Subject: Researchers Offer New Theories To Unravel Mysteries of AIDS 
Date: Published: 8/4/92 (100 lines)
Source: Wall Street Journal. Copyright Dow Jones & Co. Inc.

    Technology & Health:
    Researchers Offer New Theories
    To Unravel Mysteries of AIDS
    ----
    By Marilyn Chase
    Staff Reporter of The Wall Street Journal

    After more than a decade of investigation by thousands of
 researchers world-wide, persistent mysteries remain in how AIDS
 devastates the body.
    Scientists, armed with the latest research from the recent
 international conference on acquired immune deficiency syndrome, are
 seeking to uncover the riddles of the human immunodeficiency virus,
 which invades the body through the bloodstream or sexual contact and
 cripples the immune system until AIDS develops in the form of
 opportunistic infections or cancers.
    Most scientists initially believed that HIV was straightforward,
 simply killing the cells it infects.  But that doesn't explain why it
 is difficult to detect HIV in the blood for up to 10 years after
 infection.  During this latent period, individuals are largely free
 of symptoms, but the body's levels of infection-fighting immune
 cells dwindle until AIDS develops.
    With better tests, Anthony S. Fauci, director of the National
 Institute of Allergy and Infectious Diseases, and others are trying
 to establish that lymph nodes filter the virus out of the
 bloodstream, trapping it in certain lymph cells that normally play a
 key role in fighting disease.  Dr. Fauci believes the cells
 eventually break down, releasing a "burst of virus" into the blood.
    Scientists also are trying to understand why HIV kills more cells
 than it infects.  Some believe in an "innocent bystander" effect, in
 which uninfected cells get spattered with HIV protein, which
 provokes other cells to attack.  Others believe HIV creates a potent
 substance called "superantigen" that aggravates these immune cells
 so they're more vulnerable to HIV infection.  A few scientists go a
 step further, adding that this superantigen may signal the doomed
 cells to commit mass suicide known as "apoptosis," a term first
 applied to AIDS by Jean-Claude Ameisen of the Pasteur Institute.
    To many researchers, the ultimate frustration is their inability
 to determine why drugs can't restore immune cells.  In advanced AIDS,
 the immune cell count plunges to 70 or below from the norm of about
 1,000.  Drugs can boost that count to, perhaps, 150.  "But why not
 back to 700?"  asks Samuel Broder, director of the National Cancer
 Institute.  "Is there some damage to the thymus gland, which acts as
 a drill instructor for immune cells, or to the bone marrow, that
 renders them beyond repair?"  he wonders.
    "Is it that our drugs are weak?  Is it because drug-resistant
 mutants of HIV emerge?"  he asks.  "Or is it that drugs can't reach
 deep pockets of the virus, located in different compartments of the
 body?"
    This last idea poses a new challenge for drug developers.  "The
 more we learn, the more we know different drugs work on different
 cellular compartments," Dr. Broder explains.  AZT, the most widely
 used AIDS drug, works best in actively multiplying immune cells,
 while other drugs are better at reaching dormant ones.  Certain brain
 cells "might act as a sanctuary for the virus," helping it elude the
 drugs.
    Cancer research already has found certain sites of the brain and
 testicles that appear to deflect the cancer-fighting action of drugs
 or the immune system, and, therefore, could conceivably harbor cells
 that sow the seeds of relapse.  However, Dr. Broder cautions,
 applying this to AIDS is so far "just speculation."
    Researchers seek to understand why people fall ill with AIDS
 despite having high levels of infection-fighting antibodies -- the
 proteins produced by immune cells to fight infection.  They wonder if
 somehow the antibodies alter their behavior and actually enhance
 infection.
    Increasingly, researchers are looking at immune cells known as
 suppressor cells and killer cells.  Jay Levy of the University of
 California San Francisco says long-term survivors who remain healthy
 with the virus in their bodies possess high levels of suppressor
 cells, and he believes such cells produce a substance that holds the
 virus in check.
    In a different line of research, scientists are looking for clues
 in patients whose immune systems fight back.  Gene Shearer of the
 National Cancer Institute found people who were exposed to HIV yet
 remained uninfected.  While these people made no antibodies against
 HIV, they did have a robust "cellular immunity," including killer
 cells.  Such findings prompted polio vaccine pioneer Jonas Salk to
 propose redirecting the goals of vaccine research away from sparking
 antibodies and more toward mounting a cellular defense.
    Adding to the AIDS mystery are recent reports of AIDS-like
 illness without HIV.  Some see these cases as bolstering the view of
 University of California, Berkeley virologist Peter Duesberg, who
 argues that HIV alone doesn't cause AIDS.  However, the medical
 establishment remains convinced of HIV's pivotal role in the AIDS
 epidemic, says Dr. Fauci, citing nearly 250,000 cases in the U. S. 
    In medical history there have been viruses that guard their
 secrets to the end, even after doctors find practical solutions.
 "There are persistent mysteries in every infectious epidemic, for
 example polio.  Most people exposed to polio virus get a harmless
 gastrointestinal infection and never develop paralysis," says Dr. 
 Broder.  "We still don't know why most microbes cause disease."

[This article is made available here by Dow Jones Co. for the
 personal and non-commercial use of callers to this bbs, in the
 hope that it will be of some help to those who are suffering
 from the disease and others who are seeking to help them.]