Subject: AIDS Virus Is Planted in Mouse Genes
Date: Published: 1/13/88 125 lines
Source:  WALL STREET JOURNAL. Copyright Dow Jones & Co. Inc. 

   AIDS Virus Is Planted in Mouse Genes;
   Some Say Danger Offsets Research Gains
    ---
    By Marilyn Chase
   Staff Reporter of The Wall Street Journal

   Like the Chimera of Greek mythology -- part lion, part
goat, part serpent -- a new hybrid has been born at a
National Institutes of Health unit in Bethesda, Md.  And like
its mythological ancestor, this creature has some people
frightened.
   The new animal is a "transgenic mouse," a benign-looking
white laboratory animal that carries the genetic code for the
virus causing acquired immune deficiency syndrome in every
cell.
   Transgenic mice have been bred before, for use in cancer
research and in biotechnology, but these are the first to
carry the blueprint for such a lethal contagious disease.
Their creators' hypothesis is that the mice will mimic AIDS'
long latency phase, which is a choice target for all
anti-viral drugs because it precedes the onslaught of the
disease.  They hope the mice will help solve the mystery of
the disease and serve as subjects for testing drugs.
   But critics fear a mouse will bite a lab worker or escape
and breed with wild mice, spreading the lethal virus like a
20th century plague.  One suit has already been filed seeking
to stop production of the hybrids.
   From the beginning of the AIDS epidemic, scientists have
bemoaned the lack of a perfect research animal.  Rare and
expensive chimpanzees can be infected by the AIDS virus, but
they don't get sick from it.  Mice are cheap and plentiful,
but they aren't susceptible to the infection.
   Malcolm Martin, a senior scientist at the NIH's National
Institute of Allergy and Infectious Diseases, set out to
change that.  A year ago Dr. Martin reported initial success
transplanting into mice a piece of the AIDS genetic code
called the LTR, the nerve-center of the virus.  "So we
wondered, why not do an experiment that would (also) mimic
one phase of the virus infection in man...  .  Maybe what's
going on (in latency) is that there are copies of the viral
DNA that are totally silent, nonfunctional, sitting in
regions of the (host) chromosome," he says.  "Why not try to
duplicate this, by having a copy of the (whole genetic code)
in every single cell of the mouse?  "
   So Dr. Martin's team bred a female mouse and harvested the
fertilized eggs.  Using a microscopically fine needle, they
injected the viral genetic code into the nucleus of the eggs,
 then reimplanted them into a surrogate mother mouse.  Those
eggs grew into baby mice harboring the AIDS virus in every
cell.  But the process is tricky; the transplant has fully
spread the virus in only 10% of the embryos.
   "So far, we have four animals in which we know the
injection worked.  Now we're breeding them, and freezing the
embryos" for later use, Dr. Martin says.  Next he will watch
for signs that a latent disease state may be taking over in
the parents and offspring.  Dr. Martin has until April, the
deadline under an agreement with NIH. Then he must destroy
the mice.
   Opinion is divided both on the worth and the safety of the
experiment.  The most alarming specter is being raised by
Jeremy Rifkin, whose Foundation on Economic Trends last month
 filed suit in federal court in Washington, D. C., asking that
the government halt attempts to breed the hybrids, update its
biosafety standards and file environmental-impact statements
covering all such genetic manipulations.  The government's
reply is expected soon.
   "Escape isn't a remote possibility," Mr. Rifkin warns,
adding that once an animal is loose there's no way to get it
back.
   He isn't the only one who is concerned.  Liebe F. 
Cavalieri, a scientist at Sloan-Kettering Memorial Cancer
Institute in New York, says that due to the closed nature of
the scientific fraternity, "Others might not want to talk
about (their reservations)."  But he insists that the danger
of biting or escaping rodents "is of concern not only to me
but to others."
"I imagine they can rationalize it," he says, but adds:  "I
think that the risk isn't worth it."
   Other scientists dismiss Mr. Rifkin as a "cynical"
obstructionist.  That's the view of Philip Leder, chairman of
the department of genetics at the Harvard Medical School.  Dr. 
Leder has used transgenic mice to explore the origins of
breast cancer.  He says they are a legitimate tool, even if
limited by the differences between injecting AIDS genes into
mouse cells and a natural case of human infection.
   And Dr. Martin dismisses Mr. Rifkin's catastrophic vision
as a "National Enquirer scenario."  The mice are locked in a
maximum security lab of the kind reserved for such killers as
smallpox or Lassa fever, he explains.  They live in a sealed
glass cage, reachable only through gloved portholes.  The cage
is antiseptically bordered by bleach-filled "dunk-tanks," and
a device to heat-sterilize animal waste is nearby.  The lab is
secured behind four locked doors and one screened vestibule,
 all mined with mousetraps.
   "I would like to say (chances of escape) are zero," Dr. 
Martin says.  "But since I'm a scientist, I'll just say
they're very, very slim."
   NIH's Institutional Biosafety committee voted 5-0 to
approve the experiment, says its chairman Dinah Singer, a
Ph.D. molecular biologist.  The committee also added safety
measures, such as a clear plastic door through which an
entering scientist can see "if a mouse is scratching to get
out."  Ms. Singer also urged NIH to breed some special,
enfeebled mouse strains that couldn't survive outside the
lab.
   Mr. Rifkin argues that such measures aren't enough.  He and
his group want the court to force NIH to do (environmental
impact statements) on all labs, government and commercial,
under contract to the government, he says.  He says this
hasn't been done since 1976 -- before AIDS and before recent
refinements in genesplicing.
   Ms. Singer counters that her committee approached the
experiment with the utmost caution.  "It's very easy to say
no," she says.  "But all of us at NIH feel a responsibility to
do something about AIDS. And research isn't without risk."

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