Fected Cells, Which Produce High Frequency of Lysogeny, Show a Pattern of DNA Synthesis Similar to That of C+-Infected Complexes

VOL. 52, 1964 ENGINEERING: J. A. RAJCHMAN 363

fected cells, which produce high frequency of lysogeny, show a pattern of DNA synthesis similar to that of c+-infected complexes. The functions of the cl and c2 loci are interpreted as controlling DNA synthesis during infection leading to lysogeny. The cl locus represses phage DNA synthesis in the first few minutes of the infection, and the c2 locus maintains the repressed state after the recovery of cellular replication. The assistance of Mrs. Margaret Dunson in the performance of these experiments is greatly appreciated. * This work was supported by U.S. Public Health Service grant GM-09252-02. t Postdoctoral research fellow of the U.S. Public Health Service. I Lederberg, E., and J. Lederberg, Genetics, 38, 51 (1953). 2 Lennox, E. S., Virology, 1, 190 (1955). 3Jacob, F., Virology, 1, 207 (1955). 4 Levine, M., Virology, 3, 22 (1957). 6 Levine, M., and R. Curtiss, Genetics, 46, 1573 (1961). 6 Smith, H. O., unpublished results. 7Kellenberger, E., K. G. Lark, and A. Bolle, these PROCEEDINGS, 48, 1860 (1962). 8 Sechaud, J., Arch. Sci., 13, 427 (1960). 9 Luria, S. E., P. K. Fraser, J. M. Adams, and J. W. Burrous, in Exchange of Genetic Material: Mechanisms and Consequences, Cold Spring Harbor Symposia on Quantitative Biology, vol. 23 (1958), p. 71. 10Kaiser, A. D., Virology, 3, 42 (1957). 1 Bertani, L. E., Virology, 12, 553 (1960). 12 Egan, J. B., and B. W. Holloway, Austral. J. Exptl. Biol. Med. Sci., 39, 9 (1961). 13 Kaplan, R. W., U. Winkler, and H. Wolf-Ellmauer, Nature, 186, 330 (1960). 14 Kaiser, A. D., and F. Jacob, Virology, 4, 509 (1957). "5Jacob, F., and A. Campbell, Compt. Rend. Acad. Sci., 248, 3219 (1959). 16 Zinder, N. D., Virology, 5, 291 (1958). 17 Levine, M., and H. 0. Smith, unpublished results. 18 Jacob, F., and J. Monod, J. Mol. Biol., 3, 318 (1961).

INTEGRATED MAGNETIC AND SUPERCONDUCTIVE MEMORIES BY JAN A. RAJCHMAN RCA LABORATORIES, PRINCETON, NEW JERSEY Communicated by V. K. Zworykin and read before the Academy, April 29, 1964 1. Introduction.-Memory in computers: Electronic techniques allow the execution of millions and even billions of arithmetic or other elementary logic functions in minutes or at worst in hours. This great speed is significant only for long sequences of computations, and sequences that are strictly specified by detailed instructions. These instructions must be available at speeds compatible with those of the computation, and it must be possible to select automatically among alter- native instructions according to the results of computation in progress. The intermediate numbers occurring in a long numerical computation and the instructions forming the program for the execution of the problem must be stored. This is the role of the "memory." It must be possible to dispose of incoming information, or to "write-in" the "memory," at any desired location, or "address," Downloaded by guest on October 1, 2021 364 ENGINEERING: J. A. RAJCHMAN PROC. N. A. S.

and similarly to extract information, or "read," from any desired address. Such selective addressing must be possible not only in a short time but, preferably, in a time independent of the selected address or any previously selected addresses. In other words, it must be possible to access the memory at "random." The realization of high-speed random-access memories made possible the universal computers which are such an important reality today. The first truly digital high- speed random-access memory was the selectron,I an electrostatic storage tube using a matrix of selectable electron beams striking discretely made storing elements.

