Blebbistatin points to new therapeutic options and a few pressing ethical questions.
Image by Nevit via Wikimedia Commons
Last month, scientists at Florida’s Scripps Research Institute announced that they’d developed a treatment capable of selectively erasing the memory of a methamphetamine high in mice. Known as Blebbistatin, the chemical cocktail targets a specific protein used in encoding memories that acts in a strange way while one is on meth. With one dose, Blebbistatin apparently zaps the protein’s aberrant form, exclusively wiping out about 30 days of memories formed while an individual was on meth. The researchers hope that this ability to make targeted erasures of the memories addicts form, which often draw them out of rehab and back to their drug of choice, will help those recovering from meth avoid common relapses, making treatment faster and more effective.
At first blush, this proclamation sounds like a sci-fi revolution—like we’re about to enter the Eternal Sunshine era and should prepare to face the bundle of ethical questions that lie beyond. But in truth, the Blebbistatin breakthrough, while groundbreaking, isn’t as extraordinary as you might think. Scientists have been able to selectively alter and erase memories for decades now. And for at least a decade, researchers have been brewing up functional and targeted memory-based treatments for things like drug abuse and post-traumatic stress disorder, some of which are already available for public use if you know where to look. Blebbistatin is in some ways just the latest in this long chain of developments. But it is a development that marks a new plateau in selective memory erasure, making a strong case for using memory-based solutions as at least one component of addiction treatment in the very near future.
Humans have been messing around with memory alteration ever since we started to figure out how memories were physically created in our brains in the mid-20th century. Although memories are stored across a vast swath of neural areas, only a few chemicals, we learned, are involved in creating the bonds between those areas that facilitate joint activation and the recall of specific events or ideas. Every time a memory is created there is an opportunity to mess with it, as there is every time it is recalled—a chemical and structural explanation for the malleability of our recollections. Blocking these chemicals, knocking them out, or even providing different stimuli during memory recall could alter or completely wipe out memories over time. But for quite a while, the ways by which we did this in animal subjects were crude, invasive, and broad.
Yet just within the past few years there’s been a flurry of new research, mainly focused on drugs that sophisticate and refine the scope of memory erasure technology. In 2011, Israeli researchers figured out how to use a drug to, over the course of two weeks, erode the connection between an event and the memory of a drug fix in mice, although they were unclear what the scope of the effect was beyond drug-based memories. In 2013 and 2014, some researchers started shining laser lights on mice’s neural cells to track memory creation, allowing the scientists to trigger certain emotions from one memory alongside another, potentially overwriting the pain or pleasure of one memory with the opposite. They could create fake memories of, say, pain associated with a once-safe space by firing that place and emotional memory at once. But this approach just rewrote rather than erased memories, and was far too invasive for use in humans. Earlier this year, researchers in Texas also discovered that an in-use high blood pressure medication was able to block a channel used in memory and learning to reverse addiction-fueling memories of reward tied to drugs. But again, this was just altering, not erasing a memory.
While most of these developments are still in animal trials, a few are used regularly in humans. Propofol, or “milk of amnesia,” has been around forever as a means of altogether knocking out the last few minutes of a patient’s memory, but that does little good for eliminating specific memories. More promisingly, researchers have shown that inhaling the relatively harmless gas xenon, a common anesthetic agent, while recalling a traumatic or addiction memory, can break the connection between this memory and linked feelings or associations. At least one Serbian doctor is already offering this memory alteration treatment as a detox cure for humans. And numerous other studies have been conducted on the power of basic narcotics like MDMA or beta-blockers (like propranolol) to block neurotransmitters during memory recall, allowing therapists to help patients rewrite these memories’ associations and lessen the impact of addiction, PTSD, or any other number of memory-based disorders that give humans endless pain.
Authors of the new study included (left to right) Scripps Florida’s Sherri Briggs, Ashley Blouin, Courtney Miller and Erica Young. Image courtesy of Scripps.
But Blebbistatin, the memory drug currently making headlines, one-ups most of these existing theoretical or practical treatments, in that it allows one to knock out an entire drug memory, not just reprogram it. This is a bit of a breakthrough, because previous efforts by the same Scripps team to selectively target and destroy memory-association proteins had a nasty habit of messing with the ability of muscles (including the heart) to properly function. Blebbistatin manages to target meth-related memories without that side effect. And it can do so without one having to directly recall the memory and associated cravings. Using the drug also doesn’t require an invasive procedure—it can be injected into a peripheral body part and still take its full effective course, making it exceptionally versatile, low-impact, and powerful among memory treatments.
That said, the Blebbistatin discovery is not a sign that memory-based cures will be at your pharmacy tomorrow, nor that they are the silver bullet for meth addiction or any other ailment. For one thing, the drug still needs to go into human trials, which researchers suspect could take at least five years. And once there, there’s always only a slim chance that what works for mice will work the same way and just as effectively in our bodies. Plus, we still need to figure out what other drugs or conditions this might interact with and whether it or a related chemical can target memories other than those created on meth (or if meth memories turn out to be a chemically peculiar phenomenon with a powerful but non-transferrable memory treatment).
Even if Blebbistatin proves to be a functional and safe method for eliminating meth or other drug- or trauma-linked memories, it can only work so far back in time, making it impractical for long-term addicts seeking help. Plus psychologists point out that memory and addiction are complex and diffuse, meaning that many other factors could still drive an addict back to abuse aside from direct memories. (An Eternal Sunshine analogy is actually apt here: like how the protagonists are still somehow drawn to each other even after losing their memories of each other.) And none of this gets into the infinite ethical concerns we’d need to address regarding the selective power to destroy memories, which might allow someone to delete memories in another person, or even commit a crime on meth and then erase his or her own memory after the fact.
The Scripps researchers behind Blebbistatin seem to understand all these complicating issues very well and have been measured in predicting the benefits of their discovery. If it ever does become available for human use, they stress, it ought to be just one component in a larger addiction treatment, used mainly as an aid in preventing relapses that could torpedo larger psychological progress. And that’s not nothing—93 percent of meth addicts relapse, which is a big factor in determining why only 16 to 20 percent of these addicts manage to make a full recovery.
Yet even with all of these caveats, and even if Blebbistatin never makes it through human trials, the drug is still a fascinating find and a new plateau in memory-alteration research. It’s a sign that we’re getting better, not just at altering, but at effectively targeting and fully eliminating specific memories. And it’s a sign that there are great theoretical therapeutic benefits within this advance, even if they come to us years down the line. There are a good number of ethical issues to work out, but the benefits such treatments promise for addicts and trauma-sufferers mean that going through those debates and continuing this line of research is well worth the challenges.