[Type the company name] 1 Honors Science, Period 6 15 December 2014 Semester Project – Animal Research in Medicine Task 1: Interpreting Scientific Research – Animal Research Is Vital to Medicine The purpose of the lab was for Louis Pasteur to determine if microorganisms were responsible for diseases. The significance is that it will help the advancement of medical science. Louis Pasteur’s experiment with chickens is detailed from the 1800’s before advanced technology. If you put an organism of a disease in a healthy chicken, it will develop the disease. However, if you keep giving the organism to the chicken, it develops immunity. This was the foundation for vaccines and flu shots (Botting and Morrison 83). The problem/question being addressed is whether animals should be used for medical testing. The purpose is that animal testing is necessary because it plays a large role in the development of modern medical treatment and the cure for new diseases. The hypothesis is that if it is proven true that microorganisms are responsible for diseases, then animal testing will lead to advancements in medicine including preventing viral and bacterial infections by reusing the microorganisms. To test his hypothesis, Pasteur examined the chicken guts of chickens suffering from a disease called cholera. Then he isolated the microbe and grew the organism in a culture. Next, he sampled the culture and gave it to healthy chickens and rabbits which produced cholera. This proved that he had identified the disease-causing organism. He noticed that over time, cultures of the microorganisms lost their ability to infect, but birds given the cultures became resistant to fresh batches that were deadly to untreated birds. Previously, physicians had noticed that people who had suffered a severe attack of a disease rarely contracted it again. Pasteur found a way of producing this resistance without risking disease. The experience caused him to identify that the [Type the company name] 2 weakened culture of the disease-causing bacteria would offer doctors the opportunity to give patients immunity to infectious diseases. This led to the development of shots such as the flu shot. The established control group was the untreated, healthy chickens that were not exposed to the weakened organism. The established experimental group was the chickens previously given the disease that when given it a second time developed immunity to cholera. The independent or changing variable of this experiment was the strength of the pathogen whether full or weak. The dependent variables or data Pasteur was collecting was the health of the chickens or severity of the illness after exposure to the more deadly culture. The variables that were necessary to control for this experiment include differences in bacteria, which is why Pasteur used cultures of the organism to ensure similarities in the bacteria. Also, the health of the chickens needed to be controlled for; while the journal did not specifically describe these variables, I can hypothesize that they could have included the same temperature, food, and living conditions. These variables would have been controlled so that Pasteur could better isolate the impact of the pathogens. The method that was used for representing the data was a qualitative description in this particular journal article. It was appropriate in this context because it was among many examples of how animal research is important to medicine. Other examples used data in text such the later impact of vaccines in saving lives and other animal research statistics. There was no specific quantitative data provided around the cholera chicken experiment. The scientific experiment resulting in the discovery of vaccines was described qualitatively by referencing that the healthy chickens given the disease became sick but when given the pathogen a second time, they developed immunity. As noted, this scientific journal article did not include specific quantitative data on the chicken cholera experiment, so there were no tables or graphs. However, there were numerous examples of the work that Pasteur influenced in establishing vaccines for [Type the company name] 3 infectious diseases such as diphtheria, tetanus, rabies, whooping cough, tuberculosis, measles, mumps, and rubella. Specific data referenced in paragraph form included: “….scientists developed a vaccine against Hemophilus influenzae type B (Hib), a major cause of meningitis, which before 1993 resulted in death or severe brain damage in more than 800 children each year in the U.S. Early versions of a vaccine produced only poor, short-lived immunity. But a new vaccine, prepared and tested in rabbits and mice, proved to be powerfully immunogenic and is now in routine use. Within two months of the vaccine's introduction in the U.S. and the U.K., Hib infections fell by 70 percent” (Botting and Morrison 86). The conclusion restates the original problem that doctors might be able to make their patients’ immune to infective diseases through animal testing, which does support the original hypothesis. The original hypothesis was that microorganisms were