She Has Her Mother's Laugh: The Powers, Perversions, and Potential of Heredity (19 page)

Fifty years would pass after Følling and Penrose proposed that PKU was caused by recessive factors before scientists finally saw the factors with their own eyes. By then, however, the lives of people with PKU had already dramatically improved. A child born with PKU, if properly cared for, would never have to face a future like that of Carol Buck.

The journey to a treatment started in 1949, when a British woman named Mary Jones brought her seventeen-month-old daughter, Sheila, to a Birmingham hospital. Sheila couldn't stand or even sit up. Nor did she take an interest in her surroundings. A doctor at the hospital named Horst Bickel examined Sheila and informed Jones that she had PKU. “
Her mother was not at all impressed when I showed her proudly my beautiful paper chromatogram with the very strong phenylalanine (Phe) spot in the urine of her daughter proving the diagnosis,” Bickel later recalled.

Jones wanted to know what Bickel was going to do now that he had discovered Sheila's disease. There was nothing to do, Bickel explained.

Jones rejected his answer. She came back the next morning to demand
help. When he turned her down, she came back every morning with the same demand.

“She was very upset and did not accept the fact that at the time no treatment was known for PKU,” Bickel said. “Couldn't I find one?”

At the time, Bickel had little reason to think he could. Lionel Penrose had already tried to design a diet for PKU, without any results to show for it. Penrose became convinced that mental retardation wasn't caused by the inability to convert phenylalanine. Instead, he thought, the two symptoms both arose from an unknown source. A diet was no more likely to cure PKU retardation than eyeglasses would make an old man's wrinkles disappear.

Jones was so insistent, though, that Bickel decided to talk to some of his colleagues about a diet for PKU. He learned that a biochemist in London named Louis Wolff had tried concocting a broth that could provide protein to people with PKU without poisoning them with phenylalanine. When he proposed feeding his broth to patients, his superiors at Great Ormond Street Hospital told him his job did not involve crazy treatments for the incurable. Wolff gave his recipe to Bickel, who followed the directions, working in a frigid lab kept cold to prevent the concoction from spoiling.

Eventually, Bickel prepared enough of the stuff for Sheila. He instructed Jones that the girl was to eat nothing else. To his delight, the phenylalanine in Sheila's bloodstream dropped, and did not bounce back the way it had in Penrose's experiments fifteen years earlier. The diet even showed signs of improving her brain. Within a few months she began to sit up, then to stand, then to walk with assistance. Her musty odor even disappeared. But when Bickel told his colleagues at the hospital, they scoffed. They were sure Sheila had improved merely thanks to the extra attention she was getting. Bickel decided there was only one way to persuade them: take Sheila off of the diet.

Without telling Jones, Bickel secretly added phenylalanine to the formula. Within a day on the altered diet, Sheila started deteriorating. Soon she stopped smiling, making eye contact, or even walking. Bickel and his coworkers told Jones of their secret maneuver, and put her back on the low-phenylalanine formula. While the transformation was enough proof for Bickel, he didn't
think it would be enough to persuade skeptical colleagues. He got Jones's permission to bring Sheila into the hospital and feed her phenylalanine again. This time, Bickel captured her decline by
filming a silent movie.

In the first scene in the movie, Sheila is on Bickel's phenylalanine-free diet. She looks healthy and alert. She sits in a high chair, and behind her is draped a curtain covered in fleurs-de-lis. An arm, swathed in a lab-coat sleeve, moves into the frame, dangling a ring of keys. Sheila looks up at the keys. She studies them, and then reaches upward. As she taps the keys, she watches them swing back and forth. Sheila then grasps one of the keys in her own fingers. Now another lab-coat arm moves into the frame, bringing forward a rattle. She makes the difficult choice between keys and rattle calmly. She takes the keys and flings them to the floor.

The next scene was shot after Sheila went back on an ordinary diet for three days. She is a profoundly different child. She sits on the floor, gazing into middle space, her hair a chaotic tuft. When someone shows her keys, she takes several seconds to notice them. She reaches slowly, drooling, but can't grasp them.

