The Forgetting Pill

Canst thou not minister to a mind diseas’d,
Pluck from the memory a rooted sorrow,
Raze out the written troubles of the brain,
And with some sweet oblivious antidote
Cleanse the stuff’d bosom of that perilous stuff
Which weighs upon the heart?
-Macbeth

I've got a new article in Wired this month on the brave new world of memory erasure. The piece focuses on the confluence of two seemingly unrelated threads of research. The first important discovery has been the ubiquity of memory reconsolidation, which refers to the process by which our memories get rewritten every time they are remembered. Here's how I summarize memory reconsolidation in the article:

I can recall vividly the party for my eighth birthday. I can almost taste the Baskin-Robbins ice cream cake and summon the thrill of tearing wrapping paper off boxes of Legos. This memory is embedded deep in my brain as a circuit of connected cells that I will likely have forever. Yet the science of reconsolidation suggests that the memory is less stable and trustworthy than it appears. Whenever I remember the party, I re-create the memory and alter its map of neural connections. Some details are reinforced—my current hunger makes me focus on the ice cream—while others get erased, like the face of a friend whose name I can no longer conjure. The memory is less like a movie, a permanent emulsion of chemicals on celluloid, and more like a play—subtly different each time it’s performed. In my brain, a network of cells is constantly being reconsolidated, rewritten, remade. That two-letter prefix changes everything.

The second important thread has been continued progress on the short list of molecules that are responsible for the maintenance of long-term memories. In the piece, I focus on PKM-zeta, first discovered by Todd Sacktor and colleagues and SUNY-Downstate Medical Center:

What does PKMzeta do? The molecule’s crucial trick is that it increases the density of a particular type of sensor called an AMPA receptor on the outside of a neuron. It’s an ion channel, a gateway to the interior of a cell that, when opened, makes it easier for adjacent cells to excite one another. (While neurons are normally shy strangers, struggling to interact, PKMzeta turns them into intimate friends, happy to exchange all sorts of incidental information.) This process requires constant upkeep—every long-term memory is always on the verge of vanishing. As a result, even a brief interruption of PKMzeta activity can dismantle the function of a steadfast circuit.

If the genetic expression of PKMzeta is amped up—by, say, genetically engineering rats to overproduce the stuff—they become mnemonic freaks, able to convert even the most mundane events into long-term memory. (Their performance on a standard test of recall is nearly double that of normal animals.) Furthermore, once neurons begin producing PKMzeta, the protein tends to linger, marking the neural connection as a memory. “The molecules themselves are always changing, but the high level of PKMzeta stays constant,” Sacktor says. “That’s what makes the endurance of the memory possible.”

For example, in a recent experiment, Sacktor and scientists at the Weizmann Institute of Science trained rats to associate the taste of saccharin with nausea (thanks to an injection of lithium). After just a few trials, the rats began studiously avoiding the artificial sweetener. All it took was a single injection of a PKMzeta inhibitor called zeta-interacting protein, or ZIP, before the rats forgot all about their aversion. The rats went back to guzzling down the stuff.

Now here's where things get interesting (and frightening). By coupling these amnesia cocktails to the memory reconsolidation process, it’s possible to erase particular memories, at least in rodents.

Nader, LeDoux, and a neuroscientist named Jacek Debiec taught rats elaborate sequences of association, so that a series of sounds predicted the arrival of a painful shock to the foot. Nader calls this a “chain of memories”—the sounds lead to fear, and the animals freeze up. “We wanted to know if making you remember that painful event would also lead to the disruption of related memories,” Nader says. “Or could we alter just that one association?” The answer was clear. By injecting a protein synthesis inhibitor before the rats were exposed to only one of the sounds—and therefore before they underwent memory reconsolidation—the rats could be “trained” to forget the fear associated with that particular tone. “Only the first link was gone,” Nader says. The other associations remained perfectly intact. This is a profound result. While scientists have long wondered how to target specific memories in the brain, it turns out to be remarkably easy: All you have to do is ask people to remember them.

The larger point is that even our sturdiest recollections turn out to be exceedingly fragile. Given the heavy toll exacted by traumatic memories - life overflows with sorrow - it's not hard to imagine a near future (5 years? 10 years? 20 years?) in which people begin experimenting with these newfangled forms of memory erasure. (Cognitive enhancers get all the ethical attention, but the inhibition of learning and memory seems to be, in many respects, a less formidable technical challenge. It's always easier to break something than to fix it.) Before long, the act of remembering will become a choice.

I'll blog more about the article, related research and these ethical issues over the next week. Thanks for reading.