The Next Pandemic

           If it is a terrifying thought that life is at the mercy of the multiplication of the minute bodies (microbes), it is a consoling hope that science will not always remain powerless before such enemies.

—Louis Pasteur

We had been in the jungle for about two weeks when a kid on a motorbike rode up and told us that the rebels had overwhelmed government forces and that all these combatants were coming our way: Laurent Kabila’s guerrillas, hot on the heels of Mobutu Sésé Seko’s army.

This was in a province called Kasai-Oriental, just about in the center of Zaire, which is just about in the center of Africa. We were there on behalf of the World Health Organization and the Centers for Disease Control and Prevention to investigate an outbreak of monkeypox, a less deadly but still highly problematic cousin of smallpox. If it could be spread indefinitely by person-to-person contact, it could become a global pandemic. So the degree of sustained transmission was the central question we were trying to resolve. But suddenly the more pressing issue was how the hell we were going to get out of there.

We called the American embassy, which advised us to wrap up our investigation and evacuate immediately. “They’ll likely take your vehicles and gear,” they told us. “But they probably won’t kill you.”

This was not an entirely reassuring assessment. We were next door to Rwanda, scene of one of the worst genocides in recent history. Mobutu’s forces were known to loot, pillage, and kill in the best of times, and the word was out that they had not been paid in months. “Why do you need to be paid?” Mobutu had scolded them once, or so the story goes. “You have guns.”

The nearest airstrip, a trail of red dirt hacked out of the ever-encroaching vegetation, was seventy-five miles away in Lodja. But that was our only way of making it back to the capital.

Our team of disease detectives had been spread out to interview the locals and to collect mice, monkeys, squirrels, and rats so we could take their blood. Despite the name, monkeypox is more often found in rodents, and the primary means by which people get sick is contact with the bodily fluids of these animals, often when captured for food.

I sent some of the local villagers out to round up our team, and once everyone was accounted for, we attacked our own camp, running back and forth collecting equipment. I was dumping out vials of liquid nitrogen, which filled the jungle with plumes of white vapor, then burning my fingers as I retrieved the supercold canisters to consolidate our samples into a single tank. We were looking over our shoulders the whole time, as one of my colleagues with a military background used the satellite phone to call his contacts in the US Department of Defense.

They said, “If need be, we can pick you up in a few hours.” My colleague asked, “How is that possible? You don’t have any assets in this part of the world.” They curtly answered, “That’s our business, not yours.”

But we weren’t sure we had two hours to spare in that location. Better to get out of there now and find a plane in a couple of days. So we left behind our trucks and piled our ten people into three 4×4s and sped off into the bush toward the nearest town, a day’s drive away.

We rumbled along for two or three hours in tense silence, worried about the abrupt ending of our study, worried about our gear, worried about the villagers who might now be targeted for having helped us.

Then when we got to the river our hearts sank—there was no bridge. For a moment, it looked like were going to have to leave everything behind and swim for it. But the locals had rigged up a rudimentary ferry system consisting of a flatbed on a giant pontoon and a cable system for pulling us hand over hand, which allowed us to get to the other side.

For the next eight hours we continued through the overgrown, mosquito infested, muddy, rough terrain until we arrived at the Catholic mission in Lodja, a low cinder-block building with all the frills of a Motel 6, but to us it could have been the Paris Ritz. Hot meals with no concern about dysentery, and hot showers where accumulated dirt ran off each of us like a muddy river. The priest and novices were wonderful people, a reminder of why the human race is worth trying to help.

But first I placed a satellite call to our contacts in Kinshasa, who told us that a French film crew would be flying in the next day to shoot a documentary.

So we were ready the next morning when a thirty-seat twin-propeller plane touched down. Unfortunately, dozens of panicked villagers trying to flee the rebels and the army had also shown up hoping to get aboard. This led to a mad scramble around the airplane with security guards firing into the air to get everyone to back off.

A few minutes later our group of scientists, guides, and our single, eccentric mammologist were buckled in and ready for takeoff. But no sooner were we airborne than the skies let loose a horrendous thunderstorm with pounding rain and vicious turbulence that had us bouncing around like the passengers in Airplane! Then the liquid nitrogen tank we had with us in the cabin broke loose and started smashing into things.

