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|Posted: Wed Oct 04, 2006 6:56 am Post subject: (Gen) Nobel Prizes in the Sciences
2 October 2006
The Nobel Assembly at Karolinska Institutet has today decided to award
The Nobel Prize in Physiology or Medicine for 2006
Andrew Z. Fire and Craig C. Mello
for their discovery of
"RNA interference – gene silencing by double-stranded RNA"
This year's Nobel Laureates have discovered a fundamental mechanism for controlling the flow of genetic information. Our genome operates by sending instructions for the manufacture of proteins from DNA in the nucleus of the cell to the protein synthesizing machinery in the cytoplasm. These instructions are conveyed by messenger RNA (mRNA). In 1998, the American scientists Andrew Fire and Craig Mello published their discovery of a mechanism that can degrade mRNA from a specific gene. This mechanism, RNA interference, is activated when RNA molecules occur as double-stranded pairs in the cell. Double-stranded RNA activates biochemical machinery which degrades those mRNA molecules that carry a genetic code identical to that of the double-stranded RNA. When such mRNA molecules disappear, the corresponding gene is silenced and no protein of the encoded type is made.
RNA interference occurs in plants, animals, and humans. It is of great importance for the regulation of gene expression, participates in defense against viral infections, and keeps jumping genes under control. RNA interference is already being widely used in basic science as a method to study the function of genes and it may lead to novel therapies in the future.
The flow of information in the cell: from DNA via mRNA to protein
The genetic code in DNA determines how proteins are built. The instructions contained in the DNA are copied to mRNA and subsequently used to synthesize proteins (Fig 1). This flow of genetic information from DNA via mRNA to protein has been termed the central dogma of molecular biology by the British Nobel Laureate Francis Crick. Proteins are involved in all processes of life, for instance as enzymes digesting our food, receptors receiving signals in the brain, and as antibodies defending us against bacteria.
Our genome consists of approximately 30,000 genes. However, only a fraction of them are used in each cell. Which genes are expressed (i.e. govern the synthesis of new proteins) is controlled by the machinery that copies DNA to mRNA in a process called transcription. It, in turn, can be modulated by various factors. The fundamental principles for the regulation of gene expression were identified more than 40 years ago by the French Nobel Laureates François Jacob and Jacques Monod. Today, we know that similar principles operate throughout evolution, from bacteria to humans. They also form the basis for gene technology, in which a DNA sequence is introduced into a cell to produce new protein.
Around 1990, molecular biologists obtained a number of unexpected results that were difficult to explain. The most striking effects were observed by plant biologists who were trying to increase the colour intensity of the petals in petunias by introducing a gene inducing the formation of red pigment in the flowers. But instead of intensifying the colour, this treatment led to a complete loss of colour and the petals turned white! The mechanism causing these effects remained enigmatic until Fire and Mello made the discovery for which they receive this year's Nobel Prize.
The discovery of RNA interference
Andrew Fire and Craig Mello were investigating how gene expression is regulated in the nematode worm Caenorhabditis elegans (Fig. 2). Injecting mRNA molecules encoding a muscle protein led to no changes in the behaviour of the worms. The genetic code in mRNA is described as being the 'sense' sequence, and injecting 'antisense' RNA, which can pair with the mRNA, also had no effect. But when Fire and Mello injected sense and antisense RNA together, they observed that the worms displayed peculiar, twitching movements. Similar movements were seen in worms that completely lacked a functioning gene for the muscle protein. What had happened?
When sense and antisense RNA molecules meet, they bind to each other and form double-stranded RNA. Could it be that such a double-stranded RNA molecule silences the gene carrying the same code as this particular RNA? Fire and Mello tested this hypothesis by injecting double-stranded RNA molecules containing the genetic codes for several other worm proteins. In every experiment, injection of double-stranded RNA carrying a genetic code led to silencing of the gene containing that particular code. The protein encoded by that gene was no longer formed.
After a series of simple but elegant experiments, Fire and Mello deduced that double-stranded RNA can silence genes, that this RNA interference is specific for the gene whose code matches that of the injected RNA molecule, and that RNA interference can spread between cells and even be inherited. It was enough to inject tiny amounts of double-stranded RNA to achieve an effect, and Fire and Mello therefore proposed that RNA interference (now commonly abbreviated to RNAi) is a catalytic process.
Fire and Mello published their findings in the journal Nature on February 19, 1998. Their discovery clarified many confusing and contradictory experimental observations and revealed a natural mechanism for controlling the flow of genetic information. This heralded the start of a new research field.
