Archive for the ‘Nobel Prize’ Category

John B. Gurdon and Shinya Yamanaka awarded the 2012 Nobel Prize in Physiology or Medicine

Monday, October 8th, 2012
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John B. Gurdon (left) and Shinya Yamanaka (right) awarded the 2012 Nobel Prize in Physiology or Medicine

John B. Gurdon (left) and Shinya Yamanaka (right) awarded the 2012 Nobel Prize in Physiology or Medicine

The Nobel Prize in Physiology or Medicine 2012 was awarded today, October 8, 2012, jointly to Sir John B. Gurdon (Gurdon Institute, Cambridge, United Kingdom) and Shinya Yamanaka ( Kyoto University, Kyoto, Japan, and Gladstone Institute, San Francisco, CA, USA) “for the discovery that mature cells can be reprogrammed to become pluripotent“. The Nobel Assembly at Karolinska Institutet (Stockholm, Sweden) decided to award The Nobel Prize in Physiology or Medicine 2012 jointly to John B. Gurdon and Shinya Yamanaka. According to the published Press Release: “The Nobel Prize recognizes two scientists who discovered that mature, specialised cells can be reprogrammed to become immature cells capable of developing into all tissues of the body. Their findings have revolutionised our understanding of how cells and organisms develop“. The International Society for Transgenic Technologies (ISTT) wishes to congratulate both excellent scientists for their outstanding achievements and the very much deserved Nobel Prize they have just been awarded.

John B. Gurdon demonstrated in 1962 that adult frogs could be obtained by the transplantation of nuclei from endoderm cells of Xenopus laevis donors ranging from late blastulae to swimming tadpoles.  In 1966, John B. Gurdon continued his studies on cellular reprogramming in frogs and reported that fertile adult male and female frogs, genetically marked as of solely donor origin, had been obtained from the transplantation of nuclei from intestinal epithelial cells of Xenopus laevis feeding larvae. In 1975, John B. Gurdon reported that tadpoles could be obtained from nuclei transplanted from keratinized skin cells of adult frogs. However, no adult frogs were obtained from nuclear transfer experiments involving adult somatic cells. As concluded by Gurdon and Byrne in 2003, these first series of results obtained by John B. Gurdon, “established the general principle that the process of cell differentiation does not necessarily require any stable change to the genetic constitution of a cell. Thus, cell differentiation depends on changes in the expression not content of the genome“. Similar principles had been envisaged and proposed, but could not be proved, in 1938 by the German embryologist Hans Spemann (awarded the 1935 Nobel Prize in Physiology or Medicine).

Forty years later, after the outstanding results obtained by John B. Gurdon, Shinya Yamanaka reported in 2006 the identification of  four transcription factors (Oct3/4, Sox2, c-Myc, and Klf4) capable of reprogramming any somatic cell into a cell with properties of a pluripotent stem cell, similar to embryonic stem (ES) cells. Those cells were named as inducible pluripotent stem cell (or iPS cells) and greatly revolutionized the regenerative medicine field and cellular reprogramming studies since then. Yamanaka’s experiment provided a totally innovative method to obtain human pluripotent stem cells, with great regenerative potential, without requiring the use of human embryos, an achievement that has been greatly acknowledged by members of the society who did not accept, according to their private beliefs, the previous use of human embryos to obtain pluripotent stem cells. John B. Gurdon and Shinya Yamanaka had already been awarded jointly the 2009 Albert Lasker Basic Medical Research Prize “for discoveries concerning nuclear reprogramming, the process that instructs specialized adult cells to form early stem cells — creating the potential to become any type of mature cell for experimental or therapeutic purposes“.

The history of nuclear transplantation and cellular reprogramming has been silently advancing since the beginning of last century, and progressed through a series of phenomenal milestones that were regularly achieved. Starting with the pioneer experiments and the vision of Hans Spemann (1938), then the first nuclear transfer success in frogs by Briggs and King (1952), of course the experiments carried out by John B. Gurdon in the 60′s and early 70′s, already mentioned, and also the studies by Marie DiBerardino (1967) on the effect of cell cycle in the nuclear transfer success, and other, more recent, describing the role of single transcription factor being able to change the fate of a cell (Harold Weintraub, 1987) or the direct reprogramming experiments, betweeen different cellular haematopoietic types, pioneered by Thomas Graf since 1990. However, in my opinion, the one single study that, for the first time, demonstrated that a nucleus from an adult terminally and fully differentiated somatic cell (i.e. a cell derived from mammary gland tissue) could give rise to a fertile normal adult, closing the circle of life, was the birth of Dolly, the sheep, obtained by Ian Wilmut and his collaborators from the Roslin Institute in 1996 and reported in a famous paper in Nature in February 1997.

