The keystone of Kendrew's research is the three-dimensional analysis of the structure of myoglobin for which he shared with M.F. Perutz the Nobel Prize in Chemistry in 1962. His Nobel Lecture, and the adapted version published in Science, 139, 1963, give a clear account of the stages of the research, the particular problems encountered and the techniques evolved to deal with them. The lecture also makes plain that Kendrew's overriding interest in the structure of protein ("I had no doubt that this problem above all others deserved the attention of anyone concerned with fundamental aspects of biology" art.cit., p.1259) dates from the later part of the Second World War. Thus the early prewar research on reaction kinetics had no sequel and the remainder of the material is all related to some aspect of protein analysis.
From the first, and long before the choice of a suitable material had been achieved, Kendrew realised how important a factor would be the rapid handling of very large amounts of data and information. It is interesting to see the fascination with note-keeping, filing and organisation present in the schoolboy (Section A) and fostered by operational research in war (Section B) finding a kind of bureaucratic apotheosis in the sustained effort of accuracy required for the long haul to the final successful three-dimensional picture - a task which Kendrew himself said he would not wish to undertake a second time. Be that as it may, Kendrew was certainly ahead of many of his colleagues in seeing the necessity to harness the full range of automatic information handling techniques.
This perception shows itself in two lines of enquiry. One, immediately after his return to Cambridge in 1946, is the organisation of his, and later his team's, rapid access to all the relevant literature via a system (then relatively new) of punched cards; these cards, and the punch, both of which he designed himself, remained in use for many years. The other is the investigation of computation and data processing, dating from 1949 and aimed in the first instance at the resources of the EDSAC I machine at the Cambridge University Mathematical Laboratory. As the research developed, more sophisticated machines became available and were put to use in Cambridge and elsewhere, so that the work was always going forward at the limit of technical practicability.
The material presented under the heading "Protein Analysis Projects" generally antedates the main myoglobin programme; it may include projects that were not taken further by Kendrew and his team, or the application of X-ray diffraction techniques to other research topics. Of considerable interest is the correspondence which shows Kendrew's search, over a long period of time, for suitable protein material and his work with new materials referred to him by others. This provides in many ways a bridge between the preliminary work and the launch of the main programme.
The Nobel Lecture already mentioned is of course a retrospective discussion of a completed project, when lines of strategy may be more easily discerned from the final eminence of success. It is of special interest therefore to have the brief annual reports which Kendrew sent to the Master of Peterhouse during his tenure of a Research Fellowship and chronicle the slow steps towards the goal as they were actually being taken. They confirm two of the principal problems: the choice of a suitable protein for analysis in adequately sized crystals, and the devising of high-speed computational techniques to process the data. The reports, which run from 1947 to 1953, conclude in very positive terms both on a personal level with the granting to Kendrew of "unlimited tenure" by the Medical Research Council, and on the professional level with the sense that technical difficulties had been overcome, experimental material identified and the way cleared for the main diffraction programme. (The identification of sperm whale as the most promising source of myoglobin crystals occurred in December 1952 and is referred to in appropriately enthusiastic terms in Kendrew's correspondence of that date.
Optimistic as this may have later appeared, it was sufficiently the case for it to be taken here to mark the end of the preliminary work and the opening of the assault on the myoglobin molecule which is very fully documented, presented in the order shown in the list of contents, and including notebooks, data, observations, diagrams and charts, calculations, draft routines, printouts and corrections, correspondence and "think-pieces" by Kendrew and the team of short- and long-term collaborators at Cambridge and the Royal Institution in London. The main lines of the work are clear from the Nobel Lecture and other publications: the narrowing of choice of material to Type A sperm whale myoglobin; the progressively more complex analysis at 6-Å (approximately 1955-57, using EDSAC I), 2-Å (1959, using EDSAC II and Mercury), and 1.4-Å (begun 1960 using IBM 7090), and the use of X-ray evidence in correlation with chemical data for amino-acid sequencing. In addition to the published papers which marked the progress of the research (particularly the collaborative communications in Nature, 181, 1958, 185, 1960, 190, 1961 and, for the earlier work, the extended follow-up papers in Proc. Roy. Soc.), several of the notebooks include project diaries, charts of progress, allocations of responsibility and the like, written "from the bench" or in correspondence.
It may be appropriate here to point out that for all the stress laid on mechanical computation, and indeed the presence of EDSAC and other printouts, the notebooks are remarkable for the sheer quantity of calculations and tabulations, phase diagrams, electron density maps and the rest laboriously worked by hand, by Kendrew as well as his collaborators, not to mention the careful logging and summaries of experimental programmes which were always his personal charge.
The excitement of the final complete syntheses at 6-Å and 2-Å and their publication is well captured in the correspondence. W.L. Bragg contributes characteristically warm-hearted letters and Kendrew's own letter of thanks and congratulation to his collaborators is enthusiastic as well as informative.
- Creation: 1939-1981
Language of Materials