Generation Next, Part 1, Xenotransplantation
Air Date: Week of April 12, 2002
In the first of a five part series we examine the ways in which medical technology is shaping the future of the human species. Producer Bob Carty has the story of one man who is breaking new ground by having brain cells from pigs inserted into his own brain to help him cope with Parkinson’s disease. The procedure is called xenotransplantation. Proponents say it can help many ill people regain their health, and shorten the wait for donor organs. Critics say xenotransplantation may spread diseases that could get out of control.
CURWOOD: Welcome to Living on Earth. I'm Steve Curwood. It seems hardly a week goes by without some announcement of yet another breakthrough in medical technology. These discoveries, we're told, will revolutionize our lives and give humans the power to direct our own evolution. These technologies include stem cell research, genetic testing, gene therapy, cloning, and xenotransplantation.
In the not-too-distant future, they will make it possible to design our children, clone ourselves, genetically manipulate our intellectual and physical performance, and meld our minds with the artificial intelligence of computers. These technologies will not only revolutionize medicine, they will also change who we are as human beings.
This week, we begin a special series examining how medical science is changing the way we're evolving. The series is called "Generation Next: Remaking the Human Race." It begins with a story about a remarkable procedure called xenotransplantation. It's a term that comes from the Greek word xeno, meaning foreign. And that's what it's all about, putting animal parts into humans.
Xenotransplantation could save thousands of lives and put an end to the terrible tragedy of patients dying while waiting for a human organ transplant. But, there's also a real fear it could set off a terrible pandemic on the scale of AIDS. Here's producer Bob Carty with a documentary he calls "Who is the Real Guinea Pig?"
[SOUND OF RADIO STATIONS BEING SCANNED]
FINN: This is one of my prized collector's items.
[SOUND OF RADIO TUNING]
FINN: It's a Zenith AM Transistor Radio, about 1962. It's an old-timer. I had to put new transistors in the chasse, and a new speaker, and a new battery holder.
[SOUND OF RADIO TUNING]
CARTY: Fixing radios was Jim Finn's passion and his profession. Jim fell in love with radios when he was a boy. And the back room of his home in Newport, Rhode Island is crammed with tubes and transistors, and dozens of radios in various states of disrepair, and repair.
FINN: I was an electronics repair technician--TVs, and stereos, and that sort of thing. I've collected radios all my life and got to the point that I couldn't work on them anymore because my hands just wouldn't cooperate. They were stiff, and they wouldn't move properly. I came down with Parkinson's Disease when I was 32 years old, back in 1980.
CARTY: Jim Finn shares Parkinson's with Mohammed Ali, the Pope, Billy Graham, Yasser Arafat, Michael J. Fox, and half a million Americans. It's a progressively debilitating disease. For some reason, the brain cells of Parkinson's victims stop producing dopamine, a chemical that helps control their muscles. They begin to tremble, shake and jerk. Eventually, they can no longer move voluntarily. Sufferers call it "a living death."
Jim and his partner, Ray, have been living together for 17 years. And over that time, they've watched as Parkinson's gradually began to take over Jim's life.
FINN: The disease progressed and just continued to get worse. I couldn't walk most of the time. I would sleep 18 hours a day because of the sheer exhaustion of this disease. I would shake uncontrollably.
RAY: We used to wheel him around in a wheelchair to get to the supermarket, or to go out for dinner. I used to have one hour a day that he could walk. The rest of the time, he would either be overly medicated, or he just had to crawl.
FINN: By 1996, my Parkinson's had progressed to, what they call, end stage, where they could do nothing more for me. No pills would work. There were no other procedures available to me. And that's when they did a video on me.
[SOUND OF VIDEO PLAYING]
FINN: This is a stand-up test to see if you can stand, which I could not do at that time.
CARTY: You almost fell over.
CARTY: In the video, Jim Finn is 48 years old. He looks like he's 90. He twitches, speaks with a slur. He can't move one foot in front of another. He can't get up out of a chair. And then, realizing that, he stares straight at the camera with an expression of confused panic and fear.
RAY: We had been back and forth to Boston University Hospital, and tried multiple, multiple different type of medications. And nothing was working. Nothing was working. He was getting quite depressed.
FINN: I was nearing the point of no return. I thought I was going to die. In fact, I knew I was going to die. I was going to kill myself. It was that horrible.
RAY: And, I could see how somebody would make up their mind that it's not worth going on to live in this manner. So, there was nothing to lose.
