The Science and Ethics of Gene Drives: An Active Learning Lesson in Genetics
Editor: Lisa McDonnell
Published online:
Abstract
Coursework connecting biology to socially relevant issues and ethical questions can help students think about biology in interdisciplinary terms. Gene drives represent one topic involving both advanced biology concepts and societally relevant ethical questions. Gene drives are a genetic modification technique that could potentially be used to modify populations of wild, sexually reproducing organisms. Possible applications of gene drives include eradication of invasive species or reduction of mosquito-borne diseases, but this technology also raises significant ethical questions. Here, I describe a biology lesson that teaches undergraduates about the fundamental science of gene drives. This lesson uses an active learning approach to discuss the mechanisms of gene drives, and it exposes students to an example gene drive from a previously published primary literature study. The lesson ends with a bioethics activity in which students propose their own ideas for guidelines regulating gene drives.
Primary Image: Inheritance of a gene drive in mosquitoes. A simplified visual representation of the inheritance patterns of a gene drive system, in which a male mosquito carrying the gene drive (rectangle in first row, shaded) mates with a female unaffected by the gene drive (circle in first row, not shaded) and all offspring inherit the gene drive (all shapes in second row, all shaded).
Citation
Rundell EA. 2024. The Science and Ethics of Gene Drives: An Active Learning Lesson in Genetics. CourseSource 11. https://doi.org/10.24918/cs.2024.21Society Learning Goals
Genetics
- Transmission - Patterns of Inheritance
- What are the mechanisms by which an organism’s genome is passed on to the next generation?
- Molecular biology of gene function
- How is genetic information expressed so it affects an organism's structure and function?
- Evolution and Population genetics
- What are the processes that can affect the frequency of genotypes and phenotypes in a population over time?
Lesson Learning Goals
Students will:- understand examples of mosquito-borne infectious diseases and how they are connected to socioeconomic disparities.
- understand CRISPR-Cas9 technology and its uses in gene drives.
- understand experiments involving gene drives from primary literature.
- make and defend an argument about the ethics of gene drives.
- Students should be able to identify and critique scientific issues relating to society or ethics.
Lesson Learning Objectives
Students will be able to:- identify examples of mosquito-borne infectious diseases and explain their links to socioeconomic disparities.
- identify and describe the purpose of the components of CRISPR-Cas9 required for DNA editing.
- explain how CRISPR-Cas9 technology is used in gene drives.
- predict the outcomes of gene drives and contrast them with the outcomes of simple Mendelian inheritance.
- discuss examples of ethical questions raised by gene drive technologies.
Article Context
Course
Article Type
Course Level
Bloom's Cognitive Level
Vision and Change Core Competencies
Vision and Change Core Concepts
Class Type
Class Size
Audience
Lesson Length
Pedagogical Approaches
Principles of How People Learn
Assessment Type
Introduction
Active learning, compared to courses consisting solely of lectures, can improve exam scores and promote equitable course outcomes in student populations (1). Instructors can use active learning not only to teach “textbook” concepts, but also to help students strengthen skills in critically analyzing primary literature, an important component of undergraduate biology education as discussed in Vision and Change (2). Examples of active learning-based approaches to primary literature include CREATE, a structured framework for teaching primary literature (3), and Just Figures, an approach focusing on specific figures (4).
Active learning can also be used to connect biology concepts to broader societal issues. Ideological awareness, or connection of scientific topics to societal biases and inequalities, helps students understand connections between science and society (5). Students value ideologically aware classrooms (6), and instructors are interested in incorporating such discussions, though in some cases they worry about ramifications of discussing controversial topics in the classroom (7). Discussing health disparities in biology courses can be an example of ideologically aware teaching (8).
Here, I describe a lesson that uses an active learning approach, including discussion of primary literature, to teach students about a recent advance in biology and its ethical implications. This lesson focuses on gene drives, a genetic modification technology that could conceivably be used to modify organisms at a population level. Gene drives have the potential to reduce mosquito-borne disease transmission (reviewed in [9]), or locally eliminate invasive species (reviewed in [10]). However, this technology raises significant ethical and scientific questions. One area of concern is the potential for unintended ecological impacts (11). Gene drives could also be potentially deployed in low-income regions impacted by diseases such as malaria, raising significant questions about how local human communities would be involved in decisions about gene drives (12).
