Why I, as an undergraduate student studying science, enjoyed this conversation
In Illumina’s SPARK 2021 Conference (April 26-27, 2021), Frances Arnold and Jennifer Doudna discuss the joys, challenges, and ethics of gene editing, as well as entrepreneurial advancements in science, being a woman in the field of science, and what the future of science holds. I think conversations like these often lose the background of personal narrative that is essential to developing a thorough understanding of this kind of research. Especially in the world of academia and as an undergraduate student, it can be too easy to develop tunnel vision and solely focus on the science, consequently forgetting the story behind it. Because of this, I sincerely enjoyed the personal touch Doudna incorporated into her journey to winning the Nobel Prize during this interview.
- Frances Arnold, the host of the conversation, is currently a chemical engineer and the Linus Pauling Professor of Chemical Engineering, Bioengineering and Biochemistry at the California Institute of Technology. In 2018, she was co-awarded the Nobel Prize in Chemistry for her work in using directed evolution to engineer enzymes. She currently serves as co-chair of President Biden’s Council of Advisors on Science and Technology and has co-founded several companies.
- Jennifer Doudna is a biochemist who is currently the Li Ka Sing Chancellor’s Chair professor in the Department of Chemistry and the Department of Molecular and Cell Biology at the University of California, Berkeley. In 2020, she was awarded (jointly with Emmanuelle Charpentier) the Nobel Prize in Chemistry for her progressive development of a method for genome editing. In other words, Doudna, in collaboration with Charpentier, found a way to employ the CRISPR-Cas9 system to add, remove, or alter genetic material at specific locations in the human genome.
Why CRISPR is revolutionizing the field of genetics
Frances Arnold and Jennifer Doudna primarily discuss Doudna’s work leading to her becoming a recipient of the Nobel Prize in 2020. CRISPR-Cas9 has revolutionized biomedical research and has immense potential for biological innovations and clinical applications.
- CRISPR refers to Clustered Regularly Interspaced Short Palindromic Repeats, unique DNA sequences that lie within other continuously repeating DNA sequences in bacterial genomes.
- Cas9 refers to the CRISPR-associated endonuclease that uses a guide RNA to cut DNA at a specific location.
- The CRISPR-Cas9 system was adapted from a naturally occurring genome editing system in bacteria. In bacteria, DNA snippets from invading viruses would be captured and used to form DNA segments. These segments allow bacteria to “remember” these viruses so that if the same viruses attacked again, the bacteria were able to produce RNA segments and target the viruses’ DNA. Then, the bacteria would employ Cas9 or a similar enzyme to cut the DNA, thus disabling the virus. In the lab, researchers create a piece of RNA using a short “guide” sequence that binds to the Cas9 enzyme and a specific target sequence of DNA in a genome. The attachment of RNA signals DNA sequence recognition which allows the Cas9 enzyme to cut the DNA at the specified location. After the DNA is cut with Cas-9, researchers use the cell’s own DNA repair machinery to alter the genetic material.
- The use of the CRISPR-Cas9 system in gene editing has exploded in the scientific community due to its efficiency and accuracy compared to other existing gene editing methods. In addition to that, it has incredible potential in treating single-gene disorders like cystic fibrosis, hemophilia, and sickle cell disease.
When prompted if she believes CRISPR-Cas9 can cure genetic disease, Doudna strongly affirms that she believes it can. She points out that CRISPR has already been used to treat sickle cell anemia, as well as other genetic diseases that result from an error in a single gene. As a result, instead of having to take a drug for the rest of their life to manage a disease, CRISPR goes to the root of the disease and corrects the source code.
Doudna: “I think first and foremost, we have to encourage transparency about the science. We have to be realistic about where it’s headed. The field is moving very, very quickly. […] I think it’s increasingly possible to essentially make any kind of edit to cellular DNA that somebody might like to make, so that just brings along both incredible opportunities but also risk and responsibility, so those have to go together.”
The ethical implications of human genome editing
Although the ability to alter human genomes has many positive, medicinal implications, there is a large host of questions and concerns from the scientific community regarding the ethics of human gene editing. Given that Doudna is heavily involved in the ethics of CRISPR-Cas9, I appreciated how she shared her thoughts on how to approach something like human gene editing that may reach a slippery slope. Doudna underlines the importance of transparency when dealing with genome editing, and points out that while there are incredible opportunities, there is also incredible risk and responsibility that the scientific field must be conscious of.
I found it refreshing that Doudna underscores the importance of awareness and education of gene editing ethics, rather than shying away from what may be an uncomfortable topic to think about. She discusses the example of the human embryo editing in twin girls in China, and how it woke up the international science community to realize this was not a fantasy. Genetic editing was occurring in real time, progressing rapidly, and with these developments came an urgency to better understand it. I love how Doudna addresses this, as it is crucial to scrutinize and weigh both the possible benefits as well as drawbacks of such a powerful tool. Doudna goes on to commend the scientific community and its accountability….
