When Per Uhlén was fourteen, he ended up in a wheelchair. Since then, he has become a professor, started three companies, and competed in two Paralympic Games. "Sometimes I feel like my life is a film," he says.
Per Uhlén was not quite fifteen and was riding a light motorcycle, even though he was not allowed to. A crash landed him in a ditch, where he lay all night.
"There were no mobile phones back then, and I was injured and unable to get up. A dachshund out for a morning walk and its owner found me," he recalls.
Per Uhlén had suffered a spinal cord injury, which left him wheelchair-bound from that day on. It took six months of rehabilitation before he was back at school. He missed much of his final year of lower secondary school, and his grades were not great. So he enrolled in the upper secondary programme called the E-telelinjen at the time (Electrical and Telecommunications programme) and started working as a radio repairman. But one day, he found an old "My Friends" book in which his father had written that he wanted to become an engineer.
"When I read that, I thought, that is what I want too. My father's parents did not allow him to continue his studies, even though he was very talented at school. I saw an opportunity to fulfil his dream," says Per Uhlén.
He began studying at KomVux (adult education college) and then applied to Engineering Physics at KTH Royal Institute of Technology, where he was accepted. Per Uhlén found his time at KTH stressful.
"There were parallel scheduled courses and constant exams. I missed having time to delve deeper. When I started my doctoral studies, I thought it was the height of luxury. It felt like I had all the time in the world, and I loved being able to immerse myself in interesting questions that I had formulated myself. I still feel that way," he says.
When a lecturer at KTH was looking for a doctoral student at Karolinska Institutet, Per Uhlén jumped at the chance. It was a stroke of luck: as a physicist with technical expertise, he brought new approaches to medical questions.
"That was quite unusual at the time," says Per Uhlén.
Research suited him, and in the lab he tried all sorts of experiments.
"One strategy that I still think works in research is to start off a bit 'quick and dirty'. When you find an interesting result, you dig deeper into that particular question, and at that stage you need to be much more thorough. I sometimes see young doctoral students spending too much time on control experiments early in a project, before it is clear whether there is anything to their hypothesis," he says.
A recurring theme in Per Uhlén's research career is microscopy. One of his lab's most recent works was published in one of the most prestigious scientific journals, Science, and presented a new method for three-dimensional visualisation of RNA expression in the mouse brain. An image from the article was selected for the cover of that same scientific journal. What made it unique was that the researchers had managed to image RNA in intact tissue, just as it appears in reality.
"We live in a three-dimensional world. Why not study it in three dimensions? Today, this is used in research but not yet in clinical practice. However, I believe that in the future we will measure and study most processes in three dimensions. I often compare it to printers, which in the past were only available in black and white. Nowadays, all printers are in colour, just like the real world," says Per Uhlén.
The methods they have developed are used to map cell types and their activity. In one project, his research group is studying a gene called CACNA1C. It is already known that a mutation in this gene, which codes for a calcium channel, significantly increases the risk of developing autism. By studying how the brain looks and develops in mice-both with and without the mutation-the researchers are trying to understand how it affects the process.
"We believe that the mutation causes neurons in the brain, for example, to function differently or end up in different locations in the brain as it develops. Our method is well suited to investigating this development, and hopefully it can provide greater insight into the causes of autism," says Per Uhlén.
It is not just brain cells that are interesting to study; Per Uhlén's group has also examined cells from various types of cancer. In one project, they studied tumour cells in the bladder.
"In certain forms of this cancer, it is difficult to determine the best course of treatment. But this is crucial for the patient; if the tumour has spread to the surrounding muscle tissue, the entire bladder needs to be removed. At the same time, it is a major procedure that can significantly impact on the patient's quality of life, so it should be avoided, it if possible. In a smaller study, we found that our three-dimensional imaging method could improve the accuracy of such assessments, but we need to repeat the study with more patients," says Per Uhlén.
In another project, they investigated the possibility of detecting cancer stem cells in breast cancer. Cancer stem cells are a small group of cells believed to be the origin of the tumour. They periodically lie dormant and are therefore not as easily killed by chemotherapy.
"There is a risk that they survive if they happen not to be active during treatment. And if you examine the tissue two-dimensionally, as diagnostics are performed today, you can easily miss them. You might think the treatment has worked until this small group of cells becomes active again.
With their method, it is possible to examine an entire organ in three dimensions and thus detect the cancer cells if they are there.
"But the method is not yet used in clinical practice," says Per Uhlén.
His own spinal cord injury as a young man has also sparked his interest in how to prevent the kind of disability that comes from losing the ability to walk. More than half of all spinal cord injuries are incomplete, meaning the spinal cord is damaged but not completely severed. Depending on where the injury is located, the symptoms vary. It is common to retain some sensation and motor function, but not enough to be able to walk.
"It may sound surprising, but immediately after my injury, I was able to move my legs and walk. However, a few days later, inflammation and immune cells caused secondary effects which resulted in permanent motor impairment," says Per Uhlén.
In an ongoing research project, he is investigating the early inflammatory process after spinal cord injury in mice and zebrafish to gain a more detailed understanding of what happens.
"My aim is to halt this destructive process at an early stage and thereby save as much function as possible after the injury. Every percentage that can be preserved is worth its weight in gold," says Per Uhlén.
He himself does not seem to have let being in a wheelchair hold him back.
"I have realised, from meeting many others with spinal cord injuries, that it is often easier for those who are affected when they are young, not least mentally. You have not yet become accustomed to a walking life and can adapt more easily to the new situation," says Per Uhlén.
He continued playing in his rock band, got his drives licence at sixteen, and took up wheelchair basketball.
"It took me to both the Paralympics Games in Atlanta in 1996 and in Sydney in 2000, where our best result was fifth place out of twelve nations. But as a researcher, it is my brain and my practical mindset that I compete with. I have only ever been met with respect in the scientific community. Sometimes I feel like my life is a film," says Per Uhlén.
Facts about Per Uhlén
Name: Per Uhlén
Title: Professor at the Department of Medical Biochemistry and Biophysics, Karolinska Institutet. Head of the research facility Biomedicum Imaging Core Facility.
Age: 56
Family: Wife and two children
Motto: Fall seven times, get up eight.
How I relax: Watching films.
Role model: My father. He was a maths and physics teacher and inspired my scientific interest by showing me many exciting experiments.
Most unexpected research finding: As a doctoral student, I discovered that calcium levels in kidney cells began to oscillate when treated with the bacterium E. coli. I measured calcium levels in 400 cells, and all oscillated at 12-minute intervals. My hypothesis is that these oscillations act as a bodily signal. Since then, I have tried to decode calcium signals in different cell types.
Best researcher qualities: I am positive, meticulous, and persistent. I also do not let myself get too stressed.
Per Uhlén on…
…how he met his wife
She is from Japan, where it is more difficult for women to advance as researchers. When we had a conflict over the order of authors on our publication, she was impressed when I offered her to be listed as first author.
…friends in wheelchairs
I have two friends who suffered spinal cord injuries on exactly the same day as I did, 31 May 1984. As recently as last year, we celebrated 40 years of life in a wheelchair at Operakällaren in Stockholm.
…being able to weigh oneself
There was no bathroom scale for people in wheelchairs that you could have at home and easily roll onto. So, I designed one and had it manufactured in China. So far, more than 200 units have been sold.
…playing in the lab
You should not be afraid to try different experiments-it is fun to play a bit. It can lead to interesting discoveries. I have investigated how various cells react to coffee, tea, snus, and mobile phones.
