High-tech Body Shop Doctors are now using cartilage cultured in labs to repair injured knees

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 1/2
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."

If Peterson wants one more spokesman for the effectiveness of
his procedure, he need look no further than Amy May, a 5'11"
junior forward on the McKendree College basketball team in
Illinois. Three years ago May had a carticel implant. This past
season, she averaged 5.2 rebounds in 21.8 minutes and enjoyed
the game more than she had in years. "I used to be more
concerned about my knee than I was about playing," she says.
"Now it's like I can do anything. Every step is pain-free."

COLOR ILLUSTRATION: ENID V. HATTON thighbone (femur) damaged cartilage healthy cartilage meniscus anterior cruciate ligament shinbone (tibia)

Joint Project

In a carticel implant to repair a knee, the procedure pioneered
by Dr. Peterson, an arthroscopic biopsy is performed first to
harvest a sample of healthy cartilage (1). From this sample, new
cartilage cells are grown in a petri dish or flask (2). When the
cultured cells are ready, they are inserted under a periosteal
patch (3) that has been taken from the shinbone and grafted onto
the implant site (4). The implanted cartilage then slowly
spreads like moss.

Mandelbaum imagines the day when all kinds of tissues will be
repaired by growing them.