AI Cancer Vaccines, Strange Fish, Ketamine, and Ancient Life (EP. 34)

Hosted by Lester Nare and Krishna Choudhary, this episode is a fast-moving science rundown covering four remarkable stories from across AI, genetics, neuroscience, and paleontology. We dig into the story of a machine learning engineer who used AI tools to help design a personalized cancer vaccine for his dog, explore how an all-female fish species has survived far longer than evolutionary theory would predict, unpack new brain-scan evidence for how ketamine may rapidly relieve severe depression, and look at new research suggesting life rebounded shockingly fast after the asteroid that killed the dinosaurs. Summary AI and personalized medicine — a striking case study in how AI tools may help accelerate highly customized treatments, starting with a rescue dog named Rosie. Evolution gets weird — the Amazon molly fish appears to challenge the usual assumptions about why asexual reproduction should fail over long time scales. Why ketamine works so fast — new PET imaging research points to brain-region-specific changes in AMPA receptors in treatment-resistant depression. Life after catastrophe — microscopic plankton may have evolved into new species within just a few thousand years after the Chicxulub impact. Support the showDonate: FFPod.com/donateFollow: @FFPod on X / Instagram / TikTok / Facebook Show Notes AI-designed dog cancer vaccine story https://finance.yahoo.com/news/mans-dog-riddled-tumors-dying-210500037.html?guccounter=1 Amazon molly / gene conversion paper https://www.nature.com/articles/s41586-026-10180-9 Ketamine / AMPA receptor PET imaging paper https://www.nature.com/articles/s41380-026-03510-w Post-asteroid plankton recovery paper https://www.yokohama-cu.ac.jp/english/news/20260306takahashi.html

Speaker names marked ? are inferred from speaking time and the show’s known hosts — they are not voice-verified.

• 0:00Lester Nare?

  So we're gonna start today with our first story about a man who fixed his dog's cancer with ChatGPT. And no, this is not clickbait.

• 0:11Krishna Choudhary?

  It's fully female.

• 0:14Krishna Choudhary?

  And it's incredible that it survived for so long because it uses cloning. Ketamine seems to work on them. And it's weird for two reasons. One, why does ketamine work when all these other antidepressants don't? And two, ketamine works at a really fast timescale.

• 0:29Lester Nare?

  Life rebounding shockingly fast after the asteroid that killed the dinosaurs. Hello, Internet. This is your captain speaking, Lester Nare, joined as always by my co-host and our resident PhD Krishna Choudhary. We are here for another casual rundown episode where we're gonna touch on four stories that we did not do a deep dive on this week, but are also interesting and exciting breaking news stories. Categories we will cover today include AI, genetics, neuroscience, and we'll end with a paleontology and ancient life story.

• 1:07Lester Nare?

  And squeezed in the middle there, we will do another lovely, exciting round of Are You Smarter Than a Scientist? Where you can test whether your knowledge of the universe is greater than our resident PhD Krishna.

• 1:25Lester Nare?

  We are gonna learn about the science from the ground up today as always, because this is from first principles.

• 1:46Lester Nare?

  So we're gonna start today with our first story about a man who fixed his dog's cancer with ChatGPT. And no, this is not clickbait. There was a man's dog who was riddled with tumors and dying, and he used ChatGPT to design a custom cancer vaccine, which is stunning. Researchers, this is a, he's a Sydney tech entrepreneur. No background in sort of this research area of oncology.

• 2:14Krishna Choudhary?

  Yeah.

• 2:15Lester Nare?

  Used chat GPT and some other AI tools to design a world's first personalized cancer vaccine for his dying rescue dog Rosie, who had advanced mass cell cancer. And then working with the University of New South Wales, they sequenced the dog's DNA, identified the cancer mutations using AI and created the custom mRNA vaccine that shrank the tennis ball sized tumor by seventy five percent.

• 2:46Krishna Choudhary?

  Yeah.

• 2:46Lester Nare?

  Within months. This is fascinating.

• 2:47Krishna Choudhary?

  It's an incredible story. And I mean, we've covered AI a lot on our podcast. And usually it's all been doom and gloom. But, you know, one of the things that gets me excited about AI is this is this idea of the democratization of science and the democratization of technology and capability. And this is a spectacular example.

• 3:11Lester Nare?

  Right.

• 3:11Krishna Choudhary?

  Of what it's capable of in the right hands.

• 3:14Lester Nare?

  Mm hmm.

• 3:15Krishna Choudhary?

  I think that's so cool. So there was a Sydney Tech entrepreneur, Paul Cunningham, and his rescue dog Rosie. The rescue dog Rosie had months to live. And he just did not accept that prognosis from the veterinarians. So what he did was use chat GPT to build a personalized cancer vaccine. It's pretty incredible. He had no, as you were saying, no background in biology, just seventeen years as a machine learning engineer. So reasonably tech savvy.

• 3:45Lester Nare?

  Sure.

• 3:45Krishna Choudhary?

  Reasonably has probably a first principles background of how stuff works at the DNA level. And here's what he did. Okay, so first always you go to chemotherapy. Chemotherapy slowed down the spread, but you know, it couldn't actually shrink the tumors of his dog. So he spent three thousand dollars to have Rosie's healthy DNA sequenced. And then the tumor DNA sequenced as well.

• 4:11Lester Nare?

  Okay.

• 4:11Krishna Choudhary?

  From the University of New South Wales. They've got, you know, biomedical labs, so they can do this. And then now that you have the DNA sequencing of what normal. cells in his dog look like and what the cancer cells in his dog look like. You can find mismatches of where the cancer mutations are.

• 4:28Lester Nare?

  Yep.

• 4:28Krishna Choudhary?

  Okay, and then he used the mRNA vaccine, which is the same vaccine that Moderna.

• 4:36Krishna Choudhary?

  Sort of pioneered for COVID nineteen. The technology is the following. You insert a piece of mRNA. That then gives your body a blueprint of what to look for in order to have that immune response. Right, so in the COVID nineteen vaccine, the mRNA is for the spike protein on the COVID virus. The mRNA goes into our body, our body then translates that mRNA into protein, makes the spike protein. Our body then creates antibodies that recognize that spike protein so that when the real thing comes in. We can recognize the spike protein, we can recognize the virus. We don't get full fledged COVID, we actually have an immune response the first time.

• 5:18Lester Nare?

