America 250: The Breakthroughs That Built American Science — Part 2 (EP 47)

Hosted by Lester Nare and Krishna Choudhary, this episode is part two of our July 4th America 250 special: a celebration of the scientific, technological, institutional, and cultural breakthroughs that helped shape the United States into one of the most important scientific nations in human history. In part one, we traced American science from Benjamin Franklin and the founding documents through Sputnik, NASA, DARPA, Bell Labs, the transistor, information theory, nuclear physics, molecular biology, and the birth of the modern American science state. In part two, we pick up after Sputnik and follow the explosion of American science from 1958 to today. This episode covers the visual system, solar wind, perceptrons, impact cratering, pacemakers, neurotransmitter reuptake, cochlear implants, the genetic code, quarks, Bell’s theorem, density functional theory, the fast Fourier transform, immigration policy, electroweak unification, ARPANET, Apollo 11, dark matter, MRI, GPS, Unix, gravitational waves, ozone depletion, lithium batteries, Voyager, RNA splicing, recombinant insulin, quantum computing, the Space Shuttle, prions, PCR, cellular networks, telomeres, laser cooling, backpropagation, the Hubble Deep Field, Deep Blue, Sagittarius A*, cosmic acceleration, the Human Genome Project, CRISPR, mRNA vaccines, reusable rockets, LIGO, transformer models, black hole imaging, quantum supremacy, and the James Webb Space Telescope. The larger story is not just that America produced extraordinary discoveries. It is that those discoveries came from an ecosystem: universities, national labs, government agencies, industrial research labs, immigrant scientists, public investment, basic research, private enterprise, and a culture that repeatedly turned curiosity-driven science into civilization-changing technology. The episode closes by connecting that 250-year legacy to the current debate over federal science funding and the future of American scientific leadership. Explore the interactive timeline ffppod.com/America250 Support the show Donate: FFPod.com/donate Follow: @FFPod on X / Instagram / TikTok / Facebook

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

• 0:00Lester Nare?

  Hello, Internet. This is your captain speaking, Lester Nare, joined as always by my co-host and our resident PhD, Krishna Choudhary. We are back for part two of our two-part special, celebrating America's birthday for this July 4th weekend, our 250th anniversary. And to celebrate, we are going through the history of science advancement in our country from birth to today. In part one, we ended at Sputnik, and we are going to continue discussing some of the greatest scientific advancements in areas like physics, biology, chemistry, medicine, as well as some of the institutional changes

• 0:44Lester Nare?

  that enabled the funding and talent to flow into our great nation that led us to have over 400 Nobel Prize winners in our young 250-year history. As always, we are going to talk about the science from the ground up today, because this is From First Principles.

• 1:19Lester Nare?

  So we are going to pick up where we left off in part one in 1958 during the Sputnik crisis, which led to the mobilization of American science across various agencies. And for those who are following along at home, if you would like to follow along with us, our interactive timeline for America 250 is available at ffpod.com/america250. So our next event is also in 1958, Decoding the Visual Cascade: From Retinal Photochemistry to Cortical Feature Detection.

• 1:58Krishna Choudhary?

  Right, so, you know, obviously, we see things as human beings, but before 1958, it was a bit unclear how images, right, the photons that are coming in into our eye, get translated into electrical signals and go all the way to the brain. Because at the end of the day, what needs to happen is photons need to get registered somehow, and then that needs to get processed into like objects and things like that, right?

• 2:25Krishna Choudhary?

  Biochemist George Wald at Harvard University discovered the molecular photochemistry of the retina. He found rods and cones and he figured out what is the chemical cascade that lets rhodopsin, which is the protein that gets a photon and then actually changes shape to register that it caught a photon. He discovered all of that. So it's really like this quantum biochemistry type stuff where, you know, nowadays we've got cameras with like little detectors. The silicon registers the photon and creates an electrical current. Well, now we've got the biological analog to that, which I think is really cool. That was in 1958. He earned the share of the Nobel Prize in 1967.

• 3:09Krishna Choudhary?

  And then later on in 1959, just a year later, Hubel and Wiesel, also at Harvard, discovered cortical feature detection. What they were doing was looking at the visual cortex of cats and they noticed that certain neurons would only fire when a bar, a little dark bar in a white background, a black bar, was oriented in a certain direction. Like the neurons would only fire when the black bar was at this angle and not at any of the other angles. So you've got like now higher order feature detection happening in the retina. And they figured out what types of neurons? How do we get that type of feature detection?

• 3:51Krishna Choudhary?

  If we string together multiple neurons into a single neuron and create this type of object feature detection, right? This is the precursor to not just understanding the neural system and our brain, but also to later theories about how to use this for artificial neural networks. Because at the end of the day, artificial neural networks take a bunch of neurons, they input into one neuron and layer by layer create more and more complexity.

• 4:20Lester Nare?

  Right? Yep.

• 4:21Krishna Choudhary?

  So huge, huge thing. The Hubel and Wiesel won the Nobel Prize in 1981. All of this stuff is now in textbooks.

• 4:28Lester Nare?

  Hundred percent. We're still in 1958 with theorization of the solar wind.

• 4:35Krishna Choudhary?

  Yes, this is near and dear to me because my father is a solar physicist and this is one of his great.

• 4:43Krishna Choudhary?

  You know, seminal papers in America. So this, this one, shout out to my dad. He actually told me to put this in there. This was Eugene Parker at the University of Chicago. He published a landmark paper at, in the Astrophysical Journal, where he theoretically predicted that there should be something like the solar wind. He looked at the corona and the fact that the corona is millions of degrees Kelvin. And he said that this is not something that can be sustained just around the sun. There has to be an offshoot. The corona needs to be extending its atmosphere all the way to Earth and all the way out into space. It was later confirmed in 1962 by NASA's Mariner 2 mission. And when he published, when he submitted this paper to the Astrophysical Journal,

• 5:26Krishna Choudhary?

  Subramaniam Chandra Shaker, who is the great physicist Nobel Prize winner for the white dwarf limit, he was the editor and he sent it out to referees or he, he sent it out to, you know, yeah, the, the referees to like give feedback. And the referees came back being like, the math is correct, but this can't possibly be true. I think this guy needs to look at basic solar physics to figure out what went wrong. And it was scathing, scathing remarks. Turns out, turns out he was all right.

• 5:56Lester Nare?

  It's also, Chandra Shaker, also known as the Thunder Shaker, was referenced in, I believe it was your interview with Dr. Michael Blanton.

• 6:05Krishna Choudhary?

  Yes.

• 6:05Lester Nare?

  Um, in one of the NASA space-based detection platforms. We are moving on to still in 1958, invention of the perceptron.

• 6:16Krishna Choudhary?

  Yes. This is the building block of every artificial neural network. It started here in 1958 by Frank Rosenblatt at the Cornell Aeronautical Laboratory. He developed this neural network hardware, actually. So it was hardware, not software at the time, where you've got these nonlinear units that are artificial neurons that get signal and only fire to the next round if that signal.

• 6:44Krishna Choudhary?

  Goes above a certain threshold, just like normal neurons do, but a very, very simplified form. It's the foundation of modern feed forward neural networks.

• 6:54Lester Nare?

  Which are all around us today. We're moving to astrophysics in 1960. Proof of impact cratering.

• 7:02Krishna Choudhary?

  Yes. We talk about the meteor crater in Arizona a lot on this podcast. In 1960 was when Eugene Shoemaker first confirmed that the meteor crater came from a meteor and it wasn't some innate geological feature of Earth. Before this, there was a lot of doubt about whether meteors, even in recent times, would come and strike planets. The meteor crater in Arizona is less than 100,000 years old. Okay, so it's quite recent in the geological time scale. He discovered like shocked quartz and all of these other geological features that could only have happened if there was a meteorite coming into Earth.

• 7:47Krishna Choudhary?

  Very big deal.

• 7:49Lester Nare?

  1960, discovery of spontaneous symmetry breaking.

• 7:54Krishna Choudhary?

  Yes, this was theoretical physicist Yochiro Nambu. He introduced the concept of spontaneous symmetry breaking in quantum field theory at the University of Chicago. Basically, this is the foundation for a lot of subsequent work that was done in quantum field theory. For example, the Higgs mechanism that gives us the Higgs boson and things like that. That uses symmetry breaking in the same way that Yochiro Nambu was talking about. And for all of those who are theoretical physicists in the audience, you will recognize the Mexican hat potential on the right hand side. That is literally what we call it. I mean, it's a radially symmetric potential that looks like a Mexican hat.

• 8:37Krishna Choudhary?

  And that is the same type of mechanism that gives.

• 8:42Krishna Choudhary?

  You know, things like the W and Z bosons mass through the Higgs mechanism. This was the genesis of that idea.

• 8:48Lester Nare?

  There's a lot of Mexican hat potential for the upcoming England Mexico match at the Azteca, but we are moving on to another 1960 invention of the implantable pacemaker, a big one.

• 9:00Krishna Choudhary?

  This is big, right? Just for human longevity or medicine in general. Electrical engineer Wilson Greatbach and thoracic surgeons William Chardak and Andrew Gage. They invented and successfully planted the first totally self-contained cardiac pacemaker at the University of Buffalo. This has saved countless lives and it's pretty self-explanatory, right? You now wear this thing and it keeps your heart going.

• 9:29Lester Nare?

  Just to keep the World Cup references going, there is a player who has had heart issues, who has the pacemaker that was activated during this World Cup.

• 9:39Krishna Choudhary?

  Wow, really?

• 9:40Lester Nare?

  Yes, on the field and it was implanted because he had had a cardiac issue previously. It might not be specifically a pacemaker. It might be a more specific technical device.

• 9:48Krishna Choudhary?

  Yeah, yeah, yeah. But the genesis of those types of wearable, you know?

• 9:52Lester Nare?

  Exactly. The idea that you could have an implant.

• 9:55Krishna Choudhary?

  Yeah.

• 9:56Lester Nare?

  Related to your heart started in 1960, 1961, discovery of neurotransmitter reuptake.

• 10:04Krishna Choudhary?

  Yes, we've heard about SSRIs, selective serotonin reuptake inhibitors. That's what this is talking about. It's the idea that when neurons talk to one another, they release little chemical signals in their synapse, right? And that's how those junctions work. Now, when you release neurotransmitters, you can imagine that you're going to flood this little gap with a bunch of chemicals. Well, how come that junction doesn't remain on the whole time? It's because of reuptake, the idea that you dump these chemicals and then the nerve has a way to bring the chemicals back out of that synaptic cleft.

• 10:44Krishna Choudhary?

  And so the talking between neurons can be a very fine time resolution thing. It doesn't go on. For a really long time. I mean, this transforms psychiatric medicine and neuropharmacology because it provides a direct mechanical foundation for modern antidepressants, anti-anxiety medications like the SSRIs that I'm talking about, that modulate this concentration of neurotransmitters in the synaptic cleft. Huge deal.

• 11:12Lester Nare?

  Almost like a neurological version of the riptide. When you're at the beach and it goes out.

• 11:17Krishna Choudhary?

  Yes.

• 11:17Lester Nare?

  And then it comes back in.

• 11:18Krishna Choudhary?

  And it won the 1970 Nobel Prize in Physiology and Medicine.

• 11:23Lester Nare?

  1961 invention of the cochlear implant and skull-based microsurgery.

• 11:28Krishna Choudhary?

  Yeah, again, another self-explanatory little bit of medical device. Otolgist William House, neurosurgeon Robert Rand, and engineer Jack Urban. They pioneered a skull-based microsurgery and an auditory prosthetic in Los Angeles, California. It's huge because, you know, this gives you the ability to reverse deafness in certain individuals. They started using it very quickly on, you know, children and it's been used ever since.

• 12:04Lester Nare?

  The medical inventions are really, really fascinating. The history of that. 1961, cracking the genetic code.

• 12:11Krishna Choudhary?

  Right, so we know about DNA and we know that DNA somehow makes enzymes and proteins, right? And previous iterations of our timeline have talked about how there's the one gene, one enzyme hypothesis, meaning that the gene creates a single enzyme. But now, we've got to go from the DNA alphabet, which is A, T, G, and C. Those are the nucleic acids. We've got to go from that alphabet and translate it to amino acids, which there's 20 of. We've reviewed this before about how you take three

• 12:48Krishna Choudhary?

  you take three of those nucleotide bases and you create a single amino acid because you need four times four times four to get to 64. If you only have four times four, that's only 16. Carbonatorically, you need three to create a single. Codon is what it's called.

• 13:03Lester Nare?

  Yes.

• 13:03Krishna Choudhary?

  And that code of how to get from DNA to proteins was discovered by these three individuals, biochemists Marshall Nirenberg, Hergobind Corana, who's of Indian descent, and Robert Hawley. They deciphered the universal genetic code at NIH in Bethesda, Maryland, and at the University of Wisconsin Madison and Cornell University. They earned the 1968 Nobel Prize in Physiology and Medicine.

• 13:30Lester Nare?

  And another example of why these bureaucratic national institutions like the NIH are relevant in combining with the university ecosystem, which we also talked about in part one, and how that became a huge enabling layer for many of these discoveries. The Eightfold Way and the Quark Model.

• 13:50Krishna Choudhary?

  Yes. This is kind of a cute name, the Eightfold Way. Murray Gell-Mann at the California Institute of Technology, Caltech in Pasadena, he was worried about why protons and neutrons have the same mass but weigh different charge. Seems like there's something inside, right? Seems like there might be some constituents that together make up the same mass, but because of their identity, create the different charge. The proton having a positive charge, the neutron having a neutral charge. He figured out the Eightfold Way and he introduced this Quark model. And he organized the particle zoo using SU3 symmetry, which is a type of rotational symmetry, has to go back to Yang Mills and things like that.

• 14:35Krishna Choudhary?

  And he earned the 1969 Nobel Prize in Physics. I want to do a deep dive on just Murray Gell-Mann and his beef with Richard Feynman, because they were both at Caltech Physics and they both hated each other. And I think Murray Gell-Mann, for good reason, like there's stories of like... Feynman making fun of Galman for washing his hands after using the bathroom. And he's like, oh, you're just one of those, you know, you know, those non-thinker types.

• 15:03Lester Nare?

  The woke non-thinker.

• 15:04Krishna Choudhary?

  Yeah, yeah, you're one of, you're just one of those, you know, the NPC is effectively what he said. Like, you don't think for yourself. It's like, dude, I'm just washing my hands after I pee. Anyways, it's quite hilarious. Murray Galman, Caltech, won the Nobel Prize in 1969.

• 15:21Lester Nare?

  We do like to talk about first principles and sometimes that interacts with academic beef, which we both have an appetite for. We're moving to 1962, invention of DC cardioversion and the AED.

• 15:34Krishna Choudhary?

  Yes. Cardiologist Bernard Loan and engineer Baru Berkovitz, they invented the direct-current synchronized cardioversion at the Harvard School of Public Health, Harvard Medical School at Boston, Massachusetts. They basically paired a timed DC pulse with an inductive capacitor circuit, and it gives you the defibrillator.

• 16:00Lester Nare?

  Yeah.

• 16:00Krishna Choudhary?

  This is the origin of the defibrillator.

• 16:02Lester Nare?

  Defibrillator.

• 16:03Krishna Choudhary?

  And you can see on the left, that's the first defibrillator. It's got these like two little leads that you put on. And nowadays, you know, it's used in every single emergency kit all over the world.

• 16:14Lester Nare?

  I think it's in every airport, stadium.

• 16:16Krishna Choudhary?

  Yeah, yeah.

• 16:17Lester Nare?

  You see them on the walls.

• 16:18Krishna Choudhary?

  You can also have one like personalized in your house. Like, this is huge.

• 16:21Lester Nare?

  We're moving forward to 1963, independence of the continuum hypothesis.

• 16:27Krishna Choudhary?

  Yes, this is a math one, but I kind of know something about it.

• 16:31Lester Nare?

  Okay.

• 16:31Krishna Choudhary?

  This was mathematician Paul Cohen. He invented the technique of forcing at Stanford University, and he demonstrated that the continuum hypothesis is independent of Zermelo-Frankel set theory.

• 16:44Krishna Choudhary?

  The continuum hypothesis has to do with sizes of infinity. For example, like the natural numbers, 1, 2, 3, 4, 5. Naturally, you can count them, right? You can be like, 1 is the first one, 2 is the second one, so on and so forth. If I were to ask you, um, are there more natural numbers than even numbers? Naively, you would say yes, because, you know, even numbers don't have 1 and 3 and 5. But there's infinite of both. So it's not really a good argument to say that there's more of the natural numbers when both are infinity. In fact, what I can do is I can count all the even numbers. I can say 2 is the first one, 4 is the second one, 6 is the third one. And now I have a one-to-one mapping, right?

• 17:28Krishna Choudhary?

