The Immortalist (33 page)

“Kyttaropylin? What's that?”

“It's, uh . . . a gene from the Methuselah Vector. You asked me to use it as a negative control.”

“The Methuselah Vector?” asked Cricket, half in disbelief. She looked carefully at the photo. “It's not negative, is it? What about these other lanes—four and five?”

“I did a second round of PCR on the herpes simplex fragment I showed you earlier,” Waggoner replied. “The one that was two thousand base pairs too long. As you can see, for both Sample Number One and Sample Number Two, it's also positive for kyttaropylin.”

“So both Emmy and Yolanda were infected by the Methuselah Vector?”

“Not exactly. You see these blank lanes? These are PCR reactions for aetatin and other parts of the Methuselah Vector. Negative. No reaction. Only kyttaropylin.”

Freiberg produced a paper of his own, covered with multicolored sawtooth tracings from an automated DNA sequencer. “I analyzed Dr. Waggoner's mysteriously long PCR product. The extra two thousand base pairs are all kyttaropylin. What's more, in Emmy's case, about ten percent of the gene has been lost.”

“Are you saying they merged—herpes simplex and the Methuselah Vector?”

“Exactly,” said Freiberg. “We now know what our nemesis is.”

“Nemesis?” asked Hank.

“For want of a name,” said Freiberg. “The Nemesis virus
.
Has a ring to it.”

“Charles is gonna shit bricks over this,” said Hank.

Cricket turned to Waggoner. “Excuse me, Wig. What the hell is kyttaropylin?”

“It's Greek for the Cell Gate. It's what that the Methuselah Vector uses to bind to the MHC-1 complex. It's the main product of the circular form of the Vector. But it's inactivated in the linear form.”

“Circular, linear—what are you talking about?”

“There are actually, uh, two forms of the Methuselah Vector. Two life stages, like caterpillar and butterfly.”

Figure 2.
PCR to test for the presence of three different genes from the Methuselah Vector.
Lanes 1 and 10
: standard DNA size markers.
Lanes 2 and 3
: both Yolanda and Emmy have the kyttaropylin gene in their blood.
Lanes 4 and 5
: the kyttaropylin gene is embedded in the abnormal capsid protein of Human herpesvirus, type 1, found in Yolanda's and Emmy's blood on the first PCR test (see
Figure 1
). Although Yolanda has a slightly longer version of the full kyttaropylin gene, the PCR reaction here amplifies only a small part of it; this sequence happens to be the same size for both Yolanda and Emmy.
Lanes 6 through 9
: neither Yolanda nor Emmy carries the aetatin or insertin genes from the Methuselah Vector in her blood.

“Life stages?” Cricket frowned. “Wig, the more you talk, the more confused I get.”

Waggoner sighed condescendingly, then went to the whiteboard and drew a caterpillar eating its own tail. “The first form—what actually gets injected into a patient—is a circle of DNA, surrounded by a shell of kyttaropylin. This is the caterpillar. The only thing it can do is make more kyttaropylin”—he drew a cluster of wavy lines emerging from the caterpillar—“plus a special splicing enzyme called insertin.”

“And insertin
is—what?”

Waggoner redrew the caterpillar stretched out to full length. Then he added wings to it, turning it into a butterfly.

“Insertin cuts open the caterpillar circle and splices it into a chromosome of the host cell. There, it becomes the butterfly—the beautiful thing that actually makes aetatin, the gene for immortality.”

“Why two different forms?” asked Cricket.

“When the G-man—Dr. Gifford—was designing the Methuselah Vector, he had a couple of Matterhorns to climb—dosage and uniformity.

“Early experiments made it clear that too much aetatin was not a good thing. The host cells would go into overdrive and burn out. The ideal was about two copies of aetatin gene per cell. Unfortunately, you couldn't really control how many Vector particles got in. Sometimes a lot did, sometimes only one, or even none. It was a crapshoot.

“What the G-man did was design the Vector so that it could only make aetatin if it were incorporated at a very specific site on the host cell's nuclear DNA—a locus called q17.34 on chromosome number six. This was a stretch of noncoding, nonregulatory DNA, part of that ninety-nine percent of all our genome that we arrogantly call junk DNA, because our puny human minds don't know what it does. Since every cell has two and only two chromosomes number six, this got the dosage exactly right.”

“Okay, I follow that,” said Cricket.

“The second problem—uniformity—goes back to the crapshoot again. Some cells got a lot of Vector particles, others got none. What sucked about that was, if you didn't get the Vector into nearly all the cells, the Methuselah effect wouldn't take hold. The untransformed cells went on aging.

“One way you could make sure all the cells get the Vector was to use brute force—to flood the system with so much Vector that, say, ninety-nine percent of the cells would get at least one copy. The problem was that would take a shitload of Vector—between one and ten grams of something that would cost, using our current methods, one hundred billion dollars a gram to make. And 99.999 percent of this would have been wasted.

“What the G-man did was absolutely elegant. He designed the Vector so that it only needs to transform one in one hundred thousand cells with the first injection. Only one nanogram—about ten-billionths of an ounce—is needed for that. Each of those transformed cells can make a few new copies of the Methuselah Vector, which it passes on to its neighbors. Those neighbors pass on some more to their neighbors, and so on, until every last cell has been reached. Then the Vector stops reproducing itself.”

“Stops? How?”

“Once again, the major player is insertin. Only the caterpillar form of the Vector can reproduce itself and make new Vector particles. Once insertin cuts open the circle, it tries to splice the linear form into chromosome number six. But if another Vector particle is already there, insertin does nothing. The host cell has its own horde of DNA-eating enzymes that will promptly chop the loser DNA into bits. Dead caterpillar.

