CRISPR: A Bacterial Immune System:
CRISPR-Cas9 is a gene-editing tool inspired by the natural immune system of bacteria. It allows researchers to edit DNA with precision, opening up possibilities in medicine, agriculture, and environmental science. CRISPR has the potential to create permanent changes in DNA that can be inherited by future generations (germline editing).

Discovery of CRISPR’s Potential:
Jennifer Doudna’s lab initially studied CRISPR to understand how bacteria fight viral infections. A collaboration with Emmanuel Charpentier’s lab in 2011 focused on understanding the CRISPR-Cas9 protein. Researchers realized that Cas9 could be programmed to find and cut specific DNA sequences, including viral DNA.

Molecular Mechanism of CRISPR-Cas9:
Cas9 protein, guided by RNA molecules, finds and cuts viral DNA. The molecular basis of this process allows CRISPR-Cas9 to be harnessed as a technology for gene editing.

CRISPR’s Potential as a Gene-Editing Tool:
CRISPR-Cas9 enables precise editing of DNA, including insertion, deletion, and replacement of genetic material. This technology has the potential to correct genetic defects, develop new therapies, and improve agricultural crops. Ethical considerations surround the use of CRISPR for germline editing, which could create permanent changes inheritable by future generations.

How CRISPR-Cas9 Works:
CRISPR-Cas9 is a molecular scissors or scalpel that literally cuts DNA. It uses an RNA guide to find the target DNA sequence and then cuts it. The cut DNA is then repaired, and scientists can control how the repair happens to make specific changes to the DNA sequence.

CRISPR-Cas9’s Power and Versatility:
CRISPR-Cas9 is programmable, meaning scientists can target specific genes or DNA sequences. It can be used to disrupt genes, introduce new genetic material, or correct genetic mutations. This makes it a powerful tool for both research and real-world applications.

Early Applications of CRISPR-Cas9:
Within months of its publication, CRISPR-Cas9 was used to change the DNA in whole organisms, such as zebrafish. This demonstrated its potential for manipulating the DNA of entire organisms and passing on those changes to future generations.

Research Applications of CRISPR-Cas9:
CRISPR-Cas9 has been used to address fundamental questions in biology that were previously difficult or impossible to study. Examples include understanding the genetics of butterfly wing patterns and studying gene regulation in various organisms.

CRISPR-Cas9 and Developmental Biology:
CRISPR-Cas9 has helped scientists understand the mechanisms that link specific genetic sequences to specific developmental outcomes. This has provided a deeper level of understanding than previous methods.

CRISPR-Cas9’s Potential Impact on Genetic Diseases:
CRISPR-Cas9 has the potential to revolutionize the treatment of genetic diseases by correcting disease-causing mutations. This could lead to new therapies for diseases like sickle cell anemia and muscular dystrophy.

The Future of CRISPR-Cas9:
CRISPR-Cas9 is a rapidly developing technology with enormous potential for research and applications. Its continued development and refinement hold promise for addressing a wide range of challenges in biology and medicine.

CRISPR’s Potential and Challenges:
CRISPR has revolutionized genetic research and opened the door to understanding genetic functions in various organisms. It allows for precise manipulation of DNA, enabling the study of genes and the development of potential cures for genetic diseases.

Clinical Successes:
CRISPR has shown promising results in clinical trials for treating genetic diseases like sickle cell disease, potentially leading to cures. Recent trials have also shown progress in treating genetic eye diseases, offering hope for restoring eyesight.

Germline Editing:
Germline editing involves altering DNA in a way that can be passed on to future generations. While it offers the potential to eliminate genetic diseases, it raises complex biological, ethical, and societal concerns.

Moratorium on Germline Research:
In 2015, Jennifer Doudna and others called for a moratorium on germline editing to allow for careful consideration of the technology’s implications. The goal was to prevent potential harm and encourage transparency and discussion within the scientific community.

International Collaboration:
Two international summits and various reports have been organized to discuss the ethical and responsible use of CRISPR in the human germline. The consensus is that there should be a cautious approach until the technology is better understood and its benefits outweigh potential risks.

Ethical Considerations:
The rush to use CRISPR in the human germline raises concerns about scientists seeking personal recognition and the potential for unethical applications. Experiments with CRISPR on human embryos have been conducted in some countries, highlighting the need for international collaboration and oversight.

He Jianghui’s Announcement:
In November 2018, Jennifer Doudna received a note from Chinese scientist He Jianghui, informing her about his use of CRISPR in human embryos and the birth of edited babies. This announcement shocked the scientific community and raised ethical concerns.

International Summit on Human Germline Editing:
Doudna attended the second international summit on human germline editing in Hong Kong. He Jianghui presented his work, which was met with criticism from many attendees and experts.

Unethical Motivation and Backlash:
The primary motivation for He Jianghui’s work was believed to be personal recognition and fame rather than the well-being of the parents and children involved. This led to a strong international backlash against the rush for clinical use of human germline editing.

Current Status of Research:
Since the controversy, there has been a slowdown in the clinical use of CRISPR for human germline editing. However, research is ongoing to understand how CRISPR works in human embryos.

He Jianghui’s Intention:
He Jianghui’s stated purpose for using CRISPR was to protect the babies from future HIV infection by altering a gene that makes T cells susceptible to the virus.

