Jennifer Doudna (UC Berkeley Professor) – CRISPR Biology and the New Era of Genome Engineering (May 2016)


Chapters

00:00:08 Carnegie Institution for Science Welcomes Council of Scientific Society Presidents
00:02:20 Carnegie Scientists: Unbridled Passion, Insatiable Curiosity, and Never-
00:05:39 White House Science Policy and Awards
00:14:34 Presidential Leadership in Science, Technology, and Innovation
00:17:37 Harnessing Partnerships and Talent for STEM and Innovation
00:22:06 CRISPR Biology and the New Era of Genome Engineering
00:27:08 CRISPR: A Revolutionary DNA Editing Technology Inspired by Bacterial Defense
00:34:38 CRISPR: A Bacterial Adaptive Immune System
00:39:16 CRISPR: Molecular Scalpel Innovation
00:43:01 CRISPR-Cas9: A Revolutionary Genome Editing Tool
00:51:18 CRISPR-Cas9: Ethical Considerations for Germline Editing
01:00:44 CRISPR Editing: Potential, Ethical Considerations, and Societal Impact
01:14:12 Ethical and Practical Implications of Genetic Engineering Technology
01:16:55 CRISPR-Cas9: Implications and Future Developments
01:24:52 Advances in Gene Editing and Ethical Considerations
01:27:39 Discovery and Applications of CRISPR-Cas9

Abstract

The Revolution and Responsibility of CRISPR-Cas9: Transforming Science and Society (Updated)

The Carnegie Institution for Science’s recent event highlighted the transformative potential of CRISPR-Cas9 genome editing. President Matthew Scott emphasized the interplay of curiosity-driven research, technological innovation, and ethical responsibility. Topics ranged from the Obama administration’s contributions to science and technology to the challenges and ethical considerations of gene editing, including Jennifer Doudna’s groundbreaking work in CRISPR-Cas9 research, illuminating both the immense possibilities and profound responsibilities of this powerful technology.

John P. Holdren’s Summary of Barack Obama’s Leadership in Science and Technology

Dr. John Holdren, the former Assistant to the President for Science and Technology and Director of the White House Office of Science and Technology Policy, offered a comprehensive overview of President Obama’s leadership in science and technology. His tenure was marked by a strong focus on attracting top scientific talent, leveraging the presidential platform to advance science, and spearheading numerous initiatives in STEM education, information technology, and energy.

CRISPR-Cas9: A Beacon of Innovation

Jennifer Doudna’s seminal research, which centered on understanding RNA’s role in gene regulation, led to groundbreaking insights into the CRISPR-Cas9-mediated bacterial immunity system. This revolutionary discovery, which has transformed the fields of genetics, molecular biology, and medicine, was acknowledged as Science Magazine’s Breakthrough of 2015. Doudna’s journey, starting from fundamental queries about bacterial immunity, culminated in uncovering a pathway that could be harnessed for precise DNA alteration.

The discovery of CRISPR revealed that bacteria have intricate ways of combating viruses, including a newly identified pathway named CRISPR, characterized by unique DNA sequences within bacterial chromosomes. These sequences, derived from viruses the bacteria have encountered, act as a genetic vaccination card, allowing cells to record and transmit viral DNA across generations. This suggests the existence of a conserved bacterial system with a specific purpose, involving CRISPRs often found adjacent to Cas genes that encode proteins near the repetitive sites.

Jillian Banfield’s research into RNA’s role in viral defense sparked further interest, leading to collaboration with experts in RNA research to investigate CRISPR’s mechanism in viral immunity.

Obama Administration’s Scientific Legacy

The Obama administration, under the guidance of Dr. John Holdren, significantly contributed to the advancement of science and technology, both in the U.S. and globally. Major accomplishments included promoting scientific integrity, advancing STEM education, and formulating policies to address environmental change, energy technologies, and public health. Dr. Holdren’s tenure was distinguished by strengthening partnerships, recruiting science and technology talent, and applying research to improve STEM education and healthcare. He also received the Council of Scientific Society Presidents (CSSP) Supportive Science Award for his outstanding contribution to U.S. science and free science communication.

Challenges in Science and Technology

The scientific community currently faces several challenges, such as inadequate research funding, slow practical application of research, underrepresentation in STEM fields, and limited public understanding of science. Addressing these issues is critical for future scientific and technological progress.

The Ethical Landscape of Gene Editing

CRISPR-Cas9’s capability to edit any cell’s genome, including human embryos, poses significant ethical and societal questions. The contentious issue of germline editing, which can alter DNA in developing organisms and impact future generations, is being debated globally. Countries like Sweden, the UK, China, and Japan have approved CRISPR-Cas9 for human embryo editing in research, while international discussions continue on ethical guidelines and regulations.