Gene drive technology is an application of CRISPR-Cas9, a versatile genetic modification tool (reviewed in [13]). Originally discovered in bacteria, CRISPR-Cas9 in research settings usually relies on two components: a protein, Cas9, with nuclease activity, and a guide RNA that determines the target sequence cleaved by Cas9. CRISPR-Cas9 can be used to make precise alterations to genomes. In gene drives, CRISPR-Cas9 systems are designed to copy themselves from one chromosome to the other homologous chromosome, typically during meiosis, which allows the gene drive system to be inherited at greater rates than possible with simple Mendelian inheritance. This accelerated inheritance could hypothetically allow for the design of gene drives that could spread alleles through a population more rapidly than would otherwise be possible, enabling the genetic modification of wild organisms. Gene drive technology presents an engaging and informative topic for undergraduate teaching. Understanding gene drives requires integrating concepts in molecular biology, Mendelian genetics, and population genetics. It also offers opportunities for students to connect those fundamental biology concepts to contemporary issues in bioethics, with relevance to socioeconomic disparities.
Previously reported examples of CRISPR-Cas9 being taught in undergraduate courses include the use of CRISPR-Cas9 to teach molecular biology skills (14–18), primary literature readings involving CRISPR-Cas9 (19), and bioethics discussions related to the potential use of CRISPR-Cas9 in humans (20). A 2018 National Science Foundation workshop focused on CRISPR-Cas9 in the undergraduate classroom (21), and the NSF-funded “CRISPR in the Classroom” network offers training and resources to instructors looking to teach CRISPR in their biology courses (22).
Despite widespread interest in integrating CRISPR-Cas9 into undergraduate coursework, there are few published examples of undergraduate courses specifically discussing gene drives. In one instance, during an independent research project, multiple students chose to research gene drives, demonstrating interest in the topic (23). In another unique case, undergraduates competing in an international science competition attempted to independently design a gene drive and a system to reverse it, prompting the competition to implement new restrictions on gene drives in future competitions (24). A master’s thesis briefly described gene drives as a potential example topic for the discussion of ethics-related issues in biology teaching (25), but other than these examples, reports of gene drives being taught in undergraduate classrooms are rare.
The lesson I describe here focuses on the science and ethics of gene drives in mosquitoes for infectious disease control. The instructor leads a brief discussion introducing mosquito-borne illnesses and their connections to health disparities, provides an overview of CRISPR-Cas9-based gene drives, leads a discussion of a previously published gene drive conducted in a controlled laboratory setting (26), and finally leads a bioethics activity in which students propose their own ideas for regulatory constraints on gene drives.
Intended Audience
This lesson is suitable for intermediate or advanced undergraduate biology courses. I first taught this lesson in an intermediate 200-level genetics course with 42 students, all of them life sciences majors, and all of them sophomores, juniors, or seniors. I taught it a second time in an advanced 300-level genetics course with 15 students, all of them juniors or seniors and all of them life sciences majors. Students in the advanced course had more prior exposure to primary literature, allowing for the primary literature to be covered more quickly in that context and for more class time to be spent on the bioethics activity at the end of the lesson.
Required Learning Time
This lesson can be taught in a 75-minute class period.
Prerequisite Student Knowledge
Prior to this lesson, students should be familiar with fundamentals of molecular genetics, including DNA structure and the definition of a gene, as well as simple Mendelian inheritance and its molecular mechanisms. Prior exposure to pedigree analysis will help students approach several of the active learning questions used in this lesson. A conceptual understanding of natural selection and fitness will be helpful in discussing potential effects of gene drives.
The primary literature discussion in this lesson requires an understanding of alternative splicing in eukaryotic transcription, and an understanding of the definition of knockouts in genetics.
A pre-reading was not assigned prior to this lesson; however, asking students to read a brief overview of gene drives and related ethical questions, such as (27), could help prepare students for discussing the day’s material. Similarly, students could be asked to view a brief video, or videos, prior to class, such as a video introduction to CRISPR-Cas9 technology and/or a video overview of gene drives. For an advanced seminar course, students could read portions or all of the primary literature paper discussed in this lesson (26) prior to class. If the paper will be assigned as reading, I would suggest asking the students to focus their reading on the specific figures that will be discussed in the lesson: Figures 1A, 2A, 3, and 5.
Prerequisite Teacher Knowledge
In addition to the concepts described above for Prerequisite Student Knowledge, the instructor should understand CRISPR-Cas9 and gene drive systems. Familiarity with mosquito-borne infectious diseases and socioeconomic factors influencing their transmission will also help instructors be fully prepared to teach this lesson.
This lesson includes discussion of a previously published gene drive (26); instructors should read that publication closely and be familiar with its rationale, methods, findings, and implications. The instructor will also benefit from understanding recent advances in the field; for one relevant review, see (9).
