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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 discipline that uses medical imaging to diagnose diseases and guide their treatment, within the bodies of humans and other animals. It began with radiography (which is why its name has a root referring to radiat ...
at
Georgetown University School of Medicine Georgetown University School of Medicine, a medical school opened in 1851, is one of Georgetown University's five graduate schools. It is located on Reservoir Road in the Georgetown neighborhood of Washington, DC, adjacent to the University's ...
, 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 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 Hi ...
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 U.S. patent of significant technology. Besides the Hall of Fame, it also opera ...
. 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 * Flushing, Cornwall, a village in the United Kingdom * Flushing, Queens, New York City ** Flushing Bay, a bay off the north shore of Queens ** Flushing Chinatown (法拉盛華埠), a community in Queens ** Flushin ...
, 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 physical chemist and a pioneer in the field of bioinformatics. Dayhoff was a professor at Georgetown University Medical Center and a noted research biochem ...
, 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 that develops methods and software tools for understanding biological data, in particular when the data sets are large and complex. As an interdisciplinary field of science, bioinformatics combi ...
. Ledley attended the
Horace Mann School , motto_translation = Great is the truth and it prevails , address = 231 West 246th Street , city = The Bronx , state = New York , zipcode = 10471 , count ...
, from which he graduated in 1943. As an undergraduate student at
Columbia University Columbia University (also known as Columbia, and officially as Columbia University in the City of New York) is a private research university in New York City. Established in 1754 as King's College on the grounds of Trinity Church in Manhatt ...
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 3rd 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 Isidor Isaac Rabi (; born Israel Isaac Rabi, July 29, 1898 – January 11, 1988) was an American physicist who won the Nobel Prize in Physics in 1944 for his discovery of nuclear magnetic resonance, which is used in magnetic resonance ima ...
(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 (later naturalized American) physicist and the creator of the world's first nuclear reactor, the Chicago Pile-1. He has been called the "architect of the nuclear age" and ...
,
Hans Bethe Hans Albrecht Bethe (; July 2, 1906 – March 6, 2005) was a German-American theoretical physicist who made major contributions to nuclear physics, astrophysics, quantum electrodynamics, and solid-state physics, and who won the 1967 Nobel Prize ...
, 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 Queens borough of New York City. It is part of the City University of New York system. Its 80-acre campus is primarily located in Flushing, Queens. It has a student body representing more than 170 ...
, and sister of
Herbert Wachtell Herbert Maurice Wachtell (born May 24, 1932) is an American lawyer. He is the co-founder of the law firm Wachtell, Lipton, Rosen & Katz. Education and early career Herbert Maurice Wachtell was born on May 24, 1932 in New York City. His parents we ...
. 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 Georgetown University School of Medicine, a medical school opened in 1851, is one of Georgetown University's five graduate schools. It is located on Reservoir Road in the Georgetown neighborhood of Washington, DC, adjacent to the University's ...
. 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 neurodegeneration, neurodegenerative disease that usually starts slowly and progressively worsens. It is the cause of 60–70% of cases of dementia. The most common early symptom is difficulty in short-term me ...
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 , date = {{Ubl, 25 June 1950 – 27 July 1953 (''de facto'')({{Age in years, months, weeks and days, month1=6, day1=25, year1=1950, month2=7, day2=27, year2=1953), 25 June 1950 – present (''de jure'')({{Age in years, months, weeks a ...
, 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)known as Walter Reed General Hospital (WRGH) until 1951was the U.S. Army's flagship medical center from 1909 to 2011. Located on in the District of Columbia, it served more than 150,000 active and reti ...
, 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, and are supported by the surrounding soft and hard tissues of the oral cavity. Conventional dentures are removable (removable partial denture or ...
) 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 sci ...
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 DYSEAC was the second Standards Electronic Automatic Computer. (See SEAC.) DYSEAC was a first-generation computer built by the National Bureau of Standards for the U.S. Army Signal Corps. It was housed in a truck, making it one of the first m ...
) 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 ( en-GB, operational research) (U.S. Air Force Specialty Code: Operations Analysis), often shortened to the initialism OR, is a discipline that deals with the development and application of analytical methods to improve deci ...
. 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 variables are the truth values ''true'' and ''false'', usually denoted 1 and 0, whereas in e ...
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 argumen ...
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 The Operations Research Office (ORO) was a civilian military research center founded in 1948 by the United States Army. It was run under contract by Johns Hopkins University and is regarded as one of the founding institutes of operations research ...
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 (March 4, 1904 – August 19, 1968), born Georgiy Antonovich Gamov ( uk, Георгій Антонович Гамов, russian: Георгий Антонович Гамов), was a Russian-born Soviet and American polymath, theoreti ...
. Gamow, who was renowned for his contributions to the
Big Bang The Big Bang event is a physical theory that describes how the universe expanded from an initial state of high density and temperature. Various cosmological models of the Big Bang explain the evolution of the observable universe from the ...
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 proposing the double helix structure of the DNA molecule. Watson, Crick and ...
