Accueil > Critique de la biologie moderne, Texts in English > Erwin Chargaff, Amphisbaena, 1963

Erwin Chargaff, Amphisbaena, 1963

To the memory of my teacher, Karl Kraus.

Chapter 11 [of Essays on Nucleic Acids, 1963] is a specimen of many conversations that I have participated in over the last few years; it is, of course, a composite of many such talks, a collage, as it were: no single person could be so dim.

There will be some, I am certain, that will find the application to scientific problems of the means of humor, of satire, and even of puns, these metaphysical hiccups of language, most unbecoming and frivolous. But there are many levels at which criticism ought to be exercised; and the critique of some of the concepts of modern science, and especially of its aberrations, has virtually disappeared at a time when it is more necessary than ever; at a time when the polarization of science has gone so far that one now “runs” for scientific awards as for a political office; that scientific lectures begin to sound like keynote speeches at political conventions; that scientific reporting has replaced the intimate gossip from Hollywood; that the persuasiveness of truth has been replaced by the strength of the acclamation; in other words, that cliques are surrounded by claques. The emergence of a Scientific Establishment, of a power elite, has given rise to a remarkable phenomenon: the appearance of what is called dogmas in biological thinking. Reason and judgment are inclined to abdicate when faced with a dogma; but they should not. Just as in political life, a stiff upper lip often conceals a soft underbelly. It is imperative that the most stringent criticism be applied to tentative scientific hypotheses that disguise themselves as dogmas. This criticism must come from within; but it can only come from an outsider at the inside.

If the title of the last chapter requires an explanation, I may quote Webster’s New Collegiate Dictionary: “amphisbaena – a fabled serpent with a head at each end, moving either way”. Whether strand separation was observed in the Middle Ages, is not recorded.

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Chapter 11 Amphisbaena

“…et tu in te manes, nos autem in experimentis volvimur?”
Augustinus, Confessiones | IV, 5

“‘Tis all in peeces, all cohaerence gone;
All just supply, and all Relation.”
Donne, An Anatomie of the World,
The First Anniversary, 213-4

“Nay, so devoted are we to this principle, and at the same
time so curiously mechanical, that a new trade, specially
grounded on it, has arisen among us, under the name of
‘Codification’, or code-making in the abstract; whereby any
people, for a reasonable consideration, may be accom-
modated with a patent code; – more easily than curious
individuals with patent breeches, for the people does not
need to be measured first.”
Carlyle, Signs of the Times (1829)

Two men sit on a bench, in August 1961, an Old Chemist (O) and a Young Molecular Biologist (Y).

O: Now that I have you here for a few minutes of quiet talk, I shall start by saying: The cell is not a machine.

Y: But what kind of a start would that be? Do you want me to agree? This would be surely stupid, for there are all sorts of machines, and you have probably never heard of the theory of automata. I should much rather turn your saying around and offer: A machine is a cell.

O: We are then already in the middle of model building, the favorite occupation of modern biophysics. It is all done in front of mirrors, with wire and plastic, glue and papier-mâché; the knowledge of a child combined with the naivete of the grown-up.

Y: But really, why are you so much against machines?

O: Of course, I am not; some of my best friends are machines. But I am very much against a strictly mechanomorphic view of living nature. A machine is a deterministic construction; someone – an intelligence – has had to make it; and even if it could be “programmed” to make itself, who did the programming? A self-reproducing machine that was not built by a primordial engineer is an abomination thrown up by turbulent and sick times which, in chiliastic dreams mixing superpower and impotence, have created a mythology of a most maculate conception. I shall not formulate the secret of life sitting on this bench on a summer day; but I can say that we shall not have a satisfactory theory of biology before we have learned to combine, in one concept, the dialectic play between determinism and accident – a sort of random nonrandomness – which seems to characterize the living and reproducing cell.

Y: It would seem to me that you are simply an angry old man preaching some sort of dialectical biochemistry in which the observer is walking simultaneously on both sides of the street in opposite directions. One could call this also schizophrenic.

O: Well, as to being an angry old man, there is plenty to be angry about, and it makes more sense for an old man to be angry than for a young one; like most things, anger must be earned. King Lear was an angry old man. We are no longer used to passion in the natural sciences; it has been replaced by ambition. Our young geniuses are passionately ambitious instead of being passionately passionate; and it has become very difficult to distinguish between what is an ardent search for truth and what is a vigorous promotion campaign. What started as an adventure of the highest has become the survival of the slickest or the quickest. “Cloak and dagger” has changed to “cloak and suit”. We now have DNA tycoons and others have “made a killing” in RNA. A generation of scientific quiz kids knowing the answer to everything. But to throw pearls before young molecular biologists is not the purpose of this talk. Let’s return to the beginning and I will ask you “What is molecular biology?” Now, if physics is the science of the states, and chemistry that of the conversions, of matter and biology comprises the application of their laws to animate nature, what could be meant by molecular biology? You can, of course, apply any adjective to any noun, but the results are most often bizarre.

