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Seed Magazine, February/March
2006
Trial Phage
Why antibiotics are so 1990’s, and how
their complement may be squelched by the FDA
Cholera, syphilis, scarlet fever, tuberculosis, typhoid,
leprosy -- antibiotics have I helped hold these and other
diseases in check since the beginning of the 20th century, and
the prospect of their return is what keeps epidemiologists up at
night. But antibiotic resistance is cropping up all around, even
in some of the most well-outfitted hospitals in the richest
country in the world.
The solution to this problem is unlikely to come from Big
Pharma: Doctors often hold
the newest antibiotics in reserve to forestall the advent of
resistant infections, and while it makes sense from a health
standpoint, the practice discourages sales of new medications,
preventing investment. Instead, the answer may come from tiny US
biotech firms and a once-decrepit lab in Tbilisi.
The history of antibiotics is a cat-and-mouse game of "bugs
versus drugs." A disease crops up, a drug is produced to fight
it, and the bacterium evolves resistance to the drug, rendering
the medicine ineffective. Mass production of antibiotics vastly
increases the selection pressure on bacteria, causing them to
evolve mare rapidly. And over-prescription of the drugs, along
with their use in mass farming operations, has made it worse.
Hospital infections treatable just a few years ago are now
killing patients again.
But there is another way: tiny viruses that attack bacteria
called bacteriophages, or phages. Developed primarily in the
former Soviet Republic of Georgia, some strains are commonly
used as a tool in genetic engineering, but their potential for
fighting bacterial infections has remained obscure to physicians
in the West for decades. Now, some doctors hope soon to develop
treatments.
While antibiotics are stable chemical compounds that invite
the evolution of resistant bacterial strains, phage viruses are
living organisms that evolve right alongside a bacterial
infection. In this antagonistic co-evolutionary race, resistance
to phage treatments is rarely a problem.
Bacteriophages are incapable of infecting humans. Because
they live off the bacteria they fight, they concentrate at the
site of infection, and since they reproduce as they kill, a
small dose is effective.
Plus, they're easy to come by: Phages are everywhere in the
environment. There seem to be at least one that preys on every
strain of bacteria, and to find those that fight infections, one
need only find a repository of human bacteria. In an apparent
inversion of all of Pasteur's and Lister's principles, cures are
found in pus, urine and feces.
And unlike with antibiotics, which cost millions to develop
and bring to market, on the rare occasions when bacteria do
become resistant to a phage drug, microbiologists need only
return to the sewer for a new strain of killer.
Hurdles to US clinical trials, however, are many. Though
widely used in the former Soviet Union, Western researchers have
found little they can sink their teeth into in the way of
scientific studies on phages by the Soviets: There were no
double-blind trials, and the remaining studies are often viewed
as unsatisfactory.
"There are a lot of applications in Russian [medical]
literature that describe the use of phages, and many of them
include controls," says Alexander Sulakvelidze, a Georgian
microbiologist and professor at the University of Maryland
Medical School who, with physician Glenn Morris has launched a
startup, Intralytix, Inc. to pursue phage treatment. "The
problems with those publications are that they are in
non-English literature, their scientific style is very different
from what one is used to seeing in English [language] scientific
publications and some of them are censored. For example, the
military was one of the heaviest users of phages so you won't be
able to find exactly how many patients were involved in their
studies or other crucial data”.
"This is something [the FDA] has never approved before," says
Sulakvelidze. "There is nopre-made list of things that need to
go into this approval process. There's no list to go down...and
the end say everything is done you can get approval."
One clear requirement that the agency appears to have set is
that all the phage viruses in a treatment be thoroughly
characterized, genetically sequenced and kept constant. Firms
currently seeking FDA approval have agreed to this approach, but
those further from trials, like Phage International, in the Bay
Area, are critical, claiming that limiting the genetic
variability of the phages will eliminate their inherent
strength.
"The FDA says that our requirement is that you stop the very
process that makes it work," says International's Ronald Gossens.
But, like a true entrepreneur, Sulakvelidze is optimistic about
phage: "I think their time is going to come”.
-Josh Braun |