The RNA interference machinery is unraveled
The components of the RNAi machinery were identified during the following years (Fig 3). Double-stranded RNA binds to a protein complex, Dicer, which cleaves it into fragments. Another protein complex, RISC, binds these fragments. One of the RNA strands is eliminated but the other remains bound to the RISC complex and serves as a probe to detect mRNA molecules. When an mRNA molecule can pair with the RNA fragment on RISC, it is bound to the RISC complex, cleaved and degraded. The gene served by this particular mRNA has been silenced.
RNA interference – a defense against viruses and jumping genes
RNA interference is important in the defense against viruses, particularly in lower organisms. Many viruses have a genetic code that contains double-stranded RNA. When such a virus infects a cell, it injects its RNA molecule, which immediately binds to Dicer (Fig 4A). The RISC complex is activated, viral RNA is degraded, and the cell survives the infection. In addition to this defense, higher organisms such as man have developed an efficient immune defense involving antibodies, killer cells, and interferons.
Jumping genes, also known as transposons, are DNA sequences that can move around in the genome. They are present in all organisms and can cause damage if they end up in the wrong place. Many transposons operate by copying their DNA to RNA, which is then reverse-transcribed back to DNA and inserted at another site in the genome. Part of this RNA molecule is often double-stranded and can be targeted by RNA interference. In this way, RNA interference protects the genome against transposons.
RNA interference regulates gene expression
RNA interference is used to regulate gene expression in the cells of humans as well as worms (Fig 4B). Hundreds of genes in our genome encode small RNA molecules called microRNAs. They contain pieces of the code of other genes. Such a microRNA molecule can form a double-stranded structure and activate the RNA interference machinery to block protein synthesis. The expression of that particular gene is silenced. We now understand that genetic regulation by microRNAs plays an important role in the development of the organism and the control of cellular functions.
New opportunities in biomedical research, gene technology and health care
RNA interference opens up exciting possibilities for use in gene technology. Double-stranded RNA molecules have been designed to activate the silencing of specific genes in humans, animals or plants (Fig 4C). Such silencing RNA molecules are introduced into the cell and activate the RNA interference machinery to break down mRNA with an identical code.
This method has already become an important research tool in biology and biomedicine. In the future, it is hoped that it will be used in many disciplines including clinical medicine and agriculture. Several recent publications show successful gene silencing in human cells and experimental animals. For instance, a gene causing high blood cholesterol levels was recently shown to be silenced by treating animals with silencing RNA. Plans are underway to develop silencing RNA as a treatment for virus infections, cardiovascular diseases, cancer, endocrine disorders and several other conditions.
Fire A., Xu S.Q., Montgomery M.K., Kostas S.A., Driver S.E., Mello C.C. Potent and specific genetic interference by double-stranded RNA in Caenorhabditis elegans. Nature 1998; 391:806-811.
Andrew Z. Fire, born 1959, US citizen, PhD in Biology 1983, Massachusetts Institute of Technology, Cambridge, MA, USA. Professor of Pathology and Genetics, Stanford University School of Medicine, Stanford, CA, USA.
Craig C. Mello, born 1960, US citizen, PhD in Biology 1990, Harvard University, Boston, MA, USA. Professor of Molecular Medicine and Howard Hughes Medical Institute Investigator, Program in Molecular Medicine, University of Massachusetts Medical School, Worcester, MA, USA.
3 October 2006
The Royal Swedish Academy of Sciences has decided to award the Nobel Prize in Physics for 2006 jointly to
John C. Mather
NASA Goddard Space Flight Center, Greenbelt, MD, USA,
George F. Smoot
University of California, Berkeley, CA, USA
"for their discovery of the blackbody form and anisotropy of the cosmic microwave background radiation".
Pictures of a newborn Universe
This year the Physics Prize is awarded for work that looks back into the infancy of the Universe and attempts to gain some understanding of the origin of galaxies and stars. It is based on measurements made with the help of the COBE satellite launched by NASA in 1989.
The COBE results provided increased support for the Big Bang scenario for the origin of the Universe, as this is the only scenario that predicts the kind of cosmic microwave background radiation measured by COBE. These measurements also marked the inception of cosmology as a precise science. It was not long before it was followed up, for instance by the WMAP satellite, which yielded even clearer images of the background radiation. Very soon the European Planck satellite will be launched in order to study the radiation in even greater detail.
According to the Big Bang scenario, the cosmic microwave background radiation is a relic of the earliest phase of the Universe. Immediately after the big bang itself, the Universe can be compared to a glowing "body emitting radiation in which the distribution across different wavelengths depends solely on its temperature. The shape of the spectrum of this kind of radiation has a special form known as blackbody radiation. When it was emitted the temperature of the Universe was almost 3,000 degrees Centigrade. Since then, according to the Big Bang scenario, the radiation has gradually cooled as the Universe has expanded. The background radiation we can measure today corresponds to a temperature that is barely 2.7 degrees above absolute zero. The Laureates were able to calculate this temperature thanks to the blackbody spectrum revealed by the COBE measurements.
