Louis Sokoloff Papers

Collection

Identifier: MS C 591

Abstract

Dr. Louis Sokoloff was a neurochemical researcher who conducted and directed research projects at the National Institute of Mental Health (NIMH) for 50 years, most of that time as Chief of the Section (later Laboratory) of Cerebral Metabolism. He was best known for his use of PET imaging to examine chemical reactions in the brain.

Dates

Creation: 1923-2016

Extent

110.85 Linear Feet (155 boxes + 6.7 GB born digital electronic records)

Creator

Sokoloff, Louis, 1921-2015 (Person)

Physical Location

History of Medicine Division. National Library of Medicine

Language of Materials

Collection materials primarily in English

Access Restrictions

Collection is restricted. Portions of the collection are restricted according to HMD's Access to Health Information of Individuals policy. Contact the Reference Staff for information regarding access. For access to the policy and application form, please visit https://www.nlm.nih.gov/hmd/manuscripts/phi.pdf.

Copyright and Re-use Information

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Biographical Note

Dr. Louis Sokoloff spent most of his career as a neurochemical researcher with the National Institute of Mental Health (NIMH). From 1957 until his retirement more than 40 years later, he served as Chief of the Section (later Laboratory) of Cerebral Metabolism. In 1981 he won the Albert Lasker Award for Clinical Research for developing methods of visualizing biochemical activity in neural pathways that led to development of positron-emission tomography (PET).

Louis Sokoloff was born in Philadelphia in 1921. He earned the B.A., M.A., and M.D. degrees at the University of Pennsylvania. Influenced by Lewis V. Heilbrunn and other faculty, he decided on a career in scientific research, more specifically mammalian physiology and biochemistry. His experiences during a medical internship at Philadelphia Medical Hospital and on active duty in the Army Medical Corps at Camp Lee, Va., from 1946 to 1949, fostered an interest in physiological and biochemical mechanisms of the brain in mental disease. In 1949 he began grant-funded research at the University of Pennsylvania under former instructor and neuroscientist, Dr. Seymour S. Kety. During his four years there his primary research projects were studies of peripheral circulation, and, with Benton King and Richard Wechsler, the effects of epinephrine and norephinephrine and epinephrine on cerebral blood flow (CBF) and cerebral 02 consumption (MCR02).

In 1953 Sokoloff joined Dr. Kety at the National Institute of Mental Health, Bethesda, Md., where Kety had relocated as NIMH's first scientific director. As Associate Chief, Section on Cerebral Metabolism, Laboratory of Neurochemistry, Sokoloff spent the next six years studying thyroid hormones. Collaborating with Seymour Kaufman, he demonstrated that thyroid hormones stimulated protein synthesis. His study of thyroid mechanisms gradually broadened into interests in the relationship between biochemical processes and physiological functions in the nervous system.

Sokoloff's thyroid studies during the 1950s were conducted using the N20 method. Developed by Dr. Kety and C. S. Schmidt in 1948, this method enabled researchers to measure the average blood flow in the brain as a whole. By the late 1950s his research interests had progressed beyond cerebral blood flow to looking at brain metabolism, specifically glucose metabolism, which provided the brain's energy. However, the N20 method could not produce evidence of changes in cerebral energy metabolism during changes in mental function, even including functional psychoses.

A new technique arose during the mid-1950s when Drs. Kety, William Landau and Walter Freygang used isotopes of iodine to develop the [131]triflouroiodomethane ([131]CF31) method to study local cerebral blood flow and, indirectly, metabolic rates. Sokoloff attempted to adapt this method but by 1959 had not found a glucose compound that worked well. By 1965, however, NIMH's Dr. Martin Reivich modified the CF3I method in a way that allowed better autoradiographic resolution. This technique, using [14C]iodoantipyrine, suggested possibilities for Sokoloff's metabolism studies. 2-deoxyglucose (DG), whose actions during metabolism, would make autoradiographic studies of local glucose utilization possible.

