15 Oct Nobel History

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1999 Nobel Peace Prize goes to Médecins Sans Frontières ^top^
     It is in recognition of the organization's pioneering humanitarian work on several continents.
      Since its foundation in the early 1970s, Médecins Sans Frontières has adhered to the fundamental principle that all disaster victims, whether the disaster is natural or human in origin, have a right to professional assistance, given as quickly and efficiently as possible. National boundaries and political circumstances or sympathies must have no influence on who is to receive humanitarian help. By maintaining a high degree of independence, the organization has succeeded in living up to these ideals.
      By intervening so rapidly, Médecins Sans Frontières calls public attention to humanitarian catastrophes, and by pointing to the causes of such catastrophes, the organization helps to form bodies of public opinion opposed to violations and abuses of power.
      In critical situations, marked by violence and brutality, the humanitarian work of Médecins Sans Frontières enables the organization to create openings for contacts between the opposed parties. At the same time, each fearless and self-sacrificing helper shows each victim a human face, stands for respect for that person's dignity, and is a source of hope for peace and reconciliation.
—      La Organización No Gubernamental Médicos sin Fronteras, gana el Premio Nobel de la Paz por su trabajo humanitario "profesional", "eficaz" e "independiente", desempeñado a lo largo de 28 años, y por su contribución a generar un rechazo social a las violaciones de derechos humanos y a los abusos de poder.

1993 Nobel Peace Prize goes to apartheid terminators.
The Norwegian Nobel Committee has decided to award the Nobel Peace Prize for 1993 to Nelson R. Mandela and Frederik Willem de Klerk for their work for the peaceful termination of the apartheid regime, and for laying the foundations for a new democratic South Africa. From their different points of departure, Mandela and de Klerk have reached agreement on the principles for a transition to a new political order based on the tenet of one man-one vote. By looking ahead to South African reconciliation instead of back at the deep wounds of the past, they have shown personal integrity and great political courage. Ethnic disparities cause the bitterest conflicts. South Africa has been the symbol of racially-conditioned suppression. Mandela's and de Klerk's constructive policy of peace and reconciliation also points the way to the peaceful resolution of similar deep-rooted conflicts elsewhere in the world. The previous Nobel Laureates Albert Lutuli and Desmond Tutu made important contributions to progress towards racial equality in South Africa. Mandela and de Klerk have taken the process a major step further. The Nobel Peace Prize for 1993 is awarded in recognition of their efforts and as a pledge of support for the forces of good, in the hope that the advance towards equality and democracy will reach its goal in the very near future.
— Los dirigentes sudafricanos Frederik de Klerk y Nelson Mandela obtienen El Premio Nobel de La Paz.

1990 Mikhail Gorbachev wins Nobel Peace Prize ^top^

     The Norwegian Nobel Committee has decided to award the 1990 Nobel Peace Prize to Mikhail Sergeyevich Gorbachev, president of the Soviet Union, for his leading role in the peace process which today characterizes important parts of the international community. During the last few years, dramatic changes have taken place in the relationship between East and West. Confrontation has been replaced by negotiations. Old European nation states have regained their freedom. The arms race is slowing down and we see a definite and active process in the direction of arms control and disarmament. Several regional conflicts have been solved or have at least come closer to a solution. The UN is beginning to play the role which was originally planned for it in an international community governed by law. These historic changes spring from several factors, but in 1990 the Nobel Committee wants to honor Mikhail Gorbachev for his many and decisive contributions. The greater openness he has brought about in Soviet society has also helped promote international trust. In the opinion of the Committee, this peace process, which Gorbachev has contributed so significantly to, opens up new possibilities for the world community to solve its pressing problems across ideological, religious, historical and cultural dividing lines.

     Soviet leader Mikhail Gorbachev wins the Nobel Peace Prize for his work in ending Cold War tensions. Since coming to power in 1988, Gorbachev had undertaken to concentrate more effort and funds on his domestic reform plans by going to extraordinary lengths to reach foreign policy understandings with the noncommunist world. Some of his accomplishments include four summits with President Ronald Reagan, including a 1987 meeting at which an agreement was reached to dismantle the U.S. and USSR intermediate-range missiles in Europe. He also began to remove Soviet troops from Afghanistan in 1988 and exerted diplomatic pressure on Cuba and Vietnam to remove their forces from Angola and Kampuchea (Cambodia), respectively. In a 1989 meeting with President George Bush, Gorbachev declared that the Cold War was over. Gorbachev also earned the respect of many in the West through his policy of nonintervention in the political upheavals that shook the Eastern European "satellite" nations during the late-1980s and early-1990s. When Czechoslovakia, East Germany, Poland, and other Iron Curtain countries began to move toward more democratic political systems and free market economies, Gorbachev kept Soviet intervention in check. (This policy did not extend to the Soviet republics; similar efforts by Lithuania and other republics were met with stern warnings and force to keep the Soviet Socialist Republics together.)
—     Mijail Gorbachov obtiene El Premio Nobel de la Paz.

1986 El alemán Ernst Ruska y El equipo suizo-alemán (Heinrich Roher y Gerd Binning) ganan El Premio Nobel de Física.

1986 Nobel Prize in Physics for microscopic advances.         ^top^
      The Royal Swedish Academy of Sciences has decided to award the 1986 Nobel Prize in Physics by one half to Professor. Ernst Ruska, Fritz-Haber-Institut der Max-Planck-Gesellschaft, Berlin, Federal Republic of Germany, for his fundamental work in electron optics, and for the design of the first electron microscope and the other half, jointly to Dr Gerd Binnig and DR Heinrich Rohrer, IBM Research Laboratory, Zurich, Switzerland, for their design of the scanning tunneling microscope.

