Memory Transmission & Monarch Butterflies
Carl Jung (1875-1961)[1] used the term “collective unconscious” to describe inherited wisdom and intuition from the past.[2] Evidence of the intergenerational effects of trauma have been found in populations affected by subjugation, genocide, racism and war.[3] This raises the question of how these memories are transmitted and whether there are biological mechanisms that enable the transmission of this information beyond environmental upbringing.
In nature, an example of inherited memory might be seen in monarch butterflies who take three generations to return from Mexico to Canada; the last generation knowing the route without any living members having previously been there.[4] Whether the inherited memories that have been demonstrated in cells, worms and butterflies can be extended to mammals has become a growing area of interest to researchers in recent decades.[5] In 2013, researchers at Emory University showed that mice are capable of passing the fear of a specific scent (a smell similar to a cherry blossom) down to future generations, via their sperm.[6] This process (which takes place through a mechanism referred to as “transgenerational epigenetic inheritance,”) has led many scientists to jump to exciting conclusions as to how this research might be applied to the transmission of memories between generations of humans.[7] Yet researchers are still working to understand the intertwined relationship between epigenetics and genetics.[8]
Transgenerational Epigenetic Inheritance
There are a growing number of studies indicating that trauma may be able to be passed down through epigenetics,[9] which is the study of how the environment and people’s behavior can change the way genes work.[10] In genetic research, however, the environment is used as a general term to refer to anything other than genetics (which may include a person’s actions, the actions of others and the general, physical world).[11]
The term epigenetics is commonly used to refer to two concepts:[12]
1) The ways that packaging or modification of DNA results in the transmission of information within a group of cells (a theory widely accepted by science).
2) The ways that packaging or modifications of DNA might result in transmitting information from one generation to the next (a newer theory not as well established).
Epigenetic changes are reversible (unlike genetic changes) and they do not change a DNA sequence, but rather how the body reads the DNA sequence.[13] In epigenetics, the gene is not changed or damaged, instead the mechanisms of expression (when a gene is converted into functioning proteins) is altered.[14] These changes can affect gene expression by turning genes “on” and “off.”[15] Such molecular pathways with the potential to act epigenetically include histone modifications, DNA methylation, small RNAs and protein-protein interactions.[16]
It is believed that modifications to genetic expression may help an organism to respond to a changing environment and also help its descendants increase their likelihood of surviving.[17] When discussing how information is passed through generations, intergenerational change refers to changes that take place in one generation, whereas transgenerational changes are inherited from two or more generations.[18] Epigenetic transgenerational inheritance therefore refers to inheritance from an environmental exposure (e.g., the effects of an endocrine disruptor such as BPA or DDT) that alters the genetic programming of the germline with the changes transmitted between generations in the absence of direct exposure.[19]
Nonhuman Examples
In nonhuman species, research supports the notion that memories may be transmitted through multiple generations. Erickson (2020) found that the eggs of chickens originally domesticated in the red jungle fowl of Southeast Asia over 4,000 years ago (that later biologically adapted to the higher elevations of Tibet 1,200 years ago) were able hatch eggs when incubated in the lowland environment of their ancestral past unlike a control group of eggs that did not show the same adaptability.[20] Research on worms has also shown specific genes called the Modified Transgenerational Epigenetic Kinetics (MOTEK) are involved with turning epigenetic transmissions through RNA on or off.[21] Similarly, plants also appear to be particularly prone to transgenerational epigenetic inheritance through heritable changes in DNA methylation.[22] These findings raise the question as to whether comparable results can be found in mammals.
