U.S. DEPARTMENT OF HEALTH, EDUCATION, and WELFARE The Public Health Service Seeds of National Institutes of Health Artificial Intelligence

SUMEX-AIM For Ie lIy tho SupulnLend~nt 01 Doc:um~nU, U.S. Oonmmtnt Prlntlnc omce, Wuhlnclon, D.C. !!Ot02 A publication of The Division of Research Resources National Institutes of Health Seeds of Bethesda, Maryland 20205 Artificial Intelligence

Prepared by SUMEX-AIM Research Resources Information Center 1776 East Jefferson Street Rockville, Maryland 20852 under contract N01-RR-9-2114 ; I

March 1980

U.S. DEPARTMENT OF HEALTH, EDUCATION, and WELFARE Public Health Service National Institutes of Health

NIH Pubicabon No 8G-2071 -

This publication was written by Gregory Freiherr

I The efforts of many people Acknowledgements made this publication possible. Special thanks go to Mr. Thomas Rindfleisch; Drs. Joshua Leder­ berg, Herbert Simon, Edward Feigenbaum, Bruce Buchanan, Paul Armand, William Baker, Jack Myers. and Harry Pople; and Mr. Edward Post.

3 In the past century, science has the defect of their virtues. They are not only changed our conceptions too detailed, too exhaustive and, Foreword about the world, it has changed it­ most important, too focused on self. Driven by an explosion of in­ Single areas of rapidly expanding formation, specialties in science disciplines. To understand this new have sprung up, inevitably giving branch of computer science, called rise to subspecialties. But staying artificial intelligence (AI) , it is nec­ abreast of new knowledge, even in essary to understand the founda­ narrowly specialized areas, is be­ tion, the broader base, on which it coming increasingly difficult. One rests. way to manage the continuing This publication will present a flood of new information may be to general view of AI , the concepts create entities of intelligence. from which it evolved, its current The proposed tool is the intelli­ abilities, and its promise for re­ gent machine, a device that mimics search. The focus is on a commu­ the expert's reasoning power and nity of projects that use the can retain in retrievable form much SUM EX-AIM (Stanford University of the knowledge currently avail­ Medical Experimental Computer able to experts in a given specialty. for Artificial Intelligence in Medi­ Most systems of this type are still cine) network. immature. But some are already SUMEX-AIM is a nationally moving into the real world and shared computing resource de­ others will make the transition voted entirely to deSigning AI within the next few years. As these applications for the biomedical sci­ activities become more formalized, ences. It is funded by the NIH Divi­ a new branch of applied science sion of Research Resources, will arise. Most likely it will be Biotechnology Resources Pro­ called knowledge engineering. gram. Although SUM EX-AIM does What systems will be available? not include all AI projects directed Who will they help? How will they toward medicine and related re­ work? search in this country, many of the Many answers are contained in programs now using AI techniques existing books and articles. But for medical decision-making were technical publications suffer from developed using this facility.

4 Foreword 4 Table Introduction Artificial Intelligence-What's in a of Name? 6 History of Computing Contents Abacus to EN lAC-and Beyond 9 Processes of Computing The Heuristic Mind 20 SUMEX and the Science Community The Seeds of Artificial Intelligence 24 Biochemistry 25 Clinical Medicine 33 Psychology 54 AI Tool Building 62 Future of AI Prospectus 64 Appendix A Organization and Facilities Available 69 Appendix B Management 71 Appendix C SUM EX-AIM Directory and Project Funding 73

5 For centuries, philosophers and computers are only research tools, linguists have grappled with the machines programmed to do Introduction question of defining intelligence. things that would require intelli­ Most have approached the issue gence if done by people. Dr. Mar­ by describing the function of intelli­ vin L. Minsky, artificial intelligence gence, or the way it appears in be­ (AI) researcher at the Massachu­ havior. An exact definition for this setts Institute of Technology and term is elusive. advisor for SUMEX-AIM, agrees. As might be expected, machine He says artificial intelligence is the intelligence is equally, if not more, science of making machines do difficult to define. According to Dr. things that people need intelli­ Margaret Boden in her book Artiti­ gence to do. ciallntelligence and Natural Man, Others take a somewhat differ-

Artificial Intelligence- What's In• a Name?

6 ent view. Dr. Edward Feigenbaum, areas of medical diagnosis and gained from real-world experience. principal investigator of SUMEX­ chemical structure analysis, some When used in AI, heuristics AIM, says the field is not primarily programs can already rival human focus the program's attention on oriented toward technology, but capabilities. Still, many people are those parts of the problem that are toward investigating the nature of skeptical of the computer's poten­ most critical and those parts of the intelligence as information process­ tial. knowledge base that are most rel­ ing, whether the intelligence is ex­ Nobel Prize winner Dr. Herbert evant. The result is that these pro­ pressed by man or machine. A. Simon, psychologist-computer grams pursue a line of reasoning, One point of emphasis in current scientist at Carnegie-Mellon Uni­ rather than a sequence of arith­ AI research is to design computer versity and SUMEX-AIM advisor, is metic steps. programs that capture the knowl­ convinced that this potential is Use of complex symbolic struc­ edge and reasoning processes of generally underrated. He says tures is necessary when construct­ highly intelligent specialists. The human behavior is based on a ing computer applications for practical goal of such work is to complex but definite set of laws. If domains that cannot be well­ make specialized expertise more these laws are discovered and re­ formulated in mathematical terms generally accessible. To do so, duced to computer software, Dr. -either because they are not fully researchers are attempting to Simon believes machine intelli­ understood, as in medical diag­ understand how experts go about gence comparable to man's will nosis, or because the underlying acquiring and using knowledge. become a certainty in specific concepts are intrinsically non­ Principles of how knowledge ac­ areas of expertise. numerical. "Seldom are there crues and how it is retrieved in log­ To capture these higher level equations, in the mathematical ical sequence are extracted. They functions, AI researchers are de­ sense, that relate measurements are then programmed into the veloping a new approach. It IS of body parameters to the diag­ computer. called symbolic computation, a set nosis of disease," says Mr. Within the SUMEX-AIM system, of methods by which abstractions Thomas Rindfleisch, director of the the reasoning processes of physi­ can be expressed and managed in SUMEX computing facility. "Rather, cians, chemists, and other biomed­ the computer to solve non­ the process of diagnosis is charac­ ical scientists are being analyzed. mathematical problems. They em­ terized by a set of strategies hav­ At present, the ability of most pro­ phasize manipulations of symbolic ing to do with rules of experience grams is limited and much less rather than numeric information, and judgmental knowledge. These flexible than the corresponding and they use largely informal or rules govern the interpretation of human intellect. In specialized heuristic decision-making rules observations and guide decisions Dr. Herbert A. Simon, SUMEX-AIM advisor: sorting out the recipe of intelligence.

7 about what other information is come of research such as this at needed to determine the disease SUMEX-AIM is eliciting, organiz­ process involved." ing, and polishing a body of knowl­ For example, INTERNIST, a edge that rarely sees the light of diagnostic computer program in day," he says. "It is the knowledge the SUMEX-AIM network, is fo­ that underlies the expertise of cused on the broadest of medical practice, the knowledge that is specialties-internal medicine. It normally transmitted by a kind of analyzes patient cases by mimick­ osmosis process from master to ing the expert's reasoning process. apprentice. That knowledge will "The method used by physicians to now be codified, taught, used, and arrive at diagnoses requires com­ critiqued." In essence then, a key plex information processing which goal of artificial intelligence re­ bears little resemblance to the search in the SUM EX-AIM com­ statistical manipulations of most munity is to capture in computer computer-based systems," says programs the knowledge and Dr. Jack D. Myers, coprincipal in­ problem-solving abilities of ex­ vestigator of the project at the Uni­ perts. After studying this process in versity of Pittsburgh. "As a result, many specialized areas of exper­ the focus of research in this field of tise, Mr. Rindfleisch says, it may ul­ medical applications has shifted timately be possible to capture in during the past few years from computer programs something of models of statistical inference to the process of creativity and dis­ those using the heuristics of artifi­ covery itself. Programs then would cial intelligence." possess the ability to detect pat­ "In final form, INTERNIST will terns that establish order from amplify intelligence," Dr. Feigen­ chaos, to draw connections be­ baum says. It will supply expert tween seemingly unrelated ideas, advice to the general practitioner and to establish the principles for and physician's assistant, ac­ solutions to new classes of celerating and improving their problems. work. "An equally important out- Dr. Edward Feigenbaum, principal investigator of SUMEX-AIM: "The laws of expertise will be taught, used, and critiqued .•

8 In the millennium before Christ, called it, "the music of the amid the great cities and con­ spheres." He became the first to History quests of Greece and Rome, realize the importance of geomet­ dreamers and theorists were laying ric shape, which governs all nature of the groundwork for today's thinking from crystalline rock to the human machines. Like seed crystals in a body. In so doing, Pythagoras set Computing supersaturated solution, these the direction of mathematical visionaries drew from nature, as­ thought for centuries to come. sembling conclusions from obser­ Mathematics was soon regarded vations about the universe. Their as exact. It became the corner­ efforts brought important advances stone of all science. For centuries in mathematics, astronomy, and scholars believed that its logic was medicine. infallible. But in the 19th century Much of the early work in for­ the first inklings of doubt surfaced. mulating the laws of mathematics Two mathematicians, one in Hun­ may appear to have little connec­ gary and the other in Russia, es­ tion with the computer of today. But tablished irrefutably that it was im­ Abacus each step forward in this elaborate possible to prove Euclid's postulate science was indispensable to the of parallels, which states that no to ultimate arrival of the computer. more than one line parallel to a Pythagoras, a 5th century B.C. given straight line can pass philosopher known as the founder through a given point. Alternate ENIAC­ of Greek mathematics, was the theories sprang up, threatening to harbinger. He first described the scatter the focus of science. Math­ and Beyond "mystical significance of numbers" ematics, the mainstay of scientific and established the relationship certainty, was suddenly uncertain. between musical harmony and If there are two or more geomet­ mathematics. ries, which is right? Perceiving in the skies a regu­ After much thought and delibera­ larity similar to that of music, tion, Jules Henri Poincare, a 19th Pythagoras studied movements of century philosopher and mathe­ the heavenly bodies, or as he matician, found the solution. He Boethius (left) and Pythagoras: a fanciful battle between arithmetic calculatIon and the abacus.

9 answered simply that the question The Phoenician word ABAK, the of those who had gone before. is meaningless. Poincare, de­ name of a flat slab covered in sand An alternative to the use of scribed as one of the most eminent in which figures could be drawn, mathematical tables was soon scientific thinkers of his generation, provided the root for the English developed-an analog device asked, "Is the meter more true word. During Greek and Roman known as the slide rule, which than the foot? Are Cartesian coor­ times, the primitive abacus was a consists of two numbered scales dinates false and polar coordinates flat wooden board with counters. It mounted side-by-side in a manner correct?" One geometry cannot be developed into the now familiar ar­ to permit sliding them easily back more true than another, just more rangement of beads threaded on and forth. Whereas the modern convenient, he concluded. wires or laid in grooves. digital computer counts, the analog Through his philosophy, Poin­ With the advent of arithmetic device measures quantities. The care provided the flexibility neces­ signs in the 15th century, the popu­ slide rule scale is arranged so that sary for science to advance from larity of the abacus began to numbers fall at distances corre­ an age of scientific complacency. decline in Europe. John Napier sponding to their logarithms. Es­ Few realized the significance of further reduced the labor of long sentially, multiplication is accom­ Poincare's study of mathematical multiplication and division with the plished by adding two lengths truth. Even fewer guessed that, in invention of logarithms. Multiplica­ together. Division is done by sub­ 2 decades, absolutes of classical tion and division were then facili­ tracting two lengths. science such as space, time, and tated by adding or subtracting the As with all analog devices, the substance would become approx­ "logs" of numbers. accuracy of slide rules is limited by imates, and the most respected as­ Before this technique could be the accuracy of measurement. tronomer would agree that, if man widely used, accurate tables of Their use did not solve the problem could look deep enough into logs and antilogs had to be com­ caused by incorrect tables, but space, he would see the back of piled and printed. Despite valiant rather introduced a lack of preci­ his head. efforts by mathematicians to make sion. The solution, of course, was But the human mind is capable these tables accurate, the to produce reliable tables. of much more than just abstraction. drudgery of figuring , printing, and In 1812 this thought occurred Driven by the social pressures of copying the numbers led to errors. to Charles Babbage and John war, business competition, and Often, mistakes were handed Herschel, two young mathemati­ ego, labor-saving machines were down from generation to genera­ cians, while they were checking developed. The first mechanical tion as mathematicians built, all too logarithm tables for errors. As re­ aid to calculation was the abacus. faithfully, on the wobbly shoulders counted by Babbage in later writ-

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,. I. I. I f 3 I. '. I, I. I. I. g 0 00(• t · • ~ l r 111111, I f • I Schematic of the Analytical Engine designed by Charles 8abbage in the 19th century: a grand exercise in 10 futility. ings, he exclaimed: "I wish to God nical assistant. But these prepara­ was abandoned. If completed, the that these calculations had been tions cost money and the initial engine would have been a remark­ executed by steam." Herschel re­ sum provided by the British Treas­ able piece of work-2 tons of plied: "It is quite possible." And so ury soon dwindled away. Five brass, steel, and pewter, cut to occurred the idea that was to dom­ years after beginning the project, tolerances never before attempted. inate Babbage's life--elimination of Babbage was asking the govern­ Embittered by failure, Babbage, error through mechanized calcula­ ment for more money. His request a man of considerable wealth, hav­ tion. was granted. But again, the ing inherited £100,000 from his Because his ideas were so ad­ amount was not-and could not father, devoted much time and vanced and his standards so high, have been-enough. money to insulting and slandering Babbage experienced one disap­ After almost a decade of work figureheads of the scientific and pointment after another. In many and some £35,000 of government political establishment whom he ways the 19th century inventor's and personal monies, the project blamed for the engine's failure. But work belongs more to our time than to his own. Babbage's first project, the Dif­ ference Engine, was to be a large, complex adding machine designed for compiling mathematical tables. Unfortunately, the machine was doomed to fail. The mechanical tolerances required for the ma­ chine to work exceeded capabili­ ties of the time. The accuracy with which gears could be cut was in­ adequate. Clocks, the nearest me­ chanical cousins to the Difference Engine, were still laboriously fitted together by hand. Undaunted by this challenge, Babbage designed new machine tools. He hired and trained a tech-

Scientific American illustrates use of the Hollerith Tabulator in the 1890 census: the era of data-processing begins.

11 he did not abandon his goal. After again, Babbage's ambition had later formed IBM, Hollerith built 1833 Babbage elaborated on a transcended his time. Even with machines for sorting such cards, "gigantic idea" which he had first today's technology the engine comparing one to the other, and conceived while working on the Dif­ would be difficult to construct be­ printing data. To include more in­ ference Engine. If built, this mas­ cause of the mechanical toler­ formation for business use, Hol­ sive device, dubbed the Analytical ances required. Still Babbage's ef­ lerith increased his punch cards to Engine, would have been the first forts were not altogether in vain. the size of the dollar bill of his time, general-purpose computing ma­ His enthusiasm spread to others, which later became an industry chine. notably Herman Hollerith, who de­ standard. Babbage's scheme contained, Signed the first machine devoted to His inventions opened the door for the first time, most of the essen­ data processing. to an era of computing machines, tial features of the modern com­ Hollerith's machine, which used ushered in by the first efficient puter. An arithmetic unit called "the punch cards, was the easy winner key-driven calculating machine. mill" was designed to carry out ad­ in a contest staged by the U.S. Called a comptometer, it was built dition, subtraction, multiplication, Census Office to pick an efficient by Dorr E. Felt from a macaroni and division. A memory unit was to system for tabulating the 1890 box. have room for 1,000 numbers, census. His device completed the The rising popularity of calculat­ each 50 digits long-a capacity test in half the time needed by his ing aids and machines in business beyond technology until the first competitors, whose entries used characterized a shift in attitude to­ electronic computer appeared manual methods. ward the kind of work people could a hundred years later. Data in the form of "yes" or "no" or should do. Calculating machines Instructions and data were to be answers were translated onto soon entered into head-on compe­ fed into the machine on punch punch cards, which were compiled tition with people hired as "rapid cards, which had been invented in in a machine that electromechani­ calculators" by businesses trying to 1800 by Joseph Jacquard for use cally sensed positions of holes. keep pace with expanding mar­ with his automatic loom. After cal­ Cards passed under a set of kets. Besides the tedium associ­ culations were completed, resulting brushes that transferred a pulse of ated with mental calculation, health numbers would be printed up to 29 electricity through each hole to a was also a consideration. Mental digits. metal cylinder. calculators, as experts in the trade The Analytical Engine was as After forming the Tabulating Ma­ were called, often complained that farsighted and intricate in design chine Company in 1896, which was their evenings were haunted by as it was impossible to build. Once one of several businesses that unending processions of figures

The Great Brass Brain: predicting tides accurately and effiCIently in 1914.

12 shaped like numbers. Torres combined electromechani­ ocean tides on the basis of 37 fac­ William S. Burroughs, a bank cal calculating techniques with tors, displaying the results on dials. clerk, was forced to change principles of automata, demonstrat­ During the first World War, ships careers because the "monotonous ing that such machines can per­ used information from the machine grind of clerical work" had de­ form any desired sequence of to maneuver into shallow water stroyed his health. At the turn of arithmetic operations. and elude German U-boats. the century, Burroughs entered the Torres' electromechanical After World War I, Vannevar comptometer field and from his Arithometer, exhibited in 1920, Bush of the Massachusetts Insti­ early venture grew one of today's realized theories of automata that tute of Technology invented the dif­ major manufacturers of digital he had pioneered 7 years earlier. ferential analyzer, an analog device computers, Burroughs Corporation. Arithmetic problems were typed in assembled from gears, cams, and As the calculating machines by the operator, and the Arithome­ differentials that mechanically gained acceptance, more and ter printed the answers on a type­ completed the various functions more applications were found. One writer. Torres became the first per­ necessary to solve a differential called Millionaire, developed in son to use a system of time­ equation. Bush's machine was 1893 and widely used in business, sharing when he linked several applied to many different tasks, re­ found immediate and key uses in typewriters to one Arithometer. placing devices such as "network science. Percival Lowell began One of his other inventions was analyzers" built by utility com­ using Millionaire in 1905 to search a remote-controlled guidance sys­ panies in the 1920's to analyze for a "Planet X" located some­ tem that successfully steered a load requirements. These ma­ where beyond Neptune. Calcula­ boat through Spain's Bilbao harbor, chines produced scale models of tions were completed in 1914, but dramatizing the fact that machines power networks, but they could not the planet, later named Pluto, was could perform tasks formerly re­ predict large power surges that not sighted until 1930, 14 years served for human intelligence. Tor­ might cause blackouts. The differ­ after Lowell's death. res later built the first decision­ ential analyzer was the first ma­ At the same time that manufac­ making device-a chess-playing chine with such a capability. Its turers were converting to mass machine that matched a rook and success seemed to indicate that production techniques, Spanish in­ king against a human opponent's big, general-purpose analog com­ ventor Leonardo Torres y Quevedo king. puters would dominate scientific was demonstrating a theory that In 1914 Scientific American an­ calculation in the future. heralded the oncoming age of the nounced the arrival of "a great In the 1930's servomecha­ programmed machine in industry. brass brain" which computed nisms-automatic devices that Vannevar Bush and the 1930's differ­ ential analyzer: ., was trying to solve such problems of electric circuitry as the one connected with failures and blackouts in power networks. I had been thoroughly stuck because I could not solve the tough equations the investigation led to .•

13 controlled other machines by ears. At the inauguration of pas­ rettes, and could distinguish be­ monitoring their output-came into senger air service between New tween red and green with the aid of use. Oil refineries and syrup­ York and San Francisco, Willie a photoelectric cell. Sparko barked, production plants were among the made a speech, wished everyone wagged his tail, sat up, and first to use these "machines that bon voyage, helped start the en­ begged. boss other machines." As control gines, and after his official duties In the late thirties, engineers problems were reduced, more and were completed, relaxed with a turned their collective genius to more applications were found for cigarette in the company of a problems raised by the second the servomechanisms. Steam tur­ lovely model hired for the occa­ coming of world war. The U.S. bines, airplanes, and chemical sion. Army set out to improve differential processes were soon included in Eight years later, Willie's metal analyzers used at Maryland's the domain of the new device. cousin, Elektro, a stocky, tough­ Aberdeen Proving Grounds to cal­ As machines surprised society looking robot, appeared at the New culate firing tables for artillery bat­ with newfound abilities, their York World's Fair with his faithful teries. Modifications increased creators took to flights of fancy, companion Sparko, the first robot speed and accuracy by a factor of building robots in exaggerated dog. Elektro walked, talked, 80, allowing the machine to pro­ human forms. Inventors built tin­ counted on his fingers, puffed ciga- duce one trajectory every 15 min- can contraptions that walked, talked, and responded to me­ chanical commands. The robots' lifelike actions were an elaborate illusion, as they were controlled by simple automatic devices or, re­ motely, by human operators. As such, they were no more than novelties, commonly used in prod­ uct and company promotions or fairs. Willie Vocalite, built by Westing­ house in 1931 , was one of these. Willie had a stovepipe head, ex­ pressionless face, and cauliflower A. Elektro and Sparko en route to the 1939 New York World's Fair: tin-can contraptions that walked, talked, and responded to mechanical commands.

