Frameshift (10 page)

Pierre called Tiffany Feng and told her to go ahead and put in his health-insurance application at the first of the year. Condor might have disputed the informal testing if the result had been negative, but there was no conceivable advantage to lying about having Huntington’s. Tiffany said Pierre’s statement on Human Genome Center letterhead, notarized by the campus archivist, would be acceptable proof that the test had indeed been conducted.

Pierre went back to spending his evenings in Doe Library. Periodically he’d look up, look around, look for a familiar face.

She never appeared.

He spent each evening reading, searching the literature for information on junk DNA — now, more than ever, he knew he was in a race against time. He was already seven years older than James D. Watson had been when he’d made his great breakthrough — and only two years younger than Watson had been when he’d accepted his Nobel Prize.

A wall clock above Pierre’s chair was ticking audibly. He got up and moved to another table.

He’d started with current material and was working his way backward.

A reference in a magazine index caught his eye. “A Different Kind of Inheritance.”

Different kind of inheritance…

Could it be?

He asked Pablo to dig up the June 1989
Scientific American
.

There it was — exactly what he’d been looking for. A whole different level of information potentially coded into DNA, and a plausible scheme for the reliable inheritance of that information from generation to generation.

The genetic code consisted of four letters: A, C, G, and T. The C stood for cytosine, and cytosine’s chemical formula was C H,N O — four carbons, 4 3 five hydrogens, three nitrogens, and an oxygen.

But not all cytosine was the same. It had long been known that sometimes one of those five hydrogens could be replaced by a methyl group, CH, — a carbon atom attached to three hydrogens. The process was called, logically enough, cytosine methylation.

So when one wrote out a genetic formula — say, the CAG that repeated on and on in Pierre’s own diseased genes — the C might be either regular cytosine or the methylated form, called 5-methylcytosine. Geneticists paid no attention to which one it was; both forms resulted in exactly the same proteins being synthesized.

But this article in
Scientific American
, by Robin Holliday, described an intriguing finding: almost always when cytosine undergoes methylation, the base next to the cytosine on the DNA strand is guanine: a CG doublet.

But C and G side by side on one side of a DNA strand meant that G and C would be found on the opposite side. After all, cytosine always bonds with guanine, and guanine with cytosine.

In the article, Holliday proposed a hypothetical enzyme he dubbed “maintenance methylase.” It would bind a methyl group to a cytosine that was adjacent to a guanine
if and only if
the corresponding doublet on the other side was already methylated.

It was all hypothetical. Maintenance methylase might not exist.

But if it did—

Pierre looked at his watch; it was almost closing time. He photocopied the article, returned the magazine to Pablo, and went home.

That night he dreamed of Stockholm.

“Good morning, Shari,” said Pierre, coming into the lab.

Shari was dressed in a beige blouse under a wine-colored two-piece suit. She’d cut her long, dark hair recently and was now wearing it fashionably short, parted on the left, and curving in toward her neck at the bottom. Like Pierre, Shari was burying herself in her work, trying to get over the loss of Howard.

“What’s this?” she said, holding up an autorad she’d found while tidying up. The lab would have been a pigsty if it weren’t for Shari’s periodic attempts to restore order.

Pierre glanced at the piece of X-ray film. He tried to sound nonchalant.

“Nothing. Just garbage.”

“Whoever this DNA belongs to has Huntington’s disease,” said Shari matter-of-factly.

“It’s just an old sheet.”

“It’s yours, isn’t it?” asked Shari.

Pierre thought about continuing to lie, but then shrugged. “I thought I’d thrown it out.”

“I’m sorry, Pierre. I’m so sorry.”

“Don’t tell anyone.”

“No, of course not. How long have you known?”

“Few weeks.”

“How is Molly taking it?”

“We — we’ve broken up.”

Shari put the film in a Rubbermaid garbage pail. “Oh.”

Pierre shrugged a little.

