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Dr. Oded Rechavi: Genes & the Inheritance of Memories Across Generations | Huberman Lab Podcast

Andrew Huberman・122 minutes read

Dr. Oded Rechavi and Andrew Huberman discuss genetic inheritance, the influence of the epigenome, and the transmission of traits across generations in various organisms. They explore the complexities of memory inheritance, touching on RNA mechanisms, the Wiseman Barrier, and the challenges in transferring neural circuit information into heritable molecular form.

Insights

  • Genetic inheritance involves passing genes from parents and includes the influence of the epigenome, shaped by environment and experiences.
  • Memories and traits can be passed transgenerationally in worms, flies, mice, and humans, showcasing the impact of genetic and environmental factors.
  • The conversation addresses the complexities of inheritance, discussing Lamarckian evolution, Darwin's natural selection, and the dangers of misinterpretation like in the case of Kammerer's fraudulent experiments.
  • The Wiseman Barrier, separating soma from germline, is crucial in understanding the transmission of information to subsequent generations, challenging notions of memory inheritance.
  • The study of C. elegans reveals the role of RNA molecules in transmitting acquired traits across generations, offering insights into genetic inheritance mechanisms and the limitations of memory transfer.

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Recent questions

  • What is the Huberman Lab podcast about?

    The Huberman Lab podcast, hosted by Andrew Huberman, focuses on discussing science and tools for everyday life. The podcast aims to provide science-related information to the public for free, covering a wide range of topics related to science and its applications in daily life.

  • What are the key concepts in genetic inheritance?

    Genetic inheritance involves passing on genes from parents to offspring, but it also includes the epigenome, which is influenced by environmental factors and experiences. Memories and traits can be passed on transgenerationally in various organisms, including worms, flies, mice, and humans. Dr. Oded Rechavi explains genetics, the genetic passage of traits, and how experiences can modify genes across generations.

  • How do acquired traits pass to offspring?

    Acquired traits, such as memories and experiences, do not transfer to germ cells but are stored in the brain's synaptic connections. Lamarckian evolution, focusing on acquired traits, has been debunked, with Darwin's natural selection being the correct explanation for evolution. The transmission of acquired traits is complex and controversial, involving terms like epigenetics and transgenerational epigenetics.

  • What are the implications of the Wiseman Barrier?

    The Wiseman Barrier, named after August Wiseman, posits that only the germline can transmit information to the next generation, a fundamental concept in biology. This barrier separates soma cells, excluding germ cells, from transmitting acquired traits. The discussion on environmental influence on germ cells potentially affecting the next generation contrasts with the strict interpretation of the barrier.

  • How do worms inherit resistance to viruses?

    Worms can inherit resistance to viruses through small RNAs, even if they lack the machinery to produce them. Injecting worms with double-stranded RNA leads to gene silencing throughout the body, including germ cells and subsequent generations. The study of C. elegans provides valuable insights into the inheritance of acquired traits through RNA molecules, offering a model for understanding genetic inheritance mechanisms.

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Summary

00:00

Genetics and Epigenetics in Everyday Life

  • Andrew Huberman hosts the Huberman Lab podcast, discussing science and tools for everyday life.
  • Dr. Oded Rechavi, a Professor of Neurobiology at Tel Aviv University, studies genetic inheritance.
  • Genetic inheritance involves passing on genes from parents, but also includes the epigenome, influenced by environment and experiences.
  • Memories and traits can be passed on transgenerationally in worms, flies, mice, and humans.
  • Dr. Rechavi explains genetics, genetic passage of traits, and how experiences can modify genes across generations.
  • The podcast aims to provide science-related information to the public for free.
  • Roka offers high-quality eyeglasses and sunglasses designed for performance.
  • HVMN Ketone IQ is a supplement increasing blood ketones for cognitive and physical performance.
  • Eight Sleep offers smart mattress covers with cooling, heating, and sleep tracking capabilities.
  • DNA contains genetic instructions in every cell, while RNA translates these instructions into proteins. Germ cells contribute to the next generation.

13:08

Inheritance of Acquired Traits: Lamarck vs Darwin

  • Soma cells, excluding germ cells, are crucial for not passing acquired traits to the next generation.
  • Information learned, like architecture, is stored in the brain's synaptic connections, not transferred to germ cells.
  • Muscles built at the gym cannot be inherited by offspring; each generation must work out independently.
  • Every cell in the body has its genome, with the next generation formed by the combination of sperm and egg genomes.
  • The discussion on inheritance of acquired traits is complex and controversial, with various terms like epigenetics and transgenerational epigenetics involved.
  • Lamarckian evolution, focusing on acquired traits, is considered wrong, with Darwin's natural selection being the correct explanation for evolution.
  • Lamarck's belief in the transmission of acquired traits led to dangerous ideas and actions, like those in the Soviet Union under Lysenko.
  • Paul Kammerer's experiments with toads in Vienna, claiming to prove inheritance of acquired traits, were later found to be fraudulent.
  • Kammerer's fraudulent results led to his suicide, with speculation on whether his assistant was involved in the deception.
  • Kammerer's travels to present his findings likely involved showcasing the toads as evidence, despite the fraudulent nature of his experiments.