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 helical struc ...
elucidated the
double helix A double is a look-alike or doppelgänger; one person or being that resembles another. Double, The Double or Dubble may also refer to: Film and television * Double (filmmaking), someone who substitutes for the credited actor of a character * ...
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 the suggestion ...
; 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, known for his work in the path integral formulation of quantum mechanics, the theory of quantum electrodynamics, the physics of the superflu ...
,
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 ( hu, Teller Ede; January 15, 1908 – September 9, 2003) was a Hungarian-American theoretical physicist who is known colloquially as "the father of the hydrogen bomb" (see the Teller–Ulam design), although he did not care fo ...
, 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 work ...
.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 Nucleobases, also known as ''nitrogenous bases'' or often simply ''bases'', are nitrogen-containing biological compounds that form nucleosides, which, in turn, are components of nucleotides, with all of these monomers constituting the bas ...
and any
amino acid Amino acids are organic compounds that contain both amino and carboxylic acid functional groups. Although hundreds of amino acids exist in nature, by far the most important are the alpha-amino acids, which comprise proteins. Only 22 alpha am ...
(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 Sci ...
.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 The Nirenberg and Matthaei experiment was a scientific experiment performed in May 1961 by Marshall W. Nirenberg and his post-doctoral fellow, J. Heinrich Matthaei, at the National Institutes of Health (NIH). The experiment deciphered the first o ...
, 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. 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 an English 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 p ...
’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 discipline that uses medical imaging to diagnose diseases and guide their treatment, within the bodies of humans and other animals. It began with radiography (which is why its name has a root referring to radiatio ...
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 The Institute for Operations Research and the Management Sciences (INFORMS) is an international society for practitioners in the fields of operations research (O.R.), management science, and analytics. It was established in 1995 with the merger o ...
. 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 endeavor that builds and organizes knowledge in the form of testable explanations and predictions about the universe. Science may be as old as the human species, and some of the earliest archeological evidence for ...
'', which introduced operations research techniques to medical workers. Areas covered included:
symbolic logic Mathematical logic is the study of formal logic within mathematics. Major subareas include model theory, proof theory, set theory, and recursion theory. Research in mathematical logic commonly addresses the mathematical properties of formal ...
, Bayes’ theorem (probability), and
value theory In ethics and the social sciences, value theory involves various approaches that examine how, why, and to what degree humans value things and whether the object or subject of valuing is a person, idea, object, or anything else. Within philosophy, ...
. 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 allowed efficient sorting and s ...
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 Homer Richards Warner (April 18, 1922 – November 30, 2012) was an American cardiologist who was an early proponent of medical informatics
, who emulated Ledley and Lusted’s methods at his research clinic at
LDS Hospital LDS Hospital (formerly Deseret Hospital) is a general urban hospital and surgical center in Salt Lake City, Utah. The hospital was originally owned by the Church of Jesus Christ of Latter-day Saints (LDS Church), but is now owned and operated by I ...
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 an ...
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 networks to implement the TCP/IP protocol suite. Both technologies became the technical fou ...
, 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 pharmacist and politician who served as the 38th vice president of the United States from 1965 to 1969. He twice served in the United States Senate, representing Mi ...
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 () or Yehoshua ( ''Yəhōšuaʿ'', Tiberian: ''Yŏhōšuaʿ,'' lit. 'Yahweh is salvation') ''Yēšūaʿ''; syr, ܝܫܘܥ ܒܪ ܢܘܢ ''Yəšūʿ bar Nōn''; el, Ἰησοῦς, ar , يُوشَعُ ٱبْنُ نُونٍ '' Yūšaʿ ...
, 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, commonly referred to as NIH (with each letter pronounced individually), is the primary agency of the United States government responsible for biomedical and public health research. It was founded in the late ...
’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 (; see § Etymology) 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 program. It sent a radio signal back to Earth for t ...
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 the first minicomputer and a forerunner to the personal computer. Originally named the "Linc", suggesting the project's o ...
. 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) or non-profit organisation, also known as a non-business entity, not-for-profit organization, or nonprofit institution, is a legal entity organized and operated for a collective, public or social benefit, in co ...
, initially based in an NAS-NRC-owned building near
Dupont Circle Dupont Circle (or DuPont Circle) is a traffic circle, park, neighborhood and historic district in Northwest Washington, D.C. The Dupont Circle neighborhood is bounded approximately by 16th Street NW to the east, 22nd Street NW ...
, 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 biomedical research and educational organization that responsible for over 80% of Georgetown University's sponsored research funding and is led by Edward B. Healton, MD, the Executive Vice President for He ...
. 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 respon ...
, 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 metaphase 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 disce ...
analysis, which is used to detect conditions such as
Turner syndrome Turner syndrome (TS), also known as 45,X, or 45,X0, is a genetic condition in which a female is partially or completely missing an X chromosome. Signs and symptoms vary among those affected. Often, a short and webbed neck, low-set ears, low hair ...
and
Down syndrome Down syndrome or Down's syndrome, also known as trisomy 21, is a genetic disorder caused by the presence of all or part of a third copy of chromosome 21. It is usually associated with physical growth delays, mild to moderate intellectual dis ...
