Erwin Chargaff – a life ratioed

In the short but eventful history of molecular biology, Erwin Chargaff must rank as one of the most interesting and one of the most tragic. I also feel that he is long overdue for – if not a reassessment – than at least a re-appreciation.

Chargaff is best known for what are now called the “Chargaff Rules,” the observation that in DNA:

1) A + G = C + T
(i.e. the sum of the purines equals the sum of the pyrimidines)
2) the molar ratio of adenine to thymine = 1
3) the molar ratio of guanine to cytosine = 1

This is a simplified version of the Chargaff Rules. The truth is more complicated and more interesting (both scientifically and historically), but that is the subject of another post.

Other than for his rules, Chargaff is best remembered as a fleeting character in Jim Watson’s The Double Helix where, if Rosalind Franklin appears as a villainness to be reckoned with, Chargaff is comic foil – the nub of Watson’s mockery. It wasn’t exactly fair of course, although Chargaff made himself an easy target as being a world-class expert in the art of mocking – a snob, a great admirer of the satirist Karl Kraus, sardonic, sarcastic, not afraid of making enemies. He referred to Watson and Crick as “two pitchmen in search of a helix” (1). He was classically-trained, erudite, given to obscure literary allusions, a European, a product of the Viennese fin de siecle living uneasily in America. He was claret and chateaubriand and Michaelis-Menten whereas Watson and Crick were hamburger and hotdogs, shandy and lager, two men not only ignorant of history but hostile to it, nakedly ambitious, barely literate not only of literature but of chemistry. No, it would not work. Chargaff was a biochemist and saw himself in the tradition of Staudinger and Kekulé, but he also saw himself as an outsider – perhaps as someone who loved language and literature deeply (his English was extraordinary, others must judge the quality of his native German) working amongst those who saw language as merely a tool of communication (“an outsider on the inside” (2)). It was ironic that this outsider to biochemistry found himself its most ardent defender against a new upstart science’s encroachment. “My definition, incidentally, would be that molecular biology is essentially the practice of biochemistry without a license.” Regarding his fellow scientists, he wrote “… 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” (1). He was rough with his contemporaries, but gentle with his students (2). He was a European Jew living uncomfortably, unwillingly, in New York City – a faculty member at Columbia University’s College of Physicians and Surgeons. He tried desperately to pry his mother from Hitler’s claws (his father was already dead), but failed. “My mother’s name was Rosa Silberstein. She was born in 1878 and died, only God knows where and when, having been deported into nothingness from Vienna in 1943.” He outlived his wife and his friends, and died alone, in 2002, at the age of 96, in New York City.

One has to wonder if Chargaff’s penchant for literary allusions worked against him and drew him up for suspicion. His was not exactly on a level with Crick quoting Keats. Chargaff’s own, very uneven but fascinating, memoir/rant was entitled Heraclitean Fire (3), which is only an indirect reference to Heraclitus, and in fact is a nod to That Nature is a Heraclitean Fire and of the comfort of the Resurrection, a poem by the experimental religious poet Gerard Manley Hopkins. Chargaff’s comment about molecular biology and practicing biochemistry without a license is from a dialogue he wrote called Amphisbaena and begins, Two men sit on a bench, in August 1961, an Old Chemist (O) and a Young Molecular Biologist (Y). Amphisbaena (Wikipedia tells me) is a “mythological, ant-eating serpent with a head at each end.” From this, one can assume that molecular biology is of one body with biochemistry and has an independent head which, coming from Chargaff, seems like quite a concession. What would a graduate student make of this, having found a Platonic dialogue on modern science wedged into a book entitled Essays on Nucleic Acids (4)?

Some choice Chargaffian quotes:

1) On scientific discoveries:

My life has been marked by two immense and fateful discoveries: the splitting of the atom, the recognition of the chemistry of heredity and its subsequent manipulation. It is the mistreatment of nucleus that, in both instances, lies at the basis: the nucleus of the atom, the nucleus of the cell. In both instances do I have the feeling that science has transgressed a barrier that should have remained inviolate. As happens often in science, the first discoveries were made by thoroughly admirable men, but the crowd that came right after had a more mephitic smell.

2) On Oswald Avery:

… 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 honored the world more, had it honored him more.

3) On Watson and Crick:

The impression: one, 35 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 underdeveloped at 23, a grin, more sly than sheepish; saying little, nothing of consequence; a gawky young figure, so reminescent 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.

4) On anger and passion:

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.

1) Judson, The Eighth Day of Creation
2) Cohen and Lehman, Erwin Chargaff 1905-2002 (National Academy of Sciences, Biographical Memoir, 2010)
3) Chargaff, Heraclitean Fire (The Rockefeller University Press, New York, 1978)
4) Chargaff, Essays on Nucleic Acids (Elsevier, 1963)