Written by Christopher Kelly
Oct. 21, 2016
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Christopher: Hello and welcome to the Nourish Balance Thrive podcast. My name is Christopher Kelly. And today I'm joined by Dr. Dawn Kernagis. Hi, Dawn.
Dawn: Hi, Chris. Thank you so much for having me on the show.
Christopher: It's my pleasure. Thank you very much for coming. I have been utterly enamored by the STEM-Talk podcast as I think you probably know. For people who have not heard the STEM-Talk, you absolutely must find the link that I will put in the show notes for this episode. It's by far my favorite podcast at the moment. Dawn, can you talk about some of the work that you've been doing at the Institute for Human & Machine Cognition?
Dawn: Absolutely. I can talk about that for just a second. At STEM-Talk we interview the most interesting people in science and technology which had been an eclectic group of people. So we've had anywhere from former astronauts, we've had Apollo astronauts, to planetary researchers, to physicists, to meteorologist, to biomedical researchers, all across the board, and even people who work in the field of looking at longevity and human performance. So it's been absolutely fascinating having a chance to chat with these people and talk to them about their research and how they got into the work that they do and how it impacts their lives. So that's one part of what I do, is a small part of what I do at IHMC. I'm one of the co-host for STEM-Talk.
My research is focused on human performance in extreme environments. So I do research looking at optimizing performance and minimizing risk for people who work in things like undersea environments, space and high altitude, just for example.
Christopher: Talk to me about why you started the STEM-Talk podcast.
Dawn: STEM-Talk was actually the brilliant thought of our director, Ken Ford. And Ken, just by virtue of his expansive network of contacts and people that he's worked with over the years, knows a very interesting group of people in the world of science and technology.
Christopher: I can imagine.
Dawn: So it's been amazing to be able to tap into that network of people that he either personally knows or people that he's heard of. He finds their research fascinating or we find fascinating at IHMC. So that's how it all got started. So I've been at IHMC for about a year and four months now. A few months before I was a getting ready to move down he contacted. He said, "What do you think about hosting a podcast?" That was not on my original plans at IHMC but it's just been part of what I do and it's been the best opportunity. I've had a chance to talk to people that I would never get the chance to speak with. So it's just been a really great opportunity and a great learning opportunity to talk to people from completely different fields from what I do.
Christopher: I think it was ken that pointed this out to me and now I really, really appreciate it, is that you get a very different sort of interview when you have one scientist or two scientists interviewing a third scientist. It's very different from what you get with someone like me who's a layperson interviewing a scientist. It's great. You often use words that go over my head by getting general thrust of the conversation. And then I got to show notes and I look at some of that review papers that you link or some of the other information there. It's a great way for me to learn.
When I go back to maybe what I would’ve listened to in the past like an NPR style piece on machine learning, for example, I listened to the other day, I just couldn't do it. I got seven minutes into it and I thought I just can't listen to this guy anymore, dumbing this stuff down to [0:03:19] [Indiscernible] I think was what I called it. No more. That's enough. I really, really appreciate what you're doing with STEM-Talk. So thank you so much for that.
Dawn: Thank you for listening and thank you for the shout out. It's been, like I said, an incredible opportunity. We got plenty more coming up, really interesting episodes that are coming up and hopefully continue to do so as we move down the road.
Christopher: People should go check out Ken Ford's interview for the Keto Summit. He was just amazing, absolutely amazing. I enjoyed that so much. He's just full of so much wisdom and he gave a very evidence-driven presentation or backgrounds and research on the ketogenic diet. It's actually fantastic. So people should definitely check that out.
Dawn: Yes, he's definitely become one of the experts in that area. There is also a recent Outside Magazine article that came out. I'm not sure if you had a chance to see that but that was really good too with T.J. Murphy.
Christopher: I will link to that as well, of course. I'm really interested to know the kind of nuts and bolts of what you do at IHMC and maybe asking you about your recent NEEMO expedition. It would kind of go some way to answer that question.
Dawn: Right now a lot of the work that I do is kind of working off with some previous research that I did at Duke University both as a grad student and as a postdoc that was looking at genetics and how our genes are turned on or off in response to extreme environments and specifically looking at how they respond to scuba diving. And this is of interest to the Office of Naval Research. So this is research I did as a grad student and I continued it as a postdoc at Duke. So now we're just continuing that work there.
And so we're looking at genetic still, kind of genetic predisposition to certain potential injury processes that you can experience as a diver and also looking at epigenetic changes, so changes in how our genes are expressed as kind of like an adaptive response to being in these extreme environments.
