Leo S. Jensen
The University of Georgia
Athens, GA 30612
This opportunity to honor Dr. A.L. Moxon for his distinguished career involving the biology of selenium is truly a pleasure. In the preface of the book entitled, The Moon Element: An Introduction to The Wonders of Selenium, E.E. Fourier D'Albe wrote, "In this book the reader will find the first connected account of the properties and applications of a chemical element which has raised -- and disappointed -- more hopes than any other element known. Selenium is now just coming into its own, . . .". The book, published in 1924, referred, of course, to its value as a conductor of electricity when illuminated. Even Dr. Moxon was not working on selenium then, but his subsequent pioneering investigations led to a story that could more richly deserve the title bestowed on the 1924 book.
Nutrition scientists proclaim the year 1957 for the start of the selenium story as an essential nutrient. However, if we had paid more attention to a paper published by Moxon and his colleagues in 1941, we might have appreciated its importance much sooner.
The paper (Poley et al., 1941) involved a study of the toxicity of seleniferous grains grown in selenium-rich soils in South Dakota. A combination of corn, barley and wheat containing selenium levels from 8 to 20 ppm was added to chick diets in one experiment to provide concentrations of 0, 2, 5, 8 or 10 ppm. The diets were fed to pens of male and female Barred Plymouth Rock chicks for eight weeks. Growth of the chicks fed the diet with 2 ppm grew significantly more rapidly than those fed the diet containing none of the high selenium-grains (Table 1). Growth declined with higher levels and was less than the control when they provided selenium at 10 ppm.
| Table 1. Effect of adding selenium from toxic grains on chick growth. | ||
|---|---|---|
|
Added Se |
Chick body weight (8 weeks) | |
| Males | Females | |
| (ppm) | (g) | (g) |
| 0 | 533 | 495 |
| 2 | 612* | 567* |
| 5 | 546 | 492 |
| 8 | 513 | 505 |
| 10 | 495 | 427 |
| Poley, Wilson, Moxon and Taylor (1941). | ||
| *Significantly increased over 0 level (P < .05). | ||
My interest in vitamin E started in 1952 when I was a graduate student at Cornell University. My major professor, Milton L. Scott, took a year's sabbatical leave and left me with the responsibility of continuing his experimental work in his absence. Achieving good reproduction in turkey breeders was a major industry problem then. We set up an experiment to determine if supplementing a practical diet with niacin or vitamin E would be of value in increasing hatchability of turkey eggs. Niacin had no effect, but 44 mg alpha tocopheryl acetate per kg markedly improved hatchability of fertile eggs (Jensen et al., 1953).
At the time there were hundreds of feed mills manufacturing feed for turkey breeders across the United States and Canada. In November 1953, I presented the results at the Cornell Nutrition Conference in Buffalo. After feed and poultry trade magazines picked up the report for publication, I received 30 to 40 letters asking for more information. This made me realize that we were doing something important for the public and not just satisfying an intellectual curiosity. This work led to the first use of synthetic vitamin E as a supplement of feeds for animal food production.
Most scientific discoveries end as a single sentence in a student textbook. All the human drama -- the joys and sorrows of successes and failures of the competitors -- soon fades into antiquity. The scientific literature tells us that Schwarz and Stokstad (Schwarz and Foltz, 1957; Patterson et al., 1957) independently discovered the positive nutritional significance of selenium. Before the discovery, I was aware of five laboratories attempting to identify the unknown factor that could prevent disease in animals fed diets without vitamin E.
Klaus Schwarz at the National Institutes of Health originated the assay using rats that developed necrotic liver degeneration. Milt Scott at Cornell adapted the assay for chicks and showed that they developed exudative diathesis, a disease first described by Dam and Glavind (1938). In my last months at Cornell, I witnessed the effects of the torula yeast-based diet on chicks and decided that there was something important to be discovered. After arriving at Washington State University as an assistant professor, I established a project to attempt to identify the factor in brewer's yeast and other supplements that prevented exudative diathesis. Russ Couch at Texas A&M University also picked up the assay from Scott and attempted to find the factor. Later Bob Stokstad entered the competition and used his great mind and the resources of the American Cyanamid Company to study the problem.
