What Makes You Sick? It Isn't What You Think 

By Gunjan Sinha

Infectious microbes are to blame for cancer, heart disease, and most other ailments, says controversial biologist Paul Ewald. 

On a blustery and frigid evening in early December, Professor Paul Ewald is huddled inside an auditorium with a group of 30 Amherst College students. 

It's the last day of classes, and as part of their final project for "Seminar in Evolution," the students are presenting data suggesting that almost every disease under the sun -- including common killers such as heart disease and cancer -- might be caused by bacteria, viruses, or other infectious organisms. 

Ewald, an evolutionary biologist whose book "Plague Time" about this very subject had recently been released, sits attentively in the front row with his legs casually crossed... 

One student points to the clustering of multiple sclerosis cases as evidence that the disease might be caused by something infectious. Another suggests the seasonal variation in births of autistic children is a reason to suspect that an infection during pregnancy induces the disease. 

If I hadn't just spent the entire day with Ewald, I would have found the presentations almost laughable. Like most students of science, I was taught that statistical associations are soft science: They can't prove cause and effect. But that's exactly the kind of thinking that Ewald is out to dispel. 

In "Plague Time," Ewald argues that the majority of chronic diseases -- any disease that progresses gradually over time -- are caused by infections. Just because you haven't proven cause and effect is no reason to ignore the data, he says. 

To back up his arguments, Ewald goes beyond curious associations such as those found for multiple sclerosis and autism, and argues his case from an evolutionary point of view: Diseases such as cancer, heart disease, and even schizophrenia and obsessive-compulsive disorder are too common to be caused primarily by bad genes, Ewald claims. 

Natural selection, he says, should have weeded those genes out of the population long ago. Instead, some genes might merely be making people more susceptible to infectious organisms, which are the true culprits of chronic disease ... 

But Ewald is more like a lone wolf than the leader of a pack. While some scientists, such as famed virologist Robert Gallo (the co-discoverer of the AIDS virus), agree in part with some of Ewald's ideas, others of equal stature are downright dismissive… 

"Much of it is flagrant nonsense," says Robert Weinberg...a cancer researcher at the Whitehead Institute of Biomedical Research in Cambridge, Massachusetts... 

As Weinberg points out, the average life expectancy of humans today is much higher than in the past. Until recently, most people didn't live long enough to get diseases like cancer and Alzheimer's. "Traditionally, human life was 30 or 40 years," Weinberg argues," and there was not any selective pressure against a genetic defect that manifested itself at the age of 60 or 70." 

Ewald counters that there is no evidence proving that at least some of our ancestors didn't live to be old. "One must not look at average ages but rather at whether a substantial part of the population lived to be 60 or 70." 

Besides, Ewald adds, similar skepticism was leveled against the now-famous Barry Marshall -- an Australian doctor who finally, despite much guffawing and finger-pointing from his peers, proved in 1984 that a bacterium called Helicobacter pylori causes most peptic ulcers. 

Marshall's theory challenged widely held and seemingly unassailable notions that ulcers were primarily caused by stress. 

[Worse than ridicule is the autoimmune disease disinformation campaign -- perhaps sponsored by organizations who want to cut costs by denying treatment with antibiotics. 

Any mammal would have a selective disadvantage if it tended to destroy itself when invaded by micro-organisms. The increasing number of people who are color blind to various degrees can be pointed to as an example of the survival of defects, but this does not apply to our response to parasites: 

Humans have substantially reduced their chances of coming in contact with macro - predators such as tigers; and this security has been with us for at least 10,000 years -- plenty of time for the effect to show itself of no penalty for not being able to distinguish green from yellow. 

This is not the case with micro - predators. Polio, diphtheria, syphillis, tuberculosis, and HIV have wrecked havoc on us within the last hundred years. For every smallpox we put down, it seems that ten more species of pathogens rise in its place. 

It was only in the 19th century that the germ theory of disease began to be accepted; and, even today, genetic tendencies and environmental stresses are the preferred explanations. In the 19th century, for example, doctors at the University of Vienna hospital had their collegue Semmelweis fired because he cut the maternity death rate of one mother for every eight admissions to one in thirty by having the staff on his ward wash their hands. (See "Plague Time" p. 17)] 

However controversial, Ewald's ideas do have scientific legs to stand on. In the past few decades, a handful of cancers have been unquestionably linked to infections. 

Take the case of cervical cancer and the human papilloma virus (HPV), for example. The Centers for Disease Control reports that the sexually transmitted virus is responsible for as much as 93 percent of all cases of cervical cancer. 

But because most women infected with HPV never develop cervical cancer (the CDC estimates that 20 million Americans carry the virus), and the cancer takes years to kick in -- characteristics very uncharacteristic of infectious disease -- figuring out the connection took years. 

"Over 100 years ago," Ewald explains, "people noticed that the frequency of cervical cancer was higher in prostitutes, and also that there were couples with penile and cervical cancer. But people didn't accept an infectious cause until the organism was identified over a century later." 

Also pegged as cancer culprits are a herpes virus that causes Kaposi's sarcoma, a human T-cell leukemia virus (HTLV 1) responsible for a rare form of leukemia, and hepatitis viruses that cause liver cancer. 

