Darwin's Children

by Greg Bear

  Polite smiles around the room. A little shuffling of feet.

  Cross cleared her throat. “We certainly wouldn't want to confuse anybody,” she said, her voice dropping an octave. Most of the time, it hovered between a quavering soprano and a mellow alto. Many had compared her to Julia Child, but the comparison was surface only, and with age and hennaed hair, Cross had gone well beyond Julia and into her own stratospheric realm of uniqueness. “I've looked over the team reports from our vaccine project, and of course the chimpanzee and mouse ERV knockout projects. Dr. Jackson's report was very long. Also, I've looked over the research reviews and audits from the fertility and general immunology groups.” Cross's arthritis was bothering her; Kaye could tell from the way she massaged the swollen knuckles on her hands. “The consensus is, we seem to have failed at everything we set out to do. But we're not here for a postmortem. We need to decide how to proceed from where we are at this moment. So. Where are we?”

  Glum silence. Kaye stared straight ahead, trying to keep from biting her lip.

  “Usually, we toss a coin and let the winner start. But we're all familiar with this debate, up to a point, and I think it's time we begin with some probing questions. I'll choose who goes first. All right?”

  “Fine,” Jackson said nonchalantly, lifting his hands from the tabletop.

  “Fine,” Kaye echoed.

  “Good. We all agree it sucks,” Cross said. “Dr. Nilson, please begin.”

  Lars Nilson, a middle-aged man with round glasses, had won a Nobel twenty years ago for his research in cytokines. He had once been heavily involved in Americol's attempts to resolve retroviral issues in xenotransplants—the transplanting of animal tissues into human recipients—a prospect that had come to a drastic halt with the appearance of SHEVA and the case of Mrs. Rhine. He had since been reassigned to general immunology.

  Nilson peered around the room with a wry expression, looking to Kaye like a gray and disconsolate pixie. “I presume I'm expected to speak first out of some notion of Nobel oblige or something more awful still, like seniority.”

  A small, very slim elderly man in a gray suit and yarmulke entered the room and looked around through friendly, crinkled brown eyes, his face wreathed in a perpetual smile. “Don't mind me,” he said, and took a chair in the far corner, crossing his legs. “Lars is no longer senior,” he added quietly.

  “Thank you, Maurie,” Nilson said. “Glad you could make it.” Maurie Herskovitz was another of Cross's Nobel laureates, and perhaps the most honored biologist working at Americol. His specialty was loosely labeled “genomic complexity”; he now functioned as a roving researcher. Kaye was startled and a little unnerved by his presence. Despite his smile—built-in, she suspected, like a dolphin's—Herskovitz was known to be a demanding tyrant in the lab. She had never seen him in person.

  Cross folded her arms and breathed loudly through her nose. “Let's move on,” she suggested.

  Nilson looked to his right. “Dr. Jackson, your SHEVA vaccines have unexpected side effects. When you work to block transmission of ERV particles between cells in tissue, you kill the experimental animals—apparently in part because of a massive overreaction of their innate immune system—whether they be mice, pigs, or monkeys. That seems counterintuitive. Can you explain?”

  “We believe our efforts interfere with or mimic some essential processes involving the breakdown of pathogenic messenger RNA in somatic cells. The cells seem to interpret our vaccines as a byproduct of the appearance of viral RNA, and stop all transcription and translation. They die, apparently to protect other cells from infection.”

  “I understand there may also be a problem with shutting down function of transposases in T cells,” Nilson continued. “RAG1 and RAG2 are apparently affected by nearly all the candidate vaccines.”

  “As I said, we're still tracking that connection,” Jackson said smoothly.

  “Most expression of ERVs doesn't trigger cell suicide,” Nilson said.

  Jackson nodded. “It's a complicated process,” he said. “Like many pathogens, some retroviruses have developed a cloaking ability and can avoid cell defenses.”

  “So the model that all viruses are interlopers or invaders may not apply in these cases?”

