John S. O'Brien Papers, 1968 - 2000 (MSS 0606)

Extent: 5 Linear feet (12 archives boxes)

Papers of John S. O'Brien, UC San Diego professor of neurosciences, internationally known for his discovery of the genetic cause of Tay-Sachs disease and his development of screening tests for the disease.

John Smith O'Brien was born in 1934 in Rochester, New York. He attended Loyola University in Los Angeles, then earned his M.S. in physiology (1958) and his M.D. (1960) at Creighton University in Omaha, Nebraska. After graduating with academic honors, he was a postdoctoral fellow at the City of Hope Medical Center at the Department of Biochemistry in Duarte, California. O'Brien was recruited to the UC San Diego School of Medicine in 1968 after six years as a faculty member at the University of Southern California.

His research was focused on the lipid metabolism of storage diseases which are characterized by the accumulation of waste materials in cells preventing normal function and often leading to early death. In this family of diseases, he especially investigated Tay-Sachs and Gaucher diseases. He discovered the primary enzyme deficiency of Tay-Sachs disease, a hereditary disorder which leads to mental retardation, blindness, and death in infancy or early childhood. Once thought to primarily affect people of Central and Eastern European Jewish ancestry, Tay-Sachs has now been documented in other populations. O'Brien also discovered and described the structure, biological functions, and role in nervous system development of the saposin proteins that stimulate regeneration and neuronal survival. His laboratory investigated possibilities for exploiting the saposin proteins for treatment of pain associated with post-polio syndrome, Alzheimer's disease, and central nervous system disorders.

O'Brien was a founder of Myelos Neurosciences Corporation, which resulted from technology developed at UC San Diego with saposin proteins. The company was started to expedite the development of treatments for neurodegenerative central nervous system disorders based on research findings.

O'Brien was a member of the Society for Neuroscience, American Society for Neurochemistry, the American Association for the Advancement of Science, and the Federation of American Societies for Experimental Biology. He was honored with the 1995 Supelco Award from the American Oil Chemists' Society for outstanding original research on fats, oils, lipid chemistry or biochemistry; the Jacob Javits Neurosciences Investigator Award from the National Institutes of Health; the Foster Elting Bennett Lecturer Award from the American Neurological Association; and the National Foundation of March of Dimes Award for Distinguished Voluntary Leadership in the Fight Against Birth Defects. He also received the UC San Diego Chancellor's Associates Merit Award for Excellence in Research, and a Distinguished Alumni Award from Loyola University.

In addition to his scientific and scholarly work, O'Brien was an accomplished painter and a jazz pianist. O'Brien died in La Jolla in 2001.

The papers of John S. O'Brien, UC San Diego professor of neurosciences, internationally known for his discovery of the genetic cause of Tay-Sachs disease and his development of screening tests for the disease. The papers primarily document his research on Tay-Sachs and similar hereditary diseases, many of which are characterized by the accumulation of waste materials in cells preventing normal function and often leading to early death. The files comprise correspondence, writings, laboratory notes, and newspaper clippings discussing his discovery of the genetic cause of Tay-Sachs disease. Also included are his writings and administrative materials related to his later work on a family of proteins called saposins responsible for regeneration and normal neuronal function of the central nervous system.

The papers are arranged in seven series: 1) BIOGRAPHICAL MATERIALS, 2) CORRESPONDENCE, 3) WRITINGS, 4) TEACHING, 5) TAY-SACHS, 6) RESEARCH, and 7) ORGANIZATIONS.

Container List

BIOGRAPHICAL MATERIALS

Scope and Content of Series

Series 1) BIOGRAPHICAL MATERIALS: Curricula vitae, photographs, and materials pertaining to O'Brien's postdoctoral fellowship with the National Heart Institute.

Box: 1 Folder: 1
Biographical sketch
Box: 1 Folder: 2
Curriculum vitae, 1961
Box: 1 Folder: 3
Photographs of O'Brien, 1969
Box: 1 Folder: 4
U.S. Public Health Service - Postdoctoral research fellowship, 1958 - 1961

Applications and correspondence.