  So for every single natural number, there's an even number, which means they're really the same size of infinity. It turns out, um, George Cantor discovered, um, way back, that even rational numbers, so fractions, you can imagine fractions seems like there's more fractions than natural numbers, because you've got, even for just the number 1, I can make 1 half, 1 third, 1 fourth, 1 fifth, 1 sixth, right? I can, I can make an infinite number of rational numbers that are just corresponding to the number 1. But it turns out, there's a schema for counting the rational numbers, such that every single one has a one-to-one mapping to the natural numbers. So rational numbers are the same size of infinity as the natural numbers. What about real numbers?

• 18:11Krishna Choudhary?

  Things like pi, or e, or, ah, pi squared, you know? Turns out, those you cannot count. George Cantor proved that as well. So the continuum hypothesis is, you've got 2 sizes of infinity. You've got the size of the natural numbers, which is countable, and then you've got the size of the real numbers, which is uncountable, meaning there's no way that I could assign, like, this is the first real number and the second. The continuum hypothesis is, is there something in between? Is there a size of infinity that is intermediate? Yep. Um, the hypothesis is no.

• 18:45Krishna Choudhary?

  And he proved this very specific thing, saying that it's independent of this certain type of set theory. It resolved Hilbert's first problem and earned him the 1966 Fields Medal. This is a big one. I mean, America has a lot of Fields Medals. I picked this one partially because I kind of understand it, and partially because in a lot of the lists, this is a big one.

• 19:06Lester Nare?

  Hilbert had a whole lot of problems that seemed to be getting solved over the course of this list. 1963, Atya Singer, index theorem?

• 19:18Krishna Choudhary?

  I think Atiya, maybe?

• 19:19Lester Nare?

  Atiya Singer?

• 19:20Krishna Choudhary?

  This was Michael Atiya and Isidore Singer at the Institute for Advanced Study. They proved the index theorem, bridged topology and elliptic differential operators. I know what topology means. I don't know what the other one means, but apparently unified geometry and analysis. I know what analysis means. Geometry, I kind of know what it means, but I don't think I know in this context. Anyways, they earned the 2004 Abel Prize in Mathematics, which is the real Nobel Prize in Mathematics, and apparently a very big deal.

• 19:51Lester Nare?

  As we referenced in our part one as well, 1964, the famous 1964, discovery of CP violation.

• 19:59Krishna Choudhary?

  Yes. This is the second layer to the parity violation stuff that we were worried about in that first lecture, and we had a huge deep dive in the Shending Young episode last year. The idea of parity violation is, is the universe symmetric in the mirror? Is the universe the exact same in the mirror? Turns out it's not, because the universe can tell whether I'm left or right based on whether the thing that is shooting out of the nucleus is an electron or an anti-electron. So perhaps antimatter and parity are together asymmetry. That's the next idea, right? It's like, what if I, what if I flipped everything in the

• 20:42Krishna Choudhary?

  universe from left to right, but I also flipped all of the matter to antimatter? Then, would the universe not be able to tell the difference? That was called CP symmetry. This experiment showed a violation of that symmetry as well. So it showed that antimatter and matter are really not the same thing. This was James Cronin and Val Fitch. They were working at Brookhaven while employed at Princeton University. So they were professors there. And they demonstrated that the weak interaction violates charge parity symmetry. Won them the 1980 Nobel Prize in Physics.

• 21:16Lester Nare?

  These are some of my most favorite episodes, the Channing Young, Young Mills episode. And these ideas of symmetries are really, really deep philosophical as well as grounded scientific things. It's fascinating. 1964, prediction of the cosmic microwave background, the CMB.

• 21:35Krishna Choudhary?

  Yes, so the Big Bang happened, right? According to at least every astronomer, right? Up until that point, but the way that people were thinking about the Big Bang was the same style as Edwin Hubble. Edwin Hubble had figured out the, that the galaxies go away from us, right? And the farther out the galaxy is, the faster it's moving. So that means that the universe is expanding. Well, I just turn back the clock. If the universe is expanding, at some point in the past, it was smaller and smaller and smaller, all the way down to the point. So there should have been a point where the universe was exceedingly small and then it blew up into the Big Bang.

• 22:13Lester Nare?

  Right.

• 22:14Krishna Choudhary?

  Theoretical astrophysicist Jim Peebles and Robert Dickey at Princeton University predicted that if that were to have happened, there should be something like a cosmic microwave background. Meaning there's leftover radiation from the Big Bang itself. There's a bunch of energy that was released and all of that should take the form of light. It should take the form of light at millimeter wavelengths and have a temperature of about three Kelvin. They were on their way to creating the necessary radio antenna to measure this when down the street at Bell Labs, Penzias and Wilson were trying to figure out what was going on.

• 22:57Krishna Choudhary?

  And that is for the next one, because this is a prediction, right?

• 23:01Lester Nare?

  Yes.

• 23:01Krishna Choudhary?

  And this is showing that.

• 23:04Krishna Choudhary?

  They could predict that there was a cosmic microwave background. Jim Peebles won the 2019 Nobel Prize in Physics because Penzias and Wilson won the real Nobel Prize back in the day for discovering the cosmic microwave background at Bell Labs. Robert Dickey didn't get the Nobel Prize very controversially. And I think after all those years, as a nod to Robert Dickey and his work, Jim Peebles won the Nobel Prize as well.

• 23:27Lester Nare?

  It's interesting, the timing difference there for the discovery versus the prediction. Who really deserves it more, the one who predicted or the one who discovered?

• 23:34Krishna Choudhary?

  Yeah.

• 23:34Lester Nare?

  But 1964, we have the formulation of Bell's theorem.

• 23:38Krishna Choudhary?

  Yes. Everyone thinks that John Stuart Bell, the theoretical physicist behind Bell's theorem, was always at CERN. But his day job was at CERN. He actually took a year sabbatical and he traveled America. He researched at Stanford University and the University of Wisconsin. And during this sabbatical, he published his most famous paper called Bell's theorem. He derived a mathematical inequality that said, there could be an experimental way to disprove Einstein's EPR paradox. Okay, Einstein said that there should be some hidden variables inside of the universe that create this spooky action at a distance. It's not actually real.

• 24:21Krishna Choudhary?

  Okay, there's actually stuff that's saved when I send a particle this way and its partner the other way. So that when I measure, you know, when I get this like weird correlation, that's just because there's something saved. And so there's nothing like happening, right? Bell said, well, not too fast, right? Actually, if I measure two different observables that can't be measured simultaneously.

• 24:43Lester Nare?

  Yes.

• 24:43Krishna Choudhary?

  For example, the spin this way and the spin the other way. Then I should be able to figure out correlations within these that can only be explained if the wave function is truly collapsing in this weird.

• 24:57Krishna Choudhary?

  Quantum wave, or if the, you know, many worlds hypothesis is correct or whatever. I mean, we don't know which hypothesis of quantum mechanics is correct, but we can certainly rule out hidden variables that are local to whatever is happening within these particles. This was huge.

• 25:12Lester Nare?

  Big deal. Let us know in the comments if you think we should care about the quantum wave function collapsing or not. Are you a many worlds person or not?

• 25:21Krishna Choudhary?

  Or do you think it's just a philosophy thing?

• 25:23Lester Nare?

  Yes. Yes. Is it meaningful or is it philosophical? We're moving over to 1965, development of density functional therapy, excuse me, theory.

• 25:34Krishna Choudhary?

  Yes. This was theoretical physicist Walter Kohn. He developed density functional theory at UC San Diego. Effectively, before, when we were trying to use computers to do quantum simulations, we'd have to worry about every single electron ever in our system. Now, that can quickly become super stupid. Okay? And he figured, why don't I replace that multi-dimensional wave function with something like an electron density, which is there's parts of the system that I can assume to be static, right? Like maybe the atoms don't move around that much. So all of the electron clouds can effectively be blurred out electron densities.

• 26:19Krishna Choudhary?

  And then whatever thing is dynamic, that's the part that I worry about in my simulation. Seems trivial, but you gotta, you gotta be careful when you do that, right? This enabled complex quantum chemical modeling and it earned him the Nobel Prize in 1998 in chemistry.

• 26:36Lester Nare?

  1965, we have the invention of the fast Fourier transform, which again is a topic we've covered previously on the show.

• 26:44Krishna Choudhary?

  Yes. The Fourier transform is this idea of taking signal in the time domain. For example, you've got a microphone, I speak into it. The microphone vibrates based on the sound waves that are coming. And then from that vibration, I can then play it back on the speaker. The speaker will simply imitate what the vibration is. Now.

• 27:07Krishna Choudhary?

  Doing that is, is, is gonna be quite expensive data wise. Because I've got to send all of that data, right? It would be really nice if we could decompose that time signal into a frequency. For example, you know, when I, when I, when I play a chord on a piano, one way to send all of that sound data is to send the microphone data. Or I could just send the notes that I played on the piano, the frequencies that I played. It's a way cheaper way of sending information. And in order to do that, you'd like to do a Fourier transform. Now notoriously, this thing is extremely expensive to do computationally. Mathematicians John Tukey and James Cooley

• 27:49Krishna Choudhary?

  developed the fast Fourier transform at Princeton University. And they reduced that computational complexity to something that was totally manageable. The complexity went from order of n squared to n over log n, n, n log n, which is, which is way lower, like n squared goes like this. And log n kinda goes way, way slower when it comes to like large n. And it launched modern digital signal processing. This is probably the most used algorithm in the entire world, if I'm completely honest. Because no one's made a better way to do a Fourier transform fast.

• 28:26Lester Nare?

  Except for the guys at Pied Piper in Silicon Valley. 1965, Immigration and Nationality Act, the Hart-Seller Act.

• 28:36Krishna Choudhary?

  Yes, 1965, this thing abolished discriminatory national origin quotas. And it shifted immigration policy to prioritize skilled labor through like numerical limits that we now see, per-country caps now, you know, they, they create friction. Now we've got a new way of, of doing immigration, which is like, we want the best in the world.

• 29:02Lester Nare?

  The best people.

• 29:02Krishna Choudhary?

  This, this, this created a huge, huge, like unlock for American industry and American research moving forward. And we're gonna see its effects as we go through the timeline.

• 29:13Lester Nare?

  And we are back to debating this exact point in. Our modern context, which is why it's important to know your history. 1967, Electro Week Unification.

• 29:25Krishna Choudhary?

  Yeah, the the story of physics is always the story of unification. It's trying to take all of the disparate phenomenon that we see in the universe and distill it down to the fewest rules and the fewest constituent parts that we can think of. The great big unification in the late 1800s was by James Clerk Maxwell. He discovered that electricity and magnetism are the same thing, electromagnetism. And he came up with the four Maxwell's equations that define everything that has to do. The second big one is this one, okay? This one showed that electromagnetism and the weak nuclear force, which is something that we thought is just related to beta decay, right? The fact that a neutron will spit out a neutrino, an electron, and a positron,

• 30:10Krishna Choudhary?

  or a proton, an electron, and an anti neutrino. And these little processes are limited to the nucleus itself. It turns out that beta decay, which is governed by the weak nuclear force, is the same force as electromagnetism. It was unified into Electro Week by theoretical physicists Sheldon Glashow and Steven Weinberg at Harvard and MIT. They won the 1979 Nobel Prize in Physics.

• 30:37Lester Nare?

  And we are still on the journey for a grand unified theory, but we are moving to 1968, the mother of all demos.

• 30:45Krishna Choudhary?

  Yeah, this one's pretty interesting. This was computer scientist Douglas Engelbart. He presented the mother of all demos in San Francisco, California during a presentation. Like, he was giving a talk. This is pretty huge and way ahead of its time. He debuted the computer mouse, hypertext, video conferencing, windowed user interfaces, and it laid the structural blueprint for modern personal computing. Way ahead of his time. None of it was real, but he was saying, this is what we are capable of, guys.

• 31:22Lester Nare?

  This is, this is crazy because it literally all, we still use all of those things literally right now.

• 31:27Krishna Choudhary?

  Yeah.

• 31:27Lester Nare?

  And today, and this is the prototype for the Steve Jobs demo format.

• 31:32Krishna Choudhary?

  Yep, yep.

• 31:32Lester Nare?

  That made Apple famous.

• 31:34Krishna Choudhary?

  Yeah, I mean, this is what inspired, this is what inspired Apple Macintosh, Microsoft Windows, the World Wide Web, all of it.

• 31:41Lester Nare?

  We're still in 1968, the discovery of quarks.

• 31:44Krishna Choudhary?

  Right, so Murray Gell-Mann had theorized quarks.

• 31:49Krishna Choudhary?

  Here, physicist Jerome Friedman, Henry Kendall, and Richard Taylor proved that quarks are actually a thing using deep inelastic scattering experiments at SLAC, the Stanford Linear Accelerator.

• 32:03Krishna Choudhary?

  It earned them the 1990 Nobel Prize in Physics. Over there, you see a photo of like the apparatus that they used at SLAC. It's a giant room and they have these giant catchers. Okay, particles are coming through and you can see the catching experiment that is showing that when you probe the inside of the nucleus, inside of a proton, there's stuff that's happening inside the proton that is inelastic. Meaning it's not just like billiard balls. There's stuff that's going on that's causing stickiness and a little bit of weird momentum transfer. There's gotta be stuff inside.

• 32:39Lester Nare?

  This is not the last level we can go down in the maze. 1968, detection of solar neutrinos.

• 32:47Krishna Choudhary?

  Yes, so this was physical chemist Raymond Davis, Jr. He detected solar neutrinos at the Home State Gold Mine Experiment in South Dakota for Brookhaven National Lab. They got a mine in South Dakota and they filled it with a giant physics experiment to look at the sun and look at the neutrinos from the sun. Because the proton-proton chain, which was devised by Hans Bethe way back then for how the sun shined, that showed that not only should the sun be creating photons, the light that we see, but also neutrinos. John Bacall at Princeton University, he was calculating the number of protons that were coming through. And Raymond Davis at the Home State Gold Mine Experiment,

• 33:30Krishna Choudhary?

  and there you see the photo of both John Bacall and Raymond Davis. He was catching only a third of these neutrinos. And for the longest time, it was like, who's wrong? Is the experiment wrong? Is John Bacall wrong in his calculations? Everyone checked both. They're both all right. Turns out, this was the discovery that neutrinos come in three flavors and they change flavor on the way from the sun to the earth. And that's why I'm only catching a third, because I was only sensitive to a third of the neutrinos. On top of that, so he won the 1995 Nobel Prize. In 2002,

• 34:03Krishna Choudhary?

  So Davis won the 2002 Nobel Prize, I should say. And in 1956, Frederick Rhines won the Nobel Prize for the discovery of the neutrino itself. That was at UC Irvine.

• 34:13Lester Nare?

  This is what laid the foundations for the ice cube neutrino detector in Antarctica, which we've also covered in a previous episode because we need to know all three flavors. It's a Neapolitan ice cream of neutrinos.

• 34:26Krishna Choudhary?

  Yeah.

• 34:27Lester Nare?

  1968 to 1970, viral integration and reverse transcription.

• 34:32Krishna Choudhary?

  Yes, this is virologists Renato Del Buko, David Baltimore, and Howard Temin. They unmasked how tumor viruses, which had been discovered earlier by another American earlier on our list, they alter host cell DNA by integrating their own genetic material into the DNA. But how is that possible if some of these viruses are made out of RNA? Well, it turns out there's this thing called reverse transcriptase that upends the central dogma model where DNA only goes to RNA. It turns out reverse transcriptase can take RNA back to DNA. This was at the Salk Institute, MIT, and University of Wisconsin-Madison. It earned them the 1975 Nobel Prize in Physiology.

• 35:15Lester Nare?

  Another topic we've covered a lot on the show. 1969, discovery of antibody structure.

• 35:22Krishna Choudhary?

  Yeah, we all know what antibodies are. There are so many episodes that we talk about antibodies. This is the bread and butter of how our immune system recognizes foreign threats. The structure of that antibody, it's always depicted as a Y. There's a part that is stationed within the cell, and then there's two protruding parts that change shape in order to discover all of the pathogens that are coming in. Immunologist Gerald Edelman at the Rockefeller University in New York City, he discovered this molecular structure of antibodies, which is now ubiquitously known in all of the textbooks. He'd received the 1972 Nobel Prize in Physiology.

• 36:03Lester Nare?

  Another quick turnaround. We love these quick Nobel turnarounds. This one was good. We're gonna give him the Nobel immediately.

• 36:08Krishna Choudhary?

  Yeah, this one, because everyone was after it. Everyone knows what antibodies are. Nobody knew exactly how all these antibodies can recognize so many different things. There you go.

• 36:17Lester Nare?

  Immediate, immediate. Now, one of the things we also talk about on this pod a lot. 1969, invention of the CCD image sensor, the basis for all of our tools we look into the cosmos with.

• 36:31Krishna Choudhary?

