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The medical school application process is a long one. It starts the year before you intend to start medical school, i.e., your junior year spring if you are going straight through or senior year spring if you are taking a gap year. That is all to say that the process starts relatively quickly if you are planning on going straight through. It is the first three years of your undergrad that will truly affect your application. In addition, the process is rolling and there is a significant demonstrated advantage to applying as early as possible, once you have your final spring junior year (or senior year) grades and MCAT scores. 

We recommend following the timeline below and applying no more than 1-2 weeks after the initial application opens. This means looking at the application in advance and preparing all your answers and essays a few months before to be ready to submit once it opens. Furthermore, although you do have to wait for validation, most schools will send you secondaries immediately upon validation and will expect a turnaround of no more than 1-2 weeks for you to return them. This is difficult to do for multiple schools at once. However, most of the classic secondary questions are available online. We would recommend finding the questions for the schools you applied to and carefully preparing the secondaries during that validation period so that, once again, as soon as you are invited to complete that secondary, you can complete and submit it. This readiness will give you a decided advantage in the process. 

A Strong Application

Ok, so you know how to time it all. And you know you have to be quick. But now you’re thinking “How do I make it a good application that gets me in?” The simple answer is that there are several checkboxes that get you in the door with the committee. Check off a reasonable number of these boxes and you’ll have a strong application that will get you considered. But it’s a little more complicated than just that so let’s dive into it! 

I find the best way to think about your application is to think about it as an optimization problem. You have three to four years and need to maximize the underlying area between all of these checkboxes or points. Remember, NO ONE has a perfect application and no one can maximize all of these things. So don’t be discouraged if you feel one aspect is lacking. Your grades and scores will get you in the door so they are important. You need to not sacrifice that, although again, it’s ok if it’s not perfect. The other thing schools give weight to is that you show you know what it’s like to be in the hospital. This means doing some shadowing and some meaningful involvement with patients (but again, doesn’t need to be perfect). And for everything else, choose what you think you can maximize and focus on maximizing it rather than trying to do everything and doing a poor job. 

Let’s look at some examples. 

Student A: This student has fantastic grades and MCAT scores. They have done great research and have been involved in clinical and basic science research for a long time, showing commitment and a clear interest. They have publications from their work, including 1-2 first-author publications that they can talk about independently. They have evidence of leadership in research and extracurriculars. However, although they have shadowed a little bit and volunteered some of their time, they don’t have a strong history of being involved in the hospital. This student is still a strong candidate. They should think carefully about hospital-related experiences because they will be asked in interviews. However, even though they didn’t maximize everything, they have shown a strong deep commitment and they will likely see the return on it in the application process. 

Student B: This student has good grades and MCAT scores. They are heavily involved in public health outreach and in working with patients. They have worked for a long time at a diabetes clinic and have started their own initiatives there, showing strong leadership and a good understanding of what you can achieve as a physician and how it feels to work with a wide variety of patients. They have been involved peripherally in a few papers on their public health work but have not deeply invested in the research aspect of things. However, again, this is a strong candidate because they have a clear interest and have invested in it, and maximized their curve differently. 

Student C: This student has good grades and MCAT scores. They have been involved in some clubs and have some minor leadership roles. They have done a little research but have bounced around a few labs to try different things and have some peripheral publications. They have volunteered at the local hospital but haven’t had a chance to take on a key role given the way volunteers get involved at that hospital. This person, in theory, checks all the boxes but they are mediocre in all of them. They may well still get in the door but they haven’t made as strong a case for themselves as they could have if they had focused their interests a little bit more. 

*Emotional intelligence is a key aspect of this grid and is usually assessed in your interviews and essays. Even someone who is perfect on paper may not get in because they are perceived to be not a team player or not likable. Keep that in mind as you go through interviews! 

A Note on Grades

In our experience, pre-meds focus on grades to the exclusion of everything else. This is not necessarily wrong. As we discussed above, it is one of those key checkboxes. However, it’s important to remember that most competitive schools want more than just grades. Decent to good grades will get you in the door. But remember, good grades aren't everything. Many people get into medicine without perfect grades and many people with perfect grades don't make it. 