Scientific Teaching Themes
Active Learning
This lesson uses Poll Everywhere prompts, think-pair-share activities (28), and group work (29) to engage students in active learning. The active learning activities in this lesson span multiple levels of Bloom’s taxonomy (30), focusing on the higher levels of “Apply,” “Analyze,” “Evaluate,” and “Create.” In questions focused on applying knowledge, students combine prior knowledge of Mendelian genetics with newly acquired knowledge about gene drives to predict the outcomes of crosses. At the “Analyze” level of Bloom’s taxonomy, students discuss primary literature, considering the data and its implications. At the “Evaluate” level, students independently assess the ethics of gene drives, and at the “Create” level, students create a document of their own ideas for guidelines regulating gene drives.
Assessment
Poll Everywhere questions allow the instructor to assess student understanding in real time. Based on student responses, the instructor may adjust the lesson to address misunderstandings. Think-pair-share activities create an additional opportunity for assessment. At the end of the lesson, students in small groups complete a brief written assignment summarizing their views on the ethics of gene drives. With this assignment, instructors can assess whether students are successfully connecting the biological concepts covered in class with broader societal issues. A suggested rubric for the bioethics writing activity is provided (Supporting File S2).
Inclusive Teaching
This lesson emphasizes active learning, which promotes equitable course outcomes (1, 31). This lesson also uses several of the strategies for inclusivity suggested by Tanner (32), including the use of open-ended “brainstorming” questions, think-pair-share, asking multiple students to share their thoughts, and use of diverse, societally relevant examples in the classroom. By discussing health disparities and their connection to infectious diseases and bioethics, this lesson encourages students to think about science’s broader connections to societal inequalities. The bioethics activity that concludes this lesson encourages and empowers students to bring their own unique perspectives into the classroom, sharing their views on a contemporary bioethics issue.
This lesson, as I taught it, uses Poll Everywhere questions, which require access to cellular data or to the internet. I notified students at the beginning of the semester that tablets or laptops could be provided in class if access to an internet-connected device was a barrier for any students.
Lesson Plan
Introducing Mosquito-Borne Infections and Their Connection to Socioeconomic Inequalities
Begin the lesson with an outline of the topics covered (for slides see Supporting File S1, and for a timeline see Table 1). Proceeding into the first section, ask students for examples of mosquito-borne infectious diseases they may have previously heard of. For questions such as this, I use the “open ended” Poll Everywhere question format, in which students can anonymously type responses, and I combine this with hand-raising verbal responses from students. Examples to mention in the classroom include malaria, chikungunya virus, West Nile virus, yellow fever virus, dengue virus, and Zika virus.
Table 1. Timeline for the lesson.
Activity | Description | Estimated Time | Notes |
---|---|---|---|
Instructor-led discussion with active learning questions and think-pair share |
|
60 minutes |
|
Small group bioethics activity |
|
15 minutes |
|
Explain that, worldwide, multiple mosquito-borne diseases have a particularly severe impact in low-income countries; for example, malaria is a leading cause of death in countries considered low-income by the World Bank, but not in high-income countries (33). Local correlations of lower socioeconomic status with increased mosquito exposure or risk of infection have also been reported (for example, [34] and [35]), although these findings vary between studies (36).
In a think-pair-share activity, ask students to consider why mosquito-borne infectious disease rates might be higher in lower income countries. After giving students a minute or two to discuss their thoughts with each other, ask a few volunteers to share their thoughts. Using a combination of suggestions from students and supplemental information that you provide, discuss examples of how socioeconomic factors can impact risk of vector-borne diseases (reviewed in [37]). Example factors to discuss include impact of housing conditions, availability of medical resources, and access to running versus standing water sources (standing water can serve as a breeding ground for mosquitoes) (37). Note also that worldwide variations in mosquito population density, influenced by environmental factors, can interact with local infrastructure and healthcare resources to influence mosquito-borne disease rates. Briefly discuss public health interventions that could reduce the spread of mosquito-borne disease, including mosquito netting and improved housing conditions, improving medical or sanitation infrastructure, and use of pesticides or mosquito trapping (37). This point in the lesson is an opportunity to comment on drawbacks of some strategies for mosquito control, such as pesticides as potential sources of environmental and health concerns.