Y: Here you go again. I could, of course, be witty, as you think you are, and say that molecular biology is what is published in the journal carrying that name. All academic gowns carry, strictly speaking, the color of their respective payrolls…

O: Here I interrupt already. Your jocular definition cannot hold, since the irregular rate of appearance of this admirable journal is vastly inferior to that at which molecular biologists are produced nowadays. My definition, incidentally, would be that molecular biology is essentially the practice of biochemistry without a license.

Y: This is, as you must know, a completely frivolous definition. There is naturally much more to molecular biology. In order to prevent you from going on endlessly, I shall agree that the naming of a new science – or a new name for an old one – has also its practical reasons. Symposia, congresses, new journals, more money to be had more easily…

O: And the feeling to be a pioneer at no extra cost. And how the publishers love these new handles by which to extract the old money. In fact, this is not the end: soon we shall have molecular sociology, molecular history, and a little later perhaps molecular theology. The fragmentation of the sciences proceeds via adjectives.

Y: I believe, even among your age group you are a horrible exception.

O: Very likely. In a time in which everything that is new is true, the older the fogy the more he must galvanize himself into being able to participate in the exuberant initiation dances that greet each new molecule before it is replaced by an even newer one. But I must say, you can’t escape senility by trying to become a juvenile delinquent.

Y: I shall ignore this. What I said a moment ago about the advantages of having a new science was not meant satirically. This is the way sciences grow in our day; they have become a mass movement, a corporation in which the majority of the population carry stock. Their development must be studied by the methods of sociology.

O: Another stew of a science.

Y: Let’s slaughter one at a time. To return to our subject – if we still have one – this is, I believe, the way our new science came about. It started with the recognition of the importance of macromolecules in biology, of their chemically distinct and precisely describable structures, and of the specific functions which very often could be clearly assigned to them. Take the enzymes…

O: I will take them. But who did the assigning? You isolate a protein, you ask it a very limited number of questions by bringing it together with a few substances. If it happens to react with one or the other, you call them “substrates” and you proceed to assign a specific function to this particular protein. Did you notice the man that passed us a moment ago? He limped; and you would rightly say that this was because he had one shorter leg. But how could I refute someone who claimed that this man had one leg too short in order to limp? You say that this enzyme is present in the cell, in order to perform this reaction. Hic Rhodus, hic salta! But maybe this is not Rhodes or maybe he does not jump, or maybe he jumps somewhere else. How sure can you be, for instance, that all the various phosphatases that can be fished out of a cell mush really act as such in the living cell, that this is their “function”? Ours – and yours – still is a post mortem science; we are forced to destroy the overriding, the overpowering category of life.

Y: Don’t tell me you are a vitalist.

O: Of course, not. But a discussion between us about the meaning of life would be stupid: I am too rigid and you are too flexible. All I can say is: Life is what’s lost in the test tube. Better tell me what you think about what I said concerning the assigning of functions.

Y: I think there are such enzymes and such. Many have the functions that we have given them, others may not be called upon to act under normal circumstances; they may be a memory that the cell has retained of past events. But surely even you cannot deny that, for instance, the energy relationships of the cell and their enzymic basis are well understood and are the best example of the concept of the unity of biochemistry?

O: This I will not deny, though I cannot say that I am particularly fond of this concept of unity. It has done a lot of mischief. Life, as we know it, seems to be characterized by two antithetical principles: unity and diversity. And it is very difficult to decide, in a concrete case, with which of these principles we are dealing. The unity of nature is usually laboriously pieced together by combining, in a spuriously serial or cyclic fashion, snips and bits taken from the most widely distant organisms. It is a sort of biomontage. The fact that we all live and die in one and the same world should not conceal another fact: that we are all different. Even life is only one, and a minor, form of nature: a tiny foam on the crystals of the earth. For an old man who is in love with what goes on around him and with the multiformity of its appearances there can be only one battle cry: Vive la difference! Is it really so important that both torturer and victim enjoyed the same hearty meal and digested it in the same manner? Besides, similar mechanisms do not always foreshadow similar functions. The combustion oven designed by Liebig and the combustion ovens constructed in Auschwitz, though based on the same scientific principles, can hardly be taken as a proof of the unity of nature. But your little speech about the processes of parturition that resulted in the forceps delivery of molecular biology stopped at the enzymes. Perhaps you go on.