CARTY: At that point, at the point when Jim felt he had nothing to lose, in the summer of 1996, a Boston doctor approaches him with a proposition. Would he participate in a high-risk medical experiment? It involves injecting 12 million embryonic cells into Jim's brain. Though, that's not what makes the procedure revolutionary. It's that the cells would come from a pig.
This is xenotransplantation, or xeno. It's been on the margins of medical science for almost a century. But it broke into public consciousness in 1984, with a shocking announcement.
MALE NEWS REPORTER: Tonight, last chance for life. A baby girl is given the heart of a baboon.
CARTY: She was known in the media only as "Baby Fae," a tiny, 14 day-old baby girl born with a fatal heart problem.
MALE NEWS REPORTER: They took out her heart, which would have failed within days, and replaced it with the heart of an infant baboon. It's being called a "major breakthrough" for medical science. And doctors say the baby girl is doing remarkably well after the operation.
CARTY: There had been other xenotransplants before. Chimpanzee and baboon kidneys and hearts had been used in the '60s and '70s. But all the recipients died, their immune systems rejecting the transplanted organs.
In 1984, however, there were new anti-rejection drugs. And doctors were eager to be the first to make the breakthrough. For three weeks, the public was transfixed with gripping headlines of a medical miracle in progress. Maybe, just maybe, xenotransplantation could work. And then the life began to ebb from the tiny Baby Fae.
MALE NEWS REPORTER: Doctors tried cardiac massage before they finally pronounced Baby Fae dead. She survived 21 days. That's the longest any person has survived with a transplanted heart from an animal.
FANO: From reports that I've read there was no effort made to find a human heart for Baby Fae. It showed that people who are trying to try new technologies will do it at the expense of a human life.
CARTY: Alix Fano, is the Director of the Campaign for Responsible Transplantation, a coalition of physicians, scientists, and public interest groups opposed to xenotransplantation.
FANO: What the Baby Fae incident, I think, showed is that these procedures were a failure, and that they were dangerous. Since 1905, about 82 whole organ xenotransplants have been performed, and they have all failed. The patients have all died, mostly within minutes or hours after the xenotransplant. The history, certainly, is very disappointing.
CARTY: Jim Finn knew about this disappointing historical record. But since Baby Fae, research had intensified. Some of it turned towards the use of animal cells, in addition to whole organs. And, more and more, the research turned away from primates.
Animal rights groups had become incensed that reports of experiments with chimpanzees and baboons, intelligent primates, who are our closest relatives. And so, xenotransplantation scientists turned to an animal which, while as intelligent as a dog, it is said, is one we eat: the pig.
[SOUNDS OF PIGS SQUEALING]
GREENSTEIN: You're seeing our miniature swine facility where we're breeding the pigs that we would eventually like to use for human transplantation.
CARTY: These are the kind of pigs they would use for Jim Finn's xenotransplant. Julia Greenstein is the president of Inmerge Biotherapeutics, a company located in a renovated warehouse in the old dockyards of Boston. She shows off her pigs on a video because their exact location is confidential, a precaution against protests or actions by animal rights groups. Julia Greenstein's company specializes in producing pigs that are bred, cloned or genetically altered to make body parts for humans.
GREENSTEIN: We have a certain strain of pig which is called a miniature swine. And we're using that pig because we think the organ size match is better than an outbred pig, which grows to be about a thousands pounds at full adult weight, which is clearly much bigger than most human recipients. It's actually surprising that the physiology is very, very close to man. So, heart rate, blood pressure, respiration rate are all very similar. So, the organs are very similar in function.
CARTY: Xeno research is driven by the huge gap between the number of human organs being donated, and the number of patients desperately waiting for a new heart, or liver, or kidney. Human organs have to come from healthy donors, usually the victims of traffic accidents who are declared brain dead, but whose organs are still alive and can be harvested for transplantation. Seat belts in safer cars mean fewer fatalities, and fewer organ donations.
GREENSTEIN: In the United States alone, there are 75,000 people on various organ waiting lists. And, 15 of those people will die every day because of the unavailability of human donor organs. We believe that, given that need that there is in the population today, there will not ever be enough organ donors to treat everyone who could benefit from an organ. And the overwhelming clinical need means that there is a big potential marketplace, $6 billion a year, to use animals as organ donors. So, there's a big potential win for both society and for a commercial venture in this area.
CARTY: But critics question whether xenotransplants really are needed. Alix Fano of The Coalition for Responsible Transplantation argues that the demand for organ transplants, like lungs, and hearts and livers could be reduced by healthier diets and better living, and that there are other ways to increase the effectiveness of human to human transplants.
