A Butler Grad Goes Big-Time at Yale — And Just Might Cure Alzheimer’s | Butler Stories
Levi Smith looks through a microscope

Levi Smith was unstuck in time.

He’d been in the Yale University lab for who knows how long—sans sunlight, the 18-hour days were starting to bleed together. With some straining, he remembered: He was on his third day of four in this cycle.

A rustling startled him: It was the janitor, in for his 4:30 PM round. Another eight hours had elapsed.

It’s all going to be worth it soon, he thought.

He was exhausted—tired didn’t even begin to cover it. He was shellacked by numbers and formulas. His mind was a maze of molecules, the lab in front of him and the one in his mind swimming in a brain-fog limbo.

“He described to me that when he’s doing an experiment, he imagines in his mind how the molecules interact within the space of the tube or inside the cell,” Alex Erkine, a professor of Pharmaceutical Sciences at Butler University whose lab Smith worked in while investigating anti-cancer therapy, says. “As if his mind is a hugely magnifying microscope.”

That vision, Erkine, says, is the gold standard in molecular biology. It’s like perfect pitch in music.

“This quality to see the world of molecules and participate in it experimentally is the superb golden quality of a talented molecular biologist,” Erkine says.

Smith was immersed in a world of unbroken concentration, his body screaming for sleep, his brain eager to forge on.

And he couldn’t wait to do it again the next day. And the next.

This was the type of work, he realized, he wanted to spend the rest of his life doing.

 

The ‘Miracle of Tylenol’

Smith graduated from Yale in March with a doctorate in cell biology, one six years in the making. And he spent six years at Butler University before that, earning a master’s degree in pharmaceutical sciences and a doctorate of pharmacy, the first student in a dual-degree pilot program.

Now he’s a senior research scientist at Halda Therapeutics, a start-up biotech company based in New Haven, Connecticut.

But first, he had to get there.

Smith didn’t grow up in Silicon Valley, or on one of the coasts. He’s from Camden, Indiana, a town just under 90 minutes north of Indianapolis that has fewer residents than many high-school graduating classes (just over 600, according to the 2010 census).

Camden was a place where a “nerdy” kid who was dumbstruck by “the wonder of Tylenol” in middle school could stand out.

“I remember thinking how extraordinary it is that my back could hurt, and I could take Tylenol to fix it,” Smith says. “Or if my hand hurt, I could take Tylenol to feel better. It was that naiveté of ‘Wow, how does it know what to fix?’”

But there was one big obstacle to his scientific ambitions: Neither of his parents had graduated from college. His dad had been out of his life since he was 10, and his mother was taking classes online at Indiana State University while raising him and his year-younger brother solo.

Smith was never ashamed of his family’s financial situation, but he was aware they weren’t exactly well off. 

“I remember bringing groceries home from Dollar General once,” he says. “My mom sat down at the table with her checkbook, and we had to take some back because the check would’ve balanced if we’d have kept all of them.”

That moment that would later inspire him as a low he never wanted to return to.

“I didn’t want my mom to ever be in that situation again,” he says. “She was doing the most she could, not having a college degree.”

His mom worked as a teacher’s aide at his Camden elementary school, picking up cleaning jobs on the side. Smith delivered copies of the Logansport Pharos-Tribune newspaper on his bike for extra cash.

“Everyone in Camden knew me,” he says.

But it wasn’t enough to be known. He wanted to be liked.

Shannon Sterrett, a Camden classmate of Smith’s who’s known him since he was 2, says Smith always had a snarky comment at the ready.

“Which often times made his fellow students laugh, but his teacher, not always so much,” she says. “I can remember a time or two in middle school when he got sent out into the hall.”

Smith wasn’t, in other words, your stereotypical brownnoser. But neither was he popular with his classmates.

So he turned to drugs—the study of them, that is.

“I never got into [using] drugs because I feared losing my 21st Century scholarship,” he says. “That scared the hell out of me.”

But as for the chemistry and biology behind them? Now that he could digest.

He wanted to know how to make new medicine. And how to treat diseases. And just how, exactly, did Tylenol know what part of his body hurt, again?