Y: What you like to call my little speech did not stop, it was stopped. In any event, the recognition that polypeptides of high molecular weight could show great specificity as enzymes in metabolic reactions and as antigens or antibodies in immunology led to many studies of their physical and chemical structures. Ultracentrifugation, X-ray diffraction, electrophoresis, electron microscopy, the many wonderful separation methods carrying the name of chromatography: all these were instrumental in bringing about these exciting times. It became possible not only to analyze proteins completely but even to determine their amino acid sequence in many cases. The triumphs of structure determination were so great that everywhere young people were flocking to the banner of the helical nature of things.

O: You are spiraling a little too fast for me. Even Lucretius had to stop for breath. Your dithyrambic tone reminds me that not long ago I have heard a gushing voice on the radio speaking of “DNA, this miracle monocule”.

Y: What of it? Some people have difficulty pronouncing “molecule”; but this will change. Just as there were times when people found it easy to say “transubstantiation”. As to DNA, I shall soon come to it. Let me continue. The advances I mentioned a minute ago were, of course, not the only ones. Even before they had come to fruition, studies had begun on other fronts. Certain viruses had been purified sufficiently so as to warrant their chemical examination and had been recognized as nucleoproteins. First came the plant viruses which were found to contain RNA, as do also most of the animal viruses. The bacteriophages, on the other hand, contain mostly DNA. But perhaps the most exciting thing that happened was the discovery that microbial transformation – a phenomenon known for quite some time – was due to specific forms of DNA. This had the effect of placing DNA very near to what the geneticists at that time were still calling the gene.

O: If you don’t mind let us still stick to this hoary term. I know, the packaging has been changed lately; but since it still is the same old thing, why not conserve the convenient brand name? After all, if you want to describe a syndrome you must first give it a name. The one advantage, for instance, that I can see in using the term “molecular biology” is that it puts nearly all that is unknown in biochemistry into one convenient corner. But I wanted to say a word about transforming DNA. I well remember the great excitement with which I followed the first discoveries concerning specific pneumococcal deoxyribonucleic acid. Then we still spoke of “desoxyribonucleic”. In fact, this was probably the main reason for my becoming interested in the nucleic acids at about that time, 1944 or 1945. But there has been a considerable period since then and not so very much has happened in this field; and I must confess that my misgivings about the justification of expanding these few observations on micro-organisms to the entire realm of life have been growing at an ever increasing rate. Generalization has its definite uses in science; without it we should all soon be without a job. But at the same time, there is a great danger of its gliding into glibness. It was in 1889 that the great Swiss historian Jacob Burckhardt wrote a letter to a friend in which he warned of the oncoming of what he called “les terribles simplificateurs”. Just as the locusts, once they are through with a field, have simplified it horribly, could we not say that this is also true of some of the great generalizations in biology? Color and variety, the pulsations of accident and fate, the tremendous urges and instincts, the pendulum of birth and death: all have disappeared and we are left with what I once called “a plantation of match sticks”. So, when I listen to the arguments that microbial transformation proves the gene character of DNA, I must ask: is this discovery one of the features of the unity of nature or one of the facets of its diversity? That’s where the dialectics has to come in to which we referred at the beginning of our little disputation.

Y: I can see, you want to keep your cake and sell it. You are an intolerable mystic, and I have had the feeling that, while you speak of nature, there should be a slight music of harps. Why do you keep plucking the feathers out of the goose that lays golden eggs for all of us? After all, you are one of the classics in this field.

O: Thank you, I should rather not be. In your definition, a classic in science is a man who does not have to be quoted any longer. For the pickpocket, the man with the widest pockets is a classic. And it has been remarked that Banquo is seldom quoted in Macbeth’s papers.

Y: All right, then I shall call you a Cassandra in long pants. But my story was not yet entirely finished. I had been talking about transforming DNA; and if you had not broken in, I should have continued by mentioning other instances in which nucleic acids were assigned direct roles in the determination of hereditary properties. For instance, there are the bacteriophages attacking E. coli which seem to do it by injecting their specific DNA into the bacterial cell. This is enough to set off an entire chain of events terminating in the production of many phage particles and the rupture of the host cell. And then we have the plant viruses; they contain specific types of RNA which are infective; that means, the nucleic acid itself, when applied to the plant, can give rise to the formation of innumerable complete virus particles. These are all definite and specific molecules exerting definite and specific biological effects; and here you have the quintessence of our new science, molecular biology. But this is not all.