Health of the Edited Babies:
The health status of the edited babies is unknown as it has not been made public. The potential long-term effects of the genetic engineering raise concerns about their health.

Comparison to Past Experimentation:
Doudna expressed shock at He Jianghui’s work, likening it to unethical human experimentation practices during the Second World War.

Parents’ Desperation and Ethical Considerations:
Doudna acknowledges the desperation of parents who carry genes that pose risks to their children’s health. However, she emphasizes the need for careful ethical considerations and transparency in the use of gene-editing technologies.

Ethical Considerations:
Scientists and clinicians debated the ethics of using CRISPR to edit the human germline, acknowledging that it could be used to prevent genetic diseases but also raising concerns about potential unintended consequences and equity issues. Balancing the potential benefits of CRISPR with the need for caution and careful consideration of ethical and societal implications is crucial.

CRISPR’s Therapeutic Potential:
CRISPR is primarily used in clinical settings to impact individuals without creating heritable changes, such as treating genetic diseases like sickle cell disease and muscular dystrophy. In the next couple of decades, CRISPR-based cures for various genetic diseases are expected to emerge, offering hope for patients with conditions caused by single-gene defects. CRISPR’s potential extends beyond treating genetic diseases; it could also be used to enhance human health by manipulating genes to improve health span and reduce the risk of chronic diseases.

Gene Editing in Adults:
CRISPR can effectively edit DNA in living adults, even though the body consists of trillions of cells with “wrong” DNA. In many cases, editing only a small percentage of cells can have a therapeutic benefit, as demonstrated in animal models of genetic diseases. Ongoing research explores methods to deliver CRISPR-based therapies to specific tissues or cell types in the body, potentially enabling targeted editing without the need to edit every cell.

Therapeutic Potential of CRISPR:
CRISPR can be used for therapeutic purposes by editing a small fraction of cells, targeting specific tissues, and employing stem cells as sources of edited cells. CRISPR-mediated manipulation in animal models has demonstrated therapeutic benefits.

CRISPR Applications in Agriculture:
CRISPR is being utilized to enhance crop traits, such as drought resistance and reduced reliance on chemical fertilizers, making them more accessible and climate-resilient. CRISPR enables the improvement of crop yield and nutritional value, potentially addressing global food security and malnutrition.

Comparison with Traditional GMO Methods:
CRISPR offers precision in genetic manipulation compared to random mutagenesis in conventional plant breeding. CRISPR allows for targeted editing of specific genes responsible for desired traits, minimizing unintended changes and undesirable side effects.

Addressing Concerns about CRISPR-Edited Crops:
CRISPR-edited crops can be considered GMOs, but with more precise and controlled genetic modifications. Traditional plant breeding also involves random genetic changes, often leading to undesired traits. CRISPR provides a safer approach by enabling targeted gene editing, reducing the introduction of unwanted changes.

Future Possibilities for CRISPR in Agriculture:
CRISPR can contribute to the development of crops with improved taste, texture, and nutritional content. CRISPR-edited crops could reduce food waste and improve the overall quality of our food supply.

Positive Applications of CRISPR:
CRISPR technology offers promising applications in addressing climate change. Initiatives are underway to manipulate soil organisms for enhanced carbon capture, improved interaction with plants, and reduced reliance on chemical fertilizers. CRISPR can contribute to controlling insect-borne diseases, such as malaria, by targeting the vector population responsible for disease transmission.

Ethical Concerns and Risks:
Concerns arise regarding the potential misuse of CRISPR technology by individuals with malicious intent. The ease of access to CRISPR tools raises the possibility of rogue actors unleashing harmful pathogens or causing widespread disruption. Risks associated with CRISPR technology extend beyond biological manipulation and include electronic and computing realms.

Staying Optimistic and Responsible:
Despite these concerns, CRISPR holds immense potential for positive impact if made widely available, safe, and effective. Efforts are focused on clinical applications and mitigating climate change using CRISPR. The responsible use of CRISPR technology requires staying on top of its developments and acknowledging the accompanying ethical and societal implications.

CRISPR’s Integration into Everyday Life:
CRISPR technology is expected to become an integral part of our lives, influencing various aspects beyond direct DNA manipulation. New therapies, improved genetic understanding, and positive environmental manipulation are anticipated. Despite optimism, a realistic approach is necessary to ensure responsible and ethical utilization of this powerful technology.

Conversation Recap:
Chris Anderson expressed his gratitude for the opportunity to converse with Nobel Prize winner Jennifer Doudna, recognizing the rarity of such conversations and the significant impact she has made in the world.

Feedback Request:
Anderson encouraged listeners to share their feedback on the show by sending emails directly to him at tedchriss at ted.com, emphasizing that he reads each email.

Podcast Details:
The TED Interview is part of the TED Audio Collective, a collection of podcasts dedicated to sparking curiosity and sharing impactful ideas.

Production Team Credits:
Kim Naderfein-Peterser produced the show, while Grace Rubinstein and Sheila Orfano edited it. Sam Baer was responsible for the mixing, and Charles Wallace and Julia Dickerson conducted the fact-checking. Special thanks were given to Michelle Quint, Colin Helms, Nicole Bode, and Anna Phelan for their contributions.

Appreciation for Listeners:
Anderson expressed his gratitude to the listeners for their engagement and support.