COBE also had the task of seeking small variations of temperature in different directions (which is what the term 'anisotropy' refers to). Extremely small differences of this kind in the temperature of the cosmic background radiation – in the range of a hundred-thousandth of a degree – offer an important clue to how the galaxies came into being. The variations in temperature show us how the matter in the Universe began to "aggregate". This was necessary if the galaxies, stars and ultimately life like us were to be able to develop. Without this mechanism matter would have taken a completely different form, spread evenly throughout the Universe.
COBE was launched using its own rocket on 18 November 1989. The first results were received after nine minutes of observations: COBE had registered a perfect blackbody spectrum. When the curve was later shown at an astronomy conference the results received a standing ovation.
The success of COBE was the outcome of prodigious team work involving more than 1,000 researchers, engineers and other participants. John Mather coordinated the entire process and also had primary responsibility for the experiment that revealed the blackbody form of the microwave background radiation measured by COBE. George Smoot had main responsibility for measuring the small variations in the temperature of the radiation.
John C. Mather, 60, (US citizen). PhD in Physics in 1974 from the University of California at Berkeley, CA, USA. Senior Astrophysicist at NASA's Goddard Space Flight Center, Greenbelt, MD, USA.
George F. Smoot, born 1945 (61) in Yukon, FL, USA, (US citizen). PhD in Physics in 1970 from MIT, Cambridge, MA, USA. Professor of Physics at the University of California, Berkeley, CA, USA.
Prize amount: SEK 10 million to be shared equally between the Laureates
4 October 2006
The Royal Swedish Academy of Sciences has decided to award the Nobel Prize in Chemistry for 2006 to
Roger D. Kornberg
Stanford University, CA, USA
"for his studies of the molecular basis of eukaryotic transcription".
A family story about life
In order for our bodies to make use of the information stored in the genes, a copy must first be made and transferred to the outer parts of the cells. There it is used as an instruction for protein production – it is the proteins that in their turn actually construct the organism and its function. The copying process is called transcription. Roger Kornberg was the first to create an actual picture of how transcription works at a molecular level in the important group of organisms called eukaryotes (organisms whose cells have a well-defined nucleus). Mammals like ourselves are included in this group, as is ordinary yeast.
Transcription is necessary for all life. This makes the detailed description of the mechanism that Roger Kornberg provides exactly the kind of "most important chemical discovery" referred to by Alfred Nobel in his will.
If transcription stops, genetic information is no longer transferred into the different parts of the body. Since these are then no longer renewed, the organism dies within a few days. This is what happens in cases of poisoning by certain toadstools, like the death cap, since the toxin stops the transcription process. Understanding of how transcription works also has a fundamental medical importance. Disturbances in the transcription process are involved in many human illnesses such as cancer, heart disease and various kinds of inflammation.
The capacity of stem cells to develop into different types of specific cells with well-defined functions in different organs, is also linked to how the transcription is regulated. Understanding more about the transcription process is therefore important for the development of different therapeutic applications of stem cells.
Forty-seven years ago, the then twelve-year-old Roger Kornberg came to Stockholm to see his father, Arthur Kornberg, receive the Nobel Prize in Physiology or Medicine (1959) for his studies of how genetic information is transferred from one DNA-molecule to another. Kornberg senior had described how genetic information is transferred from a mother cell to its daughters. What Roger Kornberg himself has now done is to describe how the genetic information is copied from DNA into what is called messenger-RNA. The messenger-RNA carries the information out of the cell nucleus so that it can be used to construct the proteins.
Kornberg's contribution has culminated in his creation of detailed crystallographic pictures describing the transcription apparatus in full action in a eukaryotic cell. In his pictures (all of them created since 2000) we can see the new RNA-strand gradually developing, as well as the role of several other molecules necessary for the transcription process. The pictures are so detailed that separate atoms can be distinguished and this makes it possible to understand the mechanisms of transcription and how it is regulated.
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Joined: 06 Jul 2005
Location: Angel C. de Dios
|Posted: Wed Oct 10, 2007 2:12 pm Post subject: Nobel Prizes - 2007
8 October 2007
The Nobel Assembly at Karolinska Institutet has today decided to award
The Nobel Prize in Physiology or Medicine for 2007 jointly to
Mario R. Capecchi, Martin J. Evans and Oliver Smithies
for their discoveries of "principles for introducing specific gene modifications in mice by the use of embryonic stem cells"
This year's Nobel Laureates have made a series of ground-breaking discoveries concerning embryonic stem cells and DNA recombination in mammals. Their discoveries led to the creation of an immensely powerful technology referred to as gene targeting in mice. It is now being applied to virtually all areas of biomedicine – from basic research to the development of new therapies.