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And so you're talking about the NEEMO Mission. I just finished that up this summer. Experience of a lifetime. I got to work with NASA's undersea mission this summer. And we were down in the Florida Keys for about a month. And every year NASA runs this undersea mission or just about every year since about 2000. They run an undersea mission where they send astronauts. And just to make it more interesting, they added to the group of astronauts, researchers and engineers.
We lived undersea for upwards of 16 days. It's the longest mission that they've had so far. We lived in an undersea habitat. We do excursions out into the ocean floor. And we test a variety of different protocol, hardware, software that's being developed for space or even being used in space right now. We test out maybe additions or updates to that software or hardware.
My research there was looking at epigenetic changes, so again, changes to how genes are expressed in response to living in this extreme environment at NEEMO. And so we're looking at epigenetic changes and we're also looking at gut microbiome. So we collected samples from the crewmembers, which there were six of us, before during and after the mission to see how our epigenetic change and also to see how the gut microbiome changes in response to living in that environment.
Christopher: Wow. That's amazing. So NASA is interested in the deepwater expedition because it's an environment that mimics space. Is that right?
Dawn: Correct. They feel it's one of the better analogs for being in space. You have the simulated microgravity. So we were weighted out when we were doing excursions outside to simulate partial gravity which is fantastic. That was just really cool to be able to walk on the ocean floor stimulating partial gravity. You're making decisions on a daily basis and especially when you're outside of habitat that are specific to life or death. You're not living in an environment where if you make a bad decision it's recorded in the logbook. If you make a decision in this environment it could potentially affect you in a very bad way or your teammates. So there's that kind of constant edginess to the work that we were doing and realizing that you have to really stay on top of your game and keep your situational awareness up.
So that's incorporated into all the other testing that we're doing, just like they do in the space station right now. So we lived in a very small environment similar to International Space Station testing out all these different, like I said, software, hardware, procedures that they put in there. We had about a dozen and a half mission objectives as far as research studies went. So that kept us on our toes and kept us busy but it's very similar to what they do in International Space Station in that manner.
Christopher: So how do you test epigenetic changes underneath the sea?
Dawn: So we just collected samples. And all those samples are processing now. And so we collected blood samples, saliva samples, cheek swab samples and we'll just be processing those. We're in the process of going through those samples right now to get the data back. And so we're kind of looking across a variety of different markers to look at what's been changed in response to that environment.
Christopher: What's the overarching goal of that work? Is it to try and understand what's going to happen to humans once you put them in space?
Dawn: So this specific study is of interest more to the undersea medicine community. The changes might be very different to what you see in space. But NASA's definitely interested in epigenetic changes in response to living in microgravity and changes to the gut microbiome. And they have studies like that going on right now. Actually the Twin Study was kind of the first round of that with the Kelly twins.
Specific to the work that I'm doing, it's more of interest to the Navy. And so it's a great thing about NEEMO is that we have projects where we're tying in with collaborators in the Navy, from different universities who are doing different types of research projects. And so it's not just research that's of interest to NASA but also to the collaborating entities.
So the Navy's interested specifically because we're living in an undersea saturation environment, meaning our tissues and blood are saturated with nitrogen or inert gas which is very similar to commercial diving operations, Navy military diving operations that use saturation diving. And so the question is what epigenetic changes are there? And kind of downstream we want to look and see how is this impact things like our immune function or just kind of overall health as sort of adaptive response that we experience in that environment.
Christopher: Can you describe any of the changes that you’ve seen?
Dawn: So I haven’t seen any of the data yet.
Christopher: You must have some ideas about what you're going to find.
Dawn: No. The great thing is that it's completely unbiased. So we're just going after this to see what the results are, hoping to see changes. It wouldn’t make sense that we would but there's really nothing out there that's been done up to this point that would show us -- there hasn’t been a study like this out there yet. So we're kind of just seeing are there any changes at all. And I would expect so just given the extreme nature of living in saturation, living in -- someone put in kind of a high-pressure locker room for the better part of eight days. But also you're living in a place where you have the inert gas uptake but you also have high-pressure oxygen and you're living in this kind of high oxidative stress environment for a long period of time. So we definitely expect to see changes but I don't have any expectations right now. So I'm just going into this pretty unbiased.
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I will say that there's a study that was ran in parallel with my studies. So we collected samples at the same time mostly to keep our crewmates from being angry with us for getting too many blood samples from them. He was looking at changes in telomere length which is really interesting. I won't go into too many specifics about it. But it turns out that there was telomere shortening in response to living in that environment. So I thought that was really interesting, what comes out of that. That's just kind of the initial results that he saw. He got these results about a week ago or so. It hasn’t been published yet but at least it's got some preliminary results. It shows that there are changes in response to living in that environment.
