David Botstein, a pioneering molecular biologist and geneticist who discovered a method for finding disease-causing genes in human DNA, died on 27 February at the age of 83.
Botstein exposed a solution to one of the defining problems in the study of the human genome at a time when little was understood about the way the thousands of individual genes in a human body interacted with one another to compose a person’s DNA. Through experiments with yeast samples in 1977, Botstein discovered that he could map out the genes by looking for variations in the “spelling” of DNA, which he could then use as markers of nearby genes. The discovery allowed scientists to locate genes for a plethora of diseases including cystic fibrosis and Huntington’s disease, as well as inherited risk for breast cancer and thousands of other afflictions.
“I can’t tell you how huge a problem this was,” Eric Lander, a molecular biologist at the Broad Institute of MIT and Harvard University, said in an interview. “David Botstein is the first person who solved that problem. It was a heroic, amazing contribution. He cracked open the biggest problem in human genetics.”
David Botsztejn, born on 8 September, 1942 in Zurich, was the oldest of three children by parents Chaim and Anna, who were clinical research physicians from Poland. They had come to Switzerland 10 years earlier as medical students, evading the Nazi takeover of their home country, and remained there while many members of their family died in the Holocaust.
When the Swiss government denied the Botsztejns citizenship because they were Jewish, the family immigrated to the US and arrived in New York in 1949, at which point Chaim and Anna’s names were changed to Charles and Anne Botstein.
“I did everything possible to fit in,” Botstein told the New York Times in 2003. “I lost my German accent. I joined the Cub Scouts and the Boy Scouts. I was the pioneer in the family in all things American.”
From an early age, Botstein showed an interest in research science. After graduating from the Bronx High School of Science, he earned a degree in biochemistry from Harvard in 1963 before switching to the study of human genetics in a PhD at the University of Michigan.
His career began in the early 1970s when he became a genetics professor at the Massachusetts Institute of Technology (MIT), and it didn’t take long for him to reach the forefront of genetic research. Before the human genome was sequenced as it is today, Botstein found a way to construct genetic linkage maps that could estimate the likelihood of two genes being connected based on how often they separated when the DNA split and recombined during sexual reproduction. This discovery paved the way for the Human Genome Project, a landmark international scientific study that began in 1990 to determine the base pairs that make up human DNA and map all the genes in the human genome.
When a scientific idea excited him, Botstein would shout the Yiddish word “azoy!”
He was elected to the US National Academy of Sciences in 1981 and in 1987 he left MIT to become the vice president of biotech company Genetech. Three years later he took on the role of genetics department chairman at Stanford before becoming the director of the Lewis-Sigler Institute for Integrative Genomics at Princeton University in 2003, where he stayed until 2013 when he then became the founding chief scientific officer of the biotech company Calico. Botstein remained there until 2023, when he retired.
He met his wife, Renee Fitts, in 1987 after two earlier marriages ended in divorce. She told the New York Times that, in addition to science, Botstein was passionate about classical music, and could play the piano, violin and cello.
Botstein’s cause of death, according to his wife, was Parkinson’s disease. He is survived by his brother and sister; a son, Sam Botstein; a daughter, Ruth Botstein; and two grandchildren.
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