This is a super helpful section!

Typo — the "H" in GitHub is capitalized. Be sure to find and adjust all mentions (looks like there are five)

I would make this a main figure — it seems almost like a graphical abstract of the entire paper and shows readers at a glance how different programs they might be familiar with can all work harmoniously. It might also be good to show this high-level view of the system before showing the more nitty-gritty views in Figure 2

You might want to mention to readers that Airtable also enables no-code automations (and you can use Zapier for some more complicated but still no-code automation) since some labs lack even basic scripting ability. You describe "no-code implementation" early in the manuscript, so it seems important to clarify exactly what can be done without code and what strictly requires it.

Separately, you could also mention that Airtable can communicate with Slack (I see Telegram in Supp Fig 3, but I believe Slack is probably more common among scientists), Google Drive, etc.

You might want to define this like you did for "single source of truth" since you're using it in a bit of a unique way. How do you define an atom (aka the smallest unit) in this context?

Typo — should be "object." I'd streamline this sentence though, it's a little redundant

I'd link to the example base again here too — looking at that is probably the easiest way for someone to quickly understand the concept! You've laid it out really nicely

Can you specify how many/what proportion?

How did you do this survey? This seems like a useful dataset that others might want to cite if you provide some more methodological info (e.g., Who are the respondents? Did you post this on social media? Do you know that each respondent is from a different lab or might this not really represent 233 distinct labs?)

This is a really cool preprint! We use Airtable to run the internal aspects of our publishing system at Arcadia Science and would love to see more scientists taking advantage. Your example base is perfect for helping readers understand and adapt what you've built.

I've added some thoughts that I had while reading, hopefully they're helpful.

In "Conclusions and Future Outlook," you note that you created this program and are presumably sharing this paper to help other genome editing researchers implement partnerships with local schools. This is awesome and I think you could make it clearer in the abstract. Since this is most readers' first introduction to your content, it's a good place to specify your intended audience and emphasize that you've included all the resources necessary for them to replicate or adapt your program.

I think this could be clearer in specifying what exactly you're depicting in panel A

Perhaps cite a review that general genome editing researchers might read to get more familiar with base editing should they choose to implement your program.

This could be a little cleaner (italicize E. coli, add degree symbol, etc.). At a glance, I'm not sure what the italicized purple letters in the pSel panel are supposed to indicate.

This definition is a little misleading. Perhaps rephrase: "Genome engineering (or genome editing) is the manipulation of the genomic sequence of a living organism through the addition, deletion, correction, or replacement of DNA. Ideally, this occurs in a precise, efficient, and controllable manner."

I know germline editing is the go-to ethics discussion topic, but I wonder if you might engage students more deeply by discussing the concept of enhancement. This could tie in really well with the hands-on experiment because adding GFP to E. coli is itself an enhancement.

You can make allusions to superheroes, which tends to hook younger audiences. Imagine adding GFP to a person and knocking out myostatin... could we make the Incredible Hulk?

You could also discuss whether enhanced people should be able to compete in professional sports, how genetic enhancement does/doesn't differ from plastic surgery or tattoos, etc. Lots of ground for connection with high school students.

Kudos for developing this program, I know how hard it is to make these topics accessible to lay audiences! This manuscript does a great job of articulating the need for practicing scientists to engage with students and provides a useful framework for others to do so.

My main feedback is that you could make the content even more useful by including practical details and tips. For example, how do you recommend that scientists get in touch with local educators? Do you recommend a small trial run of just the experiment before implementing the full program with multiple classes? What is an effective ratio of scientist volunteers to students? In the materials list, what quantity of each material is required per student group? What were your main challenges as instructors and how do you recommend that others overcome them?

I think anything that can make this process less intimidating will encourage readers to commit to such a time-consuming but rewarding effort. I've also made annotated comments throughout that pertain to this (and other topics).

I also wonder if you might make the slides and worksheet available in editable format so that they're easy for readers to use and change. It would be great to include a link to a publicly viewable/downloadable Google Slides version of the deck and Google Doc version of the worksheet (and possibly other supplemental resources).

Suggest replacing with "may be" since there are others in the field who might disagree

I think the diagram could be a little clearer and maybe it would help the students understand better. For example, making the DNA and RNA strands different colors would make them easier to quickly distinguish. Same for the Cas9 protein vs. the DNA-modifying enzyme. You could also put a box around the target base location just to make it very clear where that empty label box is pointing.

I would make sure that however you depict the system in the worksheet, it's identical to how it's shown in the slides.

This is not a hugely important comment, but "GFP-itis" feels awkward to pronounce out loud, and also feels a little inaccurate because GFP is not something E. coli would normally express. I wonder if you might brainstorm some other names, like "Chronic blandness" or "Swag deficiency" or something that's still light-hearted but easy to pronounce.

Unclear what "this" refers to, perhaps replace with "the dead GFP"

I would definitely encourage more active learning! Or perhaps replacing some of the slides about base editing with an animation could make them a bit clearer. It's definitely a lot for students to wrap their heads around basic genome editing, let alone base editing. I wonder if you could get away with skipping traditional editing just to reduce the complexity.

Very glad to see these plasmids already available on Addgene! That's crucial to make this replicable

Would add "and restoring fluorescence."

Would be nice to have the supplemental info as part of the preprint, not sure if you can just combine the PDFs and upload

👏

I think you could write the instructions in a simpler way for the students, especially since you note that administering this portion of the program is the most challenging. Breaking the protocol up into short, imperative steps might help.

For example, Step 1 can just be labeling the tubes and putting them on ice. Step 2 can be "Add 70 ul sterile DI water and 20 ul 5x KCM to each tube." etc.