26:44

Memory Inheritance: Truth, Fraud, and Barriers

  • Oded Rechavi and Andrew Huberman discuss the issue of replication in scientific research, citing examples like Sasai's fraudulent results leading to his suicide.
  • They agree that most scientists seek truth and are honest, even when wrong, attributing errors to various reasons beyond intentional fraud.
  • The conversation shifts to McConnell's controversial experiments with Planaria worms, where he claimed to transfer memories through feeding chopped worms to others.
  • McConnell's work attracted attention and led to further experiments in memory transfer, including breaking down animals into different fractions to identify the memory-transmitting element as RNA.
  • Despite initial popularity, McConnell's work was later dismissed as pseudoscience, with barriers like the Wiseman Barrier separating soma from germline explaining why memory inheritance is unlikely.
  • The Wiseman Barrier, named after August Wiseman, posits that only the germline can transmit information to the next generation, a fundamental concept in biology.
  • Wiseman's idea of environmental influence on germ cells potentially affecting the next generation is discussed, contrasting with the strict interpretation of the barrier.
  • The conversation delves into the theoretical and practical implications of memory inheritance, highlighting the complexities and barriers involved in such processes.

39:19

"Epigenetics: Inheritance Beyond DNA, Environmental Influence"

  • Sailing involves a sail open, powered by wind, not an engine.
  • Natural selection plays a role in organisms breaching barriers.
  • Epigenetics, defined by Conrad Weddington in the 40s, involves gene interactions influencing development.
  • DNA bases (A, T, G, C) can be chemically modified, like cytosine methylation.
  • Modifications of DNA and histone proteins affect gene accessibility and expression.
  • Epigenetics involves mechanisms like methylation, acetylation, and serotoninlation.
  • Epigenetic inheritance occurs across cell divisions or generations through mechanisms beyond DNA changes.
  • Epigenetic reprogramming erases most modifications between generations, preserving genetic instructions.
  • Imprinting, a form of epigenetic inheritance, affects gene expression based on parental origin.
  • Environmental factors can influence offspring traits, but distinguishing between genetic and epigenetic inheritance is crucial.

54:02

Generational effects of stress, diet, and genetics

  • Stressing males can be done in various ways, such as separating them from their mothers or subjecting them to social defeat, resulting in subsequent generations showing reduced stress and anxiety levels.
  • While the threshold for stress may increase in these generations, they might experience memory deficits and metabolic issues.
  • Exposure to nicotine in one generation can lead to increased tolerance to similar drugs in the next generation, even if using an antagonist to block nicotine receptors.
  • Nicotine's impact on systems like cholinergic, dopaminergic, and epinephrine may explain the crossover effect on tolerance to other drugs like cocaine and amphetamine.
  • Starving worms can lead to longer lifespans in subsequent generations, but this may come at the cost of reduced fertility and health.
  • A cult in San Diego aimed at living longer through caloric restriction, castration, and other extreme measures, ultimately ending tragically.
  • Overeating shortens lifespan, with examples like big-bodied species living shorter lives compared to smaller ones.
  • Environmental factors like overfeeding or starving parents can affect body weight, glucose tolerance, and reproductive success in the next generation.
  • The transmission of genetic information through sperm and eggs can be influenced by the environment, affecting metabolism and development.
  • Studies on epigenetic inheritance through IVF and embryo transfer aim to separate genetic inheritance from environmental factors, challenging traditional beliefs and requiring more extensive research.

01:07:23

"Model organisms predict offspring traits and health"

  • Selecting for traits like reliability can predict nurturing ability and potentially offspring traits.
  • Biological traits like immune function may be selected for without direct evidence.
  • Mechanisms like RNA transmission between generations are crucial in mammalian biology.
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  • Model organisms like C. elegans are essential in understanding basic cell functions.
  • Model organisms include E. coli, phage, flies, worms (C. elegans), zebrafish, mice, and plants.
  • Model organisms share evolutionary history with humans, aiding in studying human health.
  • C. elegans, a model organism, has 959 cells, including 302 neurons, with a mapped connectome.
  • C. elegans offers transparency, genetic control, and rapid generation time for neuroscience research.

01:20:30

"RNA inheritance in C. elegans study"

  • C. elegans has a short generation time of three days, allowing for multiple generations within a PhD study.
  • Each worm produces hundreds of genetically identical progeny, providing robust statistical data for experiments.
  • Worms efficiently defend against viruses using RNA molecules, specifically small RNAs that destroy viruses.
  • The mechanism of RNA interference, discovered by Andrew Fire and Craig Mello, regulates gene expression through small RNAs.
  • Injecting worms with double-stranded RNA leads to gene silencing throughout the body, including germ cells and subsequent generations.
  • Worms can inherit resistance to viruses through small RNAs, even if they lack the machinery to produce them, showcasing transgenerational inheritance.
  • In experiments, worms infected with a virus pass on small RNAs to their offspring, enabling resistance to the virus without the ability to produce small RNAs themselves.
  • RNA sequencing confirms the inheritance of specific small RNAs matching the viral genome in descendants of infected worms.
  • The specificity of inherited small RNAs indicates a targeted and specific mechanism of transgenerational resistance.
  • The study of C. elegans provides valuable insights into the inheritance of acquired traits through RNA molecules, offering a model for understanding genetic inheritance mechanisms.

