“They deplete the membrane, but it’s all rather gentle and controlled. The viruses stress the cells, but they don’t kill them. And it looks like about one in twenty of the virus particles are viable—five times better than HIV.”
The simulation suddenly zoomed in to molecules created along with the viruses, wrapped in cell transport packages called vesicles and pushed out with the new infectious particles. They were labeled in bright orange: PGA? and PGE?
“Hold it there, Fiona.” Kushner pointed and tapped her finger on the orange letters. “SHEVA doesn’t carry everything it needs to cause Herod’s flu. We kept finding a large clump of proteins in SHEVA-infected cells, not coded for in SHEVA, and like nothing I’ve seen. And then—the clump would break down, there would be all these smaller proteins that shouldn’t have been there.”
“We looked for proteins that were changing our cell cultures,” Bierce said. “Really doing a number on them. We puzzled over this for two weeks, and then we sent some infected cells over to a commercial tissue library for comparison. They separated out the new proteins, and they found—”
“This is my story, Fiona,” Kushner said, waggling her finger.
“Sorry,” Fiona said, smiling sheepishly. “It is just so cool we could do it this fast!”
“We finally decided that SHEVA turns on a gene in another chromosome. But how? We went looking . . . and found a SHEVA-activated gene on chromosome 21. It codes for our polyprotein, what we call the LPC, the large protein complex. A unique transcription factor specifically controls expression of this gene. We looked for the factor and found it in SHEVA’s genome. A locked treasure chest on chromosome 21, and the necessary keys in the virus. They’re partners.”
“Astonishing,” Kaye said.
Bierce ran the simulation through again, this time focusing on the action in chromosome 21—the creation of the polyprotein.
“But Kaye—darling Kaye, that is far from the last of it. We have a mystery here. The SHEVA protease cleaves three novel cyclooxygenases and lipooxygenases from the LPC, which then synthesize three different and unique prostaglandins. Two of them are new to us, really quite astonishing. All look very powerful.” Kushner used a pen to point out the prostaglandins being exported from a cell. “This could explain the talk about miscarriages.”
Kaye frowned in concentration.
“We calculate that a full-bore SHEVA infection could produce enough of the new prostaglandins to abort any fetus in a pregnant woman within a week.”
“As if that isn’t strange enough,” Bierce said, and pointed to series of glycoproteins, “the infected cells make these as byproducts. We haven’t analyzed them completely, but they look a lot like FSH and LH—follicle stimulating hormone and luteinizing hormone. And these peptides appear to be releasing hormones.”
“The old familiar masters of female destiny,” Kushner said. “Egg maturation and release.”
“Why?” Kaye asked. “If they’ve just caused an abortion . . . why force an ovulation?”
“We don’t know which activates first. It could be ovulation, then abortion,” Kushner said. “Remember, this is a liver cell. We haven’t even begun investigating infection in reproductive tissues.”
“It doesn’t make sense!”
“That’s the challenge,” Kushner said. “Whatever your little endogenous retrovirus is, it’s far from being harmless—at least to us women. It looks like something designed to invade, take over, and screw us up royally.”
“Are you the only ones who’ve done this work?” Kaye asked.
“Probably,” Kushner said.
“We’re sending the results to NIH and the Genome Project today,” Bierce said.
“And giving you advance notice,” Kushner added, putting her hand on Kaye’s shoulder. “I don’t want you to get stepped on.”
Kaye frowned. “I don’t understand.”
“Don’t be naÏve, dear,” Kushner said, her eyes bright with concern. “What we’re looking at could be Biblical bad news. A virus that kills babies. Lots of babies. Someone might regard you as a messenger. And you know what they do to messengers who bring bad news.”
14
Atlanta
October
Dr. Michael Voight strode ahead of Dicken on long, spidery legs down the hallway to the residents’ lounge. “Funny you should ask,” Dr. Voight said. “We’re seeing lots of obstetrics anomalies. We’ve had staff discussions already. But not about Herod’s. We see all kinds of infections, flu, of course, but we still don’t have the test kits for SHEVA.” He half-twisted to ask, “Cup of coffee?”