To frame the next section of the course, mention that some scientists are interested in developing genetic modification-based strategies for reducing the spread of mosquito-borne infectious diseases. In theory, targeting mosquitoes for genetic modification might reduce the spread of disease, but it also raises significant ethical questions. Explain that this lesson will explore the science and ethics of a method that could genetically alter wild mosquito populations. Before proceeding, pause for any questions or comments, and then ask students, in a think-pair-share exercise, to brainstorm: what types of mutations, if introduced into mosquitoes, might potentially reduce the spread of infectious diseases? Gather perspectives from several students before proceeding into discussing approaches that could, potentially, be used to genetically modify mosquitoes.
Defining CRISPR-Cas9 and Explaining Its Utility for Genetic Modification
I taught this lesson twice in two different courses; the first time, students had not previously discussed CRISPR-Cas9, and the second time they had already been introduced to it by an earlier lesson. If students have not previously learned about CRISPR-Cas9, at this point, introduce them to CRISPR and its uses. If students have already been introduced to CRISPR-Cas9 technology, this section may be skipped. This section of the lesson may be aided by a video, shown in class or required as viewing before class meets (for example, this video).
Explain that CRISPR-Cas9 is a tool for genetic modification. Broadly speaking, it allows researchers to introduce double-stranded breaks at specific target sites in a genome. As the cell repairs those double-stranded breaks, researchers can exploit natural repair pathways to introduce novel mutations or insertions at the original site of the break.
Explain that CRISPR-Cas9 consists of two components: the Cas9 enzyme, which cleaves DNA, and the guide RNA (gRNA), which “targets” Cas9 to a specific DNA sequence. Explain that the gRNA is a single-stranded RNA molecule that is complementary to the target DNA sequence. The Cas9 protein interacts with the gRNA and, together, they bind to the target DNA sequence at a site determined by the gRNA sequence. At this point, students might ask for clarification about how the gRNA interacts with the target DNA; explain that the two DNA strands separate in a manner facilitated by Cas9 to allow the gRNA to base pair with its target sequence.
The Cas9 enzyme then introduces a double-stranded break in the DNA. Explain that, after the double-stranded break is introduced, researchers often rely on the natural, but error-prone, double-stranded break repair pathway present in cells (called non-homologous end joining, or NHEJ). This pathway repairs the double-stranded break, but often introduces mutations at the break site during the process. These mutations may result in frameshifts or other loss-of-function mutations when double-stranded breaks are introduced into coding sequences of genes. Thus, by targeting a gene’s coding sequence, CRISPR-Cas9 can be used to generate loss-of-function alleles within that gene. Pause for questions at this point.
Explain that CRISPR-Cas9 systems can also be used to introduce new genetic material into a target genome. The cell’s homology-directed repair pathway can repair a double-stranded break using homologous DNA as a template. When researchers supply partially homologous DNA sequences that also contain novel sequences, homology-directed repair can introduce those novel sequences into the genome during repair of the break. Visuals included in Supporting File S1 will help illustrate these concepts. Pausing for questions will be helpful at this stage to make sure students are comfortable with the concepts before proceeding.
Students might ask what makes CRISPR-Cas9 unique compared to other tools for genetic modification; explain that, because researchers can design gRNAs, they can target Cas9 to almost any location in the genome provided that it is a unique sequence.
Defining Gene Drives and Discussing the Resulting Inheritance Patterns
Explain to students that gene drives are a CRISPR-Cas9-based method that could hypothetically be used to modify entire populations of wild organisms. Also note that this raises important ethical questions that will be discussed later in the lesson.
Explain that gene drives are designed to alter populations at faster rates than possible with simple Mendelian inheritance. To briefly review Mendelian inheritance, while illustrating its limitations compared to gene drives, walk students through the following scenario. Researchers have engineered mosquitoes to carry a dominant allele, passed down by simple Mendelian inheritance, which reduces malaria transmission. These engineered mosquitoes are released into a larger population of wildtype mosquitoes, and they begin interbreeding with the wildtype mosquitoes. Show students Figure 1, which visually represents one heterozygous mosquito carrying the dominant allele crossing with a wildtype mosquito. In a Poll Everywhere question, ask students to predict the outcome of this cross: what percent of offspring will inherit the dominant allele? The correct answer is that 50% of offspring are expected to inherit the dominant allele. This exemplifies the fact that, with simple Mendelian inheritance alone, attempts to “spread” a desired allele through a mosquito population would quickly encounter limitations.
![Figure 1 Figure 1](/publications/4824/5160?media=Image:Figure%201-24989.png)
Explain that gene drives are CRISPR-Cas9 based tools designed to allow alleles to be inherited at higher ratios than would be possible with Mendelian inheritance alone. Gene drives are designed to, once integrated into one chromosome, copy themselves onto the homologous chromosome in sexually reproducing organisms. This self-copying of the gene drive is usually designed to occur during meiosis, so that an organism heterozygous for the gene drive will pass it down to all, or nearly all, offspring.
