Frontier of gene research moves to Amish country

A harvard-trained doctor is helping Amish children

August 04, 1999|By Denise Grady | Denise Grady,New York Times News Service

STRASBURG, Pa. -- This was not the typical audience for a medical conference, but then again, this was no typical conference. At an inn set in the lush farmland of Lancaster County, doctors attending scientific lectures were joined by young Mennonite and Amish couples, the women in bonnets and the men in suspenders, babies fussing in their laps.

The Amish and Mennonites may travel by horse and buggy and forgo most modern conveniences, but there is one bit of progress that they are eager to embrace: gene therapy.

If all goes as planned, conference participants learned, three children from these communities will become the first human beings ever to test a new method of gene therapy. If it works, it will spare them the devastating effects of a rare but deadly inherited disease.

In the condition, Crigler-Najjar syndrome, a substance called bilirubin, a waste product from the destruction of worn-out red blood cells, builds up in the body. Bilirubin is produced constantly in the human body, and normally, it is broken down by an enzyme in the liver and excreted through the intestines.

But in people with the syndrome, the enzyme is either absent or scarce. Bilirubin accumulates, causing jaundice, a yellowing of the skin and the whites of the eyes. More important, bilirubin is toxic to the nervous system, and the children live in constant danger of brain damage. The only way they can survive is to spend 10 to 12 hours a day under special lights that break down the bilirubin. But as they reach their teens, the light therapy becomes less effective. Unless they can get a liver transplant, they will suffer brain damage or die.

If the gene therapy works, the children will have a chance to lead more normal lives. But previous attempts at gene therapy have been disappointing. If the new approach, called chimeraplasty, works against Crigler-Najjar syndrome, it would finally open the door to treatment of a host of other, more common genetic disorders, according to Dr. Michael Blaese, a gene therapy expert who left the National Institutes of Health in January to join a Philadelphia company specializing in the new therapy. The other disorders that might be treated include sickle cell anemia, cystic fibrosis and a failure of the immune system known as ADA deficiency.

"I left what I thought was the best job in the world to do this because I believe so strongly in it and believe we'll be successful," Blaese said. "I think it will really fundamentally change the way we practice medicine."

Blaese and other researchers, leaders in genetics and disorders involving bilirubin, were drawn to Lancaster County largely through the efforts of Dr. Holmes Morton, a slight, graying man of 49 who still speaks with the twang of his native West Virginia.

A Harvard-trained pediatrician, Morton first encountered Amish youngsters with genetic diseases while he was working at a Philadelphia hospital during the 1980s. He had trained in biochemical genetics, and he recognized that some of the children had metabolic disorders, not previously diagnosed, that could be managed with specific diets and careful treatment of minor illnesses. But without proper therapy, the diseases could rapidly cause brain damage. Some parents whose children had died or become handicapped sought his help for younger siblings.

"I knew I could take care of them," Morton said.

In 1988, he began commuting to Lancaster County, driving from one house call to another. A year later, he and his wife, Caroline, and their three children moved to Strasburg. Morton was 39, and highly regarded by his colleagues, including some who were dismayed to see him put aside a bright future in science and academia to disappear into a small town and treat children with obscure diseases that had resulted from inbreeding.

But where others saw a backwater, Morton saw a need and an opportunity to make a difference, to develop treatments for diseases that were taking a cruel toll on children. In 1990, he opened his non-profit clinic.

"I think of myself as a pediatrician who knows a little more than average about biochemistry and genetics, and can use that in a primary care setting to prevent problems," he said.

His patients think of him in another way: "He is a gift to us," said Miriam Martin, whose three young children are all under his care for Crigler-Najjar syndrome.

For generations, the Amish and Mennonites, descendants of Swiss and German Anabaptists who settled in Pennsylvania during the 1700s, have suffered from unusually high rates of dozens of genetic disorders. The diseases occur because the communities arose from a small population of founders, and members, who are forbidden to marry outside their religion, marry each other. As a result, many people in the groups today are related, increasing the odds that both members of a couple will unknowingly be carriers of a hereditary disease that does not affect them but will show up in their children.

Scientists have eagerly studied the Amish for decades, making discoveries that filled at least one textbook on genetic disorders. But the experts who gathered their data from Lancaster County did not stay to take care of the diseases they identified.

As children approach puberty, phototherapy becomes less effective and bilirubin begins rising to dangerous levels. At that point, a liver transplant is considered.

But Morton tries to keep children well enough to put off transplants for as long as possible.

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