  Jackson vehemently disagreed. His argument was rigidly traditional: DNA in the genome was a tightly constrained and efficient blueprint. Viruses were simply parasites and hangers-on, causing disorder and disease but, in rare instances, also creating useful novelty. He explained that putting viral promoters in front of a necessary cellular gene could cause more of that gene's products to be manufactured at a key moment in the cell's history. More rarely, within germ cells—egg or sperm progenitors—they might land, randomly, in such a way as to cause phenotypic or developmental variation in the offspring. “But to call any such activity orderly, part of some cellular reaction to the environment, is ridiculous. Viruses have no awareness of their actions, nor are the cells specifically activating viruses for some wonderful purpose. That has been obvious for more than a century.”

  “Kaye? Do viruses know what they're doing?” Cross asked, turning in her chair.

  “No,” Kaye said. “They're nodes in a distributed network. Greater purpose as such lies with the network, not the node; and not even the network can be described as self-aware or deliberately purposeful, in the sense that Dr. Jackson has purpose.”

  Jackson smiled.

  Kaye went on. “All viruses appear to be descendants, directly or indirectly, of mobile elements. They did not pop up from outside; they broke free from inside, or evolved to carry genes and other information between cells and between organisms. Retroviruses like HIV in particular seem closely related to retrotransposons and ERV in the cells of many organisms. They all use similar genetic tools.”

  “So a flu virus, with eight genes, is derived from a retrotransposon or retrovirus with two or three genes?” Nilson asked with some disdain. His brows dropped into a puzzled and stormy expression at this patent absurdity.

  “Ultimately, yes,” Kaye said. “Gaining or mutating genes, or losing them, is mediated by necessity. A virus entering a new and unfamiliar host might take up and incorporate useful genes found within the host cell, but it's not easy. Most of the viruses simply fail to replicate.”

  “They go in, hoping for a handout at the gene table?” Jackson asked. “That's what Dr. Howard Urnovitz believed, isn't it? Vaccinations led to HIV, Gulf War Syndrome, and every other illness known to modern man?”

  “Dr. Urnovitz's views seem closer to yours than to mine,” Kaye replied evenly.

  “That was more than twenty years ago,” Cross said, yawning. “Ancient history. Move on.”

  “We know many viruses can incorporate genes from ERVs,” Kaye said. “Herpes, for example.”

  “The implications of that process are not at all clear,” Jackson said, a rather weak-kneed response, Kaye thought.

  “I'm sorry, but it simply is not controversial,” she persisted. “We know that is how Shiver arose in all its variety, and that is how the virus mutated that gave our children lethal HFMD. It picked up endogenous viral genes found only in non-SHEVA individuals.”

  Jackson conceded these points. “Some of our children,” he amended quietly. “But I'm willing to concede that viruses may be enemies from within. All the more reason to eradicate them.”

  “Just enemies?” Cross asked. She propped her chin in one palm, and looked up at Jackson from beneath her bushy eyebrows.

  “I did say ‘enemies,’ not handmaids or subcontractors,” Jackson said. “Jumping genes cause problems. They are rogues, not handmaids. We know that. When they're active, they produce genetic defects. They activate oncogenes. They're implicated in multiple sclerosis and in schizophrenia, in leukemia and all manner of cancers. They cause or exacerbate autoimmune diseases. However long they can lie dormant in our genes, they're part of a panoply of ancient plagues. Viruses are a curse. That some are now tame enough to get by without causing their hos
ts major damage is just the way disease evolution works. We know that HIV retroviruses mutated and jumped from one primate species to another, to us. In chimps, the HIV precursor evolved to be neutral, a genetic burden and little more. In us, the mutation proved to be highly immunosuppressive and lethal. SHEVA is little different. The ERV we are fighting are simply not useful to the organism in any fundamental way.”

  Kaye felt as if she had traveled back in time, as if thirty years of research had never happened. Jackson had refused to change despite massive strides; he simply ignored what he could not believe in. And he was not alone. The number of papers produced each year in virology alone could fill the entire meeting room. To this day, most such papers stuck to a disease model for both viruses and mobile elements.

  Jackson felt safely enclosed by thick walls of tradition, away from Kaye's mad, howling winds.

