The Viral Storm (3 page)

Amazingly, in a time when we can sequence an entire human genome for under ten thousand dollars and build massive telecommunications infrastructures that will soon make cell phones available to most people on the planet, we still understand surprisingly little about pandemics and the microbes that cause them. We know even less about how to predict or prevent pandemics before they spread from small towns to cities and the rest of the world. As I’ll argue in part II, pandemics will increase in frequency in the coming years as the connections between human populations and the animals in our world continue to grow. Whether it’s a mosaic virus with the deadliness of H5N1 and the potential to spread like H1N1, a resurgent SARS, a new retrovirus like HIV, or perhaps most frighteningly, a completely novel microbe that blindsides us, microbial threats will grow in the coming years in their ability to plague us, kill people, destroy regional economies, and threaten humanity in ways more severe than the worst imaginable volcanoes, hurricanes, or earthquakes.

A storm is brewing. The objective of this book is to understand this coming storm—to explore the nature of pandemics, to understand where they come from and where they are going. But it will not paint a completely grim picture. In the one hundred years since we first discovered viruses, humans have come a long way in understanding them. Much hard work remains. Yet if we do it well, we will harness the numerous technological advances of our time that provide tools to predict pandemics—just as meteorologists predict the course of hurricanes—and ideally prevent them from occurring in the first place. This is the Holy Grail of modern public health, and in the coming pages, I will argue that it is within our grasp.

PART I

GATHERING CLOUDS

1

THE VIRAL PLANET

Martinus Beijerinck was a serious man. In one of the few images that remain of him, he sits in his Delft laboratory in the Netherlands, circa 1921, just a few days before his reluctant retirement. Bespectacled and in a suit, he’s presumably as he’d like to be remembered—among his microscopes, filters, and bottles of laboratory reagents. Beijerinck had some peculiar beliefs, including the idea that marriage and science were incompatible. According to at least one account, he was verbally abusive to his students. While rarely remembered in the history of biology, this strange and serious man conducted the pivotal studies that first uncovered the most diverse forms of life on Earth.

Among the things that fascinated Beijerinck in the late nineteenth century was a disease that stunted the growth of tobacco plants. Beijerinck was the youngest child of Derk Beijerinck, a tobacco dealer who went bankrupt due to crop losses caused by this blight. Tobacco mosaic disease causes discoloration in young tobacco plants, leading to a unique mosaic pattern on leaves and radically slowing the growth of the adult plants. As a microbiologist, Beijerinck must have been frustrated by the unclear etiology of the disease that had wiped out his father’s business. Despite the fact that it spread like other infections, microscopic analysis did not reveal a bacterial cause of disease. Curious, Beijerinck subjected the fluids of one of the diseased plants to intense filtration using a fine-grained porcelain filter. He then demonstrated that even after such filtration the fluids retained their capacity to infect healthy plants. The tiny size of the filter meant that bacteria, the usual suspects for transmissible disease at the time, would be too large to pass through. Something else must have caused the infection—something unknown and considerably smaller than everything else recognized to be alive in his time.

Dr. Martinus Beijerinck.
(
Undated photo
)

Unlike his colleagues, many of whom believed a bacteria would emerge as the cause, Beijerinck concluded that a new form of life must cause tobacco mosaic disease.
1
He named this new organism the
virus
, a Latin word referring to poison. The word
virus
had been around since the fourteenth century, but his use was the first to link it to the microbes to which it refers today.
2
Interestingly, Beijerinck referred to viruses as “contagium vivium fluidum,” or “soluble living agent,” and felt they were likely fluid in nature. That is why he used the term
virus
—or poison—to denote its “fluidity.” It wasn’t until later work with the polio and foot-and-mouth-disease viruses that the particulate nature of viruses was confirmed.

In Beijerinck’s time a new microscopic perspective began revealing itself to scientists. Looking through microscopes and applying gradually smaller filters, these microbiologists realized something that continues to amaze us today: shielded from our human-scaled senses is a wide, teeming, startlingly diverse, unseen world of microbial life.

*   *   *

I teach a seminar at Stanford called Viral Lifestyles. The title was meant to evoke curiosity among prospective students but also describe one of the course’s objectives: to learn to envision the world from the perspective of a virus. In order to understand viruses and other microbes, including how they cause pandemics, we need to first understand them on their own terms.

The thought experiment that I give my students on the first day is this: imagine that you have powerful glasses allowing you to perceive any and all microbes. If you were to put on such magical bug-vision specs, you would instantly see a whole new, and very active, world. The floor would seethe, the walls would throb, and everything would swarm with formerly invisible life. Tiny bugs would blanket every surface—your coffee cup, the pages of the book on your lap, your actual lap. The larger bacteria would themselves teem with still smaller bugs.

