Researcher profile: Kerstin Lindblad-Toh

Explorer in genetics

Sometimes all it takes is a simple question from a Swedish postdoctoral researcher in exile in the U.S. Twenty years later Kerstin Lindblad-Toh has directed the mapping of the genetic makeup of 230 mammal. Now she is preparing to bring perhaps the greatest scientific revolution of our time – understanding the human genome – all the way into health care.

Kerstin Lindblad was born an early summer day in 1970, but she entered the world without a pulmonary artery. Skilful doctors and high-tech medical care succeeded in saving her life in this critical situation. As time passed, this achievement also had great significance for many people who had not yet been born. This is because it planted the first seed of curiosity about diseases and cures that yielded a number of key advances in comparative genomics 49 years later. Progress that in turn paved the way for awarding the 2019 Olof Rudbeck Prize in October to Kerstin, whose married surname is Lindblad-Toh.

“The fact that Upsala Medical Society chooses to recognise my work is both inspiring and meaningful. Not only does it follow a lengthy sick leave during which I have not been able to deliver the scientific contributions I had hoped for, but even more it serves as validation that my research really will benefit patients, which for me is the essential driving force that propels the science forward.”

And it is indeed possible to be a prophet in one’s own city. Shortly after the medical doctors came the veterinarians – or to be exact, the Swedish University of Agricultural Sciences’ Faculty of Veterinary Medicine – which awarded Kerstin Lindblad-Toh an honorary doctorate. The press release attests to a unique aptitude. Pioneering contributions. More than 180 published articles, many in the most highly ranked journals. Here it would be tempting to get carried away, to anticipate future events. But let’s slow down and rewind to the late nineties. After undergraduate studies in molecular biology and years as a doctoral student at Karolinska Institutet, we land in the midst of a life-changing moment. The place is the state of Massachusetts in the United States.

“At the time, I served as a postdoctoral student in a laboratory in Boston, where I inherited a project experimenting with genetic variations in mice. One day I mentioned to my boss, Eric Lander, that we should characterise the genetic makeup of mice more accurately to find genes involved in human diseases. It turned out that he needed someone just then who could head a large-scale mouse genomic project, and if I was ready, the job was mine. At that same moment my period as a postdoctoral researcher was over, and we devoted the next few years to defining the genetic relationship between mice and humans.”

Along the way the same Lander received a philanthropic billion-dollar grant to establish a completely new environment for biomedical and genomic research. The prestigious universities of Harvard and the Massachusetts Institute of Technology jointly launched the Broad Institute, a scientific hub in Cambridge, Massachusetts, focusing on interdisciplinary collaboration and openness. The funding organisations remained favourably disposed, and soon the finances and technology existed to further extend the scientific frontiers. Lindblad-Toh soon was heading new projects characterising the genome of horses, rabbits, sticklebacks, coelacanths and especially dogs, an animal that has long shared both genes and surroundings with humans and whose genome has undergone relatively little study. A series of successes ensued, and before long Lindblad-Toh stood at the helm of The 29 Mammals Project, an ambitious venture to map the genomes of 29 selected mammals.

“Somewhere or other an invitation came from Uppsala University to work as a visiting professor alongside Leif Andersson, a professor of functional genomics. By that time I had married and had children, so I welcomed the opportunity to introduce my family to Sweden. Initially we planned to stay for 15 months, but when the time came to return westward, I was offered a professorship in comparative genomics and involved in an application to establish a national initiative in technology for molecular biosciences at Uppsala.”

Many assumed the initiative was earmarked for Stockholm, but Lindblad-Toh’s experience with the Broad Institute came into play. In its application, Uppsala’s promoted both collaboration and generosity. Jan Björklund, the Minister of Education and Research at the time, liked what he heard. In 2010 the Science for Life Laboratory, commonly known as SciLifeLab, was launched, with Uppsala University as one of the two nodes and Lindblad-Toh as site manager. In a reorganisation three years later, the nodes in Stockholm and Uppsala merged. Kerstin Lindblad-Toh was appointed as the new co-director. The next recognition came amid two parallel careers in different parts of the world. The Knut and Alice Wallenberg Foundation named Lindblad-Toh a Wallenberg Scholar. The title was accompanied by SEK 15 million to be applied to free research over a five-year period.

“The 29 Mammals Project at Broad had been concluded at that time, but at the starting block instead was its sequel: The 200 Mammals Project. I commuted between the United States and Sweden and tried to perform three jobs simultaneously. And, of course, that did not work.”

In the spring of 2015, Lindblad-Toh became ill. This led to a prolonged absence, and she resigned from her position at SciLifeLab. Upon returning she instead presented an idea for studying canine genetics and brains to better understand the origin of various diseases. The idea has been with her for almost two decades, and now the technology has caught up. Shortly afterwards the Knut and Alice Wallenberg Foundation announced an appropriation of nearly SEK 30 million to the project, which is expected to generate entirely new insights in genomics.

“My starting point is the fact that the behaviour and brain of dogs is quite similar to our own, and with current methods we can study the parts of the cerebral cortex that affect interaction and behaviour. For example, we have already identified a number of genes related to obsessive-compulsive disorder in dogs. In addition, we find many common diseases in dogs that are genetically relevant. Because with the selection of specific genes through dog breeding, a risk arises that the disease genes will be preserved and intensified. If this can help us to identify which gene mutations cause which diseases or characteristics, we may eventually contribute to the development of better pharmaceuticals for both humans and animals.”

And this is where we find Lindblad-Toh in the autumn of 2019. Still divided between two continents. But every month she flies home: To the U.S., where husband, son and the Broad Institute await. And to Uppsala where her 15-person-strong team of researchers is a major contributor to the city’s renown in the field of genomics. On both sides of the Atlantic, she makes scientific bonds far beyond her own academic domiciles. The 200 Mammals Project brings together leading research environments from throughout the world. Just the kind of bridge building necessary to take genomics to the next level.

“The Broad Institute and Uppsala University unite American large scale with Swedish ingenuity. The combination has brought us a long way, but if we are to extend all the way to health care, the entire scientific world needs to meet and work together on the huge amounts of data still remaining to collect and analyse. This will place great demands on generosity and openness, but Eric Lander has already shown all of us that it is entirely feasible.”

So Kerstin Lindblad-Toh continues her journey. With her she takes and brings the best of both worlds. Not just the academic. In the U.S. and Boston, the cultural melting pot bids welcome. In Sweden and Uppsala, the proximity of the mushroom forests and mountains entices. What the future holds remains to be seen. With one exception: On Friday, 18 October, just before the clock strikes 15:00 in the Uppsala University Hospital Grönwall Hall. That is when Kerstin Lindblad-Toh receives the 2019 Olof Rudbeck Prize. At that moment she also takes her place in a very exclusive circle of researchers and previous prize-winners. “This is a distinction that really spurs me on into the future,” says Lindblad-Toh.

That is something we can all be thankful for.

Magnus Alsne
2019-08-21

Facts: Kerstin Lindblad-Toh

Title: Professor of Comparative Genomics (Uppsala University), Scientific Director of Vertebrate Genomics (Broad Institute)
Age: 49
Resides Alternately in Uppsala and Boston.
On the bedside table: A novel by Elizabeth Peters, who provides both comic and badly needed, easily accessible evening entertainment.
A quality I appreciate: Honesty and willingness to cooperate, both at work and in private life.
As soon as I have time: I head out to nature. I especially would like to spend more time in the Swedish mountains.
Finally, I want to urge everyone to: Do their very best; if possible, be in the right place at the right time – and seize the opportunity when it arises!