• 1)jIMA J

Bovine Somatotropin: Review of an Emerging Animal Technology'

\

ABSTRACT

One of the first Jotential biotechnol­ogy products for animal production is bST. Research in the technology of bST has involved scientists and support from federal agencies, universities, and private industry. As a consequence of this exten­sive cooperation, more than 1000 bST studies have been conducted, which in­volved over 20,000 dairy cows, and results have been co~umed by scientists throughout the world. This quantity of published research is Wlprecedented for a new technology and greater than most dairy technologies in use. In contrast to steroids. bST is a prot~in honnone. Milk yield and persistancy responses to bST have been observed for all dairy breeds examined. Quality of management is the major factor affecting magnitude of milk response to bST.

The mechanism of action of bST in­volves a series of orchestrated changes in the metabolism of body tissues so that more nutrients can be used for milk syn­thesis. It is these coordinated changes that allow the animal to achieve an in­creased milk yield while remaining nor­mal and healthy. Bioenergetic studies demonstrated that bST -supplemented animals are not stressed. Similarly, there are no adverse health effects from bST

Received June 18. 1990. Accepted April 12, 1991. lRcview prepared for a study of "Emerging Agricul­

tural Teclmology: Issues for th~ 1990s" by Office of Technology Assessment, Congres,s of the United States. Washington, DC. Study was requested by Senate and House Agricultural Committees; th,is specific re,,;ew was a component of the Animal Techno)ogy Panel (M J. Phil­lips, Office of Technology Assessment Project Director) and foUows the Office of Technolbgy Assessment generic outline.

DALE E. BAUMAN Department of Animal Scienoe

Comell University Ithaca. NY 14853-4801

even under poor management conditions. Composition of milk (fat, protein, lac­tose, cholesterol, minerals, and vitamins) is not substantially altered when bST is used and does not differ in manufactur­ing characteristics.

Public perception is of paramoWlt im­portance if bST or any new technology is to be effectively implemented.. New tech­nology must be Wlderstood and per­ceived as safe and beneficial both by farmers, who would utilize it, and con­sumers, who would purchase the dairy products. With bST use, a unit of milk is produced with less feed and protein sup­plement and with a reduction in animal excreta (manure, urine, and methane). Nationally, the use of bST simply rein­forces, but does not fundamentally change, dairy industry trends of in­creased milk yield per cow, reduced number of cows, and declining dairy farm numbers. For individual farms, bST technology is size-neutral. However, poorly man ed farms where animals are stressed, e ed., or sick are at an eco­nomic di a vantage because they will achieve negligible milk response to bST. (Key words: somatotropin, animal tech­nology, review)

Abbreviation key: hST = human somato­tropin, IGF -I = insulin-like growth factor-I.

INTRODUCTION

Improvement of efficiency and economic return is an important goal in dairy fanning, as in any agricultural enterprise. Economists de­fine (technical) efficiency as units of output per units of input. Because provision of feed constitutes a major component of dairy fann expenditures, efficiency of animals often is expressed as the amoWlt of salable product per

1991 J Dairy Sci 74:3913-3932 3913

3914 BAUMAN

unit of feed input. Productive efficiency for dairy cows, therefore, can be defined as "the yield of milk and milk components in . ratio to the nutritional cost of maintenance, lactation and of returning the cow to the level of body condition that existed before the onset of lacta­tion" (11. p. 583).

Physiological limits of animal production were reviewed in 1952 by Sir John Hammond (37). He pointed out that with each major improvement in productive efficiency some have expressed concern that these practices may be "pushing" the dairy cow too far, thus compromising health and shortening produc­tive lifespan. Hammond did not share that concern, and, indeed, milk yield per cow has more than doubled over the past fOUI decades, resulting in substantial increases in productive efficiency of dairy cows. These changes have OCCWTed without any adverse effect on produc­tive lifespan as assessed from national DHI records for the average age of the lactating dairy herd. From the performance of genet­ically superior cows, such as Beecher Arlinda Ellen, who averaged 69 kg of milkJd for her record lactation, it is apparent that dairy cows can achieve substantially greater milk yield and productive efficiency without compromis­ing health and longevity.

Biotechnology has been heralded as a de­velopment that will have a revolutionary im­pact on agriCUlture. In large part, the applica­tion of biotechnology to animal production depends on developing an understanding of the physiological basis for animal differences in productive efficiency. Genetically superior animals differ from lesser animals mainly in their regulation of nutrient utilization, and con­cepts of how this regulation occurs have been established (9, 11). Recent work has demon­strated that somatotropin is a key control of nutrient use. When administered exogenously, bST markedly improves productive efficiency in lactating cows. Thus, it is one of the first potential biotechnology products for animal production. My literature search on bST indi­cates that there are well over 1000 references involving over 20,000 cows. The Animal Health Institute (c. J. Peel, personal commun­ication) indicates that bST studies cWTently in progress worldwide involve an additional 21,000 dairy cows. Throughout the remainder of this review, logic and space constraints re-

Journal of Dairy Scieoce Vol. 74, No. 11, 1991

quire that references be limited with emphasis on review citations.

STATE OF THE ART

Background

Somatotropin is a hormone, that is, a chem­ical produced by one organ or ceU and then transported to another to cause a biological effect. Thus, a hormone is a chemical mes­senger that allows communication among dif­ferent ceUs and organs of the body. Somato­tropin is produced by the anterior pituitary, a small gland located at the base of the brain, and is transponed by the blood to various body organs where it has biological effects. The term "hormone" has taken on negative conno­tations in recent times, primarily because of athletes illegally using massive doses of steroids. However, the chemistry of hormones is as diverse as their biological functions. For example, vitamin D is a steroid hormone, and pasteurized milk. is fortified with vitamin D.

Somatotropin is a protein. This is in con­trast to steroids, which are nonprotein hor­mones. All proteins, including protein hor­mones, are composed of amino acids. There are 20 different amino acids, and these are combined in specific sequences to form the more than 10,000 different proteins in the body. The amino acid sequence of somato­tropin is known for many species, including cattle (47, 91). The bST produced by the pitui­tary gland can either be 190 or 191 amino acids long and can have either of two different amino acids (leucine or valine) at position number 126 in the protein sequence (92). Thus, fOUI different variants of bST are produced naturally. Typically, pituitary pro­duction of bST involves approximately equal amounts of the 190 and 191 amino acid pro­teins, and about two-thirds of the total produced has leucine at position 126, while the remaining one-third has the amino acid valine at position 126.

Somatotropin must be injected to be biolog­ically active (43). The digestive tract secretes enzymes that break. proteins down to amino acids that then are absorbed. If somatotropin is given orally, it is broken down to amino acids in the digestive process just like any other dietary protein. This is true for all large protein

REVIEW: BOVINE SOMATOTROPIN 3915

hormones in all species. For example, human diabetics have to take insulin injections be­cause insulin, another protein hormone, is in­active if taken orally. Similarly, humans defi­cient in somatorropin must take injections of human somatorropin (hST) because it is inac­tive when consumed orally. The rat has been used as a test species because bST is biologic­ally active if injected into rats. Studies have demonsrrated that, when fed to rats, bST was inactive even at a daily dose (W1.its per BW) equivalent to 2.3 million times what a human would be exposed to in five 8-oz glasses of milk (43, 78) .

Somatotropin is referred to as "species spe­cific" in the scientific literature, but "species limited" would be a more accurate description. This means that there are differences in the ability of somatotropin from one species to elicit biological effects in other species. In order to have a biological effect, a protein hormone must first bind to a specific receptor located on the cell surface. The amino acid sequence of somatotropin gives it a unique three-dimensional shape, and this shape deter­mines whether the protein will be able to bind to tissue somatotropin receptors and elicit a biological response. Over 25 yr ago, it was discovered that some types of human dwarfism were due to an inadequate pituitary production of somatotropin. Because hST was scarce, physicians conducted an extensive series of studies treating these patients with injections of bST. These clinical studies unifonnly demonstrated that bST elicited none of the biological actions of somatotropin in humans even if injected (43 , 47, 91). Similarly, somat­otropin isolated from the pituitary glands of sheep, pigs, and whales was also ineffective in humans. Biological activity in humans is only observed if somatotropin from primates is used. The basis of the lack of effect of bST became clear when the amino acid sequence was identified.; the sequence of bST differs by about 35% from hST (91). Thus, the three­dimensional shape of bST differs from hST, and bST is not able to bind to the somatotropin receptors of human tissues (40, 43). In con­trast, ovine somatotropin and bST differ in only one amino acid position, so bST is bio­logically active in sheep.

Recombinantly derived bST products differ slightly from the bST produced by the pituitary

gland in that the manufacturing process can lead to a few extra amino acids attached to the end of the bST molecule. The number of extra amino acids varies from 0 to 8, depending on the particular manufacturing process (43). Lay articles have claimed that this change and the fact that recombinantly derived bST is produced by bacterial ribosomes render the product hyperpotent and dangerous to humans (25 . 52, 53, 76). Such claims reveal an inade­quate knowledge of biology and protein chemistry. The additional few amino acids on the end of the protein do not alter the biologi­cal activity of bST in dairy cows or the lack of activity of bST in humans because the three­dimensional shape of the active part of the molecule is not changed (91). Similarly, the three-dimensional shape of bST is determined by the sequence of amino acids and not by whether bacterial ribosomes or bovine ribo­somes were utilized for the synthesis. When purified in the same manner, recombinant bST and pituitary bST are equally potent in a b0-vine liver receptor-binding assay or rat growth bioassay (55, 92). The pituitary-derived bST purified by A. Parlow (for National Institutes of Health and USDA) has a number of artifacts inrroduced in the purification process (12), and milk yield responses of dairy cows to these preparations is lower than to recombinantly derived bST (10, 56). When these same ar­tifacts were produced with recombinantly der­ived bST, the effect on milk yield also was lower than with authentic recombinant bST (48).

Somatotropin was discovered over 50 yr ago. Initial investigations showed that when growing rats were injected with a crude pitui­tary extract, growth rate was increased. This extract factor was called somatotropin from the Greek derivation meaning "tissue growth". Based on this derivation, somatotropin is sometimes referred to as growth hormone, or GH.

It was not until a number of years later that scientists discovered that this crude pituitary extract also affected lactation in rats. The first studies with lactating cows were reported in 1937 by Russian scientists (2). Through the next 40 yr, there were advances in protein chemistry such that the somatotropin prepara­tions gradually improved in purity, and several dozen studies were conducted with dairy cows.