Christopher: Do you think it's going to be all bad news? It would make sense to me if it was all bad news, if you put humans in some environment that they weren't adapted to exist in.
Dawn: Not necessarily. So what's interesting is even in the diving, not saturation diving but just regular scuba diving, there have been studies that have shown as far as immune response goes, there's kind of this adaptive response. It's almost protective response that occurs. We don't know a lot of the molecular basis for that but seems to be kind of a protective response that keeps people protected against things like decompression sickness. So it'll be really interesting to see that some of this might just be adaptation to kind of protect you from something like a high oxidative stress environment. So it doesn't necessarily have to be a bad thing. It could be a good thing.
Christopher: Are there certain genotypes that handle the stress well? The Office of Navy Research, do they ever genotype a diver and say, "No, sorry. This is not for you, son"?
Dawn: Not yet. That's pretty controversial, just idea of genotyping anybody in and excluding them based off of genetics. But one of the things that we have talked about is kind of precision approaches in diving medicine. So you look at somebody and say, "You have genotype X. And so we're going to give you this drug that we know will kind of enhance and help protect you because we know that otherwise you would be at risk." So it's kind of like a precision medicine approach but specific to diving and diving performance and diver health.
One of the things that we're interested in looking at down the line is looking at something like the ApoE gene. I don't know how much you know about ApoE.
Christopher: Nothing. This is what inspired me to originally get in touch with Dawn. I listened to the fantastic interview with Dale Bredesen on the STEM-Talk podcast. You mentioned that you had studied ApoE as part of your education. I really wanted to know. What does Dawn know about ApoE? Maybe we should start from the beginning. Can you explain what Apolipoprotein E is?
Dawn: Absolutely. I did this research as a postdoc. This is part of my other postdoc research. So I had multiple projects going at once. This is part of the research I did at Duke University as well. It's working with a group. The bulk of the research is looking at Apolipoprotein E. ApoE gene encodes for Apolipoprotein E protein.
Apolipoprotein E was previously shown to be involved in cholesterol transport. And what's interesting about Apolipoprotein E is that over the years they discovered that it has a huge role in neuroinflammatory response. So back in the early '90s they actually discovered, and this is originally out of Duke University, that ApoE genotype plays a significant role in potential for development of late-onset Alzheimer's disease.
And so they showed that if you were an ApoE 44 genotype -- so you have two copies of the ApoE4 LDL -- you had over 20-fold increase risk of developing Alzheimer's disease. If you have one copy ApoE4 you had over 4.5-fold risk of developing Alzheimer's disease. And so this is really something of significance as far as having potential increased risk for development of disease.
So other researchers started to look at ApoE. Does it have any role in other types of brain injury or recovery from brain injury? And so they looked at things like subarachnoid hemorrhage, different types of strokes, so ischemic stroke, chronic traumatic encephalopathy, repetitive head injury, development of post traumatic epilepsy and even just basic acute traumatic brain injury. And what they found in all these different types of injury processes or disease processes, ApoE4 played a role in worsen patient outcome in all those settings. And so that was really interesting because they started to look at kind of a common theme between all these disease processes.
People talk about genetics and gene X increases your risk for disease. Why? A lot of times there's not a very clear-cut explanation as to why that is but with ApoE it seems to makes sense. So in all these different disease processes you have microglial activation. Microglia cells are the kind of brain's first responder cells. And so when you first have an injury process this microglia kind of activate and ApoE will come in and bind ApoE3 -- which is, if you want to call it, the good genotype -- ApoE3 will come in and bind those microglia cell surface receptors and help dampen the initial inflammatory response that they have. So they have the initial planetary response to kind of help clean up the mess after the initial injury.
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The problem with ApoE4 is that that protein will come in and it binds but that initial inflammatory response exacerbates the injury. And so you have this worsen secondary injury and this worsen patient outcome with people with ApoE4. So it seems to make sense as to why ApoE3 versus ApoE4 is, if you want to call it, good versus bad in those settings of brain injury, both acute and chronic brain injury.
So the question has come in. Does ApoE play a role in something like recovery from something like CNS decompression sickness? This is the bends that have affected the brain tissue. Does it play a role in susceptibility to something like CNS oxygen toxicity? A lot of times this is a concern for military divers breathing 100% oxygen on rebreather systems. They go in, they breathe this at depth, and there's this increased risk for developing underwater seizures because of the increased partial pressure of oxygen that they're breathing. This exacerbated oxidative stress inflammatory response that’s occurring in ApoE4 carriers compared to ApoE3 that might predispose them to developing CNS oxygen toxicity.
So this is something that we're really interested in looking at down the line. We haven't looked at it yet but it's definitely of interest.