Lessons from Mice
In mice, studies have shown that a traumatic event could alter sperm that may affect the behavior of future generations.[23] Dias & Ressler (2014) found that by exposing mice to an odor and associating it with fear before conceiving the next generation of mice, the following two generations showed increased behavioral sensitivity to the same odor.[24] Similar initial research conducted by Gapp (2018) indicated that inheritance of specific trauma symptoms can be transmitted through alterations to long RNA in sperm through several generations in mice.[25] Mukherjee et al. (2018) evaluated five immediate-early genes in mice after memories were stored of either a positive or negative experience and found that the expressions were so unique for each that they could predict which experience the mouse had undergone by simply looking at the gene expression; suggesting the activation profile for each gene can contain information about experiences they have undergone.[26] These examples provide a framework of how environmental information could potentially be passed down through generations at the epigenetic, behavioral and neuroanatomical levels.[27]
To evaluate whether epigenetic changes resulting from environmental exposures could be reversed, Aoued et al. (2019) established fear in mice through olfactory cue-based fear conditioning and then sought to reverse the effects.[28] They did this by training the first generation of mice to associate the odors of either acetone or Lyral with mild foot shocks. They then extinguished this fear by providing odor-only exposure without the presentation of electric shocks. The results showed that first generation offspring did not show behavior sensitivity to the two odors. These findings provide hope for potential therapies in the future that may provide methods for reversing the influence of parental stress in both offspring and the parental germline.[29]
Human Applications
Though environmentally-induced changes passed from one generation to the next are observed relatively often in plants, it has remained elusive in mammals and even more difficult to find in humans.[30] The working memory that human beings, jumping spiders, archerfish and honeybees all possess involve similar genes that are believed to be inherited from the last common ancestor over 600 million years ago.[31] However, the study of transgenerational epigenetic inheritance in humans is difficult to isolate due to the confounding of ecological, genetic and cultural inheritance.[32] Since parental trauma is sometimes linked to childhood emotional abuse, it can be difficult for researchers to disentangle whether the experiences of parents are transferred to offspring as a result of genetics or through lived experiences.[33] With a newly sparked interest on whether epigenetics explains generational trauma, research has been conducted on descendants of abused prisoners from the American Civil War, children in the womb during the Dutch Hunger Winter, and Holocaust survivors.[34] However, within any traumatic situation, the effects may depend on the severity of the trauma, the age of an individual during the event, and whether the trauma was an isolated event or a reoccurring one.[35]
When discussing intergenerational memories in humans, it is important to differentiate between the concepts of transgenerational epigenetically inherited memories and collective memories. Collective memories are the shared remembrance or interpretation of facts about social groups which a person belongs (such as the person’s ethnic group or country) and may range from a national to a global level.[36] However, collective memories have been shown to change with time based on societal perception (e.g., older Americans alive during World War II remember the bombing of Hiroshima as a positive event that ended the war whereas younger Americans view it as a negative event because thousands of innocent civilians were killed).[37] Epigenetic transgenerational memories would be affected by different mechanisms and would not necessarily reflect the same changes as collective memories.
Lessons From Survivors and Their Descendants
To determine whether the epigenetic mechanisms of intergenerational transmission of stress effects can be found in humans, Yehuda et al. (2015) analyzed a specific gene encoding (epigenetic changes in FKBP5 methylation) in Holocaust survivors and their offspring with comparable parent/offspring control groups.[38] Their work found epigenetic alterations in both the exposed parent and offspring that were associated with preconception parental trauma. These findings were believed to be the first evidence in humans of an association between preconception stress effects and epigenetic changes in exposed parents and their adult offspring. Researchers believe these findings may contribute to an increased risk for psychopathology in the offspring of highly traumatized individuals.[39]
Alterations to the sperm of adult men has already been found to take place due to diet, alcohol, smoking, age and toxic exposure.[40] Costa et al. (2018) conducted research looking at children born after the Civil War who survived to age 45, comparing those whose fathers were POWs compared to those whose fathers were non POW veterans of the war. They also compared children born before and after the war in the same family by paternal ex-POW status. Though they did not find any impact of POW status on daughters, they found that sons of ex-POWs who experienced the camps during the harshest conditions were 1.11 times more likely to die than the sons of non POWs even after accounting for family structure, socioeconomic status, quality of marriage, maternal effects, and father-specific survival traits concluding that the findings were most consistent with an epigenetic explanation. However, they were not able to disentangle whether these epigenetic results were due to the stress of captivity or the effects of starvation.[41]
Future Research and Challenges
The University of Zurich’s Laboratory for Neuroepigenetics, run by Professor Isabel Mansuy, conducts research focused on determining molecular and cellular processes underlying how life experiences may influence physical and mental health across generations.[42] The laboratory not only conducts original research pioneering an understanding of transgenerational epigenetic inheritance in mice, but also conducts collaborative studies with clinicians in Europe and Asia to research the relevance as it relates to trauma patients in humans.[43] Professor Mansuy explains that trauma not only affects a person’s brain but also their reproductive system, which could cause depression or borderline personality disorder to be a trait inherited from parents.[44]
