Column

Column

How the important people view?

To lead iPS cell research for clinical applications (2) -All 2 episodes-

Dr. Masayo Takahashi

Interviewer :
You often give lectures for patients and the general public, and provide them with logical and detailed explanations about this treatment and clinical research. I hear that many patients look forward to your lectures. It seems that it is important to have close communication with these people in order to put the new treatment into clinical practice.

Takahashi :
When we conduct clinical trials in Japan, it is essential to obtain social consensus from the general public. How to see and deal with treatments involving risks? It seems that the idea of risk-benefit balance has not yet taken root in Japan, It is the point that I am most afraid of. It is possible that, after 30 years, I will be taken for a criminal.

Interviewer :
What do you mean?

Dr. Masayo Takahashi

Takahashi :
When we begin to try the new treatment in patients, we will have no problem in the first 10 cases. At this scale, we will be able to monitor the situation and have trust relationship with the patients. However, when the treatment is used more widely, there will be many unexpected problems. In such cases, somebody may sue me.
I made a survey on the contents of newspaper articles dealing with cases of drug-induced sufferings in the past. I found that there was no article mentioning the benefits of the drug in question, and all articles are mentioning the risks. Readers cannot make a judgment when they read such articles. They are not allowed to compare the benefits and risks. It is very scary to use the new treatment in such a situation. We have to make up our mind to do it in Japan

Interviewer :
If something bad happens, benefits are likely to be forgotten. Maybe patients are expecting too much.

Takahashi :
There is a gap between expectations and results. If patients are worried about unfavorable results, they should not choose the treatment. I have long been trying to explain the current situation of development of the treatment on the occasion of meetings with patient associations to fill the gap.
However, the problem is probably that nobody has organized occasions for discussing the balance of risks and benefits. It is understandable that the greater the criticism from the general public is, the more the government is afraid of risks, and this may result in tighter regulations. I hope the media will play a role in improving this situation and promoting regenerative medicine.

Interviewer :
It is quite natural that patients, for whom no other treatment is available, have great hopes for the treatment.

Takahashi :
Why they do so may be that eye diseases, including retinal diseases, have been left behind in Japanese medicine. Some patients with pigmentary degeneration of the retina (PDR) are glad when they only find the name of this intractable disease in the newspaper, feeling that they are not forgotten.
Visual disorders are very poorly understood in the Japanese society. When I have an opportunity to give a presentation at a symposium, I always emphasize the importance of understanding visual disorders. Patients with visual disorders are not simply divided into those who can see and those who cannot. What means "difficult to see" is not well understood. In fact, some patients who walk with a white cane have an eyesight of 1.0. Such patients have good eyesights, but can hardly walk because they have a narrowed vision. Patients with AMD cannot read letters but spend normal lives, and other people often do not understand that they have a disease. There seem to be many cases in which the patients unreasonably lose opportunities for work.
Pharmaceutical companies were not very interested in eye diseases. The number of AMD patients is equivalent to that of patients with a certain cancer. There are several tens of drug types and many treatment methods for cancers, while only two types of drug were finally launched on the market for AMD five years ago. These drugs, that are very effective, had a great success soon after their launch, and have been bringing a great amount of sale to their manufacturers. There are not many pharmaceutical companies in the world who understand eye diseases well, and, hence, patients with visual disorder are given little opportunity to enjoy benefits of scientific progress. They are left behind as far as drugs are concerned. It is said that there are two million patients with visual disorder in Japan.

Interviewer :
There are other diseases responsible for visual disorders, including glaucoma and diabetic retinopathy, and the number of patients with each of these two diseases is larger that that of PDR.

Takahashi :
The leading cause is glaucoma, second is retinopathy and third is PDR. The number of patients with PDR is approximately 30,000, whereas the numbers of patients with glaucoma and diabetic retinopathy are respectively ten times that with PDR. There are much more patients with these diseases in number, but among these patients only those who have been diagnosed with the diseases at a too advanced stage or those who have omitted receiving a treatment go to develop visual disorders. Therefore, for glaucoma and retinopathy, promoting awareness and prevention is much more effective than spending tens of billions of yen to develop a new treatment. Of course, there are many treatments available for these diseases.
On the other hand, there is no sufficient treatment for PRD and AMD and, hence, world ophthalmologists are working hard to develop a treatment. It is said that, in developed countries, 80% or more of the causes of visual disorders are found in retina. Kyoto University, from which I graduated, is good at treating retina. It is Kyoto University who performed the first retinal detachment surgery in Asia.

Interviewer :
When and where did you start to think of treating retina with stem cells?

