EPISODE TRANSCRIPT
Content may be slightly edited for clarity.
Angelica
Hello, world, and welcome to So Curious, presented by the Franklin Institute.
Bey
In this season Human 20, we will be talking to scientists and non-scientists alike about technology and innovation surrounding the human experience.
Angelica
We’re your hosts. I’m Angelica Pasquini.
Bey
And I’m the Bul Bey. But you can just call me Bey.
Angelica
In today’s episode, we’ll be talking to the director of the Gene Editing Institute, Dr. Eric Kmiec, and chief bioscientist at the Franklin Institute, Dr. Jayatri Das. Today we’re going to be talking about personalized health and genetics.
Bey
Personalized health and genetics is like, what, 23andMe, spitting into tubes, DNA tests. Have you done any of this?
Angelica
Yeah. You know what, I did? My roommate was moving to Beijing and she had a 23andMe and was like, listen, I’m not going to be able to do this. I’ve got to go. And I was like, okay, I’ll do it. So we’re just sitting in the apartment and I tried it, and then I got information back, and it turned out that I was a little more Italian than some of my siblings. And it’s funny because your genetics aren’t the same necessarily as everyone in your family. Each of us has our own breakdown. And do I regret it? Yes. Because then later I found out that they sell the data, but we’ll get into that later. How about you?
Bey
I haven’t done any swabbing or spitting them myself, but my brother took an African ancestry test that traces, I think, the maternal line, essentially the mothers of the family all the way back to the continent. There’s some accuracy there. But you brought up such a great point. There’s so much more diversity within one small group than we ever give credit for. Like a small nucleus of family members. The gene genetics and the diversity in there is a lot. And we think everybody’s just like identical, and we’re all a little distinct.
Angelica
Yeah. Also, I think that sometimes with personalized health and genetics, you can take a test that will show you what you could be mindful of in the future as far as your health is concerned and how to be aware of what you have dispositions towards in your health.
Bey
Right. And we’ll be going into all of these little tidbits, but things evolve and grow. DNA and genes and things like that do the same. And what’s good for you may not be good for someone else. What’s good for your mom may not be good for you. These little health tips that she might give you. Or at least maybe I’m projecting. Maybe I’ll talk about my mother right now. I’ll just stop.
Angelica
No, go on. I think that, yeah, I mean, if I knew that… I think a lot of people do breast cancer testing and things like that, just like if they have a certain type of gene, they can know, they can get ahead of it before it could get potentially dangerous for them. That kind of thing is actually, I think, a really amazing innovation.
Bey
I think it’s time to transition into our first expert interview with Dr. Eric Kmiec.
Angelica
Our next guest is Dr. Eric Kmiec. Dr. Kmiec has directed the Gene Editing Institute of the Helen F. Graham Cancer Center and Research Institute at Christiana Care since 2014. He is widely recognized for his pioneering work in molecular medicine and gene editing. Throughout his career, Dr. Kmiec has led research teams developing genetic therapies for inherited disorders like sickle cell disease. He is the author of over 140 scientific publications and has been awarded multiple research awards from the National Institute of Health and the American Cancer Society. Hello and welcome. Dr. Kmiec. Can you start by introducing yourself?
Eric Kmiec
I’m Eric. I’m the Director of Christiana Care’s Gene Editing Institute. And over the past few years, with some recent discoveries, there’s a movement now to be able to put some genetic medicine and gene therapy into the clinic and actually begin treating patients.
Angelica
And you work with clustered regular….oh, here we go.
Bey
Can you say it five times fast?
Angelica
Can you talk about CRISPR? The technology?
Eric Kmiec
Gene editing is a process that’s like genetic “spell checking.” Our DNA can be thought of as a series of letters, actually, over 3 billion of them. They are broken up into words, which can be functionally considered genes. And occasionally one of those words is misspelled. Then, up to this point, it’s been really hard, no matter how hard we’ve tried, to be able to replace or fix or repair or do a genetic “spell check” on genes.
Bey
And real quick, when you say “misspelled,” you mean flawed?
Eric Kmiec
Yeah.
Bey
And in what way?
Eric Kmiec
There are four bases in DNA, and let’s say there’s supposed to be a T in one position and it’s an A, and that just comes from inheriting malfunctioning genes or sequences from your parents.
