Presentation Speech by Professor Bertil Andersson of the Royal Swedish Academy of Sciences, December 10, 1997.
Translation of the Swedish text.
Your Majesties, Your Royal Highnesses, Ladies and Gentlemen,
Life requires energy. Our muscles require energy when we move. We need energy to think. Energy input is required for the production of new biological molecules. This year’s three Nobel laureates in Chemistry have contributed in different ways to our knowledge of how living organisms can obtain and utilize energy. Common to their discoveries is the unique adenosine triphosphate (ATP) molecule, which can store and transport energy in all organisms, whether it be a simple bacterium, a dandelion, a finch or a human being. Large quantities of ATP must be formed and consumed. Each day an adult converts a quantity of ATP roughly equivalent to his or her own body weight, and in case of physical exertion, many times more.
All energy on earth originates from the sun. Green plants can absorb sunlight and convert it into chemical energy through the process of photosynthesis, in which carbon dioxide and water form sugar, starch and other complex carbon compounds. Other organisms, such as humans and animals, are in turn dependent on these carbon compounds as sources of energy, and they burn them with the help of oxygen. That is why we breathe. Nature can thus be said to have chosen a combination of solar and coal-fired power plants for its energy supply. Although these two energy conversion systems may seem different in purely technical terms, in many respects they operate in the same way in living cells. The most important similarity is that the energy released is utilized with the help of the ATP molecule.
According to Peter Mitchell, the 1978 Nobel Laureate in Chemistry, the energy released in photosynthesis and cell respiration initiates a stream of positively charged hydrogen ions. These hydrogen ions, in turn, drive the production of ATP with the aid of a membrane-bound enzyme called ATP synthase. Two of this year’s laureates, Paul Boyer and John Walker, have studied this important enzyme and have shown that it functions in a unique way. Among other things, they have demonstrated that ATP synthase can be compared to a molecular machine, whose rotating bent axle is driven in a step-wise process by “biological electricity” – that is, the flow of hydrogen ions. Because of the asymmetry of the rotating axle, three subunits of the enzyme assume different forms and functions: a first form that hinds adenosine diphosphate (or ADP) and phosphate building blocks, a second form where these two molecules are chemically combined into a new ATP molecule, and a third form where the ATP that has been formed is released. In the next twist of the axle, the three subunits switch form and thus also function with each other, and another ATP molecule can be formed, and so on. This “binding change mechanism” was put forward by Boyer in the late 1970s, but only in 1994 did his ingenious model gain general acceptance among researchers. In August of that year, Walker and his colleagues published three-dimensional images of ATP synthase that had been obtained by X-ray analysis of enzyme crystals. These X-ray images, magnified several million times, showed how an asymmetrically elongated protein molecule interacted with three other protein units that all showed mutually different forms. Walker had finally revealed the detailed blueprint of the molecular machine and shown that Boyer’s theory of ATP formation was correct.
Let me now leave ATP production and instead turn to the use of ATP. In 1957, Jens Christian Skou discovered an enzyme called sodium, potassium ATPase (or Na+,K+-ATPase), which maintains the right ion balance in living cells. This enzyme, too, can be described with a technical analogy: It functions as a biological “pump” that transports potassium ions into a cell, while transporting sodium ions in the opposite direction out of the cell. This is a process that requires a lot of energy, and up to one third of the ATP formed in the body may be used to drive the Na+,K+ pump. Today, we are also aware of a number of other ion pumps, which have been discovered as a consequence of Skou’s pioneering work. All these ion pumps are prerequisites for various important life functions such as transmission of nerve impulses, muscle contraction and digestion. The effects of many pharmaceuticals, such as heart and ulcer medicines, are related to the action of cellular ion pumps.
Skou’s discovery clearly illustrates the unpredictability of basic research – in 1957, no one could have imagined that his somewhat odd experiments, which consisted of studying the effects of various salts on tissue from a shore crab, would be important 40 years later to industrial operations and the production of new pharmaceuticals. Research breakthroughs and their applications cannot be custom-ordered. Instead they emerge from a combination of curiosity, scientific excellence and far-sightedness.
Dr. Boyer, Dr. Skou and Dr. Walker,
I have tried to describe how your pioneering studies on the enzymology of ATP metabolism have contributed to our understanding of how living cells can store and make use of energy. Your work has revealed new principles for enzyme function, opened up new areas of chemical research as well as providing the basis for biomedical applications for the benefit of mankind. In recognition of your services to chemistry the Royal Swedish Academy of Sciences has decided to confer upon you this year’s Nobel Prize for Chemistry.
On behalf of the Academy, I wish to convey to you our warmest congratulations and I now ask you to receive the Prize from the hands of His Majesty the King.