You should show involvement in more than just school, and those activities should show depth and commitment. If it is research, show long involvement in projects over years, with clear impact and publications. If you do bench research, supplement with some faster-moving clinical research to ensure you have publications out before you apply. If you volunteer, choose an experience where you get to truly interact with patients and have a role on their team rather than just shadowing or helping with small tasks. If you are in a club or activity, take on leadership roles and be able to talk about how you contributed.

Clinical Experience

Aside from grades, this is one of the key components of your application out of everything described above. You are applying to medical school and they want to know that you understand what it means to become a doctor - what the highs and lows are, what the limitations can be of your practice, what it is like to work with patients, and what it is to go through the grueling training. They want to know that you have seen some patients, had some experiences in the hospital, and that you can express how you might deal with challenging situations that we commonly encounter as physicians. 

Given all of this, it is incredibly important to not just shadow or just volunteer at a hospital where you have no real interaction with patients. It’s easy to make this mistake and volunteer at the biggest hospital in your area but this often means you are very limited in your role and your interactions with patients. Instead, we would recommend occasional shadowing at that large hospital so that you can understand what doctors do daily and see difficult pathologies and patient situations. (I say occasional because shadowing has limited return beyond a point if you are not able to participate actively). However, we would also recommend that you find a smaller clinic where you can have a more significant role in calling, coordinating, or counseling patients. Examples include performing intake surveys, transporting patients, volunteering as happiness ambassadors, or visiting patients who have no family. Those are roles that will allow you to develop those meaningful interactions. They will allow you to find your reasons to do medicine and describe what drives you. 

The Secret Sauce

All of the above is going to get you considered and get you in the door. BUT the secret sauce that makes a great application is building a clear picture of what your passions are and how you’ve fully committed to them. Think of it as an application spike - all of your activities and interests come together naturally to describe your single passion and this passion logically leads to what you want to do in the future. This means doing multiple things that relate to your core interests (which should happen naturally) and then highlighting all those activities, classes, research projects, and experiences on your application as all building towards one clear interest and goal. This makes you unique, memorable, and interesting to schools because you bring a passion that you can then contribute to the class and continue to build on. 

For example, if you are very interested in preventative health initiatives, you may have majored in biology and taken classes on public health and cost-effectiveness of preventative healthcare, etc., and then done research that studies the cost-effectiveness of these interventions, volunteered at free clinics that could especially benefit from that approach, and perhaps started some initiative of your own or written something that also contributes to that idea. Putting these activities together in your application with a clear goal of pursuing public health in your future career will make a compelling case to the school that you are passionate about medicine, have truly explored it, and that will bring a unique angle to the class and add diversity. Of course, you may have other meaningful experiences that you should also talk about, but it helps if many of your activities align toward one clear common goal. It creates a memorable and compelling picture of who you are. 

We hope this helps! Comment below with any questions or feedback. We are always here to help, and if research is one of your interests, this site will help you build that aspect of your application! 

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The Big Picture

The overall picture to keep in mind is that you have four years (or perhaps five, with a gap year) to get your application as ready as possible for medical school. The last year is typically not included in the application, since you will submit over a year before your intended start date, so that should be factored into your planning. In the beginning, you should focus on figuring out if a career in medicine is right for you. Use your classes, activities, experiences, mentors, etc to really explore and decide. After that, the next two years should be spent building up the components of your application. Traditionally, these components are thought of as (1) good grades and scores (2) research (3) clinical activities and volunteering to show exposure to and interest in medicine (4) a clear interest in something within or beyond medicine that a number of your activities, classes, and experiences relate to (5) evidence of leadership and commitment throughout the above. The last year will be spent on the application process, which starts in May of your junior year (for people going straight through) or May of your senior year (for people taking one gap year).

This hexagon essentially encompasses the significant components of your application that you would want to show strength in. No single application is strong in all of these factors so don't expect that of yourself. Identify things that you want to focus on and excel in. Try to make sure they naturally build towards one clear goal or interest that can align with why you want to go into medicine.

Disclaimer: There are, of course, deviations to this timeline and many different paths to medicine. Perhaps you take multiple gap years, or perhaps you decide in your last year of college and do a post-bac. Either way, if you've decided medicine is for you, don't be discouraged. However, this specific tutorial focuses on a traditional timeline.

