VACCINE—Weakened or killed germs or part of a germ that when injected into a body stimulates antibody production and immunity against the germ but is incapable of causing a disease.
By infecting animals with certain microbes, Koch, Pasteur, and other researchers were able to identify the germs causing anthrax, rabies, diphtheria, and plague. These discoveries have allowed scientists to develop vaccines for animals and people made from weakened germs. The safety and effectiveness of these vaccines are also tested in laboratory animals. One of the first vaccines developed was against anthrax. Louis Pasteur weakened anthrax bacteria by heating it so that it could no longer cause illness. He then vaccinated one group of sheep with the weakened anthrax bacteria. This vaccination caused the sheep's immune system to recognize the anthrax bacteria and produce antibodies against it. He later infected the vaccinated group and a nonvaccinated group with live anthrax. The vaccinated group all survived, proving that the vaccinated animals' immune systems would recognize and fight the live anthrax and thus prevent the disease. Pasteur used animals to prove that vaccination was generally safe and would prevent disease, which in turn has saved many farm animals and people from death by anthrax.
Unfortunately, developing a vaccine is not always simple or easy. Take for instance malaria, another disease that Koch studied during the late 19th century. Malaria is one of the most ancient parasitic diseases affecting humankind, and its very name summons up a time when the origins of disease were shrouded in mystery. The Italian phrase mala aria (bad air) was first used to describe the supposed cause. Malaria is characterized by high fever, shivering, joint pain, headache, vomiting, and possibly convulsions and coma ending in death. Malaria remains a public health problem of staggering magnitude. There are 300 to 500 million new infections and 1.5 to 2.7 million deaths throughout the world each year, most of them among children.
Koch's Postulates—1. The agent must be present in every case of disease 2. The agent must be isolated from the host and grown in a laboratory dish. 3. The disease must be reproduced when a pure culture is inoculated into a heathy, susceptible host. 4. The same agent must be recovered again from the experimentally infected host.
Malaria is caused by a parasite called Plasmodium. This small single-cell organism invades the liver and metamorphoses so that it can burrow into red blood cells. The parasite then multiplies until the red blood cells burst, causing the host body (human or animal) to be assaulted by waves of fever as the body attempts to destroy the parasite. In some cases, the infected red blood cells become stuck in the arteries and veins of the head, leading to death. In the early 20th century, Robert Ross used Koch's Postulates to prove that bird malaria was transmitted from bird to bird by mosquitoes. The next year, a team of Italian scientists showed that human malaria was also spread by mosquitoes, paving the way for a series of simple measures to interrupt the transmission of the disease, such as the use of bed nets and insecticides. But because the malaria parasite metamorphoses as it moves from the liver to the red blood cells, it has been difficult to develop a vaccine that will stimulate the host's immune system into recognizing the two different forms of the parasite.
Even though scientists have not yet been able to develop a malaria vaccine, animal research has played an important part in developing drugs to treat malaria and helps scientists understand how to develop a vaccine for a parasite with two different forms. Dr. Nirbhay Kumar, professor in the Department of Molecular Microbiology and Immunology at the Johns Hopkins Bloomberg School of Public Health, has been studying malaria using several animal model systems including chicken and rodent models of malaria, even though these animal malaria parasites cannot infect humans. Results from the research on these animal models allow him to understand how the parasite infects liver and blood cells and completes its transmission through an extensive development inside the mosquito vector. The major life-cycle events of this deadly human parasite are very similar if not identical among all the different animal models. Dr. Kumar points out, “The knowledge that we gain from animal malaria studies can often extrapolate to human malarias.”
Dr. Kumar is using the knowledge that he has gained by studying chicken and murine malaria to develop new vaccines. He tests these new vaccines in mice and nonhuman primates to help assess whether the vaccines will stimulate the correct type of immune responses to cure people of malaria, another example of how studying animals with similar but not identical diseases is helpful.
Dr. Kumar points out that scientists must think carefully about using animals in their research. “We must be careful and judicious in our use of animals,” he says. “We should use them only because there is no other way. There must be real justification for animal use.” With a child dying of malaria every 20 seconds somewhere in the world, he notes, “in this case, there is a justification.”
The Baltimore Zoo is located in Druid Hill Park, a green oasis in the midst of a concrete desert. But the large colony of penguins living at the zoo must cope with a bloodthirsty adversary capable of transforming this oasis into an intensive care unit: the plasmodium-laden mosquitoes that infest the park and transmit a deadly strain of malaria. “This is a problem in zoos throughout North America,” says Dr. Thaddeus Graczyk, Associate Research Professor in the Department of Molecular Microbiology and Immunology at the Johns Hopkins Bloomberg School of Public Health. “This is a huge problem for the zoo because there is very high mortality among the newly hatched and juvenile penguins.” The penguins hatch in winter and are still young and vulnerable in May or June, when the mosquitoes in Baltimore begin to bite. “We've captured a few of the mosquitoes and have seen that they all carry the parasite,” says Graczyk. But malaria is not just a problem for penguins in zoos. Malaria is also becoming a problem for wild populations, such as African penguins. African penguins are particularly vulnerable to the malaria parasite because they are a “naive” population; they have never encountered malaria before. African penguins are found on islands off the coast of South Africa, in a harsh climate where at one time there were no mosquitoes or malaria. But human development brought mosquitoes, and African penguins are now catching malaria, just like the Baltimore Zoo penguins. The penguins of the Baltimore Zoo have become an important ally in the quest to develop a malaria vaccine for African penguins and even people. If a penguin survives the first time it becomes infected with malaria, it is much more likely to survive a second bout. By studying the Baltimore penguins, Graczyk and his colleagues have identified antibodies created by the penguins' immune systems that attack the malaria parasite and help them survive the disease. By identifying antibodies against malaria, this may help develop a malaria vaccine for penguins. Because of the similarities between malaria in penguins and humans, this development may also lead to a malaria vaccine for people.
National Academies Press (US), Washington (DC)
National Research Council (US) Committee to Update Science, Medicine, and Animals. Science, Medicine, and Animals. Washington (DC): National Academies Press (US); 2004. Vaccines.