Basic Science Is at the Ground Floor of Discovery

Originally published December 13, 2021, by University of Arizona Health Sciences.

Basic scientists are patient when running experiments and undaunted by setbacks. These traits are necessary for discovery.

When the Kuhns Lab created its first successful batch of T cells studded with five specially engineered antigen receptors and co-receptors, the room was bursting at the seams with eager anticipation.

“There were four of us in the lab late at night, huddled around the flow cytometer, watching as the data came across the computer screen. We were waiting with bated breath to see what the results might be,” recalled Michael Kuhns, PhD, associate professor of immunobiology at the University of Arizona College of Medicine – Tucson. “To invent something that’s never existed before, to taste discovery — that is really rewarding.”

Dr. Michael Kuhns demonstrates how engineered immune cell receptors might fit together into a more complex molecular machine. Photo: Noelle Haro Gomez, University of Arizona Health Sciences Office of Communications

Building on previous discoveries about how cells talk to each other, the lab designed a new T cell that could kill overactive immune cells. They relished this accomplishment as a victory unto itself — the fruits of years of eavesdropping on cells and carefully decoding their conversations. But nonscientists might not appreciate how tinkering with T cells in the lab could benefit them one day.

Dr. Kuhns calls himself an “unabashed basic scientist,” a researcher who investigates the fundamental biological mysteries of how cells and molecules interact in the body. If those discoveries someday lead to treatments for debilitating diseases, that’s the icing on the cake. But for nonscientists, separating the process of initial scientific discovery from the innovations society reaps down the line can be difficult.

Dr. Kuhns says basic scientists are motivated by pure curiosity.

“I’ve got an engineer’s mindset. I like to take things apart and figure out how they work. We look at these molecular machines and ask how these parts fit together,” he said. “We can use evolution’s blueprint for these molecular machines to build new molecular machines that may have a therapeutic function.”

A nonlinear process

The nonscientist might assume science is conducted like a lot of jobs, with clear objectives and timelines. But scientists operate a little differently, continually refining their experiments to get more reliable or detailed results, using what they call an iterative process.

Dr. Shenfeng Qiu (right) works with postdoctoral fellow Dr. Hee-Dae Kim of Dr. Deveroux Ferguson’s lab. The two researchers’ labs collaborate to tackle big questions in neuroscience.

Shenfeng Qiu, PhD, MD, MPH, associate professor of basic medical sciences at the UArizona College of Medicine – Phoenix, says the scientific process isn’t linear.

“Sometimes science can circle back on itself,” he said. “You extract useful ideas and then build on those ideas further. Successive reinvestigations may lead back to the same question. During this process, you probably find something that’s even more interesting. You’re asking a different question, which may be deeper and give you more profound answers. This iterative process is one way science advances itself.”

In this sense, science starts out like a rough sketch on a napkin, which over time is filled in with details and colors. Eventually, the picture moves from the napkin onto an expansive mural. A nuanced view of biology slowly emerges, thanks to the work of countless scientists adding small flourishes to the portrait of life. This incremental accumulation of information might frustrate those who don’t understand why science hasn’t already found cures for diseases like cancer or Alzheimer’s disease, but it allows scientists to look at old questions with fresh eyes and get one step closer to the answers.

Michael D.L. Johnson, PhD, assistant professor of immunobiology at the College of Medicine – Tucson, compares science’s iterative process to cleaning a house.

“That moment when you know something nobody else on the planet knows — that’s the thrill.”

“You make up the bed, you vacuum the floor, you clean the windows, but you can’t call the whole job done. On its surface, it looks clean, but underneath the surface, there are all these other things we need to do,” Dr. Johnson said. “Did you use an air purifier? Did you change the filter? Have you dusted the ceiling fan lately? Wait, you have to actually clean your ceiling fans? The more we research, the more we learn what’s underneath the surface.”

