The Heraclitean Fire

Heraclitean Fire
Sketches from a Life before Nature
Erwin Chargaff
The Rockefeller University Press
New York 1978

There are many science books that try to bring the beauty of science to the non-scientist. Many of those manage to convey the beauty of discovery, the joy of the pursuit, and the personalities of the investigators. The books are largely driven by a consensus feeling shared by most scientists and science journalists that science is a beneficent agent of good and that the activities in the lab or the field, small as they may seem, are bricks in the grand edifice of knowledge that sometimes turn out to be cornerstones. The Heraclitean Fire is a book, part autobiography, part philosophical broadside, that does not share the basic premise of positivism; that views science as a complicit agent of the great crimes of the 20th century; that sees in the changing landscape of science funding a death to individual scientific pursuit. It is a book that is full of deep learning, witty comment, and bitter observation. It is shockingly different from most science books; it is worth reading.

Erwin Chargaff’s fame has been whittled down to the phrase “Chargaff’s Rules” due to his elaboration of the abundance of nucleotides bases within the nucleic acid polymers. The ratio of Adenine to Thymine and Cytosine to Guanine remains invariant across species and suggested an important relationship that was made crystal clear when double helix structure was determined. Although obviously important in hindsight the nucleic acids were the last major class of biochemicals to be studied and Chargaff was a key player in understanding and elucidating their biochemistry although he would never get even remotely as famous as Crick/Watson, and probably not even as famous as Oswald Avery, a man that he ranks with Darwin and Mendel in laying the foundations of molecular genetics.

Here is his response to the Avery/MacLeod/McCarty paper on the transforming principle.

On Reading The Transforming Principle Paper#

It is difficult for me to describe the effect that this sentence, and the beautiful experimentation that had given rise to it, had on me. My reaction is, perhaps, best represented by some words I spoke much later in an address commemorating 100 years of nucleic-acid research.

As this transformation represents a permanently inheritable alteration of a cell, the chemical nature of the substance responsible for this alteration had here been elucidated for the first time. Seldom has more been said in so few words. The man who had written them, Oswald Theodore Avery (1877-1955), was at that time already 67: the ever rarer instance of an old man making a great scientific discovery. It had not been his first. He was a quiet man; and it would have honored the world more, had it honored him more. What counts, however, in science is to be not so much the first as the last. This discovery, almost abruptly, appeared to foreshadow a chemistry of heredity and, moreover, made probable the nucleic acid character of the gene. It certainly made an impression on a few, not on many, but probably on nobody a more profound one than on me. For I saw before me in dark contours the beginning of a grammar of biology. just as Cardinal Newman in the title of a celebrated book, The Grammar of Assent, spoke of the grammar of belief, I use this word as a description of the main elements and principles of a science. Avery gave us the first text of a new language, or rather he showed us where to look for it. I resolved to search for this text. Consequently, I decided to relinquish all that we had been working on or to bring it to a quick conclusion, although the problems were not without interest and dealt with many facets of cellular chemistry. I have asked myself frequently whether I was not wrong in turning around the rudder so abruptly and whether it would not have been better not to succumb to the fascination of the moment; but these biographical bagatelles cannot be of interest to anybody. To the scientist nature is as a mirror that breaks every 30 years; and who cares about the broken glass of past times?

Interestingly, Chargaff grasped that the species-level differences in different pneumonococcus species meant there must be differences in the nucleic acid composition, a fact that in retrospect was obvious but was unappreciated/unbelieved at the time. Over the course of several years he developed the requisite methods (paper chromatography, fluorescence spectrometer) for characterizing nucleic acids from different species, formulating the ratios that would become his fame. His vision of the importance of the base-pairings were not off and his description of his famous encounter with Watson/Crick is similarly wonderful for the student of molecular biology. However, his efforts were not to be recognized as the glory would go to a duo whose model put the Chargaff rules in striking, undeniable relief. Chargaff’s account of the meeting is superb, if not a bit unkind.

On Meeting Watson and Crick#

The first impression was indeed far from favorable; and it was not improved by the many farcical elements that enlivened the ensuing conversation, if that is the correct description of what was in parts a staccato harangue. Lest I be accused of crimen laesarum maiestatum, I have to point out that mythological or historical couples-Castor and Pollux, Harmodios and Aristogeiton, Romeo and juliet-must have appeared quite differently before the deed than after. In any event, I seem to have missed the shiver of recognition of a historical moment: a change in the rhythm of the heartbeats of biology. Moreover, the statistical likelihood of two geniuses getting together before my eyes here at Cavendish seemed so small that I did not even consider it. My diagnosis was certainly rapid and possibly wrong. The impression: one, thirty-five years old; the looks of a fading racing tout, something out of Hogarth (“The Rake’s Progress”); Cruikshank, Daumier; an incessant falsetto, with occasional nuggets glittering in the turbid stream of prattle. The other, quite undeveloped at twenty-three, a grin, more sly than sheepish; saying little, nothing of consequence; a “gawky young figure, so reminiscent of one of the apprentice cobblers out of Nestroy’s Lumpazivagabundus.” I recognized a variety act, with the two partners at that time showing excellent teamwork, although in later years helical duplicity diminished considerably. The repertory was, however, unexpected.