B. ENIAC, the world's first electronic computer, begins operation in 1946: an unwieldy collection of vacuum tubes and relays that could only be programmed by manually changing plug-and-socket connections and by setting switches.

14 utes as compared to the 20 hours The calculator was mainly used to the Ballistics Research Labora­ needed by a skilled mathematician. by the U.S. Navy for ballistics and tories. But the machine was limited by its ship design. Science and industry People were necessary to gen­ design to processing differential later used the machine to generate erate firing tables on Bush's differ­ equations: it could only calculate astronomical tables and specifi­ ential analyzer, and the human role the functions of vectors. cations for lens design. It was also slowed production. Completion of "There exist problems beyond used in military studies at Wright one table, on the average, took 2 our ability to solve, not because of Patterson Air Force Base and in or 3 months. theoretical difficulties, but because research for the Atomic Energy With the new machine, lengthy of insufficient means of mechanical Commission. and repetitive calculations for each computation," Howard H. Aiken A year before ASCC was fin­ 60-second trajectory could be said of the analyzer in 1937. He ished, John Mauchly and J. Pres­ completed in just 30 seconds. But then proposed a new kind of cal­ per Eckert, Jr., of the University of ENIAC was not completed until culating machine. Pennsylvania, proposed the next 1946, and the huge device, com­ In 1938 IBM began building a logical step in mechanized calcula­ posed of some 18,000 vacuum forerunner of the device for Har­ tion. First described as an elec­ tubes and 1,500 relays, was never vard University. It was called the tronic difference analyzer, the used for ballistic computations. It Automatic Sequence Controlled scientists predicted their new cal­ did find wide-ranging applications Calculator (ASCC). After its com­ culator would execute all functions in scientific calculation, however. pletion in 1944, the ASCC, in computing firing tables, produc­ Until the early 1950's ENIAC dab­ nicknamed Mark 1, became the ing each complete table in only 2 bled in weather prediction, atomic first automatic, general-purpose days. The device promised to get energy research, cosmic ray digital calculator. around a major failing of the differ­ studies, and thermal ignition. Mechanical switches called re­ ential analyzer by allowing input of Germany may have entered the lays routed electrical signals In the such data as atmospheric resist­ field of electronic computers ahead ASCC. During its 15 years of use, ance defined by numbers rather of America, although little is known ASCC proved to be a reliable and than by mathematical formulae. about the true dimensions or oper­ effective machine, but its more Built in secrecy at the University ation of these machines. The most than three-quarters-of-a-million of Pennsylvania, the new device, successful version, Z4, was de­ parts and 500 miles of wiring made which ultimately became known as stroyed in an Allied bombing raid. maintenance expensive and diffi­ ENIAC (Electronic Numerical Inte­ Designed by Konrad Zuse and built cult. grator and Calculator), was moved at the German Aircraft Research Institute, Z4 was used in develop­ socket connections and by setting EDVAC, EDSAC, JOHNNIAC ing the HS 293, a flying bomb switches; in Z4 by instructions (which was named for von launched from Nazi aircraft. punched into discarded 3Smm Neumann), SEAC, SWAC, and At the war's end, Zuse could not movie film. The concept of NORC were the first few to appear. convince Allied interrogators that software programming provided As computers became increas­ he had any scientific expertise to the basis for the next generation of ingly powerful, these machines offer, and his research came to a computers. moved into new areas. In his book sudden stop. Not until the midfifties The first machine with a com­ Cybernetics, Norbert Wiener ex­ did he resume his work, this time pletely "logical design," which von plored the potential uses of au­ as owner of a computer man­ Neumann described at the time of tomata. In 1948 W. Grey Walter en­ ufacturing company, which was ENIAC's construction, was to be tered the field of cybernetics (the later absorbed by a large German called EDVAC (Electronic Discrete comparative study of automatic electronics firm. Variable Automatic Computer). control systems) with an elec­ As technology flourished during While EDVAC was still under con­ tromechanical "tortoise" built to the 1940's, a major breakthrough in struction in 1948, ENIAC, after study simple reflex motion. "These the burgeoning field of computer special wiring modifications, be­ machines are perhaps the simplest science occurred. Although the came the first computer to embody that can be said to resemble ani­ exact source of the concept is the stored-program concept. Using mals," Walter wrote. "Crude though uncertain-John von Neumann, ENIAC's new capabilities, von they are, they give an eerie im­ Mauchly, Eckert, or British mathe­ Neumann and several pression of purposefulness, inde­ matician Alan M. Turing-it was meteorologists completed the first pendence, and spontaneity." suggested that instructions could computer-based weather forecast. Von Neumann, decidedly a be stored as numbers in the ma­ Computations for the hydrogen "software scientist," hoped to use chine itself. The idea raised the bomb were begun on ENIAC and automatic machines such as the mechanized kingdom several completed on its successor MANI­ modern computer to draw conclu­ rungs on its evolutionary ladder. AC (Mathematical Analyzer, sions about complex natural or­ For the first time, logical choices of Numerical Integrator and Com­ ganisms. He built on the idea of program sequences would be puter). MANIAC was one of many the Universal Turing Machine, ad­ made inside a machine. stored-program computers that fol­ vanced by Turing in 1936. Turing Earlier, programming ENIAC and lowed in the wake of the new pro­ described, in theory, a machine Z4 had been extremely tedious: in gramming concept, although each that could do any calculation within ENIAC by changing plug-and- differed considerably in design. the realm of human intellect. The

A modern integrated circuit: putting 4o-times the memory of ENIAC on a chip the size of an aspirin.

l 16 Universal Turing Machine, which tubes and magnetic drums for in­ square, the lid restraining wide­ contains ideas later built into all formation storage and vacuum spread application of computers general computing machines, pro­ tubes for logic and arithmetic func­ blew off. Private business began vides a standard for measuring the tions, experts in the field had esti­ using computers to process orders, complexity of a computer. mated that only some 50 com­ inventories, and payrolls. Com­ Around 1950 the computer panies would eventually find use puters set copy for newspapers emerged as a general tool. It had for computers. and processed checks for banks. become applicable not only to mili­ But with the development in the Airlines used computers to make tary use, but also to functions in late fifties of computer languages, and record seat reservations. government, industry, commerce, which simplified programming, and Even in medicine, an area best science, education, and social sci­ with the introduction of integrated characterized as inexact and highly ence. The computer's spectacular circuits in the midsixties, compres­ subjective, computers fitted into growth in capability, applications, Sing the equivalent of 1,400 tran­ very specific and important niches. and numbers surprised most sistors, resistors, and diodes onto Applications have included such people. In 1954, using cathode ray silicon chips an eighth of an inch areas as electrocardiogram analy- sis systems, aids for managing gence (AI) to biomedical problems. intelligence. clinical routines, and instrument At Stanford University, under the The first attempts to use ACME data collection. Statistical cluster­ direction of Nobel Prize winner Dr. for AI were undertaken at Stanford, ing techniques were applied to Joshua Lederberg and Dr. Edward and DENDRAL was the first major diagnostic programs and were one Feigenbaum, a team of scientists effort. In the beginning the ma­ of the first diagnostic approaches began the development in 1966 of chine's size and speed were suffi­ to prove useful in medicine. DENDRAL, a chemistry program cient. But as DEN ORAL grew, and Just as these new methods of whose offspring now rivals experts other research was added, more numerical calculation were being in figuring out the structures of cer­ and more computing time and tested, the first inklings of a new tain organic molecules. DEN ORAL memory space were required. By approach to computing were intro­ was the unlikely outgrowth of a the early 1970's, Stanford's AI duced. The first application of this system c:tlled the Advanced Com­ needs completely outstripped the approach-symbolic computing­ puter for Medical Research machine's capacity and DENDRAL was the establishment of data (ACME), which had been sup­ appeared to be doomed. banks stocked with patient informa­ ported by the Biotechnology Re­ During this period Dr. William tion. It was an application of sym­ sources Program (BRP) of the NIH Baker of the BRP arrived for a site bols to algorithms, matching Division of Research Resources visit. In light of ACME's inadequate names to numbers, and it carried (ORR) since 1965. Originally capacity and the interest in AI at along the guarantee that if ACME was dedicated to real-time Stanford and elsewhere around the pattern-matching was properly analysis of data gained during nation, Dr. Baker suggested that applied, the answers would be biological and clinical research. ACME be dropped in favor of a found. The computer was oriented entirely system devoted to the develop­ But medical diagnosis, on the toward numerical calculation, or ment of this new type of comput­ same level as practiced by the batch processing of biomedical re­ ing. Stanford applied for a grant, physician, required much more in search data. another site visit was made, and the way of programming tech­ By the midsixties, prinCipal in­ the National Advisory Research niques. To grapple successfully vestigator Dr. Lederberg believed Resources Council of the NIH rec­ with the problem, prototypes of that ACME had proved its worth as ommended funding. A machine high level analysis and symbolic a data analyzer. At the urging of Dr. designed to handle symbolic com­ representation were developed. Feigenbaum, he proposed that the putation was installed and, through Many of these resulted from early system host a new type of com­ the use of a nationwide communi­ work in applying artificial intelli- puter science application, artificial cations network called ARPANET,

"All these delays-a thousandth of a second here, a millionth of a second ther&-we'li have to get the darn thing fixed."

i f J 18 i a national computer community in medicine, biochemistry, or full stride, as will the trend toward was established. An advisory psychology. miniaturization, which made com­ group, Drs. Lederberg, Feigen­ Today's AI experts believe that puting available to the general pub­ baum, and Baker, recommended computers will find many non­ lic. A single silicon chip, measuring that 40 percent of the computer's professional and small business only a few millimeters square, will capacity be made available to applications as the potentials of the be able to follow 20 million instruc­ Stanford researchers, another 40 field become better understood. tions per second, using 10 million percent spread among the national Home computers may someday cells of internal memory storage. community, and the remainder as­ regulate heating and cooling sys­ And just as imagination and signed to development of the new tems, notify fire or police depart­ hardware have gone hand in hand system. ments in emergencies, and do tax since the early 1900's, scientists In 1973 SUMEX-AIM was formed statements, among other chores. predict that programming tech­ as a community resource for the At work, letters will be typed, or­ niques and the science of software development of AI techniques. ders placed, bills paid, and files will keep pace with developing From its inception, the resource searched by computer. At neigh­ technology. has been supported by the NIH borhood shopping centers, payroll Division of Research Resources' records will be maintained and Biotechnology Resources Pro­ stock automatically reordered ac­ gram. Drs. Lederberg and Feigen­ cording to need and profitability. baum directed the network that Some scientists characterize this was to become a major medium for revolution as a race to put more the development of projects like and more function, processing DEN ORAL among a national group power, and storage capacity onto of biomedical researchers. In mid- each semiconductor chip. Since 1978 Dr. Lederberg left to become the midsixties, the amount of func­ president of The Rockefeller Uni­ tion on a chip has risen by a factor versity. He remains an advisor of of 10,000. The cost of a chip, SUM EX-AIM. Dr. Feigenbaum is meanwhile, has remained approx­ now principal investigator of the imately constant at $5 to $50. resource, which currently includes By the end of the century, com­ some 20 autonomous projects, puter buffs predict, this trend of each targeted for application broadening applications will be in

19 In the course of 30 years the medical diagnosis, because com­ Processes computer has graduated from prehensive mathematical formula­ vacuum tubes and mechanical re­ tions do not exist. For example, the lays to silicon chips, each one no relationship of a symptom-such of larger than a pencil eraser. But the as "burning pain in the upper transition from ENIAC, one of the abdomen"-to disease diagnosis Computing first electronic number-crunchers requires the manipulation of sym­ of the late forties, to the "thinking" bolic information. machines of today required more Projects currently in SUMEX­ than advances in hardware. It re­ AIM include areas of medicine, quired advances in programming biochemistry, and psychology. The concepts. key goal of an AI program is to ex­ Over the last few decades, there plain conclusions and allow the has been an increasing emphasis professional to interact in the deci­ on the design of knowledge-based sion process. systems. At the lowest level, these As a result, AI programs depend programs differ from traditional largely on decision-making strate­ The programs in two key ways. They gies composed of heuristics, or emphasize manipulations of sym­ rules based on judgment and ex­ Heuristic bolic rather than numeric informa­ perience, which are expressed tion, and they use largely informal symbolically. These strategies or heuristic decision-making rules starkly contrast with numeric com­ Mind gained from real-world experience putation, which is largely al­ rather than mathematically proved gorithmic, following a mathe­ algorithms. At a higher level, these matically fixed set of procedures tools of symbolic processing are when evaluating functions or used to construct understandable tabulating results. However, the lines of reasoning in solving prob­ two classes of computation are not lems and to interact with human totally dissimilar. users. Clinical flowcharts are al­ Symbolic computation is neces­ gorithms used by diagnosticians sary in certain domains, such as when deciding how best to man-

20 age a patient. Often these fixed groups of patients to produce tients. In systems such as this, the procedures are designed by expert statistical summaries. analysis of alternatives and the de­ physicians for use by paramedics Although the earliest systems cision about the best therapy are charged with performing certain seldom did more than maintain solely up to the physiCian. routine tasks. As such, data are records, there have been recent at­ More complex decision-making represented symbolically. Because tempts to create programs that can programs attempt to assist the clinical algorithms are relatively complement this function by ana­ physician in evaluating the best simple, computers are seldom lyzing the stored information. treatment strategy. The decision necessary. ARAMIS (American Rheumatology criteria used in such programs take But automated record-keeping Association Medical Information various forms. Some decision rules and data banks, more intricate System) is one of the most suc­ may have rigorous statistical jus­ examples of the clinical algorithm, cessful projects in this category. In tification, while others may be only require the computer. In these sys­ addition to search and statistical approximate rules based on tems, patient names and histories functions, the data bank offers human experience and judgment. and other relevant information are analysis of prognosis as it relates These latter strategies are called manipulated as symbols, and are to a specific type of patient. Pro­ heuristics. Each type can be effec­ connected to numeric data that grams systematically search the tive in providing solutions to prob­ give specific values to the data base to locate case reports lems. information- for example, patient and summarize the outcomes of In statistical approaches to diag­ age: 21 . Pattern-matching al­ various alternative treatments, noses, the decision criteria have gorithms can be used to locate matching recorded case histories records of similar individuals or with descriptions of current pa-

The ARAMIS data bank: meeting needs in the study and practice of rheumatology. (Abbreviations: A/= ar­ tificial intelligence, ARA = American Rheumatism Association, CCC =cooperating clinical trials committee of the ARA, SLE =sys­ temic lupus erythematosus, SCCS =scleroderma cooperative criteria study, JRA =juvenile rheumatoid arthritis, Canadian RA = Canadian Rheumatism Association, UDB =uniform data base for rheu­ matic disease, FDA = Food and Drug Administration, VA = Veterans Admin­ istration.)

21 been codified to a certain degree. tree are of two kinds. At decision reasoning techniques. The objec­ Baye's theory of probability is one nodes, the clinician chooses from a tives have been to capture the example. Essentially, Bayesian set of possible actions. One action judgmental or heuristic knowledge analysis relates specific patient might be deciding to perform a cer­ of experts for decision-making, and data to different disease signs ex­ tain test. At chance nodes, the to construct reasoned and explain­ hibited by selected groups of pa­ possible responses of the patient able solutions for diagnostic prob­ tients. In establishing these rela­ to some action that has been taken lems. Generally the logic built into tionships, it is sometimes possible are represented. When performing these programs is composed of six to compute the most likely cause a diagnostic test, the patient's major elements. for symptoms observed in a pa­ response-whether he develops tient. complications, for example-is a • Plan-Generate-and-Test. In this One of the earliest such pro­ matter of statistical likelihood. By framework, the program uses grams, developed in the 1960's, using the decision tree, a clinician heuristics to select the general was used to diagnose congenital can come to a more informed con­ area in which the answer is likely heart disease. In some case clusion about the range of alterna­ to be found. It generates plausi­ studies, the program reached tive strategies. ble solutions within these boun­ diagnoses with accuracy compara­ Modifying the tree by attaching daries, and tests conclusions ble to those rendered by two expe­ patient-oriented values to decision against observed data, appro­ rienced physicians. As researchers nodes makes the simulation more priately revising conclusions until honed and polished the program, realistic. For example, a definitive one that best fits the data is un­ applications for other disease diagnosis might not be pursued if covered. areas were discovered. Today the required tests were expensive • Domain-Specific Knowledge. many types of diagnostic programs and painful, if the health of the pa­ Much of the power that using Bayesian analysis are in op­ tient were not threatened by this decision-making programs hold eration. But Bayes' theory is just inaction, and if rendering a defini­ is derived from specific rules and one of several techniques used in tive diagnosis would not signifi­ knowledge about the target area medical decision analysis. cantly improve his health. of application. Such knowledge Another displays sequences of The effort to develop these ap­ bases encode factual informa­ steps representing various possi­ plications into programs using arti­ tion about the domain and the ble actions and events. Sequences ficial intelligence began in the early heuristic rules used by experts of this type resemble tree-shaped 1970's. The intent was to focus to rapidly find solutions to prob­ networks. Nodes or junctions in the primarily on the use of symbolic lems.

