One cannot avoid the question: why Finland? It’s not like Mark Daly (@dalygene) didn’t have other options, if the professor of genetics at Harvard Medical School even felt the need to go anywhere at all.
Daly has been asked this question many times over the year he has spent at the University of Helsinki. “Finland is a unique environment for a researcher of genetics,” Daly emphasises.
Daly, a man of more than 130,000 citations, is now working in Meilahti, on the third floor of Biomedicum 2. He is also the head of FIMM, Institute for Molecular Medicine Finland. When he moved from Boston to Helsinki, his wife and four children arrived with him.
“I wasn’t looking for a job. I had written the job description myself for my position in Boston, and it was a fantastic place for research. But Finland has opportunities that Boston doesn’t.”
“Every Finn has a personal identity code. This means that it is possible to track large groups of people from the cradle to the grave in a way that we can only dream of in the US.”
“Finland also has a comprehensive national healthcare system which collects information on patients, archives it appropriately and releases it to researchers. No system outside the Nordic countries functions this well.”
The third aspect that fascinates the geneticist is the Finns’ unique DNA. “The research opportunities are exceptional. My goal is to turn FIMM into a research centre that could attract the best researchers and students of biology from around Europe, similarly to how CERN attracts physicists to Switzerland.”
The baby-faced researcher
The University of Helsinki was delighted to be able to recruit such a top-level researcher. At 51, Daly already has a career spanning over three decades at the forefront of genetic research.
Professor Aarno Palotie (@APalotie), who became acquainted with Daly in the early 1990s, remembers how the young man was met with some degree of amusement. “Mark was so young, it was almost like he showed up at the Broad Institute with a pacifier in his mouth,” Palotie reminisces.
But it was already apparent that Daly was an exceptional researcher, even on the scale of the scientific circles in Boston. “Mark has always demanded perfection in the quality and purity of data. If you try to come to him with figures that are not precise, he will show no mercy,” Palotie says.
From space to biology
Daly chose genetics by chance, it wasn’t instilled in him at home. Growing up in the small town of Broxton in a family of two English teachers, Mark was an avid reader as a child. However, in high school he began to be more interested in mathematics than literature.
Daly got into MIT, where he funded his studies with a student loan, initially majoring in physics and considering a career working with numbers. One of his options was to become a professional poker player.
After his first year at MIT, he wound up with a summer job at a laboratory that analysed genetic data. “When I was young, I thought that the future of science was in conquering space. At college, I realised that we were on the cusp of a new century of biology,” Daly explains.
This realisation was helped along by inspiring company. The head of the laboratory where Daly worked was Eric Lander, who would later become one of the leading figures of the Human Genome Project. Lander was a supervisor for Daly’s doctoral dissertation.
Daly loved crunching numbers, and enjoyed genetics with its masses of data.
“The history of genetics is largely the history of computation. Long before we could understand the structure of DNA and genes, we could make calculations to track how characteristics are passed on. For example, if the father is AA and the mother is AB, how are the characteristics passed on to their offspring and to the following generations.”
Daly’s work in using statistical methods to calculate the genes that cause rare diseases was similar, but much more complex. Among other things, he has studied Crohn’s disease, an inflammatory bowel disorder that has proven difficult to map: there are more than 200 genes associated with the illness.
In recent years, Daly has become particularly interested in schizophrenia, which seems to be even more directly hereditary than diseases such as diabetes.
Gel and calculations
In the late 1980s, genetic research was very different from what it is today. The human genome was yet to be mapped. We had no clear understanding of the number of base pairs or genes.
Research largely consisted of studying bits of DNA that were only a few hundred base pairs long. Mainly, researchers looked to them to find the causes of hereditary diseases. Considering that there are more than three billion base pairs, the samples were extremely small at the time.
When Daly started as a researcher, the samples had to be treated with radioactive gel, so that the radiation could trace the base pairs onto film. Researchers would then look through the films to find differences.
It was around this time that Daly met with Finnish geneticists with whom he discussed the manifestations of the hereditary diseases that are common in Finland.
In the 1990s, genetics took a major leap forward. Daly was a part of mapping the human genome, and developed computational methods to analyse the data. The significance of these computational tools is reflected in the record-breaking numbers of citations that they have received.
Technology has gradually overtaken the innovations of the 1990s. “These days we can easily and cheaply map the whole genome if we want – we just pop a sample in a machine.”
Daly had his major breakthrough in 2000, when the Human Genome Project was nearing its end. He was studying changes in the fifth chromosome.
“We began to notice some strange systematics in the samples. This tremendously long DNA strand had correspondences that spanned much further than just the neighbouring bases. If there was an A-T base pair, there would always be a C-G pair further down the chain.”