It was clear to me that I was faced with a novelty: enormous ambition and aggressiveness, coupled with an almost complete ignorance of, and a contempt for, chemistry, that most real of exact sciences - a contempt that was later to have a nefarious influence on the development of “molecular biology.” Thinking of the many sweaty years of making preparations of nucleic acids and of the innumerable hours spent on analyzing them, I could not help being baffled. I am sure that, had I had more contact with, for instance, theoretical physicists, my astonishment would have been less great. In any event, there they were, speculating, pondering, angling for information. So it appeared at least to me, a man of notoriously restricted vision. I told them all I knew. If they had heard before about the pairing rules, they concealed it. But as they did not seem to know much about anything, I was not unduly surprised. I mentioned our early attempts to explain the complementarity relationships by the assumption that, in the nucleic acid chain, adenylic was always next to thymidylic acid and cytidylic next to guanylic acid. This had come to nought when we found that gradual enzymic digestion produced a completely aperiodic pattern; for if the nucleic acid chain had been composed of an arrangement of A-T and G-C dinucleotides, the regularities should have persisted.

And these accounts are just about all that Chargaff’s mention in the content of his personal scientific study leaving some 200 pages remaining, that contain vignettes about various stages of his life including his boyhood in Vienna, a PostDoctoral period in Yale, his time in Berlin between the wars and his fortuitous arrival at Columbia University where he would spend the majority of his long career. These “sketches” are really that - the pages of a poet describing in a stacatto, literature-infused format the various people and places that influenced him, with a special place for books, works of art and the cultural zeitgeist of his homes/travels. These sketches are an introduction to the Western Canon, with a strong Germanic influence and, like his early intellectual idol Karl Krauss, he places an inordinate stress on language - especially when condemning the state of affairs of science and American culture in general. The particulars of his dislike seem to source from two, semi-independent loci - his natural inclination and feeling of an outsider through all of his life (a recurrent theme in the book), and the hard circumstances of his life that will not be unfamiliar to anyone in continental Europe of the first half of the 20th century. This sense of being an outsider and finding a sense of beauty and truth in the words of great poets and writers and only later, and secondarily, in the mysteries of nature informs his forceful intellect, and reinforces the image he creates of himself of a self-made intellect, a rogue academic. And his independence gives him wide latitude to say what he will (“Nevertheless, if at one time or another I have brushed a few colleagues the wrong way, I must apologize: I had not realized that they were covered with fur.”"), an independence he uses to blast the many forces of modernity he views as a detestable unbeatable foe that he should struggle against nonetheless. Among this foe are the culture of science in general and many of its practitioners.

Chargaff’s anger against modern culture and America are sometimes hard to separate. Take the following passage for example in which he manages to highlight the history, architecture and culture of his homeland while sharply disparaging American culture in general:

The larger cities of the Habsburg monarchy all carried a strong family resemblance, which, despite the vicissitudes of recent history, they still retain. When a few years ago I visited Zagreb in the Croatian part of Yugoslavia, there was my birthplace again. The same eclectic style-a sort of fiscal renaissance-of the centrally placed, solid city theater, the university, the courthouse, usually called ]ustizpalast, the Gymnasium, the Volksgarten. I suppose similar tears of melancholy recognition fill the eyes of some Americans when they come upon a Hotdog Emporium or a Hamburger Haven in Yokohama. But the Austrian coffeehouses spread a better kind of civilization.

This sensation arises again and again - in his perpetual use of the word “shabby” to describe the American university and its treatment of him, as well as his belief that the modern spirit of science - mass science - is decaying the quality of the pursuit. On the one hand the commercialization and professionalization of science is bringing ever more people into science, and on the other hand the “successes” of reductionist science eat into the foundation of all that makes science noble to Chargaff: the religious sentiment, the mystery,“the darkness” that are required for the true scientific impulse to live. He calls himself a radical conservative towards the end of the book although I wouldn’t know where to place him on the contemporary spectrum.