And then he went all in.

 

Landing at Butler

Though neither of Smith’s parents graduated from college, it was always the assumed next step for him and his younger brother, he says. 

Smith’s mom was taking online classes through Indiana State when he was in middle and high school. She’d do homework in the bleachers at his soccer matches and track meets. 

“She was a single mom going to school online while raising two teenage boys,” Smith says. “How do you even do that?”

When she earned her bachelor’s degree in Human Resources from Indiana State in 2006, she was the first in Smith’s family to do so.

Now, it was Smith’s turn.

To understand how improbable Smith’s ascent from Camden to Butler to Yale is, you need to understand his mentality toward standardized testing. Yes, he took a few AP classes, but he didn’t realize studying for a test was something people did.

“In my naiveté, I thought you just showed up and demonstrated your intelligence,” he says. “It was only later that I realized, ‘Wait, people study for those?’”

When the navy-and-white envelope from Butler University arrived in his mailbox, it was good news.

He was headed to Indianapolis to study pre-pharmacy.

 

“Failure Was Not an Option”

This is the fanciest place I’ve ever been, Smith remembers thinking when he visited the Butler campus for the first time in 2007. The brick-and-glass buildings, the fieldhouse that could fit nearly 15 Camdens inside it, the meticulously manicured lawns…

He says Butler’s assistant director of financial aid, Jacque Mickel, was crucial to his success as a first-generation student—even when he felt like a fish out of water.

“My mom and I showed up to this nice-looking building for our first financial aid meeting, and I felt very out of place,” he says. “I was trying to walk so [Mickel] wouldn’t see the holes in the seat of my jeans when I left her office.”

What Mickel remembers about that meeting is that Smith took the lead.

“He is the one that led the discussion, not his mother,” she says. “The majority of the time students sit in financial aid meetings and don’t say a word…with Levi, this wasn’t the case. He took an active role in knowing about financial aid and the impact of loans, as he knew he was going to have to take them out.”

Smith says Mickel was the blessing he didn’t know he needed.

“I’d get emails from her like, ‘You’d be a perfect fit for this scholarship!’ or ‘Can you go to this breakfast on this day?’” he says.

At every opportunity, he took advantage. By the time he graduated from Butler in 2013 in the top 10% of his class, he’d received six scholarships, including the A.J.W. LeBien Scholarship from the College of Pharmacy and Health Sciences, the Thomas Stein Scholarship for fourth-year pharmacy students, and the Indiana 21st Century Scholars Scholarship.

And then came even better news.

“When we found out I got a stipend for grad school [at Butler], and I wasn’t going to have to take out any more loans, [Mickel] cried,” Smith says. “She really, really cared.”

Yet Mickel doesn’t get all the credit keeping Smith afloat financially. The frugal mindset from his Camden years never left him.

Before starting college, Smith remembers a heart-to-heart with his mom.

Some of the people you meet are going to be talking about vacations, or where they’re going on Christmas break, she told him. You know the fact we can’t do that doesn’t change—just know you’re going to have a different experience.

Yet Smith says he never remembers feeling “without.” He kept himself so busy he didn’t have time to spend money. And he had a pharmacist’s preference for generics over brand names.

“I was buying Great Value everything,” he says.

His lunch was a jar of Great Value peanut butter, spread on Great Value bread with Great Value chips.

But there was one exception to his Great Value mindset: Ritz crackers.

They were his holy grail. His grandma would bring the last few sleeves from a box every time she saw him. He was unwilling to splurge on a full box himself. 

“I was cognizant of my financial situation, and I wasn’t foolish enough to think it was any different than what it really was,” he says. “I’d cook food at home—it’s not hard to boil pasta. I had family in Crawfordsville about an hour away, and my grandma would bring me some food from her cupboard.”

HIs number one priority, bar none, was doing well in school. He knew he had one shot at college, and he wasn’t about to waste it.

His goal, he says, was to ensure future Levi would never be frustrated with past Levi.

“I worked very hard to never put myself in a position to disappoint myself,” he says. “There was no safety net if I didn’t do well.” 

And he was willing to work—whenever and wherever he could.