Clinical Applications and Ethical Considerations

The potential of CRISPR-Cas9 for therapeutic applications, such as treating muscular dystrophy and sickle cell trait, is considerable. However, the possibility of enhancing human traits and the current limitations in our understanding of the human genome raise ethical dilemmas. The technology, still years away from clinical use, necessitates thorough ethical and practical considerations.

Public Perception and Engagement in Science

The public’s growing interest in gene editing underscores the need for scientists to effectively communicate its implications. Understanding its complexity and potential impacts is vital for informed decision-making. Engaging the public through personal stories and tangible representations can help demystify the technology.

Navigating the Risks and Benefits

It is essential to balance the potential benefits of CRISPR-Cas9 with its risks. Precedents like the Syllabar Meeting on molecular cloning provide a framework for addressing concerns about inappropriate or dangerous applications. Ensuring responsible use, especially regarding germline editing and gene drives, is crucial.

CRISPR-Cas9, a revolutionary genome engineering tool, enables precise and targeted DNA modifications. It uses a protein called Cas9, guided by a short RNA molecule, to locate and cut specific DNA sequences. The versatility, ease of use, and precision of CRISPR-Cas9 surpass traditional methods, facilitating its application across various organisms and fields. Current research aims to tackle challenges like off-target effects and efficient delivery methods, with ongoing evolution in the technology promising further advancements.

Function of Cas9 Protein in the CRISPR-Cas Bacterial Adaptive Immune System

The central dogma of molecular biology posits that DNA stores and accurately replicates genetic information. In bacteria, CRISPR sequences are converted into RNA molecules that recognize foreign DNA, such as from viruses. The CRISPR-Cas system, involving RNA-protein complexes, searches for DNA sequences matching the RNA sequence derived from viral DNA, providing immunity by cutting the viral DNA. Jennifer Doudna and Emmanuel Charpentier’s collaboration focused on studying the Cas9

protein’s structure and function, a key component of this adaptive immune system.

Harnessing CRISPR-Cas9 as a Technology

The CRISPR-Cas9 system, a molecular tool that recognizes and cleaves DNA, relies on a protein called Cas9 that binds to DNA sequences matching a 20-nucleotide sequence in an RNA molecule. This RNA molecule, derived from the CRISPR region, guides Cas9 to its target DNA. The system originally required two RNA molecules for efficient targeting and cleavage: the guide RNA carrying DNA recognition information and the tracer RNA essential for forming the targeting complex. However, Martin Jinek, a biochemist, simplified this system by creating a single guide RNA molecule, thereby enhancing the programmability of CRISPR-Cas9 and marking its transition from fundamental research to technological innovation.

Commercialization, Regulation, and Future Prospects

The commercialization of CRISPR technology, primarily facilitated by universities, is pivotal for developing new therapies and treatments. Researchers are actively exploring ways to regulate, shut down, or reverse CRISPR’s activity to ensure safe and responsible use. The Office of Science and Technology Policy plays a key role in addressing government regulation of gene editing.

Balancing Wonder with Responsibility

The discovery of CRISPR-Cas9, initially driven by curiosity, has sparked a sense of wonder and the potential for significant technological breakthroughs. Collaboration among scientific societies, governments, and the public is essential for responsibly harnessing this technology’s power. Striking a balance between the excitement of scientific discovery and its ethical, societal, and environmental responsibilities will be crucial in shaping the impact of CRISPR-Cas9 on our world.

Recent Developments and Ethical Considerations in CRISPR-Cas9 Genome Editing

The USDA has classified CRISPR-Cas9 modifications as non-GMO, sparking enthusiasm in the agricultural sector for the introduction of CRISPR-engineered plants. In biomedicine, CRISPR-Cas9 shows promise for modifying stem cells for disease treatments and modeling human diseases in animals, as demonstrated by the correction of a muscular dystrophy-causing mutation in a mouse model. Germline editing, which affects future generations, raises significant ethical concerns, evidenced by a successful experiment in 2013 targeting a gene responsible for black coat color in mice, resulting in white offspring. Global discussions continue on the ethical use of CRISPR-Cas9, with a meeting held to discuss its prudent employment in germline cells and a summit organized by the National Academies of several countries.

Collaborative efforts and funding from both public and private sectors have been essential in advancing CRISPR research. During a Q&A session, questions were raised about the timeline for CRISPR-Cas9’s clinical applications in humans. Ethical implications, particularly regarding human germline editing, are a major focus, with the scientific community mostly agreeing that current knowledge is insufficient for its implementation. Early targets for therapeutic applications include muscular dystrophy and sickle cell trait, with potential initial human clinical trials expected within 12 to 18 months. Additionally, CRISPR offers opportunities in agriculture and synthetic biology, including the development of pathogen-resistant plants and sustainable chemical production. However, the environmental impact of gene drives requires careful evaluation.

Gene editing has received significant media attention, emphasizing the need for scientists to engage with the public and explain the technology’s complexities. Public understanding is crucial for informed discussions on gene editing’s ethical and practical implications.


Notes by: Simurgh