These and other viruses are responsible for between 15 and 20 percent of all cancers. The rest, say most scientists, can be blamed on rogue genes and non-infectious environmental factors such as diet and smoking. 

Ewald, however, is convinced that evidence from other cancers, including those of the breast, will soon tip the scales in favor of infectious causes ... 

Despite the lack of data proving a cause-and-effect relationship, scientists shouldn't disregard the possibility of an infectious cause, says Ewald. 

Take the case of HTLV 1, which causes a rare form of leukemia prevalent in western Japan. The virus can be transmitted sexually or via mother's milk. People typically don't develop the cancer until 50 or 60 years after they've been infected, and some infected people never develop leukemia. 

"It's not like chicken pox or some other organism that follows the established rules of infection," says Ewald, "and because it's transmitted in families, people could mistakenly assume it's hereditary." 

Like HTLV 1, an infectious organism may be causing breast cancer but operating too cryptically to be detected with the tools available. 

AIDS researcher Gallo, who also discovered HTLV 1, agrees: "Sure, there may be a breast cancer microbe, difficult to find, present rarely or occasionally, which in the right circumstances contributes to breast cancer, but that's still a very open issue." 

Ewald argues that, from an evolutionary perspective, breast cancer is simply too common in the population for it to be caused by rogue genes. 

His reasoning, backed up by mathematical calculations, goes something like this: Older people are still subject to natural selection after they stop reproducing because they pass on their care and wisdom to their children and grandchildren (as in some societies where grandmothers are responsible for preparing food). So a child without a grandparent will presumably be less "fit" than a child with a grandparent. 

Over many generations, children with grandparents will prevail over children without grandparents (whose genes presumably made them more vulnerable to disease). 

Ewald applies the same rationale to Alzheimer's and cardiovascular disease. Studies have shown that people with a gene called APO E4 appear to be more susceptible to both diseases. 

But Ewald argues that a faulty gene is too prevalent (between 10 and 50 percent of a given population carries APO E4) to have been conserved through evolution, and that it is merely making people more susceptible to infection. 

An airborne bacterium that infects the respiratory system, Chlamydia pneumoniae, may be one of the real culprits. 

People with E4 are much more likely to be infected by Chlamydia, and several studies have confirmed the bug's presence in the fatty lesions associated with coronary artery disease. 

But it's difficult to discern whether the organism initiates the disease, exacerbates the disease, or is even contributing at all. 

[In "Plague Time", Professor Ewald, p. 109, writes concerning a Finnish study: "... 70 percent of the samples from heart attack patients had antibodies to Chlamydia [pneumoniae]. This percentage was significantly higher than the percentage in the control serums from people who had not had heart attacks."

Is it possible that all the deaths in recorded history from bubonic plague are miniscule compared to the people who are dying right now from heart disease due to chronic bacterial infection?] 

Chlamydia's role in Alzheimer's disease is much more tenuous. In 1998, microbiologist Alan Hudson reported that he had found the bug in 22 out of 23 brains of Alzheimer's patients, whereas only one out of 25 normal brains tested positive. 

"I couldn't believe my eyes, so I spent three years using every tool known to man confirming that the organism was really there, before going public with it," recalls Hudson. 

Although Hudson and Ewald have become close collaborators, one can't help but wonder whether it was mutual professional interest that truly drew them together, or their shared experience of being treated like pariahs by the medical establishment. 

A self-described "gene jockey," Hudson has spent his career studying how genes enable organisms to do what they do. He stumbled onto the Alzheimer's research through a former colleague when he was at the Philadelphia College of Osteopathic Medicine. 

When Hudson submitted his Alzheimer's work to a journal for publication, the editors sent it out for peer review, as is standard practice among all journals. "The Chlamydia reviewers said `publish the thing,' the Alzheimer's people hated it," he says. 

The journal initially rejected the paper, and it was only after some reviewers pressured the journal that they finally published it. 

Hudson's experience is all too common in a field where arguments over scientific ideas can devolve into something akin to turf war ... 

Just as the medical establishment ridiculed Barry Marshall and his germ theory of ulcers, says Ewald, scientists who have spent a lifetime studying the genetic basis of disease are of course going to reject alternative explanations. "They've simply got too much invested in existing theories," he argues. 

Nevertheless, researchers are working to confirm Hudson's findings. As of this writing, a group based in the Netherlands has also found an association between Alzheimer's and C. pneumoniae, as has Chlamydia expert James Mahoney at McMaster University in Hamilton, Ontario. 

One of the problems, says Hudson, is that identifying the organism is very difficult and the slightest deviation in established protocol can throw off results. 

As for Ewald's evolutionary argument, most scientists agree that grandparents do contribute to fitness -- the question is how much. Evolutionary arguments don't prove cause and effect. 

To this, Ewald responds: "We always have to keep on the table the various hypotheses, even though we don't see direct evidence of them. One can never jump to the conclusion that infection is not important just because we find genes and environment are important." 

"In most cases there's little evidence to exclude infectious causation of chronic disease. That kind of thinking has been responsible for a lot of death over the past 40 years."