Takahashi :
It was when I was studying at the Salk Institute in the US. I was there when the world's second neural stem cells were generated and I understood what the nature of stem cells was. I am an ophthalmologist and when I saw neural stem cells, an idea came up to my mind that these cells were to be used for retinal treatments. Most researchers around me were studying the brain, and were not interested in the retina, which means I had no competitors. At that moment, I was almost sure that it would be easier to treat retinal diseases than brain diseases with stem cells. And this led me to take up for the first time in the world an idea of using stem cells in retinal treatments. I had an opportunity there to be in contact with scientists working in a different field, and it was good for me.
After returning to Kyoto, I was working on retinal treatments using neural stem cells. Neural stem cells are somatic stem cells and it is difficult to grow them in culture to a large number. They often lose their original characteristics during the course of culture to give different cells when they reach a certain number. So I thought it would be difficult to continue this work with somatic stem cells, and came to use ES cells that are able to differentiate in any type of cells without difficulty.. In the field of ES cells, Dr. Sasai Yoshiki at RIKEN, a former classmate of mine, was doing interesting studies and trying to build a brain. I asked him to give advice to me and we jointly succeeded in generating retinal cells from human ES cells for the first time in the world.
What I learned at the Salk Institute was that "if I want to work with somebody, I have to choose a first-class scientist as a partner". It is not a large institute, but there were many Nobel Prize winners. There are specialists of gene therapy, and if I work with these specialists, we will complete a research project in 6 months, while it will take 2 years to complete the same project if we do it in a group of ophthalmologists alone. I realized the importance of working with specialists in different fields. After returning to Japan, I had an opportunity to work with Dr, Sasai, one of the leading scientists in this field, and this joint work led to our success.

Interviewer :
However, you never tried to study clinical applications of these cells before the advent of human iPS cells.

Takahashi :
Patients with AMD have a loss of vision only at the center of their visual field, and they are old. One reason was that I was not sure if a treatment including administration of an immunosuppressant would be appropriate for such patients. In addition, at that time, everyone thought human ES cells could not be used for treatment, and I hesitated to use them. In such a situation, I did not publish my experimental data. When we culture pigment epithelial cells derived from human ES cells, the cells look like black dots. There might be other scientists who also saw this phenomenon, but nobody thought these cells could be used for treatment. When I saw such black dots around 2001, I was convinced that they would be the first human ES cell derived tissue cells that could be used for treatment.
When iPS cells were generated after a while, we understood that we would not have any problem of immune rejection with iPS cells, and recommenced our research. Subsequently to our team, some research teams in the US began to create retinas from human ES cells. These teams, supported by private companies, were able to continue their research despite various opinions around them, and have already started clinical trials.
We were sure that we would obtain favorable results with human ES cells, but we did not continue our research to develop a treatment. I regret a little about this now. I have repeatedly been calling for participation of private companies, but no company has answered to it. As for iPS cells, however, we have continued our research without hesitation, even if iPS cells are said to have risks, and this has led us to the present stage.. In fact, the situation has changed since 5 years and there are now some companies who are interested in our research.

Dr. Masayo Takahashi

Interviewer :
Recently, there are more and more female researchers, but not many who become a leader are still few.

Takahashi :
That is true. When I am invited to give a presentation at a symposium, I am always the only female speaker among many. Women may tend to be unwilling to lead others. To work as a researcher is a good choice of occupation for women. I am sure they can continue as long as they are prepared for any situations, such as having children. I wanted to continue my research and to have children, so I chose to be an ophthalmologist. However, it is difficult for me to do both research and housework at satisfactory levels, and in this sense I have some pain. You have to be prepared for this situation, if not you have to save your work.

Interviewer :
I guess your husband is also supporting you.

Takahashi :
Yes, he is. That is the greatest support.


Interviewer :
Furugori Etsuko
Interview date : February 18, 2011

  1. 1
  2. 2

Dr. Masayo Takahashi

Physician, Doctor of Medicine, and team leader at the Laboratory for Retinal Regeneration, Center for Developmental Biology, RIKEN (the Institute of Physical and Chemical Research).

1986 : Graduated from the School of Medicine, Kyoto University
1986 : Medical intern at the Department of Ophthalmology, the School of Medicine, Kyoto University
1987 : Physician in Kansai Electric Power Hospital
1988 : Student of the Doctoral course in ophthalmology and visual science at the Graduate School of Medicine, Kyoto University
1992 : Assistant at the Department of Ophthalmology, the School of Medicine, Kyoto University
1995 : Research fellow at the Salk Institute, USA
1997 : Assistant at the Department of Ophthalmology, the School of Medicine, Kyoto University
2001 : Assistant Professor at the Department of Experimental Therapeutics, Translational Research Center, Kyoto University Hospital(leader of the Retinal Regeneration Project)
2006 : Team leader at RIKEN (the Institute of Physical and Chemical Research) Kobe Institute October 2006 : Team leader at the Laboratory for Retinal Regeneration, Center for Developmental Biology, RIKEN; Part-time physician at the Department of Ophthalmology, Kobe City Center General Hospital
2008 : Visiting Vice Director at the Department of Ophthalmology, Institute of Biomedical Research and Innovation hospital (concurrent post); Leader of the Visual Regeneration Research Group at the Institute of Biomedical Research and Innovation laboratory
2009 : Visiting Associate Professor for courses of advanced international medicine at the Graduate School of Medicine, Kyoto University
January 2010 : Visiting Professor in the Center for iPS Cell Research and Application (CiRA), Kyoto University (concurrent post)

References

Movie

See more

Page top

Movie

Movie

  • MEXT
  • Japan Science and Technology Agency
Page top