Next, scientists hope to generalize their results to dogs, since we share so many genes, and perhaps also to humans.
SMART FLIES AND DUMB MICE
The NR2B gene is not the only gene being studied by scientists for its impact on memory. In yet another groundbreaking series of experiments, scientists have been able to breed a strain of fruit flies with “photographic memory,” and also a strain of mice that are amnesiac. These experiments may eventually explain many mysteries of our long-term memory, such as why cramming for an exam is not the best way to study, and why we remember events if they are emotionally charged. Scientists have found that there are two important genes, the CREB activator (which stimulates the formation of new connections between neurons) and the CREB repressor (which suppresses the formation of new memories).
Dr. Jerry Yin and Timothy Tully of Cold Spring Harbor have been doing interesting experiments with fruit flies. Normally it takes ten trials for them to learn a certain task (e.g., detecting an odor, avoiding a shock). Fruit flies with an extra CREB repressor gene could not form lasting memories at all, but the real surprise came when they tested fruit flies with an extra CREB activator gene. They learned the task in just one session. “This implies these flies have a photographic memory,” says Dr. Tully. He said they are just like students “who could read a chapter of a book once, see it in their mind, and tell you that the answer is in paragraph three of page two seventy-four.”
This effect is not just restricted to fruit flies. Dr. Alcino Silva, also at Cold Spring Harbor, has been experimenting with mice. He found that mice with a defect in their CREB activator gene were virtually incapable of forming long-term memories. They were amnesiac mice. But even these forgetful mice could learn a bit if they had short lessons with rest in between. Scientists theorize that we have a fixed amount of CREB activator in the brain that can limit the amount we can learn in any specific time. If we try to cram before a test, it means that we quickly exhaust the amount of CREB activators, and hence we cannot learn any more—at least until we take a break to replenish the CREB activators.
“We can now give you a biological reason why cramming doesn’t work,” says Dr. Tully. The best way to prepare for a final exam is to mentally review the material periodically during the day, until the material becomes part of your long-term memory.
This may also explain why emotionally charged memories are so vivid and can last for decades. The CREB repressor gene is like a filter, cleaning out useless information. But if a memory is associated with a strong emotion, it can either remove the CREB repressor gene or increase levels of the CREB activator gene.
In the future, we can expect more breakthroughs in understanding the genetic basis of memory. Not just one but a sophisticated combination of genes is probably required to shape the enormous capabilities of the brain. These genes, in turn, have counterparts in the human genome, so it is a distinct possibility that we can also enhance our memory and mental skills genetically.
However, don’t think that you will be able to get a brain boost anytime soon. Many hurdles still remain. First, it is not clear if these results apply to humans. Often therapies that show great promise in mice do not translate well to our species. Second, even if these results can be applied to humans, we do not know what their impact will be. For example, these genes may help improve our memory but not affect our general intelligence. Third, gene therapy (i.e., fixing broken genes) is more difficult than previously thought. Only a small handful of genetic diseases can be cured with this method. Even though scientists use harmless viruses to infect cells with the “good” gene, the body still sends antibodies to attack the intruder, often rendering the therapy useless. It’s possible that the insertion of a gene to enhance memory would face a similar fate. (In addition, the field of gene therapy suffered a major setback a few years ago when a patient died at the University of Pennsylvania during a gene therapy procedure. The work of modifying human genes therefore faces many ethical and even legal questions.)
Human trials, then, will progress much more slowly than animal trials. However, one can foresee the day when this procedure might be perfected and become a reality. Altering our genes in this way would require no more than a simple shot in the arm. A harmless virus would then enter our blood, which would then infect normal cells by injecting its genes. Once the “smart gene” is successfully incorporated into our cells, the gene becomes active and releases proteins that would increase our memory and cognitive skills by affecting the hippocampus and memory formation.
If the insertion of genes becomes too difficult, another possibility is to insert the proper proteins directly into the body, bypassing the use of gene therapy. Instead of getting a shot, we would swallow a pill.
