Sveriges Riksbank Prize in Economic Sciences in Memory of Alfred Nobel
Monday 10 October, 1:00 p.m. CET at the earliest
Nobel Prize in Physiology or Medicine
Bruce Beutler, Jules Hoffmann and Ralph Steinman.
The 2011 Nobel Prize in Physiology or Medicine was divided, one half jointly to Bruce A. Beutler and Jules A. Hoffmann "for their discoveries concerning the activation of innate immunity" and the other half to Ralph M. Steinman "for his discovery of the dendritic cell and its role in adaptive immunity".
This year's Nobel Laureates have revolutionized our understanding of the immune system by discovering key principles for its activation.
Scientists have long been searching for the gatekeepers of the immune response by which man and other animals defend themselves against attack by bacteria and other microorganisms. Bruce Beutler and Jules Hoffmann discovered receptor proteins that can recognize such microorganisms and activate innate immunity, the first step in the body's immune response. Ralph Steinman discovered the dendritic cells of the immune system and their unique capacity to activate and regulate adaptive immunity, the later stage of the immune response during which microorganisms are cleared from the body.
The discoveries of the three Nobel Laureates have revealed how the innate and adaptive phases of the immune response are activated and thereby provided novel insights into disease mechanisms. Their work has opened up new avenues for the development of prevention and therapy against infections, cancer, and inflammatory diseases.
Two lines of defense in the immune system
We live in a dangerous world. Pathogenic microorganisms (bacteria, virus, fungi, and parasites) threaten us continuously but we are equipped with powerful defense mechanisms (please see image below). The first line of defense, innate immunity, can destroy invading microorganisms and trigger inflammation that contributes to blocking their assault. If microorganisms break through this defense line, adaptive immunity is called into action. With its T and B cells, it produces antibodies and killer cells that destroy infected cells. After successfully combating the infectious assault, our adaptive immune system maintains an immunologic memory that allows a more rapid and powerful mobilization of defense forces next time the same microorganism attacks. These two defense lines of the immune system provide good protection against infections but they also pose a risk. If the activation threshold is too low, or if endogenous molecules can activate the system, inflammatory disease may follow.
The components of the immune system have been identified step by step during the 20th century. Thanks to a series of discoveries awarded the Nobel Prize, we know, for instance, how antibodies are constructed and how T cells recognize foreign substances. However, until the work of Beutler, Hoffmann and Steinman, the mechanisms triggering the activation of innate immunity and mediating the communication between innate and adaptive immunity remained enigmatic.
Discovering the sensors of innate immunity
Jules Hoffmann made his pioneering discovery in 1996, when he and his co-workers investigated how fruit flies combat infections. They had access to flies with mutations in several different genes including Toll, a gene previously found to be involved in embryonal development by Christiane Nüsslein-Volhard (Nobel Prize 1995). When Hoffmann infected his fruit flies with bacteria or fungi, he discovered that Toll mutants died because they could not mount an effective defense. He was also able to conclude that the product of the Toll gene was involved in sensing pathogenic microorganisms and Toll activation was needed for successful defense against them.
Bruce Beutler was searching for a receptor that could bind the bacterial product, lipopolysaccharide (LPS), which can cause septic shock, a life threatening condition that involves overstimulation of the immune system. In 1998, Beutler and his colleagues discovered that mice resistant to LPS had a mutation in a gene that was quite similar to the Toll gene of the fruit fly. This Toll-like receptor (TLR) turned out to be the elusive LPS receptor. When it binds LPS, signals are activated that cause inflammation and, when LPS doses are excessive, septic shock. These findings showed that mammals and fruit flies use similar molecules to activate innate immunity when encountering pathogenic microorganisms. The sensors of innate immunity had finally been discovered.
The discoveries of Hoffmann and Beutler triggered an explosion of research in innate immunity. Around a dozen different TLRs have now been identified in humans and mice. Each one of them recognizes certain types of molecules common in microorganisms. Individuals with certain mutations in these receptors carry an increased risk of infections while other genetic variants of TLR are associated with an increased risk for chronic inflammatory diseases.
A new cell type that controls adaptive immunity
Ralph Steinman discovered, in 1973, a new cell type that he called the dendritic cell. He speculated that it could be important in the immune system and went on to test whether dendritic cells could activate T cells, a cell type that has a key role in adaptive immunity and develops an immunologic memory against many different substances. In cell culture experiments, he showed that the presence of dendritic cells resulted in vivid responses of T cells to such substances. These findings were initially met with skepticism but subsequent work by Steinman demonstrated that dendritic cells have a unique capacity to activate T cells.
Further studies by Steinman and other scientists went on to address the question of how the adaptive immune system decides whether or not it should be activated when encountering various substances. Signals arising from the innate immune response and sensed by dendritic cells were shown to control T cell activation. This makes it possible for the immune system to react towards pathogenic microorganisms while avoiding an attack on the body's own endogenous molecules.
From fundamental research to medical use
The discoveries that are awarded the 2011 Nobel Prize have provided novel insights into the activation and regulation of our immune system. They have made possible the development of new methods for preventing and treating disease, for instance with improved vaccines against infections and in attempts to stimulate the immune system to attack tumors. These discoveries also help us understand why the immune system can attack our own tissues, thus providing clues for novel treatment of inflammatory diseases.
Nobel Prize in Physics
The 2011 Nobel Prize in Physics is awarded "for the discovery of the accelerating expansion of the Universe through observations of distant supernovae" with one half to Saul Perlmutter and the other half jointly to Brian P. Schmidt and Adam G. Riess.
