by Nathan Wolfe
What we do know about HCV is that it’s on the move. During the past hundred years, the virus has spread rapidly through blood transfusions, the use of unsterilized needles to deliver medicines, and through injection drug use. But genetic analyses by Pybus and others have shown that the virus is somewhere between five hundred and two thousand years old, so these contemporary technologies likely do not tell the whole story. Essentially, it seems there were places, most likely in Africa and Asia, where HCV existed on a much smaller scale prior to the massive expansion that needles and injections permitted.
Since HCV is not effectively transmitted sexually or by normal contact between people, other routes of transmission must somehow explain how it persisted many centuries ago. The virus can be transmitted from mother to offspring, but that too is an unlikely explanation since so-called vertical transmission is not particularly efficient. Certainly, cultural practices like circumcision, tattooing, ritual scarification, and acupuncture probably played a role. In an interesting twist, Pybus and his colleagues have used a combination of geographic information systems (to which we’ll return in chapter 10) and mathematical models of disease spread to show that another possibility would be some kinds of blood-feeding insects. These insects could have contributed to historical transmission by acting as natural contaminated needle sticks and carrying virus-infected blood from one host to the next on their mouthparts.
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Unsafe injection practices contributed to the spread of much more than HCV in the twentieth century. In a series of thoughtful articles, the Tulane virologist Preston Marx and his colleagues have argued that injections helped launch the HIV pandemic. Some mysteries still persist on the early spread of HIV. While the genetic data points to an early twentieth-century jump of the chimpanzee virus that would become HIV, understanding what sparked its true global spread in the 1960s and 1970s remains up for debate. For many scientists, the expanding air routes discussed in chapter 6 are sufficient to explain this phenomenon. But Marx and his colleagues add another potential cause.
The period that coincides with the global spread of HIV also coincided with a dramatic expansion in the availability of cheap injection systems. Prior to the 1950s, syringes were handmade and relatively expensive. But in 1950 machines began churning out glass and metal syringes, and in the 1960s disposable plastic syringes became available. Effective ways to inject drugs and vaccines contributed to the increased use of injections for medications and vaccines in the late nineteenth century. Often medical campaigns used the same unsterilized needle to vaccinate hundreds or more individuals at a time, setting up unique conditions that could potentially launch epidemics.6 An individual hunter who had been infected with a virus from a hunted chimpanzee could theoretically transmit that virus to many other individuals in just this way, the conditions under which Marx and his colleagues think that the global launch of HIV began in earnest.
Smallpox vaccinations being administered outside Kintambo Hospital during a smallpox outbreak in Leopoldville, Republic of the Congo, 1962. (© WHO Archives)
It’s important to note that Marx’s work is distinct from the oral polio vaccine hypothesis for HIV origins that appeared first in a Rolling Stone article in 1992. Marx and his colleagues suggest that unsafe injection practices helped to spread HIV; they do not, however, argue that these techniques contributed to its introduction from chimpanzees to humans. Alternately, the OPV hypothesis argued that since oral polio vaccine was grown on fresh primate tissues HIV jumped directly from such tissues to vaccines and spread as they were administered.
The OPV hypothesis is no longer taken seriously by the scientific community for four primary reasons: (1) retrospective analysis of the original vaccine stocks showed no evidence they were infected by the chimpanzee virus that seeded human HIV; (2) genetic analyses suggest HIV has been around for roughly one hundred years, far predating the period of OPV use; (3) the chimpanzee strains in the region where the purportedly contaminated vaccine stocks were produced are distinct from the chimpanzee virus that seeded HIV; (4) the pervasive human exposure to these viruses through hunting and butchering of wild primates provides a more parsimonious explanation for the distribution of the multiple primate viruses in the HIV family that have crossed into humans.
Further highlighting the end to the OPV debate in 2001, four separate articles published in the leading scientific journals Nature and Science laid it to rest. Doing so was important for a number of reasons, including the fact that the hypothesis was misinterpreted in a way that severely compromised ongoing vaccine campaigns, which use vaccines that are universally acknowledged as both safe and effective. An accompanying editorial to the Nature articles sums it up well: “The new data may not convince the hardened conspiracy theorist who thinks that contamination of OPV by chimpanzee virus was subsequently and deliberately covered up. But those of us who were formerly willing to give some credence to the OPV hypothesis will now consider that the matter has been laid to rest.” More blunt were the words of my colleague Eddie Holmes, one of the world’s most distinguished virologists, who said, “[The] evidence was always flimsy, and now it’s untenable. It’s time to move on.”
While unsafe injections may very well have contributed to HIV’s spread, as they did with HCV, they did not lead to its introduction. This, however, doesn’t mean that we should ignore vaccine safety.
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Right now around one in fifteen individuals reading this book are infected with a virus that jumped into them from a monkey. To be more specific, if you’re one of these individuals, you’re infected with SV40, a virus of Asian macaques, and you acquired it from a contaminated vaccine.
During the 1950s and 1960s, poliovirus vaccines were grown on cell cultures derived from macaque kidneys. Some of these kidneys were infected with SV40, which then contaminated the vaccines. The results were dramatic.
