964
`
`NATURE
`
`May 30, 1953
`
`voL. 171
`
`which has never been since surpassed. Dr. Schonland
`expressed disappointment
`that. the membership
`in recent years has been but a little more than a
`thousand, for South Africa has expanded enormously
`since 1906 and with this expansion the need for, and
`potential value of, such a body as the Association.
`The general aims of the Association have not
`changed at all with the · passing of years :
`''We
`exist," he said, "primarily to create and foster a
`scientific fraternity in South Africa, not to publish
`original work. We exist to provide a common
`meeting-ground for South African scientists and a
`forum for general discussion of the problems of this
`country from the scientific angle.'' He defended the
`use of Afrikaans by those who preferred it, for "we
`were intended by our founders to be parochial, and
`we should pride ourselves on being parochial. I would
`suggest that if we try to be anything else we will
`have mistaken our real aim".
`Having thus firmly and, most people would agree,
`wisely placed the Association in its proper perspective,
`Dr. Schonland went on to make some concrete sug(cid:173)
`gestions. The South African Journal of Science should
`have a series of semi-popular articles reviewing and
`surveying the new ideas of science and so bridge the
`gap between those who teach and do advanced
`research work and those who pay for it. This, he
`thought, is the proper function of the Journal, and
`it is but one aspect of the Association's duty, as
`representative of all sections of scientific opinion in
`South Africa, "to take a stronger, a more continuing
`and a more active interest in all scientific develop(cid:173)
`ments, national and university, in South Africa and
`to study carefully what is being done in other
`countries".
`Besides his plea that the Association needs to form ·
`a standing committee to watch over scientific educa(cid:173)
`tion in schools, Dr. Schonland suggested that the
`Association might consider taking a part in the
`formation of a body on the lines of the British
`Parliamentary and Scientific Committee and also
`help in the creation of better facilities for advanced
`research in South Africa. On this last-named point,
`he cited the instances of the National University in
`Canberra and the Institute for Advanced Studies in
`Dublin, but he made the interesting suggestion that
`a more acceptable solution might be the creation of
`a number of specialized institutes for advanced
`study, attached to and forming part of those univer(cid:173)
`sities which for one reason or another are best
`suited for them.
`
`is required at all levels : at present it is wholly
`inadequate for future needs, while the practical
`content of general education is also inadequate for
`the needs of future citizens of a technological society.
`The cultural content of technical education is also
`generally inadequate ;
`technical education requires
`special consideration, and training for adaptability is
`an outstanding requirement in an age of ultra-rapid
`technological change. The education. of women and
`girls also demands particular attention in view of
`their dual role as workers and home-makers, and
`improved administrative arrangements are essential
`if education is to fulfil its true function in such a
`society.
`The report does not suggest that all these pro(cid:173)
`positions apply equally to every country, though the
`Conference considered that, so far as its knowledge
`extended, they are generally valid for the world as
`a whole. The stress is laid on the need for adapting
`technology to man, not man to technology. The
`questions formulated in this report-and which merit
`attention in current discussions on the expansion of
`both technical and technological education in Great
`Britain-are raised in the belief that mastecy of the
`machine by man is not an end in itself: it is a means
`to the development of man and of the whole society.
`The distinction between technician and techno(cid:173)
`logist is not always kept clear in this report, par(cid:173)
`ticularly in the chapter on the content of technical
`education. Nevertheless, the report directs attention
`to some fundamental issues which no sound policy
`for either type of education can disregard. In both
`fields it must be recognized that we are concerned
`not simply with the efficiency of production, but also
`with the fundamental attitude which the men and
`women of to-morrow will adopt in facing the problems
`of a techno1ogical society. Both, too, in seeking to
`foster flexibility, must recognize that flexibility is
`determined not only by education and training but
`also by social, economic and technical conditions ;
`and the administrative measures required to ensure
`that education becomes more adapted to the needs
`of a changing technological society are themselves
`likely to be most· effective when they are informal
`and varied rather than concentrated and uniform.
