ESSAY REVIEW

•^ THE HISTORY OF MOLECULAR BIOLOGY ^

The Path to the Double Helix. By Robert C. Olby. London: Macmillan,

1974. Pp. xxiii+510. £12.50.
A Century of DNA: a History of the Discovery of the Structure and
Function of the Genetic Substance. By Franklin H. Portugal and
Jack S. Cohen. Cambridge, Mass. & London: MIT Press, 1977. Pp.
xiii+384. £12.95.
This century has seen two major conceptual revolutions in science, the
first of them in theoretical physics, the second in biology. With the passage of
time the significance and drama of these events has begun to attract the
attention of historians, and—as one might expect from their order of appear-
ance—historical studies of twentieth-century biology have yet to establish
themselves on the scale of work on physics. Nonetheless, this is an expanding
area of scholarship, as one can see from the growth of oral history programmes
and the establishment of archives, catalogues, and newsletters.1 Articles,
journals, and monographs devoted to this topic continue to appear.2 It is an
area of activity for which the historiographical principles and intellectual
concerns are still being selected, under the influence both of historical studies
of science from earlier epochs, and of molecular biologists and biochemists who
are anxious to protect the image of the science they helped to create and to
assist in the construction of a historical picture that is consistent with their
experience.
This is the context in which Robert Olby's important book, The path to the
double helix, was published nearly four years ago, with a claim to be the first
comprehensive history of molecular biology. Previous work that might be so
described, by Carlson, Jacob, and Fruton, was in each case slightly differently
conceived.3 The period since the appearance of Olby's book has provided time
for historians of science to use and reflect upon his research, and to give it
serious appraisal.4 The magnitude of this achievement has recently been thrown
into relief by the publication of another part-history of molecular biology,
Portugal and Cohen's A century of DNA, which is a shorter, more schematic, and
less scholarly work. I want to discuss these two books in the order of their
publication.
The path to the double helix is the product of around six years' dedicated
research in Britain and America, and it is therefore a study on an ambitious
scale. It is a very extensive and careful discussion of the scientific activity of a
century, based on wide reading of the primary literature. Olby has supple-
mented this analysis by examining archival material on the funding of research
and on the organization of laboratories and other institutions, together with
scientists' correspondence. He has also interviewed a considerable number of
the people concerned, and checked his argument in correspondence with them.
The transcribed interviews are, so we are assured in the preface, to be made
available to other scholars under the auspices of the Royal Society.
From this considerable amount of textual material Olby has assembled a
very dense intellectual pattern that repays careful attention. He writes in a
distinctive style that is certainly readable, whilst laying before the reader a
very complex narrative based on a firm grasp of the scientific issues from the
fields of genetics, cytology, structural chemistry, crystallography, biochemistry,
and microbiology. It is in fact a book that makes considerable demands on the
THE BRITISH JOURNAL FOR THE HISTORY OF SCIENCE Vol. 11 No. 39 (1978)
274 Essay Review
scientific competence of anyone reading it, and this is impressive but exhausting.
Despite the richness of the argument, and the wealth of technical detail, it
is nonetheless clear at each stage where the analysis is going. The structure of
the book is divided into five sections, the first four of which set the scene for a
detailed account of the elucidation of the double-helical structure of DNA,
carried out by Francis Crick, James Watson, Maurice Wilkins, Rosalind
Franklin, and their respective colleagues, associates, and rivals in 1952 and
1953. The argument is also built around a simple periodization, representing
successive versions of the biological principle, now known as the 'central
dogma'. Olby charts in great detail the replacement of the belief that protein
molecules are the bearers of hereditary information by the contemporary one,
around which molecular biology is organized, that nucleic acids carry and
transmit this information, from which cellular proteins are constructed. This
paradigmatic change—for Olby presents it thus—was not at all instantaneous,
and was finally confirmed, so the argument goes, by the double helical model of
DNA.5 The clear outlines of the resulting historical picture are achieved at a
certain historiographical price, namely that throughout the book one has the
strong sense of being impelled ineluctably towards the illuminations of 1953. In
fact this is probably too harsh a judgement, and certainly one that only a
historian would feel compelled to make, since Olby clearly has considered the
teleology of his argument and sought at various points to moderate it. Seem-
ingly, that is more than Portugal and Cohen have done.
