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Medicine, but Really Personal
Episode 222nd January 2022 • So Curious! • The Franklin Institute
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Genes! We all have them. In this episode, Angelica and Bey with Dr. Eric Kmiec about how technology and gene information can cater our healthcare experience to an individual's needs. Later in the episode, Dr. Jayatri Das is back to add her thoughts about the future of personalized medicine. 

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Hello, world, and welcome to So Curious, presented by the Franklin Institute.

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In this season Human 20,

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we will be talking to scientists and non-scientists alike about technology

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We're your hosts.

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I'm Angelica Pasquini.

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And I'm the Bul Bey.

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But you can just call me Bey.

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In today's episode, we'll be talking to the director of the Gene Editing Institute, Dr.

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Eric Kmiec, and chief bioscientist at the Franklin Institute, Dr.

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Jayatri Das.

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Today we're going to be talking about personalized health and genetics.

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Personalized health and genetics is like, what, 23andMe, spitting into tubes, DNA tests.

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Have you done any of this?

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Yeah. You know what, I did?

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My roommate was moving to Beijing and she had a 23 andMe and was like, listen,

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I've got to go.

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And I was like, okay, I'll do it.

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So we're just sitting in the apartment and

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I tried it, and then I got information back,

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and it turned out that I was a little more Italian than some of my siblings.

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And it's funny because your genetics aren't the same necessarily as everyone in your family.

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Each of us has our own breakdown. And do I regret it?

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Because then later I found out that they sell the data, but we'll get into that later.

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How about you?

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I haven't done any swabbing or spitting them myself, but my brother took an African ancestry

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test that traces, I think, the maternal line, essentially the mothers of the family

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all the way back to the continent.

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There's some accuracy there.

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But you brought up such a great point.

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There's so much more diversity within one small group than we ever give credit for.

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Like a small nucleus of family members.

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The gene genetics and the diversity in there is a lot.

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And we think everybody's just like identical, and we're all a little distinct.

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Also, I think that sometimes with personalized health and genetics,

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you can take a test that will show you what you could be mindful

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of in the future as far as your health is

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concerned and how to be aware of what you have dispositions towards in your health.

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Right.

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And we'll be going into all of these little tidbits, but things evolve and grow.

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DNA and genes and things like that do the same.

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And what's good for you may not be good for someone else.

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What's good for your mom may not be good for you.

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These little health tips that she might give you.

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Or at least maybe I'm projecting.

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Maybe I'll talk about my mother right now.

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I'll just stop.

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No, go on.

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I think that, yeah, I mean, i f I knew that...

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I think a lot of people do breast cancer testing and things like that,

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just like if they have a certain type of gene,

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they can know, they can get ahead of it before it could get potentially dangerous for them.

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That kind of thing is actually, I think, a really amazing innovation.

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I think it's time to transition into our first expert interview with Dr.

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Eric Kmiec.

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Our next guest is Dr.

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Eric Kmiec. Dr.

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Kmiec has directed the Gene Editing Institute of the

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Helen F. Graham Cancer Center

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and Research Institute at Christiana Care since 2014.

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He is widely recognized for his pioneering work in molecular medicine and gene editing.

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Throughout his career, Dr.

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Kmiec has led research teams

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developing genetic therapies

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for inherited disorders like sickle cell disease.

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He is the author of over 140 scientific

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publications

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and has been awarded multiple research awards

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from the National Institute of Health

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and the American Cancer Society.

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Hello and welcome, Dr. Kmiec.

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Can you start by introducing yourself?

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I'm Eric.

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I'm the Director of Christiana Care's Gene Editing Institute.

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And over the past few years, with some recent discoveries,

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there's a movement now

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to be able to put some genetic medicine and gene therapy

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into the clinic and actually begin treating patients.

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And you work with clustered regular....oh, here we go.

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Can you say it five times fast?

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Can you talk about CRISPR?

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The technology?

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Gene editing is a process that's like genetic

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"spell checking." Our DNA can be thought of

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as a series of letters,

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actually, over 3 billion of them.

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They are broken up into words, which can be functionally

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considered genes.

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And occasionally

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one of those words is misspelled.

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Then, up to this point, it's been really hard,

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no matter how hard we've tried, to be able to replace

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or fix or repair or do a genetic "spell check" on genes.