Remind students of the fundamentals of CRISPR-Cas9, including the fact that homology directed repair can introduce new genetic material after Cas9 introduces a double-stranded break. In a gene drive, the genes encoding Cas9 and the gRNA are, themselves, inserted into the target genome at a specific site selected by researchers. The gene drive may be inserted at a site impacting a phenotype of interest: for example, researchers might design a gene drive to insert itself into a gene required for mosquito feeding. With the insertion of the gene drive inside a gene’s coding sequence, that gene’s function will be disrupted.
Explain that once the gene drive is integrated into the genome, the cas9 and gRNA genes will be expressed, and the gRNA will target Cas9 to introduce a double-stranded break into the same site on the homologous chromosome. Then, by homology-directed repair, the genes encoding the gene drive system are copied onto that chromosome. Thus, the gene drive duplicates itself and will be passed down at greater rates than would be possible with Mendelian inheritance alone.
Students may need additional time to walk through this concept together; using visuals drawn on a whiteboard may help with clarifying, step-by-step, how the process works. The instructor might also further clarify this portion of the lesson by including a video walking through the concept (for example, this video). Once the idea of a gene drive is clear and students have no further questions, proceed to the next active learning question.
Show students a cross between a mosquito carrying a gene drive and a wildtype mosquito lacking the gene drive (see Supporting File S1). Ask students to predict: what percent of mosquitoes from this cross will inherit the gene drive? The correct answer, in this case, is that all offspring will be expected to inherit the gene drive. Because one parent carries the gene drive, that parent can be assumed to always pass the gene drive down to offspring. Furthermore, each mosquito that inherits the gene drive will pass the gene drive to 100% of its offspring as well, because the gene drive will duplicate itself. Thus, a gene drive can be passed down at greater rates than would be possible with simple Mendelian inheritance. Hypothetically, a gene drive could spread to all mosquitoes in a population given sufficient passage of time and multiple generations. Note again that gene drives can be designed to disrupt the function of selected target genes.
Ask students to consider a scenario: what if a gene drive introduces a mutation that reduces mosquito fitness? How might it impact the results of the attempted gene drive? In a think-pair-share format, give students a few minutes to discuss, and then gather perspectives from a few groups. Ask students to, as they consider this question, draw a pedigree to predict inheritance of the gene drive.
Students might correctly note that, even if a gene drive is inherited at greater-than-Mendelian ratios, if the gene drive reduces mosquito fitness, mosquitoes carrying the gene drive might be selected out of the population before the allele can spread adequately. Selection pressures against a gene drive could therefore limit a gene drive’s efficacy.
Ask students to brainstorm: how might researchers design a gene drive to both reduce infectious disease transmission and avoid such a severe fitness cost in mosquitos that the gene drive is selected out of a mosquito population? After giving the students a few minutes to consider ideas, ask for multiple groups to share their thoughts. Students might suggest multiple ideas: what if a gene drive disrupted disease transmission without disrupting mosquito fitness? What if a gene drive only disrupted fitness in one mosquito sex, allowing the other sex to continue transmitting the gene drive?
Note that the lesson will now shift into a discussion of one example gene drive from a primary literature study.
A Primary Literature Case Study: Discussion of Select Figures From an Example Gene Drive
The following section of the lesson discusses a previously published gene drive carried out in a controlled laboratory setting (26).
Use an “open ended” Poll Everywhere question to ask students: if a gene drive causes female mosquitoes to lose fertility, but does not harm the fertility of male mosquitoes, how might the gene drive’s inheritance patterns be impacted, assuming a starting population of male mosquitoes carrying the gene drive and interbreeding with wildtype mosquitoes? Students might accurately predict that affected male mosquitos could pass down the gene drive while affected female mosquitos would be unable to produce offspring. Some students, however, might need clarification about how the gene drive spreads in a population. For instance, some students might note, correctly, that if an affected male mosquito breeds with an affected female mosquito, no offspring would be produced. Note that the gene drive spreads when affected male mosquitos breed with unaffected “wildtype” female mosquitos. In a wild population with many wildtype female mosquitos, hypothetically releasing a large starting population of males carrying the gene drive would allow for the gene drive to begin spreading as the mosquitos breed.
