Reverting cells to their embryonic state, without the embryos


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.

Yamanaka’s 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. On Nov. 10 he received the $610,000 Kyoto Prize, which recognizes “significant contributions to the betterment of humankind,” for his stem cell work. He has also won the Albert Lasker Basic Medical Research Award, the Shaw Prize and the Robert Koch Prize. He recently spoke with The Times.

What prompted you to start working on iPS cells?


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.

What advantages do iPS cells have over embryonic stem cells?

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.

Do they have any disadvantages?

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.

What is the long-term potential of these cells?


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.

What surprised you most about your research as it unfolded?

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.

What are the primary scientific hurdles that remain with iPS cells?

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.

In the United States, the first clinical trial involving a therapy derived from human embryonic stem cells has just gotten underway. How do you feel about the pace of translating research into actual treatments?


The clinical trial using embryonic stem cells took a long time partly because use of the cells has caused an ethical controversy around the world. It is also true that it generally takes many years to turn basic research into clinical applications.

Some question why human embryonic stem cell research should continue when your discovery allows scientists to generate similar cells without destroying human embryos. What do you think?

Embryonic stem cells are still important for the development of iPS cell research. Findings from research on embryonic stem cells, such as methods to create various types of cells, have been applied to iPS cell research. That’s why iPS cell research has evolved so rapidly. In addition, embryonic stem cells are used as control [comparison] materials when researchers conduct experiments on iPS cells and analyze their quality.

Many people speculate that you will win a Nobel Prize one day. Does that make it hard to get your work done?

I know some people have high expectations, but my concern is not thinking about winning a Nobel Prize. I worry about what I should do to bring iPS cell technology from the laboratory to the bedside as soon as possible.


This interview was edited for clarity and space.