Plague: A New Thriller of the Coming Pandemic

Sometimes fiction can do more to change public opinion than nonfiction. It took Upton Sinclair’s 1906 novel, The Jungle, to awaken the public to the dangers of sausage and the meat-packing industry in general. Another example, if I can be so presumptuous, is my 1977 novel Coma, which opened readers’ eyes to the dubious side of the medical profession after years of misleadingly warm and fuzzy treatment of doctors and hospitals in novels, movies, and TV series. Today, there is a crying need for a new such socially conscious novel to shake up the complacent public about the high risk of an imminent, serious pandemic. And I don’t mean the much-publicized swine flu. While the world media has obsessed, and rightfully so, about this fast-spreading illness, I’m worried about the next crisis, something much deadlier and much more catastrophic, indeed the kind of crisis most people wrongly believe could not happen in this day and age. If I were the author, this urgently needed novel would have to be called Plague.

Everyone has heard of plague and knows it means a sudden outbreak of a virulent disease. But it also has a very common, very specific association in the public mind: It’s synonymous with the Black Death, the scourge caused by the bacterium Yersinia pestis that swept through Europe (as well as much of the rest of the world) from 1348 to 1350. Viewing this monumental and even Malthusian event from the vantage point of nearly seven centuries later, one cringes at having to contemplate the horror, the excruciating pain, and the terror its victims had to suffer. Knowing the pain involved with a tiny boil, it is almost impossible to imagine what it was like being deathly ill with most of one’s lymph nodes swelling to the point of becoming visible, blackened lumps with their interiors necrotizing and liquefying — and all of that happening without analgesics and certainly without antibiotics. If David Letterman presented a top-10 list of the worst possible ways to leave this world, dying of the plague in the 14th century would have to be at the top.

And the horror of the Black Death went far beyond individual physical pain. Given the speed with which the illness spread through cities, it must have caused ultimate anxiety and panic as the wildfire disease left rotting, infective corpses, oozing putrefaction, piled in the streets. Urban society was unable to cope and, in many places, essentially collapsed due to the number of victims (some cities lost 90 percent of their residents). Adding to the chaos, war between two of the era’s more significant powers — England and France — raged fitfully on and off after 1337. Commerce stagnated, especially in regard to food, causing famine. And perhaps cruelest of all, paroxysms of gruesome mass murders erupted as minorities were scapegoated. All in all, the Black Death had to have been hell on Earth, especially because no one — not the doctors, not the priests, and not the scientists of the age — had even the slightest idea of what was causing the calamity, how it was spread, or how it could be treated.

With such associations, a medical thriller titled Plague would certainly get people’s attention, especially because it wouldn’t be a historical novel that could be dismissed as “that was then; this is now.” Instead, it would be a novel of a horrendous contemporary event: a new Black Death. Of course, this plague won’t be a revisit of Y. pestis; we won’t see black buboes and excruciatingly painful suffering. But death is death, and in the plague I speak of there will be a lot of it, possibly equal in scale to the Black Death, but unfolding even faster. If that is the case, there will be a degree of worldwide societal chaos that taxes the imagination. And this is no far-fetched fiction. Despite all we know about biological science and despite all the wizardly powers of modern medicine, with its vast pharmacopeia and its array of sophisticated devices, this new plague might well happen. I say this not just as an author of medical thrillers, but as a medical doctor with four decades of experience in surgery, infectious disease, and emergency medicine.

Before I reveal the infectious agent of this putative coming plague, I would like to refer the reader to my 17th book, Contagion, published in 1995. A cautionary tale about the hazards of bioterrorism, the story involves a microbiology technician who is bent on starting an epidemic but who has to learn on the job, so to speak, about the critical importance of both virulence and transmissibility. He starts with Y. pestis, but his intended plague quickly fizzles with only a few victims because the necessary perpetrators of the scourge, rats and their disease-transmitting fleas, are not available. Undeterred, he finally comes to recognize that for a really scary epidemic to occur, it needs three things: the availability of a self-sustaining reservoir (usually an animal as an asymptomatic carrier), easy human-to-human transmissibility, and impressive virulence. By the end of the book he finds his agent: the influenza A subspecies H1N1 that caused the 1918-1919 Spanish flu, which he obtains from digging up in Alaska the frozen corpse of a victim of that dreadful pandemic.

Influenza A is perfect not only for my villain in Contagion but also as the infectious agent in Plague. It has a normal reservoir in the guts of birds, spreads via aerosols (the easiest and most efficient method of disease transmission), and can be amazingly virulent. By some estimates, as many people died from the Spanish flu as from the Black Death. Contemporary anecdotes of the Spanish flu describe asymptomatic people boarding the subway in Brooklyn and being dead by Manhattan. Such a death is hardly the torture of bubonic plague, but singularly impressive for its rapidity nonetheless. With today’s medical knowledge, such an event would be explained as a “cytokine storm,” in which the stricken individual’s immune system reacts against the invading virus with such ferocity and such inflammation in the victim’s lungs that death results from drowning in one’s own secretions.

