ISSCR President Sean Morrison on challenges and future of stem cell field

Sean Morrison M.D.I recently chatted with Sean Morrison, current President of ISSCR, on his goals for the Society, where the stem cell field stands today, top challenges, and the future.

What are your goals for your tenure as President of ISSCR?

SM: ISSCR is the international voice for research in the scientific community. There’s been less effort though amongst policy makers and the general public. I want to expand the reach beyond just the scientists. ISSCR will be building its capacity to participate in stem cell policy issues worldwide and also it’s capacity to communicate with the public.

What’s the plan to make this happen?

SM: A range of things. Beefing up ISSCR communications programs. Blogging, twitter and other efforts.

What are the main challenges & opportunities that ISSCR faces now?

SM: ISSCR has had steady and remarkable growth. It has grown and its scope has grown too. Managing the growth is a challenge. Prioritizing future opportunities. How can we have the most impact for the membership? How can we grow that impact? The annual meeting continues to grow. International ISSCR symposia have grown. Publishing activities have expanded including with Cell Stem Cell and now Stem Cell Reports. We continue to expand those kinds of activities. There is a set of opportunities related to going beyond the science. Our mission is to improve human health through stem cells. We can’t do that solely by meetings and publishing. Those are critical core activities, but there’s more that we can do such as in industry. Reaching out to those stakeholders. Expanding the activities of the Global Advisory Council (philanthropists, Susan Lim, and Deepak), stem cell policy, and communication.

How can ISSCR bring in more industry people?

SM: I do think more involvement of industry is important. How best can we do that? I attended the Industry Committee meeting at ISSCR meeting in Stockholm, where we had that conversation. I really do hope that we can increase the attractiveness and value provided by the annual meeting to people in industry. We want people talking about exciting unpublished data. One difficulty comes up though in this regard: who from industry is willing to talk about unpublished data? Some people have shown up in the past and are not willing to talk about data. The program committee needs to address that.

What’s your view on the evolution of the IPSC subfield?

SM: I’m excited about stem cells generally. We need all kinds of stem cell research to move forward. Historically we’ve not been very good at predicting which cell type will work. I’m very excited about somatic stem cell research and pluripotent stem cells, both embryonic and IPSC. Look at the things going on at Shinya’s institute. They’ve been bold at diverse ways that they can have impact. With each year that goes by, the more plausible scenarios arise for possible therapies using pluripotent stem cells.

The pioneering IPSC trial in Japan was put on hold. How serious is that?

SM: If you’ve been culturing cells, some of the time there’s going to be mutations. The fact that they found the mutations says that the process that they have in place worked. It’s not uncommon in clinical trials for things to go on hold. It’s not unique to stem cell trials or IPSCs. I have every expectation that they’ll get that back on track. 

What are you most excited about with your own research?

SM: We’re doing a lot of work to characterize the HSC niche. We’ve now identified the cells that are sources of the key factors for stem cell maintenance. In many ways the hematopoietic system is a paradigm. This will allow us to understand at a single cell level how the niche works and look for novel growth factors. Each time we identify one of those it has the potential to provide new tools.

What do you see as the most important and exciting stem cell development or trend of 2015 so far?

SM: We’re at an inflection point in terms of stem cell therapies moving into high-quality clinical trials. In 2008 when we were fighting the public policy battles about where the line should be drawn on ESC research. Also there were people making claims about difficult problems. I was skeptical at the time. I felt that a lot of the problems could be too biologically complicated for cell therapies to work. Yet the science has surged forward much more quickly. There’s really exciting preclinical data and actual clinical trials that are about to start or have started. Spinal cord. Macular degeneration. And others. Some people have spent 10-20 years trying to understand the biology. Parkinson’s with Lorenz Studer. Cell therapy for heart disease with Chuck Murry. It’s important for the general public to understand the timeframe and that some will fail. In the past some were just squirting cells into tissues…sort of like buying a lottery ticket. People now understand the biology better. Now we have a rational chance of success.

