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January 10, 2005 | A version of this story appeared in Volume 83, Issue 2

Teaching a lesson

Amanda Yarnell's story about Howard Hughes Medical Institute's Janelia Farm reports that the facility's director, Gerald Rubin, sees the enterprise as part of HHMI's mission "to free creative scientists from the constraints that limit their ability to do groundbreaking research" (C&EN, Oct. 11, 2004, page 46).

The story notes in particular that to reach that end, researchers will not be "burdened" with teaching responsibilities. I find this perspective disturbing, particularly for an organization that has demonstrated a rich history of support for education. I have no doubt that what was meant by "burden" was traditional, formal classroom instruction. But such infelicitous language runs the risk of demeaning and minimizing the commitment of those who indeed dedicate themselves to the classroom.

Furthermore, HHMI surely recognizes that even those scientists whose primary activity is the creation of new knowledge have a larger educational responsibility that goes beyond the traditional classroom: to their colleagues and certainly to their graduate students and postdoctoral associates. Most important, given the intellectual strength anticipated to converge at Janelia Farm, the researchers have a responsibility for communication to the larger public. Not to recognize that responsibility as education would be a missed opportunity of extraordinary proportions, especially in a societal environment that is rapidly growing increasingly antiscience.

And it would be nice to see some undergraduates and high school teachers in those labs too.

Robert L. Lichter
Atlanta, GA

Crystal unclear

I would like to point out that Stu Borman's interesting synopsis of Nicholas A. Meanwell and Mark Krystal's RSV inhibitor quotes George Fu Gao as saying that "we would need a clear crystal structure to show the real binding mode" (C&EN, Nov. 1, 2004, page 30).

This kind of generalization is frequently made despite the knowledge that crystal structures are subject to structural perturbations compared to solution even when obtained at the best resolution, as pointed out previously in C&EN (April 5, 2004, page 56). In fact, I draw your attention to two publications with which I am familiar that illustrate this point and the value of photoaffinity labeling clearly for another viral protein-protein interaction inhibitor: Analytical Chemistry [76, 2095 (2004)] and Biological Chemistry [279, 6976 (2004)]. Nonspecific cross-linking is a concern in conducting photoaffinity labeling experiments, but the method has been successful in detecting covalently modified products that correlate with the binding site region by other structure methods, including crystallography.

Graham A. McGibbon
Hamilton, Ontario


Gao responds: "I do not know the biology until I see it." This is something that late structural biologist Don C. Wiley, one of my mentors at Harvard University, used to say. Seeing how proteins interact with their partners is a crucial step for our understanding of true biology. To see protein-protein or protein--small-molecule interactions, it is generally accepted that obtaining a structure of the complex is the best way, though other methods can help provide a better explanation of the structural data. To date, X-ray crystallography is the best method for reliable complex structures. Therefore, the crystal structure of the complex would be better for a "final observation" of the binding mode, in addition to the photoaffinity labeling used by Meanwell, Krystal, and coworkers. We do believe their work is a breakthrough for the field, but the complex structure would help us "see" the real binding.

In support of NIH's road map

I was disappointed to read that some leaders of the academic chemistry community object to the National Institutes of Health's road map initiative (C&EN, Nov. 8, 2004, page 40; Nov. 29, 2004, page 3). Since we all agree that the translation of scientific discoveries into improved public health is a good thing, the issue is presumably whether the creation of this new program will facilitate achievement of that goal.

Unlike the untested road map initiative, NIH's traditional approach has proven to be inefficient. The gap between what we know about human biology and what we can offer patients has never been larger. Despite huge increases in NIH's budget over the past decade, the rate of introduction of novel medicines has been decreasing steadily, and the future looks even bleaker.

We must ask ourselves why these increases are not proportionately improving public health. Remember that NIH funding is a gift from taxpayers, based on their expectation that biomedical research will improve their lives and the lives of their children. It is our responsibility to optimize the collective progress, even if it means that our scientific independence is compromised.