responsible for diseases, so the experiments on animals proved that this was true and that organisms develop immunity to diseases after being exposed to the disease. The hypothesis supported the conclusion because it showed how animal research identified that microorganisms do indeed cause diseases and can be used to give people immunity to infectious diseases. The explanation for the results refers back to the scientific background information by referencing that there was a “black hole” and that no advancement in the treatment of disease took place until experiments on animals put biomedical science on a “sound, empirical basis” (Botting and Morrison 85). It references the early research of Pasteur which utilized all of the techniques available at his time to answer the questions, including animal experimentation. This valuable information is useful because it has led to vaccines for many infectious diseases and has led to treatments for kidney failure, techniques for suturing blood vessels, and open heart surgery. The information would be applied to other fields of study in terms of other [Type the company name] 4 ways that animals can be used in research and testing. Genetic engineering requires animals for research on how to identify, change, and replace genes. Researchers use similar techniques as Pasteur by removing a gene from a mouse to see how it develops without the gene or by placing the genes of one species into another (Woods 20). Another example is applying to product safety testing to ensure that people do not get hurt by household cleaners, pesticides and other chemical products by using animal trials (Hayhurst 22-23). The general public would use this information to understand the benefits of animal research through numerous medical developments. The scientific community would use it in advancing the critical importance of animal research as a necessary means to respond to existing and new diseases. The problem or source of error in Pasteur’s experiment was the need to isolate the disease-causing organisms. He did this by examining the internal part of chickens with cholera, isolating possible microorganisms, and growing them in culture. Through testing of the cultures, he was able to eventually identify the correct microorganism. This affected the results by allowing him to successfully determine how a weakened culture can induce immunity to infectious disease. He went on to also isolate the organism that causes anthrax and develop a vaccine against that. Finally, the conclusion addresses what could be done to find out more about the subject by reinforcing that animal research is critical to the progress of biological and medical science. It does this by addressing the arguments of opponents and by providing examples of progress underway. The authors suggest an exercise that opponent should try to describe how an alternative procedure could have provided the same benefit as animal research; for example, they ask how opponents would have advanced the treatment of mitral valve insufficiency caused by a defect in the heart. An artificial valve was developed after 20 years of experimentation on dogs. Further, they refute arguments that animal research is inaccurate because of differences in physiology between animals and [Type the company name] 5 humans by stating that both control their internal biochemistry by releasing similar hormones, both send out similar chemical transmissions from the nervous systems, and both react to infection or tissue injury the same way. In terms of future progress, they reference how transgenic animals with a single mutant gene are providing new information on the role of proteins in disease, as well as animal research on nerve regeneration which is assisting the treatment of central nervous system traumatic injury. [Type the company name] 6 Task 1: Interpreting Scientific Research – Animal Research Is Wasteful and Misleading; Framingham Heart Study The purpose of the lab was to demonstrate that there are better research methods available than animal testing. The significance is that the authors want to prove that more reliable methods than animal experiments will provide a better investment of research funds in addressing the more current health problems of our times such as heart disease, cancer, stroke, AIDS, birth defects, etc. There is much background information provided on scientific concepts as to why animal tests are not applicable and that better methods are available. The journal describes that the multiple systems of organs interact in a complex manner, so that applying a stimulus to a specific organ affects the animals’ overall physiology in a number of ways. They identify this as a weakness in correlating animal data to humans. For example, studies on monkeys indicated that the polio virus infects the nervous system, but scientists learned that this was because they had given the viral strains through the nose and this affected the brain tissue. However, research using human cell cultures showed that the virus could be produced on tissues from the intestine and limbs. The U.S. General Accounting Office reviewed 