Christopher: What's the E4 [0:16:20] [Indiscernible]? I can't imagine that it's really good versus body. It must be the E4 does something else, right?
Dawn: They think that it stayed around in certain populations potentially for protection of malaria is the one thing I've heard. It's the best explanation. In certain populations that would make sense. But they're still trying to hush all that out. But like I said, it stuck around in the human population for a reason. What that reason is, we're still trying to figure out.
Christopher: What did you think when you got to the end of that interview with Dale Bredesen? You said that you could carry on talking forever but you had to end the interview somewhere. What were you thinking at that time? This is functional medicine all over again. It's the death by 1, 000 cuts. Maybe your ApoE genotype is not really going to define the outcome but that was just my opinion. What did you think at the end of that interview?
Dawn: Yes, absolutely. It makes perfect sense. Just like so many other disease processes that we're learning more about, it makes sense that it's not just one -- he talked about the holes in the roof which I think is a fascinating analogy. So it's not just one hole in the roof. There are issues everywhere and you have to kind of piece together all those things to clean up the mess. So it makes perfect sense that it would be kind of an imbalance essentially that you've reached based off of a number of different factors.
I really like the idea too that there are different types of Alzheimer's disease and it makes a lot of sense as well the more that we're learning about things like cancer. Cancer is not a one-all disease. Cancer is 1,000 different diseases plus as we learn more about it. And so I think it would make perfect sense that Alzheimer's disease is the same thing.
Christopher: I know you're not a doctor. You're a researcher. You can't possibly give medical advice out over the Internet but appease me for a moment. Let's just speculate. Say that somebody's done a genetic test, say they had 23andMe genetic test. And they found out that they're 34 or maybe a 44. What do you do next?
Dawn: Things that we all should be doing regardless of whether or not you're a 34 or 44 or if you're just a 33 -- trying to minimize inflammation in your system. So whether that's diet or sleep or the type of exercise that you do, those are going to be keys regardless of what your genotype is. I think it'll be interesting down the line to see if there are drugs that are developed based off of the "good" ApoE3 version especially for those people who have ApoE4 LDL, at least one or both copies of ApoE4 LDL. It would be really interesting to see if we have medicine that we can give prophylactically to say. "Here, here's your dose of ApoE3 for the day since you're not getting it naturally." But that's a long way. There's nothing that's been developed up to this point yet. I know that there are different groups that are working on ApoE3 based pneumatics and other types of approaches that would do something similar to prophylactic treatment.
Christopher: Do you have any opinions on changes in diet based on the ApoE genotype? I was recently at the Ancestral Health Symposium in Boulder. There was a doctor there Steven Gundry. I don’t know if you know him. Do you know him?
Dawn: I don't know him. No.
Christopher: He's a medical doctor that's managing people with ApoE for a long time. And he described what I thought was basically the olive oil diet. Quoting him directly, vegetables are just a vehicle to get olive oil into your mouth. That specific change to the polyunsaturated fat was based on ApoE genotype. This video is available online so I can think to this in the show notes. What do you know about the change that people might want to think about with their diet if they find out they're of a 34 or 44 genotype?
Dawn: That would make sense. I don't know enough as far as on the diet side of things so I'll claim that right now. But like I said, probably one of the most important things would be focusing on minimizing inflammations, so a low inflammation diet. Things like ketogenic diet would make a lot of sense or something along those lines that would try to minimize kind of global inflammation I think would make sense. But like I said, that’s not just for 34 or 44s. It's for anybody in the population, I think.
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Christopher: Let's take this subject of ApoE. It says here in your bio that your goal is to increase human resilience and performance. What are the things you find most interesting to achieve those endpoints?
Dawn: I think the nutrition aspect is really interesting. It's not my specific area of research. Dominic D'Agostino at University of South Florida has been doing a lot of work in that area. And I think it's really interesting to follow what he's been doing. I think this whole idea of precision approaches based off of genetics or even epigenetic changes or looking at how we can potentially engineer the gut microbiome to help protect against some those environments, this is all just very new. We're just starting to tap into these areas of research.
Brain function, looking at things like brain lymphatic -- so I think it's going to be really interesting as far as clearance of metabolites and kind of keeping the brain "clean" after some of these extreme exposures or even during extreme exposures will be really interesting. So those are kind of the areas that we're tapping into right now with respect to optimizing human performance and resilience in those environments.
