The Viral Storm (18 page)

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?

*   *   *

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 spots 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.

*   *   *

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.

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.

*   *   *

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.
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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.”