In 2012, Kyoto University Prof. Shinya Yamanaka won the 2012 Nobel Prize in Physiology or Medicine for his research in developing induced pluripotent stem cells (iPS cells). Proving that a cell can artificially return to a state similar to a fertilized egg, he won the prize just six years after he presented a paper on iPS cells that had been created using mouse cells. His work was highly valued as it opened new possibilities for regenerative medicine and research into intractable diseases. "I hope iPS cells will help advance cell therapy or drug discovery. I'd like to devote my life to helping patients suffering from diseases," Yamanaka said in a speech ahead of the prize-giving ceremony in Stockholm. Yamanaka is the second Japanese recipient of the physiology or medicine prize. The first was Susumu Tonegawa, a professor at the Massachusetts Institute of Technology, in 1987.

Yamanaka, a professor at Kyoto University, announced he had created iPS cells from mouse cells in August 2006 and from human cells in November 2007. Nicholas Wade wrote in the New York Times: “Two scientists who were awarded the Nobel Prize in Physiology or Medicine helped lay the foundation for regenerative medicine, the hotly pursued though still distant idea of rebuilding the body with tissues generated from its own cells. They are John B. Gurdon of the University of Cambridge in England and Shinya Yamanaka of Kyoto University in Japan.” The two men split a handsome cash prize of 8 million Swedish krona, worth about $1.2 million. [Source: Nicholas Wade, New York Times, October 8, 2012]

Their discoveries concern the manipulation of living cells, and lie at the heart of the techniques for cloning animals and generating stem cells, the primitive cells from which the mature tissues of the body develop. Dr. Gurdon was the first to clone an animal, a frog, and Dr. Yamanaka discovered the proteins with which an adult cell can be converted to an egg-like state. Both men had to overcome false starts in life. Dr. Gurdon was told as a boy that he was wholly unsuited for biology, and Dr. Yamanaka trained as a surgeon only to find he was not so good at it.

The techniques they developed reach to the beginnings of life, and have generated objections from people who fear, on ethical or religious grounds, that scientists are pressing too far into nature’s mysteries and the ability to create life artificially. Dr. Gurdon’s discovery came in 1962, when he produced living tadpoles from the adult cells of a frog. His work was at first greeted with skepticism, because it contradicted the textbook dogma that adult cells are irrevocably assigned to their specific functions and cannot assume new ones. (His prize was the first Nobel to be awarded to a cloner.)

Dr. Gurdon’s technique was to extract the cell nucleus, containing the frog’s DNA, from a mature intestinal cell and inject the nucleus into a frog egg whose own nucleus had been removed. The egg was evidently able to reprogram the introduced nucleus and direct its genes to switch from the duties of an intestinal cell to those appropriate to a developing egg. But how did the egg cell body accomplish this reprogramming feat? The answer had to wait 44 years, while molecular biologists gained a more intimate understanding of genes and the agents that control them.

Working with mice, Dr. Yamanaka discovered in 2006 that the reprogramming can be accomplished by just four specific gene control agents in the egg. The agents, known to biologists as transcription factors, are proteins made by master genes to regulate other genes. By injecting the four agents into an adult cell, Dr. Yamanaka showed that he could walk the cell back to its primitive, or stem cell, form. Stem cells generated by this method, known as induced pluripotent cells, or iPS cells, could then be made to mature into any type of adult cell in the body, a finding with obvious potential for medical benefits.

Biologists hope the technique will enable replacement tissues to be generated from a patient’s own cells for use against a wide variety of degenerative diseases. For the moment, that remains a distant prospect. But the cells have already proved useful in studying the genesis of disease. Cells generated from a patient are driven to form the tissue that is diseased, enabling biologists in some cases to track the steps by which the disease is developed.

Shinya Yamanaka, iPS Stem Cell Pioneer

Shinya Yamanaka of Kyoto University made one of the most important stem cell breakthroughs: giving adult cells many of the same characteristics of embryonic stem cells thus avoiding many of the negative issues that surround stem cells such as harvesting them from aborted fetuses. The new cells, known as induced pluipotent stem (iPS) cells, live a long time while retaining the ability to form all of the different tissues in the body and have the potential of replacing cells, tissues or organs damaged or lost to disease.

