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11/28/2000

Deceptive Beetles and Viruses

Although not very likely, by the time you read this we may know
the identity of our leader-elect. Hopefully, the opposing camps
will eventually close ranks and learn to cooperate sufficiently for
all of us to enjoy the fruits of our complex democratic system.
Perhaps the politicians could use as a model the Mojave Desert''s
blister beetle larvae, which employ cooperative behavior to enjoy
their own fruits, in the form of pollen. These blister beetles,
probably better known to you as Meloe franciscanus, were the
subject of a paper in the May 4 issue of Nature by workers at San
Francisco State University.

Like Winnie the Pooh, the brittle beetle larvae have a fondness
for bees'' nests. Apparently, they find it difficult to wend their
way to the nests and prefer to use subsonic air transport, one of
the subjects of last week''s column. However, instead of buying a
ticket for the shuttle flight to the nearest nest, they resort to a
clever subterfuge that must have involved a lot of years of
evolution. First, they gather themselves together by the hundreds
to form a clump. Not just any old clump, but one that has the
general shape and color of a female bee. Naturally, when a male
bee sees this clump his hormones kick in and he tries to mate
with it! The beetle larvae grab onto his chest hairs and as he flies
off in disgust at being deceived, the male bee serves as the carrier
for the first leg of the itinerary. Finally, the eager suitor finds a
legitimate subject for his amorous advances. At that point, the
beetle larvae switch connections and hitch a ride on the back of
the female, who serves as the final leg of the flight to the nest.
The beetles then feast on the pollen in generous abundance in the
nest. According to the excerpt of the article I saw in the July
Scientific American, the authors of the Nature article also tried
using painted models of the beetle clump to attract the male bees.
The males were not fooled. This led the investigators to
conclude that the larval clump not only looks realistic, but also
manages to smell like a female bee.

Nature works in curious ways. Quite aside from the above insect
behavior, I was intrigued by a number of articles dealing with
another kind of critter, the bacteriophage, or phage for short.
Like the beetle larvae, the phage uses deception to accomplish its
objectives, in this case attaching itself to a bacterial cell. You
might deduce that the net result is generally not benign for the
bacterium from the fact that the word "phage" is derived from
"phagein", a Greek word meaning "to eat." The bacteriophage
"eats" bacteria. I was attracted to the phage by a picture of one
variety of so-called "tailed" phages in an article in a recent
Smithsonian magazine. There are a wide variety of phages but
this particular one had a hexagonal head and sort of resembled a
stick figure with no arms but with several "legs". The body was
like a coil forming a hollow rod or tube. Other tailed phages
dispense with the "legs". The dining habits of bacteriophages in
"eating" bacteria are somewhat unsettling to me.

I should have pointed out that these phages are actually viruses,
that class of objects that seem in a kind of limbo between the
living and nonliving. You need electron microscopes to see
viruses but phages are positively stunning when it comes to their
population. I searched the Web site of the American Society for
Microbiology and found that the number of tailed phages in just
a couple drops of seawater or fresh water could range from the
millions to a billion. It was estimated that if you could gather up
the humongous number of such phages on our planet, they would
weigh a thousand times or so more than all the elephants on
earth. I have no idea how many elephants there are but you get
the point.

Why should you be concerned about phages? We''ve all heard
about unpleasant viruses such as the HIV virus, the poliovirus
and the Ebola virus. Hopefully, you''ve not experienced any of
these personally. Almost certainly, you''ve had many contacts
with various adenoviruses, which cause the common cold. But
do you know that your very life could someday depend on your
doctor employing "phage medicine" to fight off drug-resistant
bacteria?

But back to the way phages "eat" bacteria, those single-cell
microorganisms. In that hexagonal shaped head, the phage
contains a number of strands of DNA. That hollow coil that
forms its "body" can contract and act like a hypodermic needle.
The phage comes up to the unsuspecting bacterium and latches
onto one of the bacterium''s receptors. The phage then injects the
DNA from its "head" into the bacterium. This is the part that
bothers me. When the virus gets rid of its DNA, is it in effect
committing suicide or, since a virus is not a self-sustaining
creature, is the DNA really the "life" of the phage? Or, if the
phage isn''t a living thing at all, what does it matter? It seems to
me that these questions are just as profound as "Is there a sound
when a tree falls in the forest and nothing is around to hear it?"

