Badylak

[Guest guest]

Esquire Magazine:

The Cincinnati branch of HobbyTown USA is located in an old strip

mall on the outskirts of the city, in between a Payless shoe store

and an H & R Block. One recent Sunday morning, the assistant manager,

Lee Spievack, stood behind the cash register licking his fingers,

having just devoured a Krispy Kreme chocolate doughnut. Spievack is

sixty-nine, and the accumulation of years has made him less imposing

than he was thirty-five years ago, when he won a Silver Star during

the Vietnam War. He was wearing his HobbyTown USA uniform: a crisp

yellow button-down shirt with his name stitched in red letters that

was tucked tightly into khaki pants pulled well higher than his

waist. Model airplanes hung from the ceiling, and on the shelves

around him were trains, railroad tracks, remote-control cars,

rockets, and kites.

Spievack has been building and flying remote-control airplanes since

he was ten years old. If someone in or near Cincinnati has a problem

with an aircraft smaller than anything regulated by the FAA, they go

see him. Not long ago, on a Friday evening, a customer who bought a

remote-control plane on eBay dropped by because its propeller was

spinning the wrong way. On his own planes, Spievack uses wooden

propellers; if the plane falls out of the sky and lands on someone,

which happens more than you'd think, wooden propellers are less

likely to slice anything off. But this plane had a plastic propeller

more than a foot long. Spievack and the customer took his plane

behind the store for testing, and sure enough, after gassing up the

engine, the whirling blades spun the wrong way. Spievack had never

seen a plane act this way. He got down on his knees for a closer

look, and just as he said, " You've got to get rid of this thing, " he

pointed at the engine, inserting his middle finger directly into the

propeller's path. " And that's how I cut my finger off, " he says.

Over the years, Dr. Badylak has had problems explaining what

he does for a living. He used to say, " I do biomedical engineering. "

But then he'd have to explain biomedical engineering. After a while,

as a default response, Badylak would simply say, " Well, I'm in

medical research. " He hoped that would be enough, but it often

prompted, " What are you researching? " Badylak says, " I got tired of

struggling with it. So now I just tell them I make body parts. "

Badylak has regrown sizable portions of esophagi, tendons, ligaments,

bladders, urethras, abdominal walls, blood vessels, and hearts within

animals and humans.

Badylak, fifty-four, has sharp blue eyes and is tall and fit. He

walks on the balls of his feet, probably owing to his obsession with

running, which he does for three miles every morning at 4:30.

Endurance is a trademark. Badylak has trained and worked as a

veterinarian, a pathologist, and a general practitioner, and he spent

several years as team doctor for Purdue University's football team.

He now works at the University of Pittsburgh's McGowan Institute for

Regenerative Medicine, which is located on the site of an old steel

mill near the banks of the Monongahela River.

Badylak is the son of an Indiana steelworker, and his office window

has a view of the Hot Metal Bridge, but steel is now mostly a memory

in Pittsburgh. Badylak works in one of the city's more modern

successful industries -- organs. The city boasts one of the busiest

and most well-known transplant centers in the world. From his office,

Badylak can hear helicopters buzzing by, hauling coolers containing

chilled livers, hearts, and kidneys.

The flight path of the choppers reminds Badylak almost hourly of the

need for body parts and the fundamental problem with our system of

procuring them. If someone needs a new heart, he often has to wait

for someone else to die. And even if that new heart is a match, the

patient must take powerful immunosuppressant drugs for the rest of

his life, which can make a person sicker than he was before the

surgery. Many people live happily ever after with transplanted

organs, but many more die waiting for them, or because of them.

And then there are people like Lee Spievack, who severely damage or

lose a limb. The answer for them is either a prosthesis or a nub.