Yamanaka screened 24 candidate proteins and found four that were able to reprogram adult cells, reverting them to their embryonic state, by imbedding them into the skin cells of a newborn infant. He first used mouse cells and then showed that these factors are also effective in human cells. The mechanism that led to the creation of the iPS cells is still not well understood.

Eryn Brown wrote in the Los Angeles Times: “Perhaps no scientist has had a greater impact on stem cell research than Dr. Shinya Yamanaka. While most of his colleagues were looking for ways to grow human embryonic stem cells into replacement tissues for treating patients, the Japanese researcher took the opposite approach and figured out how to rewind mature body cells to a flexible state in which they could again become many types of cells. His 2006 discovery of induced pluripotent stem cells, or iPS cells, paves the way for pursuing regenerative medicine therapies without the need to destroy embryos.” [Source: Eryn Brown, Los Angeles Times, November 27, 2010]

Yamanaka is from Osaka and a graduate of Kobe University. His primary lab is at Kyoto University in Japan, but he spends part of the year at UC San Francisco's Gladstone Institute of Cardiovascular Disease, where he was a postdoctoral fellow in the 1990s.

Yamanaka has received a number awards and prizes including the $700,000 Blazan Prize in biology, the Albert Lasker Basic Medical Research Award, the Shaw Prize and the Robert Koch Prize. In May 2011 he shared Israel’s $100,000 Wolf Prize for medicine with MIT researcher Rudolf Jaenisch. In November 2010 he received the $610,000 Kyoto Prize, which recognizes "significant contributions to the betterment of humankind," for his stem cell work. On his success Yamanaka told the Los Angeles Times, “When our group succeeded in generating iPS cells, I never imagined so many researchers would begin working on this new technology — or that the research would advance at such a rapid pace.”

John B. Gurdon’s Stem Cell Research

Nicholas Wade wrote in the New York Times: “Dr. Gurdon’s early academic career did not hint at what the future might hold. “I believe Gurdon has ideas about becoming a scientist; on his present showing this is quite ridiculous,” his high school biology teacher wrote. “If he can’t learn simple biological facts he would have no chance of doing the work of a specialist, and it would be a sheer waste of time, both on his part and of those who would have to teach him.” [Source: Nicholas Wade, New York Times, October 8, 2012]

At Oxford University, a more positive mentor encouraged him to try transplanting the nucleus of adult cells into frog eggs. The idea was to see if the genome — the hereditary information — stayed unchanged during development or underwent irreversible changes. In producing living tadpoles from the nucleus of adult frog cells, Dr. Gurdon showed that the genome of both egg and adult cells remained essentially unchanged.

But the possibility that animals, including humans, could be cloned did not seriously impinge on the public imagination until his work was reproduced in mammals with the generation of Dolly, the cloned sheep, in 1997. The following year saw generation of the first human embryonic stem cells, which are derived from the early human embryo. Such cells are called pluripotent because they can develop into any of the mature tissues of the body. The two developments led to the concept of therapeutic cloning — take a patient’s skin cell, say, insert it into an unfertilized human egg so as to reprogram it back to pluripotent state, and then develop embryonic stem cells for conversion into the tissue or organ that the patient needed to have replaced. Since the new tissue would carry the patient’s own genome, there should be no problem of immune rejection.

Discovery of iPS Cells

Yamanaka announced his discovery with mice iPS cells in December 2005; and with human cells in November 2007. Kyoto University received a patent for the method to create the iPS in September 2008, giving the university exclusive rights to create iPS cells of all type of animals, including humans. The discovery of iPS cells has made the production of embryonic stem cells by placing the nucleus of a human somatic cell into an ova obsolete.

