The Nobel Prize in Physiology or Medicine 2011
Bruce A. Beutler, Jules A. Hoffmann, Ralph M. Steinman
Presentation Speech by Professor Göran K. Hansson, Secretary of the Nobel Assembly at Karolinska Institutet and of the Nobel Committee for Physiology or Medicine, 10 December 2011
Your Majesties, Your Royal Highnesses, Honoured Nobel Laureates, Ladies and Gentlemen,
We live in a dangerous world. During the hour you spend here in the Concert Hall, you will be exchanging millions of bacteria and viruses with each other. Fortunately, you are equipped with a strong defence, and we do not expect that this hour will lead to any significant reduction of our guest list.
This defence constitutes our immunological protection against bacteria, viruses and other microorganisms. It consists of two lines of defence: the first one stops the invaders and the second one eliminates them.
Much research has been focused on the second line of defence with its antibodies and killer cells. But a major question remained unanswered: How can we survive an infection until antibodies have been formed? It can take several weeks before the antibody levels are sufficient, and by then we may already have recovered from our infected wound or our common cold. The first line of the immune defence, which is also called innate immunity, must have recognised and stopped the bacteria long before the antibodies had arrived on the scene.
Jules Hoffmann went on a quest to reveal the secrets of the first line of defence. He knew that insects lack the second line of defence, and therefore chose fruit flies as his research model. It turned out that flies with defects in a gene called Toll could not combat infections successfully. Hoffmann and his colleagues were able to unravel a detector system involving Toll that is activated by molecules derived from microorganisms, leading to mobilisation of the immune defence against the intruders. Thanks to Hoffmann's discovery, the sensors of the first line of host defence were finally identified.
Bruce Beutler was searching for the solution to another problem. He wanted to understand how bacteria such as Salmonella can elicit a life-threatening septic shock – what used to be called blood poisoning. By comparing the genome of different mouse strains, he could demonstrate that a single gene initiated the shock reaction. This gene turned out to be the mammalian counterpart of Toll, and it encodes a receptor that serves as a sensor on the cell surface. When bacterial components bind to this receptor, the immune system is activated, and antibacterial defence mechanisms are mobilised.
Thanks to Beutler's discovery, we understood how the sensors of the innate immune system operate to recognise infectious agents. Together, the two Nobel Laureates had clarified how the first line of defence is mobilised.
In parallel with these discoveries, Ralph Steinman was studying the activation of the second line of defence, which is also called adaptive immunity. More than 30 years ago, he isolated a new cell type called the dendritic cell. Through systematic research, he showed that dendritic cells patrol the organs searching for pathogens, and mobilise the second line of immune defence, with its antibodies and immunologic memory. The dendritic cells themselves are in fact activated by the Toll receptor that Beutler and Hoffmann had identified. This mechanism ties together the two lines of immune defence.
The three discoveries now awarded the Nobel Prize have identified the triggers for the innate and the adaptive immune system, and taught us how these two lines of defence are interconnected to protect us against infections. Today, knowledge about the sensors of innate immunity is exploited to improve vaccines and therapies, and dendritic cells are used to treat infections and cancer.
Dear Professor Beutler and Professor Hoffmann,
Your research has identified the gatekeepers of the immune system. Not only have your discoveries resolved a major enigma in immunology, they have offered new hope for mankind in its combat against infections, cancer, and inflammatory diseases. On behalf of the Nobel Assembly at Karolinska Institutet, I wish to convey to you our warmest congratulations.
Dear Mrs Steinman,
Your late husband's research has taught us how adaptive immunity is initiated and provided us with new tools in the struggle against disease. We deeply regret that Professor Steinman is no longer with us but we are happy that you are here to accept his Nobel Prize.
Professor Beutler, Professor Hoffmann and Mrs Steinman,
May I now ask you to step forward to receive the Nobel Prize from the hands of His Majesty the King.
Copyright © The Nobel Foundation 2011
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