CORRESPONDENCE

Scope and Content of Series

Series 2) CORRESPONDENCE: Correspondence with Michael M. Kaback, who organized and led the first Tay-Sachs screening program among Jewish citizens of Baltimore and Washington in 1971. Also chronological files documenting O'Brien's medical research.

Box: 1 Folder: 5
Kaback, Michael M., 1970 - 1993
Box: 1 Folder: 6-10
Chronological files, 1959 - 1965
Box: 2 Folder: 1-7
Chronological files, 1965 - 1967
Box: 3 Folder: 1
Chronological files, 1968 - 1977

WRITINGS

Scope and Content of Series

Series 3) WRITINGS: O'Brien's published and unpublished writings on folic acid, lipids, and lysosomal storage diseases. Arranged in two subseries: A) Articles, and B) Notes.

A) Articles: Typescripts, notes, correspondence, and photographs for O'Brien's research articles. Arranged chronologically.

B) Notes: O'Brien's notes on lysosomal storage disorders, including Gaucher disease and metachromatic leukodystrophy (MLD).

Articles

Box: 3 Folder: 2
List of publications, 1958 - 1998
Box: 3 Folder: 3
A Bioautographic Technique for Assay of Folic and Folinic Acids, 1958

Typescript of master's thesis in physiology, Creighton University.

Box: 3 Folder: 4
Simultaneous Fe-59 and Cr-51 Study in Evaluation of Erythrokinetics, 1958 - 1964

Typescripts, notes, and correspondence.

Box: 3 Folder: 5
The Folate Coenzymes. I. The Occurrence of Folate Forms in Leucocytes. II. A Review of the Chemistry and Biology of the Folate Coenzymes, 1960

Typescript of M.D. thesis, Creighton University.

Box: 3 Folder: 6
Hypogammaglobulinemia and Hypersplenism Associated with Lymphosarcoma of the Spleen: Normal Gamma Globulins Post Splenectomy. With John R. Walsh, 1961

Typescripts, notes, and illustrations.

Box: 3 Folder: 7
Role of Folate Coenzymes in Cellular Division, 1961 - 1962

Typescripts, correspondence, and illustrations. Published in Cancer Research.

Box: 3 Folder: 8
Folinic Acid Activity in Leucocytes. With John R. Walsh, 1962 - 1963

Drafts and typescripts. Published in Proceedings of the Society for Experimental Biology and Medicine 109: 843-847, 1962.

Box: 3 Folder: 9
Tissue Distribution of Glycosphingolipids in a Case of Fabry's Disease. With James M. Schibanoff and Shigehiko Kamoshita, 1966

Drafts, notes, correspondence, photographs and illustrations. Published in The Journal of Lipid Research, Vol. 10.

Box: 3 Folder: 10-11
Lipid Composition of the Brain in Late Infantile Amaurotic Idiocy (Jansky-Bielschowsky Type). With Hyakuji Yabuuchi and George B. Reed, 1967 - 1969

Typescripts, photographs, research notes and correspondence.

Box: 3 Folder: 12
Fucosidosis: Diagnosis by Serum Assay of Alpha-L-Fucosidase. With Klaus Zielke, et al, 1968

Typescript, notes, and illustrations.

Box: 4 Folder: 1
Lipid Composition of the Nervous System in Refsum's Disease. With Monica C. MacBrinn, 1968

Typescripts, correspondence, and photograph.

Box: 4 Folder: 2
I-Cell Disease: Biochemical Studies. With Jules G. LeRoy, et al, 1968 - 1972

Typescripts, notes, photographs, and correspondence. Published in Pediatric Research 6: 752-757 (1972).

Box: 4 Folder: 3
Sanfilippo Disease Type B: Detection of Homozygotes and Heterozygotes by Leucocyte Alpha-Acetylglucosaminidase Assay, 1971 - 1973

Typescript and research notes.