In the mid 2000s Yamanaka formed a team researchers at Kyoto University’s Institute for Frontier medical Sciences motivated by Yamanaka’s theory that if special genes were inserted into skin cells iPS cells could be created. The researchers often hashed out ideas while sitting around eating meat at a yakuniku restaurant. Certain candidate genes were selected and tried in experiments with genetically-modified mice. Among the most skilled researchers was Kazutoshi Takahashi, then a 31-year-old researcher at Kyoto University. He was known for putting in long hours and quickly and skillfully conducting many experiments.

The first iPS cells were created in the summer of 2005 by Takahashi. He told the Daily Yomiuri that when the moment of discovery came he told his professor, Shinya Yamanaka, “We’ve done it!” Yamanal replied, “No way!” But there in a 10-centimeter petri dish was a cluster of cells in a bowl shape — the first iPS cells.

Yamanaka’s Work with iPS Cells

Yamanaka told the Los Angeles Times, “In 2000, I became interested in how embryonic stem cells maintain their ability to develop into different kinds of cells. At the time, many laboratories were trying to turn embryonic stem cells into various functional cells. I thought the field was highly competitive, so I decided to go the opposite direction — [turning body cells] back to the embryonic state.” [Source: Eryn Brown, Los Angeles Times, November 27, 2010]

On the advantages of iPS cells, Yamanaka told the Los Angeles Times, “IPS cells can circumvent two obstacles faced by embryonic stem cells. One is the ethical controversy — we have to destroy embryos to isolate embryonic stem cells. The other is the risk of immune rejection when cells derived from embryonic stem cells are transplanted into a patient's body.” On their disadvantages he said, “The safety of the cells. They are made by using retroviruses to introduce genes into mature cells, but the process can cause iPS cells to grow tumors if the retrovirus is inserted in the wrong part of the genome.”

On the long-term potential of iPS cells, Yamanaka told the Los Angeles Times: “IPS cells can become an effective research tool for modeling drugs, screening drug compounds and testing for side effect or toxicity. In the future, when the safety and other issues are solved, iPS cell-derived functional cells may become sources for cell transplantation therapies.” On the primary scientific hurdles that remain with iPS cells he said, “Scientists need to find out the methods to generate safer iPS cells, how to turn those cells into functional cells, and how to transplant resultant cells into a body. We also need to figure out how to use the cells to study diseases in the lab.”

Boldness of Yamanaka’s iPS Discovery

Nicholas Wade wrote in the New York Times: “But human eggs are not so easily obtained. Of course, the reprogramming might be accomplished without human eggs if only the relevant factors in the egg could be isolated. But that seemed a distant prospect until Dr. Yamanaka’s discovery that 24 transcription factors, later whittled down to four, could reprogram a nucleus when introduced into cells on the back of a virus. [Source: Nicholas Wade, New York Times, October 8, 2012]

Hirofumi Imazu and Makio Hattori wrote in the Yomiuri Shimbun: “In an August 2006 paper, which was instrumental in his winning the award, Yamanaka wrote that creating iPS cells was shockingly simple. When he made public an outline of his studies at an international meeting of experts in Canada in March 2006, researchers from around the world were incredulous, as his theory seemed hardly believable. Although the human body comprises a huge number of cells and has a wide variety of tissues such as muscles and organs, all the cells have the same genetic background. The difference lies in which genes are actually at work in the cells. The critical question revolved around the possibility of turning a skin cell, for example, back into an embryonic stem cell by manipulating its genes to return it to the state before cell differentiation took place. This was Yamanaka's idea for creating iPS cells by reprogramming somatic cells. [Source: Hirofumi Imazu and Makio Hattori, Yomiuri Shimbun, October 10, 2012]

Yamanaka and his team identified the four genes--"Oct3/4," "Sox2," "Klf4" and "c-Myc"--and combined them with a retrovirus and implanted them in mouse skin cells. The four genes started working within the cells, transforming them into iPS cells. Creating iPS cells is so simple even a student can master the technique in just a few months, according to Yamanaka. Yamanaka's success lies in using a specific combination of genes to create an iPS cell.

