The Connecticut General Assembly
OFFICE OF LEGISLATIVE RESEARCH
(860) 240-8400
FAX (860) 240-8881
olr@po.state.ct.us
Room 5300
Legislative Office Building
Hartford, CT 06106-1591
February 28, 1994
94-R-0111
TO:
FROM:
David K. Leff, Senior Attorney
RE:
Bovine Somatotropin (BST)
You asked what the human and animal health arguments are for and against use of bovine
somatotropin (BST).
SUMMARY
Bovine somatotropin (BST) is a natural protein hormone that regulates milk production in
cows. The hormone can be produced using recombinant DNA technology. This synthetic hormone is
called rBST. When injected in cows, rBST can increase milk production by 10% to 20%.
The Federal Food and Drug Administration (FDA) approved rBST on November 5, 1993, but
use was delayed for 90 days pursuant to a provision in the Omnibus Budget and Reconciliation Act
passed by Congress in August 1993. Sales of Monsanto's rBST product, Posilac, were allowed to begin
on February 3, 1994 following completion of a report by the federal executive branch reviewing
available evidence on the impact of rBST use.
Despite the FDA approval and the availability of Posilac for use on dairy farms, there continues
to be a great deal of controversy surrounding rBST. Some have expressed concern about human health
effects due to potential increases in milk antibiotic residues resulting from alleged higher levels of
mastitis in cows administered rBST. Other human health concerns include increases in IGF-1
(Insulin-like growth factor) levels, and the possible spread of a central nervous system disorder known
as spongiform encephalopathies. Other potential human health concerns have also been expressed,
but these are the principal ones. Among bovine health concerns that have been raised are lowered
resistance to infectious diseases, increased stress, increased mastitis, and lowered fertility.
-1-
This memo describes rBST and the principal human and animal health concerns of those
opposed to and in favor of its use. We do not critique the logic or basis of the positions, or try to
reconcile them. Indeed, the proponents and opponents of rBST use are often not addressing identical
concerns or using the same data, and interpretations of the same data vary. The memo presents the
major human and animal health issues in the debate over rBST, providing general background to
facilitate more in-depth evaluation and a basis on which further questions can be posed to both sides.
BOVINE SOMATOTROPIN
Bovine somatotropin (BST), also known as bovine growth hormone (BGH), is a natural protein
hormone that controls the amount of milk cows produce. Unlike steroids, it is a metabolic, not a
growth hormone that is released from the anterior pituitary gland of cattle, a small gland located at the
base of the brain. As with any hormone, it is transported in the bloodstream to the body organs it
affects.
Recombinant bovine somatotropin (rBST), also known by its Monsanto trade name Posilac, is
a biosynthetic version of the naturally occurring pituitary hormone in cows. BST research with milk
cows was first reported by Russian scientists in 1937 who found that injecting the animals with bovine
pituitary extracts increased milk yield. Until the introduction of recombinant DNA technology only
small and impure amounts of BST could be obtained from slaughterhouses. The use of such
technology made it possible to put the BST gene into bacteria which could then be induced to produce
commercial quantities of the hormone. Somatotropin is a protein, and like all proteins is composed of
amino acids which are combined in particular sequences. According to the federal Office of
Technology Assessment (OTA), recombiantly derived rBST differs slightly from pituitary gland
produced BST by the addition of a few extra amino acids that may become attached to the end of the
BST molecule in the manufacturing process (OTA, U.S. Dairy Industry at a Crossroad:
Biotechnology and Policy Choices (1991).
rBST is administered to cows by injection beginning the ninth week after calving. rBST is
carried to the liver where it stimulates that organ to produce Insulin-like Growth Factor (IGF-1), a
protein hormone that aids in turning nutrients to milk. IGF-1 is carried to a cow's mammary gland
where it stimulates milk production. Studies have found that rBST can increase milk production 10%
to 20%. According to the January 1994 federal executive branch study, rBST “tends to increase milk
production per cow by an absolute amount regardless of the cow's initial level of milk production”
(Use of Bourke Somatotropin (BST) in the United States: Its Potential Effects (1994)). Thus, while
responses vary among and within herds, cows with low or medium production tend to show a higher
proportional increase.
According to the executive branch study, pituitary BST has no biological activity in humans,
even if injected, because its molecular structure is substantially different from that of human
somatotropin due to at least a 35% difference in amino acid sequence. Heating by cooking or
pasteurization inactivates BST that may exist in milk or meat. Traces of BST is found in all milk, and
the amount in milk from cows injected with rBST is no greater than from those not administered the
supplement. Because it is impossible to differentiate between BST levels in milk from cows given
rBST supplements and those that are not, there is no test to distinguish between milk from
supplemented and nonsupplemented animals.
