Margaret Oakley Dayhoff

Margaret Oakley Dayhoff
Born	Margaret Belle Oakley (1925-03-11)March 11, 1925 Philadelphia, Pennsylvania
Died	February 5, 1983(1983-02-05) (aged 57) Silver Spring, Maryland
Known for	Substitution matrices one-letter code
Scientific career
Fields	Bioinformatics
Institutions	Columbia University
Doctoral advisor	Duncan A. MacInnes

Margaret Belle (Oakley) Dayhoff (March 11, 1925 – February 5, 1983) was an American

Dayhoff was born an only child in

Dayhoff began a PhD in quantum chemistry under George Kimball in the Columbia University Department of Chemistry. In her graduate thesis, Dayhoff pioneered the use of computer capabilities – i.e. mass-data processing – to theoretical chemistry; specifically, she devised a method of applying punched-card business machines to calculate the resonance energies of several polycyclic organic molecules. Her management of her research data was so impressive that she was awarded a Watson Computing Laboratory Fellowship. As part of this award, she received access to "cutting-edge IBM electronic data processing equipment" at the lab.^[6][7]

After completing her PhD, Dayhoff studied

In the early 1960s, Dayhoff also collaborated with Ellis Lippincott and Carl Sagan to develop thermodynamic models of cosmo-chemical systems, including prebiological planetary atmospheres. She developed a computer program that could calculate equilibrium concentrations of the gases in a planetary atmosphere, enabling the study of the atmospheres of Venus, Jupiter, and Mars, in addition to the present day atmosphere and the primordial terrestrial atmosphere. Using this program, she considered whether the primordial atmosphere had the conditions necessary to generate life. Although she found that numerous small biologically important compounds can appear with no special nonequilibrium mechanism to explain their presence, there were compounds necessary to life that were scarce in the equilibrium model (such as ribose, adenine, and cytosine).^[2]

Dayhoff also taught physiology and biophysics at

In 1966, Dayhoff pioneered the use of computers in comparing protein sequences and reconstructing their evolutionary histories from

One of Dayhoff's most important contributions to bioinformatics was her Atlas of Protein Sequence and Structure, a book reporting all known protein sequences (totaling 65) that she published in 1965.[11] This book published a degenerate encoding of amino acids. It was subsequently republished in several editions. This led to the Protein Information Resource database of protein sequences, the first online database system that could be accessed by telephone line and available for interrogation by remote computers.^[12] The book has since been cited nearly 4,500 times.^[2] It and the parallel effort by Walter Goad which led to the GenBank database of nucleic acid sequences are the twin origins of the modern databases of molecular sequences. The Atlas was organized by gene families, and she is regarded as a pioneer in their recognition. Frederick Sanger's determination of the first complete amino acid sequence of a protein (insulin) in 1955, led a number of researchers to sequence various proteins from different species. In the early 1960s, a theory was developed that small differences between homologous protein sequences (sequences with a high likelihood of common ancestry) could indicate the process and rate of evolutionary change on the molecular level. The notion that such molecular analysis could help scientists decode evolutionary patterns in organisms was formalized in the published papers of Emile Zuckerkandl and Linus Pauling in 1962 and 1965.

Table of Dayhoff's encoding of amino acids

Dayhoff's husband was Edward S. Dayhoff, an experimental physicist who worked with magnetic resonance and with lasers.[14] They had two daughters who are also academics, Ruth and Judith.^[15]

Judith Dayhoff has a Mathematical Biophysics PhD from University of Pennsylvania and is the author of Neural network architectures: An introduction and coauthor of Neural Networks and Pattern Recognition.^{[15][16][17][18]}

Dayhoff's Atlas became a template for many indispensable tools in large portions of DNA or protein-related biomedical research. In spite of this significant contribution, Dayhoff was marginalized by the community of sequencers. The contract to manage GenBank (a technology directly related to her research), awarded in the early 1980s by the NIH, went to Walter Goad at the Los Alamos National Laboratory. The reason for this attitude was unknown, with theories ranging from sexism to a clash of values with the experimental science community.^[19] Despite the success of Dayhoff's Atlas, experimental scientists and researchers considered their sequence information very valuable and were often reluctant to submit it to such a publicly available database.^[20]

During the last few years of her life, she focused on obtaining stable, adequate, long-term funding to support the maintenance and further development of her Protein Information Resource. She envisioned an online system of computer programs and databases, accessible by scientists all over the world, for identifying protein from sequence or amino acid composition data, for making predictions based on sequences, and for browsing the known information. Less than a week before she died, she submitted a proposal to the Division of Research Resources at NIH for a Protein Identification Resource. After her death, her colleagues worked to make her vision a reality, and the protein database was fully operational by the middle of 1984.^[2]

Dayhoff died of a heart attack at the age of 57 on February 5, 1983.^[3] A fund was established after her death in 1984 to endow the Margaret O. Dayhoff Award, one of the top national honors in biophysics. The award is presented to a woman who "holds very high promise or has achieved prominence while developing the early stages of a career in biophysical research within the purview and interest of the Biophysical Society."^[21] It is presented at the annual meeting of the Biophysical Society and includes an honorarium of $2,000.

She was survived by her husband, Edward S. Dayhoff of Silver Spring; two daughters, Ruth E. Dayhoff Brannigan of College Park, and Judith E. Dayhoff of Silver Spring, and her father, Kenneth W. Oakley of Silver Spring.^[5]

Her seminal contributions as the mother of the science of bioinformatics, now routinely used as part of the process for naming bacteria, were acknowledged with a bacterium being named after her in 2020, Enemella dayhoffiae.^[22]

References