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Robert Steven Ledley (June 28, 1926 – July 24, 2012), professor of physiology and
biophysics Biophysics is an interdisciplinary science that applies approaches and methods traditionally used in physics to study biological phenomena. Biophysics covers all scales of biological organization, from molecular to organismic and populations ...
and professor of
radiology Radiology ( ) is the medical specialty that uses medical imaging to diagnose diseases and guide treatment within the bodies of humans and other animals. It began with radiography (which is why its name has a root referring to radiation), but tod ...
at Georgetown University School of Medicine, pioneered the use of electronic digital computers in biology and medicine. In 1959, he wrote two influential articles in ''Science'': "Reasoning Foundations of Medical Diagnosis" (with Lee B. Lusted) and "Digital Electronic Computers in Biomedical Science". Both articles encouraged biomedical researchers and physicians to adopt computer technology. In 1960 he established the National Biomedical Research Foundation (NBRF), a non-profit research organization dedicated to promoting the use of computers and electronic equipment in biomedical research. 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 th
Automatic Computerized Transverse Axial
(ACTA) whole-body
CT scanner A computed tomography scan (CT scan), formerly called computed axial tomography scan (CAT scan), is a medical imaging technique used to obtain detailed internal images of the body. The personnel that perform CT scans are called radiographers or ...
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 The Protein Information Resource (PIR), located at Georgetown University Medical Center, is an integrated public bioinformatics resource to support genomic and proteomic research, and scientific studies. It contains protein sequences databases H ...
in 1984. Ledley also served as editor of several major peer-reviewed biomedical journals. In 1990, Ledley was inducted into the
National Inventors Hall of Fame The National Inventors Hall of Fame (NIHF) is an American not-for-profit organization, founded in 1973, which recognizes individual engineers and inventors who hold a US patent of significant technology. Besides the Hall of Fame, it also operate ...
. He was awarded the
National Medal of Technology The National Medal of Technology and Innovation (formerly the National Medal of Technology) is an honor granted by the president of the United States to American inventors and innovators who have made significant contributions to the development ...
in 1997. He retired as president and research director of the NBRF in 2010.


Family and education

Robert Ledley was born on June 28, 1926, in
Flushing Meadows Flushing may refer to: Places Netherlands * Flushing, Netherlands, an English name for the city of Vlissingen, Netherlands United Kingdom * Flushing, Cornwall, a village in Cornwall, England * The Flushing, a building in Suffolk, Englan ...
, Queens, New York City, US."Lemelson Center for the Study of Innovation & Innovation"
''Smithsonian-Lemelson: Robert Ledley Papers 1972-1981'', Retrieved Apr 14, 2012.
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 Margaret Belle (Oakley) Dayhoff (March 11, 1925 – February 5, 1983) was an American Biophysicist and a pioneer in the field of bioinformatics. Dayhoff was a professor at Georgetown University Medical Center and a noted research biochemi ...
, 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 Bioinformatics () is an interdisciplinary field of science that develops methods and Bioinformatics software, software tools for understanding biological data, especially when the data sets are large and complex. Bioinformatics uses biology, ...
. Ledley attended the
Horace Mann School Horace Mann School (also known as Horace Mann or HM) is an American private, independent college-preparatory school in the Bronx, founded in 1887. Horace Mann is a member of the Ivy Preparatory School League, educating students from the New Yo ...
, from which he graduated in 1943. As an undergraduate student at
Columbia University Columbia University in the City of New York, commonly referred to as Columbia University, is a Private university, private Ivy League research university in New York City. Established in 1754 as King's College on the grounds of Trinity Churc ...
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 The New York University College of Dentistry is the dentistry school of New York University. As the third oldest dentistry school in the United States, it offers both graduate programs and clinical training in oral healthcare. History The College ...
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 Enrico Fermi (; 29 September 1901 – 28 November 1954) was an Italian and naturalized American physicist, renowned for being the creator of the world's first artificial nuclear reactor, the Chicago Pile-1, and a member of the Manhattan Project ...
,
Hans Bethe Hans Albrecht Eduard Bethe (; ; July 2, 1906 – March 6, 2005) was a German-American physicist who made major contributions to nuclear physics, astrophysics, quantum electrodynamics and solid-state physics, and received the Nobel Prize in Physi ...
, and J.A. Wheeler. Ledley received a MS in physics from Columbia in 1950.Ledley, Robert. (1990) "Medical Informatics: A Personal View of Sowing the Seeds." p. 90. In 1949, Ledley married Terry Wachtell (born 1926), a mathematics teacher at
Queens College Queens College (QC) is a public college in the New York City borough of Queens. Part of the City University of New York system, Queens College occupies an campus primarily located in Flushing. Queens College was established in 1937 and offe ...
, 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. Robert Ledley died of
Alzheimer's disease Alzheimer's disease (AD) is a neurodegenerative disease and the cause of 60–70% of cases of dementia. The most common early symptom is difficulty in remembering recent events. As the disease advances, symptoms can include problems wit ...
in Kensington, Maryland, USA on July 24, 2012.


