Frameshift (9 page)

“Of course. We don’t have time to waste on fighting.”

He was silent for several moments, chewing on his lower lip. “There is a test,” he said at last.

“Whatever it is, I’ll try,” said Molly.

Pierre laughed. “No, no, no. I mean, there’s a test for Huntington’s disease. There’s been one for a while now; they discovered the Huntington’s gene in March 1993.”

“And you haven’t taken the test?”

“No… I— no.”

“Why not?” Her tone was one of curiosity, not confrontation.

Pierre exhaled and looked at the ceiling. “There’s no cure for Huntington’s. It’s not like anything could be done to help me if I knew. And— and—” He sighed. “I don’t know how to explain this. My assistant Shari said something to me today — she said, ‘You’re not Jewish,’ meaning there were parts of her that I could never understand because I hadn’t walked in her shoes. Most people at risk for Huntington’s haven’t had the test.”

“Why? Is it painful?”

“No. All that’s needed is a drop of blood.”

“Is it expensive?”

“No. Hell, I could do it myself, using the equipment in my lab.”

“Then why?”

“Do you know who Arlo Guthrie is?”

“Sure.”

Pierre lifted his eyebrows; he’d expected her ignorance to be the same as his had been all those years ago. “Well,” he went on, “his father Woody died of Huntington’s, but Arlo still hasn’t had the test.” A pause. “Do you know who Nancy Wexler is?”

“No.”

“Everyone with Huntington’s knows her name. She’s the president of the Hereditary Disease Foundation, which spearheaded the search for the Huntington’s gene. Like Arlo, she’s got a fifty-fifty chance of having Huntington’s — her mother died of the disease — and she’s never taken the test, either.”

“I don’t understand why people don’t take it. I’d want to know.”

Pierre sighed, thinking again of what Shari had said to him. “That’s what everyone who
isn’t
at risk says. But it’s not that simple. If you find out you’ve got the disease, you lose all hope. It’s inescapable. At least now, I have some hope…”

Molly nodded slightly.

“And — and, well, I sometimes have trouble getting through the night, Molly. I’ve… contemplated suicide. Lots of Huntington’s at-risks have. I’ve… come close a couple of times. What’s kept me from doing it is the chance that maybe I don’t have the disease.” He sighed, trying to decide what to say next. “One study showed that twenty-five percent of those who do take the test and are found to have the defective gene actually attempt suicide — and one in four of those succeeds. I’m… I’m not sure I could make it through all the dark nights if I knew for sure I had it.”

“But the flip side is that if you found you didn’t have it, you could relax.”

“Flip side is almost exactly right. It
is
a flip of the coin; the chances are exactly fifty-fifty. But I’m afraid you’re wrong when you say I could relax.

Fully ten percent of those who take the test and find they don’t have the disease still end up with severe emotional problems.”

“Why on earth would that be true?”

Pierre looked away. “Those of us who are at risk for Huntington’s live our lives based on the presumption that they might be cut short. We often give up things because of that. I — before you, I hadn’t been involved with a woman for nine years, and, to be honest, I didn’t think I ever would be again.”

Molly nodded, as if a mystery had finally been explained. “This is why you’re so driven,” she said, her blue eyes wide. “Why you work so hard.”

Pierre returned the nod. “But when you’ve made sacrifices and then discover they were unnecessary, the regret can be too much to bear. That’s why even some of those who discover they don’t have the disease end up killing themselves.” He was quiet for a long time. “But now — now, it isn’t just me. I guess I should have the test.”

Molly reached out and stroked his cheek. “No,” she said. “No. Don’t do it for me. If you ever want to take it, do it for yourself. I was serious: I want to marry you and, if you do turn out to have the disease, we’ll deal with that at the time. My proposal wasn’t contingent on your taking the test.”

Pierre blinked. He was close to tears. “I’m so lucky to have found you.”

She smiled. “I feel the same way about you.”

They held each other tightly. When their embrace ended, Pierre said, “But I don’t know — maybe I
should
take the test anyway. I did do what you asked, you know: I met with someone from Condor Health a couple of weeks ago. But I couldn’t get a policy.”

“You
still
don’t have health insurance?”

