She thought of her last appointment with Dr. Pober, a year earlier. The effects of puberty had been obvious enough even then that the genetic counselor who assisted Dr. Pober had recommended a few resources to help Eli understand and cope with the changes. One was a book called What’s Happening to Me?—a guide to puberty that blended cartoon illustrations with anatomical sketches of the changing teenage body, male and female. Gayle had read parts of the book with Eli, showing him the cartoon characters and skipping the anatomical sketches. She wasn’t sure he was ready to see those.
The genetic counselor had also recommended a film, Hand Made Love: A Guide for Teaching About Male Masturbation. It was explicit, she acknowledged, but it had been developed specifically for people with developmental disabilities. According to the video summary, it discussed “privacy, pleasure, and the realities of sharing living spaces with others.”
“Watch it first,” the counselor said. “See if you think it would be useful for him.”
Gayle never even picked up a copy. It wasn’t that she couldn’t accept that her baby was growing up; it was that he was still a baby in so many ways, trapped in a body that was suddenly becoming an adult’s. Gayle felt as reluctant to show her son a video about masturbation as she would have been to show the same video to a five-year-old. Then again, a five-year-old didn’t run the same risk of being knocked out by some girl’s boyfriend or father for a lingering hug.
The advances both Gayle and Eli had made at camp seemed to have evaporated back in the real world. Eli steamrolled through social boundaries more than ever before, which meant that, instead of giving him space, Gayle planted herself even more firmly by his side wherever they went. If she turned her back for a moment, social disaster ensued. At practice for Eli’s special-needs soccer league one Friday evening, Gayle had gotten caught up in conversation with some of the other parents when she heard Eli greet a teammate’s buxom mother: “Hi! I like your shirt!” She turned to see him lean in sideways for a hug and nestle his head in the woman’s cleavage. Gayle dashed over, put her hands on Eli’s shoulders, and guided him away while the woman giggled awkwardly.
“Eli, you have to stop manhandling people!” Gayle said in a hoarse whisper. “And there are other conversation starters besides, ‘I like your shirt.’ ”
“I like your . . . pants?” he tried tentatively.
“You don’t have to say you like anything,” Gayle said. “Maybe try ‘It’s nice to see you,’ or ‘How are you?’ ”
Eli nodded. “How are you?” he said gamely.
But when they stopped at a Greek diner later that night, he couldn’t keep his hands off their waitress—even after Gayle told him she would take away his favorite toy du jour, a plastic tiki head, if he hugged or touched anyone. He violated the no-touching policy right after breaking Gayle’s rule against begging favors, first by asking the waitress to turn on the overhead fan (she obliged, even though it was a chilly winter night), then by asking for a paper menu and something to color with.
“Can you give me some coloring pencils?” he asked.
“No! Eli . . .” Gayle interrupted, but the waitress seemed not to hear her.
“I’ve got crayons,” she told Eli. “You want crayons, honey?”
“Yes,” he said, avoiding Gayle’s eyes.
The waitress turned to Gayle and said, “He’s a good boy.”
“Yes, he is,” Gayle said stiffly. She never knew what to make of strangers who said things like that. He is a good kid, but I’m trying to teach him not to do these things, she thought. Did they think she was being too hard on him? Or that they needed to placate her—that if she thought he was a bad boy, she’d beat him when they got home?
Eli, on the other hand, took the waitress’s comment as sincere praise.
“I’m being so good,” he said when she walked away, smiling angelically as if to preempt any claim to the contrary.
“No, you’re not,” Gayle said.
“I’m sorry,” he said. “I will be good, I promise.”
When the waitress brought their food, she set Eli’s plate down first. As she did, her fingernails, painted a glittery silver color, sparkled tantalizingly close to his face. His gaze followed her fingers, and while she still held Gayle’s sandwich in one hand, he reached out to shake the other one.
“You like my nails?” she asked, seeing him stare at them while he lingered over the handshake. He nodded but, seeing his mother’s glowering look, said, “I’m sorry.”
“Don’t be sorry, sweetie!” the waitress said as he finally let go. She set down Gayle’s plate and then lifted a glass coffeepot to refill Gayle’s mug.
“I’m sorry,” he repeated, but while she poured the coffee, he reached for her empty hand again. He stretched his other arm out, hoping she’d scratch it.
“I like tickles,” he said when she didn’t take the hint. “Tickle me!”
“I can’t right now, honey,” she said. “I’ve got to work, OK?”
“OK, I’m sorry,” he said. The waitress whirled away to check on the next table. Gayle’s face, meanwhile, had gone white with embarrassment and anger. This was the most brazen she had ever seen Eli in his quest for physical contact.
“I don’t know what to do,” she said quietly, shaking her head. “I can’t even eat right now.”
“I’m sorry. I didn’t mean to do that,” Eli said, then added defensively, “She’s my friend.”
“You lost a lot of privileges doing that,” Gayle said.
Eli hung his head for a moment, then seemed to forget all about his transgression and its consequences. He dug into his turkey dinner and smiled.
“Smell it,” he said happily, looking up at Gayle and pointing to his dinner. She sighed.
