I often tell my students at the beginning of our term together, talking about cancer biology. By the end of the term, I think you'll be amazed that we don't always get cancer because of all of the things that can go wrong in our day to day lives. And every moment in our cells. Welcome. So today we have Summer Morrill. She is currently teaching high school biology, but she has her roots from MIT and we'll hear more about her story and what, she knows about cancer. Welcome, Summer. Thank you. I'm glad to be here. So my first question is really thinking about what we hear in the media about cancer. We often hear things like the BRAC1 or BRAC2 gene, BRAC1 and BRAC2 staining.

BRCA stands for breast cancer, right BRCA. So do you have the BRAC1 gene? I do. Do I have the BRCA1 gene? You do. What about the men that are in the back room who are helping us record this podcast? Definitely. So is that maybe surprising for people? Because the way that it's spoken about in the media? Yeah, I think often when folks are thinking about, inherited forms of cancer, it gets phrased as I have the BRCA1 gene, I have the BRCA2 gene. But really what they mean as they have a mutation, a change to the genetic code. That means that that gene is no longer functioning as it should. So, for example, BRCA1 is involved in our ability to repair our DNA.

So inevitably in life, we encounter things that will damage our DNA, even just the normal day to day stuff like needing to make new skin cells, or needing to replace the lining of your digestive tract. You're going to get mutations and your body has to be prepared and ready to fix them. And so the idea that someone does or doesn't have the gene, we should all have that gene. It's when that gene has a few mistakes in it or something goes wrong, that we end up maybe having a predisposition to a certain type of cancer. You know, so let's back up and look at the bigger picture. Yeah. And why you're a great person to explain this to us today.

Let's start with the subject of cancer. Just as a broad definition. Viewpoint? Sure. Right now you're teaching high school. Do you teach about cancer to your students in high school? At Phillips Exeter Academy? Absolutely I do. So, I teach everything from introductory biology to advanced biology. And I even have the pleasure to teach, a course called the Genetic Basis of Cancer. And so when I'm starting off with my students, when we think about the question, what is cancer? We often are talking about it in the context of cells and when cells divide. And cancer is often described as uncontrolled cell division, meaning they're the cells are dividing when they shouldn't.

Ignoring normal cues. But when I get into the advanced courses and we really get to think about the question, what is cancer? I'll ask my students to answer that at the beginning of the term, and ask them to answer it at the end of the term. Yeah. And just the ways that I can see them expanding their understanding of what is cancer. It's not one disease, right? It's not something that has a clear cure. Right. We talk about the cure for cancer as if it's on the horizon constantly. But it's not one disease. So can you explain that more? What does it mean that cancer is not one disease? But we have this term that's broadly used as this disease.

Yeah. I think it's because there are so many things that can go wrong to cause cancer. So we're not just talking about, a cell constantly having the gas pedal on. Right. That's kind of the analogy that many people use is that, you know, we've got this uncontrolled cell division. Your foot is all the way down on the accelerator. And there's no brake to stop it. But really, when we're talking about cancer, it depends on what the origin of, the tissue origin is. It depends on what? Other things are going on in that environment. Is there inflammation? Has our body's immune system been able to detect it? Is there enough blood supply?

And so when you start really looking at cancer, it's so many different factors that you have to consider, that it's not one disease. Yeah. Let me help some people understand why there is not a treatment or a cure right now, or it's not so simple as, you know, solving it quickly. Yeah. And so let's back up to. How did you become interested in cancer originally, because you have made the leap from becoming a scientist and a researcher in biology, because you were a student and a graduate student here to becoming a teacher. And, you know, for a brief period, two we also were colleagues and teaching at MIT in biology.

So now, if we go back and think about your initial interest in this, subject area, what really motivated you to learn more about biology? Yeah, I think I find it really fun to get to look back as a current teacher, kind of at my journey through education. And the people that really got me to where I am. Who sparked that interest and sparked that love, I think. My first love for biology came from genetics and all of the puzzles that it takes to kind of figure out, what's going on in terms of genetic inheritance. But from a personal standpoint, I've been interested in cancer biology because of my family history with cancer.

