Sample text for Virus hunter : thirty years of battling hot viruses around the world / C.J. Peters and Mark Olshaker.
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There's an old adage in medicine that goes something like this: Common things occur commonly. Uncommon things don't. Therefore, when you hear hoofbeats, think horses, not zebras.
Each of us has a worst nightmare, the kind of fevered dream that wakes us up in a cold sweat, overwhelmed by the sheer physical relief of realizing this dark and vivid reverie isn't real. Mine has to do with the zebras. What if the hoofbeats, this time, aren't horses? What happens if a deadly virus for which we have no treatment or cure explodes into the middle of a major city?
On Monday morning, November 27, 1989, it looked like my nightmare was coming to life.
I was in my office at USAMRIID--the United States Army Medical Research Institute of Infectious Diseases at Fort Detrick, Maryland--preparing for a meeting I didn't want to go to. As chief of the Disease Assessment Division, one of my many responsibilities was to distinguish between outbreaks of common, treatable bugs and rare, unknown diseases, between the horses and the zebras. Disease Assessment was a new division at RIID, housed in a temporary building, a prefab structure thrown up on a concrete slab. When any of us had to go to the bathroom, we had to go to other buildings, and until they caught us, we used to empty our coffeepots out the fire escape. By government logic, if our temporary facility had had plumbing, it would have been a permanent building and Congress on high would have had to approve it.
My colleague Peter Jahrling and I had different philosophies about difficult meetings. I put them off as long as I could, but once I schedule them, I go. Peter, the division's senior research scientist, would schedule anything in a heartbeat but would then try to find some excuse at the last minute not to go. This was one neither one of us wanted to go to: a meeting in Rockville on the simian immunodeficiency virus (or SIV) project with Don Burke and the Walter Reed Army Institute of Research people. They were top-notch scientists and had the same goals we did, but we had disagreements with them about the science, the funding, and the politics. But the bottom line was that simian immunodeficiency was a good model for studying HIV, and so it was an important project. If we could get some insight into the mechanism of disease in monkeys, it could help us figure out how to treat it in humans, and this could also be a real breakthrough for vaccine development. Peter and I had made a deal with each other that no matter what else came up, we'd both go to all the meetings.
About ten minutes before we had to leave for the half-hour drive to the suburb north of Washington, D.C., I was rummaging around my office checking to make sure my uniform had all its costume jewelry in the right places. I've never been a very snappy dresser, maybe because it was so hot in West Texas, where I grew up. I've always favored jeans and bright-colored shirts with strong prints rather than a regular uniform--a habit not always appreciated by my superiors in the military hierarchy. But I had picked up a tenacious form of athlete's foot fungus years before, working in the jungles of Central America, which I used as my excuse for wearing casual clothes and sandals with white socks to the office. I didn't start wearing a uniform regularly until I became a colonel, at which point I had to start setting a "good example" for the others. I still wasn't very good at it, though, and every time I had to represent RIID to the outside world, I had to double-check to make sure everything was where it belonged.
When Peter showed up at my door, I thought he'd come with some excuse why he couldn't go. With him was Tom Geisbert, a twenty-seven-year-old grad student Peter had just recruited away from John White in pathology to give us electron microscopy capability. John had worked with Tom's father, an engineer, "behind the fence" in the old days when Detrick housed the army's secret biological warfare program.
Tom was holding a manila folder. "C.J.," Peter said, "you need to take a look at this."
Tom handed me the folder. There were several eight-by-ten glossy photos inside. Electron micrographs. As I flipped through them, inner alarm bells were beginning to sound.
Peter gave me a minute, then asked, "What does this look like to you?"
I saw rod-like particles in the cells, some curved at the end like a shepherd's crook, others in bizarrely twisted shapes. "It looks like a filovirus," I responded apprehensively. I was suddenly gripped by what we refer to as "the pucker factor," an uncomfortable and unpleasant tightening of certain sphincter musculature. "Where does it come from?"
"These are the samples from Reston, Virginia."
Oh shit, I thought. I knew that Dan Dalgard, the supervising veterinarian for Hazelton Research Products over there, had contacted Peter after some of his monkeys started dying at their primate quarantine unit. Reston was an upper-middle-class bedroom community, one of the first of the "new towns," about twenty miles outside Washington, D.C.
Hazelton imported macaques from the Philippines for medical research throughout the United States. It isn't unusual for a few monkeys from a shipment to die during the quarantine period before they can be certified disease-free and sent out to the labs. But normally, when they die it's either something so vague that you never find out what the cause was, or they have weight loss and diarrhea before they die of dysentery. These monkeys were bleeding internally and externally before dying a very unpleasant, dramatic death. They had firm, enlarged spleens, which probably meant they were packed full of white blood cells, a healthy immune response. Dissecting the organs had been like cutting through sausage. Equally troubling to Dan Dalgard, all the bleeding deaths had occurred in one room--Room F--of the single-story, brick-faced quarantine facility. He was worried he was dealing with an outbreak of simian hemorrhagic fever (SHF), a disease which doesn't affect humans but is absolutely devastating to certain species of monkeys. He had sent samples from all the monkeys that had died in Room F over to Peter to work up, looking for SHF virus. And they'd found some.
Electron microscopy requires hours of careful processing of tissue or cells by a skilled technician before the test can be carried out. Looking at the slides under the electron microscope, Tom had discovered something else disturbing the cells, and it sure as hell looked like a filovirus. There were only two known filoviruses--Marburg and, even worse news, Ebola, two of the deadliest of the African hemorrhagic fevers. Both caused the kind of symptoms the monkeys in Room F were dying from. Only they caused it in human beings.
