Excerpt

The Race to Find ‘Viagra for the Brain’

One of the most fascinating frontiers in the world of bio-engineering is research in memory enhancement. And it starts with fruit flies.

Photo Illustration by Lyne Lucien/The Daily Beast

In The Body Builders, Adam Piore takes us on a spellbinding journey into the field of bioengineering—which can be used to reverse engineer, rebuild, and augment human beings—and paints a vivid portrait of the people at its center. In the excerpt below, he looks at the race to create “Viagra for the brain,” i.e., a drug that could endow humans with photographic memory. This excerpted chapter has been abbreviated from the version that appears in the book.

Someone was bound to get hurt. But if you knew the cast of characters in the Midwestern neighborhood where Tim Tully and his five rambunctious Irish Catholic brothers and sisters grew up, you’d understand.

Washington, Illinois, was the kind of place where dozens of kids ran through streets lined with neatly trimmed hedges and modest split-level houses in the hot summer months spraying each other with water guns, wrestling, and playing manhunt. Like most packs, there was often an alpha male or female, and nothing helped you climb the hierarchy for the day like a good showing in the local neighborhood’s version of “chicken.” In the summer they used their bicycles, with two competitors powering toward one another head-on at full speed. The goal was to run your opponent off the road. In the winter, Tully and his pals put their bikes away and got out their sleds.

That explains the events of that snowy Christmas Day in 1968. Presents had been opened and now it was game time. So the gang gathered at the top of a hill behind the Tully house to play a variation of chicken they’d invented more suited for this unique terrain. The object was to drive other sledders over a fearsome overhang the kids called the “cliff.” The playing field consisted of a gentle slope running north to south along three yards. (The Tully house was in the middle.) At the back of these yards was a ridgeline, below which the terrain dropped twenty-five feet, at an angle of roughly 80 degrees. This fall concluded about a third of the way down, with a sheer, ten-foot drop onto the frozen creek below. Most sledders, when forced off the “cliff,” deployed a standard survival tactic. The best approach was to roll off your sled and try to grab on to a tree to slow your descent. It wasn’t so bad. After retrieving your rig, you made the humiliating climb back to the top, pulling yourself up the steep hill and steadying your ascent by using roots and branches as handholds. At the top, after you endured a brief bit of razzing, you had a chance for revenge.

That day, Tully, 14 at the time, was having a blast, barreling down the hill on his Flexible Flyer, yelling and raising hell—when a good blow from a competitor sent him hurtling over the side of that steep cliff head first. Feeling daring, Tully made a snap decision to forgo normal evacuation procedures. Instead, he decided to enjoy it. There was, in his estimation, between two and three feet of snow on the ground in front of him, which he figured would cushion the reckoning when he finished his descent at the bottom. Clutching the sides of his sled tightly, he hunkered down. It probably would have worked were it not for a buried tree stump, obscured by the snow. When the sled hit the stump, Tully was catapulted forward into a series of airborne acrobatics and ground-smacking somersaults so improbable they would become a permanent part of neighborhood lore.

In the process, Tully slammed his knee into his face and knocked himself unconscious. Months later, after the snow had melted, he would return to the site and find one of his front teeth, still attached to its root, lying in the grass. Tully had no memory of losing it. In fact, Tully had no memory of the events of that day at all. Remarkably, when he’d awoken groggy and concussed in a bed back home, his mouth swollen shut, Tully was certain it was the Friday two weeks prior. Somehow, he had “lost” the previous 14 days. It was as if the accident had wiped part of Tully’s hard drive clean. His memory gap was so solid, his insistence on the incorrect date so unyielding, that his parents rewrapped his Christmas gifts so he could experience the joy of opening them anew.

In the years that followed and into his college years, Tully would often contemplate the mysteries of recall and wonder about that sled ride. How was it that a knock on the head could cause his memory of two full weeks to disappear? And if new memories were discrete things that could be separated from the rest of our experiences and somehow erased just like that, might it be possible to do the opposite—to capture new experiences and instead somehow imbue them with the instant clarity and permanence of a painting or a photograph? Might it be possible to reverse the inevitable decline in recall we all seem to face as we age? Was there a way to untangle the mysteries of memory?