  It's effectively training the body's defense forces for what the enemy is going to look like before the enemy is on your shore.

• 5:24Krishna Choudhary?

  Exactly, and over here, the enemy is already on our shore.

• 5:27Lester Nare?

  Yes.

• 5:27Krishna Choudhary?

  But the problem is that cancer is very deceptive. Cancer has a lot of mechanisms to suppress the immune response. And then also the cancer is our own DNA. So our immune system isn't like as good at targeting cancer versus something that is fully foreign. Right, because when it's fully foreign, it's like obvious.

• 5:46Lester Nare?

  Right.

• 5:46Krishna Choudhary?

  But with cancer, it's like your own cells are actually acting up. So here's what he did, he pinpointed the mutations that were driving the cancer in that tumor. And then he made an mRNA that would train Rosie's immune system to target that specific tumor. Okay, he also actually had to additionally put in things that would suppress that immune suppression. So it's like a double negative.

• 6:14Lester Nare?

  Yeah.

• 6:14Krishna Choudhary?

  Right, because like the cancer is telling the immune system, I'm, don't, don't come at me. So there's a suppression there, he had to put in a bunch of drugs that actually like told the immune system to ramp back up.

• 6:25Lester Nare?

  Right.

• 6:25Krishna Choudhary?

  Okay, so this double, double edged sword kind of went in and it's incredible. Less than two, two months, less than two months after the sequence was finalized. Rosie received her first injection in December and by March, seventy five percent of that tennis ball sized tumor was gone.

• 6:43Lester Nare?

  There's a great quote from this article from Paul Conningham, who said at the start of December, her mobility was way down at the beginning. She started to shut down and was a bit sad. And towards the end of January, she was jumping over a fence to chase a rabbit.

• 6:59Krishna Choudhary?

  Yeah.

• 6:59Lester Nare?

  So not only the biological decrease by March, but even the behavioral change.

• 7:04Krishna Choudhary?

  Yes.

• 7:05Lester Nare?

  Even sooner than that is just unbelievable.

• 7:08Krishna Choudhary?

  It's unbelievable and it's like so incredible, such a cool story. As a former dog owner, you know, like the, the ends of the earth that this guy went to, to save his dog, I really identify with that. I thought this was so cool. And it's also the first time that there's a personalized cancer vaccine.

• 7:27Lester Nare?

  Right.

• 7:27Krishna Choudhary?

  That's been designed for a dog.

• 7:29Lester Nare?

  Yes.

• 7:29Krishna Choudhary?

  Ultimately, this is going to help in humans as well. I'm sure, I'm sure the New South Wales researchers at the university are like writing a paper right now.

• 7:40Lester Nare?

  Right now.

• 7:40Krishna Choudhary?

  This is a great paper. If you're not, you really shouldn't. Like this is, this is something that I can see coming out in a very top journal.

• 7:47Lester Nare?

  Yeah.

• 7:47Krishna Choudhary?

  Um, yeah. And the bigger picture is actually very cool. Moderna and Merck, the two companies are actually leading the pack when it comes to personalized mRNA vaccines.

• 7:56Lester Nare?

  Yes.

• 7:57Krishna Choudhary?

  For this purpose. So in humans, where they're gonna, you know, again, sequence the DNA from the tumor and then go back, create the mRNA vaccine. If you can make this cheaper and if you can iterate on this faster, this is huge for, you know, cancer in human beings as well. I think the next step, what he's gonna do is every single tumor on the body is actually different. Right? Because every single tumor is a few mutations here and there. So that's why only 75% of the tumor went away.

• 8:27Lester Nare?

  Yeah.

• 8:27Krishna Choudhary?

  Because the core of the tumor likely has other mutations.

• 8:30Lester Nare?

  Right.

• 8:30Krishna Choudhary?

  That he didn't sequence.

• 8:32Lester Nare?

  Right.

• 8:32Krishna Choudhary?

  So you can iterate on this.

• 8:34Lester Nare?

  You can apply, now you can get to the smaller inner orbit.

• 8:37Krishna Choudhary?

  Yeah.

• 8:38Lester Nare?

  Sequence that.

• 8:38Krishna Choudhary?

  Yeah. So it's like the second order, third order, so on and so forth. I just thought this was a very cool, hopeful story in the. Potential that AI has for just like average people.

• 8:52Lester Nare?

  Yes.

• 8:52Krishna Choudhary?

  You know, like $3,000 sounds like a lot, but I don't know, I would have paid that for another year or two.

• 8:58Lester Nare?

  Based on the cost of cancer.

• 8:59Krishna Choudhary?

  Yeah.

• 9:00Lester Nare?

  Uh, uh, treatments now, uh, I think that's probably bargain basement or close.

• 9:04Krishna Choudhary?

  Yeah.

• 9:04Lester Nare?

  It's on, it's not necessarily, it's, it's not, it is, it's not cheap. But healthcare, as many of us know in the United States, especially in cases like this, is extraordinarily expensive.

• 9:15Krishna Choudhary?

  Yeah.

• 9:16Lester Nare?

  So at anything you can do to chip away at the cost, uh, while still being safe and having efficacy in all the checkboxes is, is huge.

• 9:24Krishna Choudhary?

  And if you were to compare it to, let's say, like, you get a consultant who's a cancer researcher and you get a whole team to actually do this. It's like pennies compared to like actually hiring a full-fledged team.

• 9:37Lester Nare?

  Right.

• 9:38Krishna Choudhary?

  To dedicate to your dog, right?

• 9:40Lester Nare?

  Yeah, yeah, yeah.

• 9:40Krishna Choudhary?

  The time and the resources. So I think, I think it's really, really cool. And a lot of these, um, the Moderna and the Merck vaccines, they've jointly developed these for melanoma. It's already shown a 49% reduction in the risk of cancer recurrence and death over a five-year range. So should be coming out soon.

• 9:59Lester Nare?

  Yes, this is good.

• 10:00Krishna Choudhary?

  Pretty exciting.

• 10:01Lester Nare?

  The only way to have made this a more, uh, heartfelt, lovely story if, if, if the, uh, Sydney dog owner's name was John Wick.

• 10:10Krishna Choudhary?

  Oh, yeah. Yeah, yeah, yeah.

• 10:12Lester Nare?

  That, that would have just rounded out the story perfectly. Um, but great.

• 10:17Krishna Choudhary?

  But Cunningham is a good enough name. Paul Cunningham.

