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The Replacements
Why the Vacanti brothers are the Fab Four of tissue engineering
By Jeffrey Krasner, Globe Staff, 3/11/2001
r. Joseph Vacanti is looking for the ear.
He and his researchers at Massachusetts General Hospital grew it, implanting living cartilage cells in a substrate of plastic. The cartilage cells multiplied, grew a network of blood vessels, and the plastic gradually dissolved.
The end result, when it is located, is about an inch long, and sits in a test tube looking a lot like a boiled Peking ravioli. It is undeniably ear-shaped.
''I'll go get the heart out,'' says Vacanti, 52, eager to show another experiment.
There's no longer anything novel about the idea of taking an organ out of a dead body and sewing it into a living patient. But there aren't enough hearts, livers, or lungs to go around. That's why researchers like Vacanti, known as Jay, are trying to grow the replacements in the laboratory. The field is known as tissue engineering.
But Vacanti isn't working alone. Many of the field's key developments in the past few years have been spearheaded by his three brothers, Charles, Francis, and Martin, who are also doctors and tissue engineering researchers.
That's why specialists in the field think of the Vacantis as the first family of tissue engineering. Some liken the brothers to the building blocks of their field, stem cells - the undifferentiated cells that can be coaxed into developing into different types of tissue.
''They are the stem cells for the entire field,'' says Dr. Peter Johnson, chairman of TissueInformatics Inc., a Pittsburgh biotech firm, and president of the Tissue Engineering Society International, the trade group for the young field. ''They made some of the seminal observations that have enabled many people worldwide to develop many types of tissues. I think they own a big chunk of the founders stock in this field.''
Along the way, the Vacanti brothers have amassed a cache of patents and processes that could create vast wealth for themselves, companies they partner with, and their sponsoring educational institutions. Charles Vacanti, 50, says he holds or co-holds between 10 and 20 patents covering the uses of certain stem cells for particular uses. With self-deprecating humor, he says, ''If it all holds up, it should be worth a trillion.''
There may be less hyperbole in that statement than he intends. According to Michael Becker, an analyst with Wayne Hummer Investments in Chicago, the worldwide market for just one tissue-engineered product, replacement skin, is worth between $5 billion and $7 billion a year. Sales of existing tissue-engineered products are exploding, he says. ''You're probably looking at rapid growth in the neighborhood of 100 percent at least during 2001,'' Becker says.
As in all family histories, there is dispute as to why the four Vacanti brothers wound up as doctors. Their father, Charles, was a professor of dentistry at Creighton University in Omaha and a pioneer in root-canal therapy. They all tagged along to classes and clinics.
But it was Jay, the eldest boy, who first displayed medical prowess. At age 5 or 6, he pored over his father's anatomy texts and even drew pictures that were used in his father's classes. His mother, JoAnne Vacanti, 77, recalls buying Jay a toy called the Visible Man, a sort of anatomy erector set that enabled a child to build a body, organs and all. Jay Vacanti says he never had a moment's doubt: ''I can never remember a time when I didn't want to be a surgeon,'' he says.
For Martin, the third and most unassuming of the brothers, Jay's decision had a strong impact. ''If he had a cowboy outfit, you wanted the cowboy outfit,'' Martin, 49, recalls. He says he followed the path blazed by his older brother after a childhood infatuation with psychiatry faded.
Not so for Charles, the second boy. His epiphany came during a childhood camping trip, when he encountered a leaky toilet in a bathhouse. He reached into the tank, figured out the connection from the handle to the drain, and stopped the leak. ''I was very proud of myself,'' he recalls. He became a tinkerer and builder, but was steered away from engineering by a relative. He became an anesthesiologist in part because the equipment, with its valves and pipes and gauges, appealed to his mechanical side. ''I don't remember reading an anatomy book until I was forced to,'' he says.
Francis, 47, says he resisted medicine for as long as he could, but eventually made a conscious decision to pursue it. ''Medicine has a lot of memory in it, and memorizing things is not my idea of a good time,'' he says. But anesthesia appealed to him because it involved physics - one of his favorite subjects - and it could be mastered with logic rather than memory.
It was Jay, still the leader, who first became involved with tissue engineering. As a young surgical resident at Children's Hospital in Boston, he treated patients with liver failure. He says he quickly realized that the biggest problem facing these patients was the shortage of donor livers to transplant. The obvious solution: growing livers, and any other tissues needed, to help patients with all kinds of reconstructive surgery.
But cells grown in a petri dish tend to form thin films. What was needed were thick structures that could replace actual pieces of tissue. In the mid-1980s, Jay began collaborating with Robert Langer, a chemical engineer at the Massachusetts Institute of Technology. Their solution: materials that would serve as a scaffold, a temporary framework upon which living cells could proliferate. Langer contributed polymers which supported the cells and helped them grow into the right shape, but would later dissolve naturally, leaving only the living cells.
