Reactions

More on 'Top Pharmaceuticals'

I always enjoy C&EN's special issues, and "Top Pharmaceuticals" is no exception (C&EN, June 20). Last February, I became one of the approximately 27 million Americans who take thyroxine (T₄, or tetraiodothyronine), one of the 46 drugs featured in the issue (page 128). Before I started taking the drug, I jumped headfirst into the medical literature, not because I was a chemistry professor working on a research project, but because I was feeling ill and needed some answers. I was eventually diagnosed with Hashimoto's autoimmune thyroiditis, a disease that is mentioned in your profile.

Although I thoroughly enjoyed reading the story of thyroxine, I was disappointed to see that you quoted an endocrinologist who dismissed the use of T₃ (triiodothyronine)--another key thyroid hormone, which as your article states, is much more potent than T₄. The statement by Jeffrey R. Garber, chief of endocrinology at Harvard Vanguard Medical Associates, that "most of the studies have not panned out" has no scientific ground. There is significant evidence--both in the form of sound scientific double-blind studies reported in reputable medical journals and in patient testimonies--that demonstrates how successful T₃, along with T₄, has been in the treatment of hypothyroidism. Some studies even discuss T₃'s potential use in treating asthma and depression.

The T₄/T₃ story has been told, but it seems to have been missed by many. Perhaps this is a case of medical researchers getting ahead of practicing doctors. As Benjamin Franklin said a long time ago, "You will observe with concern how long a useful truth may be known, and exist, before it is generally received and practiced on."

I hope to someday open an issue of C&EN to find T₃--made by Jones Pharma and sold under the name Cytomel--featured as a key pharmaceutical for the treatment of hypothyroidism. The use of T₃ has changed many lives, including my own.

Cindy Samet
Carlisle, Pa.

The special issue on pharmaceuticals is, like the past issue devoted to chemical elements (C&EN, Sept. 8, 2003), a marvelous gift. As a chemist teaching the organic chemistry of drugs, most compounds and their stories are familiar to me. There are some relevant omissions, but one can certainly say that the mentioned drugs changed the world. I would like to add a few anecdotes that illustrate both serendipity and the role of events outside academia in drug discovery.

One article says that phenobarbital and barbiturates were named by Johann Friedrich Wilhelm Adolf von Baeyer after St. Barbara, patron saint of artillerymen (page 98). There are actually both romantic and nonromantic explanations for the naming, as von Baeyer never revealed what the prefix "barb" meant. Perhaps the German chemist courted a lady named Barbara. Nonromantics prefer other hypotheses: The substance was prepared on or just before St. Barbara's Day (Dec. 4), or it is a key substance--"the beard of a key" (in German, Schluesselbart). Barba is the Latin word for beard, and the suffix "uric" suggests the close structural similarity with uric acid.

The essay on prontosil is obscure in clarifying why Bayer launched the drug, speculating that the company wanted to have the patent first (page 102). Even if this were true, Bayer was reluctant to get prontosil into the market, although Gerhard Domagk had successfully demonstrated protection against Streptococcus in mice. In late 1935, Domagk's daughter cut her hand and was about to die of an infection. Her father gave her prontosil and she recovered rapidly, which gave credibility to the drug.

Finally, the story on thalidomide is rather incomplete (page 122). There is no doubt that Frances Kelsey deserves credit and admiration. As the Food & Drug Administration's reviewer, she most likely prevented a major disaster by refusing to approve thalidomide without further testing of side effects, despite the massive pressure on the agency by the chemical industry. However, the first person who recognized and published a rigorous study (Deut. Med. Wochens. Stuttgart 1962, 87, 1232) on the damage caused by thalidomide was German geneticist Widukind Lenz (1919-95). A few months earlier, Australian gynecologist William G. McBride also suggested the danger in a letter submitted to Lancet (1961, 2, 1358). The German pharmaceutical company Chemie Gruenenthal continued to deny teratogenic effects of the drug for years.

Pedro Cintas
Badajoz, Spain

C&EN should give due credit to chemists. Regarding your article on RU-486 (page 112), Emile Baulieu deserves credit for pushing the introduction of this drug. However, contrary to the caption under Baulieu's picture, he did not synthesize the compound. That honor goes to Georges Teutsch, as shown by the initial patents in this field. In addition, Teutsch's methodology for introducing 11-ß substituents into steroids not only made the synthesis of RU-486 feasible but also has been used extensively by other workers in the field (Tetrahedron Lett. 1979, 22, 2051).

In spite of this omission, the entire issue was most interesting.

C. Edgar Cook
Staunton, Va.

It may seem boorish for me to submit a correction on the story on oral contraceptives, when the article treated me almost hagiographically (page 92). But the statement "In the 1930s, Russell Marker of Pennsylvania State University found that, for hundreds of years, Mexican women had been eating wild yams of the Dioscorea genus for contraception, apparently successfully" cannot be left unchallenged.

