Secrets to the Significant Research Essay

Jake Khoussine
11 min readOct 7, 2022


The final major essay for the primary application to MD/PhD programs is the Significant Research essay. This is your opportunity to demonstrate that you have the research experience necessary for the MD/PhD career path and that you can communicate your research effectively. Excellent essays are a blend of narrative and scientific writing. You must convey how your research experiences have shaped your perspective as a developing scientist. It does not matter how strong your technical research skills are at this point. What matters is that you can talk about the conceptual foundations of your work, describe its implications, and reveal the lessons you have taken from your journey.

Also, write this essay with your Personal Statement and Why MD/PhD essays in mind. What lessons have you already conveyed? Aim to limit redundancy and maximize cohesion across the “big 3 essays”. After a reviewer reads the 3 essays, what is the takeaway message you want them to bring to the admissions committee?

The Significant Research essay can be intimidating because of its 10,000 character count. Unlike the other essays, space limitations are unlikely to be the problem. Instead, avoid wordiness and do not fill space with impressive, meaningless words to describe your research. Write concisely. I don’t need to know about obscure protocols or technicalities.

I remember the first draft of my Significant Research essay clearly. I was excited to talk about my project studying the sand scorpion’s sensory organ called a pecten. The pecten is an appendage on the underbelly of the scorpion that has finger-like projections which tap the sand as it walks to pick up on chemical trails for navigation. Frankly, no one cares about the pecten except for scorpion scientists; though, most people love hearing that I studied sand scorpions. I will never forget interviewing with an MSTP director at one of my “reach” schools and seeing how their face lit up when I started talking about sensory neuroscience of scorpions. Take cues from your interactions with peers and mentors to identify the stories that stick, and which fall flat. While you cannot simply say a bunch of buzzwords in compelling sentences, your writing must capture the attention and intrigue of a busy reviewer. Overall, I feel that the Significant Research essay is more about the narrative than the technical science. Nonetheless, it is important to write your experiences through the lens of scientific method and to explain clearly how you contributed at each stage of a project’s development. I want to see how you thought critically about your research and how you solved problems to define your path. This essay is the research version of the personal statement.

Moreover, in the secondary application, many programs have additional essay prompts in which you will be asked to write more specifically and technically about your research. The ability to adapt your research narrative in each essay is what differentiates the good from the great applicants. To be excellent, you will also need to communicate your science well in conversation. I will write in depth about how to approach secondary applications for MD/PhD programs soon, but to show you what I mean, here is an essay prompt from the Stanford MSTP secondary:

“Describe your most significant research experience. Include the rationale, results, and conclusions, and the role you played in each of these components. Please be very specific, including the dates and amount of time you were engaged; mention publications or presentations that resulted or will result from this work. Please refer to publications by the last name of first author followed by the year (e.g. Last name, 2020). Full citations of your publications should be included in the “peer-reviewed publications” section of this application. Please limit your answer to 2,500 characters including spaces.”

  • Seems redundant, right? This is your language fluency exam. Pick your central research experience and explain it like a scientist. Show me that you can talk science and remain clear to audiences outside your field. Also prove to me that you had a hands-on experience and took initiative in your project. From writing the Significant Research essay, your “research talk” will continue to get more pointed as the admissions cycle progresses. In the interview, you will convey this story in an even more refined structure. See my post on interview prep here and read question #4 for more information on communicating your research in interviews.

Therefore, use the Significant Research essay to tell the story of your research background. What was your first introduction to research? What inspired you to continue this path? It’s OK if your research experiences are disconnected. I want to know what led you from one experience to the next. Be specific. What drives you? Were you consistent in your commitment? How did you confront failure? Two things to keep in mind: 1) your reviewers are most likely not in your field and 2) they are tired from reading all the other essays. Write clearly at the graduate-school level for a broad scientific audience. Imagine a no-bullshit older white male assistant professor with a PhD who has spent his research career studying mechanisms of neurodegeneration in glaucoma reviewing your application. Also imagine a busy 25-year-old Latina grad student studying cancer immunology who hustled to do an MD/PhD reviewing it. Excellent essays resonate across backgrounds. Your goal is to receive a secondary application and continue refining your story. Convince me that you can communicate your science and make me want to know more about you and your research. The application process is a long journey. Play the game wisely. Part of playing wisely is to be courageous with confidence, cautious with embellishment, and unambiguous with humility.