That's because the adult human body has evolved to scar, avoiding

infection and moving on with life. But that life would be a lot

better for a lot of people if their bodies could be manipulated into

fixing and replacing lost or damaged body parts -- similar to what

happens to fetuses the first few months in the womb. If a fetus loses

an arm or a leg, it grows back. " Humans can grow an entire human

being in nine months. That's pretty remarkable, " says Badylak. " If

you think about it that way, you can say we just want an arm, you

know, or we want a leg. Just give us enough information that we can

do that. "

Badylak happened upon this quest twenty years ago, early in his

research career, while working on Rocky. Rocky was a dog, a mixed

breed, and Badylak was conducting an experiment that required

replacing a segment of the aorta around Rocky's heart. Sitting around

having lunch one day, Badylak wondered, What in the body has the same

shape and size as an aorta? What's tubular? He settled on the small

intestine, and replaced part of the dog's aorta with part of his

small intestine. " When we came in the next morning, " says

Badylak, " he was just standing, wagging his tail, and wanting

breakfast. " That was surprising, but not nearly as shocking as what

happened next. Over the next weeks and months, as Badylak examined

the new part of the aorta, he discovered that the intestine had not

become simply a tube to pass blood through but had literally morphed

into an aorta. And no scar tissue had formed. This defied what we

previously knew about healing. Badylak had accidentally performed the

biological equivalent of a magician turning a handkerchief into a

dove. But this was no illusion.

Lee Spievack's finger didn't hurt, but the amount of blood squirting

from it was worrisome. He raced inside the store and grabbed a roll

of paper towels, furiously wrapping up what was left of his finger.

His coworkers dialed 911. Spievack didn't get a chance to examine the

damage until paramedics unwrapped the paper towels in the ambulance.

He looked down and saw that it wasn't as catastrophic as he feared,

but the tip -- about half an inch -- was gone. " It was a clean cut, "

he says. " There were no jagged edges. It was like you took a knife

and cut it off. " If he looked closely, he could see bone. Back at the

store, his coworkers shined flashlights around outside hoping to

locate the missing chunk of his finger, but they came up empty. " It

probably landed on the roof and a bird had lunch, " he says.

Seeing that there was nothing left to reattach, the doctors at the

hospital bandaged his wound and told him to follow up with a hand

surgeon, which he did a couple of days later. The surgeon was matter-

of-fact: In a few days, he would take skin from Spievack's forearm or

thigh, then paste it over the finger, leaving a nub. Spievack made an

appointment for the procedure, then went outside and called his older

brother, Alan, a retired Harvard Medical School surgeon. He told Alan

they wanted to do a skin graft. " That's crazy, " he said. " Instead of

having one wound, you will have two. I want you to go back in there

and cancel that appointment. " Lee Spievack did what his brother

advised, and the nurse told him he was going to get an infection.

When they were teenagers, the Spievack brothers raised salamanders.

Alan Spievack was introduced to the creatures during his freshman

year at Kenyon College, after acing a biology exam. Nobody had ever

aced this professor's exam before, and so he asked to see Alan after

class. " Instead of congratulating me, he began to ask questions --

suggesting maybe I had cheated, or the test was too easy, or maybe

the course was, " Spievack says. " He was worried about his reputation

as a tough guy teaching a tough course. I almost promised him I would

never do it again. " A week later, the professor called Alan in again

and said he had a project for him. He took him down to the nearby

Kokosing River and told him to roll up his pants, get in the water,

and catch what appeared to be tiny black insects, which were

salamander larvae. Spievack's job: raise them, then snip off their

arms, legs, and tails, taking notes about how long it took for the

limbs to grow back. Salamanders can regenerate almost any part of

their bodies. Cut off an arm, it grows back. Gouge out an eye, same

thing.

When the semester ended, Spievack took the salamanders back to his

family's home in Cincinnati, where he nurtured them in his mother's

pie pans. (He made his younger brother Lee feed them once a week with

tweezers loaded with hamburger meat and fish food.) Alan eventually

leveraged his interest in salamander regeneration into a Fulbright

scholarship, then medical school at Harvard, and then a lengthy

career in surgery.

