New Yamanaka interview gives key insights into future of IPS cells

Shinya yamanaka

Wikipedia photo

Where is the field of IPS cells going and how will this impact the overall field of stem cell-based regenerative medicine?

Nobel Laureate Shinya Yamanaka, the discoverer of IPS cells, gave a really interesting recent interview to Nikkei that provides some fascinating insights into the future of this exciting technology that is now more than a decade old.

For simplicity I have indicated top highlights from the Yamanaka interview below as bullet points.

  • More IPS cell trials are on track to start as soon as 2018 in Japan.
  • Yamanaka said that trials for Parkinson’s, Spinal Cord Injury, and Heart Disease are amongst the planned IPS cell trials in Japan.
  • There are also plans for clinical studies on cancer and kidney disease, perhaps further down the road such as 2019-2020?
  • Immune rejection and cancer risks must still be evaluated, he said.
  • There are likely to be important differences in the new studies versus use in the eye.
  • CiRA has started working with Takara on QC of IPS cells and products.
  • Their main focus for all these trials still seems on allogeneic use from IPS cell banks.

It will be interesting to see how trials in Japan develop versus those in other countries such as here in the US where I know of planned autologous IPS cell clinic efforts.

Michael Cea’s conversation with Jeanne Loring: frank views on all things stem cell

By Michael Cea

Jeanne Loring of the Scripps Research Institute in La Jolla, California kindly sat down with me at the ISSCR annual meeting for a broad discussion of her history, views on the field and developments in the science.

I found Jeanne a refreshing character, as I did a number of others I was fortunate to meet in Sweden. Her style I can only best describe as natural. It must be the Southern California air or something but there is a definite quality of relaxed confidence about her. I liked her a lot and hope to have the opportunity to meet her again sometime – perhaps at the birth of her “to be” Northern White Rhino! If she invites me 🙂 that would be something.

The format of the interview was free flowing and what was clear to me from her long standing scientific focus and deep knowledge of the sector was it takes determination and a varied set of skills to maintain one’s position in today’s fast paced world of cutting edge science and more so even to successfully translate that to the clinic.Jeanne Loring

Kudos to Jeanne for her efforts to continue the fight to bring forward a therapy for Parkinson’s after near on 30 years and for her passion to help our planet’s most endangered.

Hope you find the interview interesting, as much as I enjoyed it.



M: Tell me a little about your background

JL:  I was trained in embryology and neurobiology, I studied neural crest cells, which are actually stem cells and I was fascinated by them. Then when I finished graduate school I got a job as an assistant professor at the University of California Davis and I then realized I could either teach or do research but not both. There were not enough hours in my day, so I took the opportunity to join a biotech company in California called Hana Biologics. There were lots of companies around in 1987. I joined specifically because they were planning a stem cell therapy for Parkinson’s disease. I was getting a little bit tired of generating just knowledge. I wanted to generate practical knowledge, which made me a little bit different from most biologists at the time.


Lewy Body characteristic of Parkinson’s

M: Was that motivated by personal experience?

JL: No, I didn’t know anybody who was sick at all; it was just I wanted to have more impact than just writing papers. I wanted to do something more important. When you go into biotech there’s a high probability that you’ll not be at the same job for more than 5 years. I didn’t know that at the time but I’ve learned it now- it’s good for learning how to survive. The first company I went to work for (in the late 1980’s) was developing a cell therapy for Parkinson’s disease, but there were no pluripotent stem cells yet so we were using fetal cells -trying to expand them. That was the heyday of the fetal transplants for Parkinson’s disease and it was clear they were working for some people, so why couldn’t we take fetal cells and expand them and treat more patients?

M: I attended the pre-meeting symposium @ Karolinska on the aging brain. The eye and brain are related of course but the brain is less accessible.

Lewy Body characteristic of Parkinson’s. Image from Wikipedia.

JL:  The eye is accessible; therefore it is a good testing ground for therapies. Once you put things in the brain you pretty much don’t know what’s happened until the person dies.

M:  Why did the fetal work not continue?