There can be no doubt, therefore, that Olby has written the definitive
work on this area of the life sciences for some years to come. It will be a constant
source of information because of its scope and its scrupulous attention to detail.
It will also be consulted on matters less specific to molecular biology, to corro-
borate independent research and to stimulate new lines of investigation. Even
those historians who want to go in very different directions will scarcely be able
to ignore the massive amount of material collated and evaluated in this book.
That having been said, there are some criticisms to be made, but such
remarks will only make sense if one knows more about the content of The path
to the double helix. I want therefore to describe briefly the analysis in it, and to
make some critical comments in passing and in conclusion; I will then con-
sider several themes in the book which I believe that historians of science will
want to explore further.
The first section concerns the development of the concept of the macro-
molecule, and the application of crystallographical techniques to the study of
biological polymers. It begins with Hermann Staudinger's fight in the late
1920s to establish the ideas of very large molecules, and the collateral support
for this from work with Svedberg's ultracentrifuge. In the same period,
Mark and Meyer in Germany pioneered the study of organic polymers by
X-ray diffraction, and in Britain W. T. Astbury established an important
crystallographic research group at Leeds, concentrating particularly on the
structure of keratin, the fibrous protein in wool. In 1938 he and Florence Bell
published the first X-ray photographs of DNA, and from these Astbury, in his
characteristically vigorous way, created a model of chromosome structure.
Olby gives him extended treatment in this section, and here and elsewhere in the
book his statements about this pioneer of 'molecular biology' (a term he was
one of the first to use) are carefully judged. Perhaps the most striking theme in
Astbury's work is his conviction that the analysis of molecular structure would
reveal the order, simplicity, and unity of the natural world: 'It had been a
long way from the elasticity of wool to 6the molecular architecture of the gene,
but Astbury believed he had got there'. Portugal and Cohen also present him
 Essay Review 275
as having played an important role in the formation of a biology 'at the
molecular level'.7 What emerges from both accounts is the confidence with
which many of the leading figures in the history and pre-history of the subject,
like Muller, Pauling, Bernal, Delbriick, Astbury, and Crick, have advanced
arguments about the structure of living matter explicitly linked to physical
theory.
Having described the demise of the colloidal paradigm, and the enthusiastic
generation of new structural models by a new school of biophysicists, Olby
goes on to consider work on the chemistry of nucleic acids, and the appearance
of another hypothesis—the tetranucleotide hypothesis for the structure of DNA
—that in its turn became too securely established, in that it served to mislead
biologists about the nature of the hereditary material. This idea is introduced
in a very dense chapter on the work of Kossel and Levene, which is followed by
another on the 'Nucleoprotein theory of the gene'. Here Olby discusses the rise
of the chromosome theory of heredity and Caspersson's studies of nucleic acid
synthesis using new techniques of ultraviolet microscopy. Both these areas of
research yielded new information, but this was nevertheless fitted into the
framework defined by the nucleoprotein theory of the gene. This idea recurs in
the book, as Olby illustrates how biologists repeatedly used new data to confirm
an existing theory or conceptual scheme. This is certainly interesting, and adds
another level to his analysis, but one cannot help feeling that the historio-
graphical and philosophical argument is now much more complicated than
simple reliance on Kuhnian notions allows.
Chapter VIII introduces another important historical theme, the problem
of deciding what genes are and how they act, and Olby traces the course of
work on this problem from Garrod, through physiological genetics in Germany,
to the work of Beadle and Tatum in establishing biochemical genetics in the
late 1930s and 40s. This leads in turn to studies of the chemistry of viruses.
In the winter of 1936/7 Stanley had every reason for playing down Bawden's and Pirie's
isolation of phosphorus and carbohydrate—only 0-5 per cent phosphorus anyway. Even if
nucleic acid was a genuine constituent of TMV it could hardly have an important function,
since RNA was still thought to be a tetranucleotide . . . and Levene's authority was still
behind this opinion. Moreover, the staff of the Princeton branch of the Rockefeller Institute
were just as bound to the Protein Version of the central Dogma as were the staff of the New
York Laboratories. The suggestion that viral activity and specificity should be associated
with a nucleoprotein, rather than simply with a protein, was not to be entertained without
strong evidence, in the intellectual milieu of the Rockefeller, the home of Levene, Lansteiner
and Mirsky, the scene of the crystallization of enzymes by Sumner, Northrop and Kunitz.
