There is a kind of student, and for a while most of us are that kind, who can recite the Krebs cycle perfectly provided he is allowed to begin at citrate. Ask him what comes after fumarate and something interesting happens behind his eyes. He goes back to the top and runs the whole sequence under his breath until he arrives, the way a child finds the letter before R by singing the alphabet from A. The answer comes out correct. It has simply been fetched through the only door the memory knows.
The cycle usually turns up first in a chapter on respiration, in the biology of the pre-medical years, and then again in medical school biochemistry with more names, more arrows and considerably less mercy. For me that first meeting would have belonged to the Khalsa College years, 1994 to 1996. I will not pretend to recall the occasion, or the textbook, diagram, mnemonic or examination question that went with it; anyone who claims perfect recall of his study technique from three decades ago is describing a method he wishes he had used. What I can describe is the cycle itself, which has not changed, and the odd relationship between a memorised sequence and the thing it is a sequence of. That relationship is worth an essay because it is not confined to biochemistry. It is the relationship between knowing names and knowing what they are names of, and medicine depends on both.
The difficulties begin before the chemistry does. The same circle answers to three names: the Krebs cycle, the citric acid cycle and the tricarboxylic acid cycle, usually shortened to the TCA cycle. A student therefore has to memorise the names of the cycle before he can start on the names in it, and the textbook, the lecturer and the question paper are under no obligation to use the same one.
The three names are not quite synonyms, and the difference is a small lesson in itself. One honours a person. One names the cycle after its first product, citric acid. The third names a chemical family: citrate and isocitrate each carry three carboxyl groups, which is what tricarboxylic means. A person, a station and a class of molecule; each name points at something different, and each quietly suggests that the thing it points at is the important part. The student, who has eight more names to learn and an examination in a fortnight, is in no position to notice that naming is already a choice of emphasis.
Then come the stations. Generations of students have carried them in sentences built for the purpose. A well-known one runs: Citrate Is Krebs’ Starting Substrate For Making Oxaloacetate, whose initial letters give citrate, isocitrate, alpha-ketoglutarate, succinyl-CoA, succinate, fumarate, malate and oxaloacetate. It is a good sentence. It is also slightly shameless, since it opens by simply stating the first answer. Other mnemonics have been handed down through student hostels for decades in versions unsuitable for publication here, and they work at least as well.
What every such sentence does is turn a circle into a line. The line has a beginning, which is why the reciter must start there, and an end, after which he stops. The circle has neither. That small geometric betrayal turns out to be the whole subject.
Into the Throat #
Before deciding that the reciting student is a figure of fun, it is fair to ask what memorisation can be at its best, because the languages I grew up with take it far more seriously than any mnemonic does.
Hindi speaks of a text learned by heart as कंठस्थ, kaṇṭhasth, seated in the throat. In Punjabi the throat is ਕੰਠ, kanth, and a poem or a passage that has been learned thoroughly is said to be there, in the place the voice comes from. It is an exact image. A text in the throat is not looked up; it is spoken, and it arrives with breath and rhythm attached. The same languages keep a harsher word for the same act. Hindi रटना, raṭnā, and the Punjabi ਰੱਟਾ, raṭṭā, name memorising by repetition without understanding, the parrot’s method, and it is a word students often use about themselves, half rueful and half proud. One practice, two words, and the difference between them is not the amount of repetition. It is what the repetition was for.
The most rigorous memorisation I know of is the tradition of Vedic chanting, which UNESCO has recognised as part of the intangible heritage of humanity. Its reciters did not learn a text once. They learned it in several patterns, called pathas. In the continuous recitation, the samhitapatha, the words run together as the rules of euphony join them. In the padapatha each word is spoken separately, with a deliberate pause. In the kramapatha the words are taken in overlapping pairs, so that a sequence a, b, c, d is recited as ab, bc, cd. In the jatapatha the pairs are braided, recited forward and backward and forward again, and in the ghanapatha, usually considered the hardest, the words swing back and forth in a pattern likened to the shape of a bell. The patterns cross-check one another. An error that slipped into one would collide with the others.
