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Beyond DNA: The Search for Alien Biology · The Last Observer: Science and Beyond

• 0:00
  Speaker 1: I want you to just picture something for a second.
• 0:03
  Speaker 1: If I were to ask you to imagine the absolute,
• 0:06
  Speaker 1: like the most fundamental ingredients of life, what immediately pops
• 0:10
  Speaker 1: into your head?
• 0:11
  Speaker 2: Oh? Well, probably the same thing everyone thinks.
• 0:13
  Speaker 1: Of, right exactly. Yeah, if you're like most people, you're
• 0:16
  Speaker 1: probably picturing two things. You're picturing water, so you know,
• 0:21
  Speaker 1: maybe shimmering blue ocean or just a drop of morning dew, right,
• 0:25
  Speaker 1: and then a DNA. Yeah, that classic like twisting double
• 0:29
  Speaker 1: helix we've all seen in every single biology textbook ever. Yeah,
• 0:33
  Speaker 1: the classic ladder, right, And I mean it makes perfect
• 0:37
  Speaker 1: sense what you would think of those two things. They
• 0:39
  Speaker 1: are literally the absolute bedrock of everything alive on this planet. Everything,
• 0:44
  Speaker 1: literally every single thing, from like the microscopic bacteria clinging
• 0:48
  Speaker 1: to some superheated deep sea hydrothermal event, you know, all
• 0:52
  Speaker 1: the way up to a massive blue whale just gliding
• 0:56
  Speaker 1: through the Pacific. And obviously you and me, we all
• 0:59
  Speaker 1: share it. Yeah, we all shared this exact same fundamental recipe.
• 1:02
  Speaker 2: It really is. It's the unifying thread of all known existence.
• 1:07
  Speaker 2: I mean, you look at the sheer diversity of the
• 1:09
  Speaker 2: natural world, right, the millions of species, the extreme environments
• 1:13
  Speaker 2: they somehow survive in the wildly different ways they consume energy.
• 1:17
  Speaker 2: It's crazy, it is, But all of it ultimately boiled
• 1:21
  Speaker 2: down to that exact same, elegant but incredibly specific chemical.
• 1:26
  Speaker 1: Architecture, just water and DNA.
• 1:28
  Speaker 2: Exactly. You have water acting as the universal solvent, kind
• 1:33
  Speaker 2: of providing the fluid stage where all the biological action
• 1:36
  Speaker 2: actually happens. Yeah, and then you have DNA acting as
• 1:39
  Speaker 2: the script, like the genetic blueprint, dictating exactly what the
• 1:42
  Speaker 2: molecular actors should do. Right.
• 1:44
  Speaker 1: And because it's literally everywhere, it feels fixed. It does
• 1:47
  Speaker 1: like it feels like a fundamental law of physics or something.
• 1:50
  Speaker 1: But and this is the thing that is exactly the
• 1:52
  Speaker 1: assumption we're going to completely shatter today. Oh absolutely, because
• 1:56
  Speaker 1: we're exploring a reality that is, honestly, it's just mind
• 1:59
  Speaker 1: bending once you start to really sit with it. We're
• 2:01
  Speaker 1: going to look at the very real, scientifically grounded possibility
• 2:05
  Speaker 1: that Earth's biology. You know, this DNA and water recicue
• 2:09
  Speaker 1: we hold so sacred, it might just be one single
• 2:13
  Speaker 1: version of life.
• 2:14
  Speaker 2: Yeah. It requires a pretty profound paradigm shiftut because we
• 2:18
  Speaker 2: are so accustomed to just equating the word life exclusively with.
• 2:22
  Speaker 1: Earth life, right, Like they're synonyms exactly.
• 2:25
  Speaker 2: Yeah, But from a strictly scientific, like chepical standpoint, there
• 2:30
  Speaker 2: is absolutely no universal law that dictates life must be
• 2:35
  Speaker 2: built this way, no law at all, none. We basically
• 2:38
  Speaker 2: suffer from this intense observational bias.
• 2:41
  Speaker 1: So, Okay, the best way I can kind of wrap
• 2:43
  Speaker 1: my head around this is to think about the device
• 2:45
  Speaker 1: you're using right now to listen to us. Okay, yeah,
• 2:48
  Speaker 1: like your smartphone or your laptop. For billions of years
• 2:51
  Speaker 1: on this planet, we've essentially been assuming that the entire
• 2:54
  Speaker 1: universe only runs on Earth OS Earth operating system like that, right,
• 2:58
  Speaker 1: Earth OS, And in this specific so US, the core
• 3:00
  Speaker 1: programming language is DNA, and the physical environment it needs
• 3:04
  Speaker 1: to you know, run smoothly is liquid water. We've just
• 3:09
  Speaker 1: assumed that's the only software and hardware combination that can
• 3:12
  Speaker 1: possibly boot up and create a living thing. But like,
• 3:15
  Speaker 1: what if there are entirely different operating systems out there?
• 3:18
  Speaker 2: Well, there almost certainly are, right, Like what if.
• 3:20
  Speaker 1: There's a Mac to our PC or something so completely
• 3:23
  Speaker 1: alien it doesn't even use a recognizable file system at all?
• 3:27
  Speaker 2: That is fundamentally what we are deconstructing today that fixed formula, right,
• 3:32
  Speaker 2: because we're going to look at how the cutting edge
• 3:35
  Speaker 2: field of synthetic biology is proving that alternative genetic codes
• 3:39
  Speaker 2: aren't just science fiction anymore.
• 3:41
  Speaker 1: They're real.
• 3:41
  Speaker 2: They're actively being synthesized in laboratories right now.
• 3:44
  Speaker 1: That's wild.
