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THIS WEEK IN
CALIFORNIA WILD

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Second Chances

An Interview with Robert P. Lanza

California Wild: You’re on the Conservation Commission for the town of Clinton, Massachusetts. What are your interests there?

Robert Lanza: I founded the South Meadow Pond and Wildlife Association, which works in conjunction with that commission and with other regional groups in Massachusetts such as the Greenway Conservation Trust. The goal of all of these is habitat preservation, conservation, and protection. I live on a ten-acre island where there are blue herons, eagles, and an American bittern that runs around. So I have a very keen interest, and always had, in nature and preserving the wild.

CW: What are the goals of your company, Advanced Cell Technology?

RL: Well, there are two main goals. One is agricultural, and the other is medical. When I came on board a little over three years ago, Mike West was President and CEO. During the first few weeks, Mike, Jose Cibelli [v.p. of research at ACT], and myself got together and decided that the company should put its emphasis on human medical applications. We didn’t take the decision lightly, because we knew it was controversial—though we didn’t think it would be quite this controversial! We knew that we were going to take a lot of heat, as there was very little support for cloning and stem cell research at the time. Even today, we’re the only company in the United States working on this technology.

CW: I believe you’ve also cloned wild animals, especially endangered species.

RL: I have a medical degree and originally went to Advanced Cell Technology for medical purposes. However, after joining, I immediately realized that “hey, wait a minute, there may be an application here for using cloning as a conservation tool.” And as much as we’ve been beat up for this—including the argument that our work would decrease genetic diversity—the truth of the matter is, if an animal is killed right now, the genetics of that animal is lost from the planet forever. There is no technology to reintroduce those genes back into the pool, and in some species there are only a few dozen animals left.

The bucardo, a species of mountain goat found in Spain, recently went extinct. That’s a perfect example, because the last three animals were alive just a few years ago. Biologists in Spain were making the case back then that we should try to get a few cells from the animals to preserve these genes. They suggested the cells could possibly even be used to clone the animals in the future. They were laughed at—“It’s science fiction, what a joke, you could never do that,” many were saying. It took them years and years to finally get permission, and the critics kept saying it was science fiction. Even the woman who finally convinced the government to let them get the cells didn’t think they’d be able to use cloning technology within her lifetime. They eventually got gene material just a few months before the last animal died and the species went extinct.

A year later, I approached the Spanish authorities and said that we could clone the bucardo from the cells without too much effort—that it would be more of a demonstration than an experiment. We had already carried out studies with the gaur [an endangered cattle species found in southeast Asia]. Up until the time we cloned ‘Noah’ the gaur, the scientific community was in consensus that you could not clone across species, that the mitochondrial genome of one species could not talk to the nuclear genome of another, that there was a fundamental incompatibility.

No one had ever gotten a pregnancy using what we call cross-species nuclear transfer, cross-species cloning. But we took some skin cells from a gaur that had died nine years earlier at the San Diego Zoo and fused them with the empty eggs of ordinary cows. Not only did we get beautiful little gaur embryos, but for the very first time ever we got pregnancies! And at the same rate as we did with ordinary cow-to-cow cloning. Of six pregnancies that we generated, one fetus went all the way to term. Noah was born in January 2001, and healthwise, was rated in the top ten percent of calves. He was absolutely beautiful, just like a little baby reindeer.

We wanted to send the message to the conservation groups that you should be protecting genetic diversity now. And although we still may not have the technology to do it very efficiently, it is real. When an animal dies, all you have to do is freeze a few cells to preserve the genetics of the animal forever. So that’s what this was all about—a way to show that what the scientific community said was impossible was not the case.

CW: Are you going to do it again?

RL: As a matter of fact, another conservation project is being organized as we speak. We’re also working on a new technology. You see, the technology we used to clone the gaur will eventually be obsolete—the cloning efficiency is very low. We’re hoping to develop a new method that will solve many of the problems that we’ve encountered in the past. For instance, the giant panda is an animal that people would love to see more of. However, at present there is no surrogate animal genetically close enough to generate an embryo. We have preliminary data that suggests that this new technology could overcome that evolutionary gap.

