Robert Ledley

Robert Ledley was born on June 28, 1926, in Flushing Meadows, Queens, New York City, US. His father, Joseph Levy, was an accountant and his mother, Kate Levy, was a schoolteacher before becoming a homemaker. Robert had a sister, Marion, and a half-brother, Ralph. All three siblings were surnamed Ledley.

Among Ledley’s childhood friends in Flushing was Margaret Oakley Dayhoff, who would later spend most of her career working at the National Biomedical Research Foundation and who would become a founder of the field of bioinformatics. Ledley attended the Horace Mann School, from which he graduated in 1943.

As an undergraduate student at Columbia University Ledley excelled in physics, taking undergraduate and graduate courses within his first two years as a student. When, however, he informed his parents of his desire to become a physicist, they objected on the grounds that a career in physics would not be feasible for him given the scarcity of steady jobs in that field. Instead, they urged him to make his living as a dentist. Ledley attempted to follow both paths at once; he enrolled in the New York University College of Dentistry while continuing to pursue his education in physics at Columbia. During the day, Ledley would take dentistry training courses at NYU, then he would take the subway to Columbia to take evening courses in physics. After receiving his DDS from NYU in 1948, Ledley became a full-time physics graduate student at Columbia, where he took courses from many noted physicists including I.I. Rabi (who joked that Ledley was the only physicist who could pull a man’s tooth), Enrico Fermi, Hans Bethe, and J.A. Wheeler. Ledley received a MS in physics from Columbia in 1950.

In 1949, Ledley married Terry Wachtell (born 1926), a mathematics teacher at Queens College, and sister of Herbert Wachtell. The couple had two sons, Fred (born 1954) and Gary (born 1957). When the couple moved to the DC area in the early 1950s, Terry was employed as a computer programmer until leaving work to raise their sons. Both sons graduated from Georgetown University School of Medicine. Fred Ledley is Professor of Natural and Applied Sciences at Bentley University and is the author of numerous scientific papers as well as the novel, Sputnik’s Child (2011). Gary Ledley is a practicing cardiologist associated with Drexel University.

In 1950, shortly after the outbreak of the Korean War, Ledley was contacted by a U.S. Army recruitment officer, who offered him a choice: he could volunteer to join the U.S. Army Dental Corps as a first lieutenant or be conscripted into the infantry as a private. Ledley promptly volunteered, and was sent to the U.S. Army Medical Field Service School for training. Because Ledley was also trained in physics, he was assigned to a dental research unit at Walter Reed General Hospital, in Washington, D.C.

During his time in the army, Ledley was responsible for improving prosthetic dental devices (such as dentures) then widely used by Army personnel. Notably, Ledley drew on his training in dentistry and physics to develop a system that optimized the process of fitting dentures by allowing dentists to determine the “angle of chew,” or the mean slope of each tooth relative to the surface of an object (e.g. a piece of food) being bitten. Ledley presented this work to the American Physical Society in 1952, and it generated nationwide attention via an Associated Press newspaper story titled “Mathematics Used to Keep False Teeth in Place.”

Ledley's work on dental prosthetics brought him into collaboration with researchers based at the National Bureau of Standards Dental Materials Research Section, where he was offered a research job in 1952 following his discharge from the Army. There he encountered the Standards Eastern Automatic Computer, one of the earliest stored-program electronic digital computers. Ledley's first interaction with SEAC came via his wife, Terry, who worked as one of the machine's programmers – Robert taught himself to program by examining programs (on perforated paper tape) and manuals Terry brought home. Ledley started to use SEAC himself for his dental research, but after proving an adept programmer and troubleshooter, he found himself working with SEAC (and later DYSEAC) full-time on a wide variety of projects, including a remote-controlled aircraft guidance system.