They looked at each other for a moment. Pierre’s mind did what he supposed every male’s did in moments like these. He thought for an instant about him and Shari, about the possibilities there. Both of them carried diseased genes. He was thirty-two and she was twenty-six — not an outrageous difference. But — but there were other gulfs between them. And he saw on her face no indication, no suggestion, no inkling. The thought had not occurred to her.

Some gulfs are not easily crossed.

“Let’s not talk about it,” said Pierre. “I — I’ve got some research I want to share with you. Something I found in the library last night.”

Shari looked as though she wanted to pursue the subject of Pierre’s Huntington’s further, but then she nodded and took a seat on a lab stool.

Pierre told her about the article in
Scientific American;
about the two forms of cytosine, the regular one and the 5-methylcytosine variant; and about the hypothetical enzyme that could turn the former into the latter but would do so only if the cytosine in the CG doublet on the opposite side of the strand was already methylated.

“Hypothetically,” said Shari, stressing the word. “If this enzyme exists.”

“Right, right,” said Pierre. “But suppose it does. What happens when DNA reproduces? Well, of course, the ladder unzips down the middle, forming two strands. One strand contains all the left-hand components of the base pairs, maybe something like this…” He wrote on the blackboard that covered most of one wall:

Left side: T-C-A-C-G-T

“See that CG doublet? Okay, let’s say its cytosine is methylated.” He went over the pair again with his chalk, making it heavier:

Left side: T-C-A-C-G-T

“Now, in DNA reproduction, free-floating nucleotides are plugged into the appropriate spots on each strand, meaning the right-hand side of this one will end up looking like this…”

His chalk flew across the blackboard, writing in the complementary sequence:

Left side: T-C-A-C-G-T

Right side: A-G-T-G-C-A

“See? Directly opposite the left-hand CG pair is the right-hand GC pair.” He paused, waiting for Shari to nod acknowledgment of this. “Now the maintenance methylase comes along and sees that there isn’t parity between the two sides of the strand, so it adds a methyl group to the right-hand side.” He went over the GC pair, making it darker, too:

Left side: T-C-A-C-G-T

Right side: A-G-T-G-C-A

“At the same time, the other half of the original strand is being filled in with free-floating nucleotides. But maintenance methylase would do exactly the same thing to it, duplicating cytosine methylation on both sides, if originally present on one side.”

Pierre clapped his hands together to shake off chalk dust. “
Voila!
By postulating that one enzyme, you end up with a mechanism for preserving cytosine-methylation state from cell generation to cell generation.”

“And?”

“And think about our work on codon synonyms.” He waved vaguely at the wall chart labeled “The Genetic Code.”

“Yes?”

“That’s one possible additional level of coding hidden in DNA, if the choice of which synonym used is significant. Now we’ve got a second possible type of additional coding in DNA: the code made by whether cytosine is methylated or not. I’m willing to bet that one or both of those additional codes is the key to what the so-called junk DNA is really for.”

“So what do we do now?” asked Shari.

“Well, as Einstein is supposed to have said, ‘God is subtle, but malicious he is not.’” He smiled at Shari. “No matter how complex the codes are, we should be able to crack them.”

Pierre went home. His apartment seemed vast. He sat on the living-room couch, pulling idly at an orange thread coming unraveled from one of the cushions.

They were making progress, he and Shari. They were getting close to a breakthrough. Of that he felt sure.

But he wasn’t elated. He wasn’t excited.

God, what an idiot I am.

He watched Letterman, watched Conan O’Brien.

He didn’t laugh.

He started getting ready for bed, dumping his socks and underwear on the living-room floor — there wasn’t any reason not to anymore.

He’d been reading Camus again. His fat copy of the
Collected Works
was facedown on one of the couch’s orange-and-green cushions. Camus, who had taken the literature Nobel in ‘57; Camus, who commented on the absurdity of the human condition. “I don’t want to be a genius,” he had said. “I have enough problems just trying to be a man.”

