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08/17/2005

Strange Fliers

How long has it been since you saw a G-rated movie? If you
haven’t seen “March of the Penguins”, you’re missing a movie
with everything – a passionate love story with sex, violence,
tragedy, fulfillment, stark realism, spectacular scenery and a
moving narration by Morgan Freeman. The Emperor penguin is
at once a most stately, yet ridiculous looking bird that becomes
an agile, streamlined creature in the sea, its favorite habitat.
Why did the penguin choose to hang around as Antarctica drifted
to its current position, with one of the coldest, inhospitable
climates on Earth? I could go on about the penguin’s hard and
inspiring life but don’t want to spoil the story if you haven’t yet
seen this wonderful movie about a bird that can’t fly.

Let’s turn to a creature that can fly. The fruit fly is a favorite of
scientists, the subject of a huge number of papers published over
the past century or so. When I saw mention of the results of one
fruit fly study in the September 2005 issue of Discover, I
couldn’t help thinking of chickens. One of the houses we rented
in Mechanicsburg, Pennsylvania, when I was a child, had a
chicken coop and we used it. My mother would select a chicken
for dinner and, wielding a hatchet, would chop off its head.

I found this a distressing sight, a bloody, headless chicken
flopping around on the ground for some time after losing its
head. I had to be convinced that the chicken really wasn’t alive
and that its movements were some kind of reflexive muscular
thing. I preferred that my mother just buy a “dressed” chicken,
all set to be stuck in the oven or to be chopped up to make fried
chicken. Later, in my first year of marriage, a chicken almost led
to divorce.

My pregnant wife sent me to a farmers market in Cleveland to
pick up some produce and a chicken. I dutifully found a nice,
plump “dressed” specimen and proudly presented it to my wife.
It was then that I found the term “dressed” did not mean the same
thing in Cleveland as it did in Pennsylvania. In Cleveland, it
meant that the chicken’s feathers were removed but not the inner
contents! My wife was not happy to learn of this regional
difference as she went to put the foul in the oven. A tearful and
disgusted trip to the laundry area to properly “dress” the chicken
followed; she has not trusted my shopping since that time.

But I digress. Back to fruit flies and the work of Gero
Miesenb ck and graduate student Susana Lima at Yale,
published in the August 8 issue of the journal Cell. Parkinson’s
disease is a prime example of a disease involving the loss of
control over one’s motor skills. In Parkinson’s, the dopamine
receptors don’t do their job and one well-known treatment is L-
dopa, which works for a limited time in many cases. Fruit flies
also have dopamine neurons, which stimulate walking and
control the path that a fruit fly follows.

What the Yale researchers have done is to genetically engineer
so-called “phototriggers” for different sets of fruit fly neurons.
They have engineered these phototriggers to affect not only
dopamine neurons but also neurons in the “giant fiber” system in
the fruit fly. When giant fiber neurons are stimulated, the escape
response is activated – there’s beating of the wings, jumping and
flight. You know these neurons do their job very quickly if you
try to catch or swat a pesky fly. Normally, if researchers want to
try to study individual neurons or small groups of neurons, they
wire up electrodes in contact with the neurons. Apply a voltage
to the electrode to prod the neuron into action. By observing
what action occurs, you can trace it back to that neuron.

It’s obvious that wiring electrodes to neurons in a fly must be a
delicate and difficult task. Here’s where Miesenbock and Lima’s
phototriggers provide a distinct advantage. Their phototriggers
respond to light, no electrodes required. When they illuminate
their giant fiber phototriggers with laser light, the fruit fly flaps
its wings, jumps and/or flies away. Blind flies respond in the
same manner. The laser light penetrates through the cuticle, or
skin, of the fly to reach the phototrigger. If the photriggers are
associated with the dopamine neurons, the researchers can
stimlate walking and control the path the fly takes. (I’m not sure
whether the dopamine neurons respond in a blind fly.)

So, what Lima and her professor can do is shine the laser light on
the genetically engineered flies and control what they do, at least
most of the time (60-80%). Some might see this as a disturbing
step towards mind control but what if there’s no mind to control?
Here’s what reminded me of my mother and the chicken. It
seems that flies can be kept “alive” up to a day if kept moist –
without their heads! So, what happens if you shine laser light on
a headless fruit fly that’s been in the hands of the Yale
researchers? It jumps, walks around and even flies away! The
implications for science fiction movie scenarios are endless!

How do they do it? Something called an ion channel is one
player. Ion channels play an important role in our bodies and let
certain charged ions pass through them. Lima and Miesenbock
managed to genetically engineer ion channels not normally
attached to the selected neurons. When a compound known as
ATP, a compound found in all plant and animal cells, latches
onto one of these ion channels it causes the neuron to fire and do
its thing. The Yale scientists made a “cage”, another compound
that traps ATP. They inject the caged ATP into the fruit fly.

