Crispr Pioneer Jennifer Doudna Has the Guts to Take On the Microbiome

I SEE YOU, reader. You drink the probiotic seltzer, with its gut-improving bacteria, and the fiber-filled prebiotic. You regularly consume eclectic fermented foods and burly amounts of kale to diversify those precious microbesin your digestive tract.

Because, after all, what isn’t the microbiome responsible for? It’s been all the rage for the past few years, with scientists hoping it could help treat everything from immune disorders to mental illness. How exactly that will work is something we’re just starting to explore.

This spring, the effort got a boost when UC Berkeley biochemist and gene-editing pioneer Jennifer Doudna, who won a Nobel Prize in 2020 for coinventing Crispr, joined the pursuit.

Her first order of business, spearheaded by Berkeley’s Innovative Genomics Institute: fine-tuning our microbiome by genetically editing the microbes it contains while they’re still inside us to prevent and treat diseases like childhood asthma. (Full disclosure: I teach at Berkeley.)

Oh, she also wants to slow climate change by doing the same thing in cows, which are collectively responsible for a shocking amount of greenhouse gas.

As someone who has written about genetic engineering in the past, I have to admit that my first reaction was: No way. The gut microbiome contains around 4,500 different kinds of bacteria plus untold viruses, and even fungi (so far: in practice we’ve only just started counting) in such massive quantities that it weighs close to half a pound. (Microbes are so tiny that 30 trillion bacteria would weigh roughly 1 ounce. So half a pound is a lot.)

Figuring out which ones are responsible for which ailments is tricky. First you need to know what’s causing the problem: like maybe something is producing too much of a particular inflammatory molecule. Then you have to figure out which microbe—or microbes—is doing that, and also which gene within that microbe. Then, in theory, you can fix it. Not in a petri dish, but in situ—meaning in our fully active, roiling, squishing stomach and intestines while they continue to do all the stuff they usually do.

Until recently, it would have seemed insane—not to mention literally impossible—to edit all the microbes belonging to a species within a vast ecosystem like our gut.

And to be fair, Doudna and her collaborator, Jill Banfield, still don’t know quite how it will work. But they think it can be done, and in April, TED’s Audacious Project donated $70 million to support the effort.

My own gut feeling (right?) was that this was either brilliant or terrifying, or possibly both at once. Brilliant because it had the potential to head off or treat diseases in an incredibly targeted and noninvasive way. Terrifying because, well, you know … releasing a bunch of inert viruses equipped with gene-editing machinery into the vital ecosystem that is our gut microbiome—what could go wrong?

With that in mind, I invited Jennifer Doudna to my house for a chat about the future of microbiome medicine.







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