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    112 | Fyodor Urnov on Gene Editing, CRISPR, and Human Engineering

    enAugust 31, 2020
    What advantages does Indeed offer for candidate hiring?
    How does gene editing raise ethical implications?
    What is Regeneron's contribution to RNAi medicine?
    Why prefer epigenetic over genetic editing in research?
    What caution does the Department of Defense advise regarding gene editing?

    Podcast Summary

    • Find quality candidates efficiently with IndeedIndeed's 350 million monthly visitors and matching engine help employers find high-quality candidates quickly and manage the hiring process directly on the platform. With 93% of employers agreeing on the highest quality matches, Indeed is the go-to choice for hiring.

      When it comes to hiring, instead of searching for candidates, you can rely on Indeed. With over 350 million monthly visitors and a matching engine, Indeed helps you find quality candidates quickly and efficiently. You can even schedule, screen, and message candidates directly on the platform. Moreover, 93% of employers agree that Indeed delivers the highest quality matches compared to other job sites. As for gene editing, it's an exciting and potentially transformative technology, but also raises concerns about accessibility and ethical implications. Fyodor Ornov, a world-renowned expert in the field, acknowledges that it's becoming increasingly easy for anyone to engage in gene editing, and we'll need to grapple with the consequences. In the meantime, if you need to hire, trust Indeed to help you find the best candidates.

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      The pandemic has significantly disrupted the usual focus of molecular and cell biologists, with many being diverted from their basic research to contribute to clinical testing efforts. The skills learned in molecular and cell biology, such as testing for viruses, have proven essential in dealing with the pandemic. This unexpected application of decades-old techniques highlights the unpredictable relevance and resonance of scientific research. Despite the shift from academic research to clinical applications, the fundamental mechanics of diagnosis remain rooted in foundational knowledge. This experience underscores the importance of maintaining a versatile skill set and the potential for scientific discoveries to have far-reaching impacts on the world.

    • Understanding CRISPR: Editing Genes Like a DocumentCRISPR is a game-changing gene editing tool that enables precise modifications to DNA, revolutionizing disease treatment and agriculture, but it's a complex process.

      The ongoing battle against viruses and diseases has led to a renewed focus on molecular biology and gene editing, specifically CRISPR. While most people may not fully understand the intricacies of these scientific concepts, they have become part of everyday conversation due to their impact on our lives. CRISPR is a revolutionary gene editing tool that allows for precise modifications to DNA, much like editing a document on a computer. Human DNA is incredibly long and complex, and most living organisms, including humans, protect the integrity of their DNA. The development of CRISPR and other gene editing technologies has opened up new possibilities for treating diseases and improving agriculture, among other applications. However, it's important to remember that the process is not as simple as copying and pasting genetic material, but rather involves carefully manipulating the complex structure of DNA.

    • The Importance of DNA Repair MachineryOur bodies have ancient and sophisticated DNA repair machinery to address damage from various sources, ensuring the continuity of our genetic material.

      Our DNA is constantly under attack from various sources, and the ability to repair this damage is crucial for our survival. Without effective repair machinery, individuals with rare diseases may suffer from damage that cannot be fixed, such as sunlight-induced damage to their DNA. Our DNA is also susceptible to damage from chemicals and physical forces, like those found in X-rays. If the damage is severe and results in a broken chromosome, the cell may not be able to tolerate the loss of genes and could die. Fortunately, our bodies have ancient and sophisticated repair machinery to address these issues, ensuring the continuity of our genetic material. This machinery has been with us since the dawn of life on Earth, and its importance cannot be overstated.

    • The connections between yeast and human DNA repair mechanismsScientists use the same names for yeast and human DNA repair genes and processes due to their significant similarities. Gene editing, which has led to breakthroughs like curing sickle cell disease, is built upon these fundamental discoveries.