The guy to my left was praying. I looked over and saw that the French physician sitting next to me was writing a farewell note to his family. Which got me thinking. If today was my last day, was I ready to die?

When I went to medical school, becoming a geek version of Indiana Jones was not what I had in mind. I’d been inspired to study medicine by my father. He’d been a fourteen-year-old peasant farmer with an elementary school education who made the multiweek trek from a remote village in Kashmir to Bombay at the beginning of the Second World War, lied about being nineteen, and joined a Scandinavian freighter as a wiper in the engine room.

My scientific interests, immunology and infectious disease, had been spurred by childhood readings of how Louis Pasteur refuted the theory of spontaneous generation. But after my residency in pediatrics and internal medicine, I was selected for a two-year fellowship to work as a disease detective at the Centers for Disease Control and Prevention (CDC) in Atlanta, or what I lovingly refer to as CSI:Atlanta. I wound up staying for almost twenty-five years, leaving in 2014 to become dean of the College of Public Health at the University of Nebraska Medical Center.

My job during those years took me from jungle outposts, to Chilean villages reachable only on horseback, to crowded Asian cities locked down under quarantine, to the abattoirs of Persian Gulf sultanates where migrant workers slaughtered goats and sheep under appalling conditions. My colleagues and I worked to stop the spread of Ebola, SARS (severe acute respiratory syndrome), MERS (Middle East respiratory syndrome), and lots of other scary diseases. I was also directly involved in trying to contain the spread of anthrax after the 2001 bioterrorism attack in Washington, and in rebuilding the public health infrastructure in New Orleans after the devastation of Hurricane Katrina.

I hope these tales of my adventures in public health will be entertaining in their own right. But I tell them to dramatize and particularize the disconnect between the outbreaks of hysteria that come with huge headlines, only to be forgotten within weeks, and the very real, long-term structural dangers that should, yes, genuinely scare the pants off us, but more importantly, should lead to long-term structural change in how we address global public health.

Just as we know about (but so far have done precious little to address) huge problems with our physical infrastructure—crumbling rail lines, leaking combined sewers, bridges that are on life support—we have maintained a short-sighted and fickle approach to emerging infections and possible pandemics that have us frothed up one moment, oblivious the next. I started this manuscript just as the Ebola outbreak in West Africa began to make headlines. As the book goes to press, Ebola is a distant memory, and the world’s attention has shifted to Zika. Our failure to more deeply understand and more consistently attend to the bigger issues leaves us, as they say along the fault lines in California, just waiting for the big one.

The Centers for Disease Control and Prevention is the successor to a wartime federal agency called Malaria Control in War Areas, which was set up in 1942 to protect stateside training bases from malaria during World War II, many of which were in the South, which has been known to harbor a few mosquitoes. Just after the war, in 1946, it became the Communicable Disease Center (CDC), but was still focused on malaria and typhus. It had roughly four hundred employees, most of whom were engineers and entomologists. The following year, the center paid a token $10 to Emory University for fifteen acres of land on Clifton Road in Atlanta, where the greatly expanded CDC is still headquartered today.

The program where I got my start, the Epidemic Intelligence Service (EIS), was established in 1951 by Dr. Alex Langmuir to address biological warfare concerns that arose during the conflict in Korea. Its mission was to train epidemiologists on extant public health problems while they kept a watch for foreign germs. Since that time, the EIS has been a two-year postgraduate training program in epidemiology, with a focus on fieldwork. It’s like a traditional medical residency program in that much of the education occurs through hands-on assignments and mentoring.

Rather than making rounds in hospitals, though, EIS officers evaluate public health surveillance systems; design, conduct, and interpret epidemiological analysis; and conduct field investigations of potentially serious public health problems in the United States and around the world. EIS officers have worked on issues as varied as polio, lead poisoning, cancer clusters, smallpox, Legionnaires’ disease, toxic shock syndrome, birth defects, HIV/AIDS, tobacco, West Nile virus, E. coli contaminated water, natural disasters, and fungal meningitis. But my first assignment was not nearly so impressive.

I was a twenty-six-year-old rookie (I looked about twelve despite the mustache I’d grown in the hope of adding a few years) when I conducted my first Epi-Aid, an investigation of patients with chronic fatigue syndrome that eventually proved that a controversial study linking the illness to a retrovirus infection (like HIV that causes AIDS) was due to sloppy lab work.

