ABSTRACT
Alcoholism is a serious disease that affects many people. About 76 million Americans are in someway affected by alcoholism. Current prescribed medications can only do so much. The solution lies in finding the roots of the problem. It has been believed that alcoholism runs down family lines, generation after generation. Is there scientific truth to this? Could the addiction be embedded in the human genome? John Crabbe and Justin Rhodes invite you to study their 10 years of research. Taking mice and making them alcohol-dependent, studying their human-like tendencies; alcohol tolerance, withdrawal symptoms, and voluntarily drinking alcohol and in some instances doing extra work for the tipple intoxicant. Using methods of genetic engineering, gene expression profiling and quantitative locus mapping, the two colleagues are equipped to haunt down the chromosome and location where alcoholism lay. With the genome being so outstandingly large, can a gene for alcoholism be merely pinpointed? After years of trying the scientists come closer then anyone before them, but it is Dr. Tamara J. Philips who furthers the journey and exploration. New strategies are needed to stop and treat this disease; a location in the genome is imminent upon us.

For centuries, alcoholism has been destroying many lives. The act of an addiction to something as harmful has alcoholism demolished families, relationships, and one’s own body. Alcohol on average is responsible for 100,000 deaths in America per year, whether it is from drunk-driving accidents, health problems, or various others means (Harwood, 1992). Children of addicts often feel isolated or depressed, because they tend to think the problem with their addictive parent(s) is their fault. Friends of addicts begin to feel rejected, because addicts often will start decline being with their friends to drink or hangout with people with similar alcoholic problems and patterns. Spouses will often deny the problem and will consequently suffer from depression or low self-esteem (CRH Health Group). Serious law cases have arrived involving the restriction of alcohol in the history of the United States in their short 235-year history. In 1920, alcohol abuse became such a problem that congress passed the 18th amendment, which prohibited the use, manufacturing, and sale of all alcoholic beverages. It was known has prohibition or the temperance movement; the movement was spearheaded by women in the country who were indirectly victims of alcohol abuse. Their addictive husbands were beating them, their addictions would financially drain their families and they overall suffered psychological damage as result (Curtis, 2007). The 21st amendment to the Constitution in 1933 ended prohibition, because the problems got worse. Addictions were still there and people began to make their own alcoholic drinks, which had more volume of alcohol on average (Curtis, 2007). In 2003 a trial called “People v. Gilligan” began; the case went as follows, Stacy Gilligan gave birth to a child and the baby tested positive for alcohol. Gilligan was then arrested on account of endangering the welfare of a child because she “knowingly fed alcohol to her baby via the umbilical cord.” Gilligan won the case, because by saying it is illegal to drink during a pregnancy denies the women of their rights. It also concludes that if alcohol-dependent women were legally not permitted to drink during a pregnancy would be hesitant to seek help from doctors and counselors for fear of law enforcement finding out (Glens Falls City Court, 2003). I personally have experienced many devastating instances of alcohol abuse in my life. My godfather has been paralyzed since he was 18 due to drinking and driving. My brother actually overcame alcoholism, but for a time he was heavily drinking and would become extremely violent and aggressive. Thankfully he overcame this and it was just a brief moment of his life. My friend’s brother is currently an alcoholic who is constantly getting in trouble with the law and creates a lot of tension in his house. Unfortunately, my friend also shows great signs of struggling with the addiction and I can relate to the feeling of rejection. Often he will choose going to bars and surrounds himself with others of similar problems instead of myself. These are real-life examples, enough about my life. Alcoholism is a disease that about 14 million Americans suffer from; this is an astonishing 1 in every 13 adults. Alcoholism for centuries has been known to run down family lines. However people have wondered if this was in the genome and if so they have wondered what gene or maybe what genes carry this trait down the family tree (New York City Department of Health). There has been much research and development on medicines that attempt to help people overcome alcoholism, however these pharmaceuticals have had little success. The majority of these medicines attack the medulla, the psyche rather then attacking what could be the genes responsible for alcoholism (Pub Med Health, 2008). For example, one medication prescribed to alcohol abusers is disulfiram, this is a chemical developed in the 1920’s which aims to produce more of the natural chemical acetaldehyde; this chemical produced by the body is assigned to break down ethanol or alcohol. In doing this people experience “hang-overs;” therefore people who drink while taking this medicine will experience extreme discomfort. This is an example of the psychology term, operant conditioning. This is what Pavlov did with his dogs; it is an act of conditioning in order to establish a response to a stimulus. In the case of this drug, it is conditioning people to associate consuming alcohol to a negative response, hangovers. However aside from this method being somewhat cruel, it is ineffective because the drug disulfiram has been known to cause symptoms such as seizures, heart failure, respiratory depression, and even death. (Pub Med Health, 2008) The current medications and methods of treating alcoholism are so ineffective, because they are not attacking the source the problem. Mainly because people didn’t know exactly where the source was. Has mentioned the disulfiram method was established in the 1920’s, The Human