We met with each other at the conference of the Federation of Biological Societies in Atlantic City, New Jersey and discussed the progress we were making. Visits with Schwarz were delightful. After the discovery, I was told the following story. In Stokstad's laboratory, a technician who had previously worked in South Dakota detected the odor of garlic as he prepared fractions of the unidentified factor. He recalled this odor as coming from volatile selenium and asked if this element could be the factor. Adding sodium selenite to the assay diet prevented exudative diathesis and stimulated growth. Stokstad phoned Schwarz about the results and suggested that selenium could be the factor preventing liver necrosis in rats. Schwarz tested selenium, and it was. Stokstad, a scholar and gentleman, allowed Schwarz to independently publish the finding. He realized that the real discovery came when Schwarz first developed the assay and that it would be just a matter of time before someone identified the factor.
In early 1957, I received an envelope from Klaus Schwarz containing a few grams of pulverized corn. In it was a hand-written note saying, "Dear Leo: Try this in your assay. Best regards, Klaus." I tried it and, of course, it prevented exudative diathesis. He had added a little sodium selenite to the corn. I never inquired, but he may have sent the same to Russ Couch.
Deficiency diseases in chicks involving inadequate vitamin E or selenium include encephalomalacia, exudative diathesis, nutritional muscular dystrophy and nutritional pancreatic atrophy. Only vitamin E or some synthetic antioxidants prevent the first disease. Either selenium or vitamin E prevents exudative diathesis. To produce muscular dystrophy, the diet must be marginal in cystine. Vitamin E will prevent it, but selenium is only partially effective. Thompson and Scott (1969) found that pancreatic atrophy resulted from a specific deficiency of selenium and that vitamin E (100 IU/kg) could not prevent it. Later studies by Whitacre and Combs (1983), however, showed that very high levels of vitamin E or synthetic antioxidants could prevent the disease.
A vitamin-selenium deficiency in turkey poults differs from that in chicks. The major sign is muscular dystrophy, particularly of the gizzard and heart, but also of the breast muscle. In contrast to chicks, adding high levels of sulfur-containing amino acids has no influence on the myopathy (Walter and Jensen, 1963). Muscular dystrophy in turkeys is caused primarily by a selenium deficiency with vitamin E modifying the amount of selenium needed to prevent the disease.
Despite the discovery of selenium as an important element in the nutrition of animals, the animal industry did not rush to demand its use as a feed supplement. This resulted partly from articles published in Feedstuffs by Stokstad and Scott on the role of selenium in nutrition after the discovery. In his last paragraph, Stokstad (1957) said, "The question arises whether a deficiency of selenium may occur under practical conditions. The present evidence suggests that in the presence of adequate vitamin E, there is no need for selenium or it is less than 0.03 ppm." Scott (1957) concluded by stating, "Although present information indicates that selenium supplementation in present-day practical chick rations is probably unnecessary, only the future will tell how much influence this discovery will have upon the study of other problems . . ." Later, Bieri (1960) stated in a review that "on the evidence to date, selenium is not an essential element nor is it essential that it should be added to poultry feeds." Most feed industry people concluded that, although it is an interesting discovery, it had little relevance to them.
Even if clear evidence had appeared early that practical rations needed selenium supplements for optimum poultry production, a development new to nutritional progress altered the picture. A small study with rats showed that some developed cancer when fed a high level of selenium (Nelson et al., 1943). Because of the Delaney Clause, the Food and Drug Administration forbade the use of carcinogenic compounds in animal feeds. Later, very detailed studies at Oregon State University failed to confirm the Nelson study, but FDA still continued the ban.