Christopher: Talk to me about the gut microbiome. It's like ketosis. I just can't get away from this subject when I interview interesting people. I recently interviewed Lauren Petersen who's a postdoctoral associated at The Jackson Laboratory, and that's also in the East Coast, I believe. She's been looking at the gut microbiome in elite athletes. They've already found the difference between normal people and elite athletes. And now she's trying to kind of pin down is the change along for the ride or is it causing the improvements in elite athletes. So I know that this is a really interesting area. Can you talk about some of the things that you’ve been looking at?
Dawn: We just started to look at this, and this is specific in the study that I did with NEEMO, like I said, looking at changes in gut microbiome in response to living in extreme environments. The whole concept is that it's not just affecting the gut but it's also affecting kind of epigenetic changes and helps kind of drive those epigenetic changes. So there's definite interest in our field. And, again, in the field of extreme environments, this has barely been touched on. I'm the one kind of touching on it right now. So it'll be really interesting to see where it goes as we move forward and as we get more data. So NEEMO will be kind of the first round of data that we get in that topic.
Christopher: When I interviewed Lauren I was really interested because she's not just doing the 16S, she's also doing metagenomics shotgun and metatranscriptomic. Did I even say that right?
Dawn: Transcriptomic.
Christopher: Transcriptomic, yes. So technologies I've not even heard about. I knew about the 16S but the other two were completely new to me.
Dawn: We're using 16S just as a first start, first crack at it. I think that as we start to delve more into this topic and I think -- a big part of it too is just getting the funding to use that type of technology. I think it would be fascinating to incorporate some of the high throughput sequencing technology that really allows for compositional and functional analysis that we never thought were going to possible but now we know they're right at our fingertips. So I think we'll be expanding on that as we move down the road with that type of research.
Christopher: What does the experiment look like? Do you sequence the microbiome before you go down underwater and then you sequence it again under and then back when you come up? How does it look?
Dawn: Yes, correct. We have baseline samples. We actually have several baseline samples. So we have one from a month out prior to the mission itself. We have another one just before going down. But there are some stresses that occurred just in response to training and living in a different environment and our diets changed. We go down to the Florida Keys and are living in a different environment, eating together, diving every day. So we wanted to take that into account for kind of baseline analysis.
So we got actually two baseline samples that week. We don't have any samples during mission. A large part of that was because of the sample kits that we have trying to get them back up to normal pressure would have possibly been an issue. So we didn't want to risk that. Plus the original plan for bathroom facilities and the habitat was that we would have to go outside to go the bathroom and actually go out in the water. And the samples would've been contaminated. There are ways that we could've worked around that and everything but essentially we just made the decision to only get before and after samples for the gut microbiome. So then we got samples after. And then we'll also get another follow sample down the line in about a month just to compare to see if there's any adjustment once you're kind of back into normal everyday life and normal everyday food.
One of the things to take into consideration too for this is that living in that environment our diets changed significantly.
Christopher: You're going to see changes.
Dawn: You're going to see changes. We're eating freeze-dried camping food that's reheated and very little fresh food. It's very different from what all of us typically would eat on a regular basis in normal everyday living. So there's definitely going to be changes. We just have to take that in consideration. We didn't control for it for the study. This is just kind of an initial pilot study just as to see are there changes.
There are some people that are looking at gut microbiome changes in response to living in other environments like a submarine environment and some other places like that. So it'll be really interesting to see how some of those things compare as we get results down the line.
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Christopher: I'm going to be on the second phase of Lauren's trial.
Dawn: [0:25:26] [Indiscernible]
Christopher: Yes. So I'm sitting here looking at a large polystyrene box. It's full of all kinds of paraphernalia that needs to be frozen before It's FedExed back to the lab. So I can't imagine how difficult it would make it if you were trying to do all this whilst underwater. It's totally crazy.
Dawn: We actually ended up with a toilet in our habitat. So that made things a lot better. And I will say that it was nice working with the populations. Some of the people are astronauts. When we all first met each other we were talking about some of the research that we were going to be doing, they didn't flinch because they have to deal with that all the time when they're in space apparently. So they didn't even flinch which is great because I think a lot of the populations are like, "Oh, that sounds discussing." But they're like, "This is going to be really important for us to know." And they've been doing microbiome studies already on the space station. I haven’t seen the results from that yet but I think we should be seeing results from that really soon. So it'll be really interesting to see what kind of changes they see. And like I said, it's probably not just in response to microgravity but also just changes in their diet advantage changes in everything else that they experience out there.
Christopher: Do you have all the sciences and the technology and the know-how to do that at the IHMC? You cover such a broad range of things. I can't imagine that you employ someone that understands all of these things or do you?
Dawn: We have collaborators. So that's a great thing. A lot of the researchers at IHMC, we collaborate. We have tons of great partners in a lot of the research that we do. Really, with the evolving technology that's out there right now, it makes more sense to have different partners that are specific to different areas. So I do work in genomics, epigenetic. So we have partners for all these different things that have the evolving equipment so we don’t have to keep updating that equipment on-site, that way we can all kind of optimize working with each other.
