Glossary

Structural biologist who came to the LMB and worked on virus structures.

Exploit naturally high quantities to avoid purification.

A class of mutagens that cause frameshift mutations by intercalating into DNA.

Crick's prediction that small molecules would link codons to amino acids.

The coordination substrate for multi-agent research sessions.

A particular version of a gene at a specific position in the genome.

A mutation creating a UAG stop codon, named after Bernstein (German for 'amber').

A mutation creating the UAG stop codon, named for its discoverer's translation.

The building blocks of proteins: 20 standard types coded by DNA.

Enzyme that attaches the correct amino acid to its tRNA.

Enhance weak signals until they become measurable (↑).

Ordering genes in a pathway by combining mutations.

Isolate gross parts first before fine purification: chunk before fractionate.

A stable reference to a transcript section (§n format).

Programmed cell death: cells that deliberately kill themselves.

Biochemist who discovered DNA polymerase and lectured Brenner on metabolism.

A structured output from a research session (hypotheses, tests, etc.).

Explicit list of load-bearing assumptions and what would break them.

Detecting radioactive molecules by exposing photographic film.

A mutant organism requiring a specific nutrient to grow.

Viruses that infect bacteria; the workhorse of early molecular biology.

A chemical mimicking a DNA base that causes point mutations when incorporated.

The prior probability of something in a population before specific evidence.

A ratio measuring the evidence for one hypothesis versus another.

Revising beliefs by combining prior probability with new evidence.

The issue tracking system used in BrennerBot development.

A mutant with altered behavior rather than altered structure.

A genetic screen that selects mutants based on abnormal behavior.

Brenner's preference for working against conventional wisdom.

Sinsheimer's proposal that the genetic code might use only purines vs pyrimidines.

Chargaff's dismissive description of molecular biologists.

The requirement that theories must be biochemically realistic.

A design where the experimenter doesn't know treatment assignments.

The iterative research cycle: hypothesize, design discriminative test, run, update.

Sydney Brenner's approach to scientific research: function before mechanism.

A strategic intervention that transforms a stuck problem into a tractable one.

Genetic steam engineering: solving problems by exhaustive screening.

A tiny transparent worm (~1mm) that became a model organism for genetics and neuroscience.

The Cambridge physics lab where Brenner first saw the DNA model.

The complete ancestral history of a cell, tracing back to the fertilized egg.

Information flows from DNA to RNA to protein, never backward to DNA.

The mechanism by which protein synthesis stops at stop codons.

Distinguish 'won't happen' (chaste) from 'can't detect' (impotent).

Minimize time between hypothesis and test; optimize for iteration speed.

Sperry's theory that neurons find targets through molecular matching.

Movement toward or away from chemical signals.

Benzer's term for the functional unit of the gene defined by complementation.

The correspondence between gene sequence and protein sequence order.

A three-nucleotide sequence that specifies one amino acid.

The Long Island laboratory that hosted the phage meetings and shaped molecular biology.

Crick's hypothesis that overlapping frames would produce nonsense.

Test whether two mutations affect the same or different genes.

The goal of exhaustively describing an organism at cellular resolution.

Brenner's claim that organisms can be computed from their DNA.

Brenner's philosophy that computers should serve scientists, not dominate them.

A mutation that kills only under specific conditions, enabling study of essential genes.

A hidden variable that varies with treatment and could explain results.

The complete wiring diagram of all neural connections in a nervous system.

The baseline condition an experiment compares against.

Thinking out loud as cognitive technology: externalize half-formed ideas.

The primary source documents in BrennerBot (transcripts + distillations).

Borrow techniques or concepts from other fields (⊕).

Comparison table showing how different model distillations map the same concepts.

The craft of growing and maintaining experimental organisms.

A stress-resistant dormant larval stage in C. elegans.

An experiment whose result forces a choice between hypotheses.

Deriving specific conclusions from general principles.

Multiple codons specifying the same amino acid.

Using chromosomal deletions to rapidly localize mutations.

A structured update to an artifact from an agent.

Make expensive techniques cheap and accessible (⇓).

Separating molecules by mass using heavy isotopes and centrifugation.

Move out of phase with fashion to find open territory (∿).

Pure description of phenotypes without mechanistic understanding.

