Memoir - David Harker

David Harker

October 19, 1906 - February 27, 1991

Condensed by David Haas

From the National Academy of Sciences biographical memoir by Herbert Hauptman, with permission from the National Academy of Sciences, Courtesy of the National Academies Press, Washington, D.C. http://www.nasonline.org/publications/biographical-memoirs/memoir-pdfs/harker-david.pdf

David Harker (AIP Emilio Segre Visual Archives,
Physics Today Collection)

The focus of David Harker's life, around which all his thoughts and actions revolved, was the science of crystallography, which he dearly loved. To crystallography he gave everything—his time, his energy, his total devotion. So complete was his dedication to this science and so fundamental and many-faceted were his contributions that he influenced forever the course of its development. To this day, the Harker section and the Harker construction play essential roles in the determination of the structures of very large molecules. The Harker-Kasper inequalities provided the inspiration for a new branch of X-ray crystallography, the so-called direct methods of phase determination.

David was born on October 19, 1906, into a scientific and medical family in Mill Valley near San Francisco. His father, George Asa Harker, was a medical doctor from the University of California at Berkeley. David's father introduced the concepts of shape, symmetry, and structure into David's life. His mother, Harriette Butler Harker, graduated from Vassar in 1898 and received her M.D. from the University of California at Berkeley. His mother, together with faculty members from Berkeley, taught classes at his high school in exchange for free tuition.

In 1928 David graduated with honors in chemistry from the University of California at Berkeley. In 1930, David married Katherine De Savich, who, as the daughter of the imperial prosecutor under the tzar, fled Russia in 1917. Katherine later aided David in translating scientific books into English. They also spent ten years working on the translation of a Soviet physics journal for crystallography, until her death in 1973. They had two daughters, Tatiana Harker Yates and Liudmilla Harker. Following the death of his first wife, David married Deborah Maxwell in 1974. She died in 1997, six years after David's death.

After graduation from Berkeley, David continued on as a graduate student, but in 1930 he left to take a job as laboratory technician at the research laboratory of the Atmospheric Nitrogen Corp. in Solvay, N.Y. (near Syracuse). There he weighed samples, made mixtures, and occasionally read scientific journals. In one of these he read a paper on the crystal structure of sodium nitrate and its change as the nitrate groups rotate at elevated temperatures. This beautiful result so impressed him that he resolved to study crystal structures in greater depth at some future time.
In 1933 (the depth of the Depression) David lost his job. He returned to California with his wife and child, and entered the graduate school of the California Institute of Technology. There, under the supervision of Linus Pauling, he began to work on the determination of crystal structures using the technique of X-ray diffraction. After some preliminary studies of three or four simple structures, he undertook the solution of his dissertation problem: to determine the structures of the ruby silvers, proustite (Ag₃AsS₃) and pyrargyrite (Ag₃SbS₃), which are isomorphous (i.e., they have the same structure).

Then, at one of the weekly seminars of Pauling's students, A. L. Patterson's famous 1934 paper on the Patterson function was presented. This function relates the experimentally observable X-ray diffraction intensities with the totality of interatomic vectors in the crystal. Owing to the large number of interatomic vectors, interpreting the Patterson function was, and still is, no easy task. A few nights after the seminar, he had envisioned that the relationships between symmetrically related atoms would produce peaks in the Patterson function on certain planes or along certain lines determined by the known crystallographic symmetries. These "Harker" peaks often lead directly to the atomic position vectors and the crystal structure, particularly in those cases when the Patterson function itself is not readily interpretable. Thus was born the famous Harker section, which effectively made the Patterson function useful. In this way David quickly deduced the structures of proustite and pyrargyrite and earned his Ph.D. in 1936. The Harker section has withstood the test of time and even today is indispensable for the determination of macromolecular structures, particularly in those cases where the structure contains a small number of heavy atoms, when Patterson techniques are useful.

Having become a physical chemist in 1936, David took an academic job in chemistry at the Johns Hopkins University, where he taught freshman chemistry, graduate courses in crystal structure, crystal chemistry, and quantum mechanics. During David's tenure at Johns Hopkins, Dorothy Wrinch came to visit the university for about a year. She and Irving Langmuir, who visited Johns Hopkins occasionally, engaged in extended discussions concerning her theories of protein structures. David was drawn into their conversations and soon became interested in the problem of protein structure determination. In addition, during this period, W. T. Ashbury of Leeds gave a colloquium on the structures of fibrous proteins. David, in his words, "became infected with the protein structure virus, but for many years it lay dormant."

