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Vol. 25 No. 6 SY 2005-2006 ISSN 0117-7060
SOPHOMORE
Articles
• The Fear Factor
Gene
• Pharmacogenomics
Activities
• What’s Your
Fear?
• Medicine for You
e-Pages
The Fear Factor Gene
F
By Josephine Ann A. Aparte
ear is the short-term physiological response produced by the brain and the body in response
to stress. Sometimes, it has its roots in traumatic events. Sometimes, it can be for no
apparent reason. Whatever its cause, fear is one of the most powerful emotions in humans
and animals. That is why we have literature passages such as, “…see the fear in her eyes…” or
“…the animal smelled his fear…” Fear is visceral emotion. Its effect on persons can range from
nagging discomfort to disabling anxiety.
Innate and Learned Fear
There are two types of fear: innate and learned. Innate
fear is something humans and animals are born with.
Without this type of fear, animals would not recognize
their natural predators or enemies. Humans would blunder
into life-threatening situations. Innate fear is built into our
genome. It helps us respond to natural threats.
Learned fear is acquired through individual experiences. It has been described as “a baggage of
bad experiences” and rightly so. Post-traumatic stress disorder and phobias are examples of learned
fear.
It’s Not All in Your Head
Scientists have discovered a gene that, when suppressed or removed, apparently banishes fear.
So if you have some kind of phobia or another, don’t worry. You may not be as loopy as you
suspect.
The gene is stathmin. Scientists working with laboratory mice discovered that when they took
out this gene, mice became bolder about exploring unknown territory and were less intimidated by
cues that they previously associated with danger. The mice, in short, became less “mousy.”
Fear or anxiety makes this part of the
brain (amygdala) more active.
Turning Wimps into Jocks
The scientists who discovered this wanted to find out
the mechanisms that program fear in the brain. They set
out to study the amygdala, that tiny region of the brain
known to be active when animals and humans were fearful
or anxious. They found that the protein stathmin (produced
by the stathmin gene) was plentiful in the amygdala and in
other parts of the brain’s fear circuitry. One of the scientists
involved in the study said that stathmin “was localized in
the pathway of the learning process and in the pathway of
instinctive fear.”
Armed with this knowledge, the scientists bred mice
from which the stathmin gene had been removed and
proceeded to test whether stathmin had a role in innate and
learned fear.
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To test the gene’s role in learned fear, they trained the
mice to associate an electric shock with either an auditory
tone or a particular location in a cage. After the training
period, normal mice would freeze when they heard the tone
or were put in a location that they had learned to associate
with electric shock. Stathmin-deficient mice, however,
went about their activities boldly even when presented
with the same stimuli that frightened the normal mice. This
indicates that stathmin is necessary for fear learning.
In the case of innate fear, scientists subjected the mice
to the “open field test,” a typical measure of innate caution.
Mice have a natural fear of open spaces. When left alone
on an unfamiliar white surface, the engineered mice readily
explored the open areas and were slower to leave the open
space than normal mice. The latter simply cowered on the
edges or scurried for cover.
In all other aspects, such as spatial skills and memory,
both the normal mice and the genetically engineered mice
were the same, indicating that the removal of the stathmin
gene did not affect the animals’ development in other
ways.
Amygdala: The Brain’s Fear
Center
The amygdala is the brain’s
emotional core and is responsible
for triggering the fear response.
Information that passes here
is tagged with an emotional
significance.
When the brain is startled, it
pushes an emergency button
connected to the amygdala. Once
the latter is activated, it alerts the
other brain structures. The result
is the classic fear response:
sweaty palms, racing heartbeat,
increased blood pressure, and a
rush of adrenaline.
The amygdala quickly primes
the body to either fight or flee. A
neuroscientist, Joseph LeDoux,
called it “the hub in a wheel of
fear.”
Potential Uses
The study was done in mice but the findings may be applicable to humans as well because the
brain system that registers fear is the same in all mammals.
First, it may help us understand better how fear works in the brain and provide new insights into
the genetic underpinnings of such fear-related mental disorders as anxiety, phobias, post-traumatic
stress disorder, and borderline personality disorder.