When Ledley lost his job at the NBS in 1954 due to budget cuts, he turned down an offer to work for IBM (which hired Ledley’s colleagues en masse). Instead, he found employment as an “Operations Research Analyst” at the Operations Research Office at Johns Hopkins University. There, his work remained mostly focused on military problems, but his expertise in biology, physics, mathematics, and computing caught the attention of one of his new ORO colleagues, George Gamow. Gamow, who was renowned for his contributions to the Big Bang cosmological model, had taken an interest in molecular biology immediately after James D. Watson and Francis Crick elucidated the double helix structure of DNA in 1953. Gamow believed Ledley’s skills could be instrumental in helping to crack the genetic code, that is, by solving the problem of how a DNA sequence translates into proteins. In 1954, Gamow invited Ledley to join the elite RNA Tie Club; some other members of the club were Watson, Crick, Richard Feynman, Max Delbrück, Edward Teller, and Sydney Brenner.

Ledley’s main work for the RNA Tie Club was an effort to generate a set of contingency tables for the purpose of writing a computer program that would determine the correspondence between any three-letter sequence (triplet) of nucleotide bases and any amino acid (the building blocks of proteins). Sponsored by Gamow, Ledley published his work in 1955 in the Proceedings of the National Academy of Sciences. Though Ledley had produced a combinatorial table that could theoretically be used to determine which three-letter sequence of DNA bases corresponded to which amino acid, the problem required several thousand years of computation time on the world’s fastest computers (circa 1955) to produce a solution.

In 1956, Ledley was hired as an assistant professor of electrical engineering at the George Washington University School of Engineering and Applied Science. There, he taught some of the earliest courses on computer programming and wrote his first book, Digital Computer and Control Engineering (1960). At GWU, Ledley acquired the Florida Automatic Computer I and II, two descendants of SEAC that had been discarded by the US Air Force as surplus, for the purpose of establishing a “computation center” that would use the computers to automate Frederick Sanger’s process of determining the amino acid sequence of proteins. The center was never built, however, because the National Institutes of Health rejected Ledley’s request for a grant to fund it, and because the university balked at the prospect of installing and supporting the two enormous computers.

Lee B. Lusted (1922-1994), a radiologist with a background in electrical engineering, became aware of Ledley’s work in 1956 after Ledley gave a presentation titled “An Operations-Research View of Medicine and Health” to the annual meeting of the Operations Research Society of America. After the meeting, Lusted telephoned Ledley, and the two found that they shared a strong interest in using electronics and mathematics to improve medicine. The two men immediately began to collaborate on developing ways to teach physicians and biomedical researchers, who rarely had much training in electronics or mathematics, to use electronic digital computers in their work.

In early 1957, Ledley was hired on a part-time basis by the National Academy of Sciences - National Research Council (NAS-NRC) to conduct a national survey of current and potential computer use in biology and medicine in the United States. Supported by Senator Hubert Humphrey and NIH Director James A. Shannon, the NAS-NRC commissioned the survey in an effort to help physicians and life scientists overcome their reluctance to use computers.

In 1959, Ledley and Lusted published “Reasoning Foundations of Medical Diagnosis,” a widely read article in Science, which introduced operations research techniques to medical workers. Areas covered included: symbolic logic, Bayes’ theorem (probability), and value theory. In the article, physicians were instructed how to create diagnostic databases using edge-notched cards to prepare for a time when they would have the opportunity to enter their data into electronic computers for analysis. Ledley and Lusted expressed hope that by harnessing computers, much of physicians’ work would become automated and that many human errors could therefore be avoided.

Ledley’s survey and article also shaped the National Institutes of Health’s first major effort to encourage biomedical researchers to use computers. This effort began shortly after the Soviet launch of Sputnik in October 1957—in reaction to Sputnik, the U.S. Congress sought means boost U.S. scientific and technological productivity. Beginning in 1960, Congress allocated roughly $40 million to the NIH for the purpose of stimulating computer use in biomedical research. Ledley’s survey recommendations, particularly his call for biomedical workers to train extensively in mathematics and engineering, served as a guide for the NIH effort, which was carried out by the NIH’s Advisory Committee on Computers in Research (ACCR). The ACCR was led from 1960 to 1964 by Ledley’s collaborator, Lee Lusted. During those years, the committee established several major biomedical computing centers around the USA and sponsored the development of the LINC. The ACCR’s successor, the Computers in Research Study Section, was headed by Homer Warner, one of the first research physicians to employ Ledley and Lusted’s techniques in a clinical setting.

