Molecules Made Me Do It: Life, the Mind, Sex and Future Cures

What is a thought, and how do neurons, synapses, ion channels and electrical signals in the brain give rise to consciousness? In this episode we explore the molecular and physical basis of thinking, from fleeting patterns of neuronal activity to the possibility of simulating an entire human brain on a computer.We encounter Donald Hebb's cell assemblies, the philosophical puzzles of consciousness, and fascinating experiments at Harvard revealing how individual neurons encode elements of language before we speak. Could a thought be a temporary, self-sustaining pattern of electrical activity in a network of neurons?Drawing on my own experiences working with Nobel laureate Martin Karplus, we then explore how molecular dynamics, neuroscience and supercomputing might eventually combine to create a digital twin of the brain. Could such simulations explain memory and consciousness, and  reveal  how the movement of atoms becomes a thought?A journey from molecules to the mind, with a few philosophical zombies, a roundworm and the occasional tot of whisky along the way.Molecules Made Me Do It is written and presented by Prof. Jeremy Smith. A popular-science podcast about the beautiful and devious molecules behind life, the mind, sex and the cures of the future. No scientific background required. Music written and performed by Jeremy Smith. Follow or subscribe to Molecules Made Me Do It wherever you get your podcasts.

How do action potentials, ion channels, synapses and neurotransmitters allow the brain to see, think and make decisions? We explore how potassium channels distinguish between ions, how a million nerve fibers carry electrical signals from the eyes to the brain, and why those signals consist of identical, all-or-none pulses. We also discover that vision is surprisingly slow, and that the brain compensates by predicting the future — particularly useful when trying to hit a baseball traveling at 95 mph.Next, we meet the molecular prison break gang: proteins including synaptotagmin and SNAREs that release neurotransmitters from tiny vesicles into synapses. We discover why the brain uses chemical signaling rather than simply wiring all its neurons together electrically, and how neurons make decisions through a form of cerebral democracy — synapse voting. Glutamate enthusiastically encourages neurons to fire through AMPA and NMDA receptors, while GABA acts as a grumpy editor, suppressing unnecessary activity and sharpening the messages. Meanwhile, the professor has spotted an attractive woman, but after four episodes of neuroscience, he still hasn't managed to have a conscious thought about her.Molecules Made Me Do It is written and presented by Prof. Jeremy Smith. A popular-science podcast about the beautiful and devious molecules behind life, the mind, sex and the cures of the future. No scientific background required. Music written and performed by Jeremy Smith. Follow or subscribe to Molecules Made Me Do It wherever you get your podcasts.

How do neurons transmit electrical signals from the eye to the brain? In this episode we explore the molecular machinery behind nerve impulses, or action potentials. Starting with the retina, where visual information is processed before being sent to the brain, we discover why the electricity of the nervous system is quite different from the electricity flowing through a wire. Instead of electrons, neurons use electrically charged atoms called ions. We meet the sodium-potassium pump, which uses energy from ATP to maintain ion concentration gradients, and discover why relying on pumps alone would make the professor's romantic adventures at a party painfully slow.We then explore how ion channels, diffusion and electrical forces create the resting membrane potential. When voltage-gated sodium and potassium channels open in sequence, they generate a brief electrical pulse that travels along the neuron's axon without fading. Finally, we discover why a nerve impulse resembles a Mexican wave in a football stadium: individual ions move only short distances, but the electrical disturbance travels rapidly onward, carrying information toward the brain.Molecules Made Me Do It is written and presented by Prof. Jeremy Smith. A popular-science podcast about the beautiful and devious molecules behind life, the mind, sex and the cures of the future. No scientific background required. Music written and performed by Jeremy Smith. Follow or subscribe to Molecules Made Me Do It wherever you get your podcasts.

How do our eyes see color, and why does the brain sometimes deceive us about what we're looking at? We explore the molecular biology and neuroscience of color vision, from the light-sensitive retinal molecule and opsin proteins to the three types of cone photoreceptors that allow us to distinguish millions of colors. Discover how evolution produced our remarkable visual system, how the brain uses red–green and blue–yellow opponent channels to interpret light, and why we can see purple but never reddish-green or bluish-yellow. We also uncover one of the brain's cleverest tricks: making us see yellow even when not a single yellow photon enters our eyes.But what if human vision could distinguish thousands of different wavelengths instead of relying on just three types of cones? Sunsets might become unimaginably beautiful, television screens would reveal their colorful deceptions, and cosmetics and fashion would never be the same again. Finally, we investigate  the ability of the brain to make objects appear the same color under radically different lighting conditions. Along the way, our professor discovers that the brain is an accomplished con artist - and that seeing the world as it really is would pose an  interesting dating conundrum.Molecules Made Me Do It is written and presented by Prof. Jeremy Smith. A popular-science podcast about the beautiful and devious molecules behind life, the mind, sex and the cures of the future. No scientific background required. Music written and performed by Jeremy Smith. Follow or subscribe to Molecules Made Me Do It wherever you get your podcasts.

