Dr. Oded Rechavi

Sponsors: ROKA, HVMN, Eight Sleep

DNA, RNA, Protein; Somatic vs. Germ Cells

Lamarckian Evolution, Inheritance of Acquired Traits

Paul Kammerer & Toad Morphology

AG1 (Athletic Greens)

James McConnell & Memory Transfer

Weismann Barrier; Epigenetics

Epigenetic Reprogramming; Imprinted Genes

Nature vs. Nurture; Epigenetics & Offspring

Generational Epigenetic Inheritance

Sponsor: InsideTracker

Model Organisms, C. elegans

C. elegans & Inheritance of Acquired Traits, Small RNAs

RNA Interference, C. elegans & Virus Immunity

RNA Amplification, Multi-Generational Effects

Response Duration & Environment

Generational Memory Transmission, RNA

Germ Cells & Behavior; Body Cues

Transmission of Sexual Choice

Fertility & Human Disease; 3-Parent In Vitro Fertilization (IVF); RNA Testing

Deliberate Cold Exposure, Learning & Memory

Zero-Cost Support, Spotify & Apple Reviews, YouTube Feedback, Sponsors, Momentous, Social Media, Neural Network Newsletter

This podcast episode discussed the idea of genetic inheritance and epigenetics, which is the way our environment and experiences can change our genome. It also discussed the controversial concept of Lamarckian evolution, which is the inheritance of acquired traits, and the research of Paul Kammerer, who experimented on toads. It also discussed the Wiseman barrier, epigenetics, imprinting, and how environment can affect the next generation. It also discussed the model organism C. elegans, RNA interference, and the research of Andrew Fire and Craig Mello, who won the Nobel Prize in 2006 for discovering small RNA molecules. It also discussed the research of McConnell, Catherine Dulac, and Oliver's lab, as well as the potential for inheritance of acquired traits in mammals. Finally, it discussed the research of Dana Lanshaft, which found that cold exposure can extend memory in C. elegans.

- Genetic inheritance is the idea that we inherit genes from our parents
- Epigenome is the way our environment and experiences can change our genome
- Evidence suggests that memories can be passed from one generation to the next
- Experiences can modify our genes and be passed from our parents to us and across multiple generations
- Dr. Rehavi explains how our genes and different patterns of inheritance shape our experience of life and who we are

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- Exposure of the mother can affect the transmission of genetic information from the father
- Population geneticists are less likely to believe in heritable trauma than psychologists
- Bigger studies are needed to understand the extent of epigenetic inheritance
- Partner selection is driven by subconscious selection of traits related to vigor
- RNA has potential to transmit information between generations

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- Model organisms are organisms that many people work on to learn about biology, including humans
- C. elegans is a model organism that is a small worm, 1mm long, found in rotten fruits and leaves
- It has a fixed number of cells, 302 neurons, and each neuron has a name
- It has a connectome, a map of which neurons talk to each other
- It is transparent, so neurons can be seen firing
- It has a short generation time of 3 days and produces hundreds of progeny
- It is easy to manipulate and study, and does not require a sensitive environment

- C. elegans provides clear proof of inheritance of acquired traits
- Andrew Fire and Craig Mello won Nobel Prize in 2006 for discovering small RNA molecules that regulate genes
- Small RNA molecules find messenger RNA and lead to its destruction
- Drugs now use this mechanism in humans
- Craig Miller is a kite surfer and Andy Fire and Craig Miller are nice people

- RNA interference is a mechanism by which genes can be silenced, and it can spread throughout an organism's body and to its progeny
- McConnell's experiments with planaria can potentially be explained by double-stranded RNA
- Fio and Melo did experiments showing that worms can resist viruses using small RNAs
- Oliver's lab demonstrated that worms can pass on small RNAs to their progeny, even if they don't have the genes to make them
- This small RNA inheritance is specific to the virus the parent was exposed to

- Stress in one generation of mammals may lead to offspring with a higher stress threshold
- RNA-based transmission of stress resilience may be possible in mammals
- Worms have a machinery for amplifying small RNAs to pass on stress resilience for multiple generations
- Genes regulate the duration of the inheritance, typically 3-5 generations
- MET2 is a gene that functions in methylation of proteins that condense the DNA
- Other genes affect production of small RNAs

- Adaptive traits can be passed on to offspring for two generations, as humans typically live between 0-100 years
- Worms typically inherit traits for 3-5 generations, which could be related to their environment
- Plants also show evidence of epigenetic inheritance
- Stress responses are generic and not specific to certain events
- Reward systems are also governed by generic neural circuitry
- Resilience to viruses could be passed on, if it occurs