Summary
One half of this year's Nobel Prize in Physics has been awarded to Ernst Ruska for "his fundamental work in electron optics and for the design of the first electron microscope". The significance of the electron microscope in different fields of science such as biology and medicine is now fully established: it is one of the most important inventions of this century.
      Its development began with work carried out by Ruska as a young student at the Berlin Technical University at the and of the 1920's. He found that a magnetic coil could act as a lens for electrons, and that such an electron lens could be used to obtain an image of an object irradiated with electrons. By coupling two electron lenses he produced a primitive microscope. He very quickly improved various details and in 1933 was able to build the first electron microscope with a performance clearly superior to that of the conventional light microscope. Ruska subsequently contributed actively to the development of commercial mass-produced electron microscopes that rapidly found applications within many areas of science.
      Electron microscopy has since been developed through technical improvements and through the advent of entirely new designs, among them the scanning tunneling electron microscope. A number of researchers have taken part in both this and the earlier development, but Ruska's pioneering work is clearly the outstanding achievement.

The other half of this year's prize has been awarded to Gerd Binnig and Heinrich Rohrer for "their design of the scanning tunneling microscope". This instrument is not a true microscope ( i.e. an instrument that gives a direct image of an object) since it is based on the principle that the structure of a surface can be studied using a stylus that scans the surface at a fixed distance from it. Vertical adjustment of the stylus is controlled by means of what is termed the tunnel effect - hence the name of the instrument. An electrical potential between the tip of the stylus and the surface causes an electric current to flow between them despite the fact that they are not in contact. The strength of the current is strongly dependent on the distance, and this makes it possible to maintain the distance constant at approximately 10-7 cm (i.e. about two atom diameters). The stylus is also extremely sharp, the tip being formed of one single atom. This enables it to follow even the smallest details of the surface it is scanning. Recording the vertical movement of the stylus makes it possible to study the structure of the surface atom by atom.
     The scanning tunneling microscope is completely new, and we have so far seen only the beginning of its development. It is, however, clear that entirely new fields are opening up for the study of the structure of matter. Binnig's and Rohrer's great achievement is that, starting from earlier work and ideas they have succeeded in mastering the enormous experimental difficulties involved in building an instrument of the precision and stability required.

Background information
The invention of the conventional microscope represented a great step forward for science, particularly in biology and medicine. As better and better microscopes were built, it was discovered that there exists a limit that cannot be exceeded. This is connected with the wave characteristics of light. Using light waves, it is impossible to distinguish details smaller than the wavelength of the light. The term "resolution" refers to the distance between two details of an image that can just be distinguished. For a conventional microscope using visible light, the resolution is some 4 000 Å (1 Å, ångstrom = l0^-8 cm).
      The great breakthrough in microscopy came when it was found possible to produce an image of an object using an electron beam. The starting point was the discovery that a magnetic coil can function like an optical lens. A divergent bundle of electrons passing through the coil is focused to a point. A suitable electric field can also act as an electron-optical lens. Using a lens of this type, an enlarged image can be obtained of an object irradiated with electrons the image is recorded on a fluorescent screen or a photographic plate. It also proved possible to combine two or more lenses to increase the magnification. The work was carried out at the Technical University of Berlin at the end of the 1920's.
      The scientist who has made the greatest contribution to this development is Ernst Ruska. As a young student together with his supervisor Max Knoll, he began studying simple magnetic coils, He found that the use of suitably-designed iron encapsulation improved their electron-optical properties. Above all, it now became possible to build a lens of short focal length. This is essential if high magnification is desired. Using two coils in series, Ruska achieved a magnification of fifteen times. Even though this was a modest result, it nevertheless represents the first prototype of an electron microscope. Ruska subsequently worked purposefully to improve the details, and in 1933 he built what can be described as the first electron microscope in the modern sense - an instrument with considerably better performance than a conventional light microscope 's. He was then appointed by Siemens and took part in the development of the first commercially-available, mass-produced electron microscope, which entered the market in 1939. This event may be considered the real breakthrough for electron microscopy.
      Since then, development of the electron microscope has been very extensive. Its resolving power could be considered theoretically unlimited, since the electron is a pointlike particle, However, according to quantum mechanics, every particle has wave characteristics which introduce an uncertainty into the determination of its position. This sets a theoretical limit to resolution for the acceleration potentials normally used of the order of 0.5 - 1 Å. In practice, resolutions down to about 1 Å have been achieved.
      The type of electron microscope developed by Ruska is called the transmission microscope. The object to be examined is in the form of a thin section. The electron beam goes right through this in the same way that light pierces the object in a light microscope. There are, however, several other types of electron microscope, the most important apart from the transmission microscope being perhaps the scanning electron microscope. In this extremely sharply focused electron beam strikes the object The secondary electrons emitted are collected by a detector and the current is recorded. Magnetic coils cause the electron beam to scan the object in the same way as the beam of a TV tube. The variations in the emission of secondary electrons can be used to build up an image. The advantage is the large depth of focus which gives a three-dimensional image as opposed to the sectional image obtained with a transmission microscope. However, the resolution is poorer. These two types of microscope thus complement each other.
      Electron microscopy has developed extremely over the last few decades, with technical improvements and entirely new designs. Its importance can scarcely be exaggerated and, against this background, the importance of the earliest, fundamental work becomes increasingly evident. While many researchers were involved Ruska's contributions clearly predominate. His electron-optical investigations and the building of the first true electron microscope were crucial for future development.
      The latest contribution to the development of microscopy is what is termed the scanning tunneling microscope. Its principle differs completely from that of other microscopes. A mechanical device is used to sense the structure of a surface. To this extent, the principle is the same as that of Braille-reading. In Braille, it is the reader's fingers that detect the impressed characters but a much more detailed picture of the topography of a surface can be obtained if the surface is traversed by a fine stylus, the vertical movement of which is recorded. What determines the amount of detail in the image - the resolution - is the sharpness of stylus and how well it can follow the structure of the surface. Obviously if the tip of the stylus is too sharp, it rapidly becomes destroyed. At the same time, small structural details of the surface can be damaged by mechanical contact, One solution to this problem would be to maintain the stylus at a small, constant distance from the surface The first to succeed in doing this was the American physicist Russel Young at the National Bureau of Standards in the USA. He used the phenomenon known as field emission. If a sufficiently high potential is applied between stylus and surface, a current flows with a strength depending on the stylus-surface distance. If regulated by a servo mechanism controlled by the current, this distance can be kept constant without mechanical contact. Young succeeded in building an instrument that worked on this principle. The distance between the stylus tip and the surface was approximately 200 Å. Its resolution was thus considerably poorer than that of an electron microscope
      However Young realized that it should be possible to achieve better resolution by using the so-called tunnel effect This is a quantummechanical effect that allows an electron (and also other particles to cross an area where, according to classical physics it cannot exist since it lacks sufficiently high energy. It makes its way so to speak, through a potential mountain by quantum-mechanical tunneling; hence the name tunneling microscope. This means here that if the tip of the stylus is near enough to the surface (10 Å, i.e. 1-2 atom diameters) a current flows even at low voltages. In the same way as field emission, it should be possible to control the stylus without mechanical contact. However, Young was unable to convert this idea into practice owing to the exceptionally large experimental difficulties involved
      The first researchers to succeed in building a scanning tunneling microscope were Gerd Binnig and Heinrich Rohrer at the IBM Research Laboratories in Zürich, Switzerland. The reason for their success was the exceptional precision of the mechanical design One example of this is that disturbing vibrations from the environment were eliminated by building the microscope upon a heavy permanent magnet floating freely in a dish of superconducting lead. Less bulky but equally effective devices for stable, disturbance-free suspension of the microscope have now been developed. Piezoelectric elements are used to control the horizontal movement of the stylus in two perpendicular directions so that it scans the surface a long parallel lines - hence the name scanning microscope The vertical movement of the stylus is controlled and measured using another piozoelement. Using a special technique it has been possible to produce styluses with tips consisting of a single atom. Consequently, the precision of the image is particularly great. Horizontal resolution is approximately 2 Å and vertical resolution. approximately 0.1 Å. This makes it possible to depict individual atoms, that is, to study in the greatest possible detail the atomic structure of the surface being examined.
      It is evident that this technique is one of exceptional promise, and that we have so far seen only the beginning or its development. Many research groups in different areas of science are now in using the scanning tunneling microscope. The study of surfaces is an important part of physics, with particular applications in semiconductor physics and microelectronics In chemistry, also, surface reactions play an important part, for example in connection with catalysis. It is also possible to fixate organic molecules on a surface and study their structures. Among other applications, this technique has been used in the study of DNA molecules.

