At the heart of an industrial revolution is an innovation that changes everything. Building AI Boston sees artificial intelligence as a renaissance. From the heart of innovation and the mecca of tech learning, we bring you AI for real people. A conversation for everyone. Dr. Catherine Brownstein is an assistant professor in pediatrics at Harvard Medical School and a research associate in the division of genetics and genomics at Boston Children's Hospital. She specializes in the discovery of new genes for rare and orphan diseases and today we'll discuss her work in the fields of genome sequencing and analysis and how AI is impacting medical research. Welcome to the show, Catherine. Thanks so much for having me. You know, the Boston Children's Hospital is home to the world's largest pediatric research enterprise and we've only mentioned a few of your accomplishments, but I gather you're a very busy woman. So I just want to start by saying we're honored that you're here with us. Thank you. Thank you. We're going to get into some of the challenges that you face in the field of rare diseases and genomics but I'm wondering if you can just start by telling us a little bit about what first inspired your interest in this field. So I kind of fell into it. I always thought I was going to be a forester actually and biologist like working in the outdoors and did my master's in forestry and public health working in toxicology and the professor I was working with actually was cross-listed in genetics. So I wanted to go back from my PhD and I applied to work with him and then he ended up leaving but then I was in the genetics department without ever having taken a genetics course and I had to really, it was trial by fire, but I loved every second of it and just feel incredibly lucky to be working in this field right now. It's a really exciting time and you know, I've gotten to be a part of it which I just feel extremely fortunate. I love that answer. I love the kind of, it speaks to a work-life balance that I think you inherently look at bigger picture things. I know that when you had me at forestry because I really like the bigger picture. I love relaxing in nature and I can relate to the tuning into the beauty of nature as a basis for just mental health. So it sounds like an incredible beginning. I still really enjoy that and my house is like a zoo. I have to get my animal fix a different way now but yeah, I definitely think it's so important that we never forget the importance of nature. Agreed and Cara would agree with that too. Absolutely. I have many dogs and probably they'll start barking during this podcast recording because why not? Why wouldn't that happen? So I do love that and I think there's so much more to sort of, people seem to be understanding forests and trees and the impact all the different sort of green space has on our state of well-being. So it's kind of an interesting space to look into. I love my dog out but she'll probably start barking at some point too. They'll talk to each other. It's good. Dogs are amazing. So I actually have a background not like yours, not science space but was in public health communications for a long time. And one of the things we tried to do and I still try to do in science communications, which isn't always easy, is to take really complicated things like genetics and make it somewhat understandable to a lay audience. So how would you describe what genetics really is doing? What are we trying to do in a very basic way with studying the human genome? We're trying to understand the human body and health and disease and some diseases you're born with and figuring out what is causing that at the very basic level helps us learn how to treat it and prevent it from happening if it's not something that you're born with but happens gradually as you get older. A lot of the conditions we look at are in Boston Children's are de novo, which means they're not in either parent. They just happened in this child like lightning striking during very early development or sometimes you inherit like need both parents or carriers. They don't actually have the condition but then the child just gets two faulty copies of the gene or something like that from one from each parent and unfortunately has the condition. I think Karin and I can both appreciate the parent's point of view. I want to just you know highlight something that's unique to Boston Children's is that you tackle rare diseases. Can you break down exactly what an orphan disease is, a.k.a. a medical refugee? So an orphan disease like a lot of times people use the word orphan or phrase orphan disease and rare disease interchangeably but there is a little bit of a difference between the two of them rare diseases are just that rare but orphan diseases are include rare ones but that researchers aren't investigating that much or if at all. And sometimes it's because they're just so rare it's only been seen one time or we think it's only one time but like now due to people speaking to each other across the globe. You can a lot of times turn that one case and find a couple more and which is always wonderful for making sure that you have the right gene that you think is causative and also it's nice sometimes for families to connect and have shared experiences. And share what works for them. And in terms of medical research, it feels to me like if I put myself in the shoes of that parent that suddenly facing an orphan disease that that maybe doesn't get the kind of research attention. Let's just say I'm awfully grateful that that's your expertise that that's what you're going for. And can