15 Minutes with Rachel Haurwitz at Pioneers Festival 2017

We talked to Rachel Haurwitz, co-founder and CEO of Caribou Biosciences and one of this year’s speakers about the future of genome editing

Can you explain how CRISPR-Cas technology works in layman’s terms and how it’s different from previous genome editing tools?

CRISPR-Cas9 is basically a way to go inside of cells and precisely change DNA-sequences. We aspire to it being as easy as opening a manuscript in Microsoft Word, picking a few sentences and make really precise changes. We’re not quite that sophisticated yet, but that’s the idea. You could look at the DNA inside a cell as a living, breathing code that we can make precise changes to. The way it actually works is: You use the system to cut the DNA at the site you want to change. Then, as most cells really don’t like having their DNA broken, they try very hard to fix it. And the different ways that they can fix it result in all the different types of edits and changes that are possible. And so, what makes CRISPR really special – compared to everything before – is how easy it is to use. There have been other types of gene editing technologies that were known for 10-15 years, but they were really hard to make and use. You basically had to have a PhD in gene editing to do gene editing. This has changed with CRISPR; People like to say that CRISPR has democratized gene editing. And that’s because the system is actually really simple. It’s a protein called Cas9. That’s what actually does the cutting, but on its own, it’s totally non-functional. It needs another little molecule called an RNA to actually pair with it and drag it to the right place in the DNA; so a researcher can just spell out the sequence that they want to target, make that little piece of RNA – maybe you order it from a company and it shows up 2 days later – and you can run your experiment. This is not for every man, woman and child to use, but it’s made it much easier across the life sciences. You don’t have to be a deep expert in gene editing just to figure out how to do it.

You co-founded Caribou Biosciences. So what do you focus on at Caribou Sciences?

We’re mainly focused on the technology itself, really trying to make it into something that’s robust and industrializeable. We carve up the world into four major markets: therapeutics, agriculture, industrial biotech and basic research; and thus far, we’ve used a pretty flexible business model to create value across these different areas. We partner with companies that are already big in these markets and help them use gene editing whenever they develop new products. We also look at the opportunity to actually spin out new start-up companies to focus on certain areas. And we’ve done that once so far: with a human therapeutics company in the U.S. We’re also starting to look into products that we can develop ourselves as well.

Besides the widely discussed medical potential, what are other possible applications of CRISPR-Cas technology?

Other than health, I think I’m most interested in food and how gene editing could really transform it. As we think about our growing world population, there are a lot of mouths to feed in the next couple of decades and our systems aren’t really set up to scale in terms of production. I think one of the real challenges is – especially with climate change – crops that used to be very good in certain areas but are now very poor, with traditional breeding is actually incredibly slow. To get a new product, it can take 7 to 10 plus years. And so to try to breed new plants that are more drought-resistant or otherwise better prepared to survive climate change; we’re looking at a really long timeline. And so, gene editing has the ability to get to that same end point of drought resistant, disease tolerant crops – but faster. So we see tremendous opportunity there. And not only in just the major grow crops, which is really where biotech has been before – mainly corn, soy and a few others – but much more broadly than that. There’s a lot of untapped potential in terms of how you can use the understanding of genetics in plant breeding. One goofy example is: A lot of vegetables have been bred selectively for years to fit ideally in extremely large trucks so they can get carted around the country, flown around the world and then sit on a grocery store shelf for a while. Tomatoes have been selected for being really red and beautiful; they don’t taste like anything though. It turns out the genes that control flavor have been basically lost in this process, so it would be great to use gene editing to actually recover and make all tomatoes like heirloom tomatoes that actually taste good but are still hardy enough for large-scale commercial production.

What is your opinion on the social and ethical implications of editing the human genome? Especially germline editing, which Chinese scientists have tried already?

They’ve done a little bit of research. There are actually a few European labs that have done it as well. For us, it’s a hard line that we are not going to cross with the company. We’re not going to edit human embryos. It’s just a clear ethical line that we don’t feel is justified to cross. And I would say part of it is: for a small company, there are only so many things we can work on. There are so many pressing needs, both in terms of human health and food that there’s no reason we shouldn’t be putting all of our efforts towards these real problems right now. But we also think it’s really important to have a rigorous global discussion around these questions. And so we participate in a variety of meetings and conferences to learn from others and to share our thoughts and what we think is ok and not ok. It’s definitely an evolving international debate right now.

So where do you personally draw the line when it comes to the use of CRISPR?

One of the other controversial topics is called gene drive. It’s actually not necessarily CRISPR-technology, but you can use CRISPR to make a gene drive. It’s basically the idea that you can create a gene that is selfish and actually makes the other copy of the gene in that cell turn into its version and then propagates through a population very quickly. There are a few groups that are looking at ways to try to use this to modify mosquitoes and get rid of malaria or other vector-born diseases. On the one hand that sounds incredibly exciting, on the other I think that we should approach this with caution as you’re talking about releasing thousands of these engineered organisms into the environment; and it might be very challenging to control if something goes badly. In the laboratory, you’ve got everything under lock and key and you can change things very quickly. Once you release them into the wild, you can’t. So it’s not something that we are working on as an organization right now and it’s something where I personally would urge a lot of caution from regulatory bodies and other places before someone actually releases these bugs.

What kind of regulations should there be to actually keep CRISPR from becoming the sci-fi nightmare some critics make it out to be?

I think that in the very near term, even if someone really wanted to “CRISPR” a better, smarter or taller human it would be very challenging. Our genetics are incredibly complicated, and there’s still a lot we don’t understand about what makes me look like me and you look like you. To change those in a directed way, we still don’t really know that as a field. So there’s probably a lot of basic learning that’s going to have to happen over years for that to be a relevant tool. I think that’s what we are already seeing – in some countries there’s very clear regulation that completely prevents scientists from editing human embryos for any purpose, and in other places like the United States, some of the funding agencies that are getting involved explicitly say they will not provide new funds for that type of research. So we’re seeing that not only governments but also funding bodies and other organizations try to influence what’s allowed and what’s not.

Considering the state of CRISPR, How long will it actually take to be widely used to treat specific diseases?

Developing a new drug takes a long time. It’s obviously a highly regulated process. You have to approve safety efficacy. That said, the first handful of trials is basically kicking off right now: The first clinical trial started last year in China. There are some that are going to be starting here in Europe and in the United States in the next 2-3 years. So I’d say in the next 5-10 years, we might see the first few products ready for approval – and that will only be the tip of the iceberg as there will be many other products at this point.

Before you came to Pioneers, what didn’t you know about Vienna and the biotech scene here specifically?

I would say in general that I don’t feel very educated on the European biotech scene at large. There’s a little bit of a closer tie between the London and San Francisco biotech scene and I’m not really sure how that started, but I have a little more visibility into what’s happening there – it’s certainly very impressive to see how much the U.K. government has invested directly in synthetic biology, one of it’s grade-a technologies. So I’m excited to be here and learn about what’s happening in many of the other European countries right now and meet so many amazing entrepreneurs.



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