The idea that you can inherit the memories of your ancestors seems preposterous, yet somehow intriguing.
In November 2018, researchers from Princeton University discovered a strange behaviour among roundworms (Caenorhabditis elegans). A tiny roundworm had been trained to avoid a strain of bacteria (of the genus Pseudomonas). It retained the memory of this training throughout its lifetime, and avoided the bacteria whenever it was at risk of encountering it.
Curiously, they found that the next generation of roundworms that the trained mothers had given birth to inherited the memories of their parents’ experiences, and displayed a similar aversion to the bacteria.
Around 30% of the worms’ natural environment is populated by Pseudomonas. So at the outset, this ability to distinguish between pathogenic bacteria, inherited from its ancestors, could save a roundworm’s life.
The brain of a C. elegans worm has precisely 302 neurons. The researchers examined them to uncover the neural basis of this behaviour.
When exposed to the bacteria, a gene called daf-7 was expressed more in some neurons, specifically the ASI and the ASJ neurons in the parent worms.
When they looked at the roundworm’s offsprings, they observed a similarly elevated expression of daf-7 in the ASI neurons. It was a hint that the ASI neurons had something to do with the inheritance of memories.
To further test their hypothesis, the researchers turned to mutants. Mutants are fully functional organisms similar to their counterparts in the wild – but with a specific alteration, either in a particular gene or in a pathway or in a particular cell type. This way, the difference between the mutant and the non-mutant would reflect the role of that particular gene/pathway/cell type in the entire system.
The researchers thus used mutant worms with genetically destroyed ASI, and observed that they learned to avoid the bacteria but their offspring did not show any aversion towards the pathogen. This supported the idea that ASI neurons play a role in transmitting learned behaviour.
“It is important to realise that when you hit genes, you’re just breaking the system,” Veena Prahlad, a researcher working at the intersection of genetics and neurobiology at the University of Iowa, Iowa City, told The Wire. But despite her – and in fact the general – caution, mutants have played an important role in genetics. “This is the only way to try and figure out things.”
As if the offspring inheriting their parents’ memories wasn’t strange enough, the researchers found something mind-boggling when they checked the offsprings’ descendants.
The roundworms inherited the memory across four generations. The great-great-grand roundworms’ brains also showed an increased expression of the daf-7 gene in their ASI neurons.
An adult hermaphrodite C. elegans. Credit: Bob Goldstein, UNC Chapel Hill/Wikimedia Commons, CC BY-SA 3.0
By this time, the researchers knew the ASI neurons were definitely involved. But what exactly were they doing to impart the worms with such abilities?
They wondered if epigenetics was at play. If the study of genes is genetics, then the study of mechanisms that turn these genes ‘on’ and ‘off’ is epigenetics.
They examined a list of epigenetic players that might’ve been involved in manifesting this behaviour across generations. They trained adult worms to avoid the pathogen and then knocked down one epigenetic player at a time in the progeny.
From this experiment, they found a plausible candidate, called prg-1 (an RNA regulator). When knocked out, it did not affect their learning (to avoid the bacteria), but the offspring of a worm so changed didn’t display an aversion towards the pathogen. So it looked like prg-1 may have had an epigenetic role to play in transmitting behaviours from the mother to her descendants.
Kavita Babu, an associate professor and a neurobiologist at IISER Mohali, said that the experiments to come will likely study daf-7 expression in the ASI neurons of the mutant worms.
Prahlad advised caution at this juncture. For one, a memory is not an actual physical entity that’s out there, to be retrieved from some part of the brain. As she put it, “Memory is not a thing. It’s not a genetic thing. It’s not a placeholder. There’s no place in the genome for a memory, or in a cell.”
Instead, memories are only reprocessed and resynthesised. And thinking of memories this way suggests that the worms’ progeny are resynthesising behaviour from their many experiences. Even if some aspects of it might have been recapitulated from the parent, its own memory is unlikely to be exactly the same as its ancestors’.
In fact, this study in toto is at the forefront of our understanding of how behaviour is transmitted down generations. It highlights several interesting questions that will have to be answered – and which we’re far from doing – before we can generalise.
“A broader understanding of memory would provide the context that would allow us to understand the beauty of these studies and their place, their constraints,” Prahlad said. “It is just the beginning of our understanding of how behaviour is inherited, and how it persists.”
Notwithstanding these gaps in our knowledge, and remembering that similar data about humans is far from conclusive, the overarching takeaway from this study is still wonderful. As Erika Hayasaki, a science writer, put it, “It makes for an uncomfortable solace, thinking that the memories of generations before may reside within our genes. It gives us explanations.”
Pratik Pawar is a science writer and a recipient of the S. Ramaseshan science writing fellowship.