CRISPR technology could change the world. Essentially, CRISPR is a technique that allows scientists to make precision edits to any DNA, whether bacterial or human. The potential for this technology is huge: if scientists have the accuracy to replace just a few faulty genes, it might be possible to cure genetic disorders as serious as cystic fibrosis and Huntington's disease and as common as lactose intolerance and color-blindness. Dr. Sam Sternberg, CRISPR expert and protein-RNA biochemist, joins the Curiosity Podcast to explain the science, ethics, and future of this cutting-edge technology. Samuel H. Sternberg, PhD, will be starting his own research laboratory at Columbia University in early 2018, as an assistant professor in the Department of Biochemistry and Molecular Biophysics. Along with Jennifer Doudna, he is the co-author of A Crack in Creation, a popular science book about the discovery, development, and applications of CRISPR-Cas9 gene editing technology. Additional resources discussed: Samuel H. Sternberg, PhD official website "A Crack in Creation: Gene Editing and the Unthinkable Power to Control Evolution" "Gattaca" (1997 film starring Ethan Hawke and Uma Thurman) 'Three-parent baby' claim raises hopes — and ethical concerns (Nature) Genome-editing revolution: My whirlwind year with CRISPR (Jennifer Doudna's article in Nature) Useful Mutants, Bred With Radiation (New York Times) Sorry Hipsters, That Organic Kale Is a Genetically Modified Food (Smithsonian) Gene Editing Makes Cows Without Horns (Popular Science) Ben Mezrich's Woolly Mammoth Book Being Adapted Into Movie by Fox "Woolly: The True Story of the Quest to Revive One of History's Most Iconic Extinct Creatures" How to Extract DNA from a Strawberry (YouTube) 23andMe direct-to-consumer genetic testing Neutron-Star Collision Reveals Origin of Gold, Astronomers Say (Live Science) Astronomers Strike Gravitational Gold In Colliding Neutron Stars (NPR) Follow Curiosity Daily on your favorite podcast app to get smarter withCody Gough andAshley Hamer — for free! Still curious? Get exclusive science shows, nature documentaries, and more real-life entertainment on discovery+! Go to https://discoveryplus.com/curiosity to start your 7-day free trial. discovery+ is currently only available for US subscribers.
CRISPR technology could change the world. Essentially, CRISPR is a technique that allows scientists to make precision edits to any DNA, whether bacterial or human. The potential for this technology is huge: if scientists have the accuracy to replace just a few faulty genes, it might be possible to cure genetic disorders as serious as cystic fibrosis and Huntington's disease and as common as lactose intolerance and color-blindness. Dr. Sam Sternberg, CRISPR expert and protein-RNA biochemist, joins the Curiosity Podcast to explain the science, ethics, and future of this cutting-edge technology.
Samuel H. Sternberg, PhD, will be starting his own research laboratory at Columbia University in early 2018, as an assistant professor in the Department of Biochemistry and Molecular Biophysics. Along with Jennifer Doudna, he is the co-author of A Crack in Creation, a popular science book about the discovery, development, and applications of CRISPR-Cas9 gene editing technology.
Additional resources discussed:
Follow Curiosity Daily on your favorite podcast app to get smarter with Cody Gough and Ashley Hamer — for free! Still curious? Get exclusive science shows, nature documentaries, and more real-life entertainment on discovery+! Go to https://discoveryplus.com/curiosity to start your 7-day free trial. discovery+ is currently only available for US subscribers.
Full episode transcript here: https://curiosity-daily-4e53644e.simplecast.com/episodes/customizing-the-human-race-with-crispr-cas9-genome-editing-technology
CODY GOUGH: Hi. I'm Cody Gough with the award winning curiosity.com, and today we're going to talk about the future of the human race.
ASHLEY HAMER: I'm Ashley Hamer and yes, today's topic really is that big of a deal. What if you could customize your children, pick their eye and hair color, or eliminate genetic diseases.
CODY GOUGH: Or what if you could rewrite DNA to improve intelligence or athletic ability both in humans and in animals.
ASHLEY HAMER: Science fiction is becoming reality thanks to a technique called CRISPR-Cas9, and today we'll talk to a leading expert about what's next for that cutting edge science.
CODY GOUGH: Every week we explore what we don't know because curiosity makes you smarter.
ASHLEY HAMER: This is the curiosity podcast.
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CODY GOUGH: Today we're going to talk with Dr. Sam Sternberg, an assistant professor in the biochemistry and molecular biophysics department at Columbia University. And we're going to be talking about CRISPR-Cas9 technology, which is one of his specialties. But before we dive into today's interview, I was hoping that Ashley could help us understand a little bit about what CRISPR-Cas9 is to set the stage.
ASHLEY HAMER: Yeah, it's really exciting stuff but it's also really complex. So CRISPR is a technique for editing DNA, which is the blueprint behind every cell in your body. When you can edit DNA you can potentially change anything about an organism, whether that's making a potato healthier or reducing an embryo's risk of genetic diseases, or even fighting cancer in a living human.
CODY GOUGH: So when you edit DNA does that edit every cell in your body's DNA, or just certain cells?
ASHLEY HAMER: So that depends on what you're doing it to. If you do it to an embryo, you can potentially change every single cell in that embryo's body. But you can also do it on living humans and that will only change the certain cells you affect. And we don't know whether those get passed on to offspring.
CODY GOUGH: OK. Because when an embryo is developing it's growing lots and lots of cells. So if you edit some of those original cells, potentially, when it's dividing all these cells, they're dividing in the same way as that modified cell. And so, let's say, you edit a gene that is supposed to pass down a chronic illness. Supposedly, hypothetically, when the embryo is multiplying its cells, all of those cells are now multiplying based off of that edited gene where they have fixed the chronic illness. And that means that when the baby is done producing all these genes, that chronic illness will no longer be there.
ASHLEY HAMER: Yes. And that is called editing the germline, I believe, and that is one way that CRISPR can change the scope of human existence.
CODY GOUGH: Kind of a big deal.
ASHLEY HAMER: Yes, yes. A very big deal. So that's what it can do. Now, let me tell you how it does that. And to explain that, I'm going to talk a little bit about a bacteria's immune system. And I promise that it'll make sense in a second. So when a virus attacks a bacterial cell, it injects that cell with its DNA. If the bacteria didn't have an immune system that DNA would take over and just kill the cell. But it does have an immune system, and here's how that works. When that viral DNA invades, the cell sends out special CAS proteins, and those break apart that DNA, copy it into the bacteria's own DNA.
So that the next time the virus attacks, those CAS proteins can use the DNA that it saved to create a custom weapon called CRISPR RNA and that will fight it more effectively.