Gene targeting is often used to inactivate single genes. Such gene "knockout" experiments have elucidated the roles of numerous genes in embryonic development, adult physiology, aging and disease. To date, more than ten thousand mouse genes (approximately half of the genes in the mammalian genome) have been knocked out. Ongoing international efforts will make "knockout mice" for all genes available within the near future.
With gene targeting it is now possible to produce almost any type of DNA modification in the mouse genome, allowing scientists to establish the roles of individual genes in health and disease. Gene targeting has already produced more than five hundred different mouse models of human disorders, including cardiovascular and neuro-degenerative diseases, diabetes and cancer.
Modification of genes by homologous recombination
Information about the development and function of our bodies throughout life is carried within the DNA. Our DNA is packaged in chromosomes, which occur in pairs – one inherited from the father and one from the mother. Exchange of DNA sequences within such chromosome pairs increases genetic variation in the population and occurs by a process called homologous recombination. This process is conserved throughout evolution and was demonstrated in bacteria more than 50 years ago by the 1958 Nobel Laureate Joshua Lederberg.
Mario Capecchi and Oliver Smithies both had the vision that homologous recombination could be used to specifically modify genes in mammalian cells and they worked consistently towards this goal.
Capecchi demonstrated that homologous recombination could take place between introduced DNA and the chromosomes in mammalian cells. He showed that defective genes could be repaired by homologous recombination with the incoming DNA. Smithies initially tried to repair mutated genes in human cells. He thought that certain inherited blood diseases could be treated by correcting the disease-causing mutations in bone marrow stem cells. In these attempts Smithies discovered that endogenous genes could be targeted irrespective of their activity. This suggested that all genes may be accessible to modification by homologous recombination.
Embryonic stem cells – vehicles to the mouse germ line
The cell types initially studied by Capecchi and Smithies could not be used to create gene-targeted animals. This required another type of cell, one which could give rise to germ cells. Only then could the DNA modifications be inherited.
Martin Evans had worked with mouse embryonal carcinoma (EC) cells, which although they came from tumors could give rise to almost any cell type. He had the vision to use EC cells as vehicles to introduce genetic material into the mouse germ line. His attempts were initially unsuccessful because EC cells carried abnormal chromosomes and could not therefore contribute to germ cell formation. Looking for alternatives Evans discovered that chromosomally normal cell cultures could be established directly from early mouse embryos. These cells are now referred to as embryonic stem (ES) cells.
The next step was to show that ES cells could contribute to the germ line (see Figure). Embryos from one mouse strain were injected with ES cells from another mouse strain. These mosaic embryos (i.e. composed of cells from both strains) were then carried to term by surrogate mothers. The mosaic offspring was subsequently mated, and the presence of ES cell-derived genes detected in the pups. These genes would now be inherited according to Mendel’s laws.
Evans now began to modify the ES cells genetically and for this purpose chose retroviruses, which integrate their genes into the chromosomes. He demonstrated transfer of such retroviral DNA from ES cells, through mosaic mice, into the mouse germ line. Evans had used the ES cells to generate mice that carried new genetic material.
Two ideas come together – homologous recombination in ES cells
By 1986 all the pieces were at hand to begin generating the first gene targeted ES cells. Capecchi and Smithies had demonstrated that genes could be targeted by homologous recombination in cultured cells, and Evans had contributed the necessary vehicle to the mouse germ line – the ES-cells. The next step was to combine the two.
For their initial experiments both Smithies and Capecchi chose a gene (hprt) that was easily identified. This gene is involved in a rare inherited human disease (Lesch-Nyhan syndrome). Capecchi refined the strategies for targeting genes and developed a new method (positive-negative selection, see Figure) that could be generally applied.
Birth of the knockout mouse – the beginning of a new era in genetics
The first reports in which homologous recombination in ES cells was used to generate gene-targeted mice were published in 1989. Since then, the number of reported knockout mouse strains has risen exponentially. Gene targeting has developed into a highly versatile technology. It is now possible to introduce mutations that can be activated at specific time points, or in specific cells or organs, both during development and in the adult animal.
Gene targeting is used to study health and disease
Almost every aspect of mammalian physiology can be studied by gene targeting. We have consequently witnessed an explosion of research activities applying the technology. Gene targeting has now been used by so many research groups and in so many contexts that it is impossible to make a brief summary of the results. Some of the later contributions of this year's Nobel Laureates are presented below.
Gene targeting has helped us understand the roles of many hundreds of genes in mammalian fetal development. Capecchis research has uncovered the roles of genes involved in mammalian organ development and in the establishment of the body plan. His work has shed light on the causes of several human inborn malformations.