Ian Wilmut and Dolly the sheep in 1997

Ian Wilmut and Dolly the sheep in 1997

The impact of Wilmut’s study on Biology, Biomedicine, Biotechnology and on the entire Society was phenomenal, tremendous (unfortunately not always positive, independent of him, with intense and never ending debates beyond science) and triggered many subsequent studies, including the use of human pluripotent stem cells, isolated by Thomson and Gearhart teams in 1998, and their potential in regenerative medicine, and eventually the work by Yamanaka and many other. The Nobel Assembly has limited this Nobel award to Gurdon and Yamanaka, who fully deserved the Nobel Prize, but, unfortunately, they did not include other scientists that were instrumental for the progress in reprogramming studies, particularly Ian Wilmut. Dolly’s experiment  is only referred briefly in the advance information provided to interested readers. After discussing this issue the whole day with many colleagues, I believe I speak on behalf of many by stating that a Nobel Prize awarded to Gurdon, Wilmut and Yamanaka, could have been a much better and balanced choice. Gurdon himself stated that he would have liked to share this Prize with Ian Wilmut.  But this is just wishful thinking and the reality is, as usual, different. Having said that, I want to congratulate once again John B. Gurdon and Shinya Yamanaka for this Nobel Prize.

On a final sad note, after all the excitement associated with this Nobel Award to reprogramming techniques, we have been informed of the sudden death of Keith H. Campbell, biologist (1954 – 2012), who passed away last Saturday, October 6, 2012. Keith H. Campbell was one of the main co-authors, together with Ian Wilmut, of Dolly’s Nature paper in 1997 (Viable offspring derived from fetal and adult mammalian cells. Wilmut I, Schnieke AE, McWhir J, Kind AJ, Campbell KH, Nature 1997 Feb 27;385(6619):810-3). Keith H. Campbell was currently working at the School of Biosciences, University of Nottingham, UK.

 

Penn Symposium in honor of Ralph L. Brinster, Aug 24-25, 2012

Monday, June 11th, 2012
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Penn Symposium in honor of Ralph L. Brinster, Aug 24-25, 2012

Penn Symposium in honor of Ralph L. Brinster, Aug 24-25, 2012

The University of Pennsylvania and the University of Pennsylvania School of Veterinary Medicine are organizing a two-day symposium (24-25 August 2012) in honor of Ralph L. Brinster, PhD, the Richard King Mellon Professor of Reproductive Physiology at Penn Vet. Dr Brinster, often regarded as the father of transgenesis, was awarded, in 2011, the prestigious National medal of Science for his life’s work to date, and the ISTT Prize at the TT2011 meeting in Florida for his outstanding contributions to the field of transgenic technologies.

This Symposium features talks by top scientists around the globe, including: Richard Behringer, Michael S. Brown (Nobel Prize in Physiology or Medicine 1985), Allan Bradley (our next ISTT Prize awarded scientist, at the TT2013 meeting, in China) , Ina Dobrinski, John Gurdon (awarded the 2009 Albert Lasker Basic Medical Research Prize), Robert Hammer (ISTT Member), Kathy High, Rudolf Jaenisch, Richard Palmiter, Janet Rossant, Hans Scholer, Richard Schultz, Takashi Shinohara, Jamie Thomson, Ken Zaret.

Space is limited, register for this symposium here.

