Wednesday, June 18, 2008

Nobel Laureates: Gerald Edelman and Rodney Porter


The Nobel Prize in Physiology or Medicine 1972.
"for their discoveries concerning the chemical structure of antibodies"

Gerald M. Edelman (1929 - ) and Rodney R. Porter (1917 - 1985) received the Nobel Prize in Physiology or Medicine for elucidating the structure of immunoglobulins (antibodies). They determined that immunoglobulins were composed of two heavy chains and two light chains. There are three domains in the molecule. Two of them form binding sites for antigens and the third one links the two heavy chains together.

Edelman and Porter founded the field of molecular immunology, a field that today encompasses hundreds of labs. If you count all the clinical immunologists and cellular immunologists, there are as many immunology labs in the world as there are biochemistry labs. That was not true in the 1950's when Edelman and Porter began their work.

The presentation speech was in Swedish by Professor Sven Gard of the Karolinska Medico-Chirurgical Instit.

Nobel Laureates
Your Royal Highnesses, Ladies and Gentlemen,

Immunebodies or antibodies is the designation of a group of proteins in the blood, that play an important part in the defense against infections and in the development of many different diseases. Their perhaps most characteristic property is the capacity to react and combine with substances, foreign to the organism, so-called antigens and to do so in a highly specific manner. There probably exist more than 50,000 different antibodies in the blood, each of them reactive against one particular antigen. Their main features are similar but they show individual characteristics and constitute, therefore, an extremely heterogeneous group. Since, in addition, they appear as very large molecules of a complex structure, it is understandable that the study of their chemistry for a long time offered great difficulties.

Up to 1959 the knowledge about their nature and mechanism of action was rather incomplete. That same year, however, Edelman and Porter separately and independently published their fundamental studies of the molecular structure of antibodies. Both of them had aimed at splitting the giant molecule into smaller, well defined fragments that might be more easily analysed than would the whole complex.

Porter's aim was to separate those parts of the antibody which are responsible for their specific reactivity. He hoped by this means to obtain a preparation lacking most of the biologic functions of the antibody but, on account of its capacity of combination, capable of competing with the antibody for the binding sites of the antigen. He succeeded in achieving this by means of treatment of the antibody, under strictly controlled conditions, with a protein-splitting enzyme called papain. By this treatment the antibody split into three parts. Two of these could combine specifically with the antigen and they were almost identical in other respects as well. The third fragment differed distinctly from the others, lacked binding capacity but possessed certain other biologic characteristics of the intact molecule.

Edelman for his part assumed the molecule, like those of many other proteins, to be composed of two or more separate chain structures held together by cross links of some kind, most probably so-called sulphide bonds. His assumption turned out to be correct. By means of a fairly rough treatment he was able to sever the cross bonds and release a number of separate chain molecules. Both he and Porter could later show that the antibody was in fact composed of four chains, one pair of identical, "light" chains and one pair of like- wise identical, "heavy" chains.

On the basis of the collected evidence Porter built a model of the molecule which has later, with overwhelming probability, been proven correct.

Accordingly the antibody molecule appears in the shape of the letter Y, with a stem and two angled branches. Each branch is composed of one light and one half of a heavy chain in side by side arrangement. The stem is made up of the remaining halves of the heavy chains. The specific combining capacity is accounted for by the structure of the free tips of the branches and in like measure by the light and the heavy chain; separately they are inactive. Porter's papain treatment attacks the molecule exactly at the point of branching and splits off the branches from the stem.

These discoveries incited an intense activity in laboratories in the four corners of the world. Apparently there existed a latent need for immunochemical research that could not be satisfied until today's prize winners had opened the way and provided the means. During the two decades that have since past our knowledge about the processes of immunity has broadened and deepened to an extent that perhaps has not yet been fully appreciated, even by some specialists in closely related fields. Many novel and fascinating aspects on problems in the fields of molecular biology and genetics have grown out of the immunochemical studies. We have now a new and firmer grasp of the question of the role of immunity as defense against and as cause of disease. Our possibilities to make use of immune reactions for diagnostic and therapeutic purposes have improved. It is, thus, a very important pioneer contribution that has been rewarded with this year's prize in physiology or medicine.

Gerald Edelman, Rodney Porter,

By clarifying the principal chemical structure of immunoglobulins you achieved an extremely important break-through in the field of immunochemistry. You, so to speak, opened the sluice-gates and gave impetus to the flood of research that soon started gushing forth, irrigating previously arid land, making it fertile and producing rich harvests. By awarding you the prize in 'physiology or medicine the Karolinska Institute has recognized the great significance of your accomplishments for biology in general and medicine in particular. On behalf of the Institute I wish to express our admiration and extend to you our heart-felt felicitations.

Now I ask you to proceed to receive your prize from the hands of His Royal Highness the Crown Prince.

[Image Credit: The cartoon of an immunoglobulin molecule is from the Genetics Home Reference website of the National Institutes of Health (USA).]

1 comment :

  1. way off topic but Gerald Edelman's daughter makes music, though she doesn't tour anymore as she mostly does scores for documentaries and such.