Robert Lanza, M.D. is considered one of the leading scientists in the world. He was born in Boston, Massachusetts in February, 1956 and is currently Chief Scientific Officer at Advanced Cell Technology (ACT) (OTCBB:ACTC.OB), a pioneer of embryonic stem cell research. Dr. Robert Lanza is also an Adjunct Professor at the Institute for Regenerative Medicine, Wake Forest University School of Medicine. John Eastman discusses his groundbreaking work, and future plans of ACT as they take center stage as a driving force in embryonic stem cell research.
You’re the chief scientific officer at Advance Cell Technology (ACT), which is, by industry standards, a small research and development firm. Why have you decided to conduct your research there?
DR ROBERT LANZA: I’ve been at ACT for a decade. I had many decades of experience doing transplant medicine, and the problem in the past has always been the same: rejection, rejection, rejection. So I started out in my early days in medical school doing heart transplants, actually with Christian Barnard in Cape Town South Africa and we had to use these heavy immunosuppressant drugs. At that time there was a new drug called cyclosporin and everyone said ‘ah, in the next coming years we’re going to have new drugs with no side effects, that have immune tolerance. We’re going to have universal cells’. Well, here we are several decades later, and the drugs of choice are still the same drugs. So along the way, I was at UCLA trying other strategies to prevent immune rejection. The two main hurdles of regenerative medicine or transplant medicine have been – one) a serious shortage of cells and tissues, and two) the problem of immune-rejection. Then, while I was at a company about ten or fifteen years ago that was trying to solve that problem, along comes Dolly the sheep and cloning. And at that point, I realized this is a strategy. If we could do the equivalent of somatic cell nuclear transfer, then not only could we create an unlimited number of cells, and through tissue engineering reconstitute them into more complex tissues and structures, but we could make them patient specific. So that way you not only solve the problem of limited numbers of cells and tissues, but also the problem of immune rejection. And it turns out that the only other major cloning company was literally right up the street. It was Advanced Cell Technology, and Michael West had just recently come on board as the president, and at the time they had not yet discovered the embryonic stem cell, but I knew that this was the way to go. So I went up and I spoke with Michael West. At that time ACT was an agricultural company, it was a subsidiary of Avian farms which was a chicken/poultry genetics company. They were in the process of cloning cattle; it was purely agricultural. So, given my medical degree, we talked and decided that if I came on board we could take this in the direction of medicine. Of course we knew that this was very controversial – not only nuclear transfer or cloning, but also embryonic stem cell research.
Harold Varmus was the head of the NIH, and I was tasked to get all the Nobel laureates’ signatures supporting embryonic stem cell research, which I did. I don’t know the exact number, but it was 60-70 Nobel laureates signed the letter. So then they hired me. And then we moved, slowly, in the direction of human therapy and eventually, we split off the agricultural branch and are now exclusively working on human therapies.
Your research at ACT has led to a patent being awarded for treating certain degenerative disorders of the retina?
DR ROBERT LANZA: Yes – I believe we have several patents, at least two that were just recently awarded.
And for Stargardt’s disease and macular degeneration, my understanding is that these diseases affect about 30-40 million people world wide?
DR ROBERT LANZA: Yes, age-related macular degeneration alone affects about 30 million people world-wide. Stargardt’s, which has orphan status with the FDA, is a much smaller group. It actually affects one out of every 8-10,000 patients, so about 30,000 Americans have it. But it is one of the leading causes of juvenile diabetes in the world, and it is a terrifying, a horrific disease. It affects children as young as six years of age, and when they’re teenagers they are often blind. So we obviously filed our first IND to treat Stargardt’s and hopefully in the coming weeks we’ll be filing one to also treat macular degeneration. But of course there are many dozens of retinal degenerative diseases, for instance retinitis pigmentosa which Steve Winn, for instance, has. Most of these diseases have one thing in common, which is that the retinal pigment epithelial (RPE) layer degenerates. And when that degenerates, you lose your cones and rods, which are the photoreceptors we see with. So the hope is, that by putting in new RPE, we can prevent that from occurring.