Atlanta’s Olympic City Hospital was six years old, built at city and federal expense to take the pressure off other hospitals in the inner city. Private donors and a special set-aside from the Olympics had made it one of the best-equipped hospitals in the state, attracting some of the best and brightest young doctors, and a few disgruntled older ones, as well. The world of HMOs and managed care was taking a toll on skilled specialists, who had seen their incomes plummet in the past decade and their patient care practices controlled by accountants. Olympic City at least gave the specialists respect.
Voight steered Dicken into the lounge and drew a cup of coffee from a stainless-steel urn. Voight explained that interns and residents alike could use this room. “It’s usually empty this time of night. It’s prime time out there—time for life to lurch on and deliver its careless victims.”
“What sort of anomalies?” Dicken prompted.
Voight shrugged, pulled a chair away from a Formica table, and curled up his long legs like Fred Astaire. His greens rustled; they were made of tough paper, completely disposable. Dicken sat and held his cup in his hands. He knew it might keep him awake, but he needed the focus and the energy.
“I handle extreme cases, and most of the weird ones haven’t qualified for my care. But in the last two weeks . . . would you believe, seven women who can’t explain their pregnancies?”
“I’m all ears,” Dicken said.
Voight spread his hands and ticked off the cases. “Two that took birth control pills religiously, so to speak, and they didn’t work . . . Not so unusual, maybe. Still, there was one who didn’t take birth control, but said she hadn’t had sex. And guess what?”
“What?”
“She was virgo intacta. Had heavy bleeding for a month, it went away, then morning sickness, period stopped, she went to a doctor, he told her she was pregnant, she comes here when the whole thing goes wrong. A shy young woman living with an elderly man, a real peculiar relationship. She insisted no sex was involved.”
“Second coming?” Dicken asked.
“Don’t be profane. I’m born again,” Voight said with a twitch of his lips.
“Sorry,” Dicken said.
Voight smiled half-apologetically. “Then her ‘old man’ comes in, tells us the real story. Turns out he’s very concerned for her—wants us to know the truth so we can treat her. She’s been letting him get in bed with her and rub up against her . . . Sympathy, you know. So that’s how she gets pregnant the first time.”
Dicken nodded. Nothing very shocking here—the versatility of life and love.
Voight continued. “It’s a miscarriage. But three months later, she comes back, she’s pregnant again. Two months along. Her elderly friend shows up with her, says he hasn’t been rubbing against her or anything, and he knows she hasn’t been seeing another man. Do we believe him?”
Dicken tilted his head to one side, lifted his eyebrows.
“All sorts of peculiar stuff going on,” Voight said softly. “More than usual, I think.”
“Did they complain of illness?”
“The usual. Colds, fevers, body aches. I think we may still have a couple of specimens in the lab, if you want to look at them. Have you been over to Northside?”
“Not yet,” Dicken said.
“Why not Midtown? Lot more tissue for you over there.”
Dicken shook his head. “How many y
oung women with unexplained fever, nonbacterial infections?”
“Dozens. That’s not unusual either. We don’t keep tests more than a week; if they’re negative for bacteria, we dump them.”
“All right. Let’s see the tissue.”
Dicken took his coffee with him as he followed Voight to the elevator. The biopsy and analysis lab was in the basement, just two doors down from the morgue.
“Lab techs go home at nine.” Voight switched on the lights and did a quick search in a small steel card file.
Dicken looked the lab over: three long white benches equipped with sinks, two fume hoods, incubators, cabinets neatly arrayed with brown glass and clear glass bottles filled with reagents, neatly ordered stacks of standard test kits in slim orange and green cardboard boxes, two stainless-steel refrigerators and an older white freezer; a computer connected to an ink-jet printer with an OUT OF ORDER note posted on it; and jammed in a back room behind a Dutch door, rolling stock steel storage shelving in standard gray and putty.
