James D. Watson - Career in Molecular Biology

Career in Molecular Biology

Originally, Watson was drawn into molecular biology by the work of Salvador Luria. Luria eventually shared a Nobel Prize for his work on the Luria-Delbrück experiment, which concerned the nature of genetic mutations. Luria was part of a distributed group of researchers who were making use of the viruses that infect bacteria, called bacteriophages. Luria and Max Delbrück were among the leaders of this new "Phage Group", an important movement of geneticists from experimental systems such as Drosophila towards microbial genetics. Early 1948, Watson began his PhD research in Luria's laboratory at Indiana University. That spring he met Delbrück first in Luria's apartment and again that summer during Watson's first trip to the Cold Spring Harbor Laboratory (CSHL).

The Phage Group was the intellectual medium where Watson became a working scientist. Importantly, the members of the Phage Group sensed that they were on the path to discovering the physical nature of the gene. In 1949 Watson took a course with Felix Haurowitz that included the conventional view of that time: that genes were proteins and able to replicate themselves. The other major molecular component of chromosomes, DNA, was widely considered to be a "stupid tetranucleotide", serving only a structural role to support the proteins. However, even at this early time, Watson, under the influence of the Phage Group, was aware of the Avery-MacLeod-McCarty experiment, which suggested that DNA was the genetic molecule. Watson's research project involved using X-rays to inactivate bacterial viruses. He gained his PhD in Zoology at Indiana University in 1950 (at age 22).

Watson then went to Copenhagen University in September 1950 for a year of postdoctoral research, first heading to the laboratory of biochemist Herman Kalckar. Kalckar was interested in the enzymatic synthesis of nucleic acids, and he wanted to use phages as an experimental system. Watson, however, wanted to explore the structure of DNA, and his interests did not coincide with Kalckar's. After working part of the year with Kalcker, Watson spent the remainder of his time in Copenhagen conducting experiments with microbial physiologist Ole Maaloe, then a member of the Phage Group.

The experiments, which Watson had learned of during the previous summer's Cold Spring Harbor phage conference, included the use of radioactive phosphate as a tracer to determine which molecular components of phage particles actually infect the target bacteria during viral infection. The intention was to determine whether protein or DNA was the genetic material, but upon consultation with Max Delbrück, they determined that their results were inconclusive and could not specifically identify the newly labeled molecules as DNA. Watson never developed a constructive interaction with Kalckar, but he did accompany Kalckar to a meeting in Italy where Watson saw Maurice Wilkins talk about his X-ray diffraction data for DNA. Watson was now certain that DNA had a definite molecular structure that could be elucidated.

In 1951, the chemist Linus Pauling in California published his model of the amino acid alpha helix, a result that grew out of Pauling's efforts in X-ray crystallography and molecular model building. After obtaining some results from his phage and other experimental research conducted at Indiana University, Statens Serum Institut (Denmark), Cold Spring Harbor Laboratory, and the California Institute of Technology, Watson now had the desire to learn to perform X-ray diffraction experiments so that he could work to determine the structure of DNA. That summer, Luria met John Kendrew, and he arranged for a new postdoctoral research project for Watson in England.