The student who can reach fumarate only by starting at citrate should find this humbling. One of the oldest and most exacting technologies of memorisation had already solved his problem. A reciter trained in overlapping pairs can enter the text at any word and move in either direction, because he has learned not only each item but each item’s neighbours. His memory has many doors. And the reason for all the effort was fidelity: a text that can be entered only from the beginning is fragile, since a single lost link strands everything after it.
There is a limit to the comparison, and it is instructive. The pathas, as they are described, were designed to transmit a text exactly, sound by sound and in order. A sequence preserved perfectly is still a sequence. A student who learned the Krebs cycle in krama fashion, citrate–isocitrate, isocitrate–alpha-ketoglutarate, and so on round, would be a far better reciter than the one who must begin at the top, and he would be able to answer what comes after fumarate without going back. He would still not know why anything comes after anything. For that he needs a different kind of question, one that no recitation, however well braided, has been rehearsed to answer.
The Unvarying Answer #
Plato saw the problem from the other side. In the Phaedrus, Socrates tells a story of the Egyptian god Theuth, who brings the invention of letters to the king Thamus and recommends it as a remedy for memory. Thamus is not persuaded. In Benjamin Jowett’s translation, the king replies that writing will create forgetfulness in the learners’ souls, because they will trust to external characters and not remember of themselves; that it is “an aid not to memory, but to reminiscence”; and that its users “will be hearers of many things and will have learned nothing.”
The word Jowett renders as “specific,” in the old sense of a remedy aimed at a particular complaint, is the Greek pharmakon, and pharmakon means a drug in both directions: a cure and a poison. It is hard not to hear both senses when a student is handed a mnemonic. The sentence about Krebs’ starting substrate really does cure a complaint, the inability to produce eight names in order under the pressure of an examination hall. It may also, quietly, poison something else, by making the production of the names feel like the end of the task.
Socrates then adds the complaint I find most useful. Written words, he says, are like paintings, which have the attitude of life but keep a solemn silence when questioned. “If you want to know anything and put a question to one of them, the speaker always gives one unvarying answer.” Against this he sets another kind of word, “an intelligent word graven in the soul of the learner, which can defend itself, and knows when to speak and when to be silent.”
The irony for the reciting student is sharp. Socrates sets writing against memory, and the student has done the memorising; the sequence is inside him, not on the page. Yet when he is asked a question it was not shaped for, it behaves exactly like the writing Socrates distrusted. It gives one unvarying answer, and it gives it from the top. A list memorised without its relations is a piece of writing carried inside the skull. It has moved address without changing its nature. What would make it a living word, in Socrates’ sense, is not where it is kept but whether it can answer a question it has not heard before: not only what follows fumarate, but what happens to the whole wheel if one of its stations is drawn away.
Dickens set the same problem in a Victorian schoolroom. Hard Times, published in 1854, opens with a man demanding facts: “NOW, what I want is, Facts. Teach these boys and girls nothing but Facts.” Mr Gradgrind turns to a girl he addresses as number twenty, Sissy Jupe, establishes that her father works with horses in the circus ring and that he “doctors sick horses,” and asks her to define a horse. She cannot. A pale boy called Bitzer can: “Quadruped. Graminivorous. Forty teeth, namely twenty-four grinders, four eye-teeth, and twelve incisive. Sheds coat in the spring; in marshy countries, sheds hoofs, too. Hoofs hard, but requiring to be shod with iron. Age known by marks in mouth.”
The scene is usually read as a straightforward triumph of acquaintance over definition: the girl who has lived among horses against the boy who has memorised a description of one. That reading is right about the schoolroom, which rewards the wrong child. It is less fair to Bitzer’s facts, which are true, and some of which are exactly what a horse doctor needs. Age is indeed estimated from the teeth. A physician would recognise the situation at once. Medicine needs Bitzer’s list and Sissy’s familiarity, and the list is not the enemy. The danger lies in a system of teaching and examining that cannot tell them apart, and that gives full marks to the list on the assumption that the familiarity must be somewhere behind it.