Philosophy aside, once the phage''s DNA is in the bacterium, it
can do a couple things. If it''s a "virulent" phage, the phage DNA
will tell the bacterial cell to make more copies of itself (the
phage). In this case, the number of phages multiplies until the
cell breaks open, releasing a whole bunch more phages to
continue their dirty work. On the other hand, the phage can be a
"temperate" phage and its DNA can just worm its way into the
normal DNA of the bacterium and sit there without causing any
real problems. This is called ''lysogeny", which sounds a bit
obscene but really is much better for the bacterium than if it were
invaded by a virulent phage. Some time later, however, the
temperate phage DNA has the option of getting nasty and
starting to reproduce phages.

Now that we know roughly how the phage "eats" bacteria, let''s
consider some history. Bacteriophages were first discovered by
an English fellow, Frederick Twort and then by a French-
Canadian, Felix d''Herelle during the period of World War I. The
ability of phages to kill undesirable bacteria spurred a lot of
research and the use of phages developed an enthusiastic
following in some areas. One of these was in Tblisi, Georgia,
where some of the best work was done. One of the problems in
the early work was that nobody had a microscope powerful
enough to see a virus. Consequently, it wasn''t realized that each
kind of bacteria had its own special brand of phage that could eat
it. As a result, it was common to dump a phage mixture of
unknown identities into the fight to kill off bacteria responsible
for a particular malady. As a result, there were both successes
and failures, causing a lot of controversy and skepticism over the
usefulness of phages in treating bacterial diseases.

An exception to the generalized approach to phage therapy was
followed in Tblisi. There, they continued to sort things out and
over the years developed a catalog of different phages specific to
different kinds of bacteria. Meanwhile, since the 1940s, when
sulfa drugs and penicillin and other antibiotics arrived on the
scene, phage medicine was abandoned in most places. Today,
the worst scenario has come to pass with the evolution of drug-
resistant bacteria. Thousands of patients are said to be dying
every month with infections that have become resistant to even
Vancomycin, the drug of last resort.

One of the terms that you''ll hear in hospitals these days is VRE,
for Vancomycin Resistant Enterococcus. Enterococcus faecium
bacteria are bacteria that we live with in our intestines quite
happily. However, if your immune system is compromised, the
bacteria grow too vigorously and you can become quite ill and
even die. According to an interview with various medical
authorities published on the ABC Web site, 60 percent of this
Enterococcus is now of the VRE variety. In some hospitals, a
third of the patients now sport colonies of VRE. Furthermore,
VRE is everywhere in the hospitals, on stethoscopes, doorknobs,
etc. Washing or antiseptics don''t kill VRE. Not a pretty picture!

As a result of the failure of antibiotics to quash these evolving
bacteria, there is renewed interest in the field of phage therapy.
In the ABC interview, Dr. Betty Kutter, of Evergreen State
College in Washington, described her visit on a scholarship to
Tblisi a decade ago. One case affected her so strongly that it
changed her life. A fellow came in to have his leg amputated,
having had an infection for months that did not respond to any of
the treatments. It was decided to try phage therapy and a
certainly type of phage was applied after they had split open the
fellow''s foot in the area of the wound. When they opened up the
wound some time later it was perfectly clean. Today, Dr. Kutter
runs a nonprofit group called PhageBiotics in a network of
researchers studying phage medicine.

My general impression of the field of phage medicine is that the
phage is in the forefront of what might be a holding action. The
decoding of the genomes of humans and various bacteria should
eventually lead to well designed drugs to combat all kinds of
bacterial diseases and infections. However, this could take
decades or maybe even a century. In the interim, we face a crisis
of major proportions and the phage could play an important role
in holding the line against certain infectious diseases until the
reinforcements arrive on the scene. Nevertheless, it is clear that
phage therapy is no panacea and we''re in for a major battle that
could make our election conflicts pale in importance.

My wife had surgery a couple months ago. I, of course, was
concerned that the surgery''s objective be achieved but, in truth, I
was more concerned that she might pick up one of the drug-
resistant infections. Thankfully, she did not.

