computer mrie~.27
edited by Eastern Michigan University.JOHN Ypsilanti. w.MIMOORE 48197
Chemistry and the Microcomputer Revolution Raymond E. Dessy Virginia Polytechnic Institute and State University Blacksburg. VA 24061
The progress of man has heen aided remarkably by those devices which have augmented his natural abilities. The lever provided an extension for the power of his arm. The steam engine and the wheel augmented his ability to move. The telephone and television, in conjunction with optics, have increased his ability to communicate. There are many who helieve that the computer revolution provides man with the first real extension to his mind. This revolution has been possible hecause of the ability of the electrical engineer to place nearly a million circuit components in one square centimeter of "real-estate" on a silicon substrate. Such high density permits the fabrication of the entire heart of a computer, the central processing unit (CPU), in a few integrated circuit packages at low cost. They are true computers capable of executing a program stored in associated memory, making intermediate decisions based on the results of arithmetic and logic operations conducted in the CPU's arithmetic and logic unit (ALU),sensing external signals, and controlling external devices. These microcomputers and minicomputers have found a place in process control, intelligent instruments, and small one-on-one computer systems. Inexpensive and relatively user-cordial, these non-intimidating computers have excited large numbers of professional scientists and hobbyists alike. The classic large main-frame computer traditionally has not been very user-cordial. T o have i t serve as a useful slave required a large expenditure of time, often spent learning an arcane andlor archaic control language, in order to implement functions only vaguely understood by the user because of his physical and temporal isolation from the computer. Political harriers, understanding harriers, and cost harriers all tended to make the large main frame appear more a master than a servant. This atmosphere set the stage for the revolution that is occurring with the advent of the microcomputer. The revolution is not just a technical one hut a true revolution of people fleeing from the tyranny of computer centers, systems programmers, passwords, and funding request sheets to their own hands-on, in the lab, self-controlled computer. Like the "Sorcerer's Apprentice," this delightful new servant can run amuck. I t can require quantities of time and at-
tention. I t can create data as rapidly as water flowed from the Apprentice's bucket. I t can create bad data! Some reputable educators ahd scientists already spend much of their time sweeping a*ay the water and have turned from being first class teachers and " eood researchers to heine" second class programmers. A look a t how this valuable new tool has been used and misused may both stimulate your interest in computers and help you to avoid some common pitfalls. Computers Help Solve a Chemical Problem A useful exercise in understanding the microprocessor revolution is to examine how today's computers impact a single chemical problem. The process forms the basis for an interesting tutorial [for students and skeptical staff alike]. A natural product, derived from a plant source, is found to he therapeutically active. A chemist is asked to discover its structure and mode of pharmacological action. The ultimate coal is to svnthesize other related compounds with a better therapeutiE index and then manufacture the material. Every step of the wav is commonls aided by computers of various sizes, see tahl;. A natural product chemist, with a little information on the source of the natural product in hand, ran search the hihliographic literature for pertinent infmrnati~m.Elec~runicretrieval of surh information I 1 I from a varietv ofabstractine services such as Chemical hi tracts or id logical ~ h s t r a c t s are available from either DIALOG (2) or ORBIT (3). These vendors provide access to centralized data bases and use large time-share facilities and telecommunication links. With some idea of previous chemical knowledge, an examination of the natural product by spectral means can then he undertaken. The NMR and mass spectral equipment used for this purpose are automated usually by minicomputers, the infrared equipment hy microcomputers. These computers not onlv aid in instrumentluser dialog, hut also they take over the task of collecting data and present it to the us& in an orderly manner using computer-generated graphic displays. In many cases these units support simple library searches which attempt to provide structural information directly to the chemist. ~
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The Range of Available Hardware Serves the Range of Functions Reason Memory Size
Minimal
Minimal
O~eratin~ System Single user, single task
Micro~omputer~ Concurrent control operations,with mathematical calculations
Mcderate
Intermediate
Single user, multiple tasks
Minicomputers
Moderate multi-instrument, multi-user environments
intermediate
Large
Multiple users, multiple tasks
Midicomputers
Time-share,multi-programming
Complex
Phenomenal
Very advanced resource-
Hardware Microprocessors
Function Process control, simple sense and control operations
Mathematical Abilitv
and time-sharing