The movie jumps ahead two days. Now Sheila doesn't even bother to reach for the keys. She just looks at them and cries. The screen turns black again: “Four weeks after resuming her low-phenylalanine diet,” a card reads. In the next scene, Sheila is walking, pushing a chair across the room with stubborn determination. She looks up with an intense gaze—not sad, not happy, perhaps just wondering what she's been put through.

Bickel's movie was impressive enough to change the minds of doctors at Great Ormond Street. Wolff, Bickel, and their colleagues got the green light to put more children on the low-phenylalanine diet. In every case, they saw significant improvements. The diet wasn't a panacea by any means. While the children scored better on intelligence tests, they remained far below average because they had already suffered so much irreversible brain damage. The researchers also saw that the benefits could vanish if parents didn't sustain the diet every day. Sheila Jones kept getting better, learning to scribble with a crayon and build a tower of bricks. But her mother, a single parent struggling with mental illness, couldn't keep up Sheila's demanding diet. Eventually, Mary Jones ended up in an institution, and Sheila had to
be put in one as well. Without the diet Bickel and Wolff had invented, Sheila Jones was doomed to live there the rest of her life. She learned to feed and dress herself, but she never learned to speak.

Bickel and Wolff's breakthrough inspired other scientists and pharmaceutical companies to concoct better formulas. As scientists studied how children on these diets turned out, they found that the earlier they got away from phenylalanine the better off they were in the long run. In the 1950s, however, doctors were still using Følling's test to detect PKU, which works only after children have built up relatively high levels of phenylpyruvic acid in their urine. To make the diets more effective, they'd need an earlier test.

At the time, scientists knew that PKU was caused by a recessive gene, and they also knew that the gene must be a specific sequence of DNA on a chromosome. But no one knew where it was. Even if they had known, they wouldn't have been able to sequence it, because the technology required would not become available for many decades. Instead, researchers tried to invent new tests for PKU that could detect lower levels of phenylalanine.

In 1957, a California pediatrician named Willard Centerwall figured out how to diagnose PKU by dabbing a child's diaper with ferric chloride. His test made it possible for doctors to identify children with the disease when they were still just a few weeks old. Soon afterward, an American medical researcher named Robert Guthrie developed a test that used blood rather than urine. Guthrie's test was quick, reliable, and cheap. Even better, it could detect PKU in a newborn with just a pinprick's worth of blood.

These advances were celebrated in the
Saturday Evening Post
,
Time
, and the
New York Times.
Before 1960, only
25 percent of people with PKU lived to the age of thirty, the majority dying young of infections in institutions. But now doctors could detect it and then treat it. Although PKU affected only a few hundred Americans, the press hailed the work of Guthrie and others as an unprecedented victory over heredity.

At the same time, thanks in part to Pearl Buck's
Child Who Never Grew
, many parents of retarded children had cast off their shame and were organizing. While there were many causes of retardation, the parents put the spotlight on PKU to inspire more support for care and research. As part of the 1961 National Retarded Children's Week, President John F. Kennedy
welcomed two sisters with PKU, Kammy and Sheila McGrath, to the White House.

Both girls had PKU, but it had affected their lives in fundamentally different ways. Sheila, the older sister, had been diagnosed with PKU when she was a year old. By then she had suffered so much brain damage that at age seven she was now living in an institution. When the McGraths had Kammy two years later, their doctor used Centerwall's diaper test to diagnose her with PKU at three weeks. The McGraths immediately put her on a diet of special protein powder and low-protein foods. She had avoided Sheila's toxic exposure, and now, at age five, she was healthy and living at home.

When the McGrath family came to the Cabinet Room of the White House, Kennedy greeted them personally. He led Kammy to a rocking horse and watched her rock on it.

“
Attagirl,” the president said. “They are the best behaved children we've had in the White House—and that includes those who live here.”

The McGrath family visit is
memorialized by an official White House photograph. Kammy and her parents stand by the president, looking at Sheila. She sits on a rocking horse, gazing away. In May the following year,
Sheila and Kammy appeared in
Life
, posing for a photo essay about Guthrie's test. Kammy, her hair in pigtails, grins over a mountain of protein powder poured onto a table. Sheila, her hair chopped short, is wearing a dark dress and sitting in a rocking chair set back from the table.