  • Focus on exploring at first. Join clubs and activities that allow exposure to healthcare or other interests.
  • Identify and speak to potential advisors. Discuss course selection and specific experiences or opportunities that exist at your school that may be relevant to your interests within or outside medicine.
  • Attend campus pre-med meetings and make sure you are on email lists to get relevant updates and information
  • Figure out what you might be interested in studying and what kind of research you may be interested in pursuing. Through your classes, research, and volunteering, start to develop relations with faculty, advisors, and mentors.
  • Seek opportunities to volunteer, shadow a doctor, and, if interested, identify research opportunities on campus.
  • Start taking the required portions of the premed core curriculum at your school, geared for freshmen.
  • Towards the end of the year, line up a plan for the summer, ideally focusing on some combination of volunteering and research. 
  • During the summer, get involved in medicine-related activities - consider internships, volunteering, research, and leadership opportunities. Take summer courses through a university if desired or necessary. However, we would not recommend this unless you absolutely need to. Otherwise, it is better to spend the time investing in an experience or opportunity that you can meaningfully gain from.
  • Check in with your pre-health advising office about your progress during first year
  • Continue to pursue meaningful clinical experience, medically-related activities, volunteer work, research, and/or leadership roles
  • Continue to develop relationships with faculty, advisors, and mentors.
  • Apply for summer research, internship, or enrichment programs. Ideally, continue or expand on your activities of the previous summer. However, if it wasn't a good fit, this is a good time to switch and invest in something new. 
  • We would recommend a depth of activities over quantity - i.e., if you had a good experience, invest in that experience rather than bouncing around and trying new things because that will allow you to develop long-term relationships and experiences.
  • During the summer, Continue your summer research, internship, and enrichment plans developed during the year. By this summer, if you are planning to apply straight through, you should have been able to identify which activities you really want to invest in. Use this summer and the beginning of your third year to really develop those relationships, push forward publications, gain leadership positions, etc. to bolster the upcoming application.
  • Identify and pursue leadership opportunities within organizations you have been deeply involved with through college
  • Consider which faculty, advisors, and mentors on your campus you have close relationships with, and whom you can approach to write letters of recommendation for your applications.
  • Continue your participation in meaningful clinical experiences, other medically related activities, volunteer work, research, and/or leadership roles on campus; if possible, consider taking on a more substantial role.
  • Meet with your pre-health advisor to strategize about your application timeline, whether it be for immediately following graduation or after one or more gap years. Discuss your schedule for completing the remaining premedical coursework and other school-specific degree requirements.
  • Identify the best time for you to take the MCAT® exam; visit the MCAT website to find the best options for test dates and locations. Take the exam by the end of this year if you plan to apply straight through.
  • If you are considering a gap year, investigate a meaningful paid or volunteer medically-related experience to complete during that time.
  • Research medical school curricula and joint, dual, and combined-degree programs and start templating a list about where you will apply towards the end of this academic year.
  • Request letters of recommendation and committee letters and start preparing your personal statement and the rest of your application materials.
  • During the summer, continue your involvement with your selected summer activities - paid, volunteer, internship, medically related, research, and leadership experiences.
  • If you are applying to medical school going straight through, this summer is the time to complete and submit AMCAS and secondaries. Admissions are rolling so the earlier you do this the better.
  • In the fall through early spring, if you are going straight through, you should be interviewing with schools and doing campus visits this year
  • Continue investing in your activities
  • Toward the end of the year, send letters of interest (with key updates) as needed
  • Say yes to the school of your choice and plan to start medical school in the fall!
  • Enjoy this summer if you are going straight through. Remember, it will be one of your last real vacations for a long time. Travel, relax, and do something you are really excited about.

If you are taking gap years, move all application-related components in the timeline above (AMCAS, essays, recommendations, etc.) the appropriate number of years out. Use your gap years to deepen your application - pursue meaningful research, work in a hospital, gain medical exposure by being an EMT or a scribe, or do a post-bac if you need to complete pre-med requirements. Talk regularly with advisors at your school or mentors you have identified throughout the process to determine when you are ready to apply.