So, my mom had breast cancer when she was in her 40s. I was a very young child. And I've seen firsthand the impact that that that can have on a family. Thankfully, she is 30 years in remission, which is wonderful. That's amazing. And it has had kind of long lasting impacts. The treatments that she had. Both of her parents passed away from cancer. Her sister has also had breast cancer. And so watching kind of how a family navigates that has really been a motivational driver for me. So when I merged a love of genetics, a love of puzzles and biology, and this personal interest in cancer biology, that's kind of where I ended up in terms of studying the genetic basis of cancer.

And, you know, your story really probably resonates with a lot of people because almost every family is impacted by cancer in some ways. You had this very early experience because it was your mother at that point. As you grew up, though, did you become concerned about your own health and think about this in your own context? Because now there's more testing that can be done, more ways to know more about your own family history. Did you explore any of those options? Yeah, it's really interesting. So my mom, when genetic testing first kind of became available to your average person, my mom decided to undergo genetic testing.

Thinking about me and thinking about my future. And so she was tested down in Boston for the Brca1 and Brca2 mutations we were talking about earlier. And since then, I've now undergone genetic testing to better understand my own genetic landscape. Her two tests for Brca1 and BRAC2 came back negative, but the new panel is now 80 plus different genes that are associated with breast cancer. Breast cancer alone. Alone. Yeah. And so this idea that I can go in and talk to a genetic counselor, understand my own genetic landscape. I think some people might find that daunting or, a little bit scary. But for me, it felt really empowering to have that information.

And often what they come back at you with is a variant of unknown significance. It's a mutation that we're not sure yet what that means. It's still undergoing active research. And so even with a result like that, I can say, okay, I know what research to pay attention to. I know what my risks are and how to better, do screening and have preventative treatments. Yeah. So you don't know with these tests, even, you know, a black and white result, like, yes, I'm at risk or no, I'm not at risk. Right. Right. And these panels of, you know, possible 80 genes they're testing for. Is it really like we started testing for a gene, or is it testing for a mutation of a gene?

Yeah, it's testing for a specific mutation with known association with a particular cancer, in this case breast cancer. And often, we're using different computational programs to actually think about, okay, this is a new type of mutation. We know this is different from what we find kind of widespread in the population. But is it going to cause problems. And I think that's the power of kind of blending computational science and bench science is that you can start to see okay, even though I don't have a lot of information yet on what this mutation might do, I can make predictions and use those to test in the lab.

Yeah. So you mentioned a genetic counselor. So can you explain that career field and how that also crossed paths with your own interest over time. Yeah I think so. There was when I first started at college, I really thought the intersection between genetics and psychology was something I was interested in, which lands at this particular career path called a genetic counselor. So this is someone who can sit down with you, really explain the genetics behind your particular condition. So whether that's something associated with cancer or even, something associated with another form of an inherited disease, often a person will see a genetic counselor, a set of parents will see a genetic counselor when they're trying to have a baby, or when they have a baby who's not quite thriving early on in life.

And they're concerned about a metabolic disorder. So I found that fascinating, right? You get to be in the room with someone, helping them to understand possibly one of the most difficult pieces of information that they'll ever receive. Not only is it emotionally difficult, but they're also having to think about what is this? Yeah, they need to understand. Right. And it's not going to be obvious if you just tell someone those test results. Right. What does that mean. Right. And so while my career path didn't exactly take me down that route, I have immense respect for genetic counselors and have really appreciated kind of the insight.

For as much as I know about genetics and as much as I know about cancer, having that person talk me through what my results meant has been really, really meaningful and impactful. So how did you make the transition from undergrad studies in biology to finding yourself wanting to do research in biology, and specifically in these types of fields related to cancer? Yeah. So I think, as I mentioned earlier, having people in your life who can walk alongside you and help to guide you in your career path and your decisions is something I love reflecting on. And I think about one of my professors from Tufts University, where I went for undergraduate, and he was a new professor at Tufts, doctor Stephen Fuchs and he really kind of pulled out of me that when I talked about a love of puzzles and a love of genetics, he was able to show me how much I was able to channel that through research, where, you know, there's going to be a question that you're interested in, and there's so many different pathways to answer that question.

And as you start to get more and more evidence, how do those pieces fit together into a full story? And so in undergraduate, that's really where I found my love of research. And I think from there, the logical next step is applying to graduate school. And I am thankful to my advisor every day, because I had this clear vision for myself because I was interested in cancer biology. I really, really wanted to apply to a cancer biology specific program. So across the country I was looking at all of these big name programs, mostly associated with medical schools. And she looks at me and says, you know, I really think you should take a look at MIT.