***

Tim Tully and I are standing in the middle of an expansive, sun-draped atrium, surrounded by glass windows rising several levels. It’s hard to imagine the man next to me as the young teenager with the missing front tooth from tiny Washington, Illinois.

Both Tully’s neatly cropped beard and the thick mop of graying hair he’s swept rakishly across his forehead lend him an air of respectability. And inside this sprawling 200,000-square-foot former Noki a cell phone plant perched on a hill on the outskirts of San Diego, Tully doesn’t have to brave head-on collisions to win the rank of top dog. He runs the show every day.

As we gaze up at the tiers of glass-windowed laboratories, I can see young, white-jacketed researchers buzzing about, performing protein crystallography and other feats of scientific magic. Nearby, precision robotic arms with long metal pincers grip tiny plates, each containing one of 1,536 different pharmaceutical compounds. The arms swivel the trays back and forth, moving them between incubators and imagers.

In another area, biochemists are constructing an 800,000-molecule-strong chemical library, much of it from scratch, which can then be used to create new drugs.

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“We keep our nose down; we don’t need to raise money,” Tully tells me. “But this is the real deal.”

This is where the journey that began on that steep cliff more than four decades ago has led. Today Tully is at the forefront of efforts not just to unlock the many secrets of memory, but to go far beyond. With the backing of a reclusive billionaire who is prepared to kick in up to $2 billion to fund the scheme, Tully is attempting to create and win approval for drugs that might someday allow all of us to function with superior recall and minimize those dreaded “senior moments.” He is, in other words, attempting to artificially produce the opposite effect of a tooth-rattling, concussion-inducing knee to the face. Tim Tully is making a “memorization pill.”

That it is possible to find a way to give us all something like photographic memories, Tully has no doubt. He has already done so in fruit flies, mice, and other mammals.

“Oh, we’ll find it,” he says. “Don’t worry about that.”

***

Dart NeuroScience, where Tully serves as executive vice president of research and development and chief science officer, is perched on a high ridge overlooking miles of green, rolling hills and the distant stripe of Southern California’s Interstate 15 far below, a few miles east of San Diego’s golden Pacific beaches.

It’s one of those idyllic, Southern California afternoons on a balmy, cloudless December day when I visit, a welcome respite from the miserable East Coast winter I’ve escaped back home. In front of the main entrance, an oversize company flag billows in a supple breeze, with its blue crescent and a cluster of small dots meant to represent molecules.

Tully is dressed casually in a pair of black jeans and a button-downshirt, rolled up at the sleeves.He shows me the outdoor Zen garden with its burbling fountain, aplace where a scientist might retreat for a little solitude tocontemplate vexing questions (if he or she has the mental strength toblock out the drone of the freeway drifting up from far below). Wepeer into the fitness room with its immaculate equipment, straightout of the box. Tully leads me into his company’s custom-built hundred-person auditorium, where state-of-the-art video facilities stream live lectures for the staff from the brightest minds at the nearby University of California, San Diego, and the Scripps Institute (two lectures a week in neuroscience, one in cognitive sciences). His pride in the still relatively new results of a multimillion-dollar gut renovation seems to extend almost down to the level of houseplants.

“It’s an incredible opportunity,” he tells me. “I mean look at it.”

All of this is possible thanks to the vision and ambition of a secretive billionaire named Ken Dart, who read an article about Tully in Forbes magazine and speculated on the impending arrival of what it dubbed “Viagra for the Brain.” At the time, Tully held a secure, quiet job and his own lab at Cold Spring Harbor Laboratory, a well-regarded not-for-profit research facility in Long Island, New York, run by the Nobel laureate James Watson. There Tully attempted to unravel the biochemical and genetic basis of memory. He published often, engaged in the sharp-elbowed battle for prestige and scientific credit, and delivered lectures at academic conferences on topics most would consider obscure, like “CREB-binding” proteins and “the expression patterns of genes.”