O: I am sure, it is not. Even to sell soap nowadays, you need an a cappella choir. What baffles an old-fashioned chemist in all this is what has become of the chemical concept of a molecule. I have heard people of a still older generation claim that this concept ends with the applicability of Avogadro’s law. But never mind. In any event, it must have been a pleasant surprise for some biologists to learn that at last they were dealing with molecules. I should have thought that this was what they had been doing all the time. It reminds me a bit of Monsieur Jourdain in Moliere’s Bourgeois Gentilhomme who is astonished to hear that what he has been speaking all his life is called “prose”.

Y: Surely, you must have heard the term “molecular disease”?

O: Alas, I have; and for a time I thought that this was a disease to which molecules were particularly prone, a sort of molecular measles. But I soon learned that this was another symptom of the general sloganification of science, everything – like in a poor cartoon – having a pithy label hanging from the mouth. Some of these slogans may have been convenient or useful at one time, such as “energy-rich phosphate bonds”, “dynamic state of body constituents”; of others, for instance, “messenger RNA”, I am less sure. But there are so many of them, and they are so glittering, so glib! The more I hear them, the less I enjoy them. The peculiar relationship between names and understanding has often been discussed, best perhaps by Mephistopheles.

Y: Great concepts require great names.

O: Or perhaps great names can substitute for great concepts. But I believe, you had not yet finished.

Y: This is correct, for I now have to introduce the crowning concept, namely, “biological information”.

O: Do you mean to say that life itself has now acquired a press agent?

Y: Of course not; but there has arisen all over the world a group of young, militant and successful practitioners – evangelists, you might call them – who are spreading the new knowledge with devotion and perseverance. All seems to fit.

O: Or at least you disregard what doesn’t. Such must have been the atmosphere when Phlogiston went strong: all seemed to fit until a little balance was brought into play. Even the great Ockham with his immortal razor would no longer succeed in shaving the multicolored beard that is now sprouting all over the beautiful face of biochemistry. Opening one issue of a journal, I am assailed by an abysmal cackle of terms, ill-fitting, yet strident, garish and banal. The shockate, the grindate and the sonicate, the suicide and the abortion, the fingerprints and the hot spots, the repressors and the co-repressors, the feedbacks, the pools and the templates, the regulators, the operators and the operons; and floating over the entire allegorical cesspool, the mysterious messengers, angelic or diabolic in their evanescent everywhereness. Have we really arrived at the stage of non-objective biochemistry, of molecular action painting?

Y: You have left out the hybrids and many other things; but I am glad to see that you are fairly familiar at least with our nomenclature. Let me say, however, that to make a scientific revolution one must break many eggheads. Your objections are ineffective and they will not count in the end. Biological or, if you prefer, genetic information is an extremely important and useful concept which even a Shakespearean fool cannot laugh off. Before I go on, I should like to ask you a question. When trying to understand the life of the cell and the functions of its individual parts, don’t you believe in the division of labor?

O: Frankly, I don’t; at least not in the crudely mechanomorphic way – the wheels and the gears and the levers – in which this is usually done. Even if Nature were one gigantic servo-mechanism, I am afraid the beards of the cybemeticists, entrusted with servicing it, would get into the way of the feedbacks. In the living cell there must be a way in which quantity – or, better, density or compression – regulated on an as yet undescribable time scale, becomes a new and unique quality, namely, that of life.

Y: I am afraid, you are, after all, a vitalist. Returning now to this business of information and disregarding all you have said, this is what it amounts to. We do believe in the division of labor in the cell, with each part, yes, with each molecule, having a definite and recognizable function. And we believe in the existence of a strict hierarchy.

O: I know, I know. Mix anything with everything in the right proportions and the resulting puree will say: Papa! But tell me, since you mention the hierarchy of the cell, reading the recent literature I get the impression that the cell is a society of slaves that have no master.

Y: Not at all. In the beginning was DNA…

O: I hear the start of a new apocryphal gospel with DNA as the logos of our times.

Y: Is it possible that you don’t believe in DNA?

O: If I don’t believe that the moon is made of green cheese, does this necessarily mean that I don’t believe in the moon?