“Rather than saying ‘We’re never gonna go there’, we need to say, ‘If we go there, how do we do it? How do we do it safely, ethically, and in ways that will enhance and not harm humanity?”
The future directions of science
“I believe the future of science will be a combination of new science and new fundamental discoveries. Some of it will be enabled by CRISPR, for sure, while we’re also seeing increasing convergence of different kinds of technologies. I’m very excited about the opportunities machine learning offers and the ways data are being managed now[…]Having access to these technologies that help us better understand the genome will be really important for the future”
- New sciences and technologies: In developing new sciences and technologies – as exhibited by the rapid development of mRNA vaccines in response to the SARS-CoV-2 pandemic – Doudna has great hope about the future of science and the direction it is going. She encourages investments in the kind of work that will lay the foundation for future discoveries.
- Entrepreneurship & start-ups: One of the most interesting, and simultaneously unexpected aspects about CRISPR for Doudna was the opportunity to partake in start-up companies, specifically biotechnology companies that were developing technologies for specific applications. This was especially due to their vision with questions like “Where is science going? Where can it have a broader, bigger impact?”. With the inevitable intertwinement of basic research and applied research, one can always inform the other in a very powerful way. As more and more people go back and forth between companies and academia, fresh, innovative ideas are being developed in the context – necessary for tackling the immense problems that society faces, such as the pandemic, climate change, etc.
The importance of female representation in Nobel laureates
Historically, the pool of Nobel Laureates has always been male-dominated. However, for the first time in history, women almost matched the number of men to win a Nobel Prize in a given year across all categories in 2020. Doudna and Charpentier are the 6th and 7th women to win the Nobel prize for chemistry in all of history (only 57 women in total have been awarded the Nobel Prize with Marie Curie being honored twice) and Doudna recounts the biggest obstacles she had to overcome in order to achieve such a prestigious honor. She reveals that the biggest obstacle for herself has been her own self-doubt and questions about herself. While this is true for most people, this is often more so for women due to the way they are raised. Some interesting quotes Doudna voiced during the discussion:
- Imposed societal gender roles: “Women have a disproportionate responsibility for their families – whether it’s for children or for parents – and that often comes at the same time when they’re working on their careers and building up their research programs, if they’re scientists….There’s no one size fits all answer.”
- External prejudices: When Doudna was a sophomore in high school, her counselor asked what she wanted to do in the future, and she replied, “I want to be a scientist”. Her counselor looked at her and said ‘oh, that’s not a good career for a girl”.
- How Doudna chooses to respond: “I really try to view the challenges that we all face along the way in our career as opportunities – ways to try to be better. We all have failures, experiments that don’t work, papers that get rejected, and grants that don’t get funded. But I think for me, when those things happen, I try to turn it around and say ‘What can I learn from that? How can I do better next time? How can I rise to that challenge?”
- How women can respond: “You can respond in two ways. You can allow it to build up your own negative feelings or voices, or you can turn it around and see it as a challenge and say ‘I’m going to rise to that challenge and just see if I can make that work”.
- How the scientific community should respond: “We should build an adaptable community of scientists who are supportive of each other and recognize that we are dealing with different things at different times in our lives, and have a system that is supportive of scientists to enable all of us to do our best work”.
With this empowering mindset, not only can women rise up and claim their rightful place in a predominantly male dominated field, but the scientific community can also progress towards equity.
Doudna: “We all have failures, experiments that don’t work, papers that get rejected, and grants that don’t get funded. But I think for me, when those things happen, I try to turn it around and say ‘What can I learn from that? How can I do better next time? How can I rise to that challenge?”
A couple of recent CRISPR highlights in the clinical field
- New York Genome Center (NYGC) and New York University (NYU) scientists have developed a genetic screening platform that jointly captures CRISPR gene perturbations and single-cell chromatin accessibility genome-wide. This new platform could help researchers study how links between genetic changes and chromatin accessibility may contribute to diseases such as cancer.
- Genome-wide programmable transcriptional memory by CRISPR-based epigenome editing This paper describes a new gene editing technology called CRISPRoff that allows researchers to control gene expression with high specificity while leaving the sequence of the DNA unchanged. This new technology offers unrivaled control of epigenetic inheritance .
More about CRISPR on our blog
- Gene Editing Revamped with CRISPR Prime Editor – Result Is A High Efficiency, More Precise Gene Editor With Versatile Editing Capabilities And Lower Off-Target Effects
- CRISPR Base Editors: An Upgrade for Treatment of Genetic Disease
Jane Xie is a rising senior at Emory University studying Biology and Religion while on the pre-med track. She is also presently the Digital Marketing and Communications Intern at enlightenbio. After graduating, Jane hopes to facilitate the convergence of science and religion through a career in medicine domestically, and ultimately internationally, with special areas of interest in whole person care, global medicine, and serving underserved populations.