Monday, Aug. 27, 1984

The Miracle of "Test-Tube" Skin

By Anastasia Toufexis

How a new technique gave life to Glen and Jamie

Six-year-old Glen Selby and his five-year-old brother Jamie were spending July 1, 1983, the way they passed many a summer day: just hanging around their neighborhood in Casper, Wyo. A small friend from down the street joined the sandy-haired boys, and the three quickly conjured up some devilry. A nearby house, which was up for sale, stood temptingly empty, and the boys decided to go exploring. Sneaking inside through an unlocked back door, the youngsters discovered cans of paint and solvent, and they began splattering paint on walls, floors and themselves. Then they went to a small bedroom to clean up. They removed their paint-flecked clothes and splashed a gasoline solvent over their bodies, letting it pool on the floor. Then, for some reason, one of the boys struck a match, and mischief turned to tragedy.

The room exploded like a fire bomb, and the youngsters ran out of the house screaming, their bodies aflame. Neighbors, who called paramedics, said the children were so charred that they seemed to be covered with mud. The brothers' friend had the most severe injuries: he died two days later. The Selbys' condition was also grim, with scorched skin over 97% of their bodies. At least 83% of the wounds were of the most serious kind: third-degree burns in which both the upper and lower layers of the skin, the epidermis and dermis, are destroyed and there is damage to underlying tissue. Even if the boys were able to ward off the myriad deadly complications, including shock and infection, they had very little skin left to heal the wounds and provide grafts to cover the massive injuries. And yet today, one year after the accident, the Selby brothers are alive and well, thanks to a new method of growing large patches of skin in laboratory flasks, using postage stamp-sized scraps retrieved from a burn victim's body.

The technique, developed by Dr. Howard Green of Harvard Medical School, has been used on six other burn patients, none with injuries as serious as those of the Selby boys. Says Plastic Surgeon G. Gregory Gallico III of Massachusetts General Hospital and the Shriners Burns Institute, both in Boston, and head of the team that treated the brothers: "These boys had no other hope for survival, so we agreed to try." That the experimental treatment could even be attempted is a tribute to the heroic efforts of the emergency room at Memorial Hospital of Natrona County, Wyo., where the children were rushed after the accident. The hospital staff labored over the youngsters for four hours, maintaining their breathing and starting replacement fluids and chemicals to keep them from going into shock. That night the boys were flown to Children's Hospital in Denver, where "we worked on them almost around the clock for 48 hours," remembers Dr. William Bailey, director of the hospital's burn center. Once the brothers' condition was stable, the staffs attention turned to how to replace the missing skin.

The boys' big break came when Bailey heard that the Shriners Institute had done cultured skin implants on a limited basis. "I thought, 'That's the ticket. That's what they need,' " he recalls. The children were flown east one week after the accident. As described in last week's New England Journal of Medicine, the Boston team took fragments of uninjured skin from the boys' armpits and groins, diced them into groups of cells and then separated them chemically. The isolated cells were then placed in flasks and bathed in a growth-stimulating solution.

After ten days the cells had reproduced and were covering the inside surfaces of the containers. This gave the researchers enough skin to grind down again to start skin cultures in several more flasks. Explains Green: "When the colonies are small, they double every 17 hours." Indeed, each original piece of skin was multiplied ten-thousandfold.

A serendipitous finding ten years ago by Green made this procedure possible. While studying cultures of a mouse tumor, he found flourishing colonies of cells resembling those of the upper layer of living skin. Investigation showed that these epithelial cells grew because of the presence of fibroblasts, a type of cell common to the connective tissue that makes up the dermis. Green realized that the discovery had implications for burn patients: Cultured skin, derived from the victim, would not be rejected by the body's immune system. Another major advance came when Green discovered that a certain bacterial enzyme could remove skin cultures from a flask in entire sheets by loosening the bond between the cells and the plastic surface of the container.

Retrieved in 3-in. by 2-in. patches, the skin was placed over the brothers' injuries and sewed in place. Over a period of four to five months, each boy received half a square yard of cultured skin. About 60% to 80% of the grafts took hold, and now cover more than 50% of the brothers' bodies. The remainder of the burn wounds healed naturally or were covered by grafts of skin taken from healed sites. Doctors believe that the new technique could help about 10% to 15% of the 100,000 people hospitalized for burns in the U.S. every year. Other potential beneficiaries: those with congenital skin damage, ulcers or wounds left after the removal of large tumors.

"The test-tube" skin is "shiny and pink and smooth," says Gallico. But it differs from normal tissue in several ways. It lacks hair follicles and sweat glands, which does not appear to be a problem. The new skin is also thinner than natural tissue, having no dermis. The Boston team cautions that it will take years to assess the success of cultured skin, but, says Gallico, "it appears permanent and durable." Still, Jamie and Glen Selby "shouldn't go out and play football," warns Green. The brothers face more skin grafts, plastic surgery and physical therapy, but their most important battle is behind them: they are alive. "The logistics of skin reproduction as reported are truly remark able," says Dr. Jack Fisher of the University of California, San Diego, in an editorial in the New England Journal.

This achievement, he adds, "cannot be overstated." -- By Anastasia Toufexis. Reported by Meg Grant/Los Angeles

With reporting by Meg Grant