Pierre shook his head. “See, right now, they’d reject me based on my family history. But in two months, on New Year’s Day, a new California law comes into effect. It doesn’t bar the use by insurance companies of family-history information, but it does bar the use of genetic info, and the latter takes precedence over the former. If I take the test for Huntington’s, regardless of the results, then they have to insure me; they can’t even charge me a higher premium, so long as I have no symptoms.”

Molly was quiet for a moment, digesting this. “I meant what I said: I don’t want you to take the test for me, and, well — if you can’t get insurance down here, we could move to Canada, no?”

“I — I suppose. But I don’t want to leave LBL; being here is the opportunity of a lifetime.”

“Well, there are thirty million Americans without health insurance. But they mostly manage—”

“No. No, it’s one thing to let you risk being married to someone who might become very sick; it’s quite another to ask you to additionally risk financial ruin. I should have the test.”

“If you think it’s best,” said Molly. “But I’ll marry you either way.”

“Don’t say that now. Wait till we have the test results.”

“How long will that take?”

“Well, normally a lab requires you to go through months of counseling before they’ll administer the test, to make sure you really want to take it and are going to be able to deal with the results. But…”

“Yes?”

Pierre shrugged. “It’s not a hard test — no harder than any other genetic test. As I said, I could do it myself in my lab at LBL”

“I don’t want you to feel pressured into doing this.”

Pierre shrugged. “It’s not you doing the pressuring; it’s the insurance company.” He was quiet for a while. “It’s all right,” he said finally. “It’s time I found out.”

“Explain what’s going on to me,” said Molly, sitting on a stool in Pierre’s lab. It was ten o’clock on a Saturday morning. “I want to understand exactly what’s happening.”

Pierre nodded. “Okay,” he said. “On Thursday, I extracted samples of my DNA from a drop of my own blood. I separated out my two copies of chromosome four, snipped off particular segments using special enzymes, and set about making radioactive images of those segments. It takes a while to develop those images, but they should be ready now, so we can actually check what my genetic code says in the specific gene associated with Huntington’s disease. That gene contains an area called IT15 — ‘interesting transcript number fifteen,’ a name given to it back when people didn’t know what it was for.”

“And if you’ve got IT15, you’ve got Huntington’s?”

“It’s not as simple as that. Everybody has IT15. Like all genes, IT15’s job is to code for the synthesis of a protein molecule. The protein IT15 makes has recently been dubbed ‘huntingtin.’ ”

“So if everyone has IT15,” said Molly, “and everybody’s body produces huntingtin, then what determines whether you have Huntington’s disease?”

“People with Huntington’s have a mutant form of IT15, which causes them to produce too much huntingtin. Huntingtin is crucial to organizing the nervous system in the first few weeks of an embryo’s development. It should cease to be produced at a certain point, but in those with Huntington’s disease it isn’t, and that causes damage to the developing brain. In both the normal and mutant versions of IT15, there’s a run of repeating nucleo-tide triplets: cytosine-adenine-guanine, or CAG, over and over again. Well, in the genetic code, each nucleotide triplet specifies the production of one specific amino acid, and amino acids are the building blocks of proteins. CAG happens to be one of the codes for making an amino acid called glutamine. In healthy individuals, IT15 contains between eleven repeats and thirty-eight repeats of this CAG triplet. But those who have Huntington’s disease have between forty-two and a hundred or so CAG repeats.”

“Okay,” said Molly, “so we look at each of your chromosome fours, find the beginning of the run of CAG triplets, then simply count the number of repeats of that triplet. Right?”

“Right.”

“You’re sure you want to go through with this?”

Pierre nodded. “I’m sure.”

“Then let’s do it.”

And they did. It was painstaking work, carefully examining the autoradiograph film. Faint lines represented each nucleotide. Pierre used a felt-tipped marker to write in the letters beneath each triplet: CAG, CAG. Molly, meanwhile, tallied the number of repeats on a sheet of paper.

Without blood samples from Elisabeth Tardivel and Henry Spade, there was no easy way to tell which of his chromosome fours had come from his father, so he had to check them both. On the first one, the string of CAG triplets ended after seventeen repeats.

Pierre breathed a sigh of relief. “One down, one to go,” he said.

He began checking the sequence on the second chromosome. No reaction when they reached the tally of eleven; that was the normal minimum. When they got to twenty-five, though, Pierre found his hand shaking.

Molly touched his arm. “Don’t worry,” she said. “You said you could have as many as thirty-eight and still be normal.”