Daly’s observations have helped understand how the genome is passed on in regular groups which were dubbed haplotypes. By analysing the haplotypes of human DNA, we can now determine where an individual’s ancestors came from. Haplotypes underlie many of the popular commercial DNA tests.
Haplotypes have also made it possible to identify hidden predispositions to hereditary diseases, even in carriers who have not developed the disease.
Looking for a football star
What are the risks of genome data? Should my doctor or employer be allowed to see my DNA? “Many are concerned about this, but we should not exaggerate the role that our DNA ultimately plays,” Daly points out.
Our genes cannot reveal who is a good employee or a motivated student. Our environment, lifestyle, effort and even pure chance are more significant factors than genetics.
For example, had a genetic test been done on Lionel Messi as a child, his parents may have found out that he would never be tall, and decided that there was no point in supporting his athletic career. Messi might not have become the best football player in the world, as he is today.
Or could it be possible to use genetic information to draft individualised dietary regimens? It might be possible to identify the group of genes that makes an individual immune to the cholesterol-raising effects of eggs. This would mean that everyone would not have to avoid the same foods.
Daly suggests that we think about the actual benefit of such information in relation to the difficulty and potential risks of acquiring it. “Conducting a controlled long-term study would be labour-intensive: one group would have to eat 10 eggs a week, the other would eat three a week, and then we would see what happens.”
Napping in boring meetings
In America, Mark Daly sees himself as an introvert, but in Finland he’s an extrovert. The top researcher is not one to boast about his own achievements, but he praises his colleagues at every opportunity. Of his own success, he says modestly:
“I’ve been in the right place at the right time.”
The first rule of scientific work is to remember to question your hypotheses,” Daly emphasises.
“Sometimes people fall in love with their theories, but then new innovations often pass them by. You have to always compare your own ideas with new information. Findings have to be re-evaluated time and again.”
This uncompromising attitude is apparent in other situations as well. Daly is not known for his constructive reactions to mistakes, and if a meeting doesn’t get to the point, he may take a nap. He couldn’t care less about university politics. A researcher is a researcher, even if he’s the director of an institute.
Every sample is valuable
Daly is more eager to talk about the future of science than himself. He’s particularly interested in FIMM’s massive FinnGen project, which intends to compile more than 500,000 Finnish genetic samples. “I’d love to get even more samples if possible.”
With help from hospitals, the researchers can acquire samples from genetic carriers of diseases who can otherwise be difficult to reach, for example, patients whose diseases have only begun to manifest late in life. “With rare diseases, each additional sample is valuable.”
The Finnish genome has both harmful and positive variants. “There’s a gene variant in Finland that protects the carrier from type 2 diabetes. It would be very interesting to find out how it works. The variant may have spliced a gene, or silenced another.”
With its €60 million budget, FinnGen is the second most expensive research project at the University of Helsinki. Only the iCAN Digital Precision Cancer Medicine competence cluster, set to launch this year, has more funding. FinnGen has also received funding from international pharmaceutical companies.
Daly emphasises that these companies will not have exclusive rights to the resulting information. “The companies are interested in our findings, because they can then use them as a basis for their own research. They can lead to the development of new drugs.”
A good time to see the world
FinnGen is Mark Daly’s answer to the question “why Helsinki”. This was no jump into the unknown.
The whole family had spent time in Finland during many summers, and they had got to know Helsinki. They picked their home in western Helsinki for the children’s music classes: they now live close to a familiar music school which had previously lent them a cello.
Last spring Daly lived in Helsinki on his own, but in autumn 2018 the whole family settled in Finland. The eldest daughter also found a student exchange position at the University of Helsinki. While in Finland, Daly’s wife intends to work on her doctoral dissertation after a long hiatus.
One motivation for the move was the political atmosphere in the US. Daly has posted tweets that are critical of President Trump. “The family and I felt that now’s a good time to see the rest of the world.”
USA or Finland?
Daly has tweeted a photo where he is posing on the icy shore of Munkkiniemenranta. He’s standing next to a sign announcing that the beach is closed.
The Bostonian is no stranger to snow, but the darkness of the winter was more of a challenge. The long work days mean less sleep for the researcher. After the children go to bed, Daly often begins another shift as he starts making Skype calls to Boston.
Daly still holds his professorship at Harvard, to which he dedicates a quarter of his working hours. The professor visits the US about every six weeks.
“We have a great deal of cooperation between Helsinki and Boston. So it’s not really easy to say which part of my job belongs where.”
Is the plan to return to Boston in four years? “I wouldn’t want to give up Harvard, but on the other hand, leaving Helsinki seems insane,” Daly muses. “I think I will be able to continue working at both universities also in the future.”
The article was originally published in Finnish in the Y/03/19 issue of Yliopisto-lehti.