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Dr. Horta Talks of Vaccine For Ending Substance Abuse

Dr. Javier E. Horta, Instructor in Chemistry, gave the fourth and final lecture of the year in the Science Faculty Seminar Series on Wednesday night. The presentation, entitled “Organic Chemistry at Work in the Development of Vaccines in the Treatment of Substance Abuse,” focused on the ways in which organic chemistry can be applied to remedy substance abuse and addiction. Dr. Horta began the presentation with an overview of the leading causes of death in the world. The number one cause of death in industrialized countries is vascular disease, which includes coronary artery disease and stroke. The second leading cause of mortality is cancer, and of those cancers, lung cancer is the most prevalent. The primary, most preventable and major underlying cause of these deaths is smoking. Over 50 million people in the US alone are smokers. Each year, 440,000 people die from smoking related health problems, and 4,000 young people smoke their first cigarette each day. The industry’s profit is $157 billion dollars a year, which is spent on tobacco and smoking-related products. Smokers, however, are not ignorant; over 70% of smokers wish to quit smoking, but less than 5% of smokers are able to stay smoke-free for over three to months after stopping. Dr. Horta presented a slide displaying a photograph of the “red, fleshy and healthy-looking lungs of a non-smoker,” followed by a picture of charcoal-looking lungs of a long-time smoker. “I know that with college comes a lot of experimenting; you will want to try different things. However, if you do choose to smoke, this is what you will be walking around with in your chest,” said Dr. Horta. Nicotine, the addictive substance in tobacco, is a natural neurotransmitter that acts on the central and peripheral nervous system, particularly the mesolimbic dopaminergic system of the brain, which consequently causes dependencies. Currently, the most effective widely used method for the treatment of smoking addiction that works against dependency causing molecules is a slow, tapering process. This approach is generally more successful than an attempt at quitting “cold turkey.” Often the treatment of substance abuse involves the usage of other drugs that counteract the withdrawal effects. However, these substitutes are often just as addictive, and a cycle can easily ensue. Examples of these methods of treatment are nicotine patches and nicotine-releasing gum. “These products are replacements for cigarettes, but the nicotine does nothing to stop the release of the neurotransmitters that cause the physical and psychoactive effects of smoking,” said Dr. Horta. Dr. Horta presented further statistics on the results and health benefits a smoker will receive after quitting. After only two weeks to three months after quitting, one’s risk of heart attack begins to drop. Ten years after quitting, the risk of developing cancer will decrease, and 15 years after quitting, the risk of coronary heat disease is on par with that of a non-smoker. Quitting at any age will reduce a person’s risk of mortality or other serious health risks associated with smoking and tobacco usage. While the list of health problems associated with smoking is very extensive, the most commonly cited health implication of smoking is lung cancer. Over 90% of lung cancer cases are smoking related. The percentage is similar for laryngeal cancer, the vast majority of cases of this form of cancer are due to smoking. Next, Dr. Horta presented how vaccines could be used to fight the effects of addictive substances like nicotine. Acknowledging that the “immune system very effectively uses antibodies to intercept any foreign substances that enter the body,” Dr. Horta showed how the production of antibodies against an offending agent required it to have certain structural and chemical components. “To elicit an antibody response, a foreign protein must be recognized by antibodies on the surface of B lymphocytes, which themselves are a subclass of a what are termed ‘antigen presenting cells,’ or APCs,” said Dr. Horta. Dr. Horta continued with an overview of an immune response to foreign substances. If the body were to have antibodies of several different hapten variants, it could effectively block the effect of nicotine on the brain. According to Dr. Horta, this might mean that if non-smokers were able to produce antibodies of nicotine, they could experiment with smoking, and would consequently have a significantly lower chance of becoming addicted, simply because the brain intercepts it. Dr. Horta then explained the hapten variants and structures that have been explored. To effectively elicit an antibody immune response against nicotine. it must be linked to a highly immunogenic protein. When scientists design a drug, they attempt to produce as much as possible in a specific orientation– the more diverse types of orientations means more possibilities for the “linker” to attach. However, Dr. Horta said, “Constraining nicotine conformations yields an enhanced immune response as compared to a flexible nicotine hapten.” So far, a variety of experiments have been conducted using rats. According to Dr. Horta, one particular experiment demonstrated that “immunization with the nicotine-protein complex prevents the acute stimulation of burst firing in mesolimbic dopaminergic neurons after small nicotine doses equivalent to those ingested by smoking one or two cigarettes.” In other words, rats with the immunization were recorded as having lower locomotive activity, meaning something “traps” the nicotine. “Presence of antibodies in blood stream greatly diminishes effects of nicotine,” said Dr. Horta. Just two weeks ago, news of a product called NicVAX was released to the public. The treatment is currently in the final stages of phase II clinical trials. Patients who showed continuous abstinence from smoking had higher antibody levels than those who did not quit. NicVAX patients showed a high rate of abstinence during a four-week period. While this was the last science seminar of the school year, presentations will continue next year. According to Dr. Hagler, instructor in Biology, the seminar series will remain in a similar format, occurring every other week. There is a possibility that high-level science students will have an opportunity to present on a specific area of focus, and outside speakers may be included in the weekly schedule as well.