And there are no known treatments for these types of diseases?
DR ROBERT LANZA: Well, there are some treatments. [But] there is currently no treatment for Stargardt’s. We are hoping that this cell approach has a number of advantages. We are certainly seeing some amazing results in animals, and we are hopeful that this will translate into the clinic.
This will be the first treatment from stem cell research though?
DR ROBERT LANZA: This would be the first using embryonic stem cell-derived replacement cells. There’s only been one other FDA approval, and that is Geron for spinal injury. This would be the second. So we would be the first in the world to be treating eye disease using cells derived from human embryonic stem cells.
And the FDA approval is, would you say, imminent for human testing? Is it right around the corner?
(Note: Citing nondisclosure reasons, Dr Lanza could not discuss this specifically. The approval by the FDA was made Monday Nov 22, 2010.)
So how will these therapies affect people who currently have these diseases? Are we talking about improvement of eyesight? Are we talking about perfect eyesight?
DR ROBERT LANZA: There are two ways of looking at this – the main goal is that we replace the RPE so that we prevent further progression of the disease, and so obviously in the early patients, the patients who have advanced disease – [the goal] is to show they are safe and tolerated well. And of course, at any stage in this disease, these are progressive diseases, not only have you already lost photoreceptors, there are obviously many cells that are not in very good shape, they’re not very happy – to put it in generic, broader terms. So by putting in new healthy RPE we are hopefully going to improve the environment of photoreceptors, so that those photoreceptors that may not be in optimal shape can recover. And we may actually see an improvement in vision, just for that reason. But eventually, if everything goes as hoped for, and as planned, we would move to younger patients with earlier disease so we could prevent onset of blindness all together.
Why did you choose this disease as a focus?
DR ROBERT LANZA: Well, there are multiple reasons. One is that in the early days of embryonic stem cells, these cells have minds of their own – you have cells that differentiate in a petri-dish that can become every type of cell in the body. So the first hurdle, is [determining] how to get the cells to do what you want them to do. How do you get them to turn into some cell that is of medical importance? And it turns out that one of the defaults for cells is the neuroepidermal pathway, which includes the RPE. So spontaneously on their own, [they develop] these little freckles in the petri-dish that are pigmented. So they’re very easy to spot, and we were able to identify those, then they were able to expand as they normally would if they were damaged. In other words, they go through a differentiation, dedifferentiation phase. So once you have these retinal cells, [and] scrape them, they will dedifferentiate and fill the void, expand to confluence – and then reestablish their pigmented cobblestone morphology. And they can go through this cycle over and over and over so that you can generate very large numbers of cells. So that was the first hurdle – to have a population that grows robustly, that you can generate in very high numbers and in pure form, because to go into patients, you need to get these with high purity.
The second [hurdle] is that once you have these cells, there is a major medical need. There are more than 30 million people with macular degeneration, it is billions and billions in dollars of cost to the economy. And the other thing here is, is that they eye is privileged, so until we are able to produce patient-specific (cells) which is very, very labor intensive, going into an immune privileged site means that you have an attenuated response to the tissue, so that you can create a master bank that, hopefully, can be used for everybody. So there are a couple of these immune privileged sites that are the main sites – one is the brain, the central nervous system and the other is the eye. We have that advantage as well as a very small number of cells going into a very local area. So we’re putting these into an area, we know where they are, and we know they’ll stay there, and, equally as important, we have instruments that enable us to look into the eye and actually see the retinal cells. So we can actually monitor, in real time, what’s going on in these patients. If there is any infiltrate or any adverse affects, we would hopefully be able to see it directly. So there are many, many advantages, and like I said, we have been fortunate that this potential therapy is ideal in all of those respects. And also, importantly too, when we tested it in animals, we saw very significant improvement. We saw, for instance, in the Royal College of Rats study (the RCS rat), at 100 days, these rats were essentially blind, and the ones that were treated with the RPE cells – which again are the same human cells we would be using in patients – we saw that in the one layer that was left, in the treated animals there was a very robust 5-7 layers thick in the photo receptors. If we saw this kind of photoreceptor rescue in patients we would have a home run. We also were able to do a number of tests, [including] a visual acuity test – we were able to show there was a 100% improvement over the controls in their visual acuity. We studied the Stargardt’s mouse model over the first 60 days and saw that in the untreated animals they started to develop Stargardt’s, and lost some of their visual acuity while those that received the transplanted cells continued to have normal vision. So we’re seeing very significant results in these various animal models.