you tell me a little bit about how the role of AI has really stepped that up and allowed you to do so much more. Oh, it's amazing. So just before I was here, I was cleaning up a data set and I thought I had cleaned it up completely and gotten out duplicate entries. And then I ran it through and I said, are there any duplicates. And even though like I had looked at it manually and like done all the checks that you normally do. And I had caught like eight things that I had messed up. And, you know, and that's just like the example that that that I was doing right before speaking to you. And if I had gone on use that data set, it would have been like slightly wrong. So like, I mean, it probably wouldn't have been enough to like change the results dramatically but like, you know, it's making everything a little more correct and little better, you know, of being able to work faster, not spend so much time on on mundane things that suck up a ton of time and being able to like switch gears really quickly when a gene is a dead end and you know okay it's not that and go on to the next thing and it just really has streamlined life. And that's because I like that. And a couple things. So it just increases the human ability, sort of to computational power that that right in the ability that you have to parse the data because, you know, medical research, any kind of medical work you're you're just dealing with loads and loads and loads of information right to find the right answer so in medical research, in the way that you're dealing with the right answer, you can't look at it all and especially if you're looking at something as complex as the human genome right so tell us about that I mean I can't even imagine the variables that must exist in that world when you're trying to trace down a specific cause. So so how does how does AI extend your ability to solve problems. It can't be an expert in everything like it's impossible. And right now, it's really manually find a gene you look it up you go through you see if it matches the patient symptoms or phenotypes and now we can just do that a heck of a lot faster and it takes the human error rate. Well, it will take the human error out of it, which is always a huge advancement. It's amazing if we and then just the ability to reanalyze and you know knowledge doubles so quickly and to go back and go through every single case like at the I work at the mountain center for orphan disease research within Boston Children's Hospital and no case is ever closed no family is ever considered like definitively solved because like you know some patients can have two things and you know variants get go from being uncertain significance to Pat likely pathogenic or they get downgraded to likely benign so like you always want to go through and reanalyze and being able to make it just much more simple and inexpensive and accurate to reanalyze it's a total game changer is going to be a game changer for patients and for everyone. You know, the cost, the cost per gets me excited because, as you know, in mirror diseases right very well. And especially we think about treatment like one of the barriers is the pharma companies it's it's a big amount of R&D money to put into maybe something has a very small patient pool so that's just hopefully seems like a place where I could significantly change. I get rid of bottlenecks yeah. Yeah, you know, right now, even the bottlenecks to to for patients matching each finding each other will hopefully be reduced with, you know, being able to find each other easier. That seems like a broader impact on just you can extrapolate what we've just said and talk about research in general but particularly particularly in genomics, it's such a massive innovation in and of itself and now we're on the verge of another massive innovation with AI, which seems to to the untrained eye or ear those listening to us it seems like AI changes week by week there's so many advancements. I know that in particular I know that this is a brand new announcement for you but I know in particular you've just developed a partnership with open AI, and you may not be able to speak to that specifically but do you see this as just yet another evolution and a larger evolution of research and in particular to what you're doing. I think it's, you know, I always tell the story that like, I did my PhD I graduated in 2008, and it took me six years to map a translocation now you can do it in six days, like, or less maybe three days. I mean I'm old I'm not that old like it's just moving so quickly and then I think AI again it's going to be this huge thing that increases the speed and the ability to make these discoveries that you know it's just going to be a game changer, or what's a translocation. Sorry, what's a translocation. Oh, it's when chromosomes break and reattach in the wrong spots. Like, like, a piece of chromosome nine will go on to chromosome 1313 will go back on to nine like that's, you know, and even though the genome was published like I had to like, really slow pain stinking work to figure out where the chromosomes broken reattached, but now we have like machines that can just like read directly across like and just a matter of a couple days to get the actual like result of that and it's just kind of blows my mind and I think like, it's going to be another thing where we're explaining to our grandkids like how we had to do work before AI and look everything up and then look at us and be like, oh man, that was terrible. Well, I don't you know what, if you were allowed or you want to I mean some of the background stuff that I've