CODY GOUGH: So you've got a cell, a virus comes in. The cell is like, yo, I'm not having any of that. The cell kind of copies the virus in a way, but modifies it so that it's not damaging that cell, and then they kind of push it out, right?
ASHLEY HAMER: Yeah. It basically takes a token of that virus that invaded and it's like, I'm saving this. I'm going to remember you, and it puts it into its own DNA for safekeeping.
CODY GOUGH: So kind of like if you're playing Megaman and you beat Cut Man, for example, you've beaten that boss and then you get Cut Man's power. So then you can use Cut Man's scissor weapon, but you're still Megaman.
ASHLEY HAMER: Totally like that. Yes.
CODY GOUGH: So basically, this is Megaman on a genetic level. I really hope our listeners have played one of the Megaman games because they're really fun.
ASHLEY HAMER: I haven't, but I'm still following along. So that whole thing that is happening in a bacterial cell, we've figured out how to do in any cell. So we can use that CRISPR-Cas9 system in any DNA. Cas9 by the way, that's just-- I said CAS protein, but Cas9 is just one type of CAS protein, and you'll learn more about that in the interview. But you can tell a Cas9 protein to remove a snippet of whatever DNA you don't want, then either leave it out completely or replace it with whatever snippet of DNA you do want.
CODY GOUGH: That makes a lot of sense. So rather than just cells curing diseases, you could have a cell change your eye color or change your height, or how much you grow hair, things like that?
ASHLEY HAMER: Yeah. Potentially. If we know that there's a gene for it we could potentially change that gene.
CODY GOUGH: There's genes for a lot of things. So that seems like there's a lot of implications there.
ASHLEY HAMER: Absolutely. So that's CRISPR-Cas9. Hopefully you understand a little bit more about it. Dr. Sternberg will explain all of the cool stuff that he's doing with it.
CODY GOUGH: Yeah. He'll be able to cover it all in this conversation, but this is such an advanced, really cool technology that we-- this is the first time we've done this. We've had to have a primer where Ashley actually sits me down and says, OK, here's overall what this is all about. But I was able to follow what Dr. Sternberg was saying during our conversation, even without an intimate understanding of the technology. But hopefully, this is helpful in helping you understand a little bit more of the context before we dive in.
ASHLEY HAMER: Totally.
CODY GOUGH: I'm here with Dr. Sam Sternberg and you work on CRISPR-Cas9. And I have to tell you this quote from my coworker. So I was talking to Ashley Hamer, and I said, I'm going to interview Dr. Sternberg. Did you have any suggestions for questions or anything? And she said, just keep in mind quote, "it's one of the biggest things to hit science in like forever. This is E=MC squared-level." Unquote. So do you think that's about right?
DR. SAM STERNBERG: Yeah. I mean, of course, I'm biased so I have to talk it up. I did recently walk back someone who had described it as the biggest breakthrough in all of humankind. So I wouldn't go that far, but I think in the last couple of decades in biotech it's really transforming how almost all biologists do science right now. And there's definitely the dream of tackling disease in a whole new way with CRISPR. We haven't gotten there yet. There's still going to be a lot of research and development that we need to do. But I think the dream is there. And now we have a really powerful tool to begin thinking about tackling disease at the level of DNA in a way that really wasn't possible before.
CODY GOUGH: So high level, what is CRISPR-Cas9?
DR. SAM STERNBERG: Well, the analogy that is used often is a pair of molecular scissors. It's basically a way to target and modify particular DNA sequences inside of cells. So the CRISPR-Cas9 enzyme itself is actually just cutting the DNA, but you can do that in a way where can bias the way that cut DNA gets repaired to install new sequences. But what's special about CRISPR is it gives you a very powerful and easy way to target any sequence you'd like in the context of a 3 billion letter human genome.
Previously, people have done gene therapy where you might randomly splice healthy genes into the genome. You have no control over where they go, how much they get expressed, what dosage they get expressed at. With CRISPR you have much finer control because you can really target precise genes, precise sequences at the single letter resolution.
CODY GOUGH: So you mentioned being able to kind of heal in the way that we want. So you cut out a little bit in the middle and then you tell the genes, right, heal in this particular way. Kind of like how a surgeon will make an incision and then stitch it in such a way so that the wound heals in a particular way?
DR. SAM STERNBERG: Yeah. I think in the book we use an analogy. I wrote this book with my PhD advisor, Jennifer Doudna.
CODY GOUGH: What was the book called? We should have mentioned that earlier.
DR. SAM STERNBERG: "A Crack In Creation."
CODY GOUGH: "A Crack In Creation." Actually, the full title-- "A Crack In Creation-- Gene Editing and the Unthinkable Power to Control Evolution."
DR. SAM STERNBERG: Yeah. I think in the book we use an analogy, old-- I guess-- film play editors would kind of cut reels and paste them back together in different ways if you want to splice out a couple of frames of a scene. So you're cutting the DNA as a way to stimulate the repair, and then you can basically coax the cell into stitching the two ends of the DNA back together in a way that changes that sequence in a particular fashion. The other analogy that I often use is like find and replace.
So the same way that in the word processing document, you might put in a search term, a replace term, and then through programming you can basically find any iteration of that search term anywhere in a document and replace it with anything you'd like. CRISPR is allowing you do the same thing with a genome, and you can do it across a 3 billion letter genome. No problem.
CODY GOUGH: And when you're talking about the genome you're talking about that, ACGT. What are those called? Nucleotides?
DR. SAM STERNBERG: Or bases. Bases is an easier term that gets used more often, but both work.
CODY GOUGH: Sure. For those bases. And you mentioned they're billions of characters long, right? How do you identify which one you want to clip out of there?
DR. SAM STERNBERG: Well, in terms of what change you'd like to make I mean, that depends on are you targeting some disease-associated mutation, or maybe some gene involved in the plant's ability to grow in extreme weather conditions. But how you do the targeting, that's why CRISPR was such a revolutionary development for gene editing. Gene editing existed well before CRISPR came along, but it was very hard to design protein molecules to target particular sequences within that vast expanse of the genome. Because how do you find the right letter in 3 billion letters, right?
CRISPR gives you a way to do that targeting with much more ease than was ever possible because the key molecule is RNA. So RNA stands for ribonucleic acid. It's kind of like DNA's molecular cousin. It's also made up of the same kinds of bases. So just like a DNA double helix is held together with base pairs, RNA and DNA can form base pairs to form an RNA DNA double helix. And because they form base pairs the same way that DNA does, it's as easy as saying, here's the 20-letter DNA sequence I want to target. You make an RNA sequence with the same matching 20 letters, and there are your GPS coordinates to tell that Cas9 protein how to find its match.
