Controlling Elements: Cold Spring Harbor, 1942-1967

In 1942, McClintock's one-year position in the Department of Genetics at Cold Spring Harbor became that of a full-time researcher. This simple act changed the course of her life and career. The Cold Spring Harbor position gave McClintock the freedom to pursue her own research without the obligations of teaching or constantly applying for outside funds. The extensive resources of the institution provided her with land on which to cultivate maize. McClintock's position at Cold Spring Harbor also enabled her to avoid much of the scrutiny often imposed upon women scientists. She was free to do as she pleased.

McClintock knew that she was in an uncommon situation; as she wrote to Curt Stern in 1947, some young women in science "grasp at any small bit of evidence that will help maintain their morale... If I ever have a chance to talk with such girls, I can usually help overcome some of their frustrations by being realistic about women in professions." McClintock's status as role model of such women was significant enough that, in April 1947, the American Association of University Women gave her an award. "The award ceremony "was unexpectedly pleasant," McClintock recalled afterward. "It was the handsomest group of women I have ever seen--handsome as only intelligent, middle-age women can be."

At Cold Spring Harbor, McClintock continued her work with the breakage-fusion-bridge cycle, using it as a substitute for X-rays as a tool for mapping new genes. An experiment she performed in the summer of 1944 changed her research focus radically and permanently. Among the plants she grew that summer, she found two new genetic loci that she named "Dissociator" (Ds) and "Activator" (Ac). Contrary to its name, Dissociator did not merely dissociate, or break, the chromosome. It turned out to have a variety of effects on neighboring genes, but only when Activator was also present. In early 1948, she made the surprising discovery that both Dissociator and Activator could transpose, or change position on the chromosome. These were not ordinary genes--in fact, to McClintock, they were not genes at all, they were gene controllers. Between 1948 and 1950, she developed a theory by which these movable elements regulated the genes by selectively inhibiting or modulating their action. She referred to Dissociator and Activator as "controlling units"--later, as "controlling elements"--in order to distinguish them from genes. She believed that controlling elements were the answer to the decades-old problem of development: how complex organisms could develop many different kinds of cells and tissues when each cell in the organism had the same set of genes. The answer was in the regulation of those genes.

Despite these provocative new theories, McClintock was acutely aware that her work departed from the common wisdom that genetic material was static and unchanging as it passed from one generation to another. In McClintock's theory of controlling elements, genetic material in chromosomes was anything but constant. As she told Charles Burnham in January 1950, "You can see why I have not dared publish an account of this story. There is so much that is completely new and the implications are so suggestive of an altered concept of gene mutation that I have not wanted to make any statements until the evidence was conclusive enough to make me confident of the validity of the concepts."

Whether or not McClintock's proposal for a system of controlling elements in maize was applicable to genetic systems in other species was a different matter. This was the great question, one that would continue to propel her research. In summer 1951, she reported on her work on gene mutability in maize at the annual symposium at Cold Spring Harbor. By the time of this meeting, her work on the transposition of maize genes, the moving of genetic material from one part of a chromosome to another, had been confirmed by researchers Royal Alexander Brink and Robert A. Nilan of the University of Wisconsin. That discovery was not her focus; McClintock used most of her talk to discuss her ideas of controlling elements as gene regulators. According to popular stories that have circulated about the symposium, the scientists treated McClintock's theories with indifference. As historian Evelyn Fox Keller has written, McClintock's work was greeted with "stony silence." Yet such interpretations of this historic symposium might be unwarranted, according to those who were there. As Nobel Laureate Joshua Lederberg wrote in 1983, "Barbara McClintock would not have been invited to the 1951 symposium unless the organizers had some glimmer of the importance of her work." Furthermore, perhaps historians have confused professional recognition of McClintock's role in genetics, which had been steady since the early 1930s, with an almost complete lack of public recognition. "Between 'stony silence' and 'instant appreciation,'" Lederberg argued, "is the reality of how to integrate the startling evidence she presented into a coherent scheme. That was hardly possible before...the science of molecular biology caught up with [McClintock]. Perhaps some of the biochemists in the 50s were not well versed in maize genetics and it is their voices [we] hear."

McClintock remained unfazed by her critics, whether real or imagined. She continued to do her own work, conducting her research according to her own methods and reaching her own conclusions. In 1967, she announced her formal retirement from the Carnegie Institution and was awarded with its Distinguished Service Award. At age 65, she nonetheless elected to stay on in the Cold Spring Laboratory as scientist emerita. At this juncture in her career McClintock summarized her life's work and the prospect for its fulfillment in a letter to a colleague, "[W]e are sadly ignorant of the organization of the chromosome and of the possible types of changes in this that may occur to the chromosome as a whole or at the locus level. We are beginning to learn of some types of change and these are producing surprises. I am convinced that we should expect some startling surprises in the future."