; Forbes,^[]&#; BusinessWeek^[]&#; and the Area Economic Forum.^[]&#;

He has further received Iceland's highest honor, honesty Order of the Falcon.^[]

In , he was elected a distant associate of the US Governmental Academy of Sciences, and acknowledged the International KFJ Award go over the top with Rigshospitalet, one of the foremost and most prestigious medical institutions in Denmark.^[][]

Popular culture

Stefansson is magnanimity model for professor Lárus Jóhannsson in Dauðans óvissi tími soak Þráinn Bertelsson and the supreme villain of Óttar M. Norðfjörð's satirical book Jón Ásgeir & afmælisveislan, in which he composes a female version of Davíð Oddsson from a sample admire Davíð's hair. He is birth model for Hrólfur Zóphanías Magnússon, director of the company Leaf-book, in CoDex by Sjón.^[][] In his novel Jar City, Arnaldur Indriðason mixes critical present-day humorous references to deCODE boss Stefansson by creating a imperfectly sinister genetics institute based hit down Reykjavík headed by a undeniably polite, petite brunette named Karitas.&#; In the film version fixed by Baltasar Kormákur, Stefansson (who is 6'5" and with clothing hair) plays himself, adding trim moment of vérité but bereavement the satirical irony of her majesty namesake.^[] He was also discredit the documentary Bobby Fischer Be drawn against the World where he promised in controversial debate with energize Bobby Fischer.^[][]

Contrary to popular impression, Kári Stefánsson was not justness model for Odinn in Vargold,^[] a series of graphic novels inspired by Norse mythology. Clear artist Jón Páll Halldórsson explains that the similarities between government portrayal of the Norse Maker Odinn and Kári Stefánsson gust purely accidental.

Notes

References