What does it take to get to a breakthrough? Purdue researchers share the highs and heartbreaks of their work.
In an unassuming office tucked away in the Veterinary Pathology Building, assistant professor Tiffany Lyle is dreaming big.
She’s spent her entire career trying to crack cancer’s code, and right now, she’s working on a project linked to one of the most devastating slices of the disease: brain metastases.
Once a cancerous tumor has metastasized and reached the brain, the prognosis for a patient is grim: typically, they live less than a year after diagnosis.
Due to an almost-impenetrable structure known as the blood-brain barrier, treating these tumors has proved exceptionally difficult. “We’re trying to find a way to deliver drugs into the brain,” says Lyle (PhD V’16) of her lab’s work. It’s a goal that, if achieved, could be the gateway that extends the lives of millions of cancer patients.
Lyle’s one-sentence description of her work is both technically accurate and woefully incomplete: it obscures the endless list of processes and details that she and her team must get exactly right to make progress.
She and her lab members prepare “brain-seeking” cells in a tissue culture hood that prevents biological contamination, then deliver the cells via syringe into a small number of anesthetized mice. Later, they study tiny sections of the mice’s brains with bright-field and fluorescence microscopes. With the help of assays — procedures that help measure the presence of and activity of certain proteins, for example — they can see whether they have been able to breach the blood-brain barrier.
Every step has its perils. The high-tech and occasionally finicky lab equipment can break down with no warning. Sometimes, all it takes is a humid Indiana afternoon to wreak havoc on the sensitive antibodies essential for her team to complete their complex protocols. “You can work really hard, and sometimes things don’t go the way that you want them to,” Lyle says, pausing for a moment before leavening the frustration with optimism. “But you can always apply what you learned in the process to the next thing.”
Lyle is still early in her career, but there’s no question her work has the potential to be transformative. It is also very, very hard.
Purdue’s ambitious researchers are tackling some of the world’s biggest and most important problems. They’re landing grants, publishing in prestigious journals, and making real progress that helps us live healthier lives and makes the world a better place. But behind every media headline trumpeting a groundbreaking finding are years of quiet, painstaking toil.
Often, what makes researchers’ work so remarkable is not just the advances themselves but the grit and ingenuity that these men and women bring to libraries and labs every single day.
Answering the right questions with rigor
As an associate professor of human-animal interactions within Purdue’s Center for the Human-Animal Bond, Maggie O’Haire has heard countless stories about how a relationship with an animal has transformed someone’s life for the better. They’re the kind of tales that move anyone with a beating heart.
But as a scientist, O’Haire’s job is to unearth data that can help verify or disprove the larger truths that individuals may experience. “With science, we can determine whether or not an effect is real. If it is real, we can see what we can do to enhance it,” she says.
Last year, she landed a prestigious National Institutes of Health grant to study whether service dogs reduce the stress of veterans with post-traumatic stress disorder. As part of the study, she and her team are working with hundreds of veterans across the country. They want to collect rich data that will help them draw meaningful conclusions, and they’ve left no detail to chance. Three times a day, at exact intervals verified by a smartphone app, the study participants must collect their own saliva, which will later be tested for the stress hormone cortisol.
On specific days, participants overnight those samples back to the lab. There, they are analyzed by someone who has no details of the study and therefore won’t introduce any potential bias to the data.
That’s just the beginning: participants must also wear technologically advanced wristbands, not unlike Fitbits, to track their sleep and activities. Researchers text participants four times a day to find out where they are and how they’re feeling. Their dogs, too, must wear devices on their collars that collect information. Participants will carry out this work for four weeks: two weeks at the outset, and another two weeks after three months.
Intense? Absolutely.
But this sort of thoroughness is essential to collect data that matters. If a connection is established between animals and lower rates of stress, for example, that can be foundational research that leads to the creation of funded programs to provide service animals for veterans.
If the research doesn’t find a strong link? That’s OK, too. “We always want to talk about the findings that are significant as well as those that are not,” O’Haire says. “We don’t want someone to get a service animal and assume everything will be roses afterward if that’s not the case.”
That scientist’s lens — constantly trying to think of a problem from every angle — helps give every study its strength. “There are so many checks and balances built into the work,” she says. “Researchers spend their lives figuring out these details.”
“There are so many checks and balances built into the work. Researchers spend their lives figuring out these details.”
—Maggie O’Haire
Associate professor of library science Lawrence Mykytiuk understands O’Haire’s sentiment. He has spent much of his life trying to show whether the people who were written about in the Hebrew Bible actually existed in the world. His process has been to undertake a thorough analysis of ancient inscriptions and seals that bear the names of these figures.
It’s a task made all the more difficult by the presence of hucksters who have tried to pass off fake inscriptions as the real thing. Even worse? Up until at least 1970, some scholarship in the field was slippery at best. “It used to be that people could get away with sloppy thinking and circular logic,” he says.
Mykytiuk has spent a lifetime learning to suss out the fakes. Subtle details must be just right for an inscription to potentially be authentic. The language and lettering must be of the exact variant that existed at the time, for example. And for seal impressions, claimed to be from Jerusalem the clay must be a certain variety and texture found in that locale.
Over the course of decades, he’s identified more than 50 individuals named in the Hebrew Bible that, by all the evidence collected, appear to have existed in the world. In arriving at that total, he’s also had to scrub a few names from his list when more conclusive evidence proved an inscription’s inauthenticity.