A SMART PILL
Ultimately, one goal of this research is to create a “smart pill” that could boost concentration, improve memory, and maybe increase our intelligence. Pharmaceutical companies have experimented with several drugs, such as MEM 1003 and MEM 1414, that do seem to enhance mental function.
Scientists have found that in animal studies, long-term memories are made possible by the interaction of enzymes and genes. Learning takes place when certain neural pathways are reinforced as specific genes are activated, such as the CREB gene, which in turn emits a corresponding protein. Basically, the more CREB proteins circulating in the brain, the faster long-term memories are formed. This has been verified in studies on sea mollusks, fruit flies, and mice. The key property of MEM 1414 is that it accelerates the production of the CREB proteins. In lab tests, aged animals given MEM 1414 were able to form long-term memories significantly faster than a control group.
Scientists are also beginning to isolate the precise biochemistry required in the formation of long-term memories, at both the genetic and the molecular level. Once the process of memory formation is completely understood, therapies will be devised to accelerate and strengthen this key process. Not only the aged and Alzheimer’s patients but eventually the average person may well benefit from this “brain boost.”
CAN MEMORIES BE ERASED?
Alzheimer’s may destroy memories indiscriminately, but what about selectively erasing them? Amnesia is one of Hollywood’s favorite plot devices. In The Bourne Identity, Jason Bourne (played by Matt Damon), a skilled CIA agent, is found floating in the water, left for dead. When he is revived, he has severe memory loss. He is being relentlessly chased by assassins who want to kill him, but he does not know who he is, what happened, or why they want him dead. The only clue to his memory is his uncanny ability to instinctively engage in combat like a secret agent.
It is well documented that amnesia can occur accidentally through trauma, such as a blow on the head. But can memories be selectively erased? In the film Eternal Sunshine of the Spotless Mind, starring Jim Carrey, two people meet accidentally on a train and are immediately attracted to each other. However, they are shocked to find that they were actually lovers years ago but have no memory of it. They learn that they paid a company to wipe memories of each other after a particularly bad fight. Apparently, fate has given them a second chance at love.
Selective amnesia was taken to an entirely new level in Men in Black, in which Will Smith plays an agent from a shadowy, secret organization that uses the “neuralizer” to selectively erase inconvenient memories of UFOs and alien encounters. There is even a dial to determine how far back the memories should be erased.
All these make for thrilling plot lines and box-office hits, but are any of them really possible, even in the future?
We know that amnesia is, indeed, possible, and that there are two basic types, depending on whether short- or long-term memory has been affected. “Retrograde amnesia” occurs when there is some trauma or damage to the brain and preexisting memories are lost, usually dating from the event that caused the amnesia. This would be similar to the amnesia faced by Jason Bourne, who lost all memories from before he was left for dead in the water. Here the hippocampus is still intact, so new
memories can be formed even though long-term memory has been damaged. “Anterograde amnesia” occurs when short-term memory is damaged, so the person has difficulty forming new memories after the event that caused the amnesia. Usually, amnesia may last for minutes to hours due to damage to the hippocampus. (Anterograde amnesia was featured prominently in the movie Memento, where a man is bent on revenge for the death of his wife. The problem, however, is that his memory lasts only about fifteen minutes, so he has to continually write messages on scraps of papers, photos, and even tattoos in order to remember the clues he has uncovered about the murderer. By painfully reading this trail of messages he has written to himself, he can accumulate crucial evidence that he would have soon forgotten.)
The point here is that memory loss dates back to the time of the trauma or disease, which would make the selective amnesia of Hollywood highly improbable. Movies like Men in Black assume that memories are stored sequentially, as in a hard disk, so you just hit the “erase” button after a designated point in time. However, we know that memories are actually broken up, with separate pieces stored in different places in the brain.