Following his survey work for the NAS-NRC and the publication of his and Lusted’s articles in Science, Ledley sought federal government and university support his efforts to development computers and computer programs for use by biomedical researchers. With the support of the NAS-NRC, Ledley chartered in 1960 the National Biomedical Research Foundation (NBRF), a nonprofit organization, initially based in an NAS-NRC-owned building near Dupont Circle, Washington, D.C.

The NBRF’s earliest area of emphasis was developing optical pattern recognition technology. Working with Wilson in 1960 and 1961, Ledley built the Automatic Device for Antibiotic Determination (ADAD), a computerized light-measuring device that tested for efficacy of antibiotic drugs by measuring transparency in petri dish cultures. Areas that were transparent were likely areas where the antibiotics had killed the bacterial populations; areas that were opaque likely areas where the bacteria were still alive. The NBRF sold several ADAD units to the Food and Drug Administration, and to large pharmaceutical companies.

Having established that computers could not be used reasonably quickly to decode DNA, Ledley drifted away from the RNA Tie Club. Ultimately the code was broken in the 1961 Nirenberg and Matthaei experiment, which did not use computers and which was not carried out by RNA Tie Club members.

To facilitate discussion among users and developers of FIDAC, Ledley founded in 1969 the peer-reviewed journal Pattern Recognition, the official journal of the Pattern Recognition Society. Ledley remained the editor of Pattern Recognition until 2010.

During his long career at the NBRF, Ledley served as editor of four major peer-reviewed journals. In 1969, he launched the Pattern Recognition Journal and Computers in Biology and Medicine. The former focuses on computerized approaches to pattern recognition, while the latter publishes articles, algorithms, and technical descriptions related to the use of computers in biomedicine. In 1972, Ledley started Computer Languages, Systems and Structures, the mission of which is to publish “papers on all aspects of the design, implementation and use of programming languages, from theory to practice.” In 1976, following the success of ACTA, Ledley initiated Computerized Tomography, which was renamed Computerized Radiology in 1977, and subsequently renamed Computerized Medical Imaging and Graphics in 1981. It serves as “a source for the exchange of information concerning the medical use of new developments in imaging diagnosis, intervention, and follow up.” Ledley served as editor of all four journals until his retirement in 2010. The journals are currently published by Elsevier.

In 1970, the NBRF began its affiliation with the Georgetown University Medical Center. The university, which had allocated space for a biomedical computing facility that had never been built, provided office and laboratory space for the NBRF, while the NBRF would serve as a computing resource for the university as well as bring funding and prestige to the university through its research and development activities.

While at the NBRF, Ledley also carried out work related to computer design. In 1970, when Moore’s Law was still a relatively new idea, and when the most powerful computers had 1,000 to 2,000 logic gates, Ledley wrote a paper titled “Realization of a Billion-Gate Computer” in which he speculated on the capabilities of a transistorized computer that had 1,000,000,000 logic gates. He proposed that such a machine would: 1) have no fixed logic design; 2) be capable of redesign some of its own components; 3) be able to “self-heal.” Billion-transistor microprocessors have been commonplace in personal computers since 2010, though these machines are not as dynamic (in terms of logic structure) as Ledley had predicted.

