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Superbug Killers
Western scientists discovered a potent weapon against
antibiotic-resistant bacteria in an unlikely place: Soviet-era
medical labs
By Anna Kuchment
NEWSWEEK INTERNATIONAL
Dec. 17 issue — Alfred Gertler had never been so ill. In 1997
the 45-year-old jazz musician was hiking in Costa Rica when he
fell and broke his ankle. He contracted a staphylococcus
infection so severe that flare-ups kept him in bed for weeks at
a time. Antibiotics were of no use: the circulation in his ankle
was too poor to transport the medicine to its target. When
doctors told him that they might have to amputate his foot,
Gertler buried himself in books and magazines, looking for a
solution. He found one: bacteriophage therapy, a little-known
medical treatment that doctors in the former Soviet Union had
been using for decades.
LAST FEBRUARY, GERTLER flew to the Eliava Institute in
Tbilisi, Georgia. He found doctors laboring by the light of
kerosene lanterns in poorly heated buildings with just one hour
of running water per day. They applied a solution of
bacteriophages—tiny viruses that destroy bacteria—directly to
his ankle. It worked. “The infection was completely gone in
three days,” says Gertler. He plans to have foot-saving surgery
early next year. Soon it won’t be necessary to fly to Tbilisi.
Many scientists believe bacteriophages will be an important new
weapon in the fight against antibiotic-resistant infections. In
the past decade, chronic overprescribing of antibiotics has
weaned new strains of superbugs, and pharmaceutical firms have
begun to run out of drugs to fight them. Fortunately, biotech
start-ups from Baltimore to Bangalore are developing phage
treatments that fight infectious diseases such as tuberculosis
and salmonella, as well as anthrax and other bioweapons. Even
though the treatment has logged eight decades of use in eastern
Europe, its success has been largely anecdotal. ”[Soviet
scientists] took for granted that phages work,” says Nina
Chanishvili, a senior microbiologist at the Eliava Institute.
“They didn’t feel they needed to justify how safe it was, and
nobody bothered to build up any data on them.”
That’s what scientists are doing now, more than 80 years
after phages were first administered in Paris to four patients
with severe dysentery. (All four recovered.) The treatment was
first popularized in Sinclair Lewis’s 1925 novel “Arrowsmith,”
about a young doctor who stumbles upon a bacteria-eating virus.
“You may have hit on the supreme way to kill pathogenic
bacteria!” exclaims one character. At one time German and Red
Army soldiers carried vials of phages in their medical kits, and
the U.S. firm Eli Lilly marketed seven different phage
preparations to fight staph, streptococcus and E. coli .
Antibiotics, which proved more effective and simpler to use,
eclipsed them in the 1940s, but now phages are undergoing a
renaissance. “I call it ‘back to the future’,” says Alexander
Sulakvelidze, cofounder of Intralytix, a Baltimore biotech firm.
Scientists still have some hurdles to overcome. One is
political: the lingering distrust of Soviet medicine. Some
doctors are also reluctant to administer live viruses for fear
they’ll make patients ill. (Experts are quick to point out that
phages target bacterial—not human—cells.) And phages, like
laser-guided missiles, are very specific: one phage kills only a
specific subgroup of bacteria. (Salmonella, for example, has
more than 2,400 subgroups.) Whereas antibiotics, medicine’s
weapons of mass destruction, kill many different types of
bacteria in one go, a physician would need to make a very
specific diagnosis before prescribing a phage treatment. To make
it easier, scientists at Intralytix are developing phage
“cocktails,” and Phage Therapeutics in Seattle has genetically
engineered superphages that attack bacteria across subgroups and
species. When they eventually hit the market, phages will prove
to have distinct advantages over antibiotics, say researchers.
Practice has shown phages to be safe: no patient has ever been
known to suffer an allergic reaction to them. That may be
because phages are the most ubiquitous living organisms on
earth, found in soil, water, plants and humans. And, unlike
antibiotics, phages multiply at the site of an infection. “It’s
the only drug that makes more of itself as it works,” says
Richard Carlton, president of Exponential Biotherapies in New
York. The tiny viruses—200 million fit in a drop of water—kill
by attaching to a bacterial cell and injecting phage DNA. Once
inside, new phages replicate until the cell bursts, sending
“daughter” phages scurrying off in search of more prey. The
specificity of phages would be an advantage in treating patients
whose immune systems have been compromised by AIDS or cancer
treatment. Because antibiotics destroy good cells that keep bad
ones at bay, these patients often succumb to deadly secondary
infections. And even though bacteria can develop a resistance to
phages as well as to antibiotics, researchers say it takes only
a few days to isolate a fresh and effective phage, as opposed to
years to make a new antibiotic.
Progress in introducing phages to Western medicine has been
rapid, though marketable products are still at least three years
away. Exponential Biotherapies recently completed the first
phase of clinical trials for a treatment against the superbug
VRE (vancomycin-resistant enterococci), which kills thousands of
cancer and AIDS patients each year. Intralytix is working on a
treatment for the same bacteria, and also has a patent pending
for PhagoBioDerm, a phage-impregnated bandage that helps heal
serious skin infections. The company, which expects to close its
second round of financing in January (it is asking for $8
million), is about to move into its new lab: a 5,000-square-foot
facility overlooking Chesapeake Bay, where its researchers find
most of their phages. Other companies aren’t far behind. Phage
Therapeutics has gone public and hopes to start clinical trials
in March for eyedrops that fight staph infections that can cause
blindness if not treated quickly. “With antibiotics,” says
president and CEO Richard Honour, “it can take days for blood
levels to get high enough [for the medicine to work]. But when
you put a phage drop in the eye it begins to act immediately.”
Late last year Janakiraman Ramachandran, former president of
AstraZeneca, found-ed Gangagen in Bangalore, India. With money
from a U.S. venture capitalist who prefers to remain anonymous,
three months ago he opened an office in Palo Alto, California,
and plans to double its staff in the next year. Phage
researchers are exploring the virus’s effectiveness against
anthrax—particularly strains genetically engineered to resist
antibiotics. Intralytix and Exponential Biotherapies are also
applying phages to salmonella and E. coli bacteria in poultry
and meat products. One treatment being developed by Intralytix
can be sprayed on eggs, chicks or chickens before packaging.
Both companies have partnerships with meat-processing plants in
the United States and western Europe. Nobody expects phages to
be a magic bullet that will replace antibiotics. “They’re an
important addition to the tools we already have,” says
Sulakvelidze. “For some patients, they may prove to be the only
thing that works.” With superbugs on the rise, the number of
such patients will surely grow.
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With Ian MacKinnon in New Delhi and Eve Conant in Moscow
© 2001 Newsweek, Inc.
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