• 10:19Lester Nare?

  Paul.

• 10:20Krishna Choudhary?

  Props to you, man.

• 10:20Lester Nare?

  Yeah, awes- awesome stuff.

• 10:22Krishna Choudhary?

  Yeah.

• 10:22Lester Nare?

  Really, really awesome stuff. Uh, take life into your own hands.

• 10:25Krishna Choudhary?

  Yeah.

• 10:25Lester Nare?

  Great start with, uh, that sort of interesting angle to an AI story. Our second story is, uh, a, a similar gene kind of story, but this one I'm very curious.

• 10:38Krishna Choudhary?

  This one's weird.

• 10:39Lester Nare?

  To, to, to talk to you about. So the title on this one is gene, uh, gene conversion empowers natural selection, uh, in fish species. So there's a tiny Amazon, uh, fish that has been, uh, A fascinating look for researchers for some time. And it should not have survived as a species.

• 10:59Krishna Choudhary?

  Yes.

• 11:00Lester Nare?

  And there's an interesting reason why it should not have survived as a species. And this is out of University of Missouri, as well as the Ludwig Maximilian Universitat in Munich, Germany.

• 11:11Krishna Choudhary?

  That's a unlat, so it's a universit. Universitat.

• 11:14Lester Nare?

  Universitat.

• 11:15Krishna Choudhary?

  Yeah.

• 11:16Lester Nare?

  So you're good, you'll do the German.

• 11:17Krishna Choudhary?

  I'll do the German.

• 11:18Lester Nare?

  And I'll do the French.

• 11:18Krishna Choudhary?

  You do the French, yeah. This is a really cool story because this particular fish, it's found in southern Texas, northern Mexico. It's called the Amazon Molly, and it's named after the Amazonian tribe of legend, which were an all-female tribe, no men, and they had just figured out a way to procreate. This fish, all-female, doesn't actually like have sexual reproduction.

• 11:47Lester Nare?

  Oh, interesting.

• 11:47Krishna Choudhary?

  With other males.

• 11:48Lester Nare?

  Interesting.

• 11:49Krishna Choudhary?

  Yeah.

• 11:49Lester Nare?

  Okay.

• 11:49Krishna Choudhary?

  It's fully female. And it's incredible that it survived for so long because it uses cloning effectively.

• 11:57Lester Nare?

  Oh.

• 11:57Krishna Choudhary?

  To reproduce.

• 11:58Lester Nare?

  Yeah, yeah, yeah.

• 11:58Krishna Choudhary?

  And all evolutionary theory says that that is a really bad idea. Why? Because when you clone, you don't get genetic variability.

• 12:05Lester Nare?

  Right.

• 12:05Krishna Choudhary?

  And so if there's any kind of change in environment, evolutionary pressure, you're gone.

• 12:10Lester Nare?

  Right.

• 12:11Krishna Choudhary?

  Because everyone is identical.

• 12:12Lester Nare?

  Right.

• 12:13Krishna Choudhary?

  So the big question has been, this thing is at least 100,000 years old.

• 12:17Lester Nare?

  How?

• 12:18Krishna Choudhary?

  How did it happen?

• 12:19Lester Nare?

  Yeah.

• 12:19Krishna Choudhary?

  So it formed when there were two fish species. I believe it was the Atlantic Molly and the sail Molly. They mated, they produced this hybrid. This hybrid now was a female, and every single Amazon Molly today can be traced back to that single parentage, that single person.

• 12:40Lester Nare?

  Mm-hmm.

• 12:40Krishna Choudhary?

  Okay? That single fish, I should say. What's weird about it is... That, you know, as I said, they don't sexually reproduce.

• 12:47Lester Nare?

  Right.

• 12:48Krishna Choudhary?

  So they still actually have sex with males. But there's no sperm that is going to fertilize the egg.

• 12:55Lester Nare?

  Okay.

• 12:55Krishna Choudhary?

  That sexual process, the act of having sex starts, triggers the special kind of meiosis in the fish that causes this cloning to happen. So you get egg cells that are identical to the mother.

• 13:07Lester Nare?

  Yes.

• 13:08Krishna Choudhary?

  And then those egg cells become.

• 13:09Lester Nare?

  Yes.

• 13:10Krishna Choudhary?

  Um, Amazon fish.

• 13:11Lester Nare?

  Baby fish.

• 13:11Krishna Choudhary?

  Okay. So the question becomes, all right, how did it survive, right? How do you, how do you actually, um, you know, if there's a deleterious mutation? If there's like something that goes wrong during the replication of DNA? You might be completely.

• 13:25Lester Nare?

  Right.

• 13:26Krishna Choudhary?

  Sidelined.

• 13:27Lester Nare?

  Right.

• 13:27Krishna Choudhary?

  Right? They use, um, a process where they're actually using gene conversion. This is the idea where you've got multiple sets of chromosomes, right? If there's ever a mistake, their genetic repair mechanism can use the other copy to make that fix. That repair mechanism also creates, um, genetic variation at exactly the right frequency to have a pretty healthy population. That is, that is not completely genetically identical.

• 13:57Lester Nare?

  That's interesting.

• 13:57Krishna Choudhary?

  But it's got this mechanism such that it can stop mutations from going bad.

• 14:03Lester Nare?

  Yeah.

• 14:03Krishna Choudhary?

  And also create tiny little mutations to create variation.

• 14:07Lester Nare?

  So the, the genetic variability is deriving from the sort of, uh, the, the internal cloning reproductive process as opposed to sharing the chromosomes from the.

• 14:20Krishna Choudhary?

  Exactly.

• 14:21Lester Nare?

  Mother and the father, or, you know, one into male and female.

• 14:23Krishna Choudhary?

  Exactly.

• 14:24Lester Nare?

  And that's kind of a dis- an important distinction and the difference with how it drives its own sur- ability to survive over long periods of time by, uh, while still not having, uh, a classic sexual reproduction between, uh, a male sperm and a female egg.

• 14:41Krishna Choudhary?

  Yes, exactly. And usually that's how we get genetic variability, right? Is like from the combination of two individuals' genes. That's most life, actually, even trees, plants, like everything.

• 14:54Krishna Choudhary?

  Does this kind of mix and match. But these guys are doing a copy and paste. But that copy and paste has enough little tricks. That like shows this is actually possible. It challenges this traditional assumption that, you know, asexual reproduction is going to cause

• 15:09Lester Nare?

