[Paleopsych] NYT: More Diseases Pinned on Old Culprit: Germs

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More Diseases Pinned on Old Culprit: Germs
http://www.nytimes.com/2005/05/17/health/17infe.html

    By NICHOLAS BAKALAR

    Infectious disease used to be a simple matter: this germ causes that
    illness. Doctors just had to find the germ, kill it, and cure the
    disease.

    But the old rules no longer apply.

    A report issued last month by the American Academy of Microbiology
    paints a much more complex picture of infectious disease. Germs,
    scientists are learning, are probably the cause of many illnesses that
    were never thought to be infectious, and determining exactly how a
    germ contributes to disease is no longer simple.

    The old rules date to 1883, when the German bacteriologist Robert Koch
    laid down three laws - now called Koch's postulates - that infectious
    disease specialists have used ever since to determine whether an
    organism causes a disease: The suspected germ must be consistently
    associated with the disease; it must be isolated from the sick person
    and cultured in the laboratory; and experimental inoculation with the
    organism must cause the symptoms of the disease to appear.

    In 1905, a fourth rule was added: The organism must be isolated again
    from the experimental infection.

    Using Koch's postulates as a starting point, scientists figured out
    the cause, prevention and treatment for one infectious disease after
    another. In the mid-20th century, some experts began to believe that
    infectious disease might be permanently conquered. But microbes have
    been found to metamorphose into new and more destructive forms, to
    jump from animals to humans, to hide where they are hard to find and
    to resist the most powerful antibiotics available.

    Moreover, said Dr. Ronald Luftig, an author of the academy's report
    and a professor of microbiology at the Louisiana State University
    Health Science Center, "There have been a lot of chronic human
    illnesses thought to be genetic or environmental, but when you look at
    them in more detail, it turns out there's involvement of bacteria,
    groups of bacteria or viruses."

    Microbes use a variety of mechanisms to attack cells and create havoc.
    Human papillomavirus, for example, inserts its nucleic acid into host
    cells, integrating into the cell's genes and altering the normal
    process of cell division to cause the uncontrolled growth of cervical
    cancer.

    Hepatitis B invades the liver, provoking an immune response that
    stimulates the scarring, cirrhosis and fibrosis that can lead to liver
    failure. At the same time, it causes genetic mutations that promote
    tumor growth and deadly liver cancer. Crohn's disease, a chronic
    inflammation of the intestines, may result from the presence of an
    infectious organism combined with a person's genetic susceptibility.

    By suppressing the immune system, inhibiting cell division and
    directly affecting the function of cells, germs demonstrate an
    astounding subtlety and resourcefulness in creating biological chaos.

    And it gets worse. Some microbes can contribute to more than one
    disease. The papillomavirus, for example, can lead not only to
    cervical cancer, but also to cancer of the penis and anus, venereal
    warts, common warts and cancers of the head and neck. Epstein-Barr
    virus, the cause of infectious mononucleosis, is almost as versatile,
    associated with Burkitt's lymphoma in Africa and with throat cancer
    and Hodgkin's disease, among other cancers.

    Helicobacter pylori, found in the mid-1980's to be a cause of peptic
    ulcer disease, was later implicated as a contributor to gastric
    lymphoma as well.

    Even saying that a microbe "causes" a cancerous lesion is problematic.
    Dr. David S. Pisetsky, a professor of medicine at Duke University
    Medical Center, points out that most infections do not lead to cancer,
    and he hesitates to alarm patients by overstating the connection.

    "These viruses are associated with cancer, but causality is
    complicated," he said. "In many instances, the viral infection is part
    of a chain of causality, and not the sole factor."

    The important questions to ask, Dr. Pisetsky adds, are "What's the
    risk, and how can I reduce the risk?"

    "If you have a virus associated with neck and head cancer," he said,
    "that's one more reason to quit smoking." In the case of a virus known
    to lead to cervical cancer, he went on, increased vigilance is in
    order, with Pap smears and regular examinations.

    All of this, combined with the fact that many germs (especially
    viruses) are impossible to culture in a laboratory, make it all the
    harder to find the microbe that causes the illness.

    Often, the first step is a simple observation of patients by
    clinicians, really little more than a hunch: a doctor notices a
    chronic illness that always seems to be associated with something that
    looks infectious.

    This is exactly what happened when Dr. N. M. Gregg, an Australian
    ophthalmologist, discovered congenital rubella syndrome. He made the
    connection between the cataracts he was seeing in children and their
    mothers' German measles during pregnancy.

    Sometimes epidemiological patterns offer the initial hint, as was the
    case with Kaposi's sarcoma, once a rare lesion caused by a type of
    herpes virus that began to occur frequently in gay men whose immune
    systems were compromised.

    Once the association is made, the search for the organism can begin.
    The gut is inhabited by hundreds of species of microbes, and the
    guilty party may be hiding among them. Germs can lurk in the nervous
    system, like the varicella virus that causes chickenpox and then lies
    in wait to cause herpes zoster, or shingles, decades later. And some
    germs can cause infection in one place in the body, and a disease in
    an entirely different place. Even the most sensitive molecular
    techniques are sometimes not good enough to find the guilty microbe.

    There are almost certainly still unknown microbes creating chronic
    illness. "One of the suspects in multiple sclerosis is Epstein-Barr
    virus," Dr. Luftig said. "The DNA of the virus integrates into your
    cells; it's there permanently. Is it a cause? Maybe."

    Dr. Luftig suggests several other diseases that may have microbial
    triggers. "There's an enterovirus that's involved in destroying
    pancreatic islet cells," he said. "Maybe diabetes is caused by an
    immune reaction to infection. Intrauterine exposure to infection may
    play a role in schizophrenia."

    No one yet knows for sure. But researchers - doctors, microbiologists,
    epidemiologists, geneticists - have their suspicions, and are
    searching carefully.

    "We're not saying that everything is due to microbes," Dr. Luftig
    said. "But the more investigative tools we develop and the more we
    have interacting groups of researchers with varying specialties, the
    more we can start to pick out potential agents that were never before
    suspected."