Navigating the Transition: From Medical School to the Laboratory as an MD/PhD Student

Jake Khoussine
10 min readJan 17, 2023

The best MD/PhD programs have a curriculum that exposes students to clinical medicine before transitioning into the PhD phase. My year of clinical training fulfilled a long held desire to put textbook knowledge into action to help patients in need. However, it was also the most exhausting year in terms of studying for multiple-choice exams, including the Shelves, STEP1 and STEP2. By the end of all that studying, I felt like I had become a test-taking robot. The constant objective measures of my knowledge and comparisons to “average” were tiresome. Therefore, walking into my research lab on day 1 offered a much needed respite from it all. Now that I’ve roughly crossed the halfway point for my PhD, I want to share my experience with the transition from MD to PhD.

As an MD/PhD student in a Cellular and Molecular Biology PhD program, I do not have to take much additional coursework during graduate school. My time is dedicated to reading scientific literature, conducting experiments and analyses, and presenting my research. No longer am I concerned with my objective performance; rather, my goal is to improve my skills as an experimentalist to become a productive and independent scientist. While objective data underpin scientific research, the practice of experimental skills is a more subjective endeavor. Different people have different approaches, and indeed, different expectations for what constitutes “good” and “rigorous” science. Depending on your lab and mentor, you might have widely distinct experiences in research training.

Choosing your lab and mentor carefully is crucial for success in graduate school

Before I get into my experience in graduate school, it’s worthwhile to spend a moment explaining how I decided on my research lab and mentor. My research background is in molecular neuroscience and genetics, and I knew that I wanted to continue in this area for my PhD research. After talking with senior MD/PhD students in my program who share my interests, I identified a lab studying the cellular trafficking mechanisms of motor neurons implicated in a set of genetic diseases called Hereditary Spastic Paraplegias. The PI was well-established and rapidly ascending the academic ladder, but they still had time for weekly check-ins. The research was heavily molecular, and I lacked experience with the methodology. I quickly learned that I did not enjoy the PCR, western blots, and plasmid design that was integral to the research, but the questions were interesting to me. Overall, the research was time-intensive and tedious, and I wasn’t convinced it was my best match.

Since lab rotations typically occur the summer after the first year of medical school, I had taken some time to evaluate the clinical specialties that most interested me: pediatric neurology, neurosurgery, and ophthalmology. Serendipitously, it turns out that the form of Hereditary Spastic Paraplegia that I was studying in my first lab rotation has a phenotype of progressive blindness in many individuals. As I became more excited about the prospects of a career as an ophthalmologist, I decided to explore labs that focused on retinal neuroscience. Thus, my second lab rotation was with a physician-scientist who is renowned for their work on modeling retinal development and disease with human-derived iPSCs. This PI is at the peak of their career: tenured, director of research programs, large clinical practice, and CEO of a business focusing on stem cell therapies. I went to their pediatric ophthalmology clinic in the morning and was working in their lab in the afternoon. It was a picturesque MD/PhD experience. I admire this PI greatly, and my career trajectory has been positively influenced by their path. However, I found the growth and maintenance of stem cell culture to be even more time intensive and tedious than the molecular work. Perhaps at some point all research has these qualities, but I do believe that there are certain flavors of experimentation that can be more energy giving than draining. So, I continued to search for my match.

Finally, there was also a new PI who had recently started their lab studying retinal structure-function relationships in development and disease, and I was curious about working with a younger PI who was tenaciously developing their laboratory. Furthermore, since undergrad, I had been deeply interested in becoming a patch clamp electrophysiologist, and this PI had worked at the Max-Planck Institute of Neuroscience in Germany where she learned patch clamp technique from one of the Nobel Prize winners who established the technique. It was an incredible opportunity. Ironically, patch clamp electrophysiology of the retina is probably the most challenging and tedious experimental technique of any I had been exposed to at this point, yet I loved it. Studying the fundamental biophysics of retinal neurons in normal vision and blindness offered me a chance to become an expert in the field that interested me the most. I was able to communicate well with the PI, and I appreciated her rejection of the “sink or swim” philosophy that some PIs adopt in their training of students. I needed guidance, because the truth was that my research skills were underdeveloped relative to other MD/PhD students. I felt like I was an imposter who snuck into the MD/PhD program. Now I had to demonstrate that I was up to the challenge and that I had what it takes to succeed in scientific research.

Style of mentorship is an important consideration for success in graduate school

The hands-on mentor will make sure you don’t get lost in a sea of literature and will help you hit the ground running. My PI is a hands-on mentor, which I have benefitted from greatly. I’m an MD/PhD student who had 2 years of research experience at the time of my application. In my view, this is the minimum experience required for MD/PhD, and I would have benefitted from additional post-bacc research. My technical research skills were limited, but I was skilled at communicating about ideas and applying scientific theory to design experiments. The reality is, however, that being an effective science communicator doesn’t do much for you when it’s time to carry out careful experimentation. There is a major learning curve to overcome, which is why having a mentor who was able to sit with me at the bench to show me experimental technique was crucial. It is important that you have open communication with your PI about your needs so that you can find the right balance. The first year in the lab is a learning period for you and the PI. You have to demonstrate your independence and initiative to earn trust and autonomy. Having someone constantly checking your work over your shoulder can become annoying if you don’t set boundaries, and I am grateful that my PI and I could talk about this arrangement openly.

