Olle Lindvall’s early academic interests did not suggest a future in neuroscience. “Before I took my high school exams," he recalls, "Biology was not on my radar. I was more interested in mathematics, theoretical physics, and literature." His decision to study medicine was more a process of elimination than passion. “I didn’t feel comfortable with medicine during the first months of medical school,” he admits. “I was very close to leaving. But then, we had a course on the anatomy of the brain, and that caught my interest. That was really a turning point for me.”
This newfound fascination with the brain led him to seek research opportunities in neuroanatomy. Working in a lab during his medical school years, Lindvall quickly learned that scientific breakthroughs don’t come easily. “I had to take initiative myself,” he says. “Nothing was going to be served to me.”
After years of hard work, his first big discovery came while working on his doctoral thesis, where he developed a new method to visualize nerve cells containing neurotransmitters like dopamine and noradrenaline. “I had been working with it, and then suddenly, it started to work one day,” Lindvall reminisces. This discovery opened new avenues in brain research, providing insights into neural networks and potential repair mechanisms.
The Early Years of Cell Repair in the Brain
After earning his doctorate, Lindvall’s focus shifted to cell repair in the brain, a new field at the time. He had the idea to use cell transplantation to treat neurological disorders—a concept that many were unsure of in the early 1980s. Already then, his former mentor Dr. Anders Björklund had begun experimenting with transplanting rodent fetal dopaminergic neurons into rat brains.
Together they went on to perform translational studies using dopaminergic neurons from aborted fetuses for transplantation in a rat model of Parkinson’s disease. The aim was to see if these human-derived cells could integrate into the brain and repair damaged neural circuits, and they did. The next step was to test this in patients.
“As a clinician at Skåne University Hospital, then a specialist in neurology, and later a Professor in clinical neurology at Lund University, I’ve treated patients throughout my career. Working with my patients made me want to get on to do something more. I think that was really my luck.” he reflects. “It would have been difficult to do this translational research without my training in both basic science and clinical neurology.”
But the journey from lab experiments to clinical applications had its challenges. There were ethical concerns about using fetal tissue and skepticism within the global scientific community. Lindvall recalls a moment in 1986 when he presented his research on the transplantation of adrenal medulla cells into the brain’s of patients with Parkinson’s disease at a conference in New York. “People really threw rotten tomatoes at me,” he remembers. “They all said that this was too early. It’s absolutely crazy. Cell therapy will never work.”
The Journey Towards the Clinic
Despite the criticism, Lindvall pushed forward. In 1987, Lindvall and his colleagues performed the world’s first human fetal tissue transplantation, a significant milestone in the field. And by 1989, they had improved their transplantation techniques, leading to better survival rates for grafted cells in patients. This achievement garnered global attention and raised hopes for cell-based therapies for Parkinson’s disease.
“The moment that was published in Science, there was enormous media interest from all over the world,” Lindvall recalls. “But it was only a first step. Some patients had improved clinically…but what this really showed was how cell therapies, cell transplantations, could potentially work.”
Despite these successes, the journey was far from smooth. Over the next decade, further attempts had varying outcomes among patients. Then, a major setback came in the early 2000s when two large sham surgery-controlled clinical trials -conducted in other parts of the world- failed to show significant improvement, casting doubt on the viability of fetal tissue transplantation as a long-term solution. “That was a severe blow to the whole procedure,” Lindvall admits. “But when you analyzed the data, you could identify factors that influenced patient outcomes.”
Shifting Focus: The Promise of Stem Cells
Recognizing the limitations of fetal tissue transplantation, Lindvall turned his focus to stem cell research, which offered a potentially unlimited source of cells for transplantation. This shift marked the beginning of a new chapter.
Realizing the need for a dedicated research hub in Sweden, Lindvall played a crucial role in founding the Lund Stem Cell Center at Lund University. “We realized that with fetal tissue, we would not be able to develop any clinically useful procedure that could be offered to many patients,” he explains. “At that time, stem cells had emerged as a potential source for generating dopamine neurons. That was the situation when the Stem Cell Center was created.”
Since then, the work has continued, with researchers like Malin Parmar and Agnete Kirkeby leading efforts that have resulted in a new round of clinical trials, known as STEM-PD. “I think it’s incredible that a research field which has now been going on for more than 40 years is still active and there is now a lot of interest,” he says. “It is great to have researchers like Malin and Agnete driving the science forward and navigating these regulatory aspects. I very much admire their work.”
A Lifetime of Discovery and Friendship
Beyond his scientific achievements, Lindvall’s legacy is defined by his commitment to mentorship and collaboration. He speaks fondly of his long-standing collaborations with colleagues and friends, Anders Björklund, and Merab and Zaal Kokaia, who were once his students.
Their collaborative efforts have led to some of the most cited papers in the field. One particularly important study, demonstrating for the first time self-repair in the brain after stroke by its own neural stem cells, was published together with Zaal Kokaia in Nature Medicine in 2002. “Many of my best ideas have come from a good discussion with my students,” he says with a smile.
In May, Professor Olle Lindvall received his jubilee doctorate from Lund University, marking over five decades of innovative research. Even today, Lindvall remains actively involved, sharing his insights and passion for discovery with the next generation of scientists.
Reflecting on his career, Lindvall emphasizes the importance of passion in science. “As a scientist, you must have a passion for science. The main driving force cannot be to get a new position or more funding but instead the passion for what you’re doing,” he says. “I think that’s why I still go to the lab, and I still discuss with the young people because I still love this, to see something, to understand how it works, and how I can take it one step further.”
His advice to aspiring scientists is simple: believe in your ideas, stay passionate, create scientific friendships, and be prepared for setbacks.
“You have to believe in your ideas, and you have to realize that in science, things go up and down,” he says. “Sometimes, it is just how it is. It’s like Winston Churchill said, ‘Success consists of going from failure to failure without loss of enthusiasm.’”
