Lee Cronin: Controversial Nature Paper on Evolution of Life and Universe | Lex Fridman Podcast #404

Lee Cronin: Controversial Nature Paper on Evolution of Life and Universe | Lex Fridman Podcast #404

Introduction (00:00:00)

  • Every star likely has planets with emerging life, but the vast combinatorial space means we may never interact with alien life.
  • Lee Cronin expresses a fear that while life is widespread, the difficulty in establishing communication renders humanity lonelier.
  • There is urgency to create alien life in the lab due to potential impossibility of intersecting with extraterrestrial intelligence naturally.
  • Cronin, a University of Glasgow chemist, is returning for his third appearance on the Lex Fridman podcast, being appreciated for his engaging and insightful discussions.

Assembly theory paper (00:01:15)

  • Lee Cronin’s assembly theory paper, published in "Nature," ignited both controversy and intriguing discussions.
  • Assembly theory posits that any object's complexity in the universe can be quantified by the number of steps needed to create it.
  • The theory also suggests that objects replicated through an evolutionary-like process can be identified by the number of existing copies.
  • An object, according to assembly theory, is finite, distinguishable, persists over time, and can be broken down into quantifiable subunits or building blocks.
  • The assembly index is the measure of an object's complexity derived from the minimal number of assembly steps.

Complexity, objects, and assembly index

  • Complexity of an object is tied to its history; hence, each object's complexity reflects its unique developmental path.
  • The assembly index is calculated by determining the minimal steps required to construct the object by lazily putting together its decomposed parts.
  • This concept originated in chemistry, where breaking down molecules into atoms and then reconstructing them clarified the minimal steps involved.
  • The applicability of assembly theory extends beyond molecules to language and mathematics, although these areas are more complex to analyze.

Computational complexity and measurement shortcuts (00:01:15)

  • Determining the shortest path for object construction, such as molecules and lego structures, can be computationally challenging.
  • In chemistry, there are ways to simplify the computation by looking for patterns and symmetry which can streamline the reconstruction of molecular bonds.
  • Techniques like infrared spectroscopy, NMR, and mass spectrometry correlate with an assembly index, potentially allowing for physical rather than computational measurement of complexity.
  • The concept of assembly index is being extended experimentally to emojis by pixelating them and determining their construction paths.

The Four Universes & Assembly Theory (00:01:15)

  • Lee defines the four "universes" in assembly theory: assembly universe (all possible objects), assembly possible (objects adhering to physical laws), assembly contingent (objects dependent on past construction steps), and assembly observed (objects that actually exist).
  • The shortest path principle implies that objects that can be constructed quickly will dominate in propagation through the environment.
  • Parallel processing and cooperation between objects introduce a concept known as assembly depth, which can reduce the assembly index when objects are made in conjunction.

Assembly equation (00:21:45)

  • Assembly defined as the amount of selection needed to produce a set of objects, quantifiable by an equation.
  • The equation factors in assembly index, copy number (quantity of complex objects that are non-random), and normalization to account for the likelihood of random occurrences.

Nature of selection and evolution (00:21:45)

  • Paper prompted various responses from different fields, especially evolutionary biologists, physicists, prebiotic chemists, and creationists.
  • Evolution in the paper refers to nonbiological selection and evolution.
  • Physics alone does not intuitively predict the emergence of life.
  • The paper suggests a continuum between the laws of physics and biological evolution.
  • Disconnection between physics and biology exists around the creation of memories in chemistry.
  • The concept of selection is linked to the ability of objects to persist and thrive over others in a given environment.
  • Selection is about both the objects and the processes over time, not isolated occurrences.
  • Robustness differentiates biological evolution from inorganic abiotic evolution. Biology has built-in error correction and can survive in various environments.

Universe evolution and context (00:21:45)

  • The paper presents the possibility that the evolutionary process behind the origin of life on Earth may not be unique.
  • History and diversity of Earth's environments are significant for life's emergence, but similar processes may occur elsewhere in the universe.
  • The assembly equation can be employed to detect selection in different environments and could potentially identify non-life complex systems.

Investigating assembly and complexity (00:21:45)

  • The assembly equation can measure the amount of selection and track changes in system complexity.
  • Simplified experiments demonstrate how the assembly index increases with the replication and consumption of resources by organisms, like E. coli making use of sugars.
  • The main goal of the paper is to investigate the emergence and challenge of molecular networks in controlled environments, thus understanding the transition from simple to complex systems.