Evans applied gene targeting to develop mouse models for human diseases. He developed several models for the inherited human disease cystic fibrosis and has used these models to study disease mechanisms and to test the effects of gene therapy.
Smithies also used gene targeting to develop mouse models for inherited diseases such as cystic fibrosis and the blood disease thalassemia. He has also developed numerous mouse models for common human diseases such as hypertension and atherosclerosis.
In summary, gene targeting in mice has pervaded all fields of biomedicine. Its impact on the understanding of gene function and its benefits to mankind will continue to increase over many years to come.
Mario R. Capecchi, born 1937 in Italy, US citizen, PhD in Biophysics 1967, Harvard University, Cambridge, MA, USA. Howard Hughes Medical Institute Investigator and Distinguished Professor of Human Genetics and Biology at the University of Utah, Salt Lake City, UT, USA.
Sir Martin J. Evans, born 1941 in Great Britain, British citizen, PhD in Anatomy and Embryology 1969, University College, London, UK. Director of the School of Biosciences and Professor of Mammalian Genetics, Cardiff University, UK.
Oliver Smithies, born 1925 in Great Britain, US citizen, PhD in Biochemistry 1951, Oxford University, UK. Excellence Professor of Pathology and Laboratory Medicine, University of North Carolina at Chapel Hill, NC, USA.
9 October 2007
The Royal Swedish Academy of Sciences has decided to award the Nobel Prize in Physics for 2007 jointly to
Unité Mixte de Physique CNRS/THALES, Université Paris-Sud, Orsay, France,
Forschungszentrum Jülich, Germany,
"for the discovery of Giant Magnetoresistance".
Nanotechnology gives sensitive read-out heads for compact hard disks
This year's physics prize is awarded for the technology that is used to read data on hard disks. It is thanks to this technology that it has been possible to miniaturize hard disks so radically in recent years. Sensitive read-out heads are needed to be able to read data from the compact hard disks used in laptops and some music players, for instance.
In 1988 the Frenchman Albert Fert and the German Peter Grünberg each independently discovered a totally new physical effect – Giant Magnetoresistance or GMR. Very weak magnetic changes give rise to major differences in electrical resistance in a GMR system. A system of this kind is the perfect tool for reading data from hard disks when information registered magnetically has to be converted to electric current. Soon researchers and engineers began work to enable use of the effect in read-out heads. In 1997 the first read-out head based on the GMR effect was launched and this soon became the standard technology. Even the most recent read-out techniques of today are further developments of GMR.
A hard disk stores information, such as music, in the form of microscopically small areas magnetized in different directions. The information is retrieved by a read-out head that scans the disk and registers the magnetic changes. The smaller and more compact the hard disk, the smaller and weaker the individual magnetic areas. More sensitive read-out heads are therefore required if information has to be packed more densely on a hard disk. A read-out head based on the GMR effect can convert very small magnetic changes into differences in electrical resistance and there-fore into changes in the current emitted by the read-out head. The current is the signal from the read-out head and its different strengths represent ones and zeros.
The GMR effect was discovered thanks to new techniques developed during the 1970s to produce very thin layers of different materials. If GMR is to work, structures consisting of layers that are only a few atoms thick have to be produced. For this reason GMR can also be considered one of the first real applications of the promising field of nanotechnology.
10 October 2007
The Royal Swedish Academy of Sciences has decided to award the Nobel Prize in Chemistry for 2007 to
Fritz-Haber-Institut der Max-Planck-Gesellschaft, Berlin, Germany
"for his studies of chemical processes on solid surfaces".
Modern surface chemistry – fuel cells, artificial fertilizers and clean exhaust
The Nobel Prize in Chemistry for 2007 is awarded for groundbreaking studies in surface chemistry. This science is important for the chemical industry and can help us to understand such varied processes as why iron rusts, how fuel cells function and how the catalysts in our cars work. Chemical reactions on catalytic surfaces play a vital role in many industrial operations, such as the production of artificial fertilizers. Surface chemistry can even explain the destruction of the ozone layer, as vital steps in the reaction actually take place on the surfaces of small crystals of ice in the stratosphere. The semiconductor industry is yet another area that depends on knowledge of surface chemistry.
It was thanks to processes developed in the semiconductor industry that the modern science of surface chemistry began to emerge in the 1960s. Gerhard Ertl was one of the first to see the potential of these new techniques. Step by step he has created a methodology for surface chemistry by demonstrating how different experimental procedures can be used to provide a complete picture of a surface reaction. This science requires advanced high-vacuum experimental equipment as the aim is to observe how individual layers of atoms and molecules behave on the extremely pure surface of a metal, for instance. It must therefore be possible to determine exactly which element is admitted to the system. Contamination could jeopardize all the measurements. Acquiring a complete picture of the reaction requires great precision and a combination of many different experimental techniques.
