Look forward to the rest of this series Elliot! Especially curious to hear your thoughts on DNA synthesis, and how enzymatic approaches might evolve over time.

I might also add that beyond breakthrough technologies enabling us to understand how our genomes impact health, our ability to make meaning out of this new information is critically important. I shared some brief thoughts on this today: https://healthandwealth.substack.com/p/genetic-counseling

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Apr 11, 2022Liked by Elliot Hershberg

Great post! Given the general interest focus of this series, I hope you won't mind some noob clarification questions (coming from someone whose last exposure to Biology was AP Bio in the early 00's) about the

"[Sequencing data] will have uncontroversial benefits like finding better drug targets for diseases"

- Can you provide an example?

- If we've already sequenced a bunch of people, can you give some intuition around how and why sequencing many more will lead to finding better drugs for certain diseases?

"[Sequencing data] will greatly improve precision medicine-where patients are matched with drugs based on their genetics"

- Can you give an example?

- How can we learn this relationship? Even when the health outcomes are easy to measure (not the case in mental health, for instance) how exactly would we be able to detect that certain drugs are more effective for people certain genes? From a statistical standpoint, if there are dozens of genetic subpopulations that may respond differently to dozens drugs for a given disease, doesn't that lead to an explosion of treatment groups during clinical trials?

"Sequencing will also be used more directly in clinical care," and the two examples you give are diagnostic.

- Can you explain the first example? (What's a causal mutation?)

- In the simplest case, I understand how cheap sequencing could detect things like congenital single gene diseases. And though I don't understand what polygenic risk scores measure, exactly, I understand being able to say "people with a genetic makeup similar to yours go on to develop [insert disease here] x% of the time." And how that would lead you to take preventive steps to addresses [insert disease]. So, given that we already do seem to do this when people's lifestyle or demographics are similarly predictive of [insert disease], how much extra predictive power does sequencing give us?

- Going beyond "you were born with these genes, and we know that causes or is at least a risk factor for [insert disease]," the cancer diagnosis example seems to imply "we can detect disease before it fully develops because it's changed your DNA." Are there any other diseases that we can detect in this "non-congenital" way?

"[Sequencing gut microbes] could become essential for understanding how different diets actually impact our bodies on an individual basis." The dismal state of nutrition science suggests that we already have a hard time measuring the relationship between diet and impact on our bodies (likely because there are so many input variables, and the interesting outcomes take years if not decades to manifest). Would adding the additional variable of gut micro composition somehow make this topic easier to study, instead of harder?

Thank you!

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