Early research career


U.S. Army dental research

In 1950, shortly after the outbreak of the
Korean War The Korean War (25 June 1950 – 27 July 1953) was an armed conflict on the Korean Peninsula fought between North Korea (Democratic People's Republic of Korea; DPRK) and South Korea (Republic of Korea; ROK) and their allies. North Korea was s ...
, 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 The Walter Reed Army Medical Center (WRAMC), officially known as Walter Reed General Hospital (WRGH) until 1951, was the United States Army, U.S. Army's flagship medical center from 1909 to 2011. Located on in Washington, D.C., it served more ...
, in Washington, D.C. During his time in the army, Ledley was responsible for improving prosthetic dental devices (such as
dentures Dentures (also known as false teeth) are prosthetic devices constructed to replace missing teeth, supported by the surrounding soft and hard tissues of the oral cavity. Conventional dentures are removable ( removable partial denture or comp ...
) 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.”


Work with Standards Eastern Automatic Computer

Ledley's work on dental prosthetics brought him into collaboration with researchers based at the
National Bureau of Standards The National Institute of Standards and Technology (NIST) is an agency of the United States Department of Commerce whose mission is to promote American innovation and industrial competitiveness. NIST's activities are organized into physical sc ...
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. pp. 46-47 For Ledley, working with SEAC produced an epiphany, concerning both his career and the potential importance of computers to biomedical research. He recalled: “I had previously realized that although, conceptually, physics equations could be written to describe any biomedical phenomenon, such equations would be so complex that they could not feasibly be solved in closed form. Thus SEAC would be my panacea, because the equations would become tractable to numerical methods of solutions. Or so I truly believed at the time. That was to be my field, application of computers to biomedical problems.”