The first documented outbreak of a filovirus had occurred at a vaccine factory in Marburg, Germany, during the summer of 1967. Three employees thought they'd come down with the flu. But by the next day they'd developed severe diarrhea and spreading rashes. Then they started vomiting blood.
And that wasn't as bad as Marburg's sister virus: Ebola. During the summer of 1976, 318 people came down with Ebola in a remote area of Zaire. Two hundred and eighty of them died horribly, including nurses and Belgian missionary nuns who tended the sick in the remote village hospitals. Ebola produces one of the worst deaths I can imagine.
Tom's discovery had suddenly become a major pucker factor.
"How do you know this isn't just a lab contaminant?" I pressed Peter.
"There's no other Marburg or Ebola in the lab," he said.
Oh shit, I thought again.
There are four laboratory levels of biological containment, each one keyed to the potential threat to human life. The lowest Biosafety Level, BSL 1, is for organisms or agents not known to cause disease. BSL 2 is for viruses and bacteria which cause only mild disease or are difficult to contract in a laboratory setting, such as diseases which don't transmit by aerosols. In BSL 3 the bets are higher. It's constructed as a "box within a box," featuring constant one-way airflow to keep the germs inside, and laminar flow hooded work stations to protect gowned and gloved researchers against organisms which cause serious or fatal disease, such as rabies or Rocky Mountain spotted fever, but for which vaccines or treatment is available. BSL 4, the maximum containment lab, is the hottest of the hot zones. Here researchers who've undergone a battery of inoculations move about in full-body "space suits" connected to a constant air supply and wear double gloves taped to their sleeves as they examine and work with life-threatening biological agents like Ebola virus for which there is no vaccine, no magic bullet drug, and no cure. Decontamination tanks and filters are designed to kill off any biohazard waste from the lab before it reaches the outside world. Work in the BSL 4 lab is gut-checking, high-stakes science, where any oversight or slip-up can have disastrous consequences. It takes a particular personality, going far beyond scientific ability, to work regularly in maximum containment. There are only two Level 4 labs in the United States--one at the Centers for Disease Control in Atlanta, the other at USAMRIID.
"Have you been working up any other human samples from Africa?" I asked
"No," said Peter.
"Any other unknown viruses or mystery samples?"
The only other viral agent in the Level 3 lab was Venezuelan equine encephalitis, and never in a million years would you mistake that for a filovirus.
I turned back to Tom. "Talk to John White. He's been looking at filoviruses for years now--show him what you've got and see what he thinks. I think you're rock solid at what you do. But I don't think you have John's experience, and we're going to use every resource we have to be sure."
There had never been a filovirus outbreak in the United States. Figuring out if we had one now was going to take several hours. In the meantime, there was nothing more for Peter or me to do. So, reluctantly, we dragged ourselves out to the meeting in Rockville and spent the afternoon hacking our way through the logistic tangles and conflicting opinions over protocols for SIV monkey experiments that might get started in a few weeks and would last months before we got any answers. But every word that we said was now overshadowed by what was going on in Reston. We were puckering big time, though we kept it to ourselves. Don't let this be what I'm afraid it is.
The moment we got back to Detrick, I called Tom Geisbert.
"What did John White say?" I asked urgently. "Did he think it was a filovirus?"
"Yes," Tom replied. "He said it looked like Ebola."
It was as if my heart stopped. We had Ebola, uncontained. Right here in River City. My mind started racing: We've never seen this virus in monkeys before. How did this human-killing African virus get to a suburb nestled against the heart of the capital of the United States? How many veterinarians had treated these monkeys? How many caretakers had come in contact with them? Where in Virginia, Maryland, or Washington, D.C., had they sent all the previous lab samples and how many technicians had worked on them? Ebola spread by close personal contact in a ripple effect, an exponential network. We could find out who the monkey caretakers were. We could find out who their families and friends were that they might have exposed. But how in hell were we going to find the contacts of the contacts?
Gene Johnson, a research scientist at RIID, and I had been playing around with Ebola in the lab and had a profound respect for its power. We'd shown that under laboratory conditions we could generate an aerosol that infected primates. We had seen the virus spread from one monkey cage to another with no direct contact in the middle of a BSL 4 laboratory. If what we saw in the lab happened in the outside world, we were in serious shit. In point of fact, there was no evidence that this could or would happen in the real world. But we also knew we'd all been surprised more times than we cared to add up. And most of the time, the surprises were not happy ones.
"Did you tell John where it came from?" I asked Tom.
"Good. I want this moved to Level 4 immediately."
There was no need for any of the three of us to say anything out loud, but we were all thinking the same thing. Could this finally be the big one we've been dreading our entire careers? Ebola killed 90 percent of the folks who came down with it in Zaire in 1976--people who hideously bled to death while their internal organs shut off one by one--and we still don't know where it comes from or what the animal reservoir is. All we know is that once this thing climbs aboard an airplane, it could be anywhere in the world within twenty-four hours. And for now, we've got a fucking killer virus loose just outside Washington, D.C.!
We began hearing the approaching hoofbeats of zebras.
Library of Congress subject headings for this publication: Peters, C, J, Epidemiologists United States Biography, Virologists United States Biography, Hemorrhagic fever Epidemiology