Dr. Arvid Carlsson, a Swedish scientist whose discoveries about the brain led to the development of drugs for Parkinson’s disease and earned him a Nobel Prize, died Friday. He was 95.
His death was announced by the Sahlgrenska Academy at the University of Gothenburg, where he had been a professor of pharmacology. It did not say where he died.
When Dr. Carlsson started his research in the 1950s, dopamine, a chemical in the brain, was thought to have little significance. Dr. Carlsson discovered that it was, in fact, an important neurotransmitter – a brain chemical that passes signals from one neuron to the next.
Nobel Prize-winning researcher Dr. Arvid Carlsson smiles during a photo session at the Swedish Academy in Stockholm, on Dec. 9, 2000.HENRIK MONTGOMERY/AP
He then found that dopamine was concentrated in the basal ganglia, the portion of the brain that controls movement. He showed that rabbits lost their ability to move after they were given a drug that lowered their dopamine stores; their mobility was restored after they received L-dopa, a drug that is converted into dopamine in the brain.
Noting that the movement difficulties of his rabbits were similar to those of people with Parkinson’s disease, Dr. Carlsson proposed the illness was related to a loss of dopamine. Other scientists confirmed that dopamine is depleted in people with Parkinson’s disease, a degenerative condition that causes tremors and rigidity, and L-dopa soon became the standard treatment for the illness.
Dr. Carlsson shared the 2000 Nobel Prize in Physiology or Medicine with two American researchers, Dr. Eric Kandel and Paul Greengard, who made their own discoveries about the transmission of chemical signals in the brain. In awarding the Nobel, the Karolinska Institute of Sweden said the contributions of the three scientists were “crucial for an understanding of the normal function of the brain” and for how signal disturbances could “give rise to neurological and psychiatric disorders.”
Dr. Carlsson was born on Jan. 25, 1923, in Uppsala, Sweden, one of four siblings in “an academic middle-class family,” he wrote in an autobiographical sketch for the Nobel committee. He grew up in the Swedish city of Lund, where his family moved after his father joined the University of Lund faculty as a history professor.
“My mother had passed a master-of-arts examination and my father a Ph.D. degree at the University of Uppsala,” Dr. Carlsson wrote. “My mother had a keen interest in research throughout her life but gave priority to raising her children and to assisting her husband in his research. However, when her husband died at the age of 76 she, then 71 years old, started to devote herself entirely to her favorite area of research, that is the legal status of women in the Middle Ages in Sweden. She published a couple of books and a number of articles on this subject in Swedish, which rendered her an honorary Ph.D. degree at the University of Uppsala several years later.”
His family had a “strong orientation toward the humanities,” Dr. Carlsson wrote. His older brother and sister followed his father into the humanities, but Dr. Carlsson, in an act of youthful rebellion, chose to study medicine, a field he saw as more useful than the arts.
During the Second World War, Dr. Carlsson, who had hitchhiked to Germany with a friend as a teenager in the summer of 1939, before the war broke out, was in his first year of clinical training when, in 1944, he was recruited to examine former prisoners of German concentration camps, many of them Jews, who had been transported by the thousands to Sweden through the efforts of the Swedish royal family.
“Some of the prisoners were taken to Lund, where a big tent was erected in a park to house them,” he wrote. “As a medical student I was given the task to examine several of these prisoners. Many of them were children, suffering from undernutrition. Tuberculosis was not uncommon. However, most shocking was their mental status. They behaved like wild animals, obviously suffering from severe anguish and suspiciousness and trusting nobody.”
Dr. Carlsson received his medical degree and his doctorate in pharmacology in 1951 from the University of Lund and joined the faculty as an associate professor. After several years, he applied for an assistant professorship but was turned down; a review committee told him that his speciality, calcium metabolism, wasn’t leading edge.
“I realized I had to make a choice to either leave pharmacology and go into internal medicine, or switch into a new research field,” he wrote. His search for a new speciality led him to the United States and a five-month fellowship with Dr. Bernard Brodie, an acclaimed pharmacologist at the National Heart Institute (now the National Heart, Lung and Blood Institute in Bethesda, Maryland). His brief stint in the Brodie lab reinvigorated Dr. Carlsson’s career, and set him on the path to his Nobel Prize.
Dr. Brodie had been studying reserpine, one of the first drugs introduced specifically to treat schizophrenia, which made it a hot subject for research. Reserpine injections immobilized rabbits, but no one understood why. Shortly before Dr. Carlsson’s arrival, Dr. Brodie determined that reserpine depleted serotonin, a neurotransmitter that would later be associated with mood and depression. Assigned to study the effect of reserpine on serotonin in blood cells, Dr. Carlsson immersed himself in the emerging field of psychopharmacology.
“I can hardly overemphasize enough how lucky I was to get that opportunity to work in Dr. Brodie’s laboratory,” Dr. Carlsson wrote.
When his fellowship ended in mid-1956, Dr. Carlsson returned to the University of Lund as an associate professor and continued to study reserpine. Building on Dr. Brodie’s research, he found that the drug depleted a second neurotransmitter, noradrenaline. This discovery presented a conundrum: Was it serotonin or noradrenaline that controlled movement?
The rabbits did not improve when given a drug that spurs production of serotonin. When the animals improved on L-dopa, Dr. Carlsson thought he had solved the puzzle. Noradrenaline is synthesized in the body from dopamine, which in turn is metabolized from L-dopa. But Dr. Carlsson was in for a surprise. When he examined the brains of the revived animals, he found very little noradrenaline and plenty of dopamine.
Up to this point, scientists thought dopamine was nothing more than raw material for making noradrenaline. Dr. Carlsson discovered that dopamine was a neurotransmitter in its own right – one with a critical role in movement.
All Parkinson’s disease drugs used today work by increasing dopamine signalling in the brain. More than 50 years after Dr. Carlsson’s discovery, L-dopa remains the mainstay treatment.
In the 1960s, Dr. Carlsson showed that anti-psychotic drugs work by blocking receptors on neurons that receive dopamine signals. He was among the first to determine that some addictive drugs, such as cocaine, increase dopamine signalling in certain parts of the brain. Later, he made important contributions that led to the development of selective serotonin reuptake inhibitors, or SSRIs, a class of antidepressants that includes Prozac.
He became a professor at the University of Gothenburg in Sweden in 1959 and a professor emeritus in 1989. He was admitted to the Royal Swedish Academy of Science in 1975 and received the Japan Prize in 1994.
He and his wife, Ulla Lisa, had three sons and two daughters. A list of those he leaves behind was not immediately available.
In his later years, Dr. Carlsson was an outspoken critic of fluoridating water supplies to prevent cavities. He said that fluoride produces side effects, such as mottled teeth, and that fluoridation was contrary to the principles of modern pharmacology because there was no way to regulate the amount of fluoride individuals received. He argued that individualized preventive care was a better approach.