by Nathan Wolfe
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We live in a world fraught with risk from new pandemics. Fortunately, we also now live in an era with the tools to build a global immune system. This huge but simple idea is that we should and can be doing a much better job to predict and prevent pandemics. But the really bold idea is that we could reach a point where we become so good at this that we mark the “last plague”—a time when we are so capable of catching and stopping pandemics that we won’t even need the word.
NOTES
INTRODUCTION
1 Throughout this book, I’ll generally refer to microbes rather than the more appropriate but clunky term microorganisms, which includes all microscopic organisms. Unless otherwise specified, the term microbe will be used as shorthand to refer to the full range of microscopic organisms whose groups include species that can infect and spread in humans, namely: viruses, bacteria (and their siblings, the archaea), parasites, and the enigmatic prions, all discussed in detail in chapter 1. While no doubt irritating to some of my microbiologist colleagues, who exclude parasites from the term microbe for sensible taxonomic reasons, and haven’t quite decided what to do with prions, I hope they will excuse me in this attempt to increase the ease of reading for a general audience.
2 There is some debate about whether viruses themselves should be considered living, while there is no debate about the other microbes: bacteria, archaea, or parasites, all of which are clearly living organisms. The debate, in my opinion, is a semantic and largely unimportant one. Viruses are completely dependent on other organisms for elements of their life cycle, but that is no different than the rest of known life forms, none of which, to my knowledge could live in a world devoid of other life. Either way, it is clear that viruses are part of the living systems of our planet, and for those intent on engaging in this debate, my reference to viruses as living can be interpreted in that way. I will use the same inclusive convention with prions, despite the existence of similar debates on them.
3 In fact, the death rate for the 1918 H1N1 infection itself may be even lower than 2.5 percent, as many deaths were probably caused by secondary bacterial infections—deaths that could at least partially be prevented today due to antibiotic use. Deaths from H5N1, on the other hand, are largely due directly to viral disease.
4 In the case of rabies, vaccine delivered in short order after infection can successfully prevent death, but without it death is largely inevitable.
5 Like H5N1, the “swine flu” that began in 2009 suffers from terminology problems. Called H1N1/09 virus by the WHO and 2009 H1N1 influenza among other things by the CDC, here I will refer to it simply as H1N1, which is the commonly used shorthand among the scientists who study it. As with H5N1 and all influenza viruses, H1N1 has its ultimate origins in bird populations.
1. THE VIRAL PLANET
1 There are some who consider Dmitri Ivanovski the “father of virology” because he did similar research with tobacco mosaic virus six years earlier. But perhaps because he wasn’t the first to name the new entities (i.e., viruses) or did not as widely disseminate his findings as Beijerinck, he is not generally credited with their discovery.
2 In addition to his pivotal work as the first virus hunter, creating the foundations of what would later become the field of virology, Beijerinck remains an unsung hero for those studying the relationships between plants and bacteria. Among other notable findings, he discovered nitrogen fixation, whereby bacteria living in the roots of legumes make nitrogen available to plants through a set of biochemical reactions critical for the fertility of agricultural soil systems.
3 Among the most intriguing possibilities is that non-DNA/non-RNA forms of life, which originated completely independently of our own RNA/DNA-based life, might persist undetected on Earth. These life forms, referred to as shadow life, would almost certainly be microscopic. If discovered, they might best be described as aliens, and some believe that if we are to discover aliens within our lifetimes, looking on Earth will be our best shot.
2. THE HUNTING APE
1 Sadly, using actual fossil evidence, such as tooth wear and carbon typing methods, to address these questions remains imperfect. They indicate that just as for chimpanzees and bonobos, the majority of food for our ancestors prior to around 1.8 million years ago was of plant origin. But meat was almost certainly a part of the diet—tool-scarred bones have been found that are over three million years old, and tooth wear patterns indicate heavy meat eating by around two million years ago.
