Presentation Speech by Professor Bertil B.
Fredholm of the Nobel Committee at the Karolinska
Translation from the Swedish text
Your Majesties, Your Royal Highnesses,
Ladies and Gentlemen,
It is not very strange that a car, a television set or some other complex device sometimes stops working. No, the extraordinary thing is that these devices usually work faultlessly. When it comes to the most complicated machine we know - the human body - it is less surprising that it sometimes breaks down and we become ill, than that it works at all. After all, our body consists of thousands of billions of individual units, which must cooperate perfectly. The cooperation between the individual building blocks in our body, our cells, runs so smoothly in every possible situation that we seldom have cause to reflect on what a tremendously sophisticated communication system is required. The cells communicate with each other using chemical signals, such as hormones; we know these quite well. But efficient communication requires not only that the right signals are sent: it also requires that those signals are received in a proper way and lead to the right type of action.
The cell is enveloped in a thin membrane, which effectively separates the cell's inside from its surroundings. Nonetheless, a chemical signal that reaches the outside of the cell can evoke changes in its inner machinery, changes suited to the needs of the cell and of the entire organism. Alfred G. Gilman and Martin Rodbell have studied this particular aspect of the communication problem.
About 25 years ago, Martin Rodbell and his colleagues decided to investigate how a chemical signal - a hormone - that came in contact with the outer surface of the cell membrane could bring about changes on the inside of the same membrane. They discovered that the transduction of signals across the cell membrane could be described as a three-step process. First the cell must recognize what kind of chemical signal is reaching it from other parts of the body - this requires what Rodbell called the discriminator. The last step in the signaling pathway is an amplifier, which ensures that the signal created inside the cell is strong enough to make something happen. The major breakthrough was Martin Rodbell's realization that there was a switch between these two steps, and that this switch, which he called the transducer, could be turned on by a high-energy compound, guanosine triphosphate. The letter G in G protein stands for guanosine triphosphate.
At this point, Alfred Gilman and his colleagues took over. Using a combination of genetic and biochemical techniques they managed, after a heroic effort, to isolate the G protein from all the other parts of the cell membrane. The workings of the protein could then be studied. Among other things, Gilman showed that the G protein works like a timed switch that allows the signal to go through just long enough. G proteins might perhaps be compared to those little gadgets that can be plugged into a telephone and that make it possible - with a phone call - to turn lamps on and off, start electric heaters, or draw curtains, depending entirely on what the gadget is connected to.
Today we know that every one of the components in the signaling pathway - discriminator, switch and amplifier - exists in several varieties. Each individual cell has its own specific array of components in the signaling pathway and thus has an almost unique way of reacting to the incoming signals. In other words, each cell differs as to which of the body's myriad signals it will recognize, how and for how long the signal will be passed on, and which of the cell's own internal machines will start (or stop) working.
When our eyes perceive the procession of "Parfait glace Nobel" at the Nobel Banquet, various G proteins in the retina cooperate to transmit sensations of color, or of light and shadow. The aroma of the food activates other G proteins in our nostrils. When we taste the parfait, yet other G proteins on the tongue come into play. When, finally, all these sensory impressions are analyzed and interpreted in the brain, many different G proteins play vital roles.
Alfred Gilman's and Martin Rodbell's discoveries not only help us understand the immense diversity that is the hallmark and prerequisite of all life, but also why our bodies sometimes function less perfectly, and we become ill. For example, it has been found that changes in the function of G proteins in the intestine explain the severe diarrhoea associated with cholera. Alterations in G proteins can also be detected in connection with many other diseases. It is a reasonable hope that when we understand more about what causes diseases, it will become easier to treat them.
Drs. Alfred G. Gilman and Martin
I've tried to give some impression of the impact of your discoveries in the biomedical community. It is a privilege and a pleasure to convey to you the warm congratulations of the Nobel Assembly of the Karolinska Institute, and to ask you to receive the Nobel Prize from the hands of His Majesty the King.
From Nobel Lectures, Physiology or Medicine 1991-1995, Editor Nils Ringertz, World Scientific Publishing Co., Singapore, 1997
Copyright © The Nobel Foundation 1994
"for the discovery that proteins have intrinsic signals that govern their transport and localization in the cell"
"for his discoveries concerning the mechanisms of the action of hormones"
"for their discoveries of machinery regulating vesicle traffic, a major transport system in our cells"