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And real quick, when you say "misspelled," you mean flawed?

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Yeah.

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And in what way?

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There are four bases in DNA, and let's say there's

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supposed to be a T in one position

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and it's an A, and that just comes

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from inheriting malfunctioning genes or sequences

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from your parents.

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What does that look like on a human?

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Probably the one genetic disease

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that people have wanted to approach with this

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is sickle cell disease.

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So sickle cell disease

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is caused by a single base or a single letter that's incorrect

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in the entire human genome,

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or on all your chromosomes.

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There hasn't been a very good series of treatments developed for sickle cell.

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So actually, for most inherited diseases,

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CRISPR is now maybe the first genetic tool

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that might be able to address it.

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So a fair bit of work is going on around that.

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The people in my lab

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are pretty good at using CRISPR.

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We have a very active lab doing that work now.

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So there's actually some hope

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for something that has been a dreaded

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inherited disease for a long time.

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And you can see in the embryo, that typo?

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If we're using the Microsoft Word, we're going to use that analogy?

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Yeah.

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Shortly after a child is born,

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there are a number of genetic tests

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that are done to predict what sort of inappropriate

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genes or typos or mutations are present.

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This is also kind of important,

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on a slightly related topic, is the importance of

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having genetic counseling and genetic testing being done

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to parents prior to conception.

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We'll at least inform folks that there's a chance here

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that you could pass this gene onto your child.

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And if they make a decision to go ahead, it's not our place to tell them not to do it,

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but at least they have

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the information ahead of it.

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And CRISPR and many other practices falls under precision medicine?

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Precision medicine. Yes.

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Can you tell us about that?

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Sure.

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So precision medicine right now is not so precise.

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Got you.

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We have a dedication to try to figure out the complexities of diseases.

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Now, this actually started primarily in cancer therapy.

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What happened was

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people thought there's got to be a better way, and they started to

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understand more about the proteins

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and the DNA and the guts of the cell,

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and they developed these things called targeted therapies.

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Keytruda, you'll see advertised on television.

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Opdivo.

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These are targeted therapies that have been designed

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to attack a specific genetic trait in a specific patient.

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And that's why we call it precision medicine.

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It's going after a certain number of people.

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The problem is, it's a certain number of people.

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So Keytruda is a very good drug,

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but it only is appropriate for 19% to 20% of lung cancer patients.

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They can be treated, but it will do no good.

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And that's a tough conversation. Absolutely.

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People try everything, they do. Okay.

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So what are your conceptions of treating cancer?

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So it's a very complex issue with very complex treatment.

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If it happened to you or someone in your family,

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precision treatment is what you would hope you could be able to do?

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So the standard of care,

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chemotherapy, radiation, targeted therapies,

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immunotherapy, they actually do work.

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A lot of times the side effects are worse than the disease itself.

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And so what we try to do is we try to augment those side effects.

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And by doing that, you allow the standard of care therapy to work better.

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So if I could make you less sick

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over chemotherapy and keep you healthier in response,

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you would be able to respond better to that specific therapy.

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So that's where I think CRISPR and genetic medicine is going.

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So we're working on eliminating a gene in a tumor

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by directly placing CRISPR into the tumor,

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that causes that tumor to be resistant to chemotherapy.

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And so that allows now two things:

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number one, it allows the tumor to remain small or even

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shrink, and then that allows the surgeon to go in

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and remove it because the best therapy is surgical removal of a tumor.

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But in some cases, those tumors have gone around blood vessels and you can't do it.

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So it's a really ugly situation.

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Yeah, that's pretty low-hanging fruit.

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Just reduce the size so a surgeon can remove it, but that's a legitimate endpoint.

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You know, Dr. Kmiec,

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we did a Google search of CRISPR before you came in.

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So we're halfway there, almost where you are.

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But the auto-fill response of CRISPR was, "is CRISPR ethical?

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Is it legal?

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Is it safe?" Can you go on about that and talk about some of those worries, concerns?

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Because clearly those autofills are like what people are generally asking.

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Common concerns.

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That's a great point, and it's an important one.

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So as scientists, they are much more socially-conscious than used to be.

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So when you introduce a difficult and challenging technology, people are at different

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levels of understanding.