Journal of Dairy Science VoL. 74, No. II, 1991

.-

391 6 BAUMAN

Particularly significant were a series of srudies in the 1940s by scientists in the United King­dom (93) and later srudies by Brumby and Hancock (14) and Machlin (58). ~

Prior to the 1980s, progress was limited in 6 i bST research for two reasons. First, the availa- ~ bility of bST was limited to what could be ~ extracted with varying purity from the pituitary ~ glands of slaughtered animals. Thus, srudies

AV0<a\l9 Management

could only involve small numbers of cows treated for a few days . Second, the mechanism of action for bST was thought to involve an acute stimulation in the use of body fat reserves . Thus, scientists thought it would only work in fat cows with low milk yield, and all srudies used only low producing cows (gener­ally less than 7 kg of milkId). None used high producing cows, because the assumed mecha­nism (acute mobilization of body fat reserves) might cause ketosis and adverse health effects.

In the late 1970s, two groups, Bines and Hart (National Instirute for Research in Dairy­ing, Shinfield, England) and Bawnan and co­workers (Cornell University), began to work on bST based on two lines of reasoning. First, it became clear that the physiological basis for genetically superior cows being more efficient in milk production was due to differences in regulation of the use of absorbed nutrients (7, 11 , 13) . Second, new concepts were developed to explain how an animal regulates the use of nutrients (7). Based on those concepts, it was hypothesized that somatotropin could play a key role and that the previously proposed mechanism of action was wrong. In the last decade, a key role for somatotropin has been established, and these concepts have been ap­plied to the regulation of nutrient use during growth, pregnancy, and lactation for most spe­cies. Initially, these investigations utilized piruitary-derived bST. However, the landmark breakthroughs in biotechnology allowed pro­duction of bST by recombinant DNA technol­ogy and, in 1982, the first srudy was conducted with dairy cows using recombinantly derived bST produced by Genentech Inc. and Mon­santo Co. (8). Since that time, the quantity and scope of the research with bST have increased exponentially.

Production Responses

Quality of management will be the major factor affecting the magnirude of milk re-

Journal of Dairy Science Vol. 74, No. I I. 1991

o

SOMATOTROPIN DOSE

Figure I. Proposed effect of quality of management on milk response of dairy cows receiving bST. From Bauman (5).

sponse to bST (5, 19, 20, 69). This concept is qualitatively illustrated in Figure 1. Across 45 field trials conducted in the US, Europe, and Africa, a correlation of .58 was observed be­tween pretreatment group milk yield (an indi­cation of management quality) and milk re­sponse to bST (69) . A similar variability in gain is observed when AI (superior sires) is used in herds that vary in management quality and is accommodated in sire evaluations by using herdmate comparisons.

Facets that constitute the quality of the overall management program include the herd health program, milking practices, nutrition protrram, and environmental conditions. Sev­eral long-term srudies have had management so inadequate that a near zero response was observed with bST supplement. In three of these cases, nutritional management was inade­quate (61, 69), and, in the one case, deficien­cies existed in the environmental , nutritional, and milk:ing-marnmary health dimensions of the management program (62). Adverse health effects were not observed in any of these srudies; cows simply had negligible milk re­sponse to bST supplement. The srudy by McCutcheon et al. (61) serves as an example because the quality of nutritional management varied over the course of the 26-wk treatment period. Cows were fed only pasrure, and milk: responses to bST were greatest (+18%) in the spring when pasrure supply was adequate, declined to zero during the summer drought,

REVIEW: BOVINE SOMATOTROPIN 3917

but were again significant during the fall when pasture supply was good. Bovine somatotropin is not magic! If cows are given an inadequate amount of feed or are fed a diet without ade­quate nutrient balance, then the magnitude of response to bST will decrease according to the extent of the inadequacy (Figure 1).

Milk. yield gradually increases the first few days of bST treatment, reaching the maximwn about the 6th d (42, 68). The magnitude of response in milk yield is related to bST dose (68). A maximum milk response is achieved at a bST dose (daily injection) of about 30 to 40 mg/d, and no further increase occurs even at doses several -fold higher. Most production trials have used bST doses between 10 to 50 mg/d.

Exogenous bST must be present every day in order to continue an augmented milk re­sponse (19, 68). The reason is that bST is cleared rapidly from the bloodstream and is not stored in the body. Clearance (removal) is by normal body mechanisms and involves breaking the protein down to amino acids . Thus, to achieve a sustained increase in milk yield, one needs to give daily injections or use a prolonged-release formulation of bST. Sev­eral prolonged-release formulations have been developed that are a small volwne adminis­tered by subcutaneous injection at intervals ranging from 2 to 4 wk (19, 20).

Commercial use probably would be over the last two-thirds or three-fourths of a lactation cycle because response varies according to stage of lactation. In general, the milk response is very small or negligible when bST is admin­istered in early lactation during the interval immediately postpartum and prior to peak milk yield (5). The biological basis for this low response relates to the nutrition-endocrine sta­tus of the animal during this interval. In con­trast, substantial increases in milk yield occur when bST is administered after peak yield of milk is attained. Lactational responses to bST have been reported for all dairy breeds exam­ined, including North American and European breeds as well as Murrah buffalo. In addition, animals of different parity and genetic poten­tial are responsive to bST (18, 20, 68).

Marked improvement in persistency of lac­tation occurs in cows receiving bST (18, 19, 20, 68). The greater overall milk yield with bST supplementation occurs in part because of

an immediate increase in milk yield but espe­cially from a reduction in the normal decline in milk yield, which occurs as lactation progress­es.

Individual variation in response to bST sup­plement has been examined. When a group of cows within a herd is treated with bST and each cow 's response is compared with her individual milk yield prior to bST supplemen­tation. a range in responses among cows is observed. In a few instances. this has been cited as evidence of individual variation in response. However, this is misleading at best. All studies with bST have shown that the variation within bST -supplemented groups is similar to that of untreated groups (6, 69). Thus, to a large extent. all cows in a herd respond to bST in a fairly similar manner, and the bST -supplemented cow that "appears" to be a low responder simply matches the control cow that produced less than expected.

Nutrient requirement tables are unchanged for bST-supplemented dairy cows (9, 18, 68). The basis for this is rwofold. First. digestibili­ties of DM, C, N. and energy are not altered when lactating cows receive bST. Second, bio­energetic studies have demonstrated that bST does not alter energy expenditure for mainte­nance or the partial efficiency of milk synthe­sis. Thus, the tabular values of nutrient re­quirements for maintenance and per unit of milk remain valid when bST is used for dairy cows. [Note: use of somatotropin for growing animals will require modification of both the maintenance and growth components of the nuuient requirement tables because of the shift in the type of growth (increased protein and decreased lipid accretion rates) .]

Voluntary intake increases in bST-supplemented dairy cows. This increase in voluntary intake occurs after a few weeks of bST supplementation, persists throughout the interval of bST use, and has been consistently observed across a wide range of diets (18, 19. 20. 68). The magnitude of increase in feed intake is dependent on the response in milk yield and the energy density of the diet (20). Overall, cows supplemented with bST adjust their voluntary intake in a predictable manner related to the extra nutrients required for in­creased production of milk.

Nuuitional needs and responses to nutri­tional manipulation of bST -supplemented cows

]owual of Dairy Science Vol. 74. No. 11. 1991

3918 BAUMAN

have been reviewed (18, 19,20). Results from numerous studies are uniform and demonstrate that current feeding and management recom­mendations for lactating dairy cows also apply to those receiving bST. Nutritional needs for maintenance. milk production, pregnancy, and replenishment of body reserves over a lactation cycle for a cow producing 10,000 kg of milk! yr are the same as for a cow that achieved 10,000 kg because she received bST.

Obtaining a milk: response to bST supple­ment does not require special diets or unusual feed ingredients. In fact, substantial milk responses have been observed on diets ranging from pasture to the more typical forage and concentrate diets used in the US (18, 20, 61, 68). We would expect, with current costs of feed ingredients in the US , that use of bST will, on average, lead to a predictable increase in the energy density of the diets used (in­creased ratio of concentrate: forage). This is because income over feed cost increases with level of milk: production even though the cost for higher energy ingredients is greater. How­ever, this technology will have potential appli­cation over a wide range of diets because bST increases milk. yield even when pasture is the only dietary ingredient.

Reproductive performance is of special in­terest in terms of bST effects on reproductive variables such as conception rate (services per conception), pregnancy rate (proportion of cows becoming pregnant), and days open (days from parturition to conception). Normally, var­iation in reproductive variables is large. Effects of bST supplementation are small enough that large data sets are needed to allow definitive conclusions. Several reviews have summarized many of the studies with regard to reproduc­tive variables (31, 65, 71). In general, these summaries indicate that bST supplementation results in a decrease in pregnancy rate, but conception rate is not altered. For example, the sununarization (>3000 cows) by Ferguson and Skidmore (31) found that pregnancy rate was 89.2% for controls and 81.2% for bST­supplemented cows (bST dose ranged from 5 to >200 mg/d). Days open also has a general pattern across studies of an increase of a few days in bST-supplemented cows.

The changes in pregnancy rate and days open cited for bST-supplemented cows in­volved studies that were following manage-

Journal of Dairy Science Vol. 74, No. II. 1991

ment practices to achieve a 12- to 13-mo calv­ing interval. Thus, period of breeding (com­mencing 50 to 60 d postpartum) generally would have coincided with the early period of bST supplementation when milk yield had in­creased, but voluntary intake had not yet changed (i.e., cows would be in a lower energy balance). It is well established that changes in pregnancy rate (decrease) and days open (in­crease) are associated with increases in milk yield (16). The biological basis is the inverse relationship between level of milk production and energy balance that occurs at this early stage of lactation. Thus, the decrease in preg­nancy rate and the increase in days open with bST supplementation are to be expected. To examine the impact of milk yield, Ferguson and Skidmore (31) analyzed their multi-study data by logistic modeling to control confound­ing factors. They found that the decrease in pregnancy rate was related to the increase in milk yield rather than to the dose of bST. Similarly, Hard et al. (39) summarized a series of studies that had a similar design and found that days open increased by 5 in the bST­supplemented group. However, when data were stratified by level of milk yield, days open did not differ between controls and bST­supplemented cows (39). Thus, effects of high milk yield on reproductive performance are the same regardless of bST use.

Calving interval for optimal economic re­turn for US dairy farms probably will increase with bST supplementation. Although tradi­tional wisdom has been that a 12- to 13-mo calving interval maximizes profit, care­ful analysis shows that a number of factors can affect this (41). In the case of bST supplemen­tation, not only does milk yield increase, but persistency also is improved. Thus, it is logical that the calving interval for optimal economic return may be substantially increased when bST is used. Ferry (32) modeled the effects of 12- and 14-mo calving intervals on a herd basis and concluded that, with bST use, in­come over feed cost was considerably in­creased with a 14-mo calving interval. More extensive modeling , which included factors such as veterinary costs and replacement values, yielded a similar conclusion [(82; Skid­more, unpublished].

