Why a Good Mechanism Isn't Enough by Reynaldo

Why a Good Mechanism Isn't Enough by Reynaldo - October 2026 Scholarship Essay

Heart disease and high cholesterol run rampant in my community, and I grew up knowing it. In my metabolism courses at Florida State University, I learned how cholesterol is formed and moved through the body, and it left me with a question I couldn’t shake: how does a drug interrupt that process? My time in Dr. Parvatiyar’s lab had already taught me to ask why something works, not just record what happens. That habit pushed me to seek research at Mayo Clinic’s Clinical Research Internship Study Program (CRISP), where I joined a project on PCSK9 inhibitors, a newer class of cholesterol-lowering drugs, and their effect on carotid artery stenosis, a narrowing of the arteries in the neck that carry blood to the brain and a common site of plaque buildup.

The question that hooked me was simple. How do these drugs lower LDL, the “bad” cholesterol? Before touching any data, I wanted to understand it well enough to explain it to someone else, so I built diagrams that broke the mechanism into steps. The liver clears LDL from the blood using receptors that act like catchers. PCSK9 is a protein that signals those receptors to be destroyed, leaving fewer to do the job. The inhibitor cancels that signal, so more receptors survive and keep working. That mechanism also showed me why these drugs matter for patients who cannot tolerate statins, the standard cholesterol medication, because of muscle pain.

Our study began with screening over 500 patient charts to build a group of 62 patients: 20 on PCSK9 inhibitors and 42 on statins alone. We compared ultrasound and CT imaging of their carotid arteries, along with clinical outcomes such as strokes. Going in, I expected an elegant mechanism to produce a clear advantage. What we found was narrower. Blood flow speed through the left carotid artery, where faster flow typically signals a tighter artery, dropped significantly in the PCSK9 inhibitor group while it rose in the statin group (p = 0.02). Several other ultrasound measures trended in the same direction without reaching statistical significance, and CT imaging showed no significant difference. Outcomes favored the inhibitors, with no strokes compared with 29.2% in the statin group, but that result also fell short of significance. With only 62 patients, we could not say more than that.

At first, that felt like a letdown. I had understood the biology so well that I assumed the outcome would follow. Instead, I learned the difference between a trend and a result, and between a strong mechanism and a proven outcome. A mechanism tells you what should happen, and only enough data can tell you whether it does. I was selected to present this work at the program’s competitive oral symposium to physicians, residents, and medical students, and I presented the limitations alongside the findings.

That experience changed how I approach medicine. Curiosity gets you to the question, but honesty about what the evidence can and cannot show is what makes the answer trustworthy. As someone who wants to bridge clinical medicine and basic science, I want to be a physician who stays fascinated by why things work and stays disciplined about what has been shown.