2 The same virologist duo—Martine Peeters and Beatrice Hahn—who along with their colleagues showed that SIV was a recombinant of two monkey viruses also showed through long-term monitoring of SIV-infected chimpanzees that, like humans, they also eventually become sick.
3. THE GREAT PATHOGEN BOTTLENECK
1 The genetic similarity that dogs and wolves share is virtually identical to the genetic similarity between humans and chimpanzees. For many, this is shocking since we perceive ourselves as so different from chimpanzees yet view dogs and wolves as essentially the same. Such perceptions are more telling of our sensitivity to differences among beings similar to ourselves than they are of the actual genetic relationships between species.
2 Sadly, we do not have equivalent information about the microbial repertoires of all of our ape cousins. For example, because bonobos have smaller numbers and live exclusively in the Democratic Republic of Congo, their territory was often inaccessible during the wars of the last twenty years, so we understand much less about their microbial repertoires than we do for those of chimpanzees. As studies of these fascinating apes increase, they will certainly provide additional vital clues to the origins of our own infectious diseases.
3 In fact, humans are actually infected with multiple malaria parasites, each with its own evolutionary history. Here, when I refer to malaria, I’ll use it to mean Plasmodium falciparum, the malaria parasite that accounts for the vast majority of human illness.
4. CHURN, CHURN, CHURN
1 Unlike our ancestors forty thousand years ago who lived with no animals for protection or to assist with labor, all current hunter-gatherer populations have dogs.
2 One notable exception was populations supported by marine habitats. People living off of the ocean through fishing and the hunting of marine mammals were often able to achieve relatively large population sizes and maintain a sedentary lifestyle without domestication. While likely not sustainable in the long-term, the vast quantities of animal protein present in certain marine systems mimicked the concentrated caloric resources that subsequent domestication would provide.
3 Ant societies, like bees, consist of large colonies of female workers, all descended from a single mother (the queen) and father. The workers’ fathers (and all males) result from the development of unfertilized eggs, which means they lack half of the genetic information of fertilized offspring, or are haploid, in scientific terms. The haploid father contributes identical genetic information to each of his daughters. For this reason, the worker ants in a colony share 75 percent of their genetic information, rather than the 50 percent shared by sisters in species like our own. Because of their close genetic relationship with each other, female workers lie squarely in the middle of the continuum between sisters and cells. Ants in a colony are more accurately thought of as physically distinct cells in a large and single organism (i.e., the colony/hive) rather than as collectives of cooperating unrelated individuals.
4 There is ongoing debate among scientists as to the importance of sylvatic dengue for the human outbreaks. Unfortunately, the intense difficulties associated with isolation of dengue virus from forest settings makes ideal comparisons a challenge.
5 Recent work in Bangladesh by researchers at the International Center for Diarrheal Disease Research has shown that Nipah can enter into humans without pigs. One of the delicacies in parts of the country is sap from date palm trees, which is tapped overnight and consumed fresh in the morning. During the night, bats feed on the sap that flows into collect
ing pots, on occasion contaminating the sap with Nipah virus.
5. THE FIRST PANDEMIC
1 There is a class of viruses, the endogenous viruses, which don’t strictly speaking “infect” us but live in our genetic material. Some endogenous viruses may have an even higher prevalence than HPV, yet they differ fundamentally from the free-living, or exogenous, viruses that represent our primary concern here. We will see these fascinating viruses again in chapter 7.
2 HPV and other viruses cause a great deal of global cancer burden and provide nontraditional approaches for preventing cancer that we’ll revisit in detail in chapter 11.
3 We’ll also revisit GB virus in chapter 11. Some research suggests that not only is this virus harmless; under some circumstances, it might actually be good for you.
4 Viral hemorrhagic fevers, such as Lassa fever, Ebola, and others, all share severe symptoms, which include among other things a pronounced tendency toward swelling, broken capillaries, large-scale bleeding, low blood pressure, and shock.