But on the side, Tully had founded a small company with Watson, the legendary co-discoverer with Francis Crick of DNA’s double helix structure. The goal of Helicon Therapeutics was no less ambitious than that of Tully’s current company. But the budget could not match the dream of a memory pill and progress was slow. Like a spate of other similar companies launched around the turn of the millennium, Helicon was in and out of financial trouble, and never did seem to get much traction. But Dart, heir to the Styrofoam empire, had been intrigued enough by what he’d read in Forbes to make a modest initial investment in Helicon. And in 2007, the straight-talking magnate approached Tully with a more ambitious proposal: How would he feel if Dart started a new company, bankrolled the entire effort himself, and put Tully in charge? Dart seemed to be offering Tully access to virtually unlimited resources in pursuit of his goal to create the world’s first “memory pill.” But there was a condition: Tully would have to agree to work full-time for Dart.

Ken Dart is not particularly known for profligate spending. In fact, to hear some members of the U.S. Senate tell it, he’s a modern-day Ebenezer Scrooge. A prominent “vulture capitalist,” known for feeding on distressed assets, Dart has been in the news in recent years for moving to the Cayman Islands to avoid paying taxes, for refusing to compromise with the near-bankrupt nations of Argentina and Greece when he was a creditor holding their debt instruments, and for bankrolling research into cryonics. News reports suggest Dart funded that effort in the hopes of remaining technically “alive” forever so he can escape someday paying estate taxes.

Tully was blunt. “You have to realize it’s going to cost you one hundred million dollars a year for twenty years before you make a profit,” he warned Dart. In other words, about $2 billion.

“That’s about what I was expecting,” Dart replied.

Dart had passed Tully’s “flinch test.” So Tully took the job and set to work building his fantasy facility.

Tully is now standing outside his company’s new deli/lunchroom, which, he informs me, can be opened up to seat three hundred. I may have seen it on the news—it’s used for more than just meals. Once a year the lunchroom serves as the arena for the Dart Neuro-Science “Extreme Memory Tournament (XMT),” an annual contest that draws some of the world’s top mental athletes from far and wide to this out-of-the-way San Diego office park to show just how far memory can be pushed. The 2015 contest offered $76,000 in prize money and drew finalists from Germany, Sweden, the Philippines—even from the up-and-coming Mongolian national team. The feats of recall on display were truly astounding. To win, contestants tried to remember 80 random digits, 50 randomly ordered words, 30 pictures, and 30 face-name pairs, among other things.

To win the two-day, 2015 tournament finals, Johannes Mallow, a diminutive, 33-year-old German, memorized 80 digits in 21.01 seconds. Fellow German Simon Reinhard set the record for cards—memorizing 52 cards in 23.34 seconds. Enkhjin Tumur, a 17-year-old from Mongolia, memorized the order of 30 pictures after studying them for just 14.40 seconds. That’s about the time it probably took you to read the last couple of sentences.

Though the XMT has garnered Dart headlines in the New York Times, Guardian, and presumably across Mongolia, it is far more than just a branding tool. Each year, Dart and a team of academics from Washington University confer with the contestants and gather data as part of a larger search for the elusive white whale of memory science: a complete and total natural—a modern-day Solomon Shereshevsky, Blind Tom, or Jake Hausler. Someone, in other words, who has inherited the genes for a brilliant memory.

The memory tournament is just one part of an unprecedented global hunt for genetic variants that offer superior memory abilities. Today more than ever, Tully is convinced that by understanding the genetics of those with superior memory, he can find ways to enhance it in the rest of us. If Tully finds mutations in genes coding for specific proteins involved in memory, he believes, he can replicate the effects of the mutation with small molecular compounds created using his 800,000-strong molecular library.