 

Allan Bradley will be awarded the 9th ISTT Prize at the TT2013 meeting

Tuesday, January 31st, 2012
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Allan Bradley will be awarded the 9th ISTT Prize at the TT2013 meeting (Picture kindly provided by WTSI)

Allan Bradley will be awarded the 9th ISTT Prize at the TT2013 meeting (Picture kindly provided by WTSI)

The International Society for Transgenic Technologies (ISTT) is pleased to announce that Professor Allan Bradley, Director Emeritus of the Wellcome Trust Sanger Institute (WTSI), and leader of the Mouse Genomics Team at WTSI, will be awarded the next (9th) ISTT Prize for his outstanding contributions to the field of transgenic technologies. Professor Allan Bradley will receive the award at the next Transgenic Technology meeting (TT2013), which will be held in Guangzhou (PR China) on February 25-27, 2013. This award has been agreed upon by the ISTT Prize Committee, consisting of the ISTT President and Vice-President, the CEO of genOway, as the company generously sponsoring the award, and the previous ISTT Prize awardees.

In awarding this prize to Dr. Bradley, the ISTT Prize committee acknowledges his many fundamental contributions to the science and technology of manipulating the mouse genome. His pioneering mouse embryonic stem (ES) cell work in the 1980s, demonstrating germ-line transmission and the great potential of ES cells to generate mice carrying mutations in endogenous genes, established milestones in a field that saw the award of the 2007 Nobel Prize in Physiology or Medicine to Mario Capecchi, Martin Evans, and Oliver Smithies. Later, Dr. Bradley generated a number of broadly relevant knockout mouse models (for example p53, Rb, Wnt-1) that are still used regularly today. His subsequent research has developed new methods for the genetic analysis and genetic modification of mice (such as chromosome engineering and the functional genetic analysis of mouse chromosome 11). These developments have been instrumental for advancing mouse genetics studies and the use of mice to understand the human genome. Furthermore, his strong vision and leadership at the Wellcome Trust Sanger Institute, which he directed from 2000-2010, was key to creating the EUCOMM/KOMP (IKMC) initiative to systematically disrupt every gene in the mouse genome, resulting in a massive impact on the field of transgenic technologies.

Dr. Bradley received his BA, MA and PhD in Genetics from the University of Cambridge. His PhD studies in Martin Evans’ laboratory, completed in 1984, laid the foundation for making knockout mice.

In 1984 Allan Bradley and Liz Robertson demonstrated that ES cells could be transmitted through the germ-line of mice (Bradley et al. 1984, Nature) and two years later reported that ES cells could be used to generate mice with mutations in endogenous genes (Kuehn, Bradley et al. 1987, Nature).

In 1987, he took an appointment as Assistant Professor at Baylor College of Medicine, Houston, Texas. He was named as a Howard Hughes Medical Institute Investigator in 1993 and was promoted to full Professor in 1994. At Baylor, his laboratory played a seminal role in developing the methods, technology and tools for genetic manipulation in the mouse. As a result, mice can now be generated with changes as subtle as an alteration in a single nucleotide or as massive as the deletion, duplication or inversion of millions of base pairs with a technology now known as chromosome engineering (Ramirez-Solis et al. 1995, Nature). The Bradley laboratory used ES cell technology extensively, generating and analysing many of the first generation of mouse knockouts (McMahon & Bradley, 1990, Cell; Donehower et al. 1992, Nature; Lee et al. 1992, Nature; Jones et al. 1995, Nature; Sharan et al. 1997, Nature) while helping numerous other laboratories to utilize this technology. This work has provided key functional information for many genes with an emphasis on cancer, DNA repair and embryonic development. While at Baylor, Bradley created the Mouse Club, originally consisting of meetings among his, Phil Soriano’s, and Gerard Karsenty’s laboratories, with Richard Behringer’s lab joining later. The Mouse Club has since expanded and has been meeting for more than two decades, every Tuesday afternoon. Richard Behringer remembers: “I was always impressed that Allan would always attend the Mouse Club if he was in town. He put training of students and postdocs as a high priority.”  Many former colleagues and trainees from Allan Bradley’s lab have fond memories of his mentoring and support. Y. Eugene Yu says: “When tropical storm Allison flooded Houston and the Texas Medical Center in 2001, which killed 90,000 research animals, Allan flew in from UK immediately after the news broke. He personally led the effort in the devastated animal facility to rescue the remaining precious mouse strains, many of which were unique.”