  Cross turned to the sole woman on the review committee, Sharon Morgenstern. Morgenstern specialized in fertility research and developmental biology. A nervous-looking, thin woman, reputedly a spinster, with a withdrawn chin, prominent teeth, wispy blonde hair, and a soft North Carolina accent, she also chaired the Americol jury that approved papers before they were submitted to the journals—in-house peer review set up in part to quash publications that might reveal corporate secrets. “Sharon? Any questions while we're jumping up and down on Robert?”

  “Your test animals, when given candidate vaccines, have also been known to suffer the loss or reduction of key sexual characteristics,” Morgenstern began. “That seems exceptionally odd. How do you plan to get around those problems?”

  “We have noticed reduction of certain minor sexual characters in baboons,” Jackson said. “That may have no relevance to human subjects.”

  Nilson moved in once more, ignoring Morgenstern's irritated expression. Let the woman finish, Kaye thought, but said nothing.

  “Dr. Jackson's vaccine could be of immense importance in our attempts to neutralize viruses in xenotransplant tissues,” Nilson said. “Dr. Rafelson's endeavors also hold tremendous promise—to knock out all ERV genes in these tissues has been one of our holy grails for at least fifteen years. To say we're disappointed by these failures is an understatement.” Nilson shifted in his seat and referred to his notes by leaning over sideways and looking through the edge of his glasses, like a bird examining a seed. “I'd like to ask some questions about why Dr. Jackson's vaccines fail.”

  “The vaccines do not fail. The organisms fail,” Jackson said. “The vaccines succeed. They block intercellular transmission of all ERV particles.”

  Nilson smiled broadly. “All right. Why do the organisms fail, time after time? And, in particular, why do they become sterile if you're blocking or otherwise frustrating a viral load—all the disease-causing elements within their genomes? Shouldn't they experience a burst of energy and productivity?”

  Jackson asked that the overhead projector be lowered. Liz sighed. Kaye kicked her gently under the table.

  Jackson's presentation was classic. Within three minutes, he had used nine acronyms and six made-up scientific terms with which Kaye was unfamiliar, without defining any of them; he had entangled them all in an ingenious map of pathways and byproducts and some deep evolutionary suppositions that had never been demonstrated outside a test tube. When he was on the defensive, Jackson invariably reverted to tightly controlled in vitro demonstrations using the tumor cell cultures favored for lab research. All the experiments he cited had been tightly designed and controlled and had, all too often, led to predicted results.

  Marge Cross gave him five minutes. Jackson noticed her impatience and drew his sidebar to a close. “It's obvious that ERVs have devised ways to worm themselves into the machinery of their host's genome. We know of many instances in nature where trying to remove a parasite can kill a host. It's even likely they've created safeguards against removal—pseudogenes, multiple copies, disguised or compressed copies that can be reassembled later, methylation to prevent restriction enzyme activity, all sorts of clever tricks. But the prime proof of the malevolent nature of all retroviruses, even the so-called benevolent or benign, is what HIV and SHEVA have done to our society.”

  Kaye looked up from her notes.

  “We have a generation of children who can't fit in,” Jackson continued, “who arouse hatred and suspicion, and whose so-called adaptive characteristics—randomly invoked from a panoply of possible distortions—only cause them distress. Viruses cause us grievous harm. Given time, our group will overcome these unfortunate delays and eliminate all viruses from our lives. Genomic viruses will be nightmares from a rough and nasty past.”

  “Is that a conclusion?” Cross asked without letting Jackson's dramatic effect sink in.

  “No,” Jackson said, leaning back in his chair. “Something of an outburst. I apologize.”

  Cross looked at the questioners. “Satisfied?” she asked.

  “No,” Nilson said, once again with that special Olympian frown Kaye had only seen in older male scientists, winners of Nobel prizes. “But I have a question for Dr. Rafelson.”

  “Lars can always be relied upon to keep these sessions lively,” Cross said.

  “I'm hoping Dr. Nilson will ask equally probing questions of Kaye,” Jackson said.