Still, that left another problem: how to nourish these new living cells, which require a constant blood supply. A single gram of human tissue includes a network of tiny capillaries that, if laid out, would cover an entire square foot.
Jay Vacanti and Langer had the right training to tackle the problem. In the late 1970s, they had worked in the laboratory of Dr. Judah Folkman, the pioneering researcher who seeks to kill cancerous tumors by cutting off their blood supply. The flip side to Folkman's work was encouraging blood vessels to grow in new tissue. Says Jay Vacanti, ''It's like growing the branches of the tree, and then you add the leaves.''
A major breakthrough came in 1988, when Jay Vacanti, working with Langer, showed you could implant liver, intestine, and pancreas cells on a plastic substrate, and they would form real tissue.
Folkman compares the Vacantis to other famous tinkerers. ''It reminds you of the Wright brothers working on airplanes in their bicycle shop,'' he says. ''With Langer, they've really pioneered the field.''
But it was Charles, working at his tissue engineering lab at the University of Massachusetts Medical School in Worcester, who helped create the first poster boy, of sorts, for the nascent field.
In October 1995, with an MIT colleague, he molded a human-shaped ear out of polymer, seeded it with cartilage cells from a cow, and then implanted the whole thing on the back of a laboratory mouse. The implant grew its own arteries and veins and turned into a living part of the mouse, which was dubbed Auriculosaurus. The mouse was filmed by a BBC video crew, and the disturbing image appeared in publications around the world. ''Our goal wasn't to grow an ear,'' Charles says. ''It was to prove you could grow cartilage.''
More tangible proof of the promise of tissue engineering came in 1998, when a patient came into the UMass emergency room after a grisly accident. The last bone of his thumb had been ripped off by a machine, leaving the thumbtip and skin hanging. Using a power tool, Charles Vacanti fashioned a piece of coral into the exact shape of the thumb bone. That was ''seeded'' with bone cells, and eventually implanted onto the man's thumb. The bone is growing, the coral is slowly dissolving, and the patient has twice as much function in his hand as he would if the procedure hadn't been done, Vacanti says.
Along with the clinical success has come more evidence of the market potential for tissue engineering. Curis Inc. of Cambridge has licensed patents involving two types of tissue engineering techniques from UMass. The deal included a $750,000 payment toward research at the lab over three years. Jay Vacanti says GMP Companies Inc. of Fort Lauderdale, Fla., recently licensed some of his labs' patents for repair of nerve injuries.
Along the way, Francis and Martin Vacanti have joined the effort. In 1992, Charles sent Martin, who was then teaching at Creighton University, a sample of tissue-engineered cartilage. Under the microscope, Martin Vacanti says, there was no difference from cartilage taken from the body. He was hooked. In 1996, Martin joined his brother's lab at UMass and, at Charles's direction, began searching for ways to grow human nerve cells.
The undertaking is, in many ways, the Holy Grail of tissue engineering. Nerve cells don't grow in adult humans, and their inability to regenerate makes spinal cord injuries permanent. After more than a year of searching, Martin helped discover tiny, previously unknown cells that could help tissues regenerate after an injury. These spore-like cells seem to appear in all types of tissue and can survive being heated and frozen. The cells could be the building blocks in a new generation of engineered tissues.
Even Martin, who says he's never happier than when he's in the lab behind a microscope, allows himself a little chest-beating. ''I knew a whole new discipline was going to be created in tissue engineering neural structures,'' he says.
Francis Vacanti, the most reserved of the brothers, is also researching spinal cord injuries. His work focuses on salamanders, the brightly colored amphibians that have the ability to regrow legs and can even mend after a spinal cord injury. Vacanti is looking for ways to reawaken the same healing process in humans.
How does he find the energy to perform research after long days orchestrating the activity in the MGH operating rooms? Francis says he has no choice. ''I don't enjoy coming in at 4:30 a.m. or working Saturdays and Sundays,'' he says. ''It just needs to be done. I might be the one to do it. I see everything lining up for us to solve the problem. There's no excuse for lying around.''
Those who have worked with the Vacanti brothers say their expressions of altruism are no public relations show. Johnson, the head of the Tissue Engineering Society, says the brothers are marked by a ''generosity of spirit.''
''They have an intense family commitment, an educational base that has brought them into powerful positions in a critical mass, and a down-to-earth will to bring people together to develop things so patients will be better served. They're good scientists, but they have very good hearts.''
Jeffrey Krasner can be reached by e-mail at krasner@globe.com.
This story ran on page 01 of the Boston Globe on 3/11/2001.
© Copyright 2001 Globe Newspaper Company.
