10月8日17时30分，备受世界关注的诺贝尔生理学或医学奖终于揭开神秘面纱，授予日本京都大学教授山中伸弥(Shinya Yamanaka)，以及英国生物学家约翰﹒戈登(John B.Gurdon)，为了奖励他们发现了成熟细胞可以被重编码而具备多能性。
山中伸弥(Yamanaka)，是诱导多功能干细胞（iPScell）创始人之一。1962年出生于日本大阪府，日本医学家，京都大学再生医科研究所干细胞生物系教授，大阪市立大学医学博士（1993年），美国加利福尼亚州旧金山研究所高级研究员.，他所在的研究团队通过对小鼠的实验，发现诱导人体表皮细胞使之具有胚胎干细胞活动特征的方法。此方法诱导出的干细胞可转变为心脏和神经细胞，为研究治疗目前多种心血管绝症提供了巨大助力。这一研究成果在全世界被广泛应用，因为其免除了使用人体胚胎提取干细胞的伦理道德制约。山中伸弥也因此获得拉斯克基础医学奖。同时他在获颁邵逸夫生命科学与医学奖。并于获得国际最高学术大奖之一的沃尔夫医学奖，与其一起获奖的还有美国怀特黑德研究所的Rudolf Jaenisch。，山中伸弥与美国软件工程师利努斯·托瓦兹获得芬兰“千年技术奖”，二人分别获得60万欧元的奖金。
约翰﹒戈登（John Gurdon），生于1933年10月2日，英国发育生物学家。他在细胞核移植方面进行了开创性的研究。获得拉斯克基础医学奖。
据财经网报道，受经济危机影响，诺贝尔基金会宣布奖金将由以往1000万瑞士法郎缩水至800万瑞士法郎。
10月3日，瑞典卡罗林斯卡医学院宣布，将诺贝尔生理学或医学奖授予美国科学家布鲁斯·比特勒、法国科学家朱尔斯·霍夫曼和加拿大科学家拉尔夫·斯坦曼。1958年，他在牛津大学成功做出了体细胞克隆蛙。
The Nobel Assembly at Karolinska Institutet has today decided to award
The Nobel Prize in Physiology or Medicine
jointly to John B. Gurdon and Shinya Yamanaka
for the discovery that mature cells can be reprogrammed to become pluripotent
Summary
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.
John B. Gurdon discovered in 1962 that the specialisation of cells is reversible. In a classic experiment, he replaced the immature cell nucleus in an egg cell of a frog with the nucleus from a mature intestinal cell. This modified egg cell developed into a normal tadpole. The DNA of the mature cell still had all the information needed to develop all cells in the frog.
Shinya Yamanaka discovered more than 40 years later, in , how intact mature cells in mice could be reprogrammed to become immature stem cells. Surprisingly, by introducing only a few genes, he could reprogram mature cells to become pluripotent stem cells, i.e. immature cells that are able to develop into all types of cells in the body.
These groundbreaking discoveries have completely changed our view of the development and cellular specialisation. We now understand that the mature cell does not have to be confined forever to its specialised state. Textbooks have been rewritten and new research fields have been established. By reprogramming human cells, scientists have created new opportunities to study diseases and develop methods for diagnosis and therapy.
Life a journey towards increasing specialisation
All of us developed from fertilized egg cells. During the first days after conception, the embryo consists of immature cells, each of which is capable of developing into all the cell types that form the adult organism. Such cells are called pluripotent stem cells. With further development of the embryo, these cells give rise to nerve cells, muscle cells, liver cells and all other cell types - each of them specialised to carry out a specific task in the adult body. This journey from immature to specialised cell was previously considered to be unidirectional. It was thought that the cell changes in such a way during maturation that it would no longer be possible for it to return to an immature, pluripotent stage.
Frogs jump backwards in development
John B. Gurdon challenged the dogma that the specialised cell is irreversibly committed to its fate. He hypothesised that its genome might still contain all the information needed to drive its development into all the different cell types of an organism. In 1962, he tested this hypothesis by replacing the cell nucleus of a frogs egg cell with a nucleus from a mature, specialised cell derived from the intestine of a tadpole. The egg developed into a fully functional, cloned tadpole and subsequent repeats of the experiment yielded adult frogs. The nucleus of the mature cell had not lost its capacity to drive development to a fully functional organism.
Gurdons landmark discovery was initially met with scepticism but became accepted when it had been confirmed by other scientists. It initiated intense research and the technique was further developed, leading eventually to the cloning of mammals. Gurdons research taught us that the nucleus of a mature, specialized cell can be returned to an immature, pluripotent state. But his experiment involved the removal of cell nuclei with pipettes followed by their introduction into other cells. Would it ever be possible to turn an intact cell back into a pluripotent stem cell?
A roundtrip journey mature cells return to a stem cell state
Shinya Yamanaka was able to answer this question in a scientific breakthrough more than 40 years after Gurdon s discovery. His research concerned embryonal stem cells, i.e. pluripotent stem cells that are isolated from the embryo and cultured in the laboratory. Such stem cells were initially isolated from mice by Martin Evans (Nobel Prize ) and Yamanaka tried to find the genes that kept them immature. When several of these genes had been identified, he tested whether any of them could reprogram mature cells to become pluripotent stem cells.
Yamanaka and his co-workers introduced these genes, in different combinations, into mature cells from connective tissue, fibroblasts, and examined the results under the microscope. They finally found a combination that worked, and the recipe was surprisingly simple. By introducing four genes together, they could reprogram their fibroblasts into immature stem cells!
The resulting induced pluripotent stem cells (iPS cells) could develop into mature cell types such as fibroblasts, nerve cells and gut cells. The discovery that intact, mature cells could be reprogrammed into pluripotent stem cells was published in and was immediately considered a major breakthrough.
From surprising discovery to medical use
The discoveries of Gurdon and Yamanaka have shown that specialised cells can turn back the developmental clock under certain circumstances. Although their genome undergoes modifications during development, these modifications are not irreversible. We have obtained a new view of the development of cells and organisms.
Research during recent years has shown that iPS cells can give rise to all the different cell types of the body. These discoveries have also provided new tools for scientists around the world and led to remarkable progress in many areas of medicine. iPS cells can also be prepared from human cells.
For instance, skin cells can be obtained from patients with various diseases, reprogrammed, and examined in the laboratory to determine how they differ from cells of healthy individuals. Such cells constitute invaluable tools for understanding disease mechanisms and so provide new opportunities to develop medical therapies.
Sir John B. Gurdon was born in 1933 in Dippenhall, UK. He received his Doctorate from the University of Oxford in 1960 and was a postdoctoral fellow at California Institute of Technology. He joined Cambridge University, UK, in 1972 and has served as Professor of Cell Biology and Master of Magdalene College. Gurdon is currently at the Gurdon Institute in Cambridge.
Shinya Yamanaka was born in Osaka, Japan in 1962. He obtained his MD in 1987 at Kobe University and trained as an orthopaedic surgeon before switching to basic research. Yamanaka received his PhD at Osaka University in 1993, after which he worked at the Gladstone Institute in San Francisco and Nara Institute of Science and Technology in Japan. Yamanaka is currently Professor at Kyoto University and also affiliated with the Gladstone Institute.