A FORGETFUL DRUG
Meanwhile, scientists are studying certain drugs that may erase traumatic memories that continue to haunt and disturb us. In 2009, Dutch scientists, led by Dr. Merel Kindt, announced that they had found new uses for an old drug called propranolol, which could act like a “miracle” drug to ease the pain associated with traumatic memories. The drug did not induce amnesia that begins at a specific point in time, but it did make the pain more manageable—and in just three days, the study claimed.
The discovery caused a flurry of headlines, in light of the thousands of victims who suffer from PTSD (post-traumatic stress disorder). Everyone from war veterans to victims of sexual abuse and horrific accidents could apparently find relief from their symptoms. But it also seemed to fly in the face of brain research, which shows that long-term memories are encoded not electrically, but at the level of protein molecules. Recent experiments, however, suggest that recalling memories requires both the retrieval and then the reassembly of the memory, so that the protein structure might actually be rearranged in the process. In other words, recalling a memory actually changes it. This may be the reason why the drug works: propranolol is known to interfere with adrenaline absorption, a key in creating the long-lasting, vivid memories that often result from traumatic events. “Propranolol sits on that nerve cell and blocks it. So adrenaline can be present, but it can’t do its job,” says Dr. James McGaugh of the University of California at Irvine. In other words, without adrenaline, the memory fades.
Controlled tests done on individuals with traumatic memories showed very promising results. But the drug hit a brick wall when it came to the ethics of erasing memory. Some ethicists did not dispute its effectiveness, but they frowned on the very idea of a forgetfulness drug, since memories are there for a purpose: to teach us the lessons of life. Even unpleasant memories, they said, serve some larger purpose. The drug got a thumbs-down from the President’s Council on Bioethics. Its report concluded that “dulling our memory of terrible things [would] make us too comfortable with the world, unmoved by suffering, wrongdoing, or cruelty.… Can we become numb to life’s sharpest sorrows without also becoming numb to its greatest joys?”
Dr. David Magus of Stanford University’s Center for Biomedical Ethics says, “Our breakups, our relationships, as painful as they are, we learn from some of those painful experiences. They make us better people.”
Others disagree. Dr. Roger Pitman of Harvard University says that if a doctor encounters an accident victim who is in intense pain, “should we deprive them of morphine because we might be taking away the full emotional experience? Who would ever argue with that? Why should psychiatry be different? I think that somehow behind this argument lurks the notion that mental disorders are not the same as physical disorders.”
How this debate is ultimately resolved could have direct bearing on the next generation of drugs, since propranolol is not the only one involved.
In 2008, two independent groups, both working with animals, announced other drugs that could actually erase memories, not just manage the pain they cause. Dr. Joe Tsien of the Medical College of Georgia and his colleagues in Shanghai stated that they had actually eliminated a memory in mice using a protein called CaMKII, while scientists at SUNY Downstate Medical Center in Brooklyn found that the molecule PKMzeta could also erase memories. Dr. Andre Fenson, one of the authors of this second study, said, “If further work confirms this view, we can expect to one day see therapies based on PKMzeta memory erasure.” Not only may the drug erase painful memories, it also “might be useful in treating depression, general anxiety, phobias, post-traumatic stress, and addictions,” he added.
So far, research has been limited to animals, but human trials will begin soon. If the results transfer from animals to humans, then a forgetful pill may be a real possibility. It will not be the kind of pill seen in Hollywood movies (which conveniently creates amnesia at a precise, opportune time) but could have vast medical applications in the real world for people haunted by traumatic memories. It remains to be seen, though, how selective this memory erasure might be in humans.
WHAT CAN GO WRONG?
There may come a day, however, when we can carefully register all the signals passing through the hippocampus, thalamus, and the rest of the limbic system and make a faithful record. Then, by feeding this information into our brains, we might be able to reexperience the totality of what another person went through. Then the question is: What can go wrong?