Genome Project began researching seventy years later in 1990 (Ridley, 1999). If alcoholism is indeed found in the genome then new strategies are needed to prevent and even treat this terrible disease. This led to Justin Rhodes and John Crabbe of the Oregon Health and Science University to conduct a research experiment to find where and if alcoholism is indeed a genetic disorder (Rhodes). For the research they wouldn’t study humans; they instead would study lab mice. The question arose many times whether mice could be alcoholics and how would anyone know. To answer this they exposed the mice to alcohol by placing it in their food portions or by putting the mice in chambers that had amount of alcohol vapor. After a period of time of the exposure they took away all the alcohol; this led to some of the mice with the observable withdrawal symptoms common in humans, sweating, nausea, dyskinesia and anxiety. More tests determined how severe the withdrawal symptoms in each mouse were. Other research to prove the mice could become alcoholics were tolerance, which was represented perfectly in the mice; the mice that had a longer history to alcohol exposure were able to keep their body temperature at normal temperatures and handle performance tasks better then those with a smaller history of alcohol exposure. The most important way to measure alcoholism in the mice was voluntary drinking. The researchers placed two bottles into the cages one that had water and one that had alcohol. They then made the alcohol bottle harder to obtain, mice that wanted the alcohol would have to do certain behaviors, like step on a switch to allow the alcohol to be released. After getting the numbers and information on which mice were considered alcoholics and which weren’t and to what severity of each they began the experiment to find if a gene is responsible. Rhodes and Crabbe used three approaches to find the gene or genes: genetic engineering, gene expression and quantitative trait locus mapping (QTL). In genetic engineering they would manipulate one gene at a time to determine its effect on a possible alcohol trait. The most important method they used became the quantitative trait locus mapping. This type is the study of the observable characteristics that will vary in degree and can have polygenic effects. What this means is they would study to see if the cause of a trait was due to more then one gene working together; one characteristic is controlled by multiple genes. What the two researchers did was they made a generation of mice called F1, this means they produced offspring of mice from very distinct parents; in this case they produced mice that had all different levels and variations of alcoholism. They then made another generation of mice, which was by inbreeding the F1 mice; this is called the F2 generation. They produced numerous amounts of offspring, because this would eliminate uniformity, simply meaning they would increase the amount of alleles or recessive traits that would be passed down. The process of quantitative trait loci mapping is a complicated one, but very affective. After the desired number of F2 mice were produced; Crabbe and Rhodes began to narrow down where the potential alcohol gene(s) could be located (Rhodes). This project continued for about 10 years, but Crabbe and Rhodes could not definitively locate where the chromosome for alcoholism lay. Dr. Tamara J. Philips then took over the project on her own, determined to finish the work done for her by Justin Rhodes and John Crabbe. One of the first conclusions she was able to understand was that alcoholism not only runs down the genetic family lines, but they get stronger. She was able to conclude that alcoholics that give birth to a child could be four times more at risk to be an alcoholic then someone born from non-alcoholic parents. By using quantitative trait locus mapping and the research laid out for her, she concluded that there are three chromosomes in mice most responsible for alcoholism; these are chromosomes 11, 15, and 16 (Philips, 2010). However, little published work has been done that proves this. Dr. Tamara J. Philips has been awarded numerous amounts of awards for her career devoted to the sciences and the genome; specifically in her pursuit to find uncover the detection of the alcoholism gene (Oregon Health and Sciences University, 2011). Taking the studies done before them a group of scientist were determined to find this mysterious location. In May of 2010 Alcoholism: Clinical & Experimental Research published a report, in this report Dr. Howard J. Edenberg talked about how they narrowed down where the gene is located. “We choose to examine the entire genome, all the genes at once, as an unbiased approach that has the potential of uncovering previously unsuspected genes,” says Edenberg. So, Edenberg’s group decided not to study just particular sections as done in the past. Through much research, experimentation, and collecting data from various people, they were able to determine chromosome 11 is definitely involved and they found potential other locations for the genes. David Goldman says that the locations they identified however are not strong enough locations to begin developing treatments. Their project is ongoing to this date; however through their breakthrough research they may be able to fully be able to pinpoint this huge societal problem in the humongous genome. Alcoholism affects some many people, whether it is alcoholics or those that know alcoholics; nearly this disease affects everyone. I talked about my experience with it. However, research is proving myths from before that alcoholism affects not just the living, but also the unborn. Those who are unborn to an alcoholic parent will have the gene encrypted into their genome—it is through extended research and experiments by devoted people that may eventually find the exact genes and come up with a possible solution for alcohol-dependency (Edenberg, 2010)

Bibliography (2011). Retrieved from Oregon Health and Sciences University: OHSU.EDU CRH Health Group. (n.d.). Drug and Alcohol Additction Recocvery Magazine. Retrieved 12 2011, from www.drugalchoholaddictionrecovery.com

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