Fwd: A Host with Infectious Ideas

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    A Host with Infectious Ideas

    By Steve Mirsky


    Paul W. Ewald argues that most cancers, heart disease and other chronic
    ills stem from infections. If correct, his theory will change the course
    of medicine

    AMHERST, MASS.‹Newton had a falling apple. Darwin mused on finches. Paul
    W. Ewald's inspiration was diarrhea. "I wish I had something more
    romantic," says the Amherst College evolutionary biologist. It gets
    uglier: Ewald, then a graduate student studying bird behavior, was camped
    near a Kansas garbage dump. As he waged a three-day battle against his
    sea of troubles, he contemplated the interactions between a host‹himself,
    in this case‹and a pathogen. "There's some organism in there," Ewald
    remembers thinking during that 1977 experience, "and this diarrhea might
    be my way of getting rid of the organism‹or it might be the organism's
    way of manipulating my body" to maximize its chances of passage to the
    next victim by, for example, contaminating the water supply. "If it's a
    manipulation and you treat it, you're avoiding damage," he notes. "But if
    it's a defense and you treat it, you sabotage the host."

    Host-pathogen relationships have dominated Ewald's thoughts ever since,
    leading to numerous articles, two books and, depending on whom you talk
    to, the respect or scorn of scientists and physicians. The admiration
    comes from those who think he was on to something really big in his
    earlier publications, which he summed up in his 1994 book Evolution of
    Infectious Disease. "I think that Paul Ewald has been a pioneer in using
    evolutionary theory to attack hard questions in pathogenesis," comments
    Stephen Morse, a virologist and epidemiologist at Columbia University.
    "His work has, for the first time, shown a way to generate testable
    hypotheses to study such questions as the evolution of virulence‹once
    thought intractable‹and infectious causes of chronic diseases." Indeed,
    the Atlantic Monthly referred to Ewald as "the Darwin of the microworld"
    (to which Ewald responds, "No, Darwin is Darwin of the microworld, too").

    Any antipathy is the result of his latest research, outlined in last
    year's Plague Time. The 47-year-old Ewald argued in the book that
    infection may play a role in cancer, atherosclerosis, Alzheimer's and
    other chronic conditions ordinarily thought of as inevitable consequences
    of genetics, lifestyle or aging. "Some of his recent work is
    controversial," Morse states. "I'd personally prefer to reserve judgment
    for now on those questions, at least until more data are in." Others are
    less gracious. One prominent atherosclerosis researcher politely panned
    Ewald in public but privately referred to his ideas using an eight-letter
    word, the first half of which is "bull."

    In an April 1993 Scientific American article, Ewald smashed the old, and
    unfortunately still widely accepted, notion that parasites and their
    hosts inevitably evolve toward a benign coexistence. The tendency toward
    benignity is reserved for conditions passed directly from person to
    person. Someone too sick to mingle with others would indeed be a dead end
    for the most dangerous infections, but Ewald showed that infectious
    agents that use intermediate vectors for transmission, such as malaria's
    mosquitoes and cholera's contaminated water, are free to evolve toward
    greater destructive power. After all, a mosquito is free to feed on the
    sickest malaria victims and thus pass on the worst pathogens. Even more
    provocative was Ewald's exegesis on our potential to drive the evolution
    of pathogens through judicious public health measures. "The evolutionary
    hypothesis says that if you can make it so that sick people cannot pass
    on infections and that only healthy people can, you should favor the
    evolution of more benign strains," he explains.

    Ewald suggests an experiment that could never be ethically done: "Select
    two countries, one with bad water and one with clean water, and introduce
    cholera into both." Theory holds that water in which microbes can thrive
    serves as a vector that lets dangerous virulence continue or worsen. On
    the other hand, treated water would kill cholera strains relying on
    diarrhea for transport; only mild strains would survive because their
    hosts would be healthy enough to transmit the pathogen directly to other
    people. "Essentially, that's what happened in 1991," Ewald says,
    referring to a cholera outbreak in Peru that spread through Latin
    America. He and his students analyzed cholera from Peru and Guatemala,
    which has unsafe water, and from Chile, whose water is trustworthy. They
    found that over the 1990s Chile's cholera did indeed become less
    virulent, whereas highly toxic strains persisted in the other countries.
    This concept should motivate public health officials to do things they
    should already be doing anyway, such as providing safe water and
    mosquito-proof housing. Although these ideas have yet to permeate medical
    school curricula fully, they seem beyond reproach theoretically. When
    Ewald wanders into the fields of chronic disease, however, he steps into
    some eight-letter castigation. Given evolutionary principles and the
    available evidence, he argues in Plague Time, infectious agents should be
    considered as at least part of the etiology of apparently noninfectious
    conditions. Of course, the connection between Helicobactor pylori and
    peptic ulcers is now taken for granted, although medical texts of 20
    years ago were mute on the subject. Associations between infections and
    some cancers‹hepatitis virus with liver cancer, papillomavirus with
    cervical cancer‹have become accepted in only the past few decades. Ewald
    thinks that more cancers, perhaps the majority, as well as numerous other
    common, widespread and ancient chronic diseases, will eventually become
    linked with various infections: for atherosclerosis and Alzheimer's
    disease, he points to studies showing associations with Chlamydia
    pneumoniae. He even holds that schizophrenia may be related to infection
    with the protozoan Toxoplasma gondii.

    "People have put much more emphasis on genetic causation and
    noninfectious environmental causation," Ewald says. "And when they find
    evidence that those kinds of causation are occurring, then they make this
    fundamental error in science: throwing out a hypothesis [infection] just
    because you have evidence that other hypotheses are probably at least
    partly right." Disease instead may result from a subtle interplay between
    a gene's product and an infectious agent.

    Arguably, natural selection should have gotten rid of most of the solely
    genetic diseases long ago. (Genetic conditions such as sickle-cell
    disease get an evolutionary pass, however: one copy of the gene protects
    against disease‹malaria, in the case of sickle cell‹so the potentially
    destructive gene will survive in a population.) The standard argument is
    that genes that cause illness after the prime reproductive years don't
    get selected against. Ewald counters by arguing that the elderly‹and he
    believes that there were always people who would be considered old by
    today's standards, even at times when life was supposed to be "nasty,
    brutish and short"‹ were important sources of information and caregiving,
    and evolution does indeed try to keep them around.

    To find possible infectious relationships to seemingly noninfectious
    diseases, Ewald suggests the creation of a program akin to that used to
    monitor adverse reactions to vaccines: what he calls the Effects of
    Antimicrobials Reporting System, or EARS. Physicians worldwide may be
    sitting on a gold mine of data, in the form of anecdotes about remissions
    that accompany antibiotic treatment for a concurrent condition. "If you
    accumulate the shared experiences, real cause and effect should pop out,"
    he says. "Then we'd know if this was something we should do a controlled
    study on."

    Ewald believes that the associations between chronic diseases and
    infections will be slowly accepted, perhaps in a few decades. Should his
    viewpoint prevail some distant day, he may repeat the words his physicist
    father once spoke. The elder Ewald, recovering from a heart attack when
    Paul's 1993 article appeared in this, his favorite publication, said,
    "Well, this was worth living for."

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