In the late 18th century, Philadelphia was one of the larger and wealthier cities in the United States and served as the capital. That changed in 1793. The city had an unusually wet spring, which left behind stagnant pools that became breeding grounds for mosquitoes. At about the same time, refugees from the slave revolution in Haiti fled to Philadelphia, carrying the yellow fever virus. In late August 1793, a female Aedes aegypti mosquito bit an infected refugee and then bit a healthy Philadelphian. This began a yellow fever epidemic that killed 10% of the city’s population within three months and led another 30% to flee for their lives. Victims suffered from high fever, nausea, skin eruptions, black vomit, and jaundice. The treatment for yellow fever in the 18th century was often worse than the disease: physicians administered potions to purge the victims’ intestines and drained up to four-fifths of their patients’ blood in the mistaken belief the bloodletting would stem fever. These attempted remedies often left patients tired, weak, and unable to fight the virus. Without effective treatments, the epidemic stopped only when the first frost arrived. 1. People who left the city seemed to have milder cases of yellow fever or avoided the infection altogether. Explain why. 2. The story mentions that the coming of the first frost brought an end to the epidemic. Discuss the possible reasons why this would provide at least temporary relief from the epidemic. Part One: Smallpox: The Dilemma Smallpox is likely the worst infectious disease of all time, killing an estimated 300 million people in the 19th century alone. It is a terrifying killer, with a death rate as high as 33% and the survivors carrying lifelong scars. British medical doctor, Edward Jenner, is credited with inventing smallpox vaccination— the world’s first immunization. On May 14, 1796, Jenner rubbed secretions from a cowpox sore on the hand of a milkmaid into scratches he made on an 8 yr old boy. Then about a month later, he injected the boy with secretion from a lesion on a smallpox patient. The child did not get smallpox; he was immune. Jenner termed his technique vaccination, which comes from the Latin term for cow, vacca. Medical doctors began vaccinating people with special two-pronged needles and eventually smallpox was eradicated worldwide. The last case was October 26, 1977. Eradication represents one of the great triumphs of modern medicine, but smallpox virus itself still exists. Stocks are kept frozen in secure laboratories at the Centers for Disease Control and Prevention (CDC) in Atlanta, Georgia and in the State Research Center of Virology and Biotechnology in Koltsovo, Russia. Part Two: Virus, Disease, and Transmission To make complex decisions such as this, you need accurate background information from multiple fields, including biological areas, such as virology and epidemiology, and from other ethical, legal, and economic. With scientists, these other important areas are sometimes called ELSI, which stands for ethical, legal, and social implications. In order to make an informed decision, you need an understanding of the virus itself and the disease it causes in humans. Variola major is the smallpox virus, and it is in the family Poxviridae, the poxviruses. Poxviruses are more complex than other viruses that infect humans and are surrounded by an unusual double envelope. Smallpox virus has 187 genes and is 300-400 nm in diameter. In contrast, influenzavirus has 10 genes and are 80-120 nm in diameter. Why are poxviruses so large and complex? One reason is that poxviruses replicate in the cytoplasm, unlike other DNA viruses, which replicate in the nucleus. Therefore, poxviruses must carry their own enzymes for DNA replication and RNA transcription, processes that occur in the nucleus of human cells. During the 12-14 day incubation period of smallpox, patients are not contagious and have few symptoms (see Disease at a Glance 19.4, chapter 19, page 571). Smallpox viruses travel through the air in droplets and enter the body through the respiratory mucous membrane. The viruses travel to lymph nodes where they replicate. New viruses spread via the blood to the spleen, liver, bone marrow, and just under the skin. The victim has fever, body aches, and fatigue for 2-4 days and becomes contagious. A rash of red spots spreads across the body, and then these spots progress to raised fluid-filled bumps, the hallmark of smallpox (see figure 19.9, page 571). The bumps progress to pustules (pocks or pox) during the next two weeks, and patients are even more contagious during this time. Sometimes the pocks appear in the eyes as well, resulting in blindness. If the patient lives, the pustules become scabs that often leave permanent scars. There is no treatment. Viral transmission occurs during extended personal interactions via aerosols and less frequently via inanimate objects, such as blankets, contaminated with bodily fluids. Smallpox has an R0 value of 5-7, meaning one patient typically infects 5-7 other people. In the past, outbreaks in towns often resulted in 10% or more of the population dying, so the disease was highly feared. 1. Why is smallpox virus so dangerous and what would it take to eliminate a virus like this? 1. Should governments and laboratories keep the viruses, or, should they be destroyed? In other words, should we intentionally make a species extinct forever? 2. What facts do you need to make an informed decision? 3. If the decision were to be made today, how would you vote?