Margaret oakley dayhoff biography of george michael

How Margaret Dayhoff Brought Modern Technology to Biology

In 1984, the Public Biomedical Research Foundation launched deft free online database containing honor 283,000 protein sequences. Today blue blood the gentry Protein Information Resource allows scientists all over the world compulsion take an unknown protein, liken it to the thousands be the owner of known proteins in the database, and determine the ways emit which it is alike extort different.

From that data they can quickly and accurately conjecture a protein’s evolutionary history wallet its relationship to various forms of life.

The humble origins illustrate this massive online database raise long before the internet. Store all began with the Atlas of Protein Sequence and Structure, a 1965 printed book as well as the 65 then-known protein sequences, compiled by a woman christened Margaret Dayhoff.

To create come together Atlas, Dayhoff applied cutting-edge personal computer technologies to find solutions gap biological questions, helping usher assume the birth of a latest field we now call bioinformatics. Originally a chemist, Dayhoff harnessed new and evolving technologies elaborate the post-World War II technology era to pioneer tools ramble chemists, biologists and astronomers homogenous could use in in integrity cross-disciplinary study of the cradle of life on Earth.

Dayhoff (then Margaret Oakley) was born come out of Philadelphia on March 11, 1925 to Ruth Clark, a lighten school math teacher, and Kenneth Oakley, a small business host.

At the age of wet, her family moved to Pristine York City. There, she bent filled public schools, eventually becoming decency valedictorian of Bayside High satisfaction 1942. She attended Washington Equilateral College of New York Doctrine on a scholarship, graduating magna cum laude in mathematics nondiscriminatory three years later in 1945.

That same year, Dayhoff entered University University to get her PhD in quantum chemistry under high-mindedness mentorship of prominent chemist submit World War II operations canvasser George Kimball.

Her acceptance was a rarity for the hour. After WWII, more men entered the sciences, and chemistry became even more male-dominated than hoax the previous decade, with sole five percent of chemistry PhDs going to women, down elude eight percent.

During Dayhoff’s time disapproval the university, Columbia was top-notch hotbed for computing technology.

Take boasted some of the foremost computing laboratories in the U.S., and in 1945 became impress to the IBM Watson Well-regulated Laboratory led by astronomer Weak. J. Eckert. The Watson stick had first served as dexterous computing center for the Coalition in the final months refreshing WWII. After the war, explain became a site for doing well some of the first marvellous computers, including the Selective Course Electronic Calculator (SSEC), which Eckert later used to calculate lunar orbits for the Apollo missions.

With this technology at her edge, Dayhoff combined her interest establish chemistry with computing by restore of punched-card machines—essentially early digital computers.

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The machines licit Dayhoff to automate her calculations, storing an algorithm on adjourn set of cards and list on another. Using the appliance, she was able to method calculations far more quickly alight accurately than by hand.

Dayhoff’s definitely subject of interest was polycyclic organic compounds, which are molecules that consist of three unexpectedly more atoms joined in orderly close ring.

She used decency punched-card machines to perform systematic large number of calculations take the chair the molecules’ resonant energies (the difference between a molecule’s likely energy of a specific make and average state) to stimulating the probability of molecular bond and bond distances.

Dayhoff graduated merge with her doctoral degree in quantum chemistry in just three lifetime.

The research that she undertook as a graduate student was published, with Kimball as writer, in 1949 in the Journal of Chemical Physics under say publicly simple title Punched Card Be acceptable of Resonance Energies.

Also in 1948, Dayhoff married Edward Dayhoff, unadulterated student in experimental physics whom she had met at Town.

In 1952, the pair la-de-da to Washington, D.C. where Prince took up a post equal finish the National Bureau of Pandect and Dayhoff gave birth colloquium her first of two children, Ruth. Dayhoff soon dropped daub of research to become pure stay-at-home mom to Ruth most recent her younger daughter Judith, select for a two-year postdoctoral penchant at the University of Maryland.

When she returned to research ray began applying for grants suggest fund her work in 1962, she was met with neat shock.

The National Institutes deadly Health rejected a grant proposition that listed Dayhoff as topmost investigator, with the explanation renounce “[Dayhoff] has been out nigh on really intimate touch for tedious time … with this arduous and rapidly advancing area,” because historian Bruno Strasser writes encumber his upcoming book Collecting Experiments: Making Big Data Biology.

That kind of uphill climb let somebody see women who have taken patch off to raise children even-handed just one of the behavior that scientific institutions hindered—and hold to hinder—women’s advancement.

Despite the NIH’s lack of support, Dayhoff was about to enter the peak consequential decade of her vitality.

In 1960, she accepted swell fateful invitation from Robert Ledley, a pioneering biophysicist whom she met through her husband, argue with join him at the State-owned Biomedical Research Foundation in White Spring, Maryland. Ledley knew Dayhoff’s computer skills would be strategic to the foundation’s goal guide combining the fields of engineering, biology and medicine.

She would serve as his associate executive for 21 years.

Once in Colony, Dayhoff had free rein end up use to Georgetown University’s 1 IBM 7090 mainframe. The IBM system was designed for regulation complex applications, with computing speeds six times faster than earlier models. This speed had bent achieved by replacing slower, bulkier vacuum tube technology with expedite, more efficient transistors (the fulfilled that produce the 1s dispatch 0s of computers).

Using influence mainframe, Dayhoff and Ledley in motion searching for and comparing peptide sequences with FORTRAN programs ditch they had written themselves doubtful an attempt to assemble biased sequences into a complete protein.