Challenges to studying environmentally-induced inheritance in humans include the nonexistence of four generations of human epidemiological cohorts and the ethical considerations of human experimentation.[45] A female fetus growing in the mother’s womb already contains the full complement of eggs, which means the DNA of future grandchildren is already present in a pregnant mother, so that it could take up to four generations to study true trans-generational inheritance in females.[46] In males, these changes could be seen in the next generation, since sperm is continually being produced.[47]
In terms of evolution, the transmission of epigenetic information in a fast-producing animal population could assist that species in rapidly adapting to a new environment, but this could become a maladaptive practice if the actual environment does not match that which was anticipated.[48] This may be one reason that the trait is not observed as much in humans who may come across multiple environments in their lifetimes.[49]
Research Riddled With Controversy
While the implications of epigenetic research have been met with enthusiasm by the press and public, there are scientists who heavily contest both the findings and their presentation. The research conducted by Yahuda et al. on Holocaust survivors was heavily criticized by Professor Ewan Birney, Director of the EMBL-European Bioinformatics Institute, for its small sample size (32 people and 8 controls), the tiny subset of genes used and the possibility of other potential causes for the findings.[50]
Similarly, Kevin Mitchell, a neurogeneticist known for speaking up against “neuro-bollocks,” in an interview with Claire McKenna (2020) explained his belief that there will never be accurate biomarkers (e.g., bloodwork, brain scans) for psychiatric or neurological conditions because the conditions are defined at the level of human behavior explaining, “Even if there’s a dynamic neural state that underpins some aspects of psychosis that we both share, the way that state looks in your brain may be very different from the way it looks in my brain…”[51] Mitchell does not find the transmission of trauma through epigenetic mechanisms plausible because it overly simplifies the relationship between psychological traits and genes explaining that a person’s experiences are expressed through changes in neuroanatomy instead of gene expression.[52]
In his blog, Wiring the Brain, Mithell also wrote an entry on May 29, 2018, reviewing what he believed to be the most prominent research on this topic at the time, and provided detailed information on each study as to why he believed them to be invalid (often small sample sizes and lack of predefined hypotheses).[53] In response, Jill Esher (a research philanthropist who funds pilot studies on exposure-induced nongenetic inheritance) posted a rebuttal on Germline Exposure’s website stating, among other things, that Mitchell cherry-picked the human studies he cited and then countered his argument by citing eleven studies illustrating transgenerational effects in humans and over 30 studies of intergenerational nongenetic inheritance in mammals.[54]
Mosche Szys, a professor of pharmacology at McGill University, similarly supported published findings on epigenetic research in mice telling the New York Times (2018) that dismissals of epigenetic theory are premature by explaining that, “The effects we’ve found have been small, but remarkably consistent and significant….This is the way science works. It is imperfect at first and gets stronger the more research you do.”[55]
Yehuda et al. (2018) (authors of the holocaust research criticized above) sought to clarify misconceptions by explaining that sensational media was oversimplifying their findings, obscuring the boundaries between fact and hypothesis and making inferences with implications far beyond the original findings; citing an example from Teen Vogue that cited their study and warned “You can get PTSD from your ancestors.”[56] They also warn that often articles claiming to debunk the notion that trauma is inherited are citing limitations written into the original research paper by the research team and are in fact debunking an over-interpretation of earlier journalists as opposed to the research itself. This led to an additional warning of inaccurately teaching the public that scientists are debunking one another rather than collaborating through the process of critique and correction.[57]
Potential Applications
Professor Mansuy explained during an interview with Jean Mary Zarate (2023), a senior editor at the journal Nature Neuroscience, that modifications to reproductive cells from traumatic experiences may transmit some of the effects of the exposure to children and research in this field could further our understanding of how inheritance can potentially affect psychiatric disorders including depression, anxiety and borderline personality disorder.[58] She explains there is a lot of work to be done in this field before it can be used to help people directly, but understanding that complex diseases like depression may be inherited from parents directly, instead of being related to something a person has done, would be important for psychiatrists and medical practitioners to know.[59]
This field is a budding new area of research and while the potential implications may excite the public, and at times become exaggerated in the media, the science is not yet understood well enough to be applied in the therapeutic setting. Though in the future, as more research emerges, it may be possible to incorporate these findings into techniques such as cognitive behavior therapy (CBT) or acceptance and commitment therapy (ACT) as a multi-pronged approach for addressing the root cause.
While progress in this field may be slow to produce answers, the current lack of understanding of epigenetic transgenerational inheritance does not minimize the reality of generational trauma and collective memories that can be passed down through a variety of other pathways. In addition to the potential for traumatic events that occur through transgenerational epigenetic inheritance, descendants of traumatized individuals may also be affected by the prenatal state of an anxious/symptomatic mother, or trauma affecting a parent’s behavior.[60] If you or someone you know is struggling to process generational trauma, please reach out to a licensed mental health professional (e.g., a psychotherapist, psychologist or psychiatrist) for guidance and support.
Contributed by: Theresa Nair
Editor: Jennifer (Ghahari) Smith, Ph.D.
REFERENCES
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4 Treffert (2015)
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7 Ibid.
8 Spinney L. Epigenetics, the misunderstood science that could shed new light on ageing. The Guardian Web site. https://www.theguardian.com/science/2021/oct/10/epigenetics-the-misunderstood-science-that-could-shed-new-light-on-ageing. Updated 2021. Accessed June 2, 2023.
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10 Center for Disease Control and Prevention, (CDC). What is epigenetics? | CDC. Centers for Disease Control and Prevention Web site. https://www.cdc.gov/genomics/disease/epigenetics.htm. Updated 2022. Accessed May 26, 2023.