      The similarities between the DNA repair mechanisms in yeast and humans are so significant that scientists use the same names for the related genes and processes in both organisms. This connection highlights the evolutionary preservation of these essential repair systems. Gene editing, which has made remarkable advancements in the last 25 years, has built upon these fundamental discoveries, leading to breakthroughs like the gene editing of Victoria Gray for sickle cell disease. The journey from the discovery of CRISPR to its application in curing genetic diseases took only 8 years. This rapid progress underscores the importance of fundamental research and the curiosity-driven pursuit of understanding biological processes. The Great Courses Plus, a streaming service offering high-level courses on a wide range of topics, is an excellent resource for those seeking to deepen their knowledge in various fields. To learn more about gene editing and its history, sign up for a free trial of The Great Courses Plus at thegreatcoursesplus.com/mindscape. The two primary methods for repairing broken chromosomes are end joining, which involves reconnecting the broken ends, and homologous recombination, which uses a template for repair. These mechanisms ensure the continuity and accuracy of our genetic material.

    • Using CRISPR to disable genesCRISPR gene editing can disable genes by causing errors during DNA rejoining, leading to clinical and agricultural applications

      CRISPR gene editing technology allows scientists to cut specific genes and, due to the error-prone nature of DNA rejoining, often results in the deletion or addition of a few letters, which can disable the gene. This "gene knockout" technique has proven clinically useful, as seen in the elimination of genes that make humans susceptible to HIV or those that prevent the production of healthy hemoglobin in sickle cell disease. This technology also has applications in agriculture. While the genetic code is read as a continuous string, losing just a letter or two can render the text gibberish, a phenomenon known as a frame shift. By cutting a gene and allowing nature to rejoin it imperfectly, researchers can effectively disable it, opening up possibilities for treating diseases and improving crops.

    • Manipulating DNA repair for gene editingGene editing uses natural DNA repair process to make precise changes to DNA sequences, opening possibilities for curing genetic diseases and creating gene-edited organisms

      The natural process of DNA repair in cells can be manipulated for gene editing through techniques like gene knockout and gene repair using identical DNA templates. This process involves a broken chromosome searching for and copying missing genetic information from an identical sister chromatid to heal the break. Gene editing leverages this natural process to make precise changes to DNA sequences. This is significant because it opens up possibilities for creating gene-edited organisms and potentially curing genetic diseases. The first gene-edited crop, waxy corn, will be marketed in the US soon, using gene knockout technology. However, it's important to note that this is a complex process and not all attempts at gene editing are successful. Nevertheless, the potential applications of gene editing are vast and hold great promise for the future.

    • Gene editing in living organismsScientists have developed a method to naturally alter DNA in living organisms, called gene editing, which has potential to treat and prevent genetic diseases

      Scientists have developed a way to edit genes in living organisms by introducing a small change in DNA and having it replicate naturally. This process, known as gene editing, can be done in various ways, including using viruses to deliver the editing tool into specific organs. The gene editor itself spreads to other cells, allowing for the new genetic information to be incorporated into the organism. This process has already been used clinically for conditions like congenital blindness and hemophilia, resulting in gene-edited individuals. It's important to note that the gene editor doesn't make cells share their DNA directly, but instead spreads through the cells via the editor itself. This technology holds great potential for treating and even preventing various genetic diseases.

    • Learning a new language effectively with Babbel and saving up to 60% on subscriptionBabbel offers effective language learning in short sessions, and Mindscape listeners can save up to 60% on subscription. In genetic engineering, scientists focus on natural biological processes to combat diseases through gene editing, such as HIV protection.

      Language learning app Babbel can help you speak a new language effectively in just 10-minute sessions, and currently, Mindscape listeners can get up to 60% off their subscription. Meanwhile, in the field of genetic engineering, scientists are focusing on repairing mutations or adding healthy genes to combat diseases. However, an early success story in this field was genetic augmentation through cancer immunotherapy, where scientists engineered a molecule to reprogram immune system cells to attack cancer cells. Despite the controversy surrounding the term "gene editing," it's essential to note that current gene editing techniques are focused on natural biological processes to help the body fight diseases. For instance, removing the CCR 5 gene to protect against HIV is based on a natural discovery of people who lacked the gene and remained virus-free. Overall, whether it's learning a new language or advancing in genetic engineering, progress can be made with the right tools and knowledge.

