An interview with Marie Csete, new chief scientific officer of the California Institute of Regenerative Medicine
The California Institute of Regenerative Medicine (CIRM) recently hired Marie Csete as chief scientific officer. Previously, she directed the Human Embryonic Stem Cell Core Facility at Emory University in Atlanta, Georgia, where she also directed the liver transplant anesthesiology group. Nature Reports Stem Cells spoke with her in her first week of the new job.
Embryonic stem cells and anaesthesiology don't seem to have much to do with each other.
I did a very unusual course to get an MD/PhD. I was a practicing MD for a long time, and I had a year's sabbatical at University of California at Los Angeles and went off to Caltech, and then I got very invested in what I was doing and got a PhD quite late in life in what was basically stem-cell biology.
When I was involved in the MD/PhD directorship at Emory, I always said don't do what I did and have a clinical life that seems so separate from your basic science life. But as we are moving stem cells toward clinical therapies, I think that not only the ethical struggles that solid organ transplantation went through but also some of the scientific issues it had to solve should be lessons for us in cell therapies. So it might turn out to be a relatively good background after all.
Your predecessor Arlene Chiu had a basic science background. How will your role be different? [Csete whispers “fantastic” at Arlene Chiu's name.]
I really think we're getting awfully close to working with patients now. Marie Csete
I really think that we're getting awfully close to working with patients now. We will never institutionally neglect basic science, but the shift to translational work is definitely now a priority, so having an experienced, critical-care clinician in a position of authority here is an important part of why I was hired.
Can you outline your safety concerns with cell therapies?
The unknown is that we have no control over the cells once they're transplanted or transfused. I feel very strongly that the animal models of disease do not reflect the heterogeneity of the environments into which we will be putting the cells in diseased humans. Pharmacologically induced Parkinson's disease is not the same as the natural human disease, for example.
In solid transplants, you can go in and take a biopsy and get a sense of what's going on. Because we will be giving cells infused into the circulation, for example, we won't have that option. So the inability to directly follow the cells is an issue.
The immunogenicity issue of the transferred cells is far from solved. People are also concerned about tumorigenesis, and there's been a lot of in vitro progress in addressing that.
Those are the main things that people talk about. I am also concerned that we address compatibility of the cells with drugs taken by patients with the disease that we're targeting. So if we're giving someone cell therapy for cardiovascular disease, we'd better know a little bit about what these cells can tolerate in terms of the common drugs that the patients are on.
What about induced pluripotent stem cells (iPS cells)?
From my perspective they are incredibly exciting because they give a lot of people wider access to cells that can help them work out many of the thorny issues of in vitro human embryonic stem-cell (ES cell) biology. In terms of safety, however, iPS cells are much further from the clinic than are ES cells.
Some people object to having such a large amount of funds that must be dedicated to stem cells and not to other fields.
But I think people underestimate how expensive this research is. Yes, it's a lot of money, but it's certainly not unlimited. We have to figure out a way to be involved in clinical trials, and how best to use our resources in clinical trials. So it's important who we partner with, how we keep the money in California, how we envision clinical trials in terms of their feasibility and their generalizability to other areas of the trial itself. We are struggling with all those issues at the moment. We've got to make concrete decisions, at least as far as phase I trials, in the next couple of months.
What do you hope to accomplish in the first six months?
Even though I have some insight into CIRM as a member of the working group that evaluated grant proposals, there's a lot to learn. You see those books? [Csete gestures to a four-foot long shelf full of binders from governing board meetings and says more are hidden in drawers.] I really have to get through some of the policy issues. You don't just forge ahead without understanding the history.
I need to review where our funded investigators are, so that I'm able to do the kind of matchmaking that I think is necessary in this position. Putting together our scientists in Davis who are generating results with our scientists in San Diego who should know about them — that's an important thing for me to do.
DARPA is supposed to be really good at that.
DARPA is also really good at setting up milestones, which I think scientists aren't so comfortable with. But as we move to clinical work we're going to have to be more comfortable with it.
How will you make them more comfortable?
A lot of it will be how we structure the RFAs (requests for applications) so that they know how much time they will have to do X, and what the nature of the results have to be before they can proceed to the next step. It's not been so imposed on people before, but we have talked about it and we think this is good stewardship of the resources.
What are your biggest hopes and fears for this job?
My biggest hope is that I'll make a difference in some way. The fears are that all the decisions are made under an incredible public microscope. Scientists are used to having their arguments be quite anonymous, at both peer-review and grants level, and for most of science that's a very healthy thing. We have to have our arguments quite public because we are a state agency. It's going to take a bit of getting used to. In the end, it's going to be a great thing. Of course, when you're the bacterium under the microscope, it may not feel like it.
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Baker, M. Prepping stem cells for the clinic. Nat Rep Stem Cells (2008). https://doi.org/10.1038/stemcells.2008.59