Reengineering Life is a series from Future Human about the astonishing ways genetic technology is changing humanity and the world around us.
When the Royal Swedish Academy of Sciences announced on October 7 that she had won the 2020 Nobel Prize in chemistry, Jennifer Doudna was still fast asleep at home in California. It was just before 3 a.m. when a phone call woke her up. It was a reporter from Nature, asking if she could comment on the award.
“Well, who won it?” Doudna asked.
Doudna, PhD, of the University of California, Berkeley, and Emmanuelle Charpentier, PhD, of the Max Planck Institute in Germany, share the award for the discovery of the gene-editing technology CRISPR. The two biochemists began collaborating in 2011 and just a year later published a groundbreaking paper on CRISPR, which has revolutionized our ability to edit genes.
Short for clustered regularly interspaced short palindromic repeats, CRISPR is actually a naturally occurring bacterial immune system. When viruses attack bacteria, bacteria in turn grab snippets of genetic material from their viral invaders and incorporate these bits into their own DNA. This helps bacteria recognize viruses later on and thwart future invaders. Bacteria do this by producing an RNA molecule that acts as a guide, which cuts up the viral genome.
Doudna and Charpentier realized they could harness this cutting ability to edit genes in just about any living thing. In their 2012 paper, they described how this bacterial system could be used as “DNA scissors,” and the gene-editing technology CRISPR was born.
Declared as one of the most important discoveries of the 21st century, CRISPR is faster, cheaper, and more accurate than previous gene-editing systems and has since become ubiquitous in labs around the world. Scientists are using it in an attempt to treat serious genetic diseases, restore eyesight in people with a type of inherited blindness, engineer crops that are more resilient to disease and climate change, and eliminate disease-carrying pests like mosquitoes and mice. And researchers are already working on newer and improved versions of CRISPR that are even more precise.
The power to edit genes also opens up many ways for CRISPR to be abused. In 2018, Chinese scientist He Jiankui was widely condemned after revealing that he used CRISPR to make the world’s first known gene-edited babies. He is now serving a prison sentence, but the revelation has raised fears that CRISPR could lead to genetically enhanced “designer babies.”
After the Nobel announcement last week, I talked with Doudna about what’s next for CRISPR, the field of gene editing, and her own scientific work.
This interview has been lightly edited for grammar and clarity.
Future Human: First off, congratulations. What an incredible honor. How surprised were you to find out that you had won a Nobel prize?
Jennifer Doudna: Oh, total shock! I mean really. Coming out of a deep sleep and getting news like that — I couldn’t believe it. I said to the reporter who had called me, “I can’t talk to you right now. I have to call somebody and find out if this is official.”
We’re seeing a handful of clinical trials for CRISPR-based treatments get underway right now. What diseases do you see CRISPR being most promising for in the near future?
Certainly, diseases that are caused by single genes or genetic mutations. A great example, and we’ve already seen early results from one trial, is for sickle cell disease. But I think going forward, we’ll see opportunities to use CRISPR for other kinds of blood disorders, genetic diseases of the eye, and then, maybe in the longer term, cystic fibrosis and muscular dystrophy, which are also genetic diseases.
What do you think is going to be the biggest obstacle to getting these treatments to patients?
It’s probably delivery. One of the reasons why blood disorders have been some of the early targets of CRISPR is that the genome editing that’s used to correct those mutations can be done in cells that are taken out of a patient. The editing is done in the laboratory before reintroducing them versus a disease like cystic fibrosis or muscular dystrophy, where the editing would actually need to be done inside the body, in the right cells, to have a clinical benefit. That’s a hard challenge right now.
Your company, Mammoth Biosciences, is working on a rapid CRISPR-based test for Covid-19. What role do you think CRISPR diagnostic tests will play in the future?
There are several efforts underway to develop CRISPR diagnostics in comparable companies and academic labs. I think we’re going to see everything from high-throughput laboratory tests that require robotic equipment and experts to point-of-care tests that can be run in a research lab, a doctor’s office, or an emergency room. Down the road, we hope to have an at-home test that would work like a pregnancy test for Covid. What’s exciting with the CRISPR technology is that it’s potentially a faster and more direct way to detect the presence of the virus and also relies on a different supply chain than what’s necessary for the PCR (polymerase chain reaction) test.
What’s the status of your company’s Covid-19 test?
Mammoth Biosciences is planning on rolling out its test to a few partner labs for initial beta testing in November. Depending on how those experiments go and how those results turn out, we’ll expand to other labs after that. We want to see how it compares to the PCR test.
You recently just launched another CRISPR company, Scribe Therapeutics. What’s the focus of this new startup?
