Tuesday, December 30, 2003
Vacanti Bros of Omaha: Creating Human Spare Parts
NY Times
The ANNOTICO Report

The Vacanti boys — Jay, Chuck, Marty and Frank — from Omaha of Sicilian heritage dominate the esoteric field of tissue engineering, now all work in Boston.

Together, the brothers hold 88 patents. They have a total of 11 children and have been father figures to nearly 1,000 graduate students or doctors in training. The brothers have also written more than 300 scientific papers.

"We didn't have a lot of toys, So we ended up making things. It made us work together, and it made us creative."

They all were always also curious. When they were children, there was the episode of their dismantling the family car while methodically labeling all the parts.

Then there was the time they made the glider and lauched it off the roof. How did they choose the pilot?

Those were their earlier experiments, far less successful than their latest that involves the growing human spare parts like cartilage, bone, blood vessels and, perhaps some day, whole livers, hearts and kidneys in the laboratory.

The Vacanti family story is heart warming, inspirational, and a source of pride.
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Thanks to Bert Vorchheimer

SCIENTISTS AT WORK
FROM OLD CARS TO CARTILAGE
New York Times
By Judy Foreman
December 30, 2003

BOSTON, — It wasn't always obvious that the Vacanti boys — Jay, Chuck, Marty and Frank — were destined to become doctor-scientists, much less that they would come to dominate the esoteric field of tissue engineering.

Their specialty involves growing human spare parts like cartilage, bone, blood vessels and, perhaps some day, whole livers, hearts and kidneys in the laboratory.

There was, after all, that episode with the jalopy and all its parts while they were children. Led by Jay, the oldest and still the leader, they methodically took apart the car in their backyard.

"Are you sure you can get that back together?" their mother, Joanna Vacanti, recalls asking.

"Sure, Mom," they answered. "We're labeling everything."

Car parts piled up in the yard. "But it never ran again," Ms. Vacanti said. "That was the first experiment."

There have been many others since, and they have been far more successful.

Jay, 55, more formally known as Dr. Joseph P. Vacanti, is the chief of pediatric surgery at Massachusetts General Hospital, the director of pediatric transplantation, the director of the laboratory of tissue engineering and organ fabrication, and a surgeon in chief of MassGeneral Hospital for Children.

Chuck, the second-oldest brother, is Dr. Charles A. Vacanti, 53, chairman of the department of anesthesiology, perioperative and pain medicine at Brigham and Women's Hospital and director of the laboratory for tissue engineering and regenerative medicine.

Marty, third in line, is Dr. Martin P. Vacanti, 51. He is a pathologist at Mass General and a research scientist in Chuck's and Jay's labs.

And Frank, Dr. Francis X. Vacanti, a 49-year-old self-described "gizmo guy," is an anesthetist at Massachusetts General who, working mostly independently from his brothers, is developing a coated breast implant.

Together, the brothers hold 88 patents, a vast majority of them Jay Vacanti's. They have a total of 11 children and have been father figures to nearly 1,000 graduate students or doctors in training. The brothers have also written more than 300 scientific papers, 189 of them attributable to Jay Vacanti.

What kind of family produces such talent? A Sicilian one in Omaha, it turns out.

"We always laughed," said their mother, who won a scholarship to college and majored in chemistry until she dropped out to be married.

"We didn't have a lot of toys," Chuck Vacanti said as he sat around a table with his brothers at Massachusetts General. "So we ended up making things. It made us work together, and it made us creative."

There was the time the boys tried to make a glider.

"Yeah, and we made Cathy jump off the roof in it," Chuck said, referring to their younger sister.

"She was the lightest," Frank interjected.

"And more likely to bounce," Chuck finished.

Their father, who died 10 years ago, was a professor of dentistry, an oral surgeon and a pioneer in endodontics at Creighton University in Omaha, where, thanks to his position, seven of the eight children — three sisters plus the four brothers — went to college free on faculty scholarships. Another brother has Down syndrome.

As a 3-year-old, Jay literally devoured the Merck manual, a medical bible, ripping out the pages and chewing them. He remembers that when he was 7 he was drawing sketches of teeth and cells for his father's academic lectures.

Frank also had an appetite, if less literal, for scientific fodder. At 2, he climbed up on the couch to look at a volume of the encyclopedia.

"All you would see were feet and this huge book," his sister Mary recalled. "I don't know if he could read or just looked at the pictures."

Chuck and Marty were also guided gently toward the noble path.

When their mother heard that they planned to spend one summer driving their motorcycles to California, she bought them plane tickets to Europe.

"She bought us out," Chuck said. "We folded."

The Vacantis have an obvious penchant for collaboration.