This was the kind of thing that only a serious geek could get excited about. But immediately afterward I was summoned to my first real challenge in the field—I was shipped off to Hawaii to investigate an outbreak of diarrhea on a cruise ship.

Okay, so maybe this was still not the kind of thing that was going to win me a Nobel (either the Peace Prize or the award in medicine and physiology), but at least it was going to get me out of the office.

Now, very few cruise ships are registered in the United States, but this one sailed only the territorial waters of the Hawaiian Islands, so it flew the US flag, which meant that its owner, along with the state health department, were entitled to call up CDC and ask us to investigate. The only problem was that the viral diarrhea people at CDC didn’t have an EIS officer available so, for whatever reason, they asked me to go and respond, even though I knew nothing about the subject. However, I was reminded of the suitcase lore of EIS officers: the farther you to travel to an outbreak, the bigger expert you seem.

For most of the ten hours I spent flying west I was on the phone with my supervisor, trying to get up to speed on Norwalk virus (common gastroenteritis, or “stomach flu”), which, judging from the history, seemed to be the cause of the outbreak, which meant in turn getting up to speed on projectile vomiting and the fine points of evaluating the stool quality of diarrhea. This was in the early 1990s, when the only way to make a call was from what amounted to a pay phone in the back of the plane. I tend to be an animated phone talker, and I’m pretty sure I was loud enough to be heard in the cockpit.

When the plane landed in Honolulu, the captain said, “Would everybody please stay seated. We need to allow Dr. Ali Khan to get off the plane first.”

I looked around and all the passengers were staring at me, and I thought, Gee, how do they know I’m the doctor flying in on an emergency case?

Then it occurred to me that I was the jerk who’d ruined everybody’s vacation by talking diarrhea all the way across the Pacific.

A bunch of tourists with the runs may sound like something out of a Judd Apatow gross-out comedy, but it was no laughing matter to those who got sick, or to the owner of the cruise line, who might lose his business.

The outbreak had occurred at sea, so when the ship returned to port the crew threw out every scrap of food on board and scrubbed down everything until the local health department gave them the okay. Then the ship took on new passengers and set sail again. But within two days (the incubation period for Norwalk virus) this entirely new set of passengers began getting sick. Which is when the crew and the health department called for help. The crew headed back into port, then waited at anchor for their consulting epidemiologist to fly in and be motored out to them in a small boat.

Despite my complete ignorance, I planned to immediately launch into a series of fourteen-hour days inspecting the ship and developing a questionnaire.

And then matters took a turn for the worse.

I am prone to seasickness, and even with the gentle rocking of the ship at anchor I became violently ill. But I was from the federal government, and I was there to help, so I spent the first few hours lying on a banquette, surrounded by all the senior staff, moaning out directives, mumbling, turning green, and rushing to the bathroom, until the ship’s nurse yanked down my pants in front of all these people and gave me a shot of Compazine.

With my dignity compromised but my health improved, I collected the questionnaires and tabulated the data, which created a detailed picture of daily behavior that thoroughly invaded everyone’s privacy: who ate what, how much and how often; who consorted with whom; which bathrooms they used; how much each passenger drank; and on and on.

Fortunately, a bit of statistical analysis yielded one correlation of particular interest. It was the linkage between the number of cups of ice consumed and the likelihood of getting sick.

Bingo.

The ship’s ice was kept in a big open bin, then scooped up and sent to the dining room. Most likely the “index patient,” the first one to come down with gastrointestinal distress, had been an infected member (or members) of the kitchen crew who went for the ice. But dirty hands came in contact not just with the scoop but with the ice itself, and the virus was transferred and preserved. And while the ship was thoroughly cleaned after the first outbreak and passengers changed, the crew members stayed onboard to infect the ice again.

As is so often the case in matters of public health, once you’ve isolated the problem, the solution comes down to better hand washing, and to a rather simple intervention. I got them to change over to one of those machines where the ice drops down into a bucket from a dispenser. Then they were good to go, and I was free to return to the major land mass of the US mainland, which did not wobble.