JL: There were two main efforts – Andreas Bjorklund of Karolinska/Lund and two groups in the US who were funded by the NIH to do clinical trials. I think the people in Sweden will always argue that they had a better success rate. The researchers In the US were required to, or decided to, do a double blind clinical trial to assess placebo effects.

M: And surgery?

JL: Yes, they did sham surgeries for the double blind trial.

M: Isn’t that unethical?

JL:  I would never do it but it was the expectation of the NIH-funded trial. The patients did have the promise of treatment if they were part of the control group.

M: You mean opening them up again?

JL:  Yes, but the people who routinely do brain surgery don’t take this issue as seriously as I do, and they know what they’re doing.

To continue, the problem was that maybe 25%-30% of the patients, depending on the study, had an adverse effect that was quite dramatic, called dyskinesia. When they got the cells they had Parkinson’s disease, which was treatable with L-Dopa, but then after they had the cells they started having uncontrollable events, like the opposite of that sort of frozen kind of characteristic of people with Parkinson’s disease. They had to be treated separately and it had obviously been caused by the transplant. The question was…

M: Why?

JL: Exactly. The fetal cell therapies stopped in about 2003. I remember I was at the Society of Neuroscience meeting when the results were discussed and everyone in the room was saying… we can’t do this anymore.

M: But 75% of the patients were…

JL: Were either not helped or they were helped for the rest of their lives and went off drugs. So it was clearly a spectacular therapy.

M: This was so early, late 80s early 90s, wouldn’t you think that with more push in the science?

JL: Everything sort of dropped off the map at that stage and people just didn’t pursue it anymore.

M: Was it ethically charged?

JL: The question was: do you want to do something to people that has a clear probability of an adverse effect? Parkinson’s disease is not a life threatening disease.

M: It is a debilitating disease.

JL: Yes, it is a debilitating disease.

M: I have a relative that has Parkinson’s, in my wife’s family, and it’s not just the disease it’s what it does to you aside from that. Your whole spinal column changes and that makes everything more painful and difficult.

JL: Everything is more challenging and you can never predict whether you’re going to have a good time or bad time today or this morning or afternoon. I have a friend in Texas who has Parkinson’s disease – I talk to him on the phone every once in a while and it has to be at a particular time of day. Otherwise I can’t understand him at all.

M: Devastating disease, all the neuronal diseases are devastating.

JL: That was the whole basis for my Parkinson’s disease focus, after there was a resurgence in interest when human pluripotent stem cells were made. We can turn these cells into real dopamine neurons and do just what we want with quality control.

M: This was the question I had at the brain symposium, why wouldn’t you test the neural stem cells themselves as a method of action and let them stimulate the environment.

JL: People have tried that. There was a whole interval where people were trying to treat Parkinson’s with cells that were not dopamine neurons. Actually it damaged the field because it didn’t work and turned organizations like the Michael J. Fox foundation, an organization that had supported it, against cell therapy entirely. They’re not funding cell therapy now.

M: Were those stem cell originated?

JL: No, this was all before pluripotent stem cells were available. They were either adult cells or fetal derived stem cells, and they didn’t become dopaminergic neurons.

M: Isn’t there a big difference in terms of your understanding of the pluripotent sources in terms of that?

JL: Of course. There’s a huge difference. The cells you get from an adult or fetus have not been successfully turned into the same neuronal cell type that dies in Parkinson’s. They don’t seem to be able to.

M: So what about the pluripotent neural stem cells?

JL: Neural stem cells from brain aren’t pluripotent- they can’t develop into all cell types. We use pluripotent stem cells to make neural stem cells, which we then turn into dopamine neurons.

M: Ok

JL: So my next job, because fetal dopamine neuron precursor cells couldn’t be expanded, was to work at a company called GenPharm. This was in the early 90s and we were doing gene knockouts and deriving mouse embryonic stem cells so I got to be at the beginning of one field and the beginning of another field. That company lasted about five years.

M: What technology did you use?

JL: Using homologous recombination, which was a brand new idea at the. Mario Capecchi, who was a scientific advisor to the company, won a Nobel Prize for it in 2007. I like being in the situation where the technology I’m using wins Nobel prizes for people. I kind of think that validates it. We could just about do anything. We could knock-out genes and we could change genes. This was all pre Crispr-Cas, which is the way people are doing it now. So that was early days for that as well.