***

XMT is just one tiny part of the sprawling effort to scour the globe for individuals with exceptional memory and eventually to study their genes. In addition to memory champions, Tully and his collaborators have begun testing Jeopardy! champions, and are considering studying top crossword puzzle solvers and chess champions. The preliminary results from the Jeopardy! champions were more promising than those from XMT, because they just seemed to soak up lots of information, and were later able to easily access that information from long-term memory.

Tully has recruited help from academia to undertake this first global search phase of the plan. (The company has not yet begun identifying genes responsible for superior memorization, but is preparing to do so soon.) For the last several years Dart has provided about $250,000 a year to Henry “Roddy” Roediger III, an affable psychologist at Washington University in St. Louis who has spent his career researching the ways in which human beings access and recall memories and has been present at each XMT event. Among other things, Roediger is developing standard tests that can be used on subjects with different areas of expertise to identify superior memory. XMT contestants, Jeopardy! champs, and individuals identified in the general public may all have areas of strength. The key is designing tests that measure just the abilities Tully is hoping to find a way to augment.

The Roediger lab, Tully, and others are using a variety of methods to look for memory outliers in the general population. One of the first things the team did was create a voluntary test, place it online through Washington University, and promote it through social media. “Good with names and faces?” it read. “Test your face-name memory.” Remarkably, more than 60,000 volunteers eventually clicked on the link. Roediger and his team picked 35 individuals who seemed to score the highest, implying that unless they cheated, they had superior memorization abilities. But it’s just the beginning.

“We’re going for five million people,” Tully says, “because we need to find about one hundred people in order to have the sample size necessary to statistically identify genes in the genome that are correlated with that extreme memorization.”

Tully leads me down a long, out-of-the-way hallway, stops in front of a nondescript doorway that would be easy to miss, and beckons me into a small, darkened room. This, he tells me, is “the fly room.”

Dart’s operations and reach are truly sprawling. Dart has also opened a second research facility in western China, three and a half hours by plane due west of Shanghai in “the middle of nowhere.” Dart NeuroScience is helping pay for the research of collaborators at, among other places, New York University, the University of Edinburgh, the University of Alberta, and National Tsing Hua University in Taiwan.

“The NIH,” Tully notes, “only funds people to study dysfunction, so nobody’s ever studied superior memorization. It’s really cool to see the academic community is totally fascinated by this stuff.”

But the surprising truth is that Dart’s most potent weapon might be in this modest little corner of the building, and the modest little organisms that reside here—fruit flies. Several times during our tour, Tully has marveled at his good fortune, looking around at his dream facility, and uttered the same sentence he now repeats in that dark hallway half in pride, half in something like disbelief.

“I mean, I’m just a fly guy!”

And it’s true. None of it would have been possible without them. Studying fruit flies might seem an indirect route to unlocking the secrets of human memory and scouring the globe for humans with the most remarkable recall. It might seem entirely irrelevant to the feats of mental athletes, Greek philosophers, and Blind Tom, the 19th century blind savant who played the piano at the White House.

But in fact, in the mid ’90s, using the tools of modern genetics, Tully pulled off a feat that to many of his peers seemed every bit as exciting as anything these men ever did. Tully demonstrated he could give fruit flies the capacity to form the functional equivalent of photographic memories.

***

So far, Tully and his team have had six drugs in clinical studies. Two have been terminated for toxicity-related issues. Four remain in the pipeline. Tully is tight-lipped about exactly what kind of compounds he has created so far.

“Obviously, I can’t tell you the details of some of those targets, but we continue to be focused on the CREB pathway and its role in long-term memory formation,” he says.

Tully has big plans: He aims to continue to enter two new molecules every year into clinical studies aimed solely at improving memory.

Adam Piore is an award-winning journalist. A former editor and correspondent for Newsweek, he has had narrative features published in Conde Nast Traveler, GQ, Nautilus, Discover Magazine, Mother Jones, Playboy, Scientific American, the Atavist, BusinessWeek, and many other publications. The Body Builders: Inside the Science of the Engineered Human is his first book.