Multiple filters for stem cell research at Canadian stem cell conference

By Samantha Yammine, PhD Candidate in Derek van der Kooy’s lab at the University of Toronto. See tweets live from #TMM2016 via @SamanthaZY here.

Whistler, BC, Canada.

The location of this year’s annual TMM in Whistler, BC, Canada.

Last week, 430 Canadian scientists, trainees, industry professionals, science communicators and international guests gathered in the picturesque ski town of Whistler, British Columbia for the annual Till & McCulloch meeting (TMM). This is Canada’s premier conference for stem cell research, which is co-hosted by the Centre for Commercialization of Regenerative Medicine, the Stem Cell Network, and the Ontario Institute for Regenerative Medicine.

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Interview with Fredrik Lanner who is CRISPR’ing healthy human embryos

In the past year there has been a great deal of attention given to the potential use of CRISPR-Cas9 for gene editing in human embryos. An important recent development, described in a new NPR article by Rob Stein, is the use of CRISPR-Cas9 in healthy human embryos for developmental biology research by assistant professor Fredrik Lanner of The Karolinska Institute. Dr. Lanner, who invited Stein into his lab to observe the work, kindly agreed to do a Q&A interview with me (below) on his team’s use of CRISPR-Cas9 gene editing for research in healthy human embryos.
ssistant Professor Fredrik Lanner

Assistant Professor Fredrik Lanner. Picture by Rob Stein

PK: What got you interested in doing gene editing in healthy human embryos?

FL: I studied mouse preimplantation development during my postdoc in Janet Rossant’s lab and one of the discoveries we made was the importance of fgf-erk signaling in EPI-PE segregation (Yamanaka, Lanner and Rossant Development 2010). A couple of years later two papers showed that the same mechanism is not controlling the same segregation in human embryos. Since then it has become widely appreciated that the mouse probably is not such a great model system for the human and we really need to start studying human embryos to understand human preimplantation development. I therefore moved back to Sweden, Karolinska Institutet to start my own lab with that specific focus. As a first start we have built a transcriptional single cell roadmap of how the first cell types emerge during the first week of human development (Petropoulos et al Cell 2016). We now want to move from descriptive to functional studies. For this we are of course using pharmacological inhibitors for various signaling pathways but to be able to elucidate which transcription factors are important for how the first cell types are established and how pluripotency is controlled we need other approaches. CRISPR is therefore an obvious next step to evaluate.

PK: Did you have to get some kind of official approvals from your own Karolinska Institute? Did you also need some kind of approval from the Swedish government?

FL: We applied for and got ethical permits from the Swedish regional ethics board (EPN.SE) last spring, 2015. We have also lifted these experiments in KI’s internal ethics board, to inform the KI leadership of our plans and to make sure we had their support.

The Swedish law is clear that genome editing is only allowed within the first 14 day as long as the embryo is not transferred back for a continued pregnancy. This means that heritable genome editing for clinical purposes would not be allowed in Sweden. The clear legislation has been key in us moving ahead with these plans.

PK: What is the source of funding for this work?

FL: Towards the functional gene studies I have internal funding from KI and external funding from the Knut and Alice Wallenberg foundation and through Lau fellowship. For our embryo research I also have funding from the Swedish Research Council, Ragnar Söderberg fellowship and the Swedish Strategic Research Foundation.

PK: Did you receive any kind of bioethics training related to CRISPR’ing human embryos or discuss it with a bioethicist before beginning?

FL:  We have discussed it within the KI ethics council consisting of people with legal, ethics and research expertise. I have further presented and discussed at the symposium organized by National Academies of Sciences in Paris, and a Scandinavian meeting organized by The Norwegian Biotechnology Advisory Board. Early October I will discuss this further with The Swedish Gene Technology Advisory Board. We have followed these discussions closely during the last two years.

PK: I realize you declined to say to Rob Stein what gene(s) you are targeting, but can you name them now? My own view is that with gene editing of human embryos that transparency is needed combined with a strong base rationale, which together make for good reasons to be open publicly about the genes being targeted. If you can’t say the genes is it because you’re concerned about competition from other researchers?

FL:  We are targeting genes that we think will be involved in lineage specification and establishing pluripotency. We want to be open but I’m still not ready to disclose exactly which genes we will focus on.

PK: Are you aware of other teams in your own or other countries doing gene editing in healthy human embryos? I’m trying to get a sense of how much of this kind of work is ongoing around the world.

FL:  No I only know of Kathy Niakans’ plans to look at similar questions.

PK: Is one of your ultimate goals to aid in fertility treatments? Would this involve in the future germline gene editing of human embryos then used to make people if all went well? Or would it rather be based on the knowledge you gain, but applied in a non-gene editing approach during reproduction? How are you seeing this play out in the future?