I made a lot of mouse embryonic stem cell lines. This was the same time as Austin Smith and Rudolf Jaenisch were using, making and knocking-out genes in mouse embryonic stem cells. That’s where our histories all overlapped; we were all doing this in the early 90s, although I was at a company, and they were academics. It was a spectacular five years and we did a lot of amazing work. The work I did then is still some of the most highly cited work that I have ever done. It was really pioneering and it was fun. Then after that company failed (most of them do), I moved on to a company called Incyte Genomics. This was at the peak of the human genome sequencing era, which started around the mid-90s. I worked at Incyte for around 5 years learning how sequencing worked.

M: Uncovering the map

JL: Yes, and the technology was evolving very fast at that time. So I now had three things I knew well – the Parkinson’s neural cell transplant idea, embryonic stem cells and now genomics/DNA.

M: This all was at the same time as the other groups but your work went unheralded?

JL:  It was not a big deal- if you’re going to be heralded you have to stick in one field for a long time. My approach has been to learn something then learn something else and try to put the two things together.

M: and it’s all coming together now?

JL: It is, everything I’ve done is coming together now.

M: Tell me about that, because that’s why you’re back.

JL:  That’s why I’m back. Regarding Parkinson’s disease – we now have human pluripotent stem cells that can be turned into dopamine neurons, so all the things that were wrong with the early work I was doing in the late 80s I can now fix.

M: You’re independent in an academic setting now.

JL: Yes, I’m an academic with my own lab. I have the Parkinson’s history and I have the mouse embryonic stem cell history, which Austin and Rudolf share. You know it’s interesting people who come from a mouse embryonic background and then started working on human ES or iPS cells have been really annoyed that the human cells don’t act like the mouse cells. They’re much harder to grow. So both Rudolf and Austin have been trying to turn human pluripotent stem cells into cells like the mouse.

M: Is this kind of an internal debate?

JL: Yes, this is what they’re focused on now & intensely competing with each other over whether you can make human cells with the qualities of mouse cells. I’m not involved- I just went straight to human pluripotent stem cells and realized they were not going to be like mouse and lived with it.

M: Is that because of the quality and body of evidence in the mouse?

JL: Yes, the history is with mouse ES cells and the kind of things you can do with them. They’re much more robust than human pluripotent stem cells. Human embryonic stem cells have to be babied, but mouse ES cells you can pretty much leave in an incubator and they’re fine. The researchers have moved in the direction of trying to make hESCs be like that.

M: To perform better?

JL: Yes, so that then can take all those techniques they used in the mouse and now apply them to human. As I said, I’ve just bypassed that. My cells can become what I want them to become and that’s it – I’m done. They don’t need to be like mouse cells.

To continue, while I was still at Incyte I started a company and made a bunch of hESC derivations that were on George Bush’s original list.

M: From IVF donations?

JL: Yes, that’s right. I started a company, so I did it in my own company. There were 3 employees. I was the scientist and I had an assistant.

M: You had a number of lines. What ever happened to those lines?

JL: Well, they got acquired by another company and I have no idea, they’re probably still in the freezer somewhere. They never did anything with them. But it’s not important any more as there are so many lines out here. There are 300 lines or so on the NIH registry of lines that can be used in federal grants.

M: And they’re sufficient to do the science work?

JL: Yes. But my lab doesn’t work much on hESCs anymore. We work with iPSCs because they are equivalent to hESCs and you can get them from individual people. This is where my genome experience comes in because I learned sequencing and genomics when I was at Incyte, so I had an appreciation of the methods used to study the genomes of cells.

M: The translational aspect of what you’re working on is focused on Parkinson’s as a primary program?

JL: Yes. There are a lot of reasons for it. The person who came to me with the idea to do a therapy for Parkinson’s disease is the head of the movement disorders clinic at Scripps Health, which is across the street from me. She thought there ought to be a stem cell therapy for Parkinson’s disease and together we did fundraising to start the project. We want to do a personalized therapy, an iPSC therapy, and genomics is very important as we want to have quality control throughout the process of developing a therapy.