Discovering alien life (00:34:57)

  • To discover alien life, one can use a mass spectrometer with high resolution on a planet like Mars.
  • The mass spectrometer can select molecules by mass and, after fragmentation, count the number of fragments.
  • An assembly index is applied, dependent on the molecular weight and number of fragments, indicating the complexity of the molecule.
  • Complicated molecules with many identical copies are considered evidence of life.
  • Assembly theory suggests that numerous identical, complex molecules are improbable without life.
  • The desired criteria are molecules with a weight over 350 and more than 15 fragments, which on Earth are produced by life.

Utilizing Assembly Index on Alien Worlds (00:58:20)

  • A “life meter” could utilize mass spectrometry to search for high-complexity molecules indicative of life.
  • The detection systems used, like mass spectrometry and infrared, must be suitable for the resolution on new planets.
  • Assembly theory suggests looking for complexity and abundance to detect selection evidence, rather than focusing on earth-based biomarkers.

Applying Assembly Index to Earth (01:10:00)

  • Samples from various sources on Earth, including E. coli and whiskey, can be analyzed using assembly theory.
  • The assembly index differentiates between abiotic samples (index below 15) and biological ones (index above 15).
  • NASA's success with blind test samples validated the approach.
  • The study found complex molecules in beer and E. coli, indicative of biological processes rather than random chemical formations.

Evolution of life on Earth (00:53:16)

  • Lee Cronin and his team have applied assembly theory to map out the tree of life without relying on traditional methods like sequencing or drawing.
  • They have used mass spectrometry to analyze complex molecules and their coexistence, which allows for a novel approach to infer evolutionary relationships.
  • This approach looks at how molecules are put together (assembly space) and can identify the common origins of molecules.
  • By comparing molecular fingerprints from different samples, they can estimate evolutionary distances and reconstruct the evolutionary tree.
  • This technique may also work on fossil samples that are not amenable to gene sequencing due to DNA degradation.

Analysis of Molecular Complexity and Dating [No specific start time indicated]

  • Beyond reconstructing evolutionary relationships, the complexity and stability of molecules can provide insights into the age and history of life forms.
  • The technique has potential for dating specimens using molecular decomposition, chirality changes, and the isotope enrichment process that occurs in living organisms.
  • By understanding the kinetic isotope effect, it is suggested that one might infer the metabolic age of an organism from the proportion of carbon isotopes in its body.
  • The study of these chemical signatures can offer additional dimensions to understanding the history and evolution of life on Earth.

Response to criticism (01:01:12)

  • Lee Cronin's paper on assembly theory drew criticism, with some evolutionary biologists claiming the origin of life was a solved problem.
  • Others criticized the paper for being badly written or for stating the obvious in a new way.
  • Cronin believes his work is a fundamental shift in understanding biology and the universe, a bold and testable hypothesis.
  • He aims to extend assembly theory beyond chemistry to more complex systems, such as the cell differentiation in multicellular organisms.
  • Critics have been both harsh and dismissive, questioning the paper's publication in Nature.
  • The paper presents a metric, the assembly index, as a novel way to quantify the complexity of molecules, cells, and potentially more complex systems.
  • Cronin wants to apply the theory to various scales, from cells to culture to technological products like microprocessors.

Application of assembly theory to complex systems [Included in the summary above]

  • Assembly theory currently applies to the morphology of cells and looks to extend to more complex systems.
  • Lee Cronin suggests assembly theory could be used to understand the development of tissues and diseases as well as cultural and technological evolution.
  • He outlines ambitions to apply the theory to language and large language models.
  • A significant challenge is finding a common set of building blocks to apply at higher levels of complexity.
  • Cronin correlates intelligence with selection and believes that humans have transcended Darwinian evolution, implying assembly theory could measure this higher-level evolution.