Box: 4 Folder: 4
Partial Purification of Alpha-N-Acetylglucosaminidase and Some of its Properties. With Audre W. Loverde, 1972 - 1975

Typescript, correspondence, and research notes.

Box: 4 Folder: 5
Binding of Human Liver Beta-Galactosidases to Plant Lectins Insolubilized on Agarose. With Anthony G.W. Norden - Typescript, 1973
Box: 4 Folder: 6
Purification of Human Placental Alpha-L-Fucosidase by Affinity Chromatography. With Jack A. Alhadeff and A.L. Miller, 1974

Typescript. Published in Analytical Biochemistry.

Box: 4 Folder: 7
Human Liver Alpha-L-Fucosidase. With Jack A. Alhadeff, et al, 1974 - 1975

Typescripts, correspondence, notes, and photographs. Published in The Journal of Biological Chemistry 250 (8): 1975.

Box: 4 Folder: 8
Characterization of Canine Liver Acid Beta-D-Galactosidase. With Jeffrey J. Hubert, 1975 - 1980

Typescript, research notes, and correspondence.

Box: 4 Folder: 9-10
Adrenoleucodystrophy: Deficiency of Acid Esterase Isozymes. With M. Lois Veath and Linda Tennant, 1977 - 1979

Typescripts, research notes, and photographs.

Box: 4 Folder: 11
Electrophoretic Analysis of Glycoprotein Enzymes in the Sialidoses and Mucolipidoses. With D.M. Swallow, et al, 1979 - 1981

Reference notes, correspondence, annotated proof and photographs.

Box: 4 Folder: 12
Canine GM1 Gangliosidosis: An Ultrastructural and Biochemical Study. With Moses Rodriguez, et al, 1980 - 1982

Typescript, research notes, and photographs.

Box: 4 Folder: 13
Molecular Cloning of a cDNA for Human Alpha-L-Fucosidase. With Hisao Fukushima, et al, 1985

Abstract typescript. Published in Proceedings of the National Academy of Sciences 82: 1262-1265, February 1985.

Box: 4 Folder: 14
Molecular Biology of the Alpha-L-Fucosidase Gene and Fucosidosis. With Patrick J. Willems, et al, 1987 - 1989

Typescript, correspondence, notes, reviews, and photograph.

Box: 4 Folder: 15
Bone Marrow Transplantation in Canine GM1 Gangliosidosis. With Robert Raff, et al, 1988 - 1990

Typescript, correspondence, and research notes.

Box: 5 Folder: 1
Characterization of the EcoRI Mutation in Fucosidosis Patients: A Stop Codon in the Open Reading Frame. With Keith A. Kretz, et al, 1989

Typescript and annotated reprint. Published in Journal of Molecular Neuroscience, 1989.

Box: 5 Folder: 2
Isolation, Characterization, and Mapping of a Human Acid Beta-Galactosidase cDNA. With Yoshimi Yamamoto, et al - Typescript, 1989
Box: 5 Folder: 3
Three Lysosomal Enzymes, 1991 - 1996

Grant renewal application to the National Institutes of Health.

Box: 5 Folder: 4
Abstracts of published articles, 1996 - 1998
Box: 5 Folder: 5
Prosaposin, the Saposin Proteins and Prosaptides - Typescript, 1998
Box: 5 Folder: 6
List of abstracts and manuscripts presented or work in progress sponsored by the Myelos Neurosciences Grant, 1998 - 1999
Box: 5 Folder: 7
List of publications submitted by UC San Diego O'Brien Group, 1998 - 1999
Box: 5 Folder: 8
Chromosome 1 Localization of the Human Alpha-L-Fucosidase Structural Gene with a Homologous Site on Chromosome 2. With M.L. Fowler, et al

Typescript. Published in Cytogenetics and Cell Genetics.