And that was really interesting to me because MIT does not have a cancer biology program. They have, in fact, a general biology program for PhD students. And I looked at her and said, I don't know, that doesn't really seem to fit. And she said, all that matters is the science that's happening there and the people you're working with and the caliber of people at MIT is unmatched. So I gave it a chance. That year was the year of Snowpocalypse. I don't know if you remember when we had like a foot of snow every Monday. I was, moving that month. It started so I can never forget how Boston got about seven feet of snow in a month and a half or two months.

Yeah. So that was the year that I was interviewing and all these programs. Thankfully, Tufts is just down the street from MIT, but the T the transport system was shut down for the day of my interview. And so I had to, hail a cab. And I think I got the last cab and all of Cambridge, but I got here and was surprised to find every single professor I was supposed to interview with. Every single student I was supposed to meet made it here to. Yeah. And I think that speaks volumes to how much this community cares about their researchers, their students, and wanting to give them a place where they can ask all of those questions that they're interested in.

Yeah. So that really was the sign, given your mentor's advice. And this is a really a key story of having the right mentor at the right time, in the right moment of your path and how you end up places just because somebody told you something at the right moment. Yeah, yeah. And it's crazy to think back like it was that one person and that one conversation. But coming here, I was able to stay open and thinking about what I wanted to research, take some classes in genetics, biochemistry and research methods, and just think about, okay, if I'm interested in this subject of cancer biology, what is the biggest question or the most expansive question that I can ask related to that?

And so that's how I ended up in Angelica Amon's lab. Yeah. So Angelika Amon sadly passed away in 2020. Right? Yeah. And then that was your graduate student school mentor and your advisor during your time of your research career here? I was also a student in the department. So I think, you know, anybody in the department and during the time she was here has a story about Angelica. Is there some memory of Angelica? But I think she really embodied the caring part of people. And, you know, MIT is not always a very, showing emotion kind of place or, you know, really, indicating this, human side. And I think Angelica really did that with her students, you know, in the lab or also just, you know, I was just a student in one of her courses, but she really paid attention to who you were.

If she saw you around years later, she would run up to you and give you a hug. You want to know what's happening, right? Yeah. And so that was, you know, a very special mentor that you had and very special person we had in our department. And she has lasting impacts for the students. Yeah, like you and I, but can you explain then, in the science piece of working with Angelika, what was it like to be in her lab and be a student of Angelika during that time period? Yeah. So I first met Angelica because she was one of the teachers for the graduate genetics class that I took in the fall term of my first year here.

And immediately you're drawn in by her, as you said, her expansive personality, the way that she gets excited about what she's doing, she makes every lecture and genetics sound like you're on a journey with her. And, every finding that was ever had in genetics is this big discovery. And having that person who can, walk alongside you in your own scientific journey, I just got really excited about it. And I think the thing that sticks with me the most about her mentality towards research is that she thinks there's a quote on the a quote on the wall of Koch Institute that says, the best science is done by those who are fundamentally curious.

And that to me says everything about her attitude towards research. I think my impression heading into graduate school was, I need to study the next new cancer treatment. I need to understand how these drugs are going to make their way into hospitals and clinics. But her mentality was someone needs to understand how the cell works. Yeah. And someone needs to understand how cells divide and the genetic basis behind it all. And that drew me in. Yeah. And I'm really glad it did. So she really convinced you the value of the basic science and how that impacts research for the hospitals, the treatments that end up happening.

You worked on the model organism of yeast Saccharomyces cerevisiae and this organism. To an outsider, it doesn't really make sense as a fungus. Why would somebody study a fungus? And it grows and, it's a single cell organism grows and divides. What? How does this tie to cancer, then? And how did that relate to you know, how do you use this organism as a model organism in your studies during graduate school? Yeah, that's a great question. I mean, you think yeast and you automatically think beer and bread and wine and all of those things would be right. But, and Angelika Emin's lab, she split her lab between the study of mammalian systems.

