Has your life in the lab changed significantly since you made your major discoveries?
Shinya Yamanaka: Of course we are getting a lot of e-mails and phone calls, first of all from patients, and from many press people. We can spend very limited time on science and it isn't good. We really have to go back to science because this technology is not mature enough. There are many things we still have to overcome before we can apply this technology to clinics.
Have the restrictions on ES cell research caused scientists to leave the United States?
Shinya Yamanaka: Well, that's what I heard. Some people moved to the UK and some people moved to Singapore because of the difficulties of working on ES cells. But now we have iPS cells, I think that problem has been overcome. Hopefully many scientists will come back to the States.
In San Francisco you're working at the University of California and the Gladstone Institute of Cardiac Disease. What are your goals in attaching yourself to these institutions?
Shinya Yamanaka: The Gladstone Institute has a strong, strong research project in the three major diseases in the States and in the world. That is, cardiovascular disease, neural disease and HIV. I believe that our technology, iPS cell technology, can be used in all three of those areas of human disease. I already have a strong collaboration with many, many scientists at Gladstone.
Where do you think these developments will take science in the short-term, maybe the next five years or so at UCSF?
Shinya Yamanaka: In the next five years, I think scientists will make iPS cells from many patients so that they can study the cause of diseases more extensively, and so that they can search for more effective drugs. I think that will happen in the next three, four, five years.
We'd like to ask you about Ian Wilmut, who's also an Academy member, best known for his achievement cloning a sheep, Dolly, from a single adult sheep cell. Because of your breakthrough, he's changing the direction of his work. Would you like to comment on this?
Shinya Yamanaka: Yes. Dr. Wilmut showed that somatic cells, like skin cells, can be reprogrammed. That was the beginning of my project. From his achievement, I learned that eggs -- human or mouse eggs -- can be programmed from skin cells. From his success I thought that there must be some factors within the egg that can reprogram somatic skin cells, and I decided to search for such reprogramming factors.
Was it difficult to gain access to eggs for research? They were in limited supply.
Shinya Yamanaka: Yes. If I had to use eggs, it would have been more difficult, but another scientist in Japan saw that not only eggs, but also ES cells themselves can be programmed skin cells. So from his success, I learned that I didn't have to use eggs. Instead I can use ES cells, and ES cells are much easier to handle.
Did you have a lot of collaboration with Dr. Wilmut before your breakthrough?
Shinya Yamanaka: Actually no. We have been talking about future collaboration and it's been great fun.
What do you hope to achieve, working with Dr. Wilmut?
Shinya Yamanaka: By collaborating with him, we can make iPS cells from various patients who are not so common in Japan or in San Francisco. So we can enlarge our project by collaborating with many scientists including Dr. Ian Wilmut.
Wasn't it significant that Dr. Wilmut decided not to renew the permission he'd been granted for working with embryonic stem cells?
Shinya Yamanaka: I didn't expect such a rapid decision, because he kind of gave up doing cloning anymore. But I think this technology is still very young. There are many problems which we have to overcome. So I think we still have to study nuclear cloning, nuclear transfer. So I was very surprised to hear that he decided to stop doing any cloning experiments.
Have you talked with him about why he decided that, and why it was so quick?
Shinya Yamanaka: I did talk to him about that, but I forgot the real reason. Maybe he didn't tell me the real reason, but I can imagine it would be very difficult for a scientist like him, who studied for a new project, to say that, "I'm going to stop this." So I think he's, in a sense, very brave, and I admire him so much. And that's a good lesson for me too. Since this technology is still very young, iPS cell technology is very young, I may have to do the same thing in the future. If some other method comes up, and which, if it's much better then iPS cell technology, I think I should be brave enough to say that we should not continue iPS cell technology. Instead we should do this new technology. I hope I will be brave enough like Dr. Wilmut.
Can you talk about some of the problems of iPS? Because it is so young, there is so much that's not understood.
Shinya Yamanaka: The biggest problem is a safety issue. ES cells are derived from embryos, and embryos are pluripotent from the beginning. By contrast, iPS cells are derived from skin cells or other types of somatic cells and those cells are not really potent anymore. We have to put three or four genes into skin cells in order to convert or in order to induce pluripotency. It's kind of a de-differentiation, and de-differentiation is a common feature between deprogramming and cancer. So what I'm really afraid of is that the technology we're doing now is not only making iPS cells, but also making tumor cells. So we really have to double-check the safety, safeness of iPS cells we generated by our method. Because in the future, we want to use these iPS cells in regenerative medicine, that means we would like to transplant iPS cells -- derived cardiac cells or neural cells -- into patients. So that kind of safety issue is crucial.