  Yes, and not just into the cosmos, you know, the cameras that we have normally. CCD's CMOS is basically the same thing. It's this idea of using silicon and using hardware to detect light. Physicists Willard Boyle and George E. Smith at Bell Labs in New Jersey, they invented the charge coupled device, and it utilized basically the photoelectric effect to localize charge packets within silicon. So now I can just print a chip, and that can be my light sensor. Ushered in the first digital image sensor, and the digital imaging age earned them the 2009 Nobel Prize in Physics.

• 37:13Lester Nare?

  Unbelievable. We now go to 1969, the birth of what is allowing us to talk to all of you today, the invention of ARPANET.

• 37:24Krishna Choudhary?

  Yes, which led to the Internet. This was computer scientist Leonard Kleinrock and his team. They established the first node at UCLA in Los Angeles, California, and they successfully executed the first packaged packet switched data transmission. And over there on the right, on the left hand side is the architecture of ARPANET, and how you send these digital packets from one computer to the other. On the right hand side, it shows the growth of ARPANET. On the upper, upper left of that map, it's just got like LA, the Bay Area, and Utah randomly. Pretty soon, though, the entire country was rigged up, and pretty soon, the entire world.

• 38:04Lester Nare?

  Los Angeles is not only the birth of Hollywood, it is the birth of the Internet.

• 38:09Krishna Choudhary?

  That's right.

• 38:09Lester Nare?

  1969 is a very big year because we also have the Apollo 11 moon landing.

• 38:14Krishna Choudhary?

  Yes. What else is there to say? We put a man on the moon.

• 38:19Lester Nare?

  Moon.

• 38:19Krishna Choudhary?

  Apollo 11 mission with Neil Armstrong and Buzz Aldrin, with Michael Collins in tow around the moon. It completed this historic voyage, watched by millions. It's a spectacular engineering triumph for all of humanity, and it marked humanity's first step on another celestial body. There's nothing much more to say.

• 38:42Lester Nare?

  Nothing more to say, nothing more to say. We are moving into the 70s psychedelic. 1970 to 1971, the discovery of restriction enzymes and DNA mapping. Again, we're seeing this progression over the course of part one and part two of our understanding of this fundamental.

• 38:59Krishna Choudhary?

  Yeah.

• 39:00Lester Nare?

  Piece.

• 39:00Krishna Choudhary?

  Exactly. We're getting better and better at manipulating DNA now. This is microbiologists Hamilton Smith, Daniel Nathans, alongside Kathleen Dana, who did not win the Nobel Prize in 1978, the other two did. They discovered site-specific restriction enzymes, meaning I've got a piece of DNA, now I've got an enzyme that will look for a very specific code in that DNA, recognize it, and then cut it. Huge for genetic engineering. They used this very, very nice tool to map the SV40 viral genome at Johns Hopkins University in Baltimore, Maryland. It's the first time that we've actually mapped the entire genome

• 39:44Krishna Choudhary?

  of anything. In this case, it was a virus, but still, huge deal. Starts the race to map everything else.

• 39:50Lester Nare?

  And we will be coming to future aspects of that race later in the timeline. 1970, observational proof of dark matter.

• 40:00Krishna Choudhary?

  Right. So Fritz Vicky at Caltech had already figured that there should be something like dark matter when he was looking at the coma cluster and he saw these galaxies moving around way faster than they should, meaning something should be pulling them that we can't see. Perhaps it's dunkelmata, or dark matter. Well, here astronomers Vera Rubin and Kent Ford at the Carnegie Institution in Washington, they measured the galactic rotation curve, which is how fast are stars moving around the galactic center? If they should follow Newton's laws and Kepler's laws, then like all the planets, They should move slower the farther I get out. That's not the case. They're moving at just the same speed, which means there's more and more dark. There's more and more matter that we're not seeing that should be there.

• 40:44Krishna Choudhary?

  It's kind of the first definitive proof that there's gotta be something like a dark matter halo around galaxies.

• 40:51Lester Nare?

  We have two great episodes that relate to this. Our interview with Dan Gillman around dark matter as a dark matter researcher. And our breakdown of the Vera Rubin Observatory, which is now online and changing our understanding of the cosmos. 1970 discovery of synaptic plasticity.

• 41:11Krishna Choudhary?

  Yes. Um, you know, we've heard about Hebbian learning, which is like, you know, neurons that fire together, wire together. This is how neural networks learn things. Um, neurons that are correlated, the synapses should get bigger. But how exactly does that happen? From a biochemistry perspective, this is neurologist Eric Kandel at New York University. He discovered the cellular and molecular mechanisms of memory storage. How these synapses get big to store memories. He demonstrated learning plasticity, meaning the, the, the changing nature of synapses by working with Aplegia Californica, which is basically the sea slug. Again, model organisms are super important.

• 41:56Krishna Choudhary?

  He chose this model organism because the synapses are massive. You can just see them with a light microscope. And in fact, some of them you can see with the naked eye. Like the, the, the synapses themselves are massive. So, you know, it, it leads to readily probe for experimentation. You know what I mean? He won the 2000 Nobel Prize in Physiology and Medicine.

• 42:22Lester Nare?

  1970 resolution of Hilbert's 10th problem. We're knocking them down.

• 42:26Krishna Choudhary?

  Yeah, yeah. One by one, Hilbert's problems are going down. I don't know anything about Hilbert's 10th problem. I'm going to be honest, but apparently it's a big deal that we resolved it. This was mathematician Julia Robinson at UC Berkeley, Martin Davis at NYU and Hillary Putnam at MIT. They spearheaded this. foundational mathematical and logical framework that proved Hilbert's 10th problem undecidable and demonstrated that no general algorithm exists to determine the solvability of the Diophantine equations.

• 42:57Lester Nare?

  If you have an explanation and you want to put it in our comments, please let us know.

• 43:03Krishna Choudhary?

  Yeah, cuz I'd like to know.

• 43:04Lester Nare?

  We'd like to know the solution, the resolution, Hilbert's 10th problem, 1971, renormalization group theory.

• 43:13Krishna Choudhary?

  Yes, this is near and dear to me. This is in statistical mechanics. Theoretical physicist Kenneth Wilson formulated the renormalization group theory at Cornell University, and he provided a mathematical framework to analyze critical phenomenon and phase transitions. This is the stuff of how magnets work at low temperatures, or how gases and liquids behave at that critical point. It turns out there's something called universality, meaning gases of any type, if you look at how they behave in the critical point, when they have this critical phenomenon, they all behave exactly the same regardless of the constituents of the material.

• 43:54Krishna Choudhary?

  He proved some very deep things about like, it matters the dimensionality of your parameter. For example, if the parameter you're keeping track of is temperature, that's a one dimensional parameter. It can either go up or down. But if you're keeping track of, let's say, magnetic spin, spin is a three dimensional parameter, and that number is what matters. So it doesn't matter if you're keeping track of like, whatever thing, it's how many numbers are you using it to describe that thing? It's so deep, and it's one of my favorite courses that I ever took at grad school, was statistical field theory, where we went over renormalization group theory. It also has deep impacts to quantum field theory, because you know, we talk about the infinities that come up in quantum field theory.

• 44:38Krishna Choudhary?

  Well, renormalization is actually how you resolve them. Kenneth Wilson discovered all of that, 1982 Nobel Prize in Physics.

• 44:45Lester Nare?

  Big shout out to Kenny. 1972, first experimental test of Bell's inequality.

• 44:52Krishna Choudhary?

  Yeah, so this was physicist John Clauser and Stuart Friedman at University of California, Berkeley. He read Bell's paper, and at the time, nobody was really taking it seriously, even though Bell had proposed, hey, here's an experiment you can do.

• 45:05Lester Nare?

  Right.

• 45:06Krishna Choudhary?

  John Clauser is like, well, maybe I can do the experiment. He does that experiment there. It shows the photos of that. And he showed that the universe does indeed violate Bell's inequality. Meaning, there are no hidden variables. Later on, this became a huge topic of research and now physicists all over the world are doing bigger and bigger tests of Bell's inequality. For that, John Clauser had a share in the Nobel Prize in Physics in 2022.

• 45:34Lester Nare?

  This is the idea of the theory moving into the experimental and then continuing to scale up the experimental to make sure at the limits

• 45:41Krishna Choudhary?

  Yeah.

• 45:41Lester Nare?

  of whatever it is we can do, it's still holds true.

• 45:44Krishna Choudhary?

  Yep.

• 45:45Lester Nare?

  1972, first recombinant DNA molecule.

• 45:48Krishna Choudhary?

  Yeah, this biochemist Paul Berg and his team created the first recombinant DNA molecule at Stanford University. Recombinant, meaning you're taking a bunch of different DNA from a lot of different sources and creating a single DNA molecule that is functional and it does stuff. It's like a chimera or a sphinx where you've got the lion's head or no, human head and the lion's body. This is, we're doing that with DNA now. He surgically spliced genetic material from a bacteriophage, a virus, into the S40 tumor virus, so two different viruses. And it launched the era of modern genetic engineering because now you're literally messing with the genetic constituents, putting stuff together, breaking stuff apart.

• 46:32Krishna Choudhary?

  All of this is possible because of the discovery of restriction enzymes earlier that could let us cut stuff.

• 46:37Lester Nare?

  Exactly.

• 46:38Krishna Choudhary?

  It earned him the 1980 Nobel Prize in Chemistry.

• 46:41Lester Nare?

  And is the birthplace of Jurassic Park.

• 46:44Krishna Choudhary?

  Yes.

• 46:44Lester Nare?

  1973, discovery of asymptotic freedom.

• 46:48Krishna Choudhary?

  Yes, this has to do with the strong nuclear force. The strong nuclear force is, as its name suggests, extremely strong. It is what keeps the nucleus together because, you know, protons that are all positively charged right next to one another in the nucleus, they want to rip apart the nucleus because positive charges. Want to move away from other positive charges. And yet, the nucleus is very stable. Why is that? Well, the strong nuclear force is keeping them together. But then the question is, why isn't the strong nuclear force like everywhere? How come it only acts at this very small distance inside the nucleus? It has to do with asymptotic freedom. Theoretical physicist David Gross, Frank Wilczek, both of them were at Princeton University, and David Pulitzer at Harvard.

• 47:31Krishna Choudhary?

  They independently figured out this concept of asymptotic freedom. And it won them the 2004 Nobel Prize in Physics and initiated the formalization of quantum chromodynamics.

• 47:44Lester Nare?

  And I just want to take a brief moment to say for those of us who are still here almost an hour in, welcome. This is what we love to do here at FFP Nation. We are so glad that you joined us. If you want to see more of this incredible deep dive from a first principles perspective on the show, you can go ahead and support us by liking, sharing, commenting, bringing it to journal club, DMing the group chat, telling them this is the coolest America 250 celebration content I've ever seen. And if you'd like to become a patron of the show, you can donate directly at ffpod.com/donate. It is the two of us here who've built this studio, who've built the programming and come

• 48:28Lester Nare?

  to you every week with the best science content you can get on the internet. And we are so grateful to have you all joining us for our special July 4th episode. Moving on to the isolation of a single electron.

• 48:43Krishna Choudhary?

  Yeah, when we talk about how good physics is at describing the world, I've told you about this 12 decimal place, right? That we can describe the electron down to 12 decimal places with quantum electrodynamics. Well, what that means is we've measured something, right? About the electron down to 12 decimal places, in this case, the gyromagnetic ratio. In order to do that, we need to single out individual electrons and measure that thing. This is how we did it. Physicist Hans Demelt, he successfully isolated and trapped a single electron using a penning trap, which is this really fancy like way of spinning around magnetic fields and electric fields to isolate a single electron there at the University of Washington in Seattle.

• 49:28Krishna Choudhary?

  And it's a breakthrough that allowed us to do that ultra-precise testing of quantum electrodynamics. It's a triumph of physics, earned him the 1989 Nobel Prize in Physics.

• 49:38Lester Nare?

  And he should get a prize for that incredible facial hair. That is fantastic, those chops.

• 49:42Krishna Choudhary?

  Oh, yeah.

• 49:43Lester Nare?

  1973, invention of structural and functional MRI, something many folks have had to experience.

• 49:50Krishna Choudhary?

  Yes, we talked about magnetic resonance imaging with Bloch and Purcell earlier. They discovered that bulk matter, you could use magnetic resonance imaging to probe it. Here, chemist Paul Lauterboer developed magnetic resonance imaging at SUNY Stony Brook, and it earned him the 2003 Nobel Prize in Physiology and Medicine. He applied that to biological specimen. And over there on the right-hand side, we can see the inside of a mouse with lungs and so on and so forth. And he's like, guys, we can use this for medicine. Later on, biophysicist Seiji Ogawa at Bell Labs discovered that we can use the bold contrast, which is the oxygen level, to probe functional MRI in our brain and figure

• 50:35Krishna Choudhary?

  out what parts of the brain are lighting up when you do this or that. So, all of that happens right here in America.

• 50:41Lester Nare?

  Interestingly, another American company, Mid Journey, is trying to upend the MRI industry with a new imaging product that they just released a couple of weeks ago that we will potentially cover in a future episode. Discovery of dendritic cells.

• 50:56Krishna Choudhary?

  Yes, these are some of the staple soldiers of our immune system, and they were discovered by immunologist Ralph Steinman at Rockefeller University in New York City. He proved that these dendritic cells act as the primer antigen-presenting cells. You know, the antigens and the antibodies that we were talking about. Well, these guys take those antigens, let's say you get like COVID or some other type of flu. Those things have proteins in them that are called antigens. Those antigens are then presented by dendritic cells to other parts of our adaptive immunity, and it bridges this innate and adaptive immunity within our bodies to create that immune response.

• 51:39Krishna Choudhary?

  It earned him the 2011 Nobel Prize in Medicine.

• 51:43Lester Nare?

  And if you're interested in that, our Nobel Prize episode on the regulatory T cells covers many of these concepts as well. 1973 through 1995 development and global deployment of GPS.

• 51:58Krishna Choudhary?

  Yes, this is the US Department of Defense. It spearheaded the development of global positioning systems, which is an American constellation of satellites that provides precise time and location data. One of the best things that the US has done is provide the civilian signal, which is the standard positioning service, free of cost and restriction. Fundamentally transformed global logistics. That's why you've got GPS on your phone. It's because the US government said, hey, why don't we give this out for free? Probably because they have something better now.

• 52:32Lester Nare?

  And another example of dual-use technology, both having a military and civilian application. 1973 invention of the Xerox Alto.

• 52:41Krishna Choudhary?

  Yeah, this was computer scientists and engineers Xerox at Xerox PARC in Palo Alto. They integrated a mouse, a graphical user interface, graphics, local networking. They basically established the blueprint for modern personal computing. This is huge because it served as the direct technological inspiration for the Apple Macintosh and Microsoft Windows. And it transformed computing from this elite industrial and scientific discipline to something that is consumer-facing.

• 53:12Lester Nare?

  And it was the successor to the mother of all demos manifesting in the real world. Invention of Unix and C. The 70s again were starting to get into a lot of these computing things.

• 53:24Krishna Choudhary?

  Yeah, again, it's because now people are catching on. They're like, hey, computing is going to be everything. Computer scientists Ken Thompson and Dennis Ritchie, they developed Unix and rewrote its kernel in C programming language at Bell Labs, and it established the modern paradigm for hardware-independent portable software. Meaning I can write software now and then... Somebody else needs to worry about how to implement that on the hardware. But now, like, this is, this is programming languages.

• 53:53Lester Nare?

  Yes.

• 53:53Krishna Choudhary?

  Are coming to fruition now with C.

• 53:55Lester Nare?

  Which is, again, the basis for all the things, then, devices.

• 53:58Krishna Choudhary?

  Yeah, it's the architectural blueprint for all modern operating systems.

• 54:02Lester Nare?

  Whether you understand it or not, you do use it on a daily basis. 1974, the indirect detection of gravitational waves.

• 54:10Krishna Choudhary?

  We covered this in our LIGO episode. Astrophysicist Richard Hulse and Joseph Taylor at Arecibo, they were working at Princeton at the time. They discovered the binary pulsar PSR-V1913+16. Two pulsars that are rotating around one another. Pulsars are themselves rotating neutron stars. And by looking at the signal of those pulsars rotating, they could see that the orbit was decaying. Now, why is it decaying? Because energy is leaving the system through gravitational waves, not through normal light. They applied Einstein's general relativity, and they found an exact match from theory and experiment. That's the curve on the left-hand side.

• 54:54Krishna Choudhary?

  You see the curve of Einstein's relativity, and the data points are exactly on top of it. They earned the 1993 Nobel Prize in Physics.

• 55:04Lester Nare?

  1974, discover of ozone depletion and chlorofluorocarbon CFCs.

• 55:09Krishna Choudhary?