So a lot of my background is actually data analysis and kind of unique approaches to looking at this high throughput data that comes from a lot of these studies. And so that's where my expertise comes in. And also just contextualization, specifically in the diving side of things, being able to put into context of what we're looking at and what it might mean. My area at IHMC is pretty new. Right now I'm kind of the only one doing what I'm doing but we're expanding that. We're getting funding in place. And so we're going to be growing the program hopefully significantly over the next few years here.
Christopher: Talk to me about the type of data analysis tools that you're using.
Dawn: It kind of depends on what kind of data we're looking at. One of the things that would be really interesting as we're moving forward is looking at how these different types of data relate to each other, so different layers of data. So looking at gut microbiome to looking at the epigenetic changes, to looking at genomic, taking all that into consideration and kind of building a model of how these things interact with each other. And so that's one of the things that we're really interested in doing as we move down the line.
As a grad student and as a postdoc a lot of the work that I did was looking at some of those high throughput data and saying, "How can we take a unique approach? Not just comparing before versus after some of the standard approaches but what are different ways that we can look at patterns that are within the data and what can we learn from those patterns?"
So an example of that, as a grad student I did a study where we looked at transcript data. So this is gene expression data. And this is from microarray technology. So essentially from one tissue sample or one sample from a tumor you get the relative expression levels of -- I think for the technology we're looking at, it's over 20,000 genes. So it's a lot o data points for one sample which is fantastic but you can get a lot of false positives, a lot of false negatives when you're trying to make comparisons between groups.
So one of the things that we were looking at is what can we learn from other types of cancer and what's relevant is those types of cancer and how can we apply that to the data and look at the data in different ways. So in breast cancer there are things like estrogen receptor positive and negative, progesterone receptor positive and negative, HER2. And so what's interesting about those genes that define very clinically distinct types of breast cancer, if you look at their gene expression patterns -- so you look at 300 tumor samples and you look at HER2 gene expression across those samples, most genes would have a normal pattern of distribution. So everything kind of falls in the middle with some outliers on either side from high to low relative expression levels.
What's interesting about HER2 and ER and PR in breast cancer samples is that it has a bimodal pattern of expression. Most of the samples either have really low or really high with very few falling in between. So it's a very distinct pattern of expression across the population of samples.
So we went into ovarian cancer samples. This is publicly available data sets that have been generated from very large scale studies around the world and looked for genes that were bimodally expressed.
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And so then we went to see are these genes clinically relevant and could they define a molecular subtype of ovarian cancer which there wasn't any at that time. And so we did find a subset of genes that we kind of whittled down after a lot of multilayered analysis and identified subset of genes that are bimodally expressed in ovarian cancer and defined a very critically distinct molecular subtype of ovarian cancer. The question is could those genes be targeted for therapy or could they be used as biomarkers for prognosis or even for specific molecular diagnosis in ovarian cancer? That’s just an example of just kind of looking at the data in a different way from standard comparison between groups.
Christopher: I really want to know the tools that you're using. So I've been playing around with this myself over the past couple of weeks. We've got data from 770 athletes now, big panels of bloods -- ninety-five markers on the bloods and then maybe 75 markers in organic acids. So we got tons and tons of data. I'm really interested to know what tools you're using. So I've been looking at using Python and Scikit-Learn. I discovered Google TensorFlow library that's on the web as well. What kind of tools do you use?
Dawn: Of all the work that I did outside of using some kind of tools that have been developed commercially, for most of the work I did especially the bimodal expression work, we use R for statistical computing.
Christopher: That's publicly available as well, isn't it? R is an Open Source language.
Dawn: It is Open Source, yes. I did not think that going into my degree at Duke University and pathology that I would be doing a degree in biostatistics and learning how to program but it was really interesting. It makes you think about the data that you're looking at in a very different way than just throwing it into a program which a lot of people tend to do and kind of stop thinking about what the data is actually doing. So it's a great way to be able to look at the data from different angles that normally wouldn’t be available on a lot of software that's out there.
Christopher: Sooner or later you're going to become a programmer. I've seen it many times over. It was the original reason I went to do a computer science degree. I spent some time in research and development department of an electronics company. Ad we employ quite a lot of physicists at that company. And they will begrudgingly be dragged into programming scene assembly language. I was like, "Okay. So I just need to go to a university and learn how to do computer science properly rather than just living this life where I really hate what I do because I don’t really understand how to do it and just creating a huge mess."
