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In the footsteps of Watson and Crick

At the double helix’s half-century, four Yale professors share memories of molecular biology’s early days.

When hundreds of scientists gathered in England in April to celebrate the 50th anniversary of the structure of DNA, among them were four Yale faculty members who trained as postdocs in the late 1960s at the Medical Research Council’s (MRC) Laboratory of Molecular Biology. The lab was originally a division of the Cavendish Laboratory in Cambridge, where Francis H.C. Crick, Ph.D., and James D. Watson, Ph.D., discerned the double helix.

While the four were at the MRC lab—about a decade and a half after Watson, Crick and their collaborators had outlined their model of DNA in the pages of Nature—molecular biology was viewed as anything but a growth industry. Everyone in the field knew everyone else, few labs were training molecular biologists and only three journals were interested in articles on the topic. Joan A. Steitz, Ph.D., Sterling Professor of Molecular Biophysics and Biochemistry, recalls thinking that her interest in the molecular basis of genetic phenomena had relegated her to an “esoteric intellectual backwater.”

At the time she couldn’t imagine all that would transpire over the half-century since Crick and Watson solved the structure. “It has had an impact on every aspect of biomedicine,” said Steitz. “Look at what it has done for the pharmaceutical companies and the whole biotechnology industry that never existed. The impact on forensics is astounding.”

The biological importance of DNA’s structure, says her husband, Thomas A. Steitz, Ph.D., Sterling Professor of Molecular Biophysics and Biochemistry, lies less in its double helix than in its base pairings. “That immediately said how DNA could be copied and how DNA could be copied into RNA. It laid the foundation for the understanding of the genetic code,” he said. New tools and techniques such as sequencing, cloning and recombinant DNA have been derived from the bases spiraling along the double helix. “It’s the first important structure in structural biology.”

The Steitzes started their three-year fellowships in Cambridge in 1967. Peter B. Moore, Ph.D., Sterling Professor of Chemistry and professor of molecular biophysics and biochemistry, had arrived earlier that year for an 18-month fellowship. In their last year in Cambridge, the Steitzes overlapped with Sidney Altman, Ph.D., Sterling Professor of Molecular, Cellular, and Developmental Biology and professor of chemistry. (In 1989 Altman shared the Nobel Prize in Chemistry with Thomas R. Cech, Ph.D., for their work on the catalytic properties of RNA.)

“Of course, the lab itself was such an amazing place to work,” Altman said at the celebration. “The ideas generated whizzed around the lab, many not useful, but when one was, it was recognized as such and shone brilliantly. … You were expected to work more or less alone with no immediate help from senior people. The assumption was that everybody could do experiments well. The senior people taught by example: everybody was in the lab working.”

The invigorating atmosphere, said Thomas Steitz, extended to the canteen, where seating was limited and postdocs shared tables with Crick or Max F. Perutz, Ph.D., a 1962 Nobel laureate, Frederick Sanger, Ph.D., who won two Nobel Prizes, or Sydney Brenner, Ph.D., a 2002 Nobel laureate. The conversation, Steitz said, was “always science. You wouldn’t talk about what you saw at the theater.”

“At the time we were there Sanger was just able to sequence small RNA molecules, which was a significant advance,” Moore said. The scientists, fellows and postdocs there, he said, were encouraged to continue that tradition of discovery and tackle the most challenging problems. “What the MRC was always masterfully good at was making sure that most of its people were working most of the time on things that really counted,” he said. “It was the best 18 months of my scientific career. It was a wonderful place to do science.”