EXTENDED INTERVIEW: EUGENE REDMOND
July 2005

Dr. Eugene Redmond, professor of psychiatry and neurosurgery at Yale University School of Medicine, has been working on adding human nerve cells into monkeys as part of the search for a cure for Parkinson's disease. The following is an extended interview with Redmond.

 

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EUGENE REDMOND: Well we're doing a number of things to try to cure Parkinson's disease, which is one of our major interests over the last few years. And the research started with the use of fetal tissue and we found that there was some promise in that, but also some limitations. And so we've gradually used earlier and earlier precursor cells and eventually came to the use of stem cells, which have a lot more promise for being able to make into different kinds of cells. In addition to that, we're working with gene therapy to try to put in growth factors that might also be helpful for Parkinson's, or it might help cells to distribute themselves appropriately and more functionally. TOM BEARDEN: How do you use the stem cells? How does the experiment work? EUGENE REDMOND: Well, what we're doing is trying to replace dopamine cells, which are lost in Parkinson's disease. And so essentially what we do is eject a relatively small number of stem cells into the brain areas where the dopamine cells normally reside, and we're hoping and finding some success that they're turning into dopamine cells in small numbers, and they also are normalizing some abnormalities that occur in the brain in Parkinson's disease. Now we have an experimental Parkinson's disease in monkeys that we use the drug MPTP and that destroys dopamine cells that reproduces pretty much all the signs and symptoms of Parkinson's. TOM BEARDEN: These are human stem cells that you're using? EUGENE REDMOND: Yes, we're using human stem cells. TOM BEARDEN: Why use human stem cells in monkeys? EUGENE REDMOND: Well, we started out using human stem cells because we were eager to be moving quickly into clinical studies if we had success in monkeys, and it's very important to demonstrate the efficacy in a primate species in a really good model of Parkinson's disease to make sure that it's going to work and also to explore the various types of side effects and toxicity that might occur. However, there is a species incompatibility problem between human cells and monkey cells, so we're eager to begin actually working also with monkey cells to avoid the immune difficulties. And then we're not working across species but when we get ready to go back into the clinic, we still would have to use human cells again. TOM BEARDEN: What have you learned so far? EUGENE REDMOND: Well, we've learned that, as many things turn out to be in science, that it's more complicated, more difficult than we had hoped to begin with. But we are making some progress. We find that we can get stem cells to survive for long periods of time in the brain. They make into different types of cells, and we have some preliminary results in functionally impaired animals that the stem cells improve their Parkinsonism and make them better. TOM BEARDEN: Will this eventually lead to a cure for Parkinson's disease? EUGENE REDMOND: Well, we would like to think so. This and maybe some other techniques that are coming along will have to be combined in order to make a real cure, but one of the reasons that people are so optimistic about Parkinson's is that the deficit of dopamine cells is relatively small -- a few millimeters in the target areas. And so it's not the same problem that you would have if you were going to try to do something for Alzheimer's Disease, which is a more diffuse process, or even stroke, which is over a broader brain area. So we're very optimistic about that. The other thing is that we know that the Parkinson's is improved by replacing dopamine itself with various types of drugs. So you know all elements are there to say that if we could do this in a biological basis and have it work continuously, that you could actually have a real cure. TOM BEARDEN: When might that cure be available? EUGENE REDMOND: Well, I think that the cure in terms of Parkinson's is still a few years away. A lot of the initial studies with stem cells have been, as I said, not as promising as we had hoped. TOM BEARDEN: So a lot of research and clinical trials need to be done before there's something available on the market? EUGENE REDMOND: Oh, absolutely. Well you know, after the time that the animal studies are convincing then you would need to do early phase clinical studies and demonstrate that it really works in patients with the real disease. And that process itself is probably a three-to-five-year process.
	Controversy surrounding the research
	TOM BEARDEN: Stem cell research has been controversial. Have you in any sense been impeded by the political arguments that surround this kind of research? EUGENE REDMOND: Well, as a researcher I'm eager to try to move research along and I'd like to help out in the political process by helping people to understand what we're doing and that there are people who are thinking about the ethical issues and problems with the techniques. But at the same time you don't want to just wait for the political process. So I've been very careful to tailor my research to do things that could get grant support from the government and so we're using neural stem cells that were derived within the guidelines and we're using embryonic stem cells that also are one of the approved lines. That doesn't mean I think that's adequate for a proper national research effort. And I think we're the examples of how out of balance the funding is, is that only a small fraction of money goes into support of embryonic stem cells and there's 10 times as much money that goes into the study of adult stem cells. Scientifically, I'm interested in adult stem cells. I think they're terribly interesting but that's way out of proportion to probably a scientific promise and so you know in that sense of political debate and situation is distorting science. TOM BEARDEN: The politics have distorted the funding stream? EUGENE REDMOND: Well, I think so. But things are looking more promising in the last year or so with the California stem cell initiative and the fact that a lot of states have realized that they can't wait for the federal government to get around to doing something about it, and so many states, including my own home state of Connecticut, has recently passed some legislation and some funding for stem cell research. So that's a real plus and a first, I think. TOM BEARDEN: Some people are uncomfortable