Extending the calving interval also has some benefits on cow physiology. Increasing

REVIEW: BOVINE SOMATOTROPIN' 3919

calving interval improves conception rate (85), probably as a consequence of the nutritional status of the cows as discussed earlier. In addition, the majority of health problems and veterinary costs for dairy cows occur during the first 45 d postparrum (27). Thus, increasing the calving interval reduces health problems and costs whether considered on an annual basis for a herd or on the basis of days of lifetime for an individual cow. We would ex­pect that optimal calving interval with bST use would differ between the US and other coun­tries, particularly those having a seasonal sup­ply of feedstuffs and a beef industry largely based on the offspring of dairy cows. Overall, the actual calving interval that optimizes eco­nomic return will vary according to a number of management and economic factors, but a major component will be the magnitude of milk response and the shift in lactation per­sistency that occurs with bST use.

Genetic evaluation of sires might be af­fected by use of bST if an interaction between genotype and milk response to bST occurs or if bST is preferentially used to manipulate sire proofs. Several studies have examined the former and concluded that there is no evidence of a genotype-response interaction in bST­supplemented cows (35). Preferential use of technology to manipulate dairy records selec­tively occurs currently in the dairy industry, as is clearly evident by the bias in proofs of noo­AI-proven bulls (28). Potential for bias from the use of bST is similar and can be handled by the use of records that are properly coded, use of AI-proven sires, or both (28, 35). It also is anticipated that the rate of genetic progress may increase in a bST environment because variance increases as average milk production increases (28).

Milk CompOSition

Gross composition of milk (fat, protein, and lactose content) is not substantially altered be­cause of bST supplementation (4, 18, 60, 68, 87). However, some lay articles erroneously claim that bST supplementation alters the gross composition of milk (25, 33, 53, 75). Milk components have been examined in most bST production trials (>200 trials). There can be minor changes, primarily in fat content of milk, dwing the first few weeks of bST sup-

plementation as the cow's metabolism and voluntary feed intake adjust. However, these changes are temporary and minor when com­pared with variations normally occurring over a lactation cycle. Although the lactose content of milk is relatively constant, the content of fat-and, to a lesser extent-protein, normally varies widely because of many factors, includ­ing genetics, breed, stage of lactation, age, diet composition, nutritional status, environment, and season (57). As would be expected., these factors (e.g., stage of lactation, diet, nutritional status) affect the fat and protein content of milk in an identical manner in bST­supplemented and untreated cows (4, 18, 68).

The temporary shift in milk fat that can occur during the first few weeks of bST sup­plementation relates to nutritional status (9, 18, 68). Cows in negative energy balance produce milk with a higher fat content because of a greater reliance on lipids mobilized from body fat stores. Indeed., when bST -supplemented cows are in negative energy balance, milk fat content may temporarily increase. This is most likely to occur · when bST supplementation is initiated prior to 100 d postpartum when cows are typically in a lower energy balance. How­ever, even dwing this period, the extent of the cow 's negative energy balance with bST sup­plement is still substantially less than that which typically occurs in the first 8 wk of lactation.

Composition of milk lipids is an important consideration because of its impact on nutritive value, flavor characteristics, and manufacturing properties. Studies have demonstrated that fatty acid composition and cholesterol content of milk are not altered by bST (4). Even when cows are in negative energy balance, the typi­cal shifts in milk fat composition toward a pattern of longer chain, unsaturated fatty acids also are observed for bST-supplemented cows. Similarly, there is a substantial change in fatty acid composition due to stage of lactation, and this shift also is observed in bST-supplemented cows.

Composition of milk proteins has been ex­amined in over a dozen studies because of the impact on functiooal properties of milk used in the manufacturing of dairy products (4, 87). For casein, results have demonstnited that the content and composition (a-casein, j3-casein, lC-casein) are not altered by bST supplementa-

Journal of Dairy Science Vol. 74, No. 11 . 1991

3920 BAUMAN

tion. Some studies have indicated that casein, as a percentage of true protein, is unchanged with use of bST, whereas others have observed a small decrease (often nonsignificant). The same changes in casein occurred with stage of lactation in both untreated and bST­supplemented cows. One short-teml study re­ported a small increase in a-lactalbumin con­tent of milk in bST -supplemented cows, but trus was not observed in long-term studies. We would expect the NPN content of milk from bST-supplemented cows to show the same var­iation related to nutritional status as observed for Wltreated cows. Some COWl tries routinely test NPN levels in bulk milk. as a management tool for farmers to evaluate the protein ade­quacy of their nutritional program (73).

Mineral content and composition of milk: from bST-supplemented cows has been exam­ined in both short- and long-term studies in­volving large numbers of cows (4, 87). Results unifonnly have demonstrated that bST does not alter ash (total mineral content) or the milk: content of any nutritionally important mineral. There is only one published report on the vitamin content of milk; milk. from bST­supplemented cows did not differ in content of any vitamin (vitamin A, thiamine, riboflavin, pyridoxine, vitamin B 12, pantothenic acid, or choline) except for a slight increase in biotin (87), The increase in biotin content of milk: is too small to be considered a benefit; biotin, a member of the B vitamin family, is widely distributed in plant and animal food products and also is synthesized in the intestine of humans.

Manufacturing characteristics of milk: have been investigated in a smaller number of studies, but results have been consistent and demonstrated that milk from bST­supplemented cows did not differ from that of Wltreated cows (4, 87), These evaluations of milk have included freezing point, pH, alcohol stability, thermal properties, proteases, lipases, susceptibility to oxidation, and sensory charac­teristics, including flavor. Similarly, no differ­ences were observed in cheese-making proper­ties, including starter culture growth, co­agulation, acidification, and syneresis, or in the yield, composition, or sensory properties of the various resulting cheeses.

Minor constituents of milk: include hor­mones such as estrogen, progesterone, gluco-

Journal of Dairy Science Vol. 74, No. 11, 1991

corticoids, thyroid hormones, prolactin, and growth factors. Trace concentrations of bST also occur normally in milk, but this is not appreciably altered when cows receive exoge­nous bST (43, 77, 87). The level of bST in milk is only a small fraction of the blood concentration. Only when blood concentrations of somatotropin are increased about 30-fold by a provocative dose of bST does one obtain a small, but significant, increase in milk concen­tration of bST (77). This lack of an appreciable change in milk concentration of bST when physiological doses of exogenous bST are ad­ministered is consistent with the fact that mammary epithelial cells appear to lack recep­tors for somatotropin (21) . Pasteurization of milk results in 85 to 90% destruction of the inunWloreactive quantities of bST (36).

A portion of the biological actions of so­matotropin may be mediated by insulin-like growth factor-I (IGF-I) (9, 68). This protein hormone, a member of the somatomedin fami­ly, normally occurs in trace levels in milk. Administration of bST to dairy cows results in an increase in the amoWlt of IGF-I in milk, but the levels are still within the range typically observed in early lactation of untreated cows and less than that fOWld in human milk. (43, 77, 87). Similar to results with bST, studies with laboratory animal models have demon­strated that IGF-I has no biological activity if administered orally (43).

Mechanism of Action

Somatotropin is a homeorhetic controller that shifts the partitioning of nutrients so that more are used for milk synthesis (9, 68, 89). Thus, effects are primarily, perhaps exclusive­ly, on directing the use of absorbed nutrients. This involves coordinating the metabolism of various body organs and tissues. These orches­trated changes in tissue metabolism involve both direct effects on some tissues (e.g., adi­pose, liver) and indirect effects mediated by somatotropin-dependent somatomedins (e.g., IGF-I) for other tissues (e.g., mammary).

Physiological processes that are altered with bST treatment are summarized by tissue in Table 1 (9). These coordinated tissue responses involve the metabolism of all nutrient classes ~arbohydrates, lipids, proteins, and minerals. It is during the initial period of bST use, when

REVIEW: BOVINE SOMATOTROPIN' 3921

TABLE I. Effect of bST on specific tissues and physiological ~ses in lactating cows.l

Tissue

Liver

Actipose

Muscle

Pancrea3

Kidne;

Intestine2

Process affected during first few days and weeks of tteatment

i Synthesis of mill:: with normal composition i Uptake of all nutrients used for mill:: synthesis i Activity per secretory cell .1. Loss of secretory cells (i.e .. enhanced persistency) i Blood flow consistent with increase in mill:: yield

i Basal rates of gluconeogenesis .1. Ability of insulin to inhibit gluconeogenesis NC Glucagon effects on gluconeogenesis. glycogenolysis. or both

.l. Basal lipogenesis if in posi tive energy balance i Basal lipolysis if in negative energy balance .l. Ability of insulin to stimulate lipogenesis t Ability of insulin to inhibit lipolysis t Ability of catecholamines to stimulate lipolysis

.l. Uptake of glucose

NC Basal or glucose-stimulated secretion of insulin NC Basal, insulin, or glucose-stimulated secretion of glucagon

i Production of 1.25 vitamin OJ t Absorption of Ca. P, and other mineral3 required for mill: i Ability of 1.25 vitamin D) to stimulate Ca-binding protein i Ca-binding protein

Whole body .1. Oxidation of glucose i NEFA oxidation if in negative energy balance NC Insulin and glucagon clearance rates NC Energy expenditure for mainteDllllCe i Energy expenditure consistent with increase in mill: yield (i.e .• heat per unit of mill:

not changed) i Cardiac output consistent with increases in mill: yield i Productive efficiency (mill: per unit of energy intake)

IFrom Bauman et aI . (9) . Changes (i = increased, .l. = decreased, NC = no chaogc) that occur in initial period of bST supplementation when metabolic adjustments occur to match the increased use of nutrients for mlk synthesis. With longer tteatmen!. voluntary intake increases to match nutrient requirements.

2Demonstrated in oonlactating animals and consistent with observed performance in lactating cows.

milk yield has increased but intake has not, that the adjustments in metabolism are major and of critical importance. Overall, mammary uptake of all milk precursors increases while metabolism of other body tissues is altered simultaneously SO that a greater proportion of nutrients can be used for milk synthesis. The same adjustments in metabolism occur in genetically superior cows, and, thus, it is not surprising that high producing cows have higher blood levels of bST than inferior ones (68).

Glucose homeostasis provides a clear exam­ple of the coordinated responses that occur with bST treatment of lactating cows (9). With bST use, glucose production by the liver in­creases, and its oxidation by body tissues decreases. Overall, these changes quantita-

tively are sufficient to account for the extra glucose required for milk synthesis by bST­treated cows. Without such adaptations, ketosis could occur, but this has not been observed.