198 of the 209 new drugs marketed between 1976 and 1985 and found that 52% had risks not predicted by animal tests; the drugs had to be withdrawn or relabeled (Barnard and Kaufman 2). On the other hand, they propose that better techniques include epidemiological studies, clinical intervention trials, clinical observation with lab testing, human tissue and cell cultures, autopsy studies, endoscopic analysis and biopsy, new imaging methods, and molecular epidemiology. For example, “in vitro studies using human cells and serum allowed researchers to identify the AIDS virus and determine how it causes disease” (Barnard and Kaufman 3). The problem/question being addressed is the lack of effectiveness of animal research and testing. The purpose is that there are [Type the company name] 7 more current and relevant techniques which should be funded to lead to better treatments and medical methods. In the specific experiment example, the Framingham Heart Study, the risk factors for heart disease were studied in humans to better understand the causes of heart disease. The hypothesis is that if more effective scientific methods such as epidemiological studies are used rather than animal research, then more successful diagnosis and treatment will result. In this experiment, risk factors for heart disease, including high cholesterol levels, smoking, and high blood pressure indicated that if cholesterol levels were reduced, low fat diets were maintained, regular exercise was pursued, stressed was managed and smoking ceased, then atherosclerotic blockages could be reversed. It was assumed that heart disease did not have a single cause. The major hypotheses were that heart disease increases with age, occurs more often in males, develops faster in people with hypertension, higher cholesterol levels, diabetes, gout, or are overweight, is associated with tobacco smoke and use of alcohol, and decreases with more exercise (Framingham Heart Study 3). Scientists used a method called epidemiology to conduct the experiment. In general this technique uses information gathered from surveys of large groups of people or from medical records such as eating habits, exercise, or medical history. The analyzed data is used to determine what behavior might be putting people at risk. The Framingham Heart Study started in 1948 with doctors collecting information about residents of Framingham, Massachusetts. A randomly selected group of 6,000 people in the age where these forms of heart disease were known to develop, 30-59 years old, were selected. The town had a population of 10,000 people of this age. Based on examination, those people without signs of the disease would then be reexamined at periodic intervals and observation over a number of years. This was called a “longitudinal” study because it used the same participants over a long period of time. This would [Type the company name] 8 continue over a period of years until a significant number were found to have acquired the disease. Scientists estimated that 5,000 would not have heart disease at the baseline, but that within five years, 400 people would develop heart disease, 900 within ten years, 1,500 by 15 years, and 2,150 at the end of 20 years (Framingham Heart Study 4). The established control group was the recruited participants in the study who were free of heart disease. The established experimental group was the participants who developed heart disease over the course of time. The independent or changing variable of this experiment was the health of the participant over time. The data the researchers collected (dependent variables) was how the medical and behavioral health of those who developed heart disease differed from those who did not. The variables that were necessary to control for this experiment include smoking habits, alcohol use, physical activity, body weight, cholesterol, thyroid, rates of hypertension, thyroid functions, hemoglobin levels along with profiling data on the participants such as age/sex, etc. The variables were controlled to identify those variables that acted to increase incidence of the disease, individually and jointly with other factors. The method that was used for representing the data was primarily qualitative description. It was appropriate in this context similar to the first journal because there were numerous examples of how other scientific methods are more relevant than animal research. Data in the text described the impact on risk levels based on various factors. However, a quantitative table or graph would have increased the credibility of the article by demonstrating the results of the study over time. Quantitative data was used to demonstrate that the Framingham Heart Study went on to impact controlled human trials which showed that every 1% decrease in serum cholesterol levels resulted in a 2% lowering of risk for heart disease. The predominantly qualitative descriptions outlined the research objectives, the introduction of epidemiological study research [Type the company name] 9 design, the hypotheses, and uses. This scientific journal article did not include tables or graphs. Similar to the