The Viral Storm

by Nathan Wolfe

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  For our purposes, the utility of the chimpanzee testicle transplants as the Viagra of the roaring twenties, while interesting, is largely unimportant. What’s important about the infamous monkey gland operation is that it provides one of the most striking examples of how medical technologies have incidentally served to link humans (and sometimes animals) in ways that create new bridges for the movement of microbes.

  Given what we now know, the idea that we would consciously connect the microbial worlds of humans and chimpanzees as Voronoff did would be unfathomable and unforgivable. Although there’s no straightforward way to confirm it in the absence of specimens, Voronoff’s transplants almost certainly led to the transmission of potentially dangerous viruses into humans who received these tissues. Transplanting living tissue between very closely related animals eliminates all of the natural “barriers to entry” that microbes face, and remains one of the riskiest imaginable ways for a microbe to jump from one species to the next.

  Yet Voronoff’s work, while certainly extreme, did not exist in a vacuum. The explosion of medical technologies that has occurred over the past four hundred years has provided new kinds of microbial connections between individuals. Transfusion, transplantation, and injection, while some of the most critical tools for maintaining human health, have also contributed fundamentally to the transmission and emergence of pandemics. These technologies have connected us with one another’s blood, organs, and other tissues in ways unprecedented in the history of life on our planet. They have served to make us, among other things, the intimate species.

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  Before we dissect the role of medical technology in connecting our bodies and facilitating microbial transmission, it’s worth spending a moment to discuss this in the context of the benefits of these technologies. Injections and immunizations as well as transfusions and transplants are all technologies that have catapulted medicine into the modern age.

  Without blood transfusions, huge numbers of hemophiliacs, trauma victims, and wounded soldiers would die. Transplants permit victims of leukemia, hepatitis, and severe burns to live a normal life. And it is nearly impossible to imagine a world without injections. The use of intravenous rehydrating fluids alone saves the lives of millions of malnourished children and victims of diarrheal disease each and every year. Injections also permit immunization, and to live in a world without immunizations is to live in a world where smallpox threatens our day-to-day lives. If smallpox had not been eliminated by immunization in the 1960s, it would probably be a worse plague today than it was then due to the same sort of hyperconnectivity discussed in chapter 6.

  Examining the role that these medical technologies have played in the history of epidemics does not argue against their utility in maintaining the health of our species. Likewise, these arguments should not be interpreted as supporting the hypochondriacal fears of the anti-immunizationists, whose rhetoric has been soundly skewered in Michael Specter’s important book, Denialism, which brings to a general audience years of research on the subject. Nevertheless, understanding the ways in which the historical use of these technologies has connected human populations is important in understanding why we are plagued with pandemics. Rather than discourage us from using live-saving technologies, they serve to highlight the need for maintaining vigilance in the way that we deploy them.

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  One of the clearest examples of how medical technology increases human microbial interconnectivity is our use of blood. Historically, humans (and other animals) rarely come into contact with one another’s blood. For the vast majority of our history since the advent of hunting, we’ve had more contact with the blood and body fluids of other animals, through hunting and butchering. In the fifteenth century, that would all change.

  The first generally accepted attempt at a “blood transfusion” was given to Pope Innocent VIII in 1492 and was described by the historian Stefano Infessura.2 When the pope went into a coma, the pontiff’s medical advisers sought to cure him by feeding him the blood of three ten-year-old boys. At the time, there were no intravenous techniques, and both the pope along with the three donors, who had been promised a ducat each, all died.3

  Blood transfusions have advanced considerably since then. Today around eighty million units of blood are collected every year worldwide. Blood transfusions save countless lives. They also provide an entirely new form of connection between human populations. When a unit of blood is transfused from individual to individual, so too are the various viruses and other microbes present in that unit. The proliferation of blood transfusions creates a novel route for the movement of microbes, sometimes providing a new route for microbes that already move in other ways, as in the case of malaria. New connections made through medical technology can also provide transmission routes for agents that would otherwise never have the potential to spread among humans and can be another way in which an agent that we acquire from an animal can spread; otherwise, it might simply go extinct.

  Blood transfusions are known to spread HIV and other retroviruses, as well as hepatitis B and C, parasites such as malaria, and Chagas disease. Even prions like variant Creutzfeld-Jakob (also known as mad cow disease), an infectious agent to which we’ll return in the next chapter, can survive in blood bags, the plastic containers used to hold blood prior to transfusion.

  The field of blood products has also advanced beyond single blood transfusions that go from one person to the next. In the case of hemophiliacs, individuals lack particular blood factors that would normally allow their blood to clot, a potentially life-threatening condition. In order to accumulate the missing blood factors in sufficient quantities to solve the problem, the appropriate components of blood are often pooled from tens of thousands of donors. The consequences for connectivity are substantial. A back-of-the-envelope calculation suggests that a person living with hemophilia A in a city like San Francisco will inject themselves with up to 7,500 doses of clotting factor VIII by the time that they’re sixty. That means that this person will potentially have had contact with the blood-borne microbes of 2.5 million people during the course of their lifetime.