Lipid metabolism provides a second exam­ple of the coordination occurring with bST supplementation (9. 68. 89). Effects on lipid metabolism vary according to the animal's en­ergy balance. When bST treatment causes cows to be in negative energy balance, lipid mobilization is increased, as shown by decreases in body fat, chronic elevation of circulating NEF A, and increases in milk fat percentage and the proportion of long-chain fany acids in milk. Under such conditions, use of body fat reserves is increased to an extent related to the degree of negative energy bal­ance and quantitatively equal to increases in

Joumal of Dairy Science Vol. 74, No. 11. 1991

3922 BAUMAN

fatty acid oxidation and secretion of long-chain fatty acids in milk. This increased reliance on NEFA as metabolic fuel facilitates the reduc­tion in glucose oxidation. When bST -treated cows are in positive energy balance, lipogene­sis by adipose tissue is decreased., and body fat mobilization , milk fat percentage, and milk fatty acid composition are unaffected. The magnitude of the reduction in lipogenesis is a function of amount of excess energy available. With chronic bST use, lipid metabolism gradu­ally readjusts as voluntary intake increases. Thus, typical replenishment of body reserves can occur during lactation under a wide variety of dietary conditions (9, 18, 19, 20).

Alterations in tissue response to homeostatic signals are an important compo­nent of the adaptations that occur with bST (9, 89). When viewed in the context of whole animal metabolism, changes in response to homeostatic signals represent an exquisite coordination of metabolism (Table 1). The re­duction in ability of insulin to inhibit hepatic glucose synthesis and to stimulate glucose use by peripheral tissues represents a series of coordinated responses whereby more glucose can be used for milk synthesis while preserv­ing the ability of the animal to maintain glu­cose homeostasis. Similarly, adipose tissue re­sponse to acute signals that stimulate fat synthesis (e.g., insulin) is reduced, whereas the response to homeostatic signals that affect rates of fat mobilization is enhanced (e.g., stimulation by catecholamines, inhibition by insulin) . Overall, this results in a net reduction .in body fat accretion during the initial period of bST treatment so that nutrients can be diverted for milk synthesis.

Health and Stress

Catastrophic health effects have been postu­lated to occur with bST supplementation of dairy cows. Ketosis, fatty liver, and chronic wast.ing were all proposed as possible side effects of bST use (13, 50). Lay articles added crippling lameness, milk fever, mastitis. infer­tility, heat .intolerance, sickness, suffering. and death to the list of adverse health claims (25, 33, 52, 74, 75, 76, 97). These postulated cata­strophic effects were not based on actual data but rather on the preswnption that bST was an acute effector of lipolysis or overtly caused stress.

Journal of Dairy Science Vol. 74, No. II . 1991

Metabolic disorders would be most likely to occur during the first few days of bST use (i.e., increased milk prior to change in voluntary intake). Suffice it to say, these catastrophic health effects have not been observed in any of the short- or long-term studies, with dairy cows going back to the very first bST study in 1937. They were not even observed in chronic toxicity studies (24, 65) or in acute toxicity studies in which dairy cows were given 30,000 mg of bST over a 2-wk period., an amount approximately equal.ing that which would be administered in four lactations (90) . Nor were adverse effects observed in studies in which inadequacies in the overall quality of the man­agement program resulted in negligible milk response to bST supplementation as previously discussed. An increase in ketones (a possible indicator of subclinical ketosis) was reported in one earlier study involving two cows given bST for 9 or 10 d (49) . However, that pituitary-derived preparation was contaminated with other hormones (49, 50, 51), and this work has not been verified in acute or chronic studies using larger numbers of cows treated for longer periods with a wider dose range of purified bST [see references in (9, 18,71,90)]. Thus, bST treatment does not alter the normal relationship between blood ketones, blood NEF A, and energy balance.

Catastrophic effects on disease incidence also have been proposed. Lay articles have claimed that bST will reduce resistance to infectious and contagious diseases and thereby increase sickness and suffering in dairy cows (25, 33, 75, 76, 97) . Incidence of disease gen­erally is very low in dairy cows, and a thor­ough evaluation of these claims will require extensive summarization across studies to ob­tain a large data set. However, from the hun­dreds of investigations with bST, I could not locate a single study that observed the lower milk yield and decreased productive efficiency that would be associated with any increase in sickness and suffering. In addition, studies in basic biology actually have demonstrated the opposite of those lay article claims. Somato­tropin plays a key role in several aspects of maintaining irrunune competence [see review by Kelley et al. (45)] Inununity and disease resistance are compromised in laboratory animals and humans deficient in somatotropin, and somatotropin supplementation enhances

REVIEW: BOVINE SOMATOTROPIN 3923

immune competence. Thus far, these basic bi­ology studies have not been extended to lactat­ing cows, but Burvenich et al. (15) demon­strated that cows receiving bST treatment recovered more rapidly from experimentally induced Escherichia coli mastitis.

Stress is more difficult to evaluate, but, in this instance, there are several indices that clearly demonstrate that such claims are un­founded. First, if dairy cows Were stressed and suffering adverse health effects. they would produce less milk and be less efficient. The scientific literature is consistent and contains several hundred studies utilizing bST in which all observed the opposite effect (i.e .• increased milk. yield and productive efficiency). The du­ration of bST use in these studies has ranged from a few weeks to over four successive lactations. Although a multitude of physiologi­cal variables Were monitored relative to stress, there are none that as effectively documents the normalcy of bST -supplemented cows as do the persistent gains in milk yield and produc­tive efficiency throughout the treatment period. Second, if an animal is stressed or suffers adverse health effects, energy expended as heat will be greater than expected. One exogenous agent that has this effect is thyroprotein. which causes about a 20% increase in the heat expen­diture for maintenance (11). Recent studies spanning positive to negative energy and nitro­gen balances have demonstrated clearly that bST has no effect on the energy expended for maintenance or for partial efficiency of milk synthesis (46, 79. 86).

Subtle health effects require examination of "large numbers of animals treated under a range of environmental and management con­ditions" (23). A complete summarization of individual studies done throughout the world is beyond the scope of this review. Many have appeared as abstracts in the last 2 yr and have not yet been published. However. these sum­marizations are required of companies seelcing approval and are used by regulatory agencies in their evaluations. Phipps (71) did an impres­sive job of summarizing a substantial portion of the studies conducted through 1988. His summarization showed that the indices of ani­mal health for bST -supplemented animals were similar to controls and consistent with litera­ture values for cows at similar level of milk. production. Variables studied included physi-

cal examinations. bone radiography. blood chemistry. metabolic disorders, subclinical ke­tosis. udder health. and welfare of the treated cows as well as the health, growth. and per­formance of their offspring.

Subtle effects on the incidence and duration of mastitis will be of special interest. Major factors affecting the incidence of mastitis in­clude the milking management and herd health programs. However, incidence of mastitis and milk see also are correlated positively with milk yield [see reviews (70, 72, 81)]. Effects are quite small and amount to an annual in­crease of approximately .4 cases per cow for each 1000 kg of genetic gain in milk yield. Thus, it will take very large numbers of cows to detect and evaluate whether subtle effects, independent of milk. yield response, occur with the use of bST. Phipps (71) summarized the incidence of clinical mastitis across studies totaling over 1300 cows and found that the relative incidence of mastitis was not affected by bST supplementation. Summaries of larger data sets also should evaluate the impact of bST treatment on duration of mastitis. Given the results of Burvenich et al. (15), which demonstrated that recovery time to experi­mentally induced mastitis is reduced in cows receiving bST supplement, it is of interest to see whether the same beneficial effects of bST supplement are observed for naturally occur­ring cases of mastitis under field conditions.

MAJOR BREAKTHROUGHS NEEDED

Public PerceptIon

Public perception is of paramount impor­tance if bST or any new technology is to be implemented effectively. For a new agricul­tural technology to be used, it must be under­stood and perceived as safe and beneficial by both the farmers, who would utilize it and by the consumers, who would purchase the agri­cultural products. Public discussion of new technologies is appropriate and necessary, and there has been substantial discussion of bST in the print and electronic media. Unfortunately. much of the discussion has lacked a factual basis. This is, in part, because bST is new and different In addition, agricultural extension programs traditionally have focused on practi­cal application of technology to individual sit-

Jonmal of Dairy Science Vol. 74, No. 11, 1991

3924 BAUMAN

uations and have, therefore, initiated education programs only after a new technology was approved and available for commercial use.

Public discussion of bST, to date, has been controversial and in large part focused on responding to misinfonnation from individuals who are i.Il-infonned, anti-technology, or against the use of animals for food production. Some of the misinfonnation claims regarding bST seem designed to cause fear rather than to raise genuine public discussion. Examples are the preposterous claims by Epstein (26) that bST would lead to antibiotic-resistant infec­tions in the general population, create infec­tions in man similar to AIDS, and increase carcinogens in milk and cancer in man. In some cases, the misinfonnation appears to stem from an ignorance of animal agriculture and biology as evidenced by the article of Hansen (38) for the Consumer Policy Instirute, which claims that antibiotics routinely are added to animal feeds and that heavy doses of antibiotics are required because dairy cows are stressed. In some cases, the misinfonnation claims appear to have motivation other than a concern about bST technology. For example, Rifkin (74, 75, 76) has received substantial media coverage of his "concern" for survival of the small dairy farmer and the clJ..im that bST is anti the family farm. Yet this reported concern is difficult to reconcile with the con­clusion of one of his foundations (Greenhouse Crisis Foundation) that livestock farmers are the major source of land, air, and water pollu­tion and its recommendation that consumers minimize or eliminate consumption of all food products derived from animals .

Wisconsin and Minnesota have established a moratorium on the use of bST for the pur­pose of allowing for the education of con­sumers and dairy producers. This clearly shows the importance of public perception, because it is highly unusual to have a morato­rium established for a technology that has not yet received approval to be used.

In response to human health and safety concerns and requests from the public and from governmental officials, several groups with medical or biological expertise have eval­uated the implications of bST use for lactating dairy cows. Again, this emphasizes the impor­tance of public perception, because it is unique to have a technology undergo evaluation by such groups prior to its acrual approval for commercial use. These groups have included a

Journal of Dairy Science Vol. 74, No. II, 1991

Technology Assessment Conference by Na­tional Instirutes of Health (63), the State Medi­cal Society of Wisconsin (83), a review for the American Medical Association (22), a review for The Endocrine Society (95), and a review by the American Council on Science and Health (1). All reached the same conclusion on human safety as the FDA: m.ilk and meat from bST -treated cows is safe and poses no health hazard for humans.