Dawn: I think it was my second year in grad school that I ended up taking essentially an R course for dummies but just trying to learn. I also started to work with some of the biostatisticians while I'm learning. It was amazing to watch them maneuver through and program. They're so fluid in it. For me it would take an hour to write 20 lines of code where for them it would take a minute or less. So it was really interesting to watch but I learned a lot. And like I said, it was great because we were able to develop our own tools and optimize those for the studies that we were doing.
Christopher: That's so cool. I've send at too as well. One of the last jobs I worked before starting our business was at hedge funds. I worked with a group of quantitative analysts who we're mostly mathematicians. They use another language called MATLAB which is much the same as R's commercial version. And they were saying there were wizards on it. They pull up a chart or a model or something, like you say, 20 seconds flat. Wow. How did you just do that? MATLAB is like that. It's a very high level program language which enables you to do some amazing things with not very many lines of code.
Dawn: It's pretty impressive. I guess what you're comfortable with becomes second nature, I guess, if you do it enough. I have to say that if I went back to using R right now it would take me a little while to kind of get back on the swing of things. But I will say towards the end of me writing my thesis and doing the data analysis for my initial studies, I was getting -- I will never say confident but I was getting better at it.
Christopher: Excellent. Let's take a step back again. So you talked about diet and you talked about the microbiome. What other things do you think are really important for improving human resilience and performance?
Dawn: It's really interesting because we had a STEM-Talk with Peter Attia talking about longevity. I think a lot of those things are going to apply to --
Christopher: That was your first episode. I can't believe it. It's like the one person that nobody can get for a podcast because he's such a busy guy and you got for the first episode. That's fantastic. I really enjoyed it.
Dawn: He's so fascinating to talk to. It's such an honor to speak with him. Yes, I mean just the same things that he listed out, things like the diet, exercise, sleep, minimizing stress, not doing stupid things which -- I laughed but I have friends who do research just on that very topic actually.
Christopher: Really? What's a stupid thing? Talk to me about the stupid things.
Dawn: That's one of that things that Peter said, things like not drinking and driving and things that would just make sense. In an extreme environment scenario, it's more learning from your mistakes and doing things like following the rules, following the checklist, not getting complacent. That's sort of big in anything like flying, surgery. It doesn't matter what it is that you do.
[0:34:59]
A lot of times we see in our world, especially in the diving side of things -- that was my background before I got into research. I was a diver for a long time. I worked with the Dive Training Organization. A lot of the accidents that you see with experienced people, a lot of them are due to complacency and just a number of errors lining up, the Swiss Cheese model, and then something bad happens.
I have a friend who's actually doing research on that very topic. He's doing his PhD on the topic but he has extensive experience working with the British military actually, especially in the aviation world, looking at accident analysis and what can be learned from those accidents and how can you kind of improve safety in aviation. And now he's applying that to diving.
So it's really interesting because you hear a lot of those things in other worlds, like I said, like surgery or talking to anybody in an operational environment. If you're constantly debriefing and learning from those expenses and learning from the mistakes that are made and learning from other people's mistakes that might end up being accidents, hopefully you're going to optimize your safety and performance in those areas.
Christopher: Talk to me about the Swiss Cheese model. I've never heard of that before. What is it?
Dawn: Essentially it's mistakes that are made and everything kind of lines up. So where the holes line up, something bad happens. It's usually not just one bad thing or one mistake that's made or one bit of complacency. It's a number of things that line up in a row that lead to a really bad accident or something happening.
Christopher: What's the outcome of this research going to be? What's the physical end product going to be? Is it going to be a written protocol? Is it going to be software that prompts people to do things at certain times? What's the end outcome?
Dawn: A huge part of his work is actually education. Like I said, he's moved into the diving community. It's been really interesting to watch him as he does his research. He has been developing this educational series for instructors in the diving community but he's also been working with professional organizations, government organizations and getting them to think about their training standards, how people approach the accidents. So kind of for a long time in the diving community, specifically in certain communities like technical diving, deep diving, it's kind of like you don't want to talk about the accidents, especially the near misses. The misses are pretty easy to talk about because they're pretty blatant but the near misses -- this almost happened to me but I just barely got away with it. Well, why did that almost happen to you? Can other people learn from that almost happening to you? What did you do to prevent it?
So he's doing a lot of educational work in that area. He's also working with a lot of the training agencies to look at checklist, not just checklist but checklists that are functional and checklist that work and why just developing a standard checklist is not going to be the answer to everything, that we have to do this in a way that people are going to learn from it and not get complacent with the checklist. The whole point of a checklist is to try to replace or try to get rid of that complacency but then people get complacent with the checklist.