Box: 5 Folder: 9
Electrophoretic Forms of Human Liver Alpha-L-Fucosidase and Their Relationships to Fucosidosis (Mucopolysaccharidosis F). With Jack A. Alhadeff, et al - Typescript
Box: 5 Folder: 10
Fabry's Disease: Retention of an Alpha-Galactosidase Lacking Ceramide Trihexosidase Activity. With Anthony G.W. Norden - Typescript and notes
Box: 5 Folder: 11
Prenatal Diagnosis of Tay-Sachs Disease and Generalized Gangliosidosis. With Shintaro Okada - Typescript

Notes

Box: 5 Folder: 12
Adrenal cortex, 1973
Box: 5 Folder: 13
Cerebral lipidoses - Notes and graphs, 1961 - 1963

Notes and graphs.

Box: 5 Folder: 14
Gaucher disease, 1961
Box: 5 Folder: 15
Genetics of MLD (Metachromatic leukodystrophy)

Compiled by Alfred Knudsen and John O'Brien.

TEACHING

Scope and Content of Series

Series 4) TEACHING: Lecture notes, teaching materials, and visual aids for seminars and course lectures given at UC San Diego and other institutions. Arranged alphabetically.

Box: 5 Folder: 16
Folic Acid seminar, 1962 - 1963

Notes, typescript, and photographs.

Box: 5 Folder: 17
Lecture notes, 1961 - 1973
Box: 5 Folder: 18
Seminar talks and course lectures - Notes, 1963 - 1970
Box: 5 Folder: 19
UC San Diego Neurosciences 234: Molecular and Cellular Neurochemistry and UC San Diego Basic Neurology: Molecular Anatomy of Myelin - Lecture notes, 1969 - 1989

TAY-SACHS

Scope and Content of Series

Series 5) TAY-SACHS: Newspaper articles, press releases, correspondence, manuscript drafts, proposals, and pamphlets documenting O'Brien's discovery of the genetic cause of Tay-Sachs disease and his role in the establishment of widespread genetic screening, education, and counseling. Arranged alphabetically.

Box: 5 Folder: 20
California Tay-Sachs disease prevention program, 1977 - 1978
Box: 5 Folder: 21
Cost benefit analysis of Tay-Sachs disease, 1971 March

Typescript by O'Brien.

Box: 5 Folder: 22
Donation letter

Form letter requesting donations for Tay-Sachs research.

Box: 5 Folder: 23
National Tay-Sachs and Allied Diseases Association, 1970 - 1977

Correspondence, meeting minutes, pamphlets, and directory.

Box: 6 Folder: 1
Newspaper articles, press releases and correspondence, 1969 - 1971
Box: 6 Folder: 2
Progress in Tay-Sachs Disease to October 1969, 1969

Typescript by O'Brien.

Box: 6 Folder: 3
San Diego Tay-Sachs screening program, 1971 - 1974

Correspondence, pamphlets, notes, and news clippings.

Box: 6 Folder: 4
Tay-Sachs disease, 1961 - 1972

Notes, annotated reprints, and correspondence.

RESEARCH

Scope and Content of Series

Series 6) RESEARCH: Research notes, correspondence, and photographs relating to O'Brien's laboratory research on Tay-Sachs disease and other genetic disorders in humans and animals. Arranged alphabetically.

Box: 6 Folder: 5
4MU-Neuraminidase fibroblast assay - Research notes, 1978
Box: 6 Folder: 6
Adrenoleucodystrophy - Cholesterol lignocerate assays. Research notes, 1976 - 1977
Box: 6 Folder: 7
Alpha-galactosaminidase - Research notes, 1971
Box: 6 Folder: 8
Alpha-L-fucosidase purification - Research notes, 1981
Box: 6 Folder: 9
Antibody PPTN of beta-gal, 1975

Research notes and slides.

Box: 6 Folder: 10
Beagle beta-gal normal, 1978 - 1994

Research notes and photograph.

