The Rationing

by Charles Wheelan

  “Most of these clusters turn out to be randomness,” Tie Guy now told the members of Justman’s newly formed working group. “Six kids get cancer near the fertilizer plant. Sometimes six kids just get cancer.” Justman looked at him but said nothing.

  “And sometimes the fertilizer company is dumping poison in the water,” said a woman across from him.

  “True, but where’s our fertilizer plant here?” Tie Guy replied with confidence bordering on hubris. “If we can’t find a pattern, then it’s probably because there isn’t a pattern.”

  “Let’s see what the tissue samples show,” Justman said. “Tatiana, can you speed that along and schedule something for all of us when we have data to look at?” Tatiana, who had been quiet for the whole meeting, nodded and made a note on her phone. “Thanks, everyone,” Justman said, bringing the short meeting to a close.

  That was it. Not a lot of drama or excitement, a fairly typical meeting for anyone in public health. I was not in the room. There was no reason I would be.‡ This group was still a long way from having any idea what was going on. Only then would they call me.

  11.

  I APPLIED TO PH.D. PROGRAMS IN MICROBIOLOGY AND WAS accepted at the University of Chicago. Sloan went to law school. My parents were convinced that microbiology was close to medicine, and therefore I could still become a doctor. I never gave them this idea, but I did not disabuse them of it, either. During my third year in the Ph.D. program, when I had already adopted and abandoned three or four different potential dissertation topics, I applied to get a joint degree in public health. What was another two years and $140,000 of debt? My parents gradually accepted the notion that I was not going to become a doctor, though they never fully accepted the idea that I was a scientist. I once overheard my mother tell a friend that I worked “in medicine.” True, technically. Professor Huke’s class stuck with me, and I winnowed my doctoral research down to virulent pathogens. I really liked the scary ones. In my third year, I was able to work with Ebola, meaning that I had to put on the full level-four biohazard suit. Some people climb mountains for the thrill of it, knowing that one misstep could send them tumbling down a precipice. I felt that way when I put on two sets of gloves and entered the air-lock chamber. A little carelessness and I would be infected with a million viruses capable of making me bleed to death out of every orifice.

  Dormigen changed that, obviously. By the time I was doing my fourth year of research, the most serious pathogens were no longer as excitingly scary, as if a giant net were installed around Everest to catch everyone who slips and falls. Still, the advent of Dormigen created a different kind of excitement. The research we were doing, particularly our growing understanding of the human genome, was producing giant strides in other areas of medicine. We reckoned that cancer was the next frontier (as it had been for several decades, admittedly). Dormigen did not work on tumors because they were not recognized as foreign DNA; cancer cells are mutant products of our own body, rather than invaders like the Ebola or Marburg viruses. But all of us working at that frontier were convinced that a Dormigen-type breakthrough was possible on the cancer front.

  My doctoral research was intended to probe one possible link between viruses and cancer: the so-called “lurking virus.” What makes this kind of virus fascinating—and dangerous—is that it lies dormant in a host for years or even decades. Then, for reasons that we did not fully understand when I began my doctoral work, the virus turns spectacularly virulent, killing a high proportion of the infected population. This is entirely anomalous behavior among the hundreds of thousands of viruses that have been identified and studied. Viruses are usually benign or dangerous—not both. In the past, I have made the comparison—admittedly imperfect—to a workplace shooter. Some guy comes to work every day, settles into his cubicle, does his work, goes to the holiday party, complains about the Docu-Text scanner—normal to the point of fading into the background. That is even what witnesses sometimes say: “He was so normal” or “A very quiet guy.” Then one day he shows up with a semiautomatic weapon and starts firing at his coworkers. We are left with one overwhelming question: Why? And even if we have some insight there, we ask, Why that day? What transforms a guy from someone whom colleagues struggle to remember into a killing machine? What was different that morning, or the night before, or whenever he decided to massacre his colleagues instead of making car loans or selling motorcycle insurance? If we can understand that, we will have unlocked one of the deepest mysteries of the human psyche. And we may save a lot of lives.