  Right.

• 15:09Krishna Choudhary?

  sterile species.

• 15:11Lester Nare?

  Yes.

• 15:11Krishna Choudhary?

  It's not actually true. So maybe evolution has many more ways to actually maintain a healthy genome in that tree of life. And we've been sequestered into thinking that sexual reproduction is sort of an apex mechanism. Might not be.

• 15:26Lester Nare?

  Don't tell that to the people who want to, uh, whatever you call it, when you make people all the same.

• 15:31Krishna Choudhary?

  Oh, yeah, yeah.

• 15:32Lester Nare?

  That's, let's not let them know about that.

• 15:34Krishna Choudhary?

  Yeah.

• 15:35Lester Nare?

  This, this was in nature. Again, at a University of Missouri. And the Ludwig Maximilian Universität? In Munich, Germany.

• 15:45Krishna Choudhary?

  Tate, Tate.

• 15:46Lester Nare?

  It's okay. It's the, it's the double.

• 15:49Krishna Choudhary?

  It's the umlaut, yeah.

• 15:50Lester Nare?

  The umlaut.

• 15:50Krishna Choudhary?

  The umlaut, yeah.

• 15:53Lester Nare?

  We'll go, we will be in Germany for Oktoberfest maybe this year. So for all the fans on Germany, let us know. We are going to need to be shown around. Now, last time around, on the rundown, we introduced our new segment. And we're going to bring it back for another trial test of are you smarter than a scientist?

• 16:18Krishna Choudhary?

  Okay.

• 16:19Lester Nare?

  The game show where you at home can find out if you are in fact smarter than our resident PhD. And the question this week is name the 10 largest organs in the human body by mass. And I will make, uh, one small caveat about the answers to this, which is that the organs are discreet.

• 16:44Krishna Choudhary?

  They're discreet. Okay. All right, um, let's see, let's start with the liver. I'm pretty sure that's huge.

• 16:50Lester Nare?

  So we're going to see where is liver on the board? Is it on the board? Yes, it is at number two. And that's at 1.5, approximately 1.5 kg.

• 17:01Krishna Choudhary?

  Okay, 1.5 kilograms. What's bigger than the liver? All right, let's start with some of the easy ones, right? Let's do, um, lungs.

• 17:09Lester Nare?

  The lungs is on the board.

• 17:12Krishna Choudhary?

  All right.

• 17:12Lester Nare?

  Spot number four at 1 kg.

• 17:16Krishna Choudhary?

  Let's do the large intestine.

• 17:22Lester Nare?

  I won't give you a strike for this.

• 17:23Krishna Choudhary?

  Uh huh.

• 17:24Lester Nare?

  Because technically, it's a part of the digestive tract.

• 17:28Krishna Choudhary?

  Uh huh.

• 17:28Lester Nare?

  And would not be considered a discreet organ.

• 17:31Krishna Choudhary?

  Oh, interesting.

• 17:31Lester Nare?

  So for that first one, I'll give you a pass. I'll give you that.

• 17:35Krishna Choudhary?

  All right. Um, well then, wait, would digestive tract be on here?

• 17:40Lester Nare?

  No.

• 17:41Krishna Choudhary?

  Okay, interesting.

• 17:42Lester Nare?

  The, again, that's kind of all categorized together.

• 17:46Krishna Choudhary?

  Okay.

• 17:47Lester Nare?

  Let's kind of put that to the side.

• 17:48Krishna Choudhary?

  All right, let's put it to the side. So stomach is also not on this?

• 17:52Lester Nare?

  I'm gonna give you a strike for that one. Okay.

• 17:55Krishna Choudhary?

  Fine, fine. I'm asking too many questions. All right, uh, let's do brain.

• 17:59Lester Nare?

  Brain is on the board at number three. So we have number two, liver, number three, brain, number four, lungs.

• 18:07Krishna Choudhary?

  Um, let's do heart.

• 18:10Lester Nare?

  The heart is on the board at number five, approximately 315 grams.

• 18:20Krishna Choudhary?

  Um, let's go for, is skin on here?

• 18:26Lester Nare?

  Is skin on the list?

• 18:30Krishna Choudhary?

  Yes.

• 18:31Lester Nare?

  Big spot at number one.

• 18:33Krishna Choudhary?

  Okay, skin is number one. I have the top five.

• 18:35Lester Nare?

  Very good.

• 18:36Krishna Choudhary?

  All right.

• 18:37Lester Nare?

  Very good.

• 18:37Krishna Choudhary?

  This one's hard. Last, last, last.

• 18:40Lester Nare?

  The last five. One strike. Skin, liver, brain, lungs, heart, top five.

• 18:46Krishna Choudhary?

  Skin, um, the heart is on there.

• 18:51Lester Nare?

  Kidney. Is kidney on the list at number six?

• 18:57Krishna Choudhary?

  So we gotta get smaller than kidneys now. Um, let's do pancreas.

• 19:02Lester Nare?

  Is pancreas on the list at number eight?

• 19:07Krishna Choudhary?

  Okay.

• 19:07Lester Nare?

  So we are missing seven, nine, and 10. You are on a roll.

• 19:11Krishna Choudhary?

  Uh, gimme.

• 19:14Lester Nare?

  These ones are a little tough.

• 19:17Krishna Choudhary?

  You'll, you, you, they're.

• 19:20Lester Nare?

  Gimme the bladder. The bladder is not on the list. That is our.

• 19:26Krishna Choudhary?

  One strike left.

• 19:27Lester Nare?

  You have one strike left. We have number seven, number nine, and number 10.

• 19:35Lester Nare?

  Choose wisely, those listening. We only have one strike left.

• 19:43Krishna Choudhary?

  Man, what am I thinking of now?

• 19:47Lester Nare?

  Now, again, it's discreet.

• 19:52Lester Nare?

  I'll give you one hint here, which is one of them is only present in males.

• 20:01Krishna Choudhary?

  Oh, it's only present in males?

• 20:05Krishna Choudhary?

  Is it gonna be prostate or testes? I'll do prostate.

• 20:08Lester Nare?

  Prostate is on the board at number 10, so we are missing number 7 and number 9.

• 20:15Krishna Choudhary?

  So there's something that's about, that's in between size of kidneys and pancreas, and there's something in between size of pancreas and prostate. Okay, gallbladder.