What was the time frame, would you say, in which you were working on this particular therapy?
DR ROBERT LANZA: To give you a sense of some ideas of the time frame, we published our original paper showing that we could, for the very first time, create RPE cells from human embryonic stem cells back in 2004, and then we followed up with a couple of papers in 2006 and after, showing that we could actually impact the disease process, so those were functional studies. So it’s been many years in the works here. A lot of companies didn’t make it, but fortunately thanks to an incredible team, we hung in there, and now here we are, with approval.
I want to talk for a moment about the blastomere technique. My understanding is that this is technology that isolates the human embryonic stem cells and doesn’t require destruction of the embryo – in effect, these are embryo-safe stem cells. Considering the political and court controversies banning stem cell funding – this doesn’t affect you or ACT, correct?
DR ROBERT LANZA: Well the single cell blastomere obviously allows us to remove a single cell to create a line, without destroying the embryo, and we’ve published on that. How this all settles out in the courts, I really couldn’t speak to. The reason we initiated that research is that there were many objections – even president Bush had said in his state of the union address that he was against destroying one life to save another. And what we do is a technique that is routinely done in IVF clinics, [which] is simply to remove a single cell to test before they implant the embryo, [for] a couple that wants to have children. We’ve been able to replicate that, and indeed we were able to publish showing that we can create stem cell lines without destroying the embryo, so in theory this should solve the problem. But with politics, it’s hard to know how all of this is going to be interpreted, but in theory, this does not obviously harm the embryo.
Your results have been reproduced, peer reviewed several times. Yes?
DR ROBERT LANZA: Yes, there is a group from UCLA that put out a paper not long ago showing that they had derived a number of lines of cells from the single blastomere technology, yes.
And independent reviews are determining the same results?
DR ROBERT LANZA: Yes, they actually did that work without our knowledge. We worked with them early on, on an earlier paper, but this follow-up paper that just came out not too long ago, and they were able to derive multiple lines independently, yes.
Is the climate in the US more difficult than in other countries and regions, such as maybe Europe, for getting FDA-type approval – for human clinical testing?
DR ROBERT LANZA: I think there is the complete spectrum. There are countries that are more restrictive and countries that are more permissive. They run the whole gamut. I think there are a number of countries that aren’t caught up in abortion politics. So there are definitely countries where they are less restrictive and countries where they are more restrictive.
Given the time frame you mentioned, it is a long time between when a therapy is developed until a tangible product or cure is perfected. How do you keep your enthusiasm, your focus on the project when this can take years and sometimes positive results never materialize?
DR ROBERT LANZA: That’s a good question. And of course, this has taken years. We have a very excited, enthusiastic team of scientists, who truly believe in this, and this is what we’re here for. We’re in the lab, we’re in the trenches, and we’ve seen what these cells can do. And we’ve done research with some other cells that can cut the death rate after a heart attack in half. So as we speak, there are folks in the hospital getting limbs amputated, and some time in the future people are going to say “can you believe once upon a time people used to have their limbs cut off?” And the doctor is simply give them a simple injection of these cells and restores blood flow to their limb. So we see this – we are doing these experiments and we have the good fortune to know about them, and the rest of the world doesn’t have that first hand experience. We have our team of very dedicated excited scientists, that are incredibly talented, and they want to make a difference, and that’s what this is all about.