It may also help researchers develop new drugs and therapies to treat these conditions. For
example, the scientists who did this study suggested that stathmin may be instrumental in helping
brain cells form new memories in the amygdala, where unconscious fears appear to be stored. If the
activity of stathmin could somehow be inhibited (e.g., through some form of drug intervention), the
process of forming those memories could be prevented or delayed. This might help blunt the impact
of traumatic memories on people who would otherwise be very vulnerable to disabling memories
such experiences.
Also, it is possible that reducing stathmin activity in the amygdala might allow some people
to overcome some of their fears.
Sources
Carey, Benedict. Study pinpoints gene controlling fear. 18 November 2005. http://sfgate.com/cgi-bin/article.cgi?file=/c/
a/2005/11/18/MNG5TFQHK41.DTL
Hitti, Miranda. Unlocking the Origin of Fear. 17 November 2005. www.webmd.com/content/Article/115/111735.htm
Park, Alice. “The Anatomy of Anxiety.” Time, 8 July 2002, 42-43.
Loss of Fear Factor Makes Timid Mouse Bold. 18 November 2005. www.hhmi.org/news/kandel20051118.html
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Pharmacogenomics:
The Age of Personalized Medicine
W
By Josephine Ann A. Aparte
hat makes a person respond differently to a drug than the next person? What makes
a person more susceptible to some diseases than another person? The answer to both
questions lies in the genes, and both questions are the focus of pharmacogenomics, a
field which is still in its infancy, but which is already generating a lot of buzz.
The term pharmacogenomics is used interchangeably with pharmacogenetics, but experts
say there is a difference between the two. Pharmacogenomics refers to the general study of all the
different genes that determine drug behavior. Pharmacogenetics refers to the study of inherited
differences in drug metabolism and response. Pharmacogenetics is considered more focused in
scope and is viewed as a subset of pharmacogenomics.
One Letter Is All It Takes
The Human Genome Project (HGP) sought to identify the estimated 20,000 to 25,000 human
genes and determine the complete sequence of the three billion DNA subunits (chemical base pairs
that make up the human DNA). But even before scientists finished sequencing the human genome
in 2003, expectations were high that it would usher in a new era in medicine.
How Is This Related to Pharmacogenomics?
Armed with more detailed information about DNA variations called single-nucleotide
polymorphisms or SNPs (pronounced “snips”), scientists could identify genes responsible for
varying drug reactions in different people.
SNPs are DNA variations at a single base. These
chemical bases are A (adenosine), T (thymine), C
(cytosine), and G (guanine). They are arranged into threeletter “words” that the machinery of the cell understands.
Each gene is a “sentence” composed of a precise order of
these “words” (e.g., CGAGCG). The gene tells the cell
to make a particular protein (e.g., a digestive enzyme, an
antibody to fight off an infection, etc.). A single variation
in the order of the letters can spell the difference between
good and ill health. For example, a substitution of T for an
A in the spelling of the gene involved in the manufacture
of the hemoglobin protein in red blood cells results in
sickle-cell anemia.
A person’s response to a drug is also linked to these DNA variations. In other words, whether
a person will respond well to a drug or suffer side effects depends on his genes. This is what
pharmacogenomics is all about.
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Anticipated Benefits of
Pharmacogenomics
Pharmacogenomics is expected to result
in …
• More powerful medicines based
on proteins, enzymes, and RNA
molecules.
• Prescription of better and safer drugs
right at the start instead of through
trial and error.
• More accurate methods of determining
appropriate drug dosage rather than a
patient’s age and weight.
• Advanced screening for disease to
help a person make smart lifestyle
choices.
• Better vaccines made of genetic
material that will activate the immune
system but will not cause infections.
• Improvements in the drug discovery
and approval process using genome
targets.
• Decrease in overall cost of health care
due to less ADRs, smaller number of
failed drug trials, etc.
The Future of Drugs?
The pharmaceutical industry today makes drugs
using a “one size fits all” approach. This means that drugs
are designed to work on the “average” patient. However,
there have been many cases of patients suffering or even
dying from adverse drug reactions (ADRs) because their
bodies could not properly metabolize the medicines they
were prescribed.
In the age of personalized medicine, it is envisioned
that scientists will be able to “design” drugs or therapies
based on a patient’s genetic makeup. To some extent,
this is already being done in the United States.
