"Ideally, this is a one-time treatment"

As the Chief Executive Officer of Caribou Biosciences, Rachel Haurwitz dedicates most of her days to running one of the leading companies in the US bioscience sector. But the 32-year-old businesswoman never completely abandoned her white coat. Haurwitz uses the expertise she gathered during her time in the lab to ex- plain to investors and the general public the implications in health, agriculture and industry of six letters: CRISPR, a groundbreaking gene editing tool that promises to revolutionise its field.

CRISPR stands for Clustered Regularly Interspaced Short Palindromic Repeats. Caribou is working to develop commercial applications for the technique. The reason the six letters are creating such a buzz in the scientific community is that they al- low an enzyme (called Cas9) to act as a pair of scissors and cut our genetic code in specific places. The “scissors” could target a malfunctioning gene that causes a disease and eliminate it, for example. One team of researchers is trying to erase a mutation that causes certain types of blindness. Others are working on applications for treating cancer. "CRISPR democratised gene editing," Haurwitz says.

How do CRISPR modifications differ from other genetic modification methods?

There is a key difference between organ- isms modified with CRISPR and other genetically modified organisms, or GMOs. Most of the older methods take a piece of DNA from one organism and put it into another. The beauty of CRISPR gene editing is that you are not trying to take DNA from one place and put it elsewhere. You are working just within the genome of that organism already.

Also: Other gene editing technologies have been around for 15 years at this point, but still require specialists to work with them. The reagents are very expensive and very hard to use, so it often took a PhD in gene editing to do it. CRISPR kind of democratised the process. We have seen thousands of labs around the world picking it up as a tool they use in their standard biology research every day.

“CRISPR democratised gene editing.“

How could CRISPR be used for therapy?

The idea of actually being able to correct a genetic disease is very compelling to people. Right now, researchers are largely working on diseases originated by a single mutation in one gene, which causes a particular illness. There is a lot of work being done with sickle cells disease (a red blood cell disorder). A number of research groups are also trying to use gene editing to treat cancer, helping the patient’s immune system fight its own cancer.

When will health applications be a reality?

On the therapeutic side we are in the early stages of research. Most of the companies and the academic groups who would like to develop new drugs are doing research in the lab to ensure CRISPR is going to be safe, efficacious and successful. We are going to see years and years of clinical trials before there are approved products on the market: It’s going to be five, seven, maybe ten years until the first product gets approved. In the food industry, on the other hand, it can move quite a bit faster. Our collaborator DuPont announced a year ago that they developed their first type of corn based on CRISPR gene editing. They said at the time that they planned to commercially launch it in five years. So the clock is ticking.

“It’s going to be five, seven, maybe ten years until the first product gets approved.“
Technology Outlook panel at the 47th St. Gallen Symposium

Have trials been done in humans to assess CRISPR's safety and possible side effects?

A trial with humans kicked off in China last year, though there is no public information on how it is going. No one has reported significant events in the animal trials that have been done so far, so that is a good sign. CRISPR is the newest kid on the block for gene editing, and it is an early step in a very long process of drug development. Some of the older gene editing technologies have been tested in humans already and have had some very exciting clinical outcomes. Two patients were treated for their cancer in the United Kingdom in the past couple of years, and several other patients went through treatment for HIV. To the best of my knowledge, there were no significant adverse events due to gene editing.

There is a debate regarding the ethics of gene editing and whether we should use DNA manipulation to edit – for example – human embryos. What’s your opinion?

Our focus with CRISPR is curing diseases. Our company has drawn a pretty hard line, and said we will not edit human embryos. And I think its true for most of the companies – if not all of them – who are working in this area. There are so many severe cases of unmet medical need, so many diseases we have no way to treat right now. Everyone is totally focused on that as an application.

“Our company has drawn a pretty hard line, and said we will not edit human embryos.“

How much could a CRISPR treatment cost in the future?

We are very far away from this being a commercial product and no one is talking about drug pricing yet. It will probably be on the more expensive side rather than on the less expensive side. There is, however, a general health economic benefit: Ideally, this is a one-time treatment. You would, hopefully, be curing a disease, something a patient would otherwise be on medicine for her life or decades.

The University of California (with whom Caribou is associated) has appealed a US Patent Trial and Appeal Board decision that granted the patent on CRISPR technology to an institute at the Massachusetts Institute of Technology. How does this legal dispute impact Caribou’s work?

It does not impact day-to-day operations for us; inside the company we are pretty much head-down working on the science and technology and trying to meet our company’s goals. Certainly it impacts how investors look at the space. But in general, investors have realised they have seen this before and that sometimes intellectual property gets very complicated in biotech. They seem to understand that as long as you are holding on to something valuable you are going to find a solution to what you need in the long term. We are holding on to some pretty valuable licences, for a variety of universities and companies, and investors have been willing to make a bet on us, just as they have been willing to make a bet on some of the other companies.

“Investors are willing to make a bet on us.“
TED-talk by Rachel Haurwitz

Is Europe more resistant to genetically modified organisms and gene editing than the United States?

Looking at the regulatory infrastructure as well as general consumer feeling, the United States is more receptive to the older genetic modified technologies than Europe has been. The potential of our technologies is irrelevant if consumers are not interested in the products. So we are looking at conversations and partnerships with companies in Europe so we can help to bridge this divide. We are in early-stage conversations with a handful of food companies to understand what their consumers are looking for, and how our technology can play a role in that work.

What’s the role a scientist should play when very well-researched evidence, like the science behind global warming, is challenged by public authorities?

I am used to being in communities where people respect information coming out of scientists. Clearly, that is not true across all corners of the United States at this point. Along with other colleagues from Caribou, I participated in the March for Science in April. I certainly had not marched for science before. I had not even considered the concept of doing it. I am still very much figuring out how to have a voice in the dialogue that is happening right now, or in some cases the lack of dialogue.

“I certainly had not marched for science before. I had not even considered the concept of doing it.“

Is there miscommunication between scientists and the general public?

Scientists have a bad habit of just believing they have done all the hard work, that everybody should just trust them and that they do not have to explain anything. That is wrong. There are a lot of factors that influence any consumer’s decisions when it comes to food and medicine. We need to do a better job of talking about the science and the research we do and what they mean, rather than just dictating to the community what they should be doing.

You are a scientist who decided to become a CEO. How was the transition from the lab to the boardroom?

I wanted to be more on the business side of science because I like the idea of building the company’s strategy. I spent many years learning how to design and execute experiments, to move clear liquids from one tube to another. When I became a CEO, I found myself in the position of trying to hire people, raise money and build a company. I had a lot to learn.

“We need to do a better job of talking about the science and the research we do.“