Alan Spievack, now seventy-four, bears a striking resemblance to his

younger brother, though he talks a lot more. One of the striking

characteristics of his speech is that he ends every third sentence

with the words et cetera. When asked if he had any children, he

explained that he has a daughter who is thirty-two and another

daughter who is fifteen and " a typical teenager, et cetera. " He has

so much going on in his head that there are things he would just as

soon skip over to get to the important stuff.

Throughout his career, Alan Spievack continued his regeneration

research, and several years before the propeller sliced off his

brother's finger, he attended an orthopedic surgeons' conference in

Atlanta, where he saw a speech given by Badylak. By that

time, Badylak had been chasing answers about Rocky the dog for some

time, becoming an expert on the biological components of the

intestine -- like the fact that the inner lining of the intestine

regenerates itself every six days. Badylak honed in on the layer of

the intestine that supported the tissue replacement, called the

submucosa. He put the submucosa into other wounded organs in dogs,

and the same thing happened. Achilles tendons grew back. Urinary

bladders grew back. The implications of the discovery were profound:

The submucosa stopped the scarring process and promoted regrowth.

Badylak determined that the intestinal material was an extracellular

matrix -- the part of the tissue in the body that connects cells to

one another, like a scaffold. Only this extracellular matrix from the

small intestine -- he'd later use a similar lining from the bladder --

tricks the body's cells into rebuilding instead of scarring. It's

like the cells are in the womb again, and the extracellular matrix

alerts them that the Achilles tendons are not yet done. The cells

kick into gear and go to work. And they are joined by stem cells,

those all-powerful building blocks of life capable of growing into

any tissue in the body. Only the stem cells that show up haven't been

harvested from human embryos. They come from the body's own reserve

in the bone marrow and other places, and although these adult stem

cells are not as flexible as embryonic stem cells, they may have more

potential than previously thought to aid in the regeneration of

multiple tissues.

As his research progressed, Badylak concluded that if there was any

shot of this strategy going prime time in humans, he would not be

able to use intestines or bladders from domesticated animals like

dogs or cats (which have the strongest intestinal lining of any

animals). Using human parts was also out of the question. Badylak

tried zebras, groundhogs, prairie dogs, sheep, and cows before

settling on pigs: They are plentiful, they are similar enough to

humans in genetic makeup, and from a regulatory perspective, the FDA

is friendly toward them because they have for years been the source

of heart valves and dermatological research. And the extracellular

matrix is not rejected by the human body, because all the pig cells

are thoroughly removed. The material can be ground into a powder or

made into a sheet like waxed paper or modeled into a shape, like that

of an esophagus.

Throughout the 1990s, Badylak published one paper after another

reporting his discoveries, but the collective response of the

scientific community was basically to ignore him. In 1996, he spoke

about his research at the conference in Atlanta that Alan Spievack

was attending. Spievack recalls sitting through Badylak's

presentation with his mouth agape: When this guy gets done talking,

everyone in the room is gonna raise their hands with questions. When

Badylak was done talking, Spievack was just about the only person

with his hand up. Well, people are just being coy. When he leaves the

stage, he will be swarmed. But only Spievack approached Badylak. At

that moment, the two men began a friendship and casual working

relationship, with Badylak advising a company Spievack eventually

started to use extracellular matrix scaffolds in injured animals.

Spievack still vividly remembers asking Badylak why nobody else

seemed interested in his speech. Badylak answered, " Because they

don't believe it. "

A few days after Lee Spievack canceled his appointment with the hand

surgeon, he received a package from his older brother containing a

vial of powder that looked like Kraft Parmesan cheese. His brother

instructed him to sprinkle it on his finger every other day until the

powder was gone.

Lee Spievack is not a man who asks a lot of questions. So in the case

of the vial, Spievack didn't much care what it contained (ground-up

pig bladder) or where it came from (a little farm in Albion,

Indiana).

Albion is a speck of a town about a forty-minute drive from Fort

Wayne on some of the flattest land in America. The Whiteshire Hamroc

farm is located a few miles off the main road and its prim little

houses, around the corner from an abandoned nineteenth-century

schoolhouse, and down past some cornfields.