But it’s funny how much our view of a disease depends on context. Among generally healthy, well-fed Westerners who can afford vacations, diarrhea may be inconvenient, and it may even be embarrassing, but generally it’s no big deal. Among small children in third-world countries, however, diarrhea accounts for some 800,000 deaths each year—more than AIDS and malaria and measles combined.

It’s also amazing how often something as mundane as an ice scoop can make all the difference.

In 1854, a London physician named John Snow (not the one from Game of Thrones) set out to investigate an outbreak of cholera in Soho. In Snow’s day, the overriding explanation for infectious disease was the miasma theory, in which the source of illness was thought to be “bad air.”

But by studying the distribution of disease and putting the cases on a dot map, Snow was able to track down the source to a water pump on what was then called Broad Street. Snow’s chemical and microscopic examination of the water could not prove that it was the culprit, but he was able to persuade the local council to remove the pump handle and thus shut off this particular water source. His work, coupled with that of others, laid the foundation for one of the mainstays of modern medicine: “germ theory.” And although he did not get the recognition he deserved at the time, Snow’s study became the founding event of the modern science of epidemiology.

OUT OF SEASON

At first blush, my next assignment might seem equally as small potatoes as the outbreak of diarrhea in Hawaii. This was June 1992, when a cluster of influenza B appeared in Fairbanks, Alaska, and the state asked CDC for help.

Influenza rarely makes the list of diseases that keep ordinary citizens awake at night. In the mind of the average person, the flu fits in more easily with everyday ailments like the common cold. But while the 2014–15 Ebola epidemic, which killed 11,000 people, became a global news event, influenza causes between 250,000 and 500,000 deaths each year, every year, worldwide. The infamous influenza pandemic of 1918 sickened 20 to 40 percent of the global population and caused anywhere from 50 to 100 million deaths, including 675,000 in the United States alone. Sad to say, there is nothing to prevent a pandemic on that scale, and that deadly, from happening again. Which is why influenza is taken very seriously, and monitored very closely, by disease detectives like me.

In 1918, the victims were often young, healthy adults in the prime of life. That’s why people who don’t know much about history will often know about the flu that began to sweep across the continents just as the mass slaughter of World War I died down. It’s the perfect plot device to kill off romantic rivals in period dramas like Downton Abbey. Anytime there’s a pretty young thing who stands in the way of true love for the hero and heroine, you can be sure that the pretty young thing is going to be toast, and you can bet she’s going to be toasted by the Spanish flu.

The US population in 1918 was 103 million people, so if a pandemic on the same scale occurred today with our current population—three times larger—we’d be looking at close to 2 million dead people in the United States alone. Which is, once again, why we epidemiologists worry about influenza, and why we’re very attentive anytime it reappears with novel characteristics.

What set off the alarm bells in Fairbanks was the fact that a cluster of cases appeared in the summer, despite the fact that flu is usually a winter phenomenon in temperate countries. It’s not that the bug isn’t around all year. It’s just that in summer people spend more time outdoors, and because they’re not packed together in closed spaces, they don’t infect one another as easily. There are cases, but they usually travel below the radar.

But in Alaska, in 1992, the state public health laboratory isolated the virus from throat swab specimens obtained from nine patients in the period from June 5 to July 5. The antigenic and molecular characteristics were unknown, so we thought it would be a good idea to find out more about what was going on.

Epidemiologists often refer to “epidemics,” “clusters,” and “outbreaks,” but which term we use is more a function of art, and of the amount of attention we want to stir up, rather than some supertechnical line of distinction. Technically, a pandemic is an epidemic that spreads worldwide or occurs over a large geographical area, crossing international boundaries, and usually affecting a large number of people. Flu pandemics are usually caused by influenza A. This summer flu in Alaska was influenza B, a kissing cousin, which made the worst-case scenario unlikely, but we were still curious. And concerned. Influenza B has a habit of sweeping through nursing homes with a scythe. And when evolution rolls the genetic dice, there always can be unpleasant surprises.

Unlike Ebola, the influenza virus can travel very efficiently via large airborne droplets when infected persons sneeze, cough, and talk. So, actually, if you were out to make a horror movie about a truly scary pathogen, it wouldn’t feature an exotic foreign star like Ebola, which generally requires direct contact with blood, saliva, semen, or other bodily fluids. Moreover, with Ebola, you’re infectious mostly toward the end of your illness, when you’re probably not in the mood to go around and do much socializing anyway. With flu, you can be infectious even before you show any signs of illness.

