The FASEB Journal • Book Review Francis Crick: Hunter of Life’s Secrets An intellectual biography by Robert Olby Hugh E. Huxley1 Rosenstiel Basic Medical Sciences Research Center, Brandeis University, Waltham, Massachusetts, USA FRANCIS CRICK:HUNTER OF LIFE’S SECRETS is a fascinating and base pairs between two chains would fit into a perfectly scholarly biography of the man whose ideas and discov- regular sugar-phosphate backbone in precisely the eries provided the basis for the remarkable revolution same way as the guanine-cytosine base pairs did— in the biological sciences in the second half of the provided the two chains ran in opposite directions. twentieth century, comparable—if not exceeding—in Thus, any sequence of bases along one chain was importance the revolution in the physical sciences in permissible, and would give a regularly repeating struc- the century’s first half. It takes full advantage of the ture, provided that the complementary sequence was many contemporary records and archives which cover present on the other chain. If DNA was the sole the intellectual history of these times, and also of the repository of genetic information (as it was seeming extensive contacts that author Robert Olby had with more likely at that time), then the genetic message Crick and his family beginning in the 1960s and must be written in the sequence of the bases which continuing up to Crick’s death in 2004 at age eighty- must be translated into the sequence of amino acids in eight. the proteins by a specific genetic code. During replica- However, this has not prevented Olby from dealing tion, the two chains would separate, each would pick up very fairly with some well-known matters of controversy. a complementary set of nucleotides, and an exact The book extends to some 538 pages, including about duplication of the original gene structure would have 50 pages of source notes for the numbered text refer- been achieved. In principle, it was an extraordinarily ences, chapter by chapter, and a 24-page index. It is an simple solution to what had seemed two of the most extraordinarily interesting story from many points of difficult problems in understanding life without invok- view, with sufficient scientific detail to explain most of ing miracles. the issues involved, and it provides a very clear picture Much has been written about the ethics of Crick and of Crick and his work, though perhaps without some of Watson (in Cambridge) using Franklin’s data without the color, force, and light-hearted humor that only a her permission or knowledge and without detailed recording of a conversation with him could convey acknowledgement of the work in King’s College Lon- (also, the large photograph of Crick as a very young don in their initial Nature paper, (though it was com- graduate student, which appears on the front dust- posed with Wilkins’ agreement). Wilkins believed, per- cover of the book, will be quite unrecognizable to those haps correctly, that Franklin would not agree to be a familiar with his strong characteristic features in subse- joint author with him and he refused Crick’s invitation quent years). to be a joint author on the Watson-Crick paper because Olby does a particularly good job in placing the DNA he had not participated in the model building. That is structure in the context of the uncertainty in some why there were two papers from the King’s group quarters at that time about the nature of the gene— (Wilkins, Stokes, and Wilson; and Franklin and Gos- whether it would have to contain proteins as well as ling) immediately following the short Watson-Crick DNA in order to give a structure which contained paper describing the structure, in April 1953. sufficient information to define other protein mole- When a more detailed paper about the structure was cules, given that DNA itself was apparently a relatively written by Crick and Watson (submitted in August 1953 simple polymer of only four different nucleotides and formed fibers whose X-ray diagram indicated a very 1 Correspondence: Rosenstiel Basic Medical Sciences Re- regular structural repeat. The structure that Watson search Center, Brandeis University, Waltham, MA 02454, and Crick arrived at was indeed very regular. From USA. E-mail: [email protected] model-building, they determined that adenine-thymine doi: 10.1096/fj.10–0404ufm 976 0892-6638/10/0024-0976 © FASEB and published in Proc. Roy. Soc. A in April 1954), in the tion by them of her role in the discovery and of her section headed “Crystallographic Considerations,” it is tragic death in the intervening years would have been a stated that “the information in this section was very kind gesture and a small price to pay. And since the kindly reported to us prior to its publication by Wilkins unpublished experimental data from the King’s group and Franklin, and we wish to point out that without this had obviously been essential for the discovery of the data the formulation of our structure would have been structure, there should have been at least four names most unlikely, if not impossible.” The section then goes on the initial publication. on to spell out what that data was—that the paracrys- One of the best sections of the book relates Crick’s talline B-form of DNA had a very strong meridional role in establishing the detailed nature of the mecha- reflection at 3.4Å and a fiber axis repeat of 34Å, with a nism of transfer of information, written in the sequence sideways repeat of 22–25 Å—vital facts for the model- of the bases in DNA, to specify the amino-acid se- ing, given that on general grounds the structure was quence—and, hence, the structure and function—of thought to be helical (the “details of their X-ray pho- the proteins which carry out their cellular roles. His tographs” which were not known to Watson and Crick, realization that it was unlikely to depend on direct would have been the spacing of the Bessel functions’ reading of the shape of DNA base sequence by incom- maxima on the various layer lines). Reading this, Frank- ing amino-acids themselves so as to form a polypeptide lin must have been aware that these measurements of chain of appropriate sequence, and his postulate, be- hers had been given to Watson and Crick prior to their fore the discovery of transfer RNA, of a whole set of 20 solution of the structure, yet there is no evidence—in adaptor molecules to perform the recognition, were fact quite the contrary—that she raised any complaints, certainly logic carried to the point of genius (“the as surely she would have done if she felt she had been Adaptor Hypothesis”). Equally striking was his virtually treated unfairly. But clearly, she should have been told simultaneous recognition, with Brenner, at a memora- directly. ble meeting with Jacob in 1960 (when it had become The paper shows that for their structure to fit to- clear from Jacob, Monod, and Pardee’s experiments gether properly, the two chains must run in opposite that ribosomal RNA was not the information carrier), directions, which presumably their model building that it was in fact the Volkin-Astrakan RNA already would have revealed anyway, but they do not mention found in phage infection which itself was the messen- the space-group evidence for this, which Franklin had ger RNA. overlooked, but which Crick realized immediately upon Crick was responsible for laying down the basic reading a circulated account of the DNA work written hypotheses and “dogma” defining the mode of expres- by Franklin and shown to him by Perutz. This also sion of genes—that the genetic message is contained in should have been acknowledged. the DNA base sequence, that DNA makes RNA, and Another point that has been made much of by some that the messenger RNA makes a protein with a defined writers is that, even after her early death in 1958, her sequence, which folds up and performs its cellular contribution was not mentioned in the three separate function, and that any subsequent changes in the Nobel Lectures given by Wilkins, Watson, and Crick as protein cannot feed back and change the original DNA part of the Stockholm arrangements in 1962. This is sequence. In remarkable experiments with Brenner only partially true. Wilkins was the only one who, and other colleagues in the MRC “hut,” but carried out presumably by mutual arrangement, spoke specifically largely by Crick himself, he showed that the code must of the genesis of the discovery of the DNA structure and be written in triplets of bases, which earlier work had subsequent work on it because he had started the work shown could not be overlapping. He did this, basically, and continued to work on it later. He does say in his by showing that three single base deletion mutants, talk that Franklin “made a very valuable contribution to lying close together near the start of a message, and the X-ray analysis” and in his conclusion, he thanked each individually destroying the same function by shift- Franklin “who, with great ability and experience of ing the reading frame by one step, would, when ex- X-ray diffraction, so much helped the initial investiga- pressed together, give rise to the expression of a tion.” It is notable, however, that he does not include functional polypeptide chain, generated by the correct any of her published papers on DNA in his list of 24 reading of the subsequent triplets in the corrected references (perhaps hardly surprising, after she had reading frame.