1010 PROBABLE REGION OF 226 CRYOELECTRIC 109_X / MEMORIES ~-A ______M 224 -222 - PROBABLE REGION 08 INTEGRATED MAGNETICOF_ 220 ____--- MEMORIES WITH Q 7 \9 __ \ASINTEGRATED CIRCUITS cr ~~~~~~~~~~~~~~~~~218 STATE OF ART _ EXPERIMENTATE63 AeM.NeAL 216 W FERRITE (63) 106 I16384 (I) co - ~~~~~~~~~~~~~~4,096 FO5 MICROFEG1 RITE 1aa024dca

SOME ~~~~~~~~PROTOTYPES -256 4

-64

memories 6eedvlpd2~13 ____LAT WAFER~S(62)Ths1emreonitofary2o4nivdal- IOO1.S IOMIS FLus lO0ns l.ns FIG. 1.-Storage capacity and cycle time of various memories.

Core memory: M\ore than a decade ago, the first random-access magnetic memories were developed.2', I These memories consist of arrays of individually molded ferrite cores in the form of tiny rings which are linked by two sets of parallel and other wires. The material used is not only ferromagnetic but, due to considerable development work, its hysteresis loop is almost perfectly rectangular. As a result, it is possible to bring any core to one or the other of its remanent states of magnetization. The state of remanence stores naturally, and without standby power, the information as to which direction the core was last magnetized. This memory property is a gift of nature. Furthermore, because of the hysteresis loop rectangularity, the core not only performs the function of storage, but participates in the selecting function inherent in addressing, in that the amplitude of the addressing currents can be chosen so that the selected core switches while the other cores in the selected lines remain completely unaffected. In this way electronic switches are required only for the lines of the array and not for every core, so that their number, Downloaded by guest on October 1, 2021 VOL. 52, 1964 ENGINEERING: J. A. RAJCHMAN 365

although large, is still tolerable even when these switches are vacuum tubes. With the later advent of the transistor, the classical solution to random-access memory became the transistor-driven and sensed arrays of ferrite cores. Since its advent, the core memory has been gradually improved4' and has reached a range of capacity and speeds illustrated by the hatched area on Figure 1. Need for more storage capacity: Despite great progress, the memory is still the main limit in the further broadening of processing information by machines. The demands on memory result simply from the fact that all information as to what to do, how to do it, and what data to do it on, flows through the memory. Obviously, the storage capacity and speed of access of the memory determines the capability of the whole processing machine. Among specific examples of problems demanding more storage capacity are: solution of differential equations, aerodynamics, particle accelerators, plasma physics, etc.; problems of large matrix inversions and linear equation systems; combinatorial and symbol manipulative problems; problems involving masses of data such as weather prediction, statistical analysis, pattern recognition, etc. An indication of the demand for larger storage capacities can be seen in the growing use of electromechanical storage systems such as rotating drums, disks, and moving magnetic cards. These systems are a compromise dictated by necessity. They attain capacities of millions to billions of bits at the cost of access times measured in seconds, and the necessity for maintenance characteristic of high-speed complex mechanical devices. Clearly then, electronic random-access memories of capacities as large as hundred millions or billions of bits and with access times measured in microseconds are extremely desirable. How can they be attained? 2. Integration Techniques.-Are further gradual improvements in the ferrite core memory likely to lead to memories with billions of bits? Probably not, for the following reasons. The cores are molded and tested individually on automatic machines. Highly performing and uniform cores are thus obtained. The cores are threaded on wires by semiautomatic methods to form plane arrays. The arrays are interconnected by manual operations. Finally, the whole magnetic structure is connected to its associated transistor circuitry. This circuitry is made up of individually con- structed, mounted, and connected transistors and other circuit elements. The entire memory is therefore an example of highly evolved techniques for handling individually made components, or in modern parlance, highly evolved "nonintegrated techniques." Incidentally, there are usually one hundred to two hundred as many magnetic cores as semiconductors, but the cost of the magnetic and semiconductor subassemblies are about equal. The degree of automation required for a billion-bit memory can be appreciated from the simple arithmetic fact that a billion seconds constitute thirty years. Therefore, a production rate of one-per-second is two or three orders of magnitude too slow to be practical. Molding and testing machines have attained rates of ten cores per second; still, many such machines must be used merely to provide the cores fast enough. Threading of the cores is a much slower operation still. It is clear that enormous effort in automation is necessary to obtain assemblies with billions of cores by such inherently brute force methods. Downloaded by guest on October 1, 2021 366 ENGINEERING: J. A. RAJCHMAAN PROC. N. A. S.