In the United States alone, up to 30 percent of the poliovirus vaccines in 1960 were contaminated with the virus. From 1955 through 1963, roughly 90 percent of American children and 60 percent of American adults were potentially exposed to SV40—an estimated ninety-eight million people. And the virus is not a trivial one. It causes cancer in rodents and can make human cells living in laboratory cell culture reproduce abnormally, a worrying sign that they may have the potential to cause cancer.
The idea that more than half of the American population was placed at risk from infection with a novel monkey virus had a notable effect on science, and epidemiologists scrambled to determine if the individuals who’d received the virus had cancer. Fortunately, while the evidence is still debated to this day, it appears clear that SV40 did not pose a serious risk for cancer and, perhaps even more importantly, it didn’t have the potential to spread. We dodged a major bullet.
But because a single vaccine stock can be administered to thousands of individuals, we must remain vigilant. Contamination of a vaccine stock or multiple vaccine stocks can contribute to millions of infections with new viruses, just as we witnessed in the 1950s and 1960s with SV40. This does not mean that vaccines are not safe. They are! And they are essential to protect billions of people all over the globe. Health monitoring and vigilance in vaccine production has also never been greater. In a recent and important study, my collaborator Eric Delwart, a San Francisco–based scientist who perfects techniques to discover unknown viruses, showed that some of these new approaches, which we’ll discuss in chapter 10, can be applied to even further increase the safety of vaccines. The risks associated with current vaccines are substantively less than the risks associated with the diseases they protect against. Yet the risks are not zero. We must make sure that when we knowingly connect animal and human tissues—particularly on an industrial scale—we do so with the utmost care.
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Since the 1920s when Voronoff conducted his monkey gland operations, our planet has witnessed an explosion in the use of transfusions, transplants, and injections. These wonderful technologies have helped rid u
s of some of our deadliest diseases. Yet they have also provided powerful new biological connections between individuals, which sometimes serve as an unwelcome by-product of these beneficial tools. They provide bridges on which microbes can move, bridges that did not exist until now. They pull humans together into a completely new kind of intimate species, one unique to life on our planet and one that fundamentally changes our relationship with the microbes in our world.
8
VIRAL RUSH
Imagine the following. In a large city, let’s say Manila, residents in a densely packed residential district report foul odors to local environmental health offices. Some hours later small pets begin to fall sick. Veterinarians confirm an uptick in the number of sick animals in the neighborhood. Around twenty-four hours after the first calls reporting the strange smell, local physicians note an increase in patients reporting blisters and ulcers on their skin. A few individuals report nausea and vomiting.
At around forty-eight hours the first patients hit the emergency rooms. They have fever, headache, shortness of breath, and chest pain. Some of them appear on the verge of going into shock. At the same time some of the individuals with nausea are getting worse—they’re experiencing bloody diarrhea.
As the days go on the numbers increase. By the end of the first week, nearly ten thousand individuals have been hospitalized. Over five thousand of these people have died painful deaths. At the end they can barely breathe—their skin blue from lack of oxygen. Eventually, septic shock and severe brain inflammation strike, killing most of them. As the number of deaths increase, journalists flock to the scene. Manila residents attempt a mass exit, and despite the best intentions of the government, the city verges on the brink of widespread and crippling panic.
The case I’ve outlined is a hypothetical one. But just barely. In June 1993 the Aum Shinrikyo cult aerosolized a liquid suspension of Bacillus anthracis from the top of an eight-story building in the Kameido neighborhood in the eastern part of Tokyo. They launched a bioterror assault on one of the largest and most densely packed cities in the world.
The good news is that they failed. An analysis written in 2004 states that their choice of a relatively benign anthrax strain, low concentrations of the bacterial spores, an ineffective dispersal system, and a clogged spray device all served to make the 1993 incident in Tokyo a flash in the pan. No humans got sick, although some pets appear to have died as a result of the release.
If the Aum Shinrikyo cult had come across a more deadly version of anthrax and used even slightly better dispersal systems, things could have turned out quite similar to our hypothetical scenario above. We know that the apocalyptic cult had looked for more than just anthrax. The group set up multiple laboratories and dabbled in cultivating many agents. They played with botulinum toxin, anthrax, cholera, and Q fever. In 1993 they led a large group of doctors and nurses to the Democratic Republic of Congo, ostensibly on a medical mission, but actually in an attempt to bring back an isolate of the Ebola virus for use in their grim operations.
Asahara Shoko, the founder of Aum Shinrikyo, praying with followers in India. (© Georges de Keerle / Sygma / Corbis)
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Even if they had succeeded in their anthrax release, the deaths and disruption caused by Aum Shinrikyo would have been restricted to the individuals exposed to the spores they released. Anthrax does not transmit from person to person. Though deadly, it is not contagious. But anthrax is only one of many agents that could be used by terrorist groups. Bioterror is among the most serious concerns for security experts. It is an ideal tool for the weaker parties in so-called asymmetrical warfare, where enemies differ significantly in the resources and firepower they can draw on for battle. Even a weak opponent, like a terrorist group, can wreak havoc with the right combination of microbe and dispersal.