• 3:45
  Speaker 2: And we'll explore the thermodynamic reality of how a solvent
• 3:49
  Speaker 2: that is entirely toxic to us, like liquid ammonia, might
• 3:53
  Speaker 2: actually replace water as the perfect foundation for like a
• 3:57
  Speaker 2: cryogenic biology.
• 3:59
  Speaker 1: Ammonia just crazy.
• 4:01
  Speaker 2: Yeah, And then we'll dive into the eerie mechanics of
• 4:04
  Speaker 2: shadow biospheres.
• 4:05
  Speaker 1: Oh, shadow biospheres. I love that term.
• 4:07
  Speaker 2: It's fascinating, the idea that radically different life forms could
• 4:10
  Speaker 2: be existing right next to us, Yeah, completely undetected by.
• 4:13
  Speaker 1: Our instruments, invisible to us exactly.
• 4:16
  Speaker 2: And ultimately we're going to arrive at a concept that
• 4:20
  Speaker 2: basically redefines everything, the idea that life isn't a specific
• 4:24
  Speaker 2: chemical formula at all, but rather it's just a pure
• 4:27
  Speaker 2: pattern of information.
• 4:29
  Speaker 1: Okay, So let's start with that first big pillar, dismantling
• 4:33
  Speaker 1: the fixed formula of DNA and water. Yeah, let's do it,
• 4:37
  Speaker 1: because it's one thing to say there might be other
• 4:39
  Speaker 1: ways to make life right. But it's another to realize
• 4:42
  Speaker 1: how deeply our science has been kind of handicapped by
• 4:45
  Speaker 1: our own biology.
• 4:46
  Speaker 2: Yeah, astrobiologists and theoretical biologists, they actually refer to this
• 4:50
  Speaker 2: as the end of one problem, en of one, right,
• 4:54
  Speaker 2: because in statistics, you know, your sample size is denoted
• 4:58
  Speaker 2: by the letter N.
• 4:59
  Speaker 1: Okay.
• 4:59
  Speaker 2: Sure, But for the study of life in the universe,
• 5:02
  Speaker 2: our sympathize is exactly one Earth, just Earth. We have
• 5:05
  Speaker 2: absolutely nothing else to compare it to. Wow, So we
• 5:08
  Speaker 2: look around. We observe that every single living thing we
• 5:11
  Speaker 2: have ever sequenced or you know, examined under a microscope
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  Speaker 2: relies on DNA for its genetic code and water as
• 5:17
  Speaker 2: it's solvent.
• 5:18
  Speaker 1: Right one hundred percent of the time exactly.
• 5:20
  Speaker 2: And because it's the only template we have ever known,
• 5:23
  Speaker 2: we just erroneously elevated to a universal requirement.
• 5:26
  Speaker 1: We confuse the vehicle with the destination.
• 5:28
  Speaker 2: Oh, that's a good way to put it.
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  Speaker 1: Yeah, Like the destination is being alive, right, right, replicating, metabolizing,
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  Speaker 1: adapting to an environment. Right, But the vehicle on Earth
• 5:39
  Speaker 1: just happens to be like a Honda Civic made of carbon,
• 5:43
  Speaker 1: DNA and water, exactly. Yeah, but there's literally no physical
• 5:48
  Speaker 1: law saying you can't get to that exact same destination
• 5:52
  Speaker 1: in a completely different kind of vehicle.
• 5:54
  Speaker 2: And for decades that idea was purely theoretical.
• 5:57
  Speaker 1: Just people talking.
• 5:58
  Speaker 2: Yeah, scientists would just debate alternate native biochemistries, but they
• 6:01
  Speaker 2: had absolutely no physical proof, right. But that has completely
• 6:06
  Speaker 2: changed with the advent of synthetic biology. Okay, so what changed, Well,
• 6:10
  Speaker 2: researchers aren't just looking through microscopes at what already exists anymore.
• 6:14
  Speaker 2: They are actively playing with the fundamental chemical building blocks
• 6:19
  Speaker 2: to see what else is actually possible.
• 6:21
  Speaker 1: They're building it.
• 6:22
  Speaker 2: They're building it, and they are demonstrating that alternative genetic
• 6:25
  Speaker 2: systems are fundamentally viable.
• 6:27
  Speaker 1: Okay, let's get into the weeds on this, because this
• 6:30
  Speaker 1: is where like the biology textbooks actually get rewritten. Oh completely,
• 6:34
  Speaker 1: Because DNA is a very specific molecule, right, It has
• 6:37
  Speaker 1: a sugar phosphate backbone that forms the sides of the ladder,
• 6:41
  Speaker 1: and it uses four specific chemical bases adenine, cytosine, thymine,
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  Speaker 1: and guanine, ACT and G right, the wrongs of the ladder.
• 6:50
  Speaker 1: So how exactly are synthetic biologists changing that?
• 6:54
  Speaker 2: Well, they're attacking it from multiple angles. Actually, one of
• 6:58
  Speaker 2: the most groundbreaking examples is the creation of something called
• 7:01
  Speaker 2: hatch emogi.
• 7:02
  Speaker 1: DNA hatch emoji.
• 7:03
  Speaker 2: Yeah, so hachi means eight in Japanese and moji means
• 7:06
  Speaker 2: letter eight letters exactly. Researchers successfully engineered a synthetic DNA
• 7:11
  Speaker 2: molecule that uses eight building blocks instead of the standard four. Whoa, yeah,
• 7:16
  Speaker 2: they get the natural ACT and G, but then they
• 7:18
  Speaker 2: added four completely synthetic basis named SBP and Z.
• 7:23
  Speaker 1: And these synthetic bases like, they don't exist anywhere in nature.
• 7:27
  Speaker 2: Nowhere that we know of. Wow, they were strictly designed
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  Speaker 2: in a lab to form completely unnatural base pairs utilizing
• 7:34
  Speaker 2: different hydrogen bonding patterns. But here is the critical part.
