Jennifer Doudna (UC Berkeley Professor) – Walter Isaacson & Jennifer Doudna join Washington Post Live to discuss CRISPR (Live, 3/12) (Mar 2021)

Chapters

Abstract

CRISPR: Revolutionizing Science and Ethics in the Modern World

CRISPR, a groundbreaking genetic manipulation tool, stands at the forefront of modern scientific innovation, holding the potential to revolutionize both medicine and agriculture. Clusters of regularly interspaced short palindromic repeats, abbreviated as CRISPR, are a sequence of DNA that occurs repeatedly in bacteria and signifies a bacterial immune system. Bacteria use CRISPR to capture genetic information from viruses and protect themselves from future viral infections. Scientists, harnessing this natural system, have adapted it for gene editing across various cell types. Its applications extend from fundamental biological research to practical uses in medicine, such as gene therapy, and in agriculture for developing pest-resistant crops. However, this power comes with significant ethical implications, as highlighted in the controversial case of the CRISPR babies and the debates surrounding germline editing. The journey of Jennifer Doudna, a pivotal figure in CRISPR’s development, exemplifies the intertwining of creativity, resilience, and ethical contemplation in scientific discovery. Her story, alongside Walter Isaacson’s perspectives, underscores the critical roles of diversity, gender equality, and international collaboration in science, particularly in the context of U.S.-China relations and the ongoing COVID-19 pandemic.

The Discovery and Applications of CRISPR

CRISPR, or “clusters of regularly interspaced short palindromic repeats,” originated as a bacterial immune mechanism against viruses. Scientists, harnessing this natural system, have adapted it for gene editing across various cell types. Its applications extend from fundamental biological research to practical uses in medicine, such as gene therapy, and in agriculture for developing pest-resistant crops. Jennifer Doudna’s contributions, including her work on RNA structures and her role in discovering CRISPR as a gene-editing tool, made her an ideal subject for a narrative journey of discovery.

Germline Editing and Ethical Considerations:

Scientists are exploring the possibility of editing genes in early-stage embryos to create inheritable changes in the human race, raising ethical concerns. Editing at this stage would mean changes would be passed down to descendants, creating potential unintended consequences and long-term effects.

Walter Isaacson’s Perspectives on Creativity and Discovery

Isaacson, renowned for biographies on Leonardo da Vinci and Albert Einstein, views Jennifer Doudna as a transformative figure in science. He emphasizes creativity and the sense of being an outsider as catalysts for scientific breakthroughs, drawing parallels between Doudna’s journey and those of historical figures like Einstein and da Vinci. Doudna’s path from studying RNA to pioneering CRISPR, while grappling with ethical questions, embodies a narrative of discovery fueled by creativity.

The Importance of Feeling Like an Outsider:

Isaacson argues that many highly creative individuals, such as Leonardo da Vinci, Steve Jobs, and Albert Einstein, have felt alienated from their surroundings. This sense of alienation can drive curiosity and a desire to understand and fit into the world, leading to groundbreaking discoveries and creative achievements.

Jennifer Doudna’s Experience as an Outsider and Insider:

Doudna recounts her experience growing up in a small town in Hawaii, where she felt like an outsider due to her ethnicity and family background. This sense of isolation led her to find solace in reading and developing a passion for science.

The Challenges of Scientific Discovery:

Doudna acknowledges the difficulties and doubts that often accompany significant scientific work. She describes periods in her career when she questioned her abilities and considered giving up, but she persevered thanks to the encouragement of mentors and her own determination.

The Role of Women and Diversity in Science

The discussions between Doudna and Isaacson shed light on the progress and challenges of women in science. Doudna, despite her reluctance to be primarily identified as a female scientist, acknowledges the importance of gender recognition in scientific contributions. The story of Rosalind Franklin, a brilliant scientist who played a crucial role in discovering the structure of DNA, faced sexism and condescending treatment from her contemporaries, hindering her recognition. Her story highlights the importance of role models for women in science and the need for inclusivity. Furthermore, Doudna and Isaacson stress the necessity of diversity in the life sciences for enriching perspectives and fostering innovation.