He and his team sorted about 100 candidate genes needed to create iPS cells into 24 categories over four years by carefully following findings of evolving embryonic stem cell studies. The candidate genes were ultimately reduced to the four by removing unsuitable ones and identifying those necessary to produce an iPS cell. Yamanaka was assisted by Kazutoshi Takahashi, then a research fellow at Kyoto University and who is currently a lecturer there. Yamanaka and his coresearchers changed widely accepted views that cells, once specialized as a somatic cell, can never return to an embryonic state to be manipulated into different kinds of mature cells.

Dr. George Daley, a stem cell researcher at Children’s Hospital Boston, praised the creativity of Dr. Yamanaka’s experiment. At the time, he and others were trying to reprogram cells by adding one gene at a time. The idea of inserting 24 genes all at once “is the kind of experiment that would have been laughed out of the room” in a grant committee meeting, he said. Rudolf Jaenisch, a biologist at the Whitehead Institute in Cambridge, was another who considered that Dr. Yamanaka’s surprising experiment was correct, despite widespread doubts. “I believed it immediately because I knew him to be very careful and there was a logic to it,” he said. [Wade, Op. Cit]

Yamanaka’s Early Life and Interest in Sports

Yamanaka was born in in Higashiosaka in Osaka Prefecture in September 1962. According to the Yomiuri Shimbun Yamanaka has always participated in sports, from practicing judo and playing rugby to running marathons. He practiced judo as a student at Osaka Kyoiku University-affiliated Tennoji High School. He often suffered injuries, including one or two fractures a year. Those experiences motivated him to pursue a career in sports medicine--and eventually led him to study iPS cells--Yamanaka later recalled. [Source: Yomiuri Shimbun, October 10, 2012]

Soichi Tanaka, 50, a fellow member of the high school's judo club who now runs a metal products processing company in Higashi-Osaka, Osaka Prefecture, said Yamanaka was basically a gentle person. "However, he was aggressive when it came to judo," Tanaka said. "Today he makes steady efforts in his research--the same attitude he already had in those days.”

Yamanaka belonged to a rugby club when he attended Kobe University School of Medicine. Yukihito Hasunuma, a 51-year-old doctor who was then one of Yamanaka's teammates in the club, said: "[Yamanaka] was not a smart player, but his technique was good and he was able to keep the other team from stealing the ball. He was a serious student, and returned to his classes as soon as practice ended.”

As an amateur marathon runner, Yamanaka compared life to that sport when he gave a lecture at his alma mater in 2008. "It doesn't matter if you win or lose," he said. "As researchers, we shouldn't give up even when we find other researchers have beaten us to publication. We have to make it to the finish line." During a press conference Monday night, Yamanaka was asked what place he thought he would be in if he were running a marathon. "I'd be in the middle," he said.

Many of his friends are impressed at how Yamanaka always keeps himself in good shape despite his hard schedule. Hiroshige Seko, 49, a House of Councillors member and one of Yamanaka's middle school classmates, recalled that Yamanaka showed up at a seminar the lawmaker held in Osaka in October 2011 year, even though the scientist had just returned from the United States. Yamanaka enjoyed drinking with Seko and others until late that night. On the following morning, he guided Crown Prince Naruhito on a tour of Kyoto University's Center for iPS Cell Research and Application, for which he serves as director.

In October 2011 participated in the inaugural Osaka Marathon as a charity runner, his first full marathon for two decades. He finished in 4 hours 29 minutes 53 seconds. Yamanaka also took part in this year's Tokyo Marathon in March 2012 to raise money for basic iPS research, covering the distance in 4 hours 3 minutes 19 seconds.

Yamanaka’s Career

After graduating from Kobe University School of Medicine, Yamanaka became an assistant at Osaka City University Medical School, then a professor at Nara Institute of Science and Technology. Yamanaka said that he had trained as surgeon but “gave it up because I learned I was not talented.” Having seen how little the best surgeons could do to help some patients, he decided to go into basic research and did postdoctoral training at the Gladstone Institutes in California.

