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Volume 39
Number 22
July 12, 2007 |
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One on One: Alan Russell
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“To borrow Winston Churchill’s phrase, ‘It’s not the beginning of the end. It’s the end of the beginning,’” said Alan J. Russell, director of Pitt’s McGowan Institute for Regenerative Medicine, of his burgeoning sub-specialty of medicine. “I would say that’s really true in the field of regenerative medicine. We’re emerging from our adolescence.”
In a nutshell, regenerative medicine seeks to restore structure and function of damaged tissues and organs. It also looks for alternatives to organs that become permanently damaged. The goal of this medicine is to find a way to cure previously untreatable injuries and diseases, explained Russell, who also is University Professor of Surgery, executive director of the Pittsburgh Tissue Engineering Initiative and director of the National Tissue Engineering Center.
The McGowan Institute, a joint project of Pitt and UPMC that is located off Second Avenue near the Hot Metal Bridge, is home base for more than 175 core faculty and affiliates who focus their research in one or more of regenerative medicine’s three “pillars,” Russell said: medical devices and artificial organs; tissue engineering and biomaterials (using a combination of cells and engineering and biochemical materials to improve or replace biological functions in an effort to repair damaged tissue and organs), and cellular therapies (using stem cells from a patient or another source to enhance the recovery or regeneration of the structure and function of tissue and organs).
The overarching goal of the McGowan Institute is to accelerate research in these areas, in order, eventually, to cure human diseases.
Barely three decades old, regenerative medicine has built an enormous amount of momentum as evidenced by a number of developments, Russell said. To wit:
• Some 80 percent of Americans now say they support some form of stem cell research.
• A significant number of cell therapy human clinical trials already are underway at Pitt and UPMC, including the first FDA-approved phase I trial of a surgical cardiac stem cell therapy, and a trial treating urinary incontinence with adult stem cell therapy.
• Ten years ago, the Tissue Engineering Society International had 50 members; its successor, the Tissue Engineering and Regenerative Medicine International Society, boasts 2,500 members and is growing.
• The McGowan Institute, which in 2001 supplanted the McGowan Center for Artificial Organ Development, was the first institute for regenerative medicine in the country. Today, including tissue engineering centers, there are 64.
• The field has its first billion-dollar product, an electronic bone graft device that creates bone to fuse the spinal cord. “It’s in operation around the world, and the sales for the last quarter were $260 million,” said Russell.
But the key word in the regenerative medicine research process is “patience,” Russell told University Times staff writer Peter Hart last week, as he offered an overview of where regenerative medicine stands and where the field may be headed.
UNIVERSITY TIMES: When can society expect to benefit from new cures as a result of regenerative medicine research?
RUSSELL: What I usually say is that people who will benefit from this science are our children’s children. I think it’s very important for us to under-promise and over-deliver. The idea, for example, that new therapies will be broadly available from either adult or embryonic stem cell research in a year or two is disingenuous. It will turn people off. And we don’t need to do that, because the science in and of itself is incredibly exciting. We don’t need to think of an immediate massive clinical impact in order to have people understand how exciting the concept of regeneration actually is.
As well as attracting scientists themselves, the idea is so compelling that the public understands it. I’ve traveled the world talking to scientists and the public about it, and people love it, they’re enchanted by the idea and the simplicity of the idea.
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You say it’s simple. How would you describe the science to a lay person?
It becomes simple once they understand that mammals are regenerating all the time, like a elk growing its horn back. And there are other examples in nature, like a salamander growing limbs back.
Humans are doing internal regeneration: If you have a broken leg, you set it in a cast, you keep your weight off it for a period of time and the bone heals and it strengthens. The same is true of the liver. As long as you can provide liver function, the liver will regenerate. The lungs are the same way. Why not other organs? Why not external regeneration? Plenty of mammals do it, why can’t we humans? We use that catch phrase a lot, but it’s really true.
One of the unfortunate things is that sometimes scientists think that unless they can paint a picture that says in three-to-five years’ time this work will be important, no one will think it’s important today.
Or it won’t be funded.
But I think they’re really under-estimating the power of the message and the intellectual capacity of people to appreciate it. If you say, “If you invest in this today, your grandchild might not have to deal with diabetes,” people are very excited by that. It’s not a barrier. No one is turned off by the idea. No one says, “But I want it tomorrow.” People understand it’s a long haul. I think the barrier is when we try to convince ourselves that it should be three-to-five years.