The Arrow Krebs Found #
The history of the cycle makes the same point more elegantly than any argument, because the discovery itself was a discovery of relations.
Hans Krebs was dismissed from his post at the University of Freiburg in April 1933. He arrived in Cambridge that July as a demonstrator in the Department of Biochemistry, and in 1935 moved to Sheffield. There, with William Arthur Johnson, a postgraduate student who had joined him in 1935, he worked out the sequence of reactions they named the citric acid cycle. The experiments were laborious. They used minced pigeon breast muscle and measured its consumption of oxygen; adding a salt of citric acid extended the working life of the preparation about threefold, an effect which suggested that the citrate was doing more than serving as fuel. According to the University of Cambridge’s account, the paper was offered to Nature, whose editors replied that they had enough material for the next seven or eight weeks. It appeared in 1937 in the Dutch journal Enzymologia as “The role of citric acid in intermediate metabolism in animal tissues.” It is a consoling story for anyone who has had a manuscript declined. In 1953 Krebs shared the Nobel Prize in Physiology or Medicine with Fritz Lipmann, Krebs for his discovery of the citric acid cycle and Lipmann for his discovery of coenzyme A.
What exactly did Krebs discover? Not, for the most part, the stations. At the award ceremony Einar Hammarsten of the Karolinska Institute said plainly that what had been known before Krebs amounted to details and partial processes, found here and there. Several of the individual reactions had been described by other workers. In Hungary, Albert Szent-Györgyi, working with the same minced pigeon muscle, had shown in the mid-1930s that small amounts of four-carbon acids such as fumarate and succinate stimulated the muscle’s consumption of oxygen out of all proportion to their own quantity; the catalysis of fumaric acid was among the discoveries for which he received the Nobel Prize in 1937. In the same year Carl Martius and Franz Knoop showed that citrate could be converted, by way of isocitrate, into alpha-ketoglutarate. There were pieces of one line from one laboratory and pieces of another from a second.
What Krebs discovered, Hammarsten said, was how these individual reactions were linked to one another in a cycle. A two-carbon unit joins a four-carbon compound to form citric acid; as the citric acid is taken apart, step by step, the four-carbon compound is made again, and when the taking apart is complete it is free to react with the next two-carbon unit. Krebs found the circle. To show that it really closed, he and Johnson used malonate, a molecule that resembles succinate closely enough to jam the enzyme that acts on it. With that step blocked, fumarate added to the muscle ended up as succinate, piling up behind the obstruction, which could only happen if it had gone the long way round, through oxaloacetate, citrate and alpha-ketoglutarate, and arrived at the block from the other side. It was a prediction made by the wheel and tested on the wheel. The arrow that runs from oxaloacetate back to citrate, the one students draw last and think about least, is very nearly the discovery itself.
The identity of the two-carbon fragment remained uncertain for years. Lipmann’s coenzyme A turned out to be the carrier that brings it to the cycle in reactive form, and Hammarsten described the moment it fitted with a phrase I have always liked: “the last notch of a combination lock fell into its place.” One prize, shared, for a circle and for the key to its entrance. Most of us memorised the parts that other people had found, and took the closing arrow for decoration.
Following the Carbon #
Seen as a circle, the cycle begins to explain itself in a way the list never could. Because the four-carbon oxaloacetate is regenerated at the end of each turn, the intermediates are not used up by the work they do. A modest pool of them can handle a very large flow of fuel, which is what the threefold effect of a little citrate on minced pigeon muscle was hinting at. The wheel stays; the material passes through.
Follow the material carefully and it becomes more interesting still. Two carbons enter with each turn, carried by coenzyme A. Two carbons leave as carbon dioxide, at the two steps where the ring is shortened. The natural assumption is that the carbons leaving are the ones that just arrived, and the natural assumption is wrong. In the first turn after a labelled acetyl group enters, the two carbon dioxide molecules released come from the part of the citrate that was derived from oxaloacetate. The newly arrived carbons stay aboard. And because succinate, halfway round, is a symmetrical molecule, the cell cannot tell its two ends apart, so the label is scrambled between them, and the first of the newcomers leaves only on a later turn, at the earliest the second. A memorised list has no way of telling you this, and no reason to. A cycle traced with a labelled atom tells it at once.
