Presentation Speech by Professor Jan- Erik
Edström of the Karolinska Medico-Chirurgical Institute
Translation from the Swedish text
Your Majesty, Your Royal Highnesses, Ladies
The 1974 Nobel Prize in Physiology or Medicine concerns the fine structure and the function of the cell, a subject designated Cell Biology. There are no earlier Prize Winners in this field, simply because it is one that has been newly created, largely by the Prize Winners themselves. It is necessary to go back to 1906 to find Prize Winners who are to some extent forerunners. In that year Golgi and Cajal were awarded the Prize for studies of cells with the light microscope. Although the light microscope certainly opened a door to a new world during the 19th century, it had obvious limitations. The components of the cell are so small that it was not possible to study their inner structure, their mutual relations or their different roles. To take a metaphor from an earlier Prize Winner, the cell was like a mother's work basket, in that it contained objects strewn about in no discernible order and evidently, for him, with no recognizable functions.
But, if the cell is a work basket, it is one on a very tiny scale indeed, having a volume corresponding to a millionth of that of a pinshead. The various components responsible for the functions of the cell correspond in their turn to a millionth of this millionth, and are far below the resolving powers of the light microscope. Nor would it have helped if researchers had used larger experimental animals: the cells of the elephant are not larger than those of the mouse.
Progress was quite simply at a standstill during the first few decades of this century, but then in 1938, the electron microscope became available, an innovation that held out great promise. The difference between this microscope and the ordinary light microscope is enormous, like being able to read a book instead of just the title. With such an instrument it should now be possible to see components almost down to the dimensions of single molecules. But the early hopes were succeeded by disappointment. It was found impossible to prepare the cells in such a way that they could be used. The book remained obstinately shut, even though it would have been possible to read it.
Albert Claude and coworkers were the first to get a glance inside the book. In the mid-forties they made a break-through and succeeded in preparing cells for electron microscopy. I say a glance, because much technical development still remained to be done, and George Palade should be mentioned foremost among those who developed electron microscopy further, to the highest degree of artistry.
In addition to form and structure it is necessary to know the chemical composition of the cell components in order to understand their functions. It was hardly possible to analyse whole cells or tissues since these consist of so many different components, and so, one would get a confused picture. Each component has to be studied separately and obviously this is difficult when the components are so small. Here a new art was developed, and again Claude was the pioneer. He showed how one could first grind the cells into fragments and then sort out the different components on a large scale with the aid of the centrifuge. This was an important beginning. Palade made further contributions, but it was above all Christian de Duve who introduced brilliant developments within this field.
The functions of the cell could now be mapped with this armoury of methodology. Palade has taught us which components function when the cell grows and secretes. The Prize Winner of 1906, Camillo Golgi, discovered a cell component, the Golgi complex. Palade has demonstrated its role and he discovered the small bodies, ribosomes, in which cellular protein is produced.
Production of organic material must be balanced by scavenging and combustion of waste, even in the tiny world of the cell. de Duve discovered small components, lysosomes, which can engulf and dissolve, e.g., attacking bacteria or parts of the cell itself which are old and worn out. These are real acid baths, but the cell itself is normally protected by its surrounding membranes. Sometimes, however, the lysosomes are converted into veritable suicide pills for the cells. This occurs when the surrounding membranes are damaged, e.g. by ionizing radiation. The lysosomes play a role in many clinically important conditions and the foundations laid by de Duve are of the greatest significance for the interpretation of these states, and, thus, also for prophylactic and therapeutic measure.
To sum up, the 1974 Prize Winners have by their discoveries elucidated cellular functions that are of basic biological and clinical importance. Thus, they cover both aspects of the Prize, Physiology as well as Medicine.
Albert Claude, Christian de Duve and George Palade. During the last 30 years a new subject has been created, Cell Biology. You have been largely responsible for this development both by creating the basic methodology and by exploiting it to gain insight into the functional machinery of the cell. On behalf of the Karolinska Institute, 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.
From Nobel Lectures, Physiology or Medicine 1971-1980, Editor Jan Lindsten, World Scientific Publishing Co., Singapore, 1992
Copyright © The Nobel Foundation 1974
"for their discoveries of machinery regulating vesicle traffic, a major transport system in our cells"
"for their discoveries of key regulators of the cell cycle"
"for their discoveries of principles for introducing specific gene modifications in mice by the use of embryonic stem cells"