Yes, the lead villain in the end-of-the-world pandemic thriller would be everyday influenza, which, with its proven capacity to kill millions, can be spread by a sneeze or a handshake.

And while Ebola is scary, its terrifying reputation is out of proportion to its actual risk, in part because of the way it’s been sensationalized in the media, dating back to the urtext of Ebola narratives, Richard Preston’s The Hot Zone. There’s no doubt that Ebola is a nasty disease, but influenza is not exactly your friend.

The 1918 influenza likely killed by creating a “cytokine storm” in the bloodstream and lungs, cytokines being small proteins involved in signaling, as in the immune response. When the virus infects the lung, it overstimulates the immune system, which leads to an influx of T-cells and macrophages, cells that exist to ward off invaders. But the presence of those cells activates even more of an immune response, which stimulates the production of even more cytokines. And when you have too much of a good thing too quickly, a deadly feedback loop can start to roll, and the accumulation and concentration of immune cells—free radicals, coagulation factors, tumor necrosis factor-alpha, interleukin-1, interleukin-6, interleukin-10, and interleukin-1 receptor antagonists—can damage the tissues. When this happens in the lungs, the accumulation of immune cells can block off the airways. In other words, you drown in your own fluids.

The danger from flu is that it can undergo a dramatic genetic shift so that the population has no immunity to its new structure. But the flu virus also continually drifts or mutates, which means that each year we have to update the flu vaccine we plan to manufacture and distribute. To prepare for the fall onslaught, we have to make a final decision about what is in the upcoming season’s vaccine about six months ahead of time. Given that the manufacture of the vaccine relies on what is, essentially, 1940s technology—the virus is grown in eggs, inside the shell—the process is always time consuming and imperfect. So when there’s an early flu outbreak, the concern is how much this new preview strain matches the vaccine that’s already in the pipeline. Which means that even seemingly arcane or tangential information can be useful.

I left Atlanta at nine thirty on the morning of July 12 and arrived in Fairbanks at four thirty in the afternoon, local time. I’d never been to Alaska, and this being summer, there was bright sunshine with people out roller skating and playing in the park—it was quite lovely. But summer also meant that it was high tourist season, and the only accommodation I could find was what turned out to be a rattrap rooming house straight out of a Raymond Chandler novel. And the constant daylight meant there was no way I was going to get any sleep.

I drove my rental car to a rundown area of town that looked like Detroit on a bad day and parked at the three-story rooming house. The guy at the desk was covered in tattoos, and the only telephone and television were in the lobby. My room was on the first floor, and despite the open window and the fan, it smelled distinctly of vomit. The window being open, of course, meant that anybody could climb right in, and that included battalions of mosquitoes.

My job was to discover as much as I could about the strain of flu that had hit Fairbanks and to figure out if it was spreading. I was also supposed to send back specimens of the virus to Atlanta so researchers could compare it to known strains, to help refine the new vaccine then being prepared. Also, CDC had been running a viral surveillance system for the past five years, enrolling primary-care doctors all over the country to track cases of flu, then submit samples from their patients to a central facility. I had been asked to review how the system had been working in Alaska.

And, oh yes, I also needed to take back a photograph of a moose. I can’t remember who asked for it, but somebody at the office wanted to see what a moose looked like up close.

At nine fifteen that first brightly lit morning, I met with the head of the state virology lab, Don Ritter. A Chicago native, Ritter had come to Alaska as an army helicopter crew chief, mapping the state’s topography. He had developed an interest in wildlife that led to an interest in pathogens.

Sitting in his office, I listened as he filled me in on the ins and outs of the viral surveillance program: where the samples came from and how they made their way through the system. He also mentioned that they did get unusual viruses in Alaska, in part because, as Sarah Palin could tell you, they have significant traffic with Russia.

If this were a spy novel, that comment would be the tagline to end the scene, after which your hero would go on to discover deadly pathogens wafting over the Bering Strait in a devious scheme of biological warfare. But even without getting carried away into John le Carré territory, I made a note. Disease detectives have to consider all the possibilities. Especially when they make you feel like James Bond.