Hidden Valley Road - Inside the Mind of an American Family - Robert Kolker Page 0,106

varied directions cells take as they develop and multiply. He envisioned a bunch of marbles rolling down a slope—an obstacle course with an elaborate system of lumps and grooves. Each marble ends up taking a different journey down the slope. That slope is what he called the “epigenetic landscape”—part architecture, part chance.*

This idea made intuitive sense to Weinberger. For all of us, adolescence is a crucial period of housecleaning for brains that had been hard at work for more than a decade of extreme expansion and renovation. This demanding phase for the developing brain explains, for instance, why teenagers need more sleep, or why, after adolescence, it’s harder for most people to learn a language or recover from brain injuries. It may only stand to reason, then, that if one’s genes lay out merely a potential to develop schizophrenia, this would be when that potential is fulfilled. If nothing else, Weinberger’s developmental hypothesis explained why, for example, if one member of a pair of identical twins has schizophrenia, the chance that the twin also will have the condition is about 50 percent—but they each still have an equal chance of passing on the disease to the future generations. “The risk is passed on,” Trinity College geneticist Kevin Mitchell has written, “regardless of whether the person actually developed the condition.”

Whether you get the disease or not, it seems, depends on what happens once the bowling ball hits the lane.

In the years to come, as genetics research grew in scope and ambition, the developmental hypothesis caught on with other scientists. To effectively fight this illness, this theory suggested, one might have to treat people before they seem sick. That, it seemed at the time, would call for isolating the genetic makeup of schizophrenia. Others were joining DeLisi and Freedman in the search for genetic mutations that, in their way, might tell the whole story at last.

* Waddington’s 1957 “epigenetic landscape” model, while famous in its own right, shouldn’t be confused with the more recent use of the term epigenetics, or the idea of genes activated by the environment.

DON

MIMI

DONALD

JIM

JOHN

MICHAEL

RICHARD

JOE

MARK

MATT

PETER

MARGARET

LINDSAY

CHAPTER 28

By the time the researchers from NIMH and Denver came to Hidden Valley Road, Donald had become wordless and vacant, his weight increasing, his movements stiff. He had more or less given up on finding a job or even walking around the neighborhood the way he used to. Except for mealtimes, he was a hermit. As painful as this was for Mimi to see, having Donald at home was also helpful to her, in both mundane and profound ways: He accompanied her as she went grocery shopping and did her chores, and he gave her a purpose.

Donald managed to stay out of Pueblo for seven years, instead paying regular visits to Pikes Peak for doses of Mellaril, an antipsychotic, and Lithobid, an extended-release lithium drug that targets mania. Every so often, he would try living in a boardinghouse, but would never last long. It was during one of those stays, around Christmastime of 1986, that he decompensated completely. He was admitted to Pueblo for the eighth time in January, refusing to answer any questions about his marital status (the failed marriage to Jean still loomed large, perhaps) and preaching from the Bible. In a new development, he also was talking about how certain Lithuanians were looking for him and trying to harm him.

Donald told the staff that he had stopped his medications because his watch stopped. Asked about his mother, he referred to her as “my father’s wife.” Mimi, he had decided, was not really his mother because he was swapped in the hospital—the offspring of an octopus. Pressed to explain his relationship with his family, Donald talked about arguing with his parents about getting a car. Asked if he had a driver’s license, he said he had a “Goldilocks and Three Bears” Colorado driver’s license.

In a few weeks,