"Why don't you check with the local data bank?" 22 • Flexible Knowledge Base. If edge representing varied points chosen properly, the knowledge of view can speed the process of base is small enough to be han­ locating a solution and reduce dled adequately by the com­ the chance of overlooking alter­ puter, but large enough to be native solutions. meaningful to the prospective • Explanation. The program must user. Once the basic program is be able to explain the line of operating, knowledge can be reasoning that led to its conclu­ added, removed, or changed by sions. If not, the user cannot using an explicit and flexible en­ understand the basis for the coding of the knowledge. program's conclusions. Also, • Line-ot-Reasoning. Specialists through the explanatory function , in the target area of an applica­ flaws in the program's logic can tion must be able to follow the be located and fixed without ex­ logic used by the program when tensive study. it generates conclusions. Al­ Over the last decade, computer though not strictly necessary, scientists have used these ele­ specialists should also agree ments to build many types of pro­ with the route chosen. To ac­ grams. Some include the ability to complish these goals, computer learn. Others emulate creativity. scientists in SUMEX-AIM team Those in the SUM EX-AIM network up with experts in target fields to are devoted to expert problem­ learn the mechanics of reason­ solving in medicine, biochemistry, ing. Human logic is then trans­ or psychology. lated into computer language in the form of symbolic rules . • Multiple Sources ot Knowl­ edge. Often several practitioners lend their expertise to the design of AI programs. Textbook knowl­ edge is usually incorporated as well. Having access to knowl-

23

-~~-- - A typical strategy in some AI re­ because these problems are search is to choose a problem that open-ended and rich ." SUMEX is tightly focused and easy to con­ The key to designing a success­ ceptualize, such as a game. This ful AI project, he says, is to pick a and the approach offers certain advan­ problem limited enough to be con­ tages, most notably that ideas can quered, but not so simple that the Science be tested with minimal expense of program designed to solve it can­ time and money. not be expanded into a practical Community These games are called toy tool. Most of the time, projects in problems because they serve no SUM EX-AIM are restricted to a practical use. An example is the subsection of an intended area of missionaries' dilemma, a puzzle in application. When that segment is which three missionaries want to adequately covered, boundaries cross a river, but their efforts are are carefully extended. stymied by an equal number of An equally important criterion cannibals. A boat that holds as calls for an association between many as two people is available, the project and at least one expert but the missionaries must never be from the target field of application. The outnumbered, or they will become The collaboration must be a dedi­ the main course of that evening's cated one, according to Dr. Seeds of cookout. Feigenbaum. "You cannot have the Projects in SUMEX-AIM gen­ kind of inspirational meeting of Artificial erally shun toy problems. "Their minds needed for a project to suc­ use leads to sterility in that you ceed if the specialist and pro­ Intelligence quickly figure out the solution, but grammer meet every once in a are not faced with the additional while," he says. "It takes a challenges that a messy world pro­ quarter-time to half-time effort by vides," Dr. Feigenbaum says. "We the expert that stretches over a seek our inspiration from programs number of years." directed at diagnosing disease or The seed from which SUM EX­ assisting biologists in planning AIM grew embodies this type of DNA manipulation experiments, collaboration. Known as DEN-

A. The missionaries' dilemma: use of such toy problems in AI research is not productive. B. A technician in the Stanford mass spectrometry laboratory: generating data for use in DENDRAL.

24 ORAL, it began in 1966 when Dr. therefore, must be expressed tion of undesired substructures Feigenbaum told Dr. Joshua symbolically, Dr. Feigenbaum says. which, based on chemical or Lederberg, then chairman of the To achieve this, it is necessary to energetic grounds, are implausible. Stanford genetics department, develop techniques by which sym­ Drs. Lederberg and Feigenbaum about his interest in modeling sci­ bols can be represented and quickly realized the power provided entific thought with AI techniques. manipulated. But when oENoRAL by supplying several sources of Chemistry was chosen as the was conceived some 15 years ago, knowledge when analyzing target field for two major reasons. artificial intelligence was truly a molecular structures. In an early First, much knowledge in the field fledgling discipline. case run on DEN ORAL, con­ already existed in machine­ straints based on organic chemis­ readable form. Second, chemistry Biochemistry try principles alone would have was the field in which Dr. Leder­ admitted 1.25 million plausible berg was expert. When the project DEN ORAL candidate structures for a single grew in scope, Dr. Carl ojerassi, The project was initially begun compound under study. The scien­ Stanford professor of organic as a prototype to demonstrate that tists responded by adding informa­ chemistry, was recruited. computerized symbolic reasoning tion from proton NMR analyses, Applying AI to science was inevi­ could be successfully applied to from which the program could infer table, according to Dr. Feigen­ molecular structure problems in a few additional constraints. "The baum. "As the computer grew in chemistry. The program illustrates set of plausible candidates was power and the cost of its use de­ well the evolution of AI work. then reduced to one-the right creased, more and more spe­ In solving problems, DEN ORAL structure!" Dr. Feigenbaum recalls. cialties looked to the computer for uses instrument data from a mass "This w,s not an isolated result but assistance in information process­ spectrometer (MS) and a nuclear showed up dozens of times in sub­ ing," he says. "But very few spe­ magnetic resonance (NMR) spec­ sequent analyses." cialties in medicine and other fields trometer, together with other con­ The original DEN ORAL program of science could be modeled by straints on structural features in the was restricted to a small number of formulas and calculations, which molecule. These constraints de­ molecular families for which the are the traditional means of exploit­ scribe configurations of atoms and program had been given a special­ ing the computer." provide limits within which the an­ ist's knowledge, "namely the Programs of this type must em­ swers, structural candidates for an families of interest to our chemist­ ploy processes similar to those unknown compound, must fit. Such collaborators," Dr. Feigenbaum present in human reasoning and , constraints eliminate the produc- says. "Within these areas, DEN-

25 ORAL's performance was usually must be examined, since the data ford chemists Drs. Carl Djerassi not only much faster but also more are used mainly to verify possible and Dennis Smith , the DEN ORAL accurate than expert human per­ answers. project has evolved into one of the formance." DEN ORAL's primary limitation best known and most successful Dr. Bruce Buchanan, a member was its restriction to only a small applications of artificial intelli­ of the DENDRAL team, explains subset of organic molecules, th e gence. The CONGEN program and the general approach of DEN­ saturated, aliphatic, monofunc­ related subprograms aid chemists ORAL. "There are three phases­ tional compounds. Work carried in determining the molecular struc­ plan, generate, and test," he says. out after DENDRAL's early suc­ ture of unknown organic com­ "In approaching a problem, DEN­ cess has focused on the pounds. Because the molecular ORAL makes some rough guesses structure-generation aspects of the structure of a compound must be as to what the solution..should look plan, generate, and test paradigm. known before its other properties like. That is the planning phase. From this paradigm, the structure can be studied-properties related The generation phase works within generator, called CONGEN for to pharmacology or toxicology, for the established constraints of the CONstrained structure GENera­ example-DEN ORAL promises an plan to develop plausible solutions. tion, has been extracted. CONGEN important contribution to biomedi­ Finally, each plausible solution is is the segment of the main pro­ ci ne. Some investigators have al­ tested." gram that is not closely tied to spe­ ready capitalized on th is offer. Testing is accomplished in two cific instrumental data and is, During the past 5 years the steps, which follow a "model-driven therefore, of greatest use. CONGEN program has been used strategy. " First, the computer gen­ "Chemists have many sources of successfully by chemists working erates sets of instrument data that data for both planning and testing, on biomedical problems at Stan­ would be expected to describe so the use of DENDRAL as a ford and other institutions. About each candidate structure. These whole, which would restrict them to two dozen scientists use the pro­ sets are then compared to actual NMR and mass spectral data, gram each year when solving data about the compound. The would be a hindrance," Dr. Bu­ questions about the structures of closest fits are retained and ranked chanan says. "That is why, in the compounds. Investigator affiliations accordingly. Having enough knowl­ last 3 years, almost all the effort on are split about 50-50 between uni­ edge about the characteristics of a the project has gone into develop­ versities and private industry. The certain type of compound to do ing CONGEN, since it has the program has been exported to model-driven analysis drastically widest possible applicability." several laboratories in the United reduces the amount of data that Now under the direction of Stan- States. The British government is

26 now supporting work at the Uni­ versity of Edinburgh aimed at link­ ing industrial researchers in the United Kingdom with CONGEN. A copy of the program now runs on the Edinburgh computer. A col­ league at the Australian National Research Organization is also spearheading an effort to make CONGEN available in that country. More recent research efforts have been directed to extending CONGEN's representation of struc­ ture even further. The program will soon include principles of molecu­ lar stereochemistry, or three­ dimensional representation of structures. Stereochemistry is ab­ solutely essential in understanding structures and interactions of molecules in chemical and bio­ chemical systems, Dr. Smith ex­ plains. This new work is pointed toward a system of computer­ based planning and testing which incorporates chemical and spec­ troscopic data from several differ­ ent techniques. As the forerunner of AI's shift to knowledge-based analysis, OEN­ ORAL holds a special place in computer history. It demonstrated CONGEN printout: currently one of the most successful applications of artificial intelligence, this program helps chemists determine the molecular structure of organic com­ pounds. the superiority of domain-specific type of compound by examining spectrometry (MS) . Meta­ knowledge as a means to achieve data from a set of examples. DENDRAL also includes evidence expert performance and in so These rules can then be used to supporting each fragmentation rule doing raised important issues interpret data concerning unknown and a summary of contradictory concerning knowledge representa­ organic compounds. Both DEN­ evidence. Constraints, fed in by tion, acquisition, and use. DRAL and meta-DENDRAL use chemists, guide generation of rules But, more important than its ob­ the same rule-based logic. Criteria along desired lines. vious contributions, the program set up by expert chemists guide The program, like DENDRAL, demonstrated that AI concepts and meta-DENDRAL's generation and uses the plan-generate-test programming techniques were ad­ selection of rules. framework. The process includes vanced enough to produce useful Dr. Feigenbaum says the pro­ three steps: interpret the data and tools, although each could deal gram was evolved from DENDRAL summarize evidence; generate a with only one limited specialty. This for two reasons. First, it was de­ set of plausible candidates; test example of competence, according cided that DENDRAL has laid a and refine the set of plausible to Dr. Feigenbaum, vastly im­ foundation firm enough to pursue rules. proved the credibility of AI and the deeper study of scientific In the first step, meta-DENDRAL paved the way for other such sys­ theory formation. Second, it was cites each piece of MS data as a tems. "For us, the DENDRAL sys­ recognized that acquiring expert highly specific point of fragmenta­ tem has been a fountain of ideas, knowledge of a specific domain tion, then sums up the evidence many of which have found their was the bottleneck in building pro­ supporting such fragmentation and way into our other projects," Dr. grams targeted for real-world use. the configurations that would Feigenbaum says. Meta-DENDRAL was originally cause these atoms to separate. intended to complement the parent The next step is a heuristic search program. Its job was to formulate for general rules that govern the Meta-DENDRAL rules for interpreting data from fragmentations. The search begins The project in SUMEX-AIM most mass spectrometer analyses. In with the single most general rule closely associated with DENDRAL, such analyses, molecular frag­ and proceeds toward more de­ as might be expected by its name, ments are separated according to tailed specifications. This process is meta-DENDRAl. Developed by mass and electrical charge. continues until the program de­ Dr. Buchanan, professor of com­ Meta-DENDRAL's output is sets of cides that the rules being gener­ puter science at Stanford, the pro­ rules that describe how molecules ated are becoming too specific. gram learns rules about a specific fragment when studied with mass Meta-DENDRAL also includes a Dr. W. Todd Wipke, principal inves­ tigator of the SEeS proJect: design­ ing syntheses faster and without the bIas of past experience.

28 criterion for deciding whether an was accomplished, largely reor­ "Using SECS, chemists should emerging rule is too general. ganizing the methods by which be able to design syntheses faster In the final stage, the program the program works. With these and without the bias of past expe­ tests candidate rules, comparing changes, the ability to generate rience," he explains. "Many more positive and contradictory evi­ rules concerning a different type of possible syntheses will be consid­ dence. Those with a negative bal­ data, carbon 13 nuclear magnetic ered because of the system's ex­ ance are disregarded. Rules with resonance, was included. Several tensive library of chemical reac­ redundant features or supported papers were published in 1979 on tions, which is larger than any by the same evidence are merged. the rules generated in this area. person can remember. And the The end result is a rule-set of computer can better process and comparable quality to those that SEes record the many structures that will could be generated by human ex­ result." perts, according to Dr. Buchanan. The SECS (Simulation and Through on-site terminals or "In some tests, meta-DENDRAL Evaluation of Chemical Synthesis) telephone links, investigators from recreated rule-sets that we had project is aimed at describing the university, industrial, and private previously acquired from our ex­ logical principles used when con­ laboratories are now using SECS. perts during the DENDRAL proj­ structing molecules. Developed Versions of SECS are available by ect," he says. "In a more stringent primarily by Dr. W. Todd Wipke, a accessing SUMEX-AIM, or at the test, involving a family of com­ chemist and computer scientist at University of Pennsylvania Medical pounds for which the mass­ the University of California, Santa School, the International ADP spectral theory had not been com­ Cruz, SECS is intended to promote Network Computers, or Merck & pletely worked out by chemists, the the development of new and Company, Incorporated, among program discovered rule-sets for modified drugs, as well as syn­ others. Dr. Kenneth Williamson of each subfamily." thetic compounds modeled after Mount Holyoke College used These rules were judged by ex­ those that occur naturally. In par­ SECS to build three-dimensional perts to be "excellent." A paper ticular, the project is concentrated models of some 50 compounds describing them was published in on assisting the chemist to design particularly important in nuclear the American Chemical Society and select syntheses of biologically magnetic resonance spectroscopy. Journal in 1976. important molecules. Dr. Wipke Other scientists have successfully Emphasis during the past year says the computer offers several used the program to design chemi­ has been to make meta-DENDRAL advantages over conventional cal syntheses. One chemist used more efficient. A major overhaul methods. SECS to develop procedures for making synthetic morphine. natural target molecule and con­ use the chemist and the computer "These users have given us a lot structs a three-dimensional model as a team and to have each team of suggestions for improving the for display on a graphics terminal. member doing the tasks for which program," Dr. Wipke says. "Some Based on the analysis, SECS that member is best suited. A lot of have contributed new reactions draws from its knowledge base to AI has been directed at how to and quite a few people from indus­ select reactions that could be used make the computer do the whole try have actually contributed labor in the last step of the synthesis and thing with very little emphasis on to the project-quite sophisticated then backtracks through the re­ presenting intermediate results to labor. In one case, an organic quired precursors. the user in a form that allows the chemist from Hoffman-LaRoche "The system stimulates the search process to be guided, inter­ who had worked in the field of chemist's own creativity," Dr. Wipke rupted, stopped, or redirected." heterocyclic chemistry for 10 years says. "It presents many different Dr. Wipke and colleagues, spent a year endowing the pro­ and unbiased approaches to the mostly synthetic-organic chemists, gram with his knowledge of synthesis." The chemist guides the are currently expanding the pro­ chemistry. " computer through the process by gram to include more complex The scientist's lack of experience pointing out the most interesting strategies for designing syntheses. in computer science was not a techniques. "Essentially, the program will have problem because SECS uses a "This is a unique feature of our a more precisely directed search, special language called ALCHEM, project in terms of AI research. and it will be more selective in which was developed by Dr. Usually programs are designed to what it generates," he says. Wipke's group. He says it is com­ find one good way to accomplish a But before these strategies can posed of declaratives that describe task. We are interested in finding be put into the computer, they must how the environment of molecules all the good syntheses, and that be explicitly defined, which is often influences chemical reactions. involves dealing with plans, plans difficult to accomplish. For in­ "A chemist can understand the that have many branches and stance, strategies based on princi­ language and read a reaction with many contingencies," he says. ples of symmetry are learned from only about 5 minutes of explana­ There is another feature that experience rather than from tion," he says. "To actually use the sets the project apart from others textbooks, Dr. Wipke explains. For language well takes only a couple in the field, according to Dr. Wipke. the computer to recognize a sym­ of days." "Our program is interactive. We are metrical design, these principles When working on a problem, the tackling the problem of synthesis must be dissected and reassem­ program studies data about the from the viewpoint of how best to bled in the form of software.

30 Unlike the current version of the study of metabolism. Based on angle using the amount of metabo­ SECS, which uses ALCHEM to technology from the SECS pro­ lite that was obtained." express rules concerning chemical gram, a new computer program In recent months problems have reactions, strategies will be written called XENO has been developed been submitted to the program to using mathematical equations. Ex­ to predict metabolic pathways for test its ability to predict metabo­ preSSing knowledge in this form xenobiotic compounds-chemicals lites. Dr. Wipke says XENO has will allow the Wipke team to build not normally found in the body. The been fairly successful at identifying an explanatory function into the objective is to predict plausible metabolites found in laboratory program. If questioned by the metabolites of a given xenobiotic. studies, and also predicts metabo­ chemist as to why a certain reac­ "What you put in is the chemical lites that have not been found. tion was chosen for the synthesis, structure of the foreign compound," When discrepancies occur, Dr. the computer will be able to reply, he says. "What you get out is the Wipke says, they sometimes can citing strategies of chemistry. chemical structure of the metabo­ be traced to errors in the knowl­ In final form the strategy portion lites." edge base. "The computer may of the program will complement the Predictions of plausible metabo­ predict more metabolism than is part that deals only with reactions. lites result from knowledge of how actually going on in living sys­ "The current program decides what compounds are activated by en­ tems," he says. "That's really not to do by consulting a list of goals," zymes. Many of the mechanisms too bad, because the metabolites Dr. Wipke says, "and that goal list involved in these processes are that can be isolated will always be will be created by this higher level known and more are being discov­ included in the set of metabolites reasoning process which picks out ered. predicted by the computer. The the strategies applicable to the In addition, the metabolite's program defines a set of candi­ situation and explains why. The stereochemistry is predicted. A dates to look for." program will then select ways to compound may exist in two forms, Dr. Wipke and colleagues have implement the strategies and, fi­ each the mirror image of the other. now focused on expanding the nally, decide how to modify the One may be active while the other knowledge base, particularly to in­ molecule's structure. This multi­ is not, or they may both be active clude models of more species. step procedure allows a view of the but produce different effects. Only the rat and the mouse are problem free from human bias." "Stereochemistry in metabolism currently described in detail. Dr. Wipke hopes to demonstrate is a new frontier," Dr. Wipke says. An index of biological activities that computer-based synthesis "In the past, instruments were not associated with metabolites-for techniques can also be applied to sensitive enough to explore this example, carcinogens-is slated SEes printout: helping the chemist design and select syntheses of biologically important compounds.