Henshu Techo wrote in the Yomiuri Shimbun: “Yamanaka aimed to become a plastic surgeon for athletes but suffered a setback. It reportedly took him two hours to perform an operation that usually could be completed in 20 minutes if done smoothly. Given his exceptional clumsiness, his seniors gave him the outrageous nickname "Jamanaka"--a combination of jama (bother) and his family name--describing him as a nuisance and drag. Given the collapse of his dream of becoming a clinician, he opted to become a medical researcher. [Source: Henshu Techo, Yomiuri Shimbun, October 9, 2012]

While studying in the United States, Yamanaka learned the phrase "vision and hard work" from his academic adviser, meaning scientists must have a clear, long-term vision and do their best to realize it. Yamanaka's life as a researcher reached a turning point in 1999 when he took a post as an associate professor at the Nara Institute of Science and Technology. Before joining the institute, he had studied human embryonic stem cells in the United States at a time when their possible medical application attracted little attention. When he came home, few people in Japan could understand his research. [Source: Yomiuri Shimbun, October 10, 2012]

As Yamanaka was unrenowned, his laboratory was very small and he was given little funding for research. His now famous research started from the tiny lab with only three students, including Kazutoshi Takahashi, currently a lecturer at Kyoto University. Takahashi coauthorered a paper that led to Yamanaka's Nobel Prize.

On how he got the money to carry out his groundbreaking research, the Yomiuri Shimbun reported: “Powerful presentation skills and an "embarrassing" illustration proved to be key driving forces in pushing forward Shinya Yamanaka's breakthrough research in induced pluripotent stem (iPS) cells, which won him the 2012 Nobel Prize in Physiology or Medicine. In August 2003, after whetting his appetite for iPS cell research, Yamanaka submitted an application for a massive grant to the government. However, at the time, contrary to Yamanaka's faith in the study, iPS research was not widely regarded. Instead, scientists worldwide focused their efforts on embryonic stem (ES) cell research.

In a desperate attempt to make research fund panel juries understand the significance of his work, the Kyoto University professor created a unique illustration for a crucial presentation at a screening interview to decide the distribution of research grants. Yamanaka drew a weeping human embryo and mouse, which had a tumor growing out of its side. He used the illustration to highlight the problems of ES cells and appealed for the need to generate new cells to replace ES cells. In the applied research of ES cells in human bodies, there has always been the ethical issue that ES cells are acquired by destroying human embryos. Furthermore, scientists discovered that ES cells tend to become tumors when transplanted into a human body.

In Yamanaka's presentation, the problems regarding ES cells were clearly explained to the research fund panel. In the end, the illustration helped Yamanaka win about 300 million yen in funding for his work over five years. "Thinking back, I don't know how I could have shown such an embarrassing drawing in the presentation. It makes me break out in a cold sweat," a smiling Yamanaka recalled.

Former Osaka University President Tadamitsu Kishimoto, who oversaw the grant screenings, recalled Yamanaka's presentation, saying, "His explanation and the illustration had the power to [convince people]." "I always thought there was no way of creating things [like iPS cells]. But then, [after Yamanaka's presentation], I thought if one out of 100 studies is a fluke, that would be good enough. Something striking might come out of a man like him, so I thought 'OK, let's support him.' That's what he made me feel," Kishimoto added.

While studying in the United States for three years from 1993, Yamanaka received training in making effective presentations and learned the importance of using clear, easy words to help his audience understand his message. Yamanaka said: "When I was young, I learned in the United States how to grab people's interest. To do so, I also learned I have to be able to make them laugh, too.”

