Nuclear Weapons

A Hindsights by Michael Heylin contrasted recommendations from the Defense Science Board (DSB) on the future nuclear weapons stockpile with selected parts of a survey done by the Program on International Policy Attitudes (PIPA) (C&EN, May 10, page 36).

DSB recommended that the future U.S. stockpile be modified, with research as necessary, to meet anticipated defense needs. On the other hand, the PIPA survey suggested that, instead of nuclear weapons, the U.S. should rely on "international cooperation and arms control agreements" and accelerated implementation of "the Nuclear Nonproliferation Treaty (NPT) ... to work toward the eventual elimination of nuclear weapons stockpiles, including its own."

The article states as a background fact that "the search for security through new nuclear weapons could well become the impossible nightmare." It is important to remember that our nuclear weapons were a significant contributor to winning the Cold War with the former Soviet Union. They continue to be an important contributor to maintaining a balance of power among nuclear nations and a potential deterrent to others.

Further evidence of the article's left-leaning nature is the statement, "As has been demonstrated in Iraq, even a false alarm over nonexistent nuclear weapons can play a critical role in starting a war." Prior to the war, Iraq had a program to develop nuclear weapons. The program was not "nonexistent," nor was it a "false alarm."

It is naive to believe that the cause of international peace and liberty would be best served if the U.S. abandoned its nuclear weapons stockpile and relied instead on agreements that many nations have not signed. For the foreseeable future, a policy that combines both the pursuit of such agreements with other nations and the maintenance of a stockpile is essential for our national security.

J. Malvyn (Mal) McKibben
Aiken, S.C.

Hats off to you for your willingness to tackle a moral question in C&EN that, though not technical in nature, deserves to be considered by thoughtful persons who seek the welfare of the world beyond the technical issues that, while they have a legitimate place in our deliberations, carry little interest for most of the world's citizens.

I refer to Heylin's Hindsights piece regarding the debate over whether to build more nuclear weapons or work toward their elimination. Much of the moral high ground that not long ago was a position the U.S. shared with other nations in the free world is now recognized as having been sacrificed for shortsighted policies of military domination. One only needs to witness the falling away of most of our former allies over our unwise instigation of a war in Iraq that had nothing to do with 9/11.

Allow me to register my convictions with those who see the fallacy of the arms race and the 84% of respondents to the PIPA survey who urge the U.S. to agree to work toward eliminating nuclear weapons as part of the NPT. It may be, as your Hindsights says, "an impossible dream," but I would rather be counted as a dreamer than a participant in a nightmare.

Ernest G. Barr
Carmel, Ind.

All tied up

The question of how the protein synthesis equipment of a cell can "tie" a continuous peptide chain into a knot is a fascinating one. "Tying Up Loose Ends" by Stu Borman concentrates on circular and knotted shorter peptides and has missed an emerging class of proteins with deep trefoil knots that resemble a classic overhand knot tied in the protein chain (C&EN, April 19, page 40). An example of the knotted methyltransferases, tRNA methyltransferase [J. Mol. Biol., 333, 931 (2003)], incorporates a knot in which more than 100 residues of the C-terminus have apparently passed through the knotting loop. This knot feature forms a stable platform for cofactor binding and appears to be a critical part of the structure of these enzymes.

The strange and interesting thing about these methyltransferase knots is that the knotted methyltransferase core fold is strongly related to a basic protein fold, the Rossmann fold, which consists of a core sheet flanked by layers of helices. In the case of the knotted methyltransferases, however, the knot is not made as an overhand knot addition to a preformed structure; the knot is actually an integral part of the core sheet and is formed by three of the strands in the five-strand sheet. With the increasing number of crystal structures coming out of worldwide structural genomics consortiums, it is likely that more knotted proteins will turn up to delight and confound structural and mathematical biologists alike.

Patricia Elkins
King of Prussia, Pa.

