Decades from now, when schoolchildren learn the story of the gene-editing revolution and how it changed human history, from medicine to biology to agriculture, they’ll probably hear a story like this: A woman named Jennifer Doudna grew up in Hilo, Hawaii, then earned a Ph.D. at Harvard under a biochemist who had won a Nobel Prize. She studied the genetic blueprints of cells—DNA and RNA—for years. And then one night she was standing in her kitchen, making dinner for her family, when the proverbial apple fell on her head.
Doudna had been thinking about the bacterial immune system and how it protected bacteria from viruses by clipping out little pieces of viral DNA to save and compare in case a similar virus attacked again. She started laughing. She saw how the bacteria’s cutting tool could be applied to chop out and replace any sequence of DNA, in any organism, in real time. Doudna’s son asked her why she was laughing, and she tried to explain. She knew this was going to be huge.
And it was. Doudna, along with her French colleague Emmanuelle Charpentier, had discovered CRISPR/Cas-9, short for Clustered Regularly Interspaced Short Palindromic Repeats (and the associated enzyme, Cas-9). It’s the simplest, most accurate gene-editing tool ever discovered, a sort of molecular scissors that in the near future could edit out genetic mistakes in diseases like cancer, Huntington’s disease and sickle cell anemia in living humans, ending whole categories of disease in a fell swoop. It could create sustainable biofuels, develop more robust crops, and protect forests and the oceans. And in the wrong hands, somewhere in the distant future, it could be used to develop superhumans, with superintelligence and superstrength—which stokes fears of a eugenics revival—not to mention a list of unintended consequences for humanity and the environment we can’t even begin to comprehend.That’s how powerful CRISPR is. It could change everything.
Since CRISPR went public, Doudna is suddenly, deservedly, a very big deal. She has been asked to advise startups and science-fiction movies. With Charpentier, she won the Breakthrough Prize, which has been called the Oscar for scientists, and received a statuette and a cool $3 million from Cameron Diaz and former Twitter CEO Dick Costolo. We asked the 54-year-old professor of biochemistry and molecular biology at Berkeley about her hopes and fears for the technology, and what comes next for a scientist who has already gotten her name in the history books.
What do you think is going to be the first application of CRISPR in human medicine?
The technology has already accelerated the pace of medical discovery and taken drug development to a higher level. For example, in cancer, scientists are attempting to harness CRISPR to edit a patient’s T-cells (immune cells) arming them with the capabilities to target a particular type of tumor. Within the next 10 years we could see CRISPR-based therapies for blood disorders such as sickle cell disease, various eye diseases, as well as genetic surgeries to cure diseases.
The first trials of CRISPR to cure cancer and inherited disorders in humans are reportedly starting this year. How do you feel about that?
I hope we see positive outcomes from the clinical trials. This step is likely to be part of a complicated journey, though, since we are still building out our understand- ing of the human genome, diseases such as cancer, and the capabilities of CRISPR.
Not long after the discovery of CRISPR, you and other scientists called for a temporary moratorium on research in human embryos until we better understood what we were doing. Scientists in other countries (notably China, Sweden and the U.K.) have already begun using CRISPR to edit genes in human embryos to repair genetic diseases and study infertility and miscarriage. Do you think we are being careful enough with the technology?
My position on the profound question of human germline editing has evolved. Given our increased understanding of how CRISPR can alleviate human suffering, the discussion now is whether we have a duty to explore germline editing. [Germline editing refers specifically to altering the genes that are passed on to children, which has for many years been considered ethically dangerous.] For families with inheritable genetic diseases, the benefits might outweigh the risks. Editing the germline could literally save their lives.
To be clear, we should not expect to see “CRISPR babies” anytime soon. Some countries have approved the use of CRISPR for research involving the editing of human embryos, but not for clinical use. In the U.S., the National Academies of Science and Medicine has called for a voluntary restriction on clinical use of genome editing in viable embryos to provide time for scientific study and societal discussion around this type of application. For now, U.S. scientists and clinicians are focused on therapeutic applications that involve somatic cells, which are adult cells that cannot transmit genetic changes to future generations.
You’ve said that early on, you had a nightmare about Hitler in a pig mask asking about your research. Does that ever happen anymore?
No, but I am concerned that it could be used to enact terrible ideas of eugenics. The scientific community frequently engages with regulators, policy makers, and public and private organizations to prevent this from happening. Also, organizations like the Innovative Genomics Institute focus on using CRISPR to make the world a better place—not a scarier one.
What do you see as the worst-case scenario for a future in which CRISPR plays a large part?
Genetically encoding inequality could divide and irreparably damage our society. But currently, we do not know how complex traits like intelligence and appearance are influenced by genetics, as opposed to environmental factors, and the global research effort is focused on treating disease rather than engineering new traits.
What about a best-case scenario?
If we’re able to harness and correctly apply the full potential of CRISPR, we can positively impact the human condition. CRISPR-Cas promises to lead to new genetic surgeries to cure disease, novel ways to care for the environment, and the ability to produce tasty, nutritious food for a growing global population challenged by climate change.
What do you think about people like Josiah Zayner, the Silicon Valley biohacker who injected himself with a DIY CRISPR vaccine to make his muscles bigger?
I always encourage curious scientists to explore the boundaries of innovation and technology, but this comes with a caveat: safety. Biohackers are doing these experiments at their own risk. I hope that these risky decisions do not negatively influence the public and also damage the reputation of CRISPR. All of us, including influential voices in the DIY biohacking community, must act responsibly and promote realistic and accurate science.
You are now a role model to a lot of young scientists. What would you say to someone who finds your work inspiring and wants to make it his or her career?
Follow your curiosity! When you see an interesting scientific opportunity, pursue it: You never know where it may lead. I’ve been interested in science since I was a young student in Hawaii, and it has been such a privilege to participate in this exciting journey.
Do you have a scientific role model?
There are many scientists I admire, both historical figures and people I know personally. A historical figure who comes to mind is Rosalind Franklin, for her pioneering work that contributed to our understanding of the structure of DNA. I would also say Jack Szostak, my supervising professor while I was getting my Ph.D., an excellent geneticist and the mentor who first guided me into the field of RNA biology.
You’ve done about as well as a scientist can do in your chosen field, but if you could work in any other scientific field, what would it be?
I would’ve enjoyed being a botanist. I appreciate spending time outdoors, pondering the great diversity of plants that survive, thrive and evolve even in harsh conditions.
If CRISPR could be used to bring an extinct species back to life, which would you choose?
There’s talk about resurrecting the woolly mammoth, but I would choose a native Hawaiian species, such as the Hawaiʻi ʻakialoa bird. It had a distinctive curved beak and went extinct due to habitat loss.
You’ve said before that you’re not the kind of scientist to focus on one discovery for the rest of your career. What’s next for you?
There’s more work to be done. I plan on further understanding and developing CRISPR so we can apply it more effectively and truly help the most number of people with the greatest need. Of course, my research could open new avenues, so I expect to be surprised along the way.