5 While the human malaria parasites are transmitted by mosquitoes from person to person, they still are considered “exclusively human agents.” This is because they don’t have another known animal reservoir and can’t be sustained without both the mosquito and human part of their complex life cycles. If it’s determined that another mammal can be infected with one of these parasites, then they’ll be demoted to Category Four.
6. ONE WORLD
1 Wallace led a fascinating life. Rather than working from a cushy boat like his contemporary and natural selection codiscoverer Darwin, he traveled on the cheap, selling specimens along the way to fund his expeditions. An excellent scientific biography of him as well as an accessible but detailed discussion of his findings in the Indonesian archipelago can be found in David Quammen’s book, The Song of the Dodo.
2 The Polynesians had incredible navigation skills, and though their boats were simple, they were highly seaworthy. At a moment in history when boats in the West rarely went beyond the line of sight with land, Polynesians managed to negotiate huge swaths of the world’s largest ocean. They fabricated their ships from two canoes, each dug out from tree trunks, which were lashed to each other with crossbeam planks to form a deck. They used coconut fibers and sap to seal seams.
3 Sue Savage-Rumbaugh, a primatologist from Georgia State University, has reported that bonobos go so far as to leave trail markers to help other group members find their way when conditions don’t permit them to follow each other using footprints.
4 As discussed in chapter 2, HIV is a hybrid virus consisting of parts of two monkey viruses that chimpanzees acquired, almost certainly through the hunting of these monkeys. Note: There are multiple HIV viruses that have entered into humans (i.e., HIV-1 M, HIV-1N, HIV-2, etc.). Here, when I refer to HIV, I mean exclusively HIV-1 M, the dominant pandemic virus that is responsible for over 99 percent of human cases.
5 The latent period differs subtly but in an important way from the incubation period for some microbes. Where the latent period refers to the time between exposure and infectiousness, the incubation period refers to the time between exposure and the first signs of disease. In the case of HIV, for example, infected individuals become contagious within the first few weeks after exposure, yet at this point they experience only generic symptoms like fever and rash. Most cases of HIV transmission actually occur during this acute infection period rather than after the incubation period for AIDS itself, which is generally some years later.
7. THE INTIMATE SPECIES
1 As noted in the book Charlatan by Pope Brock, which provides excellent background on Voronoff, “The only thing that [the insemination] produced was a novel, Félicien Champsaur’s Nora, la guenon devenue femme—Nora, the Monkey Turned Woman.”
2 The account is described in a book on the papacy by the contemporary historian Peter De Rosa.
3 Interestingly, the first documented intravenous blood transfusion was from an animal to human, rather than from one human to another. In June 1667, Dr. Jean-Baptiste Denys, the physician to none other than King Louis XIV of France, administered a transfusion of sheep blood into a fifteen-year-old boy. Nothing is known about the sheep, but we know the boy survived.
4 Sadly, there is huge variation in the extent to which blood banks screen. Screening in developed countries is generally excellent, while in some parts of the world, it remains virtually nonexistent.
5 Patients with AIDS are not the only ones who are immunosuppressed. Transplant recipients commonly receive drugs that suppress the immune system in order to prevent organ rejection, which likely means that everyone receiving organs today, whether afflicted with AIDS or not, are at an increased risk of infection.
6 Marx and his colleagues argue that such multiple injections would naturally simulate the “serial passage” experiments done in laboratories with viruses. In these experiments, viruses are moved from animal to animal in a way that produces extensive opportunity for the accumulation of mutations that permit the virus to survive in a novel host.