Allen F. Bortrum



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-11/28/2000-      
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Dr. Bortrum

11/28/2000

Deceptive Beetles and Viruses

Although not very likely, by the time you read this we may know
the identity of our leader-elect. Hopefully, the opposing camps
will eventually close ranks and learn to cooperate sufficiently for
all of us to enjoy the fruits of our complex democratic system.
Perhaps the politicians could use as a model the Mojave Desert''s
blister beetle larvae, which employ cooperative behavior to enjoy
their own fruits, in the form of pollen. These blister beetles,
probably better known to you as Meloe franciscanus, were the
subject of a paper in the May 4 issue of Nature by workers at San
Francisco State University.

Like Winnie the Pooh, the brittle beetle larvae have a fondness
for bees'' nests. Apparently, they find it difficult to wend their
way to the nests and prefer to use subsonic air transport, one of
the subjects of last week''s column. However, instead of buying a
ticket for the shuttle flight to the nearest nest, they resort to a
clever subterfuge that must have involved a lot of years of
evolution. First, they gather themselves together by the hundreds
to form a clump. Not just any old clump, but one that has the
general shape and color of a female bee. Naturally, when a male
bee sees this clump his hormones kick in and he tries to mate
with it! The beetle larvae grab onto his chest hairs and as he flies
off in disgust at being deceived, the male bee serves as the carrier
for the first leg of the itinerary. Finally, the eager suitor finds a
legitimate subject for his amorous advances. At that point, the
beetle larvae switch connections and hitch a ride on the back of
the female, who serves as the final leg of the flight to the nest.
The beetles then feast on the pollen in generous abundance in the
nest. According to the excerpt of the article I saw in the July
Scientific American, the authors of the Nature article also tried
using painted models of the beetle clump to attract the male bees.
The males were not fooled. This led the investigators to
conclude that the larval clump not only looks realistic, but also
manages to smell like a female bee.

Nature works in curious ways. Quite aside from the above insect
behavior, I was intrigued by a number of articles dealing with
another kind of critter, the bacteriophage, or phage for short.
Like the beetle larvae, the phage uses deception to accomplish its
objectives, in this case attaching itself to a bacterial cell. You
might deduce that the net result is generally not benign for the
bacterium from the fact that the word "phage" is derived from
"phagein", a Greek word meaning "to eat." The bacteriophage
"eats" bacteria. I was attracted to the phage by a picture of one
variety of so-called "tailed" phages in an article in a recent
Smithsonian magazine. There are a wide variety of phages but
this particular one had a hexagonal head and sort of resembled a
stick figure with no arms but with several "legs". The body was
like a coil forming a hollow rod or tube. Other tailed phages
dispense with the "legs". The dining habits of bacteriophages in
"eating" bacteria are somewhat unsettling to me.

I should have pointed out that these phages are actually viruses,
that class of objects that seem in a kind of limbo between the
living and nonliving. You need electron microscopes to see
viruses but phages are positively stunning when it comes to their
population. I searched the Web site of the American Society for
Microbiology and found that the number of tailed phages in just
a couple drops of seawater or fresh water could range from the
millions to a billion. It was estimated that if you could gather up
the humongous number of such phages on our planet, they would
weigh a thousand times or so more than all the elephants on
earth. I have no idea how many elephants there are but you get
the point.

Why should you be concerned about phages? We''ve all heard
about unpleasant viruses such as the HIV virus, the poliovirus
and the Ebola virus. Hopefully, you''ve not experienced any of
these personally. Almost certainly, you''ve had many contacts
with various adenoviruses, which cause the common cold. But
do you know that your very life could someday depend on your
doctor employing "phage medicine" to fight off drug-resistant
bacteria?

But back to the way phages "eat" bacteria, those single-cell
microorganisms. In that hexagonal shaped head, the phage
contains a number of strands of DNA. That hollow coil that
forms its "body" can contract and act like a hypodermic needle.
The phage comes up to the unsuspecting bacterium and latches
onto one of the bacterium''s receptors. The phage then injects the
DNA from its "head" into the bacterium. This is the part that
bothers me. When the virus gets rid of its DNA, is it in effect
committing suicide or, since a virus is not a self-sustaining
creature, is the DNA really the "life" of the phage? Or, if the
phage isn''t a living thing at all, what does it matter? It seems to
me that these questions are just as profound as "Is there a sound
when a tree falls in the forest and nothing is around to hear it?"