From a historical perspective, the need for education and a concern over public perception are not un.ique for a new technology. Dairy technologies such as pasteurization and homogenization of milk., AI, DHI testing, milking machines, and bulk tanks are but a few examples of past technologies that were fa­vored by some groups and criticized by others (54) . Even the use of fear tactics rather than scientific facts was similar to the current de­bate on bST. For example, some special in­terest groups argued that pasteurization would adulterate milk., lead to an unsafe product, and result in the downfall of the dairy industry. Similarly, some consumer and producer groups claimed that AI would destroy the dairy indus­try. The arguments that Tobe (84), a consumer advocate, made about AI over 20 yr ago are almost identical to those of today. He stated

the calves that are born today are the offspring of masturbated bulls . . . and cows are being insemi­oated with diluted semen which defeats oarure's selectivity and allows inferior spermatozoa to fer­tilize ovum. Instead of improving the spec ies as scientists would like to believe. this practice acru­ally results in an inferior. decadent.. degenerative species. And it is upon these degenerate beasts that we rely for oar supply of milk. . .. Any man or woman who stands before you and claims that cow's milk is a right and proper food for human beings is either ont of his mind. has not thoroughly investigated the truth or is a tool for those commer­cial interests who seek: to exploit you and others and ma.k:e money through your use of their prod­ucts.

Needless to say, a long history of the use of these technologies provides no evidence to support such arguments; indeed, the evidence is qu.ite to the contrary.

INSTITUTIONAL ARRANGEMENTS

Research in the technology of bST has in­volved scientists and financial support from

REVIEW: BOVINE SOMATOTROPIN 3925

federal agencies (National Science Foundation. National Institutes of Health, USDA), state agricultural experiment stations, and private industry. This extensive collaboration, both in the US and worldwide, has been of great value in developing an understanding of the biology of somatotropin and the biology of lactation. To date, the num~r of publications regarding somatotropin probably is unprecedented for an animal technology that is not yet approved for commercial use and substantially greater than for many dairy technologies that are in current use.

Some claim that extensive cooperation has totally compromised the quality and value of the research with bST. Kronfeld (51, 52, 53, 96, 97) has claimed that academic and govern­ment scientists pander to industry and are "in­dentured" and "biased" because of this associa­tion. Rifkin (75, 76) and Epstein (25) have quoted Kronfeld and echoed these claims, repeatedly suggesting that the reporting of data has involved exclusion of sick cows and the suppression and deletion of adverse or nega­tive results observed with bST supplementa­tion of lactating cows. Although these in­dividuals offer no specific documentation of scientific fraud, such claims are not to be taken lightly. One certainty for scientists is that their results will be examined and repeated by others. As a consequence of the extensive co­operation and publication of results, bST studies have involved over 20,000 dairy cows, and results have been verified not only by numerous groups of university, government, and industry scientists in the US but also by scientists throughout the world. The claims of Kronfeld. Rifkin, and Epstein imply a world­wide conspiracy involving over a thousand animal scientists in academia, government. and industry and hundreds of dairy farmers in­volved in the bST experiments. The realistic possibility of such a conspiracy defies belief and raises questions about the motives of those making such claims.

TIMING OF COMMERCIAL INTRODUCTION

Approval for Commercial Use

Commercial use of bST requires approval by the FDA, and, until this occurs, bST cannot be sold legally. Currently. bST is under review by the FDA, and federal law prohibits dis-

closure of proprietary information on a drug under review. However, companies interested in bST have been relatively open about the fact that they are seeking approval and have pub­lished a considerable quantity of their own proprietary research. This extensive disclosure of information on a drug while it is under review is a rare occurrence. In order for bST to be approved by the FDA, each company wish­ing to market the product must prove that it is effective and safe (78). Effectiveness simply involves proving that it does what the com­pany claims. The safety evaluation involves three areas: safety of the animal food products for humans, safety of the bST-supplement to the target animals, and safety of using bST to the environment. In addition, each company must prove to the FDA that its manufacturing process can produce bST to consistent and acceptable quality standards.

In 1984, the FDA had sufficient scientific information to make the determination that the milk and meat from bST-supplemented cows were safe for human consumption (78) . Thus, these animal products could be marketed dur­ing the remainder of the investigational period. The scientific basis for the FDA conclusion that milk and meat of bST-supplemented cows are safe for human consumption included ex­tensive published literature and unpublished studies (43, 78). Specific items included the following:

1. Bovine somatotropin is a protein that is digested enzymatically like any food protein when consumed orally.

2. Bovine somatotropin elicits none of the biological actions of somatotropin in hu­mans even if it were accidentally in­jected. This is a unique situation in which substantial data exist showing the lack of effects in humans treated with a new animal drug.

3. A trace level of bST naturally occurs in milk, but this level is not appreciably altered in cows receiving bST supple­ment.

4. The overall nutrient composition of milk is not altered by bST treacment. The minor changes that can occur in the first few weeks of treatment because of shifts in nutrient balance are temporary and well within the normal variation encoun­tered over the course of a lactation.

Journal of Dairy Science Vol. 74, No. II, 1991

3926 BAUMAN

Many countries are at a similar stage as the US in that bST is under review for conunercial use by the appropriate regulatory agencies. The regulatory agencies for 22 countries have com­pleted the human safety evaluations and con­cluded that the milk and meat from bST­treated cows are safe for human consumption. As of July 1990, a few countries had com­pleted all facets of their review and registered bST for conunercial use (Soviet Union, Czech­oslovakia, Bulgaria, Mexico, Brazil, and South Africa).

Consideration 01 Milk Labeling

Some have suggested that all food products derived from the milk of cows supplemented with bST should be labeled as such in the market place (25) . The basis for this sugges­tion appears to relate to a concern about the safety of the products for human consumption, and there are several aspects needing further consideration.

• MILl<

• MAINTENANCE 30

20

llJ <f)

::J >-(:J>-a:~ llJ::;' z:J llJ~ 1--llJ Z

'0

o CONTROL bST

Figure 2 . Efficiency gains by reduction in the propor­tion of nutrients used for maintenance. For this example, the hypothetical control cow produced 6818 kg (15,000 Ib) of milk in a lactation and use of bST increased rn.i.l.k: yield by 20%. From Bauman (6).

Journal of Dairy Science Vol. 74, No. 11, 1991

First, is there scientific merit or basis for labeling? It seems unconscionable to handle a valid concern for consumer safety by indicat­ing that concern with labeling the food prod­uct. On the one hand, if there is a valid safety concern, then no labeling is needed, because the food should not be marketed for human consumption. On the other hand, if the current regulatory system to evaluate food safety is inadequate, then the system should be changed rather than accepting the inadequacy with the dubious practice of food labeling. Because bST is a technological product with the potential for worldwide application, food safety evalua­tions similar to that of the FDA have been conducted by analogous regulatory agencies in many other countries. To the best of this reviewer's knowledge, all of these regulatory groups have reached an identical conclusion on human safety, and the milk. from bST -treated cows is allowed to be marketed during this phase of the experimental testing.

The second consideration is verification. An effective labeling program requires develop­ment and adoption of appropriate regulations and establishment and funding of a system for implementation and verification. In the case of bST, the scientific literature offers no insight as to any test that could be used to distinguish milk from bST -supplemented cows. The FDA is not aware of any technology that could be used to distinguish the milk of bST­supplemented cows (43, 78). Indeed, the lack of any change in milk composition was one aspect in the human safety evaluation by FDA and analogous regulatory agencies in other countries. Thus, there is no known means to identify specifically milk coming from cows receiving bST supplement.

POTENTIAL PRIMARY IMPACT

Productive ENlclency

Gains in productive efficiency (milk per unit of feed) with bST supplementation occur because the proponion of feed nutrients used for maintenance is reduced. This is illustrated in Figure 2 for a cow that produced 6818 kg of milk and exhibited a 20% response in milk to bST supplementation (6). From bioenergetic studies, previously discussed, it has been es­tablished that the nutrient requirements for

REVIEW: BOVINE SOMATOTROPIN 3927

maintenan~c and per unit of milk are not al­tered by bST administration. The cow receiv­ing bST has a greater total nutritional require­ment because she is producing more milk. (Figure 2). However, she has a higher produc­tive efficiency because maintenance represents a smaller proportion of total nutrient intake.

Increasing efficiency by reducing the pro­portion of nutrients used for maintenance is also the basis for the gains achieved with other dairy technologies, including genetic selection, AI, embryo transfer, dietary formulation and nutritional management, herd health and repro­duction programs, improvements in milking practices, mastitis control, and the treatment of sick animals (5, 6). Bovine somatotropin is not magic. The only difference is that the magni­tude of gain is unprecedented. For example, the gain in productive efficiency obtained with bST supplementation would take 10 to 20 yr to achieve using a combination of AI (semen from superior sires) and embryo transfer (Ta­ble 2). One technology that would rival bST in magnitude of gain relates to manunary health. If mastitis could be eradicated, the increase in milk yield per cow and productive efficiency probably would be even larger than that achieved with the use of bST.

The impact of the productive efficiency gain on savings in dairy cattle feed would be substantial. Although the milk. response to bST on an individual farm will vary according to

TABLE 2. Comparison of theoretical gains in milk yield per cow for different dairy technologies.

Technology

AI2

AI Plus sexed semen2

AI Plus embryo transfc;r2 bS-rJ

ThCQretical annual gain in milk per cowl

(kg)

100 115 135

>1000

1 Acrnal observed gain would average less because of variation in quality of management and other factors. For example, observed gain from using AI and superior sires is approximalely 50% of the theoretical gain.

2Prom Van Vlecl: (88). Gain would be cumulative for successive generations as long as variation exists in the population.

>Prom Bauman et aI. (10) .

quality of management as previously dis­cussed, a reasonable expectation would be that successful adopters would experience an aver­age gain of 12%. Asswning 100% adoption and applying this increase to produce the same quantity of milk as produced in the US in 1988 (29), the savings in dietary energy with bST supplementation would be energetically equiv­alent to 2.5 x 109 kg of com grain, and the savings in dietary protein supplement would be equivalent to 5.6 x 107 kg of soybean oil meal (Table 3). These savings in feedstuffs would represent maximal estimates because commer­cial adoption of new technology is gradual and rarely approaches 100%.