One analogy is to call the ion channel the lock, the ATP the key
and the cage the trigger. When light of the right wavelength hits
the cage, the cage opens up and releases the ATP. (It’s the
photons that open the cage, hence the term “phototrigger”.) The
ATP keys onto the ion channel and activates the neuron. The
fruit fly flies, walks, jumps, whatever that neuron controls.

I gathered the above details from various Web sites, notably the
Yale University, University of Minnesota and Scientific
American Web sites and the abstract of the paper on the Cell site.
(Sorry, I wasn’t willing to pay the $30 necessary to get the full text!)

The use of light, instead of electrodes to activate neurons and
observe the results directly seems likely to open up a new field of
endeavor in the area of studying the control of neuron activity
and resulting motion. Down the distant road is the hope that
such studies might help those with motion problems as in
Parkinson’s patients or in paraplegics.

Thanks to the generosity of our Editor, Brian Trumbore, I had the
opportunity to move around the course at Baltusrol last week at
the PGA. Actually, with the extreme heat and humidity, this 77-
year-old had no desire for much movement but did share with
Brian a few hours early Saturday morning sitting at the signature
4th hole until the Tiger and Couples twosomes had passed
through. Fortunately we did not have any falling branches, as
happened the day before on the 4th, sending one fellow to the
hospital with a broken leg.

In this world of cellphones and other audio devices (banned from
the course), it was impressive how utterly silent the hundreds of
spectators were while Tiger and the others were putting. At the
4th, while we were there, there were none of those exasperating
loud cries of “You’re the man!” or “Get in the hole!”

Allen F. Bortrum

Addendum: Regular readers will know that I’ve shamelessly
taken every opportunity to mention my hole-in-one some years
ago. In the interest of full disclosure, I’m compelled to reveal
my experience at the 4th hole at Baltusrol. I don’t belong to a
country club and when a Baltusrol member called one night
years ago to ask if I wanted to join his group the next morning, it
took me a microsecond to answer in the affirmative. That night I
couldn’t sleep, thinking of the 4th and the water to be cleared. It
turned out to be my most embarrassing golfing experience. I
dumped several balls in the water, finally shanking a shot that
skirted the side of the pond and carded a 13! However, I now
share something with Tiger – we both have hit drives into the
water on the 4th! (If you missed it, his was on Friday and the big
tree branch fell after he hit his shot from the drop area.)



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Dr. Bortrum

08/17/2005

Strange Fliers

How long has it been since you saw a G-rated movie? If you
haven’t seen “March of the Penguins”, you’re missing a movie
with everything – a passionate love story with sex, violence,
tragedy, fulfillment, stark realism, spectacular scenery and a
moving narration by Morgan Freeman. The Emperor penguin is
at once a most stately, yet ridiculous looking bird that becomes
an agile, streamlined creature in the sea, its favorite habitat.
Why did the penguin choose to hang around as Antarctica drifted
to its current position, with one of the coldest, inhospitable
climates on Earth? I could go on about the penguin’s hard and
inspiring life but don’t want to spoil the story if you haven’t yet
seen this wonderful movie about a bird that can’t fly.

Let’s turn to a creature that can fly. The fruit fly is a favorite of
scientists, the subject of a huge number of papers published over
the past century or so. When I saw mention of the results of one
fruit fly study in the September 2005 issue of Discover, I
couldn’t help thinking of chickens. One of the houses we rented
in Mechanicsburg, Pennsylvania, when I was a child, had a
chicken coop and we used it. My mother would select a chicken
for dinner and, wielding a hatchet, would chop off its head.

I found this a distressing sight, a bloody, headless chicken
flopping around on the ground for some time after losing its
head. I had to be convinced that the chicken really wasn’t alive
and that its movements were some kind of reflexive muscular
thing. I preferred that my mother just buy a “dressed” chicken,
all set to be stuck in the oven or to be chopped up to make fried
chicken. Later, in my first year of marriage, a chicken almost led
to divorce.

My pregnant wife sent me to a farmers market in Cleveland to
pick up some produce and a chicken. I dutifully found a nice,
plump “dressed” specimen and proudly presented it to my wife.
It was then that I found the term “dressed” did not mean the same
thing in Cleveland as it did in Pennsylvania. In Cleveland, it
meant that the chicken’s feathers were removed but not the inner
contents! My wife was not happy to learn of this regional
difference as she went to put the foul in the oven. A tearful and
disgusted trip to the laundry area to properly “dress” the chicken
followed; she has not trusted my shopping since that time.

But I digress. Back to fruit flies and the work of Gero
Miesenb ck and graduate student Susana Lima at Yale,
published in the August 8 issue of the journal Cell. Parkinson’s
disease is a prime example of a disease involving the loss of
control over one’s motor skills. In Parkinson’s, the dopamine
receptors don’t do their job and one well-known treatment is L-
dopa, which works for a limited time in many cases. Fruit flies
also have dopamine neurons, which stimulate walking and
control the path that a fruit fly follows.