Operations research and the RNA Tie Club

Though Ledley had envisioned a career of employing computers to solve biomedical problems as early as the early 1950s, it would be several years before he would pursue that career full-time. At the National Bureau of Standards, Ledley’s work was primarily related to solving military problems using the techniques of
operations research Operations research () (U.S. Air Force Specialty Code: Operations Analysis), often shortened to the initialism OR, is a branch of applied mathematics that deals with the development and application of analytical methods to improve management and ...
. For instance, he published an article in the journal ''Operations Research'' showing how one could use
Boolean algebra In mathematics and mathematical logic, Boolean algebra is a branch of algebra. It differs from elementary algebra in two ways. First, the values of the variable (mathematics), variables are the truth values ''true'' and ''false'', usually denot ...
to reduce complex military decision-making problems to the point where they could be resolved using a collection of
truth tables A truth table is a mathematical table used in logic—specifically in connection with Boolean algebra, Boolean functions, and propositional calculus—which sets out the functional values of logical expressions on each of their functional ar ...
and yes-or-no questions.November, Joseph (2012). ''Biomedical Computing: Digitizing Life in the United States''. p. 48. 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 George Gamow (sometimes Gammoff; born Georgiy Antonovich Gamov; ; 4 March 1904 – 19 August 1968) was a Soviet and American polymath, theoretical physicist and cosmologist. He was an early advocate and developer of Georges Lemaître's Big Ba ...
. Gamow, who was renowned for his contributions to the
Big Bang The Big Bang is a physical theory that describes how the universe expanded from an initial state of high density and temperature. Various cosmological models based on the Big Bang concept explain a broad range of phenomena, including th ...
cosmological model, had taken an interest in molecular biology immediately after
James D. Watson James Dewey Watson (born April 6, 1928) is an American molecular biologist, geneticist, and zoologist. In 1953, he co-authored with Francis Crick the academic paper in ''Nature'' proposing the double helix structure of the DNA molecule. Wats ...
and
Francis Crick Francis Harry Compton Crick (8 June 1916 – 28 July 2004) was an English molecular biologist, biophysicist, and neuroscientist. He, James Watson, Rosalind Franklin, and Maurice Wilkins played crucial roles in deciphering the Nucleic acid doub ...
elucidated the
double helix In molecular biology, the term double helix refers to the structure formed by base pair, double-stranded molecules of nucleic acids such as DNA. The double Helix, helical structure of a nucleic acid complex arises as a consequence of its Nuclei ...
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 The RNA Tie Club was an informal scientific club, meant partly to be humorous, of select scientists who were interested in how proteins were synthesised from genes, specifically the genetic code. It was created by George Gamow upon a suggestion by ...
; some other members of the club were Watson, Crick,
Richard Feynman Richard Phillips Feynman (; May 11, 1918 – February 15, 1988) was an American theoretical physicist. He is best known for his work in the path integral formulation of quantum mechanics, the theory of quantum electrodynamics, the physics of t ...
,
Max Delbrück Max Ludwig Henning Delbrück (; September 4, 1906 – March 9, 1981) was a German–American biophysicist who participated in launching the molecular biology research program in the late 1930s. He stimulated physical science, physical scientist ...
,
Edward Teller Edward Teller (; January 15, 1908 – September 9, 2003) was a Hungarian and American Theoretical physics, theoretical physicist and chemical engineer who is known colloquially as "the father of the hydrogen bomb" and one of the creators of ...
, and
Sydney Brenner Sydney Brenner (13 January 1927 – 5 April 2019) was a South African biologist. In 2002, he shared the Nobel Prize in Physiology or Medicine with H. Robert Horvitz and Sir John E. Sulston. Brenner made significant contributions to wo ...
.November, Joseph (2012). ''Biomedical Computing: Digitizing Life in the United States''. pp. 42-43. 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 Amino acids are organic compounds that contain both amino and carboxylic acid functional groups. Although over 500 amino acids exist in nature, by far the most important are the 22 α-amino acids incorporated into proteins. Only these 22 a ...
(the building blocks of proteins). Sponsored by Gamow, Ledley published his work in 1955 in the
Proceedings of the National Academy of Sciences ''Proceedings of the National Academy of Sciences of the United States of America'' (often abbreviated ''PNAS'' or ''PNAS USA'') is a peer-reviewed multidisciplinary scientific journal. It is the official journal of the National Academy of Scie ...
.November, Joseph (2012). ''Biomedical Computing: Digitizing Life in the United States''. p. 49. See: Ledley, R.S. "Digital Computational Methods in Symbolic Logic, with Examples in Biochemistry," ''Proceedings of the National Academy of Sciences'' 41 (July 1955): 498–511. 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. 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.November, Joseph (2012). ''Biomedical Computing: Digitizing Life in the United States''. p. 52.


Electrical engineering

In 1956, Ledley was hired as an assistant professor of electrical engineering at the
George Washington University School of Engineering and Applied Science The School of Engineering and Applied Science (SEAS) at the George Washington University in Washington, D.C. is a technical school which specializes in engineering, technology, communications, and transportation. The school is located on the main ...
. 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 Frederick Sanger (; 13 August 1918 – 19 November 2013) was a British biochemist who received the Nobel Prize in Chemistry twice. He won the 1958 Chemistry Prize for determining the amino acid sequence of insulin and numerous other prote ...
’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.