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  Speaker 2: This eight letter hachimog DNA. It still forms a stable
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  Speaker 2: double helix.
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  Speaker 1: Wait, really, it still twists perfectly.
• 7:46
  Speaker 2: It still twists. Its thermodynamic properties are entirely stable and predictable.
• 7:51
  Speaker 2: It can store information, and astonishingly, it can even be
• 7:55
  Speaker 2: transcribed into RNA by engineered enzymes.
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  Speaker 1: That is insane.
• 8:00
  Speaker 2: Roofs that the four letter genetic code we have is
• 8:02
  Speaker 2: not chemically mandated by the universe.
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  Speaker 1: It's just a fluke.
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  Speaker 2: It's just the one that happened to win out in
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  Speaker 2: the primordial soup of early Earth.
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  Speaker 1: Okay, but even with hotch emoji DNA, you are still
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  Speaker 1: using the same basic structure, right, like that sugar phosphate backbone.
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  Speaker 2: That's true.
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  Speaker 1: So what if we strip away even more because I
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  Speaker 1: know researchers are also working on something called x and
• 8:22
  Speaker 1: as like xeno nucleic acids.
• 8:24
  Speaker 2: Yes, X andase take the deconstruction a whole step further. Okay,
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  Speaker 2: So instead of just changing the letters like the bases,
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  Speaker 2: they actually change the backbone of the molecule itself.
• 8:33
  Speaker 1: They swap out the sides of the latter exactly.
• 8:35
  Speaker 2: And one of the most fascinating examples of this is
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  Speaker 2: p ANDA, which stands for peptide nucleic.
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  Speaker 1: Acid peptide nucleic acid.
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  Speaker 2: Okay, So, in standard DNA, the backbone is made of
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  Speaker 2: deoxydrobose sugars and phosphate groups, right, and those phosphate groups
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  Speaker 2: carry a negative electrical charge. But in p and A,
• 8:54
  Speaker 2: that entire sugar phosphate backbone is replaced by a peptide backbone,
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  Speaker 2: which is similar to what you find in proteins.
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  Speaker 1: Hang on let me push back on this logically for
• 9:04
  Speaker 1: a second. Sure, because if you replace the negatively charged
• 9:08
  Speaker 1: DNA backbone with a peptide backbone, which is neutrally charged, right, right,
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  Speaker 1: wouldn't that fundamentally change how the molecule interacts with its environment?
• 9:18
  Speaker 2: Oh?
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  Speaker 1: Absolutely, Because in standard DNA, the negative charges on the
• 9:21
  Speaker 1: two strands they repel each other.
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  Speaker 2: Slightly, right, electrostatic repulsion, right.
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  Speaker 1: And that prevents the molecule from just like collapsing in
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  Speaker 1: on itself, and it helps it unzip during replication. So
• 9:33
  Speaker 1: without that negative charge, wouldn't a PNA molecule just clump
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  Speaker 1: together into some useless knot?
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  Speaker 2: That is exactly the kind of structural problem that synthetic
• 9:42
  Speaker 2: biologists have to solve, right, And the reality is actually
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  Speaker 2: pretty counterintuitive. Because PNA lacks that electrostatic repulsion between the strands,
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  Speaker 2: the two strands actually bind to each other much more
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  Speaker 2: tightly and stably than natural DNA.
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  Speaker 1: Oh, so it overcorrects in a way.
• 9:58
  Speaker 2: Yeah, The binding is incredibly strong, so strong in fact,
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  Speaker 2: that it might actually be too stable for life on Earth.
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  Speaker 2: Too stable, yeah, because Earth life requires DNA to constantly
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  Speaker 2: zip and unzip to read the genetic code and you
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  Speaker 2: repulatory it has to pull apart exactly, and if the
• 10:15
  Speaker 2: strands are stuck together too tightly, the biological machinery just
• 10:19
  Speaker 2: can't pry them apart at room temperature.
• 10:21
  Speaker 1: But wait, that's only a problem if you are trying
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  Speaker 1: to operate at Earth temperatures in liquid water.
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  Speaker 2: Precisely the point ah P and a's extreme stability might
• 10:30
  Speaker 2: make it a terrible genetic molecule for a warm watery
• 10:32
  Speaker 2: planet like Earth. But if you take that exact same
• 10:36
  Speaker 2: molecule and place it in an environment that is significantly hotter,
• 10:40
  Speaker 2: or utilize a completely different solvent that interacts differently with
• 10:44
  Speaker 2: neutral molecules, Suddenly that hyperstability goes from being a bug
• 10:48
  Speaker 2: to a.
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  Speaker 1: Feature that is fascinating.
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  Speaker 2: It forces us to realize that the genetic code and
• 10:54
  Speaker 2: the solvent it floats in, they are an intimately coupled system.
• 10:57
  Speaker 1: They work together.
• 10:58
  Speaker 2: Yeah, if you change the code, you might need to
• 11:01
  Speaker 2: change the ocean.
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  Speaker 1: Wow, which brings us perfectly to the second massive assumption.
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  Speaker 1: We really need to dismantle right, the absolute necessity of
• 11:10
  Speaker 1: water right, because if we swap out the genetic software,
• 11:13
  Speaker 1: we have to look at swapping out the environmental hardware
• 11:16
  Speaker 1: we do, and when you look at alternative biochemistries, liquid
• 11:19
  Speaker 1: ammonia constantly comes up as the prime candidate to replace water.
• 11:23
  Speaker 2: It does. Ammonia chemically denoted as NH three. It's one
• 11:27
  Speaker 2: of the most rigorously studied theoretical solvents for alternative life.
• 11:31
  Speaker 1: Okay, so why ammonia.
