### Gene drive proves it can wipe out mosquitoes

This set of questions asks students to analyze data presented in the Science News article “Gene drive wipes out lab mosquitoes,” (SN: 10/27/2018, p. 6), which describes how scientists used a genetic engineering tool called a gene drive. Scientists use gene drives to introduce desired changes to an organism’s DNA in such a way that the changes will quickly spread to future generations. The mosquito gene drive described in the article ensured that generations of Anopheles gambiaeinherited a mutation that kept females from laying eggs. A laboratory experiment showed that the gene drive caused an entire population of mosquitoes to go extinct within a few generations. If the success can be repeated in larger studies and proven safe in the wild, gene drives might be capable of eliminating mosquito species that spread malaria to humans.

#### Read the “Path to extinction” graphs:

1. What variable is graphed on each graph’s x-axis? Be as specific as possible.

Possible student response: The number of generations of mosquitoes since the gene drive was introduced into the population.

2. What variable is graphed on the y-axis axis of the left graph? What variable is graphed on the y-axis of the right graph?

Possible student response: The y-axis on the left graph shows the frequency of individuals (fraction of the population) with the gene drive. The y-axis on the right graph shows the egg output of the mosquito population, relative to the initial egg output.

3. What do the red and blue lines represent? What do the gray and black lines represent?

Possible student response: The red and blue lines represent two populations of caged mosquitoes in the lab experiment. The gray and black lines represent computer simulations of mosquito populations.

4. For populations represented by the red, blue and black lines, what is the frequency of mosquitoes with the gene drive and relative egg output at six generations? Make sure to label your answers appropriately.

Possible student response: At six generations, about 60 percent of mosquitoes represented by the red line had the gene drive. This generation’s relative egg output was about 35 percent of normal mosquitoes’ egg output.

About 83 percent of mosquitoes represented by the blue line had the gene drive. This generation’s relative egg output was about 20 percent of normal mosquitoes’ egg output.

The black line, which represents a computer simulation, showed that at six generations, about 83 percent of the mosquitoes had the gene drive.  This generation’s relative egg output was about 30 percent of normal mosquitoes’ egg output.

#### Manipulate the data:

1. At six generations, about how many mosquitoes have the gene drive in each of the two caged populations?

Possible student response:

2. What happens when the frequency of individuals with the gene drive reaches one? When does that occur for the red and blue lines?

Possible student response: The frequency reaching one indicates that all mosquitoes in the population carry at least one copy of the gene drive. That occurs at seven generations for the population represented by the blue line and at 11 generations for the population represented by the red line.

3. What is the value of the relative egg output at the beginning of the experiment, and why?

Possible student response: At zero generations, the relative egg output is one, which means that all female mosquitoes are capable of producing eggs.

4. When does the relative egg output reach zero in both of the experimental populations, and why?

Possible student response: The relative egg output of the population represented by the blue line reaches zero by generation eight. The relative egg output of the population represented by the red line reaches zero by generation 12.

When the frequency of individuals with the gene drive in a population reaches one, it indicates that those males and females will each pass along one gene drive copy to the next generation. Mosquitoes in this next generation will have two copies of the gene drive. Because the females have two copies of the gene drive, they develop like males and are unable to lay eggs. The mosquito population will drop to zero when mosquitoes from that final infertile generation die.

5. How do the computer simulation results compare with the experimental lab results?

Possible student response: The results are fairly similar. Lab mosquitoes died out sooner than some of the simulations predicted, but well within the range of other simulations.

6. Why do you think there is variation between the simulated and experimental results?

Possible student response: Mosquitoes’ mating behaviors could explain the variation between the experimental and simulated results. For example, if mosquitoes lacking gene drives choose mates that also lack gene drives, a population may last for more generations. But if they chose mates with gene drives, the population could die out sooner.

#### Connect the graph to the article:

1. About how many generations did it take for the gene drive to wipe out the entire experimental mosquito population?

Possible student response: In both of the lab experiments and in all of the computer simulations, the gene drive wiped out the entire mosquito population within approximately 15 generations.

2. How could gene drives be used outside of the lab, and why? How do you think the results would be similar to or different from those in this experiment?

Possible student response: Some gene drive–carrying mosquitoes could be released into the wild to breed with normal mosquitoes. As in these lab experiments and computer simulations, the gene drive should eventually spread to all of the mosquitoes in a population, wiping the population out. The initial fraction of gene drive–carrying mosquitoes would be much smaller than what was used in the lab experiment — the number of gene carrying mosquitos that would be released would be smaller compared with the total number of normal mosquitoes in the area. It would take more generations to wipe out all of the mosquitoes. Also, mutations could occur that may interfere with the rate at which the gene drive spreads.

3. How do these figures support the use of gene drive technology? What are some risks of gene drive technology?

Possible student response: The figures show that this gene drive technology efficiently spreads through a malaria-carrying mosquito population in the lab, eventually driving the population to extinction. Thus, gene drives can hopefully do the same thing in the wild, which could help prevent human deaths from malaria.

One risk is that since many more mosquito generations would be required in the wild than in these lab experiments, there would be more opportunities for mutations and possible resistance to arise in the mosquito population. Another risk is that the gene drive could unintentionally spread to other mosquito species. No one knows the ecological consequences of removing mosquitoes.

#### Analyze beyond the article:

Bonus question: What are other useful potential applications of the gene-editing tool CRISPR/Cas9?

Possible student response: Student answers will vary. Examples are provided below.

Wiping out other undesirable species such as other mosquito species or invasive plants. Adding a new trait for all members of a species, such as making all dogs and cats hypoallergenic, all humans free of hereditary diseases or all students love science.