Angelica
What does that look like on a human?
Eric Kmiec
Probably the one genetic disease that people have wanted to approach with this is sickle cell disease. So sickle cell disease is caused by a single base or a single letter that’s incorrect in the entire human genome , or on all your chromosomes. There hasn’t been a very good series of treatments developed for sickle cell. So actually, for most inherited diseases, CRISPR is now maybe the first genetic tool that might be able to address it. So a fair bit of work is going on around that. The people in my lab are pretty good at using CRISPR. We have a very active lab doing that work now. So there’s actually some hope for something that has been a dreaded inherited disease for a long time.
Angelica
And you can see in the embryo, that typo? If we’re using the Microsoft Word, we’re going to use that analogy?
Eric Kmiec
Yeah. Shortly after a child is born, there are a number of genetic tests that are done to predict what sort of inappropriate genes or typos or mutations are present. This is also kind of important, on a slightly related topic, is the importance of having genetic counseling and genetic testing being done to parents prior to conception. We’ll at least inform folks that there’s a chance here that you could pass this gene onto your child. And if they make a decision to go ahead, it’s not our place to tell them not to do it, but at least they have the information ahead of it.
Bey
And CRISPR and many other practices falls under precision medicine?
Eric Kmiec
Precision medicine. Yes.
Bey
Can you tell us about that?
Eric Kmiec
Sure. So precision medicine right now is not so precise.
Bey
Got you.
Eric Kmiec
We have a dedication to try to figure out the complexities of diseases. Now, this actually started primarily in cancer therapy. What happened was people thought there’s got to be a better way, and they started to understand more about the proteins and the DNA and the guts of the cell, and they developed these things called targeted therapies. Keytruda, you’ll see advertised on television. Opdivo. These are targeted therapies that have been designed to attack a specific genetic trait in a specific patient. And that’s why we call it precision medicine. It’s going after a certain number of people. The problem is, it’s a certain number of people. So Keytruda is a very good drug, but it only is appropriate for 19% to 20% of lung cancer patients. They can be treated, but it will do no good. And that’s a tough conversation.
Angelica
Absolutely. People try everything, they do. Okay. So what are your conceptions of treating cancer? So it’s a very complex issue with very complex treatment. I’m just going to ask: if it happened to you or someone in your family, like precision treatment is what you would hope you could be able to do?
Eric Kmiec
So the standard of care, chemotherapy, radiation, targeted therapies, immunotherapy, they actually do work. A lot of times the side effects are worse than the disease itself. And so what we try to do is we try to augment those side effects. And by doing that, you allow the standard of care therapy to work better. So if I could make you less sick over chemotherapy and keep you healthier in response, you would be able to respond better to that specific therapy. So that’s where I think CRISPR and genetic medicine is going. So we’re working on eliminating a gene in a tumor by directly placing CRISPR into the tumor, that causes that tumor to be resistant to chemotherapy. And so that allows now two things: number one, it allows the tumor to remain small or even shrink, and then that allows the surgeon to go in and remove it because the best therapy is surgical removal of a tumor. But in some cases, those tumors have gone around blood vessels and you can’t do it. So it’s a really ugly situation. Yeah, that’s pretty low-hanging fruit. Just reduce the size so a surgeon can remove it, but that’s a legitimate endpoint.
Bey
You know, Dr. Kmiec, we did a Google search of CRISPR before you came in. So we’re halfway there, almost where you are. But the auto-fill response of CRISPR was, “is CRISPR ethical? Is it legal? Is it safe?” Can you go on about that and talk about some of those worries, concerns? Because clearly those autofills are like what people are generally asking.
Angelica
Common concerns.
Eric Kmiec
That’s a great point, and it’s an important one. So as scientists, they are much more socially-conscious than used to be. So when you introduce a difficult and challenging technology, people are at different levels of understanding. We do not believe, nor will we work on anything related to germline. So we are not going to design a child by treating a fertilized egg or sperm oocyte. That’s known as germline gene editing. To us, that’s completely unethical and completely forbidden in the United States. But like anything, it’s open for abuse, so we have to police ourselves.
Bey
Is that the structure at this point? You are policing yourselves?