1986 Nobel Prize in Chemistry for studies of elementary processes.

The Royal Swedish Academy of Sciences has decided to award the 1986 Nobel Prize in chemistry jointly to

Professor Dudley R. Herschbach, Harvard University, Cambridge, USA,
Professor Yuan T. Lee, University of California, Berkeley, USA and
Professor John C. Polanyi, University of Toronto, Toronto, Canada

for their contributions concerning the dynamics of chemical elementary processes.

— Los estadounidenses John Charles Polany, Dudley R. Herbchbach y Yuan Tseh Lee Lee, y El Canadiense John C. Polanyi, ganan El Premio Nobel de Química.

The dynamics of chemical reactions - a fascinating new field of research

Summary
This year's Nobel Prize in Chemistry has been awarded to Dudley R. Herschbach, Yuan T. Lee and John C. Polanyi for their contributions concerning the dynamics of chemical elementary processes. Their research has been of great importance for the development of a new field of research in chemistry - reaction dynamics - and has provided a much more detailed understanding of how chemical reactions take place.

Dudley R. Herschbach has developed the method of crossed molecular beams, directed and well-defined fluxes of molecules, to and beyond the point where detailed studies of chemical reactions have been possible. He has also elucidated the dynamics of the basic types of reaction. Yuan T. Lee, who initially worked in cooperation with Herschbach, has developed the method of crossed molecular beams further towards its use for general reactions. Most notably, he has used this method for the study of important reactions for relatively large molecules. John C. Polanyi has developed the method of infrared chemiluminescence, in which the extremely weak infrared emission from a newly formed molecule is measured and analyzed. He has used this method to elucidate the detailed energy disposal during chemical reactions.

Background
The molecules and atoms in all substances are in perpetual motion, and collisions between the molecules in a gas or a liquid thus occur continuously. When molecules come in close enough contact with each other, redistribution of the atoms can take place between or within them. New molecules form so-called product molecules, which means that a chemical reaction takes place. To effect a reaction, the colliding molecules are often required to have some special property such as high velocity or large internal energy.

The classical description of how chemical reactions occur, and how rates of chemical reaction are measured, belongs to the field of chemical reaction kinetics. This field has developed rapidly during the last few decades, especially regarding experimental methods. The 1967 Nobel Prize in Chemistry was awarded to M. Eigen, Federal Republic of Germany , R.G.W. Norrish and G. Porter, Great Britain, for their studies of extremely fast chemical reactions. In many respects however, fundamental understanding of what molecular features influence the rate of chemical reactions has been slow in developing.