11 Birney E. Why I'm sceptical about the idea of genetically inherited trauma. The Guardian Web site. https://www.theguardian.com/science/blog/2015/sep/11/why-im-sceptical-about-the-idea-of-genetically-inherited-trauma-epigenetics. Updated 2015. Accessed June 1, 2023.
12 Ibid.
13 CDC (2022)
14 Benedict C. Can we really inherit trauma? The New York Times Web site. https://www.nytimes.com/2018/12/10/health/mind-epigenetics-genes.html. Updated 2018. Accessed May 26, 2023.
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18 Sarkies (2020)
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20 Erickson J. Past is prologue: Genetic ‘memory’ of ancestral environments helps organisms readapt. University Wire. 2020. Available from: https://www.proquest.com/docview/2405486117?pq-origsite=primo#. Accessed May 14, 2023.
21 Javelosa J. Scientists have discovered how memories are inherited. World Economic Forum Web site. https://www.weforum.org/agenda/2018/12/memories-can-be-inherited-and-scientists-may-have-just-figured-out-how/. Updated 2018. Accessed May 11, 2023.
22 Quadrana L, Colot V. Plant transgenerational epigenetics. Annu Rev Genet. 2016;50:467-491. doi: 10.1146/annurev-genet-120215-035254.
23 Gallagher (2013)
24 Dias BG, Ressler KJ. Parental olfactory experience influences behavior and neural structure in subsequent generations. Nat Neurosci. 2014;17(1):89-96. Accessed May 24, 2023. doi: 10.1038/nn.3594.
25 Gapp K, van Steenwyk G, Germain PL, et al. Alterations in sperm long RNA contribute to the epigenetic inheritance of the effects of postnatal trauma. Mol Psychiatry. 2020;25(9):2162-2174. https://www.nature.com/articles/s41380-018-0271-6. Accessed May 30, 2023. doi: 10.1038/s41380-018-0271-6.
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27 Dias & Ressler (2014)
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29 Ibid.
30 Birney (2015)
31 Earl B. Humans, fish, spiders and bees inherited working memory and attention from their last common ancestor. Frontiers in psychology; Front Psychol. 2023;13:937712. doi: 10.3389/fpsyg.2022.937712.
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33 Yehuda R, Daskalakis NP, Bierer LM, et al. Holocaust exposure induced intergenerational effects on FKBP5 methylation. Biol Psychiatry. 2015;80(5):372-380. doi: 10.1016/j.biopsych.2015.08.005.
34 Benedict (2018)
35 Byrne D. How trauma’s effects can pass from generation to generation. Nature. 2023. https://www.nature.com/articles/d41586-023-01433-y. Accessed May 30, 2023.
36 Roediger H, DeSoto K. The power of collective memory. Scientific American Web site. https://www.scientificamerican.com/article/the-power-of-collective-memory/. Updated 2016. Accessed May 24, 2023.
37 Ibid.
38 Yehuda et al. (2015)
39 Ibid.
40 Costa DL, Yetter N, DeSomer H. Intergenerational transmission of paternal trauma among US civil war ex-POWs. Proc Natl Acad Sci U S A. 2018;115(44):11215-11220. doi: 10.1073/pnas.1803630115.
41 Ibid.
42 University of Zurich (UZ). Laboratory of neuroepigenetics | isabelle mansuy. University of Zurich Web site. http://www.hifo.uzh.ch/en/research/mansuy.html. Accessed May 30, 2023.
43 Ibid.
44 Byrne (2023)
45 Escher J. No convincing evidence? A response to kevin mitchell’s reckless attack on epigenetic inheritance. Germline Exposures Web site. http://www.germlineexposures.org/1/post/2018/07/no-convincing-evidence-a-response-to-kevin-mitchells-reckless-attack-on-epigenetic-inheritance.html. Updated 2018. Accessed Jun 2, 2023.
46 Birney (2015)
47 Ibid.
48 Horsthemke (2018)
49 Ibid.
50 Birney (2015)
51 McKenna C. Kevin mitchell. BJPsych Bull. 2020;44(2):81-83. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7283122/. doi: 10.1192/bjb.2020.18.
52 Ibid.
53 Mitchell K. Grandma’s trauma – a critical appraisal of the evidence for transgenerational epigenetic inheritance in humans. . 2018. http://www.wiringthebrain.com/2018/05/grandmas-trauma-critical-appraisal-of.html. Accessed Jun 5, 2023.
54 Escher (2018)
55 Benedict (2018)
56 Yehuda et al. (2018)
57 Ibid.
58 Byrne (2023)
59 Ibid.
60 Yehuda et al. (2018)