- Bandwidth of inheritance can be very specific or very general
- Brain activity can be transferred to the next generation in worms, but not in mammals
- Memories encoded in the brain cannot be transferred transgenerationally due to the different languages of the brain and inheritance
- Memories that are very specific may be able to be transferred through the production of small RNAs
- This transfer of information requires a mechanism to translate between the language of the brain and the language of inheritance
- SAGE2 gene works in the germ cells and affects behavior in the next generation

- Changes to the germ cells can affect behavior
- Germ cells contain inheritable information
- Germ cells can secrete chemicals that affect other cells
- Castration of animals can change behavior
- Small RNAs can be amplified in worms to prevent dilution
- In mammals, small RNAs can affect the entire organism by perturbing something in the beginning
- Puberty is a great example of how the microenvironment of the germ cells can affect the rest of the body
- Hormones can modify the system in animals

- Worms are hermaphrodites, but there are also rare males. Mating with males is costly and risky.
- Mating with males dilutes the genome in half, but also diversifies it.
- In humans, incest is avoided to prevent inbreeding and deleterious mutations.
- Worms secrete a pheromone to attract males when their own sperm production is compromised.
- Studies show that older fathers have a higher chance of having autistic children.

- DNA is the genetic instructions contained in every cell of the body, condensed into chromosomes
- RNA is the instructions to make one particular protein based on the entire set of possibilities
- Somatic cells are all the cells that are not germ cells and should not contribute to the next generation
- Germ cells are the only cells that contribute to the next generation
- Acquired traits, memories, etc. cannot be inherited due to the fact that the next generation is only formed from the combination of the genomes in the sperm and the egg

- Autism is on a spectrum and there is a higher probability of offspring being on the spectrum if two people with engineering/hard science backgrounds mate.
- DNA repair machinery is well understood and there are many types of DNA repair.
- Three-parent IVF is used to correct mitochondrial damage or mutations in the mother.
- C. elegans research is ongoing and malleable.
- In the future, diagnostics may be used to look at RNAs and exercise may be used to change the profile of RNAs.

- Dana Lanshaft conducted an experiment to observe the effects of cold exposure on C. elegans memory
- The experiment found that worms placed on ice did not forget the association they had been taught, even after 10 times longer than control worms
- Further research revealed that the memory extension was connected to changes in lipid metabolism and the activity of two out of 302 neurons
- Lithium was found to switch the forgetfulness mechanism on and off
- Medieval people used cold water to instill memory in children
- The mechanism behind this is still unknown, but is thought to involve an RNA-dependent process

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- Lamarckian evolution is a controversial concept of inheritance of acquired traits
- This dates back to Lamarck and the Greeks, and was believed by Darwin
- Lamarckian evolution was heavily rejected due to its association with Lysenko in the Soviet Union, which led to massive starvation and ruin of science
- There have been attempts to prove inheritance of acquired traits, but it is generally accepted that this is not a normal way that inheritance works

- Paul Kammerer was a researcher in Vienna in the early 20th century who experimented on toads
- He claimed he could train them to live underwater and develop black nupital pads on their hands
- He became famous for his discovery, but was later accused of injecting ink into the toads to fake the results
- He killed himself due to the accusations
- 99% of scientists are honest and seek truth, but there are occasional cases of fraud and controversy

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- McConnell was an American psychologist who studied Planaria, a type of flatworm
- He claimed to be able to teach them certain things and transfer memories through feeding
- His research was controversial and could not be replicated
- Recently, a researcher from Boston replicated some of McConnell's experiments
- McConnell also claimed to be able to transfer memories through fractions of the worm, such as DNA, RNA, fats, proteins, and sugars
- His research was popular knowledge and was considered pseudoscience for many years

- Wiseman proposed the separation of the soma from the germline, which is known as the Wiseman barrier
- Epigenetics is the interaction between genes and their products that bring about the phenotype or consequences and how genes influence development
- DNA can be chemically modified, such as methylation, acetylation, and serotonin
- Identical twins can look different due to epigenetic changes or other mechanisms
- Epigenetics is the inheritance of traits across cell division or generations without changes to the DNA sequence
- RNA molecules are the most interesting players in transmitting information across generations

- Epigenetic reprogramming is the process of erasing most of the modifications in the sperm and egg to start a blank slate based on genetic instructions.
- Imprinting is a phenomena where it matters whether a gene is inherited from the mother or father.
- Catherine Dulac's work showed that the maternal or paternal copy of a gene can switch during a person's life.
- Environment does not play a role in imprinting, it is determined by whether it is passed to the mother or father.

- There is a difference between nurture and nature when it comes to heritable material
- Examples of environmental changes that affect the next generation include famine, nicotine exposure, and stress
- These changes can lead to adaptive traits, but also have downsides such as memory deficits and metabolic problems
- There is debate around the idea that caloric restriction can lead to longer life
- Metabolic changes and nutrition can lead to effects in the next generation, with contrasting effects depending on the way it is done

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