Review the four cases and respond to the following questions regarding each case: 1. What possible benefits came from the study? 2. What possible harms came from the study? 3. Were the human participants able to consent to their involvement in the study? If so, what factors would influence their participation? 4. How were the subjects for the study chosen? Do you think they were chosen fairly? 5. How should rules related to human participants research be enforced? 6. Was the treatment of humans in this case ethical? Explain your answer. Case Study #1 Yellow Fever in Cuba Following the Spanish-American War, American soldiers took control of the island of Cuba. They, like all other newcomers to Cuba, were confronted with a range of tropical diseases-typhoid, malaria, yellow fever, dengue fever-toward which they had no natural immunity. For every one soldier who died in the war, hundreds quickly died of disease. Cubans typically contracted yellow fever early in life and either died or developed life-long protection. About 30% of people who contracted yellow fever died. In 1900, researchers began work to combat the disease. One major barrier for studying the disease was that it only affected people. With no animal model to use, the researchers were obliged to do all their experiments on people. Little was known at the time about the cause or transmission of yellow fever, but mosquitoes were suspect. Could a mosquito that bit a sick person then transmit the disease by biting someone who was well? The experiments were crude but direct. A test tube containing a mosquito was inverted onto the arm of someone who was sick. The mosquito sank its proboscis into the flesh, found a vein or artery, and drank a blood meal. After two weeks, the test tube containing the mosquito was inverted onto the arm of a healthy subject. Researcher and subject then watched as the mosquito once again sank its proboscis through the flesh and into the bloodstream. There, it once again exchanged fluids with its host, injecting salivary juices and the viruses that caused yellow fever into the blood stream while drinking another blood meal. Researchers created a written "informed consent"* document, which outlined the risks of the experiments and their possible benefits. Those who agreed to be subjects in the experiments had to sign the forms. The American military governor of Cuba provided funds to set up a proper research laboratory-seven tents and a flagpole flying an American flag-and funds were also available to pay volunteers. The American soldiers who participated did not get paid but the Spanish immigrants who volunteered each received $100 in gold to participate and $100 more if they got sick. For volunteers, the risks of the yellow fever experiments even seemed worth taking, because, being new to the island, they were likely to contract the disease in any case. At least in an experiment, they would get rapid and decent medical treatments. All told, 29 people contracted the disease while participating in the commission's experiments and five died. After mosquitoes were implicated in the transmission of the disease, a thorough mosquito eradication program began, and yellow fever was wiped out in Cuba.

Case Study #2 Syphilis in African American Men In 1932, six hundred poor African American farmers and sharecroppers were subjects in a study run by the federal government to watch what happens when syphilis is left untreated. At the time, there was no reliable cure for syphilis. When a safe and effective treatment for syphilis-the antibiotic penicillin- became widely available in the early 1940s, the study continued and the men were actively prevented from receiving treatment for the disease. In the study, 399 men with syphilis were followed along with 201 men of the same age who did not have syphilis. The standard treatment for syphilis in the early 1930s was 25-30 applications of mercury. The Alabama Health Officer agreed to the study under the condition that the men receive some treatment. Initially the researchers gave the men treatment. However, money ran out for the treatments, and the researchers decided to continue on with the study anyway. They hoped that funding would be restored for treatment, but felt that there was still value in a 'natural history' study that could potentially show the disease was the same in African Americans and Caucasians. The amount of treatment was clearly inadequate according to the standards of the day, but the researchers felt justified in leaving the men untreated. The researchers wanted to observe how the disease progressed in untreated individuals and compare it to an earlier study of Norwegian men who had not received treatment (because the Norwegian study occurred before 1910, only very toxic treatments were available to those patients at that time). The researchers used the general term 'bad blood' when describing the patients' condition. None of the subjects knew that their 'bad blood' was actually syphilis. The men received painful spinal taps, which they believed were treatments because they received a letter from the government saying that they should come receive this 'special treatment'. The incentives for submitting to the taps and other evaluations were warm meals, a free burial, and free medical care for other diseases, as long as the treatment was not penicillin. The researchers worked with the local draft board to prevent the subjects of the study from being drafted for World War II. Had they entered the army, the men would have been tested for syphilis and given penicillin if they had the disease. Over the years, more than a dozen articles about the study were published in medical journals. The study did not end until 1972 after the story was brought to public attention by a researcher from the Center for Disease Control shared his concern with a news reporter. During those forty years, over 100 men died. The survivors filed a suit against the US government in 1973, eventually settling out of court for $37,500 each and a lifetime of medical care. Case Study #3 AZT and Pregnant women in Developing Countries Newborns whose mothers are infected with HIV can acquire the infection from their mothers at the moment of birth. In some developing countries with HIV/AIDS epidemics, more than 30% of pregnant women who are examined at prenatal clinics are infected with the AIDS virus. Clinical trials in 1994 showed that, if a pregnant woman took the drug AZT in pills during the last 12 weeks of pregnancy and as an injection during labor and if the baby received AZT during the first six weeks of life, the baby had a much-reduced chance of becoming infected with the virus. Since that time, in the United States, pregnant women infected with HIV are advised to use this "076 regimen" of AZT. In 1997, researchers gave a placebo, rather than AZT, as a control to pregnant women in a developing country who were infected with HIV and were participating in clinical trials. The "standard" treatments for AIDS for these women were no treatments at all. (The 076 regimen, for example, was simply too expensive for women and governments in poor countries, costing between $800-$1000 per person.) The researchers were evaluating lower and fewer doses of AZT in the studies to see if low doses might be effective. Such doses might be affordable and accessible for poor women around the world. Women involved in the study did not know whether they received the 076 regimen or the placebo. In addition, women were not told what dose- the lower experimental dose- or the standard amount of AZT they would receive during the trial. Case Study #4 Behavior in Young Boys One hundred boys in New York, ranging in age from six to ten, participated in three research projects to find out whether the levels of the brain chemical serotonin could be correlated with aggressive behavior. The boys were chosen for the study not because they had shown aggressive behavior but because their brothers had. Each boy had an older brother who was in jail or a mother who was considered by the researchers to be doing a poor job rearing her sons. All came from poor families; 44% were African American, 56% were Hispanic, and none were white. The studies took place at a New York State Psychiatric Institute between 1993 and 1996. Each boy received a single dose of the drug fenfluramine, which increases serotonin levels. The drug is one component of fen-phen, which was recalled as a diet pill in 1997, because it seemed to cause heart valve defects. Experts on the use of fenfluramine consider it unlikely that the boys in the experiments suffered any harm from the drug, as they were given only a single small dose. Those with heart damage used the drug in larger doses over a period of months. However the drug has side effects such as nausea, headache, dizziness, anxiety, and irritability. Each boy had to stay in the hospital bed for 5 hours, during which time numerous blood samples were taken. He could not eat for 17 hours. At the end of the study, each family received a gift certificate for $125 to spend at a local toy store. Guiding Questions: 1. What possible benefits came from the study? 2. What possible harms came from the study? 3. Were the human participants able to consent to their involvement in the study? If so, what factors would influence their participation? 4. How were the subjects for the study chosen? Do you think they were chosen fairly? 5. How should rules related to human participants research be enforced? 6. Was the treatment of humans in this case ethical? Explain your answer.