• 20:26Lester Nare?

  Is it gallbladder? Unfortunately, that will end your trial on round two of Are You Smarter Than a Scientist? We had two missing items. Number 7 was the spleen.

• 20:41Krishna Choudhary?

  Okay, should've gotten that one, yeah.

• 20:43Lester Nare?

  And our last one, get your guesses in now for those at home, was the thyroid.

• 20:49Krishna Choudhary?

  Yeah, I didn't even think of that, you know?

• 20:52Lester Nare?

  So our list, skin, liver, brain, lungs, heart, kidneys, spleen, pancreas, thyroid, prostate. And I will just note that this was for the male body, because you could arguably put the uterus on the list a little bit higher than some of these items. So, not a bad round. We were missing some of those answers. We're still gonna give you a nice little fire there for our second round of Are You Smarter Than a Scientist? If you are interested in the game show, or you would like to see us bring on guest contestants for a head-to-head competition, please let us know in the comments.

• 21:34Lester Nare?

  We are going to continue on to our third story, which is about brain scans revealing how ketamine can quickly lift severe depression. If you're in the UK, you might be familiar with this as being called ketamine.

• 21:53Lester Nare?

  Here in the US, it's called ketamine. This is out of the YCU Advanced Medical Research Center, and it was in molecular psychiatry.

• 22:02Krishna Choudhary?

  Yeah, this one's a very interesting paper because I've always wondered why ketamine or ketamine is so effective against depression. So, major depressive disorder, that's MDD. It's a major global health problem. Thirty percent who are diagnosed are given treatment-resistant depression. That's the tag that they're given because even normal antidepressants don't work on them. Ketamine seems to work on them. And it's weird for two reasons. One, why does ketamine work when all these other antidepressants don't? And two, ketamine works at a really fast timescale. Okay, most of the time when you take antidepressants, like in pill form,

• 22:46Krishna Choudhary?

  the effects are going to come in like a week to a month. That's the timescale that you're looking at. With ketamine, it's like minutes.

• 22:52Lester Nare?

  Really?

• 22:53Krishna Choudhary?

  Okay, yeah, yeah. It's like you're there at getting the therapy, getting it injected, and then like, it's like within the hour to like that day is like when you start feeling not depressed. Okay, so there's clearly a very different mechanism about what's going on. And for the longest time, it's been really quite nebulous, how it's actually working. And a lot of times with the brain, a lot of things are nebulous because we don't know enough. There's so many things that are working around. And at some point, you know, you just sort of say, hey, it's working. But as scientists, we always want to figure out what's actually happening because then we can model things very well. We can start thinking, okay, how is ketamine actually going to affect? What is the dosage that we want to give?

• 23:37Krishna Choudhary?

  What is the frequency with which we want to give? If we have a fundamental understanding, then we can actually start doing clinical trials for like different types of therapies, different schedules and things like that. So it's very important to actually figure out what is going on. Now, there were early studies that showed it had something to do with the AMPA R receptor. So, a brief overview of neuroscience. Our nervous system is built out of neurons. Neurons are the single unit of the nervous system. They're cells and they talk to each other using synapses. So when one cell fires or turns on, what it's going to do is talk to its postsynaptic cells, the cells that it is synapsing onto, the cells that it can talk to,

• 24:20Krishna Choudhary?

  using these structures called synapses, where one cell comes in kind of like a hand and the other cell that is downstream comes over it like a, like a, like a open palm around it, okay? But there's a gap in between. They're not actually tied together. They're separate cells and they have a tiny gap called the synaptic junction. Now, through that synaptic junction, the way you talk is you, you release the, the presynaptic cell, releases chemicals into that synaptic cleft, that gap, and then the postsynaptic cell senses those chemicals and then turns on. Okay, that's effectively most, like 99% of neuroscience

• 25:03Krishna Choudhary?

  is just a cell talking to another cell using these chemicals. Most of the time, that chemical is glutamate. It's not, you know, serotonin, dopamine, all this other stuff. We talked about this on the Dave Chang podcast.

• 25:16Lester Nare?

  This is where MSG comes from.

• 25:17Krishna Choudhary?

  Yeah, MSG is effectively just glutamate with a little bit of sodium. So glutamate is the bread and butter. It is how, it is like the cash money of how neurons talk to one another and transact information. And the receptors that sense the glutamate to trigger a response in the postsynaptic cell, in the downstream cell, those receptors, one of them is the AMPA R receptor.

• 25:43Lester Nare?

  Got it.

• 25:43Krishna Choudhary?

  Okay?

• 25:44Lester Nare?

  Yes.

• 25:44Krishna Choudhary?

  And what we've, what we've seen in previous studies is that ketamine has something to do with these AMPA R receptors.

• 25:52Lester Nare?

  Got it.

• 25:52Krishna Choudhary?

  Okay, we just don't know what.

• 25:54Lester Nare?

  Right. The receiving end of the chemical signal to turn on.

• 25:58Krishna Choudhary?

  Yes, it's it's receiving the glutamate and somehow that receiver has something to do with ketamine.

• 26:04Lester Nare?

  Yes.

• 26:04Krishna Choudhary?

  Okay, so what these guys did was they used positron emission tomography. This is an imaging method where you basically like you you have the patient inject some radioactive chemical. It's not that harmful, but it's what it does is that chemical becomes a tracer. It releases positrons as it makes its way through. Positrons are the antimatter version of the electron. And if you have a positron detector, then you can detect these positrons and you can see where the chemical is going.

• 26:33Lester Nare?

  And so it's a way it's a way to basically look at what's happening inside the body or track what's happening inside the body from outside the body.

• 26:39Krishna Choudhary?

  Yes, exactly. And so what what these guys at the City University of Yokohama, they developed a PET tracer, a posit a positron tracer that had been developed earlier. This tracer allows them to visualize that AMPR directly because it's somehow either connects to the AMPR or like interacts with it in some way. So we can actually map where the AMPR receptors are in the brain.

• 27:08Lester Nare?

  Got it.

• 27:08Krishna Choudhary?

  Okay, that's step one.

• 27:09Lester Nare?

  Yep.

• 27:10Krishna Choudhary?

  We figured out a way to trace and map out where the AMPR receptors are. Now you give your patients ketamine.

• 27:16Lester Nare?

  Because we were first identifying the location.

• 27:18Krishna Choudhary?

  Yes.

