The smart-dumb question, a key to writing about — and understanding — immunology

Newswise — BIRMINGHAM, Ala. – “The human immune system makes my head explode,” Pulitzer Prize-winning journalist Matt Richtel recently told a University of Alabama at Birmingham freshman seminar on immunology. “This is by far the hardest subject I have ever had to explore.”

Richtel, a longtime New York Times reporter, was explaining why he wrote his general interest book “An Elegant Defense — The Extraordinary New Science of the Immune System,” which the class was reading.

Richtel’s curiosity began when his boyhood buddy Jason Greenstein, “the best kind of jock,” got cancer in his 40s.

“He had 15 pounds of cancer, went into hospice and was supposed to die,” Richtel said through a video link with the UAB Honors College freshman seminar. However, when Greenstein — who had “nine toes in the grave” — got experimental immunotherapy, the cancer disappeared, though Greenstein later died. “I didn’t understand,” Richtel said. “What is this thing called the immune system, that they can tinker with to keep us alive?”

Indeed, what is this thing, which is so complex and important in human health, development and disease? The UAB seminar freshmen are just beginning to scratch its surface.

Immunology vs. neuroscience
In many ways, immunology is as challenging a major as neuroscience, another undergraduate major found in the UAB College of Arts and Sciences and at many other colleges.

Both the nervous system and the immune system are composed of a widespread network of organs, tissues, cells and soluble mediators that work together. Both systems interface with every organ in the body, as well as each other. Each plays critical roles in health and disease, and both require years of study for a student to grasp how the system works, and to tread a landslide of nitty-gritty mechanistic interactions that regulate normal function, or that misfire to cause disease, dysfunction and, sometimes, death.

Yet the two majors have a difference. Neuroscience is far more obvious. Each of us knows we have a brain. We daily experience five senses that report the world around us and convey pleasure or pain. Many of us have relatives or older friends who suffer the visible signs of neurodegenerative disease.

Immunology lacks this focus. Where or how does the immune system operate? What are its components? For most of us, the immune system is a vast, foggy landscape where many important things happen beneath our notice.

These differences explain, perhaps, why the number of neuroscience undergraduate majors has boomed in the past three decades, while in-depth immunology undergraduate majors still remain few. One of the few is UAB’s major, begun in 2017.

A broad and deep study
The UAB immunology joint-health program in the UAB Department of Biology and Department of Microbiology is a four-year curriculum. After the freshman UAB honors seminar, full-semester courses include current topics in immunology, the innate immune system, the adaptive immune system, the microbial pathogen-immune system interaction, and immunologically mediated diseases.

The education is wide-ranging, and students also work in laboratories, readying themselves for careers in the health professions or research.

“Immunology, by nature, is interdisciplinary,” said Lou Justement, Ph.D., the teacher, along with Heather Bruns, Ph.D., of the honors seminar. Both are microbiology faculty in the UAB School of Medicine. “It requires a knowledge of cellular and molecular biology, genetics, biochemistry, physiology, and anatomy. Freshmen are introduced to medically related conceptual frameworks that continue through the four-year curriculum — how immunology relates to vaccines, emerging infectious diseases, autoimmunity, allergy, transplantation, cancer and immunotherapy. Students learn how the immune system is relevant to health and disease.”

Telling the story through people
Richtel took a different approach. Rather than write an immunology textbook, he put faces on the role of immunology in health and disease. Parts of “An Elegant Defense” tell the stories of Jason, Bob, Linda and Merredith, and the burdens they faced — Hodgkin’s lymphoma, HIV infection, rheumatoid arthritis and lupus. Richtel also relates surprising twists and turns for basic researchers who studied the immune system. “It’s a story,” he writes at one point, “that begins with a bird, a dog and a starfish.”

During the video Q&A with students, Richtel wore a UAB T-shirt. Most of the UAB students asked how he reported and wrote the book. “One of the hardest things to do when writing is to find your framework that will pay off the reader as you promised,” he said.

And Richtel asked questions right back, offering guide stones of advice for the students:

• On finding their direction — “I really want to urge you to marry this,” he said, tapping the top of his head, “with thinking with your gut, because that is where truth is.”
• On the heart of learning — “I’m not afraid to be dumb. An editor calls it the smart-dumb question, like, ‘Why call it an antibody when it goes for the body, not against the body?’ I urge you — one of the ways to be smart is to be dumb. That involves being vulnerable, and getting across the shame of not knowing.”
• On the key to telling a story — “On some level, every story is the same; you have to get to the smart-dumb question.”

UAB freshman Chandni Modi was one of the enthusiastic participants in the Q&A with Richtel. Afterward, the Indian Springs School graduate said, “Honestly, at the beginning of my high school senior year, UAB wasn’t one of my top choices. However, after I started comparing my options, UAB was the only school that offered immunology as a major, and UAB offers so many ways to get involved in research.”

“Also,” she said, “I appreciated how diverse the university students and faculty are.”