On the other hand, many of my colleagues joined labs with “hands-off” mentors. This can be great if you desire more independence and freedom in graduate school, but it can also lead you to feel isolated and like you’re drowning. Without the objective measures of performance, it’s difficult to know how you’re progressing if you’re not getting frequent and consistent feedback from someone. If you’re doing computational work, this isolation can be especially challenging. Nevertheless, some people will thrive under this form of mentorship. You have to find out what works for your specific situation.

The first year of graduate school is full of creative energy and failed experiments

The change in my work schedule, lack of multiple choice exams, and new environment in graduate school filled my cup in an important way. I felt like I had awoken from a medical school-induced trance, and I was thrilled to look around at all the opportunities I could pursue with my newfound free time. I explored hobbies that I had placed on the back-burner, and I discovered interests I never knew I had. This is what we will call the “honeymoon phase”. I was learning experimental techniques, reading interesting papers, and discussing fundamental mechanisms with colleagues genuinely passionate about their research. I geeked out, in short.

The honeymoon phase lasts for about 4–6 months, then it’s time to actually collect data. My first 20 patch clamp electrophysiology experiments taught me 20 things not to do. Funnily, I became superstitious with my workflow to acquire good data. Yes, I do bow to my microscope at the beginning of each experiment to show my respect and ask for a good day of data collection. I had to learn MATLAB for my analyses as well as a multitude of analysis softwares. I also had to understand the circuit physics of the electrophysiology rig and be capable of fixing problems when they inevitably arose. Like many premeds, physics was not my strength in college; although, it’s much easier when you’re looking at a physical circuit. Nonetheless, it’s in the moments when you’re crawling behind a computer tracing wires and troubleshooting problems when the PhD truly begins. The honeymoon phase comes to a screeching halt, and the “oh, shit” moment emerges in full force. No one else is going to collect the data for you, and it’s on you to find solutions to unclear problems.

This realization causes imposter syndrome and anxiety. You might wonder: “what on earth did I sign myself up for?” You think about how after all the hustle in medical school, you were finally starting to get the hang of clinical medicine. As your medical school friends go on to apply for residency, you’re stuck in a crawl space with the computer wide open looking at wires and googling for explanations. While some people might find this tinkering to be wildly enjoyable, others may yearn for the direct and daily fulfillment of helping a patient. You must change your mindset to transition smoothly from medical school to the laboratory, and it takes time for this to take effect.

The change in mindset comes from immersion in the research and recognition that you are now playing a long-term game. You start appreciating that solutions come from trial and error and thinking critically as well as outside the box. You learn to become resourceful, and after you’ve solved several problems that at first seemed way over your head, you gain the confidence that you can do it again. Also, making friends with other graduate students allows you to commiserate and realize that feelings of imposter syndrome and anxiety are commonplace.

Moreover, the pace of research is slower than the workflow in medicine. In research, you might spend an entire week fixing a problem that happened without explanation in a moment. The PhDs know how long it takes for research projects to develop, and their sense of urgency is much less. This can be difficult for the type A med student who has been selected for and trained to work quickly. When a day of research isn’t working out and the problem cannot be solved, sometimes you just need to go home, get some rest and try again another day. In time and with persistence, you will find a solution.

Presenting your research and writing grants is an essential part of graduate school

Because of the delayed gratification of lab research, presenting and writing about your science provide checkpoints to measure your progress, evaluate your understanding, and enjoy little victories to keep momentum moving forward. As an MD/PhD, your research timeline is relatively accelerated. You should be presenting at lab meetings, local symposia, and research conferences consistently to develop your science communication skills, reveal gaps in your knowledge, and receive feedback to improve on your weaknesses.

Since beginning graduate school, I have written 3 grant applications: 1) an institutional T32 for vision research, 2) a state grant for telemedicine technology, and 3) the F30 NRSA grant for the National Eye Institute. Since grant writing is such a critical part of being an academic scientist, it’s important to practice this skill from the beginning. I will write a separate blog on grant writing, but suffice it to say for now that it is both an art and a crapshoot.

Importance of selecting a supportive and diverse thesis committee

In the past month, I completed my qualifying exam to become a PhD candidate officially. My thesis committee played an important role in this process, and I’m grateful that I took care in selecting the committee members. Two of my committee members are faculty whom I rotated with when searching for my PhD lab. While I got absolutely roasted in the Q&A portion of the preliminary exam, my committee provided great feedback on my weak areas. I was able to clarify my graduation timeline, and the expectations for completing my PhD. Especially for MD/PhD, you want a committee that recognizes your accelerated situation. You should not be on pace for a 5–6 year PhD; rather, aim for 3–4 years. A good committee will work with you and help you reach your goal with less friction.

Gratitude

I’m grateful for the opportunity to step out of medical school to conduct basic science research. The PhD phase has been a valuable time for me to reassess my career goals and consider the life I want to live. I found this clarity harder to find in the medical school whirlwind. The chance to build my personal life in my late 20s has allowed me to reach greater depth of character and self-confidence. While the research itself is a major reason why MD/PhDs are more competitive for most residency programs, I believe that the maturity and clarity that comes from this transitional time contributes significantly to this competitiveness as well. I look forward to writing in more detail about the experiences I have through this process in future posts.

If you’re enjoying this content, let me know. If there’s a topic that you’re especially interested in, I want to hear about it. I hope you find this helpful.

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Jake Khoussine

I’m a first generation student in my 5th year of MD/PhD training. This is everything I wish I knew earlier. I hope you find it helpful, feel free to reach out.