At first there was little concern about the ban in the poultry industry. In 1964, Scott found that several turkey flocks in Ohio grew poorly and suffered high mortality with no overt sign of disease other than a severe hyaline degeneration of the gizzard muscle. The corn and soybean meal in the feed originated from crops grown on soils in Ohio and Indiana containing very low levels of selenium.
Earlier trials had established that selenium was needed in the food supply of sheep and cows raised on selenium-low soils (Schubert et al., 1961). In New Zealand, Salisbury et al. (1962) reported 122 outbreaks of exudative diathesis-white muscle disease complex in chickens raised in the South Island, but none in the North Island. Adding selenium to the water supply prevented the disease. Thus, by the middle 1960's considerable evidence existed that selenium deficiency was a problem in animal production.
The interaction of selenium with other dietary supplements used in poultry feeds and with disease conditions undoubtedly influenced the quantitative requirement of the element for optimum production. Furthermore, the change from complex diets to more simple ones (mostly corn and soybean meal) for both broilers and turkeys played a role. This removed the protection of having feed ingredients grown on a variety of soils more apt to supply the needs for selenium.
Starting in the early 1950's, feed manufacturers added organic arsenicals to poultry feeds because they stimulated growth. Arsanilic acid and 3-nitro-4-hydroxyphenyl-arsonic acid (Roxarsone) were added at levels of 23 to 90 grams per ton of feed. Because Moxon (1938) showed that arsenic counteracted the deleterious effects of toxic selenium levels, it is possible that these supplements increased the requirement for selenium. Apparently no one has reported the results of experiments determining the effects of organic arsenicals on the quantitative requirement of chicks for selenium.
Researchers have found that selenium counteracts the toxicity of other elements such as silver, cadmium and mercury, but it is unlikely that these would play any role in practical poultry nutrition. A greater possibility was the presence of higher concentrations of copper and zinc that would interfere with normal metabolism. Both copper and zinc are used as dietary supplements in feed manufacturing. Broiler rations commonly contain copper supplements providing 120 to 240 ppm in addition to the 5 to 8 ppm included in the trace mineral mix. These levels have been used for years, because they improve performance and are believed to protect against fungal and perhaps other diseases.
Adding 1,000 ppm copper to diets containing toxic levels of selenium modified the toxicity (Jensen, 1975a). Seventy percent of chicks fed a diet with 80 ppm selenium died by two weeks but only 3 percent in those supplemented with 1,000 ppm copper. A more than thirteen-fold increase in the selenium content of the liver in the copper-fed chicks indicated that a nondeleterious form of the element was stored in this organ.
Copper-selenium interaction studies showed that copper level influenced the requirement of chicks for selenium (Jensen, 1975b). Adding 800 or 1,600 ppm copper to a diet containing .2 ppm selenium caused high mortality and a high incidence of exudative diathesis and muscular dystrophy. Raising the selenium to .5 ppm prevented the mortality and the pathological conditions. Adding 2,000 ppm or more of zinc also caused high mortality, exudative diathesis and muscular dystrophy in chicks fed a similar diet. Raising the selenium level also prevented these effects.
In 1973, I joined the Poultry Science Department at The University of Georgia. A parasitologist on the faculty said he frequently observed a high incidence of greenish, gelatinous edema over the breasts in experimental birds exposed to coccidiosis. Coccidiosis is a major disease in chickens. The edema suggested an inadequate level of dietary selenium. We conducted experiments in which we inoculated chicks with a mixture of five coccidial species at two weeks of age. The chicks received a practical diet with or without selenium and/or vitamin E (Jensen et al., 1978). Mortality in chicks fed the unsupplemented diet reached levels as high as 68%, while those given selenium or vitamin E had much lower mortality.