• 11:33
  Speaker 2: Well, to understand why, we have to look at what
• 11:35
  Speaker 2: makes water so special on Earth first.
• 11:37
  Speaker 1: Okay.
• 11:38
  Speaker 2: Water is highly polar meaning one end of the molecule
• 11:41
  Speaker 2: has a slight positive charge and the other has a slight.
• 11:44
  Speaker 1: Negative charge, right like a magnet.
• 11:46
  Speaker 2: Exactly like a tiny magnet. And this polarity allows it
• 11:49
  Speaker 2: to surround and pull apart other molecules. It's a brilliant
• 11:52
  Speaker 2: solvent for the chemical reactions necessary for metabolism.
• 11:56
  Speaker 1: It just dissolves things really well.
• 11:58
  Speaker 2: Yeah, and it also forms hydrogen bonds, which gives it
• 12:01
  Speaker 2: a high heat capacity and allows it to remain liquid
• 12:04
  Speaker 2: over a really broad range of temperatures.
• 12:06
  Speaker 1: It's kind of like the ultimate chemical dance floor.
• 12:09
  Speaker 2: I love that analogy, right.
• 12:11
  Speaker 1: It lets all the complex organic molecules mingle, they bump
• 12:14
  Speaker 1: into each other, and they react without letting them fly
• 12:16
  Speaker 1: apart into a gas or just lock up into a.
• 12:19
  Speaker 2: Solid, and ammonia shares many of these exact same crucial properties.
• 12:24
  Speaker 2: Really yeah, like water, ammonia is a polar molecule, so
• 12:28
  Speaker 2: it can dissolve a wide array of organic compounds just
• 12:32
  Speaker 2: like water can.
• 12:33
  Speaker 1: Oh I didn't know that.
• 12:34
  Speaker 2: Yeah, And it also forms hydrogen bonds, although they are
• 12:37
  Speaker 2: a bit weaker than the hydrogen bonds in water, but
• 12:40
  Speaker 2: it can absolutely support the complex, intricate chemical reactions necessary
• 12:45
  Speaker 2: for a metabolic system. Okay. The fundamental difference lies in
• 12:48
  Speaker 2: the thermodynamic environment where ammonia operates as a liquid.
• 12:51
  Speaker 1: Wait, okay, this is where I need a reality check. Okay,
• 12:54
  Speaker 1: because we know ammonia primarily as a gas on Earth
• 12:57
  Speaker 1: or like dissolved into water for household cleaners, right, glass
• 13:00
  Speaker 1: clean Yeah. For pure ammonia to exist as a liquid,
• 13:03
  Speaker 1: the environment has to be freezing, very cold, like it
• 13:07
  Speaker 1: boils into a gas at around minus thirty three degree
• 13:09
  Speaker 1: celsius and freezes solid at around minus seventy seven degrees CELSIU.
• 13:13
  Speaker 2: Yeah, that's the window.
• 13:14
  Speaker 1: So if an environment is that cold, wouldn't the kinetic
• 13:17
  Speaker 1: energy be so low that chemical reactions happen at a
• 13:21
  Speaker 1: like a glacial pace.
• 13:23
  Speaker 2: That is the big question.
• 13:24
  Speaker 1: Because the Erneus equation in chemistry basically says that as
• 13:28
  Speaker 1: temperature drops, reaction rates just plummet. They do, so how
• 13:32
  Speaker 1: could a complex organism possibly evolve or even just metabolize
• 13:37
  Speaker 1: before its local star dies out.
• 13:39
  Speaker 2: That is actually the most common critique of ammonia based life.
• 13:43
  Speaker 1: I mean, it makes sense, it.
• 13:44
  Speaker 2: Does, but it assumes that alien life would use the
• 13:47
  Speaker 2: exact same chemical pathways and enzymes that earth life uses.
• 13:51
  Speaker 2: Let's break down the physical chemistry here. It is absolutely
• 13:54
  Speaker 2: true that lower temperatures mean less ambient kinetic energy to
• 13:57
  Speaker 2: drive reactions. However, liquid emone has a significantly lower viscosity
• 14:02
  Speaker 2: than liquid.
• 14:03
  Speaker 1: Water, meaning it's thinner like, less sticky.
• 14:05
  Speaker 2: Considerably less viscous. So at cryogenic temperatures, molecules actually diffuse
• 14:11
  Speaker 2: and move through liquid ammonia much faster than they move
• 14:15
  Speaker 2: through water as water approaches its freezing point.
• 14:18
  Speaker 1: Oh wow, So.
• 14:19
  Speaker 2: Going back to your analogy, the dance floor is colder,
• 14:22
  Speaker 2: but the dancers are moving through a much thinner crowd,
• 14:25
  Speaker 2: so they can still meet up exactly. Furthermore, life doesn't
• 14:28
  Speaker 2: just rely on ambient heat to drive reactions anyway, It
• 14:31
  Speaker 2: relies on catalysts enzymes to lower the activation energy required
• 14:37
  Speaker 2: for a reaction to occur in the first place.
• 14:39
  Speaker 1: Okay, So an ammonia based organism wouldn't use our enzymes
• 14:44
  Speaker 1: none at all. It would have evolved a completely different
• 14:46
  Speaker 1: set of biological catalysts, specifically optimized to function at like
• 14:51
  Speaker 1: minus fifty degrees celsius exactly.
• 14:54
  Speaker 2: Their enzymes would be highly flexible, specifically designed to facilitate
• 14:57
  Speaker 2: reactions with very little thermal input.
• 15:00
  Speaker 1: That makes so much sense.
• 15:01
  Speaker 2: The metabolism would undoubtedly be slower than an Earth organism, yes,
• 15:04
  Speaker 2: but in a stable, persistently cold environment, time isn't necessarily
• 15:08
  Speaker 2: a constraint.
• 15:08
  Speaker 1: They have all the time in the world.