01:34:20

Inherited Stress Resistance in Mammals

  • Stress in one generation of mammals can lead to offspring with a higher stress threshold, potentially advantageous for survival.
  • Evolution prioritizes offspring over parents, with species aiming to reproduce and protect their young.
  • RNA in mammals, like in worms, may play a role in transmitting stress protection or harmful effects across generations.
  • Worms have a mechanism involving RNA-dependent RNA polymerase to amplify small RNAs, ensuring they are not diluted and passed on for multiple generations.
  • Genes like MoTeC genes regulate the duration of inherited effects, preventing them from lasting forever.
  • Met-2 gene functions in methylation of proteins condensing DNA, affecting the duration of inherited traits.
  • In worms, inherited traits typically last for three to five generations, possibly adapting to environmental changes.
  • Starving worms can pass on resistance to harsh starvation to subsequent generations, potentially adaptive.
  • Epigenetic inheritance is well-established in plants, where acquired traits can be passed down.
  • Stress and reward systems in humans are generic and can be passed down through generations, potentially advantageous for survival and reproduction.

01:47:14

Inheritance of Memories: Brain vs Molecular Nature

  • Stress, ice cream, sex, weather, and famine all impact biological systems, particularly the nervous system.
  • COVID-19 resilience may not be specific but could lead to general virus resilience.
  • In C. elegans, RNA inheritance can result in specific or general responses.
  • The ability to inherit memories, especially brain-encoded ones, raises questions about the bandwidth of inheritance.
  • The brain's capacity for specific and elaborate memories contrasts with the molecular nature of heritable information.
  • The challenge lies in translating neural circuit information into heritable molecular form.
  • The brain's synaptic information contrasts with heritable molecular information, posing a barrier to memory transfer.
  • Specific memories may not transfer transgenerationally due to the brain's unique language and wiring differences.
  • Changes in small RNAs in a worm's brain can alter behavior in subsequent generations without directly affecting their brains.
  • The gene SAGE-2 plays a role in this transgenerational behavior change through the germ cells, requiring RNA transfer between generations.

02:00:31

"Germ cells impact soma through secretion"

  • Germ cells impact the soma, including the brain, through chemical secretion and developmental changes.
  • In mammals, heritable information can affect early development stages.
  • Worms maintain heritable information through small RNA amplification.
  • Perturbations in early development can lead to metabolic issues and health problems.
  • Germ cells in males (sperm) and females (eggs) influence the entire body through hormone secretion.
  • The microenvironment of germ cells influences somatic cell development.
  • Puberty signifies a significant transformation in somatic cells influenced by germ cells.
  • Castration in dogs can alter personality and health, with testosterone therapy reversing changes.
  • Worms self-fertilize to maintain genetic integrity but mate to diversify their genome.
  • Stress in worms can lead to increased mating with males due to compromised sperm production.

02:12:33

"DNA Repair, Three-Parent IVF, Memory Modification"

  • Sperm are generated every 60 days, and damage at the germ cell level may result from defective DNA repair machinery in older individuals.
  • Various types of DNA repair mechanisms exist, including those using other DNA copies for correction and those recognizing and removing DNA lesions.
  • The concept of three-parent IVF involves using the nucleus from the mother, the sperm from the father, and the cytoplasm from a younger woman with healthy mitochondrial DNA to produce healthy embryos.
  • Mitochondrial damage in older females can lead to chromosomal abnormalities in embryos, necessitating the use of three-parent IVF for successful pregnancies.
  • The potential for modifying DNA repair machinery through pharmacology is being explored, although specific drugs for this purpose are not yet known.
  • Exercise and manipulating RNA composition are suggested methods to potentially alter heritable traits before resorting to genetic modifications.
  • Cold exposure in C. elegans has been found to impact memory within one generation, with worms placed on ice exhibiting extended memory retention.
  • Acclimating worms to lower temperatures before placing them on ice increases their cold tolerance and affects memory kinetics.
  • Genes expressed in specific neurons in C. elegans play a role in memory extension, with these neurons being sensitive to lithium, a drug used in treating bipolar disorder.
  • Research on the effects of lithium on memory extension in worms is ongoing, with potential implications for understanding its impact on human brains.

02:25:08

Cold and Lithium Boost Memory in Worms

  • Worms exposed to cold and lithium exhibit extended memory retention compared to control worms.
  • Lithium can toggle the forgetfulness mechanism in cold-tolerant worms on and off.
  • Historical method involved throwing children into cold water to enhance memory retention by triggering adrenaline release.
  • The memory-enhancing effect of adrenaline release applies to various types of information.
  • The mechanism behind the role of lithium and cold in memory experiments involves a general state switch.
  • The discussion with Dr. Oded Rechavi delves into genetics, inheritance, the epigenome, and transgenerational traits.
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