David Botstein
Deep Reader

My first encounter with David Botstein made a formidable impression. I was a new graduate student, listening with rapt attention as he lectured weekly in genetics. I learned the proper respect for what biologists call the “awesome power of yeast genetics,” and along the way I absorbed the principles that underpin modern molecular biology. However, my second course with Botstein—7.50: Method and Logic in Molecular Biology—had the most influence on my future.

In 7.50, my classmates and I did nothing but read research papers, from the “classics” that founded entire fields to contemporary papers that either broke new ground or went down in flames trying. The class met twice a week—the first time without the faculty, in order for the students to discuss the reading and get our story straight in anticipation of the grilling we would soon receive. At the second meeting, the faculty, including Botstein, would pick the papers apart piece by piece.

The first task was to understand the background behind each paper. What was the state of knowledge at the time? What questions did the researchers wish to ask? Then we would dissect the thinking behind the experiments. Finally, we had to summarize the authors’ conclusions, decide whether they were justified, and predict where the work might lead. Week after week, we pondered these questions as we pored over the literature, and Botstein cajoled, badgered, and encouraged us at each step.

The class profoundly shaped how I read papers and think about science. We were urged to see the bigger picture: How did the paper advance the field? How did it shape what came after? Could these consequences have been foreseen when the paper first appeared? Dr. Botstein invoked the “retrospectroscope” for this last function.

I especially remember reading Matthew Meselson and Franklin Stahl’s classic 1958 paper on DNA replication (“The Replication of DNA in Escherichia coli”). They used heavy isotopes to show that during cell division, each of the two new copies of the cell’s DNA receives half of the original material. Termed by some “the most beautiful experiment in biology,” the work was an elegant verification of DNA’s double-stranded nature. Our dissection of the original paper brought us close to the sense of discovery and wonder contemporary scientists must have felt.

Now, every day I bring the analytical skills Botstein taught me to my job as a scientific-journal editor. As I read papers, I apply the retrospectroscope by asking how much influence the findings are likely to have years down the road. Will students read these papers as 7.50 case examples 10 years hence? And each time I ask myself this question, I remember how indebted I am to Botstein and his enthusiastic tutelage.

By Charlotte Wang, PhD ’95, editor of Cell Metabolism, a journal based in Cambridge, MA.