FL:  We are trying to generate fundamental knowledge and we don’t have any ambition to move in that direction. I’m actually pretty skeptical that the technology will be used for genome editing in the early embryo anytime soon. My questions concerns efficiency, safety and competitiveness compared to preimplantation genetic diagnosis. Targeting somatic cells is already leading the development of this technology.

PK: What is the source of the human embryos being used in your research?

FL:  The embryos are from infertility treatments where the couples mostly have gotten their children. In Sweden you can only store the embryos frozen up to 5 years after which they will be destroyed. At that point they can instead donate the embryos to research. These embryos are frozen at embryonic day 2 at which time the embryo consists of 4 cells.

PK: How did you decide to invite a journalist into you lab to observe the work?

FL:  Since NPR has a good reputation I did not hesitate to let Rob Stein come and visit if he could come the date we were planning to perform the experiment and as long as it did not impact on the practical work.  However, it is clear that we can not have reporters in the lab while we perform experiments on a regular basis.

PK: Anything else you feel is important to know?

FL: I would like to emphasize that we have not rushed into this but spent extensive time evaluating targeting strategy in human ES cells. We got the ethical permit during the spring of 2015 after which we have followed and participated in national and international discussions surrounding this technology over a year. This discussion has led to several organizations recommending that the fundamental research in cultured embryos is acceptable and important whereas the clinical translation of the technology with intention to generate a person is not. This in accordance to our Swedish legislation and has encouraged us to initiate these studies to evaluate the feasibility to study gene function in early human embryos using CRISPR-Cas9. I would also like to emphasize that I strongly think these experiments should be performed in genetically normal embryos if we are to learn anything about normal human preimplantation development.

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Diverse Stem Cell Person of the Year 2014 Award Finalists

Stem Cell Award Poll 2014With more than 4,142 votes cast, the readers of this blog have chosen the top 12 finalists for the Stem Cell Person of the Year Award for 2014 from the 27 nominees.

You can see the final vote tallies at left. The votes came from more than 50 countries with some interesting geographic patterns (I may do a post on that as a follow up).

I’ve pasted the brief bios of the twelve finalists below at the end of this post.

Now comes the tough task for me to pick a single winner from this amazing group. I will announce the Stem Cell Person of the Year 2014 within 1-2 weeks.

The finalists are a diverse group. They include scientists from academia and industry, patient advocates, a blogger, and the Pope. We have six male and six female finalists who live all around the world including in the US, Japan, Sweden, Canada, and Vatican City.

I’m happy to see both some familiar faces from nominees and finalists from past years and new ones too.

Who would you pick as the one winner and why? Post in the comments.

Finalists Bios (including in bold quotes from nominators)

Chris Fasano. A principal investigator at the Neural Stem Cell Institute where he uses stem cells to study early nervous system development. “Chris stands out for his energy, enthusiasm, dedication to the field, creativity and accomplishments.”

Don C. Reed. Long-time stem cell research advocate who played a key role in the success of Prop 71 and the creation of CIRM. “A tireless stem cell advocate always there to make a positive difference.”

Janet Rossant. Professor, University of Toronto. Stem Cell Researcher and Past President, ISSCR. “She works tirelessly to create new opportunities and collaborations…globally respected for her work in early development and embryonic stem cells”

Judy Roberson. Long-time Huntington’s Disease patient advocate. “She makes concrete positive developments happen such as millions of dollars in research funding for HD.”

JuuichiJigen. Japanese blogger who investigates scientific misconduct and played a key role in revealing the STAP scandal. He was the first to investigate and bring to the public of problems with STAP papers. His investigations demonstrated the role of social media and post-publication peer review in rapid self-correction of science.”

Malin Parmar. Associate Professor, Developmental and Regenerative Neurobiology, Lund University. Top neural regeneration scientist. “Young, hard worker who is doing very well”.

Masayo Takahashi. Stem cell researcher leading the team that is doing the first ever clinical study based on human iPS cells. “Creative and courageous clinical stem cell researcher.”

Pope Francis. Leader of Worldwide Catholic Church. “Strong supporter of adult stem cell biotechs and research”.

Robert Lanza. CSO of Advanced Cell Technology, which has multiple ES cell-based clinical trials ongoing. “Visionary and practical so makes the impossible possible with stem cells”.

Susan Solomon. Co-Founder and CEO of The New York Stem Cell Foundation (NYSCF). Remarkably effective advocate for stem cell research. “Not many leaders have created their own research laboratories and raised $100 million plus. Seriously, what an accomplishment!”

Ted Harada. Leading stem cell research advocate and very effective ALS patient advocate. “An Energizer Bunny for the ALS community and stem cell advocate”

Tory Williams. Stem cell advocate and author of the 2014 book, Inevitable Collision. Co-Founder and Executive Director of the Alabama Institute of Medicine (AIM). “A true hero who inspires and makes real things happen like AIM”.

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 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.