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Podcast Interview: James Thomson
James Thomson is Director of Regenerative Biology at the Morgridge Institute for Research and
John D. MacArthur Professor at the University of Wisconsin School of Medicine and Public
Health, and Adjunct Professor in the Department of Molecular, Cellular, and Developmental
Biology at the University of California, Santa Barbara. He recently spoke with PNAS about his
research from his lab at the University of Wisconsin in Madison.
Hello and welcome again to Science Sessions. I’m Jonathan Lifland. Today we’ll meet with
James Thomson, a developmental biologist and stem cell pioneer. We’ll speak with Dr. Thomson
about his research and his recent election to the National Academy of Sciences.
Question: Thank you for being with us. Can you tell us, why are stem cells important?
Thomson: Well, for embryonic stem cells and these new pluripotent stem cells, there has been a
tremendous amount of hype about them being used as therapeutics, actually to make a cell and
use them for transplantation. I think that’s been exaggerated. I believe it’s going to be
tremendously hard to use these cells as therapeutics. There will be some examples where it is
successful, but they are going to be few and far between.
Nonetheless, there is going to be a huge impact in biomedical research, because these cells are a
broadly enabling research tool. It means for the very first time that scientists will have access to
all the basic building blocks in the human body. There are cells in your body, like heart cells,
which scientists basically can’t study, because they don’t divide in tissue culture. And if you
have a heart donor, they go right into a transplant program. So there has been no way to test
drugs on human heart cells before. It’s basically impossible. So this opens up the door so that
everything that makes up our bodies is available for study in the laboratory. This will profoundly
change our understanding of the human body and will lead to medical developments that have
absolutely nothing to do with transplantation biology.
I think there are tremendous parallels with the early days of recombinant DNA. People did not
appreciate how broadly enabling a research tool it was, and people also thought that something
like gene therapy would be pretty easy. If you think about what’s happened in about the last 30
years, recombinant DNA has completely changed our lives in biomedical research and how
medicine is practiced. Yet gene therapy is only starting to be successful. It’s been much harder
than people thought. I think there are going to be profound parallels between the trajectory of
these pluripotent stem cells, which people are saying that transplantation of these cells will be
easy, and the under appreciation of how broadly important the research tool is going to be.
Question: Can you tell us about your research?
Thomson: My basic interest is in what makes one cell a pluripotent cell, and that’s a cell that
can make everything, where most cells in your body don’t want to do that. How they choose to
become themselves again, which is called self-renewal, versus how they choose to become the
individual cell types that they become.

More broadly, I’m interested in what imparts a cell’s identity: why is your liver cell a liver cell
and your heart cell a heart cell, and why are they normally really stable? Why are they in those
conditions for life in most cases? Can we change that cell identity? That was the surprising thing
with induced pluripotent cells, it turns out that you can change cells’ identity with a relatively
small manipulation of just a few factors. I think you’ll find in the future that there will be a lot of
examples of cells changing identity, not back to a ground state, not back to the pluripotent state,
but between different cell types in the body.
Question: Are there any instances where what you have seen has surprised you?
Thomson: I guess the biggest surprise for the field, and in my lab also, is reprogramming. Dolly
[the sheep] was cloned about a year before—or at least the publication was a year before—
human embryonic stem cells were published by my lab. The two are already paired in the public
imagination from that early time. The message from Dolly was not that you can clone sheep, and
it was not that you could do somatic cell nuclear transfers and make an embryonic stem cell, it
was that transfecting stuff could reprogram an adult cell into an embryonic cell. It was only a
matter of time before people would identify that transfecting stuff. The surprise was that it
wasn’t as complicated as everybody thought. I would have guessed that it was 50-100 factors,
and it turns out that 2-4 is sufficient. But the bottom line is that a very small number of factors
can completely change the developmental state of a cell. That was unanticipated.
Question: How and why do stem cells choose to differentiate into different types of cells?
Thomson: Basically, cells talk to each other through external signaling molecules, the things
that diffuse between cells or which are linked to the cell surface, and depending on how those
signals are emitted and received, cells can turn into new cells. So for stem cells in tissue culture
dishes, we can look at all that developmental biology and say, what growth factor does this in a
normal embryo, and we can try that in a tissue culture dish, and often they are the same
molecules that can do the same thing.
Question: How do you feel to be elected into the National Academy of Sciences?
Thomson: It’s a good feeling. It means that you’re publicly accepted. An awful lot of what has
driven the publicity in stem cell research is hype, but it certainly means more to be accepted by
your peers and recognized by your peers, so it’s a big deal.
Question: Thank you very much for your time.
James Thomson is the director of regenerative biology at the Morgridge Institute for Research
and the John D. MacArthur professor at the University of Wisconsin School of Medicine and
Public Health. He was elected to the National Academy of Sciences in 2008.