David Botstein, the molecular biologist who revolutionized genetics by discovering how to locate genes in human DNA, died on February 27 in Palo Alto at age 83. His method of using DNA variations as markers to find disease-causing genes enabled researchers to map the entire human genome and identify genes responsible for conditions like cystic fibrosis, Huntington's disease, and inherited breast cancer risk.

Working at MIT in the early 1970s when little was known about gene interactions, Botstein solved what colleagues called 'the biggest problem in human genetics.' His breakthrough came in 1977 during yeast experiments, where he realized small DNA variations could serve as markers for nearby genes. The epiphany struck when he attended a University of Utah meeting where geneticists discussed hemochromatosis inheritance.

Botstein's findings proved crucial for sequencing the human genome, providing the landmarks needed to assemble the vast jigsaw puzzle of genetic information. His work launched modern genomics and transformed medical research. Beyond his scientific contributions, Botstein was known for his intellectual restlessness, moving between academia and industry throughout his career, and his passion for classical music and interdisciplinary education.