31 for inclusion. The function will ment is primarily under the direc­ synthesis experiments in which apply pattern recognition to com­ tion of Drs. Laurence H. Kedes and methods for building molecules will pounds not listed in the index as a Edward Feigenbaum, computer be described. Functional analyses means of classifying metabolites. scientists Drs. Mark Stefik and will be added as well, allowing the The XENO project is not the only Peter Friedland, and biochemist Dr. program to identify the products of spin-off from SECS. In 1978 the Doug Brutlag. MOLGEN's task is nucleic acids. SECS program led to development to advise geneticists about the de­ The success of MOLGEN as an of a daughter project that extends sign of laboratory experiments. experiment designer depends on computer-assisted synthesis into These include methods used to the quality of its knowledge base. phosphorus chemistry. Under the analyze and modify nucleic acids. Much effort has been expended to direction of Dr. Wipke, Drs. Gerard MOLGEN is mainly focused on supply the base with explicit infor­ Kaufman and Francois Choplin at organizing experimental tech­ mation about DNA structures, the University of Strasbourg in niques and determining the order restriction enzymes, a hierarchy of France created a knowledge base in which they should be applied to laboratory techniques, and a grow­ composed of reactions pertaining achieve specified goals, Dr. Brutlag ing collection of genetics-oriented to phosphorus. In analyzing sev­ says. "The enormous volume of strategies for discovering informa­ eral compounds and searching the detailed knowledge makes it likely tion about various aspects of DNA appropriate literature, the new sys­ that good experiments are being molecules. Most common ana­ tem found most of the existing missed," Dr. Feigenbaum says. lytical and manipulative methods syntheses and, more importantly, "We believe that an intelligent have already been put in the base. suggested new techniques that planning assistant can offer help in Results of the research include appear to be equally good or bet­ anticipating the results of combin­ some special-purpose programs in ter, according to Dr. Wipke. ing experimental methods in many the area of molecular genetics. ways." The most useful are highly refined MOLGEN Dr. Peter Friedland says versions of previously existing MOLGEN makes near-expert deci­ strategies. Many of these concern Experiment-planning in the sions when selecting phYSical determination of the sequences of manipulation of DNA is the goal of methods, such as electron micro­ nucleic acids in DNA. Modifications MOLGEN, a Stanford project being scopy or enzymatic modification, to are focused on technical aspects conducted in collaboration with analyze molecular structure. Even­ of the programs; those leading to scientists at the University of New tually the program will be ex­ improved efficiency, for example, Mexico (UNM) . Program develop- panded to include the design of and those addressing human en-

DNA's spiral ladder of heredity: help­ ing chemists manipulate the molecule through well-planned ex­ periments is the focus of MOLGEN.

32 gineering concerns to make it density maps, is the goal of the ployed. Rather, the system pieces easier for scientists not familiar PROTEIN STRUCTURE project at together hypotheses by concentrat­ with computers to use the pro­ Stanford. Electron density maps ing successively on specific areas grams. are data representing the struc­ of the protein. The project is under In addition to its applied orienta­ tures in three dimensions. Unfortu­ the direction of Drs. Feigenbaum tion, MOLGEN includes an AI re­ nately, these maps are usually and Robert Engelmore of Stanford search dimension: use of the crude and ambiguous. As a result, University with assistance from Mr. knowledge domain of molecular the program depends largely on Allan Terry, at the University of Cal­ genetics to create a generally ap­ background information, such as ifornia (UC) Irvine, and the strong plicable problem-solving program. the amino acid sequence in a pro­ collaboration of Dr. Stephen Freer The system is designed to allow tein, for guidance and support in at the UC San Diego. generalization into domains be­ forming hypotheses about the yond genetics in future research compound's three-dimensional Clinical Medicine and application. structure. "Integrating the many diverse Because the shape of a INTERNI ST sources of knowledge is a central molecule exerts a major effect on problem in constructing MOLGEN its performance, accurate analyses Heuristic search techniques are because the expert-planning pro­ and representations of molecular used in all SUMEX-AIM projects, cess requires a blend of biological, structure are seen by medical re­ although each differs according to genetic, chemical, topological, and searchers as essential to under­ the purpose of the project. Drs. instrument knowledge," Dr. standing the biological function of Jack D. Myers and Harry E. Pople, Feigenbaum says. "The expert's these complex molecules. mentors of INTERNIST at the Uni­ knowledge of experimental strate­ Interpreting electron density versity of Pittsburgh, reasoned that gies must also be represented and maps is the art of a protein the best way to design a computer put to use." chemist, which the system's logic program for solving difficult prob­ scheme attempts to capture lems is to simulate the mental PROTEIN STRUCTURE through the use of heuristic processes used by people. They rules. Due to the size of protein PROJECT are primarily interested in building molecules, which often contain a program that will aid skilled spe­ Building computer models of pro­ many thousands of atoms, the cialists in solving complicated prob­ tein structures from crystallo­ plan-generate-and-test strategy lems concerning internal medicine. graphic data, particularly electron used by DEN ORAL cannot be em- Spin-offs- from the program might ~_ I - =:=:: -= ------.-...... -- ::-- _ .. -- ... ---== - : := :~ =:: -...-=-~ ---- ...... -...... ---. -- ...... - .... ---..-.-.-,.- -.--.------... - - --- .• - - . ------.-- - - ... .. --~------

33 be used by physicians' assistants one disease may be present. diagnosis," Dr. Myers says. "If that or in rural health care clinics, mili­ Since beginning their work in isn't possible, it will set out asking tary outposts, and spacecraft. To 1970, Drs. Myers and Pople have questions to obtain further informa­ be effective, the program must be developed an operative system, tion, so that one or more of the able to diagnose several diseases and in so doing have partially models can be confirmed." if they are present in a single pa­ achieved these objectives. A second generation program tient, and it must render diagnoses INTERNIST accepts descriptions dubbed INTERNIST-II, wh ich may quickly to reflect the current status of disease manifestations in any speed up the diagnostic procedure, of the patient. order and asks for more informa­ is now being designed. Although Drs. Myers and Pople analyzed tion , such as historical items, experimental, the new program the diagnostic routine followed by symptoms, signs, and laboratory has shown promising results, rais­ the expert clinician and established data. These facts are not entered ing hopes that it will lead to a more a set of criteria: _ in a specific order, but rather as efficient workup of clinical prob­ • Observations fed into the com­ they are gained through tests and lems when the program is applied. puter must evoke the appropri­ observations. As facts accumulate, Dr. Myers predicts that within 5 ate hypotheses of disease. nodes of recognition are triggered years INTERNIST might be diag­ • Hypotheses must generate a list and a pattern begins to develop. nosing disease on a practical, of manifestations that would be Now, with a specific direction, rather than experimental, basis. present in the patient if the diag­ the computer fits the data together When completed, the system will nosis is correct. like pieces of a jigsaw puzzle. An be able to assist physicians work­ • The computer must be able to interlocking web of programmed ing on difficult cases and rank models of disease accord­ data is set up, beginning with cate­ paramedics serving in remote or ing to their probability of being gories such as liver disease lead­ medically underserved areas. correct and must be able to de­ ing into specifics like hepatitis A. "The computer's assessment of cide when the weight of evi­ After sufficient data have been fed a patient's condftion will be re­ dence is sufficient to permit rea­ into the computer, disease models garded as evidence to help the sonably confident judgment. are developed. The models are practitioner form a diagnosis," he • The program must be able to then compared and ranked. says. "The program is intended to group hypotheses into mutually "The computer holds the profile serve as a consultant, not as a re­ exclusive subsets corresponding for each disease in its memory and placement for the physician." to different diagnoses, in order to if the model fits that standard pro­ Currently, more than three­ handle cases in which more than file very closely, it could make a fourths of the knowledge appli- Drs. Jack Myers (pointing) and Harry Pople of INTERNIST: "No one can possibly memorize all the data in medicine .•

34 cable to internal medicine, one of testing. At each institution, Dr. edge base." the broadest specialties, has been Myers estimates, 20 case analyses The data base is being ex­ translated into symbolic data struc­ will be run each day. During the panded by fourth-year University of tures and stored in the computer trials, physicians' reactions to the Pittsburgh medical students who memory. Over the past 2 years IN­ system and their pattern of use will participate in a medical computing TERNIST's ability to translate this be recorded. On the basis of this course taught by Dr. Myers. Stu­ vast store of knowledge into accu­ information, INTERNIST will be re­ dents are assigned to the project rate diagnoses has been proved, vised, if necessary, to improve ser­ for periods varying from 6 to 18 using a variety of difficult case vice to future users. weeks. Each student focuses on a studies that were published in In the past year, Drs. Myers and group of diseases, usually in a medical journals or occurred in Pople have devised a program specific area. A complex list of dis­ Pittsburgh teaching hospitals. "In called ZOG, which makes it possi­ ease indicators is gathered from the great majority of cases the ble for a physician only casually literature and clinical experts on program has been effective in sort­ acquainted with computer science the faculty. Dr. Myers and other ing out the pieces of the puzzle to master the use of INTERNIST, clinicians review the data, making and coming to a correct diagnosis," reportedly within 5 minutes. Tests any necessary changes. Often Dr. Myers says. "The knowledge show that ZOG, developed at students gather additional informa­ base is too incomplete for a com­ Carnegie-Mellon University, is very tion. A major continuing effort is prehensive test in a clinical situa­ versatile and easy to use. Dr. required to update the information tion, although it is used on an Myers says ZOG is important be­ as new scientific and clinical data ad hoc basis at Presbyterian­ cause the computer must be easy become available. University Hospital, Pittsburgh, for to operate if it is to bridge the Within the year, the knowledge clinical guidance." ever-widening gap between what is base may address virtually all the Within 1 year, the knowledge known in medicine and what important diseases in internal med­ base is expected to reach a "criti­ physicians are able to remember. icine. The team expects to meet cal stage of completeness," ac­ "No one can possibly memorize this schedule, in view of the recent cording to Dr. Myers. Soon after, all the data in medicine," he says. full-time addition of Dr. Randolph field trials of INTERNIST are "There's just too much knowledge Miller, previously a junior col­ scheduled to begin at Presbyterian­ and that pool of information is con­ laborator on the project, and the University Hospital. If successful stantly increasing. The computer participation of Dr. Victor Yu , there, a half-dozen other health has a perfect memory and is ad­ formerly of MYCIN and now on the care centers will take part in the mirably suited for a large knowl- University of Pittsburgh faculty. The first clinical tests of INTER­ in physicians' fees and laboratory treatment, I think the paramedic NIST are tentatively scheduled for tests. would say, 'Look, th is is not for me. the early 1980's. Several groups have indicated We'd better send th is patient to a When in use, INTERNIST's interest in the program. The mili­ hospital." wealth of information and diagnos­ tary may want to use the system in INTERNIST, the consultant and tic ability may solve one problem remote outposts and submarines. librarian, is also a teacher. Th e that currently plagues physicians­ The National Aeronautics and program is being adapted to list ineffective use of time. Patients Space Administration may use basic disease manifestations and with complex diseases often re­ INTERNIST on board spacecraft or to score users on the number of quire the attention of several orbiting laboratories. additional indicators requested, the physicians, or of one physician The program's most valuable estimated cost and risk of tests over a long period of time, before application may be in rural clinics cited to obtain more information, definitive diagnoses can be where nurse practitioners and and the number of incorrect diag­ reached. The computer program paramedics serve health needs noses. The electronic "quizmaster" was specifically designed to handle with only periodic and short-term has been used by members of the such cases, according to Dr. contact with physicians. Tucked university hospital staff who have Myers, and its use should speed away in remote areas, terminals found it to be an "interesting and the diagnostic process. linked to INTERNIST by telephone educational experience." Other INTERNIST may also reduce the could type out important, some­ teaching programs are being cost of health care by sparing pa­ times vital, analyses of patients' planned. The most ambitious tients unnecessary tests. When conditions. scheme in the program's future is additional information is required to "Suppose the diagnosis comes linking INTERNIST with other draw a computer diagnosis , the back 'pneumococcal pneumonia,' computer-based diagnostic sys­ program asks for the procedure wh ich may be something th e tems. that is least expensive and pre­ paramedic thought the patient had One such interface may include sents the smallest risk to the pa­ all along," Dr. Myers says. "This a diagnostic program for hematol­ tient. Invasive methods are always confirms his idea. Treatment is ogy at Cornell University. Dr. Myers requested last. Dr. Myers em­ straightforward and the paramedic says hookups to th is and other phasizes that the operating cost of would go ahead. On the other programs may allow INTERNIST to INTERNIST has not yet been de­ hand, if the computer indicates pursue more detailed diagnoses. termined and the expense of using something much more serious or But INTERNIST's ability to gener­ the system may offset the savings complicated from the standpoint of ate diagnoses comparable to those MYCIN printout: computerized con­ sultant on infectious diseases that diagnoses, recommends therapy, and justifies its decisions.

36 of a human expert is limited to the tems. The behavior of the best "Subsequent evidence from our specialty that it embodies. Al­ general problem-solvers we know, laboratory and all others has only though expanding the program to human problem-solvers, is ob­ confirmed this belief," Dr. Feigen­ include other areas that have been served to be weak and shallow, baum says. scrutinized and defined may be the except in the areas in which the eventual goal, the consensus human problem-solver is a special­ MYCIN/ EMYCIN among AI researchers is that an ist. And it is observed that the all-encompassing diagnostic pro­ transfer of expertise between spe­ MYCIN holds true to the conten­ gram is still in the distant future. cialty areas is slight. A chess mas­ tion that program input must come As Drs. Feigenbaum and Leder­ ter is unlikely to be an expert from expert specialists, not general berg stated in 1970 when reporting algebraist or an expert mass spec­ problem-solvers. The program the first major summary of results trum analyst, etc. In this view, the specializes in the diagnosis and from the DEN ORAL project, " ... expert is the specialist, with a spe­ therapy selection for patients with general problem-solvers are too cialist's knowledge of his area specific infectious diseases. Its weak to be used as the basis for and a specialist's methods and goal is to provide sound therapeu­ building high-performance sys- heuristics." tic advice, using available informa- tion to identify all the organisms MYCIN is able to identify micro­ the complexities of diagnosis and likely to be causing the infection. At organisms, prescribe antibiotic therapy for infectious disease. Fur­ present, two major types of infec­ drugs, and explain, in detail, its ad­ thermore, access to the rules used tions are thoroughly covered in the vice. When recommending a diag­ by the program is a means to ex­ knowledge base-blood infections nosis or therapy, MYCIN lists the pand its knowledge base. Devel­ and meningitis. rules and cites literature references opers can improve the base by en­ MYCIN developers Drs. Bruce used in the decision-making pro­ tering information that may be Buchanan and Edward Shortliffe, cess. Any or all of the rules are missing or inadequately stated. in collaboration with Drs. Stanley available in detail upon request. Because there are dozens of N. Cohen and Stanton Axline, built The explanatory function allows exceptions, contradictions, and on techniques evolved through the physician rationally to reject the qualifications for each rule, and years of DENDRAL experience program's advice if there is dis­ because medical research is con­ and knowledge of how large vol­ agreement over its recommenda­ stantly generating new information umes of domain-specific informa­ tions. Physicians can ask if certain for diagnosis and therapy, updating tion can be represented. Their facts, such as the patient's age, the knowledge base is essential. model of logic is the use of "pro­ were included when forming the Like INTERNIST, MYCIN also duction rules" which represent diagnosis and therapy recommen­ has the ability to question physi­ facts and their interrelationships. dations. Or they may request the cians. Test results and symptoms The MYCIN knowledge base computer to justify a decision. may be requested, as well as currently consists of some 500 Rather than simply stating that a observations about the patient's such rules. Essentially, each rule is clinical indicator suggests a type of appearance. an IF ... THEN statement, which microorganism, the computer Although MYCIN has not yet encompasses a set of precondi­ might say that such an organism is been tried in a routine clinical situa­ tions to justify a conclusion. For more common than others in a clin­ tion, three separate tests of the example, IF the gram stain of the ical setting and is the likely cause, program have been very success­ organism is gram negative, and since the infection occurred after ful. In the most recent, the sys­ the morphology of the organism is hospitalization. In each case, the tem's recommendations concern­ rod, and the aerobicity of the or­ computer cites rules and refer­ ing therapy for patient cases with ganism is anaerobic; THEN there ences to medical literature to sup­ infectious meningitis were com­ is suggestive evidence that the port its recommendations. pared to those submitted by identity of the organism is Bac­ From MYCIN's explanatory func­ specialists, physicians of varying teroides. tion nonspecialists may learn about degrees of expertise, and one

A. MYCIN scores better than human prescribers: therapy was classified as acceptable if evaluators rated it as equivalent to their own. B. Drs. Bruce Buchanan (left) and Ed­ ward Shortliffe of MYCIN: "Building a valuable resource for the practicing physician .•

38 medical student. with the MYCIN project. These erably higher than the actual Ten cases involving infectious seven physicians and student were therapy that had been prescribed meningitis were selected by a asked to prescribe therapy for for the patients. physician who was not acquainted each case on the basis of informa­ An important point to be made is with MYCIN. All patients had been tion in the summaries. There were that MYCIN and the faculty were treated at a county hospital af­ no restrictions concerning the use relatively selective in the choice filiated with Stanford, they were of reference materials. and number of antibiotics pre­ identified by retrospective chart re­ Dr. Buchanan recognizes that it scribed (Table, column 3) . In con­ view, and each presented challeng­ is difficult to define precisely the trast, the therapeutic strategy of ing diagnoses. term "appropriate therapy." The re­ physicians caring for the patients Two criteria for case selection cent MYCIN trial defined the term had been to prescribe several ensured that the cases would be with two control standards. One broad-spectrum antimicrobials. In diverse; there were to be no more was simply whether the prescribed eight cases the physicians pre­ than three cases of viral menin­ therapy would be effective against scribed two or three antimicrobials; gitis, and there was to be at least the pathogen (Table, column 3). in six of these eight cases, one or one case from each of three This was not the sole criterion, be­ no antimicrobial would have been categories-fungal, viral, and cause failure to cover other likely preferable. bacterial. A detailed summary of pathogens and the hazards of Initial overprescribing of these each case was compiled. The overprescribing are not consid­ agents is not necessarily wrong, summary included history, physical ered. The second control was to since redundant or ineffective examination, and laboratory data. submit the decision to the judg­ therapy can be discontinued after a Patients ranged in age from 1 day ment of eight prominent specialists pathogen has been identified, Dr. to 73 years. of infectious diseases at insti­ Buchanan says. But an optimal Summaries were presented to tutions other than Stanford who clinical strategy attempts to limit MYCIN, five faculty members in evaluated the recommendations the number and spectrum of drugs the Stanford divisions of infectious (Table, columns 1 and 2). Each had prescribed, in order to minimize diseases of the departments of published clinical reports concern­ their toxic effects and the devel­ medicine and pediatrics, one ing the management of meningitis. opment of drug-resistant patho­ senior postdoctoral fellow in infec­ In these tests, MYCIN received a gens. tious disease, one senior resident higher rating than any of the nine The problem of overuse or in medicine, and one senior medi­ human prescribers. The system's misuse of antibiotics is well­ cal student. None were associated recommendations scored consid- documented in medical literature.

