Thursday, June 25, 2009

Conference in Trieste

After returning to my homeland, I spent my first weekend in Trieste, attending a conference about genetic isolates. I had no expectations of any kind, but I had to present a poster and give a short talk, which is always a nice experience. It turned out I had an even better time than I expected, despite the fact that it rained the all time.

The second day I met Augustine Kong, t, he head statistician from deCODE, after he gave a very inspiring talk. The company deCODE is a research company based in Reykjavik, Iceland. It was founded in 1997 by Kari Stefansson, an Icelandic researcher working at Harvard at the time. Stefansson at the time wanted to study, through genetic and pedigree data of all people from Iceland, that is, about 320000 people, all the genetic causes of the diseases affecting the people in Iceland. More than ten years ago he had a big dream and you can still say, nowadays, that the Icelandic genetic diseases are the ones we know the most about compared to any other genetic disease around the world.

I have known about deCODE for about three years now, and I had read many papers from Kong, but I never met him before and I was expecting someone very secretive about his work since deCODE is, after all, a private company who raised money with the idea of selling part of the intellectual property developed to big pharmaceutical companies to make innovative drugs.

Kong gave an interesting talk, one of those talks that you can tell was already tried before in front of a different audience, maybe with some slight modifications. It did not take long to notice that he is the typical researcher very enthusiast about what he does and very eccentric. The part I liked the best was when he came down from the stage and he was given a microphone to answer a question. He kept the microphone all the time at the level of his waist while he was answering. After the talk I went to talk to him and I discovered this to be no easy feat. He is extremely loquacious, and if you ask him a question he would find his way out of the answer and keep talking about something else for about fifteen minutes. Although he mainly said very interesting things. Then, at the end of the day, I had the lucky chance, together with another Italian student, to sit at the table with him and after a couple of glasses of wine he started to share everything with us.

How do you decide to raise tens of million of dollars and fund a large company? Back in 1996 Kari Stefansson, the CEO of deCODE, applied for NIH grants to study genetic diseases in Iceland using STRs, the current technology for those kind of studies back in the day. His motivation was that Iceland is the perfect location for such a study since they kept perfect pedigree information up to the seventeenth century. Although his project was extremely ambitious and the grant was rejected. People with big egos do not take rejections that easily and he decided to take a different route by raising private money.

When he approached Augustine Kong, he asked him to join the scientific team on the soon to be found company and he told him that there were good chances he could have become a millionaire although the goal was to embrace this adventure for the sake of research. According to Kong, Stefansson is not the easiest person to deal with. Maybe you heard this before, but be prepared when you put yourself between a determined man and what he is after. For the project to work, special laws had to be set in Iceland to protect the privacy of the people who gave their DNA to the company. In exchange, Stefansson promised his country a business which was going to bring a lot of wealth and jobs to the country.

More than ten years later a lot has happened. The global economic recession hit Iceland worse than everywhere else in the world. All the private banks bankrupted and they were nationalized. The Icelandic currency lost more than half of its value on the market. I happen to know a young Icelandic girl who works as an au-pair in the United States and he considered staying longer in the States as a result. Even before that happened, deCODE went almost bankrupt itself and its market value is close to nothing. Kong told us that the company made it through the recession but it has more than 200 million dollars of debts and it is unclear if it will make it during the next three years. Although, since he is paid in United States dollars, he also told us that now life for him is way cheaper.

Kong did not seem to care much about this. He really seems to be driven by the research and the fame that comes from being able to do it in a place unique in the world for it. He seems like the typical workaholic person, around 50 years old, with a plethora of papers published in Nature Genetics and Science during the past ten years. According to him he would not mind retiring from this intense job in the next three years. While in Iceland though, he lost his American green card, as it happens if you don't spend enough time in the country, and he seemed a bit worried about it. In any case, even if the company disappears, they are thinking about applying for grants to keep the research team able to analyze the data that they have collected.

During the dinner I also had some interesting scientific discussions with Kong. My research related to his work, so it was quite a lucky chance. Kong is interested in recombination events, that is, those rare events that recombine homologous chromosomes during meiosis. Without those, eggs and sperm would not be generated correctly. Recombination allows DNA to be shuffled so that favorable mutations that arose in one individual can eventually spread to the whole population and combine with other favorable mutations from other individuals. This in turn, has allowed evolution to work at a much higher pace and allow the complexity of multicellular organisms and ultimately of human people.

Not much is known about statistics of recombination events in human people. First of all these events take place only during meiosis. Second, experiments to study them are very expensive, even if recently some people managed to study recombination events in sperm. The problem is that given a person with his child, it is not possible with current technology to study which meiosis took place in the parent to generate the child. Although, the genotype information that can be analyzed nowadays can be integrated across relatives to unveil the locations of the meiosis and the database created in Iceland is the perfect place to perform this integration.

Human recombination events are a very fascinating subject and most of their mysteries will be unraveled in the next coming years. Recombination, together with random mutation, is the magic underlying force which shapes DNA of species, that allows them to evolve and adapt on the long term. If you believe that there is an invisible force shaping the events of the universe by playing with dice, then recombination is one of its dice. It is known that it happens in very specific places of the DNA, although it seems that where these places are located in the chromosomes might be person dependent to a certain degree. Females have more than males, but there is high variability in how many a person has on average across different people. It is necessary for correct segregation of chromosomes and, as you grow older, you need to have more to yield a fully working egg, which could be an explanation of why some women fail to have children after a certain age. Basically if they already have few to begin with, then these would not be enough later in life.

Nothing is known about why some people have more and some people have less, but, since it is known that it is inheritable, there are likely genetic variations for it. Where are they? My assumption is that, if Kong did not tell us and he does not know yet, then nobody does, since you need a very large dataset of relatives to carry such a statistical study and deCODE is the only place in the world where you could do that. Maybe unveiling the biology of the process might help people having kids even later in life. Or maybe knowing who in advance can and who cannot might make people take different decisions in life. Although, these are just speculations.

Are you feeling the excitement? Well, I did. Five years from now what is now a mystery might be in textbooks. It is not the knowledge per se which gives the thrills, but the process of the discovery. Knowing to be the first one to get there is what gives the excitement. As Kong said, winning the competition is his main drive, not the fact that he is doing something good for humanity and I actually respect that. Because I am bit skeptical about what is good and bad for people and I believe that research should be done, when possible, just for fun.

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