Editor-in-Chief, Handbook of Stem Cells Vice President of Medical & Scientific Development Advanced Cell Technology Adjunct Professor of Surgical Sciences at Wake Forest University School of Medicine	September 2004
	"We are able to fix hearts now for mice and cows just like you repair a bicycle tire. We've used this technology to generate cartilage, bone, skin and vital organs. The hope is that some of us alive today will be able, after a car accident, to simply go to the doctor's office and we'll grow you a whole new kidney."

How did you get to this point in your career?
In the early eighties, I worked with Christiaan Barnard, you've probably heard of him, he did the first human heart transplant and we actually wrote the first textbook on heart transplantation. At the time that we transplanted these organs, there was a new drug called Cyclosporin. We were all saying that in a few years, we would have a brand new drug that will replace it and will have no side effects. There was also talk about the fact that you might be able to create these "universal cells". The funny thing is that here we are now 20 years later and of course, the drug of choice is still Cyclosporin.

So I actually started out that way, transplanting hearts. Then I went and did work transplanting islets and pancreases for diabetics, the same problem over and over was rejection. The two main hurdles of transplant medicine that I ran into again and again were organ shortages and rejection. In the United States alone, there are over eighty thousand patients currently on the organ waiting list whereas only about twenty thousand will get their needed organs. Secondly, there is the problem of immune rejection. Once an organ is transplanted, the patient has to take a lifetime of immunosuppressor drugs that have horrible side effects such as cancer and infection. And then when stem cell technology started to develop and Dolly the sheep came along, I said "Ah Hah!" here is the answer that can solve both of these problems, the donor organ shortage as well as the problem of immune compatibility.

And so I came to ACT (Advanced Cell Technology) six years ago. Here, we have created some miniature kidneys that work, as well as having done some work where we have created certain cells that could be used to treat or even cure macular degeneration (which is the leading cause of blindness in Americans over 60). We've recently published a paper where we used a small injection of these stem cells into mice that had had very severe heart attacks and the stem cells repaired over 40% of the damaged heart within a month. So the hope here is to do the same thing in humans.

In our own laboratory, we've used stem cells in collaboration with tissue engineering to create heart patches in cows. The whole theory is to use these patches to fix damage very much like you would fix a bicycle tire. We've used this technology to generate cartilage, bones, skin and even miniature kidneys that produce urine and then transplanted them back into the animals that they were cloned from.

Again, the potential of this technology is enormous. Say for instance, you lose a kidney in a car accident, we hope some day, you'll just go to the doctor's office and they'll just grow you up a whole new kidney.

How hard is this to do?
Well, it is really amazing. These stem cells are very smart. And they know what to do in the right environment. For instance, if you inject neurons into a damaged brain, they know how to connect up and talk. One of the studies we had was a sheep model of spinobiphida where, like in humans, if they had this, they would be paralyzed. The first animal that got these embryonic stem cells was up and walking, so again, these cells are very smart and know what to do. The key of course is how do you do this? What is the promise here? There are over 3000 Americans that die everyday from diseases that could be treated using this technology in the future.

This is an extremely exciting time in the stem cell field. The Handbook of Stem Cells (Elsevier, 2004) represents the combined efforts of twelve editors who are the leading who's who in the field, thirty-one editorial advisors and hundreds of scholars and clinicians whose pioneering work ushered in this fascinating and important field. Their knowledge and expertise has added indispensable depth to the authority of the material presented in this two-volume set. And I think that it has succeeded in defining and capturing the sense of excitement, understanding and hope that has followed from the emergence of this new field.

How do you explain all of these important Editors getting on board with this book?
This must be a major project that everybody sees as having a value in being a part of.
Absolutely, I think they all wanted to be a part of a seminal book that is going to define the field. I think that for everyone in this book, the primary objective is to further the field. When this was initiated a couple of years ago, those of us in the field knew how important this was and I think we wanted to do everything within our power to see to it that this technology is brought to the clinic as soon as possible. The best way of doing that is to collect all of the information and expertise necessary to further the field. For instance, there are a couple of chapters here that give you all of the secrets and tricks to grow embryonic stem cells. You can go to the existing literature and you won't find all of the tricks - where you order all the stuff and those kind of details. So I think having this book is going to move the field along unquestionably.