The Whiteshire Hamroc farm raises a special line of genetically

linked pigs that are reared indoors and sequestered from disease. The

idea is that if pig parts are going in humans -- and they have

already been used, by the thousands -- then the pigs need to be as

clean as possible. The pigs at the Whiteshire Hamroc farm are some of

the most pampered swine in the world. They inhale filtered air. When

they are behaving, they are fed strawberry and vanilla ice cream. The

handlers tried chocolate, but the pigs demurred.

Sherry Ziobro, an attractive former student-loan executive who now

brokers pig bladders and other tissues, recently arranged a tour of

the facilities. Before entering, visitors must shower and change into

farm-approved clothing -- Fruit of the Loom boxer shorts, blue

flannel pajama pants, a gray T-shirt, tube socks, and black sneakers -

- all in an effort to prevent as much bacteria as possible from

coming into contact with the pigs. A filtration mask that covers the

mouth and nose is also required, though not for the visitors'

benefit -- even through a mask, specially raised pigs smell terrible.

Inside, the pigs seemed remarkably content. The barn housed litters

that had been born the day before (the mothers resting on their sides

while the piglets fed), adolescent pigs who tried to nip at their

guests, and some older pigs, of an age and size that would soon have

them embarking on the hour's drive to Tippecanoe, Indiana, to visit

the Vin-Lee-Ron slaughterhouse (founded by Vin, Lee, and Ron).

About eleven hundred pigs meet their maker each day at Vin-Lee-Ron.

They start in pens, then make their way forward on a conveyor belt,

snorting and whining louder the farther they get. " Pigs are smart.

They know, " explained the slaughterhouse manager. The pigs ride up

the belt until they eventually meet a man who shocks them with two

hundred volts, killing them instantly, though they still convulse for

a few seconds. Another man slits their throats, and they bleed out

for seven minutes. The pigs are then conveyed to various cutting

stations, where assembly-line workers slice out specific parts. It

takes about two seconds to slice out a bladder, which looks like a

water balloon. It is then stored in a cooler and taken to a lab,

where it is processed and either turned into a sheet like waxed paper

or ground into powder.

Spievack followed his brother's directions: Every other day for the

next eight days, he sat down at his living-room coffee table and

sprinkled the powder on his finger. Whatever powder fell onto the

table he scooped up with a piece of paper, then dropped back into the

vial. He covered his finger with a Band-Aid. A few days went by, and

Spievack could see something was happening. There was skin growing,

and tissue on the inside, too. He insists that what happened after

four weeks did not surprise him in the least, though it should have.

Because his fingertip grew back.

The fingerprint took a couple more months. The tip is a little hard

on the end, but he can feel things just fine. Spievack says he was

particularly happy this past winter; while all of his fingers chapped

in the cold weather, the new fingertip didn't. The only side effect

during treatment was that his finger began to smell like a pig's

quarters at the state fair. " It was a pretty offensive odor, "

Spievack says. He doesn't much think about his finger anymore, except

when he clips his nails. He usually cuts them once a week, but the

new nail has to be clipped every two days.

Asking Badylak what happened with Spievack's finger does not produce

an exceptionally long answer: He doesn't really know. He can't fully

explain why the scaffolds do what they do, and until he can explain

that, he cannot manipulate the technology to grow back entire digits

or organs. He's getting there, but he's not there yet.

Still, the scaffolds have already been used in more than a million

patients to regrow cartilage in sports injuries, rebuild urethras,

and repair hernias, and Badylak's lab will start testing the

technology on human esophagi soon.

Meanwhile, Alan Spievack's company, ACell, has had tremendous success

with veterinary applications. Not long ago, in his house near Boston,

Spievack pulled up an image of a horse with a deep hole in his face

as wide as a hand. " This is Classy, " Spievack said. " Now, Classy is

your typical unlucky horse, et cetera. " The horse had run into a

fence and gouged out his face, including a big chunk of bone.