learned about you or the fields of study that you're involved in are immensely intriguing to me I mean you've done research on everything from sudden infant death syndrome to what I think is really interesting is your work in early child psychosis like there are things that are presenting now as schizophrenia I don't know how much you're allowed to talk about your work but I will just ask an open ended what are you really primarily excited about in terms of treatment of the disease that you feel is really impactful or important at this time. So I think being able to diagnose patients younger and start interventions younger is going to make a world of difference and not all precision medicine is medication to it's just getting the families the support they need and you know understanding which treatments work better for which genetic diagnosis and you know one. One gene that we worked with it seemed like the children did really much better if they had a nap in the middle of the day, you know, and that's precision medicine in a way you know like okay you have this like naps really help and. And but that's in one hand the other hand is like understanding okay you know the goal is to have the right medication the first time and not have to go through these trial and errors that so many patients have to go through right now and even just getting being able to say a diagnosis I went to a family meeting once and. There wasn't a treatment for the gene that this genetic disorder and I asked a patient like well does it mean anything to have a diagnosis and he said yes because I can explain what's wrong with me and. Three seconds as opposed to like three minutes of an explanation and so as little things like that where you know it's. Every little tiny step forward is still a step forward. I will say that that is one word that jumps out at me at reading your background is clarity. Yeah, you know you're you're clarifying things and I appreciate the power of a nap. I'm selling all these people hey the first nap is the most important one for brain function cognition and that brain is building and it's you know if people really understood the phenomenon of how complex that brain development is I am I nerd out on neuroscience and brain development and. And when I studied anatomy it was all about brain stuff for me but so I'm really and I was that protective mom that beat everybody back and said don't call me between this hour and this hour that first nap means everything to me so I'm excited that you look at things holistically and I think yeah everything I read about you is true to science in the very best way you know really looking at everything so anyway. And then the word precision if we're talking about words that was one of my favorite words to love my next. We all got so used to Napster and cove it right at like master's all up but anyway so precision right so precision medicine rate. So a lot of people in public health get kind of stressed out by the idea of precision medicine because it means individualized and the people usually were you know able to afford the precision or the individualizer people with more resources but maybe and so she wants you to think about this is. I would allow precision medicine to actually be more widely applied. In that like what you're saying it can really tailor so tell tell folks what precision medicine means and maybe in the sense of genomics as well and how they're interrelated. Well I'm a PhD I'm not an MD so I don't actually treat patients so my understanding of precision medicine is tailored treatments to the actual condition and as granular as possible so. To me it would be the genetics and what is wrong at a genetic level and being able to address that. But you know. You know. It's I know that. To me the benefit here and the exciting part is the ability to scale and if you get the genetics quicker and it's also simpler to interpret the genetics because you know you can produce that accurate report in seconds as opposed to like having to slog through a ton of articles. Then it translates to treatments faster and publications faster to document that treatments and then increasing access so everyone can see those publications or they don't even need to like they can they're searchable and findable and it's just being able to scale precision medicine which is the goal here and it's not. We just don't want it to be like you know Boston Children's Hospital and a handful of these tertiary medical centers all over the world we want it to be like everybody gets the right treatment the first time based on the genetics. Yeah, I love that and then if you have a place that people like physicians or people taking care of patients in rural places are places that don't have amazing academic medical centers like we do they can plug into some sort of system and and they don't need to be genetic experts themselves but there can be a simpler way right to find out what's going on with their patient. Exactly. That's the goal. That's the goal. Well you're really fortunate to be part of the Boston Children's Hospital it's not like any other hospital and so what does it mean to you to be rooted in one of the world's most powerful medical innovation hubs. It's so inspiring like you know my colleagues are brilliant and I love being the dumbest one in the world. You know I don't want to be in that room that sounds intimidating. No it's amazing like you all you always want to be like just looking around and being like oh my gosh you see people are so cool they're super girls and I don't know I feel very lucky I feel very lucky in my lab that I have