As I mentioned, I started with scorpion research studying sensory neurophysiology and invertebrate behavior. Concurrently, I found a second research mentor studying developmental genetics and programmed cell death in fruit fly eyes. I worked in both labs for over a year, getting familiar with the research landscape, reading literature, and deciding on a topic for my honor’s thesis. I did a summer research program that allowed me to combine my neuroscience and genetics interests to study mechanisms synaptic development in the neuromuscular junction of larval fruit flies. I enjoyed microscopic dissection and learning about the complex patterns of developing nervous systems. To take this work a step further, I wanted to understand more about the cell biology of neurons. I was interested in studying neurodegenerative diseases like ALS, Charcot-Marie-Tooth, and Hereditary Spastic Paraplegia (HSP). The latter, HSP, was especially fascinating to me. HSP is a genetic disease for which over 80 different genes have been implicated in disease pathogenesis. The disease causes progressive leg paralysis and occurs in geographically isolated clusters worldwide. One of the major pathomechanisms converges on abnormal cellular trafficking of proteins from the neuronal cell body in the lumbar spine to the axon terminals in the upper thigh. The axons of these lower corticospinal motor neurons are nearly a meter-long and are an essential highway for conscious thought to travel from the brain to move our legs. It seemed that a molecular traffic jam within neurons was a principal cause of disease. This research experience allowed me to cultivate my technical acumen with cellular and molecular biology and provided an interesting avenue to expand my knowledge in the neurogenetics field. It also inspired me to reach out to a Moroccan neurologist studying the human genetics of HSP and ALS in the Near East. As I will explain in another post, I deferred my acceptance to the MSTP for one year to live in Morocco with my family and follow-up on this research opportunity. I did far more living than doing research.

Serendipitously, while reading about the symptoms that HSP patients with different mutations experience, I found something that changed my entire research path. It turns out that in addition to progressive leg paralysis, many patients with HSP also become progressively blind. I didn’t know much about vision at this point. My undergrad research focused more on the genetics of cell death in the developing compound eye, rather than on the retina. So, I started reading about the retina, and the hypotheses for how HSP might cause blindness. This led me to propose a collaboration in which I would study the retinas in a rodent model of HSP when I returned to my university. I rotated in the labs of two retinal scientists, one studying photoreceptors and stem cells, the other studying bipolar and ganglion cells. I found that the rodent model of HSP had abnormalities in retinal morphology that could contribute to the progressive blindness observed in humans. Following this collaboration, I knew that I wanted to focus my PhD research on the neural circuits of the retina in development and disease — a welcome throwback to my sensory neurophysiology and developmental genetics background.

The purpose of my example is to flex. Kidding…it’s to show you that what makes a Significant Research essay compelling is the narrative of events which takes the student from one path to the next. It doesn’t matter if they’re nicely connected like my example. If the spirit moves you from virology to neuroimaging, that’s cool. If it’s a singular, longitudinal experience, that’s fine, too. Just tell me what it was about your experiences that captured your interest, or perhaps, what turned you off about it. Show me your initiative and enthusiasm for research; I want to see that you know what you’re signing up for. It’s critical that you do because you are expected to show that you have put in the work and the time to evaluate fully whether this is the right career fit for you. You will also need to tell me about how you failed, troubleshooted, thought critically, and solved problems to progress through your research journey. Don’t forget to know your science at a high level, as well.

I will now show you examples of both how to and how not to approach the Significant Research essay in the following section. As usual, details have been changed to protect the writers’ identities.

How not to write the Significant Research essay:

1. John Snow, PhD, Rivercrest University, Physics Dept., Jun 2017 — Aug 2017

I entered college as a physics major because the field’s emphasis on statistical and programming techniques was invaluable for my goal of pursuing computational-based genomic research. In particular, I developed the rigorous mathematical thinking of a computational researcher in the MoonShot-40 (MS40) collaboration. MS40 used a dual-phase argon time projection chamber that detected particle collisions (pulses) to search for dark matter. In two exploratory projects, I analyzed 100,000+ particle collisions (pulses) in ROOT C++ and Python, clustering pulses by energy, duration, and radial position to elucidate pulse behavior. I investigated whether ‘mystery pulses’ that appeared following a detector power outage resulted from degrading equipment, a software bug, or a contaminant. I learned to cope with lab failure because mystery pulses were elusive and on several occasions I spent hours interrogating pulses that proved to be valid data before I showed that the loss of power opened an unused safety valve and introduced a contaminant. Next, I used contrastive principal component analysis (cPCA) to extract and compare pulses reconstructed inconsistently by three collaboration-designed pulse reconstruction algorithms, learning to integrate statistical validity into my problem solving. I found that the inconsistencies stemmed from the Monte Carlo simulation used to calibrate the detector, which poorly modeled certain types of pulses. I learned to communicate my science to varied audiences while giving regular updates to collaborators from Brown, Temple University, OU, and Italy, then presenting my research in one poster presentation and as two thirty-minute talks. My research was the basis for receiving a $3,000 Outstanding Student Award for excellence in physics scholarship.