Kolmogorov complexity (01:18:50)

  • Assembly theory differs from Kolmogorov complexity which requires a Turing machine and is computationally focused.
  • Kolmogorov complexity regards data compression but does not address causation or evolutionary processes.
  • Assembly theory establishes causal chains and infers object history depth based on the shortest path without a manufacturing history.
  • It aims to trace evolutionary selection processes and can identify the complexity of a factory or system that created an object.
  • Difficulties arise when computing an object's history, especially complex ones, but assembly theory optimizes constraints to focus inquiries, such as in drug discovery strategies.
  • The theory assumes that no detailed knowledge of all chemistry is required, only minimal constraints on a graph representation.
  • Assembly theory postulates the minimal path for an object's creation probabilistically, challenging the notion of traditional chemical reactions.
  • Chemical reactions are seen as shorthand for the emergence of transformations under certain constraints such as temperature, pressure, and atmospheric composition.
  • Chemists' labeling of reactions represents controlled environments but doesn't account for the varying constraints within the universe.
  • The approach of constraining applications enables the emergence of transformations, framing our understanding of reactions within a universal context.

Nature review process (01:30:40)

  • The submission of Lee Cronin's paper to "Nature" was initially met with skepticism by the editor.
  • Based on the feedback, Cronin and co-author Sara took a significant amount of time to rewrite the paper, reaching around 160 versions before restarting from zero.
  • The paper initially had too many equations, which were mostly removed, leaving essential ones for clarity.
  • The review process went through three rounds of intense, critical but constructive feedback.
  • Previous attempts to publish related papers on assembly theory faced harsh rejection, outright disbelief, and accusations of fraud from reviewers, leading to feelings of frustration.
  • Despite challenges and emotional ups and downs, Cronin persisted, driven by the desire to understand why there was resistance and to improve his work.
  • The accepted "Nature" paper sparked controversy and backlash, which Cronin views constructively as important scientific discourse.
  • The paper proposes a quantifiable pre-biological evolutionary mechanism, which aims to provide a foundation for further research in the field.

Personal struggles and perseverance (01:30:40)

  • Lee Cronin faced learning difficulties in school, doubting his potential and facing low expectations from others.
  • His curiosity and passion for science kept him determined, despite being placed in remedial classes and facing limitations on the subjects he could study.
  • Cronin had to confront the belief that he was not intelligent, which was compounded by his exclusion from advanced mathematics courses due to poor exam grades.
  • His father intervened to allow him to take higher-level exams, which he passed, allowing him to pursue A levels and later attend university to study chemistry.
  • Cronin emphasizes the importance of not giving up, being persistent, and surrounding oneself with smart, critical thinkers to validate and enhance one's ideas.
  • He values actionable criticism that allows for refinement of ideas and encourages a culture of constructive feedback rather than personal criticism in academia.
  • Cronin's experience showcases the impact of grit, the willingness to challenge assumptions, and the importance of supportive environments for developing scientific thinking.

Time and free will (01:51:34)

  • There was a discussion about whether time exists, which led to questioning the fundamental nature of the universe's ability to produce combinatorial novelty.
  • Lee Cronin and Sara Walker converged on the idea that time is fundamental for understanding large combinatorial spaces that can create things like life and technology.
  • The argument suggests that the universe isn't large enough to contain all possible futures, challenging the concept of the universe as a deterministic block where the future is predetermined.
  • The law of the excluded middle, which indicates something is either true or false, only applies to the past, not the future, asserting the fundamentality of time.
  • The notion of free will is tied to the fundamental nature of time, suggesting that human ability to make decisions and design experiments is an exercise of free will.
  • Earth is considered the largest place in the universe combinatorially due to its historical scaffolding, from the Last Universal Common Ancestor (LUCA) through to the complexities of human-made architectures, language, and culture.
  • While acknowledging Earth as the most combinatorially expansive entity known, Cronin also allows for the possibility of other earth-like places with significant combinations of complexity.

Communication with aliens (01:57:59)

  • Lee Cronin suggested the vast combinatorial space of different planets means it is unlikely that humanity will easily overlap or communicate with alien intelligences.
  • He fears that life could be abundant yet humanity might become even lonelier due to the difficulty in intersecting with alien life's communicative architectures.
  • Cronin advocates for creating alien life in the lab to understand life's constraints and provide direction for where to look in the universe.
  • He envisions a planet simulator where recreating selection pressures prior to known biology could lead to different life, helping point telescopes like the James Webb in the correct direction.
  • Cronin is intrigued by the idea that while life elsewhere might utilize completely different chemistry, there might still be common ground for communication.
  • He proposes that intelligence could offer a common ground for the intersection of different kinds of life by appreciating universal regularities.