In fact, the implications of this idea were explored in a movie, Brainstorm (1983), starring Natalie Wood, which was far ahead of its time. In the movie, scientists create the Hat, a helmet full of electrodes that can faithfully record all the sensations a person is experiencing. Later, a person can have precisely the same sensory experience by playing that tape back into his brain. For fun, one person puts on the Hat when he is making love and tape-records the experience. Then the tape is put into a loop so the experience is greatly magnified. But when another person unknowingly inserts the experience into his brain, he nearly dies because of a sensory overload. Later, one of the scientists experiences a fatal heart attack. But before she dies, she records her final moments on tape. When another person plays the death tape into his brain, he, too, has a sudden heart attack and dies.
When news of this powerful machine finally leaks out, the military wants to seize control. This sets off a power struggle between the military, which views it as a powerful weapon, and the original scientists, who want to use it to unlock the secrets of the mind.
Brainstorm prophetically highlighted not only the promise of this technology but also its potential pitfalls. It was meant to be science fiction, but some scientists believe that sometime in the future, these very issues may play out in our headlines and in our courts.
Earlier, we saw that there have been promising developments in recording a single memory created by a mouse. It may take until mid-century before we can reliably record a variety of memories in primates and humans. But creating the Hat, which can record the totality of stimulation entering into the brain, requires tapping into the raw, sensory data surging up the spinal cord and into the thalamus. It may be late in this century before this can be done.
SOCIAL AND LEGAL ISSUES
Some aspects of this dilemma may play out in our lifetimes. On one hand, we may reach a point where we can learn calculus by simply uploading the skill. The educational system would be turned upside down; perhaps it would free teachers to spend more time mentoring students and giving them one-on-one attention in areas of cognition that are less skill-based and cannot be mastered by hitting a button. The rote memorization necessary to become a professional doctor, lawyer, or scientist could also be drastically reduced through this method.
In principle, it might even give us memories of vacations that never happened, prizes that we never won, lo
vers whom we never loved, or families that we never had. It could make up for deficiencies, creating perfect memories of a life never lived. Parents would love this, since they could teach their children lessons taken from real memories. The demand for such a device could be enormous. Some ethicists fear that these fake memories would be so vivid that we would prefer to relive imaginary lives rather than experiencing our real ones.
The unemployed may also benefit from being able to learn new marketable skills by having memories implanted. Historically, millions of workers were left behind every time a new technology was introduced, often without any safety net. That’s why we don’t have many blacksmiths or wagon makers anymore. They turned into autoworkers and other industrial workers. But retraining requires a large amount of time and commitment. If skills can be implanted into the brain, there would be an immediate impact on the world economic system, since we wouldn’t have to waste so much human capital. (To some degree, the value of a certain skill may be devalued if memories can be uploaded into anyone, but this is compensated for by the fact that the number and quality of skilled workers would vastly increase.)
The tourism industry will also experience a tremendous boost. One barrier to foreign travel is the pain of learning new customs and conversing with new phrases. Tourists would be able to share in the experience of living in a foreign land, rather than getting bogged down trying to master the local currency and the details of the transportation system. (Although uploading an entire language, with tens of thousands of words and expressions, would be difficult, it might be possible to upload enough information to carry on a decent conversation.)
Inevitably, these memory tapes will find their way onto social media. In the future, you might be able to record a memory and upload it to the Internet for millions to feel and experience. Previously, we discussed a brain-net through which you can send thoughts. But if memories can be recorded and created, you might also be able to send entire experiences. If you just won a gold medal at the Olympic Games, why not share the agony and the ecstasy of victory by putting your memories on the web? Maybe the experience will go viral and billions can share in your moment’s glory. (Children, who are often at the forefront of video games and social media, may make a habit of recording memorable experiences and uploading them onto the Internet. Like taking a picture with a cell phone, it would be second nature to them to record entire memories. This would require both the sender and the receiver to have nearly invisible nanowires connecting to their hippocampus. The information would then be sent wirelessly to a server, which would convert the message to a digital signal that can be carried by the Internet. In this way, you could have blogs, message boards, social media, and chat rooms where, instead of uploading pictures and videos, you would upload memories and emotions.)