  Yes, this was a huge triumph for, I think, the global community at large. Chemists Mario Molina and Sherwood Rowland at UC Irvine, they published this landmark paper that showed that human-made CFCs, chlorofluorocarbons, which are used in, like, refrigeration and all sorts of other industrial applications, they migrate into the stratosphere and they kill ozone, which is O3, the, the, the three oxygen molecule. That ozone is critical for us because it protects us from UV radiation, and it's a big part of our ozone layer, the Earth's protective coat. This stark environmental warning directly catalyzed global climate change policy

• 55:54Krishna Choudhary?

  because the entire globe then decided... Decided, hey, let's not use CFCs anymore. Um, that was part of the Montreal Protocol. It was a big win, I think, for humanity because it showed that we could all come together and be like, hey, let's, let's not do that.

• 56:08Lester Nare?

  Right.

• 56:09Krishna Choudhary?

  Let's, we like the ozone.

• 56:11Lester Nare?

  Yes.

• 56:11Krishna Choudhary?

  Right? There's a giant hole. Let's, let's not have that hole get bigger. And actually, once we stopped using CFCs, the ozone hole came back.

• 56:19Lester Nare?

  Seen the recovery.

• 56:20Krishna Choudhary?

  And we healed, we healed the earth.

• 56:22Lester Nare?

  Which is incredible.

• 56:22Krishna Choudhary?

  Which is incredible. They won the 1995 Nobel Prize in Chemistry.

• 56:26Lester Nare?

  1974, the discovery of the Jaycee Mason.

• 56:30Krishna Choudhary?

  That's right. So, you know, at the time, we've got Yang Mills theory, we've got quantum chromodynamics, we've got this quark model, got electroweak. Um, the standard model is starting to form, the standard model of particle physics. This is the killer. This is the one where everybody who was like, the standard model ain't all that. They stopped talking. Okay? Burton, Richard, and Samuel Ting, they independently discovered the Jaycee Mason at SLAC in Stanford and the Brookhaven National Laboratory, um, as part of MIT, and they proved the existence of the charm quark, which is, you know, we've got the up and down quark that is the part of, um, protons and neutrons. This is the prediction that there is that third generation of quark

• 57:13Krishna Choudhary?

  that everybody is waiting for because there's a third generation of leptons.

• 57:16Lester Nare?

  Yes.

• 57:17Krishna Choudhary?

  Right? With the muon that was discovered way earlier. Well, where's the one for quarks? This is where it was found. Um, very, very crucial, it ushered in the November resolution. I mean, sorry, the November revolution in particle physics because right when this was announced, it was announced at a conference because both Samuel Ting and Burton Richard were giving talks at the conference and they were back to back. And they were both like, hey, I discovered this. The next guy's like, hey, I discovered the same thing that the last guy discovered. They both rushed to publish because they want that Nobel.

• 57:50Lester Nare?

  Of course.

• 57:51Krishna Choudhary?

  They both got it in 1976 together and subsequently, the November of that year, this multi-generational architecture of standard model, meaning the first generation, up, down electron, then the muon charm and, uh, strange, and then we're waiting for the third one. Um, it was really established and now everybody was looking for that third generation of quarks, which we'll get to later in the timeline.

• 58:18Lester Nare?

  1974, discovery of the Lucy Australopithecus fossil.

• 58:23Krishna Choudhary?

  Yes, American paleoanthropologist Donald Johansson. He was a professor at Case Western Reserve University. He led the team that discovered this 3.2 million year old Australopithecus fossil in Ethiopia. This is huge because this is extremely old in the human lineage from, you know, our common ancestor with chimpanzees and gorillas to now Homo sapiens sapiens. It provided the transformative evidence for that transition to bipedalism. Because this is that transition. It was huge, huge. And it's almost complete skeleton. That's the other big one.

• 59:04Krishna Choudhary?

  For something that's 3.2 million years old and something that's so rare, to get like the ribs and the arms and even a femur from the legs and part of the skull, it was really, really big deal.

• 59:18Lester Nare?

  We're moving on to 1975, coining and formalization of fractals, something very popular amongst the Southern California community.

• 59:27Krishna Choudhary?

  Yes, fractals are a ubiquitous mathematical structure that's found in basically every single discipline. And they're not just aesthetically pleasing. They have everything to do in biology. They have to do with, you know, geophysics. You name it, fractals are everywhere. This sort of self-similar structure in mathematics. Benoit Mandelbrot, he was working at IBM's Watson Research Center. And he coined the term fractal and formalized the study of this self-similar geometric shape that repeats at different scales. What you're seeing there is a photo of the Mandelbrot set, which he used a computer to actually make the first photos of. And now it's sort of one of the most famous photos in, you know, mathematics.

• 1:00:14Lester Nare?

  We're moving forward to 1976 invention of the lithium battery.

• 1:00:19Krishna Choudhary?

  Yes.

• 1:00:19Lester Nare?

  Big one.

• 1:00:20Krishna Choudhary?

  This is a big one. This is why you we've got cell phones and this laptop here. It's able to hold charge. The chemist Stanley Whittingham invented the first functional rechargeable lithium battery at Exxon Research and Engineering. And then he established that this baseline chemistry can actually give you stable charge and stable power. It earned him a share of the 2019 Nobel Prize in Chemistry. Transformed modern electronics.

• 1:00:51Lester Nare?

  1976 discovery of proto-onco genes.

• 1:00:54Krishna Choudhary?

  Yes. Microbiologists Michael Bishop and Harold Varmus, they discovered the cellular origin of retroviral oncogenes at the University of California in San Francisco. And they showed that these oncogenes derived from normal cellular genes. It's nothing like, there's no like outside influence. Sometimes the cancer can just come from within. It comes from the host's own genome. 1989 Nobel Prize in Physiology and Medicine.

• 1:01:23Lester Nare?

  1977, one of my favorites, the Voyager missions to the outer solar system.

• 1:01:28Krishna Choudhary?

  Yes. So far, we didn't have a good idea of what the planets look like. Planets are small, and all we could do is just point telescopes at them from Earth. NASA here launched the twin Voyager 1 and Voyager 2 probes. They took advantage of a great alignment of the planets where all of the planets were kind of in a line where somebody figured actually if we could use gravity assists from all of them, we could visit all of them in this epic voyage. We got historic close up data. All of the famous photos that we have of Neptune and Uranus come from these missions. And this was also, you know, one of the first missions to categorize things like Jupiter's moons, Saturn's moons. It

• 1:02:13Krishna Choudhary?

  was a huge, huge deal. Revolutionized planetary science.

• 1:02:18Lester Nare?

  1977 discovery of RNA splicing.

• 1:02:22Krishna Choudhary?

  Yes. This was Richard Roberts and Philip Sharp. They independently discovered that

• 1:02:31Krishna Choudhary?

  Genes aren't continuous pieces of DNA. There are things called introns. You know, all the stuff that we talk about like junk DNA. Only a small fraction of our DNA actually makes proteins.

• 1:02:42Lester Nare?

  Right.

• 1:02:42Krishna Choudhary?

  This was that.

• 1:02:43Lester Nare?

  This was that.

• 1:02:44Krishna Choudhary?

  It showed that like, you know, a gene can actually be a giant thing with a bunch of spots that get spliced out when the RNA is made. Okay, this is the discovery of introns. 1993 Nobel Prize in Medicine.

• 1:02:58Lester Nare?

  Now we move to 1977, discovery of archaea.

• 1:03:03Krishna Choudhary?

  Right, so we're getting better and better at sequencing DNA now, right? We've had Nobel Prizes that showed how to sequence DNA. Well, Carl Vois and George Fox at the University of Illinois Urbana-Champaign, they discovered that when you start sequencing this DNA, you find a third domain of life, a third type of organism that is different from bacteria, and it's different from the eukaryotes that you and I are. And he called them archaea. This was huge because it, one, showed us that the tree of life has actually three primordial limbs, not just two.

• 1:03:39Lester Nare?

  Yes.

• 1:03:39Krishna Choudhary?

  And it started modern molecular phylogenetics, where now we look at the DNA and we can now trace back how species are related.

• 1:03:48Lester Nare?

  Love the tree of life stuff. 1978, discovery of hepatitis C.

• 1:03:54Krishna Choudhary?

  Yeah, this is pretty simple.

• 1:03:55Lester Nare?

  Yes.

• 1:03:56Krishna Choudhary?

  They discovered the third form of hepatitis. Harvey Alter identified non-A, non-B hepatitis is what he called it. Because back then hepatitis A and B were pretty ubiquitous. And here, he had to prove in his paper that it's not A and it's not B. This was at NIH, also along with virologist Charles Rice. They provided that genetic proof. Charles Rice was at the Washington University in St. Louis, and they won the 2020 Nobel Prize in Physiology and Medicine.

• 1:04:25Lester Nare?

  We're staying with 1978 with the first synthesis of recombinant human insulin.

• 1:04:32Krishna Choudhary?

  Yeah, this was huge. Keichi Itakura, Arthur Riggs, Herbert Boyer, and Dennis Clyde. They successfully synthesized the world's first recombinant human insulin. So they wanted to make insulin and before you had to basically harvest it from like pancreas, animal pancreas. It was a hassle. It would be really nice if we could just like make it happen.

• 1:04:56Lester Nare?

  Yeah.

• 1:04:57Krishna Choudhary?

  Right? Maybe we could make the gene for insulin, grow it in bacteria. Well, making the gene for insulin is not so easy because you can't just take the human gene and put it in bacteria. The bacteria is gonna be like, I don't know.

• 1:05:07Lester Nare?

  What is that?

• 1:05:08Krishna Choudhary?

  What's going on? So they used recombinant DNA technology, which was invented earlier.

• 1:05:13Lester Nare?

  Yes.

• 1:05:13Krishna Choudhary?

  In our timeline. And at the City of Hope and Genentech, this was Genentech's actually first big project. It established the foundation of modern biotechnology.

• 1:05:23Lester Nare?

  Yeah, it's the first example of what is then rinse and repeat for a variety of other.

• 1:05:28Krishna Choudhary?

  Exactly.

• 1:05:29Lester Nare?

  Use cases in the future.

• 1:05:30Krishna Choudhary?

  Saved countless lives.

• 1:05:32Lester Nare?

  A hundred percent.

• 1:05:33Krishna Choudhary?

  Yeah.

• 1:05:34Lester Nare?

  A hundred percent. We're staying in 1978. Trapped Ion Quantum Control and the CNOT Gate.

• 1:05:39Krishna Choudhary?

  Yes. This was David Weinland at NIST, also at University of Colorado Boulder. He pioneered laser cooling of trapped ions. This is now one of the ubiquitous platforms for quantum computation today. In 1995, he implemented the first physical quantum logic gate, that CNOT gate that is the bread and butter of all quantum algorithms. Both of those achievements won him the 2012 Nobel Prize in Physics.

• 1:06:08Lester Nare?

  We are going to fast forward. Apparently, nothing interesting happened in 1979.

• 1:06:13Krishna Choudhary?

  Yeah. Tell me in the comments if something interesting happened in 1979. I couldn't find anything.

• 1:06:19Lester Nare?

  We're moving to 1980, the Bay Doyle Act.

• 1:06:23Krishna Choudhary?

  Yeah. This was a monumental legislation. It allowed universities and nonprofits to own, patent, and commercialize inventions that they had created using federal grant money. So if I get a federal grant and I discover something, I can now own it as a university and license it out. It shifted ownership away from the government and essentially birthed modern biotech and the university tech transfer offices that.

• 1:06:50Krishna Choudhary?

  Is now, you know, encourages now the universities and the individual players to start

• 1:06:55Lester Nare?

  To start.

• 1:06:56Krishna Choudhary?

  Making money.

• 1:06:57Lester Nare?

  Building.

• 1:06:57Krishna Choudhary?

  And building.

• 1:06:58Lester Nare?

  And building things that we can use and love. We have a quantum computing story for 1980 to 1981, the foundations of quantum computing, Benioff and Feynman.

• 1:07:10Krishna Choudhary?

  Yes. So Paul Benioff established a theoretical quantum Turing machine. The Turing machine is something that we covered in part one, where Alan Turing had figured out anything that is, that can be done on any computer can be done on a simple Turing machine that reads and writes stuff. He developed the idea of a quantum Turing machine. In 1981, a year later, Richard Feynman gave a landmark argument that quantum systems and describing quantum systems with a computer requires a quantum computer where the bits are not classical bits, but quantum bits. It birthed the idea of quantum computation, which now is a multi-billion dollar industry.

• 1:07:50Lester Nare?

  And everyone is rushing to be able to build a functional and operational and scalable quantum computer. 1981, the invention of the space shuttle way earlier than many people might believe.

• 1:08:04Krishna Choudhary?

  Yeah, yeah. This is NASA and its principal industrial contractors. They launched the STS-1, the Space Transportation System, which now we call the Space Shuttle. It's the world's first reusable orbital spacecraft fleet. It transformed low earth orbit infrastructure. It allowed for stuff like the Hubble Space Telescope to go up. And then when the Hubble was broken, to send up another crew with the Space Shuttle to go and fix it. It allowed for the construction of the International Space Station, low earth orbit. And it's the first reusable space vehicle.

• 1:08:39Lester Nare?

  If you watch the clip that we did on the top 10 most expensive NASA missions or projects, this was one of them, which we talked about greatly. We may need to get another Lego set of the STS to add to our Artemis Lego set that we have here with us in the studio. 1981, single particle cryo-EM reconstruction.

• 1:09:04Krishna Choudhary?

  Yes. When, when biophysicist Joakim Frank, when he started doing single particle 3D reconstruction of proteins using cryo-electron microscopy.

• 1:09:16Krishna Choudhary?

  Everybody sneered at him and called it blobology. Because what he was trying to do is use electron microscopes to discern the structure of proteins. Well, people already had the crystallization technique, where you shoot X-rays at protein crystals and you get the structure. Well, you can't make crystals out of everything, especially membrane proteins. Those are hard to make crystals out of. And Joaquin Frank thought, okay, maybe if I image a bunch of these single particles in my slide, and I have a good way to prepare them using this like really cool technique to freeze them, but not like mess with their structure. And then I apply computation, which had just been coming around, right? Computers had just been coming around. If I have some algorithms that can like discern what I'm looking at,

• 1:10:01Krishna Choudhary?

  then perhaps I can reconstruct to atomic resolution what the proteins look like. It took him like 20 years, but it started in 1981. He started with a paper that like I think was super blobby, so hence blobology. But it became a high-resolution structural tool. And in 2017, he earned the Nobel Prize in Chemistry.

• 1:10:25Lester Nare?

  Moving on to 1982, the discovery of prions.

• 1:10:28Krishna Choudhary?

  Yes, this was Stanley Prusener at University of California, San Francisco. He isolated an infectious agent behind the sponiform encephalopathies. And he showed that that pathogen is not a bacteria. It's not a virus. It's not even anything that is living. It is simply a misfolded protein with no genetic material. But it's wreaking havoc. This is huge, right? Because before, like for, for like so much of humanity, we've been worried about viruses and bacteria and like sometimes protists are like, you know, like little single-celled organisms, the stuff that malaria comes from.

• 1:11:13Krishna Choudhary?

  And now we've got something that's not even living. And it's giving us... A lot of grief.

• 1:11:18Lester Nare?

  Yes.

• 1:11:19Krishna Choudhary?

  Um, he coined the term prion. I think mad cow disease is another um example of prion disease. He won the 1997 Nobel Prize in Medicine.

• 1:11:28Lester Nare?

  Yeah, that's a big one.

• 1:11:28Krishna Choudhary?

  It's a big one because it it expands all of the things that we need to be worried about.

• 1:11:33Lester Nare?

  Right, right. There's new enemies we need to be aware of here. Uh, 1982 discovery of uh ribozymes?

• 1:11:41Krishna Choudhary?

  Ribozymes, like enzymes.

• 1:11:42Lester Nare?

  Ah, ribozymes.

• 1:11:43Krishna Choudhary?

  Yeah, before this, this is huge because, I mean, it's it sounds like enzyme because it's exactly that. Um, before it used to be thought that all organic catalysts and all biological catalysts are in the form of proteins.

• 1:11:54Lester Nare?

  Right.

• 1:11:54Krishna Choudhary?

  You need proteins to like do work in the cell.

• 1:11:56Lester Nare?

  Right.

• 1:11:56Krishna Choudhary?

  This is the first time that we're discovering RNA can do that kind of work. This was um Thomas Chek and Sidney Altman at the University of Colorado Boulder and at Yale University. They discovered catalytic RNA molecules. Like, you know that intron and exon thing? Like, there's a giant gene and then I have to splice out parts that I don't need. That's done by an RNA ribosome. Um, they also figured out that this is um a new way to think about the origin of life. Because before we used to think, well, what came first, the chicken or the egg? Is it the protein or is it the DNA? Because neither can do what the other does. The protein does all the work, but the DNA stores the memory. Now we've got a ribosome that does both.

• 1:12:39Lester Nare?

