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THE DYNAMIC DUO OF TISSUE ENGINEERING

On June 15, Dr. Joseph P. Vacanti spent 15 hours in the operating room at Children's Hospital in Boston, transplanting a liver into a 4-year-old girl who had languished for three years on a waiting list. Vacanti earned a day of rest. But he was up the next morning, evangelizing about tissue engineering at a scientific conference in Boston. In passionate language, he exhorted scientists to redouble research efforts into man-made organs so that 5 or 10 years down the road, patients would no longer die waiting for donoted organs. The intense dedication of Jay Vacanti and his close friend Robert Langer, a prominent chemical engineer, has been the driving force behind many tissue-engineering milestones over the last 10 years. Their lab has produced a huge array of engineered body parts -- cartilage, bone, ureters, intestines, and ears among them. What's more, they ''have seeded the entire country with people doing this work,'' says Dr. Pamela Bassett, president of medical consultants BioTrend in New York.

The two men, both 49, first met in the mid-1970s as researchers in the lab of Dr. Judah M. Folkman, another distinguished scientist at Children's Hospital who is renowned for his discovery some 20 years ago that the cancer cells could be killed by stopping the growth of blood vessels to the tumor. Folkman says the pair stood out from the beginning. ''Langer is a genius. Period,'' he says. Indeed, besides pioneering tissue engineering, Langer was awarded the prestigious Lemelson-MIT Prize, a sort of Nobel prize for chemical engineers, for his groundbreaking work in drug delivery systems. As for Vacanti, Folkman, who has worked with in the operating room, says ''when you have a child with a really difficult problem, he's the surgeon you go to.''

ORGAN SHORTAGE. Vacanti, a doctor's son, says he first decided to become a surgeon when he was four. Today, he is one of the nation's most respected pediatric surgeons. And it's his determination to help terminally sick children that fuels his passion for man-made tissue.

''I recognized fairly early that the biggest problem facing me as a surgeon was the shortage of organs,'' he says.

Vacanti started working on a solution in the early 1980s after learning about the work of a handful of scientists around Boston who were growing living skin in the lab. He convinced Langer that the same principles used to grow a flat tissue could be applied to more complex organs, particularly the liver. Langer started working on the materials used to as a foundation for the growing tissue, while Vacanti focused on getting the cells to grow.

First, though, the pair had to figure out how to grow a three-dimensional, densely packed organ. Vacanti came up with the solution -- one now used for most engineered tissues -- in 1986, while standing in shallow water at Cape Cod staring at seaweed. Inspired by nature's use of branching networks in plants, he returned from vacation and proposed a scaffold made out of bioabsorbable material. Cells could be seeded along the branches of the scaffold, and they would grow to fill in the spaces in between.

'IGNORANT RESPONSES.' The idea captivated Vacanti's younger brother, Dr. Charles A. Vacanti, and drew him onto the research team as well. Charles, 47, a professor of anesthesiology at the University of Massachusetts-Worcester, is now president of the four-year-old Tissue Engineering Society and a leading researcher in the field.

It has been a long haul from seaweed to organs, though. ''When we started in 1986, I was young enough to think it wasn't so hard,'' says Joseph Vacanti. But he and Langer had trouble attracting other scientists to their mission. Charles Vacanti recalls that when the team grew its first cartilage, its paper was rejected by a leading research journal. ''The editors said, 'We believe you, but we can't see any practical implications,''' Charles complains. ''That was one of the most ignorant responses.''

To prove that engineered tissue does have practical applications, the two brothers worked with a team of plastic surgeons three years ago to grow an exterior human ear -- one of the toughest shapes to reproduce -- and attach it to the back of a mouse, where it continued to live. The grotesque result got a lot of press -- and a lot of funding for tissue engineering. Even so, man-made transplantable livers and other complex organs are probably 10 years away, Langer admits with regret. But as the tissue-engineering field gains momentum, miracles may start to come true.

By Catherine Arnst in Boston



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