The debate that is shaping up for CIRM is also very important now. Stem cell research is already delivering and there’s opportunity looking ahead. More funding for CIRM makes sense and it would be a major setback to not do that, especially with declining federal funding. One thing that will distinguish the winning states from the losing states is who has the vision to keep the biomedical research enterprise going at the state level. The conversation changed with CIRM’s birth. It became, “How do we keep up with California?”

The spread of stem cell clinics selling non-FDA approved offerings in the US has accelerated. What should ISSCR and individual stem cell scientists be doing to address this growing problem?

SM: There’s a lot that you’ve done and we appreciate that. There’s also a lot that ISSCR has done. We have our A Closer Look website. ISSCR has spoken out more on this topic than any other topic relevant to the general public. Although stem cell research has enormous promise—and this is the most exciting time that we’ve ever had—unfortunately most people in the general public don’t understand how long it takes to go from the idea or proof of principle in a mouse to do it in humans. Sadly there are fraudulent people out there that are preying on patients. These are at best unproven and in many cases not even plausible therapies.

Where do you see the stem cell field in 5-10 years?

SM:  We should be excited, but I’m always wary of these kinds of predictions. If we look over the last 10 years there’s been a lot of twists in the plot. There’s been both good news and bad news. Some things have surged forward more quickly and some things that we are most excited about now weren’t on our radar screens then. We don’t really know where we’re going to be. But I’m very optimistic. The thing that we have to remember that we always forget, even when we identify an idea that works, it takes a lot of years to get that to a patient. Look how long it took for bone marrow transplant to develop. We now talk about bone marrow transplant as an example but it took 14 years. We should bear in mind that even if some of the things now in clinical trials are correct, it could take years to develop them in a safe and efficient way.

Janet Rossant, ISSCR President, on her goals, cloning, non-compliant clinics, iPS cells, and future of field

New ISSCR President, Dr. Janet Rossant, kindly agreed to do an interview with me focused on the future of ISSCR, her plans for her tenure, and some key issues in the field.

Janet Rossant

Dr. Rossant is Chief of Research at The Hospital for Sick Children in Toronto.

1. The stem cell arena is a very rapidly changing one on many levels. As President how do you see ISSCR changing and evolving in the coming 
year to effectively deal with critical emerging issues?

Rossant: Stem cell research is indeed moving fast in both fundamental discovery and clinical applications. I am personally excited by the increasing rigour of the science underlying stem cell research. In depth analysis of human stem cells and their differentiated progeny is providing new insights into normal human biological development and disease mechanisms. At the same time, we are seeing the promise of novel stem cell therapies starting to be realized- small steps but just the beginning of change ahead.  I believe ISSCR must continue to be the forum where new discoveries are presented in an open and honest manner without hype and artifice. Only by being honest about the challenges ahead can we bring together the different communities who must work to solve the challenges.  ISSCR needs to reach out beyond its current membership so that we can provide a forum for discussion of the critical issues in translation of stem cell discovery to impact on patients.

2. What are your specific goals for ISSCR during your tenure as President?

Rossant: My goals are to continue to promote open dialogue about the science of stem cells, the ethical and regulatory concerns, and the challenges ahead in translation to clinical medicine.  The annual meeting is one forum for such discussions, but we need to look to other opportunities, such as regional forums and partnered workshops.  I also strongly feel that ISSCR has an important role to play internationally in the public policy arena, as the only international entity that can claim to speak for stem cell scientists worldwide.  The society will be undertaking a major review of its communication and outreach strategy over the next few months. We will need to develop a more proactive approach to be able to respond in a rational, evidence-based manner to issues that arise worldwide. At this point, the society has been in existence for more than a decade and has grown to become a trusted voice in the stem cell arena.  We must not lose that trust.  And at the same time, we must not ignore the needs and desires of our membership, who are the constituency we serve.  In the next few months, we will be surveying our members for their views on the strategic priorities for the Society. This will be very helpful in deciding where to put our limited financial resources to the best effect for the community at large. 