Collaboration is required to solve most of the really tough medical problems. Therefore, the current system, which centers on single investigator-initiated grants, must be balanced by programs like the road map that promote a collaborative model. Academic chemistry has traditionally fostered huge research groups under the direction of a single senior investigator. These groups are often intellectually isolated, even from other groups in the same department. A little bit of "top-down" direction from NIH is necessary to ensure that self-serving behavior is not hindering collective progress and to focus public resources on important and difficult problems while eliminating redundancies. It is unreasonable to expect that such changes could ever arise from a system in which the researchers themselves are setting the priorities. (Evaluating the quality of the science should be their sole function.)

The reputation and influence of chemistry, which has diminished over the past 20 years as NIH funding has grown, could be greatly enhanced by embracing the movement toward translational biomedical science. The conversion of biological discoveries into products requires chemistry, whether it be to synthesize an enzyme inhibitor or targeted imaging agent or to create a surface that allows for sensitive protein detection in blood. I hope that the field will seize this opportunity to develop programs of its own based on the principles of the road map initiative.

Imagine the chemistry department at the University of California, Berkeley, or the University of Wisconsin devoting 10% of its resources to a collaborative, department-wide effort to develop new therapeutics for global threats such as malaria or tuberculosis. Such an effort would not compromise any educational mission and would likely result in significant scientific progress. I hope that most academic chemists will not be threatened by the road map initiative but will see it for what it can be: a golden opportunity to demonstrate the value of chemical research.

Peter T. Lansbury Jr.
Cambridge, Mass.

Number gap

It is regrettable that not even reports in scientific magazines make a clear distinction between "cause and effect" and "correlation." C&EN shows tables that correlate various U.S. presidential Administrations with employment changes and payroll changes, and you conclude in the subtitle that "Democrats have the edge in creating jobs" (C&EN, Nov. 1, 2004, page 42).

Where is the rationale in that conclusion? Do the swaying trees produce the wind? Do hospitals create all the deaths occurring in them? Isn't it industry that creates jobs? What is the voters' role in that correlation? Do voters "create" or "respond" to changes in the economy? This is data dredging at its worst. Correlations are only good to formulate a hypothesis. One would need to do an experiment to actually show cause and effect or have some knowledge from outside the correlation study to delineate cause and effect.

Harald W. Ade
Raleigh, N.C.

Benefits of a lighter touch

I could not be more in disagreement with the opinions expressed by Hans Schott in the letter "Too clever for our own good" (C&EN, Nov. 15, 2004, page 5). I have been receiving C&EN for more than 40 years. Initially it wasn't even worth bothering to open up unless I was looking for some facts and figures regarding the chemical or chemical engineering industry. But through the years that has changed, and today I at least skim every single page. There is plenty of meat in C&EN, but the light-hearted approach and such features as "What's that stuff?" make reading it much more enjoyable.

Chemistry needs more humor, not less. One of my favorite recollections was being in the front row as the late Hubert Alyea of Princeton University gave a presentation. How could anyone not be fascinated by chemistry after watching and hearing Alyea sing the Princeton fight song as, in perfect time, colors changed in a beaker? Alyea also had a burner going on the lab bench in front of him. On the bench were several Coke bottles wrapped in tape. Before his talk, he had filled them with a mixture of hydrogen and oxygen.

At totally unpredictable intervals, he would quickly grab a bottle, pull off the cork, and hold the end to the flame. We would all jump at the ensuing loud bang, but after he had done this several times during his talk, we were like proverbial Pavlovian dogs. Then he grabbed a Coke bottle that had no cork in it and quickly held it to the flame. Although we had all tensed in preparation for the loud bang, of course nothing happened, and he explained why. Would I remember that today if the fundamental principles had instead been told in a dull, pedantic manner?

It has been my experience that the most brilliant scientific minds have both a passion for their science and a finely developed sense of humor. So keep the humor in C&EN, and maybe some stereotyping about chemistry will change.

Bob Blackledge
San Diego, CA

Startled stupefaction was my initial reaction to Schott's letter complaining that C&EN uses alliteration and other devices to lighten its fare. This was followed by consternation and concern that one loses one's sense of humor with age. I seem to be in good shape at 83, but I am concerned that the letter I am referring to was a send-up, and that I missed the joke.

Marshall E. Deutsch
Sudbury, Mass.


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