  The good news is that many blood banks now screen for the usual suspects. Blood infected with HIV, for example, will not get through the donation process.4 But this was not always the case. Perhaps not surprisingly, hemophiliacs who receive pooled blood products were among the first found to be infected with HIV in the early 1980s. In the United States alone, thousands of hemophiliacs were infected, and many of them died. Even now we can only screen for the microbes we know. Undiscovered viruses, of which there are certainly many, move around daily through blood products. And a new virus that entered into humans could easily spread within the blood supply before we’d have a chance to stop it.

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  In terms of sheer number of procedures, blood transfusions trump organ transplants by far. But while the number of blood transfusions will always be greater than the number of organ transplants, the movement of an organ is a substantially more dramatic biological event. Organ transplantation involves the movement of blood as well as a large amount of tissue, so any microbes present in the blood or the tissue being transplanted will move along with the organ into the recipient.

  Organ donation risks the movement of all of the same usual suspects that will transmit during a blood transfusion and then some. For example, in the case of rabies, discussed in detail in chapter 5, I told you that rabies didn’t transmit from human to human. To be slightly more exact, there have been no documented cases of natural transmission of rabies from human to human. There have, however, been a dozen or so well-documented cases of rabies moving from one person to another. And every one of them has been due to a transplant with an infected organ.

  The majority of these cases of rabies transmission have been due to cornea transplants, perhaps because the cornea is one of the only nervous system-related tissues currently transplanted; and rabies is primarily a virus of the central nervous
system. In two fascinating cases, separate recipients from Texas and Germany received organs infected with rabies. In both cases the deaths of the donors were falsely attributed to drug overdoses, whose symptoms can sometimes mimic those of rabies. Amazingly, both donors appeared to have died of fulminant rabies without seeking medical care. It’s frightening to imagine that they reached that point in the illness while moving about, conducting their normal day-to-day affairs.

  Transplants can also transmit dormant stages of infectious diseases that can flare up later. One particular species of malaria, Plasmodium vivax, whose Siberian variant we discussed in chapter 1, has the capacity to stay latent, or dormant, in the liver. During latency, there are no symptoms of the disease and, similarly, no malaria parasites in the blood. But a liver transplant could potentially do the trick.

  In one case in Germany, a twenty-year-old male who had emigrated from Cameroon died of a brain hemorrhage and donated his organs. Among the recipients was a sixty-two-year-old woman who needed the liver because of late-stage cirrhosis. A full month after her organ transplant she developed a high-grade fever, which was later diagnosed as vivax malaria and successfully treated. She had never visited a tropical or subtropical area in her lifetime. But her liver had.

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  There’s another important rub to the problem of organ transplantation. While obtaining blood from donors is pretty simple, obtaining an organ is not. Rarely will people living in the developed world who need a blood transfusion not get one, but that is not the case with organ transplants. Currently in the United States there are approximately 110,000 people on the waiting list to receive organ transplants, and one of these people dies every ninety minutes.

  The lack of organs available for transplant has caused surgeons to look for alternatives to human organs. Animals are an obvious choice. Clearly, the elective transplantation of thousands of chimpanzee testicles into men for the purposes of “rejuvenation” presents unacceptable risks. The real chance that a known or unknown virus could enter into humans from such a closely related animal as a chimpanzee would make the choice wrong even if the illness were life-threatening. But there are other animals out there. For example, the organs of an adult pig are approximately the size and weight of an adult human’s, and while not without risk for cross-species jumps, the risks are smaller than those for a chimpanzee.

  In July 2007, Joe Tector, a pioneering transplant surgeon at Indiana University School of Medicine, gave me a call. Tector had put together a team whose goal was to genetically engineer pigs with organs that would be less likely to be rejected by humans, a problem for surgeons to this day. Within five years he wanted to begin transplanting pig livers into humans, and he wanted to understand the risks.

  He explained that he didn’t want a rubber stamp scientist to simply tell him that what he was doing was safe. He was looking for someone who loved finding new viruses and was intent on discovering any possible risk associated with the work he was doing. He spoke eloquently about his patients and how many of the people on those waiting lists never received organs in time. He also spoke about the need to determine that what he planned to do wouldn’t backfire, igniting a new pandemic in the human species. When Tector contacted me, I had already been interested for some years in xenotransplantation, the surgical term for the transplantation of organs from one species to another. By the time I got off the phone, I was hooked.

  In the 1920s, following the time that Voronoff conducted his work in Paris, the field of xenotransplantation went into a forty-year lull during which there were no documented attempts. But in the 1960s work on xenotransplantation had a rebirth. New antibiotics and immunosuppressive drugs provided hope for the success of transplanting major animal organs into people who needed them. By dampening the immune system, the immunosuppressive drugs could address the frustration of organ rejection.