What is needed is a method for making all the magnetic storing elements and all the linking windings by some batch fabrication which in a single step can produce the whole magnetic assembly. In short, an integrated technique is needed. Many different approaches to integrating the magnetic structure were undertaken. An early development was that of the apertured ferrite plate6 molded with an array of holes and covered with a metallic coating so patterned as to provide one winding linking all holes. In the more recent microferrite memory,7 the same printing of winding through the apertures permits the use of extremely small cores. In FIG. 2.-Laminated ferrite structure, 16 X 16 bits (aspirin the FLEA memory' utilizing tablet for size comparison). metallic sheets of permalloy etched with an array of holes and covered with an insulator, all the necessary windings are provided by a printed technique. Fast switching and the possibility of integrated-batch fabrication of thin films of permalloy only a few thousand angstroms thick'0 13 gave incentive to substantial research in recent years. Flat films in glass substrates either in individual circular or rectangular spots or as continuous sheets13 were mostly worked on. Wires or long cylinders coated with film were used also.14-17 Despite the substantial effort, only a few memories have become operative, and none have shown an economic advantage with respect to cores. Thin magnetic filma technology and other proposed technologies have attempted to provide an integrated method of fabrication of the magnetic structure without regard to its use with integrated semiconductor circuits, as the required drive currents are too large and the physical size is not reducible to the scale of these circuits. 3. Laminated Ferrite Memory. It is believed that the laminated ferrite memory8 announced in the fall of 1963 offers, for the first time, an integrated magnetic technique easily adaptable to use with integrated semiconductor circuits and which shows real promise to provide memories an order or two of magnitude greater than those possible with nonintegrated cores. Fabrication: The integrated fabrication technique8' 18 comprises three simple operations: "doctor blading" (name commonly used in the paint industry and a Downloaded by guest on October 1, 2021 VOL. 52, 1964 ENGINEERING: J. A. RAJCHMAN 367

FIG. 3.-X-ray photograph of an experimental laminate, 23/4 x /'cmrsig26X6m 16,384 storing elements.

technique used for spreading layers of paint of definite thickness for life tests), "conductor screening," and "laminating and sintering." The "doctor blading" technique consists of spreading a slurry of ferrite evenly on a glass substrate by the sweeping action of a blade, the "doctor blade," held at a constant distance above the glass surface. The slurry is the mixture of ferrite powders and organic binders used for molding cores. After blading, the sheet is air-dried and peeled off the surface. To form the conductors, a "screening" technique is used. A photoformed metal mask is laid on the substrate. A paste consisting of a refractory metal powder and a binder is squeegeed through the mask onto the glass. Next, the mask is removed leaving the desired pattern on the glass. Ferrite is then doctor-bladed over the conductor pattern. When peeled off the glass, the ferrite sheet contains the conductors intimately embedded in it and flush with its surface. Monolithic structures are fabricated by "laminating and sintering" together a number of such sheets. In the simplest structure, the orthogonal array, three sheets are used. Two sheets have a pattern of straight parallel lines which are placed orthogonal to each other, and a third is a spacer sheet with no embedded conductors (Fig. 2). The sandwich is then pressed at a moderate pressure and temperature in a hydraulic press, and the entire structure is thoroughly bound together. The laminated structure is next sintered at very high temperature (1100-12000C). The magnified X-ray photgraph of Figure 3 is that of a typical array of 256 X 64 lines, which create at their intersections 16,384 storing elements. The lines are spaced 0.010 inches apart, and the sandwich is only 0.005 inch thick. The magnetic properties of laminates are identical with those of individually molded cores because the identical ferrite compositions are used, and compacting pressures under the blade due to hydrodynamic forces equal or exceed those obtainable in a conventional press. The resistance of the very small conductors, typically 0.002 inch by 0.0005 inch, is as low as 2 ohms/inch. Principle of operation: Memories are usually addressed by accessing in parallel a number of bits grouped in "words." Typically, words comprise 20-60 bits. In so- called "word organized" memories, the logic of parallel accessing is also implemented by a corresponding physical organization in which all the storing elements of a word are actually on the same electrical selecting line. This is the mode of operation of Downloaded by guest on October 1, 2021 368 ENGINEERING: J. A. RAJCHMAN PRoc. N. A. S.