The directions and velocities of the molecular motion in a gas or a liquid are mainly random. Consequently, the collisions between the molecules are ill-defined as regards, for example, the kinetic energy in the collision. The details of the reaction thus become blurred and cannot be observed precisely enough. This problem had not been solved satisfactorily before the development described here.

It was finally possible to solve the problem by using molecular beams formed of directed and spatially well-defined molecular fluxes of low density, often also with well-defined velocities. When two molecular beams are caused to cross each other, the details of the reactions between molecules can be studied. The crossed molecular beam technique is thus one of the most important advances within the field of reaction dynamics.

Dudley R. Herschbach took part in the development of this method almost from the start. His extremely important achievements concerned for example studies of short-lived direct reactions, especially of the two main types, the "rebound" and the "stripping" reaction. He supplemented the commonly-used procedure of detecting the product molecules by deflecting them in magnetic and electric fields, thus circumventing one of the largely-overlooked problems inherent in the early experiments. The discovery of the first long-lived reaction complexes in crossed beams was soon followed by a theoretical description of their formation and decay. The great importance of angular momentum was observed for the first time in these reactions. Subsequent, more extensive studies by Lee, among others, have clearly shown that this type of long-lived reaction is of great general importance.

During this first stage of the development of the field of crossed molecular beams, reactions between alkali atoms and other molecules were almost the only ones which could be studied, due to the method of detection used at that time. Several research groups developed crossed-beam machines for more general reactions. One of the most sophisticated of these was developed at Herschbach's laboratory, first of all by Yuan T. Lee. This so-called "supermachine" employed two well-defined crossed molecular beams and a moveable mass spectrometric detector, incorporating electron impact ionization and several stages of differential pumping.

Both Lee and Herschbach, as well as other researchers, have used this type of molecular-beam apparatus for detailed studies of a large number of chemical reactions. Lee has led the development towards chemically important reaction systems by investigating reactions between organic molecules and fluorine or oxygen atoms. Short-lived direct reactions as well as long-lived reactions have been observed for large systems such as these. This confirms the universal validity of the early results from studies of alkali-containing reaction systems. Extremely important reactions, of immediate significance for combustion chemistry and atmospheric chemistry, have been studied by Lee during recent years.

Another very important method for the detail study of chemical reactions has been developed by Polanyi, the infrared - (IR) - chemiluminescence method. This development took place concurrently with the formation of the crossed molecular beam field. This complementary method resembles the crossed molecular beam method in many respects, but involves measurement and analysis of the extremely weak infrared emission from the product molecules in some chemical reactions. Excess energy from the reaction is deposited as internal energy in the product molecules, which after some delay emit the energy in the form of infrared light. Spectroscopic analysis of this light reveals directly the quantum mechanical states which the product molecules occupied. This gives indirect but extremely important information on the multidimensional surface describing the potential energy for the system. The potential energy surface is the fundamental, but in most cases largely unknown factor, which determines the detailed behavior of a chemical reaction.

Polanyi has to a large extent combined a description of the potential energy surface for the reactions studied with the experimental findings. He has for example described how the existence and location of an energy barrier on the potential energy surface modifies the dynamics of the reaction. Further, he has observed that the product molecules in some cases belong to two different, well separated, classes with respect to the internal energy distribution. The method which he has developed can be considered as a first step towards the present more sophisticated, but also more complicated, laser-based methods for the study of chemical reaction dynamics.

In the figure, two directed molecular fluxes are shown, .I.e. idealized molecular beams. In the crossing region, a reaction can take place and new molecules can form. In this special case oxygen atoms (open circles) react with hydrogen atoms (two filled circles), and form a long-lived complex, which is an energy-rich and thus unstable water molecule. Each complex dissociates finally to a hydrogen atom and a hydroxyl radical. This reaction has been studied in crossed molecular beams as well as with infrared chemiluminescence.

