A Trip to the Memory Doctor

Scientist Tim Tully has an idea that’s hard to forget

By Kate Torgovnick
Published: Jun 03, 2008

You’re in your doctor’s office for your annual check-up, going over your normal list of concerns—birth control, that oddly shaped freckle on your shoulder, the muscle you think you pulled in your back. “Oh, and I’m having trouble remembering people’s names,” you say. Your doctor doesn’t look at you like you’re crazy. He or she simply scribbles a prescription on a note pad and sends you to Augmented Cognitive Training—essentially, physical therapy for your memory.

Nope, this isn’t a scene from a science fiction movie. If Dr. Tim Tully has his way, memory therapy could be a thriving field of medicine in as little as 5 to 10 years.

There are very few people in the world who aren’t concerned with memory loss—who hasn’t seen an older relative battle Alzheimer’s or who doesn’t feel a tad disconcerted when they can’t remember why they walked into their living room. The study of memory has been booming since the 1800s. If you open up any health publication, you’ll see multiple stories about memory—from reports telling you that chocolate and blueberries improve it to articles claiming that ginko balboa, the popular memory-boosting herbal supplement, is a crock.

For Tully, the genetics of memory has been a lifelong fascination. In college, he had planned to go pre-med, but he found himself mesmerized by a psychology class about learning. “It was the proverbial light coming on,” he says. He changed his major to biology and psychology, and started studying how people form new memories.

Here’s how it works. Human being have two types of memories—short-term and long term. Short-term memories are immediate, and unless they are reinforced, they quickly decay. With repetition, however, a short-term memory eventually gets converted—or as scientists say, ‘consolidated’—into a long-term memory. “Long-term memories are permanent,” explains Tully. “You don’t have to rehearse them anymore to be able to recall them.”

Scientists have long wondered how exactly memory consolidation happens. Tully was one of the first to look at CREB—a sequence of DNA that creates a protein used in memory formation—as vital to the process. “Creating a new memory is like building a house,” says Tully. “CREB is like the general contractor—it comes up with the plans, it calls the brick layers, the electricians, and the plumbers and then it regulates their activities.”

Tully’s first experiments involving CREB were on, of all things, fruit flies. “I basically invented Pavlov’s flies,” explains Tully. “Pavlov would ring a bell and then feed his dogs, so they’d learn to associate the bell with food. I adapted this for a fruit fly. We’d expose them to a smell and then shock their feet.”

A normal fly took about 10 trials to learn to fly away when the smell appeared. But Tully also genetically engineered groups of the flies in two ways—some had their CREB gene turned on, while others had the CREB gene turned off. The flies with the inactive CREB gene just couldn’t learn to associate the smell and the shock. But the flies that had their CREB gene turned on—they learned to associate the smell and the shock after just one trial. By enhancing their CREB, these flies had a super-normal memory.

Ever since this experiment, Tully has been working to apply the same principle in human beings. And his company, Helicon Therapeutics, is close to creating the first CREB-boosting pharmaceutical.

“The brain is plastic—it’s evolved to look out into the world and change its function,” Tully says. “The classic example is rehabilitation after someone’s had a stroke. Part of the brain is injured and they’ve lost function of, say, an arm. But with lots of repeated exercise, they induce the plasticity of the surrounding circuitry and almost remodel the connections to regain that lost function. The drugs we’re making would significantly reduce the amount of practice needed to produce those structural changes.”

In other words, physical therapy could take weeks—not years. But the applications goes much further. “My vision is that for whatever reason—age, heredity, disease, injury—you go to your doctor and say, ‘I don’t seem to be remembering things well.’ You’ll go to what we call Augmented Cognitive Training (ACT) and you’ll be given a series of mental exercises. You’ll also be prescribed a CREB-inducing compound. Together, with very few visits, you’ll cause a structural rearrangement of the circuitry so you can get back to optimal function,” says Tully.