FANO: About 50% of transplanted human organs are rejected and fail within five years. So, before we embark on a dangerous and more complex cross-species transplantation, we should try to perfect existing human-to-human transplant techniques. The other would be to increase human organ donation by all means possible. We don't believe that we need xenotransplantation. In fact, it's a perilous road to go down.
CARTY: It's a perilous road to go down, in part, because when animal organs are put in humans, the body's defense systems often attack and kill the transplant and the patient. Now, this is not a problem if the transplant involves no blood vessels for the immune system to attack. And that's why pig insulin, and pig heart valves work, and why rejection is less of a concern in putting pig brain cells inside Jim Finn.
In the future, doctors might get around the rejection problem by using compatible human organs produced from stem cells. But that's years away. It doesn't help people needing transplants right now, people that Dr. Hugh Auchincloss see regularly, as a transplant surgeon at Harvard University.
Auchincloss contends that the rejection problem can be overcome by the use of new drugs designed to suppress the human immune system, or by attempts to "humanize" pigs, genetically engineering pigs by putting human genes into them or by taking uniquely pig genes out. Of course, engineering pigs for human transplants raises the issue of animal rights, and our rights to change the very nature of a fellow species. Hugh Auchincloss has thought a lot about the issue.
AUCHINCLOSS: I think one has to treat animals with respect, and go to great lengths to avoid pain and suffering. But I think, obviously, we make clothes, and eat animal products. And so, using their organs is, to me, no different. I, myself, am in a group of people that feels comfortable with the notion of using animals for human welfare.
FANO: Ultimately, you're killing them for their organs. Or, for example, you're deriving sterile embryos by caesarian, by a mother pig, and then killing her, and taking her embryos so you can inject them into somebody's brain. Is this necessary use of animals? I, personally, don't think so.
FINN: The use of animals for testing cosmetics and household cleaners, I think, is disgusting and deplorable. But when an animal can help mankind, I think if it's done properly and humanely, I say go for it. The people who are against these kind of procedures have never had a relative or loved one who had a serious or horrible disease. Six or eight people a day are dying of heart failure, kidney failure, liver failure. This offers help to those people. And I was one of those people.
CARTY: One of only 12 people, in fact, selected to take part in the first Parkinson's trials with pig cells. The idea is to replace some of Jim Finn's brain cells, degrading and dying, with cells from pig embryos. The hope is that, once in his brain, the pig cells will produce dopamine, and reduce the symptoms of Parkinson's. Jim has no qualms that the cells come from pigs.
FINN: Didn't make any difference to me at all whether they're pig cells, or horse cells, or cow cells, or no matter what they were. I felt I had nothing to lose. So, I went for it.
CARTY: What did you think about this technology?
FINN: I put my faith in medical science. The pig cells are specially selected from specially bred pigs that are pure, as far as they know. The pig cells are obtained from pig fetuses. I believe it takes nine fetuses for one operation.
MAN: And then we collect the fetuses from those pigs.
[MUSIC IN BACKGROUND]
CARTY: Jim Finn's pig cells are harvested by a company called Diacrin, which has bred pigs just for this purpose. In a British documentary by Carleton Television, a Diacrin scientist explains the procedure.
MAN: They're extracted under very clean conditions. And, during that procedure, we dissect out specific areas of the fetal brain.
CARTY: In the video, the pig fetuses are each about the size of a small carrot. They are poured into a laboratory tray. Then a scalpel cuts off the head, opens the skull, and extracts the cells from a particular part of the brain. That's how the cells were prepared for Jim Finn.
FINN: Everything was carefully explained to me, the possible pitfalls. The risks were relatively unknown. There was a two percent chance of a brain hemorrhage, which would not be a nice thing to go through. There was a possibility the cells would multiply beyond what they expected. And that could lead to brain damage. There was a possibility that it would have no effect at all, or any kind of side effects that were unknown.
[SOUND OF HOSPITAL INTERCOM]
CARTY: On September 24, 1996, Jim Finn checks into a Boston area hospital at 6:30 in the morning. They put him in a gown, take yet another CAT scan, and an MRI, and attach a metal frame to his head. Jim is ready to take his leap of faith in medical science.
FINN: When it come to the operation, you go to the hospital. They bolt you down to the machine. They tie your head down to the machine for two and a half hours. Your head is literally bolted to the machine. They drill a hole in your skull, in my head right there, where they put the drill. And you're awake while this goes on. And they implant the pig cells with a six- inch needle. They implanted 12 million pig cells into my brain, not knowing what the outcome was going to be.
[SOUND OF INTERCOM AND SIRENS]
FINN: The amazing thing is, after the operation, they send you home the next day. They gave me a handshake and a band-aid, and sent me home.