1985 Nobel Prize in Chemistry to Jerome Kasrle and Herbert Hauptman.
The Royal Swedish Academy of Sciences has decided to award the 1985 Nobel Prize in chemistry jointly to Professor Herbert A. Hauptman, The Medical Foundation of Buffalo, USA, and to Professor Jerome Karle, US Naval Research Laboratory, USA, for their outstanding achievements in the development of direct methods for the determination of crystal structures. Summary This year's Nobel Prize in Chemistry has been awarded to Herbert A. Hauptman and Jerome Karle "for their outstanding achievements in the development of direct methods for the determination of crystal structures". The prize is being awarded for a methodology because of the great importance of this methodology for chemical research. Through Hauptman's and Karle's fundamental achievements, the methods have been developed into practical instruments for determining the structure of molecules within both inorganic and organic chemistry - not least within the chemistry of natural products. The determination of structure involves generating a three-dimensional picture of the positions of the atoms. The picture maps the electron density within the crystal the density is greatest at the centre of the atoms. It can never be less than zero anywhere, and this is the fact upon which the Hauptman-Karle method is based. Structure determination employs radiation of so short a wavelength that it becomes possible to "see" the atoms - X-rays are normally used for this. This means that the wavelength must be shorter than the distance between each atom. X-rays striking a crystal are deflected and concentrated in different directions, and the intensity of the deflected rays is measured. In order to determine the positions of the atom in a crystal, however, is it not enough to know the direction and intensity of the rays, it is also necessary to know the "phase" of each deflected ray, that is, how much the waves in the different rays are displaced in relation to each other. The fact that electron density is positive (electrons either exist or they do not) limits the possibilities for phase displacement. Hauptman and Karle have constructed systems of equations that are based on the values of the intensities measured and that describe the limitations. The two scientists have also developed a procedure for solving the equations: the solutions give direct connections between the phases sought. Since the validity of each equation is only statistically probable, it is necessary to make a large number of measurements and to obtain many times more equations than the number of unknowns to be determined. While this makes the determinations of phase more reliable, it entails comprehensive calculations of the kind that are now feasible using modern computer techniques. The method is termed "direct" because of the fact that, in contrast with other methods, it gives the structure directly from the data collected. In order to understand the nature of chemical bonds, the function of molecules in biological contexts and the mechanism and dynamics of reactions, knowledge of the exact molecular structure is absolutely necessary Background Information This year's Nobel Prizewinners in Chemistry, Herbert A. Hauptman and Jerome Karle, have developed what are termed "direct methods" for the determination of crystal structure. This development of a method merits a Nobel Prize since the method now plays an increasingly important role in chemical research. It is therefore of importance to consider the method first. As early as the turn of the century, chemists possessed a good understanding of the geometrical arrangement of the atoms in carbon compounds. But it is only through structure determination using X-ray crystallography that we have been able to obtain a detailed picture of the distances between the atoms and of the angles between the various bonds. Spectroscopy and electron diffraction have played a complementary role, especially in the case of simpler molecules. Until the 1960's it was determination of the arrangement of the atoms that gave the most important new results. The whole of inorganic chemistry was revolutionized, hitherto completely unknown principles of structure being elucidated. Important progress was also made in natural product chemistry. A series of Nobel Prizes describes this development: von Laue in 1914, the Braggs, father and son 1915, Pauling 1954, Perutz and Kendrew 1962, Crick, Watson and Wilkens 1962, Hodgkin 1964, Barton and Hassel 1969, Lipscomb 1976 and Klug 1982. Lipscomb combined structure determination with far-reaching studies of the nature of chemical bonds, and it is precisely this theory of chemical bonding that requires knowledge of the exact structure of molecules - in other words, accurate bond distances and accurate bond angles. The need for exact knowledge of structure is great within two areas of chemistry. One of these areas concerns structural problems, especially those associated with the function of molecules in biological contexts. Here, a large number of processes are considered in similar ways under the heading "signal - receptor processes". Examples of these processes are enzyme activity, antigen - antibody and scent substance - scent receptor. For understanding these signal-receptor processes it is necessary to gain as detailed a knowledge as possible of both signal molecules and receptor molecules (active site). The signal molecules are relatively small and their structure can be determined. The structure of the receptor molecule can also be perceived by analogy with low-molecular compounds. Where giant molecules are involved, structure determination of the type for which Perutz and Kendrew received a Nobel Prize is required. For determining the low-molecular signal molecules the Hauptman-Karle direct method must be used. In the other important area, the mechanism and chemical dynamics of reactions are studied. Questions being asked also by chemists working with organic synthesis are, for instance: How, at molecular level, does a chemical reaction take place? How does a molecule move, and how is the structure changed in chemical reactions? The most important answers are coming from researchers within theoretical chemistry, but these must in turn have accurate knowledge of the structures of reacting molecules. To summarize: the last fifteen years have seen a large increase in structure determinations accomplished within both inorganic and organic chemistry, including natural product chemistry. These determinations have been carried out predominantly using "direct methods". Looking into the future we can predict a further increased need for structure determinations of this kind. While it is easy to explain the importance for chemistry of the two prizewinners' development of the methods, it is considerably more difficult without recourse to mathematical formulae to describe the achievement itself in a way that is easy to understand. When X-rays strike a crystal, they will be deflected only in certain definite directions, where the intensity of irradiation may be measured. To determine the arrangement of atoms in a crystal, however, it is not enough to know the direction and intensity. The "phase" of each ray so deflected must also be known. In special cases, it has been possible to solve this "phase problem" by making use of the fact that "heavy" atoms containing many electrons spread the X-rays more strongly than "light" atoms do. This property of heavy atoms is used both in "Patterson methodology", which has been very important in structural inorganic chemistry, and in "isomorph substition". The latter is used when determining the structure of giant molecules such as proteins. In this case the heavy atoms can be bound to the protein without its structure being appreciably altered. This however is not possible for the large number of compounds. Two facts have created the conditions for the development of the "direct" methods. The first is that electron density, which diffuses the X-rays, can never be negative. The other is that the number of measurements is much greater than the number of equations to be solved, which permits the use of statistical methods. In work done between 1950 and 1956, Hauptman and Karle laid the foundations for a rational exploitation of these possibilities, specially the use of inequalities. The immense importance of this work for subsequent development may easily be followed in the literature. This is not to say that Hauptman and Karle alone are responsible for the development, and other names must be mentioned in particular. Before Hauptman and Karle published their work, D. Harker and J.S. Kasper proposed the use of one inequality, which represents a special case in the Hauptman-Karle system, and determined a complicated structure using it. Important conceptual contributions were also made by D. Sayre, who anticipated the practical approach which has later come to be used. Isabel Karle´s and M. Woolfson's contributions to the practical utilization of direct methods have been crucial, and in this connection the development of fast computers has been a prerequisite for the full realization of the value of the method.

1985 El estadounidense Franco Modigliani gana El Premio Nobel de Economía por sus estudios sobre El ahorro doméstico y El funcionamiento de Los mercados financieros. — The Bank of Sweden Prize in Economic Sciences in Memory of Alfred Nobel 1985 is announced to go to Franco Modigliani (US, Massachusetts Institute of Technology) "for his pioneering analyses of saving and of financial markets".

1984 Medicine Nobel Prize goes for immunity theories and discoveries. ^Top^

The Nobel Assembly of Karolinska Institutet has today decided to award the Nobel Prize in Physiology or Medicine for 1984 jointly to

Niels K. Jerne, Georges J.F. Köhler and César Milstein

for theories concerning "the specificity in development and control of the immune system" and the discovery of "the principle for production of monoclonal antibodies".