In November 2000, Allan Bradley returned to the United Kingdom as Director of the Sanger Centre, now called the Wellcome Trust Sanger Institute (WTSI), shortly after the first draft of the human genome sequence was released. In 2002, he oversaw the publication of the mouse genome sequence.

His 10-year plan for the WTSI aimed to transform it from a centre that just sequences DNA to one that studies the biology of sequences. First focussing on creating the required physical infrastructure, then diversifying the institute’s research, his efforts have helped turn the WTSI into an international hub of science, with strong programs in human genetics, informatics, pathogen genetics, and model organisms. Among other projects in which the WTSI plays a leading role is the largest systematic gene knockout project ever attempted in ES cells, funded by the European Union (EUCOMM) and National Institutes of Health (KOMP), and now coordinated by the International Knockout Mouse Consortium (IKMC) (Skarnes et al., 2011 Nature; Prosser et al., 2011 Nature Biotechnology).

Under Allan Bradley’s direction, the WTSI has become a reference centre for outreach activities, offering teaching resources, welcoming students for work placements and promoting school visits that broadcast scientific achievements to the general society; in his words “inspiring the next generation of scientists.”

Allan Bradley has also been very active in commercializing the numerous novel methods his laboratory has developed over the years to engineer the genomes of mice. He is registered as a co-inventor on more than 25 patents and is a founder and Chief Scientific Officer of Kymab Limited. He also co-founded several companies, including GenPharm International and Lexicon Genetics in 1995. Using proprietary gene trapping and gene targeting technologies, Lexicon Genetics created the world’s first large repository of genetically modified mouse embryonic stem cells, known as OmniBank, and established a large-scale program to discover the physiological and behavioural functions of mammalian genes, with almost 5,000 gene knockouts studied in mice. This effort is now being extended to the entire mouse genome in a public domain project coordinated by the International Mouse Phenotyping Consortium (IMPC) and funded by NIH in the USA and other funding bodies internatioanlly.

In July 2002 Allan Bradley was elected a Fellow of the Royal Society. He has authored over 260 scientific articles and book chapters and currently runs an active research group that is exploring gene function on a large scale and continues to develop new tools and technologies for mouse genetics research.

The ISTT Prize: a piece of art created by Bela Rozsnyay

The ISTT Prize: a piece of art created by Bela Rozsnyay

Allan Bradley will join in 2013, at the TT2013 meeting, the following group of outstanding scientists previously awarded the ISTT Prize:

Ralph L. Brinster, ISTT Prize, TT2011, Florida, USA, Prize Announcement, Award ceremony
A. Francis Stewart, ISTT Prize, TT2010, Berlin, Germany, Prize Announcement, Award ceremony
Brigid Hogan, ISTT Prize, TT2008, Toronto, Canada, Prize Announcement, Award ceremony
Charles Babinet, TT2007, Brisbane, Australia, Obituary (1939-2008)
Andras Nagy, TT2005, Barcelona, Spain
Qi Zhou, TT2004, Uppsala, Sweden
Kenneth C. McCreath, TT2002, Munich, Germany
Teruhiko Wakayama, TT2001, Stockholm, Sweden

Download this Award Announcement as a ISTT Press Release Document

Shinya Yamanaka receives the 2010 Foundation BBVA Frontiers of Knowledge Award in Biomedicine

Saturday, February 5th, 2011
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BBVA Foundation Frontiers of Knowledge Awards

BBVA Foundation Frontiers of Knowledge Awards

Shinya Yamanaka

Shinya Yamanaka

The 4th Edition of the Foundation BBVA Frontiers of Knowledge Awards in Biomedicine goes to Japanese scientist Shinya Yamanaka for “showing that it is possible to reprogram differentiated cells back into a state that is characteristic of pluripotent cells“, according to the communication prepared by the Jury of these Awards, in the press release published today, February 4, 2001, at the Foundation BBVA web site.