Ledley is most widely known for his 1970s efforts to develop computerized tomography (CT) or CAT scanners. This work began in 1973, when the NBRF lost most of its NIH funding due to federal budget cuts. During this time, the NBRF had also become increasingly involved in on-campus computing projects. Quickly trying to raise enough funds to cover the NBRF employee salaries, Ledley looked for projects the organization could undertake for Georgetown University. After learning that Georgetown research physicians were frustrated by the $500,000 cost of a CT scanner they wished to buy from EMI (EMI-Scanner), Ledley promised them that the NBRF could build a similar machine for only half the price. The university agreed to give Ledley a chance, and for the next several months a team led by Ledley, Golab, Wilson, and Frank Rabbitt, worked to develop a prototype.

In 1974, after several months of working with Georgetown’s machinists and auto body specialists at a nearby Cadillac dealer, Ledley’s team completed construction of the Automatic Computerized Transverse Axial (ACTA) scanner. The machine had 30 photomultiplier tubes as detectors and completed a scan in 9 translate/rotate cycles, much faster than the EMI-scanner. It used a DEC PDP-11/34 minicomputer both to operate the servo-mechanisms and to acquire and process the images. Most importantly, ACTA could scan the entire body, whereas the EMI-scanner could only scan the head.

Ledley established Digital Information Science Corporation (DISCO) in 1974, which sold the ACTA scanners for $300,000 each. On November 25, 1975, Ledley was issued the patent for the design of ACTA. Later in 1975, DISCO sold the ACTA rights to Pfizer for $1.5 million in cash and $10 million in guaranteed research funding (paid out over 10 years) for the NBRF. Pfizer’s ACTA 0100 and its successor, the 200FS, were sold to hospitals worldwide between 1975 and 1977, but Pfizer lost the medical imaging market to GE Medical and Technicare, which both sold next-generation CT scanners.

From 1979 to 1980, Ledley and Golab developed the Computerized Electro Neuro Ophthalmograph (CENOG). This machine enabled healthcare providers to automatically analyze ocular motility, an important factor in the diagnosis of neurological and ophthalmic disorders. CENOG generated considerable media attention in the early 1980s, largely because it served as a demonstration of the feasibility of automated medical diagnosis.

After Dayhoff died suddenly in 1983, Ledley and Winona Barker (who joined the NBRF in the late 1960s) took charge of the project. During the mid-1980s Ledley and Barker led a team that developed the Protein Identification Resource (later called the Protein Information Resource or PIR), an online version of the Atlas. Researchers using modems or Tymnet could access the PIR to look up sequence information or add to the collection. As of 2012, the PIR remains an important resource for biologists; it is managed jointly by the University of Delaware and Georgetown University, and is a major component of UniProt.

As the use of CT scanners became widespread, Ledley rose to considerable prominence. The ACTA prototype was displayed at the Smithsonian’s National Museum of American History, in Washington, D.C.. The Smithsonian also established an archive for materials related to the development of ACTA. For his role in developing ACTA, Ledley was inducted into the National Inventors Hall of Fame in 1990 and was awarded the National Medal of Technology and Innovation in 1997.

Within medicine, Ledley and Lusted’s article has remained influential for decades, especially within the field of medical decision making. Among its most enthusiastic readers was cardiologist Homer R. Warner, who emulated Ledley and Lusted’s methods at his research clinic at LDS Hospital in Utah. Warner’s work, in turn, shaped many of the practices and priorities of the heavily computerized Intermountain Healthcare, Inc., which was in 2009 portrayed by the Obama administration as an exemplary model of a healthcare system that provided high-quality and low-cost care.

Believing that his career as a university faculty member would ultimately constrain his research, Ledley left his position at GWU in order to dedicate his full-time to running the NBRF. Ledley would lead the NBRF until his retirement in 2010. Early employees included: Louis S. Rotolo (Ledley’s assistant in the NAS-NRC survey), James B. Wilson (Ledley’s former graduate student at GWU), and Margaret O. Dayhoff (a quantum chemist with a Ph.D. from Columbia and Ledley’s childhood friend from Flushing).

In 2011, the NBRF was reincorporated in Massachusetts and has adopted a new mission statement.

Robert Ledley died of Alzheimer's disease in Kensington, Maryland, USA on July 24, 2012.