Box: 6 Folder: 11-12
Beta-gal purification 2 - Research notes, 1974 - 1979
Box: 7 Folder: 1
Beta-gal structural study - Research notes, 1982 - 1984
Box: 7 Folder: 2
Biochemical processes - Diagrams and charts
Box: 7 Folder: 3
Brain biopsy - Proposal, 1965
Box: 7 Folder: 4
Canine fucosidosis, 1982 - 1987

Correspondence and research notes.

Box: 7 Folder: 5
Cerebroside-beta-galatosidase and lactosylceramide galactosidase assays, 1972 - 1974

Research notes, correspondence, and photograph.

Box: 7 Folder: 6
Cerebroside SO4, 1959 - 1965

Research notes, graph, and annotated reprints.

Box: 7 Folder: 7
Cloning alpha-fucosidase, 1982 - 1991

Correspondence and research notes.

Box: 7 Folder: 8-9
Cloning alpha-hexosaminidase - Research notes, 1983 - 1984
Box: 7 Folder: 10
Cloning beta-galactosidase, 1982 - 1993

Research notes and correspondence.

Box: 7 Folder: 11
Cloning beta-galactosidase cDNA - Research notes, 1986 - 1989
Box: 7 Folder: 12
Cloning human ASA, 1983 - 1987

Research notes and correspondence.

Box: 8 Folder: 1
Cloning human beta-gal, 1982 - 1985

Research notes, photographs, and correspondence.

Box: 8 Folder: 2
Construction of E. coli beta-gal vector - Helinski's lab, 1982

Research notes and correspondence.

Box: 8 Folder: 3
Cystic fibrosis - Lab experiments, 1969 - 1978

Research notes and photographs.

Box: 8 Folder: 4
D1 goia sud leuk, 1965 - 1974

Research notes and photographs.

Box: 8 Folder: 5
DNA sequences - Alpha fuc sapl glu-cer 'ase, 1985

Research notes and correspondence.

Box: 8 Folder: 6
Fat study - Research notes, 1960 - 1961
Box: 8 Folder: 7
Fetal newborn livers vs. isoenzyme patterns, 1970 - 1971

Research notes and photographs.

Box: 8 Folder: 8
Florisil cols for cer SO4 - Research notes, 1963
Box: 8 Folder: 9
Frozen tissue - Diseased, 1962 - 1968

Correspondence, research notes, and photographs.

Box: 8 Folder: 10
Frozen tissue - Normal, 1962 - 1963

Research notes and photographs.

Box: 8 Folder: 11
Fucosidosis - Lipids, etc. Research notes, 1987
Box: 9 Folder: 1
Fucosidosis - Northern studies, 1985 - 1987

Research notes, proposal, correspondence, and photograph.

Box: 9 Folder: 2
GA2, globoside labeling, GM2, and assays, 1972-1980

Research notes and photographs.

Box: 9 Folder: 3
GA2 hexosaminidase preparation of GA2H3 and assays - Research notes, 1974 - 1975
Box: 9 Folder: 4
Ganglioside assays - Research notes
Box: 9 Folder: 5
GLC hex and hexoseam - Research notes, 1963
Box: 9 Folder: 6
GM1 - Animal models, 1973 - 1980

Research notes and correspondence.

Box: 9 Folder: 7
GM1 - Labeling, assays and ASF. Research notes, 1973 - 1988
Box: 9 Folder: 8
GM2 activator - Correspondence and notes, 1980
Box: 10 Folder: 1
GM2 assays #2, 1974 - 1981

Research notes and correspondence.

Box: 10 Folder: 2
GM2 gangliosidosis (types), 1964 - 1970

Research notes, correspondence, and photographs.

Box: 10 Folder: 3
GM2H3 hexosaminidase - Research notes, 1974 - 1975
Box: 10 Folder: 4
GM3 neuraminidase - Research notes, 1978
Box: 10 Folder: 5
Hexosaminidase in serum - Research notes, 1969 - 1972
Box: 10 Folder: 6
Hexosaminidase isol - Research notes, 1982 July
Box: 10 Folder: 7
HPLC galactosyl ligosaccharides - Research notes, 1978
Box: 10 Folder: 8
I-cell disease research, 1968 - 1976

Research notes and photographs.

