Early in the evening of June 25, 1995, hours after the birth of his first and only child, the course of Dr. Alberto Costa’s life and work took an abrupt turn. Still recovering from a traumatic delivery that required an emergency Caesarean section, Costa’s wife, Daisy, lay in bed, groggy from sedation. Into their dimly lighted room at Methodist Hospital in Houston walked the clinical geneticist. He took Costa aside to deliver some unfortunate news. The baby girl, he said, appeared to have Down syndrome, the most common genetic cause of cognitive disabilities, or what used to be called “mental retardation.”
Costa, himself a physician and neuroscientist, had only a basic knowledge of Down syndrome. Yet there in the hospital room, he debated the diagnosis with the geneticist. The baby’s heart did not have any of the defects often associated with Down syndrome, he argued, and her head circumference was normal. She just didn’t look like a typical Down syndrome baby. And after all, it would take a couple weeks before a definitive examination would show whether she had been born with three copies of all or most of the genes on the 21st chromosome, instead of the usual two.
Costa had dreamed that a child of his might grow up to become a mathematician. He had even prevailed upon Daisy to name their daughter Tyche, after the Greek goddess of fortune or chance, and in honor of the Renaissance astronomer Tycho Brahe. Now he asked the geneticist what the chances were that Tyche (pronounced Tishy) really had Down syndrome.
“In my experience,” he said, “close to a hundred percent.”
Costa and his wife had been trying to have a baby for a couple of years. Daisy’s first pregnancy ended in a miscarriage, which they knew can occur because of a genetic disorder in the fetus. When Daisy became pregnant a second time, Costa insisted they get a chorionic villus sampling, an invasive prenatal genetic test. But the procedure caused a miscarriage. (The test showed that the fetus was genetically normal.) Costa vowed that if there was a third pregnancy — this one — they would conduct no prenatal tests.
Now, with Tyche bundled peacefully in a bassinet at the foot of Daisy’s bed, and Daisy asleep, Costa sat up through most of the night crying. He had gone into the research side of medicine in part to avoid scenes like this — parents devastated by a diagnosis. But by morning, he found himself doing what any father of a newborn might: hovering by the crib, holding his daughter’s hand and marveling at her beauty.
“From that day, we bonded immediately,” he told me during one of our many talks over the last year. “All I could think is, She’s my baby, she’s a lovely girl and what can I do to help her? Obviously I was a physician and a neuroscientist who studies the brain. Here was this new life in front of me and holding my finger and looking straight in my eyes. How could I not think in terms of helping that kid?”
With no experience in the study of Down syndrome, Costa took a short walk the next day to a library affiliated with Baylor College of Medicine, where he worked as a research associate in neuroscience. Reading the latest studies, he learned that the prognosis was not nearly as dire as it was once considered. Life expectancies had grown, education reforms had produced marked gains in functioning and — of particular interest to Costa — a mouse model of the disorder had recently been developed, opening the door to experimentation. He soon made a decision: he would devote himself to the study of Down syndrome.
In 2006, using mice with the equivalent of Down syndrome, Costa published one of the first studies ever to show that a drug could normalize the growth and survival of new brain cells in the hippocampus, a structure deep within the brain that is essential for memory and spatial navigation. In people with Down syndrome, the slower pace of neuron growth in the hippocampus is suspected to play a key role in cognitive deficits. Follow-up studies by other researchers reached conflicting results as to whether the drug Costa had tested, the antidepressant Prozac, could produce practical gains on learning tests to match its ability to boost brain-cell growth. Undeterred, Costa moved on to another treatment strategy. In 2007 he published a study that showed that giving mice with Down syndrome the Alzheimer’s drug memantine could improve their memory.
Now Costa has taken the next step: he is completing the first randomized clinical trial ever to take a drug that worked in mice with Down and apply it to humans with the disease, a milestone in the history of Down-syndrome research.
“This was a disorder for which it was believed there was no hope, no treatment, and people thought, Why waste your time?” says Craig C. Garner, a professor of psychiatry and behavioral sciences and co-director of the Center for Research and Treatment of Down Syndrome at Stanford University. “The last 10 years have seen a revolution in neuroscience, so that we now realize that the brain is amazingly plastic, very flexible, and systems can be repaired.”
But the effects of that revolution on Down research may yet be cut short. A competing set of scientists are on the cusp of achieving an entirely different kind of medical response to Down syndrome: rather than treat it, they promise to prevent it. They have developed noninvasive, prenatal blood tests which would allow for routine testing for Down syndrome in the first trimester of a pregnancy, raising the specter that many more parents would terminate an affected pregnancy. Some predict that one of the new tests could be available to the public within the year.
Costa, like others working on drug treatments, fears that the imminent approval of those tests might undercut support for treatment research, and even raises the possibility that children like Tyche will be among the last of a generation to be born with Down syndrome.
“It’s like we’re in a race against the people who are promoting those early screening methods,” Costa, who is 48, told me. “These tests are going to be quite accessible. At that point, one would expect a precipitous drop in the rate of birth of children with Down syndrome. If we’re not quick enough to offer alternatives, this field might collapse.”
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