Y: Anyway, DNA is the genetic material which in the last resort is responsible for the maintenance and the transmission of the hereditary properties of the cell. We know about the mechanism of its replication which is an ingenious deduction from the generally accepted structural model of DNA: a double helix composed of two intertwined polynucleotide chains. After the separation of these strands which is very easy to explain, as it offers no thermodynamic difficulties and can be carried out with a model costing less than a dollar, each strand now proceeds to the production of its counterpart.

O: How general is general? And without wanting to offend your sense of economy, thermodynamical or otherwise, may I ask whether you mean this beautiful scheme to apply to meiosis as well as to mitosis?

Y: I am not interested in diploids.

O: I wish, your parents had felt the same way. And would you say that during the splitting of a chromosome the other constituents, the proteins, the lipids, undergo similar processes, or do they simply follow the leader out of family affection?

Y: Let’s not waste our time with trivialities. Who cares about lipids anyway? The smart cookies leave them alone. I shall give you here a purely formal scheme which you can take or leave; but you would be well advised to take it.

O: I know, scientific dogmas are phagocytes which eat only what is good for them. They cannot be refuted or dethroned; but they vanish eventually owing to the fickleness of subsequent generations who lose interest in them. In fact, the more absurd a hypothesis is, the stronger must be the belief in it.

Y: I continue. DNA is, as I said, the primary genetic determinant carrying a code, as yet unbroken, through which in the last resort the composition of RNA and of the proteins is specified. Before this code can be expressed, the two strands composing the double helix of the DNA must be separated, unwound, perhaps enzymatically. I believe, it was you who called this hypothetical enzyme an “unscrewase”. You will observe that, because of the complementary structure of the two strands, the information stored in either one really is sufficient.

O: Have the two strands been shown to exist, let alone to have a complementary structure?

Y: Well, yes and no. But you should be the last to ask such a question.

O: Sometimes I wake up in the dark of the night and I begin to think of all these claims and discoveries and models, of all this molecular prestidigitation; and I ask myself: Is this all a confidence game? They are all so brilliant; why are they so shallow? Why did the manna of the heavens turn into porridge? Why does the liquidation of a science begin at the top; why do its greatest triumphs turn into its worst disasters?

Y: I don’t believe you expect an answer. All you have to do is to take a spectra of a DNA before and after heating.

O: Now I can see that you are a modem young scientist. The use of these false singulars, a spectra, a media, a bacteria, a phenomena or even a phenomenum, etc., is this not the summa cum laude of the new generation?

Y: I have never found Latin useful in my work. If you, too, had studied more mathematics and physics, instead of wasting your time, you would have accomplished more.

O: This may very well be so. I have felt for some time that your Ph. D. should be spelled pH D.

Y: In any event, this is how it works. There is no doubt at all, the direction is: DNA to RNA to protein; but never backwards. The genetic signals emanating from the DNA go first to a special kind of RNA which turns over very rapidly, never amounts to more than a few per cent of the total RNA of the cell, and mimics, in its composition, that of the DNA. Since it carries the message contained in the DNA, we call it the messenger RNA.

O: This small and short-lived Corps of Commissionnaires, has anyone seen it?

Y: What do you mean by “seen it”? There is plenty of indirect evidence that such an RNA is formed.

O: No, I mean the message, has anyone shown that it exists? Is it not possible that the entire imposing terminological scaffold is nothing but a suitcase for the emperor’s new clothes? Is it not possible that there is no message, no messenger, that the entire question is asked, and therefore answered, wrongly?

Y: If you deny that there is such a thing as “information”, you will still have to get the same fellow, but call it by a different name.

O: You want to say what is usually said when one has no answer, that this is merely semantics?

Y: Yes. Incidentally, messenger RNA is not the only name; others have referred to it as informational RNA or pulse RNA. The men that really discovered the stuff gave it no name and will therefore be rightly forgotten.

O: This is true, never be a pioneer; not who comes first counts in science, but who comes last. But let us stay with these charming conceits for a little while and try to think things through. I know, in our days what cannot be done indirectly, isn’t being done at all any more. But chemistry is, after all, the science of substances; and if all this is true there must be a substantial basis to it. You said that it all starts with DNA. This DNA, I take it, exists in the cell as a double-stranded helix, as what people with a brilliant gift for vulgarization have called “the coil of life”. The two strands run in opposite directions with respect to their terminal phosphates and have a complementary nucleotide sequence, so that purines can pair with pyrimidines, adenine with thymine, and guanine with cytosine. And you might say that this scheme was confirmed before it was devised, since this had been shown to be true of the composition of DNA. It has been forgotten completely that the specific base-pairing in nucleic acids was discovered in an old-fashioned chemical laboratory.

