In the CRISPR pipeline – In conversation with Rachel Haurwitz, CEO Caribou Biosciences

In June I met Rachel Haurwitz at the Pioneers Festival in Vienna and we talked about the future of gene-editing and the CRISPR pipeline.

Caribou Biosciences is a biotechnology startup that develops cellular engineering and analysis solutions based on CRISPR-Cas technology. It was founded by members of the Doudna Laboratory at the University of California. Rachel is Caribou´s CEO. The Fortune Magazine named her to the “40 Under 40” list of the most influential young people in business.

Rachel Haurwitz, CEO Caribou Biosciences

WUNDERDING: What are the major challenges you are facing with Caribou Biosciences and CRISPR?
Rachel Haurwitz:
I think the fundamental challenge is that our global population is exploding. Pair that growth with climate change and the ability to just feed every human on the planet becomes incredibly challenging. And then you have to look at the traditional ways that new crops are generated, to maybe make them more resistant to drought or particular diseases or the way that new types of pigs are made to be healthier. It takes a very, very, very long time. People love to talk about how long it takes to develop a new drug; it turns out, it takes even longer to develop a new crop. And so, gene editing has the ability to dramatically speed up product development across all of agriculture. We’re already working with some of the biggest companies in this space to help them use this technology in corn breeding, in pig breeding, and in various other applications.

WUNDERDING: This is a big promise and it might be possible to keep this promise with the help of CRISPR. The genetically modified crops which currently are on the market weren’t able to do so? Is this a strain for the application of the CRISPR technology?
Rachel Haurwitz:
 Where I am cautious is that the technology is irrelevant if we can’t gain consumer acceptance for the use of gene editing. And if I think if we look back to the past 20 years or so, the field hasn’t done itself any favours. Big companies have not done a good job of explaining what it was that they were working with. It sounds scary and therefore it became scary. And there has been a very strong negative reaction from consumers. Obviously, that varies in, say, Europe vs. the US but by and large, consumers aren’t warm, fuzzy, friendly about GMO foods. Even though the science says it’s actually quite safe. And so, I think we can’t be arrogant and naïve and just believe that science will win the day. I think we have to be transparent. We have to talk to consumers about where food comes from. And we need to talk about how we want to use this technology going forward. I also I think consumers have a rjght to know more about where their food comes from today.

WUNDERDING: Many consumers associate GM crops with terms such as unnatural and dangerous. What is the reason for this?
Rachel Haurwitz:
 I think many consumers have a very romantic feeling that the foods, especially vegetables and fruits, that we see on out table are natural, healthy plants. Really these plants are the product of human intervention for centuries. Nothing that we eat today looks much at all like its “natural” ancestor plants. I think a very important part of the conversation is putting CRISPR in the context of how humans have been changing food in order to feed ourselves for a very long time. I also think there is an important distinction that because of the way older technologies work and because of how they`re regulated, they’ve really only ever been used in corn, soy, and a couple of other major crops. Really no other plants have been touched by biotechnology before. So there is a lot of genetic knowledge we can take advantage of in cucumbers or tomatoes or other crops that haven’t been worked on in this way before. Something we like to talk about a lot inside the company as an example of this is tomatoes. Commercial tomato breeding has selected for these beautifully shaped tomatoes that are nice bright red but they don’t taste like tomatoes anymore. It turns out, in the breeding process, by selecting for the bright red, we lost the variant of the gene that helped give the tomatoes flavour. And so heirloom tomatoes that look quite ugly and awful actually taste really good. So you can think about applying gene editing to try to quickly combine the two and to have a tomato that’s robust (it’s going to stand up well to trucking and sitting in a grocery store) but still actually tastes like a tomato.

WUNDERDING: A gene-edited CRISPR mushroom from Yinong Yang, a plant pathologist at Pennsylvania State University, got a lot of attention because the The US Department of Agriculture (USDA) will not regulate this mushroom.
Could you tell us a little bit more about the CRISPR pipeline?
Rachel Haurwitz: 
I would actually say, even though we had nothing to do with the mushroom, I am pretty excited about the mushroom. I am certainly guilty of all too often buying too many groceries in the grocery store and by the time I try to use the last ones, they’re already going bad and I have to throw them away. And there is some ridiculous fraction of all produce that goes straight from production into the trash can and so if we can reduce the amount of food waste, that certainly helps in terms of the overall global problem. What I can talk about is one of the projects we’re working on in pigs now. We’re in a collaboration with a British company called Genus plc who is one of the leading companies in livestock genetics. They’re breeding pigs that are resistant to a particular virus. The virus makes pigs sickly and it means they can’t go into the food stream and it also means that they can’t reproduce anymore. There’s no functional vaccine and treatments are very expensive and don’t really work. It’s bad for animal health and well-being; it’s bad for farmers because they lose hundreds of millions of dollars every year when their animals get sick. We’re working with Genus to gene edit pigs to make them resistant to this virus and it’s a really exciting project. Genus has already shown a proof of concept experiment where they have edited piglets running around that appear to be healthy and are resistant to the virus.