— Los científicos británicos Niels K. Jerne y César Milstein obtienen El Premio Nobel de Medicina por su labor sobre El sistema inmunológico.

— The Nobel Prize in Physiology or Medicine 1984 is announced to go to Niels K. Jerne of Denmark (1911~1994), Georges J.F. Köhler of Germany (1946~1995) [both at the Basel Institute for Immunology, Switzerland], and César Milstein of Argentina and the UK (born in 1927, MRC Laboratory of Molecular Biology, Cambridge, UK) "for theories concerning the specificity in development and control of the immune system and the discovery of the principle for production of monoclonal antibodies".

Summary

Niels K. Jerne is the great theoretician in immunology. In three main theories he has in a visionary way elucidated essential questions concerning specificity, development and regulation of the immune response. The natural-selection theory regarding antibody formation breaks with old views on the immune response and is a starting point of modern cellular immunology. His second theory explains how the cells of the immune system which mature in the thymus gland develop under the influence of the transplantation antigens of the host. The third, and most important theory, predicts how the immune response is regulated by a complicated network consisting of antibodies and anti-anti-bodies. The principles of the network theory are beginning to be exploited in prevention, diagnosis and treatment of disease.

The hybridoma technique for the production of monoclonal antibodies represents one of the most important methodological advances in biomedicine during the 1970s. An antibody producing cell and all its daughter cells produce an identical antibody molecule (monoclonal antibody). Since long scientists nourished the hope that it would become possible to produce monoclonal antibodies with predetermined specificities. This dream became a reality in 1975 when Georges J.F. Köhler and César Milstein described the hybridoma technique for production of monoclonal antibodies. They immortalized antibody producing cells by fusing them with tumor cells. The method allows unlimited production of monoclonal antibodies with predetermined specificity. Monoclonal antibodies has opened up completely new fields for theoretical and applied biomedical research and allows precise diagnosis and also treatment of disease.

An explanation of the diversity of the immune system

The most important task for the immune system is to defend the body against bacteria, virus and other microorganisms. The specific defense is exerted by a subgroup of white blood cells (lymphocytes). The immune system needs to recognize and react specifically with a large number of foreign substances (antigens). How the lymphocytes develop these vital properties and how they build up the highly specialized recognition system of the immune apparatus has long been an area of intensive research.

Niels K. Jerne is the leading theoretician in immunology during the last 30 years. In three main theories he has elucidated central issues concerning specificity, development and regulation of the immune system in a comprehensive and convincing way. By his theories Jerne has outlined the development of modern immunology.

Theory 1: Specificity is predetermined

In his Natural-Selection Theory of Antibody Formation from 1955 Jerne explains the development of a specific antibody response in the following way. Each individual has a large number of natural antibodies with specificities for all antigens towards which the individual can respond. These antibodies develop already during fetal life in the absence of external antigens. The foreign antigen then selects the antibody molecule which has the best fit. The antigen-antibody binding stimulates the production of this particular antibody specificity.
Jerne's natural-selection theory contrasted to the dogmatic views of the antibody response as formulated in the instruction theories which were prevailing at that time. According to these theories the antigen serves a template for the production of antibodies.
In Jerne's natural selection theory it is implied that the generation of the enormous number of antibody specificities is independent of exogenous antigens. This view on the nature of the immune system constitutes the basis for modern immunology.

Theory 2: Reactivity against self-antigens creates diversity

The natural-selection theory is mainly concerned with the maturation of the immune system after it has acquired the ability to react with antigen. In the second theory on the Somatic Generation of Immune Recognition set forth in 1971 Jerne explains how the immune system develops from stem cells to mature lymphocytes which can react with antigen. He presupposes that every individual possesses all genes needed for the production of antibodies, and antibody-like molecules, which can bind all strong transplantation antigens of the species. Jerne suggests that lymphocytes mature in the thymus gland and in other lymphoid organs where they are exposed to the transplantation antigens of the individual. Cells which recognize the antigens are stimulated and enter cell division. As mutations accumulate in rapidly dividing cells new immunological specificities may develop. At the same time the specificities of the lymphocytes for self transplantation antigens are weakened. The mature lymphocytes will recognize foreign antigen associated with transplantation antigens. The theory explains how the immune system normally matures through the influence of self antigens. It also offers an explanation for the regulation of immunological specificity by genes belonging to the transplantation system.

Theory 3. Antibodies, anti-anti-bodies.......

In his third main theory, the Network Theory from 1974, Jerne explains how the specific immune response is regulated. The theory has greatly stimulated research and led to new insights into the immune system. Recently its principles have been applied to diagnosis and treatment of disease.
A basis for the network theory was the observation that antibodies can elicit anti-antibodies directed against antigen binding structures on the first antibody (Figure 1). Moreover, anti-antibodies can stimulate the production of still another generation of antibodies, anti-anti-antibodies. Essentially, this antibody cascade is endless successively adding new specific properties to the immune system. The various antibody generations either stimulate or suppress the production of one another. Under normal conditions the network is balanced. When an antigen is introduced the equilibrium is disturbed. The immune system tries to restore balance which leads to an immune response against the antigen.

Figure 1. The Network Theory.

Antibody 1 (Ak-1) has a structure in its variable (V) region which can bind the antigen. The V-region of AK-1 contains unique structures which stimulate the production of various anti-antibodies (Ak-2). Some AK-2 express V-region structures which mimic the antigen and which therefore can stimulate AK-1 production.

Each antibody generation induces the production of still another and larger set of anti-antibodies in a cascade-like manner. The various sets of antibodies stimulate or suppress the production of each other in a complex network. Under normal conditions the network is balanced. However, the equilibrium is disturbed when an antigen is introduced and binds to AK-1 The immune system attempts to restore the balance, i.e. it leads to an immune response.