TABLE 3. Impact of bST on animal numbers, feed re­quirements, and waste production of dairy cows to achieve 1988 US milk production. I

Variable Impact bST2

Animals Cow numbers .l. 10.7% Milk yield per cow T 12.0%

Feed3

Energy equivalent as com grain .l. 2.5 x 109 kg Protein supplement equivalent as 44% soybean oil meal .l. 5.6 x 107 kg

Waste Manure4 .l. 6 x 109 kg Urine5 .l. 8 x 109 L Urinary N5 .l. 8 x 107 kg Methane6 .l. 8 X 1010 L

I US 1988 milk production values were 10.24 x· 106

cows. 6460 kg of milk per cow. and 66 x 109 kg of total milk production (29).

2Assumed 100% adoption and that use would increase average annual milk yield per cow by 12%. If commer­cially approved. expected impact would be less because technology rarely achieves 1000/0 adoption. T = Increase, .l. = decrease.

3Based on nutrient requirements for dairy cows aver­aging 650 kg of body weight and producing milk of 3.5% fat content (64).

4Based on an average diet composition of 1.62 Meal of net energy/kg, a diet digestibility of 65% . and fecal OM of 16% (H. F. Tyrrell. USDA. Beltsville. MD, personal com­munication) .

SBased on a daily urine production of 20 L per cow with 1% N in urine (H. F. Tyrrell. personal communica­tion).

6 Assumed that methane production represents 5% of gross energy intake (H. F. Tyrrell. personal communica­tion).

Journal of Dairy Science Vol. 74, No. 11. 1991

3928 BAUMAN

Environmental Impact

Environmental pollution would be reduced with bST use as a result of the gain in produc­tive efficiency that occurs. One aspect of this relates to the substantial reduction in feed re­quired to produce the same quantity of milk with a resulting reduction in erosion fertilizer and other inputs associated with ~roducing: harvesting, processing, and storing of dairy feedstuffs. A second facet involves animal ex­creta. Using the assumptions in the previous section, fecal waste would be reduced 6 x 109

kg if bST were used to achieve the same quantity of milk as was produced in the US for 1988 (Table 3). Similarly, the productive effi­ciency gains with use of bST supplement would result in an annual reduction of 8 x 109

L of urine and 8 x 107 kg of urinary N (fable 3).

Ruminants also produce methane, a gas having a strong greenhouse effect. Cattle pro­duce about 7% of the global methane emis­sion~ (17). Because of the gain in productive effiCIency when bST is used, methane produc­tion by a dairy cow would be reduced 5.5% per unit of milk produced. Using the quantity of milk for 1988, this amounts to an annual reduction of 8 x 1010 L of methane in the US (Table 3).

It should be noted that some have con­cluded that the use of bST would increase environmental pollution because manure and methane production per cow would increase (25, 34, 74, 75). This conclusion is erroneous because it does not consider the yield of milk Produ.ction of manure by an individual dairy cow IS related to her feed intake and thus would be minimal for a given diet if she were giving no milk (i.e., consuming only sufficient nutrien~ for m~tenance). However, a dairy farmer IS m busmess to produce milk. Al­tho~gh. ~roduction of manure and methane by ~ mdivldual cow increases as her milk yield mcre~ses, the amount of animal waste per unit of milk would be substantially reduced.

Dairy Industry Impact

The initial economic analysis of the impact of bST was by Kalter et al. (44). These work­~rs used a wide range of scenarios because tmportant facets of the biology of somatotropin were unknown (e.g., scenarios for both an

Journal of Dairy Science Vol. 74. No. 11. 1991

increase in voluntary intake with no change in nutrient density of the diet versus no change in voluntary intake, thereby requiring an increase in nutrient density of the diet) . Since that time, there have been approximately 100 economic studies involving almost every developed country on the impact of bST (29, 30, 94). Most have reached similar conclusions except for the few studies that have used erroneous assumptions [e.g., the extra milk. produced re­quired no additional nutrients (67)].

Several of the more extensive economic analyses have included modeling effects by ge.ographic region for different milk. support pnce and milk market order scenarios (29, 30, 80). Results indicate that regardless of the policy scenario, bST has little effect on the relative size of dairy farms or the regional location of milk production. When viewed at a national level, use of bST simply reinforced, but did not fundamentally change, dairy indus­try trends of increased milk production per cow, reduced total number of cows, declining darry farm numbers, and shifts in regional production patterns.

When viewed at the farm level, bST tech­nology is size-neutral. That is , there is essen­tially no economy of scale associated with the ~echno1ogy . Use of bST requires no capital mvestment, and the rerum (increased milk) occurs immediately. The claim in lay articles that bST is anti the small farm (74, 75 , 76) is misleading. Use of bST could prove profitable for all SIZeS of commercial dairy farms (29, 30, 94). However, milk. responses to bST are de­pendent on the quality of management, and, thus , it is anti poorly managed farms. Poorly managed farms include those on which animal.s m~y .be stressed, underfed, or experi­ence high mCldence of health disorders such as mastitis . Thus, similar to other current technol­og!es that improve productive efficiency of darry cows, the farms that are at an economic disadvantage and will receive little benefit from bST are those that are poorly managed regardless of size .

. Milk: production costs (per unit of milk) will be lowered for dairy fanners who success­fully use bST. In 1989, the US supply of milk was inadequate, but, for most of the decade milk supply was in excess of demand (66): However, the price received by fanners as well as government costs and benefits in consumer

REVIEW: BOVINE SOMATOTROPIN 3929

fcxxi prices depend, in large part, on the flexi­bility of the dairy price support program and market dynamics (29, 30, 80). Possible social impacts of bST or other new technologies on farm commWlities that could occur as a result of the decline in cow numbers (dairy farms) and the reduction in feed required (crop farms) are very much affected by US agricultural policies and programs (29, 30, 80) . Thus, it is essential that US agricultural programs be designed so that the gains from bST and other new technologies can be shared fairly between dairy producers and consumers, and the impact on the farm community can be consistent with long-range US agricultural policies.

International Competitive PosItion

The US ranked fifth highest in the most recent milk production cost estimates (exclud­ing subsidies) of seven major milk-producing cOWltries (3). Under the international trade rules that existed in the previous decade, use of bST or othl'<r technologies would have had little effect on US competitiveness in the world dairy industry (30, 59). During that interval, most developed cOWltries subsidized their dairy industries, restricted imports, and subsi­dized exports.

In the last 2 yr, the international dairy mar­ket has Wldergone substantial changes toward a freer trade environment. If these changes continue, the US will find itself at a consider­able disadvantage if bST is used in competing cOWltries but not in the US (29, 59). Thus far. regulatory agencies for six COWl tries have com­pleted their evaluations and approved bST for commercial use as previously discussed. How­ever, most cOWltries are at a stage similar to the US in that the potential for commercial use is still Wlder evaluation.

Consideration of food production from a global perspective will become of even greater importance in the future inasmuch as world population is estimated to double in the next 40 yr. One can calculate that the amoWlt of food needed over the next 40 yr is equal to the arnoWlt of food previously produced in the history of hwnankind. Clearly, the develop­ment and use of new technologies that are safe and environmentally sOWld to improve the effi­ciency of animal and plant production are of major importance for the future.

ACKNOWLEDGMENTS

Because of the breadth of this paper. the author sought comments and evaluations from a nwnber of scientists representing a range in areas of expertise. The author gratefully ac­knowledges the critiques provided by C. M. Ashdown, R. L. Baldwin, D. M. Barbano. W. V. Chalupa, D. A. Dwyer, J. M. Elliot. R. W. Everett, R. F. Fallert, J. D. Ferguson, N. A. Jorgensen, R.I. Kalter, 1. W. Lauderdale, R. K. McGuffey, M. A. McGuire, A. M. Novakovic, M. S. Partridge, C. J. Peel, H. A. Tucker, and H. F. Tyrrell. These valuable reviews were in addition to the peer reviews done by Office of Technology Assessment staff. comments from the Office of Technology Assessment Animal Technology Workshop, and peer reviews by the Editorial Board of Journal of Dairy Science.

REFERENCES

I American Council on Scien~ and Health. 1990. BST -a safe, more plentiful milk supply. Am. Counc. Sci. Health, New York. NY.

2 Asimov, G. J., and N. K. Krouze. 1937. The lacto­genic preparations from the anterior pituitary and the increase of mill:: yield in cows. J. Dairy Sci. 20:289.

3 Baker. D., M. Hallberg. J. Eltench. R. Beck. and C. Betts-Liebrand. 1990. Estimates of costs of producing mill:: in seven major mill:: producing countries, 1986. Econ. Res. Serv., USDA, Washington, DC.

4 Barbano, D. M., and J. M Lynch. 1989. Milk from bST-treated cows: composition and manufacturing properties . Page 9 jn Advanced technologies facing the dairy industry: bST. Mimeo SO'. No. 133, Cornell Coop. Ext ., Cornell Uoiv ., Ithaca, NY.

5 BallIIlBJl, D. E. 1987. Bovine somatotropin: the Cor­neU experience. Page 46 jn Proc. Nat!. Invitational Worksbop on Bovine Somatotropin. USDA ExL Ser .. Washington, DC.

6 Bauman. D. E. 1989. Biology of bovine somatotropin in dairy cattle. Page I jn Advanced technologies facing the dairy industry: bST. Mimeo Sa. No. 133. CorneU Coop. Ext., Cornell Univ., Ithaca, NY.

7 Bauman, D. E., and W. B. Currie. 1980. Partitioning of nutrients during pregnancy and lactation: a review of mechanisms involving bomeostasis and homeorbe­sis. J. Dairy Sci. 63: 1514.

8 Bauman, D. E .• M J. DeGeeter, C. J. Peel. G. M Lanza, R. C. Gorewit, and R. W. Hammond. 1982. Effect of recombinanlly derived bovine growth bor­mone (bGH) on lactational performance of high yield­ing dairy cows. J. Dairy Sci. 65(SuppL I): 121. (Abstr.)

9 Bauman, D. E ., F. R. Dunshea. Y. R. Boisclair. M. A. McGuire, D. M. Harris, and K. L. HouseknechL 1989. Regulation of nutrient partitioning: homeostasis, bomeorbesis and exogenous somatotropin. Page 306

Journal of Dairy Science Vol. 74, No. II , 1991

3930 BAUMAN

in 7th Int Conf. Prod. Dis. Farm Anim. F. A. Kallfelz, ed. Cornell Uoiv .. Itbaca., NY.

10 Bauman. D . E .. P. J . Eppard.. M. J. DeGeeter. and G. M. Lanza. 1985 . Response of rugh producing dairy cows to long-term trearmeD! with pituitary and recombinant-somatotropin. J. Dairy Sci. 68 : 1352 .

11 Bauman. D. E .. S. N . McCutcheon. W . D. Steinbour. P. 1. Eppard. and S . J. Sechen. 19!i5 . Sources of variation and prospects for improvement of productive efficiency in the dairy cow: a review. J. Anim. Sci. 60:583.