with the idea of human cells in animals. What do you say to them? How would you explain to them why what you're doing is valuable and good? EUGENE REDMOND: Well, I think that the issue that people have brought up about, technically they're chimeras, which is any type of mixing of cells of different species, and there are some areas of concern about that. And particularly where you're putting human cells into the brain and, you know, we have the idea and general belief that the brain is unique in the body and it helps to control who you are and that sort of thing. And so there are some issues that I think need to be looked at. What we're doing, however, is something that's been done for years and there was not a lot of interest in it. And really important in terms of determining adequate treatments, efficacy, as well as safety. On some of the other, well just the percentage of what we're doing in terms of putting cells into the brain, we're putting maybe 8 to 10 million cells in a brain that maybe has 20 to 40 billion cells. So this is an extremely small impact. It's not going to make a monkey into a humanized monkey. It seems extremely unlikely. The areas that I think are more of concern are where people are talking about mixing cells at the blastocyst level much earlier in development, where you could actually possibly get some kind of bizarre chimera, and that's an area that I think should be looked at and carefully examined. And I'm very much supportive of the guidelines that were recently published by the National Research Council. They paid attention to the chimera issue and indicated several different types of things that should not be done, at least for the foreseeable future. And others tried to suggest setting up mechanisms that would have review committees to look at the reasonableness and necessity of doing studies in animals with human cells. TOM BEARDEN: So you think there is adequate leadership at least in that sense? EUGENE REDMOND: Well, I'm really happy about the National Research Council, and I think the fact that they had to do this is partly because of the default on the part of the federal government and I certainly hope that many institutions will adopt them and that they become the defacto standard of good ethical research in this area. I know the dean at Yale said right away that he expected Yale was going to adopt those, and I expect a lot of other institutions will as well.
	Benefits to operating on island of St. Kitts
	TOM BEARDEN: Why do this on St. Kitts? EUGENE REDMOND: Well St. Kitts is a unique resource for primate research primarily because there's a large population of Old World's African monkeys that have lived here for several hundred years and create a lot of agricultural damage. So the monkeys are available and provide an opportunity for us to operate a primate facility that takes advantage of having many animals. And primate research has gotten so expensive in the United States that one of the other advantages is that it's a beautiful tropical environment so the monkeys can live outdoors and you don't have to provide the air conditioning and heating and all that kind of thing for them. And so it's been a really useful resource and we have lots of federal grant projects. One of the things I should say is that because of our funding, we still have to abide by all of the regulations that would be in effect if we were doing this somewhere in the states. And we're not here trying to get around some kind of regulation. If anything, one of our major initial motivations was that the monkeys were healthier and happier here than they are living in a facility in the states.
	Intricacies of using human cells
	TOM BEARDEN: Tell me what you're doing when you're going through a procedure. EUGENE REDMOND: Well, that procedure is the standard implantation procedure that if we were using stem cells, essentially, we put the animal into a special head holder that holds the brain in a fixed position in space. And then we have these micro calipers that allow us to hit any target within that space and so we know where the areas that we're trying to target with the cells. So that's a very, very minor simple operation and we have a drill that we just drill a tiny hole in the skull and then we drop a needle down and then inject the cells and then pull out again and close up. It's almost not even defined as major surgery. TOM BEARDEN: I gather it's important that you know specifically where you're putting those cells. EUGENE REDMOND: Yes, right. You want to know exactly where they are and you want to do it over again exactly the same each time. TONY VANWITSEN: You're not concerned about any problems in the kinds of chimeric animals you're creating. What would be the basis for concern? EUGENE REDMOND: I would be concerned primarily about the mixing of human and the animal cells in the early embryological stage in the blastosystic or early on after that where you could get some rather potentially serious mixes of species, and I think that's something that should probably not be done. Some of the other suggestions that have been made, for example, for a number of years, one of them is replacing a rodent's immune system with a human immune system so that you could have a rodent model of human immunity. I think that would be fantastic. And there's been some progress in doing that. Some of the other things that the National Research Council pointed out that would be of concern would be animals that are breeding that had mixes with other species because you could end up with some rather potentially, some rather bizarre outcomes, and that was another thing that they suggested should not be done at all. We haven't really had any occasion for our animals to breed, have stem cells in their brain, I wouldn't be concerned about that, but on the other hand, there's no reason to do it. TOM BEARDEN: Why has it been so hard to get the dopamine to the right place? EUGENE REDMOND: Well initially, the hope was that the cells could be put into the target areas where the dopamine is supposed to be released and it seems that that's not as effective as it was hoped that it would be. And it seems also likely that in order to really restore the circuits, you have to put the cells in the place that they originally grew instead of where they release the dopamine. And those two areas are separated from each other by a significant distance in the adult brain. And so a lot of people including our own group are working on trying to put the cells in the correct, original place and then get them to draw out their axons for dopamine release into the proper target areas.