I For instance, a Stanford University formation. And by questioning the worked out. study showed that one of every physician about the patient, Through collaboration with other four persons in the United States MYCI N pinpoints th e items of clini­ scientists working in SUMEX-AIM , received penicillin under doctors' cal data that are essential to the Drs. Buchanan and Shortliffe have orders in 1977 and nearly 90 per­ validity of the decision." learned that it is possible to de­ cent of these prescriptions were MYCIN can also plot the steady­ velop clinically useful programs unnecessary. Other studies show state blood levels of various anti­ quickly by matching the knowledge that nonspecialists often prescribe biotics, based on such patient of speci fic application areas to the antibiotics that differ significantly variables as body surface area, logic scheme of MYCI N. Extracting from those that would have been weight, and level of kidney func­ and applying the essential parts of prescribed by experts in infectious tion. Dr. Buchanan says this capa­ the program to other fields has disease therapy. bility allows physicians to pick the been dubbed the EMYCIN project. This misuse of drugs is directly most effective and least hazardous All knowledge and references to in­ related to the immediate need for dose of prescribed drug for in­ fectious disease have been re­ treatment required by patients with dividual patients. moved in EMYCIN, but not the acute infections. Although culture The program has been used by logic behind diagnosis, therapy reports can usually be obtained physicians for experimental consul­ recommendations, explanation, within 24 hours after the sample is tation, as well as for classroom and and knowledge acquisition. taken, such reports often classify professional demonstration. Com­ MYCIN has led to the construc­ the organism in general terms. puter scientists have studied the tion of two programs wh ich are al­ Due to the severity of a patient's program, seeking information ready in use. One is called condition, the physician may not be about its design and operation. But SACON, a computerized consult­ able to postpone treatment until a when judged in terms of being an ant that helps engineers pick the precise identification can be made, acceptable clinical tool , MYCI N still proper strategy for analyzing such a process that may require 48 must undergo more development. structures as aircraft wings, rocket hours or longer. To be practical, it must be able to engine casings, bridges, and build­ "In this setting, MYCIN is de­ diagnose all major infections likely ings. SACON is used in conjunc­ signed for two roles," Dr. Buchanan to be found in a hospital. Th is will tion with a program called MARC, says. "It can provide consultative require further expansion of its wh ich offers a large selection of advice to assist the physician in knowledge base. Also, refinements analysis methods, material proper­ making the best early therapeutic for convenience to physicians and ties, and geometries suited to decision possible from available in- ease of operation need to be modeling the mechanical behavior --:---

40 ..... of structures. the methods and strategies used which include methods for guiding "A year or more of experience by experts in their field." the dialogue, presenting diagnostic with this program is typically The program uses AI techniques strategies, constructing a student needed before the operator can to represent both subject material model, and responding to the stu­ use all the options to his best ad­ and teaching strategies. Course dent's initiative. vantage," Dr. Buchanan says. "The material is represented independ­ "Traditionally, teaching expertise goal of SACON is to bridge this ently of teaching procedures so is compiled into the program, com­ gap by recommending an analysis that problems and remedial com­ bining all kinds of problem-solving, strategy." ments can be tailored to each stu­ communication, and pedagogical According to Dr. Buchanan, the dent. strategies,· Dr. Buchanan says. "In expert who worked on the SACON Unlike traditional computer-aided GUIDON we make the important project found it easy to translate instruction (CAl) programs, which step of explicitly codifying this ex­ his knowledge of how to operate attempt to anticipate every wrong pertise as a body of rules within MARC into the rule-based logic student response and prespecify the program. The rules state how scheme developed for MYCIN. references to remedial teaching to teach, how to reply to a student, Another spin-off from MYCIN is material, GUIDON constructs and how to guide him." called GUIDON, a tutor for medical models of the student's knowledge, The success of these programs students that uses the mother pro­ reflecting the person's weaknesses, has generated interest in EMYCIN gram's knowledge base as a man­ strengths, and preferred style of as an academic and business tool. ual for diagnosing infections and learning. Through a video display Representatives of several corpo­ prescribing antibiotic therapy. terminal, GUIDON and a student rations, research centers, and uni­ Other manuals derived from discuss patient cases suspected of versities are exploring the possibil­ MYCIN cover knowledge from involving an infection. The com­ ity that the scaled-down version of SACON and knowledge about puter helps the student consider MYCIN could be adapted to their pulmonary function , which is in­ the relevant clinical and laboratory individual needs, ranging from air­ cluded in a separate SUMEX-AIM data for reaching a hypothesis craft design to diagnosis and man­ program called PUFF. about the causative organisms. agement of epilepsy. "GUIDON represents a signifi­ MYCIN's diagnostic rules pro­ One of the most promising med­ cant twist in AI research," Dr. vide the underlying expertise used ical projects to arise is the devel­ Buchanan says. "We are transfer­ by the tutorial program in selecting opment of an EMYCIN therapy ring knowledge from a program to topics to be discussed. In addition, management system for Stanford's people, students who want to learn GUIDON has 200 tutorial rules, oncology clinic, which provides GUIDON printout: tutoring medical students with tai/or-made clues. **HINT Hint: Look for strong, positive eviclenc~ that Diplococcus-pneumoniae is one of the organisms that might be causing th~ infection.

* * * **HELP

Let's consirler wheth~r J. Smith has a heaci in;urv.

We alrearly know that the patient has not had an injury to the central nervous system; this is evidence that he does not have a head injury [RULE 509].

We now have strong evidence that DipJococcus-pneumoniae and Neisseria-meningitidis are organisms that might be causing the infection (considering the age of J . Smith and the fact that he does not have a head injury [RULE 507]) .

It remains for us to consider other factors for determining the organisms that might be causing the infection. chemotherapy on an outpatient cause it is a research clinic in sonable time is often very slight," basis. It is separate from the rest of which clinical studies are routinely says Dr. Shortliffe, who spent time the hospital clinics and its isolation performed, some 50 therapy regi­ in the clinic during his medical res­ offers certain advantages. uCom­ mens or protocols are going on si­ idency at Stanford. puter terminals can become famil­ multaneously. The program is intended as a iar to a small subset of doctors, "There's usually one person who source of just such information. and won't be in the way of people knows an individual protocol well , Protocols will be fed into the from other clinics," Dr. Shortliffe but if a resident, student, or fellow knowledge base of a program simi­ says. Dr. Charlotte Jacobs, the on­ delivering care in the clinic has lar to EMYCIN. The reasoning cologist who directs the clinic, is some question, such as whether a process may eventually allow collaborating on the system design patient needs a chest X-ray tomor­ complicated decision-making, such and implementation. row, it's really hard to find the an­ as matching new patients with a The clinic has a definite need swer. Up-to-date copies of the pro­ set of appropriate protocols, but that can be filled by an AI program tocols are maintained but are often during the next year the scientists of the type being constructed by unwieldy and the chance of finding hope at least to accomplish simpler Drs. Shortliffe and Buchanan. Be- the needed information in a rea- tasks with their new program. The protocol for each patient will been too long a delay since the lethal doses." be available, presenting the day of last treatment. We want to make Dr. Heiser adds that these physi­ therapy and procedures required. sure that those kinds of capabilities cians may not know how such "A lot that is called for by protocols can be added on without having to medications affect a patient's gen­ is currently missed," Dr. Shortliffe suddenly redesign the system." eral health, other physical disor­ says. "Some people don't get ap­ ders which may afflict the patient, propriate X-ray or laboratory Psychopharmacology or treatments that the patient may studies called for by the protocol Advisor- be receiving for these disorders. because there is no good system HEADMED As an example, Dr. Heiser points to for reminding the clinicians that a drug that has recently drawn they should be ordered. Then, Dr. Jon F. Heiser, a psychiatrist, much attention. "For the past sev­ when the clinicians try to analyze and Dr. Ruven E. Brooks, a com­ eral years, the most prescribed the data, they sometimes realize puter scientist, both at the Univer­ drug in the United States has been that the people enrolled in the pro­ sity of Texas Medical Branch at Valium . It isn't clear why this drug tocol have not been categorically Galveston, are tailoring MYCIN's is being prescribed, and it is un­ following the protocol itself, and the logic scheme to fit a medical do­ likely that it should be prescribed to data have suffered for that reason. main much different than infectious the extent that it is," he says. So, use of the program can im­ diseases. They are developing a HEADMED is designed to rec­ prove the quality of studies and the psychopharmacology advisor ommend the use of drugs, if indi­ way care is delivered by providing called HEADMED. cated, for patients suffering from beUer access to the details of the The program, which is part of a psychiatric disorders. A side bene­ protocols in an on-line fashion." pilot project on SUM EX-AIM, ad­ fit from developing the program is The long-term goal of the project dresses the problem of drug mis­ that the rules for patient assess­ is to build on these early al­ use in psychiatry. "There are in­ ment and management will be ob­ gorithms until the program is capa­ adequate rationales for many pre­ jectively described. These rules will ble of making inferences. "Then it scriptions, and not uncommonly be of value as educational tools, starts to get more like MYCIN," Dr. the dosages are wrong," Dr. Heiser Dr. Brooks says. Shortliffe says, "when it actually is says. "If you tested physicians' The long-range goal is to design helping decide whether a patient is knowledge of how to use these a small, functional computer pro­ responding to therapy, whether the drugs, you'd probably discover that gram that can diagnose and rec­ patient has any evidence of re­ many don't know the important ommend therapy for a variety of sidual tumor, whether there has side effects, adverse reactions, or psychiatric disorders. Work has

Patient being examined by ophthal­ mologist: testing for the presenc.e of glaucoma. been focused on the diagnosis and rheumatology, they used the rea­ The approach proved useful in recommendation of a drug treat­ soning scheme of a program called designing a prototype computer ment, if indicated, for major de­ CASNET/Glaucoma which was program. Just as the CASNET/ pressive disorders. Also, attention designed for ophthalmology. Their Glaucoma project was reaching has been given to classes of efforts demonstrated that a pro­ maturity, a group of scientists at non psychiatric medical problems, gram, when developed and the University of Missouri asked if such as cardiovascular and renal adequately refined, can be applied a similar program could be de­ disorders. The program is intended to diseases totally unrelated to the signed for the field of rheumatol­ to caution against potentially harm­ original application. ogy. ful reactions from drugs that might When Drs. Casimir A. Kulikowski The Rutgers investigators are be prescribed and to give advice and Sholom M. Weiss began the now applying techniques learned concerning dosage and duration of CASNET project in 1971 , their goal while constructing CASNET to the therapy. was to develop different ways of design of a new computer program The immediate goal is to evalu­ computerizing medical knowledge for diagnosis and treatment of ate the use of EMYCIN in this proj­ used by experts to arrive at diag­ rheumatic disease. "We'll have the ect, and to make the program easy noses and treatments. "Instead of same sort of mix that we have in for psychiatrists to operate. "Es­ picking an entire area of medicine, the glaucoma program: a research sentially, we look on our efforts as we looked in great detail at the orientation of the knowledge base the first try at finding an appropri­ mechanism of one group of provided by experts in the field and ate control structure," Dr. Brooks diseases-the glaucomas," Dr. the development of a practical says. "To construct a foundation for Kulikowski says. consultative system," Dr. Kulikow­ the program, we are focusing on The two scientists, along with an ski says. "But in addition to basic the diagnosis and management of ophthalmologist from Mount Sinai research, a strong priority is to certain depressions." School of Medicine, Dr. Aran Safir, build a high-performance consult­ picked the glaucomas because ant system." these eye diseases and their CASNET Through the use of a versatile treatments have mechanisms that program called EXPERT, which, Scientists at Rutgers University are relatively well-understood. like EMYCIN, is primarily used to have built the same type of Consequently, they were good construct new consultative pro­ versatility into a new AI program candidates for in-depth modeling of grams, Drs. Kulikowski and Weiss called EXPERT. In building EX­ the causes and effects of disease made rapid advances toward their PERT, which will be applied in processes. new goal. After only 2 months on

44 the project the researchers were able to generate preliminary models of seven rheumatic dis­ eases. Currently a data base of over 150 patient cases has been established. One of the rheumatol­ ogy program's most important fea­ tures is that its medical knowledge can be rapidly organized and up­ dated. Disease models can be ver­ ified using the cases stored in the data base. MIt's amazing that the new project is going so quickly," Dr. Kulikowski says. "Through our ex­ perience with CASNET/Glaucoma, we've achieved the critical mass of tools and expertise needed to pro­ duce an expert consultant on a new subject in only a fraction of the time required for the first system." EXPERT is now being tested at the University of Missouri against difficult case histories. During the past 6 months, the program has correctly diagnosed more than 90 percent of the cases. During the early years, from 1971 to 1978, much new ground was broken and most early goals were met. When the scientists stopped active expansion of

CASNET printout: diagnosing, prog­ nosing, and prescribing treatment for patients with glaucoma. CASNET/ Glaucoma, the knowl­ opment of tests and criteria for their reasoning, the researchers edge base was virtually complete. detecting and diagnosing mixed say. Since then it has been routinely connective tissue disease. The But CASNET's reasoning behind maintained and new information computer program will be gradually diagnosis and treatment-planning, added by the Japanese glaucoma expanded to cover other rheumatic like MYCIN's, is explained in detail expert Dr. Yoshiaki Kitazawa. The diseases. In addition, Dr. William by the computer, so that physicians program is still available to select Pincus at the University of Califor­ can decide whether to accept or re­ groups for experimental consulta­ nia, San Diego, is helping the ject recommendations. Conclu­ tion. Rutgers researchers develop a sions drawn by the system are The researchers' decision to knowledge base in general rheu­ periodically revised according to switch from glaucoma to matology oriented to primary- the progress of each patient after rheumatology depended on a vari­ care physicians. treatment. For complex cases, ety of factors, but was mainly influ­ The EXPERT design program, a CASNET/Glaucoma includes al­ enced by the much greater de­ major factor in the rapid develop­ ternate opinions on various dis­ mand for consultation concerning ment of the rheumatology program, ease conditions gained from con­ rheumatic disease. The change has also been applied with prelimi­ sultants in the Ophthalmological came about 2 years ago when nary success to the construction of Network (ONET), a nationwide Dr. Gordon Sharp and other knowledge bases in endocrinology, group of investigator-consultants rheumatologists at the University clinical pathology, neuro-ophthal­ who share in the development and of Missouri explained that expert mology, and internal medicine. testing of the system. During advice on crippling rheumatic dis­ Initial development of a workable CASNET's development, these eases was in short supply outside logic scheme for CASNET/ phYSicians, tied in by telephone university centers. They suggested Glaucoma is the reason for the links, presented difficult cases to that a computer consultation sys­ new system's rapid success. A the program and weighed its per­ tem could provide valuable assist­ major problem, encountered by all formance against their own judg­ ance at primary care clinics. researchers building artificial intel­ ment. Their suggestions, following Drs. Kulikowski and Weiss are ligence systems, has been translat­ evaluation, were used to refine the now concentrating primarily on dif­ ing the human reasoning process program. fuse connective tissue diseases, into explicit language for the com­ CASNET/Glaucoma eventually such as rheumatoid arthritis and puter. In medical diagnosis, prob­ included diagnosis, prognosis, and mixed connective tissue disease. lems are relatively complex. As a treatment planning. The system Dr. Sharp is a leader in the devel- rule, physicians do not formalize could then forecast a patient's

PUFF, one of the first AI programs in clinical use: evaluates the patient's pulmonary function.

46 --. - progress under various therapies as well as possible allergic reac­ percent of ophthalmologists sur­ and cite the one most likely to pro­ tions to drugs when treatment is veyed rated CASNET/Glaucoma vide the best results. planned. Patients receiving therapy as "expert" or "very competent" Such capabilities are far more may also have different and unex­ based on cases presented during a difficult to achieve than might be pected responses. Information ob­ demonstration. Since then the sys­ imagined. A patient can have more tained during follow-up visits must tem has been used on an experi­ than one form of glaucoma, or the be plugged into the computer, and mental basis at six medical centers disease may affect only one eye. the system must reevaluate diag­ around the country. Certain key signs of the disease nosis, prognosis, and treatment. One of CASNET's biggest con­ may not have yet appeared. Since During 7 years of research, Drs. tributions to ophthalmology is in the disease is progressive, various Kulikowski and Weiss succeeded developing a better understanding stages of severity will be present in to a large extent in building a func­ of glaucoma. "In the course of different patients. tional computer-consultant on building the program, there has Once a diagnosis is verified, glaucoma. At the 1976 meeting of been a much more careful defIni­ other factors such as a patient's the American Academy of Oph­ tion of the different observational age and sex must be considered, thalmology and Otolaryngology, 77 criteria necessary to gather data in

~.JT 83.0 KG, HT 190 CM, AGE 55 SEX M SMOKING 168 PK YRS, CIG 4.0 PK QUIT 0, PIPE 0 QUIT 0, CIGAR 0 QUIT 0 DYSPNEA-AT REST , COllGH-YES , SPllTUM-I-3 TBS , MEDS-YES REFERRAL OX-ANGINA *******************************************************TEST DATE 10/23/79 PREDICTED POST DILATION (+/-50) OBSER( ~ PRED) OBSER(%PRED) INSPIR VITAL CAP ( I VC) I. 'i. I 3.8 ( 74 ) RESIDUAL VOL (RV) I. 2.4 4. I ([ 71) 3.7 (155 ) TOTAL LUNG CAP (TLC) I. 7.5 8.1 ( 107) 7.9 (105 ) RV/TLC '.: 32. 51. 47.

FORCED EXPIR VOL( FEVI ) L 3.9 2.1 ( 54 ) 2.3 ( 58) FORCED VITAL CAP (FVC) I. 5. I 4.0 ( 77) 4.2 ( 81) FEVl/FVC h 76. 53. 54. PEAK EXPIR FLOW (PEn Lis 10.0 4.6 ( 45) 3.9 ( 38) FORCED EXP FLOW 25-75% Lis 1.8 0.9 ( 24 ) 1.4 ( 35) FLOW AT 25 % FVC (F25) L/S 1.5 0.4 ( 26 ) 0.5 ( 33)

AIRWAY RESIST(RAW) (TLC = 8.1 ) 2.5 (1. 1) 6.5 3.6

OF CAP-HGB=15.3 (TLC= 7. I ) 34. 27.8 ( 82) 78%IF TLC= 7. 5)

********************************************************************************

INTERPRETATION: ~.EVATED LUNG VOLUMES INDICATE OVERINFLATION . IN ADDITION , THE RV/TLC RATIO IS INCREASED, SUGGESTING A MODERATELY SEVERE DEGREE OF AIR TRAPPING. THE FORCED VITAL CAPAC ITY, FEVl/FVC RATIO, MID-EXPIRATORY FLOW AND F25 ARE REDUCED AND THE AIRWAY RESISTANCE IS INCREASED, SUGGESTING SEVERE AIRWAY OBSTRUCTION. FOI.LOWING BRONCHODILATION, THE EXPIRED FLOWS SHOW MODERATE IMPROVEMENT. THIS IS CONFIRMED BY THE DECREASE IN AIRWAY RESISTANCE. THE LOW DIFFUSING CAPACITY INDICATES A LOSS OF ALVEOLAR CAPILLARY SURFACE, WHICH IS MILD.

CONCLUSIONS: THE LOW DIFFUSING CAPACITY, IN COMBINATION WITH OBSTRUCTION AND A HIGH TOTAL LUNG CAPACITY IS CONSISTENT WITH A DIAGNOSIS OF EMPHYSEMA. THE PATIENT'S AIRWAY OBSTRUCTION MAY BE CAUSED BY SMOKING. DISCONTINUATION OF SMOKING SHOULD HELP RELIEVE THE SYMPTOMS. THE AIRWAY OBSTRUCTION MAY EXPLAIN THE PATIENT'S DYSPNEA. IN VIEW OF THE RESPONSE TO BRONCHODILATORS, CONTINUED USE WOULD BE RECOMMENDED. THE PRESENCE OF A PRODUCTIVE COUGH INDICATES BRONCHITIS.