M: This is your approach to it?

JL: Yes. One of the things we’ve learned from studying pluripotent stem cells is that they acquire mutations if they spend a lot of time in culture. You don’t want to put cells with dangerous mutations into people, so that’s where genomics expertise comes in, essentially in assuring the quality control of the cells we want to transplant.

M: Is that the same risk factor in regard to hESCs?

JL: Yes, they will do the same thing. In fact everything we’ve done to date shows that iPS and ES cells are identical. Our approach has been to analyze lots of cell lines, not just one, to learn what to expect from cell lines in general. Almost everything we’ve done was done on 100s of cell lines so we can come up with general principles.

M: I remember you putting out a paper on this recently that was very exhaustive – 2 years of work

JL: Yes, 2 years of cell culturing. The scientist I worked with on that is here at the meeting – I’m going to take him to lunch tomorrow. The whole idea was to try to come up with things that were generalizable to cell lines and different conditions.

M: So if you use 1 cell line that is on the edge of a uniform grouping that will be different than if you select and productize something else within that sequence?

JL: Yes

M: and that’s where we’re at?

JL: Yes, right now. Here’s the challenge. If you have different cell lines we know they’ll have some diversity. They act a little bit differently, a lot due to the personal genomes, of course. The challenge we have is to develop technologies and quality control methods to allow us to know how every one of those cell lines becomes the same thing every single time.

M: Is that a far reaching goal?

JL: I think it’s actually going to work pretty well. A lot of this has been developed already. That’s been a high priority all along. Some people think it’s never going to work but I don’t believe that.

M: Is RNA a part of that process?

JL: Yes, absolutely.

M: So the work presented recently by Yamanaka will factor into this.

JL: Yes. The way we make the cells is important – we’ve investigated that. How you reprogram the cells so that the cells aren’t harmed.

M: Is that Sendai?

JL: Yes, that’s right. We’ve done whole genome sequencing on a lot of cell lines and we’ve discovered that using Sendai vectors for reprogramming is benign. The other methods are also benign, which is important to keep in mind.

M: So looking at this from a cost perspective, autologous patient specific treatments are highly personalized but are highly expensive. Is that part of the process strategically?

JL: Yes, that’s right. It’s part of the process. There’s a lot of discussion on personalized therapy and whether it’s worth the cost.

M: Of course, if it costs $1 million dollars how many people can actually be treated?

JL: Well, more than you think. It turns out for cancer treatments the amount of money that people are paying is similar.

M: Is this about annuities, is that where we’re going?

JL: No. Somebody needs to figure out how to have insurance reimburse for therapies. Right now we’re not worried about that yet. But I can see how it’s going to work because the work that’s being done now with T-Cells, CAR-T therapeutics.

M: I wrote about that 3 years ago.

JL: There you go. That’s about how much it costs for what I’m doing and yet there are multiple companies developing this technology now that it’s been shown to work.

M: There are many now but there were none before.

JL: Well I remember the first time I heard about it I thought I had no idea you could do that. I didn’t know the immune system could do that.

M: The immune system is a powerful force to employ.

JL: Yes it is, and that’s one of the reasons we’re using autologous therapy. We want the cells to be matched and don’t want them to be rejected.

M: Isn’t there a movement towards allogeneic?

JL: It’s hard to say. Yes, probably because of the effort in characterizing cells, but let me put it this way. As soon as we demonstrate we can make the same cells from 8 different patients and they all work, then the story’s over. Autologous therapy and the price point will be worth it. It will be like CAR-T therapy. It will be what you have to do for the best possible therapy.

M: Wouldn’t you want to test an allogeneic source?

JL: I don’t want to as others are doing it. I’m going to let them go ahead and do it.

M: and who are those others?

JL: The Studer Lab in the US. Actually there’s one other autologous therapy which is being done in Japan by Jun Takahashi.

M: Coming out next year.

JL: Yes, his and my projects are very similar. We’re trying to collaborate but I don’t think it’s going to work, as it’s almost impossible to exchange materials between the US and Japan.

M: Really I thought we were friends in many ways.