The Replacements
Why the Vacanti brothers are the Fab Four of tissue engineering
By Jeffrey Krasner, Globe Staff, 3/11/2001
r. Joseph Vacanti is looking for the ear.
He and his researchers at Massachusetts General Hospital grew it, implanting living cartilage cells in a substrate of plastic. The cartilage cells multiplied, grew a network of blood vessels, and the plastic gradually dissolved.
The end result, when it is located, is about an inch long, and sits in a test tube looking a lot like a boiled Peking ravioli. It is undeniably ear-shaped.
''I'll go get the heart out,'' says Vacanti, 52, eager to show another experiment.
There's no longer anything novel about the idea of taking an organ out of a dead body and sewing it into a living patient. But there aren't enough hearts, livers, or lungs to go around. That's why researchers like Vacanti, known as Jay, are trying to grow the replacements in the laboratory. The field is known as tissue engineering.
But Vacanti isn't working alone. Many of the field's key developments in the past few years have been spearheaded by his three brothers, Charles, Francis, and Martin, who are also doctors and tissue engineering researchers.
That's why specialists in the field think of the Vacantis as the first family of tissue engineering. Some liken the brothers to the building blocks of their field, stem cells - the undifferentiated cells that can be coaxed into developing into different types of tissue.
''They are the stem cells for the entire field,'' says Dr. Peter Johnson, chairman of TissueInformatics Inc., a Pittsburgh biotech firm, and president of the Tissue Engineering Society International, the trade group for the young field. ''They made some of the seminal observations that have enabled many people worldwide to develop many types of tissues. I think they own a big chunk of the founders stock in this field.''
Along the way, the Vacanti brothers have amassed a cache of patents and processes that could create vast wealth for themselves, companies they partner with, and their sponsoring educational institutions. Charles Vacanti, 50, says he holds or co-holds between 10 and 20 patents covering the uses of certain stem cells for particular uses. With self-deprecating humor, he says, ''If it all holds up, it should be worth a trillion.''
There may be less hyperbole in that statement than he intends. According to Michael Becker, an analyst with Wayne Hummer Investments in Chicago, the worldwide market for just one tissue-engineered product, replacement skin, is worth between $5 billion and $7 billion a year. Sales of existing tissue-engineered products are exploding, he says. ''You're probably looking at rapid growth in the neighborhood of 100 percent at least during 2001,'' Becker says.
As in all family histories, there is dispute as to why the four Vacanti brothers wound up as doctors. Their father, Charles, was a professor of dentistry at Creighton University in Omaha and a pioneer in root-canal therapy. They all tagged along to classes and clinics.
But it was Jay, the eldest boy, who first displayed medical prowess. At age 5 or 6, he pored over his father's anatomy texts and even drew pictures that were used in his father's classes. His mother, JoAnne Vacanti, 77, recalls buying Jay a toy called the Visible Man, a sort of anatomy erector set that enabled a child to build a body, organs and all. Jay Vacanti says he never had a moment's doubt: ''I can never remember a time when I didn't want to be a surgeon,'' he says.
For Martin, the third and most unassuming of the brothers, Jay's decision had a strong impact. ''If he had a cowboy outfit, you wanted the cowboy outfit,'' Martin, 49, recalls. He says he followed the path blazed by his older brother after a childhood infatuation with psychiatry faded.
Not so for Charles, the second boy. His epiphany came during a childhood camping trip, when he encountered a leaky toilet in a bathhouse. He reached into the tank, figured out the connection from the handle to the drain, and stopped the leak. ''I was very proud of myself,'' he recalls. He became a tinkerer and builder, but was steered away from engineering by a relative. He became an anesthesiologist in part because the equipment, with its valves and pipes and gauges, appealed to his mechanical side. ''I don't remember reading an anatomy book until I was forced to,'' he says.
Francis, 47, says he resisted medicine for as long as he could, but eventually made a conscious decision to pursue it. ''Medicine has a lot of memory in it, and memorizing things is not my idea of a good time,'' he says. But anesthesia appealed to him because it involved physics - one of his favorite subjects - and it could be mastered with logic rather than memory.
It was Jay, still the leader, who first became involved with tissue engineering. As a young surgical resident at Children's Hospital in Boston, he treated patients with liver failure. He says he quickly realized that the biggest problem facing these patients was the shortage of donor livers to transplant. The obvious solution: growing livers, and any other tissues needed, to help patients with all kinds of reconstructive surgery.
But cells grown in a petri dish tend to form thin films. What was needed were thick structures that could replace actual pieces of tissue. In the mid-1980s, Jay began collaborating with Robert Langer, a chemical engineer at the Massachusetts Institute of Technology. Their solution: materials that would serve as a scaffold, a temporary framework upon which living cells could proliferate. Langer contributed polymers which supported the cells and helped them grow into the right shape, but would later dissolve naturally, leaving only the living cells.