CODY GOUGH: So Cas9 refers to the protein?
DR. SAM STERNBERG: Exactly. So the two components you need are the protein, Cas9, and a molecule of ribonucleic acid. And I should say even within CRISPR, I mean, one of the exciting things that I'll be tackling in my lab is-- Cas9 is just one of the kinds of proteins that we can harness for gene editing. There are actually others. They have different names. Most of them are Cas with a number. So now, there's Cas13, Cas12.
CODY GOUGH: What is the Cas stand for?
DR. SAM STERNBERG: CRISPR-associated.
CODY GOUGH: Oh, and what does CRISPR stand for?
DR. SAM STERNBERG: CRISPR stands for Clustered Regularly Interspaced Short Palindromic Repeats.
CODY GOUGH: Oh, well, there you go.
DR. SAM STERNBERG: There you go. Now you know everything about it, right? Just from that acronym.
CODY GOUGH: Yeah. You should have just said that at the start. We'd be perfectly clear. And you said palindromic. That means-- I mean, I know what palindromic means, but how does that apply in this?
DR. SAM STERNBERG: For the gene editing use, it's honestly pretty much not relevant. But in terms of the discovery behind CRISPR, it's a property of these DNA sequences that are what makes a CRISPR a CRISPR. They tend to be slightly palindromic in that you can read one strand in one direction, or the other strand in the other direction and they are the same sequence kind of read backwards.
ASHLEY HAMER: Remember how I said that a bacterial cell breaks apart attacking viral DNA, and copies it into its own genome? It stores that DNA in a special area separated by short segments of other genes that are arranged in palindromes, the same sequence forward as they are backward. Imagine the name, Hannah. Except instead of H-A-N-N-A-H, the letters are some combination of ATCG.
And instead of six letters, you've got 20 to 40. That's how CRISPR got its name. Like Dr. Sternberg said, CRISPR stands for Clustered Regularly Interspaced Short Palindromic Repeats. Because that bacterial immune system is made up of snippets of viral DNA, regularly spaced out by repeating palindromic snippets of bacterial DNA. Got it? I hope so.
CODY GOUGH: So we'll zoom out a second from the science and talk about the practical applications of this. The reason that you want to edit these genes and clip out something is because you're trying to clip out diseases, right.
DR. SAM STERNBERG: I'd say, I mean, certainly in the realm of human therapeutics, that's where you would use CRISPR, but the power to rewrite DNA-- I mean, it pervades so many different fields because every living organism on the planet uses DNA as its code. And so if you want to talk about agricultural improvements, having a way to fine tune DNA sequences is very powerful. Wanting to understand how biology operates-- I mean, there were a couple of papers recently that got covered in the New York Times where they used CRISPR in butterflies to understand the genetics behind wing coloration.
That's the kind of question that may not have practical applications right now, but if you're a biologist and you study winged coloration, what you'd love to do is have a tool where you can change genes that you think might be involved, and see if the coloration is affected. Previously, you'd have no way to do that, so you might try to go find a unique species that has different coloration patterns. You can do DNA sequencing, compare it to different species of butterflies, and see maybe there's a correlation between this gene and how the coloration looks.
But with CRISPR you can do a very focused experiment where you take the gene you think is involved, you edit it, and modify it in some way. Maybe you're turning it off, maybe you're turning it back on, or turning it up or down. And now, you let the animal grow and develop and see what was the consequence of this one letter change that you made to the gene.
That's the power of gene editing from a basic research perspective is you can do the kinds of experiments that biologists have dreamed about doing for a long time. And now with CRISPR, you can do these experiments seamlessly in the lab.
CODY GOUGH: Now, when you talk about applying these to living beings, is this where some of the ethics comes into play with-- I mean, you're kind of playing with living subjects typically for this kind of experimentation, right?
DR. SAM STERNBERG: Yeah. I mean, you're editing living cells. Those could be cultured human cells in the laboratory that are manipulated every day anyway as a kind of a research model system. That might be a mouse embryo where you want to do mass genetics using CRISPR to make the same kinds of changes to understand, maybe certain pathways in mice to understand how they might operate similarly in humans, or maybe you're introducing a disease-causing mutation in mice, so that you can have a better model to study that disease progressioning.
But yeah, the ethics-- I mean, I think that comes into play when you talk about applying CRISPR to humans and especially humans very early in development. So one of the biggest controversies right now with CRISPR is whether or not it should be used early in development, such as in the embryo, to install permanent changes that would affect not only the individual that develops from that embryo, but also all of their future offspring because those changes would be passed on through the generations.
CODY GOUGH: They would be passed on through the generations.
DR. SAM STERNBERG: Well, if that individual had children. But I mean, if you modify an embryo, think about, you start with one cell that will end up dividing trillions of times to form all of the cells of the growing fetus, and the baby, and the child, including that eventual adult's own germ cells, sperm or eggs. And so by making changes that early in development you're making changes that would be passed on every time that individual reproduces. That's different than, let's say, you have a patient living with a disease, an adult patient. And you might edit their blood cells.
If they have a disease like sickle cell, that could cure the disease, but because you're only editing a subset of that patient's cells, those cells that are affected by the disease-- you're curing the disease, but it's not going to be passed on. So they would still propagate the same genes through their germ cells, sperm or eggs as they started with before the CRISPR treatment.
And so in the scientific community we talk about the difference between somatic gene editing-- editing body cells that are, of course, important in our bodies, but they don't reproduce the organism. So muscle cells, heart cells, skin cells versus germ cells like sperm, eggs, embryonic stem cells. Cells that can pass on their genetic information to future offspring during reproduction.
CODY GOUGH: The somatic treatment that you mentioned that can correct something in a living adult person, maybe fix your eyesight or something like that. That seems probably pretty not that controversial. It's just like another medical treatment. But if I've got a history-- if there's a family with a history of, pick your genetic disease, diabetes, or whatever it is, and given the chance to go into the embryo of somebody who's-- all of their relatives have had to suffer through this thing in their lives and then you've got it in the embryo. Well, you can correct that. What's the argument against that?
DR. SAM STERNBERG: I think some of the things that I talk about, I was just visiting with students this morning and how accessible would that kind of a treatment be? I mean, right now that doesn't exist. If it becomes possible it will probably only be available for people that have the money to spend on in vitro fertilization with this add on feature of CRISPR based-gene editing. And already I mean, IVF is not offered unless you have $10,000 or $20,000 to spare. Insurance usually doesn't cover it.
So I think when you start talking about changing the permanent genetic composition of a human and his or her offspring, those issues of access start to feel a bit more important because those are lasting changes and you could imagine that you go 10, 20, 50, 100, 1,000 years down the road, and you're going to have individuals that have had their genes edited, or their forefathers genes were edited and those that weren't.