Is there any way this might work without a water bath or incubator? These seem the most unlikely for a HS to have and toughest to bring with you from lab. Wondering if maybe you can leave plates out at room temp for a weekend to grow instead. Not essential, just a thought

This would be great to see. I'm extremely dubious that so many students are actually well-informed or even aware of genome editing/CRISPR/base editing.

It would be really cool to poll your scientist instructors and learn how they benefitted from the experience too. Even an informal discussion could be interesting to include, especially if you're hoping to encourage readers to do this themselves.

A lot of advanced classrooms/educators may want to verify the edit at the genetic level (this optional extension is available in many of the traditional DSB-mediated editing courses I've seen). This is probably excessive, but perhaps you might suggest primers to amplify a region that includes the editing site and suggest a restriction enzyme that will only cut (or only not cut) if editing is successful.

A lot of advanced classrooms/educators may want to verify the edit at the genetic level (this optional extension is available in many of the traditional DSB-mediated editing courses I've seen). This is probably excessive, but perhaps you might suggest primers to amplify a region that includes the editing site and suggest a restriction enzyme that will only cut (or only not cut) if editing is successful.

This would be great to see. I'm extremely dubious that so many students are actually well-informed or even aware of genome editing/CRISPR/base editing.

👏

I would definitely encourage more active learning! Or perhaps replacing some of the slides about base editing with an animation could make them a bit clearer. It's definitely a lot for students to wrap their heads around basic genome editing, let alone base editing. I wonder if you could get away with skipping traditional editing just to reduce the complexity.

I think the diagram could be a little clearer and maybe it would help the students understand better. For example, making the DNA and RNA strands different colors would make them easier to quickly distinguish. Same for the Cas9 protein vs. the DNA-modifying enzyme. You could also put a box around the target base location just to make it very clear where that empty label box is pointing.

I would make sure that however you depict the system in the worksheet, it's identical to how it's shown in the slides.

It would be really cool to poll your scientist instructors and learn how they benefitted from the experience too. Even an informal discussion could be interesting to include, especially if you're hoping to encourage readers to do this themselves.

I know germline editing is the go-to ethics discussion topic, but I wonder if you might engage students more deeply by discussing the concept of enhancement. This could tie in really well with the hands-on experiment because adding GFP to E. coli is itself an enhancement.

You can make allusions to superheroes, which tends to hook younger audiences. Imagine adding GFP to a person and knocking out myostatin... could we make the Incredible Hulk?

You could also discuss whether enhanced people should be able to compete in professional sports, how genetic enhancement does/doesn't differ from plastic surgery or tattoos, etc. Lots of ground for connection with high school students.

Is there any way this might work without a water bath or incubator? These seem the most unlikely for a HS to have and toughest to bring with you from lab. Wondering if maybe you can leave plates out at room temp for a weekend to grow instead. Not essential, just a thought

Would be nice to have the supplemental info as part of the preprint, not sure if you can just combine the PDFs and upload

I think you could write the instructions in a simpler way for the students, especially since you note that administering this portion of the program is the most challenging. Breaking the protocol up into short, imperative steps might help.

For example, Step 1 can just be labeling the tubes and putting them on ice. Step 2 can be "Add 70 ul sterile DI water and 20 ul 5x KCM to each tube." etc.

Very glad to see these plasmids already available on Addgene! That's crucial to make this replicable

This could be a little cleaner (italicize E. coli, add degree symbol, etc.). At a glance, I'm not sure what the italicized purple letters in the pSel panel are supposed to indicate.

Would add "and restoring fluorescence."

This is not a hugely important comment, but "GFP-itis" feels awkward to pronounce out loud, and also feels a little inaccurate because GFP is not something E. coli would normally express. I wonder if you might brainstorm some other names, like "Chronic blandness" or "Swag deficiency" or something that's still light-hearted but easy to pronounce.

Unclear what "this" refers to, perhaps replace with "the dead GFP"

Suggest replacing with "may be" since there are others in the field who might disagree

Perhaps cite a review that general genome editing researchers might read to get more familiar with base editing should they choose to implement your program.

I think this could be clearer in specifying what exactly you're depicting in panel A

This definition is a little misleading. Perhaps rephrase: "Genome engineering (or genome editing) is the manipulation of the genomic sequence of a living organism through the addition, deletion, correction, or replacement of DNA. Ideally, this occurs in a precise, efficient, and controllable manner."

In "Conclusions and Future Outlook," you note that you created this program and are presumably sharing this paper to help other genome editing researchers implement partnerships with local schools. This is awesome and I think you could make it clearer in the abstract. Since this is most readers' first introduction to your content, it's a good place to specify your intended audience and emphasize that you've included all the resources necessary for them to replicate or adapt your program.

Kudos for developing this program, I know how hard it is to make these topics accessible to lay audiences! This manuscript does a great job of articulating the need for practicing scientists to engage with students and provides a useful framework for others to do so.

My main feedback is that you could make the content even more useful by including practical details and tips. For example, how do you recommend that scientists get in touch with local educators? Do you recommend a small trial run of just the experiment before implementing the full program with multiple classes? What is an effective ratio of scientist volunteers to students? In the materials list, what quantity of each material is required per student group? What were your main challenges as instructors and how do you recommend that others overcome them?

I think anything that can make this process less intimidating will encourage readers to commit to such a time-consuming but rewarding effort. I've also made annotated comments throughout that pertain to this (and other topics).

I also wonder if you might make the slides and worksheet available in editable format so that they're easy for readers to use and change. It would be great to include a link to a publicly viewable/downloadable Google Slides version of the deck and Google Doc version of the worksheet (and possibly other supplemental resources).