Collaboration with Lee B. Lusted

Lee B. Lusted (1922-1994), a
radiologist Radiology ( ) is the medical specialty that uses medical imaging to diagnose diseases and guide treatment within the bodies of humans and other animals. It began with radiography (which is why its name has a root referring to radiation), but tod ...
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.November, Joseph (2012). ''Biomedical Computing: Digitizing Life in the United States''. pp. 54-57. In 1959, Ledley and Lusted published “Reasoning Foundations of Medical Diagnosis,” a widely read article in ''
Science Science is a systematic discipline that builds and organises knowledge in the form of testable hypotheses and predictions about the universe. Modern science is typically divided into twoor threemajor branches: the natural sciences, which stu ...
'', which introduced operations research techniques to medical workers. Areas covered included:
symbolic logic Logic is the study of correct reasoning. It includes both formal and informal logic. Formal logic is the study of deductively valid inferences or logical truths. It examines how conclusions follow from premises based on the structure o ...
, Bayes’ theorem (probability), and
value theory Value theory, also called ''axiology'', studies the nature, sources, and types of Value (ethics and social sciences), values. It is a branch of philosophy and an interdisciplinary field closely associated with social sciences such as economics, ...
. In the article, physicians were instructed how to create diagnostic databases using
edge-notched card Edge-notched cards or edge-punched cards are a system used to store a small amount of binary or logical data on paper index cards, encoded via the presence or absence of notches in the edges of the cards. The notches allow efficient sorting of a l ...
s 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.November, Joseph (2012). ''Biomedical Computing: Digitizing Life in the United States''. p. 60. 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. The article also brought national media attention to Ledley and Lusted’s work. Articles about the work of the two men ran in several major US newspapers. A small demonstration device Ledley built to show how electronic diagnosis would work was described in the New York World Telegram as a “A Metal Brain for Diagnosis,” while the New York Post ran a headline: “Dr.
Univac UNIVAC (Universal Automatic Computer) was a line of electronic digital stored-program computers starting with the products of the Eckert–Mauchly Computer Corporation. Later the name was applied to a division of the Remington Rand company and ...
Wanted in Surgery.”November, Joseph (2012). ''Biomedical Computing: Digitizing Life in the United States''. pp. 62-66. On several occasions, Ledley and Lusted explained to journalists that they believed that computers would aid physicians rather than replace them, and that the process of introducing computers to medicine would be very challenging due to the non-quantitative nature of much medical information. They also envisioned, years before the development of
ARPANET The Advanced Research Projects Agency Network (ARPANET) was the first wide-area packet-switched network with distributed control and one of the first computer networks to implement the TCP/IP protocol suite. Both technologies became the tec ...
, a national network of medical computers that would allow healthcare providers to create a nationally accessible medical record for each American and would allow rapid mass data analysis as information was gathered by individual clinics and sent to regional and national computer centers.


NAS-NRC survey and computer advocacy

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 Hubert Horatio Humphrey Jr. (May 27, 1911 – January 13, 1978) was an American politician who served from 1965 to 1969 as the 38th vice president of the United States. He twice served in the United States Senate, representing Minnesota from 19 ...
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.November, Joseph (2012). ''Biomedical Computing: Digitizing Life in the United States''. pp. 78-80. Ledley published his survey findings in a November 6, 1959 ''Science'' article, “Digital Electronic Computers in Biomedical Science,” in which he called on biologists to train in mathematics and engineering in order to effectively use electronic digital computers. He predicted that in the long run, “perhaps the greatest utilization of computers will be in biomedical applications." 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 Joshua Lederberg (May 23, 1925 – February 2, 2008) was an American molecular biology, molecular biologist known for his work in microbial genetics, artificial intelligence, and the United States space program. He was 33 years old when he won t ...
, who spent much of the later part of his career using computers to solve problems in biology research.November, Joseph (2012). ''Biomedical Computing: Digitizing Life in the United States''. pp. 81-85. Ledley’s survey and article also shaped the
National Institutes of Health The National Institutes of Health (NIH) is the primary agency of the United States government responsible for biomedical and public health research. It was founded in 1887 and is part of the United States Department of Health and Human Service ...
’s first major effort to encourage biomedical researchers to use computers.November, Joseph (2012). ''Biomedical Computing: Digitizing Life in the United States''. pp. 88-97. This effort began shortly after the Soviet launch of
Sputnik Sputnik 1 (, , ''Satellite 1''), sometimes referred to as simply Sputnik, was the first artificial Earth satellite. It was launched into an elliptical low Earth orbit by the Soviet Union on 4 October 1957 as part of the Soviet space progra ...
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 LINC (Laboratory INstrument Computer) is a 12-bit, 2048-word transistorized computer. The LINC is considered by some to be the first minicomputer and a forerunner to the personal computer. Originally named the Linc, suggesting the project' ...
. 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.November, Joseph (2012). ''Biomedical Computing: Digitizing Life in the United States''. p. 113.