The book has everything. It covers everything and anything that is relevant to stem cells. It goes through the embryology of all of the organ systems and how they evolve all of the genes and factors that are essential to driving these cells into the cell types that will be clinically important. And so, not only does it lay the foundation, but then it basically explains the extent of our knowledge in every organ system in the body as related to how those organs develop and what stem cells are involved. All of these insights are going to be helpful in the future to using stem cells for medical therapies. Again, one of the major hurdles now is turning these stem cells into the cell types that are going to be crucial. And we still don't know how to do that for most of the cell types, but this book covers virtually all of the knowledge that exists out there, for all of the body systems.

What does this technology enable you to do?
Well, we know easily how to create dishes full of dopamine producing cells that could be used almost immediately for treating patients who may have Parkinson's disease. We know we can readily turn stem cells into beating heart cells; it is really fascinating to look in your petri dish and see clusters of cells beating away just like a normal heart would.

On the other hand, there are over 200 million people in the world with diabetes, it is one of the leading causes of death; it is devastating. So, we'd love to know how to get these stem cells reliably into insulin producing cells, not to only treat the disease, but to wipe it off of the face of the planet all together. I don't think this is science fiction, I think this is very real. Doug Melton, one of the editors is working away at that and I would be surprised if he or some of the others here don't solve that problem in the coming years.

This handbook is literally a who's who in the field. It is virtually everybody who brought this field to where it is today, it is all of the pioneers: Bob Edwards who did the first in vitro fertilization, Martin Evans who was the first one to get mouse ES (embryonic stem) cells, Nobel Laureate E. Donald Thomas who was the first one to use cell therapy in a patient, Jamie Proxen and Ardont Gerhard, the two pioneers who were actually the first in the world to derive embryonic stem cells. These are the people who are responsible for all of the scientific developments in the field. I mean, literally all of the pioneers who got stem cell research to the point that it is at today are involved in this book.

Is it a mixed blessing to you as a scientist to have all of this public exposure?
You have to realize that in the early days, there were people who were picketing; there were people who unequivocally thought that I was a murderer. In fact, I was on a website for being a murderer for killing these embryos. I was very, very unpopular. In the early days, it was very heartening to have the Nobel Laureates come on board, then 100 college presidents came on board and slowly and surely the scientific and medical community came on-board.

Eventually, the public was educated to understand what this is all about. And so the climate that we find ourselves in today is not how it was at all. In those early days, my neighbors even became upset because they didn't understand. At that time, the goal was education and it is heartening now to see that the majority of the public is realizing this potential everywhere, people from Orrin Hatch to Nancy Reagan. As a matter of fact, we have in this book chapters by Mary Tyler Moore and Christopher Reeves, two of the very earliest advocates who went before Congress and who really tried to educate the public as to the importance of this research.

Who is this book intended for?
There is no question that there is something here for everybody and a lot of this would be accessible to people with very limited background. With almost 2000 pages, certainly there will be areas that will be of greater interest to researchers in the field, but most of the chapters start out with a general history of the subject. One of the strengths of this book is that there are many, many chapters that are devoted to nothing other than to the history of this field and to what the promise is: the prospects, the challenges. Again, I think that there certainly is a general overview for everything there and then there are areas that go into greater depth for those who may be in the field itself.

Where should Grad students be focusing if they are considering jumping into stem cell research?
Obviously, having a background in biology, molecular biology, genetics, all of those areas - this is a multidisciplinary field. Clearly even from the clinical aspects of it, there is going to be a lot of work testing these cells, so a background in life sciences, in general, is necessary.