Y: Well, I happen to remember, but who cares? What did these people whom you call old-fashioned do to make their findings known?

O: They published them.

Y: Published? Are you being jocular? Is this what you call aggressive scholarship? Did they send out mimeographed copies of their papers long before publication? Did they found base-pairing clubs? Did they distribute neckties with suitable emblems?

O: But who would want to spend his life dancing a minuet before assembled science reporters? There still are people who do not wish to join the noise boys; they have other concerns. When you start on something new, you are all alone and it is so terribly dark; and then, suddenly, you may come face to face with the Winding whiteness of reality. There is nothing more exquisite, nothing rarer in the world. Afterwards you have a choice: You stay in the laboratory, hoping that it will happen again; but it seldom does. Or you begin to travel through the country giving minstrel shows.

Y: Anyway, even if the composition of DNA had been found entirely different, we should have doubted the analysis, not our concept.

O: I can see, you are a True Believer. It is with such deductions that the road to the paradise of scientists is paved. But really, I did not wish now to attack what one is pleased to call the “central dogma”, for I know that the mythopoeic urge of humanity does not stop at the door of the laboratory. But let me continue, and I shall assume that the existence of two complementary strands, each having two ends, a head and a tail as it were, has been proved.

Y: Well, if it hasn’t, it will be.

O: This DNA, as I understand it, has two functions: it has to make itself – that is easy: unscrew, assemble, polymerize, recombine. This has now become a so-called project for the so-called Science Fairs of our so-called high-school boys. But it also has to make the rest of the cell; and this is not so easy. For in this DNA must be contained the quintessence of all this tremendous life of our earth, the flagellum and the spirillum, but also the brain that invented the St. Matthew Passion. “Dinanzi a me non fuor cose create…

Y: Don’t talk Latin at me.

O: Never mind. What I wanted to point out is that in our days DNA plays the role of a self-replicating philosopher’s stone. First we have an extremely vicious circle: DNA makes DNA makes DNA, etc.; a dreary, tragic desert, an Yves Tanguy landscape. But simultaneously – and by what delegation of functions even you could not tell me – the Dr. Jekyll side of DNA gets into the act and makes A and B and C. I am always being told that all biological information resides, in the last resort, in DNA. But organisms contain many types of specific molecules, quite apart from the proteins and the nucleic acids: the mysterious conjugated proteins, some of the lipids, cell wall substances, blood group substances, specific polysaccharides.

Y: These polysaccharides contain no information.

O: How do you know? Did you talk with them lately? But let me return to our argument. When DNA gives play to the friendlier part of its nature, the first thing it does, I am told, is to preside over the manufacture of messenger RNA. This RNA is said to show the composition regularities of the entire DNA. If the latter really consists of two complementary strands, this must mean that two complementary RNA strands, or a mixture of shorter pieces amounting in the aggregate to two such strands, have been made. To put it more concretely, a triple uracil in one messenger polynucleotide would have to correspond to a triple adenine in the complementary RNA structure. Since a ribosome – “they also serve who only stand and wait” – can make a protein only when it is “programmed” by a messenger RNA which on the whole cannot be a double strand, as it must be able to engage in specific hydrogen-bonding, the conclusion would have to be that any given section of a DNA dyad should give rise to two entirely different proteins. Would you consequently subscribe to the revised slogan “one gene, two enzymes”?

Y: Well, I don’t know. There are hundred ways out.

O: But should a scientist behave like a tracked cockroach? I know, almost anything you can write on a piece of paper will eventually be realized in a so-called system and then it will form a “fact”. I cannot help feeling, however, that not all facts are equally worth knowing. I thought it was the task of the natural sciences to discover the facts of nature, not to create them.

Y: You are just an obscurantist.

O: I have often been accused of spreading darkness. And I cannot deny that the dazzling light being thrown on a few spots to the exclusion of the rest has distorted all the proportions of our science. How many frantic about-faces someone of my age has had to live through! And the yelping is not at an end; in fact, it is getting worse. Miss Molecule of 1962 remains to be crowned; and I fear – and you hope – there will be many more. The next candidate will no doubt be messenger RNA. And some time later it will be the operon buffo: “Figaro qui, Figaro qua!” But to continue with what I was saying before. You may, of course, ascribe to my advancing years the difficulties I experience in understanding what is claimed to go on. Even if we accept the existence of a short-lived species of RNA that is made under the direct control of DNA and by mirroring the composition of the latter transfers the information from DNA to the proteins and if we add the relatively small amount of so-called soluble RNA, we are left with the bulk, almost 85 per cent, of the cellular RNA for which neither function nor mode of formation is apparent. You will, of course, with your usual originality tell me that Rome was not built in one day, to which I shall reply that less credit should be given to those who fail to solve great problems than to those that succeed in solving small ones. There is nothing easier than to fall off the Mount Everest.