JL: We are but when it comes to scientific IP, it’s very hard.

M: They do want to license a lot of their underlying technology, Japan Academia, Healios.

JL: and I would be licensing it if I were a company but I don’t have to as an academic and that’s another strategy of mine.

M: Don’t they have underlying patents?

JL: Oh yes, and if I decide to commercialize what I develop I’m going to have to license patents from Japan. But I’m going to worry about that later. I know a bit about patents too.

M: I remember that.

JL:  I think we have a good strategy. The thing is you can never be certain, but the science makes sense, the strategy makes sense.

M: To be clear on this patent issue – you don’t need a license to do clinical trials.

JL: No. I don’t need a license to develop anything, as long as I’m an academic and I’m not commercializing it,

M: The concept is Japan Academia is licensing for research purposes because they deliver a package.

JL: Yes – and I don’t need it yet because I’m a non-profit. They will license their technology for research purposes to companies but they won’t let anybody sell the iPS cells.

M: The process of development can happen independently using Sendai without a license.

JL: Yes that’s correct. I was in biotech and I was affected rather negatively by patents at times. I remember this very clearly: my friends and I wanted to challenge the WARF patents that gave them ownership of all human embryonic stem cells, and we worked on this for many years. The patents expired just before we asked the Supreme Court to hear the case for overturning the patents, and they declined to hear it. When I became an academic, as I liked to say to the WARF attorneys as many times as I could, I had the freedom to operate and not require a patent from them to do embryonic stem cell research. Our patent challenge was very interesting and very educational; as a result of our challenge, WARF narrowed the claims of their patents to limit them specifically to embryonic stem cells. Their original patents claimed all pluripotent stem cells, so if we hadn’t challenged the patents, they could have retroactively claimed iPSCs.

M: There are a few words in there which are specific to embryo derived.

JL:  What happened was, we challenged the patents, the patent office rejected all of them, and in order to get the patent office to reinstate them they had to change the language for their primary patent.

M: It was their intent in the first place.

JL: I think we caught them by surprise. I met some really great people as a result of the patent challenge. The attorney who was with me was the same attorney who brought the challenge to the Myriad patents. He was at the Supreme Court for that case and I went to the Court to watch them argue that case.

M: Interesting isn’t it?

JL: It was fascinating

M: The legal system is a world apart

JL: It’s so bizarre

M: Somewhat like the science world?

JL: No, well in theory yes. What really struck me was the fact that the Supreme Court justices, and I think lay people, need metaphors in order to understand science.

M: They do and communication from science to the world is vital as the boxed view of old school scientists just doing experiments to publish needs to change.

JL: I don’t know why people would do that, to tell you the truth.

M: I think there is a value. My curiosity brought me here. So I think there’s a great value in curiosity and the maintenance of that throughout your life

JL: I agree.

M: I like that analogy the Salk Professor, Rusty Gage, presented. He spoke of a running an experiment where brain cells develop due to vitality, even in disease states. I’m not sure how a Parkinson’s patient can actually get on a treadmill but….

JL: Exercise does help Parkinson’s patients, physically and mentally. Our funding mechanism is patient advocacy based, a partnership with patients.

M: I’m not aware of your funding mechanism.

JL: The funding comes from a private foundation that we started to fund this project

M: I remember this – just recently you did a drive. How did that go?

JL: It’s gotten enough money to get us to the pre-IND stage.

M: Did CIRM ever come in?

JL: CIRM will come through the next round, I believe. We’re certainly going to apply for CIRM money. We’ve been working up to this for a long time. The patients have been going to CIRM meetings so we can educate the panel about the importance of this.

M: How far are you away from the IND

JL: About 2 to 3 years

M: That’s pretty similar to some of the others – Malin Parmer for instance mentioned 2018. Of course the Japanese are coming on fast next year.

JL: They’re on a fast track – there are some positives and negatives about that.

M: Tell me about that. There is I guess a Japanese societal push, an industrial push. They have a tendency to like to do that in industry and it’s been beneficial in the past. Do you see that as a mechanism to dominate?

JL: Yes, absolutely.

M: and will it open up things potentially or will there be a downfall?