Some examples where the network theory has been applied to experimental and clinical medicine are given in the following.

1. Infectious diseases. Anti-antibodies have been used in animals as a kind of vaccine against parasitic infections (trypanosomiasis), urinary tract infections, hepatitis and other infectious diseases.

2. Allergy. Anti-pollen antibodies may elicit allergic symptoms when an allergic person is exposed to pollen. The production of anti-pollen antibodies has been prevented in animals by anti-antibodies.

3. Autoimmune disease. Autoimmune disease may be caused by antibodies directed against the body's own tissues. Experimental autoimmune disease has been successfully treated with anti-antibodies.

4. Transplantation. Anti-antiimmunity may be important in organ transplantation by contributing to immunological tolerance against antigen on the foreign graft.

5. Endocrinology. Anti-antibodies against hormones and hormone receptors may prevent binding of the hormone to the receptors. This has been described for insulin and its receptor.

6. Tumors. Anti-antibodies have been attempted as treatment of certain tumors of the human immune system.

Hybridoma - a technique for eternal production of monoclonal antibodies in cell cultures

Besides gene technology, which has already been honored by several Nobel Prizes, the hybridoma technique represents the most important methodological advance within the field of biomedicine during the 1970s. The development of this technique is based on several observations concerning basic biological phenomena.

There are cells in the body - immune lymphocytes - which can produce millions of different antibodies. However, each single cell can only produce antibodies with a certain predetermined specificity. A prerequisite for the formation of a multitude of antibodies is, therefore, the existence of an excess of lymphocytes. If the body is exposed to a certain foreign antigen there may be stimulation of a lymphocyte which fortuitously has been endowed with the capacity to identify this particular antigen. This lymphocyte then starts to divide and forms a clone of cells which produces identical - monoclonal - antibodies.

The development of a clone of cells in connection with a normal immune response occurs under carefully controlled conditions. In rare cases, however, the body loses control over a clone of antibody producing cells. This may lead to formation of a special type of tumor (myeloma). Myeloma cells usually retain their capacity to produce a certain antibody, but because of the accidental emergence of the tumor one normally does not know with which antigen this antibody reacts.

White blood cells responsible for producing antibodies are highly specialized cells. As a consequence they lack capacity to survive for a longer time if they are removed from the body and incubated in a tissue culture medium. In contrast, myeloma cells can occasionally be cultivated continuously. Since long, biomedical research workers have nourished the dream to be able to propagate clones of cells which produce antibodies with predetermined specificity. This dream materialized when Georges J.F. Köhler and César Milstein in 1975 introduced the so-called hybridoma technology for production of monoclonal antibodies. The principle features of the hybridoma technology is as follows (Figure 2).

Figure 2. Principal steps in the production of a hybridoma.

Spleen cells are prepared from animals, usually mice, which have been immunized with a selected antigen. These cells are then fused with myeloma cells maintained in culture in the laboratory. The product of this fusion is referred to as a hybridoma.

Surprisingly, a hybrid of two cells can survive and also continue to divide. In this particular hybrid the myeloma cells contribute the capacity for survival, whereas the spleen cells direct the synthesis of antibodies with the preselected specificity. By special arrangements it is possible to achieve a multiplication of hybridoma cells but not of isolated myeloma cells.

The hybrids obtained are propagated in a highly diluted state so that colonies deriving from single hybrid cells can be isolated. By use of a sensitive method the clones which produce the specific antibodies are identified. A particular hybridoma can then be used for future, unlimited production of a highly specific antibody.

The availability of monoclonal antibodies has opened completely new possibilities for basic as well as applied biomedical research. The following examples of the use of monoclonal antibodies can be given.

1. Detailed studies of the distribution of different functions in different parts of antigen molecules. These studies may concern building elements of infectious agents; cell products such as enzymes and hormones; surface structures of cells etc. The mapping of variations in the surface components of influenza virus which explain the occurrence of repeated infections is one example.

2. High degree purification of substances, e.g. interferon, by taking advantage of the unique capacity displayed by a particular monoclonal antibody to bind to a certain antigen. In this case one uses a technique referred to as affinity chromatography.

3. Diagnostic characterization of diseases by identification of special structures on the surface or on the inside of cells. Hereby it is possible to distinguish between different forms of tumors and follow the development of tumors Furthermore, it is possible to distinguish between different kinds of normal white blood cells. This is of importance for the characterization of certain immune deficiency conditions as seen e.g. in connection with the disease AIDS (acquired immune deficiency syndrome).
Diseases caused by infectious agents can also be diagnosed by use of monoclonal antibodies. Thus, virus infected cells and bacteria or parasites inside or outside cells can be identified with a unique degree of specificity.

4. Treatment of diseases. Monoclonal antibodies against specialized white blood cells have been used with some success in connection with transplantation. There may also be possibilities to use monoclonal antibodies for treatment of tumors.

1981 Nobel Literature Prize to Elias Canetti. ^Top^

— Elías Canetti, británico de origen búlgaro, Premio Nobel de Literatura.
— The Nobel Prize in Literature 1981 is announced to go to Elias Canetti (1905 - 1994) of the UK "for writings marked by a broad outlook, a wealth of ideas and artistic power".

Born in 1905, in the port of Rustschuk on the lower Danube, Elias Canetti belongs to a Sephardic family whose members, in 1492, were driven out of the town of Canete, situated between Cuenca and Valencia. For several hundred years, the family lived in Turkey, but in the course of time, settled in Bulgaria. In 1911, Elias Canetti went to England with his parents; after his father's sudden and premature death in 1913 - a catastrophe which has been of decisive importance to him - the family moved to Vienna. Between the years 1916 and 1924, Elias Canetti attended schools in Zürich and Frankfurt-am-Main. He then studied science in Vienna, the result being a doctorate in chemistry in 1929. Ever since then he has devoted himself exclusively to writing. In 1938 he went to France; sometime later, he moved over to London, which has remained his place of residence through the years.

