The Viral Storm (28 page)

Chronic diseases are notoriously difficult to treat. Whether for cancer, heart disease, or mental illness, treatments rarely return people to their pre-disease condition, and in many cases there are no treatment options at all. When a chronic disease is found to be caused by a microbe, the potential for cure and prevention improves dramatically. Cervical cancer, for example, which once required invasive, damaging, and only sporadically effective treatment, can suddenly be prevented by the deployment of a vaccine. Microbes make for low-hanging fruit when it comes to preventing and possibly curing chronic disease.

Cervical cancer is not the only chronic disease that is caused by a microbe. Liver cancer can be caused by both hepatitis B virus and hepatitis C virus. Researchers are currently exploring the possibility that prostate cancer, one of the leading causes of cancer death in American men, can be caused by xenotropic MLV related virus (XMRV). Stomach ulcers can be caused by the bacteria
Helicobacter pylori
. At least some types of lymphotropic virus, a virus family we discussed in chapter 9 and that we’ve discovered among the hunters we worked with in central Africa, are known to cause leukemia. It’s even possible that heart disease, the culprit in one-third of US deaths and countless deaths worldwide, has an infectious component. The innovative American evolutionary biologist Paul Ewald, who has written on the connection between infectious agents and chronic disease, suggests that the interplay between
Chlamydia pneumoniae
and environmental factors may be to blame for heart attacks, strokes, and other cardiovascular illness.

In some cases viral causes are suspected but have not yet been confirmed—perfect fodder for eager scientists. The distribution of type I diabetes cases suggest a possible connection with an infectious agent, but none to date has been identified. My own research team and our collaborators recently began work on a grant from the National Cancer Institute to screen tumor specimens from multiple types of cancer in search of viruses. It’s exploratory research, but the potential benefits as we find them could be monumental.

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Even some mental illnesses may result from infections with microbes. As we’ve seen, microbes can have an impact on behavior. Toxoplasma alters very specific neural circuits in rodent brains to decrease their fear of cats and thereby increase the chances that the parasite can complete its life cycle by ending up in a hungry cat. Rabies causes fear of water and increases aggressiveness in those infected with it, which helps accumulate virus in saliva and deliver it through a potentially fatal bite.

With these prominent examples of behavioral manipulation, it’s an obvious leap to suspect that microbes could play a contributing role in mental illness, a subject that has been the focus of a researcher at Johns Hopkins Medical School for some years. Robert Yolken studies a range of disorders, including bipolar disorder, autism, and schizophrenia, examining them closely to see if microbes might play a role. His primary focus is schizophrenia.

Schizophrenia certainly seems to invite discussion on links with infectious agents. For years, researchers have noted a relationship between seasonality of birth and schizophrenia: children born in winter months are more likely to develop schizophrenia than those who are not. This finding has long been thought to suggest that wintertime illnesses such as influenza, infecting either the pregnant mother or infant, may predispose an individual toward schizophrenia, although the results remain unclear for now.

Yolken’s most recent focus has been
Toxoplasma gondii
, or simply toxoplasma. He and others in the field have put together a plausible if perhaps not fully definitive case for the parasite’s role in this devastating mental illness.
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Multiple studies have found a correlation between schizophrenia and the presence of antibodies to toxoplasma. Some adults who experience the onset of toxoplasma disease experience psychological side effects. And antipsychotic drugs used to treat schizophrenia have also been seen to have an effect on toxoplasma in laboratory cell cultures. In a sign of the intense research that has surrounded the subject of schizophrenia, studies have documented that individuals with schizophrenia have had more exposure to cats than unaffected controls. Together these and other studies point to a connection. This connection still faces challenges since the parasite is not likely to be involved in all cases of schizophrenia, a disease that also has important genetic determinants.

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A virus may also be the cause of a complex, controversial, and somewhat mysterious disorder. Chronic fatigue syndrome (CFS) is a debilitating illness with no known origins and a variety of nonspecific symptoms: weakness, extreme fatigue, muscle pain, headaches, and difficulty concentrating, among others. Most people who have stayed up all night studying for a final or pushed themselves too hard at the gym will recognize these symptoms as familiar and common. They are also common symptoms for many other medical conditions, making it difficult to eliminate other possible root causes. As a result, medical experts and members of the public have debated the authenticity of CFS as a unique disorder. However, recent studies support those who argue that CFS is a genuine disease. Following several studies with contradicting results, a study published in August 2010 found a correlation between CFS and a virus in the murine leukemia virus family. More research is necessary to establish a causal link between MLV and CFS, but the finding has offered hope to many.

Dr. Robert Yolken with one of his subjects.
(
McClatchy-Tribune / Getty Images
)

As with cancer, a microbial cause of schizophrenia or CFS would invite quick and possibly important new diagnostics, therapies, and vaccines for these chronic disorders, which cause great pain and discomfort to victims and families. In the case of cervical cancer, the vast majority of the illness is ascribable to human papilloma virus, so a vaccine preventing it could be developed. This is not always the case. If only a percentage of people who suffer from schizophrenia or CFS do so because of a virus, it will make the associations more complicated and the discovery of links more challenging. Yet it’s worth the effort. Many chronic diseases lack good treatment options, and our ability to create vaccines and drugs for microbes is legendary. Wouldn’t you want to vaccinate yourself or your children for schizophrenia or heart disease? Even if it only protected them from one of a handful of causes of the illnesses? One day, we hope, you will be able to do just that.