After examining student answers, discuss, using the visual aid shown in Figure 2 (also found on slide 28 in Supporting File S1) how such a gene drive could be expected to be inherited. Female mosquitoes impacted by the gene drive would be unable to produce offspring; male mosquitoes impacted by the gene drive could still breed with female wildtype mosquitoes and pass the gene drive down to all offspring. Thus, over time, male mosquitoes could still spread the gene drive without experiencing any fitness effects imposed by it; female mosquitoes, by contrast, would lose fertility when affected by the gene drive. Such a gene drive could hypothetically, over multiple generations, come to dominate a population, leaving all remaining female mosquitoes infertile and leading eventually to eradication of the mosquito population.
![Figure 2 Figure 2](/publications/4824/5160?media=Image:Figure%202-24990.png)
Explain to students that the lesson will now discuss a primary literature study in which a gene drive was designed to disrupt fertility in female but not male mosquitoes. Show the students Figure 1A from the previously published report (26), and explain that the gene represented, doublesex, is alternatively spliced in male and female mosquitoes. A specific exon within this gene is found in the mature mRNA in female, but not male, mosquitoes. This exon is highly conserved. Because of its conservation and sex-specific expression, the authors hypothesized that this exon is critical for the development of female mosquitoes only, and dispensable for male mosquitoes.
Explain that the researchers tested their hypothesis by knocking out this exon and assessing how loss of this exon impacted development of male and female mosquitoes. Show the students Figure 2A and 2B from the previously published report (26). These figures show the morphology of male and female mosquitoes of three different genotypes (wildtype, heterozygotes missing one copy of the exon, or homozygotes missing both copies of the exon). In a think-pair-share exercise, ask students to take a few minutes to examine the morphologies of the mosquitoes and note any patterns they observe in the results. When sharing their thoughts, students might comment that homozygous knockout females have altered morphology relative to wildtype or heterozygote females. Students might also observe that male mosquitoes appear unaffected by loss of the exon. Confirm that these observations are correct and point out that the female homozygous knockout mosquitoes resemble males.
Next, explain that the researchers predicted that loss of this exon might impact fertility in female mosquitoes, due to the exon’s clear impact on sex-specific development. Show Figure 3 from (26) and point out that homozygous knockout females are indeed completely infertile, whereas homozygous knockout males are unaffected.
Lastly, provide background information on Figure 5 from (26). The authors designed a gene drive to disrupt the exon and they tested this gene drive in a controlled laboratory setting. They tested the gene drive by mixing 300 wildtype female mosquitoes with 150 male wildtype mosquitoes and 150 male mosquitoes carrying a gene drive targeting the exon. The figure shows frequency of the gene drive allele in the population over subsequent generations as well as number of offspring produced per generation. Give students a minute or two to examine the figures and interpret the results: how has the gene drive impacted the mosquito population? With student input, explain that, within twelve generations, all mosquitoes in the population had inherited the gene drive, and the population was no longer producing offspring. Thus, the gene drive, at least in this controlled setting, could be used to eradicate mosquitoes. Pause at this point for questions.
In-Class Assignment: Discussing the Ethics of Gene Drives
Explain to students that, having defined gene drives and examined an example gene drive, the lesson will conclude with a group assignment discussing the ethics of gene drives. Ask students to form groups of three or four. With their groups, ask them to imagine that they have been hired as expert scientific consultants for a major government or international policy group. Their task is to discuss gene drives and make policy recommendations about how gene drive technology should be regulated. Students are to discuss the topic within their group and, by the end of class, produce a bullet point summary of their recommendations. Explain that respectful disagreement within a group is not a problem, and if students do not reach a consensus about their views, their submitted assignment can also include comments on any topics where the group did not reach a consensus. Clarify that the assignment will be graded for evidence of sincere effort and thoughtful discussion. Provide a slide of prompts for students to consider, mentioning that students do not necessarily need to address all prompts, but that the prompts can be a starting point for their discussion (see the last slide of Supporting File S1).
After students submit their work, if time permits you may choose to quickly read each group’s submission in class and have a “debrief” discussion with the class about their thoughts on the topic. If teaching a larger class size where reading each submission may not be feasible during class time, the instructor might instead opt for a survey (created using Poll Everywhere or a similar technology) in real-time to end the class. The instructor could ask, for instance, whether each student would “strongly agree,” “agree,” “disagree,” or “strongly disagree” with the proposal to implement a gene drive in wild mosquito populations. Following up on survey responses, the instructor could ask a few groups to briefly share some of their thoughts from their discussion.