article on Pasteur work on animal research influencing vaccines, this article did provide numerous examples of alternative scientific methods. Like the Framingham Heart Study was used to tie population studies linking heart disease to cholesterol and other factors, epidemiological studies are also used to investigate genetic and environmental factors associated with birth defects. Human observation is used in cancer research to follow patients with diets low in fat and high in vegetables and fruit who live longer. The article notes that the Lipid Research Clinics Trial of the 1970s and 1980s built upon the Framingham Heart Study, and that autopsy results and chemical studies have also provided links between risk factors and heart disease. The conclusion restates the original problem that animal research is not the most effective use of scientific investments and that there are more effective methods. It refers to animal testing as a “rhetorical device.” By this the authors mean that scientists cite animal studies as evidence in medicine and biology, but that by using different kinds of animals in different situations, evidence can support any theory. The hypothesis supported the conclusion because it again provided examples of the weaknesses of animal testing and strengths of alternative methods. The authors reference Harry Harlow’s monkey experiments on isolating infant monkeys from their mothers, noting that this was already well known from human observation. Further, they describe human studies by Thomas Cawley, Richard Bright and Appollinaire Bouchardat in the 18th-19th centuries that uncovered the importance of pancreatic damage in diabetes, as well as work by Paul Langerhand in 1869 which led to insulin-producing islet cells as a result of human studies. (Barnard and Kaufman 3). The explanation for the results refers back to the scientific background information by reiterating that scientists are uncertain if the physiology of animals can be used to identify human issues and impacts. They note that most animal lab species in the [Type the company name] 10 drug thalidomide experiment did not develop the kind of limb defects that developed in humans; only rabbits and some primates did. This valuable information is useful because it provides an alternative perspective on the use of animal research and the benefits of alternatives. The conclusion supports how information would be applied to other fields of study by using specific examples about the role of alternative scientific methods rather than animal research. Those examples include the role of human observation in cancer research, sophisticated laboratory tests to determine the potency of drugs, epidemiological studies to provide critical information on the link between neural tube defects and folate deficiency and identifying fetal alcohol syndrome, and intervention trials to test diets that can help with cancers. The general public would use this information to more fully understand the opposition to animal research and the existing alternatives that are available. The scientific community would use it in continuing to advance the modernization of research methods. The problems or sources of error in the Framingham Heart Study included the need to modify the research hypotheses as medical learnings evolved. Four exams were needed to standardize the smoking questions, the questions on alcohol use were on exam 2 and then again on exam 7, questions on physical activity were not introduced until exam 4, and new factors were introduced along the way including HDL and LDL lipid fractions, etc. In addition, the sampling plan had to be modified for additional volunteers to increase the statistical reliability based on a low response rate for participants who returned for examinations. At the outset of the study it could not be used to determine the rate of individuals who at a given time period have a certain characteristic, or “prevalence rate,” because the control group was healthier than the general population. It was instead used to estimate “incidence rates,” or the rate of individuals who develop a condition within a time period. The conclusion addresses what could be done to [Type the company name] 11 improve on the experiment by referencing the evolution of the epidemiological heart study and the importance of more human population research being needed to advance information on genetic and environmental factors. On the opposition side, the authors are careful to point out that they intentionally did not discuss the ethical objections to animal research. They conclude that practical reasons alone should be sufficient to influence scientists and governments to allocate funding to alternative scientific methods. [Type the company name] 12 Task 2: We live in a world where animals are used for food, clothing, and transportation, and where mice, rats and other vermin are controlled. While many people accept the need for animals in medical research, others are opposed because of the rights and suffering of animals or scientific weaknesses in animal testing (“Animal Research: The Need for a Middle Ground” 2). Animals