AsianScientist (Apr. 30, 2013) – When it was announced that Dr. Shinya Yamanaka had won the 2012 Nobel Prize for Physiology or Medicine, few were surprised.
In 2006, Dr. Yamanaka sent ripples through the stem cell community when he discovered that by adding just four genes into adult skin cells in mice, he could encourage the cells to behave like embryonic stem cells. He called them induced pluripotent stem cells, or iPS cells. One year later, he announced that he had done the same with human adult skin cells, opening the door to the translation of cell therapies for clinical use.
While embryonic stem cells have always held tremendous promise in regenerative medicine and for the treatment of diseases such as diabetes, blindness, and Parkinson’s disease, its use has long been controversial – which is why Dr. Yamanaka’s discovery of an alternate source of human stem cells was so important.
In early April, Dr. Yamanaka visited the sunny city-state of Singapore under the Agency for Science, Technology and Research (A*STAR) Biomedical Research Council Distinguished Visitor Program (DVP). Addressing a packed crowd at the A*STAR Biopolis complex, he gave a public lecture on the recent progress in induced pluripotent stem (iPS) cell research.
But where the goodies were to be found was at a smaller 13-member session, also held at the Biopolis complex, where Dr. Yamanaka spoke candidly with budding young scientists and junior faculty.
Indeed, to have received science’s highest honors so soon in his career, the 50-year-old Japanese orthopedic surgeon and scientist may also feel youthful in comparison to his peers.
The audience asked the requisite stem cell questions, ranging from what type of diseases are best studied using iPSC technologies, to the statistical relevance of iPSC banked samples. Other participants were interested in the advent of personalized iPSC banking, akin to cord blood banking for infants.
As the group warmed up to Dr. Yamanaka, they started asking more probing, personal questions. It is easy to learn about Dr. Yamanaka’s science breakthroughs from the troves of publicly accessible information, ranging from his Nobel Prize acceptance speech to his many high impact publications. More difficult, however, was to understand the man behind the discoveries, his early career, the difficulties he faced, and what inspires him.
Given his gentle and quiet demeanor, it remained to be seen how much Dr. Yamanaka would reveal about himself, but the crowd was persistent.
Yamanaka’s early career
The audience asked Dr. Yamanaka to tell the story about his early scientific career. Did he start out knowing that he was going to become a scientist, and were there any detours involved?
Twice, said Dr. Yamanaka, with a chuckle.
“First of all I started as a surgeon, as I didn’t think I would do science. But for many reasons I became a scientist and I went to the States to do my post-doc training.
“I wanted to study atherosclerosis – something very different from what I am doing now. At that time in San Francisco I worked on a gene that we thought was important in atherosclerosis. We made a plasmid overexpressing that gene, hoping that that gene could make mice resistant to atherosclerosis, and to use that gene in gene therapy for familial atherosclerosis or hypercholesterolemia, which is very common in the States. But it turned out that that gene is an active oncogene, so we should not use that gene in gene therapy.
“I got very interested in how that gene could cause cancer, so I switched my topic from atherosclerosis to cancer. I went back to Japan and I made two mouse lines, hoping that I would see some tumor formation. But I found that both mice lines were embryonic lethal, and it turned out that the gene is important in mouse development and in mouse embryonic stem cells. So I had to change my topic again from cancer to stem cells.
“I think that to me, that kind of ‘unexpected result’ was very lucky, because I could start something very unique which other people did not think of, because it is a totally unexpected result. So it happened twice,” he said.
Elaborating further on the importance of serendipity, Dr. Yamanaka stressed that scientists must trust their own instincts and follow up on unexpected results in the lab.
“At least for me, it is hard for me to think of something very unique, because of the Internet, Google, we all have the same information, and we can all think of many ideas based on the same information. In this situation, it is extremely difficult – at least for me – to think of something very unique. Whatever I think, someone else is already thinking about.
“But if you do some experiments, and you do see some very unexpected results, that’s a purest chance to start something very new, something very unusual, something others cannot think of, because it is only you who knows that unexpected result.
“So one advice I can make is to respect your own result, and when something bad happens, and something unexpected happens, don’t be disappointed. It could be a very good chance,” he said.
PAD: Post America Depression
A member of the audience who was soon to start a tenure-track faculty position asked Dr. Yamanaka what was the biggest challenge he faced as a junior tenure-track professor.
“I had many difficulties. My first crisis in my scientific career was when I went back to Japan from San Francisco. In San Francisco, I had a great time, I had an unexpected result, and I was excited that I found a new gene. I was very happy. But after I went back to Japan I suffered from so-called PAD – Post America Depression. At that time, the scientific environment in the States was much better than in Japan.
“In Japan I couldn’t get good funding, I couldn’t get good support from other scientists, and so because of those reasons I suffered from PAD. I was about to escape from science; I was about to go back to the clinic.
“But I survived that crisis. I am very lucky that I was able to get my own laboratory in Japan. Then, I started my new lab – I got three new students – but in the first three years I couldn’t publish any new papers because I started something new. So that was another tough period.
“After five years, I expected to be promoted and to move to somewhere else, so that meant I had to get good results in five years, but in the first three years I could not publish any papers,” he mused.
Reflecting on the ‘mistakes’ he made in his early career, Dr. Yamanaka cautioned junior professors against trying to avoid mistakes and sticking to the tried and tested path. Mistakes are part and parcel of the discovery process, he said.
“I don’t think I made mistakes, but we tend to do something very easy like just repeating somebody else’s work just to publish something. If I did that, it must have been my biggest mistake.”
The start-up phase is also the hardest, said Dr. Yamanaka.
“I survived those initial three years… it is tough to have a new lab. It is not easy, but it is not easy for everybody. You have to know that. Sometimes we tend to think that we have the most difficult situation, but it is usually not the case.”
A member of the audience who said he was also suffering from ‘Post America Depression’ asked Dr. Yamanaka what did he do to help improve the research environment in Japan.
“The scientific environment in Japan is much better now than 15 years ago, when I came back. However, I think that it is essential to keep good connections to the States, because it is still clearly the center of science. Most of the scientific papers are in the States and many new developments, new equipment, are being developed in the States. For me, it is essential to have good connections with the US, to keep me updated and also keep me motivated,” he said.
To close the session, a member of the audience asked Dr. Yamanaka where he derived his inspiration from.
“To me, running is a way to make my brain light, so whenever I am running, I don’t think anything at all about science. Usually, I listen to music, the birds, the river, so that I can empty my brain.
“Some people say that you must be having some good ideas when you are running. In my case it is when I am taking a shower that I think of something exciting and new,” he replied to a bemused audience.
And with that candid ‘shower’ revelation, Dr. Yamanaka wrapped up a very open conversation with the young audience, who were clearly inspired to be in the presence of the humble and soft-spoken laureate. After a photo-taking session, Dr. Yamanaka said his goodbyes, jetting off to somewhere in the world to conquer another scientific challenge in his unfinished scientific story.
Copyright: Asian Scientist Magazine.
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