12 BelL J. A., K . Moffat. B . K. Vondebaar. and D. W . Golde. 1985. Crystalli.z.ation and preliminary x-ray characterization of bovine growth hormone. J . BioI. Chern. 260:8520.

13 Bines. J. A ., and I. C. Harl. 1982. Metabolic limits to milk production. especially roles of growth hormone and insulin . J. Dairy Sci. 65 :1375 .

14 Brumby, P. J .• and J . Hancock- 1955. The galac­topoietic role of growth hormone in dairy canle. N.Z. J . Sci. Techno!. 36A:417.

15 Burveoich. c., G. Vandeputte-Van Messom. E. Roets, J . Fabry, and A-M . Massart-Leen. 1989. Effect of bovine somatotropin on milk yield and milk composi­tion in peripanuriem cows experimentally injected with Escherichia coli . Page 277 in Use of somato­tropin in livestock production. K. Sejrsen. M. Vester­gaard, and A. Neimann-Sorensen. ed. Elsevier App\. Sci.. New Yor\(, NY.

16 Butler, W . R., and R. D . Smith. 1989. interrelation­ships between energy balance and postpartUm repro­ductive function in dairy cattle. J. Dairy Sci. 72:767.

17 Byers, F. M . 1990. Beef production and the green­house effect - the role of methane from beef produc­tion in global warming. Proc. West. Sect. Am. Soc. Anim. Sci. 41 :144.

18 Chalupa. W .• and D. T. Galligan. 1989. Nutritional implications of somatotropin for lactating cows. J. Dairy Sci. 72:2510.

19 Chilliard. Y. 1988. Long-term effects of recombinant bovine somatotropin (rBSn on dairy cow perform­an~s . Ann. Zootech. (Paris) 37: 159.

20 Chilliard. Y . 1989. Long-term effects of recombinant bovine somatotropin (rBSn on dairy cow perform­ances: a review. Page 61 in Use of somatotropin in livestock: production. K. Sejrsen. M. Vestergaard.. and A. Niemann-Sorensen. ed. Elsevier Appl. Sci .. New Yor\(, NY .

21 COllier, R. J .. S . Ganguli. P . T. Menke, F . C. Buono­mo. M F. McGrath. c. E . Korts. and G. G. Krivi. 1989. Changes in insulin and somatomedin receptors and upUlkc of insulin, IGF-I and IGF-Il during mam­mary growth. lactogenesis and lactation. Page 153 in Biotechnology in growth regulation . R. B . Heap, C. G. Prosser, and G. E. Lamming, ed . Butterworths. Lon­don. EngL

22 Daughaday, W. H .• and D. M. Barbano. 1990. Bovine somatotropin supplementation of dairy cows: is the m..iJk safe? J. Am. Med. Assoc. 264: 1003.

23 Eppard. P. J .• D . E. Bauman, C. R.. Curtis. H. N. Erb, G . M. Lanza. and M J. DeGeeter. 1987. Effect of 188-day rreaOIlem with somatotropin on health and reproductive performance of lactating cows. J. Dairy Sci. 70:582.

Journal of Dairy Science Vol. 74, No. I\, 1991

24 Eppard.. P. J., J. L. Vicini. W. J . Cole. and R. J. Collies. 1989. Effect of bovine somatotropin on aru­mal health. Page 74 in ?roc. Maryland Nutr. Conf .. Univ. Maryland, College Park-

25 Epstein. S . S. 1989. Petition to the Food and Drug Administration entitled "Potential Public Health Haz­ards of Biosynthetic Mill: Hormones" dated July 19. 1989.

26 Epstein. S . S. 1989. Growth bormones would en­danger rnilk. Los Angeles Times. July 27 . Metro Sect., part Il, p. 7.

27 Erb, H. N .. R. D. Smith. R. B. Hi11man.. P. A. Powers, M. C. Smith. M E. White. and E. G . Pearwn. 1984. Rates of diagnosis of six diseases of Holstein cows during 15-day and 21-day intervals. Am. J . Vet. Res. 45:333 .

28 Everert. R.. W .• D. M. Galton. and S. D . Kaclunaa 1989. Dairy genetics in a bST environment Page 81 in Advanced technologies facing the dairy indUStry: bST. Mimoo Ser. No. 133. Cornell Coop. Ext.. Cornell Univ ., Ithaca, NY .

29 FalJest, R . F., and C. B. Liebraod. 199\. Economic implications of bovine somatotropin for the United States dairy industry. J. Dairy Sci. 74{Suppl. 2): 12.

30 FalJert, R., T. McGuckin. C. Betts, and G. Bruoer. 1987. bST and the dairy industry: a national, regional and farm-level analysis. Agric. Econ. Rep . No. 679. Econ. Res. Serv., USDA, Washington. DC.

31 Ferguson, J . D ., and A. Skidmore. 1989. Bovine somatotropin--reproduction and health. Page 57 in Advanced technologies facing the dairy industry: bST. Mimoo Ser. No. 133. Cornell Coop. Ext, Cornell Univ .. Ithaca, NY .

32 Ferry, J. W. 1989. Managing the bST treated herd-a veterinarian perspective. Page 45 in Meeting the chal­lenges of new technology. Monsanto Tech. Symp. Preceding the Cornell Nutr. Conf. Feed Manuf., Anim. Sci. Div., Monsanto Agric. Co., St Louis. MO.

33 Fox.. M W. 1988. Why bST must be opposed. Paper presenred at the Athene Trust In!. Conf. (October 1988) Action al"Tt: the bio-revolutioD---<:ornucopia or pandora' s box? London. Eng\.

34 Geisler. c., and T. Lyson. 1989. There is more than O!le way to produ~ milk: social and economic conse­quences of restructuring New York:'s dairy industry. Page III in Advanced technologies facing the dairy industry: bST. Mimeo Ser. No. 133, Cornell Coop . Ext. . Cornell Univ., Ithaca, NY.

35 Gravest, H. O. 1989. Intluences of somatotropin on evaluation of genetic merit for mill:: production. Page 120 in Use of somarotropin in livestock: production. K. Sejrsen, M Vestergaard.. and A. Neimann-Sorensen. ed . Elsevier App!. Sci.. New Yor\(, NY.

36 Groenewegen. P . P .. B. W . McBride, J . H. Burton. and T . H. Elsasser. 1990. Bioactiviry of mill:: from bST-treated cows. J. Nutr. 120:514.

37 Hammond.. J. 1952. Pbysiological limits to intensive production in animals . Br. Agric . Bull. 4 :222.

38 Hansen, M . K. 1990. Biotechnology and mill::-an analysis of issues related to bGHlbST use in the dairy industry. Consumer Policy Inst., Consumers Union, Mount Vernon. NY.

39 Hard.. D. L., W. 1. Cole, S. E. Franson, W . A­Samuels , D. E. Bauman. J. T. Huber. and R. C. Lamb. 1988. Effect of long term sometribove, USAN

REVIEW: BOVINE SOMATOTROPIN 3931

(recombinant methionyl OQ~me S()ma\()tro~in), tIett­IDem in a prolonged release system on milk yield. animal health and reprod uc ti ve performan<»-p<>o led aeross foor sites . I. Dairy Sc i. 71(Suppl. 1):210. (Abstr .)

40 Hocquelle. I.-F .. M.-C. Postel-Vinay. C. Kayser. B. de Hempunne. and A. Amar-Costesec. 1989. The human liver growth hormone receptor. Endocrinology 125: 2167 .

41 Holmann, F. J. C. R. Shumway. R. W . Blake. R. B. Schwan. and E. M. Sudweeks. 1984. Economic value of days open for Holstein cows of alternative milk yields with varying calving intervals . 1. Dairy Sci. 67: 636.

42 Johnsson. I. D .. and I. C. Hart . 1986. Manipulation of milk yield with growth hormone. Page 105 in ReceDt advances in auima! nutrition. W. Haresign and DJA. Cole. ed. Butterwortbs. wndon. Eng!.

43 Juskevicll. J. c.. and C. G. Guyer. 1990. Bovine growth hormone: human food safety evaluation. Science 249:875.

44 Kalta. R. J .• R. Milligan. W. Lesser. W. Magrath. and D. E. Bauman. 1984. Biotechnology and the dairy industry: production costs and commercial potential of the bovine growth hormone. Agric . Eng. Mimeo Ser. No. 84-22. Cornell Coop. Ext. Cornell Uoiv .. Ithaca. NY.

45 Kelley. K . W .• S . Brief. H. J. Westly. J. Novalcofslci, P. J. Bechtel. J. Simon. and E. R. Wailea. 1987. Hormonal regulation of the age-associated decline in immune function. Page 91 in NeuroimmunomO<!ula­tion . B. D. Janlcovic. B. M Markovic. and N. H. Spector. ed. New York Acad. Sci ., New York, NY.

46 Kirchgessner, M, W. Schwab. and H. L. Muller. 1989. Effect of bovine growth hormone on energy metabolism of lactating cows in long-term administra­tion . Page 143 in Energy metabolism of farm animals. Y. van der Honing and W . H. Close, ed. Pudoc. Wageningen. Neth.

47 Kostyo, J. L .. and R. C. Reagan. 1976. The biology of somatotropin. Pbannacol. Theriogenol. 2 :591.

48 Krivi, G. G., W. J. Salsgiver, N. R. Staten. S. D. Hauser, E. Rowold. T. R. Kasser. T. C. White. P . J. Eppard, G. M. Lanza, and D. C. Wood. 1988. Identifi­cation of residues of somatotropin involved in recep­tor binding and biological activity. Program Abstr., 70th Annu. Mtg. Endoer. Soc., Abstr. 257, New Orleans, LA.

49 Kronfeld, D . S. 1965. Growth hormon&-induced iceto­sis in the cow. J. Dairy Sci . 48:342.

50 Kronfeld, D . S. 1982. Major metabolic determinants of milk volume, mammary efficiency and spontaneous ketosis in dairy cows. J. Dairy Sci. 65 :2204.

51 Kronfeld, D . S. 1986. Coocems about use of growth hormone ill dairy cows. FDA Seminar Notes of Sep­tember la, 1986. Ctr. Vet. Med., FDA. Roclcville, MD.

52 Kronfeld, D. S. 1987. Health risks in dairy cows given biosynthetic somatotropin. Proc. Nutr . Inst.. Natl . Feed Ingred. Assoc .. West Des Moines, IA.