During those years, David met Professor J. D. H. Donnay of Johns Hopkins and George Tunnell of the Geophysical Laboratory in Washington, D.C. From these prominent mineralogists David learned classical crystallography, some mineralogy, and the significance and measurement of crystal faces. It was Donnay's goal to correlate the internal structure and external face development of crystals. The earlier attempt to do this by Bravais resulted only in a rather poor approximation. Donnay and Harker discovered that the order of decreasing prominence of the faces of a crystal was the same as the order of decreasing interplanar lattice spacings, including the halvings, thirdings, and quarterings due to the space group symmetries. This correlation, while still not perfect, was an improvement over Bravais's earlier attempt. It is known in mineralogical circles as the Donnay-Harker law.

In 1941 David received an offer from W. D. Coolidge to work in the famous research laboratory of the General Electric Company and after some hesitation he accepted it. He became a member of the metallurgy division at General Electric and proceeded to learn properties of metals using X-ray diffraction and other crystallographic methods. Although David is known primarily for his contributions to X-ray crystallography, his metallurgical papers had a considerable impact on the physical metallurgical community. One of these, in particular, was primarily concerned with the microstructural subtleties associated with the ordering reaction in the alloy AuCu in which there is a change in unit cell from cubic to tetragonal. His theoretical analysis of the complex microstructures, which are to be expected as a means for the material to avoid long-range internal stresses, was far ahead of its time and had considerable influence on the research concerned with ordering reactions in alloys.

During his years at General Electric, David also developed an X-ray method for finding the orientation of quartz fragments, so that oscillator plates could be cut from them. In addition, he did several pieces of crystallographic work for other divisions of the laboratory. He also started work on the design of X-ray diffraction equipment with which the diffracted intensity would be measured with a Geiger-Müller or other particle counter.

It was during David's tenure at General Electric that he and his collaborator John S. Kasper produced their paper on the inequalities among the crystal structure factors, the famous Harker-Kasper inequalities. These inequalities constitute the first contribution to the direct methods of phase determination and David provided this account:

One day John Kasper was sitting at his desk staring gloomily at a lot of algebra he had been writing down. I looked over his shoulder and said something like, "What on earth is that?" and he replied "Schwartz's Inequality for a structure factor, but it doesn't seem to help." He then kept on writing, while I looked on. I said, "Oh, well, let's expand those squares of cosines into functions of double angles." So we did. Then it hit us both, I think, at the same time. "Say! We can get the signs of some structure factors from this!" Then we went madly to work, and in a couple of weeks we had enough algebraic apparatus assembled "unitary" structure factors, sum and difference inequalities, etc.—to be useful. Kasper applied this schema to the decaborane data and came out with a preliminary model which explained the diffracted intensities from one zone, and, after another couple of months, the complete structure emerged. Thus was born the subject of "sign determination" from intensities. This was in 1947.

It is appropriate to point out here the mathematical basis of the Harker-Kasper inequalities - this is simply the non-negativity property of the electron density function, a fact implicitly assumed in their analysis.

After a good deal of prodding on David's part, the X-ray department of General Electric was finally persuaded to build its first counter diffractometer for powder patterns, although not before the North American Philips Co. had already put a similar device on the market. Next, David set about adapting it to single crystal work. By 1949 he had built several models and had used them successfully, mostly on metallurgical problems. During his time at General Electric, David served as president of the Society for X-ray and Electron Diffraction (1946). He also headed the American delegation to the London conference where the formation of the International Union of Crystallography was proposed and later was established, along with its adhering body in the United States, the U.S. National Committee for Crystallography.

The next phase in David's career was triggered in the fall of 1949 by Irving Langmuir, who asked him what he would do with a million dollars. To this seemingly rhetorical question David's offhand response was that he would take ten years off and determine the structure of a protein. To David's great surprise, within two weeks Langmuir came to his office and announced that he could raise the money. David suddenly realized that determining the structure of a protein was what he had wanted to do for some time. After months of interminable negotiations, the decision finally was made to establish the Protein Structure Project at the Polytechnic Institute of Brooklyn in July 1950. There David and his team built a good single-crystal X-ray diffractometer with counter detection of the diffracted beams. The central device in this unit was a sort of theodolite arrangement for orienting the crystal in any possible way. They called this device a "Eulerian cradle," because the angular motions it could give the crystal were Euler's angles. This instrument was eminently successful, and led to the commercial goniostat, which soon became increasingly popular. Much of the success of this instrument was due to its careful design, for which Thomas C. Furnas, Jr. was primarily responsible.