CODY GOUGH: That make sense. And that's going to exacerbate any class differences with people. All the people with the money now are also all the healthiest people and then the people with less money are now the ones with the diseases and everything, which has kind of a gene reaction. So that actually is a pretty valid argument, I think.
DR. SAM STERNBERG: Yeah. I mean, I think that's kind of one of the concerns if you zoom out. Now, I would agree. I mean, I think in terms of what medical treatments should or should not be used, ultimately it should be a risk benefit analysis. And I think the same thing is true of a tool like CRISPR. And people that say it's not natural to change our DNA. I mean, I think there are a lot of medical breakthroughs that aren't really natural. I mean, a heart transplant certainly isn't natural, but if it saves someone's life I think, and it's safe, and it's proven to be effective-- then why shouldn't we do that? And I think editing DNA is no different in that regard. But there are other issues that are true for other medicines that need to be considered, like access, and inequality, and things like that.
CODY GOUGH: And your lab is going to be set up at Columbia University. So where does the US fall and how does the international community address this is? It a pretty tight international community of research, or does it-- is there a huge amount of disparity based on the policies of certain governments?
DR. SAM STERNBERG: I think there are certainly some differences. Some countries it would be illegal to edit genes or edit DNA in embryos, and use those embryos to establish pregnancies. The US is not one of them. There's actually no prohibition legally against that, but the FDA would be regulating any use of gene editing in that way. And so you'd have to go through an FDA approval process. So in that sense it wouldn't be allowed currently. And there are other countries that have similar situations where there might be kind of loose regulations surrounding it, but not hard legal prohibition.
China's a country that's been kind of at the forefront of doing some of the early experiments testing CRISPR and embryos. The first three research articles came out of China. None of them used embryos that were established for pregnancies, but the most recent paper that just came out, actually two papers came out. One was from the UK and one was from a research group in Oregon. And so I think this research is happening in a lot of different places and we'd like to have international consensus on how to proceed.
But I think the reality is, different cultures, different value systems in other parts of the world may be different than how it goes in the US. And part of the challenge is coming to some kind of agreement and preventing what one could imagine happening, which is, something's not allowed here, but it's allowed somewhere else. And so consumers or parents and physicians go to other jurisdictions to access those treatments.
And exactly that happened with an assisted reproductive technology very recently where a physician from New York conducted a procedure known as mitochondrial replacement therapy. We don't have to go into the details. But the point is, it wouldn't have been allowed to do it in the US, and so he flew the mother to Mexico and that was where the embryo implantation occurred.
CODY GOUGH: And was it successful?
DR. SAM STERNBERG: I think it was.
ASHLEY HAMER: It was. The baby boy was born in April 2016 in Guadalajara, Mexico. You might remember when this was in the News. All of the headlines called it the first three-parent baby. That's because mitochondrial replacement therapy involves putting the nucleus of an egg from a mother with a mitochondrial disorder, in this case, it was Leigh syndrome, into a healthy donor's egg with the nucleus removed. Then fertilizing it with a father's sperm.
DR. SAM STERNBERG: And you know, it wasn't so experimental that it was unsafe to do this. The same kinds of treatments have been approved for clinical trials in the UK. But just the fact that if you have regulations surrounding something, it's not going to necessarily stop people from going elsewhere to access them.
CODY GOUGH: Yeah. People are already doing that.
DR. SAM STERNBERG: Exactly.
CODY GOUGH: Crossing borders to get certain treatments or--
DR. SAM STERNBERG: Stem cell tourism is definitely a problem, and I think the concern about having overly restrictive regulations in the US is that are people going to just go elsewhere. Of course, that's also not an argument to say let's do everything here.
CODY GOUGH: Yeah. Of course, yeah. Everybody's got to decide what's best for them, and I mean getting the international community to agree on anything is difficult. So talking about something with scientific and potentially ethical implications, religious implications, whatever people believe is really complicated. Now, you're a scientist. You're doing all the research on all this stuff, but because it's such a cutting edge technology you've also got to worry about all the policy involved and all of these things. I mean, how do you balance working on all that stuff?
DR. SAM STERNBERG: Well, I'd say the policy and regulatory side of things doesn't really impact my day to day research. But as I was researching and writing the book, one thing that Jennifer has I think done an incredible job of--
ASHLEY HAMER: The Jennifer that Dr. Sternberg is talking about is none other than Jennifer Doudna, his PhD advisor, and one of the two women who first demonstrated that CRISPR-Cas9 could be used to edit DNA. Hashtag women in science, hashtag lady boss, hashtag Nobel Prize. Doudna and Emmanuelle Charpentier published their groundbreaking paper in the Journal Science in August of 2012. In an article for nature, Doudna recounted that one colleague called her up a few months later to say, I hope you're sitting down because it's unbelievable how well it's working. It usually takes a new molecular tool like this several years to gain traction, but in the next four months at least six more papers were published describing different ways science could use CRISPR-Cas9 to engineer DNA. When it came to instant popularity, CRISPR was basically the fidget spinner of the biology world.
DR. SAM STERNBERG: One thing that Jennifer has done an incredible job of is getting outside of our comfort zone, which tends to be the research laboratory, scientific conferences where you're with your fellow scientists that think about the research side of things and not always the kind of big picture and real world applications and implications. And she was one of the leading voices in bringing this controversy over editing the human germline, these making edits in a heritable way, bringing that to the public's attention. I was present at a small bioethics meeting that was one of the first to discuss this back in 2015.
In Napa Valley we ended up publishing a white paper on gene editing that we published in Science. And then at the end of that year was an international meeting that brought together representatives from the UK, China, and all around the world to actually just start discussing some of these issues. So my day to day research is so far removed from that, but I think Jennifer provides a really good example for how as scientists we can't live inside our bubble. We need to be thinking about how our work makes impacts on other parts of the world and other parts of society, and start that conversation if no one else is.
CODY GOUGH: Yeah. It seems so straightforward at first glance. Let's develop a technology that can save people. Great, that's fantastic let's do it, but then yeah as you said, the domino effect is pretty intense. Where is your research focused right now or where is this mostly being applied? Are there particular diseases, or conditions, or is it just all over the place right now?
DR. SAM STERNBERG: So there's a couple of companies going after some of the more common monogenic genetic diseases. These are diseases where there's a single gene mutation that's known to cause the disease. Some examples would be sickle cell, cystic fibrosis, muscular dystrophy, and there are three main companies that are developing CRISPR-based therapeutics, and there are others that are using gene editing with different kinds of technologies. I think the one area that we might see progress the fastest is in an area of cancer treatment, known as cancer immunology therapy. This is a type of treatment that uses the body's immune system to try to fight and kill cancer cells.