`The administrator, no less than the teacher and
`student, has need of frequent opportunities of contact
`with the industrial world, and requires experience of
`the difficultfas and problems created by technological
`development in society ;
`just as the teacher and
`student should keep a.breast of developments in
`research and of practical applications in industry.
`
`BASIS OF TECHNICAL EDUCATION
`GENERAL education to-day should be planned
`
`so as to enable the ordinary citizen to adapt
`himself to the needs of technological society and to
`understand what is happening and what is required
`of him. This was the theme of an international
`conference convened by the United Nations Educa(cid:173)
`tional, Cultural and Scientific Organization at Unesco
`House in June 1950*.
`Broadly, the Conference found that organized
`social foresight is essential to enable the educational
`system of a country to prepare children for the type
`of life and work they are likely to encounter, and
`that a substantial development of technical education
`• Education in a Technological Society : a Preliminary Inter(cid:173)
`national Survey of the Nature and Efficacy of Technical Education.
`(Tensions aµd Technology Series.) Pp. 76. (Paris: Unesco ; London :
`H.M.S.O., 1952.) 200 francs; 4s.; 75 cents.
`
`GENETICAL IMPLICATIONS OF
`THE STRUCTURE OF
`DEOXYRIBONUCLEIC ACID
`By J. D. WATSON and F. H. C. CRICK
`· Medical Research Council Unit for the Study of the
`Molecular Structure of Biological Systems, Cavendish
`Laboratory, Cambridge
`
`T HE importance of deoxyribonucleic acid (DNA)
`
`within living cells is undisputed. It is found in
`all dividing cells, largely if not entirely in the nucleus,
`where it is an essential constituent of the chromo(cid:173)
`somes. Many lines· of evidence indicate that it is the
`carrier of a part of (if not all} the genetic specificity
`of the chromosomes and thus of the gene itself.
`
`Illumina Ex. 1055
` IPR Petition - USP 10,435,742
`
`

`

`No. 4361 May 30, 1953
`
`NATURE
`
`965
`
`D.N.A.
`
`BASE -
`
`SU CAR('
`
`PHOSPHATF
`
`BASE- SUCAR " PHOSPHATE
`BASE- SUGAR " PHOSPHATE
`BASE-SUGAR " PHOSPHATE
`BASE -suGAR "' PHOSPHATE
`
`/
`
`/
`
`/
`
`/
`
`/
`.-'
`
`_Rig. 1. Chemical formula of a
`single chain of deoxyribo·
`nucleic acid
`
`Fig. 2. This figure is purely
`diagrammatic. The two ribbons
`symbolize the two phosphate(cid:173)
`sugar chains, and the hori·
`zontal rods the - pairs of bases
`holding the chains together.
`The vertical line marks the
`fibre axis
`
`Until now, however, no evidence has been presented.
`to show_ how it • might carry out the essential
`operation required of a genetic material, that of
`exact self-duplication.
`We have recently proposed a structure1 for the
`salt of deoxyribonucleic acid which, if correct,
`immediately suggests a mechanism for its self(cid:173)
`duplication. X-ray evidence obtained by the workers
`at King's College, London2, and presented at the
`same time, gives qualitative support to our structure
`and is incompatible with all previously proposed
`structures3 : Though the structure will not be com(cid:173)
`pletely proved until a more extensiVa com£>arison has
`been made with the X-ray data, we now feel sufficient
`confidence in its general correctness to discuss its
`genetical implications. In .doing so we are assuming
`that fibres of the salt of deoxyribonucleic acid are
`not artefacts arising in the method of preparation,
`since it has been shown by Wilkins and his co-workers
`that similar X-ray patterns are obtained from both
`isolated fibres and certain intact biological
`the
`materials such as sperm head and bacteriophage
`particles2•4 •
`The chemical formula of deoxyribonucleic acid is
`now well established. The molecule is a very long
`chain, the backbone of which consists of a regular
`alternation of sugar and phosphate_ groups, as shown
`in Fig. 1. To each sugar is attached a nitrogenous
`base, which can be of four different types. (We have
`considered 5-methyl cytosine to be equivalent to
`cytosine, since either can fit equally well into olir
`_ structure.) Two of the possible bases-adenine and
`gustniue-are purines, and the other two-thymine
`and cytosine-are pyrimidines. So far as is known,
`the sequence of bases along the chain is irregular.