• 27:18Lester Nare?

  Where the thing we care about is happening, but we didn't actually know where the like we needed to know where the locations were first.

• 27:24Krishna Choudhary?

  Yeah, we knew that it was this thing.

• 27:26Lester Nare?

  Yes.

• 27:26Krishna Choudhary?

  But we don't know, we have no way of figuring out where it is.

• 27:29Lester Nare?

  Yes.

• 27:29Krishna Choudhary?

  And like, what are the dynamics when somebody gets ketamine? How does that change? Now we do. Now we've got this tracer that goes in, it's going to shoot out positrons and we've got a big positron detector. So wherever the positrons are coming from, we know that's where the AMPR receptors are. Okay, then we give them ketamine.

• 27:44Lester Nare?

  Yes.

• 27:45Krishna Choudhary?

  And we look at how these antidepressant effects evolve that AMPR activity, that receptor activity. And that's what they've done.

• 27:52Lester Nare?

  Okay, interesting.

• 27:53Krishna Choudhary?

  They they use thirty four patients that were diagnosed with this treatment-resistant depression and forty nine healthy patients that were in control. They gave half ketamine, half like just, you know, placebo because you got to have that that control. And then what it shows is the the people who have this treatment-resistant depression, first of all, they had widespread abnormalities in their AMPR density, just. Without even the treatment and everything.

• 28:18Lester Nare?

  I see.

• 28:19Krishna Choudhary?

  Those who have depression have a very different AMPA R density in their brain compared to healthy patients.

• 28:25Lester Nare?

  Can I do a quick pause here on that point? Because just to double click on it, there is a structural, a physical structural difference. Uh, at the neuron level.

• 28:38Krishna Choudhary?

  Yeah.

• 28:39Lester Nare?

  For people who have this treatment resistant depression than the control than than others.

• 28:44Krishna Choudhary?

  Yeah.

• 28:45Lester Nare?

  So for all the boomers who say depression is a made up thing in people's head, it's actually, it has, it has a physical manifestation.

• 28:52Krishna Choudhary?

  Yes, it is in their head and it is like a very much physical manifestation of like literal receptors and chemicals.

• 29:00Lester Nare?

  Are structured differently.

• 29:01Krishna Choudhary?

  Yeah, there's a difference.

• 29:02Lester Nare?

  Okay.

• 29:02Krishna Choudhary?

  Right? And so now we, we get into, okay, what is the ketamine actually doing?

• 29:06Lester Nare?

  Yes.

• 29:08Krishna Choudhary?

  And surprisingly, it was not uniform. There was like, what, what they would do is figure out what is the AMPA R density before the treatment? And then you give them ketamine and then you figure out what is the after, right? Not everywhere in the brain changed. Very specific regions of the brain actually changed. There's this place where there's reward processing. It's called a habenula.

• 29:28Lester Nare?

  Okay.

• 29:28Krishna Choudhary?

  Okay. A lot of AMPA R shifts were happening there. And this region specific shift is strongly connected to the improvement.

• 29:38Lester Nare?

  I see.

• 29:38Krishna Choudhary?

  In the depressive symptoms. Okay, so we can also see that. Not only is there change, we can also see that how much change is related to how much the depression gets better. So clearly we have some mechanism here, right? And this is very early. This is very early, but I think it's very, very cool because now we're seeing these dynamic changes in something as fundamental as the AMPA receptor.

• 29:59Lester Nare?

  Right.

• 29:59Krishna Choudhary?

  This is not like serotonin. Again, this is not serotonin or dopamine or things like that, which are very specific to certain circuits that have to do with reward, that have to do with pleasure and things like that. AMPA is like how like, it's like the, again, cash. It's not a weird commodity.

• 30:15Lester Nare?

  Yeah.

• 30:15Krishna Choudhary?

  Like gold or something. This is how all neurons talk to one another, right? And so this is a very fundamental substrate.

• 30:23Lester Nare?

  Can I try to make a, a different analogy maybe here? Would it be like saying these AMPA receptors are like the? The underwater internet pipes. Whereas serotonin are like a webpage or a specific domain that is accessible on the internet, but it's not the actual system that information is sent through. Like, I'm trying to, I don't know that I quite understand the cash analogy. It doesn't track in my head as well. So I'm trying to understand how to differentiate thinking about serotonin and dopamine as different from these receptors.

• 30:58Krishna Choudhary?

  Yeah, okay, so let's go with the internet analogy, right? If you say that the AMP, the glutamate.

• 31:07Lester Nare?

  Yes.

• 31:07Krishna Choudhary?

  What I'm saying is like glutamate.

• 31:09Lester Nare?

  Yes.

• 31:09Krishna Choudhary?

  And another one, which is Gabo, that's the inhibition. Glutamate and Gabo are like your cash. What I mean by that is like, it's like, I shouldn't say cash. I should really say they're the dollars.

• 31:19Lester Nare?

  Okay.

• 31:19Krishna Choudhary?

  You know what I mean? Like, if you wanna, if you wanna transact value between one person to another, what do we normally use? We use dollars.

• 31:28Lester Nare?

  Yes.

• 31:28Krishna Choudhary?

  Or if you're in another country, you use whatever denomination is the fiat currency.

• 31:32Lester Nare?

  Yeah, okay, so, okay, got it.

• 31:33Krishna Choudhary?

  But there are other ways to transfer value. I can give you a house. I can give you land. I can give you Bitcoin.

• 31:40Lester Nare?

  Yes.

• 31:40Krishna Choudhary?

  Those are your serotonin, your dopamine, your acetylcholine, things like that.

• 31:44Lester Nare?

  That makes sense.

• 31:45Krishna Choudhary?

  Right? But you can't build an economy off of those assets. Right? You need a fiat currency that is super liquid.

• 31:52Lester Nare?

  Right.

• 31:52Krishna Choudhary?

  I mean, there's people who are gonna say Bitcoin is, uh, but look.

• 31:56Lester Nare?

  We are where we are today. It wasn't invented in whatever centuries ago.

• 32:00Krishna Choudhary?

  But does that make sense?

• 32:01Lester Nare?

  That's helpful.

• 32:02Krishna Choudhary?

  Glutamate and Gabo are your dollars.

• 32:04Lester Nare?

  Yes, yep, yes.

• 32:06Krishna Choudhary?

  And so, the fact that ketamine is tied to AMPA receptors.

