At the NBRF Ledley pursued several major projects: the early 1960s development of the Film Input to Digital Automatic Computer (FIDAC), which automated the analysis of chromosomes; the invention of the Automatic Computerized Transverse Axial (ACTA) whole-body CT scanner in the mid-1970s; managing the Atlas of Protein Sequence and Structure (created in 1965 by Margaret O. Dayhoff); and the establishment of the Protein Information Resource in 1984.

[2] 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.

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.

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.

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.

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.

[8] 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).

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.

At the National Bureau of Standards, Ledley’s work was primarily related to solving military problems using the techniques of operations research.

For instance, he published an article in the journal Operations Research showing how one could use Boolean algebra to reduce complex military decision-making problems to the point where they could be resolved using a collection of truth tables and yes-or-no questions.

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.

[14] 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.

[15] 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).

[13] 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.

[20] 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.

[22] 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.

[15] 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.

"[27] Like the earlier Science article co-authored with Lusted, Ledley’s new piece was widely read – among its most influential and enthusiastic readers was Joshua Lederberg, who spent much of the later part of his career using computers to solve problems in biology research.

[28] Ledley’s survey and article also shaped the National Institutes of Health’s first major effort to encourage biomedical researchers to use computers.

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.[31] 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.

[31] Building on the success of ADAD, Ledley, Wilson, and a newcomer to the NBRF, electrical engineer Thomas Golab, developed the Film Input to Digital Automatic Computer (FIDAC) in the mid-1960s.

[34] Quickly trying to raise enough funds to cover the NBRF employee salaries, Ledley looked for projects the organization could undertake for Georgetown University.

[34] After learning that Georgetown research physicians were frustrated by the $500,000 (equivalent to $3,431,784 in 2023) 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.

[34][35] Aside from reducing cost, the NBRF team aimed to overcome the major constraint of the EMI-Scanner, namely that it required X-rays to be shone through a water tank enclosing the object being scanned—this constraint limited the use of the scanner to only patients’ heads and required physicians to place patients’ heads into a rubber bladder extending into a water tank.

[35] 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.

Late in the prototype’s development, David C. McCullough, a pediatric neurosurgeon at Georgetown University Hospital used ACTA—without Ledley’s knowledge—to examine a child who hit his head in a bicycle accident.

Alongside Ledley's work on imaging technology, his NBRF colleague Margaret Oakley Dayhoff was developing resources for the study of life on the molecular level.

This machine enabled healthcare providers to automatically analyze ocular motility, an important factor in the diagnosis of neurological and ophthalmic disorders.

[8] CENOG generated considerable media attention in the early 1980s, largely because it served as a demonstration of the feasibility of automated medical diagnosis.