  Yes.

• 1:12:39Krishna Choudhary?

  It can store genetic information and it can do the work.

• 1:12:43Lester Nare?

  Yeah, that's fascinating.

• 1:12:44Krishna Choudhary?

  They won the 1989 Nobel Prize in Chemistry, and we're gonna have an episode coming up that talks more in detail about this.

• 1:12:51Lester Nare?

  Uh, one that we've talked about recently in 1982 formulation of the Hopfield Network.

• 1:12:56Krishna Choudhary?

  Yes, this was John Hopfield. He introduced the recurrent, fully connected, artificial neural network that functions to store memories. He was at Caltech at the time and then um later on went to Princeton and continued his work. He established this profound bridge between statistical mechanics and all of the math that we've used to describe magnets and things like that with the Ising model and computer science and this idea of artificial neural networks. It really started a lot of physicists to go down this track of, hey, maybe these artificial neural networks are something that we can make sense of. He won the two 2024 Nobel Prize in Physics, very recent.

• 1:13:34Lester Nare?

  Fascinating. 1982 formulation of the geometrization conjecture.

• 1:13:40Krishna Choudhary?

  Yeah, again, another one that I have no idea what it's about. So I will just read it. William Thurston formulated the geometrization conjecture at Princeton University, and he won the 1982 Fields Medal. Something to do with a complete geometric taxonomy for all closed, three-dimensional topological spaces.

• 1:13:58Lester Nare?

  That sounds fascinating.

• 1:14:00Krishna Choudhary?

  Yeah, again.

• 1:14:01Lester Nare?

  For the mathematicians, let us know below how we can find out more on the G's formulation of the GC there. I'm just gonna arbitrarily abbreviate it because that's probably what the cool kids do. 1983, mapping of DNA repair mechanisms.

• 1:14:16Krishna Choudhary?

  Yes, um, DNA, when it gets transcribed, when it gets messed with, there's a lot of errors that happen. And yet, the error rate for us even is like one in a billion. That seems not a lot, right? Given just the amount of jiggling that happens at 300 Kelvin

• 1:14:37Lester Nare?

  Jiggle jiggle.

• 1:14:37Krishna Choudhary?

  At our body temperature. So here, Paul Modrich at Duke University and Aziz Sanchar at UNC Chapel Hill, both from North Carolina. They systematically mapped how cells safeguard genetic integrity against mutations and UV damage. And that won them the 2015 Nobel Prize in Chemistry.

• 1:14:58Lester Nare?

  The only time you will see Duke and UNC collaborating in a positive way as, as arch nemesis in almost every other context, at least in sports. 1983, invention of PCR.

• 1:15:12Krishna Choudhary?

  Yes, the polymerase chain reaction. This is the bread and butter of every bio lab, every biochemistry lab. Carey Mullis invented the polymerase chain reaction at Cetus Corporation in Emeryville, California. And he utilized a repeated thermal cycle with a very special DNA polymerase that he had found in like bacteria in the hot springs of Yellowstone.

• 1:15:37Krishna Choudhary?

  And he used that to exponentially amplify specific DNA targets. So you can take a small sample of DNA and make. Many, many, many, many copies of it exponentially. Revolutionized molecular diagnostics because now I only need a little bit to actually sequence. Before I needed a lot of DNA in order to sequence it here. Now I can amplify and then sequence. Earned him the 1993 Nobel Prize in Chemistry.

• 1:16:00Lester Nare?

  This is a reminder to get out in nature. You may just find the inspiration for a Nobel Prize. 1983 formulation of the Haldane conjecture.

• 1:16:10Krishna Choudhary?

  Yes, this was theoretical physicist Duncan Haldane. He formulated the Haldane conjecture at the University of Southern California in Los Angeles. And it has to do with topological spin states. Topological meaning like stuff that has to do with a mathematical structure that is invariant to transformation. For example, like if I've got a mug with a hole, that's got a hole. And no matter what I do with the Play-Doh, unless I rip it apart and I squish things together, I'm not going to get rid of that hole. On the other hand, this cup right here doesn't have a hole. So I can make this look like a sphere, no problem. I could never make a mug look like a sphere. I can make it look like a donut because a donut has one hole and the mug has one hole.

• 1:16:54Krishna Choudhary?

  So this is the type of mathematical structure that I'm talking about. He discovered that there's low dimensional quantum spin chains that have topological phases, meaning like different states of being that are restricted by this topological structure. Okay, he was at University of Southern California at the time. And then he went to Princeton and he was one of my professors. He actually taught me intro E and M. He won the 2016 Nobel Prize in Physics, two years after we left.

• 1:17:23Lester Nare?

  That's, if only you were there.

• 1:17:24Krishna Choudhary?

  Yeah, that would have been crazy.

• 1:17:26Lester Nare?

  So crazy. 1983, commercial launch of AMPS and cellular engineering.

• 1:17:32Krishna Choudhary?

  Yes, this was the launch of the advanced mobile phone system in the U.S. And it marked the first commercial cellular network. It utilized this handoff protocol and switching logic that was developed at Bell Labs. Catalyzed the rapid global adoption of cellular technologies. Created the infrastructure for the modern mobile phone economy.

• 1:17:55Krishna Choudhary?

  This is why we've got cell phones, guys.

• 1:17:57Lester Nare?

  Yes. Also, as you can see, Bell Labs continues to show up throughout the decades as we make our way to another 1984 discovery of telomeres and telomerase.

• 1:18:10Krishna Choudhary?

  Yes. Elizabeth Blackburn, Jack Sostak, and Carol Greider, they discovered that at the end of chromosomes are these things called telomeres. And it's effectively repetitive bits of DNA that scaffold and protect the actual important stuff that's on the inside. The important genes that are on the inside are protected by these tails because when you replicate, you're gonna, just because of temperature and energy and things like that, you're gonna leave off the stuff in the ends. So if I just have like bookends at the ends that don't matter, then I can protect the stuff on the inside. Turns out this stuff is related to aging because as the telomeres get shorter,

• 1:18:53Krishna Choudhary?

  aging gets worse and worse, cancer gets worse and worse. They also discovered the enzyme telomerase at the University of California, Berkeley. And it solved how does the body maintain the telomeres? Well, the enzyme telomerase does that. They won the 2009 Nobel Prize in Medicine.

• 1:19:13Lester Nare?

  Margins on paper in a notebook.

• 1:19:15Krishna Choudhary?

  Yeah, that's exactly right.

• 1:19:17Lester Nare?

  As an analogy, we're moving to 1985, laser cooling of neutral atoms.

• 1:19:22Krishna Choudhary?

  Yes. These were experimental physicists at Bell Labs and National Institute of Technology, Stephen Chu and William Phillips. They developed methods to slow, cool, and trap neutral atoms using lasers.

• 1:19:37Lester Nare?

  Lasers.

• 1:19:37Krishna Choudhary?

  Very, very counterintuitive because usually you would think, you know, you shoot a laser at something, it's gonna heat it up.

• 1:19:42Lester Nare?

  Yes.

• 1:19:43Krishna Choudhary?

  They found a way of using the Doppler effect to actually cool down atoms and bring them down to way, way low temperatures. This is something that we're gonna utilize later on. They won the 1997 Nobel Prize in Physics. Probably deserves a standalone episode from us.

• 1:19:58Lester Nare?

  I like that one because cool lasers.

• 1:20:02Lester Nare?

  Great entry point for a video. 1985 and we did a deep dive on this one. Discovery of macroscopic quantum tunneling.

• 1:20:12Krishna Choudhary?

  Yep. They won the Nobel Prize just last year in 2025. These are physicists John Martinez, Michel Devore and John Clark. They were doing an experiment at Berkeley where they showed that macroscopic systems, i.e. systems of millions and billions of electrons obey quantum mechanics just like single electrons do. And they proved that this energy quantization and macroscopic quantum tunneling is happening for an extremely large system in a Josephson junction. It established the foundation of superconducting qubits and a lot of quantum technology. And fundamentally, it's just a very big discovery because it shows that the system can be extremely large and still obey quantum mechanics.

• 1:20:54Lester Nare?

  Which is fascinating and one of our most popular episodes. So be sure to check that out. Staying in 1985, invention of the Boltzmann machine.

• 1:21:03Krishna Choudhary?

  Yes, this is the next step from the Hopfield network. Terry Sainouski, who was actually a PhD student of John Hopfield. He was at Johns Hopkins at the time and Geoffrey Hinton, the godfather of AI. He was at Carnegie Mellon at the time. They developed the Boltzmann machine named after Ludwig von Boltzmann, the physicist from 1800s. It's a stochastic recurrent neural network that introduced energy based learning, the same type of energy argument that John Hopfield had used earlier. And it showed how you could learn stuff by having hidden nodes as in middle parts of the network that didn't see the input or the output, right? There's there's stuff in the middle that is now doing computation.

• 1:21:46Krishna Choudhary?

  It solved a critical limitation in training multi-layer neural networks, which are now the bread and butter of AI today.

• 1:21:52Lester Nare?

  Big shout out to Geoffrey Hinton there. 1986. Again, we're continuing in the same vein formulation of the back propagation algorithm. A fundamental in all of these chatbots and frontier models we see today.

• 1:22:07Krishna Choudhary?

  This is, and we're starting to see why Geoffrey Hinton is called the godfather of AI. The year before, he did the Boltzmann machine. Now this year with David Rumholt and Ronald Williams, he publishes this foundational paper on back propagation, which is the mathematical engine that allows multi-layer neural networks to learn efficiently by taking The guesses and the difference between the ground truth and the guess that you have, back propagating that out, changing the weights of the neural network, so that at the next iteration, you're better at your guess. This is the last time that we're gonna see Geoffrey Hinton here, because he got offered a job at the University of Toronto after this. The Canadians saw potential and they're like, let's have you come on board.

• 1:22:48Lester Nare?

  Yeah, no longer ours. I believe if I recall correctly, our episode where we did a deep dive on the DeepSeek model, touched on some of these concepts that the DeepSeek model kind of did in a slightly different way. But if you're interested in kind of understanding more about this concept of back propagation, check out our DeepSeek episode, 1987, the birth of femtochemistry.

• 1:23:09Krishna Choudhary?

  Yes, this is Ahmed Sehwaile at Caltech. He pioneered the field of femtochemistry and utilized this ultra-short laser pulses at the femtoseconds. So this is 10 to the minus 15 seconds to observe chemical bond dynamics. As in, chemical bonds are forming at that time scale, right? And he captured molecular transition states in real time, which is, it's just crazy that we can watch chemicals being formed.

• 1:23:38Lester Nare?

  It's unbelievable.

• 1:23:39Krishna Choudhary?

  Right? The atoms like, hey, and then it like becomes friends with the other atoms. It's insane. It earned him the Nobel Prize in Chemistry in 1999.

• 1:23:48Lester Nare?

  Rightly so. We are going to make a big jump to 1990 to 1992, COBE mapping of the cosmic microwave background.

• 1:23:59Krishna Choudhary?

  Yes, this was astrophysicist John Mather at NASA Goddard and George Smoot at UC Berkeley. They utilized NASA's COBE satellite and the data from that to provide definitive confirmation of the Big Bang. So before, we had Penzias and Wilson and Dickey. They had figured out that, you know, the cosmic microwave background is a thing. But they had really not categorized the map across the sky, right? The the sky is this 360 degrees on all sides. We'd like to now see is the cosmic microwave background the same over here as over here? Is the light coming from the Big Bang the same over here or over here and over here and over here? Turns out, yes, up to a very small margin.

• 1:24:44Krishna Choudhary?

  The light is almost exactly the same. And it proves that this sort of cosmic black body spectrum, right? The universe was like a giant ball of gas. Not giant, a tiny, small ball of gas that was completely in equilibrium with itself. And it proved that like these temperature anisotropies are perhaps what give structure later on, like these tiny fluctuations in the temperature of the cosmic microwave background is what gives us all of the structure that we see today with galaxies, us. You know, it's it's insane. And on the right hand side, at the top, you see the Kobe satellite image. And on the bottom, NASA sent out further refinements of that satellite to to get smaller and smaller structural detail.

• 1:25:29Krishna Choudhary?

  And it's really cool because you can see a blurred image of the baby universe. And then as we turn the resolution dial up, it's the same image. But now we're getting a clearer picture.

• 1:25:39Lester Nare?

  A little more granularity.

• 1:25:40Krishna Choudhary?

  Yeah.

• 1:25:41Lester Nare?

  And for those interested in mass sky surveys generally, check out Krishna's interview with Dr. Michael Blanton, who I might say is one of the godfathers of large scale digital sky surveys during his leadership of the Sloan Digital Sky Survey, among other things.

• 1:25:59Krishna Choudhary?

  Yes, yes. And these guys won the 2006 Nobel Prize in Physics.

• 1:26:03Lester Nare?

  We are moving to 1991, discovery of olfactory receptors. Crazy that 1991 is not that long ago.

• 1:26:10Krishna Choudhary?

  Not that long ago. But this is how we figured out how our nose works. Right? What are the chemical receptors that bind to specific? Smells and give us the sense of smell. Neuroscientist Linda Buck and Richard Axel at Columbia University, they identified the genetic foundation of that sense of smell. And they discovered this massive multi-gene family of a thousand different odorant receptors that are now in our nose. They earned the 2004 Nobel Prize in Medicine.

• 1:26:41Lester Nare?

  We are going to jump forward to 1992 to 1998. Discovery and structural elucidation of membrane channels.

• 1:26:49Krishna Choudhary?

  Yes, so you know, the cells have an inside and an outside. And then they've got a border of this lipid membrane. How does water get in and out?

• 1:26:57Lester Nare?

  Exactly.

• 1:26:57Krishna Choudhary?

  Water can't flow through that lipid membrane. It's like a bunch of fat, right? And fat obviously does not let water go through. Furthermore, in neurons, you've got potassium and calcium channels and sodium channels. Now potassium and sodium are different sizes. The ion channels that let through, let's say potassium, they should also let through sodium because sodium is smaller.

• 1:27:19Lester Nare?

  Yes.

• 1:27:19Krishna Choudhary?

  How come they don't?

• 1:27:20Lester Nare?

  Exactly.

• 1:27:21Krishna Choudhary?

  These guys are the ones who figured that out. So Peter A. Gray at Johns Hopkins, he figured out what aquaporins look like. Aquaporins is in the holes in our membranes that let us transport water through. And Roderick McKinnon at Rockefeller University, he unmasked the molecular architecture governing this potassium channel. That's the image that you see over there. And that protein is just ingenious because it only lets through potassium, which is a larger ball, but it rejects sodium, which is smaller because of some really weird physics that happens in the middle. Again, another thing for a great episode. They won the 2003 Nobel Prize in Chemistry. We'll do that one in the future for sure.

• 1:28:03Lester Nare?

  Our membranes are not a fan of open borders and have strict border control. 1993 pioneering of directed evolution.

• 1:28:11Krishna Choudhary?

  Yes, we recently just talked about directed evolution in one of our episodes. I can't remember which one. But this was Francis Arnold. She pioneered directed evolution at Caltech. It abandoned this rigid rational design of proteins where it's like, okay, I want the protein to do this and like I want. Wanted to look that way. What Francis Arnold said is, why don't we let life figure it out? How to make the protein look the way that it wants it to look? I'm only gonna optimize for the endpoint behavior and use evolution within the lab to optimize my protein. So she had these iterative loops that would run random mutations. And then she would screen out the mutations that didn't work and filter through the mutations that did.

• 1:28:56Krishna Choudhary?

  And it's been used to engineer custom enzymes ever since. She won the 2018 Nobel Prize in Chemistry.

• 1:29:03Lester Nare?

  Very similar to the concept of Ralph Loops in AI coding. Very much the exact same concept. We can think directed evolution as part of the inspiration there. 1993 to 1994, discovery of the impact of comet Schumacher Levy nine.

• 1:29:19Krishna Choudhary?

  Yes, so this is astronomer Carolyn Schumacher, Eugene Schumacher, who we had earlier, who figured out that the meteor crater in Arizona was an actual meteor. And David Levy, they discover comet Schumacher Levi nine using the telescope at Palomar Observatory, just down south here from Los Angeles. This was a comet that was captured by Jupiter's gravity and then torn apart with tidal forces. So it became this chain of cometary debris that then came back and then hit Jupiter. And we could watch it live. And we knew exactly when it was gonna happen. All of the telescopes around the planet Earth, along with the Hubble, was pointed at Jupiter. And you could literally watch the bombing of Jupiter.

• 1:30:02Krishna Choudhary?

  You know, and I mean, it released enough energy to like destroy Earth or something. It was massive.

• 1:30:09Lester Nare?

  Right, and thankfully, it wasn't pointed at Earth, but our big bro.

• 1:30:14Krishna Choudhary?

  Yeah.

• 1:30:14Lester Nare?

  The big red planet.