`The monomer unit, consisting of phosphate, sugar
`and base, is known as a nucleotide.
`The first feature of our structure which is of
`biological interest is that it consists not of one chain.
`but of two. These two chains are both coiled aroynd.
`
`a common fibre axis, as is shown diagrammatically
`in Fig. 2. It has often been assumed that sincE! there
`was only one chain in the chemical formula there
`would only be one in the structural unit. However,
`the density, taken with the X-ray evidence2 , suggests
`very strongly that there are two.
`The other biologically important feature is th~
`manner in which the two chains are held together.
`This is done by hydrogen bonds between the bases,
`as shoWn. schematically ill Fig. 3. The bases are
`joined together in pairs, a single base from one chain
`being hydrogen-bonded to a single base from the '
`other. The impqrtant point is that only certain pairs
`of bases will fit into the structure. One member of a
`pair must be a purine and the other a PYrimidine'-in
`order to bridge between the two chains-. If a pair
`consisted of two purines, for example, there would
`-
`not be room for it.
`We believe 'that the bases will be present almost
`entirely in their most probable tautomeric forms. If
`this is true, the conditions for forming hydrogen
`bonds are more restrictive, and the only pairs of
`bases possible are : ·
`
`adenine with thymine ;
`guanine with cytosine.
`
`The way in which these are joined together is shown
`in Figs. 4 and 5. A given pair can be either way
`round. Adenine, for example, can occur on either
`chain ; but when it does, its partner on the other
`chain must always be thymine.
`This pairing is strongly supported by the recent
`analytical results 5 , which show that for all sources
`of deox;Yribonucleic acid examined the amount of
`adenine is close to the amount of thymine, and the
`amount of guanine close to tha amount of cytosine,
`although the cross-ratio (the ratio of adenine to
`guanine) can vary from one source to another.
`Indeed, if the sequence of bases on one chain is
`irregular, it is difficult to explain these analytical
`results _except by the sort of pairing we have
`suggested.
`The phosphate-sugar backbone of our model is
`completely regular, but any sequence of the pairs of
`bases can fit into the structure. It follows that in a
`long molecule many different permutations are -
`possible, and it therefore seems likely that the precise
`sequence of the bases is the code which carries the
`If the actual order of the
`genetical information.
`... ,
`
`/
`
`/
`
`SUGAR-BASE
`
`PHOSPHATE
`
`'\_ SUGAR-&ASE
`/
`
`PHOSPHATE
`
`PHOSPHATE
`
`/
`
`/
`
`/
`
`" SUGA Fl-BASE
`' SUCAR-B.t.H
`PHOSPHATE "' SUGAR-BASE
`PHOSPHATE '· ..
`
`PHOSPHATE
`
`~.-
`PHOSPHA Tl
`
`/
`SUGAR
`
`BASE -
`
`/
`BA&E -SUGAR
`
`.. -......... -.. ---
`-.
`
`/
`BASE -SUGAR
`
`/
`
`/
`
`/
`
`tlASE-SUGAR '
`'
`' PHOSPHATE
`' PHOSPl'IATE
`BASE -SUGAR ' PHOSPHATE·
`
`Chemical formula of a pair ·of deoxyribonucleic acid
`Fig. 3.