"Some say the world will end in fire, some say in ice..." *
What will be the final destiny of the Universe? Probably it will end in ice, if we are to believe this year's Nobel Laureates in Physics. They have studied several dozen exploding stars, called supernovae, and discovered that the Universe is expanding at an ever-accelerating rate. The discovery came as a complete surprise even to the Laureates themselves.
In 1998, cosmology was shaken at its foundations as two research teams presented their findings. Headed by Saul Perlmutter, one of the teams had set to work in 1988. Brian Schmidt headed another team, launched at the end of 1994, where Adam Riess was to play a crucial role.
The research teams raced to map the Universe by locating the most distant supernovae. More sophisticated telescopes on the ground and in space, as well as more powerful computers and new digital imaging sensors (CCD, Nobel Prize in Physics in 2009), opened the possibility in the 1990s to add more pieces to the cosmological puzzle.
The teams used a particular kind of supernova, called type Ia supernova. It is an explosion of an old compact star that is as heavy as the Sun but as small as the Earth. A single such supernova can emit as much light as a whole galaxy. All in all, the two research teams found over 50 distant supernovae whose light was weaker than expected - this was a sign that the expansion of the Universe was accelerating. The potential pitfalls had been numerous, and the scientists found reassurance in the fact that both groups had reached the same astonishing conclusion.
For almost a century, the Universe has been known to be expanding as a consequence of the Big Bang about 14 billion years ago. However, the discovery that this expansion is accelerating is astounding. If the expansion will continue to speed up the Universe will end in ice.
The acceleration is thought to be driven by dark energy, but what that dark energy is remains an enigma - perhaps the greatest in physics today. What is known is that dark energy constitutes about three quarters of the Universe. Therefore the findings of the 2011 Nobel Laureates in Physics have helped to unveil a Universe that to a large extent is unknown to science. And everything is possible again.
The Nobel Prize in Chemistry
The Royal Swedish Academy of Sciences has decided to award the Nobel Prize in Chemistry for 2011 to Daniel Shechtman for the discovery of quasicrystals.
A remarkable mosaic of atoms
In quasicrystals, we find the fascinating mosaics of the Arabic world reproduced at the level of atoms: regular patterns that never repeat themselves. However, the configuration found in quasicrystals was considered impossible, and Daniel Shechtman had to fight a fierce battle against established science. The Nobel Prize in Chemistry 2011 has fundamentally altered how chemists conceive of solid matter.
On the morning of 8 April 1982, an image counter to the laws of nature appeared in Daniel Shechtman's electron microscope. In all solid matter, atoms were believed to be packed inside crystals in symmetrical patterns that were repeated periodically over and over again. For scientists, this repetition was required in order to obtain a crystal.
Shechtman's image, however, showed that the atoms in his crystal were packed in a pattern that could not be repeated. Such a pattern was considered just as impossible as creating a football using only six-cornered polygons, when a sphere needs both five- and six-cornered polygons. His discovery was extremely controversial. In the course of defending his findings, he was asked to leave his research group. However, his battle eventually forced scientists to reconsider their conception of the very nature of matter.
Aperiodic mosaics, such as those found in the medieval Islamic mosaics of the Alhambra Palace in Spain and the Darb-i Imam Shrine in Iran, have helped scientists understand what quasicrystals look like at the atomic level. In those mosaics, as in quasicrystals, the patterns are regular - they follow mathematical rules - but they never repeat themselves.
When scientists describe Shechtman's quasicrystals, they use a concept that comes from mathematics and art: the golden ratio. This number had already caught the interest of mathematicians in Ancient Greece, as it often appeared in geometry. In quasicrystals, for instance, the ratio of various distances between atoms is related to the golden mean.
Following Shechtman's discovery, scientists have produced other kinds of quasicrystals in the lab and discovered naturally occurring quasicrystals in mineral samples from a Russian river. A Swedish company has also found quasicrystals in a certain form of steel, where the crystals reinforce the material like armor. Scientists are currently experimenting with using quasicrystals in different products such as frying pans and diesel engines.
The Nobel Prize in Literature
Tomas Tranströmer
The Nobel Prize in Literature 2011 was awarded to Tomas Tranströmer "because, through his condensed, transluscent images, he gives us fresh access to reality".
The Nobel Peace Prize
The 2011 Nobel Peace Prize is awarded jointly to Ellen Johnson Sirleaf, Leymah Gbowee and Tawakkul Karman "for their non-violent struggle for the safety of women and for womens rights to full participation in peace-building work".
The Norwegian Nobel Committee has decided that the Nobel Peace Prize for 2011 is to be divided in three equal parts between Ellen Johnson Sirleaf, Leymah Gbowee and Tawakkul Karman for their non-violent struggle for the safety of women and for womens rights to full participation in peace-building work. We cannot achieve democracy and lasting peace in the world unless women obtain the same opportunities as men to influence developments at all levels of society.
In October 2000, the UN Security Council adopted Resolution 1325. The resolution for the first time made violence against women in armed conflict an international security issue. It underlined the need for women to become participants on an equal footing with men in peace processes and in peace work in general.
Ellen Johnson Sirleaf is Africas first democratically elected female president. Since her inauguration in 2006, she has contributed to securing peace in Liberia, to promoting economic and social development, and to strengthening the position of women. Leymah Gbowee mobilized and organized women across ethnic and religious dividing lines to bring an end to the long war in Liberia, and to ensure womens participation in elections. She has since worked to enhance the influence of women in West Africa during and after war. In the most trying circumstances, both before and during the Arab spring, Tawakkul Karman has played a leading part in the struggle for womens rights and for democracy and peace in Yemen.
It is the Norwegian Nobel Committees hope that the prize to Ellen Johnson Sirleaf, Leymah Gbowee and Tawakkul Karman will help to bring an end to the suppression of women that still occurs in many countries, and to realise the great potential for democracy and peace that women can represent.