Move ahead ten, maybe twenty years from now, political and governmental issues aside, where are we with cures for major diseases as a result of embryonic stem cell research? Do you see a particular focus?
DR ROBERT LANZA: I think we are making enormous strides. We’re moving far more rapidly than even I thought possible, and I’ve always been accused of being an optimist. Clearly, we already know how to reengineer cells to make the equivalent of embryonic stem cells. So I don’t think it will be at all unreasonable to think that we would be able to replace virtually any worn out or damaged tissue in the body. With these stem cells we can create a virtually unlimited supply of these cells. And with the reprogramming technology and/or banking of cells, we should be in a position to solve the issue of rejection. So when you combine that with the area known as tissue reengineering, we can reconstitute the cells into more complex tissues and structures, and eventually create entire organs, such as an entire heart or kidney or liver. I think some day, in two decades certainly, [if] you get into a car accident and lose a kidney, you’ll go into the doctor, they’ll scrape some skin cells and grow you up a new kidney. I don’t think this is science fiction, I think this is happening at a very rapid pace. I published a paper with Anthony Atala’s group a few years back, where we actually created miniature kidneys from clone cells that worked in cows, and removed toxic materials from the blood. His group for instance has tissue engineered entire organs, entire bladders, that have gone into patients, now for many years. So – this is going to revolutionize medicine.
Do you see the direction heading towards treating diseases which are already underway or do you see the direction going towards prevention of diseases?
DR ROBERT LANZA: I think there are applications for all those scenarios. Certainly, we’re talking about our RPE cells as preventative, and we know for a fact that we can create all of these various replacement cell types to replace damaged organs and tissues. So I think you’re not going to have just one application. There are literally hundreds and hundreds of diseases that the stem cell technology has applications for – some of them will be preventative, some will be to repair these damaged tissues, and others will be to actually incite and repair tissues. These are smart cells, they know what to do. So that the same thing would apply to, there is data that these kinds of cells could also prevent damaged heart tissue. The goal is that, there are over 80 autoimmune disorders in humans, [such as] lupus, MS, rheumatoid arthritis, Crohn’s disease, the list goes on and on. So, using that strategy, the hope is that we could treat many of these diseases. a very, very long list of things that, soon, this technology could be applied to.
What’s next in the pipeline from ACT that the public or investors, would want to know about – that you are allowed to tell me about?
DR ROBERT LANZA: Well, the only one I can tell you in this time frame right now is that we are [submitting] a new Investigational New Drug Application (IND) to go beyond Stargardt’s to treat age related macular degeneration which of course affects millions – so that will be filed in the coming weeks. There are obviously quite a few other things in the pipeline that I really can’t discuss.
DR ROBERT LANZA: I can tell you we are doing work with our joint venture so that we are able to generate entire tubes of red blood cells from scratch, and we’ve been able to now create platelets that are actually functional in animals, so there are a lot of exciting things like that which are underway.
Is ACT is going to be able to partner with other firms for further research and maybe pharma firms for development of new technology and distribution of drugs?
DR ROBERT LANZA: Absolutely – of course, we’re a small company. We can’t develop all of the potential applications. So clearly we have certain in-house expertise, but there are many, many applications that we would want to work with groups that already have established technologies to move that forward. In general we carry out collaborations, we work with teams who have been in this area for decades. We join forces, we furnish what we have expertise in and they contribute their expertise, so that we can move ahead very quickly and efficiently. Of course, as we hopefully will succeed with our clinical trials and move into phase three intervention, and hopefully phase four – manufacturing and very, very large numbers of patients – obviously that is not our area of expertise, so we’d be partnering with other groups and companies.
Dr. Lanza, thank you very much for your time and contributions.
DR ROBERT LANZA: Thank you