Revisiting old questions with new information takes patience, especially when many people would rather move from one task to the next with constant forward motion. Basic scientists, however, know that to do science correctly, they must retrace their steps as they learn more about what lies underneath the surface.

Try, try again

Most experiments don’t prove the hypotheses being tested, but scientists see these results as opportunities for growth and learning, giving themselves space to keep plugging away when things don’t work out as they envisioned.

Dr. Qiu says failure is a part of science.

“When we were kids, we all heard of Edison, who probably failed a thousand times, maybe more, before he invented the light bulb,” Dr. Qiu said. “Failure is a bad thing if you don’t learn anything from it. We need to learn from failure to advance in science, to refine our knowledge, and move on to achieve better things.”

Dr. Michael D.L. Johnson investigates how copper interacts with bacteria. His research might someday help solve problems relating to antibiotic resistance. Photo: Noelle Haro Gomez, University of Arizona Health Sciences Office of Communications

As long as an experiment is designed to generate accurate data and account for variables, the results are what matter, regardless of whether they confirm a hypothesis.

“If you disprove your hypothesis, it’s not a failed experiment. If you test your hypothesis, and you are correct or incorrect, I would call that a successful experiment,” Dr. Johnson said. “Being incorrect is not the same as failing. If you learn something, that’s not a failure. Failure is in experimental design. If you don’t design it correctly, that’s a failed experiment.”

May Khanna, PhD, associate professor of pharmacology at the College of Medicine – Tucson and a member of the BIO5 Institute, incorporates the expectation of failure into her approach to teaching. She says normal classrooms, by grading students on the A-to-F scale, don’t reflect real life, which is full of failures that make people stronger. She emphasizes this message to everyone working in her lab.

Dr. May Khanna says students need to experience failure to build resilience, empowering them to make future discoveries. Photo: Kris Hanning, University of Arizona Health Sciences Office of Communications

“The very first thing that comes out of my mouth is, ‘You have to be willing to fail, because you will not succeed until you fail.’ Then they fail, and they fail, and they fail, and boom, they succeed,” Dr. Khanna said. “Some of my best researchers have been kids who have struggled, who have had such a tough time in life, and then realize, ‘Wait, I’m used to this.’ Welcome to research!”

Taxpayers on a plane

Science is incremental and nonlinear by design, but many people are frustrated by its pace, which they might perceive as too slow.

“People expect to have a cure overnight. Like, ‘Why haven’t you cured cancer yet?’ But you can’t just speak it into existence like that,” said Dr. Johnson, who is also a member of BIO5. “It’s not a singular task to make a cure. There are all these different components that go into it.”

And anyone wondering why the Kuhns Lab is fiddling around with T cells might be frustrated by the seemingly obscure nature of basic science.

“They’re a taxpayer, and taxpayer money is funding what I do,” said Dr. Kuhns, also a member of BIO5. “We taxpayers can afford to invest in something with such a high failure rate, in a way that a company beholden to its stockholders can’t. Because you’re still going to get that 10% hit, and they’re going to lead to drugs. You can apply that knowledge in some practical way that the taxpayer on the seat next to you on a plane would really appreciate.”

As to how the Kuhns Lab’s highly customized T cells can benefit the taxpayer, Dr. Kuhns hopes their invention may someday lead to a therapy that can eliminate rogue immune cells that cause Type 1 diabetes, rheumatoid arthritis, multiple sclerosis and other autoimmune diseases, which affect more than 24 million Americans, and also be used to fight some types of cancer. The possibilities are wide open, and the daily opportunity to make fundamental discoveries that set the stage for tomorrow’s innovations gets him out of bed every morning.

“Basic science is challenging and stressful, but it’s rewarding. We had a result in the lab the other day, and I was telling the people who did the experiment, there are 8 billion people on this planet, and you two are the only ones in the world who know that answer,” he said. “For those of us who go into this business, that’s the thrill: that moment when you know something that nobody else on the planet knows.”