David chose ribonuclease as the protein on which to work, because it could be had relatively pure at a reasonable price, could be readily crystallized, and it had a quite small molecular weight. Murray King crystallized this substance in fourteen different modifications eventually. He also invented the method of attaching heavy atoms to specific sites in the protein crystals by "dyeing" the crystals with specially synthesized dyes, the molecules of which contained heavy atoms. David worked out the scheme of phase determination for protein structure factors, which involved using the intensities from three isomorphous crystals—one undyed, the other two dyed with heavy atoms in different arrangements, a scheme used by macromolecular crystallographers to this day. It turned out that Professor Bijvoet of Utrecht had found the same principle a few years earlier, but he had not emphasized it in his papers. This scheme, since called the method of multiple isomorphous replacement, led to the first successful structure determinations of crystalline proteins—those of myoglobin by Sir John C. Kendrew and of hemoglobin by Max F. Perutz, both of Cambridge University. For this work they received the Nobel Prize in chemistry for 1962.

From 1950 to 1959 David and his team worked at the Brooklyn Polytechnic Institute on the crystal structure problem presented by the protein ribonuclease. In 1959 David moved the whole project to the Roswell Park Cancer Institute (then known as the Roswell Park Memorial Institute), where he accepted the position of head of the biophysics department. Due to the efforts of visiting crystallographers, a number of critical problems had already been solved. M. V. King solved the problem of dyeing the protein molecules. F. H. C. Crick discovered the strong temperature dependence of the diffracted X rays from the protein crystals mounted in sealed capillaries and showed how to control it. V. Luzzati showed how the intensity statistics were related to the structure of the protein crystals and why the standard statistical methods could not be applied in these cases. A. Tulinsky worked out the exact structure of beryllium basic acetate and made it into a useful intensity standard. G. Kartha developed new ways of using the diffraction data from non-centrosymmetric crystals. A. de Vries showed how anomalous dispersion effects could help in determining the structures of crystalline proteins. J. Bello discovered new ways of labeling ribonuclease crystals with heavy atoms. T. C. Furnas, Jr. built their counter diffractometer, aided by that artist in instrument construction W. G. Weber.

The stage was set to begin to collect X-ray crystallographic data from which the structure of ribonuclease could be determined. This goal was finally reached in 1967 with the determination of the crystal and molecular structure of ribonuclease, the first protein structure to be determined in the United States.

In 1976 David retired from the Roswell Park Cancer Institute, but he continued his crystallographic studies as a research scientist emeritus at the Hauptman-Woodward Institute (then known as the Medical Foundation of Buffalo). He became interested in the more mathematical aspects of crystallography, in particular the theory of colored space groups and a description of several classes of infinite polyhedra.

The year 1977 marked David's election to the National Academy of Sciences and the American Academy of Arts and Sciences. Two years later, in 1979, he was nominated for a Nobel Prize. In 1980 the American Crystallographic Association honored him with the prestigious Fankuchen Award in recognition of his services to crystallography, in particular his research accomplishments and his role as a teacher of crystallography. In 1981 the State University of New York at Buffalo awarded David an honorary degree of doctor of science in recognition of his long and outstanding career in science, the first such award by this university. In 1984 David received the Gregory Aminoff Medal in Gold from the Royal Swedish Academy of Sciences in recognition of his fundamental contributions to the development of methods in X-ray crystallography and for his determination of the molecular structures of biologically important substances.

On David's eighty-second birthday, in 1988, the David Harker Endowment Fund was established by an anonymous donor at the Hauptman-Woodward Institute in Buffalo. The fund is intended to support research and lectures in crystallography. In 1989 David prepared a paper announcing his discovery of four new types of polyhedra, which he named the "tortuously corrugated two dimensionally infinite polyhedra." This paper was published shortly before his death in the January 1991 issue of Proceedings of the National Academy of Sciences. He was a tireless seeker of the truth, wherever he could find it, and in this quest he succeeded as few others have. On February 27, 1991, David died of complications due to heart disease and pneumonia.