I stride purposefully towards the exit, my luggage gripped in one hand and my passport in the other. The sliding doors part seamlessly, revealing the arrivals area. As usual, my parents spot me before I can. Our reunion feels both familiar and unfamiliar. It’s been precisely one year since I saw them last summer, a gap that now collapses in our embrace. As we drive home, I watch the
Korean landscape unfold like a living painting, towering apartment complexes punctuating the
endless mountain ranges.
“James, you should let your grandparents know you’re back,” my father suggests in Korean. I reach for my phone and start typing my grandfather’s name: 황방남. I dial his number, and the phone rings – three, four, five times. Just as I contemplate ending the call, his voice breaks through.
“Hi, grandfather. How are you doing?” I ask in Korean.
“넌 누구니?”
“Who am I? I’m James, of course, your third grandson.”
“Ah, our future doctor. I’m doing well. How are you?”
I sigh with relief as he finally recognizes my voice, and I catch up with him about my recent school year. A few minutes into our conversation, my grandfather pauses on the other side of the call.
“넌 누구니?” he asks again.
“It’s me, James, your third grandson…”
“Ah, yes, our future doctor.”
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According to The Cell: A Molecular Approach, Alzheimer’s disease results from the aggregation of misfolded proteins, forming amyloids that create plaques in the brain. According to the Mayo Clinic, symptoms of Alzheimer’s disease include memory loss, difficulty concentrating, and a decline in behavior and social skills. According to my grandfather’s physician, there is currently no cure for Alzheimer’s disease. There is currently no cure for Alzheimer’s disease.
In the summer following my sophomore year in college, I joined the Francis Tsai Laboratory in the Department of Biochemistry and Molecular Pharmacology at Baylor College of Medicine. The Tsai Lab utilizes X-ray crystallography and biochemical assays to investigate how protein quality control machines maintain proteostasis under normal and pathological conditions. In other words, we study the structure and function of proteins and how they relate to human diseases.
During my first meeting with Dr. Tsai, I shared my personal motivation to study Alzheimer’s disease. In response, Dr. Tsai entrusted me with an independent research project on Protein A 1 mutations associated with various neurodegenerative disorders. While conducting background research for my new project, I found that a significant constraint within current scientific research stems from the unresolved structure of Protein A. The prospect of uncovering this mystery sparked my enthusiasm, as I realized how my research could contribute to the development of pharmaceutical treatments for conditions such as Alzheimer’s disease.
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The elevator slides open, and in a playful rush, I race my brother to the apartment door.
My grandfather answers the door with a warm, familiar smile. A moment lingers before he asks, “넌 누구니?”
We stand there stunned but quickly respond in Korean, “It’s us, James and Jeremy, your grandchildren.” I am struck by how much my grandfather changed since I saw him the previous summer. He now grapples with significant memory loss and struggles to navigate daily tasks. I help him get dressed, find his favorite newsboy hat, and walk down the hall, all while patiently
answering his repetitive question: “Who are you?”
On the flight back to the States, tears flow as I reflect on memories shared with my grandfather, my cherished role model. He always recounted stories of his bravery in the Vietnam War and how he founded a new church from scratch. He always encouraged me to continue pursuing medicine, envisioning the day he could proudly walk into his grandson’s clinic. He always reminded me of his role in naming me at my birth. Now, he no longer knows who I am.
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After months of meticulous preparation, I successfully purified both the wild-type and mutant variants of Protein A. The final steps seemed fairly straightforward: cultivate protein crystals, subject them to X-ray exposure, and decipher the protein structure by analyzing X-ray diffraction patterns. I observed with anticipation as the pipetting robot delicately dispensed nanoliters of Protein A into the respective buffer solutions. However, my excitement quickly tempered as the mutant versions of Protein A immediately induced cloudiness in the solutions.
Dr. Tsai forewarned me about this potential outcome, emphasizing the likelihood of obtaining aggregates instead of the desired well-formed protein crystals. In “A Guide to Studying Protein Aggregation,” Housmans explained how crystal formation is necessary for X-ray crystallography. Thus, protein aggregation not only contributed to the complexities of neurodegenerative disorders but also thwarted scientific efforts to unravel their intricacies. In my next meeting with Dr. Tsai, I asked why Protein A failed to crystallize. I was somewhat frustrated by this obstacle in my scientific research, no, my personal research for my grandfather. I anxiously waited for a response as Dr. Tsai stared at pictures of my crystallization plate.
“I don’t know why,” Dr. Tsai answered.
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It’s summer once again, and the plane touches down at Incheon International Airport. I embrace my parents and begin the lengthy drive home. Now a familiar routine, I instinctively reach for my phone and type my grandfather’s name: 황방남. I dial his number, and the phone rings – only twice this time – before his voice breaks through.
“James, I’m glad you’re back in Korea. How are you doing?”
I pause.
“Hello? James?”
“Hi, grandfather. I’m doing well, and I’ve just begun applying for medical school…”
As soon as I end the call, I glance up to find my parents smiling in the front seat. They overheard my conversation, of course. Seeing my shocked and confused expression, my father explains how there are mysterious weeks when my grandfather’s dementia seems to improve. No one knows why. Our family has simply learned to savor these moments of clarity. Yet, there are
weeks when Alzheimer’s disease tightens its grip on my grandfather, and his recurrent question, “Who are you?” becomes more prevalent. I recognize that my time with my grandfather is limited, making each moment of recognition all the more precious when he proudly exclaims, “Ah, yes, our future doctor.”
Each summer, when I’m blessed with the opportunity to reunite with my grandfather, I find growing motivation to continue my research on Alzheimer’s disease. Witnessing my grandfather’s rapidly degrading condition imparts a sense of urgency as I see the clinical presentations of the molecular events I study. Despite facing countless setbacks in my attempts to crystallize Protein A, I unfailingly return to my lab bench and push forward, motivated to do science for people like my grandfather, not just for its own sake. Consequently, I often find myself meticulously scrutinizing my Protein A aggregates, posing the same question over and over again.
“넌 누구니? Who are you?”
1 Due to the competitive nature of the structural biochemistry field, Dr. Tsai advised me to refrain from explicitly
identifying my specific protein through name or citation. I thus employ the pseudonym “Protein A” to maintain
confidentiality.