Impact of Yamanaka’s Research and His Unusually Prompt Nobel Prize

Hirofumi Imazu and Makio Hattori wrote in the Yomiuri Shimbun: “The award of the Nobel Prize to Prof. Shinya Yamanaka recognizes his pioneering work that paves the way to treat diseases and injuries that have so far been considered incurable, by breaking long-held beliefs in biology. Especially noteworthy about his achievement is that creating iPS cells, when looked at retrospectively, is surprisingly simple. Because of the simplicity of Yamanaka's discovery, his achievement sparked a flurry of studies around the world on the reprogramming of cells. This led the Nobel Committee at Stockholm's Karolinska Institute to award Yamanaka just six years after publication of his work. [Source: Hirofumi Imazu and Makio Hattori, Yomiuri Shimbun, October 10, 2012]

There are other examples of fast-track Nobel Prize wins, such as the physics prize in 1987 for the "discovery of high-temperature superconductivity" one year after it was published. The Nobel Committee typically rewards research after a number of years have passed to ensure it stands the test of time. Japanese researcher Susumu Tonegawa, currently a professor at the Massachusetts Institute of Technology, received the award in physiology or medicine for his discovery of "the genetic principle for the generation of antibody diversity" in 1987, 11 years after he published a landmark paper in 1976. The 2006 prize for "RNA interference--gene slicing by double-stranded RNA" came relatively quickly, eight years after publication of the discovery.

Recommendations "came from [around the] world," said Goran Hansson, secretary general of the Nobel Assembly at Sweden's Karolinska Institute, which selects the winner of the Nobel Prize in Physiology or Medicine. Every September, the Nobel Assembly asks past prize winners and researchers to nominate candidates for the prize. The replies are received by the end of January the following year, according to Hansson. The assembly examines all recommendations and narrows down the list to several candidates with support and advice from outside experts. The finalists are then screened by 50 members of the assembly, and the winner is decided by a vote in October, he said. Details of the selection process are kept top-secret. Winning the Nobel Prize in six years after his achievement was a "very short time," Hansson said, noting that the selection process usually takes a long time because the assembly has to examine various factors.

The Yomiuri Shimbun reported: “Yamanaka’s groundbreaking work opens up possibilities in a wide range of fields, such as the development of regenerative medicine and treatments for intractable diseases. iPS cells are highly versatile, and able to replenish every type of body cell except for those in the placenta. Their capacity to multiply almost indefinitely has led to expectations they could have a number of practical applications. It is hoped they will assist the development of regenerative medicine to replace tissue damaged through injury, such as damage to the spinal cord, or through illness, such as diabetes or Parkinson's disease. They might also help clarify mechanisms that bring about the onset of intractable diseases and assist in the development of treatments for such illnesses. [Source: Yomiuri Shimbun, October 9, 2012]

Yamanaka Grateful to his Family and Students

"I couldn't have continued my research without support from my family," Yamanaka said at a press conference at Kyoto University, where he is a professor at the Center for iPS Cell Research and Application. "I am very grateful to them." Seated next to him, his wife, Chika, looked down while she listened. She then said: "I'm still stupefied after we received the news [of his winning the Nobel Prize] yesterday. I'm really happy, as so many people are also delighted with the news. Thank you very much." [Source: Yomiuri Shimbun, October 10, 2012]

Yamanaka closed his eyes as he quietly listened to his wife, who is a dermatologist and was his classmate at middle and high school. He occasionally smiled as he listened. Referring to their two daughters, who are medical students, Yamanaka said, "Seeing my children smile at home always gave me strength.”

Speaking of his wife, Yamanaka said: "She always grumbles, saying she ended up living a roller-coaster life because she married me. She really has guts and I'm no match for her.” They spent six years together at Tennoji Junior High School and High School, which are attached to Osaka Kyoiku University. Although they chose different universities, both went to medical school in the Kansai region. They continued to see each other while working as interns, married and had two daughters.

The family moved to the United States in 1993 with Yamanaka, who decided to study there, he said. Chika had just begun working as a dermatologist. Leaving her practice at such an early stage could have risked her career. Chika negotiated with a U.S. hospital to allow her to continue studying as a clinician, while supporting her husband. About three years later, the family returned to Japan and Chika returned to work as a dermatologist after working as an intern. She continued to support her husband in his struggles by helping him through the times when he hit roadblocks in his research and moved from university to university.