“I can’t believe you reached across me and asked her to tickle you. And she had hot food in her hands, on top of it,” Gayle reminded him.
“I know,” Eli said.
“What if she spilled coffee on you and you got burned?”
Eli didn’t answer. The waitress came by with some extra napkins.
“Thank you!” Eli said, then turned to his mother. “She’s nice.”
“Mm-hmm,” Gayle said, chewing slowly.
Eli struggled visibly to refrain from touching the waitress for the rest of the meal. He clapped his hands together and hid them under the table. But the impulse was overpowering. When she returned to clear their empty plates, Eli reached out to her again.
“It tickles,” he said cheerfully.
“It tickles?” she repeated, confused.
“I like tickles,” he clarified. “Tickle, tickle!”
“No,” Gayle said, reaching out for his hand and pressing it flat against the table. “Stop it! Put your hand down.” She stared at him with bulging eyes.
“I’m sorry,” he said for the umpteenth time.
“It’s OK, honey,” the waitress said gently.
“It’s OK, it’s just not appropriate,” Gayle said, struggling to keep the message clear. “You’re going to get in trouble one of these times.”
“I don’t want that,” Eli said.
The waitress picked up his plate. “Do you want to color some more?” she asked soothingly. “Do you want another paper?”
“Yes,” he said. She brought him another children’s menu and disappeared again.
He’s totally out of control, Gayle thought. I should have dragged him out of here before we even ordered.
A few minutes later the waitress set the bill on the table.
“Thank you,” Eli said.
“You’re welcome,” she said. “Have a good night.”
“Thank you,” he said. “Bye, honey!”
He reached out once more for a handshake. She accepted his hand tentatively and gave it a quick pump.
“Have a great night,” she said.
“Thanks,” Gayle said. “You too.”
As the waitress walked away, Eli turned to Gayle.
“She’s beautiful
,” he said loudly.
“Aw!” said the waitress, turning back. “You’re a sweetheart.” She shook her head and clucked, clearly touched. Gayle, however, was not charmed. She paid the bill quickly and then ushered Eli out to the car.
Eli waited out the car ride quietly. It was clear that he remembered Gayle’s warning about lost privileges but hoped she’d forgiven him by the time they arrived back home.
“Um, can I earn my tiki?” he asked politely once she’d parked the car.
“No,” Gayle said quickly, shaking her head. “Uh-uh. You lost your tiki privileges. And your computer privileges.”
“Can I do something?”
“No.”
“I can’t go to bed!”
“No?” she asked, following him upstairs from the garage to the living room.
“I can’t!”
“Go watch TV in your room.”
“I can’t,” he said, looking sorrowfully at the floor.
“What do you think you’re going to do?”
“I think I’m . . . gonna play. With the Bristle Blocks.”
“OK,” Gayle said, sighing.
He wandered into the kitchen to find the blocks. There was a sudden crash: he’d bumped into the shelf that held his toys, and blocks tumbled everywhere.
“I’m sorry! I didn’t mean to do that.”
He sat on the floor and tried to scoop some of the blocks back into their bin. Then he gave up and began spinning the blade of a pinwheel. He asked to use the internet, but Gayle reminded him that the internet was on the computer, and he had lost his computer privileges.
“Maybe I’ll earn it tomorrow?” he asked optimistically.
“You lost those privileges for the weekend,” Gayle said.
“Maybe next weekend?”
Gayle wanted to focus on tonight, not tomorrow or next weekend. She still didn’t think Eli was making the connection between his behavior and its consequences.
“What you did in the restaurant? That was very bad. Very, very bad.”
Eli sighed heavily. He spun the pinwheel and stared at it gloomily. Gayle couldn’t tell whether his distress was over the loss of computer and tiki privileges or the knowledge that he had let her down. Both seemed to weigh heavily on him. “I’m sorry about that,” he said, his voice cracking. For a moment he stopped spinning the pinwheel.
It pained Gayle to see him so despondent, but she didn’t know how else to keep him from overwhelming people with his affection. Even the harshest punishments she could come up with didn’t seem to stop it from happening. As sad as Eli was to lose his tiki head, Gayle was sure he’d do the same thing again in a heartbeat. And she was running out of time before strangers stopped finding his hugs, or his tickling requests, so adorable.
Fourteen
Treating the Friendliness Disorder
Understanding the genetics of Williams syndrome hasn’t yet equated to real-world treatments for the disorder. Hypothetically, however, it could lead to the development of gene therapy for the syndrome’s physical symptoms, and perhaps even for its behavioral symptoms. Unlike drug regimens, gene therapy would be a onetime treatment that could permanently halt or reverse the disorder’s effects—if it worked. That’s a big if, and there’s no guarantee that a genetic fix is possible. But some researchers are optimistic about the prospect, especially following recent breakthroughs that have brought renewed promise to the once-troubled field.