As a surgical resident, Jay Vacanti connected with Dr. Judah Folkman, a surgeon from Children's Hospital in Boston who has pioneered angiogenesis, or growing blood vessels.

In Dr. Folkman's lab, Jay Vacanti met Robert S. Langer, now a professor of chemical and biochemical engineering at the Massachusetts Institute of Technology. "Jay," Dr. Langer said, "has that ability to see where things could go and be correct about it."

In the mid-1980's, after other scientists had begun growing skin cells, Jay Vacanti decided that the only way to solve the organ shortage was to grow organs from scratch.

"If we can make this piece of skin," he said, "maybe we can make an organ."

Working together, he and Dr. Langer hit on the idea of using degradable synthetic polymers, chemical structures that when placed in the body slowly degrade in the presence of water into harmless chemicals, glycolic and lactic acids.

The two scientists realized that they could mold a polymer into a three-dimensional shape, seed it with living cells and implant the new "tissue" in a living animal. Over time, they reasoned, the polymer should dissolve like medical sutures, and the implanted tissue would attract blood vessels and grow.

It worked. But there was, and still is, a limit to how big a hunk of tissue they can grow, because living cells have to be within a hair's breadth or two from oxygen and nutrients, in other words a blood supply.

In 1986, Jay Vacanti was sitting on a jetty on Cape Cod when a piece of seaweed floated by. "I was watching the kids," he recalled.

"But in my mind, I was thinking, `How do I make the inside of a cell mass think it is on the surface, close to oxygen and nutrients?' " he said. The seaweed, he realized, had solved the same problem, by dividing into tinier and tinier branches.

"I was so excited, I ran back, got a dime and phoned Bob."

Back in the lab, Jay Vacanti and Bob Langer took dissolvable sutures and frayed the ends to create more surface area. Soon, they had little tissue farms that produced liver, pancreas and intestinal cells. At that time, Chuck Vacanti, the anesthesiologist, talked often with his brother Jay.

"Could you make bone?" Chuck asked.

"Sure," his brother replied.

Chuck Vacanti began hanging out after hours in his brother's lab, learning how to isolate chondrocytes, the cells that make cartilage, the tissue that holds together the skeleton.

At Jay Vacanti's suggestion, his brother put them on a polymer.

"Lo and behold," Chuck recalled, "whereas liver cells didn't attach well to the polymer, chondrocytes stuck like crazy."

Chuck Vacanti went on to create an artificial nonhearing ear made from human cartilage cells grown on an ear-shape polymer and implanted under the skin of mice.

After becoming chief of anesthesiology at the University of Massachusetts Medical School in Worcester in the early 90's, Chuck Vacanti began sending samples of lab-grown bone and cartilage to Marty Vacanti, who was teaching at Creighton.

"I was a bit skeptical," Marty said. "But when I looked under the microscope, the stuff looked as good as the real McCoy." Chuck Vacanti recruited his brother to Massachusetts.

In 1994, Chuck and Jay Vacanti performed their first human experiment, on a 12-year-old born with a deformed sternum and almost no bony protection over his heart. They took cartilage cells from the boy's sternum, grew them on a polymer and implanted the new tissue in the chest.

In 1998, Chuck and Marty Vacanti used lab-grown bone to replace the thumb of a man who had lost his in an accident. They also began trying to grow spinal cord tissue. Other scientists had already isolated neural stem cells in fetal and adult rodents. Neural stem cells are cells that turn into different types of nerve tissue.

But the Vacantis wanted to use a particular isolation method. Marty Vacanti recalls ending up with "a bunch of dead tissue and junk, as well as some very, very tiny, very round structures that were very bright under the microscope."

A colleague pronounced the structures "debris."

"I was going to throw them away," Marty Vacanti said. But he tossed them in an incubator, instead. Three days later, they seemed to have turned into "neurospheres," or small collections of neural stem cells made up mostly of DNA. Marty and Chuck Vacanti have used those sporelike cells to grow spinal cord tissue in the lab and implant it in the damaged spinal cords of rats. Some rats have regained the ability to walk.

Working with mathematicians from M.I.T. and the Draper Laboratory, Jay Vacanti has found a way to grow small circulatory systems by etching the pattern for blood vessels on silicon chips. Dozens of labs around the world are racing to bring other Vacanti ideas to fruition.

Not bad for brothers who could not rebuild a car — and still cannot.

A few years ago, Chuck and Jay Vacanti decided to rebuild "Nadine," an Oldsmobile Cutlass, for Jay's children.

"The car purred like a kitten," Chuck Vacanti said. "But the second time his kids took it out, the transmission got stuck in reverse. Nadine ended up in the same graveyard as our other cars."

Scientists at Work: From Old Cars to Cartilage
http://www.nytimes.com/2003/12/30/science/30PROF.html