It’s also not a step-by-step upward process. You go up for six months and then you might level off. At each step you might publish a paper, but that doesn’t mean that the next step will be up. The more the public understands the way science actually happens, the more satisfied they will be with the result down the road. If I don’t try to dumb down the time scale, and try to explain why it takes a long time, and should be a long time, they buy into it.
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What are the key questions that regenerative medicine researchers face?
I think you can take the challenge of regenerative medicine and boil it down to four very simple questions on the science or technical end.
The four technical questions serve to unite the field: What’s the right cell? What’s the right material for delivery of the cell? How do you put the two together, the delivery material and the cell, in vivo, that is, outside the body? How do you get it together inside the body?
The field has begun now to answer the exciting question of what cells to use, whether they’re bone marrow-derived or muscle-derived or fat-derived or amniotic fluid-derived. You’re touching on the very natural alliance between scientists who have passions for different cell types; they each believe their cell package is the very best cell source. I say, the more the merrier. The more people who think they have the best cell source the better off patients and clinicians are. As I’ve said a thousand times before, we advocate for patients, not for cells. Who cares where the cells come from if they work?
But, what’s the right delivery material? How to combine the cell and the material? We still have a lot of work to do in those areas.
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Is the research process largely trial and error?
No, no, I think it’s well-founded and a lot of it is intellectually guided. For example, if you’re trying to make a cell that would turn into a bone, would you stretch it or try to compress it? Well, think about your bones when you stand. Are they feeling a stretch or a compression? Obviously, compression because they’re bearing weight. But if it’s a muscle cell, there will be a stretching.
Researchers do a lot of thinking about how can we train cells using other materials and other signals such that the cells “think” they’re the cells you want.
Then there are other scientists who believe that you don’t need to do all that, that perhaps all you need to do is put the right material in the body, that over a period of time it releases the right factors such that the body does all the work. That’s called inductive scaffolds. You put up a scaffold, like scaffolding for a new brick wall, and all of sudden the bricks coalesce and make a building without the bricklayer.
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Is there still a minority of Americans who object to regenerative medicine as an abuse of natural order, that is, as manipulating nature?
Of course, there are always some groups of people who don’t believe in medicine, who believe that whatever happens, happens. And there is a group of people who are, let’s say, disquieted by the idea that we might be extending life to huge numbers.
But I think many of those opinions, other than faith-based opinions, are usually built on rather shaky ground.
Do I think we’ll extend life to 125 or 150? No. We’re talking about quality of life, not quantity, and about curing diseases. If you look at the impact of all of medicine in terms of life expectancy, I don’t think regenerative medicine is going to change that paradigm. There may be some small impact.
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But don’t some Americans, including President Bush who twice has vetoed bills that would allow embryonic stem cell research to be federally funded, object to such research on moral grounds?
The controversy is not about embryonic stem cell research for most people. The controversy is about pro-life and pro-choice. Pro-life/pro-choice discussions don’t often come with the opportunity to use concrete examples. Even in politics there aren’t that many votes on the issue.
The reason that embryonic stem cell research is at all controversial is it provides an ideal opportunity to state something about the sanctity of life, with a concrete example instead of in the abstract.
For people who want to draw lines it’s an opportunity to draw a line. But as I’ve said a number of times before, including in editorials, I think even for people who like to draw lines that supposedly can’t be crossed, the lines move. No one likes to admit that, but they do move.
In a field like regenerative medicine, stem cell research or cellular therapy is moving very fast, and so are the lines moving quite quickly of what is possible. The theology of it, of course, will move much slower, but it will move.
In Japan today you don’t generally get an organ transplant, because their belief is that you die only when your heart stops beating, not when you’re brain dead. Once the heart stops beating, you can’t harvest the organs as readily, so the time process of what’s acceptable in research and practice moves much slower than the scientific lines in this kind of area.
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How does the United States stack up against the world in this field? Are other countries outspending us?
First of all, there are no limitations in this country on the research, except those on federal funding. And there are a few states that have legal complications, usually with specific forms of legislation, when they couple these issues with their abortion-control acts, for example.
Pennsylvania is one of those states, but it hasn’t been tested yet in the courts for what scientists can do, for example, with privately funded embryonic stem cell research.
There are many countries where there are severe limitations on this type of research. Here it’s purely a matter of money: Who is willing to pay?