Greater Inclusivity in the Life Sciences:

CRISPR research has demonstrated international diversity, with scientists from various cultural backgrounds contributing to the field. Encouraging younger students, especially from traditionally underrepresented groups, to pursue science is crucial for achieving greater diversity.

Ethical Dilemmas in Gene Editing

The advent of CRISPR technology has reignited ethical debates, notably illustrated by the case of the CRISPR babies in China. Germline editing, with its inheritable changes, poses profound ethical questions about unintended consequences and the potential for a slippery slope towards genetic enhancement. Balancing scientific progress with ethical responsibility remains a critical challenge, necessitating international discussions and cooperation, especially between major players like the U.S. and China.

Moral Considerations:

The coronavirus pandemic has highlighted the potential benefits of editing receptors to protect against dangerous viruses, posing the question of whether it is immoral not to pursue such interventions. However, there is a moral dilemma in crossing the line of making inheritable edits, as it would have a profound impact on future generations.

Slippery Slope of Editing:

The discussion of germline editing raises concerns about a slippery slope, where editing could be used to address various traits, including deafness, blindness, shortness, or even depression. It is crucial to establish a framework for considering the ethical implications of such interventions, balancing potential benefits with potential harms.

Scientist’s Perspective:

Scientists involved in fundamental research on CRISPR technology have grappled with the ethical implications of germline editing. The realization that CRISPR allows changes to DNA that become inherited has led to a reckoning among scientists, prompting conferences and discussions on the topic. The announcement of germline editing work in China in 2018 further highlighted the need for ethical considerations and a thoughtful approach to this technology.

CRISPR in the COVID-19 Pandemic and Beyond

Doudna highlights CRISPR’s role in developing diagnostic tests for COVID-19, demonstrating its versatility beyond gene editing. The pandemic has also sparked interest in editing out viral receptors to provide immunity against future pandemics, showcasing CRISPR’s potential in addressing global health crises.

CRISPR Applications in the Pandemic:

CRISPR’s natural function as an immune system makes it a potential tool for addressing pandemics. Rapid diagnostic tests for COVID-19 and future pathogens can be developed using CRISPR. Therapeutic applications of CRISPR are more challenging due to the difficulty of delivering CRISPR molecules into infected cells.

The Journey of Discovery: Jennifer Doudna and the Wellsprings of Creativity

Walter Isaacson’s interest in understanding the creative process led him to explore the field of life sciences, specifically gene editing with CRISPR.

Conclusion

The narrative of CRISPR, interwoven with the personal and professional journey of Jennifer Doudna, encapsulates the complexities of modern scientific exploration. It brings to light the significance of creativity, resilience, and ethical contemplation in advancing scientific knowledge. The discussions around gender, diversity, and international collaboration, particularly in the context of U.S.-China relations, emphasize the need for a holistic approach to science, where cooperation and ethical considerations are as pivotal as the scientific discoveries themselves.

Views on the Ethics of Gene Editing, Sino-US Competition in Science, and International Cooperation:

– The speaker initially opposed gene editing due to ethical concerns but later realized the potential benefits in certain scenarios, provided the technology is safe and effective.

– Jennifer Doudna maintains a cautious approach, emphasizing the need for transparent international discussions on the topic.

– The Biden administration’s decision to compete directly with China in various scientific fields has the potential to drive innovation and progress, as seen in China’s advancements in CRISPR-based cancer treatments.

– The Chinese government’s response to inheritable gene editing highlights their ethical concerns, leading to legal consequences for those involved.

– International cooperation in science, particularly in gene editing and mRNA vaccine technology, can yield positive outcomes for both the U.S. and China.

– The potential for collaboration between the two countries is vast, with the possibility of using CRISPR and mRNA vaccines for mutual benefit.

Notes by: oganesson