John H. Weiss

Born: June 5, 1956 | San Francisco, CA, US

John H. Weiss grew up in San Francisco, California and attended Stanford University, to study biology and neuroscience. While at Stanford University School of Medicine, uncertainty prevented him from seeking a lab position. During his residency, he met Dennis W. Choi and entered the Stanford PhD program in neuroscience. In the Choi lab he began work on mechanisms of nerve cell degeneration in stroke and on glutamate's toxic effect on nerve cells. Research on nerve degenerative diseases on Guam led Weiss to studyß-N-methylamino-L-alanine (BMAA). He discovered that BMAA's toxicity depends on a covalent interaction with other compounds. Now at University of California, Irvine, he discusses setting up his lab, research, and collaboration with other scientists.

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Interview Details

Interview no.: Oral History 0547
No. of pages: 115
Minutes: 450

Interview Sessions

Andrea R. Maestrejuan
2-4 October 1996
Costa Mesa, California

Abstract of Interview

John H. Weiss grew up in San Francisco, California, the oldest of three children. His parents were both psychiatrists. He attended a private grade school and a less traditional high school; he found school interesting but not especially difficult. He developed his interest in math and science early, and he found that science came naturally to him as he was interested in discerning patterns in the way the world works. Weiss entered Stanford University, where he majored in biology with a focus on neuroscience. After taking an extra year of undergraduate study, he applied to medical school. He spent six months in a biochemistry research lab, and he attended science classes while at Stanford University School of Medicine, but uncertainty prevented Weiss from seeking a lab position. He found that the practical challenges of medical residency proved more difficult than course work when he started a neurology residency. During that residency he met Dennis W. Choi and entered the Stanford PhD program in neuroscience. In the Choi lab he began work on mechanisms of nerve cell degeneration in stroke and on glutamate's toxic effect on nerve cells. Choi proposed two phases of glutamate injury. Research on nerve degenerative diseases on Guam led Weiss to study β-N-methylamino-L-alanine (BMAA). His work in the Choi lab on BMAA yielded clues regarding AMPA/kainate receptor activation in nerve-degenerative diseases. He discovered that BMAA's toxicity depends on a covalent interaction with other compounds, explaining about AMPA/kainate toxicity and receptor activation, the role of voltage-sensitive calcium channels, BMAA's role in nerve-degenerative disease, and the finding that zinc accumulation in voltage-sensitive calcium channels might cause cell death (apoptosis). Weiss accepted a position at University of California, Irvine, and received a Pew Scholars Program in the Biomedical Sciences award and a National Institutes of Health grant, though he did not have lab space immediately available at Irvine. While starting his lab he had teaching and clinical responsibilities, he had to find and hire postdocs, and he had to mentor students. At the end of the interview Weiss discusses AMPA/kainate-type glutamate receptor-mediated toxicity in selective nerve cell degeneration; calcium in selective injury; a collaboration with the Choi lab to study "cobalt positive" NADPH-diaphorase cells; attempts to improve upon historically poor results of calcium imaging studies; correlating calcium influx and intercellular calcium levels with cell death; and the role of zinc in selective injury. His collaboration with Carl Cotman on β-amyloid protein's toxicity in cortical cell cultures and new directions for research on cellular functions constituted his attempts to establish a reputation separate from Choi's and to overcome the competitive pressure he felt in his field. He concludes by saying that he has found a supportive community at the Pew Scholars Program in the Biomedical Sciences annual meetings.

Education

Year Institution Degree Discipline
1979 Stanford University BS Biology
1979 Stanford University MS Biology
1983 Stanford University MD
1991 Stanford University PhD Neuroscience

Professional Experience

Stanford University Hospital

1983 to 1984
Intern, Medicine
1984 to 1987
Resident, Neurology
1987 to 1991
Postdoctoral Fellow, Department of Neurology

University of California, Irvine

1991 to 1996
Assistant Professor, Department of Neurology
1992
Staff Member, Medical Center
1996
Associate Professor, Department of Neurology
1996
Associate Professor, Department of Anatomy and Neurobiology and Department of Psychobiology

Honors

Year(s) Award
1980 to 1981

Stanford Medical Alumni Scholar

1980 to 1981

March of Dimes Medical Student Research Fellowship

1987 to 1990

American Academy of Neurobiology Research Fellowship in Neuropharmacology

1990 to 1991

Dana Fellow in Neuroscience

1990 to 1995

National Institute on Aging Clinician Investigator Award

1992 to 1996

Pew Scholar in the Biomedical Sciences

Table of Contents

Family Life and College Years
1

Family background. Parents' nontraditional values and psychoanalytic training. Early schooling. Attends an alternative high school in San Francisco during theearly 1970s. Develops a social conscience. Early interest in math and science. Interest in discerning patterns in how the world works. Stanford University. Declares a major in biology with a focus on neuroscience. Father'spsychoanalytic career and its impact on Weiss's research focus. Takes an extrayear of undergraduate study. Undergraduate life.

Medical School, Medical Practice, and Starting Graduate School
28

Applies to medical school. Six-month stint in a biochemistry research lab. Attends science classes while at Stanford University School of Medicine. Practical challenges of medical residency. Neurology residency and meeting Dennis W. Choi. Enters the Stanford PhD program in neuroscience. Lack ofleisure time as a medical student. Work on mechanisms of nerve celldegeneration in stroke. Research on glutamate's toxic effect on nerve cells. Crucial role of N-methyl-D-aspartate (NMDA) receptors. Advantages of using cell culture systems rather than whole-animal models. Preference for theory-driven science over technique-driven. Interest in doing basic research rather than applied. University of California, Irvine's Institute for Brain Aging andDementia. Research on nerve degenerative diseases on Guam leads to study of ß-N-methylamino-L-alanine (BMAA). AMPA/kainate receptor activation in nerve-degenerative diseases. AMPA/kainate toxicity and receptor activation. Role of voltage-sensitive calcium channels. Zinc accumulation in voltage-sensitive calcium channels may cause cell death.

Faculty Years and Scientific Life
72

University of California, Irvine. Pew Scholars Program in the Biomedical Sciences and National Institutes of Health grants. Teaching and clinical responsibilities. Postdocs. Hong Zhen Yin. Mentoring students. AMPAkainite-type glutamate receptor-mediated toxicity in selective nerve cell degeneration. Role of calcium in selective injury. Collaboration with the Choi lab to study "cobalt positive" NADPH-diaphorase cells. Correlating calciuminflux and intercellular calcium levels with cell death. Carl W. Cotman and ß-amyloid protein's toxicity in cortical cell cultures. Hannah Monyer.

Final Thoughts
94

Broad research questions. Belief that basic research with clear clinical reference will continue to be funded. Science funding. Pew annual meetings.

Index
112

About the Interviewer

Andrea R. Maestrejuan