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Although many of the genetic diseases the Amish suffer from are unique to them, there are several that pop up in areas where other remote or closed societies fall under the founder effect, including some in Chile, Indonesia, Ireland, and the Philippines. The clinic’s scientists, including Kelley, have published their findings in top journals, including The New England Journal of Medicine, to get the word out to physicians serving those populations and to increase the overall understanding of disease. They say they have broken new ground. For example, Morton points to a gene that controls expression of Casper II, a protein in the nervous system linked to seizures that begin in Amish children at around 18 months. That gene has also been connected to similar defects among a group of non-Amish children in California and may have something to do with autism and schizophrenia. “There’s a whole area of biological research started by the study of this gene in the Amish,” says Morton.
Some aren’t sold on the scientific value of the clinic or Kelley’s hands-on research model—including some leading researchers at Johns Hopkins who believe that, absent the rigor and objectivity of academic science, such work has diminished value. “While there is no doubt that Morton and his colleagues have made a contribution to the health of the Amish, they have chosen to work in a location where they are essentially free of the normal, critical scrutiny characteristic of academic medicine,” says David Valle, director of the McKusick-Nathans Institute of Genetic Medicine at the Johns Hopkins School of Medicine. “This choice may, in part, result from their unwillingness and/or inability to defend their practices and ideas in the normal marketplace of ideas.”
But the clinic also has its defenders. Ann Moser, a research associate at the Kennedy Krieger Institute who helped Kelley get started there in 1987, says Valle is off-base. “That’s absolutely not true. There’s some politics involved, and Richard doesn’t like to get involved with that,” she says. “If you ask people who are experts worldwide in metabolic disorders, they’ll tell you that he and his work are highly regarded. There might be some prejudice here at Hopkins, but not elsewhere.”
Kelley brushes off the matter. People need him, so he makes himself personally available. Modern medicine that demands that academic researchers compete for grant dollars designed to go to the most prevalent, most deadly diseases—and often discourages personal connections between researcher and patient—doesn’t apply to his situation, he says. (Funding for clinical research into rare diseases “is the ivory-billed woodpecker of genetic research,” he says.) Drug companies won’t invest in research into remedies for these odd diseases, but he and the clinic will do what they can.
Instead of worrying about his standing in academia, Kelley carries on in the field, visiting families, like the one with four children who suffered from Amish nemaline myopathy. All four died while in Kelley’s care. But he thought he saw some hope as the third of the four, a little girl named Lorraine, fought the disease five years ago. He had prescribed steroids in hopes of controlling her asthma and coaxing some muscle growth. He had also given her mother an inhaler filled with albuterol, an asthma-fighting drug, to use when Lorraine struggled for air.
Kelley noticed something in the months before she died that he hadn’t seen in the other chicken breast disease cases he’d handled: Lorraine’s chest cavity wasn’t massively restricted at age 1, as had been the case with her two older siblings and many others. What’s more, while children with chicken breast disease tend to go downhill very quickly when faced with an additional illness, such as asthma, Lorraine’s disease moved along more slowly, even though she later died. “It puzzled me,” he says. “How were we to explain this abnormality in how her disease progressed? Normally, you’d say the difference was in the genetics. But in this case, we had seen how the two siblings before her had done, and they did not fit this pattern.”
Something in the steroids or the albuterol must have made the difference, he thought, after scanning medical literature. When a younger brother was diagnosed with the disease, Kelley decided to put him on steroids. The dosage, administered orally, was more consistent than the inhaled albuterol, he reasoned, and might be more responsible for the different track that Lorraine’s illness took. “When you’re trying out drugs on these things, it really is serendipity,” Kelley adds.
But the brother died a textbook chicken breast disease death at 18 months old. Steroids weren’t the answer. Could it be the albuterol? When he visited tremulous Joshua at age 6 weeks, Kelley knew which drug he’d try next.
KELLEY’S LIFE AT HOPKINS involves three days each week spent on the phone with concerned parents, returning hundreds of emails from them and physicians who want to tap his far-flung expertise on odd disorders, and doing and overseeing research at the Mass Spectrometry Lab. He skips lunch and runs on a scant few hours of shuteye, sometimes pulling a bedroll out of a drawer in his closet-sized office before stretching out his long frame along almost the entire length of the floor to spend the night.
Endless days are a regular part of the gig for doctors who specialize in strange disorders. Because very few physicians focus on the 7,000 diseases categorized as “rare”—each afflicts 200,000 or fewer people in the United States—those who become experts on one or more of them often drive research for the disease, as well as provide firsthand clinical treatment and consultations. Although 25 million people suffer from rare ailments, money for research into causes and treatments is scarce. Parents of children who suffer from odd syndromes search extensively, and often futilely, for cash that could lead to a cure. Many have formed networks and foundations, such as the Barth Syndrome Foundation, of which Kelley is a scientific adviser, to garner attention from funding agencies and deep-pocketed philanthropists. (Barth syndrome, a metabolic condition that affects the heart muscles of young children, afflicts hundreds of people worldwide, and often leads to death.)