• 1:30:15Krishna Choudhary?

  And I mean, the other big thing about it is like, that's when, that's when everyone was like, oh, so this could happen. Like, we should probably be worried about it. Um, this isn't just something that the dinosaurs needed to be worried about 65 million years ago. This could still happen.

• 1:30:31Lester Nare?

  And we talked about planetary defense.

• 1:30:34Krishna Choudhary?

  Yes, that, I mean, this is when people started taking it seriously because we just watched it live.

• 1:30:38Lester Nare?

  Right.

• 1:30:39Krishna Choudhary?

  And it's like, yo.

• 1:30:40Lester Nare?

  It's a real, it's a real area of research that we definitely need to pay attention to. Uh, and then we saw, um, what was the interstellar object where we pointed the stuff as well at the same time? Uh, about a year or two ago.

• 1:30:51Krishna Choudhary?

  Mm hmm.

• 1:30:52Lester Nare?

  Uh, 1993, a binding change mechanism of ATP synthase.

• 1:30:56Krishna Choudhary?

  Yes, um, this is biochemist Paul D. Boyer at UCLA. He figured out how cells create ATP. ATP is the currency of energy for our cells. It's like, it's like cash, okay? You can think of glucose as like the industrial input, right? But from that, you've got to create something liquid that can then be transferred from party to party, from protein to protein, to make the proteins go from one state to another state. We had already discussed phosphorylation earlier and how this adding of a phosphate group makes the proteins go from one state to another.

• 1:31:32Lester Nare?

  Yes.

• 1:31:32Krishna Choudhary?

  Well, how do you get those phosphate groups in the first place? The mitochondria creates it using, um, ATP synthase. And for a long time, we didn't really know how it worked. It turns out it's a literal ratchet. Okay, it's a literal turbine, the same way that we've got a dam and the dam turns a wheel.

• 1:31:50Lester Nare?

  Yeah.

• 1:31:50Krishna Choudhary?

  And the wheel creates energy.

• 1:31:52Lester Nare?

  Yeah.

• 1:31:52Krishna Choudhary?

  Over here, we've got a dam. The dam, instead of being water, is, um, hydrogen ions, just a bunch of protons that are sandwiched in between the mitochondria. There's a little turbine that lets the protons through. And because all the protons want to get away from each other, right? Because they're all positively charged.

• 1:32:09Lester Nare?

  Right.

• 1:32:09Krishna Choudhary?

  There's a massive flux of protons and they, they can do a lot of work. And as the protons flow through, there's a ratchet that turns a wheel on the protein. And that wheel turning takes a phosphate and ADP, a di-phosphate.

• 1:32:22Lester Nare?

  Yep.

• 1:32:23Krishna Choudhary?

  And sticks another phosphate in.

• 1:32:25Lester Nare?

  Yep.

• 1:32:25Krishna Choudhary?

  And sticks another phosphate in. And it's just this absolutely beautiful mechanism that we're definitely going to cover in a, in another episode because it's probably my favorite protein of all time is ATP synthase. He discovered that rotational catalysis. It won him the 1997 Nobel Prize in Chemistry. And when I was at UCLA, there, the, um, the main biochemistry building is named after him.

• 1:32:50Lester Nare?

  Named after him.

• 1:32:50Krishna Choudhary?

  Yeah, Borre Hall.

• 1:32:51Lester Nare?

  Uh, denicine triphosphate, the fiat of our energy system, 1993 to 2000 discovery and universal conservation of micro RNA.

• 1:33:02Krishna Choudhary?

  Yes, this was Victor Ambrose and Gary Ravkun at Harvard and MIT Gen-, uh, sorry, Massachusetts General Hospital. I'm not going to give MIT more credit than it deserves. He discovered micro RNA and it proved, they proved that, um, universally it's conserved all across a bunch of species. This micro RNA is a fundamental post-transcription mechanism, meaning, you know, I've got DNA, the DNA gets transcribed into mRNA, but then that mRNA gets regulated by these micro RNA mechanisms. It's hugely important for RNA biology and developmental genetics, medical therapeutics. It opened up new dimensions for oncology and pharmacology.

• 1:33:45Krishna Choudhary?

  It revealed that 60% of human protein coding genes are actively fine tuned by these micro RNA. That's not a minority, 60%, right?

• 1:33:54Lester Nare?

  Yeah.

• 1:33:54Krishna Choudhary?

  They won the 2024 Nobel Prize in Medicine.

• 1:33:57Lester Nare?

  Phenomenal discovery, that one. Uh, we are still in 1993, a banger year where we have the invention of the mosaic web browser, where we see our favorite egghead, Mark Andreessen, still with some hair on that big brain of his and is the birth of, again, how we are reaching you all, at least one of the ways we are reaching you all today.

• 1:34:18Krishna Choudhary?

  Yeah, yeah. If you guys are watching on a web browser, you can thank Mark Andreessen and Eric Bina. They developed the NCSA Mosaic, which is a, the first sort of web browser, um, at the University of Illinois Urbana-Champaign. It created the world's first widely adopted cross-platform graphical web browser. So it can like display images, it can- Like it dismantled this high technical barrier of text only command line networking, you know, it's like not everybody wants to work with a terminal. You know what I mean? And so now you've got this point and click graphical interface because we already had the mouse. And they figured, you know, we should use it for actual stuff.

• 1:34:59Krishna Choudhary?

  It unified the text and multimedia on a single canvas. And it sparked the commercialization of the world wide web and launched the commercial internet age. So this is, um, you know, I think where Marc Andreessen really made his name. 1993 is when they're like, oh.

• 1:35:18Lester Nare?

  And now he's just been elevated to the board of technology advisors to the department of war. We'll see how that goes. I feel like we're regressing though, because now Claude code is all terminal only. I want my GUI. I want my graphical user interface. So hey, if you're out there and you're trying to figure out ways to innovate, figure out how to move stuff like Claude code into a GUI. You might be the next mosaic web browser type inventor. 1993, big year cancellation of the superconducting super collider, which again, we've talked about as one of the greatest.

• 1:35:52Krishna Choudhary?

  Failures.

• 1:35:53Lester Nare?

  Failures for America in terms of these large scale science projects.

• 1:35:57Krishna Choudhary?

  Yeah, so as we're reaching the end of our timeline, I did want to mention what happens when we drop the ball. Okay, 1993, we dropped the ball pretty big. Okay, we were planning to create the superconducting super collider in Texas. This was going to be bigger than CERN. It was going to be brighter than CERN. It was going to discover the Higgs way before CERN.

• 1:36:21Lester Nare?

  Way before.

• 1:36:22Krishna Choudhary?

  Way before CERN. And it was also going to rule out a bunch of theories that have now been ruled out after like 20 years of CERN. It was going to do it immediately. It was also going to be. American, right? It was gonna be like this American stamp on particle physics, on fundamental physics discovery, and the United States Congress canceled the construction in 1993. Bill Clinton was the president at the time, and he did nothing about it. It's really, it's really quite sad because it shifted high-energy physics to Europe. We learned our lesson, though.

• 1:36:58Lester Nare?

  Yes.

• 1:36:59Krishna Choudhary?

  And this is when scientists came together and they're like, we need to have a comeback. We'll talk about the comeback in a bit.

• 1:37:05Lester Nare?

  It's not gonna happen again. And we had a surplus at the time.

• 1:37:08Krishna Choudhary?

  Yeah.

• 1:37:09Lester Nare?

  We weren't in a deficit. It's crazy.

• 1:37:11Krishna Choudhary?

  Yeah.

• 1:37:11Lester Nare?

  It's crazy.

• 1:37:12Krishna Choudhary?

  But they're like, what are we gonna do with the Higgs? You know? Is that gonna create jobs? You know what? Maybe.

• 1:37:19Lester Nare?

  Life finds a way.

• 1:37:19Krishna Choudhary?

  Maybe in 50 years.

• 1:37:20Lester Nare?

  As Dr.

• 1:37:21Krishna Choudhary?

  Ian Malcolm says. As you can see, right? One thing that I do want to talk about this timeline is, a lot of the stuff that we're discovering, you know, in the 1990s, in the 1950s, it's giving dividends till now.

• 1:37:32Lester Nare?

  10, 50, 100 X-fold.

• 1:37:35Krishna Choudhary?

  Yeah.

• 1:37:35Lester Nare?

  And it's not always clear at the time.

• 1:37:37Krishna Choudhary?

  Yeah.

• 1:37:37Lester Nare?

  But just learning about how, again, the world around us works fundamentally, inevitably is going to have commercial applications. We want to make sure those are well-distributed. There's a balance of power issue there. But ultimately, fundamental curiosity-based science, which is in our constitution, is meaningful and improves all of our lives. And that's a great example of what happens when we fail to accomplish those tasks and cede ground to the Europeans. They already have us in football. We're not gonna let them have us in science.

• 1:38:07Krishna Choudhary?

  No.

• 1:38:08Lester Nare?

  1994, application in engineering of GFP.

• 1:38:11Krishna Choudhary?

  Yeah, so this story starts in 1962 with Osamu Shimomura at Princeton University. He discovers this protein called GFP, green fluorescent protein, in algae, in fluorescent algae. He thinks it's pretty cool. It takes another 30 years for neurobiologist Martin Shalphi at Columbia and biochemist Robert, Roger Sien at UCSD to express that green fluorescent protein, isolate the genetics of that green fluorescent. Protein and then use that in biomedical research to start tagging cellular processes. So now we can watch them live with our microscope.

• 1:38:53Krishna Choudhary?

  We can use the genetics of the GFP to tag it to a certain protein. So now, when the protein moves around in the cell, we can just watch it because it's got this little green tag. That's like a little LED light at the microscopic level.

• 1:39:06Lester Nare?

  Beacon.

• 1:39:08Krishna Choudhary?

  They won the 2008 Nobel Prize in Chemistry together.

• 1:39:12Lester Nare?

  Amazing. 1994 invention of Shor's quantum algorithm.

• 1:39:16Krishna Choudhary?

  Yeah, this is the first time that really, I think, everyone started taking quantum computing seriously. Not just as something that can, you know, okay, it can simulate materials and it can simulate quantum computers. Well, now it can break encryption. Okay, Shor's algorithm showed that you can factor extremely large numbers very, very easily with a quantum computer that would take you millions of years on a classical computer. He was working at Bell Labs at the time, another Bell Labs.

• 1:39:46Lester Nare?

  Another Bell Labs.

• 1:39:47Krishna Choudhary?

  And his mathematical breakthrough proved that these quantum computers are something that everyone needs to worry about. So now nation states get involved, a lot of funding gets poured in. It drives the global race for quantum hardware that we are still running today.

• 1:40:03Lester Nare?

  Yeah, this is a careful of your Bitcoin if we reach to get to these quantum.

• 1:40:08Krishna Choudhary?

  Yeah.

• 1:40:09Lester Nare?

  These quantum breakthroughs along with every other system that's encrypted, which is not ideal. We have to get to, what is it, post quantum encryption phraseology? 1994, proof of Fermat's Last Theorem.

• 1:40:22Krishna Choudhary?

  Yes, this starts actually in Berkeley with Ken Ribetz's proof of the epsilon conjecture. He resolved that Fermat's Last Theorem, which is a very simple theorem, actually.

• 1:40:35Krishna Choudhary?

  It was made about 358 years ago by Fermat. It was noted in the margins of his book that he had already proved it, but he's like, eh, I don't want to. Classic French, may I just say. Here's the theorem, okay? You got the Pythagorean theorem?

• 1:40:50Lester Nare?

  Yeah.

• 1:40:51Krishna Choudhary?

  Just a squared plus b squared equals c squared. There's plenty of numbers that fit that. For example, three squared plus four squared equals five squared. You have nine plus 16 equals 25. Now, the question is, are there any numbers where a cubed plus b cubed equals c cubed?

• 1:41:09Krishna Choudhary?

  For that matter, are there any such that a to the n plus b to the n equals c to the n, as long as n is not 1 or 2? If it's 1 or 2, it's like obvious, right? So, that's the question. For the longest time, the answer was no. There are no triple integers in the infinity of integers such that a cubed plus b cubed equals c cubed. Isn't that crazy?

• 1:41:33Lester Nare?

  Yeah, yeah, yeah.

• 1:41:34Krishna Choudhary?

  But we couldn't prove it. But it's a hard thing to prove, turns out. The Pythagorean theorem is super easy to prove. People do it in 8th grade, if you take a good geometry class, right? But this n equals 3, n equals 4, in all the infinity of numbers, there are no 3 numbers that you can find that obey that equation. That is Fermat's Last Theorem. So, Ken Ribbit showed Fermat's Last Theorem is the same as if you prove this other Tanayama-Shimomura-Wilde conjecture. He showed that if you prove the Tanayama-Shimomura-Wilde conjecture, then you've proven Fermat's Last Theorem. He showed the connection there. So, Andrew Wiles then made it his goal in life to prove the

• 1:42:20Krishna Choudhary?

  Tanayama-Shimomura-Wilde conjecture, okay? And he spent 10 years locked up at Princeton University's math department in his office up there in Fein Hall, doing nothing else but this one thing. And he got it. And in 1994, he finally proved that conjecture, which then in turn proves Fermat's Last Theorem. It also shows that Fermat definitely did not have a proof. He was clearly capping.

• 1:42:47Lester Nare?

  Yeah, yeah, yeah.

• 1:42:47Krishna Choudhary?

  Right? Because you didn't know about Galois groups and this Shimomura-Wilde conjecture. And like, so much needed to happen to prove Fermat's Last Theorem, that there's no way that Fermat had some trivial proof. And if he thought he did, it was most definitely wrong.

• 1:43:04Lester Nare?

  As to be expected, 1995, creation of the first and one of my favorites, Bose-Einstein condensate.

• 1:43:14Krishna Choudhary?

  Yeah, I mean, we've seen that photo in our podcast so many times, the one on the right.

• 1:43:18Lester Nare?

  Yes.

• 1:43:18Krishna Choudhary?

  Showing the cloud of atoms behaving like a single atom. That's what's happening with the Bose-Einstein condensates. This was first theorized by Bose and Einstein way back, I think in the 1920s. Okay, but realizing it is extremely difficult because you need a group of atoms and you need to cool it down to an insanely small degree. Okay, the Europeans and the Americans were both on a race to do this. Okay, this is one of the big triumphs of the American system of just trying things. And if it fails, don't worry about it and move on. Okay, Eric Cornell and Carl Weinman at Geila and NIST at Boulder and Wolfgang Ketterle at MIT, they achieved the first dilute gas Bose-Einstein condensate.

• 1:44:03Krishna Choudhary?

  Very famously, Eric Cornell and Carl Weinman, their ragtag setup was like, they were using like the lasers from CD players and things like that because they were changing their setup every month. They're like, okay, this isn't working. I don't know where the temperature is leaking from. It's getting hot after we go down to this thing. Let's just, let's just change it around. Meanwhile, the Europeans, they had a theoretical idea of how it should work. And when it didn't work, they would just get stuck on why it didn't work. And there's this really famous documentary that you can find on YouTube showing the difference between these two groups where Eric Cornell and Carl Weinman, they were just like, I don't even care to understand why this didn't work. I have a new idea.

• 1:44:47Lester Nare?

  Yeah, let's move on.

• 1:44:48Krishna Choudhary?

  Let's move on. The three of them won the 2001 Nobel Prize in Physics.

• 1:44:53Lester Nare?

  Can you remind me, does this have an overlap with the macroscopic quantum tunneling piece that we talked about earlier?

• 1:44:59Krishna Choudhary?

  Yeah, because, I mean, they're condensates in the sense that like, you know, they're condensing matter into that form. You gotta be cold.

• 1:45:07Lester Nare?

  Yes.

• 1:45:08Krishna Choudhary?

  There is something, I forget the connection though.

• 1:45:10Lester Nare?

  Because it reminded me back to that episode where we talked about the overlap between. These two concepts.

• 1:45:14Krishna Choudhary?

  Yeah, yeah, yeah, there is, there is an overlap for sure.

• 1:45:16Lester Nare?

  We will move on because that is not the focus of this episode. 1995 acquisition of the Hubble Deep Field. One of the greatest photographs.

• 1:45:26Krishna Choudhary?

  Ever taken.

• 1:45:26Lester Nare?

  Ever taken. And for those who are listening, we do understand it's, it's for the, there's a visual component to so many of our episodes. This is the picture of all of the different galaxies in the square box that you see printed in science classrooms and in museums all over the world. You've a hundred percent seen this photo at one point in your life.

• 1:45:46Krishna Choudhary?

  Yes, and taking this photo was very controversial at the time. This was astronomer Robert Williams and the Space Telescope Institute.

• 1:45:54Krishna Choudhary?