Philosophy aside, once the phage''s DNA is in the bacterium, it
can do a couple things. If it''s a "virulent" phage, the phage DNA
will tell the bacterial cell to make more copies of itself (the
phage). In this case, the number of phages multiplies until the
cell breaks open, releasing a whole bunch more phages to
continue their dirty work. On the other hand, the phage can be a
"temperate" phage and its DNA can just worm its way into the
normal DNA of the bacterium and sit there without causing any
real problems. This is called ''lysogeny", which sounds a bit
obscene but really is much better for the bacterium than if it were
invaded by a virulent phage. Some time later, however, the
temperate phage DNA has the option of getting nasty and
starting to reproduce phages.

Now that we know roughly how the phage "eats" bacteria, let''s
consider some history. Bacteriophages were first discovered by
an English fellow, Frederick Twort and then by a French-
Canadian, Felix d''Herelle during the period of World War I. The
ability of phages to kill undesirable bacteria spurred a lot of
research and the use of phages developed an enthusiastic
following in some areas. One of these was in Tblisi, Georgia,
where some of the best work was done. One of the problems in
the early work was that nobody had a microscope powerful
enough to see a virus. Consequently, it wasn''t realized that each
kind of bacteria had its own special brand of phage that could eat
it. As a result, it was common to dump a phage mixture of
unknown identities into the fight to kill off bacteria responsible
for a particular malady. As a result, there were both successes
and failures, causing a lot of controversy and skepticism over the
usefulness of phages in treating bacterial diseases.

An exception to the generalized approach to phage therapy was
followed in Tblisi. There, they continued to sort things out and
over the years developed a catalog of different phages specific to
different kinds of bacteria. Meanwhile, since the 1940s, when
sulfa drugs and penicillin and other antibiotics arrived on the
scene, phage medicine was abandoned in most places. Today,
the worst scenario has come to pass with the evolution of drug-
resistant bacteria. Thousands of patients are said to be dying
every month with infections that have become resistant to even
Vancomycin, the drug of last resort.

One of the terms that you''ll hear in hospitals these days is VRE,
for Vancomycin Resistant Enterococcus. Enterococcus faecium
bacteria are bacteria that we live with in our intestines quite
happily. However, if your immune system is compromised, the
bacteria grow too vigorously and you can become quite ill and
even die. According to an interview with various medical
authorities published on the ABC Web site, 60 percent of this
Enterococcus is now of the VRE variety. In some hospitals, a
third of the patients now sport colonies of VRE. Furthermore,
VRE is everywhere in the hospitals, on stethoscopes, doorknobs,
etc. Washing or antiseptics don''t kill VRE. Not a pretty picture!

As a result of the failure of antibiotics to quash these evolving
bacteria, there is renewed interest in the field of phage therapy.
In the ABC interview, Dr. Betty Kutter, of Evergreen State
College in Washington, described her visit on a scholarship to
Tblisi a decade ago. One case affected her so strongly that it
changed her life. A fellow came in to have his leg amputated,
having had an infection for months that did not respond to any of
the treatments. It was decided to try phage therapy and a
certainly type of phage was applied after they had split open the
fellow''s foot in the area of the wound. When they opened up the
wound some time later it was perfectly clean. Today, Dr. Kutter
runs a nonprofit group called PhageBiotics in a network of
researchers studying phage medicine.

My general impression of the field of phage medicine is that the
phage is in the forefront of what might be a holding action. The
decoding of the genomes of humans and various bacteria should
eventually lead to well designed drugs to combat all kinds of
bacterial diseases and infections. However, this could take
decades or maybe even a century. In the interim, we face a crisis
of major proportions and the phage could play an important role
in holding the line against certain infectious diseases until the
reinforcements arrive on the scene. Nevertheless, it is clear that
phage therapy is no panacea and we''re in for a major battle that
could make our election conflicts pale in importance.

My wife had surgery a couple months ago. I, of course, was
concerned that the surgery''s objective be achieved but, in truth, I
was more concerned that she might pick up one of the drug-
resistant infections. Thankfully, she did not.

Allen F. Bortrum