Gerhard Ertl has founded an experimental school of thought by showing how reliable results can be attained in this difficult area of research. His insights have provided the scientific basis of modern surface chemistry: his method-ology is used in both academic research and the indust-rial development of chemical processes. The approach developed by Ertl is based not least on his studies of the Haber-Bosch process, in which nitrogen is extracted from the air for inclusion in artificial fertilizers. This reaction, which functions using an iron surface as its catalyst, has enormous economic significance because the availability of nitrogen for growing plants is often restricted. Ertl has also studied the oxidation of carbon monoxide on platinum, a reaction that takes place in the catalyst of cars to clean exhaust emissions.
Joined: 06 Jul 2005
Location: Angel C. de Dios
|Posted: Wed Oct 08, 2008 5:57 am Post subject: Nobel Prize 2008
|6 October 2008
The Nobel Assembly at Karolinska Institutet has today decided to award
The Nobel Prize in Physiology or Medicine for 2008 with one half to
Harald zur Hausen
for his discovery of "human papilloma viruses causing cervical cancer"
and the other half jointly to
Françoise Barré-Sinoussi and Luc Montagnier
for their discovery of "human immunodeficiency virus"
This year's Nobel Prize awards discoveries of two viruses causing severe human diseases.
Harald zur Hausen went against current dogma and postulated that oncogenic human papilloma virus (HPV) caused cervical cancer, the second most common cancer among women. He realized that HPV-DNA could exist in a non-productive state in the tumours, and should be detectable by specific searches for viral DNA. He found HPV to be a heterogeneous family of viruses. Only some HPV types cause cancer. His discovery has led to characterization of the natural history of HPV infection, an understanding of mechanisms of HPV-induced carcinogenesis and the development of prophylactic vaccines against HPV acquisition.
Françoise Barré-Sinoussi and Luc Montagnier discovered human immunodeficiency virus (HIV). Virus production was identified in lymphocytes from patients with enlarged lymph nodes in early stages of acquired immunodeficiency, and in blood from patients with late stage disease. They characterized this retrovirus as the first known human lentivirus based on its morphological, biochemical and immunological properties. HIV impaired the immune system because of massive virus replication and cell damage to lymphocytes. The discovery was one prerequisite for the current understanding of the biology of the disease and its antiretroviral treatment.
Discovery of human papilloma virus causing cervical cancer
Against the prevailing view during the 1970s, Harald zur Hausen postulated a role for human papilloma virus (HPV) in cervical cancer. He assumed that the tumour cells, if they contained an oncogenic virus, should harbour viral DNA integrated into their genomes. The HPV genes promoting cell proliferation should therefore be detectable by specifically searching tumour cells for such viral DNA. Harald zur Hausen pursued this idea for over 10 years by searching for different HPV types, a search made difficult by the fact that only parts of the viral DNA were integrated into the host genome. He found novel HPV-DNA in cervix cancer biopsies, and thus discovered the new, tumourigenic HPV16 type in 1983. In 1984, he cloned HPV16 and 18 from patients with cervical cancer. The HPV types 16 and 18 were consistently found in about 70% of cervical cancer biopsies throughout the world.
Importance of the HPV discovery
The global public health burden attributable to human papilloma viruses is considerable. More than 5% of all cancers worldwide are caused by persistent infection with this virus. Infection by the human papilloma virus is the most common sexually transmitted agent, afflicting 50-80% of the population. Of the more than 100 HPV types known, about 40 infect the genital tract, and 15 of these put women at high risk for cervical cancer. In addition, HPV is found in some vulval, penile, oral and other cancers. Human papilloma virus can be detected in 99.7% of women with histologically confirmed cervical cancer, affecting some 500,000 women per year.
Harald zur Hausen demonstrated novel properties of HPV that have led to an understanding of mechanisms for papilloma virus-induced carcinogenesis and the predisposing factors for viral persistence and cellular transformation. He made HPV16 and 18 available to the scientific community. Vaccines were ultimately developed that provide ≥95 % protection from infection by the high risk HPV16 and 18 types. The vaccines may also reduce the need for surgery and the global burden of cervical cancer.