PULMONARY FUNCTION DIAGNOSIS: 1. SEVERE OBSTRUCTIVE AIRWAYS DISEASE. MIXED TYPE. ROBERT FALLAT, M.D. 47

-. ------glaucoma cases," Dr. Kulikowski smoothed out by using computer ists in respiratory diseases, and says. "Physicians have used the systems specifically developed to computer scientists Dr. Lawrence project to come up with a clearer test alternate logic schemes. Such Fagan, Ms. Penny Nii, Mr. John set of standards as to how they de­ systems have been developed at Kunz, Ms. Jan Aikins, and Ms. Di­ fine a particular clinical condition or the Rutgers Computers in anne McClung pooled their knowl­ particular diagnosis." Biomedicine Research Resource, edge to develop the PUFFNM But despite its expertise and which is directed by Dr. Saul (Pulmonary Function and Ventilator contributions, CASNET and all Amarel. Management) project. Research other computer-based medical Drs. Kulikowski and Weiss are includes development of two sys­ consultants will never be able to pleased with the transition from tems, one for the diagnosis and overcome a basic limiting factor­ CASNET/Glaucoma to EXPERT. therapy assessment of pulmonary the need for interaction with The old program is viewed as an function (PUFF), and the other for people. important prototype which has con­ monitoring automatically the condi­ "There are a lot of subtle visual firmed that medical reasoning skills tion and progress of patients con­ cues that the physician will get can be captured in the computer. fined to intensive care units who while looking at the patient," Dr. "This is probably the first time must use ventilators to assist Kulikowski says. "If your diagnosis we can comfortably talk about how breathing (VM). and treatment hinge critically on these systems can be taken into PUFF depends on some 250 one of these cues, and if the the field and applied," Dr. Kuli­ decision-making rules, which are physician doesn't know how to ex­ kowski says. "The EXPERT sys­ similar in form to those used by plain or write them into the rules of tem in rheumatology, we hope, will MYCIN. These rules are used to the program, then there is no way be a demonstration of research interpret a variety of patient signs the system's recommendations can that can be put into production and related to pulmonary function. be correct." evaluated in a practical setting." They were initially drafted from a Although this potential for human set of 100 case studies that repre­ error may never be resolved, there PUFFNM sented a wide spectrum of pulmo­ are certain areas in which the per­ nary disease states, and have formance and accuracy of artificial In a collaborative effort be­ been refined on the basis of 1,000 intelligence techniques can be im­ tween the Pacific Medical Center cases interpreted during the past proved. Software design problems, (PMC) in San Francisco and Stan­ year. As with many medical AI sys­ an important concern for AI re­ ford, Drs. John J. Osborn, Robert tems, a bonus from developing the searchers, can be partially Fallat, and Bernard Votteri, special- system has been the formalization

48 of medical knowledge used in the Then when the computer actually to information gained from the pa­ specialty. performs well , they take the at­ tient's medical history and referral Unlike many systems, PUFF is titude that it gives them more time diagnoses. evolving in a clinical setting at the for other things." PUFF interprets the physiologi­ Pacific Medical Center. "Not only is When using PUFF, the patient cal meaning of test results. It iden­ PUFF being tested in a clinic; it is breathes several times into a de­ tifies incomplete or missing data being used regularly as part of the vice known as a spirometer, from and analyzes patient response to practice of medicine by the pulmo­ which data are obtained to calcu­ bronchodilators, if used during the nary function laboratory," says late the volume of air in the pa­ tests, as well as the consistency of principal investigator Dr. John J. tient's lungs and its rate of flow. A findings with referral diagnoses. In Osborn. sensor monitors the diffusion of in­ this context, PUFF diagnoses the Patient reports drawn by PUFF haled carbon monoxide in the presence and severity of pulmo­ are reviewed by a staff physician blood. From these tests PUFF at­ nary dysfunction. specializing in pulmonary physiol­ tempts to identify respiratory Program interpretations about ogy. Most reports are accepted obstruction and restriction, and de­ diagnoses are intended only as without change and are entered fects in alveolar-capillary diffusion. aids to the physician. Another into the patient's record. Others The program also relates these equally important goal of the proj­ usually require only slight modifica­ measurements to results from ect, according to Dr. Osborn, is to tion, according to Dr. Osborn. blood-gas tests. Disease types, expose AI techniques and "The staff trusts it," he says. such as emphysema and bron­ methodologies to the medical "The computer does patient re­ chitis, can be diagnosed. communities. ports much faster than they can be Any or all of these problem types VM, the other segment of the done by hand, and it does them may be present simultaneously, project, is dedicated to providing more reliably. Of course, the physi­ each affecting the severity of the clinical advice about patients sup­ cians review the data each time." others and thereby complicating ported by mechanical ventilators in The atmosphere of trust that cur­ the diagnosis and evaluation of the the Intensive Care Unit (ICU) at rently exists at the center required seriousness of the patient's condi­ Pacific Medical Center. But VM much time to develop. "Physicians tion. PUFF interprets some 50 pa­ currently resembles a research ve­ seem to go through a series of rameters calculated from the hicle more than an operational tool reactions," Dr. Osborn explains. measurements, comparing these for medicine. "Ventilator manage­ "The first is defensive, saying 'No measured values to heuristic ment is really quite well-under­ computer is going to replace me.' models of pulmonary disease and stood." Dr. Osborn says. "VM is Dr. John Osborn with PUFF: "The staff trusts it .•

4 a way of working out methods to Because it is such a great mass of reduced, limits are appropriately develop a program with wider use numbers, doctors and nurses revised. If indicators conSistently in intensive care medicine." sometimes miss important things," go beyond either of these levels, Program designers have fo­ Dr. Osborn says. "So, we are using comments including therapy sug­ cused on including in VM the com­ VM as a model for how to embed gestions are printed out. When in plicated functions that must be clinical knowledge into a program clinical use, the physician will be characterized in ventilator man­ which will model conclusions the able to ask VM for an explanation agement. For example, VM ex­ way a clinician does and help the before corrective action is consid­ plicitly considers the effect that clinician catch things that he might ered. The program will also advise time variation has on interpreting otherwise miss." physiCians when the patient can be the patient's condition. "Meas­ Currently, the system is a natural weaned from the ventilator. urements taken at two different extension of on-line computer VM's logic scheme is related to times have different meanings," Dr. monitoring used in the ICU. VM is the one used by PUFF, but the Fagan says. "Measurements taken designed to obtain and interpret knowledge has been structured so immediately after cardiac surgery some 30 physiological indicators that one rule can be applied in might be within a normal range, but that summarize the patient's many different situations. In this a day later these same measure­ status. Changes in status are to be manner, the rules allow quick focus ments will indicate problems. To accompanied by suggestions for on knowledge that is relevant for correctly reflect the patient's condi­ corrective action and advice on ad­ different situations and develop­ tion, VM must change its expecta­ justing the mechanical ventilator. ments. tions for the patient and interpret VM is also able to detect and indi­ VM gathers data directly from the measurements in new con­ cate possible measurement errors. monitoring instruments. PhYSicians texts." The program generates guide­ interact with the system only when Dr. Osborn hopes to build VM lines for interpreting data by they want inforrnation. Also VM is into a program that can digest all analyzing the patient's medical his­ not geared to present a single the data generated in an intensive tory and current status. These diagnosis. It monitors and asses­ care unit, and present to the physi­ guidelines are used to establish ses the patient's condition every 2 cians only the information neces­ upper and lower limits of variation to 10 minutes as new meas­ sary to determine therapy. "When in measurements. They are ad­ urements become available. you get a patient in the intensive justed as therapy is changed; for Evaluating VM or PUFF will be care ward, 50 or 60 different quan­ example, when the patient's re­ difficult. As with all AI programs, titative measurements are taken. liance on the ventilator is gradually disagreements between physician

The Ventilator Management program: more a research vehicle than a prac­ tical tool for medicine.

50 and computer inevitably arise. The knowledge about the evolution and United States, computerized data situation is complicated by dis­ treatment of chronic diseases from banks have been developed to aid agreement among physicians data in patient records stored in in the study of chronic diseases. themselves on diagnoses and the computerized clinical data banks. Unfortunately, th is effort is compli­ rules to be used in making them. A The RX project is under the di­ cated by missing or contradictory more subtle problem arises when rection of Dr. Robert L. Blum, an data, as well as by potential biases physicians agree on a diagnosis, internist in the Stanford Division of in the data that may affect the ap­ but disagree on the supporting Clinical Pharmacology, and Pro­ parent utility of a particular therapy. evidence. fessor Gio C. M. Wiederhold of the By combining statistical ap­ Only a consensus opinion Stanford Department of Computer proaches with AI techniques utiliz­ gathered from a number of experts Science. ing large knowledge bases, it is in the field can solve the problem. "Chronic diseases comprise the expected that the complex rela­ Dr. Jack D. Myers of the INTERN­ majority of the diseases taking the tionships among the many vari­ IST project says medicine, like greatest toll in terms of death and ables that influence the progres­ AI , is more an art than a science. disability: arteriosclerosis, causing sion of chronic disease may be "And as such, we need a consen­ heart attacks and strokes; cancers; more clearly defined. sus of artists, if we are to ad­ high blood pressure; arthritis; dia­ The knowledge base of the RX vance," he says. To a large extent, betes; and others," says Dr. Blum. project, similar in concept to that of developers of programs such as "After years of study, the causes, the MOLGEN project, will contain INTERNIST, CASNET, MYCIN, and best treatments, and natural his­ knowledge of the various diseases, PUFF have relied on consensus tory of these diseases are still sub­ symptoms, therapies, outcomes, when conducting evaluations. jects of controversy. The main laboratory tests, and the many in­ method used to study the effec­ terrelationships which exist among RX tiveness of therapies in chronic them. The knowledge base will be diseases has been the prospective used primarily to abstract the key The advance of AI techniques trial, randomly placing subjects in events occurring in the com­ in several projects, particularly either control or test groups. How­ puterized patient charts. These MYCIN and MOLGEN, has influ­ ever, this approach has consider­ abstracted records will then be enced the design of a new medical able limitations in terms of cost, used to assess the degree of corre­ project on SUM EX-AIM called RX. generalization, ease of perform­ lation between various therapies The goal of the RX project is to de­ ance, and ethical considerations." and disease outcomes. velop a system for extracting At a number of centers in the The test bed on which the RX

5 -

project will be developed is a data great benefit to know when treat­ IMAGING system to model body base of arthritis patients. Called ment of SLE with potentially organs in three dimensions. ARAMIS (American Rheumatism dangerous drugs- steroids and Models would be used to study Association Medical Information immunosuppressants-is anatomic structures noninvasively System), it has been developed at warranted or when other forms of and to determine the volume of Stanford over the past decade therapy are best used. organs. Data obtained would be under the direction of Dr. James Because the RX project has applied to clinical diagnosis. Fries. The software which is used been on the SUMEX-AIM system "Initially, the system would be to store ARAMIS-the TOO sys­ for less than a year, only the first used to determine the volume of tem for Time-Oriented Data steps have been taken. But if the the fetus as an indicator of its base-was originally designed by program succeeds, it is expected weight," Dr. Brinkley says. "Later it Professor Wiederhold. that knowledge bases may be de­ might be adapted to measure ARAMIS includes over 10,000 veloped for other chronic diseases volume of the liver, the kidney, or patient records, accounting for such as stroke and cancer. Patient the left ventricle of the heart, for 20,000 patient-years of observa­ data on these diseases are now example." tion. These have been gathered being collected in the same time­ He explains that weight is an im­ from six university medical centers. oriented data-base format at Stan­ portant indicator of fetal health. Since the analysis of such a large ford , which will simplify the exten­ Small babies generally do poorer volume of data might swamp even sion of the RX project to these than larger ones, he says. Rate of an intelligent computer, the initial domains. growth is an indicator as well. focus of the RX project will be on Fetuses that are small compared only 270 records of patients with a to the average tend to experience ULTRASONIC difficulty following birth, which single disease type called systemic IMAGING lupus erythematosus (SLE). This sometimes leads to death. Physi­ malady is a multisystem, chronic, Building on past experience in ci ans believe that such fetuses rheumatologic disease with many the use of computers and ul tra­ may be suffering from insufficien­ perplexing diagnostic and thera­ sound techniques, Dr. James F. cies and that early diagnosis and peutic questions. It is of consider­ Brinkley, physician and computer delivery might prevent certain able interest to researchers scientist, and Dr. W. D. McCallum, complications. Further, recording because of the health risks associ­ physiologist and obstetrician, both growth curves would aid in under­ ated with both the disease and the at Stanford, have proposed the de­ standing normal physiology of the drugs used to treat it. It would be of velopment of an ULTRASONIC unborn.

52 •

Conventional ultrasound tomography of excised brain tissue: adding AI program may dramatically improve accuracy of the technique.

5 Past attempts to use ultrasound position-locating system so the ACT for these purposes produced inac­ orientation of each scan will be curate results. One reason appar­ known. Later a light-pen will be AI models of human cognition, ently was an inadequate number of used manually to sketch in the including memory, inferential rea­ measurements, Dr. Brinkley says. borders of the organ or fetus for soning, language-processing, and "The method we are working to­ input into SUM EX. The computer problem-solving, are being assem­ ward is based on the assumption will then combine the position and bled at Carnegie-Mellon University that fetal weight is directly related light-pen information into a recon­ under the direction of Dr. John An­ to volume since the density of fetal struction. Once the light-pen sys­ derson. Known as Acquisition of tissue is nearly constant," he says. tem has been shown to give accu­ Cognitive Procedures and nick­ "We hope that by using three­ rate results, the three-dimensional named ACT, the program is in­ dimensional information more ac­ ultrasound model will be used to tended to represent the develop­ curate volumes and, as a result, guide the computer in outlining ment and performance of weights can be obtained." borders automatically. decision-making. In essence, ACT In addition to its use in predicting is a basic research project in AI , fetal weight, the system might be containing a logic scheme that may used to determine the volumes of be transferable to applications in other organs. Volume of the heart's specific areas in or outside of left ventricle is routinely obtained Psychology medicine. by means of cardiac catheteriza­ "We hope that future versions of tion in order to help characterize its ACT will resemble very closely the condition. "Use of three-dimen­ Most clinical and biochemical process by which people learn to sional ultrasound should provide applications of AI attempt to cap­ make decisions," Dr. Anderson an accurate, noninvasive means of ture the effectiveness of human says. "We could then apply this assessing the state of the left ven­ expertise without necessarily trying model of skill acquisition to such tricle," Dr. Brinkley says. to model what goes on in the medical domains as diagnosis and Three-dimensional imaging is human mind. Many applications in scientific inference." expected to result from a series of psychology, however, are aimed ACTs knowledge base consists ultrasound cross sections taken in specifically at constructing working of two components. One contains an arbitrary fashion over the organ models of human cognitive be­ facts and serves as the program's to be imaged. The ultrasound havior. These systems are basi­ memory-essentially a data base. scanner will be coupled to a cally intended as research tools. The other is a set of rules used to

54 make decisions based on what is was taught to generate and explain The project is founded on contained in the memory. proofs in geometry, using some in­ studies showing that various word­ As a result, new decision-making troductory exercises in high school processing skills and arithmetic rules must be conceived and old textbooks. The system success­ procedures are underdeveloped in ones modified on a continuing fully created new decision-making children who do poorly in reading, basis. Dr. Anderson and colleagues rules and amended or discarded mathematics, or both. Models are have built learning functions into old ones. It also learned ways to being developed to test th is belief. the ACT program to accomplish reorganize its search for mathe­ One simulates the process of solv­ this. New rules are automatically matical postulates so as to in­ ing simple word problems. It is in­ created; old rules are assessed, crease speed. tended to determine the degree to adjusted, combined, and some­ which semantic and linguistic fac­ times thrown out. Simulation of tors, rather than arithmetic knowl­ A stumbling block in all learning Cognitive Processes edge, are responsible for children's systems is that rules commonly difficulty in solving these problems used in human decision-making Although ACT is continually at early grade levels. often defy description, even by being revised, versions are "fro­ "By providing a framework in those who use them. Dr. Anderson zen" at various stages of develop­ which the effects of different levels says the system can create new ment and made available to of s ill acquisition can be under­ rules only to the extent that people researchers throughout SUMEX­ stood, we hope to provide criteria understand the skill to be acquired. AIM. One version has been applied that will separate patients who Because this would leave gaping by Drs. James G. Greeno and Alan have brain damage from those holes in the decision-making ma­ M. Lesgold at the University of whose cognitive skills have devel­ chinery, a fallback has been built Pittsburgh to model the acquisition oped poorly," Dr. Greeno says. in. of reading and problem-solving "This is not something that we ex­ For relatively unstructured situa­ skills. Entitled Simulation of Cogni­ pect to result from our work in the tions, ACT uses trial-and-error. The tive Processes, the project centers immediate future. It is an example approach is an intelligent set of at­ on modeling the processes in­ of what we hope to achieve." tempts to find the correct answer volved in arithmetic and reading. based on what has been learned These two skills were chosen be­ Higher Mental Functions by past mistakes. Tests of the sys­ cause "they are very basic cogni­ tem 's ability to learn have been tive requirements for getting along The Higher Mental Functions conducted. Recently the program in the world," Dr. Greeno says. project being conducted at the

55

Dr. - REALLY? Pt. - YOU KNO\ol, THEY KNOW ME (Feel: SHAM 0 ANGR 2.40 FEAR 1.63 DSTR 0 INTR 6.15 JOY 5.79) (Conclude: *DSIMlLAR *DSOCIABLE)

Dr. - HOW? Pt. - THEY ARE OUT TO GET ME (Feel: SHAM 0 ANGR 1.80 FEAR 2.15 DSTR 0 INTR 5.85 JOY 5.19) (Conclude: *DINITIATING *DDOMINATING)

Dr. - WHY IS THAT? Pt. - YOU KNOW, I HAVE INCRIMINATING EVIDENr.E AGAINST THE MAFIA (Feel: SHAM 0 ANGR 1.20 FEAR 2.25 DSTR 0 INTR 5.55 JOY 5.25)

Dr. - WHAT EVIDENCE? Pt. - I KNOW WHO THE LOCAL CHIEF OF THE MAFIA IS (Feel: SHAM 0.32 ANGR 1.44 FEAR 3.16 DSTR 0 INTR 6.26 JOY 5.23)

Dr. - SO 00 1. Pt. - WHAT DO YOU THINK ABOUT ALL THIS? (Feel: SHAM 0.50 ANGR 1.51 FEAR 3.64 DSTR 0 INTR 6.93 JOY 4.77) (Conclude: DHOSTILE *DTRUSTtolORTHY *DHELPFUL *DDHELP)

Dr. - I FIND IT HARD TO BELIEVE. Pt. - ARE YOU TRYING TO SAY SOMETHING? (Feel: SHAM 5.34 ANGR 3.91 FEAR 5.86 DSTR 4.00 INTR 6.73 JOY 5.26) (Conclude: DNBELIEVE LYING DABNORMAL) Pt. - DO YOU KNOW WHAT YOU'RE DOING? LET'S QUIT RIGHT NOlol [This is an afterthought, interjected by the patient-model he fore the Dr. had responded to the prior statement.]

Dr. - I'M SORRY. Pt. - (EXITS) I OON'T WANT TO TALK ANY MORE (Feel: SHAM 8.78 ANGR 3.96 FEAR 6.37 DSTR 7.81 INTR 7.60 JOY 1.45) (Conclude: DBAD DDHARM DGANGSTER DMAFIA fi7l80)

PARRY: simulating the thought pro­ cesses of a paranoid patient. (Dr.-Indicates the doctor's ques­ tions: Pt.- indicates the model­ patient's answers. Feel: The model­ patient's emotional state is rated on a scale from 0 to 10 along several di­ mensions: SHAM IS shame, ANGR IS anger, FEAR is fear, OSTR is dis­ tress, INTR in interest, JOY is joy. Conclude: The computertzed patient forms opinions about the doctor who is conducting the interView. A lead­ mg " " means "NOT" and a leading "0 " means "OOGTOW).