So using tissue culture, using mice and the study of kind of more basic science systems, including Saccharomyces cerevisiae. And so these yeast are a powerful tool for studying genetics because they can replicate quickly. They're cheap, and they have pretty much all the same core proteins that we do. So proteins are the things that are carrying our actions in a cell. They make every moment of, decision in your life possible. And those proteins, when we look at their structures and the building blocks that make up those proteins, they are extremely similar between yeast and humans. When we're talking about proteins involved in cell division, proteins involved in making sure our DNA is the way it should be and replicating it.

And so that's a powerful organism to have in your pocket when you're thinking about being able to study the specifics of how those proteins work, can you give us a sitting example that takes us from the mutation in a gene to you mentioned cell cycle problems and then leading to a tumor in cancer. Can you take us through, just a simple example of how that all relates. Yeah, absolutely. Are you thinking of an example that involves, something we can see in yeast as well? Sure. You can start there. Great. So one of the things that we think about a lot in cancer is that there's different types of mutations. They can be, good genes that are driving cancers.

Now remember when I talked about kind of on the gas. That's the idea behind an oncogene is it's something that's going to push the cell through the cell cycle moving more quickly than it should in many cases and in situations that it shouldn't. What's the cell cycle. Ooh good question. So a cell cycle is thinking about whenever your skin cell needs to replace itself. It's going to need to copy its DNA. It's going to need to grow bigger. And then eventually it's going to need to split itself, including its chromosomes and the body of the cell. And so all that DNA and all of that, cell mass needs to be identical in the two also get created.

And the cell cycle is a series of steps that helps to get us there. Pushing the gas with, the cell cycle then means a sped up process of this growth and division. Right, exactly. And so thinking about the types of mutations that it can occur, we've either got something in that category or we've got something in the category called tumor suppressors that basically acts like the normal brakes in that cell cycle process we just talked about. So it's telling the cell to pause and make sure everything looks okay before it continues to divide. And so when we look at different proteins that are conserved between yeast and humans, we can look at things in either of those two categories.

Or there's actually a third category we might consider, which is all of the genes that are important in fixing the mistakes in DNA. So we talked about mutations as being changes to the DNA potentially caused by things in our environment like UV radiation or exposure to different carcinogens like smoke. But it's also that stuff that happens every day when I copy my DNA to make a new cell. Maybe I make a mistake. And so are mutations bad though? No, all mutations are not bad. Mutations can actually be the source. They are the source of all variation in the human population. So when we think about why you and I sitting at this table, look different from each other and sound different from each other, that's because we have different variants in our DNA.

And yet there are going to be mutations that we accumulate in our lifetime that make us at risk of getting this uncon trolled cell growth that we're calling cancer. And so I think when we want to talk about mutations, to pay attention to, I really like thinking about those DNA, repair proteins because they're the ones that if we're not able to fix our mistakes, we're more likely to accumulate more mistakes, and all the various drivers of cancer can then appear in our body. And so really, it's a numbers game. You're accumulating mutations over time. Some may be harmful, some may not be, some may impact the cell cycle in some, you know, many do not.

Right. Yeah, I love the way you phrased that because I think often we see in populations that as they age that cancer incidence increases. And I think with what you've just said, the idea that it's a numbers game, the more time you spend on this planet, the more time in the sun, the more times that your cells have to copy their DNA and are at risk of making a mistake, that's when you then are almost inevitably going to get a cell that doesn't do it correctly and puts you at risk of cancer. And yet, while that happens all the time in our lives, what's kind of amazing is that we have these these monitors, these sentries trolling around our bodies, looking at our DNA and looking at our cells to make sure everything looks okay.

So really, we should be getting cancer a lot more often than we are. If we didn't have these systems in place to prevent the damage or, you know, and to be able to fix, repair and prevent these mutations. Yeah, I often tell my students at the beginning of our term together, talking about cancer biology. By the end of the term. I think you'll be amazed that we don't always get cancer because of all of the things that can go wrong in our day to day lives, and every moment in our cells. And that maybe explains why there's so much to study in biology. This so we don't really know how it all works, but somehow we're able to, you know, have this all work together to be human.

Yeah, I think that's the most exciting part for students. And I think the most encouraging part for me as a teacher is that when a student can get to a point where they realize how many open questions there are and see it as an opportunity, as an opportunity to ask deeper questions, to learn more, to design new experiments. I think that's a real a real gift for students to have that outlook in the face of something that can feel really big and really discouraging. You know, since you mentioned teaching. Yeah. Now, how did you end up being the jump then, from completing your PhD to then wanting to go into teaching?