Discovery of HIV
Following medical reports of a novel immunodeficiency syndrome in 1981, the search for a causative agent was on. Françoise Barré-Sinoussi and Luc Montagnier isolated and cultured lymph node cells from patients that had swollen lymph nodes characteristic of the early stage of acquired immune deficiency. They detected activity of the retroviral enzyme reverse transcriptase, a direct sign of retrovirus replication. They also found retroviral particles budding from the infected cells. Isolated virus infected and killed lymphocytes from both diseased and healthy donors, and reacted with antibodies from infected patients. In contrast to previously characterized human oncogenic retroviruses, the novel retrovirus they had discovered, now known as human immunodeficiency virus (HIV), did not induce uncontrolled cell growth. Instead, the virus required cell activation for replication and mediated cell fusion of T lymphocytes. This partly explained how HIV impairs the immune system since the T cells are essential for immune defence. By 1984, Barré-Sinoussi and Montagnier had obtained several isolates of the novel human retrovirus, which they identified as a lentivirus, from sexually infected individuals, haemophiliacs, mother to infant transmissions and transfused patients. The significance of their achievements should be viewed in the context of a global ubiquitous epidemic affecting close to 1% of the population.
Importance of the HIV discovery
Soon after the discovery of the virus, several groups contributed to the definitive demonstration of HIV as the cause of acquired human immunodeficiency syndrome (AIDS). Barré-Sinoussi and Montagnier's discovery made rapid cloning of the HIV-1 genome possible. This has allowed identification of important details in its replication cycle and how the virus interacts with its host. Furthermore, it led to development of methods to diagnose infected patients and to screen blood
products, which has limited the spread of the pandemic. The unprecedented development of several classes of new antiviral drugs is also a result of knowledge of the details of the viral replication cycle. The combination of prevention and treatment has substantially decreased spread of the disease and dramatically increased life expectancy among treated patients. The cloning of HIV enabled studies of its origin and evolution. The virus was probably passed to humans from chimpanzees in West Africa early in the 20th century, but it is still unclear why the epidemic spread so dramatically from 1970 and onwards.
Identification of virus−host interactions has provided information on how HIV evades the host’s immune system by impairing lymphocyte function, by constantly changing and by hiding its genome in the host lymphocyte DNA, making its eradication in the infected host difficult even after long-term antiviral treatment. Extensive knowledge about these unique viral host interactions has, however, generated results that can provide ideas for future vaccine development as well as for therapeutic approaches targeting viral latency.
HIV has generated a novel pandemic. Never before has science and medicine been so quick to discover, identify the origin and provide treatment for a new disease entity. Successful anti-retroviral therapy results in life expectancies for persons with HIV infection now reaching levels similar to those of uninfected people.
Harald zur Hausen, born 1936 in Germany, German citizen, MD at University of Düsseldorf, Germany. Professor emeritus and former Chairman and Scientific Director, German Cancer Research Centre, Heidelberg, Germany.
Françoise Barré-Sinoussi, born 1947 in France, French citizen, PhD in virology, Institut Pasteur, Garches, France. Professor and Director, Regulation of Retroviral Infections Unit, Virology Department, Institut Pasteur, Paris, France.
Luc Montagnier, born 1932 in France, French citizen, PhD in virology, University of Paris, Paris, France. Professor emeritus and Director, World Foundation for AIDS Research and Prevention, Paris, France.
7 October 2008
The Royal Swedish Academy of Sciences has decided to award the Nobel Prize in Physics for 2008 with one half to
Enrico Fermi Institute, University of Chicago, IL, USA
"for the discovery of the mechanism of spontaneous broken symmetry in subatomic physics"
and the other half jointly to
Makoto Kobayashi, High Energy Accelerator Research Organization (KEK), Tsukuba, Japan
Toshihide Maskawa,Yukawa Institute for Theoretical Physics (YITP), Kyoto University, Japan
"for the discovery of the origin of the broken symmetry which predicts the existence of at least three families of quarks in nature"
Passion for symmetry
The fact that our world does not behave perfectly symmetrically is due to deviations from symmetry at the microscopic level.
As early as 1960, Yoichiro Nambu formulated his mathematical description of spontaneous broken symmetry in elementary particle physics. Spontaneous broken symmetry conceals nature’s order under an apparently jumbled surface. It has proved to be extremely useful, and Nambu’s theories permeate the Standard Model of elementary particle physics. The Model unifies the smallest building blocks of all matter and three of nature’s four forces in one single theory.
The spontaneous broken symmetries that Nambu studied, differ from the broken symmetries described by Makoto Kobayashi and Toshihide Maskawa. These spontaneous occurrences seem to have existed in nature since the very beginning of the universe and came as a complete surprise when they first appeared in particle experiments in 1964. It is only in recent years that scientists have come to fully confirm the explanations that Kobayashi and Maskawa made in 1972. It is for this work that they are now awarded the Nobel Prize in Physics. They explained broken symmetry within the framework of the Standard Model, but required that the Model be extended to three families of quarks. These predicted, hypothetical new quarks have recently appeared in physics experiments. As late as 2001, the two particle detectors BaBar at Stanford, USA and Belle at Tsukuba, Japan, both detected broken symmetries independently of each other. The results were exactly as Kobayashi and Maskawa had predicted almost three decades earlier.