Rachel Haurwitz on stage at Pioneers 2017


WUNDERDING: And are there any plant products in your CRISPR pipeline?
Rachel Haurwitz:
I can’t talk about much on the plant front. What I can say is that our collaborators at DuPont Pioneer publically announced, probably more than a year ago, the first crop that they had generated using CRISPR. It’s a type of corn called waxy corn. It’s not the sexiest product but it’s very practical from an industrial perspective. If you think about the sticky stuff in the inside of an envelope, part of what makes it sticky and the right material is actually processing waxy corn. Waxy corn has been around for a very long time. A particular trait that makes it waxy was in the background of a type of corn that has a very low yield, so very relatively few plants per acre. That actually makes it rather expensive to grow enough corn for all these industrial products. What DuPont Pioneer was able to do was to recreate the waxy trait in the background of one of their high yielding corns. From an industrial perspective it’s something they’re very excited about and it looks like something they plan to commercially launch in the next few years.

WUNDERDING: In the European Union a decision about CRISPR and the regulatory terms and conditions is supposed to be made in 2018. How do you deal with this uncertainty?
Rachel Haurwitz:
 The regulatory uncertainly builds some additional risk for us as we think about how to invest in developing either new partnerships or products in that area. In the US we have a little more clarity right now around certain ways of using the technology and how they will or won’t be regulated by certain agencies. But you’re right, in Europe there’s a complete lack of clarity in terms of EU-wide regulation. We are seeing that some of the EU states are coming up with their own internal positions that vary across the map in terms of how CRISPR might be regulated. You make a very important distinction, though, that I want to pick up on. Older technologies to make GMOs typically rely on taking a piece of DNA from one species and putting it into another species. And I think that’s caused a lot of confusion, at best, for consumers. The way we, and almost everyone else, are using gene-editing technologies in plants right now is not to move DNA from one species to another. CRISPR efforts are simply working within the genetics of the plants themselves so that you end up with a product that looks exactly the same as what you get through traditional breeding, but probably 3, 5, 7 years faster.

WUNDERDING: But what would be the consequences if CRISPR were to be regulated under the GMO law in the EU?
Rachel Haurwitz:
 My biggest fear is that somehow this gets wrapped in incredibly expensive deregulatory pathways that make it impossible to ever use in tomatoes, melons, or anything else, and we’re not able to tap into this potential as we think about feeding the growing world population. I think that one way to help both consumers and regulators feel comfortable about this is to put the technology in the hands of multiple groups, not just wall it up in one or two companies, but really put it in the hands of a lot of different breeders. They can talk to their stakeholders about what the technology is and what it isn’t and what types of new products it will let them develop. Certainly there are some really big changes right now in the ag sector including the Bayer-Monsanto merger, the Dow-DuPont merger, the acquisition of Syngenta. We’re seeing the top of the food chain condense significantly and I hope that means it helps to push down some of the innovation into smaller companies, and help create a much more vibrant ecosystem of small- and medium-sized companies in the same way as we have in the human health space.
I think some of our investors are pretty excited about the role that they can play in helping some of these entrepreneurs start companies and their new ideas. I think that Caribou can play a role in helping to enable a number of these small- and medium-sized companies to use technologies like ours and probably they’ll access a number of other cutting edge technologies from other places as well to really build the entire ecosystem.

WUNDERDING: You told us about your corporations with the big players. Why it is not more widespread amongst smaller companies or startups?
Rachel Haurwitz:
 When we were getting started and looking for potential partnerships, we were often looking for companies who have a lot of expertise and technology capabilities that we don’t, channel access for the products that they’ll develop, and funding to help us build and grow our company. That filtered down the set of potential partners to a reasonably short list. And now, as we grow as an organisation, it gives us the flexibility to not only work with some of the bigger players who have cash today but also to find mechanisms to work with earlier companies who are willing to take a bet but don’t really have real check books to whip out at this point.
Obviously these product development timelines are long. That said, both our partners Genus and DuPont have publically said that they’d like to launch their first projects within the next 5 years. That actually feels really aggressive and really fast to me and I’d love to see that happen. And I think that will just be the tip of the iceberg as then more and more groups and companies are involved in using this technology. It’s not going to change the food sector overnight. There is a lot of research and development to be done to actually bring this to fruition. But there are a lot of really smart people working on it now and I think that number will only increase in the near future.

Pioneers Festival 2017

CWUNDERDING: There is CRISPR hype at the moment and you might think that CRISPR solved or is ready to solve all kind of problems? How do you deal with such pressure and attention as the CEO of Caribou?
Rachel Haurwitz:
 Forget CRISPR – any tech start-up CEO is terrified at times that the goal, the vision, and the plan are going to fall to pieces. And I think in our world in particular the headlines promise so much that I actually spend a lot of my time explaining, either to lay audiences or technical audiences, “We’re not there yet. It’s hard. Here is all the work we are going to do to get to where we think we can go, but we’re not there yet, and here’s why.” I have tremendous hope and enthusiasm for what I think is possible and try to be clear and fair about where the field is today.

WUNDERDING: Thank you very much Rachel!

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