CARTY: Jim Finn goes home to wait. And waiting is a big part of xeno research. The pig cells they put in his brain are living things. And they grow and replicate, and can be unpredictable. And they'll be in Jim's brain forever. They can't be taken out.
Currently, xeno recipients, like Jim Finn, have to monitored for their entire lives. That's because pig cells and organs can carry diseases which could become a problem, not just for the transplant recipient, but for all of humanity. And that's what most worries Alix Fano of the Campaign for Responsible for Transplantation.
FANO: The issue is that pigs are not safe source animals for xenotransplantation. There has been a history of pig virus transfer to humans, beginning with the swine flu epidemic of 1918, which killed about 20 to 40 million people worldwide. Recently, in 1998, the Malaysian Nipa-virus was transferred from fruit bats to pigs, and then from pigs to people who worked in slaughterhouses. And, it killed over 111. Xenotransplantation is probably the best way that you could invent to create a new epidemic, in the sense that you're transplanting live pig tissues, or organs, into immunosuppressed patients. And, it only takes one transplant to start an epidemic.
CARTY: This is the big debate in xenotransplantation. Pigs do get viruses. And over millions of years of evolution, some of those viruses have become embedded in the pig's genetic code. They are called retroviruses. And over the eons, pigs have learned to live with them. The viruses don't make the pigs sick.
But viruses are dangers packets of information. And one of the things they do best is adapt and mutate. The concern is that inside a recipient's body, pig cells or a pig organ might share the pig retroviruses with our own human viruses, and create some entirely new disease.
Could that happen? "Yes," says Hugh Auchincloss, the Harvard transplant surgeon. But Auchincloss does not think the risk is great.
AUCHINCLOSS: It actually turns out that as many as three or four hundred people have had tissue from animals transplanted into them. But a large number of those people have been carefully examined to see if there's any evidence of the spread of these endogenous retro viral sequences. And there's none, none at this point.
Now, there is a very tiny, conceivable risk that there might be viruses that, so far, have not been identified, or could be created by the process of xenotransplantation, that might also be a risk for society at large.
CARTY: Tell me about that, in terms of the larger risks.
AUCHINCLOSS: It's extremely hard to assess the nature of a risk of an event that has never occurred. So you can talk yourself into a worst case scenario. Or you can be realistic and say that a worst case scenario is, in fact, really a very unlikely event.
CARTY: But others are not so quick to discount the risks of xenotransplantation. Robin Weiss is a virologist at University College in London, England. He's an expert on HIV/AIDS, an epidemic that came from a single jump of a virus from a chimpanzee to a human. Weiss decided to test whether pig viruses could affect humans. He put pig cells and human cells together in a test tube, and then looked to see if the one infected the other. He was very disturbed by his findings.
WEISS: We found, in fact, there were three infectious strains of pig retrovirus. And two of those three strains would infect human cells. This immediately set alarm bells ringing. One of the biggest safety concerns is that animal infections, particularly animal viruses, might set off an epidemic. And most transplant surgeons, and so on, say, "Oh, that's so far-fetched. Why bother about it?"
The problem is that far-fetched things do happen with animal infection spreading to humans. The worst case scenario is that we'd set off something like a new AIDS epidemic; that a pig virus would become established in the human population, be a killer virus, and would start to spread.
CARTY: What do you say to a patient who has something like Parkinson's when you understand their willingness to do almost anything versus your public health concerns?
WEISS: I think from the point of view of the ill person who may become a recipient of animal cells or organs, the risk benefits balance is fairly easy to look at. In a large proportion of cases, I think they'll say, "Well, I'm so damned ill, I'll take the chance." But there's also the public health point of view. I don't think any patient, however ill they were, would like to think that they were the cause of a new world-wide epidemic of the similar nature to AIDS.
CARTY: Robin Weiss's research has put a brake on xeno experimentation. In the U.S., testing with cells is continuing, but at a very slow pace. Testing with whole organs is now on hold, until the risks of an epidemic can be eliminated or better assessed.
But how do we make such an assessment? Fritz Bach has one idea. Bach is a professor at Harvard Medical School and a pioneer in xeno research. He wants it to work. But he says that since the public is exposed to the risks of xenotransplants, the public has to be asked to give its informed consent.
BACH: We cannot put the public at potential risk without going to the public, explaining to them, in a balanced way, what the risks are, and what the benefits are, and then getting their reaction. That cannot be decided ethically by those people who want to do xenotransplantation, like me.