Primo Levi built a book on that kind of tracing. The Periodic Table, published in Italian in 1975 and in Raymond Rosenthal’s English translation in 1984, is an autobiography by a chemist told in twenty-one stories, each named for an element. Its final chapter, “Carbon,” follows a single atom of carbon: released from a block of limestone in a lime kiln, drawn through the lungs of a falcon, carried by air and water, taken up by plants, and at last arriving in Levi himself, in his own brain, where it takes part in the very act of writing the story. In 2006 the Royal Institution of Great Britain named it the best science book ever. I think the chapter succeeds because Levi refuses the list. An atom of carbon has no stations, only passages, and the writer’s achievement is to make the reader feel the continuity of matter through forms that seem to have nothing in common.
There is a second lesson in the book’s shape. The Periodic Table is, after all, a list: twenty-one elements, chosen from the most famous memorisation exercise in all of chemistry. What turns the list into an autobiography is that each name is attached to an encounter in a life, and the encounters supply the relations that a chart of atomic numbers cannot. That is not a bad description of how a memorised cycle comes alive for a physician, if it ever does. It happens one station at a time, as a name meets a use: citrate in a collection tube, succinate on a label, succinate dehydrogenase in a genetics report. The list remains a list, but its items acquire histories, and a name with a history behaves differently in the mind from a name with only a position.
The Krebs cycle is one of the busiest crossings on such passages. The carbon dioxide we breathe out carries carbons that entered the wheel a turn or more earlier, and they will go on into the air, and some will be taken up by a leaf. Lewis Thomas, in the title essay of The Lives of a Cell, collected in 1974 from his columns for the New England Journal of Medicine, pressed the point about our own composition further. The mitochondria in which this cycle turns, he argued, descend from other organisms, and our cells are as much shared accommodation as private property. The most intimate chemistry we have is run in rooms that were, a very long time ago, let to lodgers. A student memorising the stations is reciting the floor plan of a borrowed house.
What the Cycle Does Not Make #
A second confusion survives memorisation intact, and it concerns the energy account. Many students carry away from their first encounter the belief that the Krebs cycle is where the cell makes its ATP. It is a reasonable belief, since the cycle sits at the centre of the chapter on respiration, and it is mostly wrong.
The cycle itself makes very little ATP: one molecule per turn, or of its close chemical relative GTP, at the step where succinyl-CoA becomes succinate. Its main product is something less tangible. As the carbon skeleton is taken apart, electrons are stripped from it and handed to two carrier molecules, three NAD⁺ reduced to NADH and one FAD to FADH₂ in each turn, along with the two molecules of carbon dioxide. The carriers take those electrons to the respiratory chain in the inner membrane of the mitochondrion, and it is there, as the electrons are passed finally to oxygen, that most of the cell’s usable energy is captured. Oxygen is not a reactant in the cycle at all. Yet the cycle is, in the textbook phrase, the gateway to the aerobic metabolism of fuel, because without oxygen at the end of the chain the carriers cannot be emptied, and a cycle that has nowhere to put its electrons stops.
One station makes the connection almost literal. The enzyme that converts succinate to fumarate, succinate dehydrogenase, is built into the inner mitochondrial membrane and doubles as one of the complexes of the respiratory chain itself. At that point the wheel and the chain share a piece of machinery.
The wry lesson here is about the questions students are asked. An examination that asks how many ATP the cycle produces is asking for a number, and numbers are easy to memorise. A better question would ask where the energy goes, and the answer to that is a relationship between two pieces of machinery, which no single number can hold.
A Roundabout at Rush Hour #
Then there is the traffic. A diagram of the cycle shows a closed ring, and a closed ring suggests that everything stays inside it. It does not.