Y: But you cannot deny the existence of a rapidly turning-over RNA that does mirror the composition of DNA, in base-pairing, etc.?

O: Most of the analyses that I have seen are far from convincing. A lot of good will or, better, lack of experience is necessary for such enthusiastically sweeping claims. But never mind, many people have made a good living in science by selling the emperor’s new clothes. De nihilo nihil does not hold for molecular biology. Only where there is nothing, all is possible. If you consider a cell, and the amount of packing or compression it must require, the traffic problems become so enormous as to demand the formulation of a new dimension for which we lack even the slightest intimation; instead of which we are being fed terminological cant. DNA slowly reproducing itself and at the same time rushing to make hundreds of different messengers; all these messengers milling about madly in search of ribosomal easy chairs on which to procreate and die; proteins peeling off and proceeding to their respective posts; unborn lipids and polysaccharides crying for non-existing templates: a molecular Walpurgis Night, a Federation Meeting of the universe, only even less comfortable than in Atlantic City. It would all be very funny if it did not corrupt our youth. Who, when he knew it when it was so small, would have thought of DNA as the demiurgos of a Manichaean world?

Y: You are using too many long words to say nothing. The fact that you knew DNA when it had a molecular weight of 800,000, whereas now it is up to 160 million, is of no significance, except to show that you did not know how to invest wisely.

O: Of course, this is not at all what I meant. But even if we reconcile ourselves to this bizarre situation and accept the notion that everything that happens in a cell is under the ultimate control of DNA, we encounter other difficulties. Many viruses are essentially ribonucleoproteins; and in several cases their RNA itself has been shown to be infective. You mentioned it yourself before. This RNA is presumably able to replicate itself; but where is the specific DNA that presides over this replication?

Y: I can give you two different answers. I could assume that there is something special about viral RNA that enables it to act as its own template, independently of any control exercised by DNA.

O: But this is a self- strangling argument. Shouldn’t in this case viral RNA show complete base-pairing? Besides, from the chemical point of view, there does not seem to be anything special about the RNA of viruses. Incidentally, since in this reasoning all roles are reversed, I expect to hear almost any day about a “messenger DNA”.

Y: I have an alternative answer. Let us assume that all RNA, viral as well as ribosomal, transfer or messenger, is made under the control of DNA, but only in the case of messenger are both DNA strands involved; the other RNA species reflect the composition of a single strand of DNA. By now you must credit me with enough intelligence to propose hundred plausible schemes to explain this.

O: I would not go so far; but for n problems you will always have n + 1 mutually exclusive, but equally irrefutable, explanations.

Y: Never mind. So far as virus RNA is concerned, a second assumption must, of course, be made, namely, that for a cell to be able to support a certain virus it must contain, as part of its genome, a stretch of DNA that is normally non-operative, but becomes active under the influence of the invading viral RNA molecule; and it is this DNA portion that is reflected by the infective RNA.

O: I feel like Peer Gynt in the cave of the trolls, refusing to undergo a simple eye operation that would permit him to see as straight what looks crooked to him. You, too, will undoubtedly grow into one of our synthetic geniuses – these fake celebrities, glued together with the spittle of Madison Avenue – of whom there are so many that they clutter up the place. And yet, the brain power of all these cytopractors combined would not fill the inkwell of Pascal. To them, everything is so simple. The hypnotic effect of repeating nonsensical statements over and over has produced a general trance that is mistaken for a view of nature. Altogether, I was taught that it is the task of the natural sciences to understand, not to outwit, nature. I am often told that this or that is an “educated guess” – a truly nasty expression. Much would be gained if the guessers were educated instead. Some of the discussions on microbial heredity and chemical genetics that I have heard sounded like a bunch of midwives deliberating on the immaculate conception. And what can be done to stem the evergrowing avalanche of rubbish being published? I can think of only one way: to publish all papers anonymously, without authors’ names.

Y: By the way, grapevine has told me that the code has been broken.

O: I hope, someone keeps the pieces; one may need them again.

Y: How can you be facetious before such an achievement? Don’t you see that we have entered a new era?

