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As we age, our memories decay. But does that mean we should turn over everything to genetically-enhanced mice?
August 21, 2001
When I finally mopped underneath the living-room sofa, I found my brain. My brain is a gray rubber giveaway from some dot-com. I stuck it in a place where I knew I could easily find it, should I ever need to be reminded of what an intact brain looks like.
Scientists say that we all start losing it after the age of 25. Short-term memory starts to trickle away, and the ability to remember names and written information drops about 20% between the ages of 25 and 50, down to nearly 70% by age 80.Mind Viagra
The market for improving memory functions is going to be a big one. Expect huge demand from the baby-boomer crowd: those of us who can't remember whether they left their car in the Kangaroo or Alligator parking lot at the mall.Likewise, we can expect a flood of new products aimed at supplying that demand, most of them utterly useless. According to the Federal Dietary Supplement Health and Education Act of 1994, a company can state that an herbal product improves a consumer's sense of well-being or a body function if the manufacturer has evidence of that effect. But the FDA has never defined what constitutes legit evidence, which makes for all sorts of interesting marketing claims.For example, you can chew Brain Gum for a jolt of PhosphatidylSerine, a soybean extract that's alleged to improve your cognitive recall by regulating neural functions. Now you know that high school student loudly snapping her gum is just doing so for the sake of better grades.No actual memory-enhancing drug exists yet, although gingko biloba, piracetam, and various other "smart drugs" of ambiguous efficacy are being marketed.An old Chinese proverb says, "The faintest ink is more powerful than the strongest memory." I have that written down next to my computer monitor, because I might forget it otherwise. The nasty truth is that the only proven recourses available to you and me are still pedestrian: diligently make lists; write things down on your calendar; pay attention; and get organized. Exercise your brain by doing mnemonic games and expose yourself to experiences that use your various senses. Exercise your body to reduce stress and blood pressure. If your cardiovascular arteries are getting clogged, think of what other things are ossifying as well. Get plenty of rest.Biological modeling
That doesn't mean that serious research isn't being done, or at least that research isn't being done seriously. Plant chemicals, called phytochemicals, may increase cell-membrane fluidity, nutrients, and chemical signals to boogie through cell walls more readily and reduce tissue inflammation. In a Tufts University study published in the Journal of Neuroscience in September 1999, rats given blueberry extract with strawberry and spinach seemed to be protected against oxidative stress in their brains (one of the processes of aging) and scored higher in tests of working memory.Memory is plastic. Memories are continually being laid down on top of each other and keep changing. If your brain were truly a computer, it would be a frustratingly fuzzy and inexact one, yet it is capable of handling extreme complexity.Your brain possesses exquisitely complicated circuitry, composed of several different systems that interact with each other. Humans have an estimated 1 trillion neurons, and perhaps 70 million synaptic connections between them. Scientists believe there are different types of memory systems, all working together, depending on what type of memory is being laid down, such as semantic (factual information), episodic (past experiments), and priming (unconscious recollection of visual or auditory cues).Explicit memory seems to be the conscious memory for people, places, and things. It relies on the hippocampus (Latin for seahorse), the processing center of the brain. Implicit memory (the non-conscious memory of "how," which includes perceptual and motor skills) seems to be expressed by activating the sensory and motor systems engaged by a particular learning task, such as learning a new golf swing.Your brain's ability to consolidate information, activating the "switch" that turns short-term memory to long-term memory, decays with age. Both implicit and explicit memory conversion require repetition to create the protein that stabilizes the memory and grows new synaptic connections.Current biochemical and genetic memory research looks promising. Big Pharma are sponsoring biotech research into drugs that are ostensibly aimed toward Alzheimer's patients but intended for a wider population. Drugs based on genetics, genomics, and even proteomics are still off in the distance, but interesting results are found with animal models.Companies such as Memory Pharmaceuticals and Sention, formerly Nemogen, are working on various approaches to memory recall. Drs. Tim Tully and Jerry Yin have taken their research on developing super-smart fruit flies by increasing the amount of CREB (Cyclic AMP Response Element Binding) protein, which helps nerve cells in the brain store memories. CREB exists in the brains of both fruit flies and humans. Tully and Yin's company, Helicon Therapeutics, in Cold Spring Harbor, N.Y., is trying to apply the fruit-fly research to humans.But it isn't fruit flies we need to worry about.Smart mice