57 University of California, Los tient or a computer. It was their terpreting questions presented by Angeles (UCLA) is devoted to re­ task to distinguish the paranoid pa­ interviewers and returning searching personality problems, tient from the simulation. In the paranoid answers, the AI program specifically paranoia and adult test, PARRY's responses matched in neuroses must take neurotic an­ neuroses. Another segment of the those of the paranoid patient so swers and work backward to the project involves development of closely that the psychiatrists could underlying concepts or key ideas devices that will allow patients with not tell the difference between the that distinguish the patient's language disorders, especially two. pathology from those of other pa­ those who have suffered stroke, to Although the test does not prove tients. These key ideas would then speak. All three areas call for the that the theory on which PARRY re­ be clustered to form the profile of a development and use of AI pro­ lies is all-inclusive, it shows that certain type of patient, Dr. Colby grams. the theory contains enough facets says. Under the direction of Dr. Ken­ of the paranoid personality to con­ "A key idea for the profile of a neth M. Colby, a psychiatrist at the fuse experts and to serve as a tool depressive patient might be 'I am UCLA Neuropsychiatric Institute, a in teaching students about the someone who should get more computer simulation of paranoid pathology. help.' In a normal person, this thought processes is being con­ In using AI techniques to classify might come up only once or twice structed. Called PARRY, the simu­ neuroses, Dr. Colby hopes to in an interview. In a depressive lation is used to test the consis­ sharpen the rules that identify pa­ person, the idea will surface again tency of a theory describing the tients with different neuroses. He and again." pathology. PARRY also serves as a says the officially accepted means Seven expert psychiatrists and training device in teaching students of classifying patients is unreliable. psychologists at the UCLA or psychiatric residents about vari­ "The idea is to find a better clas­ Neuropsychiatric Institute are col­ ous aspects of paranoia. The pro­ sification scheme, and one way is laborating on the neurosis project. gram has proved its ability to do to find properties or characteristics At present the work is in the "ex­ both. of each neurosis," Dr. Colby says. ploratory pilot-study stage," Dr. Recently PARRY was inter­ "The scheme as it now exists de­ Colby emphasizes. The program viewed by five psychiatrists via pends on recognized signs and that will group key ideas into pro­ teletype. Each was granted two symptoms of the patient." files is not yet written. But applica­ interviews. The psychiatrists were The program is being designed tion of AI to speech prosthesis has advised at the start that they would to work opposite to the way progressed to an advanced point. be communicating with either a pa- PARRY operates. Rather than in- In the past several years, Dr.

II

58 Colby and colleagues have de­ nunciation. through a tiny earplug speaker, signed and constructed three The two types of devices, each which gives them a chance to cor­ speech devices, each composed of no larger than a cosmetic case and rect mistakes. Although words portable microprocessors and weighing only 8 pounds, feature a generated by the synthesizer are voice synthesizers. Patients use large vocabulary of words which usually accurate, the process of symbols that are translated by can be constructed by using the communicating can be tedious for more than a thousand rules into English alphabet and a keyboard. both sides of the conversation. verbal language. The programs are used in micro­ "If the patient is typing very One device is specially suited to processors, but were developed slowly, the listener gets impatient," patients who have suffered central and are being refined on the Dr. Colby says. "There's a solution, brain damage due to stroke, tumor, SUMEX computer. Of particular but it's even more complex than or head trauma. Because these pa­ use, Dr. Colby says, is the exten­ what we are working with now." tients have difficulty remembering sive English dictionary that is By using symbols that represent certain words, the device main­ available. He and colleagues have concepts rather than letters, basic tains a vocabulary important to the used the dictionary to write and ideas could be transformed into specific patient and helps the per­ test program rules. Memory and speech. For example, the concept son by offering various candidates. word-finding functions are also of affection might be portrayed by "A stroke patient might want to being refined through use of the a heart with an arrow pointing up. say 'chair', but can't remember the computer dictionary. Unfortunately, the exact type of af­ word. But he does remember the Dr. Colby explains that rules of fection is not indicated by this word 'sit'. The program then gen­ pronunciation for each letter of the symbol. As yet, a means to narrow erates a list of possible words, and alphabet are written into the pro­ concepts until they fit the context the patient just has to hit the gram. The rules first identify the precisely is not available. number of the right one," Dr. Colby context in which the letter appears Despite the disadvantages of says. and then how the letter is pro­ speech prosthesis devices now in Devices for patients not so se­ nounced in both usual and special use at the UCLA laboratory, they verely handicapped do not include cases. The electrical codes of the are a major aid for handicapped this function. Such patients might letters are assembled and passed patients. "A speech prosthesis is a be victims of cerebral palsy, Par­ on to a commercial voice synthe­ godsend," Dr. Colby says. "If you kinsonism, laryngectomy, or might sizer, which simulates the sounds can't talk, life is hell. have tracheostomies. Their major of speech. "All the attempts to use teletypes problem is only in speech and pro- Patients hear the words first have failed because people want

5! to hear a voice. And because Communication Bliss symbols into spoken lan­ many of the patients who have Enhancement guage. The communication sym­ speech problems are homebound, bols, named after their inventor, they do all their communication Dr. Colby consults with Drs. John C. K. Bliss, are used by people over the phone, and a teletype Eulenberg and Carl V. Page, com­ who have suffered brain damage. can't work in that case." puter scientists at Michigan State Specifically, these symbols are in­ The three devices at UCLA have University, who are now directing terpreted by the semantic, nonver­ been used repeatedly by patients, the COMMUNICATION EN­ bal side of the brain. and Dr. Colby says they are ready HANCEMENT pilot project. Their When using the lap-board, pa­ to be offered to a mass market, goal also is to design intelligent tients choose symbols for various except for one stumbling block. speech prostheses for persons words. These are translated by a The business world, at the present with severe communication hand­ microcomputer into orthographic time, is not interested. icaps. Proposed research includes and phonetic strings which are "In the sixties, you could find all the design of input devices that turned into sounds by a voice kinds of people who wanted to in­ can be used by persons whose synthesizer and into typed words vest in computers, but not today, " movement is greatly restricted, de­ by a visual display unit. Grammar he says. · We need a 'plunger' or a velopment of software for text-to­ rules programmed into the com­ humanitarian willing to man­ speech production, and production puter guide the production of sen­ ufacture the devices." of a microcomputer-based portable tences. Each speech prosthesis built speech prosthesis. "When a person makes the from spare parts in the laboratory In 1978 project scientists de­ symbol for himself, it will come out costs about $2,000. If mass pro­ Signed and built a portable com­ either 'me' or 'I,' depending on duced, Dr. Colby says, the cost munication system for a 10-year­ whether it is the subject or object could drop to as low as $500. But old boy with cerebral palsy who of the sentence," Dr. Page says. most large electronics firms are cannot speak or use his hands to "These decisions are made by looking for broad markets, rather write. Although only partially suc­ grammar rules contained in the than specialized medical ones, Dr. cessful, the device influenced de­ program." Colby says. So he and his team sign of a lap-board communication But vastly extending the intelli­ are concentrating their efforts on aid, which was completed early in gence of the program is necessary refining and further developing the 1979. Called SAL (Semantically before project goals are met. "It is devices. Accessible Language), it translates a very painful process to com-

Dr. John Eulenberg (left) and speech pathologist Ms. Sue Ravlin of the Communication Enhancement proj­ ect with Mr. James Renuk, a victim of cerebral palsy: • We 're looking for a means of communication that will give people with cerebral palsy the most output for whatever input they can provide .•

60 municate with people afflicted by TION project is partly focused on artificial intelligence, Dr. Charles cerebral palsy. They're very, very developing models of the pro­ F. Schmidt, a psychologist, and slow. An enormous amount of con­ cesses people use to understand Dr. N. S. Sridharan, a computer centration is required to make information and plan actions. Dr. scientist, both at Rutgers Univer­ these symbols," Dr. Page says. Kintsch is studying the means by sity, are refining a theory of human "What we're really looking for is a which people understand and information-processing. Their goal means of communication that will summarize texts. He hopes to de­ is to define the way people assem­ give them the most output for termine ways to improve the ble facts into a coherent, under­ whatever input they can provide. It readability of texts. He believes standable pattern. has to do with finding the appropri­ that an explicit theory of normal The program, called BELIEVER, ate language or vocabulary to ex­ comprehension might lead scien­ is used to construct and test a psy­ press thought. It's not just alpha­ tists to the factors that cause learn­ chological theory called BELIEF, betical letters; it's not words; and it's ing problems in children, as well as which is intended to explain the not grammar. It is some combina­ suggest ways to overcome these process people use in understand­ tion of these things. One approach problems. ing the observed actions of others. is to build a very intelligent The other focus of the project, The scientists present situations to knowledge-based system, one that which is under Dr. Polson's direc­ the computer and compare its in­ can infer what the person means tion, is modeling how people terpretations with those of human with a minimum of input." create plans and design complex subjects. If the two sets of interpre­ systems. Specifically, Dr. Polson tations match, the theory gains Hierarchical Models of and colleagues are studying and support. If they do not agree, the comparing how experts and theory and the program may be al­ Human Cognition novices use their knowledge to de­ tered, depending on the degree of The complex cognitive pro­ sign computer software. Given a contradiction. cesses that underlie text com­ coherent formulation of these Although descriptions fed into prehension and planning are being processes, aids could be devel­ the computer are very precise, the explored in another project only re­ oped that would help people per­ BELIEF theory is composed en­ cently accepted into the SUMEX­ form this task. tirely of general principles. The re­ AIM community. Directed by Drs. searchers hope to define the broad Walter Kintsch and Peter G. PoI­ BELIEVER ideas that govern interpretation of son, the HIERARCHICAL actions, regardless of culture. MODELS OF HUMAN COGNI- Using the framework provided by "BELIEVER is a framework in

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61 which to extend the theory. In that foundation to design systems "Projects in SUM EX-AIM such sense, the project is never­ aimed at others. For example, as DENDRAL, MYCIN, and ending," Dr. Schmidt explains. "It's CASNET/Glaucoma has led to an­ MOLGEN have been creating intel­ like reading books from a library. other project dealing with ligent agents to assist human You expect to find answers, but rheumatology. MYCIN, wh ich was problem-solving in task domains of you don't expect to run out of designed to assist in prescribing medicine and biology," Ms. Nii books." therapy for patients with infectious says. "Without exception, the pro­ diseases, has spawned projects grams were handcrafted. This AI Tool Building that have application to phar­ process takes many years, both for macology (HEADMED) and pul­ AI scientists and for experts in the At present many of the re ­ monary disease (PUFFNM). An­ field of collaboration." searchers in SUMEX-AIM design other example of sharing is the AGE grew out of HEARSAY, a and build systems to suit their own adaptation of ACT programs by speech-understanding program specific needs. One side effect is a Drs. Greeno and Lesgold to simu­ that envisioned a base containing certain amount of duplication of ef­ late the comprehension processes knowledge of many different types. fort. "The effort of such redevelop­ in children performing arithmetic As a result, AGE is suited to the ment is very large for such highly and reading tasks. design of many different programs. complex computer projects as the According to Dr. Feigenbaum, a She hopes that the program will knowledge-based inference pro­ long-term goal of SUMEX-AIM is to evolve someday into a means of grams being developed in develop program frameworks that building programs for widely differ­ SUMEX-AIM ," Dr. Feigenbaum can be applied more generally. ing purposes, thereby simplifying says. "But we are taking important the process of writing software. A long-range goal, Ms. Nii says, is to steps in sharing programs that al­ Attempt to Generalize ready exist and learning to bu ild fu ­ allow researchers with only a ture programs that can be more One effort in this direction is a rudimentary understanding of easily shared." system called AGE (Attempt to computer science to design spe­ SUMEX-AIM community mem­ Generalize) being developed by ci al ized AI systems by using AGE. bers have been successful at a Ms . H. Penny Nii and Dr. Feigen­ The program is now avail able on type of community-building activity baum. It is intended to "despecial­ the SUM EX-AIM system, and has that has been called "budding." ize" software, making knowledge been used to design several exper­ Projects intended for use in one engineering more generally avail­ imental programs. One of these is area of medicine have provided the able to the scientific community. being developed as part of Drs.

62 Kintsch and Polson's text com­ volumes is expected to be printed. prehension project. It will cover techniques for heuristic search, knowledge representation, AI Handbook AI programming languages, natural language understanding, speech In another core research effort understanding, application-oriented aimed at speeding the dissemina­ research in AI , and automatic pro­ tion of information about AI tech­ gramming. The authors represent niques, Dr. Feigenbaum, Mr. Avron both academic and private re­ Barr, and colleagues are assem­ search centers. bling a handbook of artificial intelli­ "When it is finished , there will be gence. In final form, the handbook no comparable resource for AI re­ will contain some 200 articles searchers and other scientists who covering the most important ideas, need descriptions of AI tech­ techniques, and systems developed niques," Dr. Feigenbaum says. during the past 20 years of AI re­ search, Dr. Feigenbaum says. The articles, each about four pages long, will be written in language suited to the student of AI , as well as to profeSSionals outside the field. "Published research is not gen­ erally accessible to outsiders, and elementary textbooks are not nearly broad enough to be useful to scientists working in other disci­ plines who want to do something that requires knowledge of AI ," Dr. Feigenbaum says. "The handbook will fill this gap." Later this year, the first of two

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€ Computers currently touch all In recent years this nationwide segments of society, both military system has attempted to grease Future and civilian. They guide defense the wheels that carry AI products efforts, compute bills and taxes, into the marketplace by making the of AI control traffic and inventories, and programs applicable to practical supply educational and administra­ needs and easier to use. Although tive services. In short, society this role is somewhat beyond the would be crippled if all the com­ strict confines of basic research puter plugs were suddenly pulled. and development, SUM EX-AIM re­ As computers become "smarter," searchers say it is necessary to ob­ some scientists believe they will be tain information about the per­ given more responsibility. "By the formance of their programs in prac­ turn of the century, there will be a tical applications and to combat lot of computerized professional what they term the "development decision-making," Dr. Herbert gap." Essentially, this gap is the Simon says. void that currently exists between The role to be played by prototype and finished product­ Prospectus SUMEX-AIM in developing this po­ the product for which there is a tential is unclear as yet. Currently, market in the real world. the network is a major force in The aerospace industry is a basic research and development of well-established medium for devel­ AI. Many of the systems that now oping new projects in that field , but use AI techniques for medical no such industry yet exists for AI. It decision-making were developed is simply too young, too much of a using the SUM EX-AIM computing risk for business to jump into resource. Several programs are whole-heartedly. This is not to say able to reason in specialized areas that business has turned its back at the same level as experts. on this branch of science. Some Some are already in test use. companies have expressed inter­ Plans are being made to apply est. But their interest must be en­ others in chemistry laboratories, couraged by showing the worth of hospitals, and outpatient clinics. AI programs, researchers say. This

"As I see it, it's a toss-up between a Belgian data processing machine and an American electronic computer." 64 may be accomplished by develop­ The SUMEX-AIM resource soon program could dramatically in­ ing a few select programs that are will be making a special machine crease their productivity." in advanced stages and are com­ available to help move AI pro­ Programs that have ventured patible with practical applications. grams into the real world. This outside the laboratory have per­ The argument for pushing these limited capacity system will be formed quite respectably. But, even systems into clinical and laboratory tethered by communication lines to though their performance might settings is formidable. the main research computer, which have been shown to be excellent, The CONGEN program, which resides at Stanford, and will be they have been put to only limited evolved from DENDRAL, has been compatible with the languages use, pOinting up a serious short­ a pioneering research effort in AI. used for programs like DENDRAL, coming. An extraordinary amount of addi­ INTERNIST, MYCIN, and SECS. "It is an error to concentrate only tional effort has been expended to When installed, the new machine, on improving the computer's ability develop this program for real-world called DEC 2020, can be dedi­ to make decisions, when success use-an effort that extends far be­ cated to tests of the programs in depends on solving other problems yond the money involved. Dr. real-world arenas such as clinics or of acceptance," Dr. Edward Short­ Joshua Lederberg views the pro­ chemistry laboratories. According liffe concludes. gram as a prototype that may to Mr. Thomas Rindfleisch, the ex­ Paying more attention to "human bridge the development gap. perience should provide critiques engineering" will make computers "It is of very serious concern that valuable for the further develop­ more acceptable to physicians. the entire enterprise of research in ment of these programs. Also, "Doctors are just not going to sit at this area is going to be judged at practical demonstrations may help a terminal that they don't know some point by the utility of this par­ convince private industry and sci­ how to operate or don't have time ticular example," he says. "I don't entists that these programs are in­ to use," Dr. Lederberg says. "Voice think this kind of effort would be deed useful. entry of data would make a very likely to be repeated, and hopefully Dr. Dennis Smith of the DEN­ big difference, and there are some wouldn't have to be. Having had DRAL project says this is the best other technologies that need to be one successful instance of getting way to convince people such pro­ incorporated into these systems." something started on the road to grams are useful-"to have people Suggested ways of reducing re­ where it could be marketed, private sit down and use the programs, sistance range from improving the companies could be convinced at a and see exactly what they can and mechanics of interaction with the much earlier stage that other proj­ can't do. People who have done computer to building features into ects would be worthwhile to pick up." that with CONGEN feel that the the programs that make them ap- Dr. Dennis Smith, member of the DENDRAL project: · We have to show scientists that AI programs can amplify their abilities .•

65 pear more clearly as helpful tools Bruce Buchanan. hardware or techniques, because rather than complicating burdens. "It would be very easy for a per­ these will undoubtedly change in These include using display termi­ son using CONGEN to believe that unpredictable ways, just as the nals equipped with light-pens, spe­ the answer is exactly what the pro­ bulky vacuum tube was replaced cial keyboards, color, and graphics. gram tells him," Dr. Buchanan by integrated circuits and plug­ Also, programs should be de­ explains. "But if the set of assump­ and-socket programming gave rise signed to require no more time to tions in the program is not appli­ to software. Controversial specula­ operate than physicians currently cable, then the answer is going to tion on how far the computer will need to accomplish the same tasks be wrong." develop only distracts from useful on their own. Through knowledge of its own discussion of what the computer is "The tasks AI programs are scope, a program will know capable of accomplishing in the being designed to do require, at enough to warn users about its lim­ next few decades, and the prob­ present, a lot of time or drudgery itations. Whether people will heed lems that must be hurdled in reach­ on the part of the professional," Dr. these warnings, however, is un­ ing its potential. Smith says. "By giving these func­ known. "There is a very real AI researchers agree that much tions to the computer, the person danger that programs may become work remains to develop no longer has to spend time worry­ bureaucratized prematurely as knowledge-based computer pro­ ing about certain aspects of the monitors of performance," Dr. grams into more effective tools and problem and can direct his atten­ Lederberg says. "They may be to exploit their potential over the tion to those aspects for which used as external monitors of a next few decades. Experience and there is no program. We have to physician's or scientist's perfor­ the slow progress of the past 2 de­ show scientists that AI programs mance, to the detriment of good cades underscore the immensity of can amplify their abilities." medicine and good science. I think problems yet to be resolved. A more complex and essential some people might conjure up Dr. Buchanan recalls the experi­ point concerning human engineer­ fears about the abuse of such ence of building the DEN ORAL ing features is that each program tools, and some of those fears program. Work was limited in the should "know" its limitations and might be quite legitimate." Says Mr. early years by the size of available be able to convey that information Rindfleisch, "Society must learn to computers, but mostly by the pro­ to users. Experts tend to put more use these tools effectively." gramming techniques available. trust in people and, by extension, But the future seldom fulfills For over a decade, researchers AI programs that admit ignorance prophecy. No one can judge what became more and more ambitious when appropriate, according to Dr. will occur on the basis of current in the size of the areas they were Mr. Thomas Rindfleisch, director of the SUMEX computing facility: ·So­ ciety must learn to use these tools ef­ fectively. •