TMV must be a protein, and an autocatalytic one at that.8

This is just one example of the many that could be chosen of Olby's careful
depiction of why scientists, because of their professional socialization, or
institutional location, or theoretical commitment, chose quite plausibly and
rationally to accept an interpretation of the evidence that we now see as
incorrect. Observations such as these serve to mitigate the teleological character
of the narrative and—although this theme is scarcely developed in the book—
to draw our attention to the ways in which the development of scientific ideas
is structured and channelled by social and cultural forces.
The third section is concerned with the role of experiments on bacterial
transformation in throwing light on the nature of the gene, and it begins with
detailed chapters on the British bacteriologist Frederick Griffith, and the later
work of Oswald Avery and his collaborators at the Rockefeller Institute. The
significance of, and reactions to, Avery's famous paper of 1944 on DNA as the
transforming substance are carefully assessed, and this takes us to the work on
276 Essay Review
the structure of DNA by Erwin Chargaff, which broke the hold of the tetra-
nucleotide hypothesis.
The fourth section is entitled 'Intellectual migrations', and it concerns the
direct and indirect influence on studies of the gene of physicists, structural
chemists, and crystallographers, amongst them Bohr, Schodinger, Delbriick,
Bragg, Pauling, and Bernal. The section concludes with a consideration of
Pauling's seminal work on the helical conformation of proteins, an idea which
in 1950 forced crystallographers to reconsider some of the intellectual ground-
rules of their speciality, and with a chapter on Watson and Crick, the figures
who come to dominate the final section, 'Hunting for the helix'. One interesting
effect of this section of the argument is that one comes to see both these men
rather less as individuals directing themselves towards particular institutions
and problems because of some intrinsic clarity of vision, and rather more as
junior scientists being guided and educated by their scientific peers—in Watson's
case Salvador Luria, in Crick's A. V. Hill.»
The final section deals with the creation of the double helical model for
the molecular structure of DNA by Watson and Crick, building on the pre-
fatory work, clues, and incorrect assumptions described in the rest of the book.
It is an extremely detailed and assured account of the reasoning that led to the
building of yet another model in March 1953. It appears to rely heavily on
material taken from interviews with Crick, whose comments in the preface
indicate the extent to which he sees the book as a counterblast to James
Watson's account in The double helix, but the effect is always convincing. The
creation of this model, the distribution of credit for that work, and the validity
of Watson's account of this research have given rise in recent years to a number
of related controversies. Ann Sayre's recent biography of Rosalind Franklin,
the crystallographer who unknowingly provided some data on which Watson
and Crick relied heavily in their success, has re-awakened such discussion.10 It
is a measure of Olby's skill that his account is both relevant to the continuing
debate on the technical issues and, in my view, very persuasive.
Even in an extended review it is difficult to convey the complexity of the
intellectual pattern created in The path to the double helix. By the end of the
book, a large number of characters have been brought on to the historical
stage, some only for a brief appearance. Many of them, however, are brought
on without any introduction, and this soon becomes rather taxing. Similarly
Olby is more or less unrelenting in his deployment of detailed technical
arguments without any brief explanatory comment, and one wonders what
readership he had in mind. These are more than stylistic conventions; they
flow directly from Olby's conception of his book as a text very close to the
technical literature of science, addressed principally to working scientists, with
their own simple received view about how the history of science should be
written. In this connexion I find it significant that the very extensive biblio-
graphy is almost entirely made up of references to primary scientific material.
One may say, of course, that if sociologists and historians of science do perceive
science in a radically different way, then it is now up to them to appropriate the
material assembled here and re-locate it in different cognitive and historio-
graphical frameworks. There are signs that this is indeed happening. Two
examples of the directions in which future investigators might go must suffice
to illustrate this contention.
There are a number of intriguing moments in The path to the double helix
when one catches a glimpse behind the intricate technical argument of
scientists seeking support from funding agencies, peer groups, and laboratory
directors for particular projects, experiments, programmes, or approaches.