How does the human brain turn light into vision, attraction, and love at first sight? In this episode of Molecules Made Me Do It, we begin exploring the neuroscience and molecular biology of vision, following an unfortunate professor who spots an irresistibly attractive woman at a party - and promptly walks into a table. The encounter introduces us to one of biology’s most remarkable families of proteins: G-protein-coupled receptors (GPCRs). These molecular switches allow cells to detect light, smells, tastes, hormones, and neurotransmitters. We discover how GPCRs change shape through allostery, triggering elaborate biochemical signaling cascades, and how evolution has repeatedly adapted the same basic molecular machinery for everything from vision and pleasure to pain and blood pressure. Remarkably, around one-third of medicines act on GPCRs.We then dive into the extraordinary molecular mechanism of human vision. Why does the Sun's temperature determine which wavelengths our eyes detect? How does a single photon of light trigger a molecular chain reaction inside the retina? We meet retinal, opsins,  and transducin, and discover how light activates proteins that amplify a tiny signal into a measurable electrical response. Surprisingly, human photoreceptor cells detect light by switching off an electrical current that flows continuously in darkness rather than  by switching one on. We also explore the ancient evolutionary origins of light-sensitive proteins and why color vision was such an evolutionary advantage. All this from a few photons bouncing off an attractive woman. May the photons be with hue!Molecules Made Me Do It is written and presented by Prof. Jeremy Smith. A popular-science podcast about the beautiful and devious molecules behind life, the mind, sex and the cures of the future. No scientific background required. Music written and performed by Jeremy Smith. Follow or subscribe to Molecules Made Me Do It wherever you get your podcasts.

Protein folding, AlphaFold, AI and protein structure prediction come together in one of the great scientific puzzles of modern biology. How does a protein chain find its unique three-dimensional structure when, in principle, it could adopt an astronomical number of possible shapes? We explore the famous Levinthal paradox, the protein-folding energy landscapeand folding funnels see how proteins rapidly navigate an otherwise impossible for their final shapes. We then turn to an equally daunting question: how evolution found the tiny fraction of amino-acid sequences capable of folding into stable, functional proteins.Then came artificial intelligence. For half a century, predicting a protein’s 3D structure directly from its amino-acid sequence was one of science’s grand challenges—until DeepMind’s AlphaFold2 transformed the field. We look inside the AI black box, explaining machine learning, deep learning, neural networks, co-evolution and how they helped AlphaFold achieve near-experimental accuracy and predict structures for hundreds of millions of proteins. And there’s a personal confession: why I once told my computational research group not to use AI - and why, inevitably, they ignored me. Molecules Made Me Do It is written and presented by Prof. Jeremy Smith. A popular-science podcast about the beautiful and devious molecules behind life, the mind, sex and the cures of the future. No scientific background required. Music written and performed by Jeremy Smith. Follow or subscribe to Molecules Made Me Do It wherever you get your podcasts.

Proteins possess precise three-dimensional structures in order to function. Using lysozyme and chymotrypsin as examples, we explore protein structure, enzyme catalysis and the extraordinary molecular architecture behind life. We begin with Alexander Fleming’s accidental discovery of lysozyme and then enter the world of structural biology, where α-helices, β-sheets and vast protein assemblies reveal that biological molecules can be not only functional, but astonishingly beautiful.Then we find out why all that structure matters, as chymotrypsin turns protein digestion into a little piece of molecular drama. Meet the molecular steak knife: a precisely arranged charge-relay system whose three key amino-acid residues work together to attack and cut peptide bonds, accelerating a reaction that would otherwise take around a century and reducing it to less than a second. From there we follow Christian Anfinsen’s classic experiments showing that a protein’s amino-acid sequence contains the information needed to determine its folded structure, discover how an egg can - sort of - be “unboiled,” and meet the molecular chaperones that help proteins fold correctly inside the crowded environment of a cell. The result is one of biology’s central ideas: a gene ultimately encodes not merely a string of amino acids, but a functional three-dimensional protein.Molecules Made Me Do It is written and presented by Prof. Jeremy Smith. A popular-science podcast about the beautiful and devious molecules behind life, the mind, sex and the cures of the future. No scientific background required. Music written and performed by Jeremy Smith. Follow or subscribe to Molecules Made Me Do It wherever you get your podcasts.