The wordless image delivered a clear message: Modern medicine had allowed Kammy to avoid Sheila's fate. “The sentencing is not mandatory,” the
New York Times
declared. “Phenylketonuria can be kept in check, if diagnosed early enough, and
a child can live a normal life.”

In December 1961, the Kennedy administration panel moved to seek mandatory testing for PKU of all newborns. In 1963, Massachusetts passed a law that required screening for the disease, and other states soon followed. Within ten years, 90 percent of American children were being screened, and Guthrie and other researchers set up PKU testing programs in other countries as well. In later years, other hereditary disorders would be added to newborn screening, giving children as much of a head start as possible. By
the 1970s, the first generation of people treated for PKU since birth reached adulthood. They could finish school, hold jobs, have ordinary lives. In 2001, a graduate student named Tracy Beck became
the first person with PKU to gain a PhD. She became an astronomer, helping to build the James Webb Space Telescope. For thousands of years, people who inherited the mutations in Beck's PAH genes would have looked to the sky and not known the word for the lights they saw. Now Beck was helping to extend humanity's gaze to the farthest edges of the universe.

In 1957, the Vineland Training School decided to test all their students for PKU. One of the few to test positive was Carol Buck.

In one sense, the result was nothing new: Penrose had made the same diagnosis twenty years before, using Følling's crude test. But this time the school told Pearl Buck. She could finally give Carol's condition a name, nearly four decades after it had altered her own life.

The name was new to Buck. She studied up on it, and when she traveled to Norway in 1958, she sought out Følling himself. Buck learned as much as she could from the seventy-year-old doctor. Soon afterward, she wrote a letter to her ex-husband, Lossing. She explained to him that they shared an invisible bond, one that neither had known about. After Pearl and Lossing had divorced, he had remarried. He and his second wife had two healthy children. In her letter, Pearl warned Lossing that they may have inherited his dangerous legacy.

“
In Carol's case nothing matters, it is too late,” she wrote. “But I think of your children, who carry the genes in their bodies. It is essential before they marry, that this blood is tested, and the blood of the person they marry.”

In 1960, Willard Centerwall paid Pearl Buck a visit at her home in Pennsylvania. She confided in him that Carol had recently been diagnosed with PKU. From a pocket, Centerwall produced a vial of phenylacetate crystals. He invited Buck to sniff it.

“Immediately she recalled that Carol, as a child, had
the same unusual odor,” Centerwall later remembered.

Buck did not write anything about Centerwall's visit, about smelling an odor that took her back forty years to Nanking, to the bamboo garden where she watched her daughter play. We can't know what it was like for Buck to suddenly learn that this odor had actually been a signal. It might have told her about her own genetic makeup, about a rare genetic variant that she had inherited from her mother or her father, a variant that Lossing had also acquired from his own ancestry, which they had combined in their child. We don't know what it was like to discover all this at the very point when children with PKU could at least be treated, to learn that every meal she made for Carol was unwitting poison.

What little we do know comes from her other daughter, Janice. In 1992 Janice recalled that
Pearl “had trouble accepting that her family's genes may have contributed to this disorder.”

In the 1960s, as the first generation of PKU children got to grow up with healthy brains, life went on for Carol and Pearl much as it had for decades. Every December, Pearl wrote a letter to the Vineland Training School, with a list of gifts to be purchased for Carol, who was now in her forties.
Crayons and coloring books, beads, glazed fruit, candy, doll blankets, a musical top. The list didn't change from one Christmas to the next.

In 1972, Pearl paid her last visit to Carol. She had been diagnosed with lung cancer, and her treatments would keep her alive only a few months after the diagnosis. Carol Buck outlived her mother by another twenty years. She, too, was diagnosed with lung cancer. She died at age seventy-two in 1992, and was buried on the grounds of the Vineland Training School, across the street from Emma Wolverton's grave. Neither Carol nor her mother smoked, raising the possibility that they shared a different mutation that raised their risk of the disease.