This is the thing about CRISPR: There’s so many different ways that it can be deployed. For clinical applications, the reason we’re seeing a lot of early efforts focused on blood disorders like sickle cell disease and, to some extent, diseases of the eye or even the liver is because those tissues are easier to introduce gene-editing molecules into. With Scribe Therapeutics, we’re looking at opportunities to use CRISPR for neurodegenerative diseases. For those disorders, the technology obviously needs to be very robust and very safe. It also has to get into brain cells and neural tissue where it can have an impact. We want to make sure that the editing tools are the best they can be and then figure out the best way to introduce them into the brain. That’s really the focus of the company.
What do you think is going to be the next big CRISPR advance?
That’s always a hard question. We’ve so much going on in the field. I think one interesting possibility is that we’ll see CRISPR being used not to edit genomes, or at least not to make permanent changes to genomes, but instead to regulate them, to control levels of human proteins that are produced from different genes. This is a newer way of using the CRISPR technology. I think it has a lot of potential to allow control of cells that doesn’t require actual permanent chemical changes being made to the DNA.
After the birth of the CRISPR babies in China in 2018, there’s been a lot of talk around the idea of germline or heritable genome editing. Do you think that should be off-limits to scientists right now?
I don’t think it needs to be completely off-limits. I was pretty pleased with the recent report that came out from the National Academies and the U.K. Royal Society that recommends a kind of a measured approach to developing the technology for use in the human germline. They’re encouraging research to understand how the technology works in embryos. First, the technology will need to be proven safe. Secondly, any clinical use [to establish a pregnancy] would need to be restricted to cases of serious genetic disease where there are few or no other options to treat the disease. I think those are both pretty high bars. Those situations are pretty rare. I personally think there are more viable strategies today, like embryo screening and selection in an IVF (in vitro fertilization) clinic, rather than using genome editing.
The report you mentioned also calls for “extensive societal dialogue” before countries decide to permit the use of heritable human genome editing. You’ve talked in the past about public engagement around CRISPR. How do we educate and engage the public about CRISPR?
Yeah, that’s really critical. I think the media has an important role to play in terms of large-scale education. Interactive media, like videos and documentaries, can also help. The challenge of course is making sure that the science is right.
How do we make sure that the public’s voice is heard in regard to how CRISPR is used?
It’s a really important question. It’s a challenge because, on one hand, I think it’s critical to have more public engagement in important decisions like this about how technology is used. On the other hand, that requires a level of understanding about the technology that the average person might not have or maybe doesn’t want to have. So, I think it’s important to have different formats and forums for encouraging discussion. We’ve already seen this with CRISPR in some way. On the one hand, there are highly technical meetings that include discussion of ethical and societal issues from a pretty detailed technical standpoint. But there are also increasingly conferences and events that don’t get into the weeds of the science per se, but they spend a lot more effort thinking through CRISPR’s implications and its different uses. Inviting people who are nonspecialists to engage in those meetings has been really effective.
Other than medicine, where else do you think CRISPR could be transformative?
Agriculture is the other area where it’s going to be impactful. We’re already seeing a lot of use of CRISPR in making plants that have genetic changes that can enable things like better crop yield, resistance to drought, higher levels of nutritional value, things like that. I think that’s really exciting, and there’s clearly a lot more to be done there. That’s likely to be the area where we’ll see a broader impact in the near term.
Given CRISPR’s potential for misuse, how do you think it should be regulated?
Fortunately, I think there’s quite a good regulatory framework in the United States and in most places that have major research operations that can serve to regulate the use of CRISPR. That really goes back to the 1970s [at the Asilomar Conference on Recombinant DNA], when voluntary guidelines were put in place for using some of these early tools of molecular biology, like molecular cloning. That being said, as we discussed, there are certain applications of CRISPR like in human embryos, where I think there needs to be special attention.
Who are the CRISPR scientists you really admire?
Many. It’s become a huge field. It used to be tiny, and now it’s vast. One is Luciano Marraffini. He’s a scientist at Rockefeller University. He works on the fundamentals of CRISPR biology and understanding how it works in bacteria as an immune system. Jill Banfield at Berkeley is continuing to do work on bacteria that are not cultured in the lab but are growing in various environmental niches. She was one of the very early discoverers of CRISPR systems and bacteria, and she continues to find a lot of new ones. In plant biology, I really like the work of Pamela Ronald at the University of California, Davis. She’s doing work primarily in rice, where they are using CRISPR to make modifications to the rice genome that I think are going to be really important as rice farmers face the challenges of climate change. On the biomedical side, I’m really excited about the work of Charles Gersbach at Duke University.
What’s next for you?
CRISPR is going to keep us busy for a while. There are still a lot of fundamental questions about how these pathways operate that I really like to try to answer. Jill Banfield is a close collaborator of ours, and she continues to supply us with many, many new CRISPR pathways that we’re excited to investigate. We’re also really interested in genome editing in natural microbial communities. I think there’s a really interesting opportunity to be able to manipulate certain microbes. I think those are areas where I’ll be focusing my efforts in the near term.