`chains. The hydrogen bonding is symbolized by dotted lines
`
`

`

`966
`
`ADENINE
`
`THYMINE
`
`May 30, 195j
`
`voL. 171
`
`NATURE
`hydrogen bonds to one of the bases on the chain
`already formed. We now postulate that the polymer(cid:173)
`ization of these monomers to form a new chain is
`only possible if the resulting chain can form the
`proposed structure. This is plausible, because steric
`reasons would not allow nucleotides 'cr~stallized' on
`to the first chain to approach one another in such a
`way that they could be joined together into a new
`chain, unless they were those nucleotides which
`were necessary to form our structure. Whether a
`special enzyme is required to carry out the polymer(cid:173)
`ization, or whether the single helical chain already
`formed acts effectively as an enzyme, remains to be
`seen.
`Since the two chains in our model are intertwined,
`it is essential for them to untwist if they are to
`separate: As they make one complete turn around
`each other in 34. A., there will be about 150 turns
`per million molecular weight, so that whatever the
`precise structure of the chromosome a considerable
`amount of uncoiling would be necessary. It is well
`known from microscopic observation that much
`coiling and uncoiling occurs during, mitosis, and
`though this is on a 'much larger scale it probably
`level.
`reflects similar processes on · a molecular
`Although it is difficUit at the moment to see how
`these processes occur without everything getting
`tangled, we do not feel that this objection will be
`insuperable.
`Our structure, as described1, is an open one. There
`is room between the pair of polynucleotide chains
`(see Fig. 2) for a polypeptide chain to w:ind around
`the same helical axis. It may be significant that the
`distance between adjacent phosphorus atoms, 7 ·I A.,
`is close to the repeat of a fully extended polypeptide
`chain. We think it probable that in the sperm head,
`and in artificial nucleoproteins, the polypeptide chain
`occupies this position. The relative weakness of the
`second layer-line in the published X-ray picturessa,4
`is crudely compatible with such an idea. The function
`of the protein might well be to control the coiling
`and uncoiling, to assist in holding a single poly(cid:173)
`nucleotide chain in a helical configuration, or some
`other non-specific function.
`Our model suggests possible explanations for a
`number of other phenomena. For example, spon(cid:173)
`taneous mutation may be due to a base occasionally
`occurring in one of its less likely tautomeric forms.
`Again, the pairing between homologous chromosomes
`at meiosis may depend on pairing between specific
`bases. We sh.all discuss these ideas in detail else(cid:173)
`where.
`For the moment, the general scheme we have
`proposed for the reproduction of deoxyribonucleic
`acid must be regarded as speculative. Even if it is
`correct, it is clear from what we have said that much
`remains to be discovered before the picture of genetic
`duplication can be described in detail. What are the
`polynucleotide precursors ? What makes the pair of
`chains unwind and separate? What is the precise
`role of the protein ? Is the chromosome one long pair
`of deoxyribonucleic acid chains, or does it consist of
`patches of the acid joined together by protein?
`Despite these uncertainties we feel that our pro(cid:173)
`posed structure for deoxyribonucleic acid may help
`to solve one of the fundamental biological problems(cid:173)
`the molecular basis of the template needed for genetic
`replication. The hypothesis we are suggesting is that
`the template is the pattern of bases formed by one
`.. chain of the deoxyribonucleic acid and that the gene
`ooQ.tains a complementary pair of such templates.
`
`0
`5 A
`I
`I
`Fig. 4-. P.airing of adenine and thymine. Hydrogen bonds are
`shown dotted. One carbon atom of each sugar is shown
`
`GUANINE
`
`CYTOSINE
`
`Ji'ig. 5. Pairing of guanine and cytosine. Hydrogen bonds are
`shown dotted. One carbon atom of each sugar is shown
`t
`bases on one of the pair of chains were given, one
`could write down the exact order of the bases on the
`other one, because of the specific pairing. Thus one
`chain is, as it were, the complement of the other,
`· and it is this feature which suggests how the deoxy(cid:173)
`ribonucleic acid moleclile might duplicate itself.
`Previous discussions of self-duplication have usually
`involved the concept of a template, or mould. Either
`the template was supposed to copy itself directly or
`it was to produce a 'negative', which in its turn was
`to act as a template and produce the original 'positive'
`once again. In no case has it been explained in
`detail how it would do this in terms of atoms and
`molecules.