Beginning in 1967, Dr. Sokoloff collaborated with Dr. Reivich, who had relocated to the University of Pennsylvania, to develop a [14C]DG method to measure local cerebral glucose utilization. The first applications proved unsatisfactory, but while on sabbatical in 1968, at the College de France's Laboratory of General and Comparative Biochemistry, Sokoloff had an inspiration. He reformulated the [14C]DG method in terms of enzyme kinetics rather than blood flow. Work progressed through the early 1970s, and by 1976 the method was successfully used with monkeys.

The next development came in data representation. Using automated data techniques, NIMH's Charles Gouchee and Wayne Rasband reworked the autoradiographic images into colored displays representing metabolic rates.

For human application, Reivich collaborated with Dr. David Kuhl at the Department of Radiology at the University of Pennsylvania, who had constructed a section scanner which could measure concentrations of gamma-emitting isotopes in human brain cross sections. DG, however, was a poor candidate for gamma-emitting isotope evaluation. With the assistance of Brookhaven National Laboratory chemist Alfred Wolf, the [14C]DG formula was adapted to a fluorinated derivative, 2-[18F]fluoro-2-deoxy-D-glucose ([18F]FDG), which retained the properties of DG while producing positron-emitting isotopes. Dr. Kuhl, with Michael Phelps and Edward Hoffman, expanded on this method at UCLA with development of positron-emission tomographic (PET) scanning. This was an improvement over the initial single photon scanner at the University of Pennsylvania which provided better spatial resolution and accuracy.

Dr. Sokoloff received the Albert Lasker Clinical Medical Research Award in 1981 for his role in developing the vivid color images that map brain function. The technique measures the metabolism of its primary fuel, glucose, through a radioactive substitute that, unlike glucose, lingers long enough to undergo chemical analysis. The award citation stated that "the Sokoloff method has facilitated the diagnosis, understanding and possible future treatment of such disorders of the brain as schizophrenia, epilepsy, brain changes due to drug addiction and senile dementia."

Dr. Sokoloff continued his work at NIMH well into the 21st century, retiring in 2004. He was awarded Scientist Emeritus status and maintained an office at NIH until his death in 2015. Information about his life and research can be found in History of Neuroscience in Autobiography, vol. 1, edited by Larry R. Squire (1996), which contains a lengthy autobiographical essay by Dr. Sokoloff, Dr. Sokoloff describes his research in an interview available on Youtube entitled "History of Neuroscience: Louis Sokoloff."

Collection Summary

Correspondence, research notebooks, photographs, autoradiographs, reprints and article drafts, scientific conference programs and agendas, speeches, audiovisual media, computer disks and electronic files document Dr. Louis Sokoloff's research at the National Institute of Mental Health's Laboratory of Cerebral Metabolism from 1953 to 2013. The materials illustrate the development of Dr. Sokoloff's research from general cerebral blood flow studies to investigations of cerebral metabolism in specific areas of the brain. The collection focuses on his scientific research and provides little to no information about NIMH administration; a small quantity of class notes, interviews, photographs, and other personal materials provides some insight into Dr. Sokoloff's pre-NIH career and personal life.

Series 1: Correspondence, dating from 1951 to 2008, consists of professional correspondence conducted by Dr. Sokoloff covering his entire tenure at NIMH. Most of this is arranged by the names of individual correspondents, but one portion of the series addresses administrative concerns with organizations with which Dr. Sokoloff's lab collaborated (such as the University of Pennsylvania), while another portion of the series is grouped by subject matter, such as cerebral blood flow, collaboration, publishers, and parking on NIH campus (an incident notorious within NIMH lore and a rare insight into Dr. Sokoloff's persnality). There are also a group of folders pertaining to award nominations that Dr. Sokoloff submitted on behalf of colleagues. These folders contain nomination letters and forms with supporting documentation; they are restricted.

Series 2: Experimental Data is the largest portion of the collection and consists almost exclusively of written documentation of experiments and autoradiographs which the experiments produced. The series is arranged by type of information, the first being written experiment documentation arranged alphabetically by the titles assigned to each experiment; they date from 1949 to 2003. The second section is the collected research notebooks, dating from 1952 to 2002, arranged alphabetically by the titles on the covers. The third section consists of research data positron emission topography (PET) scans and associated documentation. It begins with several sets of charts, graphs, explanatory paragraphs, and photographs, most of which are numbered. It then concludes with chronological autoradiographs and rolled paper graphs restricted for containing personal health information. Though these scans range in date from 1953 to 2002, they are mostly undated.