National Biomedical Research Foundation


Establishment and goals of the NBRF

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 A nonprofit organization (NPO), also known as a nonbusiness entity, nonprofit institution, not-for-profit organization, or simply a nonprofit, is a non-governmental (private) legal entity organized and operated for a collective, public, or so ...
, initially based in an NAS-NRC-owned building near
Dupont Circle Dupont Circle is a historic roundabout park and Neighborhoods in Washington, D.C., neighborhood of Washington, D.C., located in Northwest (Washington, D.C.), Northwest D.C. The Dupont Circle neighborhood is bounded approximately by 16th St ...
, Washington, D.C.November, Joseph (2012). ''Biomedical Computing: Digitizing Life in the United States''. pp. 209-210. 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). Grounded in Ledley’s belief that computer use would substantially improve biology and medicine by helping to mathematize those areas, the NBRF’s mission was to “stimulate biomedical research scientists to utilize computers by setting an example through its own pioneering research and development in new areas of computer applications.” Starting with an annual budget of under $100,000 and a half-dozen employees, the NBRF grew into a multimillion-dollar operation with more than 20 employees by the early 1980s. Initially the vast majority of NBRF’s support came from the NIH, but by 1980 it drew support from a variety of federal, university, and corporate sources, in addition to generating revenue through the publication of journals and the sale of electronic instruments, software, and patents. In 1970, the NBRF began its affiliation with the
Georgetown University Medical Center Georgetown University Medical Center is a Washington, D.C.–based biomedical research and educational organization affiliated with Georgetown University that is responsible for over 80% of the university's sponsored research funding and is led ...
. 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. As part of the move, Ledley was appointed to Georgetown University’s faculty as a professor of radiology, physiology, and biophysics. The NBRF was physically located at Georgetown from 1970 to 2006. Between 2006 and 2010 it was based in offices in Washington, D.C. and Bethesda, MD. In 2011, the NBRF was reincorporated in Massachusetts and has adopted a new mission statement.


FIDAC and pattern recognition

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 The United States Food and Drug Administration (FDA or US FDA) is a List of United States federal agencies, federal agency of the United States Department of Health and Human Services, Department of Health and Human Services. The FDA is respo ...
, and to large pharmaceutical companies. 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.November, Joseph (2012). ''Biomedical Computing: Digitizing Life in the United States''. pp. 211-214. FIDAC was designed to scan a photograph into its memory and then send that information to a larger computer (e.g. IBM 360) in order to recognize patterns in the scanned image. To digitize a photograph, FIDAC would impose a 700 x 500 point grid (of arbitrary size) onto it and then measure the light level at each point. Depending on the light level detected at it, each point was assigned an integer ranging from 0 to 9. FIDAC could generate a 350,000-point scan in under 0.5 seconds. Ledley designed FIDAC to scan photomicrographs of chromosomes in order to automate the labor-intensive task of
karyotype A karyotype is the general appearance of the complete set of chromosomes in the cells of a species or in an individual organism, mainly including their sizes, numbers, and shapes. Karyotyping is the process by which a karyotype is discerned by de ...
analysis, which is used to detect conditions such as
Turner syndrome Turner syndrome (TS), commonly known as 45,X, or 45,X0,Also written as 45,XO. is a chromosomal disorder in which cells of females have only one X chromosome instead of two, or are partially missing an X chromosome (sex chromosome monosomy) lea ...
and Down syndrome. Once programmed to distinguish chromosomes from the background and then to recognize abnormalities in a given sample (e.g. the presence of extra chromosome(s), abnormally-shaped chromosome(s)), FIDAC could perform in 40 seconds a chromosome analysis that took a skilled technician 15 minutes to complete by hand. Beyond chromosome analysis, FIDAC was adapted to digitize and analyze photographs of
neuron A neuron (American English), neurone (British English), or nerve cell, is an membrane potential#Cell excitability, excitable cell (biology), cell that fires electric signals called action potentials across a neural network (biology), neural net ...
s and Pap smears as well as schlieren photographs. About a dozen FIDAC units were sold during the 1960s, and by the early 1970s there was considerable demand for a smaller version of the machine. Ultimately the
Jet Propulsion Laboratory The Jet Propulsion Laboratory (JPL) is a Federally funded research and development centers, federally funded research and development center (FFRDC) in La Cañada Flintridge, California, Crescenta Valley, United States. Founded in 1936 by Cali ...
was awarded an NIH grant to develop a small, FIDAC-like instrument for use in laboratories and clinics. To facilitate discussion among users and developers of FIDAC, Ledley founded in 1969 the peer-reviewed journal ''
Pattern Recognition Pattern recognition is the task of assigning a class to an observation based on patterns extracted from data. While similar, pattern recognition (PR) is not to be confused with pattern machines (PM) which may possess PR capabilities but their p ...
'', the official journal of the Pattern Recognition Society. Ledley remained the editor of ''Pattern Recognition'' until 2010.