• 15:10
  Speaker 2: Right, and this radically expands the habitable real estate in
• 15:14
  Speaker 2: the universe.
• 15:14
  Speaker 1: Oh I bet?
• 15:15
  Speaker 2: I mean we routinely point our telescopes at moons far
• 15:18
  Speaker 2: out in our own solar system, like Saturn's moon Titan,
• 15:22
  Speaker 2: and we just dismiss them because their surface temperatures are
• 15:25
  Speaker 2: hundreds of degrees below zero.
• 15:26
  Speaker 1: We just write them off as dead ice balls.
• 15:29
  Speaker 2: Right, But Titan has a thick atmosphere, It has lakes
• 15:33
  Speaker 2: of liquid methane on its surface, and compelling evidence of
• 15:36
  Speaker 2: a vast subsurface ocean of water mixed with liquid ammonia.
• 15:41
  Speaker 1: If we go back to our construction analogy for a second,
• 15:44
  Speaker 1: it's like trying to build a house. Okay, if you've
• 15:46
  Speaker 1: only ever lived in a temperate forest, you build your
• 15:49
  Speaker 1: house out of wood and nails. Sure, that's our carbon
• 15:52
  Speaker 1: and water biology. You assume it. To build a house,
• 15:55
  Speaker 1: you need a forest. But if you travel to a
• 15:57
  Speaker 1: rocky desert where there are no trees, doesn't say well, houses.
• 16:01
  Speaker 2: Are impossible here, right, They just adapt.
• 16:03
  Speaker 1: They just use different materials. They use poured concrete and rebar.
• 16:07
  Speaker 2: The ammonia chemistry is the concrete and rebar exactly.
• 16:10
  Speaker 1: The construction process handles temperature entirely differently, the foundational materials
• 16:16
  Speaker 1: interact differently. The house might look, you know, brutalist and
• 16:19
  Speaker 1: totally alien compared to your little wooden cabin, but functionally, thermodynamically,
• 16:24
  Speaker 1: it is still a house. It still works, It provides shelter,
• 16:27
  Speaker 1: it maintains an internal environment. So an ammonia based cellular
• 16:32
  Speaker 1: structure might look completely foreign, utilizing X and a's or
• 16:36
  Speaker 1: molecules we haven't even named yet, but it's still performing
• 16:39
  Speaker 1: the fundamental functions of life and.
• 16:41
  Speaker 2: That functional perspective, it forces us to confront a deeply
• 16:45
  Speaker 2: unsettling possibility.
• 16:47
  Speaker 1: Uh oh, unsettling?
• 16:48
  Speaker 2: How well? If life can be built out of completely
• 16:51
  Speaker 2: different chemical materials optimize for environments we consider toxic or dead,
• 16:55
  Speaker 2: who is to say it has to be in a
• 16:57
  Speaker 2: distant moon. Oh what if alternive biochemistry is found a
• 17:01
  Speaker 2: niche right here on earth?
• 17:02
  Speaker 1: Oh man? This is the concept of the shadow biosphere.
• 17:05
  Speaker 1: It is, and it just sounds like a science fiction thriller.
• 17:08
  Speaker 2: It really does.
• 17:09
  Speaker 1: We are talking about the possibility that alternative, radically different
• 17:13
  Speaker 1: forms of life could be existing right next to us, like,
• 17:15
  Speaker 1: completely undetected.
• 17:17
  Speaker 2: It is a highly debated but logically sound hypothesis in
• 17:21
  Speaker 2: modern microbiology. Really yeah. And the premise is not that
• 17:26
  Speaker 2: giant alien monsters are hiding in deep cave.
• 17:30
  Speaker 1: Systems right, not mole people.
• 17:32
  Speaker 2: No, The premise is that microscopic life forms utilizing a
• 17:36
  Speaker 2: completely different chemical architecture could be ubiquitous in our environment,
• 17:41
  Speaker 2: but completely invisible to our scientific methodology.
• 17:44
  Speaker 1: Oh man. So when a Mars rover or even a
• 17:47
  Speaker 1: researcher in the Atacama Desert, you scoops up a soil
• 17:50
  Speaker 1: sample and runs it through a high tech sequencer. It's
• 17:53
  Speaker 1: essentially like a colorblind robot looking for a specific painting.
• 17:57
  Speaker 2: That is a perfect way to look at it.
• 17:58
  Speaker 1: It could be drilling right through authorizing dense colony of
• 18:01
  Speaker 1: non standard microbes and reporting the sample as sterile rock.
• 18:05
  Speaker 1: Just because it's only programmed to see Earth DNA.
• 18:08
  Speaker 2: The color bind robot is a highly accurate way to
• 18:10
  Speaker 2: visualize the exact problem we have. Wow, let's look at
• 18:14
  Speaker 2: the actual mechanism of how we detect microbial life. One
• 18:17
  Speaker 2: of our primary tools is PCR polymerase chain reaction, Right,
• 18:21
  Speaker 2: we heard.
• 18:22
  Speaker 1: A lot about that during COVID Exactly.
• 18:24
  Speaker 2: It's the same technology used in DNA testing and viral diagnostics,
• 18:28
  Speaker 2: and PCR works by using primers, which are basically short
• 18:32
  Speaker 2: specific sequences of standard DNA that are designed to bind
• 18:36
  Speaker 2: to the target organism's genetic code, allowing us to amplify
• 18:40
  Speaker 2: and read it.
• 18:41
  Speaker 1: But if the organism in the dirt doesn't use standard DNA, then.
• 18:45
  Speaker 2: The primers have absolutely nothing to bind to.
• 18:48
  Speaker 1: They just float past.