mis spectrum of computers is increasingly being implemented by me Eame type of silicon technology. Function is not dependent an implementation because it is the intent and farm of tha very large scale integrated circuit central processing unit (VLSi-CPU)that is related to function. 320
Journal of Chemical Education
Alternativelv. data bases are availahle which orovide .. lareer " access to stored chemical spectral information. This allows the user. again via time-shared/telecommunication facilities. to examine NMR, IR, MS, and X-Ray spectra for matches with his unknown using Stephen Heller's and G. W. A. Milne's elegant Chemical Information System (CIS) (4). Once the structure is known, or suspected, i t is possihle to find related compounds that are already known by computer-based subst~ucturesearches. These reveal all of the compounds which contain a specific set of functional groups. The National Library of Medicine (5)and the Food and Drug Administration have such programs (6). The three-dimensional graphics capahilities of high resolution color tubes driven hv comuuter uroerams allow interactive translation and rotation of moiecuiar shapes. These permit the biochemist to explore the mechanism of interaction which might he responsible for drug action, clearly showing hydrogen bonded and polar conformations. David Duchamp a t Upjohn is a pioneer in this area (7). With a reasonable set of structurelactivity correlations availahle, i t is possible to use pattern recognition programs, such as the ones developed by Peter Jurs (a), to predict whether compounds yet to he synthesized might have physiological activity. E. J. Corey (9) and W. T. Wipke (10) have made it possihle to use a computer for assistance in designing a synthesis for the molecule. It can sureest alternate oathwavs and startine materials. The chemizmust choose Letween suggested a< ternatives. hut the memorv aid and stimulation orovided hv this partnership is being used extensively in the pharmaceutical industrv. Once a compound is targeted for synthesis, optimization techniques such as simplex or factorial design, pioneered by Stanley Deming and S. L. Morgan (I1), can be used to explore the resoonse surface for a reaction.. i.e... the relationshiu hetween concentration of various reagents, temperature, time, and product yield. This process has been totally automated a t SmithKline Corporation using some of the techniques developed by Deming (12). A computer controls the reactant ratios for a number of initial experiments, analyzing the yield automatically by liquid chromatography. It then predicts potentially hetter conditions and explores the response surface, seeking the maximum yield. Extrapolation of these conditions to the plant is possible, aiding the scale-up prohlem, often the most vexing aspect of industrial implementation of a bench scale synthesis. Typically, the plant itself is controlled by microprocessors. I t also uses larger process control comnuters to continuallv monitor the hatch or steam sc, that optimum conditions art: mainta~ned. At this w i n 1 the ~ w h l e mis returned to the chemist and his laboratory computer. Analytical service to the production and development lab increasinalv the use of intelligent ..-requires . instruments that are microprocessor based. The micro&ocessor has changed the face of today's analytical equipment hy providing intelligent, user-cordial dialog between man and the gas chromatograph, liquid chromatograph, electrochemical apparatus, balance, and spectrometer. I t rememhers protocols set up by the user and can easily repeat them. Its associated printerlplotter provides neat reports suitable for introduction into notebooks. I t automatically provides area, time. heieht. and identification information. ~ h e s 2e;ices e have increased the throughput of analytical sanoles in the lahoratorv and eased that burden. But thev are also'creating such volumes of data that in many places the chemist has become a hieh-oriced secretarv. .. . " . transcrihine information from chart to papvr. This I~c,ttleneckcall he wived bv. tvinr . - all of the comDuters in a laburalurv-intellirent instruments, minicomputers, and midicomputers-into a synergistic interactive network in which intercommunication is fully developed (13). This logical plan for laboratory antomation permits any terminal to have access to the system fa~
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cilities and suggests how even small personal computers can appear to have rather remarkable abilities. This networking concept is already in practice in many scientific laboratories, business 1 cilities, and hobby areas. However, it requires that the first acquisition and exposure to computers in a teaching or research environment he well planned. We have examined some of the exciting capahilities and oo~ortunitiesthat the suectrum of comouters available todav oiiers to the chemist. unfortunately, is all too easy to hicome enamored hv the area and attempt to substitute time for money and expertise in getting staked. Most computer technoloav at the micro end is built around transistor-transistor-lo& or TTL circuits. The simple equation: E
=
T.T.L
applies. The amount of human energy expressed in units of time and talent plus the lucre needed to introduce computers into an environment for a spwifir tnik, ran be rrpreienred as constant F:. The produrr 01' avnilal)lc 'I'IME X availahle TAI.ENT X availahle I.I'C'l