  So it is with lurking viruses. How and why does an organism that can live in perfect symbiosis with its host for years or decades suddenly turn deadly? Even more bizarre, the same virus will often return to its benign state months or years later. Imagine that the virus for the common cold suddenly became as virulent as smallpox, wiping out a large percentage of the infected population. Then a few years later the virus goes back to causing sniffles and a sore throat. The exact same virus. This is not a mutation, or a different strain. The guy goes to work one day and celebrates a receptionist’s birthday in the conference room, sharing the cake and chuckling at the bad rendition of “Happy Birthday.” The next day he tries to shoot as many of his coworkers as possible. But then a year later, this deranged killer would ask his jailers, “Hey, when can I go back to work?”

  As one of my graduate school professors once said, “It defies everything we think we know about evolution.” A tiger is not supposed to change its stripes, at least not suddenly. And if there were a sudden change—some kind of major genetic mutation that bestows a reproductive advantage—why would the organism change back? A virus typically lives without doing serious harm to its host (the common cold), getting passed along successfully. Or it kills violently (Ebola), using the dead victim (bleeding from every orifice) as a virus bomb that propagates the deadly organism to more hosts. But not both. It was hard to reconcile what we observed in lurking viruses with the most fundamental tenets of biology.

  The prevailing theory was that some kind of “trigger” causes a lurking virus to go rogue, and then later to return to normal, like some kind of genetic on/off switch. Obviously, if we could identify that switch, we could in theory turn dangerous viruses “off,” or turn benign viruses “on.” This was the potential cancer link. Tumors are benign cells that begin dividing out of control—workplace shooters. Might there be a similarity between the hypothetical on/off switch in lurking viruses and the trigger that turns normal human cells into devastating malignant tumors?

  When I began my research, lurking viruses had never been found in humans. In fact, there had been no documented cases of a lurking virus infecting any warm-blooded vertebrate. The most common hosts are amphibians, particularly in the tropics. My research took me to the Amazon basin, where I spent ten months collecting data on two species of tree frog. My Dartmouth classmates, many of whom had gone on to business and law school, liked to joke that I had gone off to climb trees in the jungle. Their observation was not entirely inaccurate; both species of frog are easiest to find just below the canopy, where they are safest from predators. I did literally climb trees, usually with the benefit of a ladder. But the jungle comments also had a tinge of judgment, as if my doctoral research were some kind of escape from “real” work. I found it amusing when I was in a good mood—and irksome when I was not—that my peers who were finding better ways to sell snack foods, or engineering mergers between giant oil companies, had the chutzpah to tell me I was shirking my social responsibility.

  Anyway, these two species (the Abiseo climbing frog and the black-eyed tree frog, for anyone who cares) were nearly wiped out by a parasitic virus beginning in the early 2000s. That was no big deal; species come and go, especially in the Amazon. But in 2016, a savvy Brazilian researcher made a startling discovery. These tree frogs had always been hosts for this parasitic virus—literally for millions of years—but for nearly all of that time the virus did not kill them. He had excavated a tar pit near an Am
azon tributary where a whole ecosystem from two million years ago had been preserved intact—the biological equivalent of Pompeii. The site was (and still is) a treasure trove for biologists. The finding that interested me was just a footnote to the many other extraordinary discoveries. Two million years ago, these two tree frogs were infected by the same parasitic virus that would later nearly wipe out their species, but they were seemingly unaffected by it. The tree frogs trapped in the tar pit all carried the virus, but analysis of the preserved tissue suggested that they died with the virus, not from it. The relationship between the host and the parasite was innocuous, maybe even symbiotic, just like all the organisms inhabiting the human gut. Happy tenants.