    • Using natural genetic variations for disease treatmentIn the next 5-10 years, expect significant advancements in gene editing for cancer treatment, sickle cell disease, hemophilia, and pain relief. Gene editing holds promise for eliminating addictive painkillers and improving overall health.

      Natural genetic variations are being used as a therapeutic modality to treat and potentially cure diseases. This approach, which involves transferring these natural variations from healthy individuals to those with diseases, holds great promise for the treatment of various conditions, including certain forms of cancer, sickle cell disease, and hemophilia. In the next 5 to 10 years, we can expect significant advancements in the application of gene editing for cancer treatment and the reduction of public health burdens for sickle cell disease, hemophilia, and other genetic diseases. Another exciting area for this technology is in the treatment of pain, particularly for conditions that don't respond to conventional painkillers. The discovery of genes that eliminate pain sensation could lead to the elimination of addictive synthetic painkillers, improving overall health and wellbeing. While it's challenging to predict beyond the next decade, the potential for remarkable discoveries in the field of gene editing is immense.

    • Gene editing holds promise for treating diseases and improving healthAdvancements in gene editing offer potential solutions for chronic pain, genetic diseases, and even aging, but face regulatory hurdles and long clinical trials.

      Advancements in gene editing are leading to potential breakthroughs in the treatment of various health conditions, including chronic pain and genetic diseases like hemophilia and sickle cell disease. Research is also being conducted to eliminate genes associated with conditions such as heart disease and HIV resistance. However, there are challenges, such as regulatory approval and long clinical trial durations, especially when dealing with aging or longevity. Despite these challenges, the potential benefits of gene editing for treating diseases and improving overall health are promising. Additionally, the discussion highlighted the existence of individuals with unique genetic traits, such as insensitivity to pain or resistance to heart attacks, which could be targeted for therapeutic applications. Overall, gene editing holds significant potential for revolutionizing healthcare and addressing some of the most pressing health concerns.

    • Managing finances and saving money with Rocket MoneyIdentify and cancel unwanted subscriptions, monitor spending, and lower bills with Rocket Money to save an average of $720 per year

      Managing our finances and saving money, even on a small scale, can have a significant impact on our lives. Subscriptions, in particular, can add up quickly and go unnoticed. Rocket Money is a personal finance app that helps identify and cancel unwanted subscriptions, monitor spending, and lower bills. With over 5 million users and an average savings of $720 per year, it's a practical solution for those looking to regain control of their finances. On a larger scale, the future holds exciting possibilities for molecular machines that could extend our lifespan and improve our health. From curing DNA damage to protecting organs like the kidneys and heart, these advancements are not only imaginable but could significantly impact public health. So whether it's managing our daily finances or envisioning a future with advanced medical technology, every step we take, no matter how small, can lead to meaningful progress.

    • Germline vs Epigenetic Editing: Different Purposes and Ethical ConsiderationsGermline editing is illegal and widely considered unethical due to potential risks and uncertain outcomes, while epigenetic editing focuses on modifying molecular marks on DNA to influence gene expression without altering genetic code, and holds promise for addressing health conditions through nutritional interventions.

      While both epigenetic editing and germline editing are methods of genetic manipulation, they serve different purposes and come with distinct ethical considerations. Germline editing, which involves making genetic changes that can be passed down to future generations, is currently illegal and widely considered unethical due to its potential risks and uncertain outcomes. Epigenetic editing, on the other hand, focuses on modifying the molecular marks on DNA that influence gene expression without altering the genetic code itself. This form of editing holds promise for addressing certain health conditions, such as neural tube defects, through nutritional interventions like folate supplementation. Overall, the debate between these two forms of editing underscores the importance of understanding their unique implications and ethical considerations.

    • Exploring Epigenetic Editing for Temporary Gene ChangesFolate supplementation is an example of epigenetic editing that reduces neural tube defects. Researchers are investigating CRISPR for temporary gene changes to protect war fighters, first responders, and cancer patients from radiation damage.

