May 2012

In case you missed it

Important career lessons from Carolyn Cohen’s reflections on seeing and knowing in structural biology



 

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Carolyn Cohen begins her first Journal of Biological Chemistry “Reflections” article by stating a truth well known to those with years of experience but perhaps not fully appreciated by those starting out in their careers: “Chance often determines how a young person finds her calling.” While she was an undergraduate at Bryn Mawr College, what she thought was going to be just another summer ended up determining the direction of her career. Feeling hopeless after a waitressing job in a disagreeable environment, she called a college friend, who talked her into spending the rest of the summer at Woods Hole, Mass., and helped her find a summer job at the Marine Biological Laboratory. It was there that Cohen heard a lecture by the English crystallographer Dorothy Wrinch on the atomic structures of proteins. The lecture and what Cohen describes as “strikingly beautiful slides” made such a profound impression on her that she decided to work on the structure of proteins.

Cohen went on to graduate school at the Massachusetts Institute of Technology, where she studied under the mentorship of Richard Bear, a pioneer in the X-ray diffraction of fibrous proteins. From this beginning, she went on to pioneer the determination of the structure of proteins at the atomic level in motile systems such as muscle. Her work has built the experimental foundations and concepts that form the basis of our understanding of the structure and function of these proteins. Today, she is a professor emerita of biology at Brandeis University and a member of the National Academy of Sciences.

In her 2007 article, which she recently followed up with a supplement, Cohen reflects on the many relationships that have shaped her career. The college friend who introduced her to the MBL is one in a long list of friends who played pivotal roles in Cohen’s career. Matchmaking efforts by a close friend at Bryn Mawr resulted in a successful match; however, instead of a romantic relationship, Cohen and Don Caspar became collaborators, and eventually the two established a laboratory together at the Jimmy Fund (now part of the Dana-Farber Cancer Institute in Boston).

In the scientific research enterprise, theories are proposed and, after intense scrutiny, remain intact or are disproved. Cohen’s “Reflections” article is filled with many anecdotes highlighting this fact. In discussing the ambiguity involved in seeing and interpreting an image, she likens it to the Delphic oracle from Greek mythology whose riddles were interpreted rightly or wrongly by supplicants, sometimes with fatal results. The advantage in structural biology is that one risks only embarrassment. Drawing from the example of Hugh Huxley and Jean Hanson’s work that led them to the sliding-filament theory as a mechanism for muscle contraction, Cohen states that “trying to disprove one’s own ideas is a common strategy for how to do good science!”

Cohen’s “Reflections” highlights some of the ways research has changed over the years. In 1958, having identified the Lotmar-Picken substance, which was thought to be crystalline myosin, as the amino acid taurine, she published the finding in a one-paragraph, one-figure paper! She also describes a very different research-funding climate, stating that in the 1950s, “National Institutes of Health research grants were relatively easy to obtain.”

With respect to recent advances in genomics and the dramatic increase in the speed with which simple structures are determined using nuclear magnetic resonance and crystallographic methods, she cautions against assuming that “an understanding of structure leads to an understanding of function” and warns that “too much information, without adequate comprehension, may not really clarify general concepts.” She uses the sliding-filament theory of muscle contraction and the packing of icosahedral virus particles as examples of proposals that did not require atomic structures.

Throughout her original JBC “Reflections,” Cohen pays homage to mentors and collaborators. In the 2011 supplementary article, she focuses on those who involved in her early education. Chance played a big role in Cohen’s career, but it did not act alone; Louis Pasteur put it well when he said “Dans les champs de l’observation le hasard ne favorise que les esprits préparés,” or, “In the field of observation, chance only favors the prepared mind.”

Karen Muindi (Karen.Muindi@fda.hhs.gov) is a postdoctoral fellow at the U.S. Food and Drug Administration.


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