When surveyed, Elias Canetti's literary work may seem split up, comprising as it does of so many genres. His oeuvre consists of a novel, three plays, several volumes of notes and aphorisms, a profound examination of the origin, structures and effect of the mass movement, a travel book, portraits of authors, character studies, and memoirs; but these writings, pursued in such different directions, are held together by a most original and vigorously profiled personality.

The exiled and cosmopolitan author, Canetti has one native land, and that is the German language. He has never abandoned it, and he has often avowed his love of the highest manifestations of the classical German culture. He has warmly emphasized what Goethe, for instance, has meant to him as medicina mentis.

His foremost purely fictional achievement is the great novel, Die Blendung, (Auto da Fé ) published in 1935 and praised then by Thomas Mann and Hermann Broch. But it can be said to have attained its full effect during the last decades: against the background of national socialism's brutal power politics, resulting in a world conflagration, the novel acquires a deepened perspective.

Die Blendung was part of an originally planned series of novels which was to take the shape of a "comédie humaine of the madmen". The book has such fantastic and demoniacal elements that associations to Russian 19th century writers like Gogol and Dostoievsky - to whom, by the way, Canetti himself has declared he owes a debt of gratitude - are apparent. The main scene of the macabre and grotesque events that the novel discloses is an apartment house in Vienna. It is an aspect of key importance when Die Blendung is regarded by several critics as a single fundamental metaphor for the threat exercised by the "mass man" within ourselves. Close at hand is the viewpoint from which the novel stands out as a study of a type of man who isolates himself in self-sufficient specialization - here, the sinologist Peter Kien surrounded by his many books - only to succumb helplessly in a world of ruthlessly harsh realities.

Die Blendung leads over to the big examination of the origin, composition and reaction patterns of the mass movements which Canetti, after decades of research and study, published with Masse und Macht (Crowds and Power, 1960). It is a magisterial work by a polyhistorian who knows how to reveal an overwhelmingly large number of viewpoints of men's behavior as mass beings. By going in particular to the primitive peoples, their myths and fairy tales, Canetti tries to pinpoint the character of the mass movements. In his field of research he introduces not only the actual masses but also the imaginary ones: the masses of "the spirits", "the angels" and "the devils", which are such important elements in many religions. He explores the nature and significance of the national mass symbols; with acumen he illustrates the psychological problems of commands and obedience. Like Gustave Le Bon, he sees the archaic components in the mass movements of the new age. In his basically ahistorical analysis, what he wants to expose and attack by scrutinizing the origin and nature of the mass is, in the end, the religion of power. According to Canetti, deep down behind every command, every exercise of power, is the threat of death. Survival itself becomes the nucleus of power. At the last, the mortal enemy is death itself: this is a principal theme, held to with an oddly pathetic strength, in Elias Canetti's literary works.

Apart from the intensive work on Masse und Macht, Canetti has written strongly concentrated, aphoristic notes, issued in several volumes. They usually emanate from concrete situations which can be regarded as metaphors for something generic. A satirical bite in the observations of people's behavior, a loathing of wars and devastation, bitterness at the thought of life's brevity are characteristic features of the continuous notes. By virtue of his abundant wit and stylistic pithiness, Canetti stands out as one of the foremost aphorists of our time, a man who, in his phrasing of life's ironies, is sometimes reminiscent of great predecessors like La Bruyère and Lichtenberg.

The plays Canetti has written are all of a more or less absurd kind: Hochzeit (Wedding), 1932, Komödie der Eitelkeit (The Comedy of Vanity), 1950, Die Befristeten (The Deadlined), 1956. In their portrayal of extreme situations, often depicting human vulgarity, these "acoustic masks", as Canetti calls the plays, are of decided interest.

With Die Stimmen von Marrakesch (The Voices of Marrakesh ), 1967, Canetti published a travel book which shows his keen eye for life in the poor outskirts of existence; with Der Ohrenzeuge (Earwitness) , 1974, he presented a collection of "characters" in the spirit of Theophrastus. Among his literary portrait studies, special mention can be made of Der andere Prozess (Kafka's Other Trial) , 1969, in which, with intense involvement, he examines Kafka's complicated relationship to Felice Bauer. The study forms itself into a picture of a man whose life and work meant the relinquishing of power.

Finally, standing out as a peak in Elias Canetti's writings are his memoirs, so far in two large volumes: Die gerettete Zunge (The Tongue Set Free), 1977, and Die Fackel im Ohr (The Torch in the Ear), 1980. In these recollections of his childhood and youth, he reveals his vigorous epic power of description to its full extent. A great deal of the political and cultural life in Central Europe in the early 1900s - especially the form it took in Vienna - is reflected in the memoirs. The peculiar environments, the many remarkable human destinies with which Canetti was confronted, and his unique educational path - always aiming at universal knowledge - are seen here in a style and with a lucidity that have very few qualitative equivalents in the memoirs written in the German language this century.

1959 El investigador español Severo Ochoa y El bioquímico estadounidense Arthur Kurnberg ganan el Premio Nobel de Medicina. — The Nobel Prize in Physiology or Medicine 1959 is announced to go to Severo Ochoa (US, New York University, and College of Medicine of New York _ 1905~1993) )and Arthur Kornberg (US, Stanford University – born in 1918) "for their discovery of the mechanisms in the biological synthesis of ribonucleic acid and deoxyribonucleic acid"

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