• 32:11Lester Nare?

  Yes.

• 32:11Krishna Choudhary?

  Which are receptive to glutamate.

• 32:13Lester Nare?

  Yes.

• 32:14Krishna Choudhary?

  Shows just how, like, nitty gritty it's getting into. And perhaps that is a clue as to why it's so fast, right?

• 32:21Lester Nare?

  Because it's, it's not waiting for the Bitcoin network to settle.

• 32:24Krishna Choudhary?

  Yeah, you don't need to produce dopamine. So on and so forth, you know?

• 32:28Lester Nare?

  Yeah, yeah, okay. That's, that's, that's very.

• 32:31Krishna Choudhary?

  So this is very early, but I think it's very, very cool. And it's only gonna get cooler and cooler.

• 32:36Lester Nare?

  And I think another piece of this that is that is interesting is being able to, you know, have, I mean, obviously, there are a variety of these new studies now that are trying to look at, you know, substances that have historically been viewed as just purely detrimental to the human condition. Yeah, yeah. And having no positive upside, primarily because they were viewed as recreational purely. But there is a clinical, a potentially clinical application here that, again, when you actually understand the structures and fundamentals of what is happening, we're kind of now starting to see why is it that ketamine can possibly, has this positive effect on treatment-resistant depression? Yeah.

• 33:21Lester Nare?

  Because the way in which it interacts with our brain is fundamentally different than, I can't remember what the terminology is for the kind of existing set of- Antidepressants? There's another like, there's another technical name for it, it's escaping me right now. No, I don't know. But, you know, all the Klonopin and all the stuff that people talk about in TV shows and things like that, which there's been a lot of both, there's been a lot of kind of pushback on what are the, while it might treat the dopamine or the serotonin piece, it has a lot of these other potentially negative consequences for people, but maybe there's a new path here. Super, super fascinating story. And we'll see where it goes early, like you said. Yeah, early, but very cool. But we need to be able to research a variety of different areas and explore

• 34:03Lester Nare?

  all opportunities in a controlled and safe environments, so we love to see that. Our last story of the day is our paleontology and ancient life story about life rebounding shockingly fast after the asteroid that killed the dinosaurs. This is out of University of Texas at Austin. It was published in Geology. And basically what they're saying is new research reveals that microscopic plankton, right? Began evolving into new species within just a few thousand years, possibly under 2,000, after the asteroid impact that killed the dinosaurs that we all remember from high school was 66 million years ago. And we all remember the amber.

• 34:46Lester Nare?

  From Dr. Hammond's staff in Jurassic Park where they extracted amphibian Dino DNA and merged it with amphibian DNA. But the idea here is that there was not an expectation that life after such a catastrophic impact would re-arise so quickly. It's an interesting way in which scientists have actually found this to be true.

• 35:07Krishna Choudhary?

  Yes, this is actually really cool. So, you know, 66 million years ago, an asteroid hit Mexico effectively and created the Chicxulpa Crater. All the dinosaurs died. There was massive extinction all over the planet. There was a bunch of climate change. It was pretty bad. And what this paper is suggesting is that within 2,000 years, there was a new species of plankton that had evolved. And 2,000 years is a blink when it comes to 66 million years ago, right? This is pretty insane. It's ridiculously fast.

• 35:40Lester Nare?

  Ridiculously fast.

• 35:42Krishna Choudhary?

  It is. And that's literally what Chris Lowry, who's the study's lead author from the University of Texas, he said, "It's ridiculously fast," is what he said. So earlier, they had done work where they had gotten samples from the Chicxulpa Crater around the Chicxulpa Crater. And you can figure out where the fossils are in the fossil record. And then you've got some kind of model for how fast sediment gets deposited. And so from that, you can figure out how old stuff is.

• 36:10Lester Nare?

  Yes.

• 36:11Krishna Choudhary?

  Right? Because the deeper you go, the older it is. And if you have some rate of how much sediment goes through, you can calculate, you can back calculate from where the boundary is. There's a layer of sediment from the meteorite all over the earth when the meteorite splashed in and like created that sediment in the atmosphere. So if that's our, you know, zero, 66 million years ago, from there, we can then figure out how fast fossils were coming up.

• 36:37Lester Nare?

  That's actually a good point in that because that impact. Surrounded the atmosphere and the planet with the ejecta from that impact. It's a it's a bookmark.

• 36:48Krishna Choudhary?

  Yeah.

• 36:48Lester Nare?

  In the sedimentary layers of it's a time bookmark.

• 36:51Krishna Choudhary?

  Yes.

• 36:52Lester Nare?

  Which that's actually interesting.

• 36:54Krishna Choudhary?

  It's actually cool, right? It actually took Luis Alvarez, who he's mentioned in the Oppenheimer movie. We're gonna do a special on all the scientists of the Oppenheimer movie and we're gonna rank them. You're gonna see where he falls, but Luis Alvarez. He's one of Lawrence's PhD students. And he actually later on in his life, he started doing lots of random stuff. Like he did this Chicksa Club crater thing. He also mapped the pyramids. Like, once he won his Nobel Prize in Physics, he was just doing side quests. And each side quest was like, wow, you know?

• 37:26Lester Nare?

  That's awesome.

• 37:27Krishna Choudhary?

  So anyways, um, so, so that's what we normally do, right? Now, that's built on an assumption, this, this whole sediment thing, right? You take the zero and then you you like figure out where the fossil is and where the sediment, how much sediment is. From that, it's it's built on the assumption that um, the rate at which sediment is deposited is the same before and after.

• 37:51Lester Nare?

  Okay.

• 37:52Krishna Choudhary?

  Now, that's not entirely true, right? Because if there's a giant mass extinction.

• 37:55Lester Nare?

  Right.

• 37:56Krishna Choudhary?

  All your trees are dead, all your plants are dead. There's gonna be more erosion, so there's gonna be faster sediment being deposited. So you might have an over or an underestimate on when actually these plankton got where they are.

• 38:08Lester Nare?

  That makes sense.

• 38:08Krishna Choudhary?

  So how do you resolve this discrepancy?

• 38:10Lester Nare?

  Yes.

• 38:11Krishna Choudhary?

