June 1, 2020

The Niche

Knoepfler lab stem cell blog

Interview with Dr. Teru Wakayama on STAP stem cells

Talking with Dr. Teruhiko Wakayama on the STAP stem cell situation.
Talking with Dr. Teruhiko Wakayama on the STAP stem cell situation.

I asked Dr. Teruhiko Wakayama, who goes by Teru to those who know him, if he would be willing to do a Q&A on the STAP stem cell situation.

Teru was senior author on the STAP stem cell Nature letter on chimerism, but was not a senior (note this is a correction from an earlier version of this post) author on the other STAP paper, the Nature article on the production of STAP stem cells.

Teru kindly agreed to my invitation. He responded straightforwardly to what I thought were direct and sometimes tough questions. He also lays out a reasonable plan for STAP looking to the future. Thank you, Teru.

To me his answers reflect his great reputation as both a scientist and person. Teru is a true good citizen of the stem cell field. Teru is what I would call a “mensch”.  I fully support Teru’s proposal that we give STAP stem cells a year to be reproduced.

Here’s the interview.

1. How did the STAP stem cell collaboration begin between the Vacanti lab and your group? What made you decide to team up with them? Can you please tell us more about the beginnings of this research?

Teru: Dr. Kojima (Vacanti’s lab) contacted me by e-mail to help with chimera experiments. At that time, the project looks very much impossible. That’s why I accepted. I like such impossible experiments.

First time, Dr. Obokata brought strange cells, and there was no chimera after blastocyst injection. However, nearly 2 year later, Dr. Obokata found a very good method to generate STAP cell. Then, we could obtain good chimera.

2. Have you talked to Drs. Vacanti and Obokata recently? How did that talk go? If they are not talking, why is that so?

Teru: I have not talked to Dr. Vacanti.

I had a talk with Dr. Obokata, but in Japan, the main problem is, not reproducibility, it is the mistakes of picture or band. Now RIKEN and outside people investigate that problem. But she said that in her lab, she can create STAP cell.

3. What is your own level of confidence in STAP cells at this point? Are you getting more concerned?

Teru: Before I left RIKEN, I succeeded to make STAP cell from spleen. But only 1 time. At that time, Dr. Obokata taught me very well.

Now, some of my friends (not Japan) sent me e-mails, which, reported partial success (Oct expression only). Therefore I believe that within one year, someone will publish about STAP generation.

4. Like most people, I am convinced that the mouse studies on STAP are solid and convincing. You personally have a top-notch reputation as a scientist around the world. People are instead more specifically concerned about the STAP stem cells themselves. One of the most common questions I am getting asked at this point is this–could the STAP cells have been contaminated with either mESCs or mouse iPS cells? Is that possible? How might that have happened?

Teru: Thank you for your comment.

I established STAP-SC several times from STAP. It is unlikely that  contamination would always have happened. In addition, we established STAP-SC from 129B6GFP mice. At that time, we did not have this strain ES cell.

When I succeeded to establish STAP-SC, the original STAP cells expressed Oct4-GFP very much. In this condition, the establishment is much easier than ES cell establishment from blastocyst.

In addition, whole mRNA expression data suggest that STAP-SC are not ES cell.

5. You mentioned that STAP stem cell is not working in your new lab. Why do you think that might be in terms of the methods? What is different now? Also, you mentioned that STAP worked for you when you were at RIKEN. Can you please be a bit more specific? Did you do 100% of the steps in the STAP induction yourself? Again, could iPS cells or ES cells somehow have gotten into the culture?

Teru: I just learned one time from Dr. Obokata, then left RIKEN.

Do you know when we moved to a different lab in the past, how difficult it was then to reproduce even my own techniques? When I moved from Hawaii to Rockefeller, I spent half a year to reproduce cloned mice. This is my technique, but I still needed a lot of time. However, the method of STAP generation is not my technique, therefore, different lab and not my discovered techniques, so this is understandably more difficult to reproduce again.

I did 100% by myself, but each step was looked by Dr. Obokata. Much the same, one of my PhD student also succeeded to establish STAP-SC.

In those early stages of the experiment, we did not culture ES cell nor iPS cell at same time. After that, as control, we sometimes culture ES cell at same time.

6.  Many people are trying the STAP method around the world and getting frustrated because it isn’t working. I know there is a methods paper in the works, but given how important this is would you consider putting a detailed step-by-step protocol out to the scientific community right now? For example, I’d be happy to post it on my blog and it would have no effect on the publication of a methods paper in a journal. This might really help people to get it to work. Waiting a month or two for a methods paper to come out might be too late.

Teru: Yes, now RIKEN will soon publish the detailed method. I contributed chimera and to establishment. However, chimera and establishment is usual protocol, not specific, because it is the same or more easier than ES cell. Unfortunately, now all responsibility is in RIKEN, and I left RIKEN. Although I want to know but I do not know now.

Finally–Do you have any other questions or concerns that I did not ask but that you want to address? If so please add more.

Teru:  I do not escape. Because in my results everything is true. However, it is going to take time to reproduce the new technique. For example, the first cloned animal, Dolly, wasn’t reproduced for one and half years after it was published. Human cloned ES cell paper has still not yet been reproduced. Therefore, please wait at least one year. I believe that during this period someone or myself will success to reproduce it.

Note: At his request, I have made a scattering of small corrections to Teru’s answers just for a few typos/spelling/grammar issues since English is not his first language, but I did not change in any way the tone or significant content of his answers.

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