ACTA and computerized tomography (CT/CAT scanning)

Ledley is most widely known for his 1970s efforts to develop
computerized tomography A computed tomography scan (CT scan), formerly called computed axial tomography scan (CAT scan), is a medical imaging technique used to obtain detailed internal images of the body. The personnel that perform CT scans are called radiographers or ...
(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 Group Limited (formerly EMI Group plc until 2007; originally an initialism for Electric and Musical Industries, also referred to as EMI Records or simply EMI) was a British transnational conglomerate founded in March 1931 in London. At t ...
(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.November, Joseph (2012). ''Biomedical Computing: Digitizing Life in the United States''. pp. 215-219. 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. Building on their experience in medical imaging, and working with
Godfrey Hounsfield Sir Godfrey Newbold Hounsfield ( ; 28 August 1919 – 12 August 2004) was a British electrical engineer who shared the 1979 Nobel Prize for Physiology or Medicine with Allan MacLeod Cormack for his part in developing the diagnostic technique of ...
's early designs for the EMI machine as well as the theoretical papers of Allan McLeod Cormack and William H. Oldendorf, the NBRF team concluded that the necessity of using a water tank could be eliminated by changing the algorithm used to assemble X-rays into a tomographic image. Unlike the EMI’s head-only scanner, which used a relaxation algorithm, the NBRF machine used a convolution algorithm. In 1974, after several months of working with Georgetown’s machinists and auto body specialists at a nearby
Cadillac Cadillac Motor Car Division, or simply Cadillac (), is the luxury vehicle division (business), division of the American automobile manufacturer General Motors (GM). Its major markets are the United States, Canada and China; Cadillac models are ...
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. ACTA was immediately successful at Georgetown. 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. McCullough used the machine to detect brain bleeding in the boy and the precise information about the location of the bleeding to quickly plan and perform life-saving surgery. News of this and other similar cases spread quickly and Ledley soon faced worldwide demand for machines like ACTA. 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 Pfizer Inc. ( ) is an American Multinational corporation, multinational Pharmaceutical industry, pharmaceutical and biotechnology corporation headquartered at The Spiral (New York City), The Spiral in Manhattan, New York City. Founded in 184 ...
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. In 1981, Pfizer sold its CT business to Elscint. 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 The National Museum of American History: Kenneth E. Behring Center is a historical museum in Washington, D.C. It collects, preserves, and displays the heritage of the United States in the areas of social, political, cultural, scientific, and m ...
, 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 The National Inventors Hall of Fame (NIHF) is an American not-for-profit organization, founded in 1973, which recognizes individual engineers and inventors who hold a US patent of significant technology. Besides the Hall of Fame, it also operate ...
in 1990 and was awarded the
National Medal of Technology and Innovation The National Medal of Technology and Innovation (formerly the National Medal of Technology) is an honor granted by the president of the United States to American inventors and innovators who have made significant contributions to the development ...
in 1997.


