By William Allen
Post-Dispatch Science Writer

(Jerry Naunheim Jr. of the Post-Dispatch contributed information for this story.)

Sept. 20, 1999

Edited by Virginia Baldwin Gilbert

A decade ago, a researcher's discovery at a university might have taken years before it reached doctors at a hospital to be put to practical use.

If that were the case today, these two little girls wouldn't be alive.

And they are very much alive.

Meagan Craig and Autumn Bailey have much in common.

Both are 5 years old and deaf. Both ride home on the same kindergarten school bus in Florida. Both had historic lung transplants five years ago in St. Louis to overcome a deadly inherited disease.

And, of course, both like to play.

So when their parents and doctors separated them for routine medical tests last week, at St. Louis Children's Hospital, their giggles and smiles changed to silence and looks of concern.

"Where is Autumn?" Meagan said in sign language to the adults in the room.

"Where is Meagan?" Autumn signed a few rooms away.

The two girls don't yet know that they're children of the genetics revolution or that they're making medical history. But they do know they're the best of friends.

Meagan and Autumn, both of the Tampa area, would have died five years ago if not for discoveries in the early 1990s at the Washington University School of Medicine.

They were born with a genetic disease known as pulmonary surfactant prot ein B deficiency. Infants with the deficiency die of respiratory failure within a few days of birth.

Only a year before their births, Washington University researchers identified the genetic mutation that caused the deficiency. They developed a rapid screening test to detect it. That made it possible to arrange for a lung transplant and other steps to care for sick infants.

Now, researchers are hot on the trail of therapies that would repair the damaged genes so an affected infant's lungs function normally.

"All of that occurred in an extremely short period," said Dr. Harvey Colten of the Northwestern University School of Medicine, in Chicago. Colten, who was chairman of pediatrics at Washington University at the time, led the team that made the discoveries.

The story of Meagan Craig and Autumn Bailey may be the first example of how new genetic knowledge can be translated quickly into effective treatment. Before the discoveries about their genetic deficiency, identifying a genetic disease and finding a rational therapy often took decades.

Their story also represents the beginning of a coming explosion of new steps to diagnose and treat many of the more than 4,000 estimated human genetic diseases.

As they sat through their daughters' tests, Lauri Bailey and Diane Craig talked about their new appreciation for the genetic revolution. "People like us are the beneficiaries," Bailey said.

Craig agreed: "It's saving lives."

The code goes bad

The lung disease that could have killed Meagan and Autumn has killed countless others. Doctors didn't know the cause until 1993, when Colten and his colleagues identified the deficiency as a genetic disease.

Shortly afterward, they identified the gene involved. It was one of the estimated 100,000 genes that all humans have embedded in their 23 pairs of chromosomes. Virtually each cell in the body contains a copy of the 23 pairs.

Each gene consists of a complex biochemical code that acts like a blueprint, telling each of our 100 trillion cells what to become, what to do and when.

When the code goes bad, a disease can develop. Depending on which gene the flaw occurs in, it can cause cancer, heart disease, diabetes, cystic fibrosis or any other genetic disease.

Such a flaw occurred in the cells of Meagan and Autumn.

Colten and his colleagues discovered that two misplaced letters in the code of one gene halted production of pulmonary surfactant protein B - a substance needed for an infant's lungs to function.

The flaw "takes the whole protein out," said Colten, who has served as dean at Northwestern.

The protein helps keep air sacs in the lungs inflated. Without it, the lungs cease to function, oxygen fails to reach the bloodstream and the baby dies.

"It turned out that the disease is much more common than suspected," Colten said. About 100 families around the world have so far been identified as carriers.

Previously, the disease could only be detected by a lung biopsy, an invasive procedure performed after birth. The rapid blood test developed by Colten's team can detect the defective gene more rapidly and easily. Today, it can be performed before birth by amniocentesis.

Nightmares and ecstasy

Rebecca Bailey, Richard and Lauri Bailey's first daughter together, died of lung problems five months after birth. Doctors in the Tampa area couldn't determine the problem.

Autumn came about a year later, in early 1994. She had the same problem.

"It was a nightmare," Lauri Bailey said.

The same nightmare played out for Mike and Diane Craig. They lost a newborn daughter and son a few years before Meagan was born.

By the time Autumn and Meagan came into the world, doctors in Tampa had heard of the blood test for the protein deficiency. They sent blood samples from the two girls to Dr. Lawrence Nogee, a member of Colten's Washington University team who had moved to the Johns Hopkins School of Medicine, in Baltimore.

Nogee confirmed the struggling newborns had the disorder.

"I was ecstatic," Lauri Bailey said. "We finally had an answer for what caused Rebecca's death."

The girls traveled to St. Louis Children's Hospital, where a team headed by Dr. Thomas Spray was pioneering infant lung transplants. The hospital still operates the largest pediatric lung transplant program in the world.

Within weeks they had received new lungs. The girls are thriving five years later, despite periodic bouts with pneumonia and hearing loss caused by drugs needed for the lung transplants.

"With each new baby, we're learning how to care even better for the next one," said Dr. Aaron Hamvas, medical director of the hospital's neonatal intensive care unit. He worked with Colten in the early '90s. "The interesting thing is how rapidly it all came together."

Autumn and Meagan attend Cross Bayou Elementary, a school in Pinellas Park, Fla., for children with special needs.

Last week, as they ran around the hospital between tests, they exuded the energy typical of any excited 5-year-old. At other times, groggy from medications given to aid the tests, they gazed up at the adults around them, asking about each other.

Preliminary results showed both girls still had good lung function, said Dr. Stuart Sweet, medical director of the lung-transplant program at Children's and one of those involved in the transplants. The girls will report back for more tests in a year.

"I'm optimistic," Sweet said. "Each has had a really big challenge. They've made great strides.