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Cholesterol Confusion

October 11, 2004 | A version of this story appeared in Volume 82, Issue 41

Cholesterol confusion

The "What's That Stuff?" article on margarine by Louisa Dalton is an example of "party line" reporting that does an injustice to the science involved (C&EN, Aug. 16, page 24). As an edible oil specialist for 45 years, with 30 years involved in the trans-fatty acid and health controversy, I was disturbed to find her total acceptance of the thesis that trans-fatty acids increase LDL and decrease HDL cholesterol. For a review of this controversy, see "Margarine Products in Health and Nutrition" [INFORM, 5, 914 (1994)]. For additional coverage, see "Trans-fatty Acids and Coronary Heart Disease Risk" [Am. J. Clin. Nutr., 62, 655S (1995)].

In addition to questionable clinical studies, a rash of epidemiological studies connecting hydrogenated fat intake to coronary heart disease, mainly from the Harvard group, have generated a lot of media hype. This is best countered by the powerful statements of A. R. Feinstein of Yale, who noted epidemiological hypotheses often are generated by "dredging of computerized data banks" without "statistical adjustments for results that can arise by chance" and that "results are accepted according to preconceived beliefs." His thoughts were that "we must insist on rigorous science, not advocacy" (C&EN, April 4, 1994, page 27).

In my opinion, the Food & Drug Administration posture on this ruling is determined more by misguided advocacy than by science. For the past dozen years, press releases, pressure from advocacy groups, and media attention, rather than science, have influenced the thinking in Washington, D.C., on this topic. The cold, hard scientific facts are that the influence of the mono-unsaturated trans-fatty acid isomers on LDL and HDL cholesterol has not been demonstrated clearly and scientifically. Every study to date has some confounding factors that can explain the results observed as related to factors other than the presence of trans isomers.

Thomas H. Applewhite
Austin, Texas

A question of ethics

As a 60-year member and one of the initiators (in 1999) of the effort to establish an ethics committee, I was appalled by the ACS Council's action in Philadelphia to "refer this proposal back to the Committee on Committees" without any meaningful discussion of its merits (C&EN, Sept. 27, page 41).

The council was probably unaware that most scientific societies in the U.S. have such committees and that our sister society in the U.K. (the Royal Society of Chemistry) has an ethics committee that even has disciplinary powers.

On the other hand, our councilors must be aware that during the past four to five years the U.S. has had a crisis with respect to ethical conduct in business (for example, Enron); in research (such as the well-publicized firing of Jan Hendrik Schön at Bell Labs); and, most recently, the mutual funds scandal, which saw about one-quarter of the mutual funds paying multi-million-dollar settlements in lieu of convictions.

The first time I was "stung" by the actions of an unethical chemist occurred when I entered graduate school at Cornell (1941). My professor wanted me to repeat some synthetic work done by a recently departed graduate student, but I was unable to do so. The same thing happened to me about six years later in industry and, as a result, I almost lost my job. (Fortunately, my boss also couldn't repeat that synthesis.) In both instances, I had the opportunity to meet the wrongdoers later and each admitted that "the synthesis did not go quite as I had described it."

Then, in 1979, someone called my attention to a paper in the Journal of Chemical Physics that dealt with an old problem that intrigued me for a long time, dealing with cis-indigo. When I read this paper, I discovered that about 15 lines in the discussion were lifted almost verbatim from a paper that I had published in the Journal of Physical Chemistry six years earlier, without any attribution. When I called this to the attention of the senior author (a member of the National Academy of Sciences), he blamed this on his Japanese postdoc and offered to "make up for it" by listing me as a coauthor on his next paper in this field. (Of course I rejected this offer, since it was just as unethical.)

My last experience with unethical chemists happened in 1999 and was too complicated to recite here, except to say that it involved a couple of well-established people. Since I was still smarting from being "stung" so recently, it wasn't surprising that the idea of an ACS ethics committee would surface during a friendly luncheon conversation with three fellow ACS members.

This idea was first submitted to the ACS president five years ago (cosponsored by former president Ernest L. Eliel and then-director Maurice M. Bursey). It has been studied up and down and approved by the Committee on Committees twice and by the Council Policy Committee during the intervening five years. U.S. chemists need such a committee just as much as mathematicians and physicists do and just as much as British chemists do. (I certainly could have used its advice in 1941, 1947, 1980, and 1999.)

George M. Wyman
Durham, N.C.

Final word on paclitaxel

I would like to clarify a statement attributed to me in a recent article on the business of making the cancer drug ingredient paclitaxel (C&EN, Aug. 30, page 12).

In 1996, my company, Phytogen Life Sciences (for which I serve as vice president of regulatory affairs and business development), became one of the first firms to start commercial production of bulk paclitaxel. Today, several newcomers have plans to enter the bulk paclitaxel market, while other companies are developing drugs that use new delivery techniques to administer paclitaxel.

When I said, "We don't have a hope and a prayer to sell. All we have is some white powder," I meant that, as a long-time participant in the business, Phytogen is past the stage of hoping for commercial success. We are a well-established company that for many years has manufactured a "white powder" used in a lifesaving drug.