Molecules leave the cycle to build other things. Citrate is carried out of the mitochondrion into the surrounding cytoplasm, where it is split to supply the two-carbon units from which fatty acids and cholesterol are made. Alpha-ketoglutarate and oxaloacetate provide the carbon skeletons for many of the amino acids, among them glutamate and aspartate. Most of the carbon atoms in porphyrins, including the haem in haemoglobin, come from succinyl-CoA. When the cell’s energy is high, oxaloacetate can be turned toward the making of glucose. Material arrives as well as leaves: amino acids broken down in the cell join the cycle at several points.
Anyone who has driven round a busy ਚੌਕ, chauk, one of the traffic circles at the crossings of a Punjabi town, at rush hour, understands this arrangement at once. Hardly anyone on a roundabout is going round. They are going somewhere else, by way of the roundabout. A student who has memorised the stations knows the names of the exits. He does not yet know that they are exits.
The withdrawals create a problem, and the way the cell solves it is one of the quieter beauties of the subject. Every intermediate taken out for building is an intermediate the wheel no longer has. Take out enough, and oxaloacetate runs short; without oxaloacetate, the incoming two-carbon units have nothing to join, and the cycle slows. So the cell refills it. The reactions that do this are called anaplerotic, from a Greek word meaning to fill up, and the classic example is the carboxylation of pyruvate to make fresh oxaloacetate. A memorised circle has no room for this. A circle understood as a crossroads needs it urgently.
I should mark the limits of my own analogy, since an attractive image can hide the chemistry it is meant to illuminate. A roundabout is a fixed structure, and the traffic on it is something else. In the cycle, the traffic and the road are made of the same molecules: the intermediates are at once the pavement on which material moves and the vehicles that leave. And a roundabout regulates its flow crudely, by the courtesy and nerve of drivers, while the cycle is regulated by enzymes that respond to the cell’s supply of fuel and its demand for energy. The analogy explains why there are exits. It explains nothing about why the traffic moves when it does.
Succinate on the Label #
The names come back in later life, though rarely where expected. A physician meets them constantly. Citrate is in the tube into which blood for clotting tests is drawn, where it binds calcium and keeps the sample from clotting before it reaches the laboratory. Succinate and fumarate appear on medication lists, because many drugs are prepared as salts, and the name of the drug’s partner ion travels with it. Each time, something old twitches in recognition. The twitch feels like knowledge. Usually it is not.
Consider a common example. Metoprolol, a medicine used for several heart and blood-pressure conditions, is sold in a form called metoprolol succinate, as extended-release tablets. The official labelling describes the tablets as containing 23.75, 47.5, 95 and 190 milligrams of metoprolol succinate, “equivalent to” 25, 50, 100 and 200 milligrams of metoprolol tartrate. The arithmetic is there because the partner ions weigh different amounts; the metoprolol is the same molecule in both. And the property that the succinate tablet is usually chosen for, its slow release over the day, comes from neither partner ion. According to the same labelling, the tablet is a multiple-unit system containing the drug in a multitude of controlled-release pellets, each of them a separate delivery unit. The release belongs to the pellets.
So the word on the label that the biochemistry student recognises is the one that explains least. It names the partner ion. It says nothing about why the drug is given, which belongs to the metoprolol, and nothing about how it is released, which belongs to the formulation. Yet in conversation it is easy to hear the salt name used as shorthand for the product, as though the succinate were doing the work. This is what retained vocabulary looks like in the wild: a reflex of familiarity attached to no understanding of the thing in front of it, and quite capable of passing for knowledge. Recognition, in a case like this, ought to open an inquiry rather than close one. The old name supplies a handle. The question is what the handle is attached to here.
When a Station Sends a Message #
Real relearning is slower and more humbling, and the cycle has rewarded it. The stations that students memorise as waypoints have turned out to have lives of their own.
