(Roughly) Daily

As the redoubtable Claire L. Evans [and here] reports, a small but enthusiastic group of neuroscientists is exhuming overlooked experiments and performing new ones to explore whether cells record past experiences — fundamentally challenging our understanding of what memory is…

In 1983, the octogenarian geneticist Barbara McClintock stood at the lectern of the Karolinska Institute in Stockholm. She was famously publicity averse — nearly a hermit — but it’s customary for people to speak when they’re awarded a Nobel Prize, so she delivered a halting account of the experiments that had led to her discovery, in the early 1950s, of how DNA sequences can relocate across the genome. Near the end of the speech, blinking through wire-framed glasses, she changed the subject, asking: “What does a cell know of itself?”

McClintock had a reputation for eccentricity. Still, her question seemed more likely to come from a philosopher than a plant geneticist. She went on to describe lab experiments in which she had seen plant cells respond in a “thoughtful manner.” Faced with unexpected stress, they seemed to adjust in ways that were “beyond our present ability to fathom.” What does a cell know of itself? It would be the work of future biologists, she said, to find out.

Forty years later, McClintock’s question hasn’t lost its potency. Some of those future biologists are now hard at work unpacking what “knowing” might mean for a single cell, as they hunt for signs of basic cognitive phenomena — like the ability to remember and learn — in unicellular creatures and nonneural human cells alike. Science has long taken the view that a multicellular nervous system is a prerequisite for such abilities, but new research is revealing that single cells, too, keep a record of their experiences for what appear to be adaptive purposes.

In a provocative study published in Nature Communications late last year, the neuroscientist Nikolay Kukushkin and his mentor Thomas J. Carew at New York University showed that human kidney cells growing in a dish can “remember” patterns of chemical signals when they’re presented at regularly spaced intervals — a memory phenomenon common to all animals, but unseen outside the nervous system until now. Kukushkin is part of a small but enthusiastic cohort of researchers studying “aneural,” or brainless, forms of memory. What does a cell know of itself? So far, their research suggests that the answer to McClintock’s question might be: much more than you think…

[Evans explains the prevailing wisdom, outlines the experiments that have challenged it, and unpacks (at least some reasons for) resistance to the notion of cellular-scale memory, both sociological and semantic…]

… In neuroscience, [biochemist and neuroscientist Nikolay] Kukushkin writes, the most common definition of memory is that it’s what remains after experience to change future behavior. This is a behavioral definition; the only way to measure it is to observe that future behavior. Think of S. roeselii snapping back into its holdfast, or a lab rat freezing up at the sight of an electrified maze it’s tangled with before. In these cases, how an organism reacts is a clue that prior experience left a lingering trace.

But is a memory only a memory when it’s associated with an external behavior? “It seems like an arbitrary thing to decide,” Kukushkin said. “I understand why it was historically decided to be that, because [behavior] is the thing you can measure easily when you’re working with an animal. I think what happened is that behavior started as something that you could measure, and then it ended up being the definition of memory.”

Behavior tells us that a memory has formed but says nothing about why, how or where. Further, it’s constrained by scale. Take Aplysia californica, a muscular sea slug with enormous neurons (the largest is about the size of a letter on a U.S. penny). Neuroscientists love to conduct memory experiments on Aplysia because its physical responses are easy to measure — poke it and it flinches — and they map cleanly to the handful of sensory and motor neurons involved.

The sea slug, Kukushkin said, can complicate neuroscience’s behavioral bias. Say you shock its tail, triggering a defensive reflex. If you shock it again the next day and find that the defensive reflex is stronger than it was before, that’s behavioral evidence that the slug remembers its initial shock. Any neuroscientist would associate it with a memory.

But what if (apologies to the squeamish) you take that sea slug apart and leave only its immobile neurons? Unlike the intact creature, the neurons can’t retract, so there will be no visible response. Is the memory gone? Certainly not, but without external validation, a behavioral definition of memory breaks down. “We no longer call that a memory,” Kukushkin said. “We call that a mechanism for a memory, we call that synaptic change underlying memory, we call that an analogue of memory. But we don’t call that a memory, and I think that it’s arbitrary.”

Perhaps a definition of memory should extend beyond behavior to encompass more records of the past. A vaccination is a kind of memory. So is a scar, a child, a book. “If you make a footprint, it’s a memory,” Gershman said. An interpretation of memory as a physical event — as a mark made on the world, or on the self — would encompass the biochemical changes that occur within a cell. “Biological systems have evolved to harness those physical processes that retain information and use them for their own purposes,” [cognitive scientist Sam] Gershman said.

So, what does a cell know of itself? Perhaps a better version of Barbara McClintock’s question is: What can a cell remember? When it comes to survival, what a cell knows of itself isn’t as important as what it knows of the world: how it incorporates information about its experiences to determine when to bend, when to battle and when to make a break for it.

A cell preserves the information that preserves its existence. And in a sense, so do we. As today’s cellular memory researchers revisit abandoned experimental threads from the past, they too are discovering what memory owes to its context, how science’s sociological environment can determine which ideas are preserved and which are forgotten. It’s almost as though a field is waking up from a 50-year spell of amnesia. Fortunately, the memories are flooding back…

“What Can a Cell Remember?” from @theuniverse.bsky.social‬ in @quantamagazine.bsky.social‬.

For more on the work that got Barbara McClintock onto the Nobel podium see here.

And, also apposite, a pair of cautionary historical examples of scientists who followed Jean-Baptiste Lamarck, who argued in the early 19th century that an organism can pass on to its offspring physical characteristics that the parent organism acquired through use or disuse during its lifetime– that’s to say that learning (a kind of memory) is heritable… and went astray: Lysenko and Kammerer.

* James Gleick, The Information

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As we muse on memory (and note that one cannot remember– and learn from– what one cannot know), we might recall that it was on this date in 1735 that New York Weekly Journal publisher and writer John Peter Zenger was acquitted of seditious libel against the royal governor of New York, William Cosby, on the basis that what he had published was true.

In 1733, Zenger had begun printing The New York Weekly Journal, voicing opinions critical of the colonial governor.  On November 17, 1734, on Cosby’s orders, the sheriff arrested Zenger. After a grand jury refused to indict him, the Attorney General Richard Bradley charged him with libel. Zenger’s lawyers, Andrew Hamilton and William Smith, Sr., successfully argued that truth is a defense against charges of libel… and Zenger became a symbol for freedom of the press.