NO mysteries

In a recent article discussing peroxynitrite biochemistry, Elizabeth Wilson writes that peroxynitrite has generally been promoted as a toxic species that mediates tissue injury (C&EN, March 8, page 39). But other reports suggest peroxynitrite production thwarts formation of other more potent oxidants, facilitating protection from oxidative stress.

Wilson's story implies that our group believes changes in the flux of NO/O₂^– preclude peroxynitrite formation in biological systems. We have maintained that peroxynitrite can be and probably is formed in biological situations, but the secondary reaction between peroxynitrite-derived oxidants substantially limits the direct chemical interactions of peroxynitrite. In fact, the kinetic simulations of Jack R. Lancaster described by Wilson were based on our previous work in vitro and within cells, and verify the supposition that NO and O₂^– scavenge reactive species derived from ONOO^– and do not prevent peroxynitrite formation.

The issue of NO/O₂^– flux and its conversion between oxidative and nitrosative chemistry may have very important biological consequences beyond mere toxicity, including the regulation of tissue function. This chemistry provides an elegant way to regulate the redox chemistry on the cellular and tissue level. The new challenge is to decipher these subtle yet important redox relationships, identify the molecular targets of each redox species, and learn to fine-tune the balance for the desired outcome.

David A. Wink and Michael G. Espey
Bethesda, Md.

Losing the R&D edge

David Hanson's report on the American Association for the Advancement of Science policy meeting (C&EN, May 3, page 23) appeared essentially simultaneously with William J. Broad's long article in the New York Times reporting that the U.S. is no longer the leader in most of science and technology. From those of us who work in the trenches, the response is surely: What took you so long to find out?

The powerful currents of unchecked market forces have irreparably destroyed the advantage that public and private investment in real science brought to the U.S. I cannot think of a single company in the U.S.--and hardly a federal agency, as even the Defense Advanced Research Projects Agency and the Office of Naval Research (ONR) become two-year development shops--to which we could sell even our most promising materials research discoveries.

The most worrying part of all such articles on the U.S.'s R&D status is the gross oversimplification that the total dollar amount spent on R&D is the measure of R&D effectiveness. Nothing could be further from the truth. We forget that the Soviet Union was the most lopsidedly R&D generous country in the world. So? It is more important to focus on what kind of research and how you find it. Paul G. Gaffney II, former chief of naval research, ascribes the success of ONR--probably the nation's most effective research-supporting agency--to its support mainly of "use-inspired" or "application-driven" basic research and to ONR's 50-year tradition of not using peer review.

Unfortunately, as only President Dwight D. Eisenhower (among recent presidents) realized, academic science is as powerful and dangerous a lobby as the military-industrial complex. Why? Because both are outside the understanding of our representatives, camouflaged as they are in arcane jargon. C&EN should dig deeper than just money figures in reporting on the nation's research effectiveness.

Rustum Roy
University Park, Pa.

In bad taste

As chemists and ACS members both employed by the U.S. government, we find your little "joke" about Governmentium both distasteful and inappropriate for publication in a magazine from a professional society for chemists (C&EN, May 3, page 56).

Some of the top chemists in the world work in U.S. government laboratories, and many of them are ACS members. They perform their work very well, both producing excellent, world-renowned research and protecting the people of the U.S. through regulatory monitoring from a variety of threats to their food, water, air, and drugs they take. Government chemists often perform under adverse conditions, including budgets cut to the bone and substandard labs, for salaries considerably less than those available in private industry, while listening to the jibes and disdain of the typically ungrateful public. Despite this, they continue to accomplish their work out of a sense of loyalty and service to the people of the U.S. and their desire to make a positive difference for the country.

Again, government bashing, even as a joke, is offensive and unsuitable in a professional society's publication--most particularly when that society is supposed to represent all chemists, industry, government, and academia alike. Articles of this nature make us seriously reconsider our ACS membership.

Robert A. Gates and Judy Summers-Gates
Philadelphia