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Using one microbe to prevent another microbe from causing disease is pretty amazing. But how about using a microbe to actually address the disease directly? This is something that’s increasingly explored in the nascent field of
virotherapy
.

All viruses infect cells as part of their life cycle, and they don’t infect cells randomly. As we’ve discussed, viruses infect cells in a lock-and-key manner: they enter into those cells that have particular proteins, or cell receptors, on their cell surfaces that the virus recognizes. If a virus existed that recognized and infected only cancerous cells, for example, then the virus could theoretically burn through those cells, killing the cancers along the way. The hope, of course, would be that when they were done with the cancer cells, they’d have nothing to infect and would die off.

Just such a virus exists. The Seneca Valley virus is a naturally occurring virus that appears to specifically target tumor cells living at the interface of the nervous and endocrine systems. It reproduces in the tumor cells, causing lysis, or rupturing and death of the cells. When released, it spreads to new tumor cells to continue its work. Now that’s a gentle virus!

Seneca Valley virus was discovered in a biotech company laboratory in Pennsylvania’s Seneca Valley. The virus had likely contaminated cell cultures from cattle or pig products commonly used in the laboratory. It was isolated and found to be a new virus in the picornavirus family, which includes polio. Testing showed that the virus had amazing selectivity to cancerous cells in the neuroendocrine system yet failed to infect healthy cells. This is a good reminder that not all viruses that cross the species barrier do harm.

The Seneca Valley virus is not alone. The small but growing group of virotherapy researchers use and adapt a range of viruses, including herpes virus, adenovirus (one of the viruses that causes colds), and the measles virus—to create viral therapies that can knock down cancer. Probably the most advanced among them is a herpes virus therapy developed by a biotech firm called BioVex, which is in the last stage of trials to determine its ability to control head and neck cancer. While the results of the trial have not yet been released, Amgen, a Fortune 500 biotech company, recently entered into the final stages of a deal to acquire the smaller BioVex as well as its herpes virus therapy.

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What about viruses that interfere with other viruses?

One brilliant example is a wonderful little virus called GB virus C, which appeared in chapter 5 and is found in a high percentage of people. This odd-sounding virus is in the same family as hepatitis C virus, but it certainly doesn’t kill us. In fact, it can save us.

In an incredible study published in the top medical journal the
New England Journal of Medicine
in 2004, researchers showed that infection with the GB virus C could help prolong the lives of men who were infected with HIV. When examined five to six years after infection with HIV, men without detectable GB virus C were nearly three times more likely to die than those who had active GB virus C infections. How GB virus C acts to save AIDS patients is still unclear, but it appears that it might interfere directly with HIV. Whatever the mechanism, this tiny organism has likely prolonged millions of lives during the course of the current pandemic.

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Viruses can also interfere with other kinds of microbes—bacteria can get sick too. Viruses infect all forms of cellular life, whether bacteria, parasite, or mammal. As we discussed in chapter 1, while nonspecialists tend to see microbes as a homogenous bunch, nothing could be further from the truth. All of the cell-based life forms (bacteria, parasites, fungi, animals, plants, and so forth) are thought to be more closely related to each other than they are to viruses.
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Furthermore, parasites fall into the class of life called eukaryotes and are more closely related to us than either they or we are to bacteria.

A fascinating Harvard virologist now at the Texas Biomedical Research Institute, Jean Patterson became interested in just this phenomenon in the mid-1980s. While her main focus had been viruses, she wanted to look closer at a group of parasites called protozoa, which includes malaria and leishmania, a harmful protozoan parasite transmitted to humans by the bite of the sand fly. Patterson was interested in how the parasites translated their genetic information into action, and she became fixated on discovering a virus that could infect this interesting parasite.

In 1988 Patterson and her colleagues discovered a small virus that naturally infects leishmania parasites; they were the first to characterize a virus from this group of parasites. Viruses that infect parasites could provide natural systems for parasite virotherapy. And as with the cancer-killing viruses, parasite viruses could potentially be adapted for efficiency and safety.

I’ve personally spent a reasonable portion of my professional life studying protozoa parasites. First, as a doctoral student working in Malaysian Borneo with my veterinary colleagues Billy Karesh, Annelisa Kilbourn, and Edwin Bosi, we tried to understand malaria in wild and captive orangutans.
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More recently, my colleagues and I searched for the origin of malaria in central Africa, a subject discussed in detail in chapter 3. Could it be possible that in some of our vials holding an ape malaria parasite resides a new malaria-infecting virus? One that could potentially kill our own deadly malaria,
Plasmodium falciparum
?

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When most people think about microbes, they frame it as a battle of people versus bugs. Perhaps if they’re being a bit more creative, they’ll consider the battles among the microbes themselves. But the reality is even more interesting than that. We’re part of an incredibly rich community of interacting microbes—with hugely complicated collaborations, battles, and wars of attrition with each other and ourselves.

Consider the human body. Only about one out of every ten cells between your hat and shoes is human—the other nine belong to the masses of bacteria that coat our skin, live in our guts, and thrive in our mouths. When we consider the diversity of genetic information on board, only one out of every thousand bits of genetic information on and in us can properly be called human. The bacteria and viruses represented by thousands of species will outnumber the human genes every time.

The sum total of bacteria, viruses, and other microbes present in our body is called the microbiota, and the sum total of their genetic information is called the microbiome. A new science has developed in the past five years to characterize the human microbiome. Empowered by new molecular techniques that bypass the nearly impossible task of individually culturing each of the thousands of microbes, scientists are rapidly figuring out exactly what the overall community of human and microbial cells in our bodies consists of.