`Now our model for deoxyribonucleic ,acid is, in
`effect, a pair of templates, each of which is com(cid:173)
`plementary to the other. We imagine that prior to
`duplication the hydrogen bonds are broken, and the
`two chains unwind and separate. Each chain then
`acts as a template for the formation on to itself of a
`new companion chain, so that eventually we shall
`have two pairs of chains, where we only had one
`before. Moreover, the sequence of the pairs of bases
`will have been duplicated exactly.
`A study of our model suggests that this duplication
`could be done most simply if the single chain (or the
`relevant portion of it) takes up the helical con(cid:173)
`figuration. We imagine that at this stage in the life
`of the cell, free nucleotides, strictly polynucleotide
`precursors, are available in quantity. From time to
`time the base of a free nucleotide will join up by
`
`

`

`No. 4361 May 30, 1953
`
`NATURE
`
`967
`
`One of us (J. D. W.) has been aided by a fellowship
`from the National Foundation for Infantile Paralysis
`(U.S.A.).
`1 Watson, J. D., and Crick, F. H. C., Nature, 171, 737 (1953).
`2 "Wilkins, M. H.F., Stokes, A. R., and "Wilson, H. R., Nature, 171,
`738 (1953). Franklin, R. E., and Gosling, lt. G., Nature, 171,
`740 (1953).
`"(a) Astbury, w. T .. Symp.No.1 Soc. Exp. Biol.,66 (1947). (b) Furberg,
`S., Acta Chem. Saand., 6, 634 (1952). (c) Pauling, L., and 9orey,
`R. B., Nature, 171, 346 (1953); Proc. U.S. Nat. Acad. Sci., 39,
`84 (1953). (d) :Fraser, R. D. B. (in preparation).
`4 Wilkins, M. H.F., and Randall, J. T., Biochim. et Biophys. Acta, 10,
`192 (1953).
`• Chargaff, E., for references see Zamenhof, S., Brawerman, G., and
`Chargaff, E., Bioehim. et Biophys. Acta, 9, 402 (1952). Wyatt,
`G. R., .J. Gen. Physiol., 36, 201 (1952).
`
`GEOPHYSICAL AND
`METEOROLOGICAL CHANGES
`IN
`THE PERIOD JANUARY-APRIL 1949
`I N a recent article 1 Lewis and Mcintosh have
`
`considered the geophysical data for the period
`January-April 1949, which we presented in an
`earlier communication2 • On the 'basis of certain
`probability criteria they appear to show that the
`apparent regular variations
`in
`ionospheric and
`meteorological phenomena which occurred in that
`period were not significant. We have studied their
`article and made a separate statistical analysis of the
`unsmoothed data, and conclude that in all respects
`our original suggestions seem to be valid.
`In our original article we presented graphs showing
`five-day moving averages
`in four parameters:
`(a) ground pressure, p; (b) E-layer critical frequency,
`JE; (c) F-layer crit.ical frequency, JF2; and (d) K(cid:173)
`index of geomagnetic activity. The connexion be(cid:173)
`tween ionospheric and geomagnetic phenomena is
`well known. Thus, Appleton and Ingram3 in 1935
`established the correlation between geomagnetic
`activity and depressions in JF2. It is worthy of note
`that in the period under discussion the inverse
`correlation between K and 6.JF2 is, as Lewis and
`Mcintosh point out, considerably less striking than
`that between p and 6.fE (cf. Figs. 1 and 2 in our
`original article). It would seem, then, that if statistical
`analysis can be successfully applied to show that there
`is no significance between the variations in p and
`6.JE, it is, a fortiori, evident that a similar analysis
`might, in the present instance, be used for discrediting
`the established relationship between K and 6.JF2.
`Conversely, of course, the fact that a phenomenon
`appears to be statistically significant over a short
`period must likewise be tr~ated with reserve. The
`need for the utmost care in the application and
`interpretation of statistical analyses to such a limited
`time series is thus clear.