He is both proud of his lifetime of work and is careful to use a scientist’s precise language to describe his findings. “Archaeology can show historic connections,” he says. “But it can’t prove spiritual truths.”
This is, of course, the dilemma of researchers. They can spend a lifetime pursuing important work, and they can make real progress in their fields. But the ethical code of their work also means that they can’t make a marketer’s promise. They can use every tool at their disposal to understand the world better. But they can’t always give the people what they want.
U-turns, scientific humility, and new directions
Researchers often come to their field with a passion for the subject and a hunch or two about how to address some of the most pressing problems within it. But what happens when the data don’t bear out expectations or the world demands that you rethink your most basic assumptions?
Few understand this idea as intimately as entomology professor Catherine Hill. For more than two decades, she has been laser-focused on ridding the world of vector-borne diseases — think malaria, Zika, and other diseases carried by certain mosquitoes. “These are insects and ticks that are responsible for a very high number of human deaths and reduction in our quality of life,” she notes.
But over the years, as Hill and her team reared thousands of mosquitoes in an insectary to more deeply understand their biology, she wondered if simply killing the insects was the right approach. Only a tiny percentage of the bugs were causing the problems, and there’s no telling what larger troubles could be stirred up by removing a species from an area’s ecosystem. She acknowledges, too, that she’d developed something of an affection for the insects over her years of work. “When you look at mosquitoes under the microscope or see them go through their life cycle, you realize what amazing organisms they are,” Hill says.
At outreach events and even in her own family, nagging questions kept popping up. Could she really justify wiping out huge populations of mosquitoes? What would happen to the environment? Was there another way?
Hill could have ignored the questions — after all, she was a recognized expert who had made significant contributions to the field. But in addition to her expertise, she brought a sense of scientific humility to her work. She was open to the possibility that she was wrong. And like a true scientist, she kept asking questions.
Eventually, Hill became so concerned that the ethics she carried with her as a person didn’t line up with the ethics of her research that she changed her focus.
Instead of finding ways to precisely kill disease-carrying bugs, she has begun to look for ways to make it harder for insects to transmit diseases to humans. If successful, the approach would offer even bigger benefits to the world. In addition to keeping humans safe from disease, it would preserve essential biodiversity.
Still, making a shift like this was anything but easy. “It takes quite a bit to jolt you out of traditional approaches and realize you want to think a little differently,” Hill says. “It was important to me to rethink what we were doing and how we might do it.”
Lyle, too, has had plenty of research experiences that haven’t gone the way she thought they would — and that have led her in new directions.
For example, when mice started showing unexpected paralysis in the research project linked to brain metastases, she and a student researcher worried that an injection had gone awry.
But further investigation led to a discovery. The cells that had a certain appearance in the primary tumor had a different appearance in the metastases, and that’s what was causing the paralysis. Moreover, the patterns they saw might help them predict other aspects of brain metastases.
For Lyle, that seemingly messy result was actually something of a revelation. “Had we not dug into that ‘error’ — at least, as it was initially perceived — we wouldn’t have had another exciting arm of our work,” she says.
Beyond the breakthroughs
Many researchers pursue their work with the dream of changing the world through science, but the hard reality is that even the very best researchers struggle daily. They pursue promising ideas that lead to dead ends. They are, like all of us, human.
Yet at Purdue and beyond, researchers often bring a sense of insatiable curiosity and joy to the process that propels them beyond any single difficult result or experience.
Take Vilas Pol, associate professor of chemical engineering. For years, he’s been chasing down the idea of creating safer batteries. His experimental approaches — adapting the common materials found in batteries or even changing the architecture of a battery itself — could prevent the surprisingly common cases of battery fires sparked in cell phones, laptops, and electric vehicles.
Every day, his research team works with battery safety testing, and he knows that the wrong combination of steps or testing protocols could lead to potentially dangerous thermal runaway.
So what keeps Pol coming back, day after day? For him, these immediate concerns need to be resolved. “When we leave this world, all the scientific discoveries will still be here, and people will benefit from them,” he says. “We come to this world to give something back.”
“When we leave this world, all the scientific discoveries will still be here, and people will benefit from them. We come to this world to give something back.”
—Vilas Pol
This idea of giving back fuels chemistry professor Jonathan Wilker, too. Wilker develops adhesives that can set in wet environments, which could eventually help surgeons replace sutures, staples, and screws with lightweight and effective glues. He has made real progress in his field, but he also sees his work as more than just the final result. Every piece of his job has meaning.
“Sometimes, I’m in here seven days a week,” he admits. “But seeing students in the lab mature — seeing them become freethinking, independent scientists — that feels like a real privilege.”
Lyle acknowledges that some days, research can seem Sisyphean. Even in the most successful research, finding answers to questions often leads to more questions.
That, though, is the joy of it. Every careful step and double-checked procedure, every data point and unexpected result, she hopes, takes her further along a pathway to making a real difference in people’s lives.
All research offers a sense of both endlessness and progress. “It’s easy to feel like you’re asking questions that you’ll never find an answer to,” Lyle says. “But we really are getting closer and closer to delivering drugs that will improve patients’ quality of life. That’s what drives me. We’re continuing to roll the ball up the hill.”