Gamow's overlapping triplet code hypothesis.

Discrete, countable markers that make a system tractable.

Cell fate determined by lineage (digital) versus gradients (analogue).

An experiment designed to distinguish between competing hypotheses.

An experiment designed to distinguish between competing hypotheses.

A processed, structured summary derived from the raw corpus.

Build your own tools when commercial ones don't exist (🔧).

Deoxyribonucleic acid: the molecule that stores genetic information.

An allele whose phenotype shows even when heterozygous.

Assume a mechanism exists and proceed; don't block on seeming impossibilities.

Neither experimenter nor subject knows treatment assignment.

Imaging with electrons to achieve nanometer resolution.

Ethyl methanesulfonate: a chemical mutagen widely used in genetics.

Gunther Stent's premature obituary for the field.

The rapid synthesis of enzymes in response to a signal.

When one gene's phenotype masks another's, revealing pathway order.

Biochemist famous for base-pairing rules and acerbic wit about molecular biology.

Physicist whose book 'What Is Life?' influenced a generation of molecular biologists.

Data or observations that update beliefs about hypotheses.

Isolate anomalies so they don't corrupt the main theory (ΔE).

A curated selection of corpus sections for a kickoff prompt.

Design tests that rule out hypotheses, not confirm them (✂).

Systematically listing all possibilities before testing them.

Proving a hypothesis wrong rather than confirming it.

Benzer's technique for mapping mutations within a gene to single-nucleotide resolution.

The moment when a solution becomes suddenly obvious.

Results that your theory says cannot occur.

Starting with a phenotype and working backward to find the gene.

A mutation that shifts the reading frame, scrambling all downstream codons.

Co-discoverer of DNA structure; Brenner's intellectual partner for 20 years.

Co-developer of the operon model; collaborated with Brenner on mRNA discovery.

The pufferfish with a compact genome; Brenner's 'discount genome' project.

Choosing problems and methods that will remain relevant as technology advances.

An imaginary organism designed to think through what's possible.

A segment of DNA that encodes a functional product (usually a protein).

Joining two genes so one's expression reports on the other.

Brenner's hypothetical equations governing limb development.

The discoverable causal rules that produce phenomena, reality's 'source code.'

The mapping from DNA triplets (codons) to amino acids.

Breaking down a phenotype by finding all the genes that can break it.

A diagram showing the relative positions of genes based on recombination frequency.

The ordered sequence of gene products that execute a biological process.

Systematic mutagenesis followed by selection for a phenotype of interest.

Building function by adding genes rather than removing them.

Large-scale effort to sequence an organism's complete DNA.

The genetic makeup (DNA sequence) of an organism.

Cosmologist who founded the RNA Tie Club and catalyzed coding theory.

The South African town where Sydney Brenner was born and raised.

Phage biologist who proclaimed molecular biology 'solved' and later wrote its obituary.

Have A Look: directly observe before elaborate inference (👁).

Have A Look biology: Brenner's term for observation-first science.

An organism with both male and female reproductive organs.

A double-stranded DNA molecule with strands from different sources.

Having two different alleles of a gene.

Having two identical alleles of a gene.

Theory architecture where all components mutually constrain: all or nothing.

A chemical mutagen that causes specific C-to-T transitions.

A proposed explanation for phenomena, to be tested by experiment.

A structured list of competing hypotheses to be evaluated.

Brenner's vivid metaphor for mRNA threading through ribosomes.

Constrain theorizing by physical reality: calculate before speculating.

Generalizing from specific observations to broader principles.

How much an experiment reduces uncertainty about a question.

The starting state required alongside DNA to compute an organism.

A second mutation within the same gene that restores function.

Non-coding sequences within genes that are spliced out of mRNA.

The fixed number of cells in C. elegans adults: exactly 959 somatic cells.

Find what stays the same across transformations (≡).

Genetically identical individuals, like a clone.

Solving the phase problem by comparing crystals with and without heavy atoms.

Crystallographer who first told Brenner about the DNA structure.

Co-discoverer of the operon model and mRNA concept.

Co-discoverer of DNA structure; drove Brenner across America in a Chevy convertible.

Crystallographer who solved the first protein structure (myoglobin).