Pierre sat down on the couch and exhaled into the darkness. The absurdity of the human condition. The absurdity of it all. The absurdity of being a man.

Bertrand Russell ran through his mind, too — a Nobel laureate in 1950.

“To fear love,” he’d said, “is to fear life — and those who fear life are already three parts dead.”

Three parts dead — just about right for a Huntington’s sufferer at thirty-two.

Pierre crawled into bed, lying in a fetal position.

He slept hardly at all — but when he did, he dreamt not of Stockholm, but of Molly.

“I can’t let you redo the exam,” said Molly to the male student sitting opposite her, “but if you undertake another research project, I can give you up to ten marks in extra credit for that. If you get eight or above, you’ll pass — just barely. It’s your choice.”

The student was looking at his hands, which were resting in his lap. “I’ll do the project. Thank you, Professor Bond.”

“That’s all right, Alex. Everyone deserves a second chance.”

The student got to his feet and left the cramped office. Pierre, who had been standing just outside the door waiting for Molly to be alone, stepped into the doorway, holding a dozen red roses in front of him.

“I’m so sorry,” he said.

Molly looked up, eyes wide.

“I feel like a complete heel.” He actually said “eel,” but Molly assumed he meant the former, although she thought the latter was just as applicable. Still, she said nothing.

“May I come in?” he said.

She nodded, but did not speak.

Pierre stepped inside and closed the door behind him. “You are the very best thing that ever happened to me,” he said, “and I am an idiot.”

There was silence for a time. “Nice flowers,” said Molly at last.

Pierre looked at her, as if trying to read her thoughts in her eyes. “If you will still have me as your husband, I would be honored.”

Molly was quiet for a time. “I want to have a child.”

Pierre had given this much thought. “I understand that. If you wanted to adopt a child, I’d be glad to help raise it for as long as I’m able.”

“Adopt? I — no, I want to have a child of my own. I want to undergo in vitro fertilization.”

“Oh,” said Pierre.

“Don’t worry about passing on bad genes,” said Molly. “I was reading an article about this in
Cosmo
. They could culture the embryos outside my body, then test them for whether they’d inherited Huntington’s. Then they could implant only healthy ones.”

Pierre was a lapsed Catholic; the whole idea of such a procedure still left him uncomfortable — tossing out viable embryos because they didn’t pass genetic muster. But that wasn’t his main objection. “I was serious about what I said before. I think a child should have both a mother and a father — and I probably won’t live long enough to see a child grow up.” He paused. “I can’t in good conscience begin a new life that I know I’m not going to be around to see through its childhood,” he said. “Adoption is a special case — we’d still be improving the child’s life, even if it wouldn’t always have a father.”

“I’m going to do it anyway,” said Molly firmly. “I’m going to have a baby. I’m going to have in vitro fertilization.”

Pierre felt it all slipping away. “I can’t be the sperm donor. I — I’m sorry.

I just can’t.”

Molly sat without saying anything. Pierre felt angry with himself. This was supposed to be a reunion, dammit. How did it get so off track?

Finally, Molly spoke. “Could you come to love a child that wasn’t biologically yours?”

Pierre had already considered this when contemplating adoption. “
Oui
.”

“I was going to have a child without a husband anyway,” said Molly.

“Millions of children have grown up without fathers; for most of my childhood, I didn’t have one myself.”

Pierre nodded. “I know.”

Molly frowned. “And you still want to marry me, even if I go ahead and have a child using donated sperm?”

Pierre nodded again, not trusting his voice just then.

“And you could come to love such a child?”

He’d been all prepared to love an adopted child. Why did this seem so different? And yet — and yet—

“Yes,” said Pierre at last. “After all, the child would still be partly you.”

He locked onto her blue eyes. “And I love you completely.” He waited while his heart beat a few more times. “So,” he said, at last, “will you consent to be Mrs. Tardivel?”