X DRIVE ADDRESS the orthogonal laminate fer- LINES rite array. For example, in STCELLE the 256 X 64 array of Figure 3, the 256 short lines are word lines, and the 64 longer lines are the digit lines. Because of the orthogonal disposition of word and digit SENSECAVITY ~~~~conductors, word read-write SIGNAL currents switch flux along a FIG. 4.-Principle of continuous sheet memory with cavity selected word conductor that sensing. does not link the digit conductor. A digit pulse applied to a digit conductor in time coincidence with a write pulse switches a component of flux mutual to both the word and digit conductors at the corresponding crossover point. The application of a read pulse switches this mutual flux and induces a sense voltage in the digit winding. The polarity of the induced sense voltage is determined by the polarity of the applied digit current. Operating characteristics: The current required to switch a magnetic element at a given speed is inversely proportional to the length of the flux path, i.e., to the effective diameter of the element. The storing elements in the laminate have an effective diameter of only 0.003 inch. For comparison, the smallest standard cores are 0.018 inch inside and 0.030 inch outside diameter. The smallness of the element can be exploited to obtain a very fast switching with the relatively large switching currents of 300 or 400 ma used in standard core memories, or else it can be exploited to drastically reduce the drive current to 30-50 ma and still keep the switching time of conventional memories. The first possibility'8 led to an experimental memory with an access time of 100 nsec. The second possibility is of great importance to the realization of very large capacities since it permits the use of integrated semiconductor driving circuits. Integrated semiconductor circuits: Circuits associated with the magnetic structure constitute usually half the cost of the memory, even though only one transistor is necessary for one to two hundred elements. Thus, a billion cores require five to ten million transistors, or about one hundred times more than found in the largest computers. Clearly, the only hope resides in integrated circuits. The electronics industry is engaged in a great effort toward integrated circuits for they are applicable to many products. A survey of integrated circuits is beyond the scope of this paper. Suffice it to say that a number of techniques are available to obtain on single chips of silicon crystal: all the necessary address, digit write, and read circuits. All these devices can easily be spaced one hundred to the inch, which is the spacing of the lines of the laminated ferrite structures. Therefore, it is possible to juxtapose the two structures in intimate contact so that all lines to be connected match precisely with one another. Considerable success has already been obtained with the laminated ferrite, and the progress with integrated circuits specific to the laminates has also been significant. Downloaded by guest on October 1, 2021 VOL. 52. 1964 ENGINEERING: J. A. RAJCHMAN 369