How about your own misgivings? I have kind of peeked at a few interviews online, it sounds like you have been fairly judicious in the public debates surrounding all of this in terms of needing to be cautious but move forward. Can you summarize some of your own concerns?
I think that clearly, in the interest of popularizing this for the public, a lot of things have been overly simplified. A lot of people are under the impression that we are going to have these cures in a year or two - don't get me wrong, for some of the simpler applications, I think we can be in the clinic in the next year or two. But most people don't understand that it usually takes five years for clinical trials. Again, for most of us baby boomers, I would be shocked that if at the end of our lives, most of these diseases were going to have therapies. I would be very, very surprised if by the time we grow old, you just go to the doctor and they'll say, We'll just grow you a new kidney, new vessels or whatever. You could reboot the immune system and give people a chance to be relieved of these terrible diseases and this isn't science fiction, there are already human trials that show that these cells can kick multiple sclerosis and these things into remission.

The other thing that is exciting here (and again, we're just talking perhaps a few years) is that you can give new immune cells to patients. I don't know if you remember the day when they gave Jeff Getty baboon cells for his AIDS (the reason that they had done this is that baboon cells are resistant to HIV infection, probably because they are missing a receptor). We know from all of this technology (and it's mentioned in the book) that you can probably knock out one of the receptors and then using the cloning technology and stem cells. One could just grow new cells that could be injected back into the body that would be resistant to HIV infection. So you could then give AIDS patients a new immune system that is resistant to infection.

So I think that is what we're talking about, we're talking about arthritis, arterial sclerosis - most of us probably already have it even in our twenties and thirties. It has been shown that when you get these stem cell injections, it actually reverses that vascular damage. That would be just unbelievable not only to fix damaged tissues, but to actually reverse damage that has already occurred.

Would it be easy to underestimate potential of this technology?
My goal is that when you are confronted with a patient who possibly has to have a limb amputated or going blind, that if we can prevent that, then we have an ethical obligation to do whatever we can. The fact that there are 2000 pages here and it took all of these experts, tells you the extent of the effort that is still going to be required to get all of these therapies working in the clinic, but on the other hand, I truly think that the promise that people are hearing about will be reached.

There is certainly a lot of room for abuse on the enhancement side of the picture, how do you feel about the possible ethical implications of this?
I think that is a concern for all of us. I think it would be an abuse of this technology to use for frivolous applications. For instance, I had an interview with Playboy in which they asked about curing baldness. To create cells just to alleviate baldness - as much as it may be something that someone wants - I think that would be a frivolous application of the technology. Now, if you happen to have stem cells already in a dish from having cured heart failure or liver failure or whatever, well then certainly we know we can grow hair follicles. At that point, if they already exist for a life threatening disease certainly they could be used for that purpose, but to derive them just for that, I think would be abuse of the technology.

Certainly, these are the things that we are going to need to watch out for. I think that is why we regulate these things. And again, that is why we have quite a few chapters in this book on the ethics of this, the regulations involved, the legal aspects, we have several of the top biomedical ethicists addressing those very concerns.

Tell me a bit about your company, ACT.
We actually started out in the early days cloning for agricultural purposes. And then when I came on board, the decision was made to shift the use of technology for human therapeutic purposes. So that is our entire focus now.

I have been very interested all of my life in conservation and have done a few studies where I cloned the first endangered species using this technology. I live on an island and have founded several pond associations and have been on the conservation commission for years. So I thought, here is a technology that we could use to increase biodiversity by rescuing genes that would otherwise be lost. So that was one of the things that we did. But other than that, the entire focus of the company is now on human therapeutics.

Tell us a bit about your home.
I have a ten-acre island with Osprey, Eagles, Blue Heron. I have a pair of swans that nest there every year, they are my buddies. They come up begging for food all of the time and everything is beautiful. Absolutely spectacular!

I collect all sorts of gems and fossils; I have a brontosaurus bone that is 800 pounds and six feet long. The first thing that people always say (because I cloned the first endangered species) is "Bob are you going to clone that?" and I always say "No, you can't clone from stone, you need a living cell."

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This article by Joe Martis
j.p.martis@elsevier.com