  “Count on it,” Nilson said dryly. “We realize how difficult it is to work with early-stage embryos in mammals, mice for example, and how much more difficult it is to work with primates and simians. As far as I have been able to review, your lab techniques have been creative and skilled.”

  “Thank you,” Kaye said.

  Nilson waved this off with another frown. “We also know that there are many ways in which embryos and their hosts, their mothers, work together to prevent rejection of the paternal components of embryonic tissues. Isn't it possible that by removing known ERVs in chimpanzee embryos, you have also shut down genes crucial to these other protective functions? I am thinking in particular of FasL, triggered by CRH, corticotropin releasing hormone, in the pregnant female. FasL causes cell death in maternal lymphocytes as they move in to attack the embryo. It is essential to getting born.”

  “FasL is unaffected by our work,” Kaye said. “Dr. Elizabeth Cantrera, my colleague, spent a year proving that FasL and all other known protective genes remain intact and active after we knock out ERVs. In fact, we're tracking the possibility now that a LINE element transactivated by the pregnancy hormone in fact regulates FasL.”

  “I do not see that in your references,” Nilson said.

  “We published three papers in PNAS.” Kaye gave him the citations, and Nilson patiently wrote them down. “The immunosuppressive function of particles derived from endogenous retroviruses is indisputably part of an embryo's protective armament. We've proven that over and over.”

  “I'm concerned in particular about evidence that a drop in corticotropin releasing hormone after pregnancy induces rapid expression of ERV responsible for triggering arthritis and multiple sclerosis,” Nilson said. “The ERV in this case are reacting to a sharp drop in hormones, not a rise, and they appear to cause disease.”

  “Interesting,” Cross said. “Dr. Rafelson?”

  “It's a reasonable hypothesis. The triggering of autoimmune disorders by ERV is a rich area for research. Such expression could be regulated by stress-related hormones, and that would explain the role such hormones—and stress in general—play in such disorders.”

  “Then which is it, Dr. Rafelson?” Nilson asked, his eyes sharp upon her. “Good virus, or bad virus?”

  “Like everything else in nature, one or the other or even both, depending on the circumstances,” Kaye said. “Pregnancy is a tough time for both the infant and the mother.”

  Cross turned to Sharon Morgenstern. “Dr. Morgenstern showed me some of her questions earlier,” she said. “They are cogent. They are in fact excellent.”

  Morgenstern leaned forward and looked at Kaye and Liz. “I will state up front that although I often agree with Dr. Nilso
n, I do not find Dr. Rafelson's laboratory procedures free from bias or error. I suspect that Dr. Rafelson came here to prove that something could not be done, not that it could be done. And now we are supposed to believe that she has proven that embryos cannot proceed to live birth, or even grow to pubescence, without a full complement of old viruses in their genes. In short, working backwards, she is trying to prove a controversial theory of virus-based evolution that could conceivably elevate the social status of her own daughter. I am suspicious when such strong emotional motivations are involved in a scientist's work.”

  “Do you have a specific criticism?” Cross asked mildly.

  “A number of them, actually,” Morgenstern said. Liz handed Kaye a note. Kaye looked over the quickly scrawled message. Morgenstern published twenty papers with Jackson over the last five years. She's his contact on the Americol jury.

  Kaye looked up and stuffed the note in her coat's side pocket.

  “My first doubt—,” Morgenstern continued.

  This was the true beginning of the frontal assault. All that had come before was just the softening up. Kaye swallowed and tried to relax her neck muscles. She thought of Stella, far across the continent, wasting her time in a school run by bigots. And Mitch, driving to rejoin an old lover and colleague on a dig in the middle of nowhere.

  For one very bad moment, Kaye felt she was about to lose everything, all at once. But she drew herself up, caught Cross's gaze, and focused on Morgenstern's stream of precisely phrased, mind-numbing technicalities.

  20

  OREGON

  They had left the dirt road twenty minutes ago and Mitch still had not seen anything compelling. The game was beginning to wear. He slammed on the brakes and the old truck creaked on its shocks, swayed for a moment, then stalled out. He opened the door and mopped his forehead with a paper towel from the roll he kept under his front seat, along with a squeegee to remove mud.