[SOUND OF HOSPITAL INTERCOM]
CARTY: Jim Finn is very aware of these issues when he checks into the Boston hospital for his xenotransplant. Before he's bolted down to the operating table, he has to sign a detailed consent form, a list of rigid rules that will govern how he lives.
FINN: They made me sign this 27 page consent form. You have to agree to be monitored for the rest of your life. Barrier sex only, with a condom. You have registered with a government agency as a xenotransplantation recipient. You have to have blood work done when they want, to be sure you're not carrying a virus.
[SOUND OF TYPING]
CARTY: When Jim and his partner, Ray, get back from the hospital, Jim starts to write a diary. Looking down on him from the desk is Priscilla, a puffy, pink toy pig. The diary is something to share by internet with other Parkinson's sufferers, a record of how Jim's body is reacting to the 12 million pig cells living in his brain.
FINN: Thirty days after, I felt results. My motions were smoother and better, more accurate. I could walk better. I could talk better. I could use my hands. Everything improved. Very subtly, but there was a definite improvement.
RAY: I'd say about three or four weeks, maybe six weeks after the surgery, we were out for dinner. And, he was cutting up a dinner roll and he was buttering it, which was something that I always ended up doing for him. That was my job. And, he was just talking away, nonchalantly, and doing it, not even realizing. And I had to just point out to him, "Do you know what you just did?" So, we did finally get rid of that wheelchair. We put it up in the garage, and that's where it's been ever since. So, he's doing great.
FINN: At the 60 day point, they measured an improvement, and they were amazed.
CARTY: And you can see the difference in Jim's before and after videos. After the operation, you see him walking smoothly, getting out of a chair without a problem. In the tests before the operation, his reading is slow, and lacking modulation.
FINN: [1st Reading] -- mind in one area, and distracting it from the hurt in the other. Dr. William Evans Trent, 1990. [2nd Reading] It's like pinching the mind in one area, and distracting it from the hurt in the other. Dr. William Evans Trent, 1990.
CARTY: Afterwards, he reads with greater energy and confidence, even joking with his nurse.
FINN: Seven, eight, nine, ten. Did I do good?
NURSE: Very good.
FINN: I was tested every 90 days for the first, I think, three years. And they showed improvement or holding my own in every test. My handwriting is still lousy. But it was lousy before I had PD anyway.
CARTY: How do you feel with cells of a pig inside you? Is there any qualms about that?
FINN: No. People were very curious about this procedure. They wanted to know if I felt differently after I had pig cells implanted in me. I said, "No, I don't feel any different. I feel better." I've heard every goddamn pig joke you can imagine. One day, when I was in my doctor's office, he asked me to turn around. I said, "Why?" He said, "I want to see if you have a tail or not." I told him to go to hell.
CARTY: There is no doubt in Jim Finn's mind that the pig cells are the cause of the improvements in his health. But scientists are not so sure. Other trials have been disappointing, or inconclusive, with those receiving pig cells doing no better than a control group given a placebo.
But Jim Finn feels xeno was the only option for him. Five years after his operation, the doctors have not found any signs of pig viruses in his blood. Jim, in fact, has become somewhat of a poster boy for pig transplants. He's on a Washington committee studying the technology. A few months ago, he was even on Oprah, talking about medical miracles. Jim knows he's not cured. And he understands that xenotransplantation may or may not have a future. But now, at least, he does.
FINN: It changed my life. It gave me my life back. I take it a day at a time. You don't know if this experiment could suddenly fail or go awry. They have no way of knowing these things. They gave it their best shot, and so did I. Now I can work on the radios. It's a little bit slow, and a little bit awkward, but I can do it.
[SOUND OF RADIO TUNING]
FINN: This is one of the pieces I've recently fixed up. I was in Boston last week for my fifth year checkup. And, I celebrate it as a birthday. Because I feel as if I've been reborn.
[RADIO MUSIC UNDER]
CARTY: For Living on Earth, I'm Bob Carty.
FINN: I'm not much of a dancer.
[MUSIC: Nick Cave, "Into My Arms," THE BOATMAN'S CALL (Mute - 1997)]
CURWOOD: Next in our series, the controversy over human cloning. Some advocates say it will give us better control over human reproduction. But critics say it's unethical, and could change human values.
WOMAN: Many of the technologies that we're talking about do turn having a child into something akin to buying a car, picking the extras, and so forth. What is society going to look like if we adapt one set of technologies, one set of laws versus another? And I think it's time to look a little bit ahead, and ask, really, "Do we want to go there?"
CURWOOD: The human cloning debate is the topic when our series, "Generation Next: Remaking the Human Race," continues on Living on Earth.
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