Timeline to medical school
Undergrad Research

Undergraduate research is often a key component of your medical school application. If you want to go to academic medicine-focused programs, having a strong research background is one of the things that is closely examined in the process. It's useful to spend your first year exploring so you can choose a lab that focuses on something you're excited about. Ideally, you would to stay in this lab for the next four years and develop a strong relationship with the PI and develop a publication record. If you do switch labs, switch early, find a good fit, and then work to develop that longevity. Finally, if you are doing basic science in a lab that doesn't publish as often, it may be good to supplement with additional faster-moving clinical projects to develop relationships with additional mentors and be able to show publications when you apply.

This website is devoted to helping you develop your research skills and walk into the lab prepared so take advantage of all the tutorials out there. We also have additional tutorials on choosing mentors, identifying projects, etc. so keep an eye out for those.

Sources: The Stanford (Unofficial) Pre-Med HandbookAAMC Guidelines

Maintaining Sterility

The first and most important rule of tissue culture is that everything must remain sterile at all times. Make sure you fully understand how to maintain sterility while working. If your lab regularly cultures cells, you should have an appropriate tissue culture hood, and often a separate tissue culture room, that contains hoods and the cell incubators. This is because it is incredibly easy for cells to get contaminated, and once bacteria or other organisms settle into your cells, the culture is lost and you must start over. As you can imagine, if you have special lines or specific cell types that are hard to culture or obtain, this will set you back massively in your work. There are some basic rules to help you maintain sterility throughout each step of your work.

As you start out and get your reagents together for TC, remember to always wear clean gloves when you reach into the hood or into the incubators. Don't ever touch anything inside the hoods, incubators, or anything that is marked as sterile with your bare hands. Touching or opening things outside will contaminate them and make them unusable. Before putting your gloved hands into the hood or into the incubator, make sure that you spray them down with 70% ethanol to ensure sterility and cleanliness.

Anything and everything that goes in the hood must be sterile. That means that any reagents used inside the hood should NEVER be opened outside the hood. They should be purchased sterile (or sterilized in your lab by autoclaving). Before bringing them into the hood, they should be sprayed down with ethanol. Before taking them out of the hood, they should be tightly closed. They should be stored in a defined location where only sterile items are stored and there should be no mixing between sterile and non-sterile items. (Do pay attention to where they should be stored though - different items may need to be at 4 degrees, -20 degrees, or room temperature). The same applies to other items - pipettes, multi-channels, etc. - they should be delineated as sterile for the hood, be autoclaved, and then only opened inside the hood.

When you work in the hood, make sure that all your items remain sterile as you work. Do not ever open cells outside the hood. Cells go straight from the incubator to the hood and are only opened briefly inside the hood as needed to work. For reagents, maintaining sterility means that anything that touches the inside of your cells or reagent bottles must never touch your hands or any other surface in the hood. (For example, if you have a pipette tip that you are working with, make sure it never touches the outside of any bottles, your hands, or anything except the reagent it is meant for and the cells). Close or cap items as soon as you are done with them. In general, if something touches or if you are unsure, throw it out and use a fresh tip. Use fresh tips for every reagent and every cell type to avoid contaminating your reagents and your cells with other materials.

Once you are done with the hood, make sure to replace all the items, clean it well with 70% ethanol, and then close it and turn on the UV to fully sterilize it for the next person.

Recognizing Contamination

Given the discussion above, let's talk about how to recognize if your cells are contaminated. At first, it can be difficult to tell but you should check your cells every day for signs of contamination. Early signs of contamination include small black dots among your cells or low cell growth and increased detachment. As it progresses, the media will often change color and become progressively cloudy and eventually the cells will detach and die. As you develop experience, you may also notice that your incubator might start to smell a little funny if there is something in it that is contaminated.

A clean culture should look like this

Pulmonary Cell Culture - PromoCell
Note the clean cells, uniform shapes, and lack of black dots or oddly shaped cells.
There are also no floaters in the media that are visible
Image source: wikipedia

A contaminated culture may look more like this:

What is the reason for my cell-line contamination at day 3?
Note the floaters, the cell death, and the cloudy forms of bacteria covering the culture.
Image Source: ResearchGate
Maintenance & Fallbacks

Since the first rule is maintaining sterility and avoiding contamination, the next thing we talk about must be what to do if you do have contamination! The best thing you can do for yourself is to start out, if you are new to the process, with a cell line that passages easily, is relatively hardy, and one that your lab has plenty of stock for in case you do have contamination. Examples of these are 293T cells or HeLa cells, which most labs have in abundant quantities. It is also a good practice to separate your media and reagents from your labmates and to keep your cells in a specific part of the incubator so that you can isolate which reagents may be affected if there is contamination.