• 18:49
  Speaker 2: Right. If a microbe in that soil sample uses a
• 18:52
  Speaker 2: peptide nucleic acid backbone like we talked about, or if
• 18:55
  Speaker 2: it utilizes a different set of base pairs like the
• 18:58
  Speaker 2: hot emoji DNA. The PCR process simply fails.
• 19:02
  Speaker 1: It just registers as zero.
• 19:04
  Speaker 2: The sequencer registers absolutely nothing. It just looks like chemical
• 19:06
  Speaker 2: noise or inert organic matter.
• 19:09
  Speaker 1: Okay, but what about just like putting it in a
• 19:11
  Speaker 1: peatrie edition seeing if it grows. We've been doing that
• 19:13
  Speaker 1: for over a century.
• 19:14
  Speaker 2: Culturing microbes presents the exact same bias. Unfortunately. Really yeah,
• 19:18
  Speaker 2: when we prepare an agar plate, we pack it with
• 19:20
  Speaker 2: the specific nutrients amino acids and sugars that earth life
• 19:23
  Speaker 2: consumes our food, right, and we incubate it at temperatures
• 19:27
  Speaker 2: earth life prefers. We only grow what eats our food.
• 19:31
  Speaker 1: That makes sense.
• 19:32
  Speaker 2: In fact, even among standard DNA based earth microbes, it
• 19:36
  Speaker 2: is estimated that we can only culture about one percent
• 19:38
  Speaker 2: of them in a lab.
• 19:40
  Speaker 1: One percent, just.
• 19:41
  Speaker 2: One percent, ninety nine percent of standard microbial life won't
• 19:45
  Speaker 2: even grow in our artificial conditions.
• 19:47
  Speaker 1: That is staggering.
• 19:48
  Speaker 2: It is now imagine trying to culture an organism that
• 19:51
  Speaker 2: relies on an entirely different set of amino acids, where
• 19:55
  Speaker 2: you know, requires a different chirality.
• 19:57
  Speaker 1: Okay, chirality. I've heard this word, the left handed versus
• 20:00
  Speaker 1: right handed molecules.
• 20:01
  Speaker 2: Yes, exactly. Many organic molecules exist in two forms that
• 20:05
  Speaker 2: are mirror images of each other, sort of like you're
• 20:07
  Speaker 2: left and right hands. Okay, and for reasons we still
• 20:10
  Speaker 2: don't fully understand, almost all known life on Earth exclusively
• 20:14
  Speaker 2: uses left handed amino acids to build proteins and right
• 20:18
  Speaker 2: handed sugars for DNA and metabolism.
• 20:20
  Speaker 1: Just completely one sided.
• 20:21
  Speaker 2: Yep. So if there were a shadow biosphere living in
• 20:24
  Speaker 2: the soil that simply swap that using right handed amino acids.
• 20:28
  Speaker 1: Or biological enzymes, couldn't even interact with.
• 20:30
  Speaker 2: It, not at all. Our proteases couldn't digest their proteins.
• 20:35
  Speaker 2: They would be biologically invisible to our metabolism, and our
• 20:38
  Speaker 2: assays would completely struggle to identify them as biological rather
• 20:42
  Speaker 2: than just you know, weird geological chemistry.
• 20:44
  Speaker 1: It is deeply humbling, it really is. I mean, we
• 20:47
  Speaker 1: are looking through a microscope with a filter fuse to
• 20:51
  Speaker 1: the lens, and the filter only lets the color red
• 20:54
  Speaker 1: pass through. Exactly, We look around the slide, we map
• 20:56
  Speaker 1: out all the red objects, and we declare we've discovered.
• 20:59
  Speaker 2: All look at all this red.
• 21:02
  Speaker 1: Right. Meanwhile, there is a sprawling complex ecosystem of blue
• 21:07
  Speaker 1: and green organisms thriving right there on the glass, and
• 21:10
  Speaker 1: we're just blissfully oblivious.
• 21:13
  Speaker 2: It fundamentally questions the very nature of our observation. Yeah, like,
• 21:17
  Speaker 2: how many anomalous chemical gradients have we measured in deep
• 21:20
  Speaker 2: rock fractures or strange isotopic ratios and ocean sediments that
• 21:24
  Speaker 2: we just wrote off as weird geology simply because we
• 21:27
  Speaker 2: couldn't sequence a standard DNA strand from the sample.
• 21:29
  Speaker 1: We probably throw away alien life constantly.
• 21:32
  Speaker 2: It's very possible our certainty about the boundaries of the
• 21:35
  Speaker 2: biological world is entirely conditioned by the limitations of our tools.
• 21:40
  Speaker 1: So okay, if life can be synthesized with an alternative
• 21:44
  Speaker 1: genetic ladder in a lab, and if it can use
• 21:46
  Speaker 1: entirely different solvents like liquid ammonia on a freezing moon,
• 21:51
  Speaker 1: and if it can potentially hide right here in the
• 21:53
  Speaker 1: dirt outside our houses, completely devoid a familiar chemistry, the
• 21:58
  Speaker 1: definition of the word life essentially breaks down, crumbles right
• 22:02
  Speaker 1: the definition we all memorized in high school biology. You
• 22:05
  Speaker 1: know that life is a carbon based, water dependent system
• 22:08
  Speaker 1: utilizing nucleic acids. It's just too small to contain the
• 22:12
  Speaker 1: actual physics of the universe.
• 22:13
  Speaker 2: It's way too narrow.
• 22:14
  Speaker 1: We have to redefine the concept from the ground.
• 22:17
  Speaker 2: We do, and this leads us to the ultimate synthesis
• 22:20
  Speaker 2: of all these fields. Ok, when you strip away the
• 22:23
  Speaker 2: rigid requirement for DNA, and when you remove the necessity
• 22:27
  Speaker 2: of liquid water, when you just stop obsessing over the
• 22:30
  Speaker 2: specific carbon molecules, what is the irreducible core that remains.
