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Friday, November 23, 2012

McClintock, Maize, and Modern Genetics

At last, Thanksgiving break has arrived! I have a moment to breath, to eat lots of turkey, and to write a proper post.

The semester is fast drawing to a close. Following Thanksgiving, we have two weeks of classes left at Avila University, and then final exams. For my course Women and Science, the last two weeks will be filled with student presentations, each one devoted to a particular woman scientist.  This is one of my favorite parts of the semester, as it renews my appreciation of the many contributions of women to science throughout history. Also, I invariably learn about someone whose story I have not yet heard.

While the students are putting their final touches on their end-of-semester reports, I want to take some time on my blog to talk about Nobel prize laureate Barbara McClintock, the woman who discovered transposons, otherwise known as jumping genes.

McClintock's story is told in a couple different biographies, including A Feeling for the Organism by Evelyn Fox Keller. 

She was born in 1902 in Hartford, Connecticut, and attended Cornell University at a time when enrollment by women in U.S. universities was on the rise. (This trend was shut down during the 1950s, only to pick up again with the women's movement of the 1960s and 1970s.)  Even though McClintock was not entirely unique in her desire to earn a college degree, her mother was opposed to the idea because she feared it would make her daughter unmarriageable.  (As it turned out, McClintock did not, in fact, ever marry...)

There are a lot of remarkable moments in McClintock's long and illustrious career.  One of these was the difficulty she had finding a job after earning her PhD at Cornell.  Even though she was greatly respected by leading geneticists of the time, no university seemed to have a place for her. 

McClintock did the best she could under the circumstances, accepting temporary positions until at last in 1941 (fourteen years after finishing her degree), she was offered a research position at Cold Spring Harbor Laboratory.  Cold Spring Harbor would be McClintock's home for the rest of her career, and it was here that she completed the work that earned her the Nobel Prize. 

Her study organism was maize -- another factor that set her apart, because at the time, the biology of maize was considered more relevant to agronomists than to "serious" geneticists.  McClintock, however, did not let this prejudice stop her.  Her experiments combined controlled breeding with careful documentation of the behavior of chromosomes during cell division. 

By monitoring the appearance, position, and size of dark patches on kernels of known parentage, she was able to determine that something internal to the cell was controlling the rate of mutation in maize.  This discovery ran counter to everything that was known and believed about chromosomes at the time.  Mutation was supposed to be a random event, and chromosomes were supposed to be in control of the cell, not vice-versa. 

As McClintock dug deeper into the evidence, she discovered something even more amazing:  The elements that controlled the rate of mutation were actually part of the chromosome itself.  Moreover, these elements could move!  They could physically dissociate from one part of the chromosome and insert themselves into another part.  Wherever these elements inserted themselves, the adjacent functional genes would be turned off.

In the summer of 1951, Barbara McClintock presented her conclusions -- supported by volumes of data gathered over the course of six years -- at the annual symposium at Cold Spring Harbor Laboratory.  The response of her colleagues was, in McClintock's own words, "puzzlement, even hostility".  The academic community was unwilling to accept these astonishing results. Within a couple years McClintock, realizing she was beginning to alienate the scientific mainstream, stopped talking about her data and its paradigm-shattering implications. She turned instead to other research questions, such as the evolutionary origin of maize, to which she also made important contributions.

Almost a decade later, in 1961, Francois Jacob and Jacques Monod described the regulation of a set of genes called the lac operon in bacteria.  McClintock was quick to recognize the similarities between their discovery and hers, and published a paper in the American Naturalist comparing the lac operon to the controlling elements she had discovered in maize. 

These parallel discoveries paved the way to wider acceptance of the existence of mobile controlling elements within the genome, and as time went on it was recognized that McClintock's data and her interpretation were not abberations, but representative of a widespread and important phenomenon in genetics. In 1983, McClintock was awarded the Nobel Prize for her discovery of transposons.

Barbara McClintock is an excellent example of a woman who made fundamentally important contributions to science, and who received due recognition for those contributions. Nonetheless, many scholars argue that her career was plagued by gender discrimination, noting for example the difficulty she had finding a faculty position. 

The mysterious lag time between when McClintock presented her results in 1951, and when they were finally recognized as valid more than 10 years later, is also a point of emphasis for many feminists.  Was her work ignored for so long because it threatened the dominant paradigm?  Or was it ignored because she was a woman?

McClintock's biographers tend to come down on one side or the other of this debate.  Personally, I suspect both gender discrimation and the inertia imposed by scientific paradigm were at play.   

Barbara McClintock never believed she was subject to discrimination on the basis of her gender at any point in her career.  Regarding the initial unwillingness of the scientific community to accept her findings, she wrote in 1973:

Over the years I have found that it is difficult if not impossible to bring to consciousness of another person the nature of his tacit assumptions when, by some special experiences, I have been made aware of them. This became painfully evident to me in my attempts during the 1950s to convince geneticists that the action of genes had to be and was controlled. It is now equally painful to recognize the fixity of assumptions that many persons hold on the nature of controlling elements in maize and the manners of their operation. One must await the right time for conceptual change.

From McClintock's point of view, it would not have mattered whether she was a woman or a man. At the time she presented her results, there was simply a reluctance among geneticists to accept data that undermined their basic assumptions about how DNA worked, and whether DNA could be subject to deliberate control mechanisms imposed by the cell.  It was a matter of waiting until the scientific community was ready for the next conceptual revolution. 

So she waited. Fortunately, Barbara McClintock was still around to enjoy the moment when the rest of the scientific world caught up with her.

McClintock's microscope and ears of maize on
display at the Museum of Natural History.