Many studies have shown that selenium and vitamin E play a role in enhancing the immunity of animals. We studied the effect of these nutrients on the development of immunity to Eimeria tenella in young chicks. The chicks, fed diets with and without .25 ppm selenium or 100 IU vitamin E, were immunized at two weeks of age, then challenged with a high dose of E. tenella at about four weeks. Diet did not influence body weight at time of challenge, but the weight gain six days post-challenge was significantly greater in those fed the supplemented diets (Colnago et al., 1984).
During the conduct of the coccidial immunity experiments pens of chicks had to be kept in two different houses. At three weeks of age the chicks in only one house contracted Malabsorption Syndrome. This disease, also called Pale Bird Syndrome, occurs worldwide in broiler flocks. The etiology of this disease is still not determined, but it appears to be caused by a combination of viral and bacterial agents. Because the chicks were fed diets with and/or without selenium and vitamin E, the effect of these nutrients on the severity of the disease could be observed (Colnago et al., 1983). Thirty-four percent of the chicks fed the basal died, while selenium and vitamin E reduced it to a normal level. The combination of the two nutrients also significantly improved body weight gain.
After the discovery of selenium as a nutrient and before its use as a feed supplement, poultry researchers continued to report the need for unidentified dietary factors. In particular, adding fish meal to diets composed mainly of corn and soybean meal stimulated growth of broilers and turkeys. Potter et al. (1980), however, found that almost all the response disappeared when selenium was added to the diet. Selenium apparently brought to an end the exciting search for unknown growth factors in poultry nutrition.
The ban by the Food and Drug Administration on the supplementation of poultry feeds with selenium created a dilemma for the industry. Selenium needed to be added to feeds for broilers and turkeys, but the only legal way was to utilize natural feedstuffs grown in selenium-adequate areas. This was more costly than direct supplementation with sodium selenite. It also raised the question of why it was legal to attain a diet with .2 ppm selenium using natural products while it was not using sodium selenite.
Some feed mills found a solution by ordering large quantities of packets of Salmonella Enrichment Media. Each packet contained four grams of sodium selenite to produce one liter of media. The selenite slows growth of E. coli and other organisms while allowing Salmonella to grow. One packet of the media mix contained enough selenium to provide .1 ppm in 30 tons of poultry feed.
Finally, in February 1974, FDA permitted feed manufacturers to use selenium as a nutrient in certain swine and poultry rations. This action came 16 years after discovery of selenium as an important nutritional factor. The year before, Rotruck et al. (1973) demonstrated that selenium was clearly an essential nutrient by discovering its role as an integral part of the enzyme glutathione peroxidase. FDA permitted supplements providing .1 ppm selenium for complete feeds for chickens to 16 weeks of age. Complete feeds for turkeys could have .2 ppm. The element could not be added to diets for laying hens. Today the rules for adding this element to feeds are modified so that it is extensively used in animal production.
The wide use of selenium as a feed supplement resulted in the distribution of this nutrient in animal food products. Thus, all nonvegetarians, regardless of where they live, get increased intakes of this element. The quantity of pure selenium added to broiler feeds in this country every year is estimated to be a couple of tons. Some of this becomes part of broiler litter. Grove et al. (1999) concerned themselves with the partitioning of selenium from broiler litter fertilizer between soil and water to evaluate vulnerability to leaching. They also determined bioavailabilty of litter selenium for growing plants. Litter selenium was tightly bound by soil and did not increase plant selenium nor soluble selenium in leachates. The widespread use of selenium in animal feeds does not appear to pose an environmental problem.
Bieri, J.G. 1960. Current aspects of vitamin A, vitamin E and selenium in poultry nutrition. World's Poultry Sci. J. 16:245.
Colnago, G.L., T. Gore, L.S. Jensen and P.L. Long. 1983. Amelioration of Pale Bird Syndrome in chicks by vitamin E and selenium. Avian Dis. 27:312.
Colnago, G.L., L.S. Jensen and P.L. Long. 1984. Effect of selenium and vitamin E on the development of immunity to coccidiosis in chickens. Poultry Sci. 63:1136.
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