Brenner's colleague who traced the complete C. elegans cell lineage.

Mathematician whose self-replicating automata influenced Brenner's thinking.

Reconstructed the C. elegans nervous system from serial sections.

The initial prompt that starts a research session.

Science that can be done with minimal equipment and resources.

Measures how different two probability distributions are.

Brenner's warning that excessive knowledge harms research creativity.

A temperate bacteriophage that can integrate into the host chromosome.

Killing specific cells with a focused laser beam to test their function.

Decompose a problem into distinct levels of organization (⊘).

How much more likely the evidence is under one hypothesis versus another.

The integration of phage DNA into the host chromosome.

The primitives a system actually computes with, not metaphors but real operations.

The low-level instructions that actually execute biological programs.

Rare males used for genetic crosses in C. elegans.

Turn abstract theory into concrete, testable predictions (⌂).

Demonstrated semiconservative DNA replication with Franklin Stahl.

Physicist who founded the Phage Group and established molecular biology's culture.

Crystallographer who determined the first protein structure (hemoglobin).

The 'most beautiful experiment in biology' proving semiconservative DNA replication.

A template that generates specific prompts for different research contexts.

A mutation that changes one amino acid to another.

A species chosen for study because its properties make experiments tractable.

Isolating and copying a specific DNA fragment in bacteria.

The Medical Research Council lab in Cambridge where Brenner spent his career.

Messenger RNA: the intermediate that carries genetic information from DNA to ribosomes.

Deliberately inducing mutations to study gene function.

A change in DNA sequence that may alter gene function.

Patterns across many mutants that reveal mechanism class and code structure.

The standard wild-type C. elegans strain used worldwide.

A democratizing EM technique discovered via cross-domain pattern recognition.

A nerve cell specialized for transmitting electrical and chemical signals.

The principle that nervous systems are built from discrete cells connected by synapses.

A triplet that signals 'stop translation' rather than coding for an amino acid.

A mutation that allows read-through of stop codons.

The default assumption that there's no effect or difference.

Switch which entity you're experimenting on (⟂).

Sweeping inconvenient facts under the rug.

A mutation creating a UAA stop codon.

A mutation creating the UAA stop codon.

The ratio of probability of an event to probability it doesn't happen.

The key prediction of messenger RNA: new genetic information on pre-existing ribosomes.

The insight that biological information is encoded in linear chains.

Early research phase with maximum freedom: develop position before committing.

Defining abstract concepts in terms of measurable procedures.

The collection of Brenner operators defined in the system.

Reusable cognitive moves for transforming stuck problems into tractable ones.

A cluster of genes transcribed together and regulated as a unit.

Brenner's strategy of working either ahead of or behind scientific fashion.

A hypothetical genetic code where adjacent codons share nucleotides.

Manipulating analysis until results appear statistically significant.

The Pardee-Jacob-Monod experiment that revealed gene regulation dynamics.

A framework of assumptions, methods, and problems that defines a scientific field.

Actively seek contradictions; they mark discovery zones (◊).

Short for bacteriophage; the model system for early molecular genetics.

The tight-knit community of phage biologists centered at Cal Tech.

The intellectual community around Delbrück that founded molecular biology.

The fundamental obstacle in X-ray crystallography: diffraction loses phase information.

The observable characteristics of an organism.

Isolating a gene by walking along the chromosome from nearby markers.

Your updated beliefs after seeing new evidence.

An experiment's power to discriminate between hypotheses.

Verify your intervention actually worked before trusting results (🎭).

The creative advantage of not knowing too much about a field.

Your beliefs about a hypothesis before seeing new evidence.

Not knowing the standard approach lets you see alternatives.

An acridine dye that causes frameshift mutations by inserting between DNA bases.

Von Neumann's insight: the genetic program must construct its own execution machinery.

Industrial-style science where a 'general' directs troops.

Phage DNA integrated into the host bacterial chromosome.

A molecular machine made of amino acids that performs cellular functions.

A bacterial cell with its cell wall removed.

Labeling molecules briefly, then following their fate over time.

Run a cheap pilot test to de-risk before committing to the full experiment (⚡).

A curated collection of Brenner quotes organized by theme.

The triplet grouping that determines how DNA is decoded into protein.