Gene therapy—introducing healthy genes to replace missing or malfunctioning ones—has been heralded as a possible cure for rare genetic disorders and a potential key to developing more efficient treatments for common maladies, from cancer and HIV to autism and schizophrenia. Its early challenges made clear, however, that it would be no simple panacea. A 1999 gene therapy trial resulted in the death of a Pennsylvania teenager being treated for a rare liver disorder, leading to a temporary suspension of similar studies in the U.S. And early trials to repair a mutated gene in the cells of young people with severe combined immunodeficiency, or SCID—better known as “bubble boy” disease—improved their immune system function but caused five of the twenty participants to develop cancer. In the face of daunting technological challenges and an alarming number of unforeseen side effects, many researchers feared gene therapy would never amount to a plausible treatment option.
Editing genes turned out to be the easiest part, although in the early days the task amounted to the laboratory equivalent of breaking rocks. The pioneering geneticists of the 1970s cut into DNA strands using proteins called restriction enzymes. But, as the science writer Michael Specter wrote in a 2015 New Yorker article, “those initial tools were more hatchet than scalpel.” Other methods were developed as the decades progressed, but they tended to be more imprecise, laborious, and expensive than researchers would have liked.
Then, in 2012, scientists announced that a system called CRISPR-Cas9—a self-defense device used by bacteria to chop up invading viruses—could allow researchers to carve away and replace genes with unprecedented precision, speed, and economy. The CRISPR system was a scalpel to succeed the hatchets of the past, although many researchers have compared it to a more modern tool: the find-and-replace feature of a word processing program. The pace of research quickened dramatically after this new technology was introduced; still, geneticists have been careful to point out that its safety and effectiveness as a cure for disease remain to be proven.
But while CRISPR made it simpler to edit genes, a number of challenges stand in the way of using it for gene therapy. Essentially, the system works by carrying a set of instructions into a cell; scientists can program it to cut the genome at a specific location, using the bacterial enzyme Cas9, and either disable a gene or insert a DNA patch to alter it. That’s the relatively easy part; the hard part is getting the editing system to the right cells, and lots of them. One possible method would require scientists to remove a number of cells—say, blood cells—treat them with CRISPR, and then return the corrected cells to the body. But since it’s impossible to remove and replace every blood cell, this method really only works well for stem cells, which can regenerate and thus, once corrected, would make more corrected versions.
The other option is to deliver the CRISPR components directly to cells within the body via an inert virus, since viruses are naturally skilled at reproducing and spreading genetic material. But the viral delivery approach has proved problematic in the past. The Pennsylvania boy who died in 1999 suffered organ failure after his immune system put up a vicious fight against the virus he’d been injected with. The SCID patients who developed cancer did so after the virus carrying a pre-CRISPR form of gene therapy landed near a so-called cell cycle gene, which codes for the production of new cells, triggering uncontrolled cell growth.
Moreover, CRISPR’s predecessors often behaved unpredictably when injected into lab animals and human test subjects. Sometimes they ended up in the wrong spot or interacted with other genes in unwanted ways. And even if CRISPR does exactly what scientists want it to, its reach will be limited. Brain cells, in particular, are nearly impossible to access with our current technology, making behavioral and cognitive disorders especially challenging candidates for gene therapy. Blood and muscle cells are much easier targets.
* * *
ETHICAL QUESTIONS RELATED TO GENE therapy abound, too, and these have only increased since CRISPR enabled new research on a massive scale. Fears that the technology could lead to the creation of “designer babies” have long haunted geneticists, although they point out that they couldn’t engineer an ideal person—whatever that might be—even if they wanted to; the science simply isn’t there yet. Even seemingly straightforward traits, like height, depend on a complex web of gene interactions that scientists haven’t yet untangled. The genetics is even more inscrutable for intellect and personality types.
More recently, scientists have debated the ethical implications of editing genes within human eggs, sperm, or embryos in their earliest stage, since tho
se edits could be passed on to future generations, potentially causing permanent alterations to the genome and changing the very nature of the human species. In 2015 an international committee of scientists called for a moratorium on such applications after a team of scientists in China conducted the first known experiment to affect these cells.II The experiment, an attempt to repair a gene mutation responsible for a rare blood disorder, was conducted on test-tube embryos that were unviable because they had three sets of chromosomes instead of the normal two, ruling out the chance that they’d grow up to pass on their altered DNA. And as it turned out, the experiment was a case study in the limitations of using CRISPR to edit human genes. The technique failed completely in about half the embryos and made unintended cuts in the DNA of some of the others. Almost none retained lasting copies of the new genes.
“As a research tool, CRISPR could hardly be more valuable—but we are far from the day when it should be used in a clinical setting,” one of the scientists who developed the technology told Specter at the New Yorker.
Yet, despite some disappointing setbacks, there have also been some remarkable successes and a host of new applications for gene editing since CRISPR revolutionized the field. Outside our own species, it has been used to make wheat resistant to mildew and to prolong the shelf life of tomatoes. It’s been proposed as a method of altering the genes of mosquitoes to prevent them from contracting (and therefore transmitting) malaria, and modifying the DNA of mice to eradicate Lyme disease among their kind—and, by extension, ours. In 2015 scientists used CRISPR to successfully treat a form of muscular dystrophy in mice by injecting their muscle tissue with a virus carrying instructions to fix a mutated gene. Researchers hope that if they can show that the treatment is safe and effective in primates, human trials won’t be far off.
The Boy Who Loved Too Much Page 17