The Viral Storm (27 page)

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When people ask me whether or not I’m optimistic about the future of predicting pandemics, the answer is always a resounding yes. Given the first two-thirds of this book, you may wonder if my optimism is warranted. A steady wave of interconnectedness among humans and animals has created a perfect storm for new pandemics. That is true. Yet the interconnectedness among humans that now exists through communication and information technology gives us unprecedented capacity to catch outbreaks early, which, when combined with amazing advances in our ability to study the diversity of the tiny life forms that cause epidemics, certainly makes optimism warranted.

What will win out in the end? Will pandemics sweep through the human population destroying millions of lives? Will technology and science ride in to the rescue?

11

THE GENTLE VIRUS

All living organisms focus huge amounts of energy on having successful offspring. In humans, this means breastfeeding and constant care of babies for the first few years of their lives. In other organisms, like sea tortoises, the energy is spent not on care for existing offspring but in creating the conditions necessary to successfully launch hundreds of instantly self-sufficient infants—accumulating nutrients to place in eggs, traveling to the right place to lay eggs, and burying eggs in sand to protect them from predators. Whatever they may look like, parents want their kids to succeed, and they deploy a range of techniques to aid them in that objective.

Among the concerned parents out there are wasps. Two families of wasps go to an extraordinary measure to protect their offspring. These wasps, of the braconid and ichneumonid families, lay their eggs on the backs of caterpillar larvae. The eggs then eat the flesh of the caterpillar as they grow. This is actually a fairly common setup on our planet, with thousands of such relationships in existence. There is an evolutionary tension between the caterpillar and the wasp. The caterpillar’s defenses change over time to thwart the wasp eggs, and the wasp eggs develop the capacity to counteract or skirt the caterpillar’s defenses, and so on.

Braconid wasp eggs on a caterpillar larva.
(
James H. Robinson / Photo Researchers, Inc.
)

In their battle to win this evolutionary arms race, the female braconids and ichneumonids do something not known among other wasps that live in this way: they coat their eggs in a special substance before they lay them on the back of a caterpillar. Slowly, this potent substance kills the caterpillar, leaving the eggs to grow unrestricted on the bounty that remains.

The wasp mothers’ truly amazing substance is not a plant toxin or a venom. It’s a concentrated dose of virus. This virus, a member of the polydnavirus family, harmlessly infects the wasp but unleashes a range of consequences in the caterpillar. It replicates in the wasp’s ovaries and is injected, together with the wasp’s eggs, into the caterpillar. The virus returns the favor by suppressing the host caterpillar’s immune system and causing severe disease and even death to the caterpillar, thereby protecting the eggs. The wasp helps the virus, and the virus helps the wasp.

Viruses operate along a continuum with their hosts: some harm their hosts, some benefit their hosts, and some—perhaps most—live in relative neutrality, neither substantively harming nor benefiting the organisms they must at least temporarily inhabit for their own survival.

In this chapter we’ll shift gears. Rather than discuss the harm viruses can cause, we’ll focus on how they can assist us in the battle against infectious and other diseases. The goal of public health should not be to eradicate all viral agents; the goal should be to control the deadly ones.

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Perhaps the most profound way that viruses have assisted us in the fight against pandemics has been in the case of vaccines. And there is no better example of this partnership than our relationship with the cowpox virus.

In the late eighteenth century, the noted English scientist Edward Jenner became fascinated with the observation that milkmaids somehow seemed to avoid becoming infected with smallpox. On May 14, 1796, taking a bit of a leap, Jenner inoculated James Phipps, the eight-year-old son of his gardener, with cowpox that he’d scraped from the hand of a young milkmaid named Sarah Nelmes. She had acquired the virus from a cow named Blossom, whose hide you can apparently still see if you visit St. George’s medical school in London.

Young James Phipps got mildly sick, a bit of fever and some discomfort but that was all. After James recovered, Jenner went on to inoculate the boy with a small amount of the actual smallpox virus.
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The smallpox did nothing. The effect, which Jenner then replicated in others, would go on to be one of the most profound findings in human history. He had developed a vaccine to prevent smallpox, one of the worst scourges of humankind. The discovery is credited by some as saving more lives than any other discovery in history.

The vaccines that were created as a result of Jenner’s work eventually led to the eradication of smallpox from the planet. I remember seeing one of the original documents certifying that smallpox had been eliminated. It was in the Johns Hopkins office of D. A. Henderson, who had led the WHO’s global smallpox eradication campaign. D. A. had kindly lent me one of his largely unused offices at Hopkins as a staging ground to accumulate the supplies I’d need to start our work monitoring outbreaks in central Africa. I remember thinking to myself about how important eradication was and how it had been accomplished.