Inherited faults in the genes for two of the cycle’s own enzymes are now known to predispose to rare tumours. Variants in the genes for succinate dehydrogenase are associated with hereditary paragangliomas and phaeochromocytomas, rare tumours of the adrenal glands and of similar tissue elsewhere in the body. Variants in the gene for fumarate hydratase, the enzyme that turns fumarate into malate, are associated with a syndrome called hereditary leiomyomatosis and renal cell cancer. The mechanism proposed for both is striking. When the enzyme fails, its substrate piles up, and the accumulated succinate or fumarate competes with alpha-ketoglutarate, another station on the same wheel, for a family of enzymes that help the cell sense oxygen. The sensing goes wrong. The cell behaves as though it were short of oxygen when it is not, and the signals of that false emergency can favour growth.
I find this almost unbearably neat. A molecule that a student learns as the fifth or sixth word of a sentence turns out, when it is allowed to accumulate, to be capable of sending a message, and the message is a lie about the air. The conditions are rare, and this essay is no guide to them. But they show the cycle in a light the examination diagram could not cast. The circle that looked so finished on the paper was more open than the drawing allowed, and its parts speak to the rest of the cell in ways nobody needed to know in order to pass.
The diagram has a fair excuse for the omission: in the ordinary working of the cell, the intermediates do not pile up, because each is passed on almost as soon as it is made. Their talkativeness is revealed by failure. That is a familiar pattern in medicine, where a great deal of normal physiology was first understood through the specific way it breaks, and it is a reminder that a sequence learned only in its working order is a sequence learned in its quietest state.
In Defence of Bitzer #
It would be easy to stop there, with the list humbled and the relations crowned. The list has a better defence than that.
Begin with speed. Much of medicine is done under time pressure, and attention is the scarcest thing at a bedside. A fact that has to be derived from first principles each time it is needed costs attention that the patient in front of you should be getting. A fact that is simply there, fluent and unreflecting, costs nothing. The physician who must reconstruct the cycle from the logic of carbon chemistry before he can read a laboratory report is not more thoughtful than the one who knows the names. He is slower, and his slowness is paid for by someone else.
Then consider what the relations are made of. Here is a phrase from a 2016 review of the hypoxia-related cancer syndromes, describing the mechanism in the case of succinate dehydrogenase: “succinate competitively inhibiting alpha-ketoglutarate in its binding to HIF1/2-α prolyl hydroxylases.” To a reader who knows the cycle only as a vague wheel that makes energy, the sentence is opaque. To a reader who knows that alpha-ketoglutarate and succinate are stations two steps apart on the same ring, that the enzyme which normally clears succinate is the one that has failed, and that a molecule which accumulates behind a failed step may start occupying sites meant for its neighbour, the sentence becomes a small story with a plot. The understanding I have been praising is assembled from the vocabulary I have been teasing. Without the names there is nothing for the relations to relate.
And then there is the order in which things are learned. Understanding often arrives after the names, sometimes years after. A student who refused to memorise anything until he understood it would never begin, because understanding in a science is built on a vocabulary already in place. The practice of learning a text by heart before one can fully grasp it rests on a reasonable wager: that meaning, given somewhere to land, will come. Sometimes the wager pays in a week. Sometimes it pays on a ward a decade later, when a station’s name in a report suddenly connects to something the student once recited without knowing why.
So the argument against memorisation, put carefully, is not an argument against memorising. It is an argument against two specific errors. One is the learner’s: mistaking the fluency of recall for comprehension, the feeling of knowing for the knowing. The other is the examiner’s: building tests that cannot tell the difference, and so rewarding the first as though it guaranteed the second. Bitzer’s facts were fine. What failed in Gradgrind’s schoolroom was the assumption that a boy who could recite the teeth of a horse would know what to do with a lame one.
A Better Examination #
At the end of On the Origin of Species, in its first edition of 1859, Darwin asks his reader to contemplate “an entangled bank,” clothed with plants, birds and insects, and to reflect that these forms, “so different from each other, and dependent on each other in so complex a manner,” have all been produced by laws acting around us. His last sentence sets the endless forms of life against the steady background of a planet that has “gone cycling on according to the fixed law of gravity.” The image of the bank is the opposite of a list. Nothing in it has a place in a sequence; everything in it has relations.