Several months ago, an MIT stem-cell researcher mentioned in a talk that he had known of researchers injecting human brain cells into mice. "At what point do [the chimerical mice] take on human characteristics?" he asked rhetorically. "Well, they won't be ordering out for pizza any time soon."I beg to differ. At the current rate of scientific progress, it's only a matter of time before the harried counter help at Dial a Pizza off of Beacon Street are going to start getting orders like this: "Extra large, white, extra cheese, hold the crust. Just leave it at the lab door and ring the bell."Mouse and rat models are useful in extrapolating what will work in humans. Though I begin to wonder about the use of that word, "extrapolate."A couple of years ago, researchers led by Joseph Tsien, a Princeton University neurobiologist, modified a gene called NR2B that helps form long-term memories by speeding up the connections between neurons. To do this, Tsien's team genetically engineered a strain of smarter mice. Nicknamed "Doogies," the transgenic mice performed 40% better on mental challenges than their ordinary brethren. Tsien's researchers found that the smart mice retained more if they sandwiched repeated learning tasks with rest periods. That method seems to work for humans, too. (Further adventures of the Doogies are chronicled in the cartoon Pinky and the Brain.)But if the learning/memory method works for humans ... why not go further?Abgenix has developed a souped-up XenoMouse with more than 80% of the human heavy-chain antibody genes and a significant amount of the human light-chain genes. XenoMouse technology further capitalizes on the natural in vivo affinity maturation process to generate high-affinity, fully human antibodies.Medarex's HuMAb-Mouse technology can be used to rapidly create new fully human high-affinity antibodies. "The HuMAb-Mouse creates fully human antibodies in a matter of months," says the company, "avoiding the need for humanization or complicated genetic engineering." While I'm happy to learn that the HuMAb-Mouse system generates high-quality human antibodies, I'm a little bemused at the company's partners. "Medarex has complimented its HuMAb transgenic mouse system with the TC Mouse through an exclusive partnership with the pharmaceutical division of Kirin Brewery Co. of Japan." Kirin Brewery?Applications
But what do you do when you forget where you hid your rubber brain? Or, conversely, I would like to selectively filter out some memories: various bad jobs, bad haircuts, embarrassing dates.Bill Platt, a NYU film student (clearly a scientist at heart) invented the term "bleach" for drugs developed to remove memories in his film short about a policeman deciding whether to wipe his memory clean of trauma. Implanting and erasure of memories remain popular in the public imagination. The Manchurian Candidate, the 1962 thriller about a Communist brainwashing plot uncovered by Frank Sinatra, is a must-see. The film was made at the eve of the Cuban Missile Crisis, when memories of the McCarthy Era were still fresh in people's minds.I talked to the FBI agent who was assigned to the local duty desk over the Fourth of July holiday. She said that she could rely on regular callers saying, "I got my information from aliens; they made an implant in my brain." The agent assured me sardonically, "When some alien force has put an implant in your head, then the bureau will pay attention. We prefer those kind of calls." However, the FBI bureaucracy has enough problems keeping track of its own information.Fortunately, you can find commercially available solutions, such as Alien Abductions Inc., whose Web site proclaims, "Thousands of individuals are abducted each year by aliens. Why haven't they chosen you?" Don't feel slighted. To save you the bother of actually getting yourself probed, Alien Abductions offers to implant some convenient memories, saying, "Most people will probably never have the opportunity to be abducted by aliens. And even those elite few who are selected for abduction receive no assurances that they will fully remember their experience--much less a guarantee that their abduction will be everything that they hoped it would be. So why wait? Why wonder if they're ever going to come for you? Why invest the time, trouble, and expense involved in an actual abduction when the highly-trained and professional staff at Alien Abductions can provide you with personalized, realistic memories of the alien abduction that you have been waiting for your entire life?" Alien Abductions offers retreats such as Great Abductions of the 1970s weekend resort package. Write them at [email protected] sounds good. I could use some new vacation memories. I've fished my brain from underneath the sofa, and packed it into my biohazard lunch box, ready to go. I'll probably not be checking voicemail, but you can contact my new assistant (who's been published in all the top scientific journals) at [email protected].Where is all this genetic research leading us? Is this a good thing for science and our future ability to recall schoolyard squabbles, or should we really be worrying about the mice? And why would Kirin Brewery be spending money on human antibodies in mice? Chat with Wendy about these and other matters in her Listening Post discussion forum. Bring your own brain; she's lost hers, again.
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