And so CRISPR is now being combined with immunotherapy to essentially edit immune cells to make them either more effective at recognizing cancer, or proliferate longer, or work when they're transplanted from a different donor. So I think cancer treatment is-- and actually, the first clinical trials in China have already begun using CRISPR modified immune cells. And recently, although this didn't use gene editing. The first gene therapy product was approved by the FDA to treat cancer using genetically modified immune cells. So I think that's an area where there's been very rapid development and where CRISPR is going to be a critical tool to kind of bring these treatments forward.
CODY GOUGH: And it was successfully utilized, I think, in some kind of eye treatment with some adolescents recently. The FDA approved that and some kids are getting-- basically, kids are getting their eyesight back, right?
DR. SAM STERNBERG: That wasn't with CRISPR. There are certain congenital forms of blindness that are also being pursued. This was a different gene therapy drug that you're speaking of, but I think these things are very related. And one of the exciting things is conventional gene therapy is adding genes kind of randomly. I mean, just getting an entire healthy gene to the cells of interest. And there's a chance that with CRISPR we can do that, but in an even more accurate and kind of safe way. And so I think hopefully we'll see down the road the same kinds of treatments but using gene editing.
CODY GOUGH: And you're talking about treatments, and so far we've talked about treatments. But for every breakthrough like this there are people who are focused on treatments and correcting problems. And then there are people who are maybe looking towards augmentation. Is that occurring yet and are governments going after trying to create superhumans and super soldiers yet, or is that really a minority.
DR. SAM STERNBERG: I don't know of anyone actually going after that. Certainly, not government funded. I think this is an issue that comes up, I mean, I just gave some questions to the students I was with earlier today. Would you use CRISPR for removing the mutations that cause Huntington's disease. Almost all of them raise their hand. What about introducing mutation that lowers the risk of heart disease. So maybe half of the people that raised their hand for the Huntington's and then the last example was a mutation that's associated with greater intelligence. And then very few people thought we should be doing that. So that last example, that seems like a clear type of enhancement mutation. But the middle case, reducing your risk of heart disease, that might fall into the bucket of disease prevention. Something that seems less ethically fraught, but at the same time it's actually enhancing your genome above it's starting point by adding any mutation that's associated with some improved condition. So the point is it's a spectrum. I think there are some things that are obviously just preventing disease, and it seems like we should be going after those. Some things that are clearly only aimed at maybe you're more obvious types of enhancements, like intelligence or greater muscle strength. But there are a lot of things in the middle that fall into this gray area where-- I think that's a question what should be permissible and what shouldn't.
CODY GOUGH: I'm reminded of-- and we talked a little bit before we started recording about the movie Gattaca, which is a fantastic movie with Ethan Hawke and Uma Thurman. But that really pretty much describes exactly what kind of a dystopian future we can end up with. How far are we from even being able to do something on that scale where you go to the doctor and you kind of shop and you pick from a list. I want this gene and this gene, and I don't want this gene and this gene. I want to say very far but I mean, one thing that's growing in use is something called preimplantation genetic diagnosis. Where parents that are using in vitro fertilization for conception can have physicians fertilize multiple egg cells and then do some kind of diagnostic sequencing, or chromosomal analysis on multiple embryos to select one that might not have one of the mutations that those two parents could give to their offspring. So it's already possible to avoid certain mutations through PGD. That's not the same as saying, let's use CRISPR to put something in that neither parent started with in the first place. But we already have the capability to select certain genetic states of future individuals using IVF combined with this pre-implantation genetic diagnosis technique.
CODY GOUGH: And that I think is exactly the way he says it in Gattaca. He says we're not necessarily, we're not giving him new genes. We're just choosing Your best what was there to begin with.
The best of what was there.
DR. SAM STERNBERG: I've actually played that clip in some of my talks so, I almost have it memorized but--
ASHLEY HAMER: In the beginning of the movie when the main character, Vincent is a toddler, his parents go to a genetics clinic to select the traits they want in their next child. Here's the clip he's talking about.
AUDIO PLAYBACK: I've taking the liberty of eradicating any potentially prejudicial conditions-- premature baldness, myopia, alcoholism and addictive susceptibility, propensity for violence, obesity et cetera.
- We didn't want-- I mean diseases, yes. but
- Right we were just wondering if it's good to just leave a few things to chance.
- You want to give your child the best possible start. Believe me, we have enough imperfection built in already. Your child doesn't need any additional burdens. And keep in mind this child is still you, simply the best of you . You could conceive naturally 1,000 times and never get such a result.
DR. SAM STERNBERG: At the same time, other things that he's talking about when he lists the conditions that he's chosen for the future child are no diabetes, no alcoholism. And those are things that are definitely not simple genetic conditions where there's one gene that either causes it or doesn't cause it. Most of those kinds of traits or characteristics are either largely influenced by environment and upbringing and/or are polygenic. Meaning, are many, many genes involved. In some cases we know some of them. In some cases, we might know very few of them, but usually there's thousands or tens of thousands of mutations, each of which plays a tiny, tiny role in that trait. And so thinking about using gene editing to kind of select for no diabetes at this point is still way in the realm of science fiction, and I think is going to stay there for many things for a very, very long time. Some things will probably never be something you can select for because we just don't know. We don't know enough about the genome to understand what you would even choose.
CODY GOUGH: We're far enough along to where you can go in front of a high school class. It was high school students you spoke with this morning, and talk to them about the ethical implications of gene therapy. I mean, this is not a thing that I would have imagined doing in elementary or middle school growing up.
DR. SAM STERNBERG: Oh, I don't think I knew a thing about DNA when I was in high school. I mean, I learned all of that stuff in college. But I think increasingly with things like 23andMe and other companies that will sequence parts of your genome or analyze your genome and tell you what that means for you-- I mean, I think increasingly we're going to have to be thinking about the role of genetics in our life, I think more than maybe 20 years ago.
CODY GOUGH: Yeah what else did you talk to them about that we haven't covered?
DR. SAM STERNBERG: Well, we didn't actually get much into this, but one of the things that I think is equally important is the use of CRISPR in non-humans. So I think a lot of agricultural companies are going to very aggressively be using CRISPR for editing crops or editing livestock, either to provide benefits for farmers in terms of how they grow, or maybe being less reliant on certain pesticides. Or also developing crops that might have traits that consumers will desire. So there's a case of a mushroom that was edited with CRISPR to be less-- that it doesn't brown. So you can imagine mushrooms that can sit in your pantry for weeks and they're never going to go brown. Or you can imagine, there's a couple of products that they're not commercialized yet, but there's a soybean that has a more favorable fat content, the soybean oil. There is a potato that has lower levels of a neurotoxin when it gets fried. And these were edited, and not with CRISPR in this case, with a different kind of gene editing tool. But I think in the world of food production there could be very major influences from CRISPR and gene editing.