I personally developed great respect for influenza as a 17-year-old when I contracted the avian H2N2 subspecies during the 1957 Asian flu pandemic — along with most everyone else at my high school. I suffered through an unpleasant illness that forever gave me a keen appreciation of the benign-sounding term “general malaise.” My respect for influenza was further reinforced by the 1968 Hong Kong flu pandemic, caused by H3N2. At the time, I was a surgical resident, confronting seriously ill patients in the intensive care unit struggling to breathe. So when a new and highly virulent subspecies of influenza, designated avian H5N1 flu, appeared in Southeast Asia in 2006 and quickly began to spread globally, I felt compelled to do something for myself and my family. Despite this new subspecies’s low human-to-human transmissibility, I stocked my isolated ski cottage with Tamiflu, antibiotics, ibuprofen, and N95 face masks. In the back of my mind was Isaac Newton’s flight to the countryside from plague-infested London in 1665.

All this begs the question: Could an influenza pandemic as bad as the one that struck in 1918 occur again? In our current state of world complacency and unpreparedness, I’d have to say absolutely yes, which is why my supplies are still in my ski cottage.

In fact, such an outbreak could be worse than the Spanish flu, even with the antiviral drugs we now have, the antibiotics that are today available for secondary infections, and the modern equipment in our intensive care units. For though medical science has learned a lot about viruses in general and influenza in particular since the World War I era, there is a long way to go. What we do know is that viruses are highly evolutionarily developed, quintessential parasites. To reproduce, they end up stealthily slipping inside and then hijacking the biomolecular machinery of other life forms, such as bacteria or mammalian cells, as they don’t have this machinery themselves. The problem, of course, is that the invaded entity is often killed in the process; for us humans, an attack from the influenza virus means that the cells lining our respiratory tract begin to die, as it is these cells that are selectively chosen. The flu is primarily a respiratory disease.

The fact that viruses such as influenza do their dirty work within cells is what makes treating them so much more difficult than treating bacterial diseases such as bubonic plague, which, in contrast, does most of its dirty work outside cells. In some respects the situation is akin to the difficulties of dealing with cancer in that killing infected cells can put normal cells in jeopardy, too. Modern medicine does have some antivirals in its armamentarium, but the highly evolved, wily viruses are quick to mount resistance. What it comes down to is that the best way to deal with influenza is to prevent it.

HULTON ARCHIVE/GETTY IMAGES

All of which brings us back to Plague, the book. And when it comes to the story line, current events are certainly lending a hand. With the Northern Hemisphere flu season beginning, today’s pandemic of H1N1 swine flu has justifiably received a lot of coverage because the organism has spread around the globe in a matter of months. But no matter how impressive its human-to-human transmissibility, this strain simply cannot be the influenza A subspecies for our novel. It’s just not hold-on-to-your-hat virulent enough. Although this disease has killed a few people, even a few seemingly healthy people, for the most part it causes a relatively mild illness, perhaps even milder than the normal yearly flu, which also kills its share of people.

But that is not the case with another flu subspecies that originally appeared in 2006 and which is now slowly spreading from Southeast Asia, particularly in its normal reservoir of aquatic birds. This is the subspecies designated HPAI A(H5N1), standing for “highly pathogenic avian influenza A of subtype H5N1,” or avian flu for short. Luckily it has very low transmissibility — which it makes up for with knock-your-socks-off lethality. A truly scary percentage, about 60 percent, of those humans unlucky enough to have contracted the illness over the last three years have quickly died.

You don’t have to be a rocket scientist to see the problem. Is there a chance these two subspecies could hook up and help each other? The answer is definitely yes, and that is the worry because one of influenza A’s most disturbing characteristics is its ability to indulge in recombination of its 11 genes, which are arranged on its eight pieces of RNA. This produces what is called genetic shift — in other words, transfer of entire genes or gene combinations, and hence traits. It will become key to our plot.

The actual Plague story might start with a farmer in China’s Guangdong province — call him Wang Lung — who takes some produce to Hong Kong in early September 2009, where we know H1N1 is already having a field day (the city reported 514 new cases of the disease in one 24-hour period this September). Let’s have Wang indulge in some social activity after he is finished with his business. During this activity he inhales aerosolized H1N1 and contracts the illness. Back home, still mostly asymptomatic yet massively contagious, he hand-feeds his pet duck, which is already harboring H5N1. The duck adds the H1N1 to its gut, and then the bird is returned to its cage, which is suspended over Wang’s bevy of pigs. Such an arrangement is frequent in Asia not only to save space but also to wrest as much caloric value out of the duck’s feed as possible by making the bird’s poop mix with the pigs’ slop.

