Margaret Oakley Dayhoff was a noted research biochemist, professor at Georgetown University Medical Center and dedicated proponent of the application of mathematical and computer techniques to the field of biochemistry.

As a pioneer in scientific computer technology, she dedicated her career to harnessing the revolution in computer technology in support of advances in biology and medicine. Among her many contributions to science, she seemed most pleased with the computerized protein and DNA sequence databases, which were developed because of her research interests in bio-molecular evolution. From them flowed advances in our understanding of the origins of life and of macromolecular evolution, as well as a large number of practical applications in the healing sciences, including the production of useful substances through genetic engoineering. It was of special importance to her for her databases to be the best of their kind. Thus they supported both her own research interests and those of science scholars as a whole.

She was born Margaret Belle Oakley in Philadelphia on 11 March 1925, the only child. The family moved to New York City around 1935, where she attended public school. She was valedictorian of the class of 1942 at Bayside High School, Bayside, NY. She was awarded a much needed scholarship to Washington Square College of New York University, from which she graduated in 1945 magna cum laude, with honors in mathematics.

Her graduate research career began with a Ph.D. in quantum chemistry, under Prof. George Kimball, in the Columbia University Department of Chemistry. In her thesis research, she pioneered the application of mass data processing equipment to theoretical chemistry (Dayhoff and Kimball, 1949). She devised a method of applying punched-card business machines to the calculation of molecular resonance energies of several polycyclic organic molecules. Due to the amount of calculation required, such calculations were considered infeasible with hand operated calculators. She received a Watson Computing Laboratory Fellowship and therefore had access to machines that were regarded as high technology in 1947, shortly before the emergence of programmable computers. The process was iterative and required manually carrying cards from one type of machine to another (4 types), as no single machine could do the whole iteration. Convergence was slow and several months could be required for a result.

After graduate school, Dr. Dayhoff received a research fellowship at the Rockefeller Institute (now Rockefeller University) in New York City from 1948 to 1951.  Here, she pursued a variety of studies in electrochemistry under Dr. Duncan A. MacInnes.  In 1952, she moved to Maryland with her family and subsequently received a research fellowship in the Department of Chemistry at the University of Maryland from 1957 to 1959.  She worked on a model of chemical bonding with Professor Ellis Lippincott. It was at Maryland that she first used a full fledged "high speed" computer (IBM 650?).

In 1959, Dr. Dayhoff joined the infant and independant National Biomedical Research Foundation (NBRF) in Silver Spring, Maryland.  She went on to become Associate Director and continued her affiliation for 21 years. The founder of this non-profit organization had the intention of doing medical engineering but was pleased to have interesting basic science projects to share the computers, other facilities and costs. Originally the organization used low cost space in overbuilt apartment houses.  Eventually NBRF formed an agreement with Georgetown University Medical School that  resulted in academic status in the Dept. of Physiology and Biophysics for the principal investigators.

Margaret was professor of physiology and biophysics for 13 years. She was the first person to be elected both Secretary and President of the Biophysical Society. She was also a Fellow of the American Association for the Advancement of Science and a member of the editorial boards of three journals: DNA, Journal of Molecular Evolution and Computers in Biology and Medicine. She was a member of the International Society for the Study of the Origins of Life since 1972 and was elected a councillor in 1980.

In the early 1960s, Dr. Dayhoff collaborated with Drs. Ellis Lippencott and Carl Sagan, among others, to develop thermodynamic models of cosmo-chemical systems, including prebiological planetary atmospheres. She decided she could use a computer to study atmospheric conditions and composition and developed a computer program that calculated equilibrioum concentrations of gases in a planetary atmosphere. The particular compounds and elements to be considered could be chosen each time the program was run. The result was a highly versatile program that could be used to model the background or average atmospheres of Venus, Juputer and Mars. In addition, it could model the present-day and primordial terrestrial atmosphere.

In her study of the primordial terrestrial atmosphere, Dr. Dayhoff showed that long-chain hydrocarbons (oils) would form naturally under reducing conditions. As the oxygen content of the atmosphere increased, a sharp cut-off point would be expected, after which such natural formation of oils would abruptly cease. The abundance of oil in the earth's crust may be explained in part by such formation of hydrocarbons before the oxygen content of the atmosphere passed the cut-off point. (Eck et al., 1966).