Bioinformatics

Alongside Ledley's work on imaging technology, his NBRF colleague
Margaret Oakley Dayhoff Margaret Belle (Oakley) Dayhoff (March 11, 1925 – February 5, 1983) was an American Biophysicist and a pioneer in the field of bioinformatics. Dayhoff was a professor at Georgetown University Medical Center and a noted research biochemi ...
was developing resources for the study of life on the molecular level. Her 1965 ''Atlas of Protein Sequence and Structure'' sought to provide a comprehensive collection of the scientific community’s data on
protein sequencing Protein sequencing is the practical process of determining the amino acid sequence of all or part of a protein or peptide. This may serve to identify the protein or characterize its post-translational modifications. Typically, partial sequencing o ...
. Published annually by the NBRF, first on paper then (as the volume of information grew much larger) on magnetic tape and finally on CD-ROM, the ''Atlas'' served as an information clearinghouse for the growing community of protein sequencers. By the mid-1970s the ''Atlas'' had become the primary repository of protein sequence data, and ultimately served as a model for the
Protein Data Bank The Protein Data Bank (PDB) is a database for the three-dimensional structural data of large biological molecules such as proteins and nucleic acids, which is overseen by the Worldwide Protein Data Bank (wwPDB). This structural data is obtained a ...
and the nucleic acid sequence database
GenBank The GenBank sequence database is an open access, annotated collection of all publicly available nucleotide sequences and their protein translations. It is produced and maintained by the National Center for Biotechnology Information (NCBI; a par ...
, both now major resources for biologists. 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 The Protein Information Resource (PIR), located at Georgetown University Medical Center, is an integrated public bioinformatics resource to support genomic and proteomic research, and scientific studies. It contains protein sequences databases H ...
or PIR), an online version of the ''Atlas''. Researchers using modems or
Tymnet Tymnet was an international data communications network developed and operated by Tymshare. It was based at the company’s headquarters in Cupertino, California. The network used packet-switching techniques, including statistical multiplexing, an ...
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 UniProt is a freely accessible database of protein sequence and functional information, many entries being derived from genome sequencing projects. It contains a large amount of information about the biological function of proteins derived fro ...
.


Other NBRF computing projects

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. 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. In the late 1980s, Ledley lead the team that developed the Bat, a three-dimensional mouse that allowed users to interact with objects in three-dimensional space (generated using stereo images).


Scientific journals

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 Elsevier ( ) is a Dutch academic publishing company specializing in scientific, technical, and medical content. Its products include journals such as ''The Lancet'', ''Cell (journal), Cell'', the ScienceDirect collection of electronic journals, ...
.


Honors, memberships, and affiliations

* Morris F. Collen Award of Excellence, American College of Medical Informatics (AMIA) (1998) *
National Inventors Hall of Fame The National Inventors Hall of Fame (NIHF) is an American not-for-profit organization, founded in 1973, which recognizes individual engineers and inventors who hold a US patent of significant technology. Besides the Hall of Fame, it also operate ...
(inducted 1990) *
National Medal of Technology The National Medal of Technology and Innovation (formerly the National Medal of Technology) is an honor granted by the president of the United States to American inventors and innovators who have made significant contributions to the development ...
(1997) *Vicennial Gold Medal for Distinguished Service,
Georgetown University Georgetown University is a private university, private Jesuit research university in Washington, D.C., United States. Founded by Bishop John Carroll (archbishop of Baltimore), John Carroll in 1789, it is the oldest Catholic higher education, Ca ...
(1990) *Member,
Institute of Medicine The National Academy of Medicine (NAM), known as the Institute of Medicine (IoM) until 2015, is an American nonprofit, non-governmental organization. The National Academy of Medicine is a part of the National Academies of Sciences, Engineerin ...
, National Academy of Sciences (1999) *Distinguished Alumnus,
New York University New York University (NYU) is a private university, private research university in New York City, New York, United States. Chartered in 1831 by the New York State Legislature, NYU was founded in 1832 by Albert Gallatin as a Nondenominational ...
(1999)


Publications

* * * (General Books, 2010). *

(xxiv+835+1 pages) * * * * * *


Notes


References

* * * * * * * * * * *


External links


Protein Information Resource
(Georgetown University) * American College of Medical Informatics (AMIA), 1998 * public lecture, National Institutes of Health, February 21, 2008. {{DEFAULTSORT:Ledley, Robert 1926 births 2012 deaths National Medal of Technology recipients Health informaticians Deaths from Alzheimer's disease in Maryland Columbia University alumni New York University College of Dentistry alumni Members of the National Academy of Medicine American physiologists American biophysicists American radiologists