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.