53 Kronfeld, D. S. 1989. Lener to the editor entitled "BST milk safety". J. Am. Vet. Med. Assoc. 195:288.

54 Kuchler, F., and J. McOe1land. 1988. The demand for food safety: an historical per~tive on recombinant

1)NA.-derived animal growth hormones. POlicy Stud. J . 17:125.

55 Langley. K. E., P.-H. Lai, J. Wypycll. R. R. Everett. T. F. Berg. L. F. Krabill J. M. Davis. and L. M Souza. 1987. Recombinant-DNA derived bovine growth bormone from Escherichia coli. 2. Biochemic­al. biophysical. immunological and biological compar­ison with the piruitary hormone. Eur. J. Biochem. 163: 323.

56 Lanza.. G. M., G. G. Krivi, L. A. Bentle, P. J. Eppasd, L. Kung, R. L. Hintz, R. L. Ryan. and M A. Miller 1988. Comparison of the galactopoietic activity of several recombinant bovine SOmal otrop in variants and piruitary derived bovine somatotropin. Program Abstr., 70th Annu. Mtg. Endocr. Soc., Abstr. 242, New Orleans. LA.

57 Linn. J. G. 1988. Factors affecting the composition of milk from dairy cows. Page 224 in Designing foods-­anima1 prOOuct options in the maricetplace. Nat!. Acad. Press, Washington. DC.

58 Machlin. L. J. 1973. Effect of growth hormone on milk prO<!uction and feed utilization in dairy cows. J. Dairy Sci. 56:575.

59 Mayer, L. 1989. The effect of bST on the dairy industry and the USDA perspective on technology. Page 91 in Advanced technologies facing the dairy industry: bST. Mimeo Ser. No. 133. Cornell Coop. Exl. Cornell Uoiv ., Ithaca. NY.

60 McBride, B. W .• J. L. Burton. and J. H. Burton. 1988. The influence of bovine growth hormone (SOmalotropin) on animals and their products. Res. Dev. Agric . 5: 1.

61 McCutcheon. S. N., A. Michel. C. J. Hoogendoorn. G. A. Lynch, and B. W. Wickham. 1989. Application of bovine somatotropin (bST) technology to pastoral dairy farming systems. Page 332 in 7th In!. Conf. PrO<!. Dis. Farm Anim. F. A . Kallfelz, ed. Cornell Uoiv., Ithaca. NY.

62 Mollet, T. A .• M. J. DeGeeta, R. L. Belyea. and R. A. Youngquist. 1986. Biosyntlletic or piruitary extracted bovine growth hormone induced galactopoiesis in dairy cows. J. Dairy Sci. 69(Suppl. 1):1l8.(Abstr.)

63 National Instirutes of Health. 1990. Technology as­se , sment conference statement on bovine somato­tropin. Dep. Health Human Serv ., Bethesda, MD.

64 National Research Council. 1988. Nutrient require­ments of dairy cattle. 6th rev. ed. Natl . Acad. Sci.. Washington. DC.

65 Noakes, D. E. 1991. Use of somatotropin in the dairy cow with regatd to cow safety. Presented bST sympo­sium: from promise to practice, August 4 and 5, Lex­ington. leY . Eli Lilly & Co ., Indianapolis, IN.

66 Novakovic, A. M 1990. The U.S. dairy situation and outlook for 1990. Agric. Eng. Mimeo Ser. No. 90-7, Cornell Coop. Exl. Cornell Uoiv ., Ithaca. NY.

67 Office of Technology Assessment 1985. Technology, public policy, and the changing structure of American agriculture: a special report for the 1985 Farm Bill. OTA-F-272. US Govt Printing Office. Washington. DC.

68 Peel C. J .. and D. E. Bauman. 1987. Somatotropin and lactation. J. Dairy Sci. 70:474.

69 Peel C. J ., D. L. Hard. K. S. Madsen. and G. dcKer­chove. 1989. Bovine somatotropin: mechanism of ac­tion and experimental results from different world

Journal of Dairy Science Vol. 74, No. II, 1991

3932 BAUMAN

areas. Page 9 in Meeting the cballenges of new tech­nology. Monsanto Tech. Symp. Preceeding the Cor­nell Nutr. Coaf. Feed Manuf .. Anim. Sci. Div .. Mon­santo Agricultural Co .. St. Louis. MO.

70 Philipsson, J .. E. Persson, U. Andersson, L. Brolund.. and H. Funke. 1978. Genetic aspects on breeding for mastitis resistance. Page I in Symp. Bovine Mastitis, Munich. Germany.

71 Phipps. R. H. 1989. A review of the influence of somatotropin on health.. reproduction and welfare in lactating dairy cows. Page 88 in Use of somatorropin in livestock: production. K. Sejrsen, M Vestergaard.. and A. Neimann-Sorensen, ed. Elsevier Appl. Sci .. New York. NY.

72 Poutrel, B. 1982. Susceptibility to mastitis: a review of factors related to the cow. Ann. Rech. Vet. 13:85.

73 Refsdal.. A. 0 .. L. BaeVTe. and R. Bruflol 1985. Urea concentration in bulk: milk as an indicator of the protein supply at the herd level. Acta Vet. Scand. 26: 153.

74 R.i.fk:i.n. J. 1986. Petition to Secretary of Health and Human Services, and the FDA. and its Division of Veterinary Medicine. Dated April I. 1986.

75 R.i.fk:i.n. J. 1987. Petition to the FDA. Dated September 16, 1987.

76 R.i.fk:i.n. J. 1989. Petition to the FDA. Dated August 23, 1989.

77 Schams, D. 1989. Somatotropin and related pep tides in milk. Page 192 in Use of somatotropin in livestock: production. K. Sejrsen, M. Vestergaard.. and A. Neimann-Sorensen, ed. Elsevier Appl. Sci.. New York. NY.

78 Sechen, S. 1989. Review of bovine somatotropin by the Food and Drug Administration. Page 101 in Ad­vanced technologies facing the dairy industry: bST. Mimeo Ser. No. 133, Cornell Coop. Ext.. Cornell Univ., Ithaca. NY.

79 Sechen, S. J., D. E. Bauman, H. F. Tyrrell.. and P. J. Reynolds. 1989. Effect of somatotropin on kinetics of nonesterified fairy acids and partition of energy. car­bon and nitrogeo in lactating cows. J. Dairy Sci. 72: 59.

80 SeUschopp, J., and R. J. Kalter. 1989. Bovine somato­tropin: its impact 00 the spatial distribution of the U.S. dairy industry. Agric. Eng. Mimeo Ser. No. 89-14, Cornell Coop. Ext., Cornell Univ., Ithaca. NY.

81 Shook. G. E. 1986. Genetic aspects of mastitis. Page 68 in Proc. 25th Annu. Mtg. Nat!. Mastitis Council, Inc., Nat!. Mastitis Counc .• Inc., ArJ..ington, VA.

82 Skidmore, A. 1990. Development of a simulation model to evaluate effectiveness of dairy herd manage­menl Ph.D. Diss., Cornell Univ .. Ithaca. NY.

83 State Medical Society of Wisconsin. 1990. New re­lease entitled "State Medical Society finds BGH milk safe for humans", and dated January 22. 1990. Madi­son, WI.

84 Tobe, J. H. 1967. Milk-Friend or fiend. Mod. Publ. Reg'd., St Catherines, ON, Can.

85 Trimberger, G. W. 1954. Conception rates in dairy cattle from services at various intervals al'ter panuri-

Journal of Dairy Science Vol. 74, No. II. 1991

tion. J. Dairy Sci. 37: 1042. 86 Tyrrell.. H. F., A.c.G. Brown. P. J. Reynolds. G. L.

Ha.a.1and., D. E. Bauman.. C. J. Peel. and W. D. Stein­hour. 1988. Effect of bovine somatotropin on metabo­lism of lactating dairy cows: energy and nitrogen utilization as determined by respiration calorimetry. J. Nutr. 118:1024.

87 van den Berg. G. 1989. Mill:: from bST-treated cows: its quality and suitability for processing. Page 178 in Use of somatotropin in livestock: production. K. Sejr­sen, M Vestergaard, and A. Neimann-Sorensen, ed. Elsevier Appl. Sci .. New York. NY.

88 Van Vleck. L. D. 1981. Potential genetic impact of artificial insemination, sex selection, embryo transfer, cloning and selfing in dairy canle. Page 221 in New technologies in animal breeding. B. G. Brackett. G. E. Seidel Jr.. and S. M Seidel ed. Academic Press, Inc., New York. NY.

89 Vernon, R. G. 1989. Influence of somatotropin on metabolism. Page 31 in Use of somatotropin in live­stock: production. K. Sejrsen, M Vestergaard. and A. Neimann-Sorensen, ed. Elsevier Appl. Sci., New York, NY.

90 Vicini, J. L., S. Hudson, W. J. Cole, M. A. Miller, P. J. Eppard., T. C. White, and R. J. Collier. 1990. Effect of acute cballenge with an extreme dose of somato­tropin in a prolonged-release formulation on milk: production and health of dairy canle. J. Dairy Sci. 73: 2093.

91 Wallis, M 1975. The molecular evolution of pituitary hormones. BioI. Rev. 50:35.

92 Wood., D. C., W. J. Salsgiver, T. R. Kasser, G. W. Lange, E. Rowold., B. N. Violand.. A. Johnson, R. M Leimgruber, G. R. Parr, N. R. Siegel, N. M. Kimack. C. E. Smith.. J. F. Zobel. S. M Ganguli. J. R. Garbow, G. Bild.. and G. G. Krivi. 1989. Purification and characterization of pituitary bovine somatotropin. J. BioI. Chem. 264:14741.

93 Young, F. G. 1947. Experimental stimulation (galac­topoiesis) of lactation. Br. Med. Bull. 5:155.

94 Zeddies, J., and R. Doluschitz. 1989. Potenlial farm level and dairy sector impact of the use of bovine somatotropin (BST) in the Federal Republic of Ger­many. Page 212 in Use of somatotropin in livestock: production. K. Sejrsen, M Vestergaard, and A. Neimann-SorenseD, ed. Elsevier Appl. Sci.. New York, NY.

REFERENCES ADDED IN PROOF

95 Etherton, T. D. 1991. Clinical review 21. the efficacy and safety of growth hormone for animal agriculture. J. Clin. Endocrinol. Metab. 72:957A.

96 Kroofeld.. D. S. 1988. Why BST may not see light of your barn. Pennsylvania Farmer (Mar 26): 14.

97 Kroofeld. D. S. 1990. Bovine growth hormone's im­pact on cow health.. hence. public health.. Page 83 in Bovine somatotropin. PrOC. Nlli Techno!. Assessment Coof .. Nat!. losl Health.. Bethesda, MD.