CODY GOUGH: Yeah. Is this what Monsanto does?
DR. SAM STERNBERG: I mean, they're one of the players, but DuPont PIONEER is another player, Cellectis I mean, they're-- or Calyxt, I guess, is a subsidiary of Cellectis. And I think there's some excitement that unlike some of the tools that we use to make genetically modified foods, with a tool like CRISPR that's much easier to harness. It's not going to only live with these few big seed producers, but it's going to be something that's more available to more breeders and more farmers.
CODY GOUGH: But this is the technology that we're talking about when people refer to GMOs?
DR. SAM STERNBERG: Well, it gets a little confusing. It depends a little bit on what definitions you're using. So some people when they talk about a GMO, they mean a food that has had a foreign gene spliced somewhere into the genome. And most GMOs to date have been transgenic. Meaning, they have a gene from some other organism integrated into the genome. So like BT cotton, for example is transgenic. Gene edited crops might not have any scar of the gene editing it might be a mutation that is no different than the kind of mutation that could have occurred through nature, through natural evolution. So it's actually causing some problems for regulators how these new kinds of gene edited crops would even be regulated. Do they fall under the GMO bucket? Do they need to be regulated as GMOs or not as GMOs? And I think some of that is actually still evolving.
ASHLEY HAMER: The issues regulators are having in deciding what counts as a GMO and what doesn't speaks to the strange ways we decide which scientific processes we deem safe and which we don't. When you use artificial selection to breed crops, you're letting nature roll the genetic dice and then choosing which plants have the traits you want. When you use genetic engineering, you choose which traits you want and insert the genes for that trait into future plants. The regulation conundrum comes down to whether those genes come from within the plant or from another organism. But the thing is, living things share a whole lot of DNA to begin with. You share 60% of your DNA with a banana, for instance, and while where a gene comes from important, there are other plant breeding techniques that a lot of people don't even know about that honestly sound a lot scarier. Take mutation breeding. That's where breeders bombard plants with radiation to trigger DNA mutations. And it's been going on for decades. That process has given rise to varieties of pears, wheat, rice, peanuts, the barley used in Scotch and beer and red grapefruit. Despite that mutation process, you can buy red grapefruit that's labeled organic. When you think about genetic modification, it's good to realize that we've been genetically modifying plants and animals for centuries. The big difference today is that people doing it wear lab coats.
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CODY GOUGH: Yeah. On average traditional interior designers charge something like $4,500 a room. And the packages with Heavenly start at just $79. Heavenly also recently launched a design quickie, which allows anybody to chat with a designer for free to get advice on any design-related questions.
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ASHLEY HAMER: What? Our podcast studio is beautiful. I don't know what you're talking about, Cody. I really like the weird cotton shower curtains that we have up.
CODY GOUGH: Those cotton shower curtains are very soundproof, thank you very much, but maybe we should go to heavenly.com/curiosity for a full $50 off a full design package with code curiosity. You mentioned non-humans, and I don't know if this sounds too silly, but my head immediately went to pets and domestic animals. I mean, certain domestic animals they're maybe really cute or really wonderful, but have a penchant for violence, perhaps. Or wanting your poodle to act more like a golden retriever, or having a Pomeranian that isn't constantly barking all the time. Things like that. Is there any of that going on yet?
DR. SAM STERNBERG: Yeah. Well, I actually was just at a biohacking conference in Oakland. And there was a panel discussion between a colleague of mine who's at Stanford and Greely and I forget this fellow's name, but he is a dog breeder and he's been lobbying to use CRISPR to treat genetic diseases in dogs. Part of the debate was how much the FDA should or shouldn't be involved in that. I think dogs is an interesting case too because people talk about if we use CRISPR in pets, I mean, isn't that wrong? Like we shouldn't be playing with their genetics. But if you look at dogs, I mean, there's nothing that natural about the full range of sizes, and types, and hair color, and hair length, and that all happened through a massive amount of genetic selection and aggressive breeding.
CODY GOUGH: Yeah. Dog breeders are-- that's a whole thing.
DR. SAM STERNBERG: So would it be that different to then add CRISPR into the mix? For a new kind of reading where you'd have a different layer of control, or ability to modify the genome. Right now we do it all the time by saying, well, only this purebred dog is going to mate with that other purebred dog. Now, you could add in CRISPR in and start selecting for new variants that maybe you couldn't access through traditional breeding. Another example I love talking about in the world of gene editing in animals-- there's a company called Recombinetics based in Minnesota. They are developing gene editing in livestock, and they have generated cattle that derived from parents that grow horns like most dairy cattle do. But these gene-edited cattle no longer have horns. They've literally used gene editing to create hornless cattle. So think about now gene editing giving you an ability to literally make a change to the genome that removes horns. I mean, that's-- talking about sci-fi, I mean, that's still unbelievable to me to think about.
ASHLEY HAMER: They didn't remove cattle horns to make them more stylish or aerodynamic or anything. They did it to make raising cattle more ethical. Each year in the US roughly 80% of dairy cattle and 25% of beef cattle get their horns removed, since horns tend to injure both people and other cows. But it's a bloody painful process, and it's sometimes done without any anesthesia. If you could breed cattle without horns it would make the whole situation a lot better. In 2016 scientists did just that.
CODY GOUGH: Yeah I mean, will we be able to create humans with wings, or anything like that in the future? I know it sounds a little crazy, but what were the limits?
DR. SAM STERNBERG: Yeah. I mean, I don't think I would say definitely no to the humans with wings. But I think the example with the cows does raise that question. I mean, nature has evolved a lot of interesting things in the more we learn about the genetics behind different kinds of traits and physical characteristics, the more you could imagine making use of that information and a technology to rewrite DNA to access things that don't already exist in our world today. Another example, there are scientists that are using gene editing to make changes in Asian elephant DNA that make the Asian elephant genome look more like the woolly mammoth genome. And there's a legitimate hope by reputable scientists that we might one day be able to resurrect something akin to a woolly mammoth using a tool like gene editing. That's actually research being done. There was just a book that came out, I think describing it, and apparently it's already been optioned for a movie. So people can go read about it if they want.
ASHLEY HAMER: The book is called "Woolly," the true story of the de-extinction of one of history's most iconic creatures by Ben Mezrich, and you can find a link in the show notes. Mezrich has already had two books adapted into films. Ever heard of a little movie called The Social Network?