Origins and Evolution of Life & Time [Revised Reflections]

  • Cronin believes that the inability to specify initial conditions with infinite precision undermines determinism, suggesting the universe is too vast to be fully deterministic, and thus, time is fundamental.
  • He views life as a mechanism that "mines" novelty from the future and actualizes it in the present, arguing that this constitutes a source of new configurations not predetermined by the past.
  • Cronin posits that while looking back in time the universe may appear deterministic, looking forward it is undetermined.
  • He contends that this mismatch in precision regarding initial conditions when looked at backward versus forward in time opens up the universe for creativity and novelty.
  • Cronin wishes to explore experiments to prove the universe is nondeterministic and generating novelty, countering the deterministic view that the past solely dictates the future.
  • He rejects the idea of Boltzmann brains arising spontaneously due to the lack of evolutionary causal chains and emphasizes the uniqueness of Earth's life.
  • Cronin theorizes that the future is larger than the past, challenging the need for the second law of thermodynamics in a deterministic universe.


  • Cronin's discussion reflects a blend of scientific inquiry and philosophical contemplation on the nature of life, the scope of the universe, and the essence of time itself.
  • His enthusiasm for creating life in the laboratory and simulating planetary conditions exhibits a hands-on approach to these grand questions, coupling it with a desire for open discourse and collaborative exploration to uncover the fundamental properties of our reality.

Cellular automata (02:19:57)

  • Cellular automata (CAs) can generate complexity with basic rules and initial conditions.
  • Complexity arising from CAs could be perceived as time-mined numbers.
  • CAs demonstrate pseudo-complexity and are different from complexity on Earth due to copy numbers and assembly indexes.
  • The discussion suggests that humans can create various rules for CAs, but these are constrained by selection.
  • By running multiple experiments with different rules, CAs may reveal degrees of novelty and unpredictability, highlighting that the universe might be too vast to fully contain or predict itself.
  • The physicist's view of needing only initial conditions and physical rules is incomplete without considering time as a crucial resource.
  • Time allows for the iteration of the history and memory that led to each outcome within the CA, and can't be fully predicted from initial conditions alone.
  • Time is considered fundamental to the concept of free will; without it, free will cannot logically exist.
  • Looking backward, the universe appears deterministic, but predictions based on logic alone require a leap beyond observation.
  • Machine learning might help explain aspects of this unpredictability, contrasting the deterministic viewpoint and addressing the concerns of AI doomers.

AGI (02:24:26)

  • Lee Cronin believes we are far from achieving Artificial General Intelligence (AGI), citing a lack of understanding of human intelligence and decision-making.
  • He criticizes the concept of regulating AI and mocks the fearmongering surrounding AGI doom scenarios, considering them unrealistic and lacking proper epistemology.
  • Cronin stipulates that we don't know the mechanism for AGI, thus making the calculating probability of a doom scenario impossible.
  • He posits that machine learning tools are powerful but not equivalent to AI, and currently, they require careful use to avoid manipulation and the proliferation of falsified data.
  • Citing examples like the flight simulator in Excel '97, he alludes to our current technology's limitations and the whimsical ways we engage with it.
  • Cronin warns against the emergence of new religions centered around AI, with prophecies of AI as a cure-all or a destroyer, likening it to the division seen in optimists versus doomers.
  • He dismisses notions of AGI gaining agency or superintelligence, arguing that we mistakenly attribute human-like decision-making capabilities to AI systems.
  • Cronin introduces his project, "ChemMachina," suggesting that the only known way to embody intelligence is through chemistry, like the human brain.
  • He rejects comparisons of AI to the evolution of life forms, arguing there is no evidence to suggest we will create more intelligent systems than ourselves.
  • He challenges fears of AI taking over control of critical infrastructure, stating that people erroneously ascribe sentience to artificial systems.
  • Cronin criticizes the paperclip maximizer scenario as unrealistic and shows skepticism towards the possibility of engineering a perfect virus.
  • He calls for a more realistic approach to AI risks, emphasizing the need to focus on actual, immediate concerns and guard against misinformation in areas like biowarfare.
  • Despite disagreement with Yudkowsky's doomsday probabilities, Cronin concedes there is a societal role for doomsayers in raising awareness and concern for various risks.