like brilliant technicians and researcher or students on the students that come through are so inspired and wanting to learn as much as possible it's I feel very lucky. And are they do you see them leaning and you can speak for all of them in one swoop but are they leaning heavily into this into relying on AI and other technologies is that just kind of part and parcel of the career path at this point. Yeah I mean it's kind of funny I tell them to use AI for certain tasks so like I think there has to be a little bit of a shift in mindset and my children's were also very lucky we have a tool and AI tool that's behind the firewall so it's not as though you're putting information out into the universe by that so we're able to keep it secure and so we don't have a lot of the worries that a lot of other places do so. Yeah, I think people are adopting it quickly because it's medical information right you have to be so powerful. Yeah, but not not perfect. Oh you probably have both you have purple and everything else. Yeah. It's tough to break down ethical considerations but I mean I just appreciate the the ecosystem and Cara I know you appreciate it too for a personal standpoint wasn't one of your kids affected when you was young. Yeah so you know being in Boston is such a gift right in so many ways and sometimes we take it for granted especially when we're trying to commute through long would to get somewhere else and get annoyed because we're sitting in traffic for you know really long time. So for folks outside of Boston Longwood is the area where there's all these incredible hospitals including Boston Children's and so it gets very crowded I think it's probably one of the densest medical areas but we have people you know coming in from all over the world for these services but yet it's in our back door so it goes about saying that when you have little kids like I did at one point you know something goes wrong it is so reassuring to know that this hospital is not going to be a good place for you. we we we we we we we we we we we we we we we we we we we we we we we we we we we we we we we we we we we we we we we we we we we we we we we we we we we we we we we we we we we we we we we we we we we we we we we we we we we we we we we we we we we we we we we we we we we we we we we we we we we we we we we we we we we we we we we we we we we we we we we we we we we we we we we we we we we we we we we we we we we we we we we we we we we we we we we we we we we we we we we we we we we we we we we we we we we we we we we we we we we we we we we we we we we we we we we we we we we we we we we we we we we we we we we we we we we we we we we we we we we we we through a x-ray machine like that. They give them sugar water to suck on. Wow. I guess you have this basically like a pacifier just full of sugar water and the baby's like, oh. That was amazing. Yeah, it was pretty cool. The nurses have all the tricks. Yeah. My daughter split her chin open, of course, the day before starting a new school. And so we went to Boston Children's ER. I'll never forget as they're stitching her up, they had a person just holding the iPad over her so she could watch a cartoon while doing this. And I just thought of everything. Like, that's just amazing. It just made it such a better experience and less stressful for her. Yeah, we're incredibly lucky to live here. And one thing is just bringing that knowledge and that research and making it wildly accessible to everybody. No, I think you hit it on the head when you said, how do we make this scalable? I mean, that's the prime concern. And we feel that way about our show. We think of Boston as a state of mind, but you've really brought that to mind when you're talking about how to bring this kind of way of thinking out to a broader audience. I know you don't have a crystal ball, and we're not asking you to be an AI expert, but I'm just wondering, is there anything as a researcher that you're really looking forward to being able to do in the future and anything that you feel really hopeful about as far as AI and how it impacts medical research? I'm just so psyched for to feel like I've done the best I possibly could when looking at a case. And right now, I feel like there's always this nagging voice in the back of my head that I miss something. If another, I have like a panic, actually, when I close the browser to look at something that I miss something. And I really am looking forward to feeling like, OK, we've analyzed it to the best of our ability at this juncture. And as our ability increases, we're going to be able to reanalyze and still feel that sense of comfort. I think also, we owe that to the families that are so generously signing up for research. And a lot of times, their children are very sick, or they're sick. And we owe it to them to do the absolute best job we can. And AI, I think, will help us do that. Now, I appreciate your insight. And I appreciate that. It's not like you're whipping up the next best recipe for cookies. You're definitely in the trenches of the most important work. As a mom, I thank you. I mean, I'm just grateful to know that this research that you're doing will go out to the world and will affect me on my side of the country and around the world. So again, we're so honored to have you here breaking this down with us. Catherine, thank you. Thank you so much for having me. Thank you so much for having me. This has been a really interesting conversation. Thank you for joining us on Building AI Boston. Stay tuned for more enlightening episodes that put you at the forefront of the conversations shaping our future.
