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

In the fascinating world of neurobiology, Dr. Oded Rechavi stands out not only for his groundbreaking research but also for his humorous approach to science communication. His laboratory delves into the complexities of genetic inheritance, exploring how our genes, passed down from our parents, shape who we are and how we experience life. But it’s not just about the genes we inherit; the epigenome plays a crucial role too. This layer of biological data is influenced by our environment and experiences, potentially altering our genetic makeup and even allowing memories to be passed down through generations.

Dr. Rechavi’s work raises intriguing questions about the nature of inheritance. For instance, while eye color is a trait directly passed down from our parents, knowledge is not. This is because knowledge and other acquired traits, such as muscle growth, do not alter the germ cells responsible for passing genetic information to the next generation. The conversation around the inheritance of acquired traits is a controversial one, with historical figures like Lamarck and Darwin offering differing views on the subject. Despite the rarity of such inheritance in nature, there are dramatic cases that suggest it’s possible, though often misunderstood or misrepresented.

The early 20th-century experiments of Paul Kammerer on midwife toads, for example, sparked controversy over whether acquired traits could indeed be passed on. Kammerer’s claims, which were later accused of being fraudulent, led to his tragic suicide. His story, along with other instances of scientific fraud, underscores the integrity of most scientists who are driven by the pursuit of truth.

In the realm of epigenetics, the inheritance of acquired traits is a hot topic. There are significant barriers to this process, such as the separation of somatic cells from germ cells and the extensive epigenetic reprogramming that occurs between generations. This reprogramming is akin to resetting to the original genetic instructions, much like returning to the original manual for assembling IKEA furniture. However, certain phenomena like imprinting, where inheritance from one parent can have a unique impact, show that epigenetic inheritance is indeed a reality.

The interplay between nature and nurture can be perplexing, with epigenetic inheritance suggesting that parental environments can influence the traits of their offspring. This is seen in various examples, from periods of famine affecting future generations to stress in male mice leading to offspring with altered anxiety levels. These biological mechanisms are often complex and can result in trade-offs, such as a longer lifespan paired with decreased fertility.

Epigenetic effects can even span multiple generations, as seen in studies using in-vitro fertilization (IVF) to investigate heritable information. Despite resistance and controversy, larger studies are needed to fully understand the extent of these effects. Interestingly, RNA molecules have emerged as potential carriers of information between generations, offering a new perspective on inheritance.

Model organisms like bacteria, flies, worms, and fish have been instrumental in advancing our understanding of human health and genetics. The humble C.elegans worm, with its fixed number of cells and neurons, has been particularly useful for studying neural connections and functions. Dr. Rechavi’s experiments on C.elegans have confirmed the inheritance of acquired traits, such as transgenerational resistance to viruses, mediated by small RNAs.

These small RNAs, which can silence messenger RNAs and prevent protein production, are a key part of the RNA interference mechanism. This discovery, which earned Andrew Fire and Craig Mello a Nobel Prize, has profound implications for therapeutic applications and our understanding of gene function. In C.elegans, these RNA molecules can be passed down to offspring, providing them with protection against specific viruses.

The implications of this research extend to mammals as well. For example, a higher stress threshold can be passed on to offspring, which is advantageous for reproduction. In worms, the transmission of resistance to viruses through RNAs affects multiple generations, thanks to a machinery that amplifies small RNAs. However, genes like MoTeC regulate the duration of inheritance to prevent it from lasting indefinitely.

The transmission of traits across generations is not just about survival; it’s also about preparing for common challenges like pathogens and viruses. While the specifics of stress and reward responses in the human nervous system may be generic, the inheritance of traits related to stress resilience and reward anticipation could be advantageous.

When it comes to memory, the situation is more complex. While C.elegans can inherit downregulation of genes through RNAs, the transfer of memories through brain activity is unlikely. The brain’s information is synaptic, and translating this into a heritable molecular form is a significant challenge. However, manipulating small RNAs in the brain can alter behavior in subsequent generations, affecting gene expression in the germline.

Germ cells, which contain inheritable information, can influence the soma, including the brain. They secrete chemicals that affect other cells and the organism’s development. Small changes in RNA or the placenta early in development can have long-term effects on metabolism and health. Experiments on worms and even castrated dogs have shown that germ cells and hormones can change behavior and personality.

In the case of hermaphrodite worms, they can choose between self-fertilization and mating with males. Self-fertilization ensures the transmission of an identical genome to the next generation, while mating dilutes the genome. In humans, inbreeding can lead to harmful mutations. Interestingly, in stressful conditions, hermaphrodite worms secrete a pheromone to attract males, increasing the chances of interaction and mating.

The topic of autism also comes into play, with discussions about the spectrum and the potential genetic factors involved. Children of older fathers, for example, have a higher chance of being on the autism spectrum, possibly due to germ cell damage or less effective DNA repair mechanisms. Understanding the role of RNA and DNA repair could lead to diagnostics and interventions in fertility.

Finally, Dr. Rechavi’s experiments on C.elegans have shed light on the relationship between cold exposure and memory. Worms taught to dislike a certain odor and then exposed to cold temperatures remember for a longer period than usual. This memory extension is linked to specific genes, and manipulating these genes can further extend memory. These findings, though not yet peer-reviewed, offer exciting insights into the nature of memory and its potential implications for humans.

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Link to podcast: https://www.youtube.com/watch?v=CDUetQMKM6g

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