JL: The good thing as far as I’m concerned, is if Jun Takahashi gets his therapy through the regulatory agency, he gets to transplant his cells to people and they’ll be doing that before I do. It’s unlikely that our FDA will let me do it sooner. So if nothing bad happens to the patients in Jun’s study, that will help me. However, if somebody else pushes through a therapy because of this fast track, a scientist who are not as careful as Jun Takahashi, there could be issues. Stem cell therapy, just like everything else, if it is strongly promoted, can have setbacks. In Japan we saw what happened with the STAP problem. As soon as there’s a lot of pressure from the Japanese society and Government to move forward there are going to be people that make mistakes. There will be people who are not careful.

M: Masayo Takahashi is trialing iPS cells.

JL: Yes and she has published preclinical work. Essentially she is trying to show equivalency of iPS to ES cells. I think that’s very important, as the FDA is still worried about iPS cells.

M: They are it seems. There was some planning to file an IND for Platelets.

JL: Yes.

M: Do you know that story?

JL: I do, yes.

M: Will you tell it?

JL: I probably can. I can publicly say I was a consultant for them [Ocata/ACT] and that I attended their pre-clinical meeting as a consultant. So I know about the reaction of the FDA about that.

M: This was back 3 years ago?

JL: Yes, I think 2 to 3 years

M: 2013

JL: It turned out that I wasn’t really necessary as an advisor. I didn’t say a word but it was fascinating to see the FDA’s response.

M: The concerns they had were GMP compliance related.

JL: Yes, but they’re getting over that. They’ve approved ES cells that were not made with the intent of using them for therapy. One of the cell lines that they approved was derived in 1998 using bovine serum, which was a concern before the safety trials showed that it wasn’t important.

M: Yes even the Ocata/ACT cell line comes from some time ago on MEF.

JL: Yes, and I’m not concerned about that. There are some issues with using xeno reagents but they are really related to whether you’re making the cells make the wrong kinds of sugars. If you were to put mouse embryonic cells or mouse iPS cells on mouse embryo fibroblasts (MEF), viruses could be transferred into the cells, but this doesn’t happen with human pluripotent stem cells. Nobody has ever shown any kind of viral infection in human cells that comes from the MEFs.

M: That’s why the safety is intact.

JL: Yes, exactly. The process is to imagine bad things that might happen, then prove that they don’t happen.

M: It’s only a transitory process as well.

JL: Yes, you’re not putting mouse cells into people. But you’re also not infecting the cells so there’s no lasting change.

M: There are a lot of other technologies that are far more dangerous – virus delivery for instance.

JL: Yes, of course, and viruses used for early gene therapy have actually been shown to be dangerous in some cases.

M: There have been a lot of adverse events and people have actually died in the CAR-T trials and no one talks about it.

JL: That’s right.

M: My feeling is the xeno movement is a good thing for standardization and some of the work shown here, the BioLamina work and the Thermo Fisher work, these are very good protocols that need to be adopted and the expansion occur.

JL: That’s fine. As long as they are necessary and they work well, I don’t really care what methods are needed. I’m not too worried about the xeno issue because the cells won’t be interspecies transplants.

M: Are they requiring it now, is that the new standard?

JL: Not yet, no. We just had a meeting with our regulatory consultant a couple of weeks ago, but of course you never know.

M: So when the Israelis and BioTime and others in the field are touting the xeno-free, it’s just marketing?

JL: Perhaps, but don’t let’s push that too far; I mean the FDA is never perfectly predictable and they could decide at any time that they think it’s dangerous to have xeno reagents.

M: But the products will be approved without a line switch.

JL: Right, that’s right.

M: What are the programs in the pluripotent space you think will reach the market within the next 5 years?

JL: Obviously there’s a lot of interest in the reagent business and there are a lot of companies that are joining in, especially in Japan. I really didn’t realize how much was involved in Japan in creating reagents for taking the cells to the clinic.

M: ReproCell?

JL: Yeah, ReproCell and others.

M: Takara?

JL: Yes. I’m giving a talk at an innovation showcase tomorrow for another Japanese company. One of my friends asked me to do it for him because he can’t make it here. They’re a very large chemistry company. They’ve been in business a long time and now they want to start to apply what they’ve done to stem cells.