I suspect that Marker is turning over in his grave over that statement. The saponins in these wild Mexican yams were indeed Marker's starting materials for his famous progesterone synthesis, but not because of any putative contraceptive use. Their soaplike and hemolytic properties were the reason for their use by the Mexican indigenous population for washing laundry and for killing fish. Their use for contraception is a fairy tale, which, if true, would surely have dramatically raised the mortality rate among those women. This may hardly be the type of birth control the article wished to cover.

Carl Djerassi
Stanford, Calif.

Serious thoughts on energy

You wrote, in "Get Serious About Energy," "the distinctive nuclear power station cooling tower, with its ever-present plume of steam rising above it, does not inspire dread in the French" (C&EN, Aug. 1, page 5). Oops. The hyperbolic cooling towers are standard on all European power stations, nuclear and nonnuclear, except those cooled by the sea and rivers.They have been standard for close to a century. We had them in the first British power station, where I started work in 1946.

The water temperature entering the cooling towers is about 140 °F and is cooled by the natural updraft of air (and evaporation). I have walked inside towers when on low load. The visible emission from the top of the hyperbolic cooling towers is not steam; steam is invisible.

My first physics homework (and yours?) in junior high school was to observe a boiling tea kettle and note the one-inch gap at the spout (steam) and then the condensed water droplets ("water vapor") that were visible. Second, the water temperature never reaches anywhere near 212 °F.

Because much, but not all, of the power produced in France is nuclear, the hyperbolic cooling towers you saw could well have been regular power plants, or even similar cooling towers used in industry.

Kenneth Hooton
Sierra Vista, Ariz.

Most analyses show that it will be impossible to increase energy-use efficiency or harvest sufficient renewable sources to fill current demands for energy. Experience with dams shows that extensive harvesting of renewable sources can cause severe environmental damage. Sequestered carbon dioxide from coal and stored high-level fission products from uranium reactors present implacable challenges for our descendents. This leaves us with fusion as the energy source for the future.

The International Thermonuclear Experimental Reactor (ITER) will be located at Cadarache, France; finally, after 13 years of procrastination, there will be action. This is good news. Raymond L. Orbach of the U.S. Department of Energy said recently that the reactor might lead to a power plant in the year 2040. This is bad news. The 35-year estimate comes from a veiled but powerful resistance to fusion from the DOE fission community, coal research groups, and the established fossil fuel industries.

To rebut Orbach's schedule, see the 1976 Energy Research & Development Agency (ERDA) report "Fusion Power by Magnetic Confinement." This report states that fusion could have been achieved in 10 to 13 years with a "maximum effective effort."

The world badly needs a maximum effective effort program to develop carbon-free energy sources. With 29 years of further research (after the ERDA report), the demonstration of positive thermonuclear energy generation in 1992, and our enormous improvement in computational analysis capabilities, a prediction of success in a decade seems reasonable.

Three actions are necessary to achieve fusion in a decade: One, make it clear that the ITER schedule of 35 years is extraordinarily unsatisfactory. Current plans have ITER built at half-scale to save money. This only increases the probability of failure. Insist that ITER be built as originally designed. Two, across the world, terminate clean-coal initiatives and dangerous fission programs. Use the funds recovered to support efficiency improvements and the development of renewable and fusion energy sources. Three, recruit a Pacific Rim group to start other maximum effective effort designs and fusion fuels.

A maximum effective effort started today, coupled with competition, will lead to the introduction of utility fusion reactors in about 2015. Then we can begin the process of abolishing carbon dioxide emissions and saving fossil fuel chemicals for higher value uses. Fusion sources will also provide a means for all nations of the world to achieve energy independence without concern for weapons proliferation.

Laurence O. Williams
Alliance, Ohio

A flat hypothesis

I enjoyed Rick Mullin's review of Thomas Friedman's book "The World Is Flat" (C&EN, July 11, page 40). But for me, the content of the book is diminished by the metaphor Friedman chose: Christopher Columbus and the flat Earth.

If Friedman is bright enough to reshape our view of history, then he should know that no educated person in the past two millennia believed Earth was flat. Friedman repeats a common, but unfounded, myth just for the sake of illustrating his point, and he repeats it three times in his first six pages, as if there were a quiz at the end of the chapter. If he had reread his freshman copy of Dante's "Commedia" (circa 1300), he would have seen clear references to a globe, because Earth was known to be round by all who could read. Columbus may have estimated the size of Earth to be smaller than it actually is, but he did not say it was a flat disk. (He could even have been doing some fudging to get public money for his research--a very modern sentiment.)

Using Columbus, Friedman asserts that the world began to shrink starting in 1492. He seems to have missed the collective yawn that the discovery of the Americas evoked in Europe for the following 200 years. Neither Shakespeare nor any other leading author of the 16th and 17th centuries writes about America, because, 100 years after its discovery, America mattered nothing to life in Europe. America was just wilderness and a disappointment, because Europe's voyages of discovery were about finding civilization. Advances in thought, particularly in experimental science, and the invention of printing a few decades before Columbus' voyage led to the beginnings of the prosperity which "flattened" the world, not the discovery of a refuge for religious dissenters.

Neil Gussman
Philadelphia