So it's the same thing in the aviation world and the same thing, like I said, in surgery. Those are probably the top two that we can have examples from. But I find it really interesting that, like I said, he's doing that work. I haven’t really put two and two together until I just said that. That kind of going back to the whole don’t do stupid things [0:38:18] [Indiscernible] Peter Attia as far as longevity goes. But I do think that plays a huge role in human performance optimization especially when we're talking about extreme environments.
Christopher: Talk to me about your education. Imagine I'm a young girl. I've been listening to the STEM-Talk podcast. And I find everything you talk about absolutely fascinating. I'm still in high school. I really don’t know what to do next. What advice would you give to a girl like that with her education?
Dawn: I would say the biggest thing is find some good mentors. I was really lucky along the way even when I first got into scuba diving. This is back when I was 15. I had a great instructor. I had amazing people around me who I sought out as mentors. I had a couple of teachers in science who were my mentors all the way through high school. I always kind of look to them for advice and for feedback. And I still stay in touch with a lot of them with is pretty cool.
That would be the biggest thing, is just finding good leadership and finding good examples around you that can help you navigate the system. Sometimes it's not always intuitive as to how to take the next step. I would not have actually gotten into research -- this kind of research at least -- had it not been for one of my mentors. I was diving all the time. I finished my undergrad in biochem. I was working in a lab time part time while I was working in the diving community, while I was doing some other things as well. I was just trying to figure out the next step.
I was like, "I really want to study kind of biomedical research and divers." Like I said, I had been in the diving community for a long time. I worked with exploration groups around the world. We had done some pretty extreme diving and been involved in a lot of other research studies where other people were studying us. But there's no direct path. There's no graduate program in biomedical researcher divers anywhere.
[0:40:05]
So I ended up talking to one of my mentors at NC State University where I did my undergrad while I was working in a lab. It's funny. It was really simple. He said, "Well, create a program."
Christopher: You can do that?
Dawn: He's like, "You've always done what you put your mind to." I was like, "Okay." So it's just a different way of thinking about it. And so I kind of went back to the drawing board and I came up with a research project. It was something that I had been interested in. This is looking at changes in gene expression in response it decompression stress in divers. And so I pitched it to a professor at Duke University. Duke has a diving medicine program but it's specific to training residents and training fellows in diving medicine. It's not on the medical side, not so much on the research side. It was just for students. And they did have students coming through there but they're usually in medical school.
So they didn't have anybody doing a PhD work in that area. So I went to them and I said, "What if I do this?" Richard Moon actually ended up being one of my advisors for PhD who's absolutely brilliant. I was really lucky to have him as a mentor. He's like, "Let's put in a grant. This sounds like a great idea but we got to get money. So let's put in a grant."
So I wrote a grant before I was ever even working in that area of research, and it got funded. And so then I left. I went to Duke University. And I said, "So if I have a grant in hand can I turn this into a PhD project? Can I go to grad school?" And so I had to go through all the normal hoops that a grad student would. If I haven’t had money I don’t know if they would've let me in to the program. But it turned our great.
And so I ended up creating a program. And I actually ended up being the first person that the Office of Naval Research funded as a grad student. So I was kind of their test case.
Christopher: That's amazing.
Dawn: So it's great because now there are other people who are following that path. And so it's kind of cool to see the follow-on students who are coming through. I'm not saying that I made that happen but it was because of the advice of the mentor that I had that opportunity.
Christopher: How do you know someone is a good mentor?
Dawn: That's a great question. Do they support what you're doing but do they also push you to be better and to learn more? Are they interactive? I've seen a lot of people who have "mentors" but their mentors never have time for them. My mentors were all busy but they always took the time to at least give me some advice or to sit down and chat about next steps or give me feedback on a paper or whatever it might. To me that’s the important thing.
You don’t have to necessarily click. I have some mentors that we have very different personalities but I've learned so much from them over the years. You don’t have to be buddy-buddy. Do they invest in me? Do they take the time? Do they take the interest in what you're doing?
Christopher: That's a great answer. Well, this had been fantastic, Dawn. I really, really appreciate you. And I will, of course, link to the NEEMO blog. If you want to see some amazing pictures of the work that Dawn's been doing underwater, then you should head over to the NEEMO blog, and I'll link to that and, of course, the STEM-Talk podcast. Is there anything else that you'd want people to know about?
Dawn: No. I think that’s it. The STEM-Talk podcast, like I said, we have episodes coming out on a regular basis. Please check us out. You can sign up for updates on the podcast. I really appreciate you taking the time to chat with me today.
Christopher: It's my pleasure. Keep up the good work. Thank you very much.
Dawn: Thank you so much.
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