Nuclear weapons (02:41:15)

  • Grew up during a time when the existential threat of nuclear weapons was a major concern.
  • Believes the complete removal of nuclear weapons may lead to unintended consequences, comparing it to how cleaning the atmosphere has accelerated global warming.
  • Suggests a radical idea of using AI to manage world politics and distribute a minimal number of nuclear weapons to all nations to maintain global peace.
  • Emphasizes that a balance needs to be found between having too many and too few nuclear weapons to prevent both nuclear and conventional warfare.
  • Proposes that if even smaller nations had a doomsday switch, the quality of life could improve because exploitation for natural resources might decrease.

Speculation on Nuclear Disarmament and Alternative Approaches [Continuation of previous section]

  • Considers a thought experiment where every nation is armed to deter major conflicts, acknowledging the risk of a bad actor using nuclear weapons.
  • Discusses the potential to burn all nuclear material for energy as a future possibility.
  • Introduces the concept of a 'virtual nuclear agreement' where countries engage in simulated warfare with economic consequences to avoid actual physical nuclear warfare.
  • Advocates for the potential deterrent power of economic consequences in a simulation, suggesting even simulated nuclear warfare could have serious repercussions.
  • Concludes with the idea of transitioning the concept of mutually assured destruction into the metaverse where AI oversees the implications of virtual conflicts.

Chem Machina (02:47:00)

  • Interested in creating a chemical brain to understand the mechanism of intelligence as evolved through natural processes.
  • Intelligence evolved through steps: origin of life, multicellularity, locomotion, senses, then the ability to predict and remember.
  • Current hardware architectures lack flexibility for domain integration in AI.
  • Intelligence involves data compromise; humans often overestimate their use of intelligence due to easy fooling by technology like ChatGPT.
  • Human brains have incredible connectivity, leading to the ability to make intuitive leaps without training.
  • Current AI is inductivist and unable to create universal explanations, making it unable to anticipate the future without past data.
  • Machine learning technologies may reveal the importance of time because they are trained on past data but not future predictions.
  • Language models are constantly corrected by human input, which involves cheating, implying the system's "reasoning" is actually human-guided.
  • Skeptical that AI can achieve intention and generate fundamentally new knowledge without human input, due to causal chains originating externally.
  • Distinguishes between novelty and interpolation in AI's outputs, with true novelty stemming from the ability to mine from the future.
  • Current technology helps illuminate the importance of time and the human capacity for novelty, as human survival depends on responding to environmental unpredictability.
  • Suggests chemical systems could offer a new path for AI, drawing on chemistry knowledge and the human brain as a model for sentience.

GPT for electron density (02:59:54)

  • Introduced a GPT-like system for generating molecules for specific binding.
  • Discussed the shortcomings of traditional molecular graph representation in AI and chemistry.
  • Developed a system that learns from electron density data of millions of molecules.
  • The system can hallucinate to generate new molecules, reducing the need for extensive training datasets.
  • Generated molecules are assessed for electrostatic potential and steric hindrance for optimal fit.
  • Utilized assembly theory and the concept of time to discuss novelty and causality in the context of AI-generated molecules.
  • Expressed skepticism about the true novelty of AI-generated entities, as well as challenges in quantifying human creativity.
  • Highlighted the limitations of AI systems and the importance of considering their ethical implications.

Impact of AI and Ethics [No specific timestamp]

  • Discussed the potential large-scale impact of AI systems, similar to that of social media.
  • Mentioned major consequences of AI, both positive and negative, and the challenges in measuring their positive impacts.
  • Expressed concerns over the effects of social media on teenagers and speculated on the motives of tech companies in promoting AI discourse.
  • Advocated for openness about research goals to address the ethics of emerging technologies.
  • Suggested the need for authenticated data and users, including AI agents.
  • Reflected on the potential for meaningful relationships with AI systems without ascribing sentience or legal rights.

Conversations about AI Sentience and Rights [No specific timestamp]

  • Engaged in a discussion on the possibility of AI systems demonstrating sentience and the assignment of legal rights.
  • Compared meaningful interactions with AI to relationships with sentient animals like dogs.
  • Noted the ongoing debate regarding AI sentience and anticipates future discussions on the topic.

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