HUMAN HEALTH ISSUES
-2-
Antibiotic Residues
Mastitis is the most common disease of dairy cows and is treated with antibiotics which leave
residues in milk. Antibiotic residues in milk can cause allergic reactions in human beings
(approximately 3% to 10% of the population is allergic to penicillin) and lead to antibiotic resistance.
According to FDA, mastitis incidence increased moderately in cows treated with rBST. But,
there was no evidence that these cases of mastitis were more difficult to treat based on their duration.
On a per-unit milk basis the increase (about 0.1 cases per cow per year) is about four-to-nine times less
than from other variables such as stage of lactation, season, the number of lactentions for a particular
cow, and herd-to-herd variation. In considering the possible increase in antibiotic use, the executive
branch study relied on the fact that state and federal regulatory bodies monitor milk supplies for drug
residues and require disposal of milk with levels above standards ( see, OLR report 94-R-0128,
Antibiotics in Milk). It also noted that the dairy industry tests every milk tanker truck load for beta
lactam (penicillin family) drugs before processing “so that even if an increase in use of these drugs—
and an increase in illegal residues—occurred as a result of increased mastitis, residues would result in
the rejection of the milk before it entered the marketplace. Moreover, dairy producers who experience
an increased incidence of mastitis would likely reevaluate their use of BST.”
The executive branch study concluded that there was a “minuscule public health concern for
beta lactam antibiotic residues” after noting that less than 10 cases of allergic reactions following
consumption of penicillin residues in milk have occurred worldwide in the past 25 years, and typically
these reactions consist of skin rashes that are not a significant health risk.
The Consumer Policy Institute of Consumers Union, publisher of Consumer Reports, finds that
FDA underestimates mastitis incidence, ignores widespread use of illegal antibiotics, and relies too
heavily on a limited program of residue testing (M. Hansen, "Testimony Before the Veterinary
Medicine Advisory Committee on Potential Animal and Human Health Effects of rbGH Use (3/93);
M. Hansen, Letter to FDA Commissioner Mande (5/93)). According to the institute's Dr. Michael K.
Hansen, FDA defined mastitis as the presence or absence of the condition in an individual cow while
scientific literature usually refers to infected quarters because a cow has four separate teats that are not
directly connected. In addition to other studies, he cites 1992 Vermont research that indicates that
while four times as many rBST cows were treated for mastitis compared to control cows, the rBST
cows had over seven times the number of mastitis cases.
Hansen cites a 1992 General Accounting Office study that found up to 82 residue producing
drugs (not all of which are antibiotics) are known or suspected of being used on dairy cattle. Only 30
of these are actually FDA approved. Some of these are used illegally and others under the “Extra-Label
Policy” which allows use under a veterinarian's supervision. Some of these drugs are used illegally to
treat mastitis and even Monsanto used a number of drugs illegally in their trials of rBST. Given this
widespread use of unapproved drugs, Hansen questions whether the FDA can effectively enforce its
safety standards for drug residues in milk.
Hansen notes that only four of six beta lactams are subject to testing in each milk tanker load,
and though FDA has expanded its monitoring program, it still only tests for 12 drugs, notifies dairies in
advance of sampling, and takes only about 500 samples per year. Although the FDA claims that 89%
of mastitis is treated with beta lactams, the study on which this data is based is faulted by Hansen
-3-
because it relied on self-reporting with no real verification. Increased mastitis, Hansen argues, will
lead to increased use of antibiotics the control over which is too limited.
Hansen maintains new evidence suggests that even FDA “safe levels” of antibiotics may
promote antibiotic resistance in disease-causing organisms. Thus, “`greater emphasis should be placed
on keeping the milk supply residue free rather than reliance on maintaining the working residue levels
suggested by the term safe levels'.”
Insulin-Like Growth Factors (IGF)
According to the executive branch study, the milk of rBST cows shows a slight increase in the
level of IGF-1. IGF (insulin-like growth factors) is a natural substance that mediates the effects of
growth hormones in cows and humans. The molecular structure of bovine IGF-1 and human IGF are
identical, and since the chemical is not species specific the impact of increased levels due to rBST is
important. IGF-1 content in milk varies over the lactation cycle and between cows in their first or
subsequent cycle. The study maintains that the amounts of IGF-1 in cows administered rBST are
within the normal of that found in untreated cows. According to FDA, IGF-1 is orally inactive and
thus should not have an effect when milk is consumed. The executive branch study states that the
amount of IGF-1 ingested from milk drinking is “much less than that reaching the stomach from saliva
and digestive secretions” in which the substance is present, and is 100 to 1,000 times lower than
endogenous human blood levels. “Thus, even if IGF-1 were ingested and not destroyed in the
digestive tract but absorbed intact, the dilution of a few nanograms of the undigested IGF-1 into the
large endogenous plasma pool in humans would be physiologically insignificant.”