Still, that left another problem: how to nourish these new living cells, which require a constant blood supply. A single gram of human tissue includes a network of tiny capillaries that, if laid out, would cover an entire square foot.
Jay Vacanti and Langer had the right training to tackle the problem. In the late 1970s, they had worked in the laboratory of Dr. Judah Folkman, the pioneering researcher who seeks to kill cancerous tumors by cutting off their blood supply. The flip side to Folkman's work was encouraging blood vessels to grow in new tissue. Says Jay Vacanti, ''It's like growing the branches of the tree, and then you add the leaves.''
A major breakthrough came in 1988, when Jay Vacanti, working with Langer, showed you could implant liver, intestine, and pancreas cells on a plastic substrate, and they would form real tissue.
Folkman compares the Vacantis to other famous tinkerers. ''It reminds you of the Wright brothers working on airplanes in their bicycle shop,'' he says. ''With Langer, they've really pioneered the field.''
But it was Charles, working at his tissue engineering lab at the University of Massachusetts Medical School in Worcester, who helped create the first poster boy, of sorts, for the nascent field.
In October 1995, with an MIT colleague, he molded a human-shaped ear out of polymer, seeded it with cartilage cells from a cow, and then implanted the whole thing on the back of a laboratory mouse. The implant grew its own arteries and veins and turned into a living part of the mouse, which was dubbed Auriculosaurus. The mouse was filmed by a BBC video crew, and the disturbing image appeared in publications around the world. ''Our goal wasn't to grow an ear,'' Charles says. ''It was to prove you could grow cartilage.''
More tangible proof of the promise of tissue engineering came in 1998, when a patient came into the UMass emergency room after a grisly accident. The last bone of his thumb had been ripped off by a machine, leaving the thumbtip and skin hanging. Using a power tool, Charles Vacanti fashioned a piece of coral into the exact shape of the thumb bone. That was ''seeded'' with bone cells, and eventually implanted onto the man's thumb. The bone is growing, the coral is slowly dissolving, and the patient has twice as much function in his hand as he would if the procedure hadn't been done, Vacanti says.
Along with the clinical success has come more evidence of the market potential for tissue engineering. Curis Inc. of Cambridge has licensed patents involving two types of tissue engineering techniques from UMass. The deal included a $750,000 payment toward research at the lab over three years. Jay Vacanti says GMP Companies Inc. of Fort Lauderdale, Fla., recently licensed some of his labs' patents for repair of nerve injuries.
Along the way, Francis and Martin Vacanti have joined the effort. In 1992, Charles sent Martin, who was then teaching at Creighton University, a sample of tissue-engineered cartilage. Under the microscope, Martin Vacanti says, there was no difference from cartilage taken from the body. He was hooked. In 1996, Martin joined his brother's lab at UMass and, at Charles's direction, began searching for ways to grow human nerve cells.
The undertaking is, in many ways, the Holy Grail of tissue engineering. Nerve cells don't grow in adult humans, and their inability to regenerate makes spinal cord injuries permanent. After more than a year of searching, Martin helped discover tiny, previously unknown cells that could help tissues regenerate after an injury. These spore-like cells seem to appear in all types of tissue and can survive being heated and frozen. The cells could be the building blocks in a new generation of engineered tissues.
Even Martin, who says he's never happier than when he's in the lab behind a microscope, allows himself a little chest-beating. ''I knew a whole new discipline was going to be created in tissue engineering neural structures,'' he says.
Francis Vacanti, the most reserved of the brothers, is also researching spinal cord injuries. His work focuses on salamanders, the brightly colored amphibians that have the ability to regrow legs and can even mend after a spinal cord injury. Vacanti is looking for ways to reawaken the same healing process in humans.
How does he find the energy to perform research after long days orchestrating the activity in the MGH operating rooms? Francis says he has no choice. ''I don't enjoy coming in at 4:30 a.m. or working Saturdays and Sundays,'' he says. ''It just needs to be done. I might be the one to do it. I see everything lining up for us to solve the problem. There's no excuse for lying around.''
Those who have worked with the Vacanti brothers say their expressions of altruism are no public relations show. Johnson, the head of the Tissue Engineering Society, says the brothers are marked by a ''generosity of spirit.''
''They have an intense family commitment, an educational base that has brought them into powerful positions in a critical mass, and a down-to-earth will to bring people together to develop things so patients will be better served. They're good scientists, but they have very good hearts.''
Jeffrey Krasner can be reached by e-mail at krasner@globe.com.
This story ran on page 01 of the Boston Globe on 3/11/2001.
© Copyright 2001 Globe Newspaper Company. |