Box: 10 Folder: 9
Leukodystrophy cat, Washington State University, Pullman, 1973 - 1976

Correspondence, research notes, and photographs.

Box: 10 Folder: 10
Lipid separation methods - Research notes, 1958 - 1963
Box: 10 Folder: 11
Lipidosis bonnet macaque, 1982

Research notes and photographs.

Box: 10 Folder: 12-13
Micrographs, 1971 and undated

Photomicrographs of cells affected by Tay-Sachs and other disorders.

Box: 10 Folder: 14
MPS - Gel electrophoresis. Research notes, 1978
Box: 10 Folder: 15
mRNA isolation - Research notes, 1982
Box: 10 Folder: 16
NANA assays - CMP-NANA synthetase preparation, 1971 - 1975

Research notes and correspondence.

Box: 10 Folder: 17
Neuraminidase assays - Research notes, 1977 - 1978
Box: 11 Folder: 1
Neurometabolic disorders (general), 1972

Diagnosis of lipidoses and leucodystrophies chart.

Box: 11 Folder: 2
Normal human beta-gal isolation - Research notes, 1979 - 1983
Box: 11 Folder: 3
Oligosaccharide purification, 1978

Research notes, photograph, and annotated reprint.

Box: 11 Folder: 4
Phospholipase assay - Research notes, 1980
Box: 11 Folder: 5
Portuguese water dogs - Storage disease, 1980 - 1990

Research notes and correspondence.

Box: 11 Folder: 6-7
Refsum's disease myelin, 1967

Research notes, photographs, and correspondence.

Box: 11 Folder: 8
Sandhoff's disease, 1969 - 1978

Research notes, correspondence, and photographs.

Box: 11 Folder: 9
Sanfilippo type B - Enzyme replacement, 1973

Research notes and photographs.

Box: 11 Folder: 10
Skin biopsies enzyme assays, 1969 - 1971

Research notes and correspondence.

Box: 11 Folder: 11
Sphingomyelinase and phosphodiesterase exps. and P32 turnovers, 1975 - 1976

Research notes and correspondence.

Box: 11 Folder: 12
Sphingomyelinase assay, 1973 - 1974

Correspondence and research notes.

Box: 12 Folder: 1
Standard preparation methods - Research notes, 1962 - 1964
Box: 12 Folder: 2
Studies on hex A and B - TS vs. normal liver, 1974 - 1975

Research notes and correspondence.

Box: 12 Folder: 3
Tay-Sachs - 1554 lipids. Research notes, 1962 - 1963
Box: 12 Folder: 4
TLC densitometry - Research notes
Box: 12 Folder: 5
Transfection - Beta-gal histo. Research notes, 1978 - 1982
Box: 12 Folder: 6
Unusual beta-gal mutants, 1974 - 1976

Research notes and correspondence.

ORGANIZATIONS

Scope and Content of Series

Series 7) ORGANIZATIONS: Minutes, correspondence, reports, and contracts regarding the Neurosciences Education and Research Foundation, a nonprofit organization of which O'Brien was president, and of Myelos Neurosciences, Inc. The corporation was founded by O'Brien to exploit research discoveries of the saposin proteins done at O'Brien's laboratory for treatment of pain associated with post-polio syndrome, Alzheimer's disease, and central nervous system disorders.

Box: 12 Folder: 7-8
Myelos Neurosciences - Consulting - Cytokine Derived Peptides as Therapeutics, 1993 - 2000

Contracts, financial reports, and correspondence.

Box: 12 Folder: 9
Neurosciences Education and Research Foundation, 1994 - 1999

Correspondence, minutes, and financial status reports.

Box: 12 Folder: 10
UC San Diego Technology Transfer Office - Invention and technology disclosure - Myelos Neurosciences, 1995 - 1998

Correspondence, disclosure forms, budget reports, and notes.