Eric Kmiec
Yeah.
Angelica
So there’s no regulations on it yet?
Eric Kmiec
Well, there’s regulations. So the law in the United States, again, the National Institutes of Health will not fund that kind of research or development. But can somebody in a private company, in a biotechnology company go do it? Yes.
Angelica
Right, now that the technology exists.
Eric Kmiec
It completely exists. I think the other thing about the consequences and the ethics of this…there is a fairly high misconception that you can engineer human traits. So you can engineer hair color, eye color, perhaps skin color, creativity, creativity, athletic abilities, things like that. And the chances of doing that now are beyond possibilities because they are controlled by so many different genes that we don’t understand. There’s a built-in safety out there that even if we were to try to design children in the way that we prefer, or induce certain traits, it would be almost impossible.
Angelica
Yeah. Right now.
Eric Kmiec
Yeah. Right now.
Angelica
I think that what’s happening is people see, when you begin, where does it go? And that’s what we don’t know, too, is like how far things go. It all starts with treating people who are not well and finding a solution for them, or maybe someone with a disability, like around hearing or sight. And then you create something like Siri for them, and then down the line, it’s sold in Mac stores, right? So everything becomes luxury that was once for a need.
Bey
Is there a technology that can detect cancer in an embryo? Can you look at that that early and say, hey, they’re likely to have cancer? Let’s gene edit, let’s CRISPR?
Eric Kmiec
There are things called genetic panels. So unfortunately, there’s not one specific test that can predict any form of cancer. We don’t know yet. We don’t have the algorithms yet to predict anything. So we’re thinking we’re going to get there. There’s a tremendous amount of money and effort and research going into develop these software programs, and it’s an area called bioinformatics. That being said, there are a few markers for breast cancer, for a certain percent of breast cancer, there’s a gene called BRCA1.
Angelica
Oh yeah. You can test for that, right?
Eric Kmiec
You can test for that. Right. And I think there’s even a home test for that now, believe it or not.
Angelica
I have friends that have done that who’ve lost their moms to breast cancer.
Eric Kmiec
Right. So unfortunately, there isn’t a lot of treatment that’s been better, although surgeons would say, no, we’re better. And that could be true. But it’s about diagnosing it early. And breast cancer, prostate cancer, are two types of cancer that can be seen early. So really the two effective things are early diagnosis, and then the other thing, of course, is surgery. Cancer is energy-draining. Your energy just leaves and your cells can’t support you and you pass on from that very wasting kind of disease. It’s very hard to watch.
Bey
Is your biggest dream and goal with CRISPR and many other different treatments to eliminate this completely, or is it just to alleviate the pain and the suffering? What are your biggest dreams around CRISPR?
Eric Kmiec
The first level is to make standard of care therapies work better and improve the quality of life. What we learn from those patients will eventually draw into preventing it or even reversing it. So we try to be as realistic as possible because the folks ahead of us who were pioneers in some ways actually went a little bit too quickly. So I think that’s the right way to approach this right now. Same with genetic disease.
Bey
That’s so tough because you want to help, you want to do some good and change the world and… Nuance, you know what I’m saying? Add gray to everything you’re doing, and I think you’ll always find a better outcome. Trying to do things absolutely just kind of backfires.
Angelica
I’ve always wanted to ask someone like you this kind of question, what is your day-to-day like with this? Do you have a lot of big picture questions all the time, or do you sort of find a way to compartmentalize doing this kind of work?
Eric Kmiec
Yeah, I think both. We always have our eye on the goal line. We definitely feel that we can contribute something, but at the same time, we’re sort of humbled by the challenge. A lot of really smart people have come before us where there were very few original ideas actually in science. Putting them in different compartments, for me is really sort of thinking about them in a different angle, different dimension. And this doesn’t stop at 05:00. There are people in the Institute lab at all hours of the night. Over Thanksgiving, half of the lab was in there in the afternoon on Thanksgiving day and the other half on Friday morning. Because if you’re drawn to this kind of work, you can’t stop thinking.
Bey
So one of the questions that we are constantly asking through this series is, not only what the science look like, but what do scientists look like?