“They haven’t put these into the computer yet; takes us about three weeks. Looks like we have one left . . . It’s procedure now for the hospital, we give mothers the choice, they can have a mortician take the tissue and arrange for a funeral. Better closure that way. But we had an indigent through here, no money, no family . . . Here.” He lifted a card, walked into the back room, rotated a wheel, found the shelf number on the card.
Dicken waited by the Dutch door. Voight emerged with a small jar, held it up to the brighter light in the lab room. “Wrong number, but it’s the same type. This is from six months ago. I think the one I’m looking for may still be in cold saline.” He handed Dicken the jar and walked to the first refrigerator.
Dicken peered at the fetus: at twelve weeks, about the size of his thumb, curled, a tiny pale extraterrestrial that had failed its tryout for life on Earth. The anomalies struck him immediately. The limbs were mere nubs, and there were protuberances around the swollen abdomen he had not seen before even on severely malformed fetuses.
The tiny face seemed unusually pinched and vacant.
“There’s something wrong with its bone structure,” Dicken said as Voight closed the refrigerator. The resident lifted another fetus in a moisture-frosted glass beaker covered with plastic wrap, sealed with a rubber band and marked with a tape label.
“Lots of problems, no doubt about it,” Voight said, trading jars and peering at the older specimen. “God sets up little checkpoints in every pregnancy. These two did not make the grade.” He looked upward significantly. “Back to Heaven’s nursery.”
Dicken did not know whether Voight was expressing heartfelt philosophy or a more typical medical cynicism. He compared the cold beaker and the room-temperature jar. Both fetuses at twelve weeks, very similar.
“Can I take this one?” he asked, lifting the cold beaker.
“What, and rob our med students?” Voight shrugged. “Sign for it, call it a loan to CDC, shouldn’t be a problem.” He looked at the jar again. “Something significant?”
“Maybe,” Dicken said. He felt a little creep of sadness and excitement. Voight gave him a more secure jar and a small cardboard box, cotton, a piece of ice in a sealed plastic bag to keep the specimen cold. They transferred the specimen quickly with a pair of wooden tongue depressors, and Dicken sealed the box with packing tape.
“If you get any more like these, let me know immediately, okay?” Dicken asked.
“Sure.” In the elevator, Voight asked him, “You look a little funny. Is there something I might like to know about early, some little clue to help me better serve the public?”
Dicken knew he had kept his face deadpan, so he smiled at Voight and shook his head. “Keep track of all miscarriages,” Dicken said. “Especially this type. Any correlation with Herod’s flu would be dandy.”
Voight curled his lip, disappointed. “Nothing official yet?”
“Not yet,” Dicken said. “I’m working on a real long shot.”
15
Boston
The spaghetti and pizza dinner with Saul’s old colleagues from MIT was going very well. Saul had flown in to Boston that afternoon, and they had gathered at Pagliacci. Talk early in the evening in the dark old Italian restaurant ranged from mathematical analysis of the human genome to a chaotic predictor for dataflow systole and diastole on the Internet.
Kaye filled up on breadsticks and green peppers even before her lasagna arrived. Saul picked at a piece of buttered bread.
One of MIT’s celebrities, Dr. Drew Miller, showed up at nine o’clock, unpredictable as always, to listen and throw in a few comments about the hot topic of bacterial community action. Saul listened intently to the legendary researcher, an expert on artificial intelligence and self-organizing systems. Miller moved several times, and finally tapped the shoulder of Saul’s old roommate, Derry Jacobs. Jacobs grinned, got up to find another seat, and Miller placed himself beside Kaye. He picked up a breadstick from Jacobs’s plate, stared at her with wide, childlike eyes, pursed his lips, and said, “You’ve really pissed off the old gradualists.”
“Me?” Kaye asked, laughing. “Why?”
“Ernst Mayr’s kids are sweating ice cubes, if they’ve got any sense. Dawkins is beside himself. I’ve been telling them for months that all that was needed was another link in the chain, and we’d have a feedback loop.”