There is a family of liver enzymes called
Cytochrome P450, which is responsible for breaking
down more than 30 different classes of drugs. Persons
with genetic variations that limit the effectiveness of
Cytochrome P450 may not be able to break down a drug
quickly enough and eliminate it from their system. If
that happens, drug overdose may result.
Enzyme testing will enable doctors to prescribe the
correct dosage—a lower dose to avoid side effects for
persons who metabolize the drug poorly and a higher dose for ultrafast metabolizers to guarantee
the drug’s effectiveness. This is just one example of pharmacogenomics at work.
What’s In It For Us
The hope riding on pharmacogenomics is that it will pave the way for the development of
better, cheaper, and more effective drugs.
Certainly, “better” and “more effective” may not be far off but “cheaper” remains to be seen.
After all, pharmaceutical companies are saying that if genetic testing conducted during clinical
trials proves that a drug’s use is limited to a certain subset of patients, then that relatively guaranteed
level of effectiveness means that they may be able to charge a higher price for the drug.
The field is still in its infancy and as with any new venture, there are kinks to be worked out.
So it maybe some time before genome-based medicine touches the average Filipino’s life. But
everyone (doctors, pharmaceutical executives, market analysts, regulators) agrees that the age of
personalized medicine is inevitable. It may take some time to become the norm, but the day will
come when it’s going to be the standard.
Sources
One Size Does Not Fit All: The Promise Of Pharmacogenomics. 31 March 2004. www.ncbi.nlm.nih.gov/About/primer/
pharm.html
Pharmacogenomics: Medicine and the New Genetics. 18 November 2005. www.ornl.gov/sci/techresources/Human_
Genome/medicine/pharma.shtml
Pollack, Andrew. New age of medicine: treatment tailored to your DNA, enzymes. 13 November 2005. http://sfgate.com/
cgi-bin/article.cgi?file=/c/a/2005/11/13/MNGD5FLESA1.DTL>
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A
C
T
I
V
I
T
Y
What’s Your Fear?
Take a guess. Draw a line to match the fear to its name.
1.
Fear of washing or bathing
Alektorophobia
2.
Fear of blood
Phronemophobia
3.
Fear of ghosts
Autophobia
4.
Fear of chickens
Ophidiophobia
5.
Fear of the number 13
Ablutophobia
6.
Fear of being alone
Triskaidekaphobia
7.
Fear of death or of dead things
Iatrophobia
8.
Fear of flying
Aerophobia
9.
Fear of crowds or mobs
Necrophobia
10. Fear of snakes
Ochlophobia
11. Fear of thinking
Phasmophobia
12. Fear of going to the doctor or of doctors
Hemophobia
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A
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T
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V
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Y
Medicine for YOU
2
3
4
5
6
7
8
9
ACROSS
DOWN
1. Pharmaco___ - study of the
1. Pharmaco___ - study of inherited
different genes that determine drug
differences in drug metabolism and
behavior
response
4. An organism’s complete set of
genetic information
2. The coded instructions for building
and operating a human being
5. Single-___ polymorphisms –
responsible for genetic variances
3. Basic physical and functional units
of heredity
7. Result of body’s inability to break
down drugs
6. The science of drugs
8. One of the chemical bases
9. ___P450 – a family of liver
enzymes involved in drug
metabolism
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Answers to Activities
What’s Your Fear?
1. Fear of washing or bathing – Ablutophobia
2. Fear of blood – Hemophobia
3. Fear of ghosts – Phasmophobia
4. Fear of chickens – Alektorophobia
5. Fear of the number 13 – Triskaidekaphobia
6. Fear of being alone – Autophobia
7. Fear of death or of dead things - Necrophobia
8. Fear of flying - Aerophobia
9. Fear of crowds or mobs - Ochlophobia
10. Fear of snakes – Ophidiophobia
11. Fear of thinking – Phronemophobia
12. Fear of going to the doctor or of doctors - Iatrophobia
Medicine for YOU
ACROSS
1. genomics
4. genome
5. nucleotide
7. overdose
8. adenine
9. cytochrome
DOWN
1. genetics
2. DNA
3. genes
6. pharmacology
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