We credit the eradication of smallpox to a vaccine. But it’s worth examining this further. The vaccine that allowed us this triumph was actually an unadulterated virus that we harnessed and used for our benefit. In fact, even the word
vaccine
itself derives from the Latin term for cowpox, or
variolae vaccinae
, where
variolae
means “pox” and
vaccinae
means “of cows.” In other words, at its very heart, the concept of a vaccine is the productive use of one virus to fight another.

Parchment signed at Geneva on December 9, 1979, by the members of the Global Commission for Certification of Smallpox Eradication.
(
World Health Organization
)

Because cowpox is close enough to smallpox that it leads to immunity but distinct enough that it does not cause disease, it becomes the ultimate weapon to fight the plague. It leads to immunity without causing death. Those first infected with cowpox are safely protected against the related smallpox. That is what a vaccine does.

Rather than think about vaccines as creative constructs of humans, another way of viewing them is as partnerships. Just as the wasp forms a mutualism with the polydnavirus to help protect its eggs, Jenner discovered that we could use cowpox to protect our children.

Although we think of vaccines as sophisticated examples of human-developed technology, the vast majority of vaccines in current use are viruses or parts of viruses. Some, like the smallpox vaccine, are simply live viral vaccines. In other words, they’re just viruses we inject into people (or animals) to create an immune response that will protect against another more deadly virus. Others, like the oral polio vaccine and the measles, mumps, rubella (MMR) vaccine, are
attenuated virus
vaccines—live viruses that we have bred in the lab to make less deadly and used in effectively the same way. Some, like the influenza vaccines, are
inactivated virus
vaccines—viruses we have made incapable of reproducing themselves yet can elicit an appropriate immune response. They are still viruses. Others, like the hepatitis B vaccine and human papillomavirus (HPV) vaccine, use selected parts of the virus. The point is that pretty much the entire contemporary science of vaccinology uses viruses themselves to protect against other viruses. Safe viruses are some of the best friends we have in fighting the deadly ones.

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The utility of using microbes to protect us against infectious diseases seems clear enough. But can microbes help us to control chronic diseases? The answer increasingly is yes.

Introductory courses in public health make firm distinctions between infectious and chronic diseases. They place infectious diseases like HIV, influenza, and malaria on one side of the aisle and chronic diseases like cancer, heart disease, and mental illness on the other. Yet these distinctions do not always hold up to greater scrutiny.

In 1842 Domenico Rigoni-Stern, an Italian physician, looked at the patterns of disease in his hometown of Verona. Among the things Rigoni-Stern noticed was that the rate of cervical cancer appeared to be substantially lower among nuns than married women. He also noted that behavioral factors like age at first sexual intercourse and promiscuity seemed related to the frequency of the cancer. He concluded that the cancer was caused by sex.

While sex itself did not end up being the cause of cervical cancer, Rigoni-Stern was on exactly the right track. In 1911 the young scientist F. Peyton Rous injected tissue from a chicken tumor into healthy chickens, while he was working at the Rockefeller Institute for Medical Research (now the Rockefeller University). Rous found that the injected tissue caused precisely the same type of cancer in the healthy chicken recipient. The cancer was transmissible! The virus that causes that chicken cancer—now called Rous sarcoma virus after its discoverer—was the first virus demonstrated to cause any cancer, and it won Rous the Nobel Prize. It would not be the last virus found to have a connection to cancer.
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Dr. Francis Peyton Rous, ca. 1966.
(
New York Public Library / Photo Researchers, Inc.
)

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In the 1970s the German physician-scientist Harald zur Hausen had a hunch about the cause of cervical cancer. Following the work of Rigoni-Stern and Rous, zur Hausen suspected it was caused by an infectious agent. Unlike the scientists of his time who thought that the cause was herpes simplex virus, zur Hausen believed that the virus that caused genital warts, the papilloma virus, was the culprit. Zur Hausen and his colleagues spent much of the late 1970s characterizing different human papillomaviruses from warts of various sorts and looking to see if they could be found in tissue samples that came from biopsies of women with cervical cancer. In the early 1980s they finally hit pay dirt. They discovered two papillomaviruses, HPV-16 and HPV-18, in a high percentage of biopsy specimens. Today, these two viruses alone are considered to account for up to 70 percent of cervical cancer.

Zur Hausen, like his predecessor Rous, received the Nobel Prize for his breakthrough. And the research they conducted went on to form the foundation for a vaccine against cervical cancer. In June 2006, Merck received approval from the US Food and Drug Administration (FDA) to market Gardasil, an HPV vaccine. Like the other vaccines discussed earlier, Gardasil uses elements of the human papillomavirus itself to elicit an immune response that prevents those inoculated from being infected if they later have contact with the actual virus. In the case of Gardasil, the vaccine utilizes virus-like particles (VLPs) that look like the actual viruses but have no actual genetic material so they cannot replicate themselves. And the vaccine works. By preventing infection from the types of human papilloma virus that cause cervical cancer, the vaccine effectively prevents most of the deadly cancer.