 Essay Review 277
Sometimes they succeed and sometimes they fail. For example, one sees
Staudinger eventually getting his ideas accepted by his colleagues, but failing
to get the money for an ultacentrifuge and, later on, failing to set up a research
programme in biology as he wanted.11 One sees Astbury attracting large
funds from the Rockefeller Foundation, but failing after the war to get money
from the Medical Research Council.12 By contrast Bernal and Needham failed
to interest the Rockefeller Foundation in the establishment of an Institute of
Physico-chemical Morphology in Cambridge,'3 and after the war Bernal was
handicapped by a curious shortage of funds until he got some support from the
Nuffield Foundation.'4 One sees Randall's proposed grant application for a
biophysics research unit doubled by the influential A. V. Hill,J5 while Bragg,
Cavendish professor at Cambridge, Nobel prizewinner, and Atheneum member,
traded on his status and connexions to solicit support for one of his proteges
from Sir Edward Mellanby, Secretary of the Medical Research Council.16 The
feature that all these incidents have in common is that they concern professional
appraisal and the attempt to gain financial support, and they involve important,
rarely discussed, historically changing criteria of scientific and practical value.
In the case of the Rockefeller Foundation, Robert Kohler has recently shown
us in a fascinating paper how complex these judgements and criteria for the
advancement of research in specific forms can be.x7 What Olby has indicated is
how interesting it would be to carry out this exercise for molecular biology as
a whole, as changing social and scientific elites gain and lose control over
funding and the resources of professional power.
My second example of further analysis suggested by Olby's work concerns
the history of ideas. One striking feature of the book is the assumption that the
development of science can be discussed adequately by constructing something
very similar to the everyday discourse of research, without regard to the deeper
intellectual structures underlying sets of theories and conceptual schemes.
There is one passage where Olby does strike down to this subterranean level,
in the chapter on Bohr and Schrodinger and their respective thoughts on
biology. In the terms of the analysis up to that point in the book, both these
thinkers were distinctly marginal to the development of molecular biology,
except in the indirect sense of having turned some people towards the subject;
but having tapped this philosophical substratum, Olby is only able to get back
to the earlier mode of argument with some fragmentary evidence about the
impact of Schrodinger's book, What is life? and this apparent digression or
thematic break seems to have puzzled some readers.18
My suggestion, then, is that in writing the history of molecular biology we
should try to deal not only with technical, experimental, and conceptual
changes, but also with the philosophical and cognitive levels which inform
scientific theory and practice. Particularly in the case of molecular biology,
this leads one immediately to some interesting issues. Why, for example, should
the concept of 'information' play such an important role in contemporary
biology ? From where was it imported ? By which group and with what purpose ?
At what point was the concept of hereditary informationfirstused in genetics ?
Was it linked to the rise of information theory and cybernetics just before and
during the Second World War?»9 The example of information presents us with
an idea that is central to the conceptual framework of modern biology but is
not the sort of artefact that is re-worked by everyday scientific practice, and is
therefore not explicit in scientists' writings and thoughts, and yet which links
the generative philosophical level of scientific discourse with the level of
social and professional institutions about which we can ask quite concrete
questions.
278 Essay Review
At several points in this review I have compared Portugal's and Cohen's
more recent book, A century of DNA, unfavourably with The path to the double
helix. This is perhaps unfair, since they are different productions. The later
book is shorter, less dense, less intricate, and spans a slightly longer period,
from the discovery of DNA by Miescher to the cracking of the genetic code. It
too has been assembled from the primary scientific literature, and from inter-
views, correspondence, and posthumous papers. It contains rather more
material on nineteenth-century biology, and the emphasis overall is rather less
on crystallography and rather more on biochemistry. More attempts are made
to explain parenthetically what particular concepts mean, and who particular
individuals were, and thus it is slightly easier to read than Olby's arcane book.
But correspondingly it is less densely packed with reflections and comments,
and therefore less interesting to the historian. For all that, it is a carefully
written, comprehensive book, and anyone who wants to learn about the history
of molecular biology should certainly read it.
Finally, the question of what purpose is served by writing histories of the
contemporary life sciences is raised by Portugal and Cohen in their introduction;
they suggest that it has a general humanistic value, particularly at the present
time.
In a more general sense, knowledge of science and technology is not essential to most
people, and indeed, many young people today reject science as too austere and rational
for their tastes. It is not necessary to understand the laws of thermodynamics or the operation
of a jet engine in order to fly in an airplane, just as it is not necessary to understand genetics
or DNA in order to reproduce. Yet surely, all of man's discoveries since the Age of Reason,
none should fascinate us more than the endeavor to understand the mystery of the basis of
life."