`From inspection of our graphs it seemed to us
`that, so far as p and 6.JE were concerned, the period
`was unusual in three respects:
`(i) there appeared
`to be four oscillattons in ground pressure showing a
`progressive diminution of amplitude, with an average
`period of about 27 days ; (ii) in like manner there
`appeared to be four marked oscillations of period
`about 27 days in 6.JE ; (iii) oscillations (i) and (ii)
`appeared to be almost exactly out of phase.
`In
`addition, we noted that the period was characterized
`by an unusual 27-day recurrence of great sudden
`commencement (S.C.) magnetic storms.
`In our original communication we merely directed
`attention to these matters, and suggested that there
`
`might be some connexion between them; We did
`not then suggest, nor do we now suggest, that from
`a period of length only four months any conclusions
`can be drawn regarding the general behaviour over
`a long period of any of the geophysical parameters
`considered. The severely limited number of observa(cid:173)
`tions available, together with the fact that there is
`considerable uncertainty about the correct statistical
`approach to time series analysis, seemed to us
`sufficient reason for not entering~into an extended
`statistical analysis.
`However, the contrary conclusions reached by
`Lewis and Mcintosh (see below) have prompted us
`to re-examine the data. Briefly, their conclusions
`are : (i) the 27-day oscillation in ground pressure
`is of no significance, since the amplitude is no more
`than would be expected from mere chance considera(cid:173)
`tions ; (ii) the 27-day oscillation in 6.fE is probably
`significant ; (iii) oscillations (i) and (ii) are exactly
`in anti-phase; (iv) there ii:; no significant correlation
`poefficient between the p and 6.JE data; (v) our
`conclusions arise from smoothing of, the data.
`We shall now outline our own analysis. In various
`communications 4- 6, Kendall has made it abundantly
`clear that most of the methods generally used for
`studying periodicities in time series (for example,
`periodograms, Fourier analysis, etc.) may yield very
`misleading results when applied to the kind of time
`series with which we are here concerned. He has
`also questioned the reliability of the usual significance
`tests for periodicities when· applied in time series
`analysis. Kendall has shown that the most reliable
`approach is that of serial correlation coefficients as
`exhibited in the correlogram. He points out that
`although the correlogram may be insensitive, it does
`give a lower limit to the oscillatory effects, and that
`if it oscillates there is almost certainly some system(cid:173)
`atic oscillation
`in
`the primary series explored. ·
`Figs. 1 and 2 show the correlograms for Ap and 6.JE
`respectively for the period under consideration. In
`both of these the original unsmoothed data have
`been used.
`It is important to note that there is a marked
`trend in the pressure data, and to eliminate this· we
`have dealt with values of pressure departures, Ap
`(as with the JE data), rather than with the absolute
`magnitudes p. The oscillations in both correlograms
`are clear, with a maximum at 26-27 days in each
`case. These correlograms provide strong support for
`our original deductions (based, as they were, on simple
`inspection of graphs), and make it essential for us
`to repeat Lewis and Mcintosh's calculations.
`At the outset we must again stress that the pressure
`data exhibit a marked downward trend (approx(cid:173)
`imately linear), and "it is imperative initially to
`eliminate this before proceeding ,with any numerical
`analysis. It appears that Lewis and Mcintosh have
`overlooked this point, and as a result have arrived
`at quite contrary conclusions. This will be clear
`from an examination of Table 1, in which we present
`the results of calculations made by us using (i)
`pressure, p, (ii) pressure departures, 6.p, and (iii) JE
`departures, 6.JE.
`The nomenclature employed
`(c, <p, a, etc.) is that used by Lewis fl.lid Mclntos~
`Without going into details, it can be stated that
`there is little significant difference between the
`present results using pressure, p, and those given by
`Lewis and Mcintosh. The slight differences in the
`values of amplitude c and first serial correlation
`coefficient r 1 are of no significance and can be ascribed
`to different ways of deducing the amplitude a:n,d phase
`
`