He was working in the lab at Butler. But he was also holding down a job as a weekend intern at a Wal-Mart pharmacy from 2009 to 2013 so he could pay his rent. He’d work Monday through Friday from 9 to 5 in the lab at Butler, then spend Friday evening, Saturday, and Sunday working at the pharmacy.

“It was a way to get extra hours when I couldn’t get paid for all of my lab work,” he says.

When he started his clinical rotations working in a community pharmacy setting during his final year at Butler—only 10-hour days five days per week, he says—it actually felt like a break.

And he was curious about everything, so much so that he initially irritated a few of his professors, who mistook his intensity for arrogance.

“Just a bit too many questions,” is how Erkine, Smith’s research mentor at Butler, characterizes his first impression of Smith, who would later become his star student.

Medhane Cumbay, a former assistant professor of Pharmacology at Butler, met Smith in 2008, during the first semester of his freshman year. Cumbay helped develop a dual-degree program at Butler in 2011 that combines a doctorate in pharmacy with a master’s degree in pharmaceutical sciences, which Smith piloted.

The dual-degree program “was designed to attract students like Levi,” Cumbay says. Smith’s hybrid program combined the clinical knowledge of the PharmD program with the M.S. program’s training in science research skills.

Yes, it was a lot of additional work and late nights in the lab. But it was perfect for Smith.

Erkine, who worked with Smith to pilot the program, remembers Smith’s unparalleled work ethic. Smith injured his thumb while working in his home’s basement one day — and was exasperated, Erkine says, not because of the physical pain, but because he couldn’t hold a pipet.

“When he starts a lab procedure, he dives into it and can stay very late or come during the weekend to push it through,” Erkine says.

And when the opportunities he craved didn’t exist, Smith made his own.

“Levi doesn’t seem to see barriers,” Cumbay says.

And though he didn’t know it at the time, his extensive research experience coupled with his doctorate in pharmacy made him competitive for one of the top research programs in the country:

Yale.

 

The Pipe Dream Becomes Reality

The results blinked back at him from atop the Google search: “Top 10 PhD programs in the U.S. for Cell Biology.”

Dream big or go home, Smith thought.

He applied to all of them.

Smith was in his last year of the dual-degree pharmacy program at Butler, ready to take the next step to doctoral research, one he says was necessary if he wanted to work in drug development. He knew Yale was a long shot because of his unconventional background — completing the dual degree program meant he had extensive research experience, but not the typical applicant’s bachelor’s degree in biology or prestige of having worked for a famous research university.

What, Yale committee members might wonder, did a pharmacist know about research?

Erkine believed in him—but Smith’s mentor also a realist.

“That’s a very good program,” he said when Smith told him he was applying to the doctoral program in Cell Biology at Yale.

A beat passed.

“No, I mean that’s a really good program,” Erkine said. “Maybe you should consider applying for a backup, just to be on the safe side.”

He needn’t have worried: Smith had that covered.

Each of the dozen-plus schools Smith applied to required three or four letters of recommendation. Cumbay and Erkine were up to the task.

Cumbay said his letter of recommendation for Smith for the Cell Biology program at Yale was “one of the most enjoyable” he’s ever written.

“It was a ringing endorsement,” he says.

Yale flew him out for an interview, one he worked extra hours in the Butler lab to make up for attending. He spent the intervening weeks trying to come to terms with what a rejection might mean. He read the rejection letter online. Once. Twice. Ten times.

He can still quote from it.

“You can tell I’ve read that a few times,” he says.

Rejection letters are infamously thin, compared to the thick packets Yale’s admitted students receive.

Finally, one afternoon, the mail arrived. Smith braced himself.

It was a thick packet.

 

Six Years, One Disease

It was the one puzzle he couldn’t solve.

“With most diseases, we have drugs that can correct something that’s going wrong,” Smith says. “We have disease-modifying drugs that, if your cholesterol is too high, will eat the rest of it. Or we can prescribe a statin, which inhibits the body’s production of cholesterol.”

But such a drug for Alzheimer’s sufferers has proved elusive.