are used in research to advance scientific understanding, develop solutions to medical problems, and protect the safety of people, animals, and the environment. Animal experimentation dates back to the ancient Greeks, Romans, Egyptians and Chinese. Alcmaeon of Croton (@ 500 BC) cut the nerves behind the eye of living animals to study vision; Erasistratus (@ 300 BC) studied the hearts and brains of animals; Galen’s (AD 130-200) work with apes and pigs led to the discovery that veins carried blood. In 1628, the English doctor William Harvey used animals to discover how blood circulated in the body. As described in my first experiment, in the nineteenth century, Louis Pasteur, a French scientist, tested on animals to discover vaccines (Woods 8-9). However, the modern era of animal research began about 150 years ago with the increase of physiology as a science (“Forty Reasons Why We Need Animals in Research” 7). In 1870, about a quarter of Americans died before they reached 25 and 50% died by the age of 50. Now, only 3% die before 25 and 10% before 50. In the 1950s heart ailments were usually fatal, but now more than 400,000 people have open heart surgery in the U.S. Animal research contributed to these medical advancements. Two-thirds of Nobel Laureates in Physiology or Medicine since 1901 have relied on animal data for their research (Woods 41). Supporters of medical research (called “vivisection) believe that helping human beings is most important and that animals should be used as necessary to improve lives. Statistics vary on the number of animals used in research and testing in the U.S.; estimates place the number at 17 to [Type the company name] 13 22 million, which is a 40% decrease since 1968. Rats, mice and other rodents make up 95% of all animals used, and primates make up one-third of one percent of all animals used (Judson 48). My goal is to provide rationale to demonstrate that this animal research is beneficial in advancing scientific knowledge because animals are similar to humans, animals themselves benefit from the discovery of life-saving treatments, and significant medical advances result from this research. Scientists and the public benefit from information sharing, discussion, and debate of different opinions to address the ethical and practical issues raised by animal research. A 2013 Gallup poll showed that the majority of Americans over 35 find medical testing on animals to be morally acceptable, while 47% of 18 to 34 year olds agree that it is acceptable. Results for this Gallup poll are based on telephone interviews conducted May 2-7, 2013, with a random sample of 1,535 adults, aged 18 and older, living in all 50 U.S. states and the District of Columbia. For results based on the total sample of national adults, one can say with 95% confidence that the margin of sampling error is ±3 percentage points. [Type the company name] 14 However, opponents of animal research are on a spectrum from those who feel it is unethical, to scientists who say it is unreliable, misleading, and wasteful, to those who believe that there are better methods available. Some animal rights groups object to all animal testing on ethical grounds, and they want to see animals viewed as “sentient (aware) beings” rather than as tools for research. They believe that animals have the right to a life that is free from harm by humans. To this end, the Animal Welfare Act incorporates Russell and Burch’s “Three Rs” concept, where scientists engaged in animal testing strive to 1) reduce the number of animals used; 2) refine experimental techniques to minimize pain and stress; and 3) replace the use of animals with other technologies when it is possible (Judson 78-79). Some scientists promote that the results of animal testing are unreliable because of genetic and species differences between animals and humans; also, strains and cell lines may differ within animal species. In some animal experiments, the methodological quality may be flawed. In addition, the stress experienced by the animal may cause test results to be inaccurate (Hooijmans and Ritskes-Holtinga 1). Others feel that given inaccurate scientific conclusions, animal testing is slower and more expensive than other alternatives. They believe that computer simulation programs, chemical studies, medical surveys (epidemiology), and in vitro testing are better alternatives. In vitro methods and computer modelling play an important part in complementing data from animal models; however, while such non-animal methods play an important part of medical research, they cannot replace all use of animals. Computers are not able to simulate how a particular cell might interact with a medical compound, or how a complex biological system will react to a new drug. Animals are the best available option for research because they have many similarities to humans. For example, chimpanzees share 99% of their DNA with humans, and mice share 98% [Type the company name] 15 with humans. In fact, humans and all mammals contain almost the same number of genes, now estimated at 25,000 (Judson 55).All animals and humans have a set of organs including a heart, kidney and lungs. This makes humans and animals prone to the same illnesses such as heart disease, cancer, and diabetes (“Should Animals Be Used for Scientific or Commercial Testing?” 