Opponents of rBST use maintain that elevated levels of IGF-1 can lead to a disease called
acromegaly which results in enlargement of hands, feet, nose and chin; glucose intolerance, and
hypertension. The Consumer Policy Institute maintains that recent evidence suggests a potential link
between IGF-1 and cancer and tumor growth. Dr. Samuel Epstein, Professor of Occupational and
Environmental Medicine at the University of Illinois at Chicago expresses “grave concerns” about the
risk of breast cancer from consumption of rBST milk (S. Epstein, letter to FDA commissioner D.
Kessler (2/94)).
The institute's Michael Hansen notes that an FDA authorized paper in the August 24, 1990
issue of Science refers to a number of industry studies which “found statistically significant increases”
of IGF-1 in rBST treat cows, ranging from 25% to 70%. Another study, not referred to in the Science
article, that took place near the end of the lactation cycle (when IGF-1 levels are normally at a
minimum), revealed IGF-1 levels at least 3.6 times the levels in untreated cows after a week of rBST
injections. Hansen notes that a problem with virtually all studies is that a number of investigators have
recently shown that the most common IGF-1 test is unreliable.
The institute disputes FDA's claim that IGF-1 is orally inactive. It cites a 1987 study that
suggests IGF-1 in milk can survive the human digestive tract and be taken up by the body. According
to the institute, the study found that IGF-1 stimulates growth in cultures of epithelial cells lining the
intestine. The institute also disagrees with the conclusions and finds fault with the reasoning of a
Monsanto sponsored study to determine whether IGF-1 is orally active in normal rats. The study was
relied on by the FDA. The institute concludes:
In sum, we believe that the lone oral feeding study involving normal rats described in
Science, is a poor study that appears to have been designed to minimize the chance of
-4-
finding IGF-1 to be orally active. In spite of this, the study contains suggestive data
that IGF-1 may be orally active. This, combined with the facts that IGF-1 stimulates
growth and division of epidermal cells in the intestine and has also been associated with
colon tumor growth and, potentially, with human epidermal carcinoma, suggests that
until we know more about the role of IGF-1, extreme caution should be exercised.
Bovine Spongiform Encephalopathy (BSE)
Cows using rBST require more energy dense foods than control cows, according to the
Consumer Policy Institute. Among these foods are supplements that come from rendering animals.
The institute argues that since use of rBST will increase the amount of rendered protein fed to cows, it
may accelerate spread of bovine spongiform encephalopathy (BSE), a disease affecting the central
nervous system, particularly the brain. It is popularly known as “mad cow disease” because the
animals act nervous and aggressive and jump around shortly before dying. A group of related diseases
known as transmissible spongiform encephalopathies occur in both humans and animals. They have a
long incubation period, are typically fatal, have as yet unknown infective agents that are resistant to
most types of sterilization, and produce no host immune response. Although a sheep form of the
disease known as scrapie has been around for hundreds of years, the bovine form was found in
England in 1985.
Cows likely develop the disease by eating scrapie-infested animal protein feed supplements of
meat and bone meal. The disease is believed to have emerged due to use of meat and bone meal in
dairy cow feed, and a change in rendering processes in the early 1980s that abandoned use of high heat
and solvents which likely killed the infectious agent.
Although the institute notes that scientists and government officials say there is no evidence
that BSE can affect humans, it cites some anecdotal reports which cast doubt on such assertions. The
institute recognizes that there are no cases of BSE in the U.S., and that officials say the disease is
unlikely to occur here. But, it describes a similar disease on a Wisconsin mink ranch where feed
produced from cows was the source of the infection, and raises the possibility that a different strain of
BSE with somewhat different symptoms may be the cause of death in some cases classified as
“downer cow disease” where apparently healthy looking cows literally drop dead.
The institute believes that “feeding of cows to cows should be discontinued, not expanded” and
that rBST “may promote dissemination of BSE, or a BSE like disease, because cows given rbGH
require high-protein feed.”
We were unable to locate any literature discussing BSE by those in favor of rBST use.
BOVINE HEALTH ISSUES
General Perspective
The U.S. Office of Technology Assessment notes that use of rBST in dairy cows has been
claimed to cause a variety of adverse health effects including ketosis (a nutritional disease), fatty liver,
chronic wasting, lameness, milk fever, mastitis, infertility and heat intolerance. OTA maintains that if
metabolic disorders occurred they would most likely appear during the first few days of rBST use, and
that none of the catastrophic health effects described above have been observed in long-or short-term
studies since the first studies in 1937, including in acute or chronic toxicity studies. Only one study
-5-
shows an increase in ketones (an indication of subclinical ketosis), but the BST preparation was
contaminated with other hormones.