“It’s the only one of the top 10 deadliest diseases [in America] that can’t be prevented or cured or even slowed,” Smith says.

He spent six years of his life trying.

He worked in Yale Professor of Neurology and Neuroscience Stephen Strittmatter’s lab as a doctoral candidate, parsing the mysteries of Alzheimer’s and drug discovery.

He developed a drug that would prevent two proteins from binding to one another to treat memory impairments in mice—the same mutations that cause Alzheimer’s disease in humans. He tested his drug on more than 100 mice using an experimental design known as the Morris water maze.

In the Morris water maze experiment, a mouse must swim through a pool of opaque water to a hidden escape platform. The platform is located in the same spot during each trial, but the mouse is released into the pool from different entry points, testing its ability to learn and recall spatial cues—that is, memory.

Smith performed the experiment both forward and in reverse, which means that after three days of the mouse learning the location of the hidden platform in one position, Smith moved the platform to the opposite side of the pool. So, now the mouse had to not only learn that the platform was no longer in the first location, it also had to learn and recall the new location.

“The first day was a 22-hour day of just doing the experiment nonstop,” Smith says. “Then the next was a 20-hour day, then day 3 was 18…I spent a total of 135 hours in the lab over eight days, doing the experiment both forward and in reverse. You’ve got to love it.”

Smith was encouraged by the result: His drug restored the memory of the mice with plaques in their brains.

“My drug goes in after neurological connections are lost and prevents a beta (what plaques are made from) from binding to neurons, so neurons can heal and make connections again, fixing memory” he says. “This test showed that my drug did that.”

Not only that, but the mice “completely recovered from their mental impairment and regained all their connections.”

If his drug could produce the same effect in humans, it would be a game changer.

Smith’s classmates would be impressed, but not necessarily surprised.

Santiago Salazar, a former classmate of Smith’s at Yale who is now a scientist at Alector, a San Francisco biotechnology firm, recalls a time he legitimately thought Smith was superhuman.

Salazar and Smith were racing the clock to beat a grant deadline. Their lab advisor asked Smith if he could perform the necessary experiment at the last minute—because Smith was the only one in the lab who knew how.

“Normally this experiment can take weeks, even months, to optimize, with hundreds of milligrams of material to burn through,” Salazar says. “Levi optimized and performed the experiment all in one week, with less than 5 mg of drug.”

But Smith’s success never went to his head, another friend, Nathan Williams, who attended graduate school with Smith at Yale, says.

“Levi stood out compared to the rest of our class because he didn’t come from money, or have Ph.D parents,” Williams says. “It’s extremely common for Yalies to look down on people who were not raised on the coasts. Levi was one of the few who didn’t implicitly or explicitly treat me differently because I was raised in Texas.”

Williams says that lack of pretension also spilled over into their conversations.

“Levi was the one person in our class with the courage to say what everyone was thinking,” Williams says, “which earned him respect from professors and me, and ire from some of our classmates.”

 

A Future in Biotech

Twelve years of higher education later, this spring, it was time to look for a job. Finally done with school at age 30, Smith found one right away.

He defended his doctoral thesis at Yale at the end of February—and started as a senior research scientist at the startup biotech company Halda Therapeutics in Connecticut at the end of March, less than five weeks later.

His Yale mentor founded the company, which Smith says is currently in the “very early stages,” but has grown from six to 14 employees over the past four months. Smith can’t disclose exactly what he’s working on at the moment (“We’re kind of in stealth mode,” he says), but rest assured he loves it.

“I always want to be involved in creating new medicines for diseases,” he says. “My thought is, ‘There’s no reason I don’t have a chance to be able to do something about this.’”

Smith will tell you he’s lucky. But the truth? He works hard. He goes long. He’d almost rather die than disappoint someone he cares about.

Sterrett, Smith’s former Camden classmate, remembers a day in their eighth grade Family and Consumer Sciences class when Smith told everyone he was going to get a doctoral degree and do pharmaceutical research.

“We all laughed at him when he told us it was going to be 12 to 14 years of post-high school education,” she says. “But he did everything he said he was going to do, and I couldn’t be prouder!”