Shinya Yamanaka,  Director of the Center for iPS Cell Research and Application at Kyoto University (Japan), and professor in the Institute for Frontier Medical Sciences at the same institution, demonstrated in 2006, in a seminal paper published in the scientific journal Cell, that only four genes were required to induce the conversion of fibroblast into cells with properties of pluripotent stem cells, thus coining the concept of the “induced pluripotent stem cells“, or iPS cells. This is one of the most outstanding, innovative and original experiments ever reported in Biology, that triggered a true revolution in Cell and Developmental Biology, where many laboratories around the world were able to quickly reproduce and, in some cases, improve the initial protocol devised by Shinya Yamanaka in Japan. The discovery of the iPS cells, showing that the idea of reversing the fate of already specialized cells was indeed possible,  is a breakthrough comparable to the first successful nuclear transfer and reprogramming experiment achieved in mammals, with the cloning of Dolly, the sheep, born in 1996 and reported one year later, in a milestone paper by Ian Wilmut and co-workers, published in Nature. Shinya Yamanaka explained that “From their work I learned that we should be able to convert somatic cells back into their embryonic state. That is what inspired me to start my project”.

The iPS cells, first envisaged by Yamanaka, have an  immense potential for regenerative medicine and studies of disease and development. Most recent experiments, published earlier this week, show that the genomic methylation status of iPS cells is surprisingly different from that of pluripotent embryo stem (ES) cells (Lister et al. Nature 2011, February 2), and that this aberrant methylation pattern is maintained in those differentiated cell types derived from the iPS cells. Further experiments would be required to assess the relevance of these new findings regarding the potential applications in Biomedicine of iPS cells. However, the central contribution of Shinya Yamanaka and the beauty and simplicity of his pioneer experiments will remain for ever.

The Foundation BBVA Frontiers of Knowledge Awards are associated with a 400.000 € (~545,000 USD) Prize. The 2010 Prize Jury in Biomedicine was chaired by Werner Arber, (Nobel Prize in Medicine in 1978, Biozentrum, University of Basel, Switzerland) and included, as remaining members: Robin Lovell-Badge (MRC National Institute for Medical Research, UK); Dario Alessi (College of Life Sciences, Dundee University, UK); Mariano Barbacid (Spanish National Cancer Research Center-CNIO); José Baselga (Massachusetts General Hospital and Harvard Medical School, USA); Angelika Schnieke, (Department of Animal Science, Technical University of Munich, Germany); and Bruce Whitelaw (The Roslin Institute, Edinburgh, UK). Both Robin Lovell-Badge and Bruce Whitelaw are members of the ISTT.

Robert G. Edwards awarded the Nobel Prize of Medicine 2010 for the development of in vitro fertilization

Monday, October 4th, 2010
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Robert G. Edwards - Biographical. Nobelprize.org. 4 Oct 2010

"Robert G. Edwards - Biographical". Nobelprize.org. 4 Oct 2010

Robert G. Edwards (Manchester, UK, 1925), from the University of Cambridge, Cambridge, UK, has been awarded today, October 4, the 2010 Nobel Prize in Physiology or Medicine, “for the development of in vitro fertilization“. Robert G. Edwards and Patrick C. Steptoe (1913-1988) performed in 1977 the first successful in vitro fertilization (IVF) in humans, resulting in the birth of the first IVF baby, Louise Joy Brown, in 1978. Since then, 32 years later, more than 4 million children have been born thanks to this IVF technique. IVF was not only developed in humans, thanks to Robert G.Edward’ s pioneer experiments, started in the late 50′s, but in rodents too. Several scientists, including  David Whittingham, managed to obtain mice by IVF in the early 70′s. IVF is a powerful technique for the treatment of human infertility and also a tool for producing synchronized embryos of high quality in many species, such as mice. IVF methods are routinely applied in many transgenic units for producing embryos that are suitable for cryopreservation. Subsequent technical developments in reproductive biology, such as ICSI (intracytoplasmic sperm injection), have enriched the toolbox available to gynecologists and scientists in general for obtaining viable mammalian embryos.

Patents in ES cell work

Wednesday, April 16th, 2008
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mouse ES cells

Recently, at the tg-list, it was discussed the issue of patents that apply in the standard ES cell work. Those patents include the usual positive-negative selection and the use of isogenic DNA. Of course, there are many more with modifications or alternative methodologies but I believe these two methodology are still the basic ones. 

