“I Was Destined to Come Back Here” Kári Stefánsson, deCODE
No other company represents the potential of genomics better than deCODE genetics. Steering the course is their straight-talking CEO, Kári Stefánsson, who has shaped the company’s scientific approach. The company may not even exist had it not been for some failed N.I.H. grant applications from Dr. Stefánsson’s time in the US as a neuropathologist.
Ahead of founding deCODE in 1996, the Icelander was keen to study possible genetic roots of multiple sclerosis in Icelandic families. The country has great genealogical records, fantastic medical records, and engaged patients. However, at the time, it was generally believed that sibling studies were the only way to get robust and statistically significant results for this kind of research. Not one to take ‘no’ for an answer, Dr. Stefánsson raised $12 million in six weeks and founded the company that would allow him to take the field of human genetics forward into a new era.
Ahead of his keynote talk at the Festival of Genomics London 2017, we spoke with Dr. Stefánsson. He will be returning for the third Festival of Genomics London in January 2018. On day one of the 2018 Festival, Kári will be speaking on ‘Genetics of function and dysfunction of the brain’. To hear from Kári simply register for your FREE Festival pass here.
FLG: This year marks the 20th anniversary of deCODE Genetics. In those 20 years, what do you recognise as the company’s greatest achievement so far?
KS: My problem is that I always think that what we discovered yesterday is the most important discovery we have made. We have made a large contribution to the study of generational diversity in the sequence by studying de novo mutations, recombinations, and gene conversions; the genome is always changing – we are always adjusting to the environment we live in and I think that our contributions there are formidable.
You can read the full interview with Kári Stefánsson in the latest issue of FLG magazine
We have made substantial contributions to the study of the common diseases of man – I would point to our discoveries in Alzheimer’s disease as among the more important. We discovered a variant in the sequence that confers almost a complete protection against Alzheimer’s disease and, in that, provided those who want to make medicine a proof of concept for the idea of inhibiting Base 1 as a way to protect against Alzheimer’s disease. We discovered another mutation in the TREM2 gene – TREM2 stands for Triggering Receptor Expressed on Myeloid Cells Type 2 – that significantly increases the risk of Alzheimer’s disease and that is also being used as a target in an attempt to develop drugs against the disease. We discovered a series of mutations ABCA7 gene that confers a risk of the disease. And what is interesting about the APP protective mutation and the TREM2 mutation is that they also affect the normal cognitive decline of the elderly. The APP mutation that protects against Alzheimer’s disease also slows down normal cognitive decline and the one in TREM2 that increases the risk of Alzheimer’s also increases the speed of normal cognitive decline, raising the possibility that Alzheimer’s may simply be an accelerated form of the normal cognitive decline of the elderly. We also recently published a paper on a mutation in a gene that protects against the coronary artery disease, and the list goes on and on. We have made very significant contributions to the study of the germline genetics of cancer and we have basically dominated
that field over the past 15-20 years. So the overall goal, for us, is to increase the understanding of how diversity in the sequence contributes to human diversity and we are very proud of the amount and the quality of the contributions that we have made there.
FLG: How big of an impact do you think large-scale genomics is having on drug development at the moment?
KS: I think it is having a very significant impact. It’s having an impact by helping big pharma to find new targets, new biochemical pathways to either up-regulate or down-regulate to contain a disease, but it can be used for so many other things; for example, when it comes to Amgen, we have been helping them to develop good ways of predicting the potential side effects of drugs. When they were developing their anti-PCSK9 antibody, one of the concerns raised was the possibility that lowering cholesterol dramatically might increase probability of dementia and so in real time we could look at variants in the PCSK9 gene that lowered cholesterol and we could ask whether it is associated with dementia and it isn’t. We could see that they were actually associated with increased life-span. So if you have large amounts of genetic data, you can use it to help you make discoveries that can yield new targets and to predict the potential desired and undesired effects on manipulated pathways. You can use it to stratify patients into clinical trials etc.
I think that the pharmaceutical industry has finally managed to get over the hype that was around genetics at the time the Human Genome Project was completed and people overhyped the potential in genetics. It took about a decade or so for the industry to get over that, but now it has started to utilise the potential that lies in human genetics and I think they are benefiting enormously from it.
FLG: What do you think is the biggest question someone is going to be able to ask from all this data one day?
KS: I am biased because I used to be a neurologist and a neuropathologist and I am extremely interested in trying to find out how the brain works. The brain is just an organ, just like the kidney; the kidney makes piss and the brain makes important emotions, and I hope that genetics will finally help us to figure out how the brain thinks and how the brain feels. That is basically at the centre of who we are; as a species and as individuals of this species, we are defined by our thoughts and our emotions and I hope that genetics can help us to figure out how all this takes place.
Visit the Festival of Genomics London website for more information on what will be going on at the event.
This is an extract from an interview which first appeared in FLG Magazine here.