. 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, neurone, or nerve cell is an electrically excitable cell that communicates with other cells via specialized connections called synapses. The neuron is the main component of nervous tissue in all animals except sponges and placozoa. N ...
s and
Pap smears The Papanicolaou test (abbreviated as Pap test, also known as Pap smear (AE), cervical smear (BE), cervical screening (BE), or smear test (BE)) is a method of cervical screening used to detect potentially precancerous and cancerous processes in t ...
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 center and NASA field center in the City of La Cañada Flintridge, California, United States. Founded in the 1930s by Caltech researchers, JPL is owned by NASA an ...
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 automated recognition of patterns and regularities in data. It has applications in statistical data analysis, signal processing, image analysis, information retrieval, bioinformatics, data compression, computer graphi ...
'', 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 (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 (originally an initialism for Electric and Musical Industries, also referred to as EMI Records Ltd. or simply EMI) was a British transnational conglomerate founded in March 1931 in London. At the time of its break-up in 201 ...
(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 an English 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 X ...
's early designs for the EMI machine as well as the theoretical papers of
Allan McLeod Cormack Allan MacLeod Cormack (February 23, 1924 – May 7, 1998) was a South African American physicist who won the 1979 Nobel Prize in Physiology or Medicine (along with Godfrey Hounsfield) for his work on X-ray computed tomography (CT). Early life ...
and
William H. Oldendorf William Henry Oldendorf (March 27, 1925 – December 14, 1992) was an American neurologist, physician, researcher, medical pioneer, founding member of the American Society for Neuroimaging (ASN), and originator of the technique of computed tomog ...
, 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 The Cadillac Motor Car Division () is a division of the American automobile manufacturer General Motors (GM) that designs and builds luxury vehicles. Its major markets are the United States, Canada, and China. Cadillac models are distributed i ...
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 pharmaceutical and biotechnology corporation headquartered on 42nd Street in Manhattan, New York City. The company was established in 1849 in New York by two German entrepreneurs, Charles 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 Technicare, formerly known as Ohio Nuclear, made CT, DR and MRI scanners and other medical imaging equipment. Its headquarters was in Solon, Ohio. Originally an independent company which became publicly traded, it was later purchased by John ...
, which both sold next-generation CT scanners. In 1981, Pfizer sold its CT business to
Elscint Elscint was an Israeli technology company that developed, manufactured and sold medical imaging solutions, including: Nuclear medicine, computed tomography magnetic resonance imaging and X-ray scanners. Elscint's shares traded on the NASDAQ as w ...
. 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 collects, preserves, and displays the heritage of the United States in the areas of social, political, cultural, scientific, and military history. Among the items on display is t ...
, 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 U.S. patent of significant technology. Besides the Hall of Fame, it also opera ...
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 physical chemist and a pioneer in the field of bioinformatics. Dayhoff was a professor at Georgetown University Medical Center and a noted research biochem ...
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. The data, typically obtained by X-ray crystallography, NMR spectroscopy, or, increasingly, cry ...
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 part ...
, 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 Hi ...
or PIR), an online version of the ''Atlas''. Researchers using modems or
Tymnet Tymnet was an international data communications network headquartered in Cupertino, California that used virtual call packet-switched technology and X.25, SNA/ SDLC, BSC and Async interfaces to connect host computers (servers) at thousands of lar ...
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 from ...
.


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 Moore's law is the observation that the number of transistors in a dense integrated circuit (IC) doubles about every two years. Moore's law is an observation and projection of a historical trend. Rather than a law of physics, it is an empiri ...
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'', the ScienceDirect collection of electronic journals, '' Trends'', th ...
.


Honors, memberships, and affiliations

*Morris F. Collen Award,
American College of Medical Informatics The American College of Medical Informatics (ACMI) is a college of elected fellows from the United States and abroad who have made significant and sustained contributions to the field of medical informatics. Initially incorporated in 1984, the o ...
(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 U.S. patent of significant technology. Besides the Hall of Fame, it also opera ...
(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 research university in the Georgetown (Washington, D.C.), Georgetown neighborhood of Washington, D.C. Founded by Bishop John Carroll (archbishop of Baltimore), John Carroll in 1789 as Georg ...
(1990) *Member,
Institute of Medicine The National Academy of Medicine (NAM), formerly called 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, E ...
, National Academy of Sciences (1999) *Distinguished Alumnus,
New York University New York University (NYU) is a private research university in New York City. Chartered in 1831 by the New York State Legislature, NYU was founded by a group of New Yorkers led by then-Secretary of the Treasury Albert Gallatin. In 1832, the ...
(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 Neurological disease deaths in Maryland Deaths from Alzheimer's disease Columbia University alumni New York University College of Dentistry alumni American scientists Members of the National Academy of Medicine