Diane Wierzbicki
Delta, British Columbia

Going alternative

I was struck by the juxtaposition of your Business Insights on the impact of increasing petroleum costs on the chemical industry (C&EN, Sept. 6, page 32) and the article a few pages later on the research into new uses for chicken feathers (page 36).

The keratin in the feathers has become a nonpetroleum feedstock for a variety of processes. Although C&EN has covered the use of alternative feedstocks in the past, it appears that the time is ripe for a comprehensive review of the barriers to widespread use of such feedstocks in the chemical industry.

The collaboration by Cargill and Dow to produce polylactic acid is but one great example of successful use of alternative feedstocks, albeit to produce a new polymer altogether. There is a great deal of historical data on the use of fermentation to produce acetone and butanol, however, as well as acetate, butyrate, propionate, and so forth. These fermentations are carried out by bacteria that are capable of metabolizing a wide variety of compounds, including cellulose, a widely available waste product. I am sure there are other routes to compounds of interest besides fermentation. If the chemical industry is already suffering from the domino effect created by high petroleum prices, what is stopping manufacturers from investing in some of these other processes?

Books recently reviewed in C&EN also allude to the presumably finite supply of petroleum; since we will continue to require it as fuel for internal combustion engines for the foreseeable future, wouldn't this be a good time to find other ways of making the chemicals we depend on for so many other things? I hope that future issues of C&EN will begin to address these issues, with particular attention to the barriers that may exist in getting processes involving alternative feedstocks on-line in manufacturing.

Kelly Smith
Jacksonville, Fla.

A haunted past

I was delighted to read of the new plant operated by BASF at Ludwigshafen, Germany--delighted, because Ludwigshafen has been a center for chemical manufacture for many years, and to those of us in my age bracket (or in an even higher one), it is reassuring to see such evidence of continuity (C&EN, Aug. 30, page 10).

It is perhaps unfortunate that to the chemical processing engineer the name Ludwigshafen is associated with two severe accidents, both a very long time ago. One was in 1943, when an explosion involving butadiene resulted in 57 deaths, hundreds of injuries, and colossal damage. The second was in 1948, when the exploding material was dimethyl ether. This resulted in 207 deaths and 3,000 injuries. It appears from the timings that the first accident occurred while Germany was at war, and the second, while it was an occupied country. Though I am unsure of exactly when chemical production at Ludwigshafen began, I am aware of an accident at Oppau, Germany, just across the Rhine from Ludwigshafen, in the early 1920s. This was an ammonium nitrate explosion and claimed 522 lives.

Major accidents in the chemical industry continue to be referred to in the literature decades after their occurrence. Flixborough is another case in point; it is featured widely in undergraduate courses on chemical industry safety, yet it happened about 10 years before the undergraduates of today were born. I confidently predict that the 1988 Piper Alpha accident will be featured in books and courses on offshore safety long after my own lifetime. It is inevitable, therefore, that if one searches books and documents for information on Ludwigshafen, the two serious accidents there will dominate. The fact that in the early years of the 21st century, expansion at Ludwigshafen is being reported in C&EN helps counterbalance the impact of those accidents, grave though they certainly were, on the name Ludwigshafen.

J. C. Jones
Aberdeen, Scotland

Conceiving birth control

Ellis Glazier's letter titled "the birth of birth control" started with an apparent compliment: "I admire the chemist Carl Djerassi and might feel the same about the author and playwright were I able to read or watch his works" (C&EN, Sept. 20, page 4). Other than blindness, what keeps Glazier from reading my books?

Reading impairment, of course, may explain the next sentence: "However, I find that calling him the father of the birth control pill, as is so often done, is a bit bizarre," and he then refers to my receiving the American Institute of Chemists' (AIC) award (C&EN, July 19, page 33). Yet that brief coverage does not contain any reference to "father of the birth control pill," but rather correctly states, "Carl Djerassi, novelist, emeritus professor of chemistry at Stanford University, and one of three Syntex scientists responsible for the first synthesis of a steroid oral contraceptive."

Does Glazier's inability to read extend to the biological literature of some 80 years ago? He credits Gregory Pincus (who did important biological work on our substance) or John Rock (who carried out important clinical studies) as actually having "conceived" of oral contraception by means of the steroid progestins synthesized by us. I recommend that Glazier have someone read to him chapter two of my book "This Man's Pill: Reflections on the 50th Birthday of the Pill" (Oxford University Press, 2001), notably pages 16–20, to learn about Ludwig Haberlandt, who anticipated Pincus and Rock by about 30 years.

The following sentence from page 20 says it all: "Haberlandt's work fell into such oblivion that the next biologist to take it up, Gregory Pincus (who clearly should have known better), did not even feel obligated to cite Haberlandt among the 1,459 references in his own opus magnum, 'The Control of Fertility' (1965). Nor for that matter did Pincus' clinical collaborator, John Rock ... Yet if there ever was a grandfather of the Pill, Ludwig Haberlandt above all others deserves that honor."

Carl Djerassi
Stanford, Calif.


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