A hitherto unexplained broken symmetry of the same kind lies behind the very origin of the cosmos in the Big Bang some 14 billion years ago. If equal amounts of matter and antimatter were created, they ought to have annihilated each other. But this did not happen, there was a tiny deviation of one extra particle of matter for every 10 billion antimatter particles. It is this broken symmetry that seems to have caused our cosmos to survive. The question of how this exactly happened still remains unanswered. Perhaps the new particle accelerator LHC at CERN in Geneva will unravel some of the mysteries that continue to puzzle us.
Read more about this year's prize
Information for the Public
Scientific Background (pdf)
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Links and Further Reading
Yoichiro Nambu, US citizen. Born 1921 in Tokyo, Japan. D.Sc. 1952 at University of Tokyo, Japan. Harry Pratt Judson Distinguished Service Professor Emeritus at Enrico Fermi Institute, University of Chicago, IL, USA.
Makoto Kobayashi, Japanese citizen. Born 1944 in Nagoya, Japan. Ph.D. 1972 at Nagoya University, Japan. Professor Emeritus at High Energy Accelerator Research Organization (KEK), Tsukuba, Japan.
Toshihide Maskawa, Japanese citizen. Born 1940. Ph.D. 1967 at Nagoya University, Japan. Professor Emeritus at Yukawa Institute for Theoretical Physics (YITP), Kyoto University, Japan.
8 October 2008
The Royal Swedish Academy of Sciences has decided to award the Nobel Prize in Chemistry for 2008 jointly to
Osamu Shimomura, Marine Biological Laboratory (MBL), Woods Hole, MA, USA and Boston University Medical School, MA, USA,
Martin Chalfie, Columbia University, New York, NY, USA
Roger Y. Tsien, University of California, San Diego, La Jolla, CA, USA
"for the discovery and development of the green fluorescent protein, GFP".
Glowing proteins – a guiding star for biochemistry
The remarkable brightly glowing green fluorescent protein, GFP, was first observed in the beautiful jellyfish, Aequorea victoria in 1962. Since then, this protein has become one of the most important tools used in contemporary bioscience. With the aid of GFP, researchers have developed ways to watch processes that were previously invisible, such as the development of nerve cells in the brain or how cancer cells spread.
Tens of thousands of different proteins reside in a living organism, controlling important chemical processes in minute detail. If this protein machinery malfunctions, illness and disease often follow. That is why it has been imperative for bioscience to map the role of different proteins in the body.
This year's Nobel Prize in Chemistry rewards the initial discovery of GFP and a series of important developments which have led to its use as a tagging tool in bioscience. By using DNA technology, researchers can now connect GFP to other interesting, but otherwise invisible, proteins. This glowing marker allows them to watch the movements, positions and interactions of the tagged proteins.
Researchers can also follow the fate of various cells with the help of GFP: nerve cell damage during Alzheimer's disease or how insulin-producing beta cells are created in the pancreas of a growing embryo. In one spectacular experiment, researchers succeeded in tagging different nerve cells in the brain of a mouse with a kaleidoscope of colours.
The story behind the discovery of GFP is one with the three Nobel Prize Laureates in the leading roles:
Osamu Shimomura first isolated GFP from the jellyfish Aequorea victoria, which drifts with the currents off the west coast of North America. He discovered that this protein glowed bright green under ultraviolet light.
Martin Chalfie demonstrated the value of GFP as a luminous genetic tag for various biological phenomena. In one of his first experiments, he coloured six individual cells in the transparent roundworm Caenorhabditis elegans with the aid of GFP.
Roger Y. Tsien contributed to our general understanding of how GFP fluoresces. He also extended the colour palette beyond green allowing researchers to give various proteins and cells different colours. This enables scientists to follow several different biological processes at the same time.
Read more about this year's prize
Information for the Public
In order to read the text you need Acrobat Reader.
Links and Further Reading
Osamu Shimomura, Japanese citizen. Born 1928 in Kyoto, Japan. Ph.D. in organic chemistry 1960 from Nagoya University, Japan. Professor emeritus at Marine Biological Laboratory (MBL), Woods Hole, MA, USA and Boston University Medical School, MA, USA.
Martin Chalfie, US citizen. Born 1947, grew up in Chicago, IL, USA. Ph.D. in neurobiology 1977 from Harvard University. William R. Kenan, Jr. Professor of Biological Sciences at Columbia University, New York, NY, USA, since 1982.
Roger Y. Tsien, US citizen. Born 1952 in New York, NY, USA. Ph.D. in physiology 1977 from Cambridge University, UK. Professor at University of California, San Diego, La Jolla, CA, USA, since 1989.
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