The Nobel Prize in Physiology or Medicine 1975
David Baltimore, Renato Dulbecco, Howard M. Temin
Presentation Speech by Professor Peter
Reichard of the Karolinska Medico-Chirurgical Institute
Translation from the Swedish text
Your Majesties, Your Royal Highnesses,
Ladies and Gentlemen,
How does a cancercell arise? What distinguishes it from a normal cell? Cancercells are social misfits, outside the control of the organism. The capacity for unlimited growth is inherited from generation to generation. The difference between a normal cell and a cancercell resides in their genes.
Transformation of a normal cell to a cancercell thus requires a change in the genetic material. This may be caused by radiation, by treatment with different chemicals or by infection with tumor viruses. This year's Nobel prize winners have clarified what happens on infection of cells with tumor viruses.
The genetic material of the cell - or with a chemical term, its DNA - is locked up in the cell nucleus. The cell is constructed in accordance with the master plan laid down in the chemical structure of the genetic material. The building job is carried out by proteins, but the instructions are given by DNA. But the master plan is locked up in the nucleus, and the instructions reach the building place in the form of blue prints which we call RNA with a chemical term. The flow of information in the cell thus occurs first from DNA or RNA and then from RNA to proteins.
How does a tumor virus interfere with this process? As all other viruses, tumor viruses contain either DNA or RNA. Renato Dulbecco clarified the process of infection with DNA-tumor viruses. When a cell becomes infected this means that viral DNA enters it. Dulbecco made the basic observation that viral DNA is incorporated in the infected cell nucleus and is there joined to the DNA of the cell. Tumor transformation involves the incorporation of viral into cellular genetic material and results in the appearance of hereditary properties resulting in unlimited cell growth. At each cell division the new "cancer" DNA is then carried to the next generation.
What happens after infection with a tumor virus which contains RNA and not DNA? Also in this case transformation to a cancer cell is the result of an influence on the genetic material, but this now occurs in a more indirect manner. Already in the early 1960's Howard Temin proposed that a RNA tumor virus can give rise to a DNA copy which is incorporated into the genetic material of the cell. This requires a reversal of the normal flow of information from DNA to RNA, a rather unorthodox idea at that time, which was not well received by the scientific establishment. But in 1970 Howard Temin and David Baltimore independently discovered that RNA tumor viruses contain a special protein which can make a DNA copy from RNA. This protein carries out precisely the chemical reaction postulated by Temin. This discovery marked not only a new chapter in cancer research but also had more general and far reaching biological consequences. Through the work of David Baltimore and others after 1970 it is now clear that infection of cells with RNA tumor viruses indeed leads to the formation of a DNA copy which is incorporated into the DNA of the cell. Thus, the mechanism of transformation discovered by Renato Dulbecco now applies to both DNA and RNA tumor viruses. Furthermore, other scientists have also found that many normal cells in their DNA contain copies of viral RNA, closely related to the RNA of tumor viruses, In some cases these DNA copies have existed and been part of the genetic material for millions of years. Even though their function as yet has not been clarified it is known that they can be released and transformed into RNA viruses if the cell is treated with certain chemicals. Part of the genetic material of the cell is then suddenly set free and is reborn as a virus particle.
What is the medical relevance of these discoveries? Is human cancer a virus disease? Certain forms of cancer of animals, such as leukemia, mammary carcinoma and cancer of connective tissues can be caused by viruses. This does not of course mean that all animal cancer is caused by viruses. I do not believe that man is an exception in this connection, even though we still lack conclusive evidence for viral involvement in any form of human cancer. In the domestic cat leukemia is today a quite common cause of death. In all probability this will not be the case in the future since one already is beginning to find a vaccine against the cat virus which causes this form of cancer. We have now the tools which should make it possible to identify human cancers caused by tumor viruses. There is thus good hope that this will lead to methods which help us to prevent the disease.
David Baltimore, Renato Dulbecco, Howard Temin: 65 years ago Peyton Rous established that cancer can be caused by viruses. Through your experiments you have shown how the virus does its job. However, the ramifications of your discoveries go further than that. The borderline between viruses and genes is disappearing. Specific genetic information which for millions of years has been an integral part of chromosomes of higher organisms may suddenly be released and be reborn as a virus particle. On behalf of Karolinska Institutet I wish to convey to you our warmest congratulations and now ask you to receive your Nobel prizes from the hands of His Majesty the King.
From Nobel Lectures, Physiology or Medicine 1971-1980, Editor Jan Lindsten, World Scientific Publishing Co., Singapore, 1992
Copyright © The Nobel Foundation 1975
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