Yeah. So I think it's not obvious. I wouldn't say there's one moment except that when I was doing my PhD, while I loved getting to be in the lab and I loved getting to ask those big questions, sometimes the best parts of my day were just sitting down with an undergraduate as mentoring, or getting to be in the classroom with other students. Thinking about how biology works and getting to help them piece their own puzzle pieces together. And so that was kind of the moment where I knew as much as I loved research, and as much as I was excited about cancer biology, that I could be a part of training the next generation of scientists to pursue those interests as well.

Yeah. And so in some ways, you have a bigger impact because you're able to, you know, exponentially grow like what? You're the number of people you're able to reach through this next generation, right? Yeah. I mean, I think I think that's the dream, right, is that you get more students and different types of students thinking about these really hard questions and all those people whose brains work in different ways than mine does are going to come up with, you know, infinitely more creative solutions. And, I find that really encouraging. Yeah. So let's go a little bit deeper into your research. You were studying understanding the cell, really, and how it grows and divides.

And you worked on something called haplotype insufficiency. And so, you know, that's, not an easy word for people to say or understand. Even if you are a biologist. So I think that's the part where, could you walk through what does that mean? In terms of the cell? Yeah, I think hablo insufficiency is certainly a word that most people would not be familiar with. But if we break it down, it feels a little more familiar. So hablo means half and insufficient, meaning not enough. And so the idea is, well, we have two copies of every gene, one that we inherit from our paternal genome, one that we inherit from our maternal genome.

We often think about those as contributing equally, and that they can even be a backup in some cases where if you receive a mutation, a change to one copy of the gene, well, at least I've got the other one, right? However, there are a group of genes that behave differently, and those are the haploid insufficient genes where even when one copy is still intact, we've got a problem. And that group of genes was really interesting to me and to Angelica for a simple reason, which is that evolutionarily, it doesn't make sense that that group of genes exists because the way our genes work, we can actually dial up the amount that the the amount of protein that they produce, and we can dial it down and over evolution every time.

If there was a gene that was so sensitive to losing a copy, it would make sense for us to dial that gene up so that were produced more protein from that one copy, so that even when one gets knocked out, we don't have any issues. So do you have really in a human case like where the gene is, you're missing one copy completely or what context would they be in? Human case? Yeah. Most often. What that's going to look like is those mutations, those genetic changes we talked about can make it such that one copy is nonfunctional. So maybe when it tries to, fold and take on its particular shape, it can't do that.

Or maybe you get a mutation. That means when it does get made, it immediately gets degraded, and no longer is able to do its job. And so while we don't often see that you only have one copy of a gene, one of your two copies can become mutated in such a way that only one is functional. Okay. So you're you studied the problem and you found, interesting results in the end related to haploid and insufficiency. But let's, like, tie this back to the starting question. Brca1 and Brca2, they, you mentioned the terms oncogene and tumor suppressor for one and bracket two. Could you explain how that relates to tumor suppressor.

Oncogene is their relationship or are they more on the repair side. You were talking about DNA repair as well. Yeah. So back A1 and Brca2 as I mentioned are involved in DNA repair. But we do often talk about them as having a tumor suppressor like quality. Right. They are really those, sentries monitoring, making sure that you don't have anything wrong with the DNA. And so they have that protective mechanism. And while Brca1 and Brca2 are present in two copies in your body, what we know is that for Brca1 in particular, there is this problem of happen sufficiency that if you inherit one copy that has a mutation that makes it nonfunctional, that you are much more likely to accumulate mutations in your lifetime, and that that puts you at greater risk of cancer at a younger age.

And so what's interesting about the research that I did is that one of the most promising new technologies related to cancer biology and cancer treatment is thinking about gene therapies. And what if that person who has a mistake in their copy of Brca1 that they have inherited from their parent, what if they could actually fix that mistake and introduce a new copy that can then take over and take the place of that nonfunctional copy? But my research actually showed that the reason why we have genes that are happened sufficient in the first place is because they can't actually be overexpressed either. So when you produce too much of those proteins, it also causes problems for the cell.