• 22:34
  Speaker 1: The essence of it?
• 22:35
  Speaker 2: Right? What is the fundamental difference between a living system
• 22:39
  Speaker 2: and a complex but dead chemical reaction.
• 22:42
  Speaker 1: It transitions from being a chemistry problem into something that
• 22:45
  Speaker 1: sounds more like computer science or like theoretical physics.
• 22:49
  Speaker 2: It actually bridges all of those disciplines. The physicist Erwin Schrodinger, oh.
• 22:53
  Speaker 1: The cat guy.
• 22:54
  Speaker 2: The cat guy, Yes, Yes, famous for his quantum mechanics work,
• 22:57
  Speaker 2: he actually tackled this exact question in the nineteen forties.
• 23:00
  Speaker 1: Really, I didn't know he did. Biology, he did.
• 23:03
  Speaker 2: He noted that the defining feature of a living system
• 23:06
  Speaker 2: is its ability to maintain its own internal organization against
• 23:09
  Speaker 2: the natural tendency of the universe to decay and to
• 23:12
  Speaker 2: chaos entropy.
• 23:13
  Speaker 1: Entropy the second law thermo dynamics basically says everything eventually
• 23:17
  Speaker 1: breaks down and spreads out like hot coffee cools down,
• 23:20
  Speaker 1: mountains of road, sells decay.
• 23:22
  Speaker 2: Exactly, everything trends toward disorder. But life is a localized
• 23:26
  Speaker 2: reversal of that process, and it fikes back, It fights back.
• 23:29
  Speaker 2: It is a system that actively draws an energy from
• 23:32
  Speaker 2: its environment to maintain its complex structure, and crucially, it
• 23:36
  Speaker 2: passes the instructions for that structural organization onto the next generation.
• 23:40
  Speaker 1: Wow.
• 23:41
  Speaker 2: So, at its most fundamental, irreducible level, life is not
• 23:45
  Speaker 2: a specific chemical. Life is a pattern of information that
• 23:49
  Speaker 2: is actively attempting to copy itself.
• 23:52
  Speaker 1: It's an instruction manual that builds a machine, and the
• 23:54
  Speaker 1: machine's primary purpose is just to harvest energy to build
• 23:58
  Speaker 1: another instruction manual.
• 24:00
  Speaker 2: Beautifully put, and once you view life through the lens
• 24:03
  Speaker 2: of information processing and replication, the physical materials it is
• 24:07
  Speaker 2: made of become entirely secondary.
• 24:09
  Speaker 1: They just don't matter as much.
• 24:10
  Speaker 2: Right. The specific molecules, whether that is the naturally occurring
• 24:14
  Speaker 2: DNA in our bodies or the synthetic X and A
• 24:17
  Speaker 2: is built in a lab, or whether the system is
• 24:19
  Speaker 2: suspended in warm liquid water or cryogenic liquid ammonia, all
• 24:23
  Speaker 2: of that.
• 24:23
  Speaker 1: Is just the hardware, the physical chassis. The hardware is interchangeable.
• 24:27
  Speaker 1: The local environment just dictates which hardware is most thermodynamically stable. Yes,
• 24:32
  Speaker 1: so like water and standard DNA happen to be the
• 24:35
  Speaker 1: optimal hardware for Earth's specific temperature and atmospheric pressure exactly,
• 24:39
  Speaker 1: But ammonia and a completely different synthetic polymer might be
• 24:43
  Speaker 1: the optimal hardware for the subsurface oceans of Titan.
• 24:46
  Speaker 2: You've got it.
• 24:46
  Speaker 1: But the software, the underlying logic of the system, you know,
• 24:50
  Speaker 1: the organized transfer of information, the selective adaptation to the environment.
• 24:55
  Speaker 1: That is what actually constitutes the phenomenon of life.
• 24:58
  Speaker 2: It elegantly un tether's biology from chemistry. I love that
• 25:03
  Speaker 2: because chemistry is merely the medium. The information is the message.
• 25:07
  Speaker 2: If a localized system can store complex data, undergo variation
• 25:12
  Speaker 2: or mutation, and selectively replicate the data that best survives
• 25:16
  Speaker 2: the environmental pressures, then it fulfills the ultimate definition of life,
• 25:20
  Speaker 2: regardless of its chemical composition.
• 25:22
  Speaker 1: Grounding this concept completely shifts how you view the world.
• 25:26
  Speaker 2: It really does.
• 25:26
  Speaker 1: Think about a song, right, Your favorite piece of music
• 25:29
  Speaker 1: can be pressed into the physical vinyl grooves of a record.
• 25:32
  Speaker 2: Okay, Yeah, or it can.
• 25:33
  Speaker 1: Be magnetically encoded onto the tape of a cassette. It
• 25:36
  Speaker 1: can be translated into digital ones and zeros, beamed through
• 25:39
  Speaker 1: the air and streamed on your smartphone. Or it could
• 25:43
  Speaker 1: just be performed live acoustically by a musician playing a
• 25:46
  Speaker 1: wooden guitar. Right the vinyl, the magnetic tape, the digital code,
• 25:50
  Speaker 1: the physical wood of the guitar. Those are the chemistries.
• 25:54
  Speaker 1: Those are the different genetic systems and solvents. The physical
• 25:58
  Speaker 1: medium completely changes in every scenario, but the melody, the
• 26:03
  Speaker 1: specific arrangement of notes, the pattern of information that makes
• 26:08
  Speaker 1: that song recognizable, that remains exactly the same across all
• 26:13
  Speaker 1: of those mediums.
• 26:14
  Speaker 2: The song is the phenomenon of life exactly, and carbon
• 26:18
  Speaker 2: based water biology is simply the vinyl record version.