Pierre nodded. “But what I didn’t say was that seventy percent of all normal people have twenty-four or fewer repeats.”

Molly bit her lower lip.

Pierre continued sequencing. Twenty-six, twenty-seven, twenty-eight.

His eyes were blurring.

Thirty-five. Thirty-six. Thirty-seven. Thirty-eight.

Damn. Goddamn.

Thirty-nine.

God fucking damn it.

“Still,” said Molly, trying to sound brave, “thirty-eight may be the normal limit, but you have to have at least forty-two…”

Forty.

Forty-one.

Forty-two.

“I’m sorry, honey,” said Molly. “I’m so sorry.”

Pierre put down his marker. His whole body was shaking.

“God, I am so sorry,” said Molly.

A fifty-fifty shot.

A flip of a coin.

Heads or tails.

Call it!

Pierre said nothing. His heart was pounding.

“Let’s go home,” said Molly, stroking the back of his hand.

“No,” said Pierre. “Not yet.”

“There’s nothing more to be done here.”

“Yes, there is. I want to finish the sequencing. I want to know how many repeats I have.”

“What difference does that make?”

“
It makes all the difference,”
said Pierre, his voice shaking. “It makes all the difference in the world.”

Molly looked perplexed.

“I didn’t tell you everything.
Merde. Merde. Merde
. I didn’t tell you everything.”

“What?”

“There’s an inverse correlation between the number of repeats and the age of onset of the disease.”

Molly didn’t seem to understand, or didn’t want to. “What?” she said again.

“The more repeats, the sooner symptoms are likely to appear. Some patients get Huntington’s as children; others don’t get it until their eighties. I — I have to finish the sequencing; I have to know how many repeats I’ve got.”

Molly looked at him. There was nothing to say.

Pierre rubbed his eyes, blew his nose, and bent back to the autorad film.

The tally kept growing. Forty-five.

Fifty.

Fifty-five.

Sixty.

Time continued to pass. Pierre felt faint, but he pressed on, marking letters over and over again on the film: CAG, CAG, CAG…

Molly got up and walked across the room. She found a box of Kimwipes — expensive, lab-quality tissues. She used them to dry her eyes.

She tried to hide from Pierre the fact that she was crying.

Finally, Pierre hit a codon that wasn’t CAG. The total count: seventy-nine repeats.

There was silence between them for a time. Somewhere in the distance, a fire-truck siren was wailing.

“How long?” asked Molly at last.

“Seventy-nine is a very high number,” said Pierre softly. “Very high.” He sucked in air, thinking. “I’m thirty-two now. The correlation is inexact. I can’t be sure. But… I don’t know, I guess I’d expect to see symptoms very soon. Certainly by the time I’m thirty-five or thirty-six.”

“Well, then, you—”

“At the outside.” He raised a hand. “The disease can take years or decades to run its course. First symptoms might just be a reduction in coordination, or facial tics. It might be years before things got serious.

Or…”

“Or?”

Pierre shrugged. “Well,” he said, his voice full of sadness, “I guess that’s it.”

Molly reached for his hand, but Pierre pulled it away. “Please,” he said.

“It’s over.”

“What’s over?” said Molly.

“Please. Let’s not make this difficult.”

“I love you,” said Molly softly.

“Please don’t…”

“And I know you love me.”

“Molly, I’m dying.”

Molly moved over to him, draped her arms around his neck, and rested her head against his chest. His thoughts were all in French.

“I still want to marry you,” Molly said.

“Molly, I only want what’s best for you. I don’t want to be a burden on you.”

Molly held him tighter. “I want to marry you, and I want to have a child.”

“No,” said Pierre. “No, I can’t become a father. The number of CAG repeats tends to increase from generation to generation — it’s a phenomenon called ‘anticipation.’ I have seventy-nine; any child of mine who got the gene from me might very likely have even more — meaning he or she might come down with the disease as a teenager, or even earlier.”

“But—”

“No buts. I’m sorry; this was crazy. It can never work.” He saw her face, saw the hurt, felt his own heart breaking. “Please, don’t make it harder for both of us. Just go home, would you? It’s over.”

“Pierre—”

“It’s over.
I’ve wasted too much time on this already
.”

He could see that the words had cut her. She headed for the laboratory door, but looked back at him once more. He didn’t meet her eyes.

She left the room. Pierre sat down on a lab stool, his hands still shaking.