An allele whose phenotype only shows when homozygous.

Change representation to make patterns visible (𝓛).

The exchange of genetic material between chromosomes during meiosis.

Building 3D structure from serial section images.

Repeating an experiment to verify results are real.

A unit of DNA that replicates from a single origin; Brenner's term with Jacob.

Restate the problem in a domain where constraints are clearer.

Whether results can be obtained again using the same methods.

Starting with a gene and asking what phenotype its mutation causes.

A mutant that has regained the wild-type phenotype.

The cellular machine that reads mRNA and builds proteins.

The phage T4 genetic region where Benzer mapped mutations to single nucleotides.

Ribonucleic acid: single-stranded molecule that carries and implements genetic information.

Gamow's exclusive club of 20 scientists working on the genetic code.

Fred Sanger's method for reading DNA sequences using chain termination.

Evolution satisfies constraints rather than optimizing: good enough beats best.

Mutagenize until you've found all genes controlling a phenotype.

The informal LMB discussion group where ideas flowed freely.

Brenner's method of learning: colleagues must explain their work with 5 minutes notice.

Physics constrains what's possible at each size (⊞).

The mistaken belief that you can calculate an organism directly from its chromosomes.

A numbered unit of the Brenner transcript, referenced as §n.

Complex structures that build themselves from their component parts.

An organism that produces both sperm and eggs and can self-cross.

The probability a test correctly detects a condition when present.

Crick's principle that DNA sequence determines protein sequence.

Cutting tissue into sequential thin slices for 3D reconstruction.

Cutting tissue into sequential thin slices for 3D reconstruction.

A research interaction between human and AI agents on a specific question.

If an effect isn't visible across seven log cycles, it's probably not real.

Pioneer of fine-structure genetics who later founded behavioral genetics.

The probability a test correctly rules out a condition when absent.

Removing introns from pre-mRNA to produce mature mRNA.

Brenner's provocative idea that we should spread ignorance rather than knowledge.

The fundamental question: is cell differentiation a stable state or an ongoing process?

Brenner's principle: keep your thinking within physical constraints.

Brenner's response to Chargaff's quip about Mercury being god of thieves.

A density gradient technique for separating molecules by size.

A second mutation that rescues the phenotype caused by a first mutation.

A junction where neurons communicate with each other or with muscles.

The specific bacteriophage used for genetic code and fine-structure mapping work.

The genetic code as a lookup table from codons to amino acids.

Brenner's original name for mRNA, invoking the Turing machine metaphor.

A mutant that functions at one temperature but fails at another.

The intellectual center where scientists prove themselves against the best.

Deliberately attempt to destroy your own hypothesis (†).

Brenner's paper proposing two classes of mutations: substitutions and frameshifts.

The 'both models are wrong' escape from false dichotomies.

A conversation stream in Agent Mail identified by a unique ID.

The trails C. elegans worms leave on bacterial lawns.

The raw 236-section Brenner interview: the primary source material.

The process of copying DNA into RNA.

Transfer of bacterial genes from one cell to another via phage.

An organism carrying foreign DNA inserted into its genome.

The process of reading mRNA to build proteins at the ribosome.

Transfer RNA: the adaptor molecule that brings amino acids to the ribosome.

Abstract computing device operating on a one-dimensional tape.

Brenner's foundational commitments: reality has grammar, understanding = reconstruction.

The advantage of organisms that live on surfaces rather than in volumes.

High-speed centrifuge for separating molecules by density or size.

Uncoordinated mutants with defective movement in C. elegans.

The gene encoding the major myosin heavy chain in C. elegans muscle.

Deliberately ignore conventional wisdom to see fresh (⊙).

Brenner's critique: the more general the theory, the more empty it is.

The Berkeley laboratory where Brenner worked with Gunther Stent.

The mysterious RNA fraction with DNA-like composition found after phage infection.

The C. elegans egg-laying structure; a model for cell fate decisions.

Schrodinger's influential 1944 book on the physical basis of heredity.

The normal, non-mutant version of an organism or gene.

The complete map of neural connections in a nervous system.

Flexible base-pairing at the third codon position allowing one tRNA to read multiple codons.

Marine biology laboratory where secret developmental biology seminars were held.