Teaching Discussion
Overall, I found that this lesson generated lively and thoughtful discussion among students. Students appreciated the public health and societal connections, with groups commenting thoughtfully on those connections in their bioethics assignments. While discussing primary literature, it was clear that the difficulty level of the paper was appropriate, with students remaining engaged and asking thoughtful questions about the rationale of the study. Areas for improvement include expanding the use of active learning exercises in the earlier portions of the lesson, and the use of clearer visuals to illustrate the concept of a gene drive at the molecular level. Here I will comment further on each aspect of the lesson, including thoughts on areas for potential expansion or improvement.
The introductory portion, describing example mosquito-borne infectious diseases and their connections to health disparities, provides a broad overview of the impacts of mosquito-borne diseases, rather than an in-depth discussion of their biology. In the context of this lesson, a brief overview of mosquito-borne diseases appeared to be sufficient for students to place the science of gene drives within a broader context. However, in a more expanded format (for instance, over the course of two lessons rather than one), instructors might add more depth by including, for example, an overview of malaria’s lifecycle and pathogenesis (reviewed in [38]), and discussion of climate change and malaria transmission (39).
Gene drives raise questions about the ecological impacts of potentially eradicating a species, something students commented on in their bioethics assignments, but that I as an instructor did not otherwise explicitly discuss. In an expanded format, the instructor could include discussion of mosquitoes in the food chain and the extent to which mosquito eradication might impact ecosystems, as well as broader discussion on the potential impact of gene drives on ecosystems (11, 40–42).
Although this lesson was taught in intermediate and advanced-level biology courses, it might be modified, with reduced emphasis on technical details, for use in introductory or non-majors’ courses. In such a course, the material would be more approachable with less emphasis on molecular mechanisms and technical details. Similarly, discussing fewer figures from the primary literature paper, and focusing on figures with the most straightforward interpretations (Figure 5 from [26] in particular), would also help make this material approachable in an introductory or non-majors’ class.
I taught this lesson twice; in one iteration, I included an introduction to CRISPR-Cas9 technology within the lesson. In the second iteration, I introduced CRISPR-Cas9 earlier in the semester, allowing this lesson to focus more exclusively on gene drives. In the future, I will continue teaching the lesson using the second approach of introducing CRISPR-Cas9 at an earlier point in the semester. By introducing CRISPR-Cas9 earlier, I found that there was more time within this lesson to focus specifically on the mechanics of gene drives, allowing students to apply prior knowledge of CRISPR and Cas9 to the discussion. Introducing CRISPR-Cas9 in a separate lesson also allowed more time elsewhere in the course to discuss additional aspects of CRISPR-Cas9 technology, such as its bacterial origin, its many other uses in research settings, and its potential clinical uses in humans. Anecdotally, prior engagement with other applications of CRISPR-Cas9 seemed to also improve student confidence in their predictions and discussions about gene drives.
The next portion of the lesson introduces gene drives, explaining both their molecular mechanism and their impact on inheritance. The molecular mechanism of gene drives was the concept that students found most difficult in this lesson. I found that this was, in part, due to my illustrations representing gene drives—although I did not realize it initially, these illustrations were somewhat ambiguous in their interpretation. I recommend replacing them with a different visual, such as the diagrams included in a recent review article (9). Adding at least one Poll Everywhere review question at this point in the lesson may also be helpful; for instance, instructors might ask students to predict the outcome of a gene drive if the Cas9 gene contained a loss-of-function mutation.
Despite initial confusion about the molecular mechanisms of gene drives, student understanding of inheritance patterns for gene drives was quite strong as indicated by their answers to the Poll Everywhere questions about the population-level impacts of gene drives. Therefore, the explanation of gene drives at the molecular level is the portion of the lesson that would benefit most from expansion and clarification.
The primary literature-based discussion was an effective exercise allowing students to apply their understanding of both Mendelian inheritance and gene drives to recent data. The figures I selected do not require a great deal of technical background knowledge to discuss, provided that the instructor introduces the paper at an appropriate point in the semester. Students were able to accurately interpret and comment on the experiments presented in the paper. I used a think-pair-share exercise during the discussion of this paper, but in the future, I will expand on the active learning components by adding additional Poll Everywhere questions, think-pair-share activities, or worksheet questions for each selected figure from the paper. For example, rather than telling students which exon in the doublesex gene was chosen as a candidate target for a gene drive, I might ask them to choose which exon, or exons, might be appropriate targets for a gene drive designed to target female mosquitos only. Additional suggestions for Poll Everywhere questions that could engage students in evaluating the figures carefully and critically are included in the notes accompanying relevant slides in Supporting File S1.