Although I am not partial to much of his tone, there resounds in his writing something of a timelessness and his sideswipes at the pace and institutions of Science may bring some rueful joy to many people in contemporary science who are in the process of being burned by the large scale influx and outflux (business cycle) of science funding. Here he is on the pace of science:

Science has, however, moved so fast in my lifetime that the actual has become the historical almost before the print has dried, and even the youngest scientists are condemned to survive themselves. Many must go around pitifully, clowns of their own achievement, beating a drum that long ago had gone out of tune. This is why I have often compared the sciences of my time to soap sculpture.

and on specialization;

The consequence of the excessive specialization, which often brings us news that nobody cares to hear, has been that in revisiting a field with which one had been very familiar, say, ten or twenty years earlier, one feels like an intruder in one’s own bathroom, with twenty-four grim experts sharing the tub.

and again,

When I look back on my early way in science, on the problems I studied, on the papers I published-and even more, perhaps, on those things that never got into print-I notice a freedom of movement, a lack of guild-imposed narrowness, whose existence in my youth I myself, as I write this, had almost forgotten. The world of science was open before us to a degree that has become inconceivable now, when pages and pages of application papers must justify the plan of investigating, “in depth,” the thirty-fifth foot of the centipede; and one is judged by a jury of one’s peers who are all centipedists or molecular podiatrists. I would say that most of the great scientists of the past could not have arisen, that, in fact, most sciences could not have been founded, if the present utility-drunk and goal directed attitude had prevailed.

and most allegorically:

The priesthood of ancient Egypt was presumably also highly compartmentalized; but I do not know whether only certain priests were entrusted with the spells designed to quiet the pain from a given molar. In our time, it would certainly be so. One man or two may decide to study a certain beetle. Whether they do this because the animal is a pest or a biological delight is immaterial. If they find something of scientific interest, there will soon be ten others and more who will do the same. Once there are a hundred men studying the beetle, they will form a society and publish a journal. A society creates a profession, and a profession cannot be permitted to die. It is up to the nation to support it. If the nation can be persuaded, there will soon be a thousand members of the society for the study of the beetle. It is obvious that at this stage the beetle can no longer become extinct, for what would all these experts do who may well outnumber the beetle? Then a foundation will arise whose lay members-influential bankers, society ladies-will neither know nor care whether their function is to help with the eradication or the preservation of the beetles. They know one thing: they must support those who study the beetle. There may even be a Beetle Ball. But what if the beetle disappears after all? The National Infantile Paralysis Foundation has avoided the worst by finally omitting its objective from its name. The American Cancer Foundation may find this more difficult. Thinking of the peculiar ways in which scientific interests become vested nowadays, I have often wondered whether the real impulse does not come from the simple and age-old desire of man for a carefree and pleasant way of life. After all, even in ancient times there must have been a few who, for a small remuneration, were eager to interpret the sun for their fellow Neanderthalers working in the sweat of their brows.

The strong dislike is clear and many scientists of that era have come to similar conclusions as the flood of money led to a “rat race” of competition. But Chargaff’s vision is far more than simply banging away at the fiscal state of science - he is mourns for its soul. His favorite writers include Pascal and Kierkegaard and he laments the loss of religious sensibility. Although it hard to say if Chargaff himself believes in a god he most certainly believes in the power of mystic sentiment, and the motivation of finding and seeking truth in the mode of the religious - worshipful, surrounded by darkness. His distaste of bourgeois science and loss in the art world of lyricism, melody, and subjects in art painting are part of a spectrum of moral collapse that devalues the lone pursuit of truth unsullied by crass material concerns. His artistic temperament and his resentment of Babbitism (he doesn’t say this but theres a bit of Sinclair Lewis in his words) combines in his dislike for the promises of molecular biology. To him, the new scientists are not only loud and obnoxious, making promises for success where there may not be, and riding around in publicly funded cars, they are also killing the beauty of nature by “explaining”, a term he uses as a derogatory, inferior substitute for “understanding.” Although he may have disliked and feared molecular biology it is hard, thirty five years later not to marvel at all of its successes. Chargaff barely saw restriction enzymes and plasmids but difn’t live to see viral oncogenes and the rise of scientific insight to cancer biology, he didn’t see enzyme replacement or genetic tests to avoid inherited diseases. He certainly could not have anticipated how CRISPR offers to take biological insights to their engineering conclusions although it is a safe bet to say he would be offended by the notion that one could engineer life.

In the end, unlike many books on science history I am unsure what to make of this book. On the one hand, the sense that is conveyed throughout the book is of a man who was often viewed by his peers as “gloomy”, as a “gadfly”, and as a “pessimist”. His acidity can be hard to bear. (I was considering putting the book down after twenty pages but wanted to find out about his role in nucleic acid history.) On the other hand the book is an education on the thought processes of science, on the history of the 20th century more generally, and of the power of the classics to shape a potent and broad intellect. Although I enjoyed the sections on science I also enjoyed the sparkling characterizations of his intellectual influences and the playful, witty depictions of his early colleagues - this Cassandra can depict delight. Although this book is not for everyone, it is a unique and interesting read that delves deeply into the mind of an unusual and scientifically important person.