For the influenza A virus, things couldn’t be better; pigs are its favorite brewing cauldrons. The avian H5N1 and the human-adapted swine H1N1 can enter pig cells simultaneously by the availability of separate pig epithelial cell receptors. And of course, this is what happens in Plague, giving the two viruses the opportunity to recombine with each other. During the millions or billions of replications of the virus inside the pigs, either the H5N1 gives its virulence to H1N1, or H1N1 gives its transmissibility to H5N1. Either way, a genetically shifted subspecies emerges, and the entire world faces something similar to what Europe faced in 1346 when the first Y. pestis-infected rat jumped ship in Crimea.

At that point, the story moves quickly as the deadly new agent races around the planet, thumbing its nose at all vain attempts to stop or contain it. Governments and individuals will do desperate things, some rational and others not so, like deploying the military to try to close borders or using firearms to keep possibly infected strangers at bay. Hospitals will be overwhelmed at first and later forced to lock their doors. To avoid interpersonal contact, people will hole up in their homes, causing government offices, schools, and businesses to close. Many public officials will be forced to quarantine themselves from a diseased population and retreat to undisclosed locations, which will only fuel the public panic. Riot police in biohazard suits (if there are even enough to go around) will increasingly be called upon to beat back waves of sick, scared, and helpless civilians, desperate for food, water, and medicine. This won’t just be the case in failing states like Somalia and Yemen, but also in successful ones like France and the United States.

But it will all be useless, and the fallout won’t be pretty. Normal travel and commerce will slow to a crawl or, in some areas, stop altogether. Some island countries will fare better than continents, but it will be temporary at best. Food distribution will be interrupted, and something akin to famine will ensue in certain parts of the world. Services of all sorts will fall off, including police protection, and marauding gangs and black-marketeers will materialize in a kind of hopeless, Darfurian Wild West. This will bring out the worst in humanity. Neighbor will turn against neighbor, fighting over newly scarce resources or simply out of fear and resentment. Old prejudices will rise to the surface, as minority groups — be they Jews, black Africans, Shiites, Hispanics, gays, or others — are blamed for bringing the plague into healthy communities. Long-simmering tensions between old rivals — Pakistanis and Indians, for example, or Iraqis and Iranians — will break out into new wars. Fanaticism, especially apocalyptic strains of the major religions, will reign. Plague will be a worldwide infectious holocaust.

The astute reader, however, will by now recognize that there is a slight problem with this story: the ending. A good cautionary novel, like any novel, only needs three things: a good beginning to pull in the reader, a good middle to keep the reader interested, and finally a good ending. And for a cautionary novel, a good ending is one that, after the readers have been scared to death by the beginning and middle, reassures them that they are not about to be victimized by a similar calamity — provided, of course, that certain appropriate steps are taken.

Unfortunately, in the very likely coming plague of influenza A, I don’t see the possibility of any particularly reassuring ending. There is certainly not going to be a Hollywood-style conclusion like the sudden appearance of a handsome couple that had been secretly toiling away in an isolated laboratory studying viruses and developing a cure while the rest of the world partied on in a false sense of security. There will be no Dustin Hoffman swooping in to save the day, as he did in the movie adaptation of my novel Outbreak. What I actually see is this modern Black Death, which could very well be 2009 H5N1/H1N1, obliviously raging around the world, acting as the Grim Reaper for countless folks, and then petering out on its own accord like the real Black Death and the real Spanish flu.

Perhaps the answer is to make Plague as long as War and Peace so that the reader will welcome any ending. But, kidding aside, I’d hope that Plague would be a super-best-seller, outselling even Dan Brown, James Patterson, and novels about vampires, for it might only be this novel’s success and, worse, its plausibility that would terrify and hence shock people out of their complacency about influenza A, a complacency made worse by false alarms such as the 1976 Fort Dix swine flu episode and the 2006 avian flu scare. Both fizzled without becoming pandemics, but journalists did not follow up their “sky is falling” blitz with explanations of why the pandemics failed to materialize yet had been very real threats.

Such complacency can be dangerous, and that is the case with influenza A. What the world needs — and considering the current swine H1N1 pandemic, it needed it yesterday — is a real plan for rapid expansion of its ability to produce vaccines against influenza A, so that output at any given time can be quickly ramped up to meet the sudden need associated with the appearance of a truly dangerous, new subspecies like our might-be novelistic killer H5N1/H1N1. Governments in both the developed and developing world must take on the job, as this is a worldwide threat. Although vaccines are a 20th-century technology, they remain the most powerful weapons we have for the very real 21st-century threat of influenza A. That is not to say that basic viral research should not also be encouraged and strongly subsidized. The more we know about these mysterious entities the better, as there surely will be far more efficacious small-molecule antivirals in the future as well as antiviral biologics, which might even have more promise in the long run.

Now that I have written this article and gotten myself terrified all over again, I’d better do two things. One is to head up to my ski cottage and make sure all the supplies are in order as they might be needed soon, and second, I’d better get working on Plague. Time is short. Like everyone else in the world, my family and I are going to be in dire need of a rapidly produced, effective vaccine when influenza A gets its ducks in a row, so to speak, and combines transmissibility with virulence.