Dr. Dayhoff was especially interested in whether a primordial atmosphere at thermodynamic equilibrium might have contained compounds necessary for the formation of life. She found that numerous small biologically important compounds can appear with no special noequilibrium mechanism to explain their presence. On the other hand, there are compounds that are critical to life, such as ribose, adenine and cytosine, which are extremely scarce in the equilibrium situation.

Dr. Dayhoff's work in the protein field, starting in 1961, included the development of computer aids to protein sequence determination, such as the reconstruction of sequences from overlapping peptides and the development of recognition and display programs for use in X-ray crystallography. She pioneered the development of computer methods for the comparison of protein sequences and for the derivation of evolutionary histories from alignments of protein sequences. She was particularly interested in the possibility of deducing the evolutionary connections of the biological kingdoms, phyla, and other taxa from sequence evidence. Toward these ends she collected all the known protein sequences and, as a service to the scientific community, made them available to others in 1965 in a small book, the first Atlas of Protein Sequence and Structure, which contained sequence information on 65 proteins. That the subsequent volumes of this have served as a valuable reference work for scientists all over the world is attested by the more than 4500 citations to these volumes over the years.

From the start, the small number of nucleic acid sequences that had been determined were included in the Atlases. Responding to the sudden increase in the rate of nucleic acid sequencing, Dr. Dayhoff established an on-line computer database and a sophisticated retrieval system, accessable by phone to outside users, in September 1980. A home computer system had been used to prove the feasibility of this approach. This nucleic acid sequence database is currently one of the largest in the world, containing over 2 000 000 sequenced nucleotides with references and annotations. Since September 1981, the Protein Sequence Database has also been available on-line as well as on magnetic tape.

In the last few years, one of Dr Dayhoff's major efforts was to obtain stable, adequate, long-term funding to support the maintenance and further development of the database. Less than a week before she died, she submitted a proposal to the Division of Research Resources at NIH for a Protein Identification Resource. Her vision was to develop an on-line system of computer programs and databases, accessable by scientists all over the world, for identifying proteins from sequence or amino acid composition data, for making predictions based on sequences, and for browsing the known information. Her colleagues were determined to see her vision realized and now this unique and very valuable resource is funded and has been fully operational since the middle 1980's.

Dr. Dayhoff also developed computer programs and model systems for detecting and evaluating distant relationships among proteins. She introduced the concept of protein superfamilies, a hierarchical organization of related sequences. She further detected conserved regions and internal duplications (remnants of earlier evolutionary stages) in sequences of certain proteins. She and her colleagues also used these methods to elucidate a number of surprising relationships, among which are the catalytic chain and bovine cyclic AMP-dependent protein kinase and the src gene product of Rous avian and Moloney murine sarcoma viruses; antithrombin-III, alpha1-antitrypsin, and ovalbumin; epidermal growth factor and the light chain of coagulation factor X ; and apolipoproteins A-I, A-II, C-i and C-III.

One of Dr Dayhoff's most significant accomplishments was the derivation of a comprehensive phylogenetic tree based on protein and nucleic acid sequence information, which provided a framework describing early evolutionary history and helped unravel the mystery of the symbiotic origins of eukaryotes. She showed that evidence from protein and nucleic acid sequences clearly indicates that mitochrondia and chloroplasts (eukaryote intracellular organelles) originated as free-living prokaryote organisms that invaded the host cell and established a symbiotic relationship with it. Dr Dayhoff and her colleagues showed that particular genes originally derived from these invading symbionts have evolutionary histories very different from those of the majority of eukaryote genes, which are derived from the host.

Throughout her career, Dr Dayhoff was especially sensitive to the difficulties that young women face in pursuing careers in fields that are largely dominated by men. She experienced many of these herself- typically from the difficulty of re-entering the career track after spending several years at home with her young daughters (both of whom now hold doctorates, one in biophysics and the other in medicine). In her family, in her own research group and in the Biophysical Society she gave much thought and personal effort to encouraging women in scientific careers. It is therefore fitting that the Margaret Oakley Dayhoff Award has been established to encourage young women in entering scientific research. This award is aimed towards women of very high promise who have not yet reached a position of high recognition within the structure of academic society. It is administered through the Biophysical Society, and candidates are judged on achievement and promise in fields within the purvue of the Biophysical Society.

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