She looked at her lap and shook her head. “No, I can’t do that.” But when she lifted her face, she was smiling. “But I do want to be Ms. Bond, who happens to be married to Mr. Tardivel.”

“Then you will marry me?”

Molly got up and walked toward him. She put her arms around his neck. “
Oui
,”she said.

They kissed for several seconds, but when they pulled apart, Pierre said, “There is one condition. At any time —
any
time — if you feel my disease is too much for you, or you see an opportunity for happiness that will last the rest of your life, rather than the rest of mine, then I want you to leave me.”

Molly was silent, her mouth hanging slightly open.

“Promise,” said Pierre.

“I promise,” she said at last.

That night, Pierre and Molly did what they had often done before they’d broken up: they went for a long walk. They’d stopped at a cafe on Telegraph Avenue for a light snack, and now were just ambling along, occasionally looking in shop windows. Like many young couples, they were still trying to get to know every facet of each other’s personalities and pasts. On one long walk, they had talked about earlier sexual experiences; on another, relations with their parents; on others still, debates about gun control and environmental issues. Nights of probing, of stimulating conversations, of each refining his or her mental image of the other.

And tonight, the biggest question of all came up as they strolled, enjoying the early evening warmth. “Do you believe in God?” asked Molly.

Pierre looked down at the sidewalk. “I don’t know.”

“Oh?” said Molly, clearly intrigued.

Pierre sounded a bit uncomfortable. “Well, I mean it’s hard continuing to believe in God when something like this happens. You know: my Huntington’s. I don’t mean I started questioning my faith last month, when we finally did the test. I started doing that back when I first met my real father.” Pierre had explained all about his discovered paternity on another long walk.

Molly nodded. “But you did believe in God before you found out you might have Huntington’s?”

Pierre nodded as they continued along. “I guess. Like most French Canadians, I was raised Roman Catholic. These days I only go to Mass on Easter and Christmas, but when I was living in Montreal, I went every Sunday. I even sang in the church choir.”

Molly winced; she had heard Pierre sing. “But it’s hard for you to believe now,” she said, “because a beneficent God couldn’t do that sort of thing to you.”

They’d come to a park bench. Molly gestured for them to sit down, and they did so, Pierre draping his arm over her shoulders. “Something like that,” he said.

Molly touched Pierre’s arm and seemed to hesitate for a moment before replying. “Forgive me for saying this — I don’t want to sound argumentative — but, well, I always find that sort of reasoning a trifle shallow.” She held up a hand. “I’m sorry; I don’t mean it to sound like a criticism. It’s just that the — the
harshness
of our world is apparent to anyone who looks. People starving in Africa, poverty in South America, drive-by shootings here in the States. Earthquakes, tornadoes, wars, diseases.” She shook her head. “I just — to me, I’m just saying to me — it always seems strange that one could go along without questioning one’s faith until something personally happens. You know what I’m saying? A million people starve to death in Ethiopia, and we say that’s too bad. But we — or someone we know — gets cancer or a heart attack or Huntington’s or whatever, and we say, Hey, there must be no God.” She smiled. “I’m sorry — pet peeve. Forgive me.”

Pierre nodded slowly. “No, you’re right. You’re right. It is silly when you put it that way.” He paused. “What about you? Do you believe in God?”

Molly shrugged. “Well, I was raised a Unitarian — I still sometimes go to a fellowship over in San Francisco. I don’t believe in a personal God, but perhaps in a creator. I’m what they call a theistic evolutionist.”

“Qu’est-ce que c’est?”

“That’s someone who believes God planned out all the broad strokes in advance — the general direction life would take, the general path for the universe — but, after setting everything in motion, he’s content to simply watch it all unfold, to let it grow and develop on its own, following the course he laid down.”

Pierre smiled at her. “Well, the course we’ve been laying down leads back to my apartment — and it
is
getting late.”

She smiled at him. “Not too late to know me in the biblical sense, I trust.”

Pierre stood up, offered his hand to Molly, and helped her stand up as well. “Yea, verily.”