“Insertin is a very stable protein, surviving for weeks after it's made. It continues to attack any excess caterpillars and eventually wipes them out completely. That's the crucial difference between the Methuselah Vector and a virus. A virus goes on infecting cells forever. The Methuselah Vector can only reproduce itself for a very short window of time—just long enough to solve the uniformity problem.”

“That's all very ingenious,” said Cricket. “But how in the name of God did the Methuselah Vector get spliced into a herpes simplex gene?”

Waggoner fell to staring at his feet.

“I think I know.” Hank had sat down at the computer console at the back of the office and was typing in some commands. “You know about redundant targeting?”

“That's your theory, isn't it? The one that got you into trouble with Charles?”

Hank nodded. “As Wig explained, the Methuselah Vector is designed to insert itself into a unique DNA sequence. But in nature, there's always a little wiggle room. The sequence match doesn't have to be exact. Even a sixty-five percent match will work under the right conditions. This means that not all of the excess caterpillars will get chopped up. A few of them may wind up being inserted at secondary sites.”

“You tried to prove this, didn't you?”

“Yes, and I failed. Charles did his homework well. The target on chromosome six really is unique. In the entire human DNA sequence there's nothing else that comes close to it.
But
 . . .”

Cricket, engrossed in the printouts on the desktop, was slow to notice that Hank's voice had trailed off. When she looked up, she saw that Hank had turned away from the computer and was staring directly at her. “Both Charles and I overlooked something,” he said once he had her attention. “The possibility of
another
genome entering the picture.”

“Nonhuman?” asked Freiberg.

“Viral,”
said Cricket, gathering the meaning of Hank's stare. “None of us is one hundred percent human, genetically speaking. We all carry bits of viral DNA—some floating around harmlessly, some spliced into our chromosomes. DNA mixing and trading goes both ways. Plenty of viruses carry genes that they stole eons ago from hosts they infected. Sometimes, they even return them in mutated form to an infected cell, leading to certain kinds of cancer. Herpes is one of those viruses that likes to stick around. So, if someone had had a herpes infection before he got the Methuselah Vector—”

“—there could be billions of viral particles available as alternative targets,” Hank finished. “Even one random collison and fusion event could create a chimera—a new viral species combining herpes and the Methuselah Vector.”

Waggoner looked as if he had inhaled a cherry pit. “What you're talking about isn't possible,” he protested. “The cellular DNases destroy all the excess Vector. We tested and proved that.”

“Were any of those tests done on cells infected with herpes?” asked Cricket.

“Of course not.”

“In fact, all the laboratory tests you and Dr. Gifford performed—whether on animals or on cells in culture—were always done under scrupulous infection control. Isn't that right?”

“It would have been negligent to do otherwise.”

“Then you really don't know what would happen in a herpes-infected cell, do you?”

Waggoner hung his head like a puppy just swatted with a newspaper. “No, not specifically.”

“Okay, look at this,” announced Hank, wheeling his chair out of the way of the computer screen. “I've just run a sequence check of the herpes simplex genome. And what do you know? There's a stretch in which fourteen out of nineteen base pairs match up with the insertin target sequence. Almost a seventy-four percent homology. That's an excellent site for redundant targeting.”

Cricket peered at the rows of
G
's,
C
's,
A
's, and
T
's on the screen. “And where is it?”

“Capsid open reading frame of the long unique region. Exactly where our Nemesis splice starts.”

Waggoner nervously crumpled the sheaf of papers on the desk. “That can't be right.”

“There's more.” Hank turned back to the computer. “I've also run a few random sequence checks against other viruses. Right off the bat, I've come up with six matches in the range of fifty to seventy percent. Coxsackie virus, measles virus, parainfluenza virus. If I ran this program all night, I could probably come up with a bunch more. Not to mention the ninety-nine percent of viruses whose sequences are completely unknown.”

Freiberg's jaw dropped. “Good God!”

Hank rapped the computer screen with his knuckles. “Thanks to insertin, it looks like our Methuselah Vector is a regular little factory for bastard viruses.”

Cricket studied Waggoner's drawings on the whiteboard. “Look what's being inserted—the Cell Gate. It's creating superviruses. Devastatingly lethal viruses that can infect every cell in the body.”

Freiberg nodded gravely. “With no natural immunity or resistance.”

“And no limit to the possibilities of creation,” added Hank. “Once the Methuselah Vector gets out into the real world, all kinds of random interactions will take place. Herpes, measles, the common cold—who knows? Supervirus after supervirus. Waves upon waves of epidemics. Like a Hydra's head—cut off one, and two grow in its place. Nemesis would be just the beginning.”

Freiberg looked pale. “Waves after waves,” he intoned, “until there's no one left to get sick.”

Cricket looked into each man's eyes in turn. “We've got to quarantine the Methuselah Vector immediately.” But Gifford's state of mind worried her. When she had confronted him over Hannibal, he had seemed anxious, hostile, even irrational. He wasn't the Charles Gifford she knew. That man would never have kept back evidence that might save Emmy's life. “Back to Nemesis. Wig, can you prepare a test to screen the population here at Acadia Springs?”

“As long as nobody touches anything in my lab. But I think we need to show these findings to the G-man and Jack Niedermann first. We could be wrong about Methuselah.”

“No. Leave Charles to me.” Cricket turned to Freiberg. “Erich, can you get a list of everyone who lives or works on campus?”

“Certainly.”

Suddenly the desk phone rang. Cricket picked it up. “Doctor, this is Jean in Bay Two. Emmy's heart rate is up to one hundred ten beats a minute. Do you want me to stop the dobutamine?”

“I'll be there in a second.” Cricket put her hand over the receiver and looked gravely at Hank. “Back to the workbench, gentlemen! We've got to figure out a way to beat Nemesis. A vaccine, a treatment, a cure. And most of all, we have to keep it from spreading.”