• 26:21
  Speaker 1: It's just one way to play it, right.
• 26:23
  Speaker 2: And to say that life can only exist as DNA
• 26:26
  Speaker 2: and water is as intellectually limiting as saying that a
• 26:30
  Speaker 2: song can only exist if it is played on a
• 26:32
  Speaker 2: vinyl record.
• 26:33
  Speaker 1: It's absurd when you put it like that.
• 26:34
  Speaker 2: It is. It fundamentally confuses the storage medium with the
• 26:37
  Speaker 2: information itself.
• 26:38
  Speaker 1: And once you stop looking exclusively for the vinyl record,
• 26:41
  Speaker 1: you start listening for the melody, you start.
• 26:42
  Speaker 2: Looking for the signatures of complex information processes.
• 26:45
  Speaker 1: Right.
• 26:46
  Speaker 2: This is exactly why the search for life is undergoing
• 26:48
  Speaker 2: a radical transformation. Right now.
• 26:50
  Speaker 1: We're changing how we look we have to.
• 26:52
  Speaker 2: We are moving away from purely chemical essays and exploring
• 26:55
  Speaker 2: what we call agnostic biosignatures.
• 26:58
  Speaker 1: Agnostic biosignatures meaning they don't care what the chemistry is exactly.
• 27:03
  Speaker 2: Instead of just looking for specific molecules, we are looking
• 27:06
  Speaker 2: for anomalous complexity. We look for chemical gradients in an
• 27:11
  Speaker 2: environment that shouldn't exist unless something is actively maintaining.
• 27:14
  Speaker 1: Them, like someone's swimming upstream exactly.
• 27:17
  Speaker 2: We look for localized decreases in entropy. We are trying
• 27:20
  Speaker 2: to build instruments that can detect the behavior of life,
• 27:23
  Speaker 2: regardless of the substrate it is running on.
• 27:26
  Speaker 1: Man, we've covered an incredible amount of ground today, We
• 27:29
  Speaker 1: really have. We started by staring down the glass of
• 27:32
  Speaker 1: water and the double helix. You know, the two things
• 27:34
  Speaker 1: we assumed were the absolute non negotiable requirements for biology
• 27:39
  Speaker 1: the earthos right, and we systematically dismantled that fixed formula
• 27:44
  Speaker 1: by looking at how synthetic biologists are literally rewriting the
• 27:47
  Speaker 1: genetic alphabet, building stable functional molecules with synthetic bases and
• 27:52
  Speaker 1: peptide backbone, right, the X.
• 27:53
  Speaker 2: And as and the hotch emogidna.
• 27:55
  Speaker 1: Yeah. And then we challenge the necessity of water by
• 27:58
  Speaker 1: exploring the thermodynamic rea liquid ammonia.
• 28:01
  Speaker 2: Which is still so crazy to think about.
• 28:03
  Speaker 1: I know, demonstrating how a lower viscosity and different enzymatic
• 28:06
  Speaker 1: kinetics could support complex metabolic reactions and environments we previously
• 28:11
  Speaker 1: just dismissed as too cold for biology.
• 28:13
  Speaker 2: And then we confronted the massive blind spots in our
• 28:16
  Speaker 2: own scientific methodology.
• 28:17
  Speaker 1: Right the colorblind robots.
• 28:18
  Speaker 2: Realizing that tools like PCR and AGAR cultures are so
• 28:23
  Speaker 2: heavily biased toward Earth's specific chemistry that an entire shadow
• 28:28
  Speaker 2: biosphere of alternative life could be thriving in the soil
• 28:32
  Speaker 2: beneath our feet, chemically invisible to our current technology, which is.
• 28:36
  Speaker 1: Just terrifying and awesome at the same time.
• 28:39
  Speaker 2: It really is.
• 28:39
  Speaker 1: And we culminated with the realization that life is not
• 28:42
  Speaker 1: defined by the atoms it uses, but by the organization
• 28:45
  Speaker 1: of those atoms, the pattern. It is a localized pocket
• 28:48
  Speaker 1: of negative entropy. It is information actively maintaining and copying
• 28:52
  Speaker 1: itself across whatever chemical hardware the local environment happens to provide.
• 28:57
  Speaker 2: It completely shatters the boundaries of what is possible.
• 29:00
  Speaker 1: It really does. It challenges us to look at the
• 29:02
  Speaker 1: universe not as a vast empty void dotted with a
• 29:06
  Speaker 1: few rare miraculous oasis of carbon and water, but as
• 29:10
  Speaker 1: this boundless landscape of potential mediums, where the complex pattern
• 29:15
  Speaker 1: of life might be unfolding in ways we haven't even
• 29:17
  Speaker 1: developed the capacity to understand yet.
• 29:19
  Speaker 2: It's beautiful, it is.
• 29:21
  Speaker 1: And so I want to leave you with one final
• 29:24
  Speaker 1: lingering thought to chew on as you go about your day. Okay,
• 29:27
  Speaker 1: if life is fundamentally just this pattern of information and replication,
• 29:31
  Speaker 1: completely untethered from any specific chemical formula, we recognize where
• 29:36
  Speaker 1: else might these invisible patterns be operating right now?
• 29:39
  Speaker 2: Wow?
• 29:40
  Speaker 1: Could the universe actually be teeming with information trying to
• 29:43
  Speaker 1: copy itself in ways that fall completely outside our current
• 29:46
  Speaker 1: scientific framework. The next time you look out your window
• 29:49
  Speaker 1: at the clouds, at a rock phase, or even just
• 29:52
  Speaker 1: down at the soil in your garden, I want you
• 29:53
  Speaker 1: to wonder what unseen patterns, what invisible, radically different melodies,
• 29:58
  Speaker 1: might be quietly rep locating in the shadows right in
• 30:01
  Speaker 1: front of you,