According to the United States Patent and Trademark Office, these are the patents alive and active:

Positive-negative selection methods and vectors
Capecchi; Mario R., Thomas; Kirk R.
US Patent: 5,464,764
Issued: November 7, 1995
Filed: February 4, 1993
Assignee: University of Utah Research Foundation (Salt Lake City, UT)

Cells and non-human organisms containing predetermined genomic modifications and positive-negative selection methods and vectors for making same
Capecchi; Mario R., Thomas; Kirk R.
US Patent: 5,487,992
Issued: January 30, 1996
Filed: June 28, 1993
Assignee: University of Utah Research Foundation (Salt Lake City, UT)

Cells and non-human organisms containing predetermined genomic modifications and positive-negative selection methods and vectors for making same
Capecchi; Mario R., Thomas; Kirk R.
US Patent: 5,627,059
Issued: May 6, 1997
Filed: June 5, 1995
Assignee: University of Utah (Salt Lake City, UT)

Cells and non-human organisms containing predetermined genomic modifications and positive-negative selection methods and vectors for making same
Capecchi; Mario R., Thomas; Kirk R.
US Patent: 5,631,153
Issued: May 20, 1997
Filed: June 5, 1995
Assignee: University of Utah (Salt Lake City, UT)

Cells and non-human organisms containing predetermined genomic modifications and positive-negative selection methods and vectors for making same
Capecchi; Mario R., Thomas; Kirk R.
US Patent: 6,204,061
Issued: March 20, 2001
Filed: January 9, 1997
Assignee: University of Utah Research Foundation (Salt Lake City, UT)

Cells and non-human organisms containing predetermined genomic modifications and positive-negative selection methods and vectors for making same
Capecchi; Mario R., Thomas; Kirk R.
US Patent: 6,204,061
Issued: February 10, 2004
Filed: November 28, 2000
Assignee: University of Utah Research Foundation (Salt Lake City, UT)

Gene targeting in animal cells using isogenic DNA constructs
Berns; Anton, Robanus Maandag; Els, te Riele; Hein
US Patent: 5,789,215
Issued: August 4, 1998
Filed: August 7, 1997
Assignee: GenPharm International (San Jose, CA)

High efficiency gene targeting in mouse embryonic stem cells
Berns; Anton, Robanus Maandag; Els, te Riele; Hein
US Patent: 6,653,113
Issued: November 25, 2003
Filed: February 19, 1999
Assignee: Genpharm International, Inc. (Mountain View, CA)

 

The First Brazilian Symposium on Transgenic Technology (1st BSTT): a most successful event

Friday, March 14th, 2008
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Prof. Oliver Smithies and Prof. Joao Bosco Pesquero

The first Brazilian Symposium on Transgenic Technology (1st BSTT) was held in Sao Paulo on March 10-12, 2008. More than 300 participants attended this most successful and interesting event, organized by Prof. Dr. Joao Bosco Pesquero, Dra. Heloisa Allegro Baptista and their colleagues from the Universidade Federale de Sao Paulo (UNIFESP). This symposium was supported and co-sponsored by the International Society for Transgenic Technologies.

This meeting included the remarkable participation of Prof. Dr. Oliver Smithies, 2007 Nobel Prize in Physiology or Medicine for “for their discoveries of principles for introducing specific gene modifications in mice by the use of embryonic stem cells“, along with several international experts within the field of animal transgenesis, who shared their results with their Brazilian colleagues, resulting in a comprehensive scientific program that covered the majority of aspects in animal transgenesis.

This symposium represents a milestone, an important step towards the dissemination and use of methods for the generation and analyses of all types of genetically modified animals in Brazil, to be applied in Biology, Medicine, Animal Health and Biotechnology.

1st Brazilian Symposium on Transgenic Technology

Sunday, February 10th, 2008
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1st BSTT

In about one month, on March 10-12, in Sao Paulo (Brazil), Prof. Dr. Joao Bosco Pesquero is organizing the first Brazilian Symposium on Transgenic Technology, an event that is co-sponsored by ISTT.

Scientists and experts in the animal transgenesis at the international field have been invited and will participate in this meeting, including Prof. Oliver Smithies, recenlty awarded with the 2007 Nobel Prize in Physiology or Medicine.

You can browse here the latest program of this meeting.

Nobel Prize in Physiology or Medicine for 2007

Friday, February 1st, 2008
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The Nobel Prize in Physiology or Medicine for 2007 was awarded 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.


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