2). As identified in my first experiment, both humans and animals control their internal biochemistry by releasing similar hormones, both send out similar chemical transmissions from the nervous systems, and both react to infection or tissue injury the same way. Ultimately, there is no adequate alternative to testing on a living, whole body system. Although useful, studying cell cultures in a dish does not allow scientists to study the interrelated processes in the central nervous system, endocrine systems, and immune system. Secondly, animals benefit from the results of animal testing. Animals have been saved from various diseases through the testing of vaccinations; without this testing, millions of animals would have died from rabies, canine parvo virus, tetanus, distemper, feline leukemia and other cancers, anthrax, infectious hepatitis virus, heartworm, brain tumors, and birth defects. Animal testing has saved endangered species from extinction like the black-footed ferret, the California condor, and the tamarins of Brazil. Koalas are being tested with vaccines for chlamydia, a disease which has contributed to them to become endangered in some parts of Australia. (“Should Animals Be Used for Scientific or Commercial Testing?” 2). Further, the surgical technique for repairing holes in the hearts of children is also used on puppies with the same congenital heart deformity. Dogs can have pacemakers, and hip problems for dogs can be repaired using the same hip surgery techniques used in people (Judson 36). Even the American Veterinary Medical Association endorses animal testing (“Should Animals Be Used for Scientific or Commercial Testing?” 2). [Type the company name] 16 Finally, animal testing has helped the creation of many life-saving cures and treatments and will continue to do so. According to the California Biomedical Research Association, nearly every medical breakthrough in the last century has been directly from animal testing research. Experiments where dogs had their pancreases removed led to the discovery of insulin which has saved the lives of many diabetics. The polio vaccine which was tested on animals reduced the disease from 350,000 in 1988 cases to 223 cases in 2012. Animal testing has also helped the treatment of breast cancer, brain injury, leukemia, cystic fibrosis, malaria, multiple sclerosis, tuberculosis, and more. Director of the University of Texas M.D. Anderson Cancer Center’s animal research facility said “we wouldn’t have a vaccine for hepatitis B without chimpanzees” and “the use of chimps is our best hope for finding a vaccine for Hepatitis C.” This disease kills 15,000 people in the United States per year (“Should Animals Be Used for Scientific or Commercial Testing?” 1). [Type the company name] 17 Works Cited “Animal Experimentation: Science, Ethics, and the Controversy.” vertebratejournal.org. Web. 29 Nov. 2014. “Animal Testing Is Bad Science: Point/Counterpoint.” peta.org. Web. 29 Nov. 2014. Barnard, Neal D. and Stephen R. Kaufman. “Animal Research Is Wasteful and Misleading.” Scientific American 267 (February 1997): 80-83. Print. (Task 1 Experiment – with addendum from “Framingham Heart Study: Epidemiological Background and Design.” framinghamheartstudy.org. Web, 28 Nov. 2014.) Botting, Jack H. and Adrian R. Morrison. “Animal Research Is Vital to Medicine.” Scientific American 267 (February 1997): 83-86. Print. (Task 1 Experiment) Bracken, Michael B., Shah Ebrahim, Pandora Pound, Ian Roberts, and Peter Sandercock. “Where Is The Evidence That Animal Research Benefits Humans?” bmj.com. 26 Feb. 2014. Web. 3 Dec. 2014. “Forty Reasons Why We Need Animals In Research.” understandinganimalresearch.org. Web, 9 Nov. 2014. “Framingham Heart Study: Epidemiological Background and Design.” framinghamheartstudy. org. Web, 28 Nov. 2014. “Gallup Values and Beliefs Poll.” gallup.com. May 2013. Web, 28 Nov. 2014/ Hayhurst, Chris. Animal Testing: The Animal Rights Debate. New York: The Rosen Publishing Group, Inc., 2000. Print. Judson, Karen. Open for Debate: Animal Testing. Tarrytown: Marshall Cavendish, 2006. Print. Lankford, Ronnie D. At Issue: Animal Experimentation. Farmington Hills: Greenhaven Press, 2009. Print. [Type the company name] 18 Levine, Herbert M. American Issues Debated: Animal Rights. Austin: Steck-Vaughn Company, 1998. Print. “Physicians Committee for Responsible Medicine Position Paper on Animal Research.” pcrm.org. 21 July 2010. Web. 28 Nov. 2014. Hooijmans, CR and M Ritskes-Holtinga. “PLOS Medicine: Progress in Using Systematic Reviews of Animal Studies to Improve.” 16 July 2013. plosmedicine.org. Web. 10 Nov. 2014. “Should Animals Be Used for Scientific or Commercial Testing?” procon.org. Web. 11 Nov. 2014. Smith, Richard. “Animal Research: The Need for a Middle Ground.” bmj.com. 3 Feb. 2001. Web. 3 Dec. 2014. Woods, Geraldine. Animal Experimentation and Testing: A Pro/Con Issue. Berkeley Heights: Enslow Publishers, Inc., 1999. Print.