Nobel Prizes are awarded annually to persons who have made contributions for the benefit of mankind in the fields of physiology or medicine, physics, literature, chemistry, peace, and economics.

The Swedish inventor, Alfred B. Nobel established the awards in 1901 under the terms of his will. Today, the Nobel Prize is administered through the Nobel Foundation.  Each award consists of a gold medal, a diploma, and a gift of money.

The medal of the Nobel Assembly at the Karolinska Institute represents the Genius of Medicine holding an open book in her lap, collecting the water pouring out from a rock in order to quench a sick girl’s thirst.
The inscription reads:

In the human brain there are more than hundred billion nerve cells. They are connected to each other through an infinitely complex network of nerve processes. The message from one nerve cell to another is transmitted through different chemical transmitters. The signal transduction takes place in special points of contact, called synapses. A nerve cell can have thousands of such contacts with other nerve cells.

Synaptic Transmission

The three Nobel Laureates in Physiology or Medicine 2000 — Arvid Carlsson, Paul Greengard and Eric Kandel have made pioneering discoveries concerning one type of signal transduction between nerve cells, referred to as slow synaptic transmission. These discoveries have been crucial for an understanding of the normal function of the brain and how disturbances in this signal transduction can give rise to neurological and psychiatric diseases. These findings have resulted in the development of new drugs.

Arvid Carlsson, Department of Pharmaco-logy, University of Gothenburg is rewarded for his discovery in the late 1950s, that dopamine is a transmitter in the brain and that it has great importance for our ability to control movements.

In a series of experiments Arvid Carlsson used a naturally occurring substance, reserpine, which depletes the storage of several synaptic transmitters. When it was given to experimental animals they lost their ability to perform spontaneous movements. He then treated the animals with L-dopa, a precursor of dopamine, which is transformed to dopamine in the brain. The symptoms disappeared and the animals resumed their normal motor behavior. In contrast, animals that received a precursor of the transmitter serotonin did not improve the motor behavior. Arvid Carlsson also showed that the treatment with L-dopa normalized the levels of dopamine in the brain.

Arvid Carlsson realized that the symptoms caused by reserpine were similar to the syndrome of Parkinson’s disease. This led, in turn, to the finding that Parkinson patients have abnormally low concentrations of dopamine in the basal ganglia. As a consequence L-dopa (which is converted to dopamine in the brain) was developed as a drug against Parkinson’s disease and today still is the most important treatment for the disease.

Apart from the successful treatment of Parkinson’s disease Arvid Carlsson’s research has increased our understanding of the mechanism of several other drugs. He showed that antipsychotic drugs, mostly used against schizophrenia, affect synaptic transmission by blocking dopamine receptors. The discoveries of Arvid Carlsson have had great importance for the treatment of depression, which is one of the most common diseases. He has contributed strongly to the development of selective serotonin uptake blockers, a new generation of antidepressive drugs.

Paul Greengard, Laboratory of Molecular and Cellular Science, Rockefeller University, New York, is rewarded for his discovery in the 1960s of how dopamine and a number of other transmitters exert their action in the nervous system.

Paul Greengard showed that the transmitter first acts on a receptor on the cell surface. This will trigger a cascade of reactions that will affect certain "key proteins" that in turn regulate a variety of functions in the nerve cell. The proteins become modified as phosphate groups are added (phosphorylation) or removed (dephosphorylation), which causes a change in the shape and function of the protein (figure 1). One important group of such proteins form ion channels in the membrane of the cell. Each nerve cell has different ion channels, which determines the reaction of the cell. When a particular type of ion channel is phosphorylated, the function of the nerve cell may be altered by, for example, a change in its excitability. Through this mechanism the transmitters can carry their message from one nerve cell to another.

Eric Kandel, Center for Neurobiology and Behavior, Columbia University, New York, is rewarded for his discoveries of how the efficiency of synapses can be modified, and which molecular mechanisms that take part.

Sea slug, a model system for learning
With the nervous system of a sea slug as experimental model he has demonstrated how changes of synaptic function are central for learning and memory. Protein phosphorylation in synapses plays an important role for the generation of a form of short term memory. For the development of a long term memory a change in protein synthesis is also required, which can lead to alterations in shape and function of the synapse.

The fundamental mechani-sms that Eric Kandel has revealed are also applicable to humans. Our memory can be said to be "located in the synapses" and changes in synaptic function are central, when different types of memories are formed. Even if the road towards an understanding of complex memory functions still is long, the results of Eric Kandel has provided a critical building stone. It is now possible to continue and for instance study how complex memory images are stored in our nervous system, and how it is possible to recreate the memory of earlier events. Since we now understand important aspects of the cellular and molecular mechanisms which make us remember, the possibilities to develop new types of medication to improve memory function in patients with different types of dementia may be increased.

Despite the enduring enigmas of the brain’s systems and networks, the work of scientists like Carlsson, Greengard, and Kendal has helped our understanding of medicine more in the last fifty years than it had helped in the previous five hundred years. The complexities unconvered in recent years offer hope, because they open many new avenues to explore. Ultimately, a better understanding of the intracellular signaling machinery will make it possible to design more effective therapies.