"My work isn't finished," Yamanaka said at the press conference. "I want to return to my research next week." Among his students Yamanaka was known for being demanding, dedicated and easy-going. He would spend at least 30 minutes reprimanding students who were even a little late for an experiment. But at night, he and his students often ate a nabe hot pot together in the laboratory. With a can of beer in his hand, Yamanaka would talk passionately about the significance of their research. "If we're successful, we can help a lot of patients," he was quoted as saying. Yamanaka never compromised, and kept saying, "We're competing against scientists all over the world." Every time he was praised for his achievements, he would talk about his passion to apply his technology to clinical medicine. "I haven't saved even one patient yet [with the technology]," he said.

Yamanaka gets Nobel Prize in Stockholm

In December 2012, Kyodo reported: “Shinya Yamanaka of Kyoto University received this year's Nobel Prize in physiology or medicine, along with Britain's John Gurdon, for discovering that mature cells can be reprogrammed into immature cells capable of turning into any kind of tissue of the human body. Yamanaka and Gurdon were given medals and diplomas from Sweden's King Carl XVI Gustaf, along with other Nobel laureates, at the annual awards ceremony in Stockholm Concert Hall. [Source: Kyodo, December 12, 2012]

Of this year's Nobel winners, Yamanaka, a 50-year-old professor, is the youngest. He received the prize only six years after developing induced pluripotent stem cells, which he named iPS cells. "If I use a marathon metaphor, the ceremony is just the halfway point," Yamanaka, who is fond of running, said before attending the festivities for the winners of the literature, physics, chemistry, medicine and economics prizes. "Like a marathon, the latter part is going to be tougher. So I continue to do my best," he said.

Yamanaka was formally clad in a tailcoat and white tie. "I was so moved I couldn't talk," Yamanaka said after the ceremony. "The nicest thing about the ceremony was that my mother was present," the 50-year-old laureate added. "I felt really relieved when I saw my mother's and wife's eyes from the stage." Yamanaka then posed for photos with his 81-year-old mother, Minako, and daughters. Minako wore the watch that was owned by her husband, who died 25 years ago. "I think my father also feels happy [that I received the honor]," said Yamanaka, who frequently says he was able to become a doctor thanks to his father. [Source: Hirofumi Imazu and Makoto Mitsui, Yomiuri Shimbun, December 12, 2012]

Upon returning to his hotel after the banquet, Yamanaka was asked by reporters how he felt. He said he felt strongly determined to realize the clinical application of iPS cells. "I still feel strange," he added. "I'm wondering if this is a dream or reality. However, I shouldn't speak of dreams any more. This prize is for real work we have done so far, work that from today becomes something of the past. I'm determined to work hard because I'm certain our future work will be important." Yamanaka's wife, Chika, expressed her pleasure, saying, "I couldn't have felt happier [during the ceremony].”

In a speech ahead of the Nobel Prize Award Ceremony Yamanaka explained how his studies and research led to the development of iPS cells and expressed how much potential iPS cells have. "I really hope in the very near future these technologies will help patients either in cell therapy or in drug discovery," Yamanaka said. [Source: Makoto Mitsui and Hirofumi Imazu, Yomiuri Shimbun, December 9, 2012]

"I was extremely lucky in two ways. I had the opportunity to observe totally unexpected results, which brought me to completely new projects," he said. "The other luck was I was able to work under two great mentors...I had two types of great teachers in my early days as a scientist." One type of teacher included the mentors he had as a graduate student at Osaka City University, for example. Yamanaka then spoke about another teacher whom he identified as "nature itself." "Nature gave me unexpected results and brought me to new projects," he said.

He said he is not the type who shows originality, but the experimental results bring themselves originality. He cited a case of a substance meant to maintain blood pressure unexpectedly lowering it as an example of nature bringing him unexpected results. Yamanaka said a gene believed to be related to cholesterol turned out to be related to cancer. Such unexpected results fueled his interest in the study of stem cells, he said. Asked for a message to young researchers, Yamanaka said: "Experimental results that were different from what had been assumed led to the production of induced pluripotent stem cells. Unexpected results should be viewed as a chance [of success] rather than a failure.”

