Exam 18: Evolutionary Medicine

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When designing a live-virus vaccine (for example, the polio vaccine), how do scientists ensure that the virus will not cause human recipients to become ill with the virus?

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When designing a live-virus vaccine, such as the polio vaccine, scientists take several steps to ensure that the virus used in the vaccine will not cause illness in human recipients. The process involves attenuating, or weakening, the virus so that it stimulates an immune response without causing disease. Here are the key steps and considerations involved in this process:

1. **Selection of Virus Strain**: Scientists select a virus strain that is less virulent or has a lower capacity to cause disease. This strain serves as the starting point for developing the vaccine.

2. **Attenuation**: The selected virus is weakened through a process called attenuation. This can be done through various methods, such as:
- **Passaging**: The virus is grown repeatedly in cell cultures or animal hosts that are less suitable for the virus, which forces the virus to adapt to the new environment and lose its virulence factors that are specific to humans.
- **Genetic Modification**: Scientists can use genetic engineering to remove or alter specific genes that are essential for the virus to cause disease.

3. **Testing for Safety and Efficacy**: The attenuated virus is rigorously tested in preclinical (lab and animal) studies to ensure that it cannot revert to a virulent form and that it elicits a strong immune response.

4. **Clinical Trials**: The vaccine undergoes a series of clinical trials in humans, starting with small safety trials (Phase I), followed by larger trials to assess the immune response (Phase II), and finally large-scale trials to test for efficacy and safety in the broader population (Phase III).

5. **Monitoring for Reversion to Virulence**: Even after the vaccine is approved and in use, ongoing surveillance is conducted to monitor for any cases where the attenuated virus might revert to a more virulent form. This is particularly important for live-virus vaccines.

6. **Regulatory Approval and Quality Control**: The vaccine must meet stringent regulatory standards and is subject to continuous quality control measures to ensure that each batch is safe and effective.

7. **Post-Marketing Surveillance**: After the vaccine is introduced to the market, health authorities continue to monitor its safety and effectiveness through various surveillance programs. This helps to quickly identify any issues that may arise in the general population.

An example of a live-virus vaccine is the oral polio vaccine (OPV), which uses an attenuated poliovirus to induce immunity. The OPV has been incredibly successful in reducing polio worldwide, but because of the slight risk of reversion to a virulent form, it is being phased out in favor of the inactivated polio vaccine (IPV) in many countries.

In summary, the development of a live-virus vaccine is a complex process that requires careful attenuation of the virus, extensive testing for safety and efficacy, regulatory oversight, and ongoing surveillance to ensure that the vaccine does not cause illness in recipients.

Once cancer cells develop within the body, selection favors their proliferation even though this ultimately may lead to the death of the individual and the cancer cells. What explains this short-sighted evolution?

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The phenomenon where cancer cells proliferate within the body despite the potential for leading to the death of the individual, including the cancer cells themselves, can be explained by the concept of "short-sighted" or "myopic" evolution. This concept refers to the idea that natural selection operates on the level of individual cells or organisms, favoring traits that increase their immediate reproductive success, without regard for the long-term consequences for the individual or the population.

Here are several factors that contribute to this short-sighted evolution in the context of cancer:

1. **Somatic Evolution:** Cancer cells undergo a process of somatic evolution. Unlike germline evolution, which concerns changes in the genes passed on to offspring, somatic evolution occurs within the tissues of an organism during its lifetime. Cancer cells acquire mutations that confer a selective advantage within the tissue ecosystem, allowing them to proliferate more than their normal counterparts.

2. **Clonal Selection:** As cancer cells accumulate mutations, those with the most advantageous traits for survival and reproduction within the local environment will expand in number. This is similar to natural selection in a population of organisms, but it occurs at the cellular level within the body. Traits that enhance cell division, evade the immune system, or resist cell death signals will be selected for, even if they are detrimental to the organism as a whole.

3. **Lack of Foresight:** Evolution does not plan for the future; it is a process that selects for traits that are beneficial in the present moment. Cancer cells do not have foresight or the ability to consider the consequences of their proliferation. They are simply following the basic biological imperative to survive and reproduce.

4. **Genetic Instability:** Many cancers are characterized by genetic instability, which leads to a high mutation rate. This increases the likelihood of developing mutations that can confer a selective advantage, accelerating the process of somatic evolution.

5. **Resource Competition:** Within the body, cells compete for resources such as nutrients and space. Cancer cells that are more efficient at acquiring resources or that can thrive in less-than-ideal conditions will outcompete normal cells.

6. **Escape from Regulatory Mechanisms:** Normal cells are subject to a variety of regulatory mechanisms that control cell growth and division. Cancer cells often acquire mutations that allow them to escape these controls, giving them a growth advantage.

7. **Microenvironmental Influences:** The tumor microenvironment, which includes the surrounding cells, blood vessels, and extracellular matrix, can also influence the evolution of cancer cells. Factors within this microenvironment can select for more aggressive cancer cell phenotypes.

In summary, the short-sighted evolution of cancer cells is driven by the immediate selective pressures acting on individual cells within the body. These cells evolve to survive and proliferate in their local environment, without regard to the long-term survival of the organism. This process is a consequence of the basic principles of natural selection and does not reflect a conscious strategy or long-term planning.

The e4 allele is common in the world population (14.5% of people are carriers) despite being a risk factor for Alzheimer's disease. Which idea best explains this?

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You are studying a virus that infects mammals. You are specifically interested in whether the virus frequently jumps from one mammal species to another or whether different strains remain specific to certain hosts over evolutionary time. How could you use phylogenetic methods to test this?

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Harmless bacteria from the environment can become pathogenic once they are inside a host because

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Viruses and bacteria can acquire additional genetic variation through

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To create a drug that would stop infections of Pseudomonas aeruginosa in people with cystic fibrosis without encouraging the evolution of drug-resistant strains, researchers are trying to target the bacteria's ability to

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Pathogens evolve rapidly because

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How can we slow the evolution of antibiotic resistance in bacteria?

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The thrifty genotype hypothesis proposes

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The relationship between the presence of malaria and high frequencies of the disease-causing HbS allele in Africa is an example of which type of selection?

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When a disease spreads across the globe this is known as a(n)

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Evolving very rapidly (hypermutation) would favor bacteria living in

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A group of antibiotic-resistant genes is known as a

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How does the fact that horizontal gene transfer among bacteria is relatively common influence the rate at which antibiotic resistance evolves?

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What were Ron Fouchier and colleagues trying to find out with their serial passage experiment in ferrets?

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Why is sickle-cell anemia more common in Africa than the United States?

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Which of the following viruses is incorrectly paired with its animal source?

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In a serial passage experiment, the evolution of bacterial virulence is no longer constrained by

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Which of the following helps to explain why antibiotic resistance can evolve especially quickly?

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