  A series of high-profile operations brought major attention to the field through the 1980s. One involved the famous Baby Fae, a twelve-day-old baby girl born prematurely with a major heart disorder. She survived for eleven days on a baboon heart. Another operation created a news flurry around Jeff Getty, a thirty-eight-year-old man with AIDS. Getty received his diagnosis at a time when AIDS was still called “gay cancer.” He went on to become a prominent activist who pushed for access to care for AIDS patients and participated in numerous experimental trials, including the one that led to his national notoriety. In the trial, he received a bone marrow transfusion from a baboon with the hope that the natural resistance that baboons have to AIDS would take hold in his body.

  Getty’s experimental therapy ultimately failed, but it brought with it a national debate about the potential that such transplants could transmit new and perhaps unknown viruses to humans. Certainly, a transplant from a closely related species like a baboon to a person with an already compromised immune system could be a recipe for disaster. A person with a highly weakened immune system, as occurs in late stages of AIDS, would provide an environment in which new viruses could better grow and adapt.5 In the extreme, it could be a Petri dish for viral exploration into a new and foreign land.

  Fortunately for the success of Tector’s work, pigs are not as closely related to humans as baboons are. Yet they are still mammals. As with other mammals (including ourselves), they have many microbes that are still unknown. And some of them undoubtedly have the potential to jump species. The real question then becomes what are the viruses that can jump and can they then spread from person to person. The fact that one person might get a deadly virus is not the end of the world, particularly if the person was about to die of liver failure. The real risk is if that virus could spread.

  In the small but active group that concern themselves with pig viruses, the agent that has provoked the most worry is PERV, the porcine endogenous retrovirus. Endogenous viruses like PERV are permanently integrated into the genetic material of their hosts. Yet from time to time they emerge from the genes and go on to infect cells and spread within the host’s body. As part of the actual genomes of their hosts, endogenous viruses cannot currently be eliminated—hence the concern that they could reemerge in humans following a pig transplant.

  The eminent CDC virologist Bill Switzer, whom I’ve worked closely with for the last ten years studying retroviruses, was one of the scientists to conduct the most comprehensive study on PERV in xenotransplant recipients. Bill and his colleagues studied specimens from 160 patients who had received pig tissues. Amazingly, they found evidence of pig cells continuing to live in about 15 percent of the recipients, even up to eight years after the transplant. Fortunately, they found no evidence of PERV.

  Whether PERV is the most important risk or not remains unknown. If it is, we may not have much to worry about. Through our studies with Tector and other colleagues, we hope to determine what else may be in those pig tissues and what risks those agents would pose. The decisions based on our research will not be easy ones. As we’ll discuss further in chapter 9, even state of the art viral discovery right now does not permit us to definitively determine all of the microbes in any sample. Yet the costs of indecision are substantial. On one side are the transplant recipients who die each day waiting for an organ. On the other is a small but important risk of an epidemic in a much larger group. Is one life saved worth a species potentially plagued?

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  We’ve been sticking ourselves with needles for a long time. The first evidence of it comes from an unusual source—an iceman. On a sunny day in September 1991, two German tourists hiking in the Italian Alps came across a corpse. The corpse became known as Ötzi, after the valley in which he was discovered. Though initially thought to have died recently, we now know that Ötzi lived 5,300 years ago.

  Among the amazing elements of this discovery is the fact that Ötzi had tattoos. In fact, this is the first evidence of tattoos in the world. Ötzi’s tattoos were located on his lower back, ankles, and knee. X-rays of the mummy showed evidence that the tattoos were positioned over spot
s where Ötzi had likely experienced pain due to orthopedic maladies, leading some to speculate that the tattoos may have served as a kind of therapy.

  Whatever his reasons for having them, Ötzi’s tattoos, like any tattoo since, represent risks. Tattooing, like a needle stick or an injection, involves blood contact. And if the same implement is used multiple times on different individuals, it can provide a bridge on which microbes can hop hosts.

  The wrist of Ötzi the Iceman, showing two of his numerous tattoos. (© South Tyrol Museum of Archaeology, www.iceman.it)

  Whether for tattoos, medicines, or vaccines, improperly sterilized needles can play an important role in transmitting microbes. Widespread use of needles, as with blood transfusions, provides an entirely novel route for microbes to move around, allowing them to maintain themselves or spread effectively in humans in order to survive and thrive.

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  Perhaps the most remarkable microbe we know of in the postinjection age is hepatitis C virus. HCV is a critically important virus that infects over one hundred million people globally and more than three million new individuals each year. It also kills through liver cancer and cirrhosis, causing over eight thousand deaths per year in the United States alone. But it would likely kill precious few of those individuals if it weren’t for needles.

  There is still a great deal that’s unknown about HCV. The virus itself was officially discovered in 1989, but it must have been in human populations for much longer. My collaborator, the prolific Oxford virologist Oliver Pybus, has made understanding this virus one of his many scientific objectives. Pybus utilizes the tools of evolutionary biology and learns more each year about viruses through computers than many others will in a lifetime of lab- or fieldwork. By using computer algorithms to compare genetic information from distinct viruses as well as mathematical modeling, Pybus has made some fascinating discoveries about HCV.