What I like about this essay:

  • The format. Much like an expanded CV, you should facilitate readability by making a heading for each experience with a discussion of your research below. Each heading should include: PI name, University, Duration of your involvement. A wall of text is exhausting to read for reviewers. Help them out by breaking your experiences into sections.
  • It’s quite interesting research. Not many applicants have a dark matter particle physics experience.
  • It presents a research problem and how the student overcame it
  • It involved multi-institutional collaboration, and the student took initiative to present their work on this project.

What I dislike about this essay:

  • The jargon and wordiness
  • Does not translate easily to people outside of physics and mathematics
  • Connection between the physics and genomics research is somewhat unclear
  • What’s a mystery pulse? The project needs more of a background set-up.
  • Who is Monte Carlo? (kidding, but explain your jargon)
  • This sentence: “Next, I used contrastive principal component analysis (cPCA) to extract and compare pulses reconstructed inconsistently by three collaboration-designed pulse reconstruction algorithms, learning to integrate statistical validity into my problem solving.” Focus on cutting excess and promoting clarity at every chance.

How could this research experience be improved?

1. John Snow, PhD, Rivercrest University, Physics Dept., Jun 2017 — Aug 2017

I entered college as a physics major because I was curious about the fundamental principles that underpin all of science, and I wanted to improve my understanding of statistical and programming techniques. Ultimately, I knew that I wanted to apply these skills to the field of computational genomics research. In this summer project, I began developing the rigorous mathematical thinking required for computational research in the Moonshot-40 (MS40) collaboration. MS40 used a dual-phase argon time projection chamber that detected particle collisions (pulses) to search for dark matter. After the lab housing the detector experienced a power outage, ‘mystery’ pulses inconsistent with particle collisions appeared. I investigated the origin of the mystery pulses, analyzing 100,000+ pulses in ROOT C++ and Python, clustering them by energy, duration, and radial position to evaluate collision behavior. I learned to cope with lab failure while pursuing multiple unsuccessful hypotheses to explain the mystery pulses, like software bugs and equipment degradation, before eventually demonstrating that a contaminant, introduced when the lab lost power, was responsible. In addition, I learned to integrate statistical validity into my problem-solving. For example, the location of a collision within the detector had to be reconstructed from energy characteristics of the pulse. Three different collaborators had written three different reconstruction algorithms, and each algorithm reconstructed conflicting locations for certain pulses. To address this inconsistency, I applied contrastive principle component analysis (cPCA), which is a technique that extends traditional PCA by subtracting background noise, to characterize the conflicts between reconstructed locations. This approach allowed me to trace the source of this inconsistency back to the Monte Carlo simulation used to calibrate the detector, which poorly modeled certain types of pulses. My contribution helped to solve a problem that limited the generalizability of the research project. The opportunity to communicate my findings with collaborators at institutions across the U.S. and Europe as well as present my summer project to audiences with varied scientific backgrounds made this an especially significant experience. Still, at the project’s conclusion, I felt motivated to apply these new skills to my growing interest in computational genomics research.

  • This student’s second research experience involved use of computational genomics tools to study the mechanisms of epigenetic regulation in disease. By leading the first experience into the second, you gain a sense of cohesion and overall direction for the student’s motivations. This is important because you are trying to paint a salient picture for the reviewer about who you are as a scientist. In your secondary applications, you will expand upon this foundation to describe the graduate program(s) that interest you, and the faculty members you want to meet. You will not be pigeon-holed into a niche based on your prior research experiences. You don’t have to be certain about a career path, either. There is plenty of time later to design your path exactly as you prefer. However, it’s important to convey a clear vision of what a potential career path might look like for you— remember, one correct answer is that you want to be an academic physician-scientist.

If you like this content, let me know at I want to hear from you. Also, I am offering a free MD/PhD preparation course to select students for the 2023–24 admissions cycle, where I will teach you strategies for application preparation. Reach out if you are interested.



Jake Khoussine

I’m a first generation student in my 7th year of MD/PhD training. This is everything I wish I knew earlier. I hope you find it helpful, feel free to reach out.