CW: So you could use the egg of an animal that’s not a close relation?

RL: Right, and have the genomes talk to one another.

CW: What happened to the bucardo?

RL: The bucardo project is proceeding slowly. Cloning goats is now routine in many laboratories. In fact, an in-vivo culture system has been worked out where 85 percent of the blastocysts generate a live kid. So the ability to use the technology to generate cloned goats is straightforward. On top of that, the Spanish group has already successfully carried out the other half of the project—embryo transfer—using surrogate animals which are a cross between the domestic goat and the Spanish ibex, which is closely related to the bucardo. Now it’s just a matter of combining the two. Fortunately, the gestation period of the bucardo is only five months instead of ten months for the gaur, so we should have had live bucardos on the ground by now.

CW: Because these clones are likely to be genetically identical, that doesn’t augur too well for their long-term survival. This must be a concern down the road.

RL: Yes, well, what really bothers me—and I’ve sent the message out there over and over and people just don’t get it—is that the whole goal of using cloning is to increase the genetic diversity, not lessen it. When people think of cloning, they think of making a thousand copies of Michael Jordan or whoever and they say “Oh, you’re going to lose all the diversity.” No serious scientist wants to disturb the balance of nature by creating a hundred copies of this animal or that.

What we’re talking about is using it very conservatively as a conservation tool for animals that have died—for instance, an animal that may have been caught in barbed wire—where the genes would be lost to the gene pool. Cloning is a tool to reintroduce genes that would otherwise be lost. Using it to create clones to put them in cages is definitely an abuse of the technology and certainly would not have my support.

CW: I noticed on your Web site that the cloning of domesticated animals, particularly farm animals, is now quite well advanced.

RL: Right. The company has a subsidiary called Cyagra. That’s their exclusive domain. They focus entirely on cloning agricultural animals. They have a very, very active program; they’ve cloned some of the top dairy and beef animals in the world.

CW: Do you think that cloning pets is far away?

RL: Well, we know that the cat has already been cloned. For me, it would be narcissistic to clone my own animal. I think you should go to a shelter, but that’s my own personal opinion. But I’m not going to say that the company would never do it. We actually licensed our cloning technology to the company that cloned ‘CC’ the cat.

CW: Can you tell us something of your work on organ replacement in humans?

RL: Creating or growing organs in the lab is an area known as tissue engineering. It’s a whole field in its own right. In fact, we just published the second edition of our book, Principles of Tissue Engineering, which I edited with Bob Langer and Jay Vacanti. They are considered the founders of the field. This is essentially a “cookbook” on how to tissue engineer virtually every system in the body. The researchers in this field have spent the last several years figuring out how to take individual cells and reconstitute them into complex structures and tissues.

For instance, we already know how to engineer skin, and there’s tissue-engineered skin on the commercial market. Likewise, there are already clinical trials underway using tissue-engineered blood vessels, bone, cartilage, tendons, and the first entire organ, which was a bladder. I’m currently writing a paper with Tony Atala [head of the Laboratory for Tissue Engineering and Cell Therapy at Harvard Medical School] on some results we have with the tissue-engineered kidney. You take individual cells and seed them into a biodegradable scaffold. You grow them on this scaffold and put them back into the patient’s body, which reabsorbs whatever is biodegradable, and you’re left with only the cells.

In the case of the tissue-engineered kidney, it’s remarkable that the cells can form all the various components of the kidney after they’re transplanted back into the body. It’s called self-assembly. These cells are smart, and in the body they pick up environmental cues and self-assemble. As a matter of fact, this is one of the things that I was always very surprised by when I was working with rodents and dogs to cure diabetes. You can take islets from the pancreas and reduce them to individual cells; however, the cells have the ability to come back together to create a tiny three-dimensional organ. The cells know how to organize on their own. For instance, the cells of the organ that will be exposed to oxygen, which will obviously be the only surface with capillaries, will all be on the outside, and so on.