I taught this lesson without any pre-reading required, but the instructor could rework the lesson and assign the paper, or portions of it, as reading before class. If students do read portions of the paper beforehand, the primary literature-based portion of the lesson could be altered to be taught, for example, using the CREATE format (3). In its current format, this lesson does not discuss every figure in the selected study, instead focusing on example figures. However, in an expanded format, the instructor might opt to discuss additional experiments from this study, or to go into additional detail about the selected figures.
For the bioethics activity that ended the class, I allowed students to self-select groups. However, there are benefits to the instructor choosing groups rather than allowing students to self-select. Instructor-formed groups that avoid isolating minority students can promote inclusivity in the classroom (43), and mixed groups of students with differing levels of comfort with the material can promote learning (44).
In group work, assigning specific roles to students can encourage participation of all students, as discussed in multiple online guides for teaching group work activities (for example, [45]). I did not assign group roles in this assignment; in a small class size, I was able to observe group dynamics directly and make note if any groups and/or individuals were not contributing. In a larger class size, however, the instructor might consider assigning group roles to give the activity more structure and encourage contributions from all group members. To further allow the instructor to assess group work dynamics in a larger classroom size, the instructor might require students to take a post-class survey in which they can anonymously notify the instructor of any issues in their group (for example, any group members who did not contribute). If multiple students indicate that a group member did not contribute to discussion, the instructor might deduct from that group member’s score on the assignment. A suggested rubric for grading the group assignment is provided (Supporting File S2).
During the bioethics activity, I provided students with a list of starting questions to guide their discussion (see Supporting File S1, slide 36). These prompts were based, in part, on points of discussion in the field (12) and were intended to guide students towards particularly pertinent ethical questions. However, these questions might “lead” the discussion in specific directions, and in the future, I might teach a version of the lesson omitting these questions to offer students a more open-ended version of the bioethics assignment.
Student views in the bioethics assignment varied, and in some cases, discussing the topic with their peers led students to change their minds in minor or major ways. Many students argued against the use of gene drives in wild organisms due to concerns about irreversibility, ecological impacts, or impacts on human communities in areas where gene drives might be used. Some students proposed safeguards or limitations. Many student comments on ethical questions were similar to those in published scholarship (12), and some student calls for safeguards had similarities to published “self-limiting” split gene drives (46) or strategies for reversing gene drives (47). In instances such as these, the instructor could explicitly mention that students are thinking like modern-day scientists, which could help foster student science identity (48).
A group discussion touching on ethical questions has the potential for disagreement among students. I explicitly mentioned that disagreement within a group is not a problem, provided that it remains respectful. Although in some cases students did disagree with one another, discussions remained cordial and friendly. Because of the potential for disagreement on this topic, the instructor might restructure the activity as a debate. Debates in the classroom can change student attitudes while allowing them to practice communication skills (49) and can impact student thinking about ethical or moral issues (50). Existing online resources for instructors teaching potentially difficult or contentious topics might be useful in preparing to teach this lesson (example resources include [51–53]).
The lesson concluded with student completion of the bioethics activity, but a more expanded follow-up discussion or “debrief” could explore the current state of gene drive research, regulations, and policy. Given additional time in the classroom, the instructor could discuss recent advances in the field while teaching additional concepts in advanced undergraduate genetics. For example, the instructor might discuss split gene drives (46), potential approaches for reversing a gene drive (47), or comparisons of multiple approaches for self-limiting gene drives (54). Follow-up discussions could also be used as an opportunity to discuss public policy and its connections to gene drives (55, 56).
After the lesson is concluded, instructors might assess the impacts of this lesson over a longer time span by evaluating whether this activity impacts student retention of relevant biology concepts or shapes their thinking about connections between science and society. This was beyond the scope of my approach to teaching this lesson so far, although anecdotal conversations with students later in the semester indicated that their understanding of CRISPR-Cas9 and their interest in the topic remained strong.
Because gene drives lie at an intersection between molecular biology, population genetics, and bioethics, lessons incorporating gene drives into the undergraduate curriculum present an opportunity to teach inspiring, interdisciplinary, and societally relevant lessons.
Supporting Materials
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S1. Gene Drives – Lesson Slides
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S2. Gene Drives – Suggested Rubric Bioethics Assignment
Acknowledgments
I wish to thank the biology departments of Spelman College and Emory University for the teaching opportunity, as well as all students enrolled in both courses where I taught this lesson. I also wish to thank Dr. Jennifer Gresham, Dr. Celina Jones, and Dr. Casey Schmidt for reading and offering insightful comments on this manuscript. My teaching was made possible by NIH grant K12 GM 000680. The work presented here represents the work of the author and does not reflect work done at the funding agency, nor does this manuscript necessarily reflect the views of the NIH.
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