Gradualism was the belief that evolution proceeded in small moves, mutations accumulating over tens of thousands or even millions of years, usually detrimental to the individual. Beneficial mutations were selected for by conferring an advantage and increasing opportunities to gather resources and reproduce. Ernst Mayr had been a brilliant spokesman for this belief. Richard Dawkins had eloquently argued the case for the modern synthesis of Darwinism, as well as describing the so-called selfish gene.
Saul heard this and got up to stand behind Kaye, leaning over the table to hear what Miller had to say. “You think SHEVA gives us a loop?” he asked.
“Yes. Complete circle of communication between individuals in a population, outside of sex. Our equivalent of plasmids in bacteria, but of course more like phages.”
“Drew, SHEVA only has eighty kb and thirty genes,” Saul said. “Can’t carry much information.”
She and Saul had already gone over this territory before she had published her article in Virology. They had spoken to nobody about their particular theories. Kaye found herself a little surprised that Miller should be bringing this up. He was not known as a progressive.
“They don’t need to carry all the information,” Miller said. “All they need to carry is an authorization code. A key. We still don’t know all the things SHEVA does.”
Kaye glanced at Saul, then said, “Tell us what you’ve been thinking, Dr. Miller.”
“Call me Drew, please. It’s really not my field of endeavor, Kaye.”
“It’s not like you to be cagey, Drew,” Saul said. “And we know you’re not humble.”
Miller grinned from ear to ear. “Well, I think you suspect something already. I’m sure your wife does. I’ve read your papers on transposable elements.”
Kaye sipped from her almost-empty glass of water. “We can never be sure what to say to whom,” she murmured. “We might either offend or give away the farm.”
“Don’t worry about original thinking,” Miller said. “Someone out there is always ahead of you, but they usually haven’t done the work. It’s someone who’s working all the time who will make the discovery. You do good work and write good papers, and this is a big jump.”
“We’re not sure it’s the big jump though,” Kaye said. “It may just be an anomaly.”
“I don’t want to push anybody into a Nobel prize,” Miller said, “but SHEVA isn’t really a disease-causing organism. Doesn’t make evolutionary sense for something to hide this long in the human genome, and then express just to cause a mild flu. SHEVA is really just a kind of mobile genetic element, isn’t it? A promoter?”
/> Kaye thought of the talk with Judith about the symptoms that SHEVA could cause.
Miller was perfectly willing to continue talking over her silence. “Everyone has thought that viruses, and in particular retroviruses, could be evolutionary messengers or triggers, or just random goads,” Miller said. “Ever since it was found that some viruses carry snippets of genetic material from host to host. I just think there are a couple of questions you should ask yourselves, if you haven’t already. What does SHEVA trigger? Let’s say gradualism is dead. We get bursts of adaptive speciation whenever a niche opens up—new continents, a meteor clears out the old species. It happens fast, in less than ten thousand years; good old punctuated equilibrium. But there’s a real problem. Where is all this proposed evolutionary change stored?”
“An excellent question,” Kaye said.
Miller’s eyes sparkled. “You’ve been thinking about this?”
“Who hasn’t?” Kaye said. “I’ve been thinking about virus and retrovirus as contributors to genomic novelty. But it comes down to the same thing. So maybe there’s a master biological computer in each species, a processor of some sort that tots up possible beneficial mutations. It makes decisions about what, where, and when something will change . . . Makes guesses, if you will, based on success rates from past evolutionary experience.”
“What triggers a change?”
“We know that stress-related hormones can affect expression of genes. This evolutionary library of possible new forms . . .”
Miller grinned broadly. “Go on,” he prompted.
“Responds to stress-produced hormones,” Kaye continued. “If enough organisms are under stress, they exchange signals, reach a kind of quorum, and this triggers a genetic algorithm that compares sources of stress with a list of adaptations, evolutionary responses.”
“Evolution evolving,” Saul said. “The species with an adaptive computer can change more rapidly and more efficiently than hackneyed old species that don’t control and select their mutations, that rely on randomness.”