Nobel Prize for 2011
in Physiology or Medicine
The Nobel Assembly at Karolinska Institute has on 03.10.2011 decided that the Nobel prize for 2011 in Physiology or Medicine for 2011 shall be divided, with 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
The award summary says that - 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.
Bruce A. Beutler was born in 1957 in Chicago, USA. He received his MD from the University of Chicago in 1981 and worked as a scientist at Rockefeller University in New York and the University of Texas in Dallas, where he discovered the LPS receptor. Since 2000 he has been professor of genetics and immunology at The Scripps Research Institute, La Jolla, USA.
Jules A. Hoffmann was born in Echternach, Luxembourg in 1941. He studied at the University of Strasbourg in France, where he obtained his PhD in 1969. After postdoctoral training at the University of Marburg, Germany, he returned to Strasbourg, where he headed a research laboratory from 1974 to 2009. He has also served as director of the Institute for Molecular Cell Biology in Strasbourg and during 2007-2008 as President of the French National Academy of Sciences.
Ralph M. Steinman was born in 1943 in Montreal, Canada, where he studied biology and chemistry at McGill University. After studying medicine at Harvard Medical School in Boston, MA, USA, he received his MD in 1968. He has been affiliated with Rockefeller University in New York since 1970, has been professor of immunology at this institution since 1988, and is also director of its Center for Immunology and Immune Diseases.
FURTHER COMMENTS BY THIS BLOG
There are a few things which are admitted and understood by all of us as absolute certainties in life.
Any one who is born – is destined to Die - is the foremost amongst them.
Any one who is born and continues to live for his optimum life – is bound to face Diseases – is also a destiny – we can’t avoid.
And, if we continue to live beyond 20-30 years of age – it is just as much certain that we will pass from youth into middle age – and from there, into Old age. This too is just as much certain.
Buddha, when he faced these three realities of old age, disease and death, all on a single day, for the first time, left his Royal Palace, his beautiful wife and loving son - and went to explore the truths of life. The rest is History. Buddha’s exploration and his solution to the problems of life are in one direction.
But, despite all that Buddha (and Lord Krishna, Christ and other Great souls) said - the average man has always been battling these 3 scourges of human life in fear, sorrow, and a certain helplessness. Even while recognizing that old age and death cannot perhaps be avoided at all – Man’s recognition is – we can perhaps avoid disease. We can perhaps live a healthy life, as long as we live.
Our struggle and our exploration to conquer disease has given us some great victories – over many epidemics, over many cruel diseases and over many minor ailments. But, a complete victory on disease is far, far away.
As we conquer one great disease, a new one is born. Nature seems determined to pose newer and newer challenges in this field for man. Human immunity system is not found capable of battling these diseases by itself. Our search is therefore on, for strengthening the human immune system against various diseases – and against disease on general.
CANCER – admittedly is one of the deadliest diseases in the world, defying a complete, effective solution so far. There are many other diseases – which are also without an effective solution – but many of them are not as life threatening as Cancer.
It is therefore heartening that this year’s Nobel Prize for Physiology or Medicine goes to 3 eminent scientists – who concentrated their attention on discovering methods to improve the human immune system. Their discoveries are bound to prove extremely valuable and highly useful in battling Cancer and winning over it. Probably, some more work is needed to turn these discoveries into effective medicines, both preventive and curative, and give complete solution to the sufferers from this deadly disease.
These discoveries will also probably help us in understanding other diseases also much better – and find solutions to them too
A Huge Hope to this scourge is now in sight. Thanks to these three Great scientists. Therefore, we salute all these three great scientists for giving us this Hope.
It is understood that Ralph Steinmann, aged 68, who shares half the Nobel prize, was himself a cancer patient and was battling his pancreatic cancer for the last four years. He died probably, hours before the decision to award him the Nobel Prize was made. His colleagues at the Rockfeller University in New York called it a “bittersweet” honour. This Blog bows down before this great soul for his tremendous initiative in finding a solution to this scourge – despite his personal suffering.
SOME SUGGESTIONS
India, China, Egypt and a few other countries had effective indigenous Medical systems for thousands of years. The western (Allopathic )system has no doubt made great strides and systematized medicinal use.
But, India has another highly effective Ayurvedic system. It is based on a very ancient wisdom that the health of the body depends on the harmony between three Doshas. It is not a micro level system but a holistic system. It is also a great science in itself.
But, right now, there is not much research into this system. What ever ancient knowledge is available, and what ever medicines are prescribed therein – they only are being used – and of course, they do prove highly effective for many diseases, even where western medicine is unsuccessful.
Here are a few suggestions – for effective utilization of both allopathic and Ayurvedic sciences.
SUGGESTIONS
Ø The Indian Government and all state Governments must come forward for promoting this indigenous research in a big way.
Ø The Indian Billionaire community must come forward to establish research centers for Ayurveda – incorporating therein, various modern methods too.
Ø Government must establish multi system (Allopathic, Ayurvedic and Siddha) studies centres in a Big way - and enable award of multi-system degrees and Post Graduate degrees – permitting practice of such systems.
Ø Ensure that Ayurvedic medicines are prepared in a scientific manner, incorporating modern systems with traditional systems. Ensure also that there are proper testing methods for these medicines.
Ø Yoga, by itself, is and extraordinary Medicine for all Ailments. It must be brought out into greater, popular use.
Body is the creator of many ailments when it does not function harmoniously. But, body itself is capable of curing most of the diseases (probably, all of them). We just do not know how, right now. Almighty has given all varieties of knowledge to us. We would be foolish to ignore any branch of such knowledge in preference to another. Allopathy will remain a half science – if it ignores Ayurveda – and Ayurveda too will remain a half science, if it ignores Allopathy.
India must bring these two sciences together – for the benefit of mankind.
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