  What they did was they used the radioactive isotope helium 3. This is an incredibly rare isotope. So already, this piqued my interest because helium 3 is incredibly rare. It's the, it's one of the most expensive substances on earth because helium 3 is used for very specific industrial applications. For example, if you have a, something called a dilution refrigerator, which is what you use to cool down things like quantum computers, you require a lot of helium 3 in order to do that. Helium 3 is two protons, one neutron, instead of normal helium 4, which is two protons, two neutrons, that's the more stable isotope. Here, you've got helium 3. That's an isotope, right? And if you look at the dynamics of helium 3,

• 38:53Krishna Choudhary?

  helium 3 actually accumulates in the ocean sediments at a steady rate. So when the sediment builds up slowly, you're gonna have higher concentrations. But if it's being deposited really fast, you're gonna have lower concentrations in that layer of sediment, whatever core that you drilled, right? So by looking at the relative abundance of helium 3 versus helium 2, or like whatever, not helium 2, obviously, but like, you know, other elements that it could decay into, we can figure out what was the rate at which the sediment was being deposited.

• 39:27Lester Nare?

  Because the helium 3's abundance level is correlated with the rate of sediment accumulation.

• 39:34Krishna Choudhary?

  Exactly, yeah. The faster it gets accumulated, the lower the density, right? Because it doesn't have enough time to really pile up. And so from that, they got the KP boundary location, you know, that layer of meteorite, like, layer. They got samples from that layer of sediment, all the way from Europe, North Africa, and the Gulf of Mexico. So all over the planet.

• 40:00Lester Nare?

  Yep.

• 40:00Krishna Choudhary?

  And they looked at this helium 3 data.

• 40:03Lester Nare?

  Yes.

• 40:04Krishna Choudhary?

  To figure out what was the sedimentation rate.

• 40:06Lester Nare?

  Yes.

• 40:06Krishna Choudhary?

  And from that, they actually figured out that the normal plankton species that we usually think about, it's called P. ujubina. I hope I'm saying that right. I don't really know how plankton is pronounced, honestly.

• 40:21Lester Nare?

  I think it's pronounced chum bucket.

• 40:23Krishna Choudhary?

  Yeah, yeah, exactly. Yeah, but this normal plankton species that we normally look for showed up about 3.5 to 11,000 years after the Chicxulpa, Chicxulub impact. So that's already pretty fast.

• 40:38Lester Nare?

  Yes.

• 40:39Krishna Choudhary?

  There were certain species, there were, that, there were certain species that appeared fewer than 2,000 years after the asteroid strike. And that's pretty ridiculous.

• 40:49Lester Nare?

  Yeah, no, that's very ridiculous.

• 40:50Krishna Choudhary?

  Right? Like 2000 years later, these guys are already like, wow, no one is alive. I have all the sun to myself.

• 40:58Lester Nare?

  Right.

• 40:59Krishna Choudhary?

  You know, like, so, so the speedy recovery shows just how resilient life is.

• 41:04Lester Nare?

  Yes.

• 41:04Krishna Choudhary?

  Right? To have, this is not, this is not like bacteria. This is plankton. So this is pretty complex life. Sure, it's still like, you know, single cell to fewer, not, not that many cells, but it's still, it reestablished itself within a geological heartbeat.

• 41:19Lester Nare?

  Yeah, which is, which is, I mean, it's unbelievable. And it's sort of, you know, there's all of the,

• 41:28Lester Nare?

  you know, when people look at the history of this planet and there's all these epics that are kind of opaque to us.

• 41:36Lester Nare?

  And, you know, how many times have we seen these either regional or global ecosystem collapses and then, you know, rebirths? And there could be a number of them. And given how quickly now we're seeing the recovery from the asteroid from 66 million years ago, introduced, again, simple life, but so quickly, it does recalibrate, you know, how you think about a variety of sort of the catastrophe scenarios you see in movies.

• 42:04Krishna Choudhary?

  Yeah.

• 42:04Lester Nare?

  Mother Earth will be okay.

• 42:06Krishna Choudhary?

  Yeah.

• 42:06Lester Nare?

  Humanity may not.

• 42:07Krishna Choudhary?

  Yeah.

• 42:08Lester Nare?

  But Mother Earth will be fine.

• 42:09Krishna Choudhary?

  Yeah.

• 42:09Lester Nare?

  And, and life will continue to find a way to live and prosper. I want to make a funny, not like a quick side note about helium 3, which is for anyone who's a fan of For All Mankind, the Apple TV show, that does the revisionist history about who got to space first and the moon first.

• 42:25Krishna Choudhary?

  Yeah.

• 42:26Lester Nare?

  Spoiler alert, one of the battles and one of the reasons for the permanent moon base location is the massive deposits of helium 3.

• 42:34Krishna Choudhary?

  Oh, okay, that makes sense.

• 42:35Lester Nare?

  Which then allows them to power all the stuff locally. And then if you have, and then there's all the movies where we run out of energy on Earth, we need to go to the moon to go get, I think also, that's part of the plot point in Don't Look Up was that there was helium 3 on the moon and the tech guy wanted to go mine it or some crazy nonsense.

• 42:53Krishna Choudhary?

  Yeah.

• 42:53Lester Nare?

  So it's like, it's one of those things people hear about in pop culture quite often. But not necessarily knowing real world applications. So this is a very interesting, maybe non-traditional use of, of, of the helium 3 isotope in terms of identifying. Fantastic. We love a dinosaur story. We hit AI, genetics, neuroscience, paleontology. We had a great round two of Are You Smarter Than a Scientist?

• 43:20Lester Nare?

  In the comments below, let us know if you would like to see us continue the game show. If you have a guest that you would like to join as a contestant, tag them in the comments and say you gotta be on this. And if you're still watching and you are a first time listener or a long time listener, this show is being able to be created and produced multiple days a week just with the two of us. And so your support is always super, super helpful for us to be able to continue to get the latest and greatest breaking science in a way that's digestible and entertaining for all those who are curious. So a like, share, a comment, bring it into the lunch, put it in your email listserv is super helpful.

• 44:01Lester Nare?

  As well as if you want to support us, you can go to our website at ffpod.com backslash donate and become a patron. Also, if you haven't checked out the website, all of the research papers we cover on every episode are right on that website. We have our episodes with chaptering and a whole bunch of features. So if you want to really dig in, if we've piqued your interest with any individual story, there's plenty to dig in and jump in on the website. I am Lester Nare, joined as always by my co-host and our resident PhD, Krishna Choudhary. Thank you all for joining us for another week and we will see you next week.