Gullible's Troubles

Gullible's Troubles

Apologies to the readers for not being able to make this week’s scheduled posts.

Instead I am posting an entertaining essay on the birth of molecular biology. It is from a autobiographical book published in 1976. Any guessing the author will earn 99.99 points :).

Gullible’s Troubles

When I first met F. H. C. Crick and J. D. Watson in Cambridge, in the last days of May 1952, they seemed to me an ill-matched pair. This intrinsically unmemorable event has so often been painted - “Caesar Falling into the Rubicon” - repainted, touched up, or varnished in the several auto- and allo-hagiographies, that even I, with my good memory for comic incidents and great admiration for the Marx Brother films, find it difficult to scrape off the entire legendary overlay. I hope that the resulting portraits will be in sharper focus than the famous picture of Parmigianino in the Vienna musuem.

This is the way it all came about. The summer of 1952 promised to be an unusually busy time for me: the biochemistry congress in Paris; lectures at the Weizmann Institute and in several European cities; trying unsuccessfully, as twice before, for a professorship in Switzerland. My first talk was scheduled in Glasgow, and on the way there I spent May 24 to 27 in Cambridge, where John Kendrew put me in Peterhouse. He asked me to speak with two people in the Cavendish Laboratory who were trying to do something with the nucleic acids. What they were trying to do was not clear to him; he did not sound very promising.

The first impression was indeed far from favoroble; 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 heartbeat 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, thiry-five years old; the looks of a fading racing tout, something out of a 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 Netroy’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.

So far as I could make out, they wanted, unencumbered by any knowledge of the chemistry involved, to fit DNA into a helix. The main reason seemed to be Pauling’s alpha-helix model of a protein. I do not remember whether I was actually shown their scale model of a polynucleotide chain, but I do not believe so, since they were still unfamiliar with the chemical structure of the nucleotides. They were, however, extremely worried about the correct “pitch” of their helix. I do not recall how much of the X-ray evidence of King’s College (Rosalind Franklin, Wilkins) was mentioned. Because - at that time, at any rate - I set little trust in the biological relevance of X-ray photographs of stretched and pickled high-polymer preparations.I may not have paid sufficient attention.

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 nuclei 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 naught 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.

I believe that the double-stranded model of DNA came about as a consequence of our conversation; but such things are only susceptible of a later judgement:

Quando Iudex est venturus
Cuncta stricte discussurus!

When in 1953, Watson and Crick published their first note on the double helix, they did not acknowledge my help and cited only a short paper of ours which had appeared in 1952 shorly before theirs, but not, as would have been natural, my 1950 or 1951 reviews.

Later, when molecular prestidigitation ran wild, I was often asked by more or less well-meaning people why I had not discovered the celebrated model. My answer has always been that I was too dumb, but that, if Rosalind Franklin and I could have collaborated, we might have come up with something of the sort in one or two years. I doubt, however, that we could ever have elevated the double helix into “the mighty symbol that has replaced the cross as the signature of the biological analphabet.”

In addition to Langmead’s course videos, we posted another tutorial with videos from Pevzner’s course in the membership section. I am still working on cross-linking the common sections so that you can compare and learn. We will have more video-tutorials coming.

Written by M. //