Surgeons at Colorado State University inserted the pig-bladder

material into the hole during several surgeries over about a year.

There were pictures of the operations, which were bloody. Then there

was a picture of Classy, with his face completely healed. " I know

that good things can happen with this as a matrix and that there are

a lot of different applications, " Badylak says. " I'm also just as

sure that people will not regrow whole digits if you just put the

powder on. There's missing pieces to the puzzle. The problem is I

don't know how big the puzzle is. "

There are scientists who question whether the powder was really the

catalyst for what happened to Spievack's finger. Ken Muneoka, a

Tulane scientist who has been working on tissue regeneration for two

decades, says his own research suggests that fingertips can grow back

on their own, even in a man Spievack's age. He cautions that

Spievack's finger did not grow back in a controlled study -- meaning

the injury and the response to it were not compared with someone

else's in the same circumstances who didn't undergo treatment.

Badylak doesn't deny the controlled-study issue, but he disputes the

notion that someone as old as Spievack could grow the tip back on his

own.

Some of this back-and-forth is the scientific equivalent of

playground trash talk. Both Muneoka and Badylak are at the center of

a sort of Manhattan Project to regrow limbs. The Defense Department

research-and-development agency DARPA, located not far from the

Pentagon in northern Virginia, has been closely watching the progress

of limb regeneration, given the thousands of soldiers coming home

from Iraq after getting body parts blown off. The agency is now

spending about $8 million to fund two teams of researchers racing to

regrow toes in mice. The upcoming year is make-or-break: They must

show DARPA that they can successfully take the first step and grow a

blastema -- a collection of cells that can form a new body part. If

they can do that, a toe is not far behind. One of the teams, led by

Muneoka, is growing extra arms on salamanders to see how the process

might eventually be stimulated in humans. Badylak leads the other

team, which is trying to understand the role of the scaffolds.

Meanwhile, Badylak is also advising surgeons at the Army Institute of

Surgical Research in San on a project to use the

extracellular matrix to help soldiers returning from the war who have

lost digits. He says the project will be successful if the soldiers

can grow back a little more than an inch of tissue. " There is some

sense of competition, " says Muneoka. " Because at the end of the day,

as we move to the next level of this type of work, not everyone's

gonna be sitting in the boat. "

Badylak is confident about his method, but he also believes that his

approach alone isn't going to fully unlock the body's regenerative

potential. There are researchers trying other methods. Many are

adamant that pig material doesn't need to be used at all -- that

artificial scaffolds can work better and faster. Other researchers

are using the scaffolds in entirely different ways. Atala, a

urologist at Wake Forest and editor of the definitive Principles of

Regenerative Medicine, takes cells from his patients' bodies and

grows them new bladders on large part-biological and part-artificial

scaffolds in a lab. Seven weeks later, he implants the bladders in

the body.

Badylak says he does not want to be known as " the guy who grows

fingers, " because he's not sure he can do it, at least not yet. But

like it or not, pleas for his help reach him daily in the form of e-

mails, letters, and phone calls. His face sinks as he describes one:

" I'm a mother from Bologna, Italy, my daughter was born with a

defective hand. She's three years old now. She's being made fun of in

school. We'd like her to have a normal life. She's a beautiful child.

You know, we read about this, and we're willing to travel to the

States. What can you do for us? "

Badylak pauses for a moment. " They're just heartbreaking. I got

another last week from the family of a little girl that fell off a

wagon and into a meat grinder -- it included a picture of her hand

all chopped up. "

For now, Badylak works at that potentially frustrating scientific

junction of having achieved something remarkable but not being able

to explain exactly how he did it. " It's a lot of fun, " he says. " Much

better than not being able to do it at all. If you know that it can

happen, then it's easy to remain enthusiastic and motivated about

looking for the reasons why. If you don't know for sure that it can

happen, then you start to wonder if there is even an answer at all. "

For Badylak, the wondering is over. The puzzle may be incomplete, but

the answer, he knows, lives in Cincinnati, snapping together parts of

model airplanes.