Eric Kmiec
One of the minorities in science beyond the obvious ones — and we need to do a lot better at that — are actually women. Interestingly, in the field of gene editing and CRISPR biology, the majority of the young scientists are women. That may be linked to the fact that the 2020 Nobel Prize in Chemistry was awarded to Jennifer Doudna and Emmannuelle Charpentier, two women. And for the first time, they shared the prize without a man standing on the podium with them. And I think we all said it’s about time. One of the things we also do is we’re really trying to get out into the communities to share gene editing as a breakthrough technology so that we have lots of color in the field. We’re tending to bring breakthrough technologies to underserved communities by back-teaching them. Oh, this really works great… CRISPR and gene editing is a current technology. So let’s work our way in there. And what we see when we do that with high school students in summer camps, they love to see women and women of color. And those are the people they want to talk to, not me. And that’s very important. So the structure of the population of this field may help to change the rest of science in general.
Bey
That’s so dope.
Angelica
Great.
Bey
Thank you so much for opening that up and giving us all this fresh information, because at the beginning, we were like what?
Angelica
We had no idea what to expect.
Bey
What is “clustered regularly….?”
Angelica
We learned so much.
Eric Kmiec
It’s been great.
Angelica
Thank you.
Eric Kmiec
All right. Take care.
Bey
All right. So we just got a lot of information and things presented to us. Time to reflect.
Angelica
Well, that was really interesting. I have to admit, I came in a little nervous about what we were going to be talking about.
Bey
So where are you now?
Angelica
Cautiously relieved. You?
Bey
I really appreciated the presence of ethics. Right. And trying to be careful and also acknowledging there is some scary parts of it. But most people are focused on the early lifecycle, the embryos, and also at the end.
Angelica
I absolutely loved that. This is another cool example of how a technology that’s developed to help people who are not well later becomes a luxury, potentially, down the line, in genetic modification. So we’re starting off first with trying to heal or detect and manipulate early-onset signs of something particular, maybe even just in the embryo and adjusting the cells early on to prevent disease later on. Right. So that’s something that we’re using for people who are unwell. That’s what the doctor said. And then later it can become something that’s a luxury tool. Right? And that’s what people’s biggest fears are. And I did love that he talked about regulation around designer babies and making a baby with a certain color eye and s certain ability to play tennis or something like that. He really knew. And he has very strong thoughts about that not being where this goes.
Bey
Right. And, you know, I came into the conversation a little pessimistic about cancer and other things that ail the human species and really kind of keeps people in unwell space, like, just sick sometimes. But some of the details that he gave left me optimistic. I’m like, maybe we can start to move towards an actual cure for cancer and an actual answer to these really hard-hitting diseases.
Angelica
Yeah. It sounds like molecular medicine and gene editing are much more multifaceted than we could have ever imagined.
Bey
Yeah.
Angelica
Let’s switch gears a moment. Okay, time for a Body of Knowledge segment. In this segment, we’re going to discuss the topic of personalized health and genetics in an open-form discussion. We’re going to be throwing ideas, asking questions with the chief bioscientist at the Franklin Institute, Dr. Jayatri Das. Welcome, Jayatri. Okay, so we are back with Jayatri, and we are talking about personalized health and genetics. What does that make you think of?
Jayatri Das
I’m going to ask you guys a question. First is, like, when you think about your DNA and who you are, what connection do you see between them?
Bey
I think of a long line of creative people, and I’m super-creative, and I can’t turn it off. And sometimes I love that about myself. And other times I’m like, oh, my God, stop making everything into a song. But that’s kind of my connection. I see a lot of creativity. I see a lot of pride.
Jayatri Das
I love the fact that you thought really about thinking back about your family. It’s not just about physical traits, right?
Jayatri Das
What you end up is more about…
Bey
Well, noses. My family has big noses. Big noses.
Jayatri Das
What about you, Angelica?
Angelica
I did think physical. Okay, so I’m Italian, so I’m like…hairy. I look at all the photos, and I’m like, you guys are all hairy! Like, it’s just the way it is, right? We’re all hairy. And I think of heart stuff has come up in my family or like, my grandma did have brain cancer. So I do think of those things, but generally I love to look at my family, and I can just see how we all look similar. And I think part of why people love having kids, too, is to see this version of themselves, of their personal health and their genetics growing. I think that that’s a fascinating part of human life and family.