4. Superconductive Memory.-In the last decade superconductivity was applied to computer elements through the development of the cryotron,19 a switch based on the fact that a super- conductor can be changed from its state of zero resistance to a normal state with some resistance by the application of magnetic field easily obtainable. from a controlling current. Recently, the continuous sheet memory was con- ceived20 which utilizes unique properties of superconductors favorable to the attainment of very large storage WS. capacities. FIG. 5.-Cryoelectric memory plane with 128 X Principle of the continuous sheet mem- 128 = 16,384 storing elements. ory: Two perpendicular sets of parallel, suitably insulated lead strips are evaporated on top of a continuous film of superconductive tin (Fig. 4). When an X strip and a Y strip carry a certain current, the magnetic field is maximum at the intersection and diminishes gradually with distance. Consequently there is a sharply defined region within which the field in the tin exceeds the critical value and renders the sheet normal. and outside of which it does not. Within that region it is possible to induce persistent currents. Their direction depends on the direction of the primary driving currents and determines whether a "one" or a "zero" is stored. An element is switched only if the primary excitation is opposite to that which previously established its state, and only if it exceeds a certain definite threshold. At each element is a stored magnetic flux. When this flux switches, it induces an electromagnetic transient underneath the sheet. The occurrence of this dis- turbance is sensed by observing the voltage induced at a suitable location in a box- like structure under the sheet (Fig. 4). This type of sensing, called cavity sensing,2' requires no fine winding zigzagging through the elements as is necessary in some types of core memories. No transient of magnetic field due to the selecting X and Y currents leaks through the superconductive memory plane other than at the selected location, because that plane is a perfect magnetic shield. Consequently there are no disturb signals due to half excitations, and the plane can be made arbitrarily large without any loss in the purity of the output signal. To address the memory, the drive currents X and Y are steered to the selecting lines by cryotron decoders. In the decoders, the cryotrons are arranged in trees, and at every bifurcation one of the cryotrons is resistive and the other super- conducting according to the value of the corresponding binary address bit. The current is steered through the only completely superconductive path to the desired memory line (Fig. 4). Present status and future of cryoelectric memories: The largest planes achieved21 comprise an array of 128 X 128 = 16,384 storing elements on a 2 " X 2" glass substrate (Fig. 5). The memory is made by successive evaporations in vacuum of tin, lead, and silicon monoxide, as shown on Figure 6. Downloaded by guest on October 1, 2021 370 ENGINEERING: J. A. RAJCHMAN PROC. N. A. S.

_-arc; Lo:-. The planes are only a step to Adz<>.wr.planes of larger area and finer pat- terns. Stacks of these planes could INSUI>LA' w reach capacities of hundreds of mil- -.-YWINDIN,, lions to a billion bits. While many technological problems remain to be _ - INSULATIOI solved, it seems that superconduc- MllEMtORYPLANE tive techniques are the most likely _lllII.; to attain these large capacities. On the other hand, since an important _||| _ ~SENSESENSE PLANE part ofd the cost is the necessary - t INSULATILO cryostat, it is unlikely that cryo- GR ND ;:., ,, electric memories with less than a few million bits can compete with magnetic memories (see Fig. 1). 5. Conclusions.-The need for X/ large storage capacity in random- access electronic computer memories motivates large efforts of many FIG. 6. Exploded view of 16,384 bit cryoelectric laboratories. We are witnessing an memory plane. extremely interesting confrontation of two philosophies: one based on perfecting the automatic high-speed fabrication of individual elements and their assembly, the other based on novel concep- tions and development of batch fabrication methods avoiding the necessity of making single elements. This is a confrontation between nonintegrated and integrated electronics. The present belongs firmly to nonintegrated memories, but the future will belong to integrated memories. The laminated ferrite and the superconductive continuous sheet memories are the most promising solutions to integrated computer memories.

1 Rajchman, J. A., "The selective electrostatic storage tube," RCA Rev., 12, 53-97 (1951). 2 Forrester, J. W., "Digital information storage in three dimensions using magnetic cores," J. Appl. Phys., 22, 44-48 (1951). 3 Rajchman, J. A., "Static magnetic matrix memory and switching circuits," RCA Rev., 13, 183-201 (1952). 4 Rajchman, J. A., "Computer memories: A survey of the state of the art," Proc. IRE, 49, 104-127 (1961). 6 Rajchman, J. A., "Computer memories: Possible future development," RCA Rev., 18, no. 2, 137-151 (1962). 6 Rajchman, J. A., "Ferrite apertured plate for random access memory," Proc. IRE, 45, 325- 334 (1957). 7 Amemiya, H., H. P. Lemaire, R. L. Pryor, and T. R. Mayhew, "High speed ferrite memories," Proceedings Fall Joint Computer Conference, 1962. 8 Shahbender, R., C. P. Wentworth, K. Li, S. E. Hotchkiss, and J. A. Rajchman, "Laminated ferrite memory," Proceedings Fall Joint Computer Conference, 1963. 9Briggs, G. R., and J. W. Tuska, "Permalloy sheet transfluxor-array memory," J. Appl. Phys., Suppl. (1962). it Pohm, A. V., and E. N. Mitchell, "Magnetic film memories-A survey," IRE Trans. Electron. Computers, EC-9, 308-314 (1960). Downloaded by guest on October 1, 2021 VOL. 52, 1964 BIOCHEMISTRY: KORNFELD ET AL. 371

