Survey
* Your assessment is very important for improving the workof artificial intelligence, which forms the content of this project
* Your assessment is very important for improving the workof artificial intelligence, which forms the content of this project
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. BATO BALANI Sophomore Vol. 25 No. 6 e-Pages 2 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 BATO BALANI Sophomore Vol. 25 No. 6 e-Pages 3 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. BATO BALANI Sophomore Vol. 25 No. 6 e-Pages 4 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> BATO BALANI Sophomore Vol. 25 No. 6 e-Pages 5 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 BATO BALANI Sophomore Vol. 25 No. 6 e-Pages 6 A C T I V I T 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 BATO BALANI Sophomore Vol. 25 No. 6 e-Pages 7 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 BATO BALANI Sophomore Vol. 25 No. 6 e-Pages 8