image of Steve McClellan

Seeking inspiration to unlock the mysteries of cancer
using CRISPR-Cas9

“A failed experiment will at some point be followed by a breakthrough.”

Meet Olivier Humbert, PhD

When asked what drives him to keep seeking answers to the challenges he faces in the lab, cancer researcher Olivier Humbert cites the “refreshing and inspiring vision and quest for life” of his two children. No wonder it filled him with pride last year when his daughter gave him a Father’s Day card that read, “I want to be a scientist because they do cool things.”

In fact, Humbert and his colleagues are doing some of the coolest, most cutting-edge research in science today. They are working to improve the efficacy and safety of CRISPR-Cas9 gene editing in blood stem cells. Derived from the components of a simple bacterial immune system, the revolutionary CRISPR-Cas9 system enables highly targeted gene editing of a wide variety of cell types.

Humbert explains that this new tool allows his team “to modify DNA in cells in virtually any way we want, so we’re trying to literally correct mutations in the DNA of patients.” The goal of his research is straightforward: take DNA from a patient’s cells, treat the DNA in the lab to delete the underlying mutation, and then transplant the modified cells back into the patient. “The system works like a molecular scissors, allowing us to cut out mutations,” he says. “We’re working with Thermo Fisher Scientific, which has really optimized the CRISPR-Cas9 tool.”

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“[Spending] time outside surrounded by nature…triggered my curiosity about how living things work.”

One of Humbert’s research projects focuses on applying this new technology to cancer research, where CRISPR-Cas9 may be used to improve the clinical outcome of cancer treatment. “Some chemotherapies used to eradicate cancer cells also target normal cells, resulting in toxicity. We have used CRISPR-Cas9 as a strategy to protect normal cells from the chemotherapy, thus drastically reducing the side effects of treatment,” Humbert explains. If successful, this approach will help patients to better tolerate these treatments and improve their overall quality of life.

While CRISPR-Cas9 gene editing already shows remarkable promise, it is still a new technology that requires perseverance. Humbert views such challenges as part of the inevitable trial and error of scientific research. “A failed experiment will at some point be followed by a breakthrough,” he says. “You have to keep reminding yourself that discoveries are built upon failures; be patient and work methodologically when designing your experiments.”

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“Whenever possible, share your ideas with your peers, who will likely offer valuable advice.”

Part of the methodological process that helps Humbert handle challenges is collaboration. He offers an example: “One time I was testing new editing enzymes that, along with some guide RNAs, had to be delivered to target cells for gene editing. The enzymes weren’t giving any detectable activity for reasons I didn’t understand. Instead of trying the same experiment over and over, I chose to walk away and talk to some colleagues who were using a similar approach. I also joined some online forums for advice. I eventually found out that I needed to chemically modify the guide RNA to protect it from degradation by the cell.”

Humbert draws on this experience to advise other scientists on how to approach their own failures in the lab: “Whenever possible—especially before you embark on a new experiment— share your ideas with your peers, who will likely offer valuable advice.”

His other solution to dealing with frustrations is sometimes simply to take a break, to take a step back and think about what could have gone wrong—and in his case, a break might turn into a bicycle ride. “When time permits, a long ride helps me reboot and clear my mind,” he explains. A bike ride may at first seem too removed from lab experimentation to function as a source of scientific problem-solving, but consider Dr. Humbert’s initial childhood interest in science: “Growing up, I spent a lot of time outside surrounded by nature,” he says. “That really triggered my curiosity about how living things work and how they’re put together—so that’s what brought me to the field of science in the first place.”

The sense of wonder Humbert discovered as a child exploring the natural world resonates with the sense of renewal he experiences now on epic bike journeys; it informs his dedication to solving important challenges in the lab; and it clearly has helped instill a love of science in his own children. If Humbert’s pioneering work with CRISPR-Cas9 leads to more effective ways to treat cancer, who knows? Perhaps his children will someday follow in his tracks and be part of a generation of scientists that makes cancer a thing of the past.

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