11 Chong, C., and G. Fedde, "Magnetic films: Revolution in computer memories," Proceedings Fall Joint Computer Conference, 1962. 12 Pohm, A. V., R. J. Zingg, T. A. Smay, G. A. Watson, and R. M. Stewart, "Large, high speed, DRO film memories," Proceedings of the International Conference on Nonlinear Magnetics, 1963. 13 James, J. B., B. J. Steptoe, and A. A. Kaposi, "The design of a 4,096 word one microsecond magnetic film store," Western Electronics Show and Conference (WESCON), Los Angeles, August 1962; Second International Conference on Information Processing (IFIP), Munich, Germany, August-September 1962. 14 Bobeck, A. H., "A new storage element suitable for large-sized memory arrays-The twistor," Bell System Tech. J., 1319-1340 (1957). 16 Long, T. R., "Electrodeposited memory elements for a nondestructive memory," J. Appl. Phys., 31, 123-124 (1960). 16 Meier, D. A., "Magnetic rod memory," Proc., Electron. Components Conf., 122-128 (1960). 17 Looney, D. H., "A twistor matrix memory for semipermanent information," Proc. WJCC, 36-41 (1959). 18Shahbender, R., C. P. Wentworth, K. Li, S. Hotchkiss, and J. A. Rajchman, "Laminated ferrite memory," presented at Intermag Conference, Washington, D. C., April 7, 1964. 19 Buck, D. A., "The cryotron-Superconductive computer component," Proc. IRE, 44, 482- 493 (1956). 20 Bums, L. L., Jr., G. A. Alphonse, and G. W. Leck, "Coincident-current superconductive memory," Trans. IRE PGEC, September 1961. 21 Burms, L. L., Jr., D. A. Christiansen, and R. A. Gange, "A large capacity cryoelectric memory with cavity sensing," Proceedings Fall Joint Computer Conference, 1963.

THE FEEDBACK CONTROL OF SUGAR NUCLEOTIDE BIOSYNTHESIS IN LIVER BY STUART KORNFELD, ROSALIND KORNFELD, ELIZABETH F. NEUFELD, AND PAUL J. O'BRIEN

NATIONAL INSTITUTE OF ARTHRITIS AND METABOLIC DISEASES, NATIONAL INSTITUTES OF HEALTH Communicated by W. Z. Hassid, June 26, 1964 Feedback inhibition-the inhibition of the first enzymatic reaction unique to a pathway by the end product of that pathway-plays an important role in regulating various biosynthetic sequences. In bacteria and also in higher organisms this mechanism serves to control the formation of purines, pyrimidines, and amino acids.' Data presented in this communication demonstrate that the biosynthesis of certain sugar nucleotides in rat liver is likewise subject to feedback inhibition. The pathways leading to the formation of UDP-N-acetyl-D-glucosamine (UDPAG)2 and CMP-N-acetylneuraminic acid (CMP-NAN) are outlined in Figure 1.3 Both sugar nucleotides represent the activated form to which the respective sugars must be converted prior to incorporation into glycoproteins and other macro- molecules. UDPAG and CMP-NAN may therefore be considered the end products of the multistep pathways leading to their formation. Each of these end products inhibits the first enzyme of the pathway which is unique to its biosynthesis. Materials and Methods.-Glycerol-1,3-Cl4 and D-glucosamine-1-C"4 were purchased from New England Nuclear Corp. Tritiated D-glucosamine was obtained by hydrolyzing UDPAG which had been tritiated by the Wilzbach method; it was purified by chromatography on Dowex 50-H + (ref. 4) and on paper, in solvent IV. C'4-labeled UDPAG was made from radioactive N-acetyl- Downloaded by guest on October 1, 2021