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Linda Marsa; The Los Angeles Times; Mar 31, 2003; pg. F.3
Enlisting viruses to battle bacteria
Early last century, bacteria-eating viruses were considered a
potentially powerful weapon against dangerous bacteria. After
all, they were a natural enemy, infiltrating disease-causing
microbes and destroying them from within.
But the track record of these viruses, known as
bacteriophages (or phages), proved spotty, and Western
physicians largely abandoned them in favor of antibiotics. Now,
it seems, disease-fighting has come full circle.
As even the most potent antibiotics lose the upper hand
against bacteria, researchers are again exploring the potential
of these virulent invaders, with several biotechnology companies
in the U.S. and Canada developing phage therapies.
"People are now desperately looking for alternatives, and
there's a lot of data showing that phages have tremendous
promise," says Alexander Sulakvelidze, an epidemiologist at the
University of Maryland School of Medicine in Baltimore who
conducted phage research in the former Soviet Union and works
for a biotech company that is developing phage products.
Scientists there and in Poland stuck with phages, which are
much less expensive to produce than antibiotics, and figured out
ways of making them more effective. Millions of people in
Eastern Europe and the former Soviet Union routinely use them to
combat a variety of infections.
Phages, one of the most abundant life forms on Earth, are
found in soil, water, plants, sewage, on our bodies and even in
our digestive tracts, where they live in relative harmony with
the other microbes carpeting our insides. These viruses bore
inside bacteria and hijack their genetic machinery, turning the
bacteria into mini-phage factories. Eventually, so many copies
of the phages are produced that the cell bursts, destroying the
bacterium, and the newborn phages invade the next bacterium.
Each strain of phage is highly specific and homes in on only
a specific type of bacteria, which means predator and prey must
be a suitable match for the phage to be effective. In the early
days, however, doctors weren't aware of this specificity, which
is why sometimes the preparations worked and sometimes they
didn't. Phage treatments also frequently weren't purified
properly, which made some people deathly ill after ingesting
them.
"They made every mistake in the book and did some really
stupid things," says Dr. Richard M. Carlton, president of
Exponential Biotherapies of Port Washington, N.Y. "They just
took what was on the shelf and assumed it would work."
Modern technology, however, can easily identify likely
targets for the finicky phages, and their fussiness is
considered a plus. Unlike the mass destruction of antibiotics,
which wipe away everything in their path and can trigger
diarrhea or secondary infections, phages only devour the
malevolent bugs, leaving the beneficial flora and fauna intact.
"It's like the difference between an H-bomb and a
laser-guided rocket," says Sulakvelidze, who also is a scientist
with Intralytix, a Baltimore biotech company that is developing
phage products. "Phage therapy would allow us for the first time
to handpick the bad bacteria that is really causing the problem,
and get rid of them without touching anything else."
Despite these advantages, many obstacles must be overcome
before phages become standard treatment. "To kill off the right
bacteria, you must use the right phage," says Dr. Carl R. Merril,
a scientist at the National Institutes of Health in Bethesda,
Md., who has studied phages for nearly 40 years. Consequently,
he says, scientists need to develop rapid methods of determining
which phage to use when someone has an infection, and reliable
ways of purifying these preparations.
"We're still in the research stage, but the potential is
enormous," says Sankar Adhya, a geneticist and phage researcher
at the National Cancer Institute in Bethesda. "Within the next
five years, human therapies may be available."
Phage therapies under development
Numerous phage therapies are being developed to combat
infections and kill food-borne pathogens.
But one phage treatment is far ahead of the pack; it is being
tested against the superbug VRE, or vancomycin-resistant
enterococci, which each year kills thousands of patients whose
immune systems have been compromised by AIDS or cancer
treatment. The therapy recently has been tested in a small
number of people, and the maker, Exponential Biotherapies, hopes
to start larger-scale human tests before the end of the year.
Other companies are in the earlier stages of research into
phage therapeutics to treat skin infections including burns and
wounds, diabetic ulcers, bedsores, respiratory infections and
treatment-resistant staph infections.
However, the first phage products to hit the market most
likely will be used in agriculture. They will help cut down on
the overuse of antibiotics in livestock, which is a major
contributor to drug resistance in humans, and improve food
safety. Several companies, such as Intralytix, GangaGen in Palo
Alto and Montreal's Biophage Pharma, are devising phage remedies
for bacterial infections in animals and phage sprays to
eradicate food-borne pathogens, such as listeria, salmonella and
E. coli, which kill hundreds of Americans every year.
Intralytix, which has permission from the Environmental
Protection Agency to test a phage against listeria in a
food-processing plant, hopes to have this product on the market
within the year.
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