This alien army is everywhere, and some of its most powerful soldiers are its smallest. These smallest of bugs have integrated themselves, quite literally, into every stitch of the fabric of earthly life. They are everywhere, unavoidable, infecting every species of bacterium, every plant, fungus, and animal that makes up our world. They are the same form of life that Beijerinck found in the late days of the nineteenth century, and they are among the most important of the microbial world. They are viruses.

*   *   *

Viruses consist of two basic components, their genetic material—either RNA or DNA—and a protein coat that protects their genes. Because viruses don’t have the mechanisms to grow or reproduce on their own, they are dependent on the cells they infect. In fact, viruses
must
infect cell-based life forms in order to survive. Viruses infect their host cells, whether they are bacterial or human, through the use of a biological lock-and-key system. The protein coat of each virus includes molecular “keys” that match a molecular “lock” (actually called a receptor) on the wall of a targeted host cell. Once the virus’s key finds a matching cellular lock, the door to that cell’s machinery is opened. The virus then hijacks the machinery of that host cell to grow and propagate itself.

Viruses are also the smallest known microbes. If a human were blown up to the size of a stadium, a typical bacterium would be the size of a soccer ball on the field. A typical virus would be the size of one of the soccer ball’s hexagonal patches. Though humans have always felt virus’s effects, it’s no wonder it took us so long to find them.

Microbes, Above: In detail; Below: To scale.
(
Dusty Deyo
)

Viruses, the most diverse forms of life, remained completely opaque to humans until a meager one hundred years ago with Beijerinck’s discovery. Our very first glimpses of bacteria came a little under four hundred years ago when Antonie van Leeuwenhoek adapted the looking glasses of textile merchants to create the first microscope. With it, he saw bacteria for the first time. This finding represented such an incredible paradigm shift that it took the British Royal Society another four years before it would accept that the unseen life forms were not merely artifacts of his unique apparatus.

Our scientific understanding of unseen life has proceeded pitifully slowly. Compared to some of the other major scientific breakthroughs over the last few thousand years, our understanding of the dominance of unseen life occurred only recently. By the time of Jesus, for example, we already understood critical elements of how the Earth rotated, its rough size, and its approximate distance to the sun and moon—all fairly advanced elements in understanding our place in the universe. By 1610 Galileo had already made his first observations using a telescope. Van Leeuwenhoek’s microscope came fifty years after that.

L: Replica of van Leeuwenhoek’s microscope, 17th century; R: van Leeuwenhoek’s microscope in use.
(
L: Dave King / Getty Images; R: Yale Joel / Getty Images
)

It is hard to overstate the paradigm shift that van Leeuwenhoek’s discovery represents. For thousands of years humans had recognized the existence of planets and stars. Yet our understanding of unseen life and its ubiquity began only a few hundred years ago with the invention of the microscope. The discovery of novel life forms continues to this day. The most recent novel life form to be uncovered is the unusual prion, whose discovery was acknowledged with a Nobel Prize in 1997. Prions are an odd microscopic breed that lack not only cells but also DNA or RNA, the genetic material that all other known forms of life on Earth use as their blueprint. Yet prions persist and can be spread, causing, among other things, mad cow disease. We would be arrogant to assume that there are no other life forms remaining to be discovered here on Earth, and they are most likely to be members of the unseen world.
3

*   *   *

We can roughly divide known life on Earth into two groups:
noncellular
life and
cellular
life. The major known players in the noncellular game are viruses. The dominant cellular life forms on Earth are the prokaryotes, which include bacteria and their cousins, the archaea. These life forms have lived for at least 3.5 billion years. They have striking diversity and together make up a much larger percentage of the planet’s biomass than the other more recognizable cellular forms of life, the eukaryotes, which include the familiar fungi, plants, and animals.

Another way of categorizing life is this: seen and unseen. Because our senses detect only the relatively large things on Earth, we are parochial in the way that we think about the richness of life. In fact, unseen life—which combines the worlds of bacteria, archaea, and viruses as well as a number of microscopic eukaryotes—is the truly dominant life on our planet. If some highly advanced extraterrestrial species were to land on Earth and put together an encyclopedia of life based on which things made up most of Earth’s diversity and biomass, the majority of it would be devoted to the unseen world. Only a few slender volumes would be dedicated to the things we normally equate with life: fungi, plants, and animals. For better or worse, humans would make up no more than a footnote in the animal volume—an interesting footnote but a footnote at best.