Microbes hold great potential for terror groups. They are much easier to gain access to than chemical or nuclear weapons. And, critically, unlike either chemical or nuclear weapons, they can spread on their own. They can go viral, which is something that neither deadly sarin gas nor a dirty bomb could accomplish. Perhaps the only comparable situation is the long-term horror of some nuclear fallout expressing itself in generations of mutated offspring and high rates of cancer, as seen in Hiroshima. But those insidious effects are environmental and thus relatively slow. A fast-acting, fast-spreading viral weapon would have that impact over days, not decades.
It would be a mistake to underestimate the risk for bioterror, and most who study it contend that it is just a matter of time before it’s unleashed on a human population.
The fact that deadly microbes can be made to proliferate under lab conditions, whether in legitimate laboratories or fly-by-night terrorist workshops, adds another dimension to global pandemic risk. While exceptionally unlikely, if terrorists ever got their hands on one of the few remaining vials of smallpox, the results would be devastating. While smallpox has been eradicated in nature, two sets of smallpox stocks remain under lock and key—one at the U.S. Centers for Disease Control in Atlanta and one in the State Research Center of Virology and Biotechnology (VECTOR) in Koltsovo, Russia. Both facilities have high containment bio-safety level 4 facilities. There’s been debate about possibly destroying the remaining stocks in these labs, but to date the decision has been deferred because of the potential benefit of access to live virus for the production of vaccines and drugs.
Interestingly, in 2004 scabs from suspected smallpox were found in Santa Fe, New Mexico, in an envelope labeled as containing scabs from vaccination. The finding points to the possibility of other unknown lots of smallpox existing in a lab freezer or somewhere else. If they were released purposely or accidentally, the consequences would be devastating. Since smallpox has been eradicated, we no longer inoculate against it. So, for smallpox, such a release would be a perfect storm. For us, it would be catastrophe.
Another risk is what is increasingly referred to as “bioerror.” Unlike bioterror, bioerror occurs when an agent is released accidentally but spreads widely. In 2009 Don Burke, the mentor of my postdoctoral fellowship, published a paper on the emergence of influenza viruses. In it he analyzes a variety of influenza viruses that have spread in humans. One of the more interesting examples is the November 1977 epidemic that affected the Soviet Union, Hong Kong, and northeastern China. The virus involved was nearly identical to a virus from an outbreak over twenty years before, and it hadn’t been seen since. Don and his colleagues echoed earlier research on the virus noting that the most likely explanation was that a lab strain had been accidently reintroduced into the lab workers and had spread from there.
Over the coming decades, as it becomes possible for the masses to have access to detailed biological information and the techniques to make or grow simple microbes, the probability of bioterror and bioerror will only grow. While most people normally think of biology as occurring primarily in secure labs, this may not always be the way it works. In 2008 two teenage girls from New York City sent away specimens of sushi to the Barcode of Life Database project, a fascinating early program to simplify and standardize genetic testing. They wanted to determine if the high-priced fish that they were buying was what it was sold as. They found that often it wasn’t. But they also found a way to get genetic information that until then was only available to scientists.
But the student sushi study was about more than discovering that some of the sushi vendors in New York City rip off their clients. It was one of the first notable examples of nonscientists “reading” genetic information. Early in the information technology revolution, only computer programmers could read and write code, like HTML. Then nonprogrammers began to read code, then write code, and now we all regularly read and write code on blogs, wikis, and games. As with any system of sharing information, what starts as something highly specialized often becomes universal. In the not-too-distant future, the small group of people conducting do-it-yourself biology may become the norm. In that world the need for monitoring to con
trol bioerror will be more than just theoretical. In a famous prediction made by Sir Martin Rees, the former president of the Royal Society of London warned, “… by the year 2020 an instance of bioerror or bioterror will have killed a million people.” The chemistry to create a pipe bomb or a meth lab becomes the biology to create a viral bomb.
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In this chapter we will explore the next big killers—the microbial threats that keep me awake at night. Certainly, bioerror and bioterror are among them. The frequency of both of these threats will rise in the coming years, but at least for the moment, the greatest risks we face are still those that exist in nature.
In some biological arenas, the age of discovery is over. We know the rate at which we’ll discover new species of primates, for example, will be very low indeed. For viruses, that’s not the case. My collaborator Mark Woolhouse, one of the early leaders in the field of emerging infectious diseases, has put together real numbers on this. He and his colleagues have plotted the rate of discovery of new viruses since 1901. Their analysis suggests we’re nowhere near the end of viral discovery; we’ll find on average one or two viruses per year over the next ten years, and that’s likely a conservative estimate.
One of the reasons contemporary scientists are finding new viruses is that we’re looking. Studies like the ones conducted by my research group, which we’ll discuss in the coming chapters, actively seek to find unknown viruses in humans and new viruses lurking in animals that might be the next to jump. Genetic techniques for uncovering the unknown microbial world are also advancing, which makes finding these new agents easier and faster than ever. But intensive research and heightened attention are not the only reasons we’re seeing new things.