Within the narrow, L-shaped laboratory of Genzyme Tissue Repair, in Cambridge, Mass., the air has been cleaned of all but 100 particles of dust per square foot—about one ten-thousandth as much as the air outside. Through thick windows one can see dozens of technicians in gowns, hoods, goggles and gloves, working with petri dishes. They are growing human-knee cartilage, which will permit hobbling and crippled athletes to run again.
Thomas Myrhe (pronounced MIRE), a 25-year-old soccer goalkeeper from Norway, began experiencing pain in his right knee in his early teens. He was told he had an inflammatory disease and was treated with physiotherapy and anti-inflammatory drugs, which didn't ease his pain. In 1995, when Myrhe was 21, a Swedish orthopedic surgeon, Lars Peterson, looked inside the goalkeeper's knee with a tiny arthroscopic camera and discovered that most of the protective layer of cartilage was gone from the lower end of his thighbone, or femur. That bone was grating agonizingly against the top of Myrhe's shinbone, or tibia, in the knee.
Peterson decided to harvest cells from healthy cartilage in Myrhe's knee and then culture them in a laboratory before transplanting them back into his knee. During a short operation in August 1995, Peterson harvested a healthy layer of cartilage about the size of a raisin from Myrhe's knee. He sent it to a Swedish laboratory, similar to the one in Cambridge, where the cells were fed and regrown in petri dishes. Two months later the goalkeeper was prepared for the transplant of his new cartilage. A sliver of tissue was taken from his shin and sewn onto the bottom of his thighbone, forming a pouch into which the cultured cells were injected.
The cells began to spread along the bone like moss. Today, 3� years after the implant, they have grown to recover and cushion the entire bottom of the thighbone. Myrhe, who was out of action for one year after the surgery and had to wear a knee brace when he resumed playing, has moved up from a small team in Norway to Everton, in England, where he is a starting goalkeeper in the Premier League, arguably the leading soccer league in the world. He also starts for the Norwegian national team. For the first time in a dozen years, thanks to the implant, he is no longer in pain. He doesn't even wear a brace.
In the U.S. this breakthrough procedure, pioneered on human patients by Peterson, is known as a carticel implant. Peterson began developing this treatment in 1982, when he spent a year doing research in New York City at the Hospital for Joint Diseases. "I realized there was a big problem," he says. "We really could find no good treatment for young athletes who had cartilage damage." The damage can begin with something as minor as a knock on the knee or as major as a tear of the anterior cruciate ligament. Anything that causes the knee to bend improperly can lead to a small crack in the protective casing of articular cartilage, and the cartilage can then deteriorate until the pain is too much to bear. Arthritis is an ultimate result. The most widely used procedure for older victims is to replace the knee with a plastic and metal joint; Joe Namath and Dick Butkus are among the former football players who have had knee replacements.
In 1987, after conducting tests on rabbits, Peterson performed the first cartilage implants on 23 patients, with mixed results. He has since learned that, but is still investigating why, the treatment is less effective when the cartilage is attached to the end of the shinbone or kneecap. Almost all of the 2,000 patients who have received carticel implants in the U.S. since March 1995 have had the cells attached to the thighbone. With the exception of Peterson's patients in Sweden, virtually all of the carticel-implant recipients in the world, almost 3,000, have had their cartilage grown at the Cambridge lab of Genzyme Tissue Repair. The lab charges $10,000, often covered by insurance, to grow new cartilage from harvested cells. Patients older than 55 usually are not candidates for the procedure.
About 85% of the patients who have their implant into the thighbone experience improvement, though not all of them are pain-free. Larry Tye, a medical writer for The Boston Globe and a 3:43 marathoner, was implanted with his regrown cartilage in August 1997, and almost two years later the patch has spread to recover an area of roughly two square inches—all but a tiny spot at the bottom of his femur. Yet this bare patch causes him intense pain, and until it also is filled in with cartilage, he won't be able to run. "I'm the rare person for whom this hasn't [fully] worked," says Tye, who will have to undergo another implant. "But I still would recommend it. If you need cartilage in your knees, this is the way to get it and hopefully prevent you from needing plastic knee replacements when you're older."
Renowned sports surgeon Jim Andrews, who has repaired the elbows, shoulders and knees of many pro athletes, is so encouraged by the success of carticel implants that he predicts that in 10 years more advanced techniques will permit pitchers' shoulders to be loosened or tightened by using gene therapy, without major surgery. Genzyme uses methods similar to those employed in cartilage culturing to grow new skin for burn victims. Last year, on his eighth birthday, Robert Middleton was doused with gasoline and set on fire, allegedly by another child, in the woods near his home in Splendora, Texas, burning all his skin except for that on the soles of his sneakered feet. Genzyme grew an entire body of skin for the boy using postage-stamp-sized grafts taken from his feet. He has undergone four graft operations and is undergoing outpatient treatment at home.
Dr. Bert Mandelbaum, physician for the U.S. men's soccer team and chief medical officer for the upcoming Women's World Cup, imagines the day when all kinds of tissues will be repaired simply by growing them. He compares the breakthrough in cartilage culturing to the Mercury, Gemini and Apollo spaceflights that ultimately placed men on the moon. "Right now we're about midway through our equivalent of the Mercury flights," he says. "If you took the Mercury flights in isolation and said to Alan Shepard in 1961, 'I think you're going to the moon in that aircraft,' a lot of people would tell you, no, he's not. But that aircraft led to advancements in other aircraft."
Peterson is encouraged by the early results on the few high-level athletes who have undergone carticel implants. "They are the ultimate test for this technique," he says. "I have been very careful not to allow them to return to demanding sports too soon. The natural healing is a slow process. After three months the tissue is soft and compressible as putty. Eventually in a 12-month period it becomes hard cartilage."