O: Thus, slowly, slowly, step by step, scream by scream, drum roll by drum roll, gold medal by gold medal, do you expect to reconstruct the fingerprints of God! But what good will it do you? You could not read them, you could not classify them. All the gimmicks in the world – to use the terminology with which you are familiar – will not help you.

Y: You talk as if we were still in the early middle ages.

O: Maybe the natural sciences will always be in the early middle ages. There goes a deep crack through our porcelain world; and even theoretical physics, perhaps the most highly developed science, feels, I am told, much malaise and intellectual discomfort. Could it be that molecular biology is the last refuge of the scientific optimist?

Y: Well, we have much to be optimistic about. This has been a marvelous period for the biological sciences, a true renaissance. We have learned more about life and heredity in the last five years than in the preceding fifty; and for this reason we can afford to disregard most of the older literature. Even you, who has difficulty in reconciling yourself to all our discoveries, will not be able to deny the tremendous upsurge.

O: There is so much to get reconciled to. In fact, that such very bad times as ours have given rise to so much good science, does this not speak against science?

Y: Not at all. You seem to have the romantically foolish idea that only a good man can be a good scientist.

O: It is always dangerous to use the argument ad hominem, and you should not judge from yourself. But is it not a desperate situation when an old proverb must be reversed to read: Wherever the fish stinks there is its head? It is getting late, though, and I had not quite finished with what I was saying before. Even if the correct code is found and the flow of so-called information takes place as postulated by the admirers of biological automation, very little of what occurs in a living cell is really clarified. What determines the specific character of a cell, which is perpetuated in a hereditary fashion, is constituted of a very large number of different compounds, many of them situated specifically within the cell; and these substances, once we break the cell and isolate and separate its constituents, will be recognized as very many different species of molecules, such as proteins, lipids, polysaccharides, nucleic acids, etc. Most of those – and not only the first and last – have a highly specific composition and structure; but how they exist, interact and are held in definite places in the functioning cell is completely obscure.

I am certainly no vitalist in the sense in which this is usually meant; but I cannot stomach people who claim that they have understood and explained Hamlet by telling me how often the word “and” appears in the first act. And I do object to the tremendous noise that is being made about trivial and often meaningless observations. In contrast to previous times, I believe, many of our reputedly great discoveries are entirely unearned. Also, the morass of alleged facts in which we are suffocating has brought it about that those who may speculate cannot do so any longer. Look at the enormous variety in the shapes of organisms, organs, even cellular components – where is the biochemistry of specific shape? Where is the biochemistry of cell differentiation? Is there a separate nucleotide code for your fingerprints which are different from mine? Is it a pairing error in position 79 which has produced the visions of Blake?

It is above all against this shabby mechanization of our scientific imagination, which kills all ability to notice the unforeseen, that I protest, against this mat finish over a chaos of unrecognized ignorance, this butcher-like brutality with things that cry for gentle caution. Our young people are being brought up in the belief that “they never had it so good”. They – and especially the best ones – are being condemned to a future of disillusion and discouragement.

Y: That’s what you say. I am not at all discouraged; quite the contrary. I only have to think of the unprecedented possibilities that are opening before us. When we know the Universal Code, we shall soon learn how to interfere with certain nucleotide sequences in DNA, how to change them specifically and thereby to produce desirable genetic changes. Artificial insemination with the stored Sperm of dead geniuses has already been proposed by eminent authorities. Two little Einsteins in every middle class household, what a vista!

O: But can the centipede survive under a duodecimal system? The more you talk about breeding geniuses the less likely you are to get them.

Y: Again one of your unscientifically mystical remarks. I only mentioned this proposal as a first modest feeler into the great future. Later on, we shall be able to look up the nucleotide sequence of every DNA; and each purine and pyrimidine will have a number; and we shall know of each what happens when we change it. And boy, will we change it!

O: And then you will get the real “human engineering”. Once you can alter the chromosomes at will, you will be able to tailor the Average Consumer, the predictable user of a given soap, the reliable imbiber of a certain poison gas. You will have given humanity a present compared with which the Hiroshima bomb was a friendly caster egg. You will indeed have touched the ecology of death. I shudder to think in whose image this new man will be made.

Y: Well, you may not be around to see it. Anyway, it was nice to have talked with you. I must still run up to the lab to turn off the Spinco.

O: is, the evening has come. I shall go home.

They leave, in opposite directions.

Erwin Chargaff (august 11, 1905 – june 20, 2002),
Essays on Nucleic Acids, 1963.

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