  So what changed? And why? Those were the central questions of my doctoral dissertation. The dissertation was mediocre by any conventional standard. That was one reason I could not find an academic job. I loved my work at the NIH, but I had “settled” when I first agreed to work there. Scientists have their own hierarchies. The researchers at the preeminent academic institutions are at the top: Harvard, Yale, and so on. The big state universities are next; what they lack in prestige they make up for in grants, facilities, and access to graduate students. Then there are the government research facilities, places like NIH and CDC, where the quality of research is good, but there are fewer freedoms than at a university. My research had its merits. I had thoroughly documented spells in which the Amazonian tree frogs had been harmlessly infected with lurking viruses and also periods during which the viruses had nearly wiped out the affected populations. Nobody had ever done this kind of fieldwork before. Still, when I gave my academic job talks (I did apply for openings in biochemistry at a handful of research universities), the faculty panels would always ask the same thing: “Why?” I had no answer, not even a compelling theory to test (which might have earned me a job at a second-tier university).

  I was the guy who came in after a mass killing and explained exactly how the killer had behaved on the day of the shooting. I could outline exactly what happened and when—but not why some twenty-one-year-old decided to open fire on his professors and fellow students. And why is really what we care about, as that is what we need to know to prevent the next campus shooting.

  I was cursed with a particularly unimaginative dissertation adviser, who discouraged a line of inquiry that might have led to more robust answers to these questions. This caused a profoundly uncomfortable moment at my dissertation defense. “I don’t see how you have moved the research frontier,” my adviser declared. I was standing at the front of a small seminar room filled with a smattering of fellow students, family members, curious faculty members, and the three professors who would determine whether I would become a Ph.D. or a failed graduate student, the dreaded ABD (All But Dissertation). My adviser was the chair of that committee and its most influential member.

  “My work provides a deeper understanding of how lurking viruses function within their hosts,” I answered.

  “But it’s not your work. You’ve summarized the work of others,” my adviser pressed. He was sitting in the back of the room; the other observers turned to look at him, then turned back to hear my response, like an academic game of tennis. My mind was working furiously, trying to figure out if he was trying to screw me or just make me sweat a little.

  “There were various strands of research on this topic, each isolated in its own way,” I said with far more confidence than I was feeling. “When you bring them together—well, that’s what I’ve done here—you get a more complete understanding of how the organisms interact.” I was thinking, What the fuck? This guy has been working with me for three years and now he brings this up?

  “Hmm,” my adviser said with mild disdain. “You have successfully woven together work already published by others—”

  “Much of this work was not published,” I interrupted.

  “Fine. That’s an irrelevant distinction,” he said haughtily. “You’ve taken Legos produced by other people and built something interesting.” There was tittering around the room in response to the Legos metaphor. “I’ll repeat my original question: Where is the original work? What Lego did you produce?”

  In my mind: Oh, my God, he is screwing me.

  I tried to compose my thoughts, but before I could respond the chair of the department interjected, “Enough of the Lego claptrap. The most valuable contribution one can make in science is to give voice to the work of others in a way that improves our overall understanding of a subject.” I looked furtively at my parents, whose body language improved noticeably after this intervention. A few of the graduate students exchanged sly smiles; they recognized this was no longer about my dissertation. The chair of the department was a well-respected microbiologist, one of the first women tenured in the department. She was fiftyish and dowdy, neither attractive nor unattractive. She was a lousy teacher but a kind person and a good administrator, making her much appreciated by students and faculty alike. She was a relative superstar in her subfield of protozoology.

  Also, she was my adviser’s ex-wife. They had been recruited to the department together in the 1990s, both with tenure. Her publication record was more impressive than his, both before they arrived at the University of Chicago and after. He had an affair with one of his graduate students, leading to a separation and then a divorce. I have no idea why they both chose to stay in the department, but they did. The department was full of faculty who hated one another; these two at least had good reason.