The Krebs cycle is a small entangled bank, and the way to examine a student on it is to ask about the entanglements. What is this arrangement accomplishing? Which parts are regenerated and which pass through? What leaves, and what comes in to replace it? What happens to the wheel if oxaloacetate is drawn off faster than it is replenished, or if succinate dehydrogenase stops working? Where do the electrons go, and why does the cycle care whether there is oxygen at the end of a chain it does not include? The answers require the names. They also require the relations among the names, and they cannot be fetched by recitation, because nobody has rehearsed them.
None of this makes me contemptuous of the old memorising. The names were handles, and no exit of the roundabout would have had a name without them. The tradition of the throat is right that a thing truly learned should be available without a book, and the pathas are right that a sequence worth keeping is worth keeping in more than one order. The handles became a problem only when holding them felt the same as understanding what they were attached to, and when examinations rewarded the holding as though it proved the understanding.
So start at fumarate. Then malate, then oxaloacetate, and then the arrow Krebs found, back to citrate and on round, with a carbon or two leaving at each turn for the air, the leaf and whatever comes after. It does not matter where you begin. That was rather the point.
Evidence and Editorial Note #
Documented findings. The essay relies on the author’s public biography: pre-medical studies at Khalsa College, Amritsar, 1994–1996. Hindi रटना (raṭnā: to memorise by rote, cram without learning) with कंठस्थ करना as a synonym, and Punjabi ਕੰਠ (kanth: throat): Wiktionary entries; the Punjabi ਰੱਟਾ (raṭṭā) and ਚੌਕ (chauk) are stated as general usage. The Vedic pathas (samhitapatha, padapatha, kramapatha, jatapatha, ghanapatha), their purpose as cross-checks on accurate transmission, and UNESCO’s recognition of the tradition of Vedic chanting: Wikipedia, “Vedic chant”. The Theuth and Thamus passage, the rendering of pharmakon as “specific,” and the remarks on writing’s “one unvarying answer” and the “intelligent word graven in the soul of the learner”: Plato, Phaedrus, trans. Benjamin Jowett (Project Gutenberg). The opening of Hard Times (1854), Sissy Jupe as “girl number twenty,” her father who “doctors sick horses,” and Bitzer’s definition of a horse: Charles Dickens, Hard Times (Project Gutenberg). Krebs’s dismissal from Freiburg in April 1933, arrival in Cambridge in July 1933, move to Sheffield in 1935, the work with Johnson on minced pigeon breast, the threefold extension of the preparation’s life by citrate, the Nature reply and publication in Enzymologia: University of Cambridge Department of Biochemistry, “Hans Adolf Krebs”. Johnson’s arrival as Krebs’s postgraduate student in 1935, the 1937 paper’s title and the use of manometry on pigeon breast muscle: Wikipedia, “William Arthur Johnson (biochemist)”. The 1953 Nobel Prize and its motivations: nobelprize.org (linked). The remarks on earlier knowledge as “details and partial processes,” Krebs’s linking of the reactions in a cyclic process, the regeneration of the four-carbon compound (paraphrased) and “the last notch of a combination lock” (quoted): Professor E. Hammarsten’s award ceremony speech, 1953, nobelprize.org. Albert Szent-Györgyi’s work on the catalytic effect of four-carbon acids in pigeon muscle and his 1937 Nobel Prize, Carl Martius and Franz Knoop’s 1937 demonstration of the conversion of citrate to alpha-ketoglutarate, and Krebs and Johnson’s use of malonate to block succinate dehydrogenase: well-established history of biochemistry, stated from standard knowledge and not separately checked for this essay. Release of oxaloacetate-derived carbons as carbon dioxide in the first turn, the symmetry of succinate and the later release of acetyl-derived carbons: Proteopedia, “Krebs cycle carbons”. The cycle’s location in the mitochondrial matrix, its yield per turn (two CO₂, one ATP, three NADH, one FADH₂), its small direct ATP yield, oxygen’s absence as a reactant and its role as gateway