8. VIRAL RUSH
1 While the changes we’ve experienced with large-scale industrialization of livestock production currently outweigh the benefits when it comes to microbes, that is not a necessary outcome. Industrial scale efficiencies in animal farming have the potential for better disease monitoring, and if done well could ultimately ensure that domestic animals remain separated from wild animals. Industrialization also serves to decrease the number of humans who have contact with living animals, which decreases the points when microbes can spill over. At the far end of this continuum would be fully artificial, or in vitro, meat. In vitro meat is animal flesh grown on cultures entirely independently from animals. The idea of cultured meat is currently unappetizing to many, and the health and other risks must be examined in depth. Nevertheless, it could have amazing benefits. Cheap factory-produced in vitro meat could address hunger issues and decrease the need for use of domestic and wild animals for meat, a situation that would radically decrease the introduction of novel microbes. Decreasing contact with domestic animals means decreasing contact with their microbes and the microbes they’ve acquired from their wild kin.
2 Cows are not the only species that have acquired prions by consuming their own kind. Another fascinating prion, kuru, a fatal neurodegenerative disease, moved in exactly this way among the Fore people of the Eastern Highlands Province of Papua New Guinea. The Fore practiced ritual cannibalism, consuming relatives and community members who had died and smearing the deceased’s brains on their bodies to help free their spirits. These mortuary feasts were determined to be the way kuru was transmitted. Following the prohibition of ritual cannibalism in the 1950s, the epidemic has now effectively come to an end.
10. MICROBE FORECASTING
1 Such swarms are also referred to as viral quasispecies in the scientific literature.
2 Ushahidi is a pioneering nonprofit technology company that works to improve collection, visualization, and mapping of information. The word ushahidi means “testimony” in Swahili, and the company was started after the postelection violence in Kenya in 2008 to help consolidate and map reports of violence.
3 The Google team that discovered that search trends correlate with actual influenza incidence included Larry Brilliant and Mark Smolinski, formerly of the Google.org Predict and Prevent project. It also included young Google engineers, who through Google policies can devote a percentage of their time to philanthropic or other endeavors. Both Larry and Mark have now joined Jeff Skoll, the entrepreneur, filmmaker, and philanthropist in his new endeavor, the Skoll Global Threats Fund, which focuses on ways to mitigate the threat from some of the most important risks of our time—they include, of course, pandemics.
4 Social networks are not the only social science approaches to early detection. Another approach is to use prediction markets. In the 2004–5 influenza season, researchers at the University of Iowa set up a futures market where nurses, pharmacists, and other health wo
rkers could trade and make money (in the form of an educational grant) on their sense of what was going on with influenza. The researchers showed that looking at market activity of local experts incentivized to choose correctly can also provide early warning.
11. THE GENTLE VIRUS
1 You may question the ethical decision of Jenner to experiment on a child with an unproven vaccine and then to expose the child to a known deadly disease. Yet while he has been critiqued for it, a more careful examination reveals something quite different. Because the rate of smallpox was relatively high, many adults would likely already have been exposed, making them inappropriate for the study, necessitating a study in children. Also, when he injected Phipps with smallpox it was part of an even earlier form of smallpox vaccination called variolation, in which patients were exposed to small amounts of actual smallpox virus (i.e., variola) in a controlled way to illicit an immune response to protect from natural infection. Variolation killed 1–3 percent, a crazy level by today’s standards but much lower than the 30 percent mortality among those who were naturally infected. Considering these factors, and that he also included his own son in these experiments, I think we can probably let Jenner off the hook.
2 Interestingly Rous didn’t win the Nobel for another fifty-five years, probably the longest period of time between a key discovery and the award of the prize! His finding was not well received in the field at the time, but some scientists recognized the importance of the discovery as he was nominated to the Nobel Committee in 1926.
3 Interestingly, Toxoplasma gondii may provide a scientific explanation for a commonly stereotyped set of behaviors. Recent attention to the “crazy cat lady syndrome,” as it is referenced in an article in the New York Times, points out that cat-hoarding behavior resembles the behavior of rodents infected with toxoplasma—affinity toward cats and immunity to the smell of their urine, for example. To date there have not been scientific studies to prove or disprove this hypothesis.