This seems to me to reveal the extent to which both these careful and intelligent
works, by Portugal and Cohen, and by Olby, are in one sense the victims of the
mythology of molecular biology. For both of them, in concentrating on the
intellectual and technical level, leave us short of the social realities of scientific
competition, interprofessional jealousy, and the drive for individual power,
status, and security through a scientific career. Whilst molecular biologists
have done a great deal in recent years to show us something of the 'mystery of
the basis of life', the peculiarly rapacious way in which they have gone about
it in the political and institutional context of post-war science has led to the
creation of a speciality renowned also for its competitiveness, intellectual
arrogance, and elitism. With that in mind it simply will not do to say, as do
Portugal and Cohen ,'That scientists compete to be the first to make a discovery
was as true in 1869 as it is today',21 for their own account provides testimony
of the differences between, say, Miescher waiting politely for Hoppe-Seyler to
be able to publish his results on the extraction of nuclein in 1869 and 1870, and
the frantic rush in the early 1960s to be the first to decipher the genetic code
which they describe in Chapter XII, and which as an editor of the Proceedings
of the National Academy of Sciences Portugal must have observed at first hand.
Only if we can bring ourselves to include these elements in our historical picture
will we get any closer to understanding why significant numbers of young
biologists were attracted by the mythology of the New Biology in the 1960s,
only to be repelled by the harshness of the institutions that the pioneers had
earlier created.
EDWARD YOXEN

University of Manchester
 Essay Review 279
NOTES
• For further information see the newsletter of the Survey of Sources for the History of
Biochemistry and Molecular Biology, available from Dr David Bearman, American Philosophical
Society Library, 105 South Fifth Street, Philadelphia, Pennsylvania 19106, USA.
* See in particular the Journal for the history of biology, Studies in the history of biology.
3 E. A. Carlson, The gene: a critical history, London, 1966; F. Jacob, La logique du vivant;
une histoire de Vhlreditl, Paris, 1970 (English translation by B. Spillman, 'The logic of living systems,
London, 1974); J . S. Fruton, Molecules and life: historical essays on the interplay of chemistry and
biology, New York, 1972.
• See M. Teich, 'A single path to the double helix?', History of science, 1975, 13, 264-83;
S. S. Cohen, 'The origins of molecular biology', Science, 7 March 1975, 187, 827-30; D. Fleming,
'Cracking the genetic code', Times literary supplement, 17 September 1976, pp. 1163-5.
5 The same argument is presented in R. C. Olby, 'The origins of molecular genetics', Journal
for the history of biology. 1974, 7, 93-100; and 'The protein version of the central dogma', Genetics,
!
975> 79, 3-14-
6
R. C. Olby, The path to the double helix, London, 1974, p. 70.
7 F. H. Portugal and J. S. Cohen, A century of DMA: a history of the discovery of the structure and
function of the genetic substance, London, 1977, p. 216.
8
Olby, op. cit. (6), p. 157.
9 Ibid., pp. 298, 306, 308-9, 310.
I
° A. Sayre, Rosalind Franklin and DNA, London, 1975. For discussions of this book of varying
perceptiveness see H. Berman, 'A restitution', Science, 14 November 1975, 190, 665; C. P. Snow,
'The corridors of DNA', New York review of books, 13 November 1975, 22, 3-4; F. Hussain, 'Did
Rosalind Franklin deserve DNA Nobel prize?' New Scientist, 1975, 68, 470; Portugal and Cohen,
op. cit. (7), pp. 251, 254, 265, 266-8.
" Olby, op. cit. (6), pp. 14-19.
II
Ibid, pp. 55, 326-7.
•3 Ibid., pp. 252-3.
"4 Ibid., pp. 261-3, 336.
•5 Ibid., pp. 328-9.
"> Ibid., pp. 264-5.
' ' R . E. Kohler, 'The management of science: the experience of Warren Weaver and the
Rockefeller Foundation programme in molecular biology', Minerva, 1976, 14, 279-306.
18
See Cohen, op. cit. (4).
•91 have tried to explore some of these issues in E. J . Yoxen, 'The social impact of molecular
biology', University of Cambridge PhD thesis, 1977.
10
Portugal and Cohen, op. cit. (7), p. xi.
11
Ibid., p. 16.