At the end of his speech, he offered a word of thanks to his family, and then joked about his mother. "My mother is in Stockholm. But she can't make it today. She said, 'Shinya, your English is terrible, so I won't understand it,'" he said. He made a few other jokes in his speech, getting some laughs from the audience. After the lecture, Yamanaka's wife, Chika, said she was moved by the memories brought up by the lecture.

Yamanaka at the Nobel Prize Banquet

Yamanaka attended a spectacular Nobel banquet with his wife and other family members. Hirofumi Imazu and Makoto Mitsui wrote in the Yomiuri Shimbun: “About 1,300 guests were invited to the formal gala to honor the Nobel prize winners, held at the Blue Hall on the first floor of Stockholm City Hall.As a fanfare sounded, Yamanaka--wearing the Order of Culture--entered the venue with a radiant expression as he walked with Princess Madeleine, 30.Yamanaka, 50, sat at the Table of Honor in the center of the hall with King Carl XVI Gustaf, 66, and other members of the Swedish royal family and guests. Next to Yamanaka was the princess, while Prince Carl Philip, 33, was seated next to Yamanaka's wife, Chika, who sat in front of her husband. The couple enjoyed a conversation over dinner with the young royal family members.

To give guests of the gala event a taste of traditional Japanese clothing, Chika suggested all female members of the Yamanaka family wear kimono. A local TV reporter repeatedly featured the women, who were the center of attention due to the beautiful kimono they wore. The tables and walls of the venue were adorned with about 8,000 flowers, mainly of a white and yellow persuasion, such as jasmine and cattleya.

The banquet also featured entertainers who balanced on a ball and did a trapeze act accompanied by a violin performance, among other delights. "The dinner was elegant and wonderful. The entertainment was more modern than I expected, and I truly enjoyed it," Yamanaka said after returning to his hotel. "It was a very long day, but at the same time, the experience was so fulfilling that time flew very quickly," the Nobel laureate said, looking satisfied. Chika said: "I can't express what it was like in one phrase. But it was a real honor.”

English translation of the Nobel banquet menu 2012: 1) Marinated Arctic char with cauliflower terrine, Kalix bleak roe and dill mayonnaise; 2) Pheasant with chanterelle mushrooms, poached pear, winter vegetables, almond potato puree and red wine gravy; 3) Trilogy of cherries with pistachio-covered mascarpone cheese and black cherry sorbet

Yamanaka After Winning the Nobel Prize

Referring to his life since being named a Nobel laureate, Yamanaka said: "I've been very busy since then as my students ask for my advice on papers almost every day. I want to go back to my normal life [as a researcher].”

The Yomiuri Shimbun reported: “More than 400 million yen ($5 million ) was donated to a fund Kyoto University established to support research on iPS cells in the first month and a half after the 8 announcement that Yamanaka had won a Nobel Prize. The iPS Cell Research Fund has received 2,600 donations from individuals, companies and other organizations since the announcement, according to the university. One individual donated tens of millions of yen, according to the university's Center for iPS Cell Research and Application. [Source: Yomiuri Shimbun, December 12, 2012]

During the 3-1/2-year period from its April 2009 establishment to Oct. 7 this year, the fund had collected 450 million yen. "We realize how amazing the Nobel Prize is," said an official at the center in charge of the fund. "We'll feel happy if a culture in which the opinions of patients and their family members are reflected in research supported by the private sector takes root [in Japan]." Based on Yamanaka's belief that it is important to create an environment for the same researchers to be able to work continuously on research for an extended period, the center uses money from the fund to pay the salaries to some of its researchers who are not provided research funds by the government.

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Text Sources: New York Times, Washington Post, Los Angeles Times, Times of London, Yomiuri Shimbun, Daily Yomiuri, Japan Times, Mainichi Shimbun, The Guardian, National Geographic, The New Yorker, Time, Newsweek, Reuters, AP, Lonely Planet Guides, Compton’s Encyclopedia and various books and other publications.

Last updated January 2013

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