66 willing to tackle. But these areas Dr. Buchanan says. "Meta- "We're nearing the time when still have to be limited to relatively DEN ORAL is now trying to get to textbooks will be read and inter­ small domains, at least in the fore­ the stage of automatic rule genera­ preted by machines," Dr. Leder­ seeable future, he says. tion or inference of generalized berg explains. Dr. Feigenbaum agrees. Be­ rules from specific observations. In Connected with this would be a cause there is no way to represent this sense it is a second-genera­ third change, a change in the style enough knowledge in the machine tion program- the next higher used by individuals to express to cover an entire area, such as in­ layer." Ultimately it may be pos­ knowledge. The working language fectious diseases, programs must sible to build a system that can in some areas of science will be be limited to subareas. Through bootstrap its way up, with human taught in terms that are less am­ the late seventies and early guidance, to higher and higher biguous for machine interpretation. eighties, it will not be possible to levels of reasoning. "Editors will demand it; libraries will make more than a large dent in Another major hurdle in the de­ demand it; and people themselves such open-ended problems, he velopment of knowledge-based will want it, in order to make that says. As a result, work will con­ programs is the assimilation of information more readily useful," tinue on problems that are very existing knowledge. Dr. Lederberg Dr. Lederberg says. nearly self-contained. "If almost all predicts that the knowledge base "Less time will be spent getting the relevant knowledge can be will soon be the equivalent of a experts to explain what they know; captured, and there is very little in­ library. He says several steps are rather, experts will oversee the edi­ teraction with anything outside that needed to make this happen. First, torial process involved in digesting specific subarea, then the chances libraries will have to become "ma­ what is in the existing textbooks," are good that successful programs chineable." This is taking place he continues. "Conversely, the can be produced," he says. "Once even now, although mostly for the books will be written in a style that this nucleus is in hand, more and retrieval of documents. But, in­ makes them more compatible and more difficult problems can be ad­ creasingly in the future, documents accessible to verification. We've dressed." themselves will be machine­ still got about 20 years until this Research is already under way composed. "There will be manual happens," he believes, "but it cer­ to generalize the capabilities of entry to be sure," he says, "but tainly won't take a hundred." Then some programs. "Early in the whatever hard copy comes out will it will be possible to use the expert game, we took chemistry rules for be through the computer." as a catalyst and guide in the de­ DEN ORAL out of the heads of Dr. Second, information will be ac­ velopment of intelligent computer Carl Djerassi and other chemists," quired using natural language. programs, rather than as the Dr. Joshua Lederberg, president of Rockefeller University and SUMEX­ AIM advisor: · We 're nearing the time when textbooks will be read and in­ terpreted by machines. " generator of information that goes says. And there will be a major into the knowledge base, he adds. side benefit as well. Through the experience gained "This knowledge, which consti­ in writing intelligent programs for tutes the expertise of practice, can specialized areas of expertise, AI then be published in a new type of researchers hope to fashion more textbook-a book that will contain general principles about intelli­ the rules of how knowledge is used gence. "We hope that by writing in a given field , not just facts," he programs able to do this kind of says. "Such a development could reasoning we will understand more produce a revolution in education." about, and draw connections be­ tween, the loose associations and judgmental knowledge that are codified in these programs," Dr. Buchanan says. Dr. Feigenbaum concludes that it is an article of faith , at the moment, that such common principles can be found . "We are all hoping that research in AI will lead to a theory of intelligence that will define in­ formation processing, whether that processing is manifested in the human brain or in silicon chips," he says. If such a theory is produced, it will allow more rapid development of AI applications and make these programs much more effective in the tasks they perform. Most likely the scope of applications will also be broadened, Dr. Feigenbaum

68 SUMEX-AIM is a national com­ called TYMNET. Those projects puter system supported by the NIH with funding from the Department Appendix I Division of Research Resources' of Defense are able to use the de­ Biotechnology Resources Pro­ partment's network ARPANET. gram. It is dedicated to the promo­ Through these links, distant inves­ tion of artificial intelligence applica­ tigators communicate with each tions in biomedicine. The main other and run programs on a computing facilities and communi­ time-sharing basis. cation tools that allow access by When the SUM EX-AIM system scientists around the country are began, TYMNET and ARPANET located at Stanford University Med­ were the only existing means of ical School. communication that allowed re­ The system is currently built mote computer links. Networks around a time-shared Digital such as TYMNET and ARPANET Equipment Corporation, dual KI-10 consist of a complex web of inter­ computer, and the TENEX operat­ connections that span the country ing system. A small part of the from the east to the west coasts. Organization Rutgers University biomedical Terminal and other data communi­ computing resource (DEC 2050) is cations are relayed from point to also available for AIM use. point along telephone lines. In­ and For the past 3 years of its 6-year creasingly, cross-oceanic com­ history, the SUMEX facilities have munication is available through been working at full capacity. Of­ cables and satellite links as well. Facilities ten , demand for computation time As other systems of network com­ has surpassed available supply. In munications become available, response, investigators on some they may be tied into the SUMEX Available projects are sharing their comput­ system. ing loads between their own uni­ To complement electronic com­ versity facilities and SUM EX . munications, face-to-face contacts Most, however, continue to use within the community are still the SUMEX computer through the needed. These are provided commercial communication link through annual workshops and in-

ARPANET: a complex web of computer-telephone links that spans the country from east to west coasts.

69 dividual contacts. National work­ They are trying to achieve a bal­ testing at times convenient to col­ shops are organized under Dr. ance among the research mission laborating physicians or other pro­ Saul Amarel, chairman of the Rut­ of SUM EX-AIM, the expanding fessional people. gers University computer science community, and the need to exper­ Use of this computer may also department. They cover a broad iment with the new AI programs serve as a model for providing range of topics and give inves­ and to validate them in the real local computing support to projects tigators from diverse disciplines, as world. in the community. As computer well as potential new users, a view Through the use of a small com­ hardware prices continue to fall, of work in progress. puter, called the DEC 2020, admin­ well-developed projects may soon As applications become more istrators hope that programs near­ be able to obtain machines to sup­ practical, the growing number of ing evaluation stages can be port their own work and relieve the users would swamp the system's tested without disrupting on-going load on SUM EX, freeing computer capacity if all attempted to use cur­ research. The new computer will time for newer projects. rent SUMEX facilities. To prevent be tethered to the main SUMEX this potential problem, administra­ computing and network facilities The SUMEX-AIM computer: a new tors are exploring several options. and can be scheduled for clinical age began here.

70 SUMEX-AIM is situated within key role in assessing the need for the Stanford Medical School and additional AIM computing re­ Appendix II serves as the nucleus for a na­ sources and in deciding the best tional community of biomedical AI placement and management per­ projects. User projects are sepa­ sonnel for such new facilities. rately funded and independently Advising the executive commit­ managed. These projects are tee is the AIM advisory group, selected for access to SUMEX fa­ which serves several functions, in­ cilities on the basis of scientific and cluding the recruitment of appro­ medical merit, as well as commit­ priate projects. The group dissemi­ ment to forwarding AI techniques nates information ranging from among members of the SUM EX­ general overviews of SUM EX-AIM AIM community. to detailed guidelines for determin­ Dr. Edward Feigenbaum, chair­ ing whether a project is appropriate man of the Stanford computer sci­ for admission. Members are I.I ence department, is principal in­ selected to review specific propo­ vestigator of SUMEX-AIM. Dr. sals for new projects, according to Management Stanley Cohen, chairman of the their field of expertise. As a whole, department of genetics and previ­ the group reviews and recom­ ously an investigator on the mends priorities for allocating facil­ MYCIN project, provides coordina­ ity use among projects, and gener­ tion between Stanford Medical ates policies and goals for the re­ School and the individual source. SUM EX-AIM projects. Mr. Thomas Current members of these vari­ Rindfleisch manages the SUMEX ous committees are: computing facility and its staff. Dr. Elliott Levinthal serves as liaison Stanford Advisory Group between SUMEX-AIM administra­ tors and the user community. Edward A. Feigenbaum, Ph.D. Computing time is divided Chairman among three groups. Projects in Department of Computer Science the Stanford Medical School re­ Margaret Jacks Hall, Room 216 ceive 40 percent, as do those in Stanford University the national community. System Stanford, California 94305 development work receives 20 (415) 497-4079 percent. Individual projects receive a negotiated share of the time Stanley N. Cohen, M.D. available to their respective com­ Department of Genetics and munities. Division of Clinical Pharmacology, Several committees assist in the Department of Medicine, L314 management. Dr. Feigenbaum Stanford University Medical Center consults with members of the Stan­ Stanford, California 94305 ford Community Advisory Commit­ (415) 497-5315 tee when selecting and allocating Carl Djerassi, Ph.D. facility use among in-house proj­ Department of Chemistry, Stauffer ects. 1-106 For the national community, two Stanford University groups play complementary roles Stanford, California 94305 in advising the principal in­ (415) 497-2783 vestigator. The AIM executive committee oversees operation of Elliott C. Levinthal, Ph .D. the SUMEX resource as related to Department of Genetics, S047 national users and makes the final Stanford University Medical Center decisions on project applications. It Stanford, California 94305 establishes policies for allocating (415) 497-5813 facility use among national projects and approves plans to develop or AIM Executive Committee refine hardware and other tools used by these projects. The com­ Joshua Lederberg, Ph.D. mittee supervises AIM activities, (Chairman) such as the workshop series cur­ The Rockefeller University rently under the direction of Dr. 1230 York Avenue Saul Amarel of Rutgers University. New York, New York 10021 Committee members also serve a (212) 360-1234 71 Saul Amarel, Ph.D. Tufts New England Medical Center Department of Computer Science Hospital Rutgers University 171 Harrison Avenue New Brunswick, New Jersey Boston, Massachusetts 02111 08903 (617) 956-5910 (201) 932-3546 Herbert A. Simon, Ph .D. William R. Baker, Jr., Ph.D. Department of Psychology (Executive Secretary) Baker Hall, 339 Biotechnology Resources Program Carnegie-Mellon University National Institutes of Health Schenley Park Building 31 , Room 5B43 Pittsburgh, Pennsylvania 15213 9000 Rockville Pike (412) 578-2787 or 578-2000 Bethesda, Maryland 20205 (301) 496-5411 Stanley N. Cohen, M.D. Edward Feigenbaum, Ph .D. Donald Lindberg, M.D. (Adv Grp Member) 605 Lewis Hall University of Missouri Columbia, Missouri 65201 (314) 882-6966 Jack D. Myers, M.D. School of Medicine Scaife Hall, 1291 University of Pittsburgh Pittsburgh, Pennsylvania 15261 (412) 624-2649

AIM Advisory Group Donald Lindberg, M.D. (Chairman) Saul Amarel, Ph.D. William R. Baker, Jr., Ph .D. (Executive Secretary) Stanley N. Cohen, M.D. Edward Feigenbaum, Ph.D. (Ex-officio) Joshua Lederberg, Ph .D. Marvin Minsky, Ph.D. Artificial Intelligence Laboratory Massachusetts Institute of Technology 545 Technology Square Cambridge, Massachusetts 02139 (617) 253-5864 William C. Mohler, M.D. Division of Computer Research and Technology National Institutes of Health Building 12A, Room 3033 9000 Rockville Pike Bethesda, Maryland 20205 (301) 496-1168 Jack D. Myers, M.D. Stephen G. Pauker, M.D. Department of Medicine- 72 Cardiology Users may gain access to Human Cognition (CLIPR SUMEX-AIM as guests of estab­ Project) 12/78 Appendix III lished projects, as temporary pilot • Peter G. Polson, Ph.D. projects, or as fully authorized re­ Walter Kintsch, Ph .D. search projects. At present, 16 re­ Computer Laboratory for search and 3 pilot projects are ac­ Instruction in Psychological tive on SUM EX-AIM. Those in­ Research (CLlPR) terested in proposing additional Department of Psychology projects should contact Dr. Elliott University of Colorado Levinthal at (415) 497-5813. Ques­ Boulder, Colorado 80302 tions about the SUMEX facility and (303) 492-6991 its operation should be directed to Funding: National Institute of Mr. Thomas Rindfleisch at (415) Education 497-5569. SUMEX staff can be National Institute of Mental contacted by letter at: SUMEX Health, NIH Computer Project, Room TB-105, Office of Naval Research Stanford University Medical 4. Higher Mental Functions SUMEX-AIM Center, Stanford, California 94305. Project 10/73 A directory is provided for those Kenneth M. Colby, M.D. interested in contacting the princi­ University of California Directory pal investigators of specific proj­ (UCLA) ects. The date that each project Department of Psychiatry and began on the system is noted in NPI, Box 26 the right column, adjacent to its 760 Westwood Plaza title. For those projects with co­ Los Angeles, California 90024 investigators, the investigator to (213) 825-4626 Project contact for additional information is Funding: National Science designated by an asterisk. Foundation, Division of Support for the computing facility Funding Computer Science/ at Stanford and management of Mathematics SUMEX-AIM is supplied totally by the Biotechnology Resources Pro­ 5. INTERNIST Project 10/74 gram (BRP) , Division of Research Jack D. Myers, M.D. Resources, NIH. Individual projects ·Harry E. Pople, Ph .D. are independently funded through Decision Systems Laboratory NIH and other agencies as indi­ 1360 Scaife Hall cated. University of Pittsburgh Pittsburgh, Pennsylvania National AIM Projects 15261 (412) 624-2649 1. Acquisition of Cognitive Funding: Bureau of Health Procedures (ACT) 11 /75 Resources Development, John Anderson, Ph .D. DHEW Department of Psychology BRP, Division of Research Carnegie-Mellon University Resources, NIH Pittsburgh, Pennsylvania 15213 6. PUFFIVM: Biomedical (412) 578-2788 Knowledge Engineering in Funding: Office of Naval Clinical Medicine 10/77 Research • John J. Osborn, M.D. 2. Chemical Synthesis Project The Institutes of Medical Sciences (SECS) 9/75 W. Todd Wipke, Ph .D. 2200 Webster Street Department of Chemistry San Francisco, California University of California 94115 (415) 567-0900 Santa Cruz, California 95064 (408) 429-2397 Edward A. Feigenbaum, Ph.D. Funding: Biotechnology Stanford University Resources Program (BRP), Division of Research Funding: National Institute of Resources, NIH General Medical Sciences National Cancer Institute, 7. Rutgers Computers in NIH Biomedicine 3. Hierarchical Models of Resource 10/73 Saul Amarel, Ph.D. 73 Department of Computer Department of Computer 7. RX Project 1/79 Science Science "Robert L. Blum, M.D. Rutgers University Margaret Jacks Hall, Room 216 Glo Wiederhold New Brunswick, New Jersey Stanford University Department of Computer 08903 Stanford, California 94305 Science (20t) 932-3546 {41S} 497-4878 Margaret Jacks Hall, Room a. EXPERT AND "Edward A Felgenbaum,Ph.D. 450A CAS NET/Glaucoma Funding: SUMEX core Stanford Uriiverslty Casimir Kulikowski. Ph.D. research. BRP Division of Stanford, California 94305 (201) 932-2006 Research Resources, NIH (415) 497-6970 Shalom Weiss, Ph.D. 3. DENDRAL Project 10/73 Funding: Ph arm aeeutieal (201) 932·2006 "Carl Djerassi, Ph .D. Manufacturers' Association Funding: BRP, Division 01 Department of Chemistry Foundation Research Resources, Staulter Building 1, Room 106 National LIbrary of Medicine NIH Stanford University b. BELIEVER Stanford, California 94305 Pilot National AIM Projects Charles Schmidt, Ph.D. (415) 497-2783 1. Communication (201) 932-2448 Edward A. Feigenbaum, Ph.D. Enhancement Project 3/77 Funding: BAP. DivIsion of Funding: BAP, Division of "John B. Eulenberg, Ph .D. Research Resources, Research Resources, NIH Carl V. Page NIH 4. MOLGEN Project 9/76 Department of Computer 8. Simulation of Cognitive "Laurence H. Kedes. M.D. Science Processes (SCP) 2/78 Veterans Administration Michigan State University James G. Greeno, Ph .D. Hospital (151M) East lansing, Michigan "Alan M. Lesgold, Ph.D. 3801 Miranda Avenue 48824 Learning Research & Palo Alia, California 94304 (517) 353-0831 Development Center (415) 497-5897 Funding: Wayne County University of Pltrsburgh Edward A. Feigenbaum, Ph.D. (Detroit, Michigan) [I 3939 O'Hara Street Douglas Lenat, Ph .D. 2. Computerized I" Pittsburgh. Pennsylvania Funding: National Science Psychopharmacology 15260 Foundation Advisor (HEADMED) 5/76 (412) 624-4901,624-4892 5. MYCIN Project 10/73 "Jon F. Heiser, M.D. Funding: Office of NalJal "Bruce G. Buchanan, Ph.D. Ruven E. Brooks. Ph.D. Research Edward H. Shorlliffe, M.D., Department of Psychiatry and National Science Foundation Ph.D. Behavioral Sciences Nationaiinstitute of Department 01 Computer UniverSity of Texas Medical Education Science Branch Advanced Research Projects Margaret Jacks Hall, Room Administrative Annex, 3rd Agency (through Office of 238 Floor Naval ResearCh) Stanford University Galveston, Texas 77550 (713) 765-3219 Stanford Projects Stanford, California 94305 (415) 497·0935 Funding: University 01 Texas 1. AI Handbook Project 4/77 Funding: EMYCIN funded by Medical Branch at Edward A. Feigenbaum, the National Science Galveston Ph .D. Foundation Anne A. Issler Endowment Department of Compu1er GUIDON JOlnlly funded by Fund, University of Science Office of Naval Research California at IrlJine Margaret Jacks Hall. Room and AdlJanced Research Pilot Stanford Projects 216 PrOjects Agency Stanford University Oncology study funded by the 1. Ultrasonic Imaging Stanford, Calilornia 94305 National Library 01 Project 11/78 (415) 497-4079 Medicine W. Desmond McCallum, M.O. Funding: partial support Irom 6. Protein Structure "James Brinkley, M.D. the Advanced Research Project 10/73 Department of Gynecology Projects Agency of the Edward A. Feigenbaum, and Obstetrics. A328 Department of Defense Ph .D. Stanford University Medical partial support from SUMEX "Robert Engelmore, Ph .D. Center core research, BRP c/o ARPA IPTO Stanford, California 94305 Division of Research 1400 Wilson Bou'evard (415) 497·6175 Resources, NIH Arllnglon. Virginia 22209 Funding: National Instil ute 01 2. Attempt to Generalize (202) 694-5037 Child Health and Human (AGE) 9/77 Funding: Nationa! Science Development, NIH 74 -H. Penny Nji Foundation ~ NIH Publicabon No 80-2071 March 1980