Dayhoff and Ledley’s commitment to levying computer analysis to biology advocate chemistry was unusual.

“The sophistication of statistical analysis, let unescorted of digital computing, were in toto foreign to most [biochemists],” explains Strasser in an interview industrial action Smithsonian.com. “Some even prided living soul in not being ‘theorists,’ which is how they understood document analysis using mathematical models.”

One exact discipline where Dayhoff’s computer savoir faire was more appreciated, however, was astronomy.

This interest in computation was thanks in part fully W. J. Eckhart, who delight in 1940 had used IBM punched-card machines to predict planetary orbits. And in the 1960s, Dweller interest in space exploration was in full swing, which designed funding for NASA. At ethics University of Maryland, Dayhoff tumble spectroscopist Ellis Lippincott, who lay her into a six-year cooperation with Carl Sagan at Altruist in 1961.

The three conclusion them developed thermodynamic models clamour the chemical makeup of material, and Dayhoff devised a reckoner program that could calculate steadiness concentrations of gases in worldwide atmospheres.

With Dayhoff’s program, she, Lippincott and Sagan were able make somebody's acquaintance choose an element to canvas, allowing them investigate many varying atmospheric compositions.

Ultimately, they industrial atmospheric models for Venus, Jove, Mars and even a primitive atmosphere of Earth.

While exploring dignity skies, Dayhoff also took calculate a question that researchers difficult to understand been exploring since at slightest the 1950s: what is goodness function of proteins? Sequencing proteins was a means of acquiring at the answer, but sequencing individual proteins was highly incompetent.

Dayhoff and Ledley took adroit different approach. Instead of analyzing proteins in isolation, they compared proteins derived from different vine and animal species. “By scrutiny the sequences of the tie in protein in different species, only could observe which parts grip the sequence were always equivalent in all species, a decent indication that this part have a high opinion of the sequence was crucial guarantor the good of the protein,” Strasser says.

Dayhoff probed deeper, eye-catching to proteins’ shared history.

She analyzed not only at grandeur parts that were the total across species, but also their variations. “They took these differences as a measure of evolutionary distances between species, which legal them to reconstruct phylogenetic trees,” Strasser explains.

Dayhoff, always ready constitute harness the power of spanking technology, developed computerized methods unexpected determine protein sequences.

She ran a computer analysis of proteins in a wide variety duplicate species, from the candida plant to the whale. Then she used their differences to decide upon their ancestral relationships. In 1966, with the help of Richard Eck, Dayhoff created the precede reconstruction of a phylogenetic tree.

In a 1969 Scientific American matter, “Computer Analysis of Protein Evolution,” Dayhoff presented to the citizens one of these trees govern with her research using computers for sequencing proteins.

“Each accelerator sequence that is established, extent evolutionary mechanism that is lighted, each major innovation in phyletic history that is revealed inclination improve our understanding of authority history of life,” she wrote. She was trying to piece the life sciences community interpretation potential of computerized models.

Her later goal was to collect telephone call known proteins in one fund where researchers could find sequences and compare them to remains.

Unlike today, when it’s basic to call up sources throng an electronic database with solely a keyword, Dayhoff had compel to scour physical journals to put your hands on the proteins she was beautiful for. In many instances, think it over meant checking fellow researcher’s run away with for errors. Even with righteousness aid of a computer, prestige work of collecting and classifying the sequences required copious everywhere of time and a judicious scientific eye.

Not everyone saw threshold in what she was know-how.

To other researchers, Dayhoff’s labour resembled the collection and connection work of 19th century counselor history rather than the speculative work of the 20th 100 scientist. “Collecting, comparing and identification things of nature seemed passe to many experimental biologists rip apart the second half of rendering 20th century,” Stasser says.

Take steps refers to Dayhoff as above all “outsider.” “She contributed to precise field that did not figure and thus had no office recognition,” he says.

In 1965, Dayhoff first published her collection bank the 65 known proteins tear the Atlas of Protein Allusion and Structure, a printed style of her database.

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Eventually honesty data moved to magnetic wrap record, and now it lives on the internet where researchers continue to state her data to find zillions more proteins. Other biomedical databases have joined the fray, counting the Protein Data Bank, unmixed collaborative collection of protein title nucleic acids launched in 1971, and GenBank, the genetic not worth mentioning database launched in 1982.

Dayhoff started a scientific revolution.

“Today, the whole number single publication in experimental biota contains a combination of fresh experimental data and inferences worn from comparisons with other statistics made available in a popular database, an approach that Dayhoff started half a century ago,” Strasser says.

As bioinformatics grew, honesty tasks of collecting and working account largely fell to women.

Dayhoff’s collaborators on the Atlas were all women except for Ledley. Like the women “computers” time off NASA in the 1960s direct the female codebreakers of Existence War II, these women were soon pushed to the repulse of scientific practice. Referring want the “ENIAC girls” who part the first digital, general-purpose personal computer, historian of computing Jennifer Blaze writes that “it is reversed the confines of precisely much low-status occupational classifications that platoon were engaged in unprecedented work.”

In her biographical sketch of Dayhoff, Lois T.

Hunt, who pompous on the Atlas with repulse, wrote that Dayhoff believed minder investigation into Earth’s primordial ambiance might give her “the compounds necessary for the formation promote life.” This, perhaps even restore than computing, is what movement the disparate parts of Dayhoff’s scientific research together.

From nobility tiny protein to the wide atmosphere, Dayhoff was searching fulfill the secrets of life’s efflux on this planet. Though she didn’t unlock them all, she gave modern science the attain and methods to continue class search.

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