Epstein maintains that information on bovine health is hampered by the small scale nature of
trials. He terms data on adverse veterinary affects as “sparse” and largely based on “incidental
findings” with an “absence of multi lactational and multigenerational toxicological studies” (S.
Epstein, “Potential Public Health Hazards of Biosynthetic Milk Hormones," r20 International Journal
of Health Services 1 (1990)).
Resistance to Infectious Disease
Some claim that rBST reduces resistance to infectious and contagious diseases in cows. OTA
maintains that "none of the hundreds of bst studies reported lower milk yield or decreased productive
efficiency, both of which are associated with any increase in sickness and suffering," and suggests that
rBST may help maintain immunity from disease.
Epstein notes increased mastitis and a “high level” of unspecified infections disease in one of
nine trials. “An increased incidence of unspecified (and unpublished) infectious disease has recently
been confirmed,” he states.
Stress
Although OTA states that stress is difficult to evaluate, the report notes that “several indices
exist that demonstrate no stress effects due to bST.” Cows that are stressed produce milk less
efficiently and use more energy as heat. “While numerous physiological variables have been
monitored to assess stress and have been shown not to change, nothing illustrates the normalcy of bSTsupplemented cows as effectively as the persistent gains in milk yield and productive efficiency
throughout the treatment period.” Recent studies, OTA maintains, on positive-to-negative energy and
nitrogen balances “have clearly demonstrated that bST has no effect on the energy expended for
maintenance or production of a unit of milk.”
Epstein finds the small size of rBST trial groups a frustration in examining stress effects on
cows. But, he notes that “the importance of stress-related diseases associated with prolonged deviation
in plasma levels of BGH has been strikingly confirmed in trangenic pigs in which there were
`significant improvements in both daily weight gain and feed efficiency.'” These pigs also developed
high incidences of gastric ulcers, arthritis, cardiomegaly, dermatitis, and renal diseases. Epstein also
claims that biosynthetic milk hormones result in a “prolonged negative energy balance” which results
in “reduced total body fat, excessive tissue loss, and hypertrophy of foregut tissue.” According to
Epstein, this negative energy balance appears to be associated with increased stress and infectious
disease susceptibility.
Mastitis
According to OTA, major factors affecting the incidence of mastitis include milking
management, herd health programs, and milk yield. The report notes it is difficult to detect and
evaluate whether mastitis increases reported in cows administered rBST result from BST use
independent of milk yield. OTA cites two reports summarizing studies that found no indication that
BST was associated with increased mastitis infections. The executive branch report, while
acknowledging a moderate increase in mastitis in treated cows, notes that it is four to nine times less
-6-
than the effects due to other variables such as season, lactation stage, number of lactations for a
particular animal, and herd-to-herd variations.
The Consumer Policy Institute states that FDA data shows a 76% increase in mastitis, rates for
primiparous cows (those with their first calf) and a 50% increase for multiparous cows (those who
have given birth more than once). But for reasons described above in our discussion of antibiotic
residues, the institute maintains that FDA understates mastitis rates, and that some data indicate much
higher rates. The institute sees “absolutely no justification for tolerating an increase in disease rates for
a drug that increases milk production, and that the FDA cannot possibly determine to be safe.”
Dairy Cow Fertility
Although recognizing the need for more data to provide definitive conclusions, OTA notes that
reviews summarizing existing data indicate that rBST treatments result in decreased pregnancy rates
but no change in conception rates. But because a decreased pregnancy rate is typically associated with
increased milk production, OTA concludes that “effects of high milk yield on reproductive performance are the same whether or not the high yield was due to the use of rBST.” OTA also maintains
that because BST improves persistency of lactation “the calving interval for optimum economic return
may be substantially increased when bST is used.” OTA maintains this will increase income over feed
cost, reduce veterinary costs, and have some benefit from a cow physiology perspective because the
majority of health problems and veterinary costs for dairy cows occur during the first 45 days
postpartum.
Epstein cites reduced fertility in four of nine milk production trials. This evidence is supported
by results in 59 industry or industry sponsored trials reported in 1987 and 1988, six of which gave
reproductive data. The “overall conception or pregnancy rates of controls in these six trials were 89%
versus 59% in injected cows.” In addition to inhibition of conception rates, at least one trial
demonstrated reduced pregnancy rates, and Epstein raises concerns that rBST may affect embryo
survival. Epstein concludes that “increased productivity from the use of synthetic milk hormones could
be more than offset by economic losses due to reproductive impairment.”
DKL:pa
-7-