  He had a crazy idea. How about we point the Hubble telescope at nothing for a week? Okay, every other astronomer is like, what are you talking about? I have like 10 different things that I want to point the Hubble telescope at. And he's just like, no, guys, let's just point it at nothing and see what happens. Turns out there's a whole lot of stuff in nothing. If you stare at it long enough, he found 3,000 ancient galaxies in a single patch of empty sky. And it showed that the universe is just like massive.

• 1:46:28Lester Nare?

  Yes.

• 1:46:29Krishna Choudhary?

  It transformed high redshift observational cosmology because these are things that are so far away that usually you don't see it. You got to stare at this patch and collect light for an extended period of time in order to capture these galaxies. Huge.

• 1:46:43Lester Nare?

  Sometimes we need to look where it doesn't seem like there's anything to see and you might see everything. 1995, discovery of the top quark.

• 1:46:50Krishna Choudhary?

  Yes, this is finally completing the particle zoo for the quarks. Physicists at the CDF and the D, D sigma, I think collaborations at Fermilab. They discovered the top quark, which is the sixth and final subatomic building block. So we started with the up and down for the protons. Then we discovered the charm with the J psi particle. With the charm came the strange. And then finally we had bottom first and then top came last from Fermilab.

• 1:47:21Lester Nare?

  Keep your head out of the gutter, folks. We're talking about Quarks. 1997 IBM Deep Blue defeats Garry Kasparov. And I was young, but I even remember this.

• 1:47:32Krishna Choudhary?

  Yeah, this is huge. Even I was in India at the time, and it was huge. Because chess was a big thing in India. Vishwanathan Anand was, you know, rising to stardom. And here chess had been considered something that only humans can play, right? Because there's that extra factor. Chess is an art. Computers can't be intuitive. And suddenly IBM's Deep Blue supercomputer defeated the world chess champion Garry Kasparov in a six-game match. Garry very famously cried shenanigans and said that they had grandmasters behind it. And like, there was definitely a human involved. And like, he accused the IBM team of cheating. They had a final press conference where like, they talked, they like, brought them all on board.

• 1:48:17Krishna Choudhary?

  And like, everyone booed the six computer scientists who had made Deep Blue. Because they thought it was gonna be the end of chess.

• 1:48:24Lester Nare?

  Right.

• 1:48:24Krishna Choudhary?

  Far from it. Chess is super popular now because of that human element.

• 1:48:28Lester Nare?

  Yes.

• 1:48:29Krishna Choudhary?

  We want to see who does the least number of mistakes.

• 1:48:33Lester Nare?

  Yes.

• 1:48:33Krishna Choudhary?

  You know, and I watch chess all the time. It's really fun. It hasn't changed because Deep Blue beat Garry Kasparov.

• 1:48:39Lester Nare?

  Arguably, right now, it's having a renaissance. What's his name, Magnus Carlsen?

• 1:48:42Krishna Choudhary?

  Magnus Carlsen, Hikaru Nakamura.

• 1:48:44Lester Nare?

  Yeah, there's a lot of very popular chess players.

• 1:48:46Krishna Choudhary?

  Yes, yes. I'm a big fan of Fabiano Caruana.

• 1:48:49Lester Nare?

  Yes, yes. In an era where you thought it was dead, it will always come back alive because the human element still matters. 1998, discovery of innate immune activation.

• 1:48:59Krishna Choudhary?

  Yes, you know, with the immune system, there's innate immunity and then adaptive immunity. Adaptive immunity is the part that learns. But innate immunity is stuff that we already know, and it's hardwired into our genetics. Geneticist Bruce Butler at the UT Southwestern, he identified TLR4, toll-like receptor 4. And that unmasked the molecular mechanism for innate immunity. It earned him the 2011 Nobel Prize in Physiology.

• 1:49:31Lester Nare?

  We're getting close to modern day. 1998, dynamical proof of Sagittarius A. I'm a Sagittarius, eh? And I'm Canadian Sagittarius, eh?

• 1:49:43Krishna Choudhary?

  Okay, this was astronomer Andrea Gez at UCLA. She watched, she watched the black hole at the center of our Milky Way. And she found definitive proof that there's definitely something there. What she did was track stars near the Milky Way and saw that them, saw they were looping around in Keplerian orbits, just like planets do around our sun. But there's nothing there in the middle. She calculated the mass of that thing and based on the trajectory of these stars, how small that thing should be. And showed that it's got to be a supermassive black hole.

• 1:50:23Krishna Choudhary?

  It's the center of every galaxy now and it earned her the 2020 Nobel Prize in Physics.

• 1:50:30Lester Nare?

  Back at your second home there at UCLA with a great team over there. 1998, discovery of RNA interference.

• 1:50:38Krishna Choudhary?

  Yes, we talk about genetic mechanisms all the time. This is one of the latest ones that's been developed. This was Andrew Fire and Craig Mello. They discovered RNA interference at Carnegie Institution and UMass Medical School. And they showed that double-stranded RNA can selectively silence targeted genes. In the last episode that we had about non-Mendelian inheritance, we talked about some of the ways that RNA interference can change the genetic genotype and phenotype relationship. This discovery earned them the 2006 Nobel Prize.

• 1:51:15Lester Nare?

  Now we move on, still in 98, discovery of cosmic acceleration, something we've touched on in a variety of different components here.

• 1:51:23Krishna Choudhary?

  We've talked about dark matter.

• 1:51:24Lester Nare?

  Yes.

• 1:51:24Krishna Choudhary?

  But we also know that most of the universe is actually dark energy. This is where dark energy was discovered. Saul Perlmutter at Lawrence Berkeley National Lab, Brian Schmidt at, in Australia, and Adam Rees at the Space Telescope Institute in Baltimore. They showed that the acceleration, they showed that the expansion of the universe is accelerating. The universe is getting bigger and someone's pumping on the gas. It's not coasting. That's very weird.

• 1:51:54Lester Nare?

  Yes.

• 1:51:55Krishna Choudhary?

  Okay? That's where dark energy comes from. They shared the 2011 Nobel Prize in Physics.

• 1:52:01Lester Nare?

  Last one in 1998, development of LeNet 5 convolutional neural networks, which we hear a lot about these days.

• 1:52:11Krishna Choudhary?

  Yes, this is Yan Le Cun and his team at Bell Labs. They developed LeNet 5, which is the convolutional neural network architecture that revolutionized computer vision by automating handwritten digit recognition. This is the first real like application, industrial application of neural networks and convolutional neural networks specifically for the problem of computer vision. Because like when you write your checks and you know, you like scan it and then it goes into your bank account, you don't have to like tell the teller and then the teller punches in something, right? All of that started with this MNIST dataset of the handwritten digits and how they get classified into 0, 1, 2, 3, 4, 5, and 6.

• 1:52:56Krishna Choudhary?

  Yan Le Cun, back in, back in those days, he did not have the sense of fashion that he does now.

• 1:53:01Lester Nare?

  I was gonna say, is that a, is that a young Le Cun with the ponytail there?

• 1:53:04Krishna Choudhary?

  Yeah.

• 1:53:05Lester Nare?

  That is a throwback photo. If you're listening, you might want to take a look at this because you see him nowadays.

• 1:53:09Krishna Choudhary?

  No, he's very fashionable, like got, his glasses are not like whatever those glasses are, right?

• 1:53:16Lester Nare?

  Definitely made that major upgrade. Another one of the godfathers of the modern AI world we live in today. Many of us will remember this as we get into the Y2K era.

• 1:53:28Krishna Choudhary?

  Yeah.

• 1:53:29Lester Nare?

  2000, first draft of the human genome sequenced. 23andMe, eat your heart out.

• 1:53:35Krishna Choudhary?

  Yes, we sequenced the human genome. This is a pretty big deal. Francis Collins, he was representing the Human Genome Project, which was funded by the government. And at the same time, they were competing against Craig Venter at Solara Genomics because he figured, well, I could just do it. They jointly announced the completion of the first draft of the Human Genome. Basically, Bill Clinton like brought them together to the White House and was like, all right, truce, guys, you both won, like, let's, let's stop. And it's a historic milestone, provided a biochemical map of human hereditary instructions, revolutionized medical science, this is how we get personalized medicine, all sorts of really cool stuff.

• 1:54:16Lester Nare?

  Really foundational. Building block, 2001, structural basis of eukaryotic transcription.

• 1:54:22Krishna Choudhary?

  Yeah, this is really the final puzzle in the central dogma. We figured out how DNA replicates itself. We figured out how DNA goes to protein with that, the dictionary of the codons mapping to the amino acids. This is, how does DNA go to RNA? It's through RNA polymerase. Roger Kornberg used high resolution 3D images of RNA polymerase at Stanford University and revealed the atomic scale, structure of this enzyme and how you get that type of transcription. It earned him the 2006 Nobel Prize in Chemistry.

• 1:55:03Lester Nare?

  We're staying in 2001 with something we talked about recently as well in our Nobel Prize episode, discovery of the Fox P3 gene and T reg regulation.

• 1:55:16Krishna Choudhary?

  Yes, this is Mary Brunkow and Fred Ramsdale. They were working at the Darwin Molecular Corporation and Cell Tech Chiroscience in Washington. They identified the Fox P3 gene that's the master transcription factor that governs regulatory T cells, which is the stuff that regulates autoimmune responses, the response of the immune system to the self. Um, huge deal. They won the 2025 Nobel Prize in Medicine and we covered that in detail. So check out that episode.

• 1:55:51Lester Nare?

  It was the, the, what do we say, the military police, the police of the police?

• 1:55:55Krishna Choudhary?

  Yeah, the police of the police. That's right.

• 1:55:56Lester Nare?

  That's the concept here. Staying in 2001 with the first direct detection of an exoplanet atmospheres. One of my favorite things we've talked about too is how we actually do.

• 1:56:07Krishna Choudhary?

  Yes.

• 1:56:08Lester Nare?

  Uh, atmosphere detection for exoplanets.

• 1:56:10Krishna Choudhary?

  Yeah. And this is the first guy to do it. He was, um, David Charbonneau at Caltech Harvard Smithsonian. He used the Hubble Space Telescope to look at the atmosphere of an exoplanet. He waited for the exoplanet to pass in front of the star and then use the spectra of that to figure out what the planet was doing to the star's spectra. Figured out that there's actually a bunch of atomic sodium in that transiting gas giant. Huge.

• 1:56:37Lester Nare?

  It's a fun, fun concept. 2003 computational de novo protein design.

• 1:56:43Krishna Choudhary?

  Yes. Um, this was David Baker at the University of Washington. He used the Rosetta software suite to engineer top seven, which is the protein that you're seeing on the screen over there. That's the world's first entirely custom synthetic protein that's designed completely from scratch. This is where we're starting to become like, you know, godlike.

• 1:57:08Lester Nare?

  Yes.

• 1:57:08Krishna Choudhary?

  In our molecular capacity.

• 1:57:10Lester Nare?

  Yes.

• 1:57:10Krishna Choudhary?

  It's really crazy that in this timeline, we've gone from, what's a gene?

• 1:57:14Lester Nare?

  Yes.

• 1:57:15Krishna Choudhary?

  Oh, it's on a chromosome to almost a hundred years later.

• 1:57:19Lester Nare?

  Yes.

• 1:57:19Krishna Choudhary?

  I designed a protein on my own using software. This is the culmination of biotechnology, artificial intelligence, computation, all sorts of stuff. It earned him the 2024 Nobel Prize in Chemistry, which he actually shared with Dennis Hassabis, um, at Google Alpha Fold.

• 1:57:38Lester Nare?

  Alpha, uh, deep, uh, Google DeepMind.

• 1:57:39Krishna Choudhary?

  DeepMind, sorry. Yes. For Alpha Fold.

• 1:57:41Lester Nare?

  For Alpha, which is again, uh, so incredible. 2004, proof of the green Tao theorem.

• 1:57:48Krishna Choudhary?

  Yes. This is Terrence Tao at UCLA.

• 1:57:50Lester Nare?

  Terrence.

• 1:57:50Krishna Choudhary?

  And Ben Green at the University of Cambridge. They proved that the sequence of prime numbers contains arbitrarily long arithmetic progressions. Meaning like progressions like, you know, three, five, seven. That's an arithmetic progression because there's three prime numbers that are two apart. They showed that the sequence of prime numbers, you, you can give me any number of how apart they are.

• 1:58:14Krishna Choudhary?

  And any number of how long and I'll find you such a sequence in all of the prime numbers, which is kind of crazy. When you think about how rare prime numbers get.

• 1:58:23Lester Nare?

  Yes.

• 1:58:23Krishna Choudhary?

  As you get larger and larger and how they're supposed to be completely random. But there's still somehow some kind of structure, but the randomness creates this structure. It's really, really cool. It bridged additive combinatorics and number theory. Again, one of the few mathematics things that I kind of understand.

• 1:58:38Lester Nare?

  We love to see it. Two thousand and five, the invention of optogenetics.

• 1:58:44Krishna Choudhary?

  Yes, we talk about this a lot. Carl Dyseroth, Ed Boyden and Feng Zhang at Stanford and MIT, they developed optogenetics. This idea of channel proteins, proteins that open and close and let stuff through the cell membrane based on light. So I can shine a light beam and turn on cells and turn off cells. They used light sensitive algae proteins, the same way that GFP is from like green fluorescent protein from like. From, from again, parts of life. This is a revolutionary technology and it's been used in every single university now to probe neural circuits of behaving animals in real time.

• 1:59:24Lester Nare?

  We had a great episode on a breakthrough paper around optogenetics a few episodes back that it's worth taking a look at. We're staying in two thousand and five. Nucleoside based modifications of mRNA vaccines. Ooh, scary.

• 1:59:38Krishna Choudhary?

  Yeah, well, Caitlin Carrico and Drew Weisman at the University of Pennsylvania. They discovered that you can replace the uridine with pseudo uridine in synthetic mRNA. And that prevents inflammatory immune responses in our body. So now effectively you can create vaccines using mRNA very quickly. You don't need to figure out how to keep a virus alive and then kill it and then all this other kind of stuff. You can just give the genetic instruction for whatever antigen, put that into an mRNA. You put it into the body, the body takes care of the rest. It makes the antigen, it trains the immune response, and then all of a sudden you're immune. This is the backbone of the COVID nineteen vaccine that. Brought us out of the pandemic arguably,

• 2:00:22Krishna Choudhary?

  and it earned them the 2023 Noel Prize in Physiology.

• 2:00:25Lester Nare?

  And it's worth understanding the mechanics here because once you understand the mechanics, the idea that it's spooky becomes way less concerning. 2007, we referenced the mother of all demos. This is maybe the closest

• 2:00:39Krishna Choudhary?

  Modern.

• 2:00:40Lester Nare?

  Modern version of the mother of all demos with the invention of the multi-touch smartphone.

• 2:00:46Krishna Choudhary?

  Yeah.

• 2:00:46Lester Nare?

  In 2007.

• 2:00:47Krishna Choudhary?

  I know a lot of haters are gonna hate me for putting this on the timeline, but I really think this was a seminal event in human technology history. Okay, Steve Jobs, John Ive, and a team at Apple introduced the iPhone.

• 2:01:04Lester Nare?

  I'm just gonna say Johnny Ive because people are gonna be like, oh, Johnny Ive, who's that?

• 2:01:08Krishna Choudhary?

  Johnny Ive, sorry, sorry.

• 2:01:10Lester Nare?

  No, no, no, he's, it's fine.

• 2:01:11Krishna Choudhary?

  It's getting late, okay, guys? But, you know, they introduced the iPhone.

• 2:01:16Lester Nare?

  Yes.

• 2:01:17Krishna Choudhary?

  It's the first commercially successful multi-touch smartphone. I mean, it completely changed the world, right?

• 2:01:22Lester Nare?

  Yeah.

• 2:01:23Krishna Choudhary?

  Mobile computing era drives the transition from desktop-bound services to now cloud-connected applications on your cellphone. I mean, we're all addicted to our cellphone. Perhaps that's this man's fault, but at the end of the day, it has completely transformed the global economy.

• 2:01:39Lester Nare?

  I mean, I look at my family in Zimbabwe, which did not have the same industrial revolution time period in terms of infrastructure that we had in the US. Anywhere you go in ZIM right now, the most remote place ever, they all have touchscreen, multi-touch smartphones.

• 2:01:54Krishna Choudhary?

  Yeah.

• 2:01:54Lester Nare?

  All their money is there. All the economies run from these devices.

• 2:01:58Krishna Choudhary?

  Same with India.

• 2:01:59Lester Nare?

  And it's a huge enabling layer. And it's very different, different cultures. It's manifested differently. In first world countries, there's some issues because it's not, it's just different.

• 2:02:10Krishna Choudhary?

  We have a curse of opulence.

• 2:02:12Lester Nare?

  Yes.

• 2:02:12Krishna Choudhary?

  You know?

• 2:02:13Lester Nare?

  Yes.

• 2:02:13Krishna Choudhary?

  But, yeah, in the world at large, this is a huge deal.