Once you are comfortable working with those cell lines and are confident that you can work without getting contamination, you can progress to more difficult cell lines. It is still always a good idea to keep your work materials separated from your lab mates, in case there are any issues.

If you do get contamination, the best thing to do is to start over. The contaminated plates should be soaked in bleach and then dumped. You should obtain fresh reagents that you are sure are sterile, clean out your incubator, sterilize it if possible, and then start afresh. If it is not possible to throw away the potentially contaminated reagents (expenses, etc.), another technique is to plate just the media overnight and see if it grows anything. If it does, you know it is the source of contamination, but if not, perhaps you can try again with the same reagents. If you truly are using a very precious cell line or resource, you may try treating with antibiotics, frequent media changes, and frequent washes to salvage the line. However, this is not a permanent solution if you have significant contamination.

To ensure that you have a fallback, anytime you obtain a cell line or create a line (with a knockout, transformation, or other modification), you should FIRST expand and freeze stock of the line. Freezing protocols are included below. Freezing the lines ensures that you will always have stock that you can start afresh with if you should need it. We would recommend freezing at least 5-10 vials if possible before proceeding with any major experiments.

Assessing Cells

Now that we've talked about avoiding contamination, let's briefly discuss the broader assessment and maintenance of your cell lines. The goal of tissue culture is maintain and propagate cells for experiments. If your lab depends heavily on cell models, chances are you will always have an incubator full of cells and at least an hour or two of your day will be spent maintaining those cells.

Part of that time, each day, should be spent looking at the cells and assessing for contamination and confluency, and then maintaining the cells appropriately based on what you find. The important things to do each day are the following

  • Check EVERY plate of cells and maintain only what you need for experiments and freezing
  • Identify cells that may be contaminated (if applicable)
  • Identify cells that are 80-100% confluent and require passaging
  • Identify cells that are not confluent but have not had media changes in 2-3 days
  • Identify cells that are required for experiments and need to be plated

The list above will determine your cell culture maintenance for the day. The contaminated cells should be disposed of to avoid spread to your other lines. Replate them from frozen if they are required for experiments. The confluent cells should be passaged out to new plates so they are less dense and have room to continue to grow and remain healthy. Cells that haven't had media changes should have fresh media to encourage growth. Finally, cells that are required for experiments should be plated out for those experiments assuming they are healthy and relatively confluent, along with additional maintenance plates so you don't lose the line. If the cells are not ready enough that you could plate your experiment and maintain extra cells, they should be given a few more days to continue growing.

Major TC Steps

In this last section, I want to briefly discuss how I think about the steps involved in TC. To me, there are four major steps:

  1. Assess cells and decide your plan
  2. Detach cells from the current plate
  3. Separate the cells from the media
  4. Isolate the cells and re-plate them for an appropriate application (maintenance vs experiment)

We discussed the first step above. This is key and easy to get lazy about but it is essential to make sure you have a good stock of cells at all times to be able to produce data.

The second step typically involves washing your cells, removing the media and then adding in some sort of enzymatic detachment solution (trypsin, EDTA, etc.). This will detach the cells from the plate and allow you to remove them so that they can be transferred to a tube.

The second step, once the cells are detached, is to separate them from the old media. This is usually done with centrifugation in 15mL or 50mL tubes. Since the cells are heavier than the media, they will settle to the bottom when spun. This will allow you to then remove the old media and maintain the cell pellet. It is important here to not lose your pellet when removing the media.

Once the pellet is isolated, you can do anything you want! Step 4 is our decision point. We can either decide to freeze the cells here, using a special freezing media. Or we can plate the cells for an experiment (with additional maintenance plates) which will require counting and then plating cells in appropriate dishes dedicated to our experiment. Or we can simply re-plate the cells into fresh plates at a lower density. When you do this, remember that you do not have to re-plate all the cells - just plate what you think you will need and either freeze or dispose of the rest.

These steps are discussed in more detail in the protocols below.