There are still a considerable number of issues that need to be resolved for the more complex structures. In addition to creating entire organs outside of the body, we’re injecting embryonic stem cells directly into the body, say into the liver or brain, to see if they’ll turn into new cells to restore function. For instance, if somebody has cirrhosis, you might be able to give them an injection of stem cells to produce new healthy hepatocytes.

We don’t really know exactly in what setting, or under what conditions, that works. We know it does work, for instance, in mice that are born with the equivalent of multiple sclerosis. The cells will migrate through the brain and rebuild the damaged neurons. There are cells that will rebuild cartilage in joints. We can inject cells into a skeleton that is at risk for fracture. In the right environment, stem cells will turn into whole discs of bone. So we’re learning almost on a weekly basis—next week I’ll be able to tell you more. We’re learning at an exponential rate, and in a few years we are clearly going to be able to turn embryonic stem cells into anything we want.

CW: Twelve years ago, in an article you wrote for this magazine [“Into the Belly of a Woodchuck,” Pacific Discovery Fall 1990], you postulated that life is all one. Is that the philosophy behind your work?

RL: Well, the truth of the matter is that you have to have some sort of ethics or philosophy to pursue something as controversial as this. We certainly do get a lot of criticism; in fact, we get beat up for almost everything we do. And if you didn’t have the courage of your convictions, if you didn’t have some underlying ethics, you’d just cave. You’d just cave with the amount of criticism you get. But if you know you’re doing the right thing, and you have a philosophy for a certain greater good—the we’re-all-one concept does motivate me. It keeps me on track, and it does give me the energy to continue.

CW: You edited a book about the health and survival of the human species in the next century. What major social and anatomical changes do you anticipate over the next hundred years?

RL: I hope, I really hope, we don’t start tinkering with the germ plasm. I think that should be off-limits. I think what we will see is that by the time you and I get old and we get in an accident or lose an organ, tissue-engineering is going to be available. Even a conservative estimate is that we’re going to be able to do this within 5 to 10 years, and certainly within 15 to 20 years. This technology is going to be mature, and we’re going to be able to just grow you a new liver, grow you up a new organ.

CW: Does that mean we’re all going to live longer?

RL: Well, it will allow us to live fuller, healthier lives, and the lifespan of a human could approach 110 or 120 years. At the turn of the last century, the average lifespan was 36, so it has already doubled. I think you’ll see it go from mid-70s to 80s to over 100.

CW: So what will be killing us?

RL: Well, the truth of the matter is that all the body cells—there are about 250 different types—have a finite lifespan. So while you might fix this organ or that organ, the body’s like a very complex fine watch, and about 120 years is probably the natural human lifespan.

The body is like a bicycle tire. You can only patch it so much before you can’t put another patch on it. So you get what is called multiple-system failure, although we are doing some studies right now that may change that paradigm. We’ve used therapeutic cloning to give new immune systems to old cows. The exciting thing here is that it’s not just going to make an old cow have a new immune system, but it turns out that those precursor stem cells that we’re putting in also give rise to stem cells that have cured arthritis in mice. We know that in humans, too, it will repair all these various autoimmune disorders. More importantly, we know that in rodents that have heart attacks, those same cells will go in and fix damage. They will go into an animal that has had a stroke and fix that.

We’re monitoring these animals now, and we suspect that when we inject these stem cell precursors into the bloodstream that not only will it give them a new immune system, but if there are damaged joints, it will fix the joints; if they’ve had a heart attack, it’ll fix the damaged heart tissue; if they have had a stroke, it’ll fix the damaged neural tissue. So any worn-out body part or tissue could in theory be repaired.

When these cells are injected into an older patient, they will go through and repair the worn-out tissues, and that will definitely increase longevity. But from my perspective, I don’t think that the goal of this technology should be to increase longevity. The world is already overpopulated. But it certainly doesn’t serve anyone’s interest to have people unhealthy and sickly. Not only is it a drain on the national economy, but I think that the quality of human life is important.