CODY GOUGH: I think we actually also have an article on curiosity.com about that. And you mentioned that we've kind of covered most of the highlights of your talk in front of the high schoolers. Do you prefer talking to high school audience about these things?
DR. SAM STERNBERG: You know, I have to say driving up here that was exactly what I was thinking. It's almost more fun to work with students that are earlier in their education. Because well, first of all, as an educator thinking about how to bridge that divide and thinking about what does your audience come into the room with, and how can you describe the work you do or the implications of the work you do in language and in a context that will make sense to them and reach them. That's always fun for myself to prepare and then to see students perking up and getting interested in some of these ethical issues is actually very rewarding. A few weeks ago I did a demo with some sixth graders. I put together a 20 question DNA trivia and then we extracted DNA from strawberries afterwards. And it was so fun. I mean, it was, I have to say, way more fun than any laboratories I taught as a PhD student. So it's something that I definitely want to do more of. And I think, thinking about ways to make genetics come alive for young students is something that I hope to continue doing even when I'm a professor, and probably getting paid to teach graduate students instead.
CODY GOUGH: Yeah. How do you extract DNA from a strawberry?
DR. SAM STERNBERG: That's an ethanol precipitation. Basically, creating solution conditions where it's no longer soluble and it precipitates out of solution. It forms kind of a stringy goo. It's very simple. You can buy-- I mean, you need rubbing alcohol, some detergent, that's mostly it. Some salt, detergent, water, crushed up strawberries, and rubbing alcohol that's cold, and that's pretty much all you need. And you can kind of spoon it out with a skewer or a toothpick. The students love to take it home, so you can putting it up indoor too for them and that pretty much made their day. So I want to do the demo again. That's fun.
CODY GOUGH: And then put it under a microscope and--
DR. SAM STERNBERG: We didn't do that, but I mean, even having gone through this trivia experiment teaching about what is DNA, and then they literally have this stringy goo that's DNA from strawberries to take home with them. I think that's very powerful.
ASHLEY HAMER: Extracting DNA from a strawberry is a really popular and super easy way to learn about DNA. We'll include a how-to video in the show notes if you want to try doing it at home.
DR. SAM STERNBERG: And you can actually also do the experiment using a cheek swab where they're extracting DNA from their own sloughed off cheek cells. So maybe next time I'll do that because then you've literally got your own DNA sitting in a tube that you can look at and think about what it means.
CODY GOUGH: When you say-- I'm trying to visualize and I thought I had a good understanding of what DNA is coming into this, but I didn't realize it could be like a physical thing of it. What do you mean like when you say extracting the DNA like I mean, physically. It's like a goo? I thought DNA was like microscopic.
DR. SAM STERNBERG: In a cell you'd never be able to see it but from many, many cells-- I mean, taking three or four strawberries, there's billions, if not more cells in those strawberries. And so all the DNA combined. I mean, that's a tangible amount of material. We actually one of the trivia questions we did is, if you took all the DNA from your body and strung it together in one long string, where would it take you? And it would take you to the sun and back many times over. So obviously, you're making it in one long double helix, which the DNA in your body would never do. But just to give you a sense for 3 billion letters of DNA. Yes, it's microscopic. Yes. it's crammed inside of a nucleus inside of your cells, but there is a lot of it. And so if you extract it from strawberries from your cheek cells I mean, that's enough to see when it's precipitated in ethanol, for sure.
CODY GOUGH: Yeah, on an earlier episode of the Curiosity Podcast we talked to an expert on prosthetics and the human touch. And he talked about decoding neurons in the brain. And basically figuring out this neuron means this, this neuron means this. In terms of DNA and RNA, you know you're talking about the billions and billions of characters. How far along are we at an understanding what does what? Do we have a pretty good grasp on, let's say, this chunk means this disease or this chunk means this disease?
DR. SAM STERNBERG: From sequencing, for diseases that are monogenic that are caused by a single mutation or a disruption of a single gene, we've advanced pretty far to understanding those causes. I think there's something like 7,000 different genetic diseases whose cause has been identified.
CODY GOUGH: Wow.
DR. SAM STERNBERG: But again, coming back to this word polygenic. I mean, most traits you would think of are not going to be one mutation or one gene. There's no gene for happiness or gene for strength. These are a combination of many, many different influences. That being said, with the explosion in DNA sequencing in recent years we're starting to learn more about at least what gene variants are involved in some of those traits. So 23andMe is this company that will analyze your DNA and and they actually through the service get access to millions of users' DNA. And they published articles analyzing those DNA sequences combined with kind of surveys that they give their consumers about sleep patterns, or heart disease risk, or kind of familial history on certain things. And so they put out a paper I think last year some time on genetic variance associated with being a morning person. So that's not to say there is a gene for being a morning person, but through their study using advanced statistics they can deduce what genetic variants are associated with being a morning person. That doesn't mean I can make you a morning person. I wish I could be made a morning person, but it means that we at least understand some of the genetic influences.
CODY GOUGH: Is there anything we didn't cover? Anything you wanted to add about any of your work, or--
DR. SAM STERNBERG: Well, yeah. I mean, ironically we didn't touch much on where CRISPR even comes from. And it's something that I think it's a lot more exciting to talk about the applications of gene editing, but what was cool for me was being in Jennifer's lab studying CRISPR before gene editing and CRISPR even made sense together. CRISPR comes from bacteria. There were a few dozen researchers around the world studying how bacteria fight off viral infections. When I started working on this back in 2010, I actually had two different kinds of PhD projects I was considering. One was studying a pathway called RNA interference that was known to be involved in cancer and development, and it seemed like kind of has the best of being a fun research topic for the lab I was in, but also having direct application to human health. And the second was CRISPR, which was this complete mystery. There were very few people studying it, so that was a bonus in terms of starting in a field that had very few people. No competition really. But it seems so far away from human health that I worried a little bit well, is this not going to be relevant. It's going to be hard to get the next job because I'm studying something that exists in bacteria and doesn't really relate to human biology. And that was literally what I thought in 2010, I decided I'm going to work on this anyway because it's this cool mystery, and who knows what we're going to find out about it. And then a couple of years later and we're learning about these enzymes and how we can harness them for something totally different. And how they're actually the most powerful way to do that thing, DNA targeting DNA editing, that we've ever had before. So I think that's something that I'm taking it to my new lab is just this curiosity-driven research and going into the invisible microscopic world in search of where the next discovery might be.
CODY GOUGH: That's really cool And now, we do end every podcast with a little segment called the curiosity challenge. And I'll try to teach you something, you'll probably know this, but I will ask you about something that I learned on curiosity.com. Scientists discovered in March 2016 that there is a component of aging, something that typically happens to a person as they become older, that they've actually discovered a gene plays a role in that process. And they knew that there were several genes involved in related ways, but this is the first time a gene for this particular aging trait has been identified. Do we know what that trait is?