      Epigenetic editing offers a way to make temporary changes to genes without altering their sequence, providing benefits in certain situations. For instance, folate supplementation reduces the risk of neural tube defects in a child through an epigenetic effect. Currently, researchers are exploring the use of CRISPR for epigenetic editing to protect war fighters, first responders, and cancer patients from radiation damage. This approach is preferred over genetic editing because it does not permanently alter the DNA and respects the natural process of cell death and potential cancer development. The Department of Defense has also expressed caution against permanent genetic enhancements for military personnel, as the long-term consequences are unknown and could potentially harm individuals after they leave the military.

    • Ethical concerns surrounding CRISPR technology and embryo/baby editingEnsuring consent and proper regulation are crucial to prevent potential harm and misuse of CRISPR technology, particularly in embryo and baby editing, while adult somatic enhancement could be acceptable with regulatory approval.

      The ease of use and potential misuse of CRISPR technology raises ethical concerns, particularly when it comes to embryo and baby editing. Zheng Que He's alleged actions have shown that this technology can be used to create "designer babies," and there are already laboratories enhancing embryos for people with excessive financial resources and a lack of scientific understanding. Making embryo and baby editing a crime everywhere and ensuring those who engage in it are prosecuted may help reduce its prevalence, but the relative ease and secrecy of CRISPR make it a significant challenge to eradicate completely. Human somatic enhancement of consenting adults, such as Botox injections, could be acceptable as long as it passes regulatory review. The key issue is ensuring consent and proper regulation to prevent potential harm and misuse.

    • Gene editing for medical treatments and cosmetic enhancementsAs gene editing becomes more accessible, ethical questions arise about free will, safety, and potential consequences. While acceptance for disease treatment is expected, it's important to remember gene editing is just one piece of the puzzle for overall public health.

      As technology advances, particularly in the field of gene editing, we are moving towards a future where people will have the ability to permanently modify their own DNA for various reasons, including medical treatments and cosmetic enhancements. This raises ethical questions about free will, safety, and the potential consequences of such modifications. Comparing it to the acceptance of piercings or statins, gene editing for disease treatment is expected to become more widely accepted and accessible in the coming years. Additionally, the ongoing pandemic serves as a reminder that real-world solutions require a convergence of various technologies and approaches. While gene editing holds great promise for treating genetic diseases and cancer, it is important to remember that it is just one piece of the puzzle in improving overall public health.

    • Exciting progress in human genetic modificationRapid advancements in gene and epigenetic engineering enable human genetic modification, with potential for preemptive vaccines against viruses like HIV and unforeseen consequences

      The rapid advancements in gene and epigenetic engineering have made human genetic modification a clinical reality within just a few years. Regeneron's discovery and development of an RNAi medicine targeting a liver protection gene is an exciting example of this progress. Looking forward, there's potential for using gene editing to preemptively vaccinate individuals against viruses like HIV in developing countries. However, ethical considerations and regulatory reviews must be addressed. The convergence of genetic engineering and technology development is reminiscent of the early days of the personal computer industry, with unforeseen consequences likely to shape the future. Nobel laureate Sydney Brenner once said that progress in science comes from new technologies, discoveries, and ideas. As we live in a technology-driven age, the potential for human genetic and epigenetic engineering in the clinic for disease protection and potential enhancement is expected to bring about unpredictably exciting advancements. So, we should prepare ourselves for this wild ride.

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    216 | John Allen Paulos on Numbers, Narratives, and Numeracy

    216 | John Allen Paulos on Numbers, Narratives, and Numeracy

    People have a complicated relationship to mathematics. We all use it in our everyday lives, from calculating a tip at a restaurant to estimating the probability of some future event. But many people find the subject intimidating, if not off-putting. John Allen Paulos has long been working to make mathematics more approachable and encourage people to become more numerate. We talk about how people think about math, what kinds of math they should know, and the role of stories and narrative to make math come alive. 

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    John Allen Paulos received his Ph.D. in mathematics from the University of Wisconsin, Madison. He is currently a professor of mathematics at Temple University. He s a bestselling author, and frequent contributor to publications such as ABCNews.com, the Guardian, and Scientific American. Among his awards are the Science Communication award from the American Association for the Advancement of Science and the Mathematics Communication Award from the Joint Policy Board of Mathematics. His new book is Who’s Counting? Uniting Numbers and Narratives with Stories from Pop Culture, Puzzles, Politics, and More.


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