Jayatri Das
Well, I think the two elements that you each brought to that conversation kind of illustrate the power of why we want to take a more personalized approach to health and medicine. Because, Angelica, you’re absolutely right that there is so much of the DNA that shapes our physical appearance and our health, but not entirely. If anybody ever told you that whether or not you can roll your tongue is based on your genetics, that’s a myth.
Bey
Wow.
Jayatri Das
Have you ever heard of any of those?
Bey
I haven’t thought about it in that way, but yeah, right. Like, speech and capabilities. If your dad can play tennis, can you?
Jayatri Das
Right. So a lot of those traits are much, much more complex than being able to boil it down to like, oh, you have a gene that tells you whether you can roll your tongue or you have a gene that makes you creative. That’s not real. There are some diseases that are caused by single changes in DNA. Turns out earwax is also affected by a single gene. It’s one of my favorite examples, whether your ear wax is wet or dry.
Bey
Whoa. Wow. What are yours?
Angelica
It comes down to one gene?
Bey
Yeah. What are yours? Is it wet? That was a weird question. Sorry.
Jayatri Das
That’s a little personal.
Bey
Your ear wax, sorry.
Angelica
You know what? It’s what I’ve seen. So it’s part of my personalized health and genetics and me and my friends and family. That’s fascinating. Wow.
Jayatri Das
Right. And so where that level of genetics comes into play is thinking about whether medicine or some sort of behavioral treatment, whether your genetic background will respond to that. Right? Because all of our genes are different. And sometimes that background makes a difference in whether or not your body will respond to one medicine or another medicine.
Bey
You mentioned some things that were not necessarily true, like rolling the Rs and being creative and so on and so forth. Are there some things that are actually understood to be passed along dynamic in genes?
Jayatri Das
So, aside from a few diseases and then the earwax trait, most things are not only influenced by a whole number of different genes, but also very much from your environment. Right? And this kind of gets, Bey, at what you brought up, this being in a creative environment from a creative family. You see that helping you become a creative person as well. And so where we’re looking now in terms of what’s possible with health and genetics and things like that is thinking about what we know about how our genes and the environment actually interact with each other. Genes don’t necessarily make up who you are, but they can be very important in thinking about how to design the most effective treatment for you.
Bey
Right.
Jayatri Das
My aunt went through this. She passed away from lung cancer several years ago. But part of her treatment was actually looking at the genetics of her cancer and thinking about, okay, which drugs are best suited for her specific cancer. And that’s the power of medicine that we didn’t have just a few decades ago.
Angelica
Yes. It feels like luxury. It does. It feels like luxury medicine, where we’re going to look at you and we’re going to help you — not just, we’re not going to just give you what works on most people. We’re going to look at what’s going on with you.
Jayatri Das
And that’s so important as we realize the genetic diversity among people. Right. That we can’t just take these shortcuts like a social construct of race, for instance, to make those assumptions about what’s going to work.
Bey
That’s so true. Okay, we’re going to move into our Body of Knowledge auto-fill segment where we turn to the Internet to see what people are asking about personalized health and genetics. These are some of the most popular questions people are asking the Internet.
Angelica
So we’re going to get into some of the questions that people have asked. “Is personalized healthcare legit?”
Jayatri Das
Yeah, definitely, for sure. I think where that term…I think there’s a reason that we’re kind of moving from “personalized medicine” to “precision medicine” is to be a little bit more intentional about what personalized means, because I feel like it’s not like somebody just monograms your medicine or something like that! Right?
Angelica
That would be cool. I would buy that. Is precision medicine the future of healthcare?
Jayatri Das
There are some complexities around that question that we don’t know the answer to yet, because some of it is very much in terms of the theory versus the practicality of it. If we could design everything to everybody’s particular genome, how much of a difference would that make? I don’t know that we know that yet. And there’s also a question of how expensive is it, right? The realities of health care in the world that we live in? Definitely.
Angelica
It seems expensive. I hope everyone gets access to it eventually. Oh, this is a cool question, and I’m glad people are asking this: “is my DNA unique?”
Jayatri Das
Well, are you an identical twin?
Angelica
I’m not. Are you guys?
Bey
No, I am not. I don’t know why I said it like that.
Jayatri Das
You had to think about it for a minute.
Bey
No, I am not an identical twin.
Angelica
Do identical twins have exact same DNA?
Jayatri Das
So their DNA sequence is exactly the same when they’re born. But what’s cool is that even identical twins, they’re not completely identical, right? And part of what we’ve learned over the last few decades is that there are ways that our genes are turned on and off in different ways that don’t just depend on the actual sequence of letters. One of the simplest examples is that even though identical twins have the same genome, their fingerprints are different.
Bey
Right.
Angelica
Wow.
Jayatri Das
Because there are so many other factors, environmental factors that affect how those genes are turned off and on. Even different parts of the body can have genes turned off and on in different ways at different times. For most of us, our DNA is unique. But even among identical twins, there are differences in terms of how you go from your DNA to who you are.
Bey
And I have a bit of a silly question, I guess. Does your DNA and genetics change as you grow in age and develop different experiences and travel and find a favorite color and eat some food and make a song and all these different things with your experiences? Does your DNA change?
Jayatri Das
So, for a lot of those experiences, that’s not going to affect your DNA. Is it changing your brain? Absolutely. Okay. But your body does accumulate mutations in your DNA just over time. Like every time your body makes a new copy of DNA, there’s a possibility of making a mistake.
Bey
Okay.
Jayatri Das
And sometimes there are environmental factors, like the sun: UV rays can create mutations in your DNA that can lead to things like skin cancer.
Bey
Okay.
Angelica
How often does your body make a new copy of DNA?
Jayatri Das
Oh, man. All the time.
Angelica
I didn’t know that. That’s amazing. So it’s constantly making new DNA?
Jayatri Das
Yes.
Angelica
Fascinating.
Jayatri Das
Yeah. We think of ourselves as kind of like…
Bey
Stagnant.
Angelica
Done?
Bey
It’s over!
Jayatri Das
Yeah, you’re making new, you’re replacing your body’s cells all the time and getting rid of all the dead ones.
Bey
Wow.
Angelica
Fascinating. I love that. Oh, I love this question. Okay. “Are my genetics good?”
Jayatri Das
Oof! There’s another value question!
Bey
They aight.
Angelica
If you have to ask, Bey, they might not be. No, I’m just kidding. If you’re looking at the mirror and you’re going, is this good? I think we all feel that way.
Jayatri Das
There’s some social pressure there.
Angelica
There is for sure. And the last one is: “is my DNA in a database?”
Jayatri Das
So that’s a really good question because a lot of people choose to put their DNA in a database. If you’ve gotten your 23andMe or Ancestry.com, then yeah, your DNA is in their database.
Bey
Low-key, I feel like Angelica put that question in there.
Angelica
That’s right up my alley!
Bey
Right?
Angelica
Yeah. I will say, I didn’t know when I did 23andMe. I didn’t read the paperwork and know that it’s now in a database. It’s one of those things.
Jayatri Das
I hate fine print.
Angelica
I will accept it, yes, it is fine print, but life ultimately goes on.
Angelica
Hi, this is Angelica Pasquini from So Curious. You know what? We love making this show, OK? But sometimes there are great fits. We just can’t fit them into the episode. So we put together a bunch of great bonus content and you can find that available at beyond fi.edu.
Angelica
Thanks so much, Jayatri, and thank you so much for tuning in to this episode of So Curious. This podcast is part of The Franklin Institute. The Franklin Institute is a science museum located in Philadelphia. The Franklin Institute’s mission is to inspire a passion for learning about science and technology. For more information on everything about The Franklin Institute, visit fi.edu. This podcast is produced by Radio Kismet. Radio Kismet is Philadelphia’s premier podcast network for businesses looking to develop their own branded podcast content. Check them out at radiokismet.com.
Angelica
There’s a lot of people who make this podcast happen. Thanks to the producers Joy Montefusco and Jayatri Das. Our managing producer, Emily Charash. Our operations head, Christopher Plant. Our associate producer, Liliana Green. Our audio team, Christian Cedarlund, Goldie Bingley, Lauren DeLuca and Brad Florent. Our development Producer, Opeola Bukola. Our science Writer, Kira Bayette and our Graphic Designer Emma Sagar. See you next week.