  Heads in the academic tennis match turned back to the rear of the classroom in anticipation of a response from my adviser. “And how have you improved our overall understanding of this subject?” he asked me. A softball. To those in the room without any understanding of the internal politics, like my parents, this whole discussion seemed to flow naturally. But to those of us who understood the Kabuki theater of academe, my adviser’s ex-wife, who also happened to be a far more impressive microbiologist than he was, had just smacked him down. He was going to lose if he went back at her. I knew that. More important, he knew that. His softball question was a white flag.

  I gave an innocuous answer, something more or less straight from my abstract. There were some other softball questions and then my adviser politely brought the discussion to a close. I walked out of the room along with the rest of the observers, leaving my committee behind to deliberate on my fate. It did not take long. Ten minutes later they filed out of the room and informed me that I was now a doctor of philosophy. “Congratulations,” my adviser said woodenly.

  His eyes betrayed what we both knew: I had been saved by the fact that he had been caught screwing one of his graduate students.

  12.

  JEFF YUN, THE HEAD PATHOLOGIST FOR THE CENTERS FOR Disease Control, was standing at the front of a conference room. Ron Justman’s task force was assembled around the table. The lights were dim; a slide showing a single virus was projected on a screen on the far wall. “That’s it,” Yun said. “Capellaviridae.” The organism was hexagonal, with short hairlike structures emerging from each of the sides. “Each of the victims had extremely high levels of the virus concentrated in their livers. As best as I can tell, that’s the cause of death. The virus attacks the liver, and to a lesser extent the pancreas. Both organs shut down relatively quickly.”

  There were blank stares around the table. Justman shrugged, “A cappella?”

  “Capellaviridae,” Yun said.

  “Never heard of it,” Justman said. “Am I missing something?”

  “No,” Yun said. “No. That’s the thing.” He had a roundish, friendly face with closely cropped hair. Small beads of perspiration gathered on his upper lip. “It’s a totally unexceptional virus, commonplace in temperate zones of the northern hemisphere. It didn’t even have a name until twenty years ago.” He looked around the table, inviting someone to make sense of this pedestrian virus turned killer.

  “Are humans the only host?” Justman asked.

  “We don’t know. I’m
telling you, nobody has ever studied this thing.”

  “And you’re sure this virus is responsible for the deaths?” Tie Guy asked.

  “I’m not sure of anything,” Yun answered. “But the concentration of viruses that we observed in each of the victims is unlike anything I’ve ever seen. I spoke to my Canadian and European counterparts this morning. They’ve observed the same thing.”

  “Hold on,” Tie Guy interjected. “Are we really sure of the causality here?” There followed a discussion of whether this virus, Capellaviridae, was killing people, or if people who were dying of something else were prone to becoming infected with Capellaviridae. Tie Guy lectured the room on what most of them already knew: many viruses are opportunistic, meaning they thrive when a host’s immune system is compromised. A cancer victim may die of viral pneumonia, but to blame pneumonia for the death would be to miss the real problem.

  Justman said, “In any event, we know that this virus is, at a minimum, a marker of the problem, yes? Maybe it’s a dangerous pathogen, maybe it thrives when something else nasty is going on. Given how little we know, we should begin by focusing on Capellaviridae. Can we agree on that?” There were nods around the table.

  “Is it harmful to animals?” the Indian-American woman asked. “We should at least know that.”

  “My people are testing that right now,” Yun said quickly, not quite cutting her off. “I’ve got everybody working on this.”

  “Let’s back up for a minute,” Justman interjected. “The Dormigen database. We’ve seen a spike in prescriptions—”

  “And those people, at least some of them, are testing positive for Capellaviridae?” Tie Guy interrupted.

  “Yes,” Yun said. “That appears to be why we’re seeing the spike in Dormigen demand. Based on the limited data we have, it seems that most, if not all, of the increase in Dormigen prescriptions can be explained by some kind of epidemic related to Capellaviridae.”