3. How does ISSCR plan to address the serious and growing problem of
both domestic and international clinics marketing unproven stem cell
procedures? For example, regarding Italy, ISSCR made a  public statement
about the conflict there over stem cells, but, within the United States,
for example, ISSCR has issued no comparable statements before or after
clinics received warning letters from the FDA over the years. How can
ISSCR take a proactive leadership position on this issue both within the
United States and at a global level?

Rossant: Many of us feel very strongly that the unregulated uses of stem cells in clinics worldwide is a major challenge that could bring the entire field into disrepute. The ISSCR has made this a major issue and has tried to address this by providing information for patients, families and physicians on the issues of unproven therapies on the website http://www.closerlookatstemcells.org. Going beyond this to take action against specific initiatives or specific clinics requires a coordinated effort that must be based on evidence, backed up by the agreed principles of the Society and supported by appropriate partners in whatever international jurisdiction is involved. Our goal in the next year is to strengthen our efforts in this area, beginning with cosponsorship of a workshop on Unproven Stem Cell Therapies with the Institute of Medicine and the National Research Council of the National Academies. Globally we will reach out to other academies, stem cell networks and medical groups to proactively develop guidelines to outline the expected steps required to validate and regulate the use of any stem cell therapy worldwide.  Although the detailed regulatory environment for stem cell therapies varies from country to country, it should be possible to agree on some simple overriding principles for stem cell therapeutic applications.

4. One thing I’m hearing on my blog is that many in the field are
starting to wonder if the field is too focused today on reprogramming
and that stem cell research in other areas such as endogenous stem
cells, stem cell developmental biology, and ES cells is suffering as a
result. I personally do not believe that stem cells are a zero sum game,
but there is limit to the total amount of resources and focus available.
iPS cells and direct reprogramming clearly are enormously exciting with
great potential, but do we need some kind of balance and are we as a
field out of balance at this time? What are your thoughts?

Rossant: Obviously iPS cells and direct transdifferentiation of cells from one cell type to another have been an incredible breakthrough in our understanding of how to control cell fate. It has shown us that it should be possible to make designer cells, once we understand the genetic regulatory networks and their key regulatory switches.  However, iPS and pluripotent stem cells are not the only stem cells of relevance to new therapies- most clinical trials in stem cells today are from hematopoietic and other adult somatic stem cells.  ISSCR tries to keep a balance between the underlying developmental biology of stem cells, both pluripotent and restricted, the differentiation pathways of such cells, the bioengineering of stem cells and their clinical applications.  All are necessary and members of the society should let us know if they think we are out of balance.

5. What is your perspective on human therapeutic cloning of ES cells?
How promising is it? Why is it important? Are there risks involved such
as paving the way, even unintentionally, for rogue human reproductive
cloning? Or is that overblown?

Rossant: It was nice to see that somatic cell nuclear transfer-derived ES cells could be derived in humans as in mice, especially after previous claims turned out to be fraudulent.  In terms of scientific importance, it is not terribly surprising. However, it is interesting to be able to compare and contrast nuclear transfer ES cells and iPS cells, in order to examine the similarities and differences between the two approaches to reprogramming. I do not see that this will become a widely used approach to personalized stem cells, given the ease of generating iPS cells, but these cells will be well studied and well used.  The slippery slope argument towards increasing the likelihood of human reproductive cloning is not very likely, given the strong regulatory and legal constraints against human cloning in most jurisdictions.

6. What excites you most about the stem cell field today?

Rossant: I really do feel we are on the cusp of real advances towards new stem cell based therapies, based on in-depth biological understanding of the stem cell state. The field has been accused of overselling the promise of stem cells, but I sense a new realism in terms of the challenges ahead.  ISSCR needs to help the public and governments understand where we stand today and ensure that we retain the support of society at large as we move forward.