How was the structure of DNA discovered, and how does DNA store and copy genetic information? We explore X-ray crystallography, Rosalind Franklin’s Photo 51, Watson and Crick’s double-helix model, complementary base pairing, genes and the central dogma of molecular biology.We begin with a fundamental principle of biology: the three-dimensional shape of a molecule determines what it can do. That takes us into structural biology and X-ray diffraction, the technique that first allowed scientists to work out the arrangement of atoms inside DNA, proteins and other biological molecules.From there we follow the discovery of the DNA double helix and the realization that A pairs with T and C with G. This complementarity did more than explain DNA’s structure — it revealed how genetic information could be copied from one generation of cells to the next.We then follow the flow of genetic information from DNA to RNA to protein, Francis Crick’s “central dogma” of molecular biology, before asking where genetic variation comes from. Mutations, DNA copying errors and chromosome reshuffling provide the raw material on which evolution acts.And then comes the battle of the sexes. Most new point mutations arise from the male line, while women contribute strongly to genetic variation through chromosome reshuffling. So are men the great innovators of evolution? Not quite. Men turn out to be prolific genetic typo-generators, while women are better at shuffling the deck.Molecules Made Me Do It is written and presented by Prof. Jeremy Smith. A popular-science podcast about the beautiful and devious molecules behind life, the mind, sex and the cures of the future. No scientific background required. Music written and performed by Jeremy Smith. Follow or subscribe to Molecules Made Me Do It wherever you get your podcasts.

How did chemistry acquire memory — and become something that could truly evolve? In this third episode on the origin of life, we explore the RNA world, the first genes, protocells and the long path toward LUCA, the Last Universal Common Ancestor.We move from messy, low-fidelity chemical networks to the idea of a portable molecular instruction manual. We look at how polymers can store information in their sequences, how complementary pairing allows that information to be copied, and why the first gene probably needed to be both useful and reproducible. RNA emerges as the prime candidate: unlike DNA, it can both carry information and catalyze chemistry, making it a plausible bridge between simple replicators and the first genetic systems.Then we tackle two more crucial steps. First, recent work on a tiny RNA called QT45 shows just how small the machinery for RNA copying might be. Second, life had to learn to “herd the cats” by trapping useful chemistry inside membranes, creating protocells with an inside and an outside.From there, RNA, proteins and eventually DNA could divide the labor, leading, about 4 billion years ago, to LUCA — the Last Universal Common Ancestor, the ancient cellular ancestor from which all modern life descends.Molecules Made Me Do It is written and presented by Prof. Jeremy Smith. A popular-science podcast about the beautiful and devious molecules behind life, the mind, sex and the cures of the future. No scientific background required. Music written and performed by Jeremy Smith. Follow or subscribe to Molecules Made Me Do It wherever you get your podcasts.

How did life begin from lifeless chemistry? In this second episode on the origin of life, we explore how life began on the early Earth, starting with the famous Miller-Urey experiment, which showed that simple gases, water and energy could generate some of life’s basic organic building blocks.But making molecules is not the same as making life. The deeper problem is how random chemistry could become organized without requiring one fantastically improbable stroke of luck. The answer may have been a long sequence of small chemical successes, each preserved and built upon rather than everything appearing at once.We then follow one possible route: self-sustaining cycles of chemical reactions driven by continual energy, sped up by catalysts, and eventually able to make more of their own components. Once slightly different versions of these chemical networks could arise and some worked better than others, something resembling evolution could begin — even before genes and cells existed.Autocatalysis, in which parts of a chemical network help make more of that same network, provides a tantalizing bridge between ordinary chemistry and the first primitive systems capable of reproducing and evolving.Molecules Made Me Do It is written and presented by Prof. Jeremy Smith. A popular-science podcast about the beautiful and devious molecules behind life, the mind, sex and the cures of the future. No scientific background required. Music written and performed by Jeremy Smith. Follow or subscribe to Molecules Made Me Do It wherever you get your podcasts.