M: Interesting how some of the non-scientific power houses in Japan are involving themselves now. A change in strategy perhaps. Digital is affecting their main lines of business and there’s an opportunity.

JL: Absolutely. They have a lot of bandwidth. Fuji Film just bought Cellular Dynamics. I mean you’re not making film anymore so you might as well make stem cell reagents.

M: I don’t want to press on the point of who’s going to come to market soon but success needs to be translated and your view on early access as being a component of adoption, proof of clinical concept, is that in your view an essential part of regulatory review & language?

JL:  Japan has fast tracked cell therapies, but I think our FDA is not going to fully adopt such regulations. Perhaps this is because the Japanese regulatory authorities have decided to trust their scientists more than the FDA trusts us.

M: In my view Japan also has a symbiotic relationship with the other parts of the system, you know, it works all together – the insurance, the legal, the funding, the university/academic and business community.

JL: I know, it’s really amazing. I’m really envious.

M: Anything else on the program front? I wanted to talk about the Zoo work.

JL: I know that’s what you actually wanted to talk to me about.

M: Yes, it was fascinating that you’re doing that work.

JL: Yes, we decided that we should try to reprogram endangered species cells, so in 2011 we published a paper to say we can – Rhinos, using human technology. We hope to use those cells to help restore the species.

M: The egg/sperm combination?

JL: All that stuff is coming. At that time we just made iPS cells from the animals and the project lay dormant for a while because the zoo we were working with thought it was a bit little creepy, too Jurassic Park. They’ve now decided to embrace it.

M: Weren’t there a number of international groups working on that before?

JL: Yes but not a lot, not in this particular thing. There was a group in Australia that was reprogramming other animals.

M: Interestingly in Spain also.

JL: Yes, that was different though, replacing one animal with another in a habitat.

M: Using an animal to host?

JL: Well they’ve done that too. The essence of our approach with endangered animals is to use the technologies that have been developed for mouse and for humans to make gametes out of the iPS cells. Then use IVF technology, that is also in development for these animals, and have a surrogate host that we’ll be able to put the embryos into and regenerate the species. Just a small thing! I’m doing this with the Northern White Rhino, as there are only 5 of them left. There’s only one male and the females I think, with one exception, are beyond reproductive age and they’re dying. [Note: another Northern White Rhino died in late July, so now there are 4].

M: So how would you approach that?

JL: The Southern White Rhino has a very similar reproductive cycle. The Northern White Rhino are a different species but they’re very similar. No one really knows if you can cross them yet. We want to make the gametes from the Northern White Rhino, inseminate the eggs in a culture dish and transfer the embryos to a Southern White Rhino.

M: The egg would come from the endangered species also?

JL: Yes, from the pluripotent stem cells.

M: Both gametes.

JL: Yes both gametes would be produced from iPS technology.

M: Have you proven that yet?

JL: No, we had no money, so we essentially have been generating more iPS cells and we’re getting better at it. But now there’s going to be an investment, that’s what they tell me. The zoo has decided.

M: Which zoo is that?

JL: The San Diego Zoo.

M: Wonderful.

JL: They’ll be announcing that when they want to, it’s not up to me.

M: Very good, I wish you luck with that.

JL: Thanks, it’s one of those things which seemed obvious at the time.

M: Well worth doing.

JL: Yes, it is worth doing and it was just a matter of timing. I think a lot of this is like that. If you’re too ahead of people’s understanding of what you’re doing then it will just sit there dormant until they understand it.

M: I think in most fields if you’re pioneering something you have a responsibility to educate.

JL: Yes but people also have to accept it. I’ve seen a lot of changes in the stem cell world since we started this in 1998 so it’s been a while.

M: The %s are way higher now.

JL: Yes, they’re higher, that’s right, and it does have to do with education and our patient advocacy approach means we educate patients and the patients educate other people because they’re motivated. They may have not wanted to be scientists but they’re driven to understand it because they want to get cured, they want to get treated.

M: Thank you Jeanne

JL: Ok


Ref: Parkinson’s review by EuroStemCells