• 2:02:17Lester Nare?

  Huge deal, huge deal. 2008, confirmation of subsurface water ice on Mars.

• 2:02:23Krishna Choudhary?

  Yeah, this was NASA's Phoenix Mars lander. It confirmed the presence of subsurface water ice. In the Martian Arctic utilizing a robotic excavation, it basically like excavated, found some ice and then started taking pictures of it repeatedly and you could see it, the ice go down, you know, and you can, you can calculate just how much there is. Um, this was huge because we're now, we found water definitively.

• 2:02:48Lester Nare?

  Yes.

• 2:02:48Krishna Choudhary?

  On Mars.

• 2:02:49Lester Nare?

  Next door.

• 2:02:50Krishna Choudhary?

  Yeah.

• 2:02:50Lester Nare?

  So water might be very pervasive everywhere as a building block of life. 2011 invention of CAR T cell therapy.

• 2:02:59Krishna Choudhary?

  Yes, this is personalized medicine, um, doing really, really great things. Carl June at the University of Pennsylvania, Steven Rosenberg at NIH and Michael Sotoline at MSKCC, they revolutionized oncology with this CAR T cell therapy. It's a living drug that programs T cells to hunt and destroy cancer cells. It's, it's pretty incredible, right? It inaugurated the modern era of cellular immunotherapy. It's leading the, leading to the first FDA approved cell-based gene therapies and creating a robust, rapidly evolving pipeline for, you know, treating these types of malignancies.

• 2:03:39Lester Nare?

  It's incredible that again, you see these things all building on each other. We are getting close to the end of our list and something we mentioned earlier about splicing made me think of this 2012 discovery, the development of CRISPR-Cas9 genome editing. Another thing we talk about often on the podcast.

• 2:03:58Krishna Choudhary?

  Yes, this is the graduation of the restriction enzyme concept.

• 2:04:02Lester Nare?

  Exactly.

• 2:04:02Krishna Choudhary?

  Before we had the idea of restriction enzymes, which were specific enzymes that looked for specific patterns in the DNA for where to cut. Here we've got a restriction enzyme that is programmable, meaning I give you the DNA that you want to look for and it'll do the rest, right? It'll find whatever DNA I want instead of having specific tools. Now I've got a generalized tool. Um, this was Jennifer Doudna at UC Berkeley along with, um, her partner Emmanuel Charpentier in France. We did a deep dive on this episode last year, actually.

• 2:04:35Lester Nare?

  Yes.

• 2:04:36Krishna Choudhary?

  In preparation for our Nobel Prize because this is one of my favorite Nobel Prizes. I remember being in college at the time when this was discovered in 2012. And immediately even at Princeton as a sophomore.

• 2:04:46Lester Nare?

  Yeah.

• 2:04:46Krishna Choudhary?

  Um, we all have recognized.

• 2:04:48Lester Nare?

  This is.

• 2:04:49Krishna Choudhary?

  That this, we were like, okay, so when's the Nobel coming?

• 2:04:51Lester Nare?

  A hundred percent.

• 2:04:52Krishna Choudhary?

  And it came, uh, pretty, pretty soon after, I think it was in 2019, so. Quite soon, no, 2020, Nobel Prize in Chemistry.

• 2:04:58Lester Nare?

  And it just is an enabling layer for so many things we can tell. There's so many stories we talk about in our rundowns and stuff that just happen to use this as a tool in the toolbox for any number of different things. And it is really a huge, we're starting to get into, we've figured out how to read and now we're figuring out how to write to our fundamental biological layers. 2015, first successful vertical landing of an orbital rocket. We will be a spacefaring species.

• 2:05:28Krishna Choudhary?

  Yes, this was SpaceX engineers. They achieved the first propulsive vertical landing of an orbital class Falcon 9 first stage booster at landing zone one. I mean, this is huge, right? It catalyzed the modern commercial space race, enabled high cadence deployment of massive low earth orbit satellite constellations. I mean, maybe astronomers don't like that because it's getting in the way of their telescopes. But at the same time, now we're getting remote access internet to places on earth where that never had access to the internet. We are becoming a spacefaring civilization because rockets are now cheap.

• 2:06:09Krishna Choudhary?

  This was SpaceX and on the right hand side, that's the full maturation of this technology. Now they're catching giant rockets that are the size of like the Empire State Building with a chopstick. It's getting crazy.

• 2:06:23Lester Nare?

  This was 11 years ago and I think to date, I'm not familiar with anyone that's replicated this feat at a scale that can be used for commercial reusability.

• 2:06:36Krishna Choudhary?

  Yeah, yeah. And I mean, now we take it for granted, but like dude, at the time, it was insane.

• 2:06:42Lester Nare?

  No one thought it was popping. Everyone was like, this is ridiculous.

• 2:06:44Krishna Choudhary?

  Yeah, yeah. Oh, like NASA's been trying for a while. Actually, no, it's like, you know, with modern computing now and the modern hardware and the fast feedback between control systems and how you can like point the rocket booster and things like that made it possible. It's amazing.

• 2:06:58Lester Nare?

  Still not replicated, so it's not that trivial. 2015, one of my favorite instruments, the detector.

• 2:07:06Lester Nare?

  First detection of gravitational, first direct detection of gravitational waves.

• 2:07:11Krishna Choudhary?

  Yeah, this is 20 years in the making. I talked about how we failed at the superconducting supercollider. That was a wake up call for science in America. They decided to start doing big projects, high risk, high reward. This was the highest risk because no one thought it was possible. I mean, you have to measure the difference in the length of a a leg of your detector that is four kilometers long by something like 10 to the minus 18 meters, right? So it's like an atom is 10 to the minus 10. You've got to go an atom within an atom and measure that tiny difference in order to measure gravitational waves. We had already discovered gravitational waves, kind of, with the Taylor-Hulse

• 2:07:55Krishna Choudhary?

  binary pulsar, where we had shown that obviously gravitational waves were permeating out of the binary pulsar.

• 2:08:01Lester Nare?

  That was an indirect.

• 2:08:02Krishna Choudhary?

  But it was indirect.

• 2:08:03Lester Nare?

  Yes.

• 2:08:03Krishna Choudhary?

  This, we're literally measuring a gravitational wave move through space and time and distort the length and the timing of photons traveling in tunnels. There are two observatories now, one in Washington State and one in Louisiana. The LIGO collaboration detected two black holes colliding, spiraling together and forming one big black hole that shone with enough energy that was brighter than all of the stars in the universe combined. Rayner Weis, Barry Barish, Kip Thorne, they won the 2017 Nobel Prize in Physics, basically two years after this because everyone was like, holy.

• 2:08:43Lester Nare?

  Holy, you know what?

• 2:08:45Krishna Choudhary?

  Yeah.

• 2:08:45Lester Nare?

  That.

• 2:08:47Krishna Choudhary?

  I can't believe you did it. Yeah.

• 2:08:48Lester Nare?

  I can't believe you actually.

• 2:08:49Krishna Choudhary?

  I can't believe you've done this. Yeah. It's absolutely amazing. We have a deep dive into the LIGO discovery and all of the shenanigans and drama that went into it.

• 2:09:01Lester Nare?

  The postdocs on the, on the top, people thought they were driving around.

• 2:09:04Krishna Choudhary?

  Yeah.

• 2:09:04Lester Nare?

  It's a great, it's a great deep dive. Definitely check it out. We are getting very close to the conclusion of our list. We have four more left. We are in 2017.

• 2:09:16Lester Nare?

  Invention of the Transformer Architecture.

• 2:09:19Krishna Choudhary?

  Yes, this is a team of researchers at Google Brain in the Bay Area. They publish Attention Is All You Need. It's a paper that has a banger title and it introduces. It introduces the Transformer Deep Learning Architecture. That's based on the self-attention mechanism. This is an architectural breakthrough. The paper itself is just about translating language. Okay, and they used it to translate language. Pretty soon it turned out this is something that can recognize and learn long-term correlations in text. Meaning, what does this word have to do with all of the words that came before it? And recognize context.

• 2:10:02Krishna Choudhary?

  And really try to distill the understanding of what the text is. This is the breakthrough that catalyzed the modern artificial intelligence revolution. It enabled large language models. Now we have ChatGPT, Claude, Gemini, Llama, DeepSeek. All of that comes from this 2017 paper.

• 2:10:22Lester Nare?

  No European models, just everyone else, apparently. Well, no, they have, what's it called? They have a La Chat? No, Mistral.

• 2:10:31Krishna Choudhary?

  Yeah. Moving on.

• 2:10:36Lester Nare?

  2019, first direct image of a black hole shadow. I remember this one breaking.

• 2:10:41Krishna Choudhary?

  Yeah, this one was great. The memes were great from this. This was the Event Horizon Telescope led by Americans at the Harvard Smithsonian Center for Astrophysics. They captured the first direct image of a supermassive black hole's shadow in the galaxy M87. They subsequently also captured the supermassive black hole at the center of our Milky Way. I mean, this is insane. It's a network of telescopes across the globe to resolve a single black hole that's the size of about the solar system, billions of light years away. Absolutely incredible. We literally are looking at a black hole.

• 2:11:19Lester Nare?

  Unbelievable. Yeah, this, this one, when science breaks through in the mainstream, this one definitely.

• 2:11:25Krishna Choudhary?

  This, I mean, this one. It was insane. Everybody was like, that's crazy.

• 2:11:28Lester Nare?

  That's crazy. Uh, that's crazy. We are still in 2019. And I remember talking to you about this experimental demonstration of quote quantum supremacy.

• 2:11:37Krishna Choudhary?

  Yeah, I think this is a pretty big deal. This was John Martinez and Google Quantum AI team at UC Santa Barbara. They achieved quantum supremacy with their 53 qubit Sycamore processor and they solved a complex sampling task. They were basically trying to sample from a probability distribution that a quantum computer would produce. Kind of a roundabout way of declaring quantum supremacy, which is this idea of solving a problem that no classical computer can solve. Right after this paper was published, IBM came out and said that actually there is a classical algorithm that'll do it. It'll take you two days instead of like the seconds that it took you, but it'll still do it. And these guys weren't that worried because this is a 53 qubit Sycamore processor.

• 2:12:22Krishna Choudhary?

  They figured, I mean, that classical algorithm, again, it's not going to be able to scale. They recently released, I think, 100 plus or 200 qubit algorithm. And that one definitively, a classical computer couldn't do for millions of years. It's a roundabout problem. It's kind of a problem that's made to show quantum supremacy, but I think it shows just how far.

• 2:12:43Lester Nare?

  Yes.

• 2:12:44Krishna Choudhary?

  Technology has gone to create actually like a workable quantum computer that can, that can take from a quantum distribution, right? That's something that a classical computer can't do. Um, I thought it was still a really cool paper.

• 2:12:57Lester Nare?

  Meaningful. I remember we were talking. I texted you immediately after I saw the headline. Like, what does this all mean? And where do we go from here? We are almost at the conclusion of our 250 year list. Thank you all for those who are still with us. Two and a half hours in 2021 launch of the James Webb Space Telescope.

• 2:13:21Krishna Choudhary?

  This is huge. The James Webb Space Telescope. It's in deep space orbit at the second Lagrange point, so it's not even orbiting Earth. We just shot it out. It's out in a little spot. That's a stable orbit between the Earth and the Sun. It sort of chases us along, or maybe we chase it. I forget which one L2 is. But in any case, it's got a giant gold coated mirror, highly sensitive infrared instruments. It's got effectively like a helium cooling system to cool the instruments down. So that it can take these pristine images and it is already rewriting astrophysics textbooks. Absolutely amazing. We talk about the results from the James Webb almost every month.

• 2:14:03Lester Nare?

  It's unbelievable. It's happening all the time and we have Vera Rubin. We have the Romans about to go up. There's just so many things that are just going to change our entire perspective of what we see in the night sky. And we are going to end with something that may feel curious on this list. But if you've stayed with us for part two only, part one and part two, or just are coming from the clips and find yourself here at this part of the episode. In 2025, we have seen a federal science funding contraction. And if you've seen the incredible advancements, the way it's impacted the lives of not only us, but all of humanity over this very short 250 year period.

• 2:14:47Lester Nare?

  All of this required an ecosystem that was willing to fund science when we didn't yet understand whether it was going to have a commercial benefit, a business benefit, help the stock market price of some biotechnology company. But we've had hundreds of thousands, millions of researchers, scientists and institutions dedicate their lives to exploring the world around us. That has given us so many of the conveniences, the advancements, the health benefits that we get to experience every day. And sometimes take for granted. And that has been funded almost primarily by the federal funding system of grants, research grants.

• 2:15:34Lester Nare?

  Other programs and unfortunately in the 2025 and 2026 time period, there's been a suspension of over 7800 federal research grants and a $3 billion shortfall across the National Institutes of Health and the National Science Foundation, which is now triggering an existential crisis within the American scientific ecosystem, which is now driving some of our best people to find stability elsewhere.

• 2:15:59Krishna Choudhary?

  Yeah.

• 2:16:00Lester Nare?

  Because they have families, they have partners and kids, they have mortgages and needs to survive. And it is so important that we understand the value of this fundamental science research ecosystem, which we've tried very hard to expose through this incredible deep dive journey, which again, you can always go back to at FFP pod.com backslash America 250 to see and understand all of these great things that curiosity driven science has given us and we hope will continue to give us for decades and centuries and millennia to come.

• 2:16:40Lester Nare?

  But it is not possible if we take away the very funding that enables it to happen in the first place. And it is a slightly morbid place to end our episode, but unfortunately.

• 2:16:52Krishna Choudhary?

  This is the reality.

• 2:16:53Lester Nare?

  This is the reality we live in today. And I just, I want to give you an opportunity to speak to this as well before we wrap up the episode.

• 2:17:00Krishna Choudhary?

  Yeah, I mean, look, American science has dominated for a reason.

• 2:17:07Krishna Choudhary?

  It's because of taxpayers like us and I am incredibly proud as an American taxpayer of all of these things that our people have been able to contribute to humanity. Just a few little numbers, right? Over the past year, 7800 research grants across the NIH and the NSF have been canceled, totaling $3 billion in lost and frozen funding. And what that means is you were alluding to a brain drain. Something like 10,000 doctoral trained STEM and healthcare professionals have left America for greener pastures. It's, it's a massive, massive thing. There's a new mandate from the Office of Management and Budget

• 2:17:51Krishna Choudhary?

  that introduces a centralized political oversight to grant making, which I think is extremely dangerous. The whole idea of curiosity driven research.

• 2:18:03Krishna Choudhary?

  And basic research is to do is to pursue questions that are interesting because of that reason only they are interesting. Okay, not because of some political agenda and blah, blah, blah, blah, blah. I think I think we're really going backwards. It's not over yet.

• 2:18:21Lester Nare?

  It's not.

• 2:18:22Krishna Choudhary?

  And I do think that American infrastructure in science is going to bounce back. But it's going to take an effort from, I think, average taxpayers like us to call our representatives in Congress, to call our senators and to pressure them to make things right when it comes to funding the NIH, funding the NSF, funding NASA science. NASA shouldn't just be like a military wing. Okay, it should be something that makes things like the James Webb Space Telescope. So, you know, I'll get off my soapbox.

• 2:18:54Lester Nare?

  No, I think it's important. And one of the ways we will try to help, you know, this is an active process that is happening now. There are budget negotiations that are going into the what will now be the funding cycle for 2027. And there are going to be ways in which we can impact that process. We are working on a couple of initiatives to help you understand what does that look like? How does this science funding actually work? What is the number? How big is it? You'd be surprised how small it actually is.

• 2:19:23Krishna Choudhary?

  Yeah.

• 2:19:24Lester Nare?

  And if we want to talk about ways in which we can attack the deficit, this is not really the best place to look because

• 2:19:30Krishna Choudhary?

  No.

• 2:19:30Lester Nare?

  I promise you are wasting money in much more egregious places, in much larger ways. But it's important to talk about the data first and understand from first principles, how science, funding and policy really works. And that's an initiative we look forward to working on in the wake of, again, our 250th America Celebration on the history, science, innovation, and the ecosystems and infrastructures that have enabled that within the US for such a long time. My name is Lester Nare, joined as always by my co-host and our resident PhD, Krishna Choudhary. We are so grateful for you for joining us on this massive

• 2:20:13Lester Nare?

  Four and a half hour, two part banger. And as you go out and celebrate at your barbecues, spend time with friends and family and enjoy so many of the benefits and the shoulders that we are standing on from innovators that have come before us. Remember, it does not happen in a vacuum and it is something in an ecosystem that we need to continue to protect and advance for the betterment of not only our own families, but for the families of our greater human family. We will see you all with our next episode that we will be back in normal attire for.

• 2:20:50Lester Nare?

  Next week. Thank you all again for joining us. And again, if you think we missed something that should have been on the list, be sure to comment below. We will see you all next week.