Growing Hope in a Lab

It sounds like science fiction.

Someday, we won't have to wait for people to die to harvest organs for transplantation. We'll grow all the organs we need in a lab.

This tantalizing prospect has not, however, been lifted from the pages of a Ray Bradbury novel. In fact, bladders, kidneys and heart tissue already are being growing in labs around the country-using cells from patients' own bodies-thanks to the pioneering work of researchers like UofL alumnus Dr. Anthony Atala.

Director of the Tissue Engineering Program at Harvard Medical School and Children's Hospital in Boston, Atala recently was selected to receive the University of Louisville School of Medicine's 2001 Alumni Fellows Award for his groundbreaking advancements in tissue research.

The work of Atala and his team has been profiled by such global media outlets as USA Today, CNN, the BBC, Discover magazine and ABC News. Simply entering the urologist's name in an Internet search engine turns up dozens of links regarding his career and medical research.

"The things he's done with the field of tissue engineering are really exciting," says Dr. Arnold Belker, a highly regarded Louisville urologist who has known Atala since he was a resident here. "He's just done outstanding work since he's been in Children's Hospital in Boston."

Desperate need for more organs

One of the greatest problems faced by transplant doctors is the fact that demand for organs far exceeds supply, Atala says. That situation is expected to worsen in coming years as the population continues to age.

"As a surgeon, there's nothing more devastating to me than knowing I don't have enough tissue to transplant," Atala says. "There are 200,000 people in kidney dialysis in the United States, and more than 60,000 are on a waiting list for a transplant. Those numbers are staggering."

Scientists have long searched for a way to increase the availability of organs for transplantation. Even organs from animals have been used in humans. In 1984, surgeons transplanted an infant baboon heart into Baby Fae, creating a firestorm of international controversy when her body rejected the organ 20 days later.

Researchers also have experimented over the years with pig hearts, which are about the right size and shape for humans, but these, too, are rejected by the body.

However, the work done by Atala's team uses a patient's own cells for growing tissues and organs, thus avoiding rejection.

A small piece of tissue is taken from the patient, the cells are grown and expanded, seeded on biodegradable molds, and then implanted back into the same patient four to six weeks later.

In July 1997 Atala made the front page of USA Today when the paper reported that he and a Harvard colleague, Dr. Dario Fauza, had created organs using fetal animal cells.

Their technique began with the removal of cells from defective organs of fetal animals using endoscopic tools. They then replicated millions of copies of the cells in a laboratory and placed them in organ-shaped molds. As the cells grew, they gradually assumed the shape of the molds. Finally, once the animals were born, the engineered cells were grafted into the newborns.

Since the cells originally came from the same animal, the newly created organs were genetically identical to the recipient.

In the fall of 1997 Atala perfected a tissue-engineered bladder, which is a fairly simple organ. He also grew heart muscle tissue, which is far more complex since it must be able to pump blood.

In 1999 Atala and his team successfully transplanted lab-grown bladders into six beagles, using cells from the dogs. The new bladders replaced their natural ones. For the first month, the dogs urinated through catheters to allow the new organs to adapt. After that, the transplanted bladders performed normally for almost a year during the length of the trial, Atala says.

Applications for the future

"A lot of people on the national transplant list are literally waiting for someone else to die so they can live," Atala says.

"Even if you do get an organ, you then have to deal with other problems such as rejection. A major problem is having patients on immune therapy, whether they reject or not -- a very high expense. Four billion dollars is spent on patients with kidney failure a year, not to mention the cost of human suffering.

"Someday we'll be able to address these problems and present better solutions in the field of tissue and organ reconstruction," Atala continues. "New technology does bring more options to make patients better."

Atala is proud of his team of researchers and physicians.

"It's truly a team effort. We have 25 full-time people from all backgrounds-microbiology, cell biology, chemical engineering-all working together to come up with tissues that may help patients in the future."

An early dream

Helping other people has fueled Atala's ambition ever since childhood.

"I wanted to be a doctor from the age of 6 or 8," recalls Atala, who grew up in Florida. "There were no doctors in our family, but we had a family doctor who made house calls. To see somebody go in and make someone feel better -- that was my goal."

Atala did his undergraduate work at University of Miami and then chose the University of Louisville's School of Medicine because of its strong surgery department. His days at UofL made a lasting impact because of those who went before him.

"Walking the halls, seeing the pictures of all the classes before ours dating back more than 100 years-it would always make me wonder: How many lives were saved and changed by the people whose photos were hanging on those walls? For me, becoming a doctor was about healing."

Belker, the Louisville urologist, remembers Atala's focus during his residency in Louisville.

"He always had six balls bouncing in the air, even as a resident, which is very unusual," Belker says, adding that Atala speaks five languages.

But Atala also had time for fun, according to Dr. Hiram C. Polk, chairman of the surgery department at UofL. Polk remembers Atala's penchant for pranks-especially his tendency to booby-trap desk drawers so that spring-loaded toy animals would jump out on unsuspecting secretaries and nurses.

"Tony genuinely enjoys life and people, making others laugh," Polk says. "He hasn't forgotten us either. He and his wife routinely send gifts back to the medical school; they're frequent contributors."

Correcting ureter defects

After Atala finished his formal training at UofL, he found a new home in Boston in 1990 as a Research Fellow in Urology at both Harvard Medical School and Boston Children's Hospital. Two years later he became an assistant professor of surgery at the hospital.

In 1995 and '96, Atala began noticing a number of cases of children suffering from kidney damage caused by urine reflux. Specifically, he observed a defect in the ureter that allows urine to flow back into the bladder. Bacteria from urinary tract infections can then cause severe damage.

Atala teamed with his associate, Dr. David Diamond, to correct the refluxing defect using a procedure that involved no cutting and the patient's own cells.

Guided by an endoscope, surgeons injected a tiny amount of cartilage cells mixed with a sugar solution at the base of the ureter. The substance then grew to create a natural "hump" that prevented urine from flowing backward into the kidneys.

Atala spent six years developing the cell product used in the procedure. Clinical trials of the procedure went well and soon were expanded to other sites around the country under FDA oversight.

Such tissue-engineering techniques have been used to conduct clinical trials for a range of applications, Atala notes.

"Today more than 80 patients have been treated with urethra replacement, more than 100 for reflux, and more than 30 for urinary incontinence," Atala says. "It's a mix of adults and kids, and they come from all over, not just Boston."

Partly as a result of the tissue engineering Atala used in developing the treatments, he was awarded the prestigious 2000 Gold Cystoscope Award from the American Urological Association. The physician also has earned more than 30 other professional honors.

Despite such recognition, Atala finds his greatest sense of accomplishment in the lives of those he helps cure.

"To see this technology in patients -- that's really the goal," Atala says. "Nothing else matters."