to aerobic metabolism: Berg, Tymoczko, Gatto and Stryer, Biochemistry, 8th ed., chapter 17 (publisher’s online text). Succinate dehydrogenase as a membrane-bound enzyme that is also Complex II of the respiratory chain, and GTP as the product of the succinyl-CoA step: Western Oregon University chemistry course notes, “Krebs Cycle Part 2: The Reactions”. Withdrawal of intermediates for amino acids, porphyrins and glucose, the need for replenishment, pyruvate carboxylase as an anaplerotic reaction and the meaning “to fill up”: the same text, section 17.5. Export of citrate for fatty acid and cholesterol synthesis, and oxaloacetate and alpha-ketoglutarate as sources of aspartate and glutamate: Proteopedia, “Citric acid cycle intermediates serve as substrates for biosynthetic processes”. The Periodic Table (Italian 1975; English, trans. Raymond Rosenthal, 1984), its twenty-one element-named stories, the “Carbon” chapter’s itinerary and the Royal Institution’s 2006 judgement: Wikipedia, “The Periodic Table (short story collection)”, and the Linda Hall Library, “Scientist of the Day: Primo Levi”. Lewis Thomas, The Lives of a Cell (1974), its origin in New England Journal of Medicine columns and the title essay’s argument about mitochondria: Wikipedia, “The Lives of a Cell: Notes of a Biology Watcher”. The composition and release system of metoprolol succinate extended-release tablets: U.S. Food and Drug Administration prescribing information (2006 label, Description section). Citrate in coagulation collection tubes: standard laboratory practice. Germline SDH variants in paraganglioma and phaeochromocytoma, FH variants in hereditary leiomyomatosis and renal cell cancer, and competitive inhibition of HIF prolyl hydroxylases by accumulated succinate and fumarate, including the phrase quoted: J. C. Henegan Jr. and C. R. Gomez, “Heritable Cancer Syndromes Related to the Hypoxia Pathway,” Frontiers in Oncology 6:68 (2016). Darwin’s “entangled bank” and the closing sentence: On the Origin of Species, first edition, 1859 (Project Gutenberg). The mnemonic quoted is in wide circulation among students. Vendor representations. None. Drug and formulation details are taken from official labelling and are not a recommendation.
Recollection and tradition. That the author studied pre-medical sciences at Khalsa College in 1994–1996 is part of his published biography; that the cycle appears in pre-medical biology and again in medical school biochemistry is stated in general terms, and the author’s first encounter with it is inferred from that, not remembered. The author’s own study method, mnemonic, textbook or examination is not described or asserted. The reciting student is a general type, not a remembered classmate or scene. The account of Vedic recitation describes a tradition as documented, not the author’s practice.
Analysis and forecast. The readings of the Phaedrus and Hard Times, the comparison with the Vedic pathas, the roundabout analogy and its limits, and the views on memorisation, retained vocabulary and examination are the author’s personal interpretation as of November 6, 2026. Independence. This essay is not sponsored by any institution, company, health system, pharmaceutical manufacturer or technology developer. It is personal reflection, not medical advice; readers seeking care should contact their own physician’s office.
About the Author #
Kanwar Partap Singh Gill, MD, traces his family roots to Khadur Sahib in Punjab’s Majha region and grew up in Amritsar. He attended Spring Dale School and completed pre-medical studies at Khalsa College in 1994–1996. He earned his MBBS from Sri Guru Ram Das Institute of Medical Sciences and Research in Amritsar in 2002.
He completed PGY-1 at the University of Arkansas for Medical Sciences in Little Rock in 2007–2008, and PGY-2 and PGY-3 with UCSF Fresno at Community Regional Medical Center from 2008 through 2010. He has practiced medicine in California since 2010.
His career has crossed four distinct information eras: predominantly paper-based medicine, early and fragmented electronic records, the integrated-EHR era, and the emerging age of generative and agentic artificial intelligence.