Series 3: Research Equipment and Materials is a small set of scientific equipment manufacturers' literature, forms used in Dr. Sokoloff's lab, registration applications for controlled substances used in lab research, methodology handouts, and some handwritten equations created for reference purposes.

Series 4: Professional Activities are primarily represented by programs and agendas for scientific conferences and symposia Dr. Sokoloff attended from 1957 to 2008. There is also a small section devoted to awards Dr. Sokoloff was nominated for and gatherings Dr. Sokoloff attended where he received awards. The series concludes with a section of folders containing membership cards, dues invoices and receipts, bylaws, procedures, brochures, and member lists for various professional societies of which Dr. Sokoloff was a member.

Series 5: Writings begins with a full set of Dr. Sokoloff's official article reprints and book chapters written between 1952 and 2005; these are arranged chronologically. There are also preliminary drafts of several titles. Dr. Sokoloff's writings are followed by a section holding collected reprints, handouts, and notes, dated 1923 to 2013, from various authors which Dr. Sokoloff accumulated for reference. They are grouped by subject representing the core/seminal aspects of Sokoloff's work, such as amino acid incorporation, PCP experiments, and protein synthesis. These subject files represent only a fraction of the total amount of subject files he meticulously maitained, however the overwhelming bulk and the tenegential nature of the majority prohibited their preservation. The series concludes with a small section of article reviews authored by Dr. Sokoloff from 1955-2007.

Series 6: Lectures and Presentations consists of materials for talks given by Dr. Sokoloff at meetings, conferences, seminars, and other professional events. The series includes speech drafts, travel arrangement records, CDs of PowerPoint presentations and lecture text, and video recordings of various presentations. Most of the Powerpoints contain just a few graphic slides with no accompanying text. A substantial number of files contain slides assembled for ready use in a variety of Dr. Sokoloff's presentations and publications; his lecturing technique was to assemble a set of slides and speak to them contemporaneously. Some of these slide files include the context for specific talks, such as title, date, or venue, while others only include broad subjects such as thyroid hormones, deoxyglucose, and physiology. The series is arranged chronologically.

Series 7: Personal and Biographical contains a small amount of material illustrating Dr. Sokoloff's background, including college course notebooks, interview transcripts, oral history recordings, retirement materials, photographs, biographical summaries, curriculum vitae, and ephemera. Researchers looking for more of Dr. Sokoloff's non-work personality will be hard pressed. The family retains much of the most personal artifacts that illustrate his non-professional life (he was an avid tennis player, wine connoisseur, home woodworker, and electronics tinkerer). There are digital photographs of retirement and lab parties, some travel photographs, and some low-resolution scans of personal photographs (he was scanning his analog slides and photos during retirement) in his electronic files that show Sokoloff socializing in and outside the lab.

Dr. Sokoloff was an early adopter of computer technology starting in the 1970s with Hewlett-Packard desktop computers and scientific graphing calculators, most notably the HP 9845 (held by the NIH Office of History Stetten Museum along with other equipment). Sokoloff and his lab scientists custom wrote many of the programs and utilities that visualized his PET research findings. Much of Sokoloff's early research is found on the computer tapes found in Series 8: Other Electronic Records and Computer Disks -- it is likely some of these same data are found printed out in Series 3: Research Equipment, Computer Programs subseries. Whenever practical, computer disks and electronic records are filed within their appropriate intellectual series--for example most Powerpoints are located in the Lectures and Presentations series; articles and drafts within the Writings series, etc. Sokoloff routinely backed up his computer to whatever contemporary physical media was was available such as floppy disks, Zip and Jaz drives, and CD-ROMs. Users will find much content duplicated across these formats--the most comprehensive set of files is the copy of his office PC captured in December 2015 and located in the Personal and Biographical series. In this same data set users will find his non-official Eudora email account -- Sokoloff's NIH email account was not preserved however anecdotally his office colleagues reported that he forwarded the most important work emails to his Eudora account and often lamented about the mostly useless emails that came from NIH. It is also unclear what electronic records he was creating as scientist emeritus post-2007.