Background on David Harker

David Harker was a reputable American crystallographer who was acknowledged for his pioneering work for the study of protein structure (Hargittai, 2023). Harker was once a graduate student in Linus Pauling’s lab and did research on X-ray diffraction (Hargittai, 2023). Prior to starting at PIB, he studied at California Institute of Technology and taught at Johns Hopkins University where he continued to pursue work related to crystallography and understanding crystal structure (Hargittai, 2023). In 1941, he worked at the General Electric Company laboratory where he studied metals using X-ray Crystallography (Hargittai, 2023). He had a name for himself as he developed well known laws in the field along with his colleagues, now called the Donnay-Harker Law and Harker-Kasper Inequalities, which was important for developing methods for X-ray Crystallography (Hargittai, 2023).

Image 1: Photo of David Harker in 1989; Photographer: I. Hargattai (Hargittai, 2023)

In 1949, Harker had an interesting encounter with Irving Langmuir that sparked his career at PIB (Hauptman, 1998). Langmuir had asked Harker what he would do with a million dollars, to which he responded that he would take 10 years off and focus on determining the structure of a protein (Hauptman, 1998). In two weeks, Langmuir raised the money and it eventually led to the establishment of the Protein Structure Project at PIB in 1950 (Hauptman, 1998).

Protein Structure Project at PIB During the 1950s:

At PIB, Harker was focused on determining the structure of the protein ribonuclease (Duax, 1992). Ribonuclease was of interest because it had several properties making it easier for study (Duax, 1992). His work was especially pertinent to the field of medical science. Ribonuclease became known as an enzyme that was important for genetic control, growth, and development (Duax, 1992).

Furthermore, in his 1953 article “Protein Structure Project”, David Goodman describes the necessity of understanding protein structure and David Harker's effort in contributing to the understanding of this science (Goodman, 1953). In regards to the importance of studying protein structure, Goodman emphasizes, “Without proteins there is no life. Proteins exist only as part of and as products of life. Many agents producing disease owe their destructiveness to the proteins they contain. Yet, the structure of not one single protein is known!” (Goodman, 1953). Goodman highlights the value of knowing a protein structure in order to be applied to medicine and also acknowledged that though the work to do it may be testing and require an multidisciplinary approach, it had a high probability of success.  

David Harker’s team at PIB consisted of physicists, chemists, and secretaries including: Dr. Murray Vernon King, Dr. Thomas C. Furnas, Jr., Dr. Beatrice S. Magdoff, William F. Weber, and Mrs. Harker (Goodman, 1953). Harker and his team were able to construct a single-crystal X-ray diffractometer that allowed for protein crystals to be accurately oriented for analyses (Goodman, 1953) The device was known as a Eulerian cradle and was the basis for a commercial goniostat (Hauptman, 1998). Furnas Jr. was credited with much of the design of it (Hauptman, 1998). Weber also contributed to the building of the instrument  (Tulinsky, 1996).

Image 2: Photograph of a half-circle Eulerian cradle; (Source: Tulinsky, 1996)

Furthermore, Murray King developed methods for dyeing the crystals, and Harker developed techniques for phase separation of the protein (Hauptman, 1998). Magdoff was a physicist that created information on structure based on diffraction data, Weber provided support for machine maintenance, and Mrs. Harker was the secretary and librarian (Goodman, 1953).

The lab was approximately 1200 square feet and contained a space for x-ray diffraction, a chemical laboratory, three offices, and a machine shop (Goodman, 1953).

In 1959, Harker ended up moving institutions and continued his work at the Roswell Park Memorial Institute in Buffalo, New York (Hargittai, 2023). Twelve years later, Harker and his research group discovered the structure of ribonuclease (Hargittai, 2023). His lab became known as the first US lab to determine the structure of a protein (Hargittai, 2023). Harker’s work became known at the national and international level and Harker was nominated for multiple awards, including the Nobel Peace Prize (Hargittai, 2023).

References

Duax, W. L. (1992). David Harker, 1906-1991. https://doi.org/10.1107/S0108767391012825

Goodman, D. (1953). Protein Structure Project. The Scientific Monthly, 77(2), 110–112.

Hargittai, I. (2023). David Harker—A life for crystallography. Structural Chemistry, 34(2), 737–739. https://doi.org/10.1007/s11224-022-02011-0

Hauptman, H. A. (1998). David Harker. In Biographical Memoirs: Volume 74. National Academic Press. https://doi.org/10.17226/6201

Tulinsky, A. (1996). Chapter 35. The Protein Structure Project, 1950–1959: First Concerted Effort of a Protein Structure Determination in the U.S. In J. A. Bristol (Ed.), Annual Reports in Medicinal Chemistry (Vol. 31, pp. 357–366). Academic Press. https://doi.org/10.1016/S0065-7743(08)60474-1