And we're not sure what the mechanism of that is, but this idea of having too much also being a problem, I like to think of it as Goldilocks. Right? Too little, too much. But we got to be right in the middle. Yeah. And so the danger of using gene therapy is, is what if I overshoot? What if I'm now overproducing something that becomes harmful to the cell as well. Yeah. And so maybe that explains some of why it's so hard to come up with the treatment. Right. It's like okay, well something's not working. Something's missing. We'll just add it back. But you're explaining why that doesn't work because you have to also worry about this really delicate balance.

The somehow the human body is figured out of the right amount of, you know, every protein that we have in our body. But in specifically in these cases, you had results indicating that was true. Yeah. I mean, for every triumph we have in science, for everything that we figure out, there's always going to be kind of this check on that, right? Like, okay, you figured out one piece of the puzzle, but what else is there kind of surrounding that? What's the context around that? And you've got to dig deeper. And so that could be frustrating. Or it could be, you know, if you're the right person with the curiosity that Angelika talked about, then science is the right place for you, and you want to go explore more and answer these questions that appear once you figure one step out.

Yeah, I think my biggest encouragement to my students is to be okay with failure to be okay with setbacks. Because that's where the interesting science is happening. And if you can understand the limitations of what you've done and what you've discovered and leverage that for coming up with future questions, then you're going to always be kind of following that trail, figuring out that puzzle. And it can be immensely satisfying. Yeah. So if you want to give a shout out to your students, the test, if they really watched the entire or listen to the entire episode of a podcast that you do, you can do it now at the end.

Amazing. So go ahead and say hi to them. I guess I'd just like to say hello to everyone over at Phillips Dexter Academy. If you're listening, come talk to me about cancer, biology and the things that you're interested in. There's nothing that I love to talk about more. Yeah. And so I think you did a really great job at bringing us from, a broad understanding of cancer, trying to understand what's going on at the cellular level and getting to the tumor and cancer stage. Is there anything important that you think people should know about this topic or that you, you know, go over with your students on a regular basis, that you think it's worth mentioning that we didn't cover you up?

Yeah. I think one of the things that I try to work with my students on is thinking about, while I love thinking about the genetic basis of cancer, cancer has so many other pieces surrounding that, and I think that's what I love. I love being connected to a city like Boston, to a school like MIT, and getting to hear about all the latest discoveries, because it's not just about the genetic mutations that are happening, but about the metabolism behind the disease, meaning how our cancer cells using nutrients differently than we in our normal cells normally use them. What are cancer cells doing to reroute blood flow?

I mentioned earlier, right. The idea that a cancer cell can actually draw blood vessels to itself. Yeah. And and the biggest field, I think, right now is thinking about how not only our immune system gets tricked by cancer cells, cells that are doing something they shouldn't be doing, but still somehow flying under the radar. And now we're realizing, hey, what if we can actually leverage that? What if we can use that as a future cancer treatment, where scientists are now training our own immune cells to be able to recognize, to not let those cells fly under the radar? And so I guess my message for my students and for those listening is just that cancer has so many pieces and requires so many areas of expertise.

Find the thing you're interested in and see if it relates right. This idea that we need chemists, we need immunologists, we need geneticists. Once you find that thing you love and something, you can apply it to an interesting question. Go for it and work together to do it. You know, and I think that represents, well how we can't just have one conversation about cancer, this, topic alone, we can have so many guests and so many conversations about cancer and what's happening in the research side, the human side, and how this all, you know, how everyone's working together to try to solve the same problem. Yeah.

You know, a surface level seems like one problem. But as we talked about today, it's really much more complicated than that. It is. And I think the idea that we can identify a mutation study in the lab, work with doctors to see what they're seeing on their side. One of my favorite books that I've ever read is Emperor of All Maladies by Siddartha Mukherjee. And he does a beautiful job of weaving together his story of being an oncologist, and also understanding the history of the disease and understanding the intense personal stories that come behind it. And so following all of those threads, makes it a really interesting area to study, even if it feels like a really big problem.

Yeah. So if you want to learn more about biology, genetics and the fundamentals of cancer science, we have more to learn at learn.mit.edu and a lot to explore. And there'll be more conversations on this topic in the future. I want to thank Summer for being an incredible guest and for sharing all of your experiences and knowledge today with us. Awesome. Thanks for having me.