Interestingly, in the last couple of elections there’s been a group of politically active people who have targeted embryonic stem cell research as a way to get people who support such research elected. I think in just about every case the pro stem cell research candidates won. It goes back to it not being a really big controversy. A few people are trying to use it as a controversy.
Some countries are outspending us. That touches on the other, non-technical side of regenerative medicine. There are two other key issues, what I would call people issues. How do you build effective interdisciplinary teams? If there’s one thing that we’ve been fortunate about here is the environment and the leadership of this University and this health system, which enable us to do that naturally, and I think that’s why we are where we are.
The other question is, who pays? Where does the money come from?
Pitt and UPMC spend through grant money and philanthropy on the order of $50 million-$70 million a year on regenerative medicine research and clinical practice. And that’s a reasonable amount for a couple of paired institutions.
But the single-year budget for the Chinese National Tissue Engineering Center in Shanghai — a single entity — last year was $250 million.
The competition is really tough, even within this country. The lieutenant governor of Rhode Island called it the technology arms race between the states in the U.S.
The California Institute for Regenerative Medicine, which was born out of Proposition 71, the first stem cell policy battle in the country, began with a budget of $350 million. Their annual budget this year is $1 billion.
We prefer the view from the front to the view from the rear, so we’ll be working very hard to continue and increase our funding.
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Because the field is so new, isn’t it true that scientists who got in on the ground floor are the only ones who can teach regenerative medicine? Do you see a potential shortage of teachers in the field?
That’s a good question. The answer is, we’re addressing it. Not just we here, but the field. I think people in the field are very conscious of it. This is what professors do for a living. We have a balance between research and teaching, and education remains at the heart of everything we do. That side of things is important.
At McGowan, we have NIH-funded training programs in tissue engineering at the undergraduate, graduate and post-doctoral levels, all three. Even at the undergraduate level, you can use these cool concepts to teach things to undergraduates that normally they would find too abstract.
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Do you think that at some future time the equivalent of a medical school devoted to regenerative medicine will emerge?
No, I don’t think that’s going to happen. The broader question is: Will cellular therapy become a field of medicine, or will cardiologists, radiologists, pulmonologists, whatever, each deliver some of the therapy? That’s a really interesting question. I’d be happy to make a prediction about that. Regenerative medicine/cellular therapy will become a field in time, because there are enough similarities that unite the issues of those kinds of specialists and that will draw people together who are from different disciplines who are, in effect, using the same set of tools.
In the same way you have clinical cancer centers that are interdisciplinary centers but with people clustered around cancer. In that case, they’re clustered around a disease, but the disease takes different forms.
I sometimes call the field head-to-toe regeneration: Someone, somewhere in the world is working on every part of the body. As cellular therapies emerge, over decades, it’s quite likely that one day you will be able to earn a PhD in regenerative medicine. In universities it’s important to think about and plan over decades. We have to plan for that.
McGowan was designed to be a bowl, not an umbrella. We’re not seeking to prevent the light from shining on the work of others, we’re just seeking to help scientists and to accelerate clinical translation. So our purpose was not to do the work of a department of molecular biology or genetics or whatever.
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Has any development in the regenerative medicine field come faster than you anticipated?
Broadly speaking, when we started the McGowan six or so years ago, my colleagues and I shared the view that we wanted to be quite circumspect about any kinds of predictions, and I think we were right to do that.
In terms of clinical activity I’d say that things in Pittsburgh have happened more quickly than I thought they might. I’ve lost count of the number of clinical trials involving cell therapy that are taking place right now, but it’s a significant number and in a variety of areas.
Some of them are in phase I, but some have transitioned into phase II. The key is that the people doing the work, in phase I or even phase II clinical trials, don’t kid themselves that just because it’s a clinical trial there is automatically broad clinical applicability. That’s true of all clinical trials, really. So, I would stick to my original prediction that it will be our grandchildren who will see the impact of this kind of medicine. We’re on track for that, maybe slightly ahead of track, here and globally.
It’s a very exciting time for us. We’ve been through a little bit of the ups and downs of adolescence. The field has seen a little bit of hype — and a lot of noise of the kind that adolescents make. We’ve seen failures and bad decisions that adolescents make, but we’ve come out of it, and as a field we’re in good shape.
(For more information on McGowan Institute projects, visit www.mcgowan.pitt.edu or www.regenerativemedicine.net.)
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