DR. SAM STERNBERG: Greying hair.
CODY GOUGH: You are correct. So it's a gene called IRF 4 and it plays a role in graying hair, not just environmental factors like stress or smoking. So I found that out on curiosity.com and it did want me to get into the question. I mean, do you think that someday people are going to be splicing genes, so that instead of having to color our hair we can just kind of cut that gene out of there and not worry about it like with the mushrooms.
DR. SAM STERNBERG: I'm much more interested in baldness, and figuring out a way that I can keep all my hair in my head that is there right now.
CODY GOUGH: There you go.
DR. SAM STERNBERG: So right now gray hair is OK as long as I have gray hair in the first place.
CODY GOUGH: All right. I like that, very optimistic.
DR. SAM STERNBERG: OK so this is a bit of a current events question. Where do scientists think that most heavy atoms have come from?
CODY GOUGH: That. I definitely have no idea.
DR. SAM STERNBERG: So if I've read the news right it's colliding neutron stars, which Legault just detected the gravitational waves from. It's like this insane news story from the last couple of weeks. They detected two colliding neutron stars, and they also detected electromagnetic radiation from it, which is I think the first time they've ever had both gravitational waves and electromagnetic radiation from somewhere in outer space.
CODY GOUGH: I knew that there was something about neutron stars in the news. I know that Ashley and Joanie covered it on our Facebook page. So they're going to kill me for not knowing the answer to that.
DR. SAM STERNBERG: And hopefully I actually gave you correct information now, but I know there was something about neutron stars flooding the universe with heavy atoms. That's where a lot of the heavy atoms come from.
CODY GOUGH: Sure, we'll fact check that one.
DR. SAM STERNBERG: Please do.
CODY GOUGH: It sounded very impressive.
ASHLEY HAMER: Dr. Sternberg is absolutely right. The lightest elements were created in the Big Bang, and the largest stars can fuse elements as heavy as iron in their cores. As for where elements heavier than that came from, scientists weren't sure. For a long time, it was thought that they were forged in the stellar explosions known as supernova. But lately all signs have pointed to collisions of neutron stars, the small dense cores left over after large stars die. We just didn't have the proof. Then on August 17, 2017 LIGO detected gravitational waves from a collision of two neutron stars, and their hunch was confirmed. According to some estimates that collision produced around 200 Earth masses of gold and 500 Earth masses of platinum.
CODY GOUGH: I mean when you're pulling out a neutron star, you're already talking about basically rewriting genes and now you're getting a neutron stars. Where's the limit with you?
DR. SAM STERNBERG: I don't know. I guess science. I can't go outside of science. It's only science.
CODY GOUGH: Are those are mean hobbies and interests?
DR. SAM STERNBERG: No, no I love playing sports and I used to be a musician. I grew up playing music, almost went to conservatory. My last thing I'm doing out in California before moving to New York is I'm subbing for Michael Jackson tribute band on keyboards. We're doing a tour up to Seattle, Eugene, and Portland. My former roommate used to be the keyboardist. He moved, but while he was still there I was subbing for him when he was out of town. So that's probably one of the funnest things I've done in the Bay Area musically since I moved out there. I played in a Funk band for a bunch of years too.
CODY GOUGH: So you almost went to a conservatory for keys?
DR. SAM STERNBERG: For classical piano, but then you grow a little bit older and you realize like no one wants to hear classical piano, but if you can play in a Funk band or play in a Michael Jackson band that is actually kind of cool.
CODY GOUGH: I don't know, Beethoven's piano sonata number eight, Pathéthique, is pretty--
DR. SAM STERNBERG: That was what I played for my auditions.
CODY GOUGH: No way, really?
DR. SAM STERNBERG: Yeah.
CODY GOUGH: I love that piece.
DR. SAM STERNBERG: I was going to try to come up with piano trivia question, but I couldn't I couldn't think of a good enough one.
CODY GOUGH: That was a great Curiosity Challenge Question. And I want to thank you again Dr. Sam Sternberg, assistant professor of biochemistry and molecular biophysics at Columbia University. Starting your own lab there. Congratulations on that. That's a huge deal.
DR. SAM STERNBERG: Thanks a lot.
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ASHLEY HAMER: You learn so much in this episode. Do you want to learn a little bit more? Because right now, I'm going to give you your extra credit question. Because it's so sad, researchers have relied on the final scene of one movie in thousands of psychology studies. Here's your question. When scientists want to make a research subject cry, what 1979 movie's final scene do they show? The answer after this.
CODY GOUGH: Have you ever been listening to the Curiosity Podcast and wanted to share a clip on Facebook or Twitter? Well, here's some super exciting news now you can thanks to Gretta.com. You can stream our podcast on gretta.com/curiosity and their podcast player will follow along with a written transcript of each episode while you listen. When you hear a clip you want to share, just find it and click Share. Gretta will build you a video for you to share with your friends so that you can help spread the word about our podcast. Again, that's gretta.com/curiosity and drop us a line to let us know what you think of this super cool new service.
ASHLEY HAMER: Explore history's surprising connections with a new podcast, The Thread with Ozy. It's like a cross between revisionist history and six of separation. You'll discover how various historical strands are woven together to create a historic figure, a big idea, or an unthinkable tragedy. Like how John Lennon's murder was actually 63 years in the making. Witness how their stories hinge on the past and influence the future. The show is already a chart topper get the thread with Ozi. That's O-Z-Y on Apple Podcasts, or wherever you listen.
CODY GOUGH: Do you like surveys? Well, I've got some really good news for you if you do. We want to hear your thoughts on the curiosity podcast, so we created a super quick and easy survey. Please visit curiosity.com/survey and answer a few questions so we can make our podcast better. Again, that's curiosity.com/survey. It's quick and easy and will really help us bring you better content every week. There's a link in the show notes too, but one more time that URL is curiosity.com/survey. We really appreciate the help.
ASHLEY HAMER: Here's your extra credit answer. The thing that researchers use to make people cry is the final scene of the 1979 film, The Champ. In that movie Jon Voight plays a gambling, hard drinking, down on his luck boxer. And the final scene is a real tearjerker. Even the death of Bambi's mother couldn't hold a candle to it. We won't spoil the ending for you, but you can find a link to the scene in the show notes. Or search for the word, Champ, on curiosity.com.
CODY GOUGH: Thanks for listening to the curiosity podcast. If you want to help us out please leave us a review on iTunes, or tell one of your friends about the show.
ASHLEY HAMER: For the Curiosity Podcast, I'm Ashley Humer.
CODY GOUGH: And I'm Cody Gough. See you next week.