What the Yale researchers have done is to genetically engineer
so-called “phototriggers” for different sets of fruit fly neurons.
They have engineered these phototriggers to affect not only
dopamine neurons but also neurons in the “giant fiber” system in
the fruit fly. When giant fiber neurons are stimulated, the escape
response is activated – there’s beating of the wings, jumping and
flight. You know these neurons do their job very quickly if you
try to catch or swat a pesky fly. Normally, if researchers want to
try to study individual neurons or small groups of neurons, they
wire up electrodes in contact with the neurons. Apply a voltage
to the electrode to prod the neuron into action. By observing
what action occurs, you can trace it back to that neuron.

It’s obvious that wiring electrodes to neurons in a fly must be a
delicate and difficult task. Here’s where Miesenbock and Lima’s
phototriggers provide a distinct advantage. Their phototriggers
respond to light, no electrodes required. When they illuminate
their giant fiber phototriggers with laser light, the fruit fly flaps
its wings, jumps and/or flies away. Blind flies respond in the
same manner. The laser light penetrates through the cuticle, or
skin, of the fly to reach the phototrigger. If the photriggers are
associated with the dopamine neurons, the researchers can
stimlate walking and control the path the fly takes. (I’m not sure
whether the dopamine neurons respond in a blind fly.)

So, what Lima and her professor can do is shine the laser light on
the genetically engineered flies and control what they do, at least
most of the time (60-80%). Some might see this as a disturbing
step towards mind control but what if there’s no mind to control?
Here’s what reminded me of my mother and the chicken. It
seems that flies can be kept “alive” up to a day if kept moist –
without their heads! So, what happens if you shine laser light on
a headless fruit fly that’s been in the hands of the Yale
researchers? It jumps, walks around and even flies away! The
implications for science fiction movie scenarios are endless!

How do they do it? Something called an ion channel is one
player. Ion channels play an important role in our bodies and let
certain charged ions pass through them. Lima and Miesenbock
managed to genetically engineer ion channels not normally
attached to the selected neurons. When a compound known as
ATP, a compound found in all plant and animal cells, latches
onto one of these ion channels it causes the neuron to fire and do
its thing. The Yale scientists made a “cage”, another compound
that traps ATP. They inject the caged ATP into the fruit fly.

One analogy is to call the ion channel the lock, the ATP the key
and the cage the trigger. When light of the right wavelength hits
the cage, the cage opens up and releases the ATP. (It’s the
photons that open the cage, hence the term “phototrigger”.) The
ATP keys onto the ion channel and activates the neuron. The
fruit fly flies, walks, jumps, whatever that neuron controls.

I gathered the above details from various Web sites, notably the
Yale University, University of Minnesota and Scientific
American Web sites and the abstract of the paper on the Cell site.
(Sorry, I wasn’t willing to pay the $30 necessary to get the full text!)

The use of light, instead of electrodes to activate neurons and
observe the results directly seems likely to open up a new field of
endeavor in the area of studying the control of neuron activity
and resulting motion. Down the distant road is the hope that
such studies might help those with motion problems as in
Parkinson’s patients or in paraplegics.

Thanks to the generosity of our Editor, Brian Trumbore, I had the
opportunity to move around the course at Baltusrol last week at
the PGA. Actually, with the extreme heat and humidity, this 77-
year-old had no desire for much movement but did share with
Brian a few hours early Saturday morning sitting at the signature
4th hole until the Tiger and Couples twosomes had passed
through. Fortunately we did not have any falling branches, as
happened the day before on the 4th, sending one fellow to the
hospital with a broken leg.

In this world of cellphones and other audio devices (banned from
the course), it was impressive how utterly silent the hundreds of
spectators were while Tiger and the others were putting. At the
4th, while we were there, there were none of those exasperating
loud cries of “You’re the man!” or “Get in the hole!”

Allen F. Bortrum

Addendum: Regular readers will know that I’ve shamelessly
taken every opportunity to mention my hole-in-one some years
ago. In the interest of full disclosure, I’m compelled to reveal
my experience at the 4th hole at Baltusrol. I don’t belong to a
country club and when a Baltusrol member called one night
years ago to ask if I wanted to join his group the next morning, it
took me a microsecond to answer in the affirmative. That night I
couldn’t sleep, thinking of the 4th and the water to be cleared. It
turned out to be my most embarrassing golfing experience. I
dumped several balls in the water, finally shanking a shot that
skirted the side of the pond and carded a 13! However, I now
share something with Tiger – we both have hit drives into the
water on the 4th! (If you missed it, his was on Friday and the big
tree branch fell after he hit his shot from the drop area.)