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We do not believe, nor will we work on anything related to germline.

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So we are not going to design a child by treating a fertilized egg or sperm oocyte.

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That's known as germline gene editing.

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To us, that's completely unethical and completely forbidden in the United States.

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But like anything, it's open for abuse, so we have to police ourselves.

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Is that the structure at this point? You are policing yourselves?

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So there's no regulations on it yet?

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Well, there's regulations.

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So the law in the United States, again, the National Institutes of Health will not

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fund that kind of research or development.

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But can somebody in a private company, in

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a biotechnology company go do it? Yes.

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Right, now that the technology exists.

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It completely exists.

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I think the other thing about the consequences and the ethics of this...

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there is a fairly high misconception that you can engineer human traits.

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So you can engineer hair color, eye color, perhaps skin color, creativity, creativity,

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athletic abilities, things like that.

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And the chances of doing that now are beyond possibilities because they are controlled by so

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many different genes that we don't understand.

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There's a built-in safety out there that even if

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we were to try to design children in the way that we prefer, or induce certain traits,

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it would be almost impossible.

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Yeah. Right now.

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Yeah. Right now. I think that what's happening is people see, when you begin, where does it go?

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And that's what we don't know, too, is like how far things go.

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It all starts with treating people who are not

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well and finding a solution for them, or maybe someone with a disability,

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like around hearing or sight.

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And then you create something like Siri for them, and then down the line,

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it's sold in Mac stores, right?

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So everything becomes luxury t hat was once for a need.

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Is there a technology that can detect cancer in an embryo?

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Can you look at that that early and say, hey, they're likely to have cancer?

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Let's gene edit, let's CRISPR?

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There are things called genetic panels.

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So unfortunately, there's not one specific test that can predict any form of cancer.

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We don't know yet.

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We don't have the algorithms yet to predict anything.

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So we're thinking we're going to get there.

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There's a tremendous amount of money and effort and research going into develop these software

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programs, and it's an area called bioinformatics.

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That being said,

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there are a few markers for breast cancer, for a certain percent of breast cancer,

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there's a gene called BRCA1.

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Oh yeah. You can test for that, right? You can test for that.

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And I think there's even a home test for that now, believe it or not.

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I have friends that have done that who've lost their moms to breast cancer.

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Right.

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So unfortunately, there isn't a lot of treatment

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that's been better, although surgeons would say, no, we're better.

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And that could be true.

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But it's about diagnosing it early.

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And breast cancer, prostate cancer, are two types of cancer that can be seen early.

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So really the two effective things are early diagnosis, and then the other thing,

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of course, is surgery.

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Cancer is energy-draining.

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Your energy just leaves and your cells can't support you and you pass on from

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that very wasting kind of disease.

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It's very hard to watch.

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Is your biggest dream and goal with CRISPR

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and many other different treatments to eliminate this completely, or is it just

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What are your biggest dreams around CRISPR?

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The first level is to make standard of care therapies work better

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What we learn from those patients will eventually draw into preventing it or even reversing it.

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So we try to be as realistic as possible because the folks ahead of us who were pioneers in some

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ways actually went a little bit too quickly.

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So I think that's the right way to approach this right now.

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Same with genetic disease.

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That's so tough because you want to help, you want to do some good and change the world and...

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Nuance, you know what I'm saying?

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Add gray to everything you're doing,

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and I think you'll always find a better outcome.

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Trying to do things absolutely just kind of backfires.

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I've always wanted to ask someone like you this kind of question,

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what is your day-to-day like with this?

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Do you have a lot of big picture questions all the time, or do you sort of find a way

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to compartmentalize doing this kind of work?

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Yeah, I think both.

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We always have our eye on the goal line.

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We definitely feel that we can contribute something, but at the same time,

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we're sort of humbled by the challenge.

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A lot of really smart people have come before us

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where there were very few original ideas actually in science.

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Putting them in different compartments,

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for me is really sort of thinking about them in a different angle, different dimension.

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And this doesn't stop at 05:00.

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There are people in the Institute lab at all hours of the night.

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Over Thanksgiving,

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half of the lab was in there in the afternoon on Thanksgiving day

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and the other half on Friday morning.

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Because if you're drawn to this kind of work, you can't stop thinking.

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So one of the questions that we are constantly

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asking through this series is, not only what the science look like,

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but what do scientists look like?

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One of the minorities in science beyond the obvious ones -- and we need to do a lot

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better at that -- are actually women.

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Interestingly, in the field of gene editing and CRISPR biology,

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the majority of the young scientists are women.

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That may be linked to the fact that the 2020

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Nobel Prize in Chemistry was awarded to Jennifer Doudna

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and Emmannuelle Charpentier, two women.

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And for the first time,

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they shared the prize without a man

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standing on the podium with them.

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And I think we all said it's about time.

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One of the things we also do is we're really

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trying to get out into the communities to share gene editing

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as a breakthrough technology so that we have lots of color in the field.

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We're tending to

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bring breakthrough technologies to underserved communities

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by back-teaching them.

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Oh, this really works great...

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CRISPR and gene editing is a current technology.

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So let's work our way in there.

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And what we see when we do that with

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high school students in summer camps,

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they love to see women and women of color.

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And those are the people they want to talk to, not me.

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And that's very important.

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So the structure of the population

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of this field may help to change

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the rest of science in general. That's so dope.

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Great.

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Thank you so much for opening that up and giving

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us all this fresh information,

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because at the beginning, we were like what?

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We had no idea what to expect.

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What is "clustered regularly....?" We learned so much.

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It's been great.

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Thank you. All right. Take care.

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All right. So we just got a lot of information

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and things presented to us.

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Time to reflect.

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Well, that was really interesting.

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I have to admit,

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I came in a little nervous about what we were going to be talking about.

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So where are you now?

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Cautiously relieved.

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You?

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I really appreciated the presence of ethics. Right.

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And trying to be careful and also acknowledging

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there is some scary parts of it.

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But most people are focused

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on the early lifecycle, the embryos,

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and also at the end.

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I absolutely loved that.

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This is another cool example of how a technology

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that's developed to help people

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who are not well later becomes a luxury,

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potentially, down the line, in genetic modification.

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So we're starting off first with trying to heal or detect and manipulate

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early-onset signs of something particular,

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maybe even just in the embryo

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and adjusting the cells early on to prevent disease later on.

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Right. So that's something that we're

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That's what the doctor said.

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And then later it can become

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something that's a luxury tool. Right?

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And that's what people's biggest fears are.

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And I did love that he talked about

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regulation around designer babies

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and making a baby with a certain color eye and s certain

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ability to play tennis or something like that.

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He really knew.

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And he has very strong thoughts about that not being where this goes.

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And, you know, I came into the conversation a little pessimistic about

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cancer and other things that

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ail the human species and really kind of keeps people

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in unwell spaces, like, just sick sometimes.

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But some of the details that he gave left me optimistic.

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I'm like, maybe we can start to move towards

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an actual cure for cancer and an actual answer to these really

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hard-hitting diseases.

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Yeah.

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It sounds like molecular medicine

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and gene editing are much more multifaceted

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than we could have ever imagined.

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Yeah. Let's switch gears a moment.

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Okay, time for a Body of Knowledge segment.

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In this segment, we're going to discuss the topic

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of personalized health and genetics in an open-form discussion.

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We're going to be throwing ideas, asking questions

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with the chief bioscientist at the Franklin Institute,

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Dr. Jayatri Das.

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Welcome, Jayatri.

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Okay, so we are back with Jayatri,

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and we are talking about

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personalized health and genetics.

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What does that make you think of?

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I'm going to ask you guys a question.

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First is, like, when you think about

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your DNA and who you are, what connection

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do you see between them?

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I think of a long line of creative people, and I'm super-creative,

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and I can't turn it off.

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And sometimes I love that about myself.

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And other times I'm like,

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oh, my God, stop making everything into a song.

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But that's kind of my connection. I see a lot of creativity.

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I see a lot of pride.

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I love the fact that you thought really about thinking back about your family.

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It's not just about physical traits, right?

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What you end up is more about...

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Well, noses.

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My family has big noses. Big noses.

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What about you, Angelica?

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I did think physical.

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Okay, so I'm Italian, so I'm like...hairy.

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I look at all the photos, and I'm like, you guys are all hairy!

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Like, it's just the way it is, right?

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We're all hairy.

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And I think of heart stuff has come up in my family or

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like, my grandma did have brain cancer.

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So I do think of those things, but generally I love to look at my family,

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and I can just see how we all look similar.

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And I think part of why people love having kids, too, is to see this version of themselves,

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of their personal health and their genetics growing.

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I think that that's a fascinating part of human life and family.

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Well, I think the two elements that you each

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brought to that conversation kind of illustrate

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the power of why we want to take a more personalized approach

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to health and medicine.

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Because, Angelica,

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you're absolutely right that there is so much of the DNA that shapes our physical

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appearance and our health, but not entirely.

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If anybody ever told you that

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whether or not you can roll your tongue is based

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on your genetics, that's a myth.

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Wow. Have you ever heard of any of those?

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I haven't thought about it in that way, but yeah, right.

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Like, speech and capabilities.

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If your dad can play tennis, can you? Right.

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So a lot of those traits are much, much more complex

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than being able to boil it down

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to like, oh, you have a gene that tells you whether you can roll your tongue

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or you have a gene that makes you creative.

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That's not real.

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There are some diseases that are caused by single changes in DNA.

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Turns out earwax is also affected by a single gene.

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It's one of my favorite examples, whether your ear wax is wet or dry.

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Whoa.

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Wow.

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What are yours?

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It comes down to one gene?

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Yeah.

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What are yours?

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Is it wet? That was a weird question.

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Sorry.

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That's a little personal. Your ear wax, sorry.

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You know what? It's what I've seen.

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So it's part of my personalized health and genetics and me

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and my friends and family.

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That's fascinating.

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Wow.

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Right.

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And so where that level of genetics comes

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into play is thinking about whether medicine

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or some sort of behavioral treatment, whether your genetic background

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will respond to that.

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Right? Because all of our genes are different.

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And sometimes that background

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makes a difference in whether or not your body

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will respond to one medicine or another medicine.

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You mentioned some things that were not necessarily true, like rolling the Rs

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and being creative and so on and so forth.

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Are there some things that are actually understood to be passed along

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dynamic in genes?

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So, aside from a few diseases and then the earwax

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trait, most things are not only influenced by a whole number of different genes,

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but also very much from your environment.

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Right? And this kind of gets, Bey,

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at what you brought up,

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this being in a creative environment from a creative family.

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You see that helping you become a creative person as well.

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And so where we're looking now in terms of

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what's possible with health and genetics

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and things like

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that is thinking about what we know about

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how our genes and the environment actually

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Genes don't necessarily make up who you are,

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but they can be very important

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in thinking about how to design the most

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effective treatment for you.

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Right.

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My aunt went through this.

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She passed away from lung cancer several years ago.

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But part of her treatment was actually looking

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at the genetics of her cancer and thinking about,

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okay, which drugs are best suited for her specific cancer.

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And that's the power of medicine that we didn't have

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just a few decades ago.

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Yes.

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It feels like luxury. It does.

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It feels like luxury medicine, where

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we're going to look at you

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and we're going to help you -- not just, we're not going to just

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give you what works on most people.

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We're going to look at what's going on with you.

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And that's so important as we realize the genetic diversity among people.

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Right.

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That we can't just take these shortcuts like

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a social construct of race, for instance,

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to make those assumptions about

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what's going to work.

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That's so true.

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Okay, we're going to move into our Body

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of Knowledge auto-fill segment

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where we turn to the Internet

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to see what people are asking about personalized health and genetics.

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These are some of the most popular questions people are asking the Internet.

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So we're going to get into some of the questions that people have asked.

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"Is personalized healthcare legit?" Yeah, definitely, for sure.

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I think where that term...

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I think there's a reason that we're kind of moving

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from "personalized medicine" to "precision medicine"

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is to be a little bit more intentional

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about what personalized means,

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because I feel like it's not like somebody just monograms your medicine or something like that!

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Right?

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That would be cool.

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I would buy that.

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Is precision medicine the future of healthcare?

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There are some complexities around that question

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that we don't know the answer to yet, because some of it is very much in terms

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of the theory versus the practicality of it.

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If we could design everything to everybody's particular genome, how much

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of a difference would that make?

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I don't know that we know that yet.

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And there's also a question of how expensive is it, right?

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The realities of health care in the world that we live in?

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Definitely.

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It seems expensive.

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I hope everyone gets access to it eventually.

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Oh, this is a cool question, and I'm glad people are asking this:

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"is my DNA unique?" Well, are you an identical twin?

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I'm not. Are you guys?

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No, I am not.

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I don't know why I said it like that.

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You had to think about it for a minute.

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No, I am not an identical twin.

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Do identical twins have exact same DNA?

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So their DNA sequence is exactly the same when they're born.

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But what's cool is that even identical twins,

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they're not completely identical, right?

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And part of what we've learned over the last few

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decades is that there are ways that our genes are

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turned on and off in different ways that don't

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just depend on the actual sequence of letters.

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One of the simplest examples is that even though identical twins have the same genome,

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their fingerprints are different.

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Right. Wow.

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Because there are so many other factors, environmental factors that affect how

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those genes are turned off and on.

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Even different parts of the body can have genes turned off and on in different

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ways at different times.

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For most of us, our DNA is unique.

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But even among identical twins, there are differences in terms of how

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you go from your DNA to who you are.

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And I have a bit of a silly question, I guess.

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Does your DNA and genetics change as you grow

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in age and develop different experiences and travel

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and find a favorite color and eat some

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food and make a song and all these different things with your

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experiences? Does your DNA change?

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So, for a lot of those experiences, that's not going to affect your DNA.

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Is it changing your brain?

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Absolutely. Okay.

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But your body does accumulate mutations in your DNA just over time.

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Like every time your body makes a new copy of DNA,

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there's a possibility of making a mistake. Okay.

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And sometimes there are environmental factors, like the sun: UV rays can create mutations

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in your DNA that can lead to things like skin cancer.

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Okay.

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How often does your body make a new copy of DNA?

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Oh, man.

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All the time.

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I didn't know that. That's amazing.

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So it's constantly making new DNA?

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Yes. Fascinating.

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We think of ourselves as kind of like... Stagnant.

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Done?

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It's over! Yeah,

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you're making new,

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you're replacing your body's cells

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all the time and getting rid of all the dead ones.

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Wow. Fascinating.

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I love that.

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Oh, I love this question.

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Okay. "Are my genetics good?" Oof! There's another value question!

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They aight.

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If you have to ask, Bey, they might not be.

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No, I'm just kidding. If you're looking at the mirror and you're going, is this good?

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I think we all feel that way.

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There's some social pressure there.

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There is for sure.

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And the last one is,

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"is my DNA in a database?"

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So that's a really good question

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because a lot of people choose to put

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their DNA in a database.

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If you've gotten your 23andMe or Ancestry.com,

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then yeah, your DNA is in their database.

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Low-key, I feel like Angelica put that question in there.

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That's right up my alley! Right?

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Yeah.

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I will say, I didn't know when I did 23andMe.

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I didn't read the paperwork and know that it's now in a database.

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It's one of those things.

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I hate fine print.

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I will accept it, yes, it is fine print, but l ife ultimately goes on.

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Hi, this is Angelica Pasquini from So Curious.

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You know what?

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We love making this show, OK? But sometimes there are great bits.

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We just can't fit them into the episode.

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So we put together a bunch of great bonus content

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and you can find that available at beyond.fi.edu.

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Thanks so much, Jayatri, and thank you so much for tuning in

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to this episode of So Curious.

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This podcast is part of The Franklin Institute.

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The Franklin Institute is a science museum located in Philadelphia.

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The Franklin Institute's mission

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is to inspire a passion for learning about

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science and technology.

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For more information on everything about The Franklin Institute,

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visit fi.edu.

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This podcast is produced by Radio Kismet.

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Radio Kismet is Philadelphia's premier podcast

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network for businesses looking to develop

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their own branded podcast content.

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Check them out at radiokismet.com.

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There's a lot of people who make this podcast happen.

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Thanks to the producers Joy Montefusco and Jayatri Das.

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Our managing producer, Emily Charash.

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Our operations